Jurnal de Chirurgie

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr.
1 [ISSN 1584 9341]
Jurnalul de chirurgie i propune s devin n scurt timp o publicaie cu impact n activitatea de cercetare chirurgical i de pregtire profesional continu. Jurnalul apare ca o necesitate n condiiile cerute de noile forme de pregtire a rezidenilor n chirurgie i se angajeaz s pun la dispoziia tinerilor chirurgi din diverse specialiti, cunotinele i modelele de baz a pregtirii lor ca specialiti pentru noul mileniu.
Editori onorifici Richard M. Satava (U.S.) Paul Allen Wetter (U.S.) Editor emeritus Robert van Hee (Belgia) Editor ef Eugen Trcoveanu Redactor ef Radu Moldovanu Secretar general de redacie Alin Vasilescu Redactori Dan Andronic Gabriel Dimofte Liviu Lefter Cristian Lupacu Drago Pieptu Valeriu Surlin Nutu Vlad Corector Oana Epure ntreaga responsabilitate a opiniilor exprimate n articolele Jurnalului de chirurgie revine autorilor. Republicarea pariala sau n ntregime a articolelor se poate face numai cu menionarea autorilor i a Jurnalului de chirurgie. Includerea materialelor publicate pe acest site pe alte site-uri sau n cadrul unor publicaii se poate face doar cu consimmntul autorilor. Copyright Jurnalul de chirurgie, Iai, 2005-2011 Comitet tiinific Alexander Beck (Ulm, Germania) Pierre Mendes da Costa (Bruxelles, Belgia) Gheorghe Ghidirim (Chiinu, Moldova) Christian Gouillat (Lyon, Frana) Vladimir Hotineanu (Chisinau, Moldova) Lothar Kinzl (Ulm, Germania) Jan Lerut (Bruxelles, Belgia) C. Letoublon (Grenoble, Frana) Phillipe van der Linden (Bruxelles, Belgia) John C. Lotz (Staffordshire, Marea Britanie) Iacob Marcovici (New Haven, SUA) Francoise Mornex (Lyon, Frana) Andrew Rikkers (SUA) Michel Vix (Strasbourg, Frana) Giancarlo Biliotti (Florena, Italia) Gianfranco Silecchia (Roma, Italia) Monica Acalovschi (Cluj) Nicolae Angelescu (Bucureti) Gabriel Aprodu (Iai)
Mircea Beuran (Bucuresti)

Eugen Bratucu (Bucureti) N.M. Constantinescu (Bucureti) Silviu Constantinoiu (Bucureti) Ctlin Copescu (Bucureti) Constantin Copotoiu (Tg. Mure) Nicolae Danil (Iai) Corneliu Dragomirescu (Bucureti) tefan Georgescu (Iai) Ioana Grigora (Iai) Avram Jecu (Timioara) Rducu Neme (Craiova) Alexandru Nicodin (Timioara) Florian Popa (Bucureti) Irinel Popescu (Bucureti) Doinia Rdulescu (Iai) Vasile Srbu (Constana) Viorel Scripcariu (Iai) Liviu Vlad (Cluj Napoca) Victor Tomulescu (Bucureti)
Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]
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EDITORIAL PRIORITI N TRATAMENTUL POLITRAUMATISMELOR CRANIO-CEREBRALE I ABDOMINALE......................................................................................1 V. Paunescu, Valentina Pop-Began, D. Pop-Began, C. Popescu U.M.F. "Carol Davila", Clinica Chirurgie, Spitalul "Bagdasar-Arseni", Bucuresti ARTICOLE DE SINTEZ EPIDEMIOLOGIA, ETIOPATOGENIA I DIAGNOSTICUL HEPATOCARCINOMULUI.................................................................................................................6 N. Vlad Clinica I Chirurgie I. Tnsescu-Vl. Buureanu doctorand, Universitatea de Medicin i Farmacie Gr. T. Popa Iai CANCERUL GASTRIC LOCAL AVANSAT SAU METASTAZAT ACTUALITI EPIDEMIOLOGICE I DIAGNOSTICE............................................................22 Florina Ptracu (1), Adina Croitoru (1), Iulia Gramaticu (1), M. Andrei (3), Adriana Teiuanu (3), M. Diculescu (2) 1. Compartimentul de Oncologie Medical, Institutul Clinic de Boli Digestive i Transplant Hepatic Fundeni (ICBDTHF) 2. Clinica de Gastroenterologie i Hepatologie, ICBDTH Fundeni 3. Clinica de Gastroenterologie i Hepatologie, SUU Elias ARTICOLE ORIGINALE GREFONUL SINTETIC N TRATAMENTUL CHIRURGICAL AL EVENTRAIILOR. STUDIU EXPERIMENTAL............................................................................27 M. Miclu (1), Codrua Miclu (2), C. Mircu (3), Romania Glaja (4), C. Mihart (1), L. Fulger (1) 1. Clinica II Chirurgie 2. Clinica Chirurgie General i Oncologie Universitatea de Medicin i Farmacie Victor Babe Timioara 3. Facultatea de Medicin Veterinar Universitatea de tiine Agronomice i Medicin Veterinar a Banatului 4. Departamentul de Anatomie Patologic, Spitalul Municipal Timioara FACTORII DE RISC N APARIIA STAZEI GASTRICE POST DUODENOPANCREATECTOMIE CEFALIC.............................................................................33 Dana Iancu, A. Barto, L. Mocanu, Teodora Mocanu, Raluca Bodea, F. Zaharie, Andra Andreescu, C. Iancu Clinica Chirurgie III, Cluj-Napoca Universitatea de Medicin i Farmacie Iuliu Haieganu Cluj-Napoca, Romnia
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TRAUMATISMELE ABDOMINALE - ATITUDINE TERAPEUTIC.......................................38 D. Popa, C. Copotoiu, V. Bud, C. Molnar, A. Pantiru, C. Rosca, M. Gherghinescu, C. Russu, T. Dudas, B. Suciu, G. Serac, A. Cotovanu, F. Constantinescu, I. Balmos Clinica Chirurgie1, Spitalul Clinic Judetean de Urgent Mure, Romnia HIPERALIMENTAIA MIXT PREOPERATORIE N ESOFAGOPLASTII..........................46 Laura Magdalena Nicolescu (1), S. Lunc (2) 1. Secia Anestezie i Terapie Intensiv 2. Clinica de Urgene Chirurgicale Spitalul Clinic de Urgen Sf. Ioan Iai Universitatea de Medicin i Farmacie "Gr. T. Popa" Iai PROFILUL CTOKINELOR N PLASMA PACIENILOR CU MELANOM MALIGN...........54 Natalia Cireap (1), R. Ilina (1), Diana Narita (2), A. Anghel (2), Elena Lazar (3), T. Nicola (1) 1. Departmentul de Chirurgie Oncologic 2. Catedra de Biochimie 3. Catedra de Morfopatologie Universitatea de Medicin i Farmacie Victor Babe, Timioara, Romnia IMPORTANA AUTOGREFELOR N RECONSTRUCIA LANULUI OSICULAR N OTITA MEDIE SUPURAT CRONIC...............................................................64 A. Vlase, V. Costinescu, T.Ghindaru Disciplina ORL, Facultatea De Medicina, Universitatea de Medicina i Farmacie Gr.T.Popa Iai HISTEROSCOPIA, METOD MINIM INVAZIV DE DIAGNOSTIC I TRATAMENT N INFERTILITATEA DE CAUZ UTERIN....................................................71 Nora (Dumitriu) Miron, Ivona Anghelache-Lupacu, Demetra Socolov, Cristina David, R.Socolov Catedra de Obstetric i Ginecologie Universitatea de Medicin i Farmacie Gr. T. Popa Iai, Romnia CAZURI CLINICE TRATAMENTUL CHIRURGICAL RADICAL AL COLANGIOCARCINOMULUI HILAR - PREZENTARE DE CAZ.............................................78 V. Gavrilovici (1), F. Grecu (2), A. Lpuneanu (2), D. Ferariu (3), Cr. Dragomir (2) 1. Spitalul Sf. Ioan cel Nou Suceava, Secia Chirurgie general, doctorand Universitatea de Medicin i Farmacie Gr.T.Popa Iai 2. Clinica III Chirurgie, Universitatea de Medicin i Farmacie Gr.T.Popa Iai 3. Departamentul de Anatomie Patologic, Sp. Sf Spiridon, Iai PSEUDOMYXOMA PERITONEI OF APPENDICEAL ORIGIN AN UNUSUAL CAUSE OF ABDOMINAL COMPARTMENT SYNDROME: CASE REPORT....................................................................................................................................86 I. Mishin, G. Ghidirim, G. Zastavnitsky, M. Vozian First Department of Surgery N. Anestiadi N. Testemitsanu University of Medicine, Kishinev, Moldova
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LARGE SPLENIC CYSTS AT THE UPPER POLE OF THE SPLEEN LAPAROSCOPIC MANAGEMENT.................................................................................................93 V. urlin (1), E. Georgescu (1), S. Rmboiu (1), Cristiana Dumitrescu (2), T. Bratiloveanu (1), I. Georgescu (1) 1. First Clinic of Surgery, County Emergency Hospital of Craiova, Romania 2. Department of Internal Medicine, CORDIS Medical Center University of Medicine and Pharmacy of Craiova BECKWITH-WIEDEMANN SYNDROME WITH CLEFT PALATE........................................101 S. Dey (1), B. Kharga (1), B. Dhar (2), V.K. Singh (1), R. Dey (3) 1. Department of Surgery, Sikkim Manipal Institute of Medical Sciences, India 2. Department of Surgery, The Mission Hospital, Durgapur, West Bengal, India 3. Department of Physiology, Sikkim Manipal Institute of Medical Sciences, India POLIPOZA HAMARTOMATOAS ENTERAL DEGENERAT MALIGN PREZENTARE DE CAZ...................................................................................................................105 N. Al Hajjar, Terezia Murean, L. Vlad, C. Iancu, Raluca Bodea, P. Boruah, Angela Pru, A. Coe, Roxana Olteanu Clinica Chirurgie III UMF Iuliu Haieganu, Cluj-Napoca, Romnia CARBAPENEM-RESISTANT ACINETOBACTER BAUMANNII POSTOPERATIVE MENINGITIS..................................................................................................109 Laura Ghibu, Egidia Miftode, Olivia Dorneanu, Carmen Dorobat Clinic of Infectious Diseases Gr. T. Popa University of Medicine and Pharmacy Iasi ANATOMIE I TEHNICI CHIRURGICALE EARLY RETROPANCREATIC DISSECTION DURING PANCREATICODUODENECTOMY - TECHNICAL NOTES...................................................114 C. Lupascu (1), D. Andronic (1), R. Moldovanu (1), Corina Ursulescu (2), C. Vasiluta (1), E. Tarcoveanu (1) 1. I Tnsescu Vl. Buureanu First Surgical Clinic 2. St. Spiridon Hospital Radiological Clinic Gr. T. Popa University of Medicine and Pharmacy Iai ARTICOLE MULTIMEDIA POT FI PREVENITE EVENTRAIILE PARASTOMALE?.......................................................123 E. Trcoveanu, Elena Cotea, A. Vasilescu, Cr. Lupacu, N. Dnil, N. Vlad, Delia Rusu Clinica I Chirurgie I. Tnsescu Vl. Buureanu, Universitatea de Medicin i Farmacie Gr. T. Popa Iai ISTORIA CHIRURGIEI WILLIAM STEWART HALSTED SI MODERNIZAREA CHIRURGIEI N S.U.A................130 Liliana Strat Catedra Obstetric Ginecologie Universitatea de Medicin i Farmacie Gr. T. Popa Iai
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RECENZII I NOUTI ELEMENTE DE ANATOMIE CHIRURGICAL GHID PENTRU EXAMENUL DE SPECIALITATE.......................................................................................................................135 R. Moldovanu, V. Filip, N. Vlad Editura Tehnopress, Iai 2010
Erat Dintr-o eroare a redaciei, la lucrarea Late Diagnosis of an End Stage Pancreatic ACTHoma: Case Report, publicat n vol. 4, nr. 3, 2008 a fost omis ca ultim autor Voichia Mogo (Clinica de Endocrinologie, UMF Iai).
ntreaga responsabilitate a opiniilor exprimate n articolele Jurnalului de chirurgie revine autorilor. Republicarea pariala sau n ntregime a articolelor se poate face numai cu menionarea autorilor i a Jurnalului de chirurgie. Includerea materialelor publicate pe acest site pe alte site-uri sau n cadrul unor publicaii se poate face doar cu consimmntul autorilor. Copyright Jurnalul de chirurgie, Iai, 2005-2011 VI
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PRIORITI N TRATAMENTUL POLITRAUMATISMELOR CRANIO-CEREBRALE I ABDOMINALE

V. Paunescu, Valentina Pop-Began, D. Pop-Began, C. Popescu U.M.F. "Carol Davila", Clinica Chirurgie, Spitalul "Bagdasar-Arseni", Bucuresti Stabilirea prioritilor n ngrijirea pacientului politraumatizat cu suspiciune de leziuni cranio-cerebrale i abdominale este dificil. Aprecierea severitii i a naturii traumatismului se face n echip multidisciplinar i se are n vedere statusul fiziologic al traumatizatului, anatomia traumei i vrsta traumatizatului [1-3]. Obiectivele urmrite sunt: identificarea i corectarea rapid a leziunilor; depistarea leziunilor altor organe; evaluarea impactului traumatismului asupra organismului; depistarea reaciei gazdei la traum [4]. Analiza multifactorial a unui pacient cu politraum urmrete: - examenul clinic la internare; - repartizarea pe grupe de vrst i pe sexe; - repartizarea n funcie de mecanismul de producere; - repartizarea politraumatizailor dup leziunea abdominal; - repartizarea n funcie de ocul traumatic; - clasificarea politraumatizailor dup scorurile traumatice; - utilizarea scorurilor traumatice n compararea rezultatelor terapeutice. Dintre cei 5725 pacieni internai cu traumatisme n ultimii doi ani n Clinica Chirurgie, Spitalul "Bagdasar-Arseni", Bucureti, 1456 au prezentat politraumatisme; 1444 dintre ei au fost internai n serviciul de terapie intensiv datorit gravitii leziunilor. Dintre cele 1456 politraumatisme, 206 pacienti au prezentat leziuni asociate cranio-cerebrale i abdominale (14,63%). Cei 206 de politraumatizai cu component cranio-cerebral i abdominal au fost urmrii prospectiv. Am ncercat s rspundem la trei ntrebri eseniale pentru stabilirea diagnosticului i tratamentului: 1. Ct atenie trebuie acordat unei afeciuni cranio-cerebrale corectabil chirurgical i ct de mult influeneaz aceasta ordinea investigaiilor diagnostice? 2. Care este importana diagnosticului i a tratamentului unei leziuni intraabdominale la un politraumatizat cranio-cerebral i abdominal? 3. Puncia lavaj peritoneal pozitiv impune celiotomia imediat chiar dac aceasta amn efectuarea unei tomografii computerizate (CT) craniene pentru diagnosticul unui eventual hematom intracranian? Tratamentul politraumatizatului se face n multe etape, ntr-un "lan de ngrijiri". Prima verig este constituit de factorii prespitaliceti [5]: ambulana i serviciile paramedicale, cnd traumatizatul poate primi ngrijiri ct mai rapid de la producerea accidentului, evitnd astfel "ridicarea de la locul accidentului a unui rnit, transportarea unui muribund i internarea unui decedat". A doua verig este reprezentat de unitatea de primire a urgenelor, unde se instituie primele msuri de resuscitare i unde se face evaluarea primar dupa formula A.B.C.D.E. (air, breath, circulation, disability, exposure) [6].
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Acest grup de politraumatizai se caracterizeaz prin dificultatea diagnosticului i a tratamentului, majoritatea fiind incontieni i cu oc traumatic hipovolemic. Este cunoscut faptul c n primele 90 de minute dup accident ajung la spital 90% dintre plgi i 60% dintre contuzii. n contuzii sunt afectate de trei ori mai mult organele parenchimatoase, abdomenul expunnd traumatismului 18% din suprafaa corpului. Severitatea traumatismelor abdominale la politraumatizaii cu leziuni craniocerbrale la internare a fost confirmat prin necesitatea ventilaiei mecanice (n=52; 25,72%), a prezenei ocului (n=69; 33,49%) i a Glasgow Coma Scale ntre 3 i 5 puncte la 72 (34,95%) cu 70 decese (97,92%). Diagnosticul traumatismului cranio-cerebral a fost stabilit prin examen clinic, evaluarea comei prin scala Glasgow, tomografie computerizata craniana (182 cazuri) si angiografie carotidian (24 pacieni). Diagnosticul contuziei abdominale a fost stabilit prin examen clinic, puncie/lavaj peritoneal, tomografie computerizat abdominal (82 cazuri), ecografie abdominal (44 bolnavi) i n ultim instan, laparotomie exploratorie (49 cazuri). Diagnosticul leziunilor membrelor s-a efectuat prin examen clinic i radiografic. Leziunile coloanei vertebrale au fost diagnosticate prin examen clinic i radiografic. Leziunile toracice au fost identificate clinic, radiografic i CT. Vrsta politraumatizailor a variat ntre un an i 84 ani, dar majoritatea cazurilor s-au nregistrat n decadele I i II de via, 44 i respectiv, 31 cazuri. Repartizarea pe sexe arat o predominan a brbailor (n=149; 72,33%), fa de femei (n=57). Incidena crescut a politraumatismelor cranio-cerebrale i abdominale la brbai s-a meninut la toate grupele de vrst. Studiul cauzalitii traumatismelor a evideniat predominena accidentelor rutiere (n=156; 75,72%), urmate la mare distan de cderi de la nalime (n=34; 16,50%), agresiuni (n=11; 5,33%) i alte cauze (n=5). Semnele predictive pentru leziunile cranio-cerebrale sunt semnele neurologice de lateralizare, care au cel mai mare risc relativ de 4, pentru p<0,05 i apoi anomaliile pupilare, cu risc relativ de 3,3. Leziunile intracerebrale decelate la pacienii studiai au fost: edem cerebral difuz (n=32), hematoame intracerebrale (n=17), dilacerare cerebral (n=8), hemoragii intracerebrale i ventriculare (n=4). Hemoragiile cerebrale au fost urmate de cea mai mare mortalitate, 100%, apoi de hematoamele cerebrale (n=14) cu 82,3% i dilacerarea cerebral, cu 75% decese. Urmrirea contientului cu ajutorul calculrii Glasgow Coma Scale, a artat c are valoare predictiv i se coreleaz semnificativ cu leziunile cranio-cerebrale identificate la CT. Glasgow Coma Scale este dificil de estimat la pacientul comatos [7]. Pacienii cranio-cerebrali cu "risc crescut" au fost apreciai dup clasificarea computer-tomografic n scala Marshall, n care leziunile difuze de tip III i de tip IV sunt leziuni cu prognostic nefavorabil [8,9]. Leziunile de tip III includ: cisternele perimezencefalice sunt comprimate sau absente; deplasarea liniei mediene ntre 0 mm i 5 mm; lipsa leziunilor hiperdense sau cu densitate mixt > 25 ml. n leziunile difuze de tip IV sunt cuprinse: deplasarea liniei mediene > 5 mm, lipsa leziunilor hiperdense sau cu densitate mixt > 25 ml [10]. La politraumatizatul cu leziuni cranio-cerebrale existena i a traumatismului abdominal impune rspunsuri la urmtoarele ntrebari: 1. Are leziune intraabdominal? 2. Dac da, necesit intervenie chirurgical?
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3. Dac necesit intervenie chirurgical, care este timpul optim? 4. Are i leziuni extraabdominale? Examenul abdomenului este dificil de efectuat la pacieni n com, aflai sub influena drogurilor, a alcoolului sau boli neurologice, ca paraplegie traumatic sau la pacienii ventilai mecanic. La politraumatizatul abdominal i cranio-cerebral, semnele abdominale pot fi mascate sau falsificate. Semnele mascate sunt: 1) absena contracturii abdominale la pacientul politraumatizat comatos; 2) absena turgescenei venelor jugulare la pacientul cu tamponad i sngerare intraperitoneal; 3) dificultatea evalurii semnelor neurologice la cei cu leziuni osoase. Semnele falsificate sunt: 1) fals contractur abdominal la cei cu fracturi costale sau traumatisme vertebro-medulare; 2) matitate pe flancuri simulnd lichid intraperitoneal la cei cu fracturi de pelvis i hematom retroperitoneal; 3) ileus dinamic n fracturile vertebrale. Dup timpul scurs de la accident la examinare, n primele ore domin semnele de hemoragie; dup cteva ore apar semnele de peritonit; dup cteva zile apar semnele de ocluzie intestinal i sfacelare tardiv; la 5-7 zile apare fibrinoliza. Hemoragia n doi timpi apare dup cteva ore sau luni de zile. CT simpl sau i cu substan de contrast permite i embolizarea prin cateter a vaselor care sngereaz activ. n traumatismele abdominale,CT are cea mai mare valoare predictiv, de 100% n traumatismele renale i peritoneale, de 85% n leziunile hepatice i pancreatice i de 83% n leziunile splenice [2,11,12]. Tratamentul chirurgical i internarea n serviciul de terapie intensiv se impune la pacientul la care presiunea arterial este mai mic de 90 mm Hg, Glasgow Coma Scale este mai mic de 8 puncte n traumatisme penetrante ale gtului i ale trunchiului i la pacienii n vrst de peste 55 ani. Nu trebuie uitat c tratamentul nonoperator este hazardat n leziunile minime i n absena hemoperitoneului, ca i existena riscului imprevizibil de ruptur tardiv a splinei. ocul hemoragic i traumatic a fost precizat prin examen clinic, determinri hematologice, msurarea presiunii venoase centrale la 77 pacieni, aplicarea metodei ASTRUP la 62 pacieni. ocul a avut drept cauz hemoragia, n 45 cazuri prin leziuni intraabdominale, n 18 cazuri prin leziuni abdominale i ale membrelor, iar n 14 cazuri ocul a fost mixt, hemoragic i traumatic. ocul hipovolemic genereaz leziuni tisulare, leziuni ale sistemului nervos central cu redistribuirea fluxurilor sanguine i scderea oxigenului tisular. Leziunile tisulare elibereaz mediatorii inflamaiei: citokine, elemente ale complementului, derivai ai acidului arahidonic i metabolii ai oxigenului cu declanarea sindromului de rspuns inflamator sistemic (SIRS), care a fost prezent n proporie de 29%. Prezena ocului a ntunecat prognosticul politraumatizailor. Dac la pacienii fara oc la internare mortalitatea a fost de 24% (32 decese), la politraumatizaii cu oc la internare, mortalitatea a crescut la 68,8%. Persistenta SIRS a indus insuficienta multipla de organe (MODS). Cele mai frecvente insuficiene au fost: insuficiena respiratorie (65%) i insuficiena renal acut (48,6%). Amploarea hemoragiei i semnele clinice de hipovolemie sunt n legatur cu gravitatea leziunii i cu organul implicat. Leziunile hepatice mici pot sngera i uneori hemostaza se face spontan.
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Sngerarea la nivelul organelor cavitare este persistent, dar nu la fel de grav ca cea de la nivelul mezenterului acestor organe. Pe de alt parte, leziunile la nivelul organelor cavitare pot perfora cu peritonit consecutiv i ale crei semne sunt dificil de evaluat la comatoi sau la cei cu leziuni ale mduvei spinrii. Adoptarea atitudinii chirurgicale la un politraumatizat este influenat de evidenierea unei leziuni tratabile chirurgical. Stabilirea diagnosticului i a indicaiei chirurgicale abdominale este ngreunat de alterarea strii de contien. Dificultatea diagnostic este maxim n prezena unei contuzii abdominale i craniene. Pentru elucidarea diagnosticului la aceti politraumatizai am folosit un algoritm de diagnostic i tratament care mparte politraumatizaii n dou categorii: hemodinamic stabil i hemodinamic instabil. Daca instabilitatea hemodinamic nu se compenseaz dup administrarea de lichide parenteral, se impune celiotomia. Traumatizaii hemodinamic stabili sunt supui investigaiilor i dac acestea evideniaz leziune intraabdominal i GCS este peste 7 i fr semne de lateralizare, se impune celiotomia. Traumatizaii cu contuzie abdominala pot fi: 1) hipovolemici, contieni sau incontieni; 2) normovolemici i incontieni; 3) contieni, normovolemici, dar cu dureri abdominale. Au fost efectuate 49 intervenii pe abdomen, 14 operaii craniene i 41 intervenii ortopedice. Cele mai frecvente leziuni intraabdominale au fost cele retroperitoneale (n=18) cu 10 decese, rupturile splinei (n=17), cu 8 decese i leziunile intestinului i a mezourilor (n=3) cu 2 decese, cu valoare statistic semnificativ fa de absena acestor leziuni (p<0,001). Mortalitatea general a fost de 41,7% (86 decese). Mortalitatea a fost mai mare n grupele de vrst 20-29 de ani (10 decese, adic 52%), peste 60 de ani (19 decese, adic 65,5%) i la cei cu mai multe organe afectate (5,44%). n concluzie atitudinea diagnostic i terapeutic la politraumatizaii craniocerebral i abdominal se face dup un algoritm bine stabilit. Studiul corelaiei dintre amploarea, sediul leziunilor i evoluia politraumatizailor permite estimarea succesului tratamentului. Au probat valoare statistic semnificativ: vrsta traumatizatului, scorul revizuit i scorul de severitate al traumatismelor. BIBLIOGRAFIE
1. Beuran M. Traumatisme: contuzii, plgi, politraumatisme. In Bratucu E. editor, Manual de chirurgie pentru studeni, Bucureti, Ed. Universitar Carol Davila, 2009; p. 25-95. 2. Kszeghi I, Dobrin N, Ianovici N. Neurological and abdominal lesional associations in polytrauma. Rev Med Chir Soc Med Nat Iasi. 2008; 112(2): 398-405. 3. Pohlenz O, Bode PJ. The trauma emergency room: a concept for handling and imaging the polytrauma patient. Eur J Radiol. 1996; 22(1): 2-6. 4. Costa G, Tierno SM, Tomassini F, Venturini L, Frezza B, Cancrini G, Stella F. The epidemiology and clinical evaluation of abdominal trauma. An analysis of a multidisciplinary trauma registry. Ann Ital Chir. 2010; 81(2): 95-102. 5. Mann V, Mann S, Szalay G, Hirschburger M, Rhrig R, Dictus C, Wurmb T, Weigand MA, Bernhard M. Treatment of polytrauma in the intensive care unit. Anaesthesist. 2010; 59(8): 739-761. 6. Teranishi K, Scultetus A, Haque A, Stern S, Philbin N, Rice J, Johnson T, Auker C, McCarron R, Freilich D, Arnaud F. Traumatic brain injury and severe uncontrolled haemorrhage with short delay pre-hospital resuscitation in a swine model. Injury. 2010 Oct 29. [Epub ahead of print] 7. Hardcastle TC, Goff T. Trauma unit emergency doctor airway management. S Afr Med J. 2007; 97(9): 864-867.
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8. Lieberman JD, Pasquale MD, Garcia R, Cipolle MD, Mark Li P, Wasser TE. Use of admission Glasgow Coma Score, pupil size, and pupil reactivity to determine outcome for trauma patients. J Trauma. 2003; 55(3): 437-442; 9. Marshall LF, Becker DP, Bowers SA, Cayard C, Eisenberg H, Gross CR, Grossman RG, Jane JA, Kunitz SC, Rimel R, Tabaddor K, Warren J. The National Traumatic Coma Data Bank. Part 1: Design, purpose, goals, and results. J Neurosurg. 1983; 59(2): 276-284. 10. Toutant SM, Klauber MR, Marshall LF, Toole BM, Bowers SA, Seelig JM, Varnell JB. Absent or compressed basal cisterns on first CT scan: ominous predictors of outcome in severe head injury. J Neurosurg. 1984; 61(4): 691-694. 11. Lesko MM, Woodford M, White L, O'Brien SJ, Childs C, Lecky FE. Using Abbreviated Injury Scale (AIS) codes to classify Computed Tomography (CT) features in the Marshall System. BMC Med Res Methodol. 2010; 10: 72. 12. Pohlenz O, Bode PJ. The trauma emergency room: a concept for handling and imaging the polytrauma patient. Eur J Radiol. 1996; 22(1): 2-6.
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EPIDEMIOLOGIA, ETIOPATOGENIA I DIAGNOSTICUL HEPATOCARCINOMULUI

N. Vlad Clinica I Chirurgie I. Tnsescu-Vl. Buureanu doctorand,Universitatea de Medicin i Farmacie Gr. T. Popa Iai
EPIDEMIOLOGY, ETIOPATHOLOGY AND DIAGNOSTIC OF HEPATOCELLULAR CARCINOMA (ABSTRACT): Hepatocellular Carcinoma (HCC) is among the most common of solid human malignancies, with an annual incidence of 100.000 new cases. The worldwide distribution of HCC is not uniform, the highest rates are found in Southeast Asia and Sub-Saharian Africa. The HCC imcidence in Romania varies between 4-10 cases to 100.000 inhabitants per year. HCC is more likely to develop in men than in women, the sex ratio being approximately 8:1 in high-incidence areas. Chronic hepatitis B virus and C virus have been implicated as important etiologic factors in the development of HCC, being responsable for 80% of the cases. The most of the carcinomas are developped on the cirrhotic liver. A number of other risk factors also are involved in HCC: diabetes mellitus, obesity, chronic ethilism, oral contraceptives, smoking and dietary intake of aphlatoxines. HCC is usually diagnosed at a late stage. The clinical presentation are not typical, suggesting only the basic liver pathology. Ultrasounds, CT- scan and MRI confirm the presence of a mass in the liver. Alfa-fetoprotein (AFP), alfafetoprotein L3 fraction and des-gammacarboxiprotrombina (also known as PIVKA II test) are considered as serological markers for HCC. The indication of screening is for the patients with liver cirrhosis or chronic hepatitis B and/ or C virus. The level of AFP and liver ultrasounds are mandatory to be done as screening tests to every 6 months to the risk patients. KEYWORDS: LIVER CIRRHOSIS; HEPATOCELLULAR CARCINOMA; RISK FACTORS; EPIDEMIOLOGY; DIAGNOSIS; ULTRASOUND; COMPUTED TOMOGRAPHY. Coresponden: Dr. Nuu Vlad, asistent universitar, Clinica I Chirurgie, Sp. Sf. Spiridon Iai, bl. Independenei 1, 700111; email: nutu.vlad@gmail.com*
INTRODUCERE Carcinomul hepatocelular (CHC) este forma dominant de cancer hepatic primar i este diferit histologic i etiologic de alte forme de cancer hepatic [1]. CHC este un cancer uman deosebit deoarece agentul cauzal adesea este clar. Cu toate acestea, exist factori multipli etiologici care favorizeaz CHC. Aceti factori variaz n funcie de localizarea geografic, au un impact direct asupra caracteristicilor acestor pacieni i influeneaz cursul bolii, fcnd CHC o patologie extrem de complex, asociat cu un prognostic prost [2]. Carcinomul hepatocelular este o cauz principal de deces prin cancer n ntreaga lume, iar incidena sa este de ateptat s creasc n continuare n urmtorii ani. Studiile epidemiologice anterioare au scos n eviden variaiile globale a incidenei CHC. Incidena este deosebit de ridicat n cea mai mare parte a Asiei de Est i n Africa sub-saharian, i mai mic, dar n cretere, n America de Nord i cea mai mare parte a Europei [2].
received date: 15.11.2010 accepted date: 15.01.2011
*
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Aceast variaie pare a fi legat de etiologia complex a CHC, cu diferii factori de risc i n primul rnd infeciile cu virusul hepatic B i virusul hepatic C. Carcinomul hepatocelular reprezint 80% din tumorile hepatice maligne primare [3]. Epidemiologia va continua s joace un rol critic n informarea i strategia de prevenire a cancerului i a bolilor, eventual n ghidarea i gestionarea pe viitor. Carcinomul hepatocelular este un domeniu de oncologie care justific investigaiile suplimentare n ce privete epidemiologia sa. Datele obinute vor juca un rol important n organizarea strategiilor de prevenire a CHC i optimizarea tratamentului n aceast boal. EPIDEMIOLOGIA Incidena CHC n lume este de 4,6% din totalul cancerelor. Incidena n lume variaz ntre 2 i 30 de cazuri/ 100000 locuitori/an, iar n Romnia dup ultimele date este de 4-10/100000 locuitori/an [3]. Cancerul hepatic este mult mai frecvent la brbai dect la femei. Potrivit estimrilor GLOBOCAN pentru anul 2002 raportul brbai/femei a fost de 2,4, iar acest raport a fost chiar mai mare n zonele cu risc crescut al CHC [4]. CHC este o boal complex asociat cu factori de risc i cofactori [5,6]. La majoritatea pacienilor CHC este precedat de ciroz hepatic [7] i, deloc surprinztor, cauzele comune de ciroz au fost identificate ca factori de risc cheie pentru CHC. De o importan deosebit este infecia cronic cu virusul hepatitei B (VHB) sau cu virusul hepatitei C (VHC). ntr-adevr, s-a estimat c VHB este responsabil pentru 50% -80% din cazurile de CHC la nivel mondial, n timp ce 10% -25% din cazuri sunt considerate a fi o urmare a infeciei cu VHC [8,9]. Pn n prezent, opt genotipuri a VHB (de la A la H) au fost identificate [10]. Pacienii cu VHB genotipul C au un risc mai mare pentru dezvoltarea CHC, precum i o mutaie genetic a fost identificat la unii dintre aceti pacieni, motiv care poate contribui la acest risc crescut [11,12]. VHB i VHC s-au dovedit a avea un efect sinergic intrahepatic i eficiena de multiplicare a VHB a fost modificat prin inducerea de instabilitate genomic de ctre VHC [13]. Terapia antiviral care duce la supresia viral este cunoscut c n mod semnificativ reduce riscul de CHC la pacienii infectai cu VHB i fibroz hepatic avansat [14]. Datele rezultante n urma studiilor epidemiologice au dus la concluzia c variaiile globale a incidenei CHC reflect n mare msur diferenele geografice n prevalena factorilor de risc diferii pentru aceast boal [15,16]. Un alt potenial contribuitor la incidena ridicat a CHC n Asia i Africa sub-saharian este expunerea prin alimentaie la aflatoxin [17], care este produs de o ciuperca din genul Aspergillus i este un contaminant comun de alimente, cum ar fi alunele, cerealele, legumele i porumbul [5]. n rile n care infecia cu VHB nu este endemic, VHC i ciroz alcoolic sunt n general considerate a fi cei mai importani factori de risc pentru CHC [16]. Att diabetul ct i obezitatea sunt implicate n dezvoltarea de steatohepatit nealcoolic care se crede c duce la CHC prin progresia cirozei [5,18]. Creterea continu a diabetului i obezitii la nivel mondial poate conduce n viitor la creterea incidenei CHC, n special n rile dezvoltate, rile n care, pn n prezent, impactul epidemiologic al obezitii a fost cel mai marcat [19]. n ultimii ani, o serie de studii epidemiologice a CHC au subliniat modul n care ratele de inciden se pot schimba peste timp, de exemplu, analiza datelor din registrele SEER au demonstrat c ratele de inciden a CHC s-au triplat n SUA ntre 1975 i 2005 [20]. Aceast cretere a incidenei CHC a fost deosebit de notabil la hispanici, negri i brbaii albi de vrst mijlocie i poate fi parial atribuit unei epidemii de hepatit viral C ce a avut loc n SUA n 1960 [20,21].
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Se crede c ratele de cretere a obezitii i a diabetului zaharat au contribuit la creterea incidenei CHC n ultimele decenii n Canada, SUA i unele pri ale Europei [22,23]. Dei n majoritatea rilor s-a introdus vaccinarea obligatorie anti-VHB, impactul complet al unor astfel de programe privind incidena CHC este puin probabil s fie simit pentru cel puin dou decenii, deoarece rmne prevalena mare a infeciei cronice cu VHB n multe regiuni n curs de dezvoltare i perioada dintre infecia cu VHB i dezvoltarea CHC este lung [24]. n unele ri n curs de dezvoltare, constrngerile economice au mpiedicat introducerea programelor de vaccinare i ca consecin a crescut mult impactul asupra incidenei VHB i CHC [25]. Dei este dificil de prezis cu exactitate viitoarele schimbri n domeniul epidemiologiei bolilor, unii experi au sugerat c incidena global a CHC va continua s creasc n urmtorii civa ani pn cnd se va ajunge la un platou n 2015-2020 [7]. Au fost prezise scderi ulterioare n ratele CHC i ele rezult, cel puin parial, dintr-un control mai eficient i mbuntit al VHB i VHC [26]. Cu toate acestea, dei contribuiile VHB i VHC diminu, factorii de risc cum sunt diabetul zaharat i obezitatea pot deveni din ce n ce mai importani n etiologia CHC. O trecere n revist a literaturii de specialitate publicate relev o variaie marcat la nivel mondial a incidenei i profilurilor factorilor de risc pentru CHC. n paralel, programele de educaie pentru sntate pot avea potenialul de a diminua creterea i impactul diabetului zaharat, obezitaii, i steatohepatitei nealcoolice, care devin factori de risc din ce n ce mai importani n CHC. Datele epidemiologice curente sunt fragmentate i provin din studii efectuate n momente diferite, folosind diferite metodologii, i cu diverse populaii de pacieni. n viitor este necesar o abordare unitar la nivel mondial privind studiul epidemiologic al CHC, folosind metode standardizate de colectare i analiz a datelor i reglementat de ctre echipe multidisciplinare. S sperm c astfel de studii la nivel mondial vor continua i vor mbogi cunotinele noastre despre aceast boal complex, iar rezultatele furnizate vor mbunti tratamentul CHC pentru pacienii din ntreaga lume. ETIOLOGIA Ficatul este un organ care se deosebete de alte organe prin procesele sale biochimice, prin particularitile hemodinamice i mai ales prin posibilitile sale de regenerare. Avnd n vedere c incidena global a CHC este n cretere, iar prognosticul rmne rezervat, este important s se dezvolte modaliti eficiente de diagnostic i tratament bazate pe cercetri biologice a hepatocarcinogenezei [16,27]. Carcinogeneza CHC este un proces complex, care poate implica diverse modificri moleculare, precum i modificri genetice, ce duc n cele din urm la transformarea maligna a nodulilor de regenerare i progresia bolii [28-30]. Aici vom analiza principalele mecanisme capabile s se implice n hepatocarcinogenez i vom discuta modul n care aceste mecanisme cancerigene difer n funcie de diveri factori etiologici. Procesul oncogen este similar dezvoltrii altor cancere, caracterizndu-se prin apariia unor modificri genice multiple induse de un iniiator, urmat de un proces de proliferare i progresie indus de un promotor. Un grup de cercettori sud-coreeni analiznd modificrile cromozomiale n CHC prin efectuarea unui genotip la nivel naional au constatat c locusul 8q21.2 adpostete gena E2F5 care a fost amplificat periodic n CHC [31]. E2F5 este un membru al familiei E2F, factor de transcriere care se leag de promotorii genelor int implicate n controlul ciclului celular i n consecin reglementeaz expresia acestor gene int [32]. Familia E2F joac un rol central n creterea i proliferarea celulelor prin reglementarea genelor implicate n
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progresia ciclului celular [33]. Prin urmare, este posibil ca membrii de familie E2F s se implice n oncogenez. Membrii de familie E2F sunt mprii n dou subclase: activatori (E2F1-E2F3) i represori (E2F4-E2F8). Excesul de activatori E2F a fost raportat ca factor ce induce proliferarea necontrolat a celulelor n diverse cancere umane, cum ar fi cancerul de sn, ovarian, pulmonar, gastro-intestinal [32]. Dei represorii E2F sunt de ateptat s se comporte ca supresoare tumorale, o parte substanial de dovezi indic posibilitatea ca unii represori E2F pot avea efecte oncogene n cancerogenez [32]. Excesul de E2F5 poate induce o progresie necontrolabil a ciclului celular n celulele hepatice i n cele din urm s contribuie la transformarea lor n celule maligne prin interaciunea cu ali factori cancerigeni [31]. n 80-90% din cazuri CHC se dezvolt pe un ficat cirotic indiferent de etiologia cirozei. Ciroza este asociat cu o cretere a esutului fibros i o distrugere a celulelor hepatice, care duce la dezvoltarea nodulilor tumorali [34]. Deoarece ciroza hepatic poate avea un impact semnificativ asupra rezervelor hepatice i este adesea o parte integrant a morbiditii i mortalitii asociate cu CHC, prezena i severitatea cirozei trebuie s fie definit la toi pacienii, cu scopul de a evalua prognosticul i a recomanda tratamentul adecvat. Mecanismele carcinogenezei la nivelul ficatului cirotic nu se cunosc, dar cel mai probabil par legate de regenerarea hepatocitelor i de proliferarea celular accentuat, care poate promova carcinogeneza produs de factorii mutageni. Ar putea interveni i o activitate mai redus a enzimelor responsabile de repararea ADNului [3]. Un grup de autori chinezi demonstreaz c polimorfizmele genei STAT1 sunt asociate cu o sensibilitate crescut a CHC [35]. Att ciroza posthepatit viral ct i virusurile n sine (virusul hepatic B VHB, virusul hepatic C VHC) sunt factori de risc pentru CHC. Principalul factor de risc pentru dezvoltarea CHC este ciroza, cauzele majore a creia sunt infecia cu VHB si VHC. ntr-adevr, exist dovezi care s arate c 50% din toate cazurile de la nivel mondial a CHC sunt asociate cu infecia VHB i nc 25%, asociate cu VHC [36]. Infecia cronic cu VHC este un factor de risc bine cunoscut pentru apariia CHC [37]. CHC legat de VHC se gsete aproape exclusiv la pacienii cu ciroz [38]. Potenialul carcinogenic al VHC este de 2,7 ori mai mare dect al VHB. VHC aparine genului Hepacivirus al familiei Flaviviridae [30]. Spre deosebire de VHB, VHC este un virus ARN care nu se integreaz n genomul celulei gazd. VHC cauzeaz CHC prin diferite mecanisme indirecte. Proteina core a VHC intr n celula gazd, se localizeaz la nivelul exterior al membranei mitocondriale, precum i la nivelul reticulului endoplasmatic i declaneaz procesul oxidativ. Acest lucru duce la activarea unor ci de semnalizare-cheie care stimuleaz apariia de citokine i inflamaie ulterioar ce provoac modificri n cile apoptotice, i duc la formarea tumorilor [29]. Proteinele nestructurale ale VHC, NS3 i NS5A sunt, de asemenea, capabile s acioneze ca mediatori-cheie pentru a induce stresul oxidativ i inflamaia [29]. Infecia cu VHB este considerat un factor etiopatogenetic n apariia CHC chiar i naintea apariiei cirozei [39]. Infecia cronic cu VHB este factorul de risc principal pentru dezvoltarea ulterioar a CHC la nivel mondial [40]. VHB este un virus ADN dublu catenar aparinnd familiei Hepadnaviridae. Infecia cu acest virus poate provoca CHC att pe cale direct ct i indirect. n primul rnd, infecia cu VHB cauzeaz un prejudiciu de necroz i inflamaie cronic important hepatocitelor, cu proliferarea ulterioar a lor, fibroz, i ciroz. Regenerarea continu n ciroz duce la creterea celulelor hepatice afectate i acumularea de mutaii n genomul gazd, care poate duce la modificri genetice, rearanjamente cromozomiale, activarea oncogenelor, i inactivarea genelor supresoare tumorale [38]. Cu toate acestea, VHB poate provoca, de
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asemenea CHC n absena cirozei [28]. VHB este capabil s integreze ADN-ul su n celula gazd i astfel poate aciona ca un agent mutagen, provocnd rearanjarea secundar cromozomial i creterea instabilitii genomice [30]. Un numr de variabile ale gazdei i caracteristicile specifice virale ale infeciei cronice cu VHB sunt factori cunoscui ce pot influena riscul de apariie a CHC. Acetea includ antigenul-e a VHB (AgHBe), prezena de boli hepatice cronice necrotico-inflamatorii (n special ciroza), genul i vrst, precum i ncrctura viral, genotipul i, eventual, subgenotipul virusului. Disponibilitatea de tehnici de laborator ce au aprut n ultimii ani i care cuantific cu exactitate numrul de particule a VHB n serul persoanelor infectate a oferit oportunitatea de a evalua pe deplin rolul ncrcturii virale n patogeneza CHC. Studii pe termen lung efectuate la purttorii de VHB n Taiwan, China i Japonia au artat c ncrctura viral mare se coreleaz cu un risc crescut de transformare malign [41-44]. Acest risc este influenat de o serie de variabile, inclusiv statusul AgHBe [45], genotipul [46], sexul masculin i, eventual, de vrst [47]. VHB este compus din 8 genotipuri (de la A la H), fiecare difer de celelalte printr-o diversitate nucleotidic total de cel puin 8% [48,49]. Subgenotipurile difer ntre ele printr-o diversitate nucleotidic total de cel puin 4% [50,51] i au fost descrise pentru 6 din genotipurilor VHB. Genotipurile au distribuie geografic diferit [50], i se dovedesc a fi un instrument nepreuit n urmrirea evoluiei moleculare i rspndirea VHB [52,53]. n regiunile n care infecia cu VHB este endemic i VHB induce CHC au aprut probe recente care arat c exist diferite riscuri de dezvoltare a tumorii n funcie de genotipul viral [54,55]. Riscul relativ pentru dezvoltarea CHC la pacienii cu VHB genotipul A este cu 4,5 ori mai mare comparativ cu alte genotipuri. Infecia cronic cu HIV nu provoac CHC la om [56]. HIV-ul se transmite n moduri similare cu VHB i VHC i co-infecia ntre HIV i VHB sau VHC este frecvent n practica clinic [57]. De la introducerea terapiei antiretrovirale foarte active (HAART) pentru HIV / SIDA, un numrul tot mai mare de pacieni infectai concomitent cu HIV i VHB sau VHC au fost raportai drept cauz de dezvoltare a CHC [58-61]. O explicaie plauzibil pentru aceast observaie este c a crescut considerabil supravieuirea la pacieni tratai cu HAART i a permis suficient timp pentru virusurile hepatitei B i C de a induce idezvolta CHC [61]. O alt posibil explicaie este c deficitul imunitar cauzat de infecia cu HIV duce la o ncrctur viral mai mare a VHB i prin urmare crete riscul de transformare maligna a hepatocitelor. Hemocromatoza ereditar o afeciune genetic autosomal recisiv, caracterizat prin absorbia de fier n exces este asociat cu un risc de apariie a CHC de peste 200 ori mai mare comparativ cu populaia general [3,62]. Boala apare mai frecvent la vrsta cuprins ntre 35-60 de ani, predominnd la brbai. Manifestrile clinice alctuiesc triada clasic: pigmentaia pielii, diabet zaharat i ciroz hepatic. Hipertrofia ficatului este considerat ca simptomul cel mai constant al bolii [63]. Mecanismele prin care excesul de fier induce transformarea malign a hepatocitelor nu au fost nc pe deplin caracterizate. Mecanismul cel mai important pare a fi generarea de forme reactive de oxigen i stresul oxidativ, ceea ce duce la peroxidarea lipidica a acizilor grai nesaturai n membranele celulelor i organitelor [64]. Incidena CHC la pacienii cu ciroz autoimun sau secundar bolii Wilson este mai redus fa de cauzele de ciroz menionate mai sus. Pe lng factorii etiologici menionai mai sus n etiologia CHC sunt incriminai i diabetul zaharat, obezitatea, consumul cronic de alcool, anticoncepionalele orale, fumatul, aflatoxinele alimentare. Diabetul zaharat, pe lng creterea prevalenei bolilor
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hepatice cronice, s-a demonstrat a fi un factor de risc independent pentru dezvoltarea CHC. O metaanaliz a 13 studii de caz-control a artat c subiecii cu diabet zaharat au un risc dublu de dezvoltare a CHC [65]. O meta-analiz a studiilor de cohort care a evaluat asocierea ntre indivizii supraponderali sau obezi i cancerul hepatic publicat n 2007, a clarificat riscul de dezvoltare a CHC. Pacienii supraponderali au avut o cretere de 17% a riscului de a dezvolta CHC, n timp ce pacienii obezi au avut o cretere de 89% a riscului [66]. Mecanismul prin care consumul de alcool crete riscul de CHC este n primul rnd prin dezvoltarea de ciroz. Riscul pare s fie proporional cu cantitatea de alcool consumat. Un studiu prospectiv caz-control din Japonia a observat c consumatorii de alcool (> 600 l de alcool n timpul vieii) au avut o cretere de cinci ori mai mare a riscului de CHC n comparaie cu non-bautorii sau cei care au consumat < 600 l de alcool [67]. nainte de utilizarea pe scar larg a contraceptivelor orale, tumorile benigne hepatice la femeile tinere au fost rareori observate. Deoarece tumorile benigne se pot transforma n hepatocarcinom se explic riscul crescut de CHC la femeile care utilizeaz anticoncepionale orale mai mult de 10 ani. Riscul malignizrii adenoamelor hepatice este de 10%, motiv pentru care aceste leziuni sunt considerate premaligne i trebuie sancionate terapeutic atunci cnd sunt diagnosticate [3]. n ceea ce privete alte expuneri, cafeaua i un nivel ridicat al consumului de legume poate avea un rol protector mpotriva apariiei CHC. Una dintre ipotezele ce susine rolul protector al cafelei n CHC arat c aportul de cafea scade nivelurile serice ale -glutamil transferaza (GGT), care la rndul su este asociat cu o inciden mai mic a CHC [68]. n ce privete repartiia pe sexe CHC este, dup diferite statistici, de 3-8 ori mai frecvent la brbai dect la femei. CHC pe ficatul noncirotic este rar i n cea mai mare parte apare ca urmare a infeciei cu VHB, descris mai devreme. Cu toate acestea, CHC pe ficatul noncirotic poate aprea, ca rezultat al contaminrii produselor alimentare cu aflatoxin B1 [69]. Aflatoxina B1 este o micotoxin produs de ciuperca Aspergillus care crete uor pe produsele alimentare atunci cnd sunt depozitate n condiii necorespunztoare. Atunci cnd sunt ingerate, se metabolizeaz n AFB1-exo-8 ,9-epoxid, care se leag de ADN-ul hepatocitului pentru a provoca daune, inclusiv producerea de mutaii ale genei supresoare tumorale p53. ntr-adevr, aceast mutaie a fost raportat la 50% din pacienii cu CHC din sudul Africii, n cazul n care aflatoxina B1 a fost factorul de risc cunoscut pentru dezvoltarea CHC [70]. Procesul oncogen a fost studiat pe modele animale i este similar dezvoltrii altor cancere, caracterizndu-se prin apariia unor modificri genice multiple induse de un iniiator, urmat de un proces de proliferare i progresie indus de un promotor. n ultimul timp sunt foarte mult studiate o categorie special de celule, recent identificate, numite celule ovale, care, dup unele preri, sunt cele din care se dezvolt carcinoamele hepatocelulare. Cercetrile asupra acestui subiect sunt nc n curs [3]. DIAGNOSTICUL Diagnosticul cancerului hepatic primar a ntmpinat tot timpul dificulti serioase. Pe un studiu efectuat de Gustafson F. n 1937 se menioneaz c diagnosticul nainte de moarte a fost pus doar la 11% din cazuri. Un alt studiu mai recent publicat de Greene L. n 1961 a artat c diagnosticul a fost stabilit n decursul vieii la 30% din cazuri. Dificultatea stabilirii diagnosticului apare datorit faptului, c manifestrile clinice de multe ori sunt atribuite patologiei de baz, pe fondalul creia se dezvolt cancerul.
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Simptomatologia n CHC depinde pe de o parte de stadiul tumorii i pe de alt parte de starea funcional a parenchimului hepatic non-tumoral. n stadiile incipiente simptomatologia clinic este de multe ori srac i nespecific [71]. Acuzele prezentate de bolnavi sunt diferite att ca aspect ct i ca intensitate. Inapetena constituie un simptom precoce ns deseori el rmne neobservat de bolnav. Scderea ponderal se ntlnete de dou ori mai frecvent la bolnavii cu CHC dect la cei cu ciroz. Odat cu progresarea procesului patologic apare astenia fizic, pielea uscat, obrajii subiri. Durerea abdominal este un simptom specific pentru cancerul hepatocelular i se datoreaz extinderii capsulei Glisson. Uneori durerile pot aprea sub form de criz, iar ulterior pot cpta un caracter permanent. Odat cu avansarea bolii simptomatologia devine mai bogat: starea general se altereaz evident, apare ascita, edeme periferice i semne de insuficien hepatic. La unii pacieni CHC poate avea un debut acut manifestndu-se clinic prin tabloul unui abdomen acut i al unei hemoragii interne. Aceast form clinic apare la 10-15% din cazurile de CHC i se explic prin ruperea spontan a tumorii atunci cnd are expresie pe suprafaa ficatului. ntr-un numr rar de cazuri debutul poate fi cu icter sclero-tegumentar sau cu febr datorit necrozei tumorale. La examenul clinic se constat hepatomegalie sau tumor palpabil n hipocondrul drept. La pacienii cu patologie hepatic preexistent, diagnosticul clinic poate fi ntrziat datorit simptomelor comune i nespecifice. Pe de alt parte agravarea tabloului clinic la un pacient cirotic ridic suspiciunea de malignizare. n cazul suspiciunii de tumor hepatic malign primitiv, este necesar evaluarea strii generale a pacientului, specificarea tarelor asociate, definirea caracteristicilor tumorale, evaluarea volumului i strii funcionale a parenchimului hepatic non-tumoral, cutarea i caracterizarea eventualelor metastaze [3,71]. Analizele de laborator evideniaz grade diferite de anemie, VSH crescut, scderea timpului de protrombin, creterea fosfatazei alcaline i 5-nucleotidazei. Aproximativ 500 de milioane de oameni sunt infectai cu virusul hepatitei B sau C la nivel mondial. n plus, numrul de pacieni cu steatoz hepatic non-alcoolic a crescut recent i poate progresa spre ciroz i CHC. Aceste boli cronice hepatice sunt principalele cauze de morbiditate i mortalitate, precum i identificarea non-invaziv de biomarkeri n aceste patologii este important pentru diagnosticarea timpurie a CHC [72]. Progresele recente n proteomic ar putea fi folosite pentru a optimiza aplicarea clinic a biomarkerilor. Diagnosticarea precoce a CHC i evaluarea stadiului de fibroz hepatic pot contribui la intervenii terapeutice mai eficiente i o mbuntire a prognosticului. Mai mult, progresele tehnicilor de proteomic contribuie nu numai la descoperirea unor biomarkeri utili din punct de vedere clinic, dar i pentru clarificarea mecanismelor moleculare ale patogenezei bolii prin analiza fluidelor corpului folosind, cum ar fi serul, probe de esut i culturi de celule. Markerii tumorali sunt compui chimici macromoleculari secretai n snge de ctre tumorile maligne. Exist o corelaie direct ntre nivelul concentraiei markerului i afectarea organismului de un proces malign. Valoarea diagnostic a markerului depinde de dou condiii: - markerul trebuie s fie secretat n snge ntr-o cantitate suficient pentru a putea fi identificat; - trebuie s fie specific pentru tumora primar care l secret. Alfa-fetoproteina (AFP), AFP fraciune L3 (AFP-L3) i des-gammacarboxiprotrombin (DCP, de asemenea, cunoscut i sub numele de testul Pivka-II) sunt utilizai pe scar larg n clinic ca markeri tumorali serici a CHC.
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Cu toate acestea, sensibilitatea AFP sau DCP pentru detectarea n stadii incipiente a CHC este de doar 30-60% [73-75]. Dei determinarea combinat a AFP i DCP poate mbunti performana de diagnostic, precizia de diagnosticare este nc sczut pentru leziunile hepatocarcinomului mai mici de 2 cm. Prin urmare, dezvoltarea unei metode de diagnostic mai sensibil n stadiile incipiente a CHC este necesar pentru a mbunti rezultatele tratamentului [76-78]. Proteomica este termenul folosit pentru analiz exhaustiv a structurii proteinelor i funcia lor ntr-un organ sau esut. Nivelurile de gene expresive i producerea de proteine nu sunt n mod constant proporionale, iar activitatea proteinelor este frecvent reglementat prin modificri posttranslaionale, cum ar fi fosforilarea [79,80]. AFP cu valori peste 400 ng/ml stabilete cu certitudine diagnosticul de CHC dar din pcate este prezent doar la o 1/3 din pacieni, indiferent de dimensiunea nodulului tumoral. Valorile AFP cuprinse ntre 10 i 400 ng/ml ridic suspiciunea de CHC i oblig la investigaii suplimentare imagistice i histopatologice [81]. Testul PIVKA II este un alt marker serologic al CHC. Pozitivarea testului depinde de dimensiunea tumorii, valoarea lui fiind superioar la dimensiuni tumorale peste 5 cm. Testul are o specificitate de 100% dar o sensibilitate mult mai mic [3]. Imagistica de cercetare avansat a ficatului este axat pe extinderea gamei de opiuni de la explorri anatomice - ecografie i CT - la tehnici care se concentreaz pe proprietile fiziologice ale esuturilor - RM, spectroscopia, IRM cu substane de contrast speciale, tomografie cu emisie de pozitroni (PET) [82,83]. Ecografia este o tehnic fundamental pentru explorarea ficatului, arborelui biliar i vezicii biliare. Avantajele sale sunt viteza i simplitatea. Dezavantajele sale, care includ oarecum rezoluia limitat pentru leziunile hepatice mici i limitarea specificitii ultrasunetelor convenionale pot fi depite prin utilizarea de ultrasunete dup administrarea diverselor substane de contrast. Ecografia este o tehnica de baz pentru procedurile ghidate, cum ar fi biopsia i ablaia. Explorrile imagistice n CHC ncep de regul cu ecografia cu sistem Doppler-color. Diagnosticul ecografic al CHC const n evidenierea unei/unor formaiuni solide hepatice bine vascularizate i n majoritatea cazurilor a semnelor de ciroz hepatic (Fig 1).
B
Fig. 1 Aspectul unui hepatocarcinom situat n segmentele VI-VII la ecografia standard (A) i la ecografia cu sistem Doppler (B).
Aspectul ecografic al CHC nu este tipic i poate avea aspect hipoecogen, izoecogen sau hiperecogen [84]. Tumorile necrotice sunt de regul hiperecogene (Fig 2) [85,86]. 13
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Pentru imagistica ficatului sunt utilizate traductoare de 3-5 MHz. Traductoarele cu o frecven mai mare pot fi utilizate atunci cnd acestea sunt aplicate direct pe ficat, n sala de operaie. Decelarea trombozei portale este extrem de sugestiv pentru CHC (Fig 3). Actualmente examinarea ecografic a fost ameliorat prin utilizarea armonicilor i a substanelor de contrast ecografic (Levovist, Sonovue). Prin administrarea substanelor de contrast este posibil o mai bun vizualizare a pattern-ului vascular tumoral [87,88]. Ecografia intraoperatorie a devenit obligatorie pentru caracterizarea tumorilor i stabilirea raporturilor cu elementele vasculo-biliare importante i pentru orientarea rezeciilor hepatice.
Fig.2 Aspectul ecografic al unui CHC termonecrozat.
Fig. 3 Tromboza venei porte la un pacient cu CHC multicentric.
Tomografia computerizat (CT) rmne indicaia de rutin la bolnavii la care ecografia evideniaz tumori hepatice. CT hepatic evalueaz ntregul ficat n mod egal i, spre deosebire de ecografie, nu este mpiedicat de coaste sau de gaz. n plus, fa de ecografie, CT ofer o evaluare sistemic a metastazelor extrahepatice [89]. Examenul trebuie efectuat neaprat cu substan de contrast pentru detecia tumorilor mici. CT spiral permite obinerea unor imagini de calitate mai bun cu posibilitatea reconstruciei tridimensionale a ficatului i precizeaz localizarea spaial a tumorii, precum i raporturile tumorii cu vasele hepatice. CT evalueaz sistematic parenchimul hepatic, venele suprahepatice, sistemul portal i arterele hepatice, n cazul n care se face o examinare multifazic (Fig. 4) [90-92]. Evaluarea volumetric a tumorii, precum i a parenchimului hepatic restant, face posibil decizia de practicare sau nu a rezeciei hepatice [93]. Volumetria hepatic presupune colaborarea cu un serviciu radiologic extrem de competent. CT a nlocuit n mare msur tehnicile invazive de explorare a ficatului, cum ar fi portografia i angiografia, pentru diagnosticul i evaluarea CHC [94]. CT poate efectua diagnosticul diferenial ntre CHC i chisturile sau hemangioamele hepatice, cele mai frecvente leziuni accidentale [95]. CT are o oarecare lips de specificitate n a distinge CHC fa de tumorile metastatice, hiperplazia nodular i adenoamele hepatice. CT este, de asemenea, util pentru evaluarea CHC dup terapii locale, cum ar fi procedurile de rezecie, ablaie sau chemoembolizare (Fig 5).
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Un obiectiv de lung durat pentru cei mai muli cercettori n domeniul cirozei a fost acela de a dezvolta o metod imagistic simpla, neinvaziv care s poat cuantifica modificrile din fluxul de snge arterial i portal la nivelul ficatului cirotic. Schimbrile microcirculaiei n ciroza hepatic influeneaz progresia bolii.
Fig. 4 Aspectul CT al unui hepatocarcinom multicentric la o examinare multifazic.
A
Fig. 5 Imaginea CT a unui cancer hepatocelular situat la nivelul lobului hepatic drept nainte (A) i dup (B) chemoembolizare.
Dezvoltarea CHC este n legtur strns cu formarea de noi vase arteriale. Cnd nodulii cirotici evolueaz spre un grad nalt de displazie i n cele din urm se transform n CHC crete semnificativ numrul de vase arteriale de neoformaie. Prin urmare,este necesar o tehnica imagistica care s poat cuantifica perfuzia att n esuturile normale ct i n cele patologice [96]. 15
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Exist diferite metode de determinare a microcirculaiei hepatice n practica clinic [97,98]. Dintre aceste tehnici de medicin nuclear, tomografie cu emisie de pozitroni i tomografia cu emisie de fotoni, au cea mai lung istorie i sunt considerate ca standarde de aur pentru determinarea fluxului de snge [96]. Tomografia cu emisie de pozitroni este o tehnic imagistic sigur i precis de msurare a microcirculaiei hepatice. n plus, aceasta ofer informaii cantitative despre angiogeneza tumoral de la nivelul parenchimului hepatic n ciroza hepatic cu i fr CHC. Rezonana magnetic (RM) folosete capacitatea radiofrecvenei, n prezena unui cmp magnetic puternic, de a perturba protonii din ap sau din lanurile acizilor grai i de a le induce s produc un semnal de radiofrecven care poate fi nregistrat de ctre bobinele receptor. RM nu implic radiaii ionizante i este mult mai puternic dect CT n caracterizarea esuturilor i tumorilor. RM folosete mai multe tipuri de imagini pentru a caracteriza esuturile i tumorile [99]. CHC bine difereniat, de regul apare ca o mas tumoral care are intensitatea semnalului mai mare dect ficatul datorit coninutului de minerale [100]. Folosirea imagisticii prin rezonan magnetic este, de asemenea, limitat n cuantificarea fluxului de snge, deoarece consolidarea semnalului de la RM nu arat o corelaie liniar cu concentraia substanei de contrast. Rezonana magnetic se consider a fi metoda de elecie pentru diferenierea CHC de leziunile benigne. La pacientul cirotic diagnosticul diferenial al CHC trebuie fcut i cu nodulii de regenerare. Arteriografia este util punnd n eviden o vascularizaie crescut i anarhic a tumorii, dar este rar folosit deoarece este o metod invaziv. n Japonia, angiografia CT (CTA) a devenit standardul de aur pentru diagnosticul tumorilor hepatice [101,102]. CTA / CTAP au fcut posibil diagnosticarea precoce a CHC i mai ales detectarea CHC microscopic care este dificil de detectat la CT convenional. Rezultatele furnizate de aceste explorri sunt importante pentru stabilirea i selecie metodelor de tratament la pacienii cu CHC [103]. O varietate de ageni din medicina nuclear sunt utilizai pentru explorarea ficatului. Dei nu exist un produs standard special pentru detectarea CHC, explorarea PET standard cu 18F-fluorodeoxyglucos (18F-FDG) poate detecta CHC n proporie 40-50% [104]. Motivul pentru aceast sensibilitate sczut se datoreaz absorbiei crescute a 18F-FDG n ficatul normal i posibilitatea de a ascunde leziunile hepatice mici. n multe cazuri 18F-FDG poate arta metastaze extrahepatice a CHC sau activitate rezidual dup terapie intervenional [105]. Utilitatea punciei-biopsie hepatice rmne controversat. Indicaiile ei sunt pentru diagnosticul diferenial cu tumorile benigne cnd alte metode diagnostice sunt neconcludente, pentru diagnostic histologic la cancerele inoperabile, n vederea instituirii tratamentului oncologic. Laparoscopia diagnostic este o metod care are indicaii tot mai extinse n prezent. Explorarea laparoscopic este completat de ecografie intraoperatorie, se poate recolta la vedere un fragment pentru biopsie att din tumor ct i din ficatul nontumoral pentru aprecierea gradului de suferin hepatic. Screening-ul pentru carcinomul hepatocelular este indicat la toi pacienii cu ciroz sau cu hepatite virale cronice cu virus B i/sau C. Screening-ul trebuie s fie nu numai util n depistarea precoce a bolii, dar trebuie s fie i ct mai puin costisitor.
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Actualmente se recomand folosirea pentru screening a ecografiei, care se efectueaz la persoanele cu risc la 3-4 luni i dozarea AFP la 6 luni [106]. n acest fel n Japonia CHC se depisteaz precoce (stadiul I-II) la circa 97% dintre pacieni. CONCLUZII Hepatocarcinomul este cea mai frecvent tumor hepatic primitiv. Incidena sa la nivel mondial este n continu cretere. Rspndirea geografic a CHC este neuniform, predominnd n Asia de Est i Africa sub-saharian. Etiologia CHC este n strns legtur cu virusurile hepatitei B i C. n peste 90% din cazuri CHC se dezvolt pe ciroz hepatic. Tabloul clinic al cancerului hepatocelular de cele mai multe ori este nespecific i mascat de boala pe care s-a grefat cancerul. Alfa-fetoproteina i desgamma-carboxiprotrombin sunt markerii tumorali serici care au specificitate pentru CHC. Ecografia, CT i RM sunt pilonii de baz n imagistica CHC. Ultrasonografia Doppler i cu substan de contrast este util pentru detectarea CHC i interveniile ecoghidate. CT-ul ofer o evaluare sistemic pentru boala metastatic i este util pentru evaluarea rspunsului tumoral la terapie. RM furnizeaz cele mai multe informaii despre caracteristicele tumorii n general i este cea mai util n diagnosticul diferenial. Dei incidena CHC continu s creasc, se estimeaz c n urmtorii ani programele de vaccinare vor reduce rata de CHC legat de VHB i c msurile luate de ctre direciile de sntate public vor face acelai lucru n privina CHC legat de VHC.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. BIBLIOGRAFIE: Yu MC, Yuan JM, Lu SC. Alcohol, cofactors and the genetics of hepatocellular carcinoma. J Gastroenterol Hepatol. 2008; 23(suppl 1): S92S97. Venook AP, Papandreou C, Furuse J et al. The incidence and epidemiology of hepatocellular carcinoma: A global and regional perspective. The Oncologist. 2010; 15(suppl 4): 513. Popescu I, Srbu-Boei Mirela-Patricia. Carcinomul hepatocelular n Popescu I, editor. Tratat de chirurgie, Vol. IX (partea II), Bucureti: Ed. Academiei Romne; 2009. p. 689-719. Parkin DM, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005; 55(2): 74 108. Gomaa AI, Khan SA, Toledano MB et al. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J Gastroenterol. 2008; 14(27): 43004308. Di Bisceglie AM. Epidemiology and clinical presentation of hepatocellular carcinoma. J Vasc Interv Radiol. 2002; 13(9Pt2): S169 S171. Llovet JM. Updated treatment approach to hepatocellular carcinoma. J Gastroenterol. 2005; 40(3): 225235. Block TM, Mehta AS, Fimmel CJ et al. Molecular viral oncology of hepatocellular carcinoma. Oncogene. 2003; 22(33): 50935107. Anthony PP. Hepatocellular carcinoma: An overview. Histopathology 2001; 39(2): 109 118. Palumbo E. Hepatitis B genotypes and response to antiviral therapy: A review. Am J Ther. 2007; 14(3): 306 309. He Y, Zhang H, Yin J et al. IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C. Carcinogenesis. 2009; 30(11): 1916 1922. Ito K, Tanaka Y, Orito E et al. T1653 mutation in the box alpha increases the risk of hepatocellular carcinoma in patients with chronic hepatitis B virus genotype C infection. Clin Infect Dis. 2006; 42(1): 17. De Mitri MS, Cassini R, Morsica G et al. Virological analysis, genotypes and mutational patterns of the HBV precore/core gene in HBV/HCV related hepatocellular carcinoma. J Viral Hepat. 2006; 13(9): 574 581. Liaw YF, Sung JJ, Chow WC et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med. 2004; 351(15): 15211531. Montalto G, Cervello M, Giannitrapani L et al. Epidemiology, risk factors, and natural history of hepatocellular carcinoma. Ann N Y Acad Sci. 2002; 963(1): 1320.
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Articole de sintez
16. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet. 2003; 362(9399): 1907 1917. 17. Poon D, Anderson BO, Chen LT et al. Management of hepatocellular carcinoma in Asia: Consensus statement from the Asian Oncology Summit 2009. Lancet Oncol. 2009; 10(11): 11111118. 18. Farrell GC. Non-alcoholic steatohepatitis: What is it, and why is it important in the Asia-Pacific region? J Gastroenterol Hepatol. 2003; 18(2): 124 138. 19. Seidell JC. Obesity, insulin resistance and diabetesa worldwide epidemic. Br J Nutr. 2000; 83(suppl 1): S5S8. 20. Altekruse SF, McGlynn KA, Reichman ME. Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol. 2009; 27(9): 14851491. 21. Armstrong GL, Wasley A, Simard EP et al. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med. 2006; 144(10): 705714. 22. Dyer Z, Peltekian K, van Zanten SV. Review article: The changing epidemiology of hepatocellular carcinoma in Canada. Aliment Pharmacol Ther. 2005; 22(1): 1722. 23. El-Serag HB. Hepatocellular carcinoma: An epidemiologic view. J Clin Gastroenterol. 2002; 35(5 suppl 2): S72S78. 24. Nguyen VTT, Law MG, Dore GJ. Hepatitis B-related hepatocellular carcinoma: Epidemiological characteristics and disease burden. J Viral Hepat. 2009; 16(7): 453 463. 25. Lodato F, Mazzella G, Festi D et al. Hepatocellular carcinoma prevention: A worldwide emergence between the opulence of developed countries and the economic constraints of developing nations. World J Gastroenterol. 2006; 12(45): 7239 7249. 26. Yuen MF, Hou JL, Chutaputti A. Hepatocellular carcinoma in the Asia Pacific region. J Gastroenterol Hepatol. 2009; 24(3): 346 353. 27. El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology. 2004; 127(5 suppl 1): S27-S34. 28. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 2007; 132(7): 25572576. 29. Sheikh MY, Choi J, Qadri I et al. Hepatitis C virus infection: Molecular pathways to metabolic syndrome. Hepatology. 2008; 47(6): 21272133. 30. Szab E, Pska C, Kaposi Novk P et al. Similarities and differences in hepatitis B and C virus induced hepatocarcinogenesis. Pathol Oncol Res. 2004; 10(1): 511. 31. Jiang Y, Yim SH, Xu HD, Jung SH, Yang SY, Hu HJ, Jung CK, Chung YJ. A potential oncogenic role of the commonly observed E2F5 overexpression in hepatocellular carcinoma. World J Gastroenterol. 2011; 17(4): 470-477. 32. Chen HZ, Tsai SY, Leone G. Emerging roles of E2Fs in cancer: an exit from cell cycle control. Nat Rev Cancer. 2009; 9(11): 785-797. 33. Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA, Dynlacht BD. E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev. 2002; 16(2): 245-256. 34. Caillot F, Derambure C, Bioulac-Sage P et al. Transient and etiology-related transcription regulation in cirrhosis prior to hepatocellular carcinoma occurrence. World J Gastroenterol. 2009; 15(3): 300309. 35. Zhu ZZ, Di JZ, Gu WY, Cong WM, Gawron A, Wang Y et al. Association of Genetic Polymorphisms in STAT1 Gene with Increased Risk of Hepatocellular Carcinoma. Oncology. 2010; 78(5-6): 382-388. 36. Gurtsevitch VE. Human oncogenic viruses: Hepatitis B and hepatitis C viruses and their role in hepatocarcinogenesis. Biochemistry (Mosc) 2008; 73(5): 504513. 37. Fassio E. Hepatitis C and hepatocellular carcinoma. Ann Hepatol. 2010; 9: 119-122. 38. But DYK, Lai CL, Yuen MF. Natural history of hepatitis-related hepatocellular carcinoma. World J Gastroenterol 2008; 14(11): 16521656. 39. Grigorescu M. Tumori hepatice maligne primitive n Grigorescu M, editor. Tratat de hepatologie, Bucureti: Ed. Medical; 2004. p. 778-812. 40. Ishikawa T. Clinical features of hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol. 2010; 16(20): 2463-2467. 41. Chen G, Lin W, Shen F, Iloeje UH, London WT, Evans AA. Past HBV viral load as predictor of mortality and morbidity from HCC and chronic liver disease in a prospective study. Am J Gastroenterol. 2006; 101(8): 17971803.
18
Articole de sintez
42. Liu TT, Fang Y, Xiong H, Chen TY, Ni ZP, Luo JF, Zhao NQ, Shen XZ. A case-control study of the relationship between hepatitis B virus DNA level and risk of hepatocellular carcinoma in Qidong, China. World J Gastroenterol. 2008; 14(19): 30593063. 43. Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ. Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med. 2002; 347(3): 168174. 44. Chan HL, Tse CH, Mo F, Koh J, Wong VW, Wong GL, Lam Chan S, Yeo W, Sung JJ, Mok TS. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol. 2008; 26(2): 177182. 45. Chu CJ, Hussain M, Lok AS. Quantitative serum HBV DNA levels during different stages of chronic hepatitis B infection. Hepatology. 2002; 36(6): 14081415. 46. Yu MW, Yeh SH, Chen PJ, Liaw YF, Lin CL, Liu CJ, Shih WL, Kao JI, Chen DS, Chen CJ. Hepatitis B virus genotype and DNA level and hepatocellular carcinoma: A prospective study in men. J Natl Cancer Inst. 2005; 97(4): 265272. 47. Tsai FC, Liu CJ, Chen CL, Chen PJ, Lai MY, Kao JH, Chen DS. Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma. J Viral Hepat. 2007; 14(3): 153160. 48. Stuyver L, De Gendt S, Van Geyt C, Zoulim F, Fried M, Schinazi RF, Rossau R. A new genotype of hepatitis B virus: complete genome and phylogenetic relatedness. J Gen Virol. 2000; 81(Pt 1): 6774. 49. Arauz-Ruiz P, Norder H, Robertson BH, Magnius LO. Genotype H: a new Amerindian genotype of hepatitis B virus revealed in Central America. J Gen Virol. 2002; 83(Pt 8): 20592073. 50. Kramvis A, Kew M, Franois G. Hepatitis B virus genotypes. Vaccine. 2005; 23(19): 2409 2423. 51. Bowyer SM, van Staden L, Kew MC, Sim JG. A unique segment of the hepatitis B virus group A genotype identified in isolates from South Africa. J Gen Virol. 1997; 78(Pt 7): 17191729. 52. Kramvis A, Kew MC. Relationship of genotypes of hepatitis B virus to mutations, disease progression and response to antiviral therapy. J Viral Hepat. 2005; 12(5): 456464. 53. Chan HL, Wong ML, Hui AY, Hung LC, Chan FK, Sung JJ. Hepatitis B virus genotype C takes a more aggressive disease course than hepatitis B virus genotype B in hepatitis B e antigenpositive patients. J Clin Microbiol. 2003; 41(3): 12771279. 54. Tsubota A, Arase Y, Ren F, Tanaka H, Ikeda K, Kumada H. Genotype may correlate with liver carcinogenesis and tumor characteristics in cirrhotic patients infected with hepatitis B virus subtype adw. J Med Virol. 2001; 65(2): 257265. 55. Thakur V, Guptan RC, Kazim SN, Malhotra V, Sarin SK. Profile, spectrum and significance of HBV genotypes in chronic liver disease patients in the Indian subcontinent. J Gastroenterol Hepatol. 2002; 17(2): 165170. 56. Giordano TP, Kramer JR, Souchek J, Richardson P, El-Serag HB. Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus: a cohort study, 19922001. Arch Intern Med. 2004; 164(21): 23492354. 57. Alter MJ. Epidemiology of viral hepatitis and HIV co-infection. J Hepatol. 2006; 44(1 suppl): S6S9. 58. Bru N, Fox RK, Xiao P, Marks K, Naqvi Z, Taylor LE, et al. Presentation and outcome of hepatocellular carcinoma in HIV-infected patients: a U.S.-Canadian multicenter study. J Hepatol. 2007; 47(4): 527537. 59. Rosenthal E, Poire M, Pradier C, Perronne C, Salmon-Ceron D, Geffray L, et al. Mortality due to hepatitis C-related liver disease in HIV-infected patients in France (Mortavic 2001 study). AIDS. 2003; 17(12): 18031809. 60. Clifford GM, Rickenbach M, Polesel J, Dal Maso L, Steffen I, Ledergerber B, et al. Influence of HIV-related immunodeficiency on the risk of hepatocellular carcinoma. AIDS. 2008; 22(16): 21352141. 61. Thio CL, Seaberg EC, Skolasky R, Phair J, Visscher B, Munoz A, Thomas DL. HIV-1, hepatitis B virus, and risk of liver-related mortality in the Multicenter Cohort Study (MACS). Lancet. 2002; 360(9349): 19211926. 62. Elmberg M, Hultcrantz R, Ebrahim F, Olsson S, Lindgren S, Lf L et al. Increased mortality risk in patients with phenotypic hereditary hemochromatosis but not in their first-degree relatives. Gastroenterology. 2009; 137(4): 1301-1309. 63. Cociug G. Cancerul hepatic primar i ciroza. Chiinu: Ed. Elan Poligraf; 2009. p. 31-60.
19
Articole de sintez
64. Asare GA, Mossanda KS, Kew MC, Paterson AC, Kahler-Venter CP, Siziba K. Hepatocellular carcinoma caused by iron overload: a possible mechanism of direct hepatocarcinogenicity. Toxicology. 2006; 219(1-3): 4152. 65. El-Serag HB, Talwalkar J, Kim WR. Efficacy, effectiveness, and comparative effectiveness in liver disease. Hepatology. 2010; 52(2): 403-407. 66. Larsson SC, Wolk A. Overweight, obesity and risk of liver cancer: a meta-analysis of cohort studies. Br J Cancer. 2007; 97(7): 1005-1008. 67. Munaka M, Kohshi K, Kawamoto T, Takasawa S, Nagata N, Itoh H et al. Genetic polymorphisms of tobacco- and alcohol-related metabolizing enzymes and the risk of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2003; 129(6): 355-360. 68. Gallus S, Bertuzzi M, Tavani A, Bosetti C, Negri E, La Vecchia C et al. Does coffee protect against hepatocellular carcinoma? Br J Cancer. 2002; 87(9): 956959. 69. Abdel-Wahab M, Mostafa M, Sabry M et al. Aflatoxins as a risk factor for hepatocellular carcinoma in Egypt, Mansoura Gastroenterology Center study. Hepatogastroenterology. 2008; 55(86-87): 17541759. 70. Bressac B, Kew M, Wands J et al. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa. Nature. 1991; 350(6317): 429431. 71. Trcoveanu E, Moldovanu R. Tumorile maligne primare ale ficatului n Trcoveanu E, editor. Patologie chirurgical hepatic tumori hepatice, Iai: Ed. Universitar Gr. T. Popa; 2007. p. 107-120. 72. Uto H, Kanmura S, Takami Y, Tsubouchi H. Clinical proteomics for liver disease: a promising approach for discovery of novel biomarkers. Proteome Sci. 2010; 8: 70. 73. Ishii M, Gama H, Chida N, Ueno Y, Shinzawa H, Takagi T, Toyota T, Takahashi T, Kasukawa R. Simultaneous measurements of serum alpha-fetoprotein and protein induced by vitamin K absence for detecting hepatocellular carcinoma. South Tohoku District Study Group. Am J Gastroenterol. 2000; 95(4): 10361040. 74. Okuda H, Nakanishi T, Takatsu K, Saito A, Hayashi N, Takasaki K, Takenami K, Yamamoto M, Nakano M. Serum levels of des-gamma-carboxy prothrombin measured using the revised enzyme immunoassay kit with increased sensitivity in relation to clinicopathologic features of solitary hepatocellular carcinoma. Cancer. 2000; 88(3): 544549. 75. Marrero JA, Su GL, Wei W, Emick D, Conjeevaram HS, Fontana RJ, Lok AS. Des-gamma carboxyprothrombin can differentiate hepatocellular carcinoma from nonmalignant chronic liver disease in American patients. Hepatology. 2003; 37(5): 11141121. 76. Ikoma J, Kaito M, Ishihara T, Nakagawa N, Kamei A, Fujita N, Iwasa M, Tamaki S, Watanabe S, Adachi Y. Early diagnosis of hepatocellular carcinoma using a sensitive assay for serum desgamma-carboxy prothrombin: a prospective study. Hepatogastroenterology. 2002; 49(43): 235 238. 77. Toyoda H, Kumada T, Kiriyama S, Sone Y, Tanikawa M, Hisanaga Y, Yamaguchi A, Isogai M, Kaneoka Y, Washizu J. Prognostic significance of simultaneous measurement of three tumor markers in patients with hepatocellular carcinoma. Clin Gastroenterol Hepatol. 2006; 4(1): 111 117. 78. Nakamura S, Nouso K, Sakaguchi K, Ito YM, Ohashi Y, Kobayashi Y, Toshikuni N, Tanaka H, Miyake Y, Matsumoto E, Shiratori Y. Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size. Am J Gastroenterol. 2006; 101(9): 20382043. 79. Espina V, Edmiston KH, Heiby M, Pierobon M, Sciro M, Merritt B, Banks S, Deng J, VanMeter AJ, Geho DH, Pastore L, Sennesh J, Petricoin EF, Liotta LA. A portrait of tissue phosphoprotein stability in the clinical tissue procurement process. Mol Cell Proteomics. 2008; 7(10): 1998 2018. 80. Kriegsheim A, Preisinger C, Kolch W. Mapping of signaling pathways by functional interaction proteomics. Methods Mol Biol. 2008; 484: 177192. 81. Carr BI, Pancoska P, Branch RA. Low alpha-fetoprotein hepatocellular carcinoma. J Gastroenterol Hepatol. 2010; 25(9): 1543-1549 82. Plathow C, Weber WA. Tumor cell metabolism imaging. J Nucl Med. 2008; 49(Suppl 2): 43S63S. 83. Frangioni JV. New technologies for human cancer imaging. J Clin Oncol. 2008; 26(24): 40124021.
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Articole de sintez
84. Cottone M, Marcen MP, Maringhini A, et al. Ultrasound in the diagnosis of hepatocellular carcinoma associated with cirrhosis. Radiology. 1983; 147(2): 517-519. 85. Rapaccini GL, Pompili M, Caturelli E, et al. Hepatocellular carcinomas < 2 cm in diameter complicating cirrhosis: ultrasound and clinical features in 153 consecutive patients. Liver Int. 2004; 24(2): 124-130. 86. Tanaka S, Kitamura T, Imaoka S, et al. Hepatocellular carcinoma: sonographic and histologic correlation. AJR Am J Roentgenol. 1983; 140(4): 701-707. 87. Lau WY, Lai EC, Lau SH. The current role of neoadjuvant/adjuvant/chemoprevention therapy in partial hepatectomy for hepatocellular carcinoma: a systematic review. Hepatobiliary Pancreat Dis Int. 2009; 8(2): 124-133. 88. Sirli R, Sporea I, Martie A, Popescu A, Dnil M. Contrast enhanced ultrasound in focal liver lesions--a cost efficiency study. Med Ultrason. 2010; 12(4): 280-285. 89. Outwater EK. Imaging of the liver for hepatocellular cancer. Cancer Control. 2010; 17(2): 72-82. 90. Ichikawa T, Kitamura T, Nakajima H, et al. Hypervascular hepatocellular carcinoma: can double arterial phase imaging with multidetector CT improve tumor depiction in the cirrhotic liver? AJR Am J Roentgenol. 2002; 179(3): 751-758. 91. Lee KH, OMalley ME, Haider MA, et al. Triple-phase MDCT of hepatocellular carcinoma. AJR Am J Roentgenol. 2004; 182(3): 643-649. 92. Murakami T, Kim T, Takamura M, et al. Hypervascular hepatocellular carcinoma: detection with double arterial phase multi-detector row helical CT. Radiology. 2001; 218(3): 763-767. 93. Zhang JW, Feng XY, Liu HQ, Yao ZW, Yang YM, Liu B, Yu YQ. CT volume measurement for prognostic evaluation of unresectable hepatocellular carcinoma after TACE. World J Gastroenterol. 2010; 16(16): 2038-2045. 94. Szklaruk J, Silverman PM, Charnsangavej C. Imaging in the diagnosis, staging, treatment, and surveillance of hepatocellular carcinoma. AJR Am J Roentgenol. 2003; 180(2): 441-454. 95. Schwartz LH, Gandras EJ, Colangelo SM, et al. Prevalence and importance of small hepatic lesions found at CT in patients with cancer. Radiology. 1999; 210(1): 71-74. 96. Li JP, Zhao DL, Jiang HJ, Huang YH, Li DQ, Wan Y, Liu XD, Wang JE. Assessment of tumor vascularization with functional computed tomography perfusion imaging in patients with cirrhotic liver disease. Hepatobiliary Pancreat Dis Int. 2011; 10(1): 43-49. 97. Goetti R, Leschka S, Desbiolles L, Klotz E, Samaras P, von Boehmer L, et al. Quantitative computed tomography liver perfusion imaging using dynamic spiral scanning with variable pitch: feasibility and initial results in patients with cancer metastases. Invest Radiol. 2010; 45(7): 419-426. 98. Zapletal C, Jahnke C, Mehrabi A, Hess T, Mihm D, Angelescu M, et al. Quantification of liver perfusion by dynamic magnetic resonance imaging: experimental evaluation and clinical pilot study. Liver Transpl. 2009; 15(7): 693-700. 99. Siegelman ES, Outwater EK. MR imaging techniques of the liver. Radiol Clin North Am. 1998; 36(2): 263-286. 100. Ebara M, Fukuda H, Kojima Y, et al. Small hepatocellular carcinoma: relationship of signal intensity to histopathologic findings and metal content of the tumor and surrounding hepatic parenchyma. Radiology. 1999; 210(1): 81-88. 101. Matsui O, Kadoya M, Suzuki M, Inoue K, Itoh H, Ida M, Takashima T. Work in progress: dynamic sequential computed tomography during arterial portography in the detection of hepatic neoplasms. Radiology. 1983; 146(3): 721727. 102. Matsui O, Takashima T, Kadoya M, Ida M, Suzuki M, Kitagawa K, Kamimura R, Inoue K, Konishi H, Itoh H. Dynamic computed tomography during arterial portography: the most sensitive examination for small hepatocellular carcinomas. J Comput Assist Tomogr. 1985; 9(1): 1924. 103. Ishikawa T, Higuchi K, Kubota T, Seki K, Honma T, Yoshida T, Nemoto T, Takeda K, Kamimura T. Usefulness of Y-shaped sheaths in CT angiography for examination of liver tumors. World J Gastroenterol. 2010; 16(37): 4704-4708. 104. Khan MA, Combs CS, Brunt EM, et al. Positron emission tomography scanning in the evaluation of hepatocellular carcinoma. J Hepatol. 2000; 32(5): 792-797. 105. Torizuka T, Tamaki N, Inokuma T, et al. Value of fluorine-18-FDGPET to monitor hepatocellular carcinoma after interventional therapy. J Nucl Med. 1994; 35(12): 1965-1969. 106. Jakab Z. Diagnostic imaging for the screening of hepatocellular carcinoma. Orv Hetil. 2010; 151(27): 1083-1090.
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CANCERUL GASTRIC LOCAL AVANSAT SAU METASTAZAT ACTUALITI EPIDEMIOLOGICE I DIAGNOSTICE

Florina Ptracu, Adina Croitoru, Iulia Gramaticu, M. Andrei, Adriana Teiuanu, M. Diculescu 1. Compartimentul de Oncologie Medical, Institutul Clinic de Boli Digestive i Transplant Hepatic Fundeni (ICBDTHF) 2. Clinica de Gastroenterologie i Hepatologie, ICBDTH Fundeni 3. Clinica de Gastroenterologie i Hepatologie, SUU Elias
LOCALLY ADVANCED OR METASTATIC GASTRIC CANCER AN EPIDEMIOLOGICAL AND DIAGNOSING UPDATE (ABSTRACT): Gastric cancer represents a major health problem worldwide. It is often diagnosed at an advanced stage, because screening, which would help an early detection is performed only in Japan. Gastric cancer rates may be decreased by reducing smoking and alcohol consumption and by increasing the number of fresh fruits and vegetables eaten. Eradication of Helicobacter pylori may also decrease gastric cancer incidence. Seventy-five percent of the patients are diagnosed in unresectable stage. They represent a challenge for clinicians as they have to choose between a strictly supportive approach or to expose patients to the side-effects of a potentially ineffective treatment. The treatment of advanced gastric cancer is essentially palliative. KEY WORDS: ADVANCED GASTRIC CANCER, DIAGNOSIS, PROGNOSIS. Coresponden: Prof. dr. Mircea Diculescu, Clinica de Gastroenterologie i Hepatologie, Institutul Clinic de Boli Digestive i Transplant Hepatic Fundeni (ICBDTHF), Soseaua Fundeni 258, Sector 2 022328, Bucuresti, Romania*.
GENERALITI Cancerul gastric (CG) constituie a doua cauz de mortalitate prin cancere n ntreaga lume, cu toate c incidena global este n scdere. Prevalena i mortalitatea CG (particular a localizrilor distale) a sczut semnificativ n toate regiunile geografice i la toate vrstele, cu 2% pn la 7% pe an, crescnd n schimb numrul pacienilor cu adenocarcinom localizat la nivelul jonciunii esogastrice i n poriunea iniial gastric, ncepnd cu jumtatea anilor 1980. Declinul incidenei a fost dramatic n SUA, unde a devenit a 14-a cauz de deces prin cancer, fiind estimate anual 21.900 noi cazuri i 13.500 de decese/an [1]. Incidena CG n Uniunea European este actualmente de 18,9 cazuri/100.000 locuitori/an, cu rate de 1,5 ori mai crescute la sexul masculin i cu vrful de inciden n decada a aptea de via. Mortalitatea este de 14,7 cazuri/100.000 locuitori/an. n Japonia, Europa de Est i America de Sud (n special Chile i Costa Rica), incidena CG este epidemic. n Japonia, incidena CG este maxim (100 cazuri/100.000 locuitori/an) i reprezint prima cauz de deces prin cancer.
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La nivel mondial, CG reprezint aprox. 930.000 de cazuri noi i determin mai mult de 700.000 de decese. Vrsta medie la diagnostic este de 71 ani n SUA i o decad mai devreme n Japonia [2]. Supravieuirea CG local avansat/metastazat la 5 ani n SUA i n rile vest europene este ntre 5-15%, explicaia fiind multifactorial. Chiar la pacienii diagnosticai n stadii incipiente, rata supravieuirii la 5 ani este de 50%. Cauzele ce determin apariia acestui tip de cancer includ factori genetici i factori din mediu. Din punct de vedere genetic sunt descrise: mutaia genic p53, pierderea heterozigoiei LOH a locusului APC, deleia sau supresia genei FHIT etc. Factorii din mediu includ: dieta bogat n sare, nitraii, produsele afumate, fumatul, infecia cu H.pylori i virusul Epstein Barr (EBV), obezitatea, consumul cronic de buturi alcoolice, interveniile chirurgicale gastrice anterioare [3]. Screening-ul pentru cancerul gastric n general nu este recomandat de rutin n rile vestice, aceast localizare de cancer nereuind s ntruneasc condiiile biologice i de istorie natural pentru screening. Singurele zone n care se utilizeaz sunt zonele cu inciden crescut. Screening-ul n mas a fost utilizat n Japonia ncepnd cu anul 1960, lucru care probabil a contribuit la mbuntirea pe termen lung a supravieuirii comparativ cu rile vestice, dei diferenele n biologie pot juca un anumit rol [4]. DIAGNOSTIC CLINIC Se tie c majoritatea pacienilor cu cancer gastric sunt diagnosticai n stadii avansate, acest lucru datorndu-se simptomelor nespecifice de tip astenie, durere minim sub form de jen/disconfort abdominal, scdere n greutate, anorexie. Cancerul gastric precoce este asimptomatic n 80% din cazuri [5]. Cnd simptomele apar, ele tind s mimeze ulcerul peptic. Cancerul gastric avansat este nsoit de scdere ponderal, dureri abdominale, grea, vrsturi, saietate precoce, disfagie, melen, obstrucie piloric. n funcie de localizarea tumorii primare se pot ntlni: disfagie (CG cardial), vrsturi i eructaii (CG antral), saietate precoce (linita plastic). Hematemeza este prezent la 10-15% din pacieni. Implantele peritoneale n pelvis pot fi palpate la examinarea rectal (semnul Blumer), extensia bolii la nivelul ficatului poate fi evideniat clinic prin hepatomegalie tumoral, metastazele ganglionare supraclaviculare (semnul Virchow-Troiser) sau axilare stngi (semnul Iris), nodulii subcutanai periombilicali (semnul Sister Mary-Joseph), semn de invazie tumoral de-a lungul ligamentului falciform. Ascita i icterul sunt semne de boal avansat. Exist, de asemenea, o serie de sindroame paraneoplazice ce pot nsoi cancerul gastric, dintre acestea cele mai importante fiind: achantosis nigricans (55%), polimiozita, dermatomiozita, eritem circinat, pemfigoid, demena, ataxia cerebeloas, tromoboza venoas idiopatic, sindromul Cushing ectopic sau sindromul carcinoid, semnul Lesser-Trelat. Uneori cancerul gastric poate debuta printr-o complicaie precum ocluzie intestinal prin tumor primar sau metastaze peritoneale, fistul gastrocolic, respectiv perforaie gastric.
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DIAGNOSTIC DE LABORATOR I EXPLORRI IMAGISTICE n faa unui pacient care prezint simptomatologia de mai sus, trebuie s suspicionm prezena unui proces proliferativ gastric. Exist o serie de investigaii de laborator [6,7] i imagistice [8] care ne pot conduce la un diagnostic corect i totodat rapid: 1. Hemograma (anemie hipocrom microcitar, hiposideremic/anemie Biermer). 2. Markeri tumorali: antigenul carcinoembrionar (ACE) care crete la 40-50% din pacienii cu cancer gastric i care este ns util n urmrire i nu n screening. AFP i CA19-9 sunt crescute la 30% din aceti pacieni. 3. Radiografia abdominal cu substan de contrast - este o metod neinvaziv, dar care are dezavantajul de a nu facilita biopsia. Poate evidenia: pierderea mobilitii peretelui gastric, defecte de umplere, alterri ale mucoasei cu imagine de ulceraie sau zon extins de rigiditate a peretelui gastric. 4. Gastrofibroscopia: prezint avantajul recoltrii de biopsii multiple n vederea unui diagnostic rapid i corect. Tumorile submucoase infiltrative sau extensia extramural la nivelul nervilor vagi pot fi detectate prin alterri funcionale, cum ar fi peristaltismul anormal, scderea distensibilitii pereilor gastrici, tulburarea funciei pilorice. 5. Tomografia computerizat de torace, abdomen i pelvis permite aprecierea extensiei tumorii primare, implicrii ganglionilor limfatici tumorali regionali, precum i existena metastazelor la distan. 6. Ecografia endoscopic (EUS) reprezint o modalitate de stadializare complementar examenului CT, mai ales pentru aprecierea extensiei n profunzime a tumorii primare, dar i pentru statusul ganglionilor limfatici regionali, perigastrici. 7. Videocapsula - dei este utilizat n special pentru patologia intestinului subire, a fost aprobat de FDA pentru utilizarea clinic nc din 2001. Realizeaz 2 fotografii/secund i s-a dovedit a fi sigur i eficace. 8. Scintigrafia osoas se realizeaz pentru depistarea metastazelor osoase la pacienii cu dureri osoase sau cu valori crescute ale fosfatazei alcaline. 9. Laparoscopia are rolul de a identifica metastazele mici, viscerale sau peritoneale pe care examenul CT nu le-a vizualizat. Trebuie efectuat nainte de terapia locoregional cu intenie curativ sau chimioradioterapia preoperatorie. 10. Laparatomia exploratoare - determin extensia bolii, fiind superioar examenului CT. 11. PET scan-ul poate fi utilizat pentru aprecierea extensiei bolii /rspunsului la tratamentul neoadjuvant, ceea ce se coreleaz cu o supravieuire mai bun. STADIALIZARE ncepnd cu 2010 a intrat n uz cea de a 7-a stadializare TNM a International Union Against Cancer (UICC) a cancerului gastric care este prezentat n tabel 1. DIAGNOSTIC DIFERENIAL Se face cu o serie de afeciuni printre care: ulcerul gastric, gastrita cronic (atrofic/hipertrofic), tumori benigne: polipi, leiomioame, tumori maligne: leiomiosarcomul, leiomioblastomul. Metastazele gastrice provenite de la neoplasme pancreatice, colecistice, colonice sau cutanate (melanom), dei rare, pot fi prezente. n toate aceste situaii enumerate, examenul bioptic traneaz diagnosticul.
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PROGNOSTICUL CANCERULUI GASTRIC n ciuda eforturilor constante de diagnostic i tratament, supravieuirea la 5 ani a pacienilor cu cancer gastric local avansat/metastazat este redus (5-15%). Doar 20% dintre pacieni se prezint cu boal rezecabil, iar dintre acetia 80% prezint risc de recidiv locoregional sau la distan, chiar dup rezecia curativ.
Tabel 1 A 7-a stadializare TNM (2010) UICC a cancerului gastric T: tumora primar N: ganglionii limfatici regionali M: metastaze la distan T: tumora primar N0: Fr metastaze ganglionare Tis: Carcinom in situ locale T1: Tumora invadeaz N1: Metastaze n 1-2 limfonoduli lamina propria/ submucoasa regionali M0: Fr metastaze la T1a: tumora a invadat lamina N2: Metastaze n 3-6 limfonoduli distan propria sau musculara regionali M1: Prezena de metastaze mucoasei. N3a: Metastaze n 7-15 la distan T1b: tumora a invadat limfonoduli regionali submucoasa. N3b: Metastaze n mai mult de T2: Tumora invadeaz 16 limfonoduli regionali musculara proprie T3: Tumora invadeaz toate straturile gastrice dar nu a Stadiul 0 TisN0M0 ptruns n mucoasa Stadiul IA T1N0M0 peritoneal sau seroas Stadiul IB T1N1M0, T2N0M0 T4: Tumora penetrez Stadiul II A T1N2M0, T2N1M0, T3N0M0 seroasa i invadeaz Stadiul IIB T1N3M0, T2N2M0, T3N1M0, T4N0M0 structurile adiacente. Stadiul IIIA T3N2M0, T2N3M0, T4aN1M0 T4a: tumora a invadat Stadiul IIIB T4aN2M0, T3N3M0, T4bN0-1M0 seroasa. Stadiul IV oriceT orice N M1 T4b: tumora a invadat organele din jur.
Una dintre problemele importante de prognostic rmne limfadenectomia regional i extensia acesteia, esenial fiind totui diagnosticul precoce al bolii. Factorii asociai cu prognosticul nefavorabil sunt: vrsta avansat localizarea proximal pierderea ponderal >10% aspectul de linit plastic gradul sczut de difereniere invazia a mai mult de 4 ganglioni limfatici aneuploidia. Dintre aceti factori de prognostic menionati, analiza mulifactorial a studiilor publicate a relevat faptul c infiltrarea peretelui gastric i prezena metastazelor ganglionare sunt cei mai semnificativi in ceea ce privesc rezultatele tratamentelor [8].
1. 2. BIBLIOGRAFIE Cancer.org [Internet] Atlanta: American Cancer Society Inc, [cited 01 dec 2010]. Available from http://ww2.cancer.org/downloads/STT/500809web.pdf Anderson W, Camargo C, Fraumeni J, Correa P, Rosenberg P, Rabkin C. Age-Specific Trends in Incidence of Noncardia Gastric Cancer in US Adults. JAMA. 2010; 303(17): 1723-1728.
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3. 4. 5. 6. 7. 8.
Ajani JA. Evolving chemotherapy for advanced gastric cancer. Oncologist 2005; 10 (Suppl 3): 4958. Blanke CD, Citrin D, Schwarz RE. Gastric cancer In: Pazdur R, Coia LR, Hoskins WJ, Wagman LD eds. Cancer Management: A Multidisciplinary Approach, 10th ed, Darien CT, CMP Healthcare Media, 2007: p. 342 -386. Abrams AJ, Wang TC. Adenocarcinoma and Other Tumors of the Stomach In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease. Pathophysiology/Diagnosis/ Management, 9th ed, Feldman, M, Friedman, LS, Brandt, LJ eds. Philadelphia, WB Saunders, 2010: p. 887-908. Allum WH, Griffin SM, Watson A, Colin-Jones D. Guidelines for the management of oesophageal and gastric cancer. Gut 2002; 50(Suppl V): v1v23. Sign. Ac.uk. [Internet] Scottish Intercollegiate Guidelines Network - Management of oesophageal and gastric cancer 2006. [cited 2010] Available from: http://www.sign.ac.uk/guidelines/fulltext/87/index.html Leung KW, Ng KWE, Sung YJJ. Tumors of the stomach. In Tadataka Yamada editor. Atlas of Gastroenterology. 4th Ed. Singapore. Blackwell Publishing, 2009: p. 263-298.
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GREFONUL SINTETIC N TRATAMENTUL CHIRURGICAL AL EVENTRAIILOR. STUDIU EXPERIMENTAL

M. Miclu1, Codrua Miclu2, C. Mircu3, Romania Glaja4, C. Mihart1, L. Fulger1 1. Clinica II Chirurgie 2. Clinica Chirurgie General i Oncologie Universitatea de Medicin i Farmacie Victor Babe Timioara 3. Facultatea de Medicin Veterinar Universitatea de tiine Agronomice i Medicin Veterinar a Banatului 4. Departamentul de Anatomie Patologic, Spitalul Municipal Timioara
SINTETIC MESH AND SURGICAL TREATMENT OF INCISIONAL HERNIA. EXPERIMENTAL STUDY (ABSTRACT): Incisional hernia is the most important complication after surgical treatment on anterior abdominal wall. The purpose of surgical treatment is to build a resistant abdominal wall with normal local and general physiology. In medium and large incisional hernia a synthetic mesh is used for abdominal wall reconstruction. The synthetic mesh can be placed in several positions in the deep of the abdominal wall. The aim of this study is to find the best placement for synthetic mesh starting from an experimental study. The experimental study was performed on small lab animals (Wistar rats) in 6 groups of 6 animals each. The synthetic meshwas pleaced deep as well as superficial in the abdominal wall on different levels. The results were evaluated histologically on the 45-th day from the procedure. Retromuscular and preaponevrotical site were the best for placement of the synthetic mesh. At this level we observed the disappearing of the fibroblastic cells, but with the presence of the collagen fibers that pass through and integrate the mesh. The strength of the abdominal wall is based on the cross-linked collagen fibers. KEY WORDS: MESH INCISIONAL HERNIA, EXPERIMENTAL STUDY. Coresponden: Dr. Marius Miclu, Clinica II Chirurgie, Spitalul Clinic Judetean de Urgenta Timisoara, Bd. Iosif Bulbuca Nr. 10, Cod 300736*.
INTRODUCERE Eventraia postoperatorie este cea mai important complicaie la distan a interveniilor chirurgicale abdominale. A cunoscut o inciden tot mai mare, n paralel cu dezvoltarea chirurgiei i creterea numrului de intervenii chirurgicale. De-a lungul timpului i atitudinea terapeutic fa de eventraiile postoperatorii s-a modificat. n cazul eventraiilor de dimensiuni mici sau medii, au fost imaginate o serie de tehnici chirurgicale care utilizeaz structurile proprii locale pentru refacerea defectului musculo-aponevrotic, tehnici care s-au impus ca tratament optim n astfel de cazuri. n faa unei eventraii de dimensiuni mari, gigante sau cu pierderea dreptului la domiciliu, aceste tehnici chirurgicale nu pot fi utilizate, iar datorit dimensiunilor mari ale orificiului de eventraie, structurile proprii locale nu mai sunt suficiente pentru corectarea defectului parietal.
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n aceste cazuri, chiar dac se pot apropia buzele defectului, vor rezulta suturi n tensiune care nu confer rezisten, calitatea esuturilor este slab i n situaia defectelor musculo-aponevrotice foarte mari, structurile proprii devin insuficiente pentru acoperirea acestora. n aceast situaie a fost necesar ca pentru refacerea defectelor musculoaponevrotice mari, gigante sau cu pierderea dreptului la domiciliu s fie imaginate tehnici chirurgicale care utilizeaz diverse grefoane pentru plastia parietal. Scopul acestor grefoane este de a conferii rezisten peretelui abdominal afectat prin ntrirea suturilor musculo-aponevrotice sau prin substituia defectelor foarte mari. La nceput au fost utilizate homogrefele, pentru ca n ultimele decenii s se recurg la utilizarea grefoanelor sintetice. Acestea au ctigat teren odat cu dezvoltarea industriei chimice cu aplicaii n medicin, care a oferit o serie de grefoane sintetice cu grad mare de tolerabilitate din partea organismului receptor. Utilitatea grefonului sintetic n tratamentul chirurgical al eventraiilor s-a confirmat n urma diverselor studii clinice efectuate n timp. Problemele care apar sunt generate de nivelul la care este recomandat a se plasa grefonul sintetic n grosimea peretelui abdominal, pentru a se obine o integrare optim, pentru a conferi rezistena necesar i a genera un numr ct mai mic de complicaii. n acest sens a fost util efectuarea unui studiu experimental care s precizeze tocmai aceste aspecte legate de plasarea grefonului sintetic. Prin acest studiu s-a ncercat s se rspund la mai multe ntrebri: - care este modul de integrare al plasei n esuturile gazdei prin realizarea unor studii morfopatologice transformrile morfologice locale, pot reprezenta posibile cauze de eec; - rezultatele obinute n funcie de nivelul plasrii grefonului; - care este utilitatea observaiilor pentru practica clinic curent. MATERIAL I METOD Pentru efectuarea studiului au fost utilizate animale mici de laborator obolani Wistar, cu greutatea ntre 350-400 grame. Au fost formate ase loturi a cte ase animale fiecare lot. Pentru efectuarea interveniilor chirurgicale s-a utilizat anestezia inhalatorie cu eter, animalele fiind plasate n decubit dorsal. Timpul mediu al interveniilor chirurgicale a fost de 20 minute. Tehnica operatorie Printr-o incizie abdominal median, dup identificarea straturilor peretelui abdominal, s-a plasat grefonul sintetic (polipropilen) la diverse nivele n grosimea peretelui: A. superficial (n dou poziii): i. subcutanat, preaponevrotic; ii. retroaponevrotic, premuscular. B. profund (n trei poziii): i. retromuscular, preaponevrotic; ii. properitoneal; iii. intraperitoneal. Animalele au fost urmrite postoperator 45 de zile dup care au fost sacrificate. Pe parcursul experimentului nu au fost consemnate complicaii postoperatorii sau decese.
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S-a trecut la recoltarea pieselor reprezentate de fragmente integrale de perete abdominal care conineau i grefonul sintetic nglobat n esuturi. Piesele recoltate au fost incluse n blocuri de parafin, secionate i fixate pe lame. Pentru analiza lamelor au fost utilizate coloraii Tricrom-Gomori i Hematoxilin-Eozin. REZULTATE Analiza histopatologic a pieselor recoltate a artat diferene n ceea ce privete modul de integrare a grefonului sintetic n funcie de profunzimea plasrii acestuia n grosimea peretelui abdominal. Cnd plasa a fost montat n poziie superficial, subcutanat i preaponevrotic, s-a evideniat un proces de remodelare cu identificarea de fibroblaste i fibre conjunctive interstiiale, edem interstiial, reacie vascular (hiperemie), care au sugerat un proces de cicatizare n curs de desfurare. (Fig. 1)
Fig. 1 Plas montat n poziie superficial, preaponevrotic - proces de remodelare: fibroblaste i fibre conjunctive interstiiale, edem interstiial, reacie vascular hiperemie (col. Tricrom Gomori, x 20).
Fig. 2 Plas montat n poziie superficial, retroaponevrotic i premuscular - proces de remodelare: fibroblaste, miofibroblaste, fibre conjunctive mai dense (col. HE, x 20).
Tot n poziie superficial dar retroaponevrotic i premuscular s-a evideniat un proces de remodelare mai intens de ct n situaia anterioar, cicatrizarea aflndu-se ntr-un stadiu ceva mai avansat. (Fig. 2). Cnd plasa a fost montat n poziie profund, retromuscular i preaponevrotic s-a constat prezena fibrelor de colagen cu orientare perpendicular pe suprafaa grefonului i aranjament ncruciat, subfuziuni hemoragice interstiiale, foarte rare fibroblaste. Cicatrizarea se afl ntr-un stadiu terminal, fibrele de colagen reprezentnd elementele de rezisten local. Orientarea perpendicular a acestora vor crete gradul de rezisten parietal. (Fig. 3). Dac plasa a fost montat n poziie profund, properitonal, s-a evideniat un proces de remodelare intens, cu fibroblaste, miofibroblaste, fibre conjunctive de colagen mai dense. Prezena acestor elemente pledeaz pentru o faz terminal a cicatrizrii, dar lipsa orientrii fibrelor de colagen plaseaz procesul ntr-o faz mai anterioar de ct situaia precedent (Fig. 4). n situaia n care plasa a fost montat n poziie profund, intraperitoneal, morfopatologic s-a constatat c stratul celulelor mezoteliale are continuitatea pstrat i subfuziuni hemoragice interstiiale. 29
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Stratul de celule mezoteliale pstrat este martorul unei integrri intraperitoneale perfecte fr complicaii de tipul aderenelor viscerale la grefon. (Fig. 5).
Fig. 3 Plas montat n poziie profund, retromuscular i preaponevrotic - fibre conjunctive de colagen cu orientare perpendicular pe suprafaa grefonului i aranjament ncruciat; subfuziuni hemoragice interstiiale; foarte rare fibroblaste. (col. Tricrom Gomori, x 40).
Fig. 4 Plas montat n poziie profund, properitoneal - proces de remodelare: fibroblaste, miofibroblaste, fibre conjunctive mai dense (col. Tricrom Gomori, x 40).
Fig. 5 Plas montat n poziie profund, intraperitoneal - stratul celulelor mezoteliale cu continuitate pstrat; subfuziuni hemoragice interstiiale (col. HE, x 20).
DISCUII Procesul de cicatrizare al plgilor are trei faze consecutive [1]. Faza A inflamaia leucocitele invadeaz plaga i fagociteaz resturile tisulare i/sau corpul strin. Faza B - formarea esutului de granulaie n timp ce procesul de fagocitoz i cel de ndeprtare al materialului necrotic se desfoar, are loc proliferarea esutului de granulaie. Acesta este format din vase de neoformaie i fibroblaste ce determin formarea unui esut edematos care reprezint matricea tisular.
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Faza C Procesul de remodelare fibroblastele ncep procesul de remodelare prin producerea fibrelor de colagen interstiial. Citokinele au rolul principal n coordonarea acestor procese celulare. Se dezvolt miofibroblastele ceea ce duce la contracia plgii. Intensitatea contraciei crete pe msur ce fibrele de colagen se formeaz, se orienteaz i interacioneaz cu miofibroblastele contractile. n acest fel procesul de cicatrizare se apropie de sfrit [2]. Cicatrizarea plgilor aponevrotice decurge ntr-un mod asemntor. Acumularea i remodelarea colagenului se face progresiv i lent (dup un an vindecarea este de 7080%) [3-6]. Cicatricea rezultat nu are elasticitatea i rezistena esutului iniial. Cu toate acestea se integreaz perfect n fiziologia local. Fibrele conjunctive sunt cele care confer rezisten peretelui. Diminuarea pn la dispariie a fibroblastelor cu prezena fibrelor de colagen denot o integrare perfect a grefonului, o cicatrizare aproape ncheiat care duce la dezvoltarea unui esut conjunctiv rezistent [7]. Pe studii experimentale s-a constatat c n cazul plasrii grefonului intraperitoneal, acesta este traversat i acoperit de un strat de celule mezoteliale. Soluia de continuitate de la nivelul acestui strat mezotelial reprezint nceputul realizrii de aderene ntre diverse viscere peritoneale i perete, grefon. Aceste aderene reprezint punctul de plecare pentru apariia altor complicaii, de tipul eroziunilor i fistulelor intestinale [8-11]. CONCLUZII Plecnd de la aceste date am constatat c exist o relaie direct ntre profunzimea plasrii grefonului sintetic n grosimea peretelui abdominal i integrarea sa. Analiznd poziiile superficiale de montare a grefonului la nivel parietal, rezultate bune au fost obinute n cazul montrii acestuia retroaponevrotic i premuscular, unde apar fibre de colagen mai dense. n poziiile preaponevrotice am constatat un edem interstiial i reacie vascular, care le-am interpretat ca reprezentnd o asimilare mai dificil i greoaie. n poziiile profunde ale grefonului, am observat c fibrele de colagen au fost mai abundente cu reducerea celularitii. Poziia retromuscular i preaponevrotic este cea mai bun pentru asimilarea grefonului. La acest nivel am constatat dispariia aproape complet a fibroblastelor dar cu prezena fibrelor de colagen care strbat ochiurile plasei integrnd-o. Pe de alt parte fibrele de colagen au o orientare ncruciat care confer rezisten. Aceste fenomene denot o integrare aproape perfect a grefonului, o cicatrizare aproape terminat fa de celelalte poziii, cu dezvoltarea unui esut conjunctiv rezistent. Este recomandat ca atunci cnd se apeleaz la grefon sintetic pentru repararea defectelor musculo-aponevrotice, acesta s fie plasat n profunzimea peretelui abdominal pentru a obine rezultate ct mai bune.
1. 2. 3. BIBLIOGRAFIE Georgescu L, Tudose N, Potencz E. Morfopatologie, Bucureti, Ed. Didactic i Pedagogic. 1982; p. 128-132. Murphy JL, Freeman JB, Dionne PG. Comparison of marlex and GORE-TEX to repair abdominal wall defects in the rat. Can J Surg. 1989; 32(4): 244-247. Peacock EE. Wound repair. Philadelphia, third edition, WB Saunders 1984; p. 1-14, 35, 38-54, 71, 107, 109, 438-439, 441.
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Hunt TK. Wound healing and wound infection theory and surgical practice. New York, Appleton-Century- Croft 1980; p. 39,43,121. 5. Irvin TT. Wound healing principles and practice. London, Chapman and Hall 1981; p. 18-19. 6. Ponka JL. Hernias of the abdominal wall. Philadelphia, First edition, Saunders 1980; p. 20, 339. 7. Miclu M. Eventraii abdominale postoperatorii. Tratamentul chirurgical cu material aloplastic. Implicaii medicale i socio-economice. UMF Timioara, Tez de Doctorat. 1999; p. 152-164. 8. Brown GL, Richardson JD, Malangoni MA, Tobin GR, Ackerman D, Polk HC Jr. Comparison of prosthethic materials for abdominal wall reconstruction in the presence of contamination and infection. Ann Surg. 1985; 201(6): 705-711. 9. Voyles CR, Richardson JD, Bland KI, Tobin GR, Flint LM, Polk HC Jr. Emergency abdominal wall reconstruction with polypropylene mesh. Short term benefits versus long term complications. Ann Surg. 1981; 194(2): 219-223. 10. Walker AP, Henderson J, Condon RE. Double-layer prostheses for repair of abdominal wall defects in a rabbit model. J Surg Res. 1993; 55(1): 32-37. 11. LeBlanc KA, Bellanger D, Rhynes KV 5th, Baker DG, Stout RW. Tissue attachment strength of prosthetic meshes used in ventral and incisional hernia repair. A study in the New Zealand White rabbit adhesion model. Surg Endosc. 2002; 16(11): 1542-1546.
4.
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FACTORII DE RISC N APARIIA STAZEI GASTRICE POST DUODENOPANCREATECTOMIE CEFALIC

Dana Iancu, A. Barto, L. Mocanu, Teodora Mocanu, Raluca Bodea, F. Zaharie, Andra Andreescu, C. Iancu Clinica Chirurgie III, Cluj-Napoca Universitatea de Medicin i Farmacie Iuliu Haieganu Cluj-Napoca, Romnia
RISK FACTORS IN DEVELOPING DELAYED GASTRIC EMPTYING AFTER PANCREATODUODENECTOMY (ABSTRACT): Introduction: Even now, the surgery for the pancreatic cancer is a very debatable subject because of its high morbidity. Among the postoperatory complications, with a high impact on the patient, is the delayed gastric emptying. Material and methods: The aim of this study is to find the potential risk factors in the delayed gastric emptying after pancreato-duodenectomy. This is a prospective study from 2008 till 2010, done in Surgery Clinic no III of Cluj-Napoca. 128 patients with periampular cancer on which pancreato-duodenectomy was performed were included in the study. Results: The rate of having delayed gastric emptying after pancreato-duodenectomy was 18%. All the patients with this complication had many postoperatory complications (p=0,00). 19% of the patients with anemia developed delayed gastric emptying. The percent of fat people that developed delayed gastric emptying was 35% vs 12% which had normal weight; these data were statistically valid (p=0,007). The patients with internal bleeding developed delayed gastric emptying in 22% of the cases instead of 9% in the ones that did not have internal bleeding. DZ, a longer intraoperative time, a soft pancreatic parenchyma will not raise the probability of developing delayed gastric emptying. Conclusions: The delayed gastric emptying is the most frequent complication following duodenopancreatic surgery. The risc factors that are involved in its appearance are: obese patients and the presence of multiple postoperatory complications. KEY WORDS: PANCREATIC CANCER, SURGICAL INTERVENTION, DELAYED GASTRIC EMPTYING, PREDICTIVE FACTORS Coresponden: Dr. Dana Iancu, Clinica Chirurgie III, Cluj-Napoca, Str. Iailor nr. 16, +40264134955*..
INTRODUCERE Tratamentul chirurgical al cancerului periampular reprezint i la ora actual o piatr de ncercare pentru majoritatea serviciilor chirurgicale. Cu toate progresele nregistrate, morbiditatea dup DPC (duodenopancreatectomie cefalic) rmne la 3040% dar mortalitatea n centrele de excelen a sczut la 2-4%. Dac fistula pancreatic reprezint cea mai redutabil complicaie dup DPC, staza gastric este cea mai frecvent [1,2]. MATERIAL I METOD Studiul este unul prospectiv, efectuat n cadrul Clinicii Chirurgie III Cluj Napoca n perioada 2008-2010; au fost selectai un numr de 128 de pacieni la care s-a practicat DPC.
*
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Datele obinute au fost analizate din punct de vedere statistic, testul utilizat fiind 2 iar intervalul de confiden este de 95 %. Am considerat ca fiind pacieni cu staz gastric pacienii care au necesitat sonda nazo-gastric mai mult de trei zile, pacieni care au necesitat remontarea sondei nazo-gastrice dup ziua trei postoperator datorit persistenei vrsturilor, incapacitatea pacientului de a se alimenta cu alimente solide dup ziua apte postoperator [3]. Am considerat ca fiind pierdere intraoperatorie de snge, hemoragia peste 400 ml. Intervenia chirurgical sub 4 ore a fost considerat ca fiind de durat medie iar cea peste acest interval de timp ca fiind lung. Culegerea datelor a fost efectuat din fia special conceput pentru acest studiu. Pentru culegerea datelor biochimice i hematologice s-a apelat la laboratorul Spitalului Clinic de Urgen "Octavian Fodor" (limitele normale pentru toate valorile studiate fiind astfel aceleai n toate cazurile). n ceea ce privete prelucrarea datelor statistice aceasta a fost efectuat unitar de ctre aceeai persoan. REZULTATE Din totalul de 128 de bolnavi, 61 au fost brbai i 67 femei, vrsta lor fiind cuprins ntre 23 i 84 de ani. Staza gastric postoperatorie a fost prezent la un numr de 22 cazuri, valoarea reprezentnd 18% din totalul de cazuri. 11 pacieni (19%) din 60 care au prezentat anemie n preoperator au dezvoltat staz gastric. Procentul este nesemnificativ mai mare dect la pacienii cu valori normale ale hemoglobinei i hematocritului (Tabel 1). Proporia de apariie a stazei gastrice a fost n jurul valorii de 16%, la pacienii cu o valoare glicemic normal i de 21% la cei cu diabet zaharat (p=0,692) (Tabel 1). Staza gastric a fost prezent la 11 pacieni (35%) obezi i tot acelai numr, 11(12%) la pacieni cu greutate normal la internare. Aceste date au evideniat diferene notabile din punct de vedere statistic (p=0,007) (Tabel 1).
Tabel 1 Date analitice comparative Staz gastric Total Absent Prezent P Anemie Absent Prezent 68 60 57 49 11(17%) 11(19%) 0.949 Absent 94 79 15(16%) 0.692 DZ Prezent 34 27 7(21%) Obezitate Absent 96 85 11(12%) 0.007 Prezent 32 21 11(35%)
Rata de apariie a stazei gastrice a fost superioar la pacienii cu pierdere crescut de snge intraoperator (22%) fa de cei care nu au prezentat aceast complicaie intraoperatorie (2%). Diferena nu a fost validat din punct de vedere statistic p=0,105 (Tabel 2). n ceea ce privete staza gastric postintervenional, aceasta este prezent cu o frecven asemntoare att n cazul interveniilor mai scurte ct i a celor cu o durat operatorie mai mare. n acest caz valoarea indicelui statistic p este 0,558 (Tabel 2).
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Staza gastric a fost prezent n 10 (22%) din 47 de cazuri cu parenchim pancreatic de consisten crescut, n 6 cazuri la pacieni cu un parenchim de consisten normal (12%) i n 6 cazuri (21%) la pacieni cu consisten pancreatic sczut. Analizele statistice au artat dinamici diferite ale apariiei stazei gastrice n funcie de consistena parenchimului pancreatic; datele rezultate nu sunt semnificative din punct de vedere statistic, p-global=0,374 (Tabel 2). Toi pacienii cu complicaii majore postoperatorii au prezentat i staz gastric (p=0,0001) (Tabel 2).
Tabel 2 Date analitice comparative Consisten parenchim Durat operaie pancreatic <4h 42 33 9(22%) >4h 86 73 13(16%) normal 52 46 6(12%) crescut 47 37 10(22%) sczut 29 23 6(21%)
Staz gastric Total 128 Absent - 106 Prezent - 22 P
Pierdere de snge <400 >400 ml ml 46 42 4(9%) 82 64 18(22%)
Complicaii Absente 74 74 0(0%) Prezente 54 32 22(41%)
0.105
0.558
GLOBAL p=0.374 0 VS 1 p=0.298 0 VS 2 p=0.448 1 VS 2 p=0.854
<0.0001
Nu s-au evideniat diferene semnificative n apariia stazei gastrice postoperatorii la pacienii cu valori modificate ale INR-ului, ale proteinelor totale, la pacienii cu comorbiditi. DISCUII Staza gastric aprut postoperator este una dintre complicaiile cele mai frecvente ale duodenopancreatectomiei cefalice [3]. Datorit lipsei unui consens n ceea ce privete definiia exact a stazei gastrice, datele referitoare la frecvena ei sunt diferite. Cu toate acestea, incidena de apariie a stazei se situeaz n jurul valorii de 12% pentru intervenii cu durat medie (sub 3 ore), putnd crete dac vorbim de intervenii majore [3-7]. Proporia de apariie a stazei gastrice postoperatorii a fost de 18%, aceste valori fiind similare cu cele citate n literatur [4]. De menionat faptul c, chirurgul care a efectuat majoritatea acestor intervenii a folosit un montaj pancreatic modificat, i anume: bontul pancreatic inserat n stomac printr-o gastrotomie posterioar a fost mai lung, de aproximativ 4 cm, fr s existe nici un fel de traciune la acest nivel. Totodat anastomoza gastro-jejunal este una larg, de aproximativ 8 cm; nu se monteaz sond transanastomotic. Dintre factorii de risc citai de literatur ca implicai n apariia acestei complicaii, menionm: hemoragia intraoperatorie, durata crescut a interveniei, frecvena crescut a complicaiilor postoperatorii. n ceea ce privete incidena de apariie a stazei gastrice la pacieni cu anemie preoperatorie, aceasta este aproximativ egal cu cea a pacienilor cu valori normale ale hemoglobinei i hematocritului. Datele obinute nu sunt semnificative din punct de vedere statistic (p=0,949). 35
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Diabetul zaharat nu a reprezentat un factor de risc pentru apariia stazei gastrice, diferenele ntre cele dou loturi nefiind semnificative statistic (p=0,692). Datele noastre au artat o cretere a incidenei stazei gastrice direct proporional cu indicele de mas corporal. n cazul loturilor noastre au existat diferene notabile din punct de vedere statistic (p=0,007). Literatura de specialitate nu citeaz diferene notabile n apariia acestei complicaii n funcie de indicele de mas corporal [7,8]. n studiul efectuat n anul 2010 de ctre Hashimoto i Traverso pe un lot de 507 pacieni consecutivi cu patologie pancreatic neoplazic la care s-a efectuat duodenopancreatectomie, se evideniaz importana hemoragiei intraoperatorii n apariia stazei gastrice postoperatorii (p=0,007) [7]. Datele obinute n studiul nostru au venit s sprijine datele din literature de specialitate, cu toate c nu au putut fi validate statistic datorit dimensiuni mai reduse a unuia dintre loturi (p=0,105). Proporia de apariie a stazei gastrice a fost de aproximativ dou ori mai mare n cazul pacienilor cu pierderi sangvine crescute intraoperator, fa de cei care nu au prezentat aceast complicaie intraoperatorie. Tot n studiul lui Hashimoto i Traverso rezultatele statistice arat importana interveniei chirurgicale prin prisma timpului operator, care, cu ct este mai prelungit cu att riscul de apariie a stazei gastrice postoperatorii este mai mare (p=0,016) [7,9]. n cadrul studiului nostru aceast ipotez nu a putut fi validat, indicele statistic situnduse la valoarea de p=0,558. n marea majoritate a studiilor de specialitate textura parenchimului pancreatic nu este un factor de risc n apariia stazei gastrice postoperatorii [7,8]. n cazul studiului nostru datele obinute nu au fost semnificative din punct de vedere statistic (p=0,374). Cu toate acestea se poate observa o uoar cretere a proporiei de apariie a stazei gastrice dac parenchimul pancreatic este unul modificat (12% fa de 22% n cazul unui parenchim modificat. Complicaiile postoperatorii au fost n mod cert un important factor de risc n apariia stazei gastrice (p<0,0001). Pentru unii autori ca i Van Berge Henegouven i Van Gulik aceste complicaii postoperatorii au fost factorul principal de risc n apariia stazei gastrice, aceasta fiind prezent la 65% dintre pacienii cu complicaii [10]. n articolul su din British Journal of Surgery din anul 2010, Welsch face printre altele o evaluare a factorilor de risc ai stazei gastrice, factorul cu cea mai mare importan din punct de vedere statistic (p<0,001) a fost apariia complicaiilor postoperatorii [5]. Aceste date au fost confirmate i de alte studii de specialitate [8,11-14]. Pancreatita acut alturi de fistula pancreatic au fost incriminate de muli autori ca fiind factori de risc ai apariiei stazei gastrice [3,13,15]. Aceste date nu au coincis cu rezultatele obinute n cadrul studiului nostru. Nici unul dintre pacienii care au prezentat staz gastric n postoperator nu au dezvoltat fistul pancreatic i pancreatit acut. CONCLUZII Staza gastric este cea mai frecvent complicaie post duodenopancreatectomie cefalic. Factorii de risc care sunt implicai n apariia acestei complicaii au fost: prezena obezitii, prezena n postoperator a complicaiilor multiple. Analiznd datele din literatur i datele obinute n cadrul studiului nostru observm c cel mai important factor de risc n apariia stazei gastrice este legat de experiena echipei chirurgicale i de capacitatea acesteia de a executa ct mai bine intervenia chirurgical.
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O intervenie de o durat mai scurt, o disecie atent care s nu produc pierderi sangvine mari intraoperatorii, o anastomoz ngrijit pot concura la un rezultat postoperator favorabil, fr complicaii majore. BIBLIOGRAFIE
1. 2. 3. 4. Riall TS, Nealon WH, Goodwin JS, Zhang D, Kuo YF, Townsend CM Jr, Freeman JL. Pancreatic cancer in the general population: improvements in survival over the last decade. J Gastrointest Surg 2006; 10(9): 12121224. Geer RJ, Brennan MF. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg 1993; 165(1): 6872. Park JS, Hwang HK, Kim JK, Cho SI, Yoon DS, Lee WJ, Chi HS. Clinical validation and risk factors for delayed gastric emptying based on the International Study Group of Pancreatic Surgery (ISGPS) Classification. Surgery 2009; 146(5): 882-887. Fathy O, Wahab MA, Elghwalby N, Sultan A, EL-Ebidy G, Hak NG, Abu Zeid M, Abd-Allah T, El-Shobary M, Fouad A, Kandeel T, Abo Elenien A, Abd El-Raouf A, Hamdy E, Sultan AM, Hamdy E,Ezzat F. 216 cases of pancreaticoduodenectomy: risk factors for postoperative complications. Hepatogastroenterology 2008; 55(84): 1093-1098. Welsch T, Borm M, Degrate L, Hinz U, Bchler MW, Wente MN. Evaluation of the International Study Group of Pancreatic Surgery definition of delayed gastric emptying after pancreatoduodenectomy in a high-volume centre. Br J Surg 2010; 97(7): 1043-1050. Wente MN, Bassi C, Dervenis C, Fingerhut A, Gouma DJ, Izbicki JR, Neoptolemos JP, Padbury RT, Sarr MG, Traverso LW, Yeo CJ, Bchler MW. Delayed gastric emptying (DGE) after pancreatic surgery: a suggested definition by the International Study Group of Pancreatic Surgery (ISGPS). Surgery 2007; 142(5): 761-768. Hashimoto Y, Traverso LW. Incidence of pancreatic anastomotic failure and delayed gastric emptying after pancreatoduodenectomy in 507 consecutive patients: use of a web-based calculator to improve homogeneity of definition. Surgery 2010; 147(4): 503-515. Lermite E, Pessaux P, Brehant O, Teyssedou C, Pelletier I, Etienne S, Arnaud JP. Risk factors of pancreatic fistula and delayed gastric emptying after pancreaticoduodenectomy with pancreaticogastrostomy. J Am Coll Surg. 2007; 204(4): 588-596. Gao HQ, Yang YM, Zhuang Y, Wang WM, Wu WH, Wan YL, Huang YT. Influencing factor analysis of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy, Zhonghua Wai Ke Za Zhi 2007; 45(15): 1048-1051. van Berge Henegouwen MI, van Gulik TM, DeWit LT, Allema JH, Rauws EA, Obertop H, Gouma DJ. Delayed gastric emptying after standard pancreaticoduodenectomy versus pyloruspreserving pancreaticoduodenectomy: An analysis of 200 consecutive patients. J Am Coll Surg 1997; 185(4): 373-379. Kimura F, Suwa T, Sugiura T, Shinoda T, Miyazaki M, Itoh H. Sepsis delays gastric emptying following pylorus-preserving pancreaticoduodenectomy. Hepatogastroenterology 2002; 49(44): 585-588. Fabre JM, Burgel JS, Navarro F, Boccarat G, Lemoine C, Domergue J. Delayed gastric emptying after pancreaticoduodenectomy and pancreaticogastrostomy. Eur J Surg 1999; 165(6): 560-565. Rty S, Sand J, Lantto E, Nordback I. Postoperative acute pancreatitis as a major determinant of postoperative delayed gastric emptying after pancreaticoduodenectomy. J Gastrointest Surg 2006; 10(8): 1131-1139. Kurosaki I, Hatakeyama K. Clinical and surgical factors influencing delayed gastric emptying after pyloric-preserving pancreaticoduodenectomy. Hepatogastroenterology 2005; 52(61): 143-148. Reid-Lombardo KM, Farnell MB, Crippa S, Barnett M, Maupin G, Bassi C, Traverso LW. Pancreatic Anastomotic Leak Study Group, Pancreatic anastomotic leakage after pancreaticoduodenectomy in 1,507 patients: a report from the Pancreatic Anastomotic Leak Study Group. J Gastrointest Surg 2007; 11(11): 1451-1458.
5. 6.
7. 8. 9. 10.
11. 12. 13. 14. 15.
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TRAUMATISMELE ABDOMINALE - ATITUDINE TERAPEUTIC

D. Popa, C. Copotoiu, V. Bud, C. Molnar, A. Pantiru, C. Rosca, M. Gherghinescu, C. Russu, T. Dudas, B. Suciu, G. Serac, A. Cotovanu, F. Constantinescu, I. Balmos Clinica Chirurgie1, Spitalul Clinic Judetean de Urgent Mure, Romnia
ABDOMINAL TRAUMA - THERAPEUTIC APPROACH (ABSTRACT): Abdominal trauma are a major cause of death and morbidity among population, affecting all age groups. Although not very common, 17-18% of all injuries, identifying major intra-abdominal injuries is difficult, the clinical manifestation of lesions often appears late or masked by the association of other injuries. The two main types of abdominal traumas: bruises or wounds, regarding bodies and various structures, mortality varies between 6-10% according to the affected organ and the associated lesions. This paper studies a group of 820 patients with abdominal traumas hospitalised in First Surgical Clinic of Tg. Mures between 20002009, analyzing the mechanisms of production, the methods of diagnosis and treatment, the single or multiple organic damage and their influence on morbidity and mortality. Most abdominal injuries were simple parietal contusions without intra-abdominal damage 482 cases (58.78%) with a void mortality . Spleen injuries were recorded in 13.05% of the cases, liver injuries in 10%, small bowel in 2.07% , and the overall mortality was 6,59% with ISS 12,41. Ranging from parietal lesions to lesions with immediate fatal potential (trauma of parenchymal organs or vascular structures) or late fatal potential (hollow organs injuries) the decision-making and therapeutic problem in abdominal traumas is a topic of constant debate. KEY WORDS: ABDOMINAL TRAUMA, INDEX SEVERITY SCORE, MORTALITY Coresponden: Dr. Daniel Popa, medic primar chirurgie generala, asistent universitar UMF Tg. Mure, Clinica Chirurgie1, Spitalul Clinic Judetean de Urgent Mure, Str. Dr. Gh. Marinescu nr. 50, 540136, Trgu Mures, Mures, Romnia*.
INTRODUCERE Managementul pacienilor cu traumatisme abdominale (Tr.A) a suferit schimbri majore de atitudine i concepie n ultimii ani. Aceti pacieni, victime ale unei adevrate epidemii traumatice [1], sunt de obicei persoane active, cu vrsta cuprins ntre 15-50 de ani [2]. Probabilitatea de deces prin Tr.A la acest grup populaional este de trei ori mare dect riscul de deces prin alte cauze [3]. Dei incidena Tr.A este relativ redus n cadrul traumelor, variind ntre 8-10% [3], ele sunt frecvent asociate cu alte leziuni n cadrul unor politraumatisme. Dac mortalitatea n cazul Tr.A simple variaz ntre 6-9% [3], ea poate atinge 30-50% n cazul politraumatismelor grave [1,2]. Traumatismele abdominale nchise (contuziile), sunt cele mai frecvente, reprezentnd 60-79% din Tr.A, majoritatea (59-73%) fiind cauzate de accidente rutiere [2]. Cel de-al doilea tip de Tr.A, cele deschise (plgile),variaz larg ca frecven n diferite ri, de la 0,05% n Japonia la 14,24% n SUA [4], ct i ca mecanism de producere plgi prin arme albe sau prin proiectile. i mortalitatea n Tr.A nchise variaz larg ntre 10,625%, n SUA plgile abdominale mpucate fiind a cincisprezecea cauz de deces [4,5]. Atitudinea terapeutic n cazul Tr.A a prezentat, astfel, o abordare variat de-a lungul timpului, terapia non-operatorie (conservatoare ) i chirurgia de control lezional (damage control surgery) limitnd interveniile clasice eroice.
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Aceast atitudine, corelat cu dezvoltarea tehnologic a dus la o cretere a ratei de supravieuire de peste 50% n cazul Tr.A majore [6,7]. Dac n cadrul Tr.A cu afectare uniorganic cuantificarea riscului de succes terapeutic este mai facil, nu acelai lucru se poate spune i despre Tr.A ce asociaz leziuni pluriorganice sau ale altor regiuni anatomice la care mortalitatea poate sa depeasc 50%. Nevoia cuantificrii leziunilor i a anselor de reuit a dus la dezvoltarea unor sisteme de scoruri Glasgow Coma Scale (GCS), Injury Severity Scale (ISS), New Injury Severity Scale (NISS) etc, iar pentru standardizarea descrierilor afectrii organelor au fost stabilite sisteme de grade lezionale. Scopul lucrrii este de a analiza mecanismele de producere a Tr.A, urmrind atitudinea terapeutic aleas i de a stabili corelaia ntre mortalitate i ISS sau gradul lezional. MATERIAL I METOD Studiul efectuat a urmrit evaluarea retrospectiv a unui lot de 820 de pacieni cu TA internai ntre 2000 i 2009 n Clinica Chirurgie I a Spitalului Clinic Judeean de Urgen Mure, analiznd mecanismele de producere, asocierile lezionale i rsunetul acestora asupra modalitilor terapeutice i a mortalitii. Datele studiate au inclus: paternul lezional, parametrii hemodinamici la internare, analizele biochimice n dinamic, aspectul imagistic i cuantificarea lezional prin calcularea ISS i a gradelor lezionale utilizate de American Association for Surgery of Trauma. Datele au fost prelucrate cu ajutorul programului Microsoft Excel si Access 2007. REZULTATE n lotul studiat Tr.A nchise au fost predominante 709 pacieni ( 86,46%). Dintre acestea 557 (67,93%) de cazuri au fost simple contuzii parietale, far rsunet visceral intraabdominal, cu mortalitate zero, atitudinea terapeutic fiind una conservatoare. n ultimii ani, incidena Tr.A a crescut constant, incidena anual putnd fi observat n Fig. 1.
Fig. 1 Incidena anual a traumatismelor abdominale
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Grupele de vrste cele mai afectate au fost cele active (20-50 de ani) 447 pacieni ( 54,51% ) (Fig. 2).
Fig. 2 Repartiia Tr.A pe grupe de vrst
Tr.A au fost predominante la brbai( sex ratio B/F= 2,96:1 ), majoritatea plgilor prin njunghiere fiind prezente la sexul masculin (45 din 48 de cazuri). Asocierea lezional n Tr.A a fost relativ frecvent, interesnd fie mai multe viscere ale compartimentului abdominal, fie ale altor regiuni anatomice. n funcie de mecanismul de producere, majoritatea au fost produse prin accidente rutiere 383 cazuri (46,7%), urmate de cele prin cdere de la alt nivel - 204 cazuri (24,87). Mortalitate general a fost de 6,59%, ea variind ns n funcie de tipul lezional. (Fig. 3)
Fig. 3 Mortalitatea general n Tr.A
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Unul dintre criteriile de gravitate evaluat de studiul nostru, a fost prezena hemoragiei i a instabilitii hemodinamice, acestea fiind prezente la 33,17% dintre pacieni. (Tabel 1)
Tabel 1 Hemoragia n traumatismele abdominale Hemoragie NR Fara hemoragie 548 Interna 253 Interna/Externa Externa Total 11 8 820
% 66.83% 30.85% 1.34% 0.98%
ocul hemoragic a fost prezent la 198 pacieni (24,14%) din care doar n 24,74% din cazuri a prezentat forme medii/grave. (Tabel 2).
Tabel 2 ocul n traumatisme NR 102 47 30 19 622 820
oc Clasa I/>15% pierdere sanguin Clasa II/15-30% pierdere sanguin Clasa III/30-40% pierdere sanguin Clasa IV/>40% pierdere sanguin Fr oc Total
% 12.44% 5.73% 3.66% 2.32% 75.85%
n ceea ce privete leziunile organelor intraabdominale, traumatismele hepatice (TH) s-au situat pe locul trei, dup cele parietale i splenice, cu 82 de cazuri (10%). Leziunea hepatic a fost singular, sau asociat altora, cele frecvente fiind cele toracice (39 de cazuri). Atitudinea terapeutic a constat monitorizarea clinic i paraclinic, reechilibrare volemic dup caz i monitorizare imagistic (eco/CT). Tratamentul conservator, non-operator, a fost posibil la 36,59% dintre pacienii cu TH (30 cazuri). Laparotomia exploratorie asociat unor gesturi minime de hemostaz, inclusiv packingul aa numita damage control surgery, a fost efectuat n 18 cazuri (22,5%). Rezeciile hepatice atipice sau tipice au fost practicate n doar 12 cazuri. ISS calculat pentru TH a prezentat o valoare medie ntre 13,87 i 75 (medie general 75). Valorile crescute ale acestuia fiind asociate cu o cretere a mortalitii. Mortalitatea general n TH a fost de 20,7%, gradele lezionale mari-4,5,6, sau un ISS > 12 au fost asociate unei mortaliti net superioare. (Fig. 4). Traumatismele splenice s-au situat pe locul II ca frecven- 124 cazuri (15,2%), toate fiind asociate cu prezena hemoperitoneului. Dintre acestea, n 109 cazuri a fost prezent ocul hemoragic manifestat clinic. Tratamentul a constat n: splenectomie 75 cazuri (60,5%), de hemostaz cu prezervarea organului 49 cazuri ( 39,5%). (Fig. 5). Media ISS a variat de la 13,55 la 75, mortalitatea fiind corelata cu valoarea ISS (Fig. 6).
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Cele mai frecvente asocieri lezionale ale traumatismelor splenice au fost fluidopneumotoracele stng sau bilateral (20%), fracturi costale (23%) i traumatismele craniene (20%).
Fig. 4 ISS si mortalitatea n traumatismele hepatice
Fig. 5 Interveniile chirurgicale n traumatismele splenice
Fig. 6 ISS si mortalitatea n traumatismele splenice
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Contuzia a reprezentat mecanismul patogenic cel mai frecvent 72%. Leziunile viscerelor cavitare au fost reduse ca i frecven, aproximativ 3,5% din TA, cel mai frecvent fiind interesat intestinul subire 17 cazuri. DISCUII Managementul pacientului cu traumatism abdominal a evoluat semnificativ n ultimele decade, cu o schimbare de la atitudinea intervenional de la nceputul anilor 60, la atitudinea conservatoare (non-operatorie) din ultimii 20 de ani [8,9]. n ultimele decade, tratamentul conservator al pacienilor cu Tr.A nchis, chiar cu leziuni evideniate ale organelor parenchimatoase, dar stabili hemodinamic, a devenit standardul terapeutic. Acest lucru a fost posibil datorit progresului tehnologic din domeniul imagistic, a dezvoltrii noilor metode de radiologie intervenional i posibilitilor de reanimare i terapie intensiv actuale. nelegerea mecanismelor patogenice corelat cu evidenierea factorilor de risc din Tr.A au fcut posibil dezvoltarea unor sisteme de scoruri lezionale i de prognostic ce permit o nuanare mai bun a actului terapeutic [10]. Ca i mecanism de producere, TH nchise cu asocierea leziunilor de organe parenchimatoase (splin, ficat ) au inciden mai mare-60-79% [1,4] i o mortalitate ce variaz n funcie de numrul i tipul organelor afectate. Diagnosticul clinic semnele ocului hemoragic, instabilitate hemodinamic (tensiune arterial sub 90 mmHg) la admisie sau care nu poate fi susinut de manevrele de reechilibrare volemic, hipotermia (sub 300C), acidoza (pH sub 7,18), PTT peste 50 sau necesar transfuzional de peste 10 uniti de snge reprezint factori importani de prognostic infaust [11]. Valori crescute ale ISS n TA par s fie asociate cu o mortalitate crescuta, dar rezultatele din literatura de specialitate nc sunt controversate [11,12]. Compararea mortalitii nregistrate la pacienii cu ISS>15 n studiul nostru arat o cretere semnificativ a acesteia (peste 20%, comparativ cu mortalitatea general de doar 6%) date comparabile cu cele din literatura de specialitate [9], exist ns studii ce nu sunt de acord cu aceast corelaie [8,11]. n ceea ce privete termenul de tratament non-operator( conservator) introdus n 1995 de Pachter HL i Hofstetter SR, acesta a ctigat din ce n ce mai mult teren, fiind posibil n condiia de stabilitate hemodinamic, constnd n monitorizarea i reechilibrarea pacientului n uniti de terapie intensiv. Avantajele includ evitarea unor laparotomii non-terapeutice, cu dispariia morbiditii legate de acestea i de o limitare a necesarului transfuzional [13]. Cu toate acestea, nici scorul traumatic, nici rezultatele examinrilor imagistice nu pot s evite incapacitatea tratamentului conservator i s elimine o laparotomie necesar ( Fang JF, 1988). n cazul Tr.A grave ISS peste 15 [11], se impun intervenii chirurgicale de control lezional (damage control surgery). Termenul a fost introdus de Rotondo et al. [14] n 1993 ca un control primar al hemoragiei i al contaminrii peritoneale, lucru realizat prin packing-ul intraperitoneal i laparorafie imediat, resuscitare adecvat n secia ATI pn la stabilizare urmat de relaparotomie i sancionarea lezional definitiv [6,15-19]. Indicaiile majore pentru aceast atitudine sunt reprezentate de leziuni majore complexe asociate cu: prezena coagulrii intravasculare diseminate, hipotermie sub 350C, necesar transfuzional mare (peste 10 uniti), exces de baze de peste 10, cu o stare general precar a pacientului [11]. n ceea ce privete tratamentul chirurgical cu tent curativ, n Tr.A grave, aceasta poate fi unica modalitate terapeutic ce poate salva viaa pacientului, n cazul eecului metodelor descrise anterior. Leziunile hepatice de grad mare (peste 4), la care riscul hemoragic persist sau reapare, necesit o sancionare prompt.
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Tratamentul agresiv este de multe ori asociat cu mortalitate crescut i necesit o bun cunoatere a tehnicilor de chirurgie hepatic i vascular, mergnd de la simple hepatorafii la rezecii mai mult sau mai puin extinse [12,13]. Traumatismele splenice, cel mai frecvent organ parenchimatos intraabdominal implicat n Tr.A, benefeciaz de asemenea de terapia conservatoare, n msura posibilitii meninerii stabilitii hemodinamice i a monitorizrii continue clinice i imagistice a pacienilor n servicii specializate [20]. Odat aprut o leziune la nivel parenchimatos, n special grade lezionale mici, prezervarea organului pare a fi posibil n 2/3 din cazuri, evitndu-se complicaiile sindromului postsplenectomie [21,22]. CONCLUZII Traumatismele abdominale,dei rare, prezint un potenial letal semnificativ, incidena lor fiind n cretere.Mortalitatea n Tr.A variaz larg de la o ar la alta, n funcie de mecanismele patogenice ce predomin n regiunea respectiv. Tr.A nchise continu s fie n continuare cele mai frecvente, recunoscnd ca principal mecanism lezional accidentul rutier. n Romnia, Tr.A deschise prezint o inciden i o mortalitate redus, fiind frecvent cauzate de leziuni prin heteroagresiune cu arme albe ce implic de multe ori o afectare uniorganic. Tr.A grave, din cadrul politraumatismelor, prezint un potenial letal mult crescut datorit asocierii plurilezionale. Splina i ficatul sunt organele intraabdominale cel mai frecvent implicate n Tr.A, prognosticul i atitudinea terapeutic aleas fiind dependente de gradul lezional, prezena ocului hemoragic i asocierea lezional intra i extraabdominal. Cuantificarea acestor factori de prognostic poate fi efectuat urmrind diferitele constante de laborator i prin calcularea gradelor lezionale organice i al ISS/NISS. Tratamentul non-operator reprezint actual regula n condiiile stabilitii hemodinamice i a absenei unor plgi penetrante profunde sau a semnelor de iritaie peritoneal. Interveniile chirurgicale reprezint n continuare modalitatea de rezolvare a Tr.A grave, variind de la chirurgia de control lezional la intervenii ample cu viz radical.
BIBLIOGRAFIE Caloghera C. Tratat de chirurgie de urgen. ediia a III-a, Timioara, Ed. Antib. 2003; p. 139-202. 2. American College of Surgeons Committee on Trauma. Abdominal Trauma. In: ATLS Student Course Manual. 8th. American College of Surgeons; 2008. 3. Feliciano VD, Mattox L, Moore EE. Trauma, 6th ed. USA, McGraw-Hill. 2008. 4. Udeani J, Steinberg RS. Blunt abdominal trauma, eMedicine, Trauma. Jan 2011; http://emedicine.medscape.com/article/433404-overview. 5. Spahn DR, Cerny V, Coats TJ, Duranteau J, Fernndez-Mondjar E, Gordini G, Stahel PF, Hunt BJ, Komadina R, Neugebauer E, Ozier Y, Riddez L, Schultz A, Vincent JL, Rossaint R; Task Force for Advanced Bleeding Care in Trauma. Management of bleeding following major trauma: a European guideline. Crit Care. 2007; 11(1): R17. 6. Kouraklis G, Spirakos S, Glinavou A. Damage control surgery: an alternative approach for the management for critically injured patients.Surg Today. 2002; 32(3): 195-202. 7. Hishberg A, Wall MJ Jr, Mattox KL. Planned reoperation for trauma: a two year experience with 124 consecutive patients. J Trauma 1994; 37(3): 365-369. 8. Gibson DE, Canfield CM, Levy PD. Selective non-operative management of blunt abdominal trauma. J Emerg Med. 2006; 31(2): 215-221. 9. Stawicki SP. Trends in nonoperative management of traumatic injuries, OPUS 12 Scientist 2007; 1(1): 19-35. 10. Giannopoulos GA, Katsoulis IE, Tzanakis NE, Patsaouras PA, Digalakis MK. Non-operative management of abdominal trauma. Is it safe and feasible in a district general hospital? Scand J Trauma Resusc Emerg Med. 2009; 17: 22. 1.
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11. Timmermans J, Nicol A, Kairinos N, Teijink J, Prins M, Navsaria P. Predicting mortality in damage control surgery for major abdominal trauma. SAJS Trauma 2010; 48(1): 6-9. 12. Salomone III JA, Salomone JP. Abdominal trauma, Blunt. eMedicine, Jan 2011, http://emedicine.medscape.com/article/821995-overview. 13. Zargar M, Laal M. Liver trauma: Operative and non-operative management. Int J of Collaborative Research on Internal Med & Public Health 2010; 2(4): 95-107. 14. Cigdem MK, Onen A, Siga M, Otcu S. Selective nonoperative management of penetrating abdominal injuries in children. J Trauma 2009; 67(6): 1284-1286. 15. Garrison JR, Richardson JD, Hilakos AS, Spain DA, Wilson MA, Miller FB, Fulton RL. Predicting the need to pack early for severe inta-abdominal hemorrage. J Trauma. 1996; 40(6): 923-927. 16. .Loveland JA, Boffard KD. Damage control in the abdomen and beyond. Br J Surg. 2004; 91(9): 1095-1101. 17. Arthurs Z, Cuadrado D, Beekley A, Grathwohl K, Perkins J, Rush R, Sebesta J. The impact of hypothermia on trauma care at the 31st combat support hospital. Am J Surg 2006; 191(5): 610-614. 18. Nicholas JM, Rix EP, Easley KA, Feliciano DV, Cava RA, Ingram WL, Parry NG, Rozycki GS, Salomone JP, Tremblay LN. Changing patterns in the management of penetrating abdominal trauma. J Trauma 2003; 55(6): 1095-1110. 19. American College of Surgeons Committe of Trauma Advanced trauma life support manual, Chicago: ACS. 1997: p. 11-242. 20. Ponifasio Ponifasio, Okti Poki H, Watters DAK. Abdominal trauma in Papua New Guinea. PNG Med J 2001; 44(1-2): 36-42. 21. Miller PR, Croce MA, Bee TK, Malhotra AK, Farlan TC. Associated injuries in blunt solid organ trauma: implication for missed injury in non-operative management, J Trauma 2002; 53(2): 238-242. 22. Bismar HA, Alam MK, Al-Keely MH, Al Samah SM, Mohammed AA. Outcome of nonoperative management of blunt liver trauma. Saudi Med J 2004; 25(3): 294-299.
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HIPERALIMENTAIA MIXT PREOPERATORIE N ESOFAGOPLASTII

Laura Magdalena Nicolescu1, S. Lunc2 1. Secia Anestezie i Terapie Intensiv 2. Clinica de Urgene Chirurgicale Spitalul Clinic de Urgen Sf. Ioan Iai Universitatea de Medicin i Farmacie "Gr. T. Popa" Iai
COMBINED PREOPERATIVE PARENTERAL AND ENTERAL NUTRITION IN ESOPHAGOPLASTY (ABSTRACT): Evidence to support preoperative nutrition support in major gastro-intestinal surgery is limited, but suggests that if malnourished individuals are adequately fed for at least 710 days preoperatively then surgical outcome can be improved. The aim of this study was to assess the effect of preoperative combined enteral and parenteral nutrition on postoperative outcome in patients with esophagoplasty. Sixty-seven patients were admitted in a retrospective study. The patients were divided into two groups: group A of 46 patients who received preoperative combined enteral and parenteral nutrition and group B of 21 patients who received only preoperative enteral nutrition. They received for ten days before the surgery parenteral supplements of amino acids and glucides. The evaluated outcomes were all in favor of group A: postoperative morbidity 34.8% vs. 57.1% (p=0.01), the length of stay in intensive care unit 89.1% vs. 66.6% (p=0.01), the length of postoperative mechanical ventilation - 69,5% vs. 52,3% (p<0.05), the time needed for complete ambulation 63% vs.42.8% (p=0.02), the days needed until the reappearance of bowel movements 61.1% vs. 52.3% (p<0.05). In conclusion, preoperative combined enteral and parenteral nutrition has benefits on postoperative outcome and has to be part of a preoperative strategy in patients submitted to major gastrointestinal surgery. KEY-WORDS: PREOPERATIVE ESOPHAGOPLASTY. NUTRITION, POSTOPERATIVE OUTCOMES,
Coresponden: Dr. Laura Magdalena Nicolescu,medic primar ATI, Secia Anestezie i Terapie Intensiv Spitalul Clinic de Urgen Sfntul Ioan Iai, Str. Gen. Berthelot nr. 2, Iai*.
INTRODUCERE Esofagoplastia reprezint una din interveniile majore din chirurgia digestiv, care rmne grevat de o morbiditate i mortalitate semnificative, cu toate progresele realizate n ultimii ani [1]. Unul din factorii potenial implicai n evoluia pacienilor cu esofagoplastie, cu impact asupra rezultatelor postoperatorii este reprezentat de starea de nutriie preoperatorie a pacienilor, aa cum au artat din 1987 Robinson i colab [1]. Este bine cunoscut c prezena unei bune stri de nutriie a pacientului n preoperator amelioreaz imunitatea, coagularea, sinteza proteinelor, anemia, iar dac nutriia este asigurat i enteral, se constat o ameliorare a funciei enterocitelor, care este esenial n prevenirea complicaiilor postoperatorii [1-3]. Scopul acestui studiu retrospectiv este de a determina impactul nutriiei preoperatorii mixte n cazul pacienilor cu esofagoplatie, asupra complicaiilor postoperatorii, duratei de ventilaie mecanic, al intervalului de timp pn la mobilizarea complet, intervalului pn la reluarea tranzitului digestiv i asupra duratei totale de internare n terapia intensiv.
*
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MATERIAL I METOD n studiul de fa am nrolat 67 de pacieni cu esofagoplastie, la care am urmrit impactul nutriiei preoperatorii mixte asupra evoluiei postoperatorii, fa de pacienii crora li s-a administrat doar nutriie enteral. Impactul postoperator a fost considerat prin: durata pn la detubare, durata pn la reluarea tranzitului digestiv pentru gaze, dezvoltarea complicaiilor majore postoperatorii (insuficien de organ, fistul, sepsis), timpul pn la mobilizarea complet independent a pacienilor, durata de internare n terapie intensiv (TI). Au fost acceptai n studiu pacieni care au corespuns criteriilor de urmrire (monitorizarea alimentaiei, a strii clinice i prezena investigaiilor clinice i paraclinice). Au fost nregistrate datele demografice, mecanismul de producere al stenozei esofagiene, patologia asociat, starea de nutriie, durata i tipul interveniei, durata de spitalizare, calitatea vieii n secia de anestezie i terapie intensiv (ATI). Pacienii au primit hiperalimentaie pe durata celor 10 zile preoperatorii, prin alimentaie mixt enteral i parenteral, asigurndu-se un aport caloric de 35 kcal/ kgc/zi. Alimentaia parenteral a venit n completarea celei enterale, asigurndu-se prin aportul enteral n principal necesarul lipidic i proteic i mai puin glucidic, iar parenteral, supliment glucidic i proteic: aminoacizi 10% n medie un flacon pe zi (50 g proteine supliment = 200 cal), i glucoz 20% tamponat cu o unitate de insulin actrapid la 2,5 g glucoz, un flacon pe zi (100 g glucoz = 400 cal). S-a realizat un supliment de circa 10 cal/kgcorp. Pe cale enteral s-a urmrit administrarea a 25 cal/kgcorp pe zi, prin preparate magistrale i suplimente farmaceutice gata preparate, conform tabelelor de compoziie. Nu am administrat parenteral lipide, datorit posibilei imunodepresii pe care acestea le pot induce. Pacienii au fost mprii n dou loturi omogene din punct de vedere statistic: lotul A de 46 de bolnavi, la care s-a practicat nutriia mixt preoperator (enteral i parenteral), i lotul B (martor) de 21 de bolnavi, al pacienilor crora li s-a administrat doar nutriie enteral. Precizm c nutriia enteral s-a realizat prin alimentaie per os, pe tub de gastrostom sau jejunostom i a coninut alimentaie mixat personal, suplimente pregtite n spital, dar i formule elementare, n cazul jejunostomiei. Cele dou loturi s-au realizat comparabile din punct de vedere statistic ca vrst a pacienilor, tipul stenozei esofagiene (benign - postcaustic, i malign) pentru care s-a practicat esofagoplastia, tipul i durata interveniei practicate, similitudinea abordrii anestezice (anestezie general balansat pe pivot volatil) i antecedentele fizipatologice ale bolnavilor: afeciuni coronariene, arteriopatii periferice, hepatite cronice, tabagism, etilism cronic, denutriie moderat sau uoar, diagnosticat clinic i paraclinic. n postoperator, pacienii au primit alimentaie parenteral din ziua 1 postoperator [aminoacizi 10% 500 ml (50 g pe zi), glucoz 20% 1000 ml( 200 g glucoz pe zi) tamponat cu 1U insulin actrapid la 2,5 g glucoz - n total se asigur 1000 cal/zi parenteral, adic 40% din necesarul zilnic], oligoelemente, imunonutrieni, terapie analgetic intravenoas i intramuscular, antiinfecioas, profilaxia tromboembolismului, antiinflamatoare, ngrijiri de tip nursing similare (aerosoli, exerciii respiratorii, igien bucal, perineal, general, tapotaj, mobilizare pasiv i activ, profilaxia escarelor). Investigarea paraclinic a urmrit n preoperator, n ziua 10 preoperator i n ziua dinaintea operaiei, parametrii antropometrici: scderea n greutate, care observ mai bine n dinamic bolnavul dect indicele de mas corporeal la un moment dat, date
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specifice de laborator ca albuminemia i limfocitele, i zilnic eliminrile de azot, ionograma i glicemia. Analiza datelor statistice s-a fcut folosind Student t-Test i Fischer Exact Test i a fost considerat semnificativ statistic o valoare p<0,05. REZULTATE Un numr de 67 de pacieni au beneficiat de esofagoplastie n clinica de chirurgie a Spitalul Clinic de Urgen Sfntul Ioan Iai n perioada ianuarie 2000decembrie 2009. Repartiia pe sexe a fost urmtoarea: 27 femei (58,6%) i 19 brbai (41,4%) n lotul A i 11 femei (52,3%) i 10 brbai (47,7%) n lotul B. Ca vrst, n lotul A au fost 11 pacieni (23,8%) sub 30 de ani, 22 pacieni (48,4%) ntre 30 i 60 de ani i 13 pacieni (21,8%) peste 60 de ani. Corelat cu etiologia, benign sau malign, pe grupe de vrst, distribuia a fost urmtoarea (Tabel 1):
Tabel 1 Repartiia etiologiei stenozei esofagiene pe grupe de vrst n lotul A Etiologie Sub 30 de ani 30 60 ani Peste 60 de ani 9,1% (1 pacient) 40,9% (9 pacieni) 84,6% (11 pacieni) malign 90,9% (10 pacieni) 59,1% (13 pacieni) 15,4% (2 pacieni) benign
n lotul B, repartiia pe grupe de vrst a fost: 4 pacieni (19%) sub 30 de ani, 12 pacieni (57,1%) ntre 30 i 60 de ani, i restul de 5 pacieni, adic 31,3%, peste 60 de ani. Pe grupe de vrst, etiologia a fost urmtoarea n lotul B (Tabel 2):
Tabel 2 Repartiia etiologiei stenozei esofagiene pe grupe de vrst n lotul B Etiologie Sub 30 de ani 30- 60 de ani Peste 60 de ani 0% 42,8% (5 pacieni) 80% (4 pacieni) malign 100% (4 pacieni) 57,2% (7 pacieni) 20% (1 pacient) benign
Conform datelor obinute, cele dou loturi au fost comparabile ca etiologie, vrst i sex, din punct de vedere statistic. Bolnavii au prezentat urmtoarele afeciuni: peste 60 % (61% n primul lot, 63% n al doilea lot) dintre pacieni au fost consumatori cronici de tutun i/sau alcool. innd cont de teren, am studiat cauzele denutriiei la pacieni. Din anamnez a reieit c 21% din cazuri aveau hepatopatie cronic, 15% aveau cardiopatie ischemic cronic, 18% prezentau arteriopatie obliterant. Pe fondul acestor condiii fiziopatologice, aprecierea statusului nutriional s-a fcut dup: pierderea din greutate (Tabel 3), hipoalbuminemie (Tabel 4), scderea numrului de limfocite < 1200/mm3 (Tabel 5).
Tabel 3 Distribuia denutriiei dup pierderea n greutate n cele dou loturi Fr denutriie Denutriie uoar Denutriie medie 6,5% (3 pacieni) 71,7% (33 pacieni) 21,8% (10 pacieni) 9,5% (2 pacieni) 76,2% (16 pacieni) 14,3% (3 pacieni) Tabel 4 Distribuia hipoalbuminemiei n cele dou loturi Fr hipoalbuminemie Hipoalbuminemie uoar Hipoalbuminemie moderat (3-3,5g%) (2,5-3g%) 17,4% (8 pacieni) 67,4% (31 pacieni) 15,4% (7 pacieni) 14,3% (3 pacieni) 71,4% (15 pacieni) 14,3% (3 pacieni)
Lot A Lot B
Lot A Lot B
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Se remarc similaritatea distribuiei celor trei criterii de denutriie, pe fiecare lot n parte. Nu au fost inclui n studiu pacienii cu denutriie sever (cu scdere mare n greutate, cu hipoalbuminemie sever i cu scdere mare a limfocitelor), la care s-a procedat la temporizarea esofagoplastiei, prin gastrostom sau jejunostom de alimentaie, asociat cu nutriie parenteral. Loturile au fost omogene din punct de vedere al distribuiei asocierilor fiziopatologice.
Tabel 5 Distribuia numrului de limfocite n cele dou loturi Fr scdere Scdere uoar (peste 1200/mmc) (1000-1200/mmc) 10,8% (5 pacieni) 69,5% (32 pacieni) 14,3% (3 pacieni) 71,4% (15 pacieni)
Lot A Lot B
Scdere medie (800-1000/mmc) 19,7% (9 pacieni) 14,3% (3 pacieni)
Dup 10 zile de pregtire preoperatorie, n ziua operaiei, pacienilor li s-au msurat: greutatea corporeal, albuminele i limfocitele. S-au obinut urmtoarele rezultate: - greutatea corporeal s-a meninut la 63 bolnavi, nsemnnd 94%, a sczut cu mai puin de 2% la 3 bolnavi, adic 4,7% i a crescut cu mai puin de 2% la restul pacienilor. - albuminele au crescut cu minim 15% la 92,5% din pacieni, au sczut cu mai puin de 5% la un bolnav (1,5%) i au rmas nemodificate la restul. - limfocitele au crescut cu minim 10% la 82,5% din pacieni i au rmas neschimbate la restul pacienilor; niciun caz nu a prezentat scderi de limfocite. S-a obinut o ameliorare a albuminelor i limfocitelor, dar nu a parametrilor antropometrici, n mod similar la cele dou loturi. n paralel cu aceste rezultate, au fost realizate coreciile necesare n cazurile de anemie prin transfuzii de snge i suplimentare cu preparate din fier, au fost corectate diselectrolitemiile i hiperglicemiile depistate prin monitorizarea zilnic. n terapie intensiv, evoluia pacienilor a fost urmtoarea (Tabel 6): 1. Dup timpul pn la detubarea postoperatorie a pacientului Lotul A: - 32 au fost detubai pn la 6 h postoperator (69,5%) - 14 au fost detubai dup 6h postoperator (30,5%) Lotul B: - 11 pn la 6 h postoperator (52,3%) - 10 dup 6 h postoperator (47,7%) 2. Dup timpul pn la mobilizarea complet (plimbare fr sprijin) Lotul A - 29 s-au mobilizat pn n ziua a 5-a postoperator (63%) - 17 s-au mobilizat dup ziua a cincea postoperator (37%) Lotul B - 9 s-au mobilizat pn la cinci zile postoperator (42,8%) - 12 s-au mobilizat dup cinci zile postoperator (57,2%) 3. Dup momentul relurii tranzitului digestiv pentru gaze Lotul A - 41 de pacieni i-au reluat tranzitul pn n ziua a patra postoperator (89,1%) - 5 pacieni i-au reluat tranzitul dup aceast zi (10,9%)
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Lotul B - 11 i-au reluat tranzitul pn n ziua a patra postoperator (52,3%) - 10 nu i-au reluat tranzitul n acest interval (47,7%) 4. Dup dezvoltarea complicaiilor postoperatorii Lotul A - 16 dintre ei au dezvoltat complicaii - pneumonie, fistul, sepsis, etc. (34,8%) - 30 au evoluat fr complicaii, n ziua 8- 14 fiind externai din TI (65,2%) Lotul B - 12 au dezvoltat complicaii (57,1%) - 9 au evoluat fr complicaii (42,9%). 5. Dup zilele de internare n secia de terapie intensiv Lotul A - 41 au stat sub 10 zile de internare n TI (89,1%) - 5 au stat peste 10 zile (10,9%) Lotul B - 14 au stat sub zece zile n TI (66,6%) - 7 au stat peste zece zile (33,4%) Diferena de procentaj este de 22,5% mai puini pacieni care i-au prelungit internarea peste 10 zile n TI din lotul A.
Tabel 6 Evoluia postoperatorie a celor dou loturi, n funcie de criteriile selectate Detubare Mobilizare Reluarea tranzitului Dezvoltarea de sub ase ore complet pn digestiv pentru gaze complicaii n ziua a patra pn n ziua a 4-a majore 69,5% 63,04% 61,1% 34,8% 52,3% p<0,05 42,8% p=0,02 52,3% p<0,05 57,1% p=0,01
Lot A Lot B
Internare n TI sub zece zile 89,1% 66,6% p=0,01
Observm c n lotul A, pacienii au o evoluie mai bun i mai rapid, cu o rat a complicaiilor mai mic dect pacienii din lotul B, determinat de suplimentarea alimentaiei enterale cu alimentaie parenteral, pe durata a zece zile de pregtire preoperatorie a bolnavilor cu esofagoplastie. Diferenele dintre cele dou loturi sunt semnificative din punct de vedere statistic, conform Fischer Exact test i Student t-test (p<0,05), conform tabelului 6.
DISCUII
Din punctul de vedere al criteriilor considerate n postoperator, detubarea la 6 ore mpreun cu durata medie a interveniei de 6 ore, constituie intervalul de 12 ore, dup care riscul de contaminare a cii aeriene crete semnificativ. Reluarea mobilizrii obinuite i a tranzitului pentru gaze se ncadreaz n evoluia normal postchirurgie digestiv i coincid cu trecerea de la faza de ebb la faza de flow n metabolismul postoperator. Evident c alimentaia postoperatorie nu are, pn n ziua a patra, cnd pacientul n mod normal trebuie s-i reia activitatea digestiv, timpul necesar unui efect favorabil. Ceea ce se obine este consecina unei bune pregtiri preoperatorii i a corectrii rapide i complete a dezechilibrelor intra i postoperatorii imediate.
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n mod specific, interveniile chirurgicale majore gastrointestinale i n particular cele pe esofag au ca urmare o imposibilitate a organismului de a se alimenta natural, att datorit afectrii funciei digestive prin anastomoze, derivaii, ct i preoperator, prin boala de fond, cu afectare intrinsec a funciei peristaltice i de absorbie (stenoze, neoplasme), dar i prin ileusul postoperator prelungit prin durata mare a interveniei i anesteziei generale, i utilizarea ca analgetice a derivatelor morfinice i mobilizarea redus a pacientului, toi aceti factori afectnd tolerana digestiv a pacientului cu esofagoplastie. Astfel, indicaia comun este montarea intraoperatorie a unei sonde nasojejunale de alimentaie, sau a unei jejunostome. Acestea vor permite iniierea precoce a decompresiei digestive, apoi testarea toleranei urmat de alimentarea enteral pe aceste ci. Pentru acoperirea necesarului hidro-electrolitic i metabolic, n perioada n care acest lucru nu este posibil pe cale enteral n mod complet, se va administra necesarul pe cale perfuzabil, deoarece alimentaia enteral este greu de cuantificat i de multe ori, autoadminstrarea alimentaiei enterale este grevat de administrare prea rapid, nediversificat, i de multe ori insuficient. n ultimii ani s-a dovedit impactul favorabil al nutriiei totale enterale asupra evoluiei postoperatorii, fa de nutriia total parenteral, aceasta din urm fiind grevat de o mulime de complicaii, de la complicaii metabolice, la complicaii infecioase i care afecteaz, uneori, chiar i prognosticul pacientului chirurgical [4,5]. n cazul studiului prezent, am asociat nutriia enteral, de multe ori insuficient din cauza condiiilor obiective ale bolnavilor, cu nutriie parenteral, bogat n oligoelemente i elemente de imunonutriie. Pacienii care urmau s fie supui unei esofagoplastii, avnd deja montate tuburi de gastrostomie sau sonde de alimentaie jejunal, nu reueau s-i compenseze doar pe cale enteral n perioada spitalizrii necesarul suplimentar caloric, determinat de multiplele investigaii preoperatorii, de prezena n salon cu mai muli bolnavi, de stresul psihic determinat de internare i intervenia iminent, de pregtirea tubului digestiv pentru intervenie. Opiniile despre durata postului complet la care poate fi supus un pacient anterior sntos fr afectri ale funciilor sistemice variaz de la 10-12 zile la 72 de ore. Un pacient bine nutrit ar avea rezerv energetic i proteic chiar i n condiiile reducerii aportului pentru 710 zile, astfel nct postul n aceast perioad, singur, n absena altor afectri fiziopatologice, este bine tolerat [4]. n timp ce unii susin c dezvoltarea malnutriiei protein-calorice nu are loc nainte de 10-12 zile de lips a alimentaiei, alii susin c stresul i hipermetabolismul din bolile critice i chirurgia major scurteaz aceast perioad la 57 zile [5]. Intervenia nutriional n perioada preoperatorie nu amelioreaz parametrii antropometrici tradiionali. Pacienii nu iau n greutate, nici nu i cresc masa muscular. Ceea ce se evideniaz dup perioada de pregtire a pacienilor pentru esofagoplastie, este o cretere uoar (cu peste 10%) a albuminei i o cretere cu minim 10% n medie a limfocitelor, dar i a hemoglobinei i tendina spre normalizare a timpilor de coagulare. Cazuri similare sunt raportate n literatur cu privire la nutriia preoperatorie a pacienilor cu malnutriie sever i fractur de col femural, fa de lotul control [6]. Studiile despre creterea n postoperator a albuminelor prin suplimentarea dietei comparativ cu subiecii de control au artat c aceast cretere este pus mai mult pe seama diminuri complicaiilor generale, dect pe baza adecvrii aportului caloric [7]. ntr-un alt studiu, msurtorile antropometrice i dinamometria minii nu s-au schimbat semnificativ ntr-un grup care a primit nutriie parenteral total fa de subiecii de control [8].
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Lipsa acestora de rspuns sugereaz c aceti parametri nu reflect ntotdeauna statusul nutriional, i pot fi neafectai, pe termen scurt, de schimbrile statusului nutriional. La ntrebarea dac intervenia nutriional afecteaz prognosticul chirurgical, au rspuns numeroase studii, care au dovedit superioritatea rezultatelor interveniei chirurgicale la pacienii cu suport nutriional, fa de pacienii care nu au beneficiat de acest suport [5-8]. Studiile care arat beneficiul net al alimentaiei totale parenterale, fa de lipsa total a suportului nutriional sunt mai puine, ns cele mai multe se refer la alimentaia necesar n chirurgia major digestiv. Exist dou studii care au artat beneficiul clar al nutriiei totale parenterale preoperatorii intraspitaliceti asupra evoluiei chirurgiei majore digestive [8,9]. n cel mai amplu studiu, realizat n dou pri de Muller i colab., pacienii care urmau s suporte o intervenie chirurgical gastrointestinal sau pentru cancer pancreatic, care au primit nutriie total parenteral (NTP) n soluie de glucoz, au prezentat o scdere la jumtate a ratei complicaiilor majore postoperatorii i o scdere de patru ori a ratei mortalitii comparativ cu lotul de control, care a fost tratat cu soluii de repletizare volemic electrolitice i medicaie obinuit postoperatorie [10]. Interesant, a treia parte a studiului a inclus pacieni care au primit o cantitate echivalent de calorii prin NTP, dar o jumtate din aceste calorii au fost asigurate prin aport de lipide [11]. Acest grup a avut complicaii postoperatorii i mortalitate similar cu cele din lotul de control, sugernd c orice beneficiu al NTP preoperatorii a fost anihilat de efectul imunosupresiv al emulsiilor lipidice [9,10]. De aceea, n studiul de fa am evitat administrarea preoperatorie a lipidelor intravenos, innd cont c alimentaia parenteral vine n completarea celei enterale. Experiena NTP perioperatorie a pacienilor cu intervenii digestive majore este foarte variat. Din ce n ce mai multe studii apar despre preponderena efectelor nedorite ale NTP n aceste cazuri. De aceea, studiul nostru a recurs la alimentaie mixt, n principal pe cale enteral suplimentat parenteral. Toate studiile se refer ns la o durat de 7-10 zile preoperator, necesare instituirii efectelor nutriiei preoperatorii, mai ales n cazul pacienilor denutrii. Dei de mic amploare studiul lui Foschi, Cavana i Callioni despre nutriia preoperatorie mixt n cazul interveniilor pe cile biliare a artat reducerea semnificativ a complicaiilor postoperatorii, a morbiditii i mortalitii [12]. Hiperalimentarea s-a fcut pstrnd alimentarea enteral n proporie de 86% (restul, de 14% din calorii administrndu-se parenteral), pe durata a 20 de zile preoperator i a artat scderea morbiditii de la 46.8% la 17.8% (p < 0.05) i o scdere a mortalitii de la 12.5% la 3.5% (p < 0.05), comparativ cu lotul de control, care nu a primit aport nutriional. n studiul lui Shukla, Rao i Banu, pacienii denutrii care au primit hiperalimentaie enteral pe o durat de 10 zile preoperator au avut ameliorri ale greutii corporeale, proteinelor serice, i ai altor parametri antropometrici fa de lotul martor [13]. Infeciile postoperatorii au fost de trei ori mai puin frecvente fa de lotul martor. CONCLUZII Hiperalimentaia preoperatorie prin suplimentarea parenteral a alimentaiei enterale se dovedete a avea efecte pozitive asupra evoluiei postoperatorii, reducnd durata internrii n secia de terapie intensiv i frecvena complicaiilor postesofagoplastie. Hiperalimentarea mixt preoperatorie, frecvent subutilizat, se nscrie ntr-un plan de pregtire al interveniei i necesit un minim suport pentru rezultate optimizate la pacienii multiplu tarai cum sunt cei care necesit esofagoplastie.
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1. 2. 3.
4. 6. 7. 8. 9. 10. 11. 12. 13.
BIBLIOGRAFIE Robinson G, Goldstein M, Levine G. Impact of nutritional status on DRG length of stay. JPEN 1987; 11(1): 49-51. Bozzetti F, Braga M, Gianotti L, Gavazzi C, Mariani L. Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: a randomised multicentre trial. Lancet 2001; 358(9292): 1487-1492. Moore FA, Feliciano DV, Andrassy RJ, McArdle AH, Booth FV, Morgenstein-Wagner TB, Kellum JM, Welling RE, Moore EE. Early enteral feeding, compared with parenteral, reduced postoperative septic complications. The results of a meta-analysis. Ann Surg 1992; 216(2): 172-183. Stack JA, Babineau TJ, Bistrian BR. Assessment of nutritional status in clinical practice. Gastroenterologist 1996; 12(4): S8-S15. Koretz RL. Nutritional supplementation in the ICU: how critical is nutrition for the critically ill? Am J Respir Crit Care Med 1995; 151(2 Pt 1): 570-573. Bastow MD, Rawlings J, Allison SP. Benefits of supplementary tube feeding after fractured neck of femur: a randomized controlled trial. BMJ 1983; 287: 1589-1592. Delmi M, Rapin CH, Bengoa JM, Delmas PD, Vasey H, Bonjour JP. Dietary supplementation in elderly patients with fractured neck of the femur. Lancet 1990; 335:1013-1016. Fan ST, Lo CM, Lai EC, Chu KM, Liu CL, Wong J. Perioperative nutritional support in patients undergoing hepatectomy for hepatocellular carcinoma. N Engl J Med 1994; 331(23): 1547-1552. Muller JM, Brenner U, Dienst C, Pichlmaier H. Preoperative parenteral feeding in patients with gastrointestinal carcinoma. Lancet 1982; 1(8263): 68-71. Muller JM, Keller HW, Brenner U, Walter M, Holzmller W. Indications and effects of preoperative parenteral nutrition. World J Surg 1986; 10(1): 53-63. Foschi D, Cavagna G, Callioni F, Morandi E, Rovati V. Hyperalimentation of jaundiced patients on percutaneous transhepatic biliary drainage. Br J Surg 1986; 73(9): 716-719. Shukla HS, Rao RR, Banu N, Gupta RM, Yadav RC. Enteral hyperalimentation in malnourished surgical patients. Indian J Med Res 1984; 80: 339-346.
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PROFILUL CTOKINELOR N PLASMA PACIENILOR CU MELANOM MALIGN

Natalia Cireap1, R. Ilina1, Diana Narita2, A. Anghel2, Elena Lazar3, T. Nicola1 1. Departmentul de Chirurgie Oncologic 2. Catedra de Biochimie 3. Catedra de Morfopatologie Universitatea de Medicin i Farmacie Victor Babe, Timioara, Romnia
PROFILUL CITOKINELOR N PLASMA PACIENILOR CU MELANOM MALIGN (ABSTRACT): Malignant melanoma is considered to be a prototype of an immunogenic tumor that express a variety of cytokines and growth factors that may stimulate tumor angiogenesis, growth and invasion. The purpose of this study was to analyze and compare the expression levels of a selected panel of twelve inflammatory cytokines/chemokines in the plasma of melanoma patients before any treatment with the expression levels of matched age and sex healthy controls. This study was performed in order to select the most appropriate profile of cytokines that could serve as markers for early diagnosis, prognostic and treatment. The study was performed on patients diagnosed with malignant melanoma that underwent surgery in 2010 compared with healthy controls, using a multi-analyte ELISArray kit. Our results showed a statistically significant increase in plasma levels of six inflammatory cytokines (IL-1, IL-10, IL-17, IFN-, TNF- and GMCSF) (P between <10-4 and 0.01). For IL-1, IL-2, IL-4, IL-6, IL-8 and IL-12, the plasma levels were also increased but the differences compared with healthy controls were not statistically significant. In conclusion, a complex network of cytokines seems to be triggered in the presence of invasive primary melanoma or metastatic melanoma and this cytokine response is involved in the regulation of melanoma cell growth and progression. Differences in cytokine profiles between melanoma patients and healthy subjects allowed for robust discrimination between these two groups, emphasize the advantage of multimarker analysis for discovery of new predictive serum biomarkers for melanoma and provide additional insights into the pathobiology of melanoma. KEYWORDS: MALIGNANT BIOMARKERS MELANOMA, CYTOKINES, MULTIPLEXED ANALYSES,
Coresponden: Natalia Cireap, Dr., Chirurgie Oncologic, Universitatea de Medicin i Farmacie Victor Babes, Timioara, Romania, e-mail: nata_cireap@yahoo.com*
INTRODUCERE Melanoamele reprezint un grup heterogen de tumori care apar pe piele, ochi, meninge i alte pri ale corpului. n timp ce stadiile incipiente ale melanoamelor sunt recunoscute prin schimbri n dimensiune, form sau culoare a nevilor, majoritatea celulelor melanice cresc n adncime i invadeaz tesuturile vecine nainte de a fi detectate ca fiind tumori metastazate n nodulii limfatici sau alte organe. Pacienii cu melanom nu rspund bine la terapiile actuale i majoritatea tratamentelor sunt ineficiente[1-6].
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Melanomul este al doilea cancer ca inciden pentru intervalul de vrst 15 - 29 de ani. Incidena melanomului crete mai repede dect oricare alt cancer, cu o rat de 4% pe an. n 2010, aproximativ 38.870 de brbai i 29.260 de femei au fost diagnosticai cu melanom invaziv. n plus, se presupune c un numr de aproximativ 8.700 de oameni (5.670 brbai i 3.030 de femei) vor deceda de melanom n 2010. Diagnosticul timpuriu i excizia chirurgical pot preveni cu succes evoluia melanomului. Totui, ratele de rspuns la tratamentul chimioterapic sau imunologic n cazul pacienilor cu metastaze avansate rmne sczut [7]. Este necesar o analiz mai avansat a comportamentului celulelor melanice pentru obinerea unui tratament mai eficient. Melanoamele sunt capabile de a produce un spectru larg de citokine i factori de cretere cu multiple funcii biologice. A fost demonstrat c celulele melanice de cultur precum i celulele melanice derivate din melanom primar i metastaze au produs: factorul bazic de cretere al fibroblastelor (bFGF), interleukinele IL-1, IL-1, IL-6, 8 factorul de cretere al celulelor endoteliale (VEGF) precum i factorul de cretere derivat din plachete (PDGF). Aceti factori de cretere acioneaz ca i factori autocrini i/sau paracrini i sunt capabili s stimuleze creterea tumoral, invazia i angiogeneza sau se manifest ca molecule de adeziune sau proteine anti-apoptotice. n acest context, studiul acestor factori ar putea mbunti nelegerea biologiei melanomului i ar putea facilita abordarea terapeutic [8-11]. Creterea concentraiilor unui numr variat de citokine, factori angiogenici i factorii de cretere ar putea servi ca biomarkeri pentru diagnosticul timpuriu al melanomului, pentru prognostic i de asemenea, ar putea permite monitorizarea bolii i a rspunsului la terapie. Unele studii au evaluat deja o serie de proteine plasmatice n ceea ce privete relevana asupra prognosticului i diagnosticului melanomului. Mai precis, nivele ridicate de IL-6 au fost asociate cu prognosticul rezervat n cazul pacienilor cu melanom n stadiul IV, iar valorile ridicate de IL-10 au fost asociate cu stadiile avansate ale melanomului (stadiul III si IV) [12-17]. Scopul acestui studiu a fost de a analiza expresia unui panel de 12 citokine sau chemokine inflamatorii (IL-1, IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-, TNF-, GM-CSF) n plasma pacienilor cu melanom, nainte de orice tratament, comparativ cu expresia acelorai citokine n plasma pacienilor de control, sntoi, folosind un kit ELISA multianalit, multiplexat. Acest studiu a fost conceput pentru a selecta un set de citokine care ar putea servi ca markeri pentru diagnosticul timpuriu, prognosticul i monitorizarea evoluiei i tratamentului n cazul melanomului malign. METOD Pacieni i caracteristici tumorale Au fost inclui n studiu 17 pacieni care au suferit intervenii chirurgicale n Clinica II de Chirurgie General i Oncologic, Timioara n cursul anului 2010 precum i 20 voluntari sntoi, potrivii ca i vrst i sex. Consimmntul a fost obinut de la toi i voluntarii sntoi, iar studiul a fost aprobat de ctre Comitetul de Etic al Universitii noastre. Tabelul 1 rezum caracteristicile pacienilor care au fost inclui n studiu. Prepararea eantioanelor Plasma a fost recoltat de la pacieni nainte de a primi orice tratament precum i de la 20 de voluntari sntoi, utiliznd EDTA ca i anticoagulant. n termen de 30 de minute de la colectare, sngele venos periferic recoltat dup metodele obinuite, standardizate, s-a centrifugat timp de 5 minute la 3000 g.
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Plasma obinut a fost imediat separat i pstrat n congelator la -80C pn la efectuarea analizelor. A fost evitat nghearea / dezghearea repetat.
Tabel 1 Pacieni i caracteristici tumorale Vrst 51 24 43 57 46 59 53 51 54 30 54 52 36 69 54 60 59 Gen F F F F M F F F F M F M M F M F M Localizare Trunchi Membru Sup Coaps Picior Abdomen Cap Coaps Membru Sup Haluce Cap Picior Cap Trunchi Cap Trunchi Trunchi Trunchi Histologie Nodular Cu cretere n suprafa Nodular Cu cretere n suprafa Cu cretere n suprafa Nodular Nodular Cu cretere n suprafa Lentiginos acral Nodular Nodular Nodular Lentigo malign Nodular Nodular Cu cretere n suprafa Nodular TNM T3bN0M0 T1aN0M0 T4bN2aM0 T1aN0M0 T2aN0M0 T2bN0M0 T2aN0M0 T1aN0M0 T3aN0M0 T4bN0M0 T3aN2M0 T3bN0M0 T3bN0M0 T3bN0M0 T4aN2bM0 T4bN0M0 T4bN3M0 Stadiu IIB IA IIIB IA IB IIA IB IA IIA IIC IIIA IIB IIB IIB IIIB IIC IIIC Clark III III V III III V III III IV V III IV IV IV V V V Breslow (mm) 4 0.9 >3.5 1 1.5 1.5 1.5 1 2.3 >3 3.5 >3 2.5 <3 >4 >4 6 Ulceraie Prezent Absent Prezent Absent Prezent Prezent Absent Absent Prezent Prezent Absent Prezent Prezent Prezent Prezent Prezent Prezent
Analiza citokinelor plasmastice Au fost analizate 12 citokine diferite utiliznd kit-ul Multi-Analyte ELISArray (SABiosciences, Qiagen, Germany). Kit-urile MultiAnalyte ELISArray sunt concepute pentru a analiza citokine i/sau chemokine multiple, simultan, folosind tehnica ELISA (sandwich-based enzyme-linked immunosorbent assay). La microplaca ELISA cu 96 godeuri a fost ataat un panel de dousprezece anticorpi int specifici, cte unul ntr-un ir de 8 godeuri, permind astfel analiza calitativ a ase probe simultan, alturi de probele control pozitive i negative. Pe scurt, etapele de lucru au fost urmtoarele: s-au pregtit toi reactivii conform protocolului recomandat de firma productoare (SABiosciences-Qiagen); s-au efectuat diluiile probelor biologice i a controalelor pozitive i negative; s-au adaugat 50 l soluie tampon n fiecare godeu al plcii ELISArray; s-au transferat 50 l de probe, respectiv probe control n godeurile corespunztoare; s-au incubat 2 ore; splare de trei ori; s-au adaugat 100 l soluie de detecie; incubare o or; splare de trei ori; s-au adaugat 100 l complex avidin peroxidaz, dup care s-au incubat 30 de minute; splare de patru ori; s-au adaugat 100 l soluie de dezvoltare a reaciei; incubare 15 minute la ntuneric apoi s-au adaugat 100 l soluie stop. 56
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S-a citit absorbana la 450 nm n maximum 30 minute, la cititorul de microplci ELISA STAT FAX 2100 (Awareness Technology Inc, USA). Analiza statistic Analiza datelor a fost efectuat cu ajutorul testului Wilcoxon (Mann-Whitney). Pragul pentru care datele sunt semnificative a fost stabilit la p < 0.05. REZULTATE I DISCUII Analiza markerilor plasmatici Pentru a analiza diferenele concentraiilor plasmatice ale citokinelor la pacienii cu melanom n comparaie cu martorii sntoi, au fost prelevate probe de plasm de la 17 pacieni nainte de orice tratament i de la 20 voluntari sntoi, potrivii ca i vrst i sex cu pacienii. Au fost dozate 12 citokine (IL-1, IL- 1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IFN-, TNF-, GM-CSF) prin metoda ELISA. Nivelurile plasmatice a ase citokine inflamatorii (IL-1, IL-2, IL4, IL-6, IL-8 i IL-12) au fost crescute la pacienii cu melanom, dar fr s prezinte diferene semnificative statistic comparativ cu martorii sntoi. O cretere statistic semnificativ (P ntre <10-4 i 0.01) a fost observat n plasma pacienilor cu melanom comparativ cu martorii sntoi pentru urmtoarele citokine: IL-1 , IL-10, IL-17, IFN-, TNF- i GM-CSF. Aceste rezultate (Tabel 2, Fig. 1) indic faptul c pacienii cu melanom au prezentat un model semnificativ diferit al expresiei citokinelor comparativ cu subiecii sntoi.
400 *
C n e tra c k e r inp s a(n /m o c n tia ito in lo la m g l)
350 300 250 200 * 150 100 * 50 0 * *
Control Melanom
Fig. 1. Modelul de expresie al citokinelor n melanom comparativ cu grupul control - *diferene semnificativ statistice (P ntre 0.01 i <10-4) Tabel 2 Expresia citokinelor la pacienii cu melanom comparativ cu grupul control Citokine Control Melanom P IL-1 0.79 1.98 0.51 IL-1 3.29 12.25 0.01 IL-2 16.15 17.55 0.26 IL-4 1.71 6.29 0.10 IL-6 1.71 4.71 0.31 IL-8 1.21 4.82 0.19 IL-10 2.45 14.31 0.0001 IL-12 0.76 5.34 0.08 IL-17 10.34 95.61 <0.001 IFN- 6.90 118.96 <0.001 TNF- 27.37 327.09 <0.001 GM-CSF 12.52 21.34 0.0002
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IL -1 2
IL -1 0
IL -2
IL -4
IL -8
IL -6
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Melanomul este considerat a fi un prototip de tumor imunogenic. Celulele melanice exprim o mare varietate de citokine i factori de cretere care pot stimula angiogeneza, creterea i invazia tumoral [18-19]. Unele citokine sau factori de cretere pot funciona ca factori autocrini n scopul stimulrii creterii tumorale, n timp ce factorii paracrini stimuleaz invazivitatea tumorii. Mai mult dect att, unele dintre ele pot trece de la o funcie autocrin la o funcie paracrin. Citokinele i factorii de cretere au un impact asupra mai multor procese biologice critice, cum ar fi reglarea expresiei genice i proliferarea celular pentru promovarea inflamaiei cronice. Aceti factori pot fi implicai n activarea mecanismelor efectoare care limiteaz creterea tumoral, acionnd n beneficiul pacienilor, sau din contr, ele pot contribui la inflamarea, transformarea, creterea i invazia tumoral. Stimularea creterii tumorale este efectul multiplelor reele de factori de cretere, iar aceste interaciuni sunt mult mai complicate in vivo, interaciuni care trebuie s fie luate n considerare atunci cnd concepem strategiile terapeutice [11,13,17]. Vom rezuma cele mai importante relaii cunoscute ntre citokinele investigate i procesul de cretere i progresie al melanomului: IL-1 este o citokin pro-inflamatorie, care iniiaz un rspuns imun mpotriva celulelor apoptotice [18]. IL-1 este produs de celulele epiteliale. S-a presupus c IL1 este o citokina epidermal [19]. Dei exist numeroase interaciuni ale IL-1 cu alte citokine, cea mai consistent i mai relevant clinic este sinergismul ei cu TNF, n timp ce IL-10 inhib sinteza IL-1. Interleukina-1 (IL-1) cu subtipurile i s-a dovedit a avea efecte anti-proliferative pe linia de melanom A375 [20-24]. IL-1 este un membru al familiei de citokine proinflamatorii, care moduleaz reacia de faza acut. Anihilarea cu siRNA a IL-1 la nivelul fibroblastelor a determinat inhibarea invaziei melanomului, fiind astfel demonstrat in vitro rolul IL-1 secretat de fibroblaste n invazia melanomului. De asemenea, tratarea unor celule melanice cu IL1 a redus cu 40-100% capacitatea lor de a activa limfocitele citolitice T antimelanomice [23]. n prezent, dozele mari de IL-2 reprezint singurul tratament aprobat, cu un efect durabil asupra recidivei i mortalitii melanomului n stadiu avansat. Singura terapie adjuvant aprobat de FDA (Food and Drug Administration) pentru stadiu avansat operabil (stadiul IIB) i melanom nodal regional (stadiul III) este doza mare de IFN-a2b (HDI). HDI a fost dovedit a avea un efect durabil asupra supravieuirii fr recdere a melanomului, cu o reducere de 27% pn la 33% a pericolului de recidiva la pacienii cu risc crescut de recidiva [24]. Acest agent induce rspunsuri clinice obiective la 16% dintre pacieni cu melanom avansat inoperabil. Rmne neclar de ce unii pacieni rspund, iar unii nu rspund deloc la terapia cu IFN-a2b, iar bazele moleculare ale efectelor antitumorale ale IFN-a2b administrate ca adjuvant au sugerat c efectul acestuia variaz de la efecte directe citotoxice, la modulare imunologic i antiangiogenic la nivelul gazdei [25-28]. IL-4R sunt exprimate pe o mare varietate de tumori umane solide, iar IL-4 singur i n asociere cu IFN pot juca un rol n rspunsul imun al gazdei mpotriva cancerului [23]. Interleukina-6 (IL-6) poate afecta difereniat proprietile de cretere ale celulelor melanice. Proliferarea melanocitelor umane i creterea numrului melanoamelor n stadiu incipient sunt inhibate de IL-6 eliberat de fibroblaste [24,25]. Sinteza de IL-6 n celulele melanice B16 determin ntrzierea creterii [24] prin
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oprirea ciclului celular la nivelul G1/G0. Melanoamele n stadiul avansat sunt rezistente la efectul anti-proliferativ al IL-6; mai mult de 50% dintre ele exprima constitutiv IL-6 ARNm i, de asemenea, secret IL-6 n mediul de cultur, fiind prin urmare n msur s prezinte o cretere autonom. A rezultat o inhibare semnificativ a creterii atunci cnd au fost adugate oligonucleotidele antisens IL-6 la cultura de celule, dar anticorpii de neutralizare au fost ineficieni. Acest lucru demonstreaz c IL-6 este o citokin bifuncional i IL-6 endogen se poate comporta ca un stimulator intracelular de cretere autocrin, care acioneaz asupra receptorilor specifici [29]. Interleukina-8 (IL-8) este o chemokin produs de macrofage i de alte tipuri de celule, cum ar fi celulele epiteliale. De asemenea, este sintetizat de celule endoteliale care stocheaz IL-8 n veziculele lor de stocare i a fost demonstrat c IL-8 endotelial inhib infiltrarea tumorii cu limfocite, rezultnd un rspuns imun sczut. Exist mai muli receptori membranari capabili s lege IL-8. Cele mai frecvente tipuri studiate sunt proteinele G care cupleaz receptorii serpentinici CXCR1 i CXCR2 secretai de celulele melanice. [30-33]. Interleukina-10 Multe studii au sugerat ca nivelurile crescute de IL-10 sunt promotori tumorali n melanom. In vivo, un numr considerabil de pacieni cu melanom avansat au prezentat nivele serice crescute de IL-10, iar celule umane melanice produc IL-10 in vivo. Alte studii au sugerat ca IL-10 este un factor de cretere autocrin pentru celulele melanice umane i IL-10 poate fi exprimat preferenial n leziuni metastatice. Aceste constatri privind rolul IL-10 n scparea tumorii de sub rspunsul imun se explic pe baza proprietilor sale imunosupresoare, prin suprimarea produciei de citokine de tip Th1, i n special IL-2. Cu toate acestea, alte studii au demonstrat c IL10 exercit activiti antitumorale i anti-metastatice prin inhibarea angiogenezei n vivo, deoarece tumorile maligne nu pot crete mai mult de 2-3 mm3 i nu pot metastaza fr stimularea formrii de noi vase de snge. Mecanismul pentru acest fenomen poate fi reprezentat prin capacitatea IL-10 de a reduce sinteza factorului de cretere endotelial vascular (VEGF) - unul dintre cei mai puternici factori angiogenici - mpreun cu IL-1, factorul de necroz tumoral, IL-6 i metaloproteinaza - 9 (MMP-9) n macrofagele asociate tumorii, care joac de asemenea un rol crucial n angiogenez. Alte studii au demonstrat c IL-10 inhib metastazele tumorale prin intermediul unui mecanism dependent de celulele natural killer. [23, 34-35]. IL-12. Celulele monocitare par a fi principala surs de IL-12, dar i alte celule cum ar fi celulele mastocitare, celulele B, keratinocitele i celulele dendritice pot produce IL-12. Receptorii pentru IL-12 au fost descrii la nivelul celulelor NK i T, celule care rspund prin mbuntirea proliferrii i creterea activitii citolitice. n plus, citokinele cum ar fi IFN- sunt eliberate de celulele T dup stimularea cu IL-12. Niveluri ridicate de interleukina-12 reprezint un marker de prognostic sczut, n special pentru pacienii cu melanom cu vrst mai naintat. Un studiu efectuat pe 150 de pacieni cu melanom n stadiul III a constatat c niveluri crescute de IL-12 sunt asociate cu un risc de deces de 5 ori mai mare. Mai mult, introducerea genei IL-12 n celulele tumorale sau n fibroblastele mixate ulterior cu celule tumorale autologe a determinat un puternic efect inhibitor al creterii, precum i efecte antimetastatice. Transferul genei IL-12 a indus un rspuns TH1 i a generat o imunitate antitumoral puternic [3639]. Cel mai notabil rol al IL-17 este implicarea n inducerea i medierea rspunsurilor proinflamatorii.
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IL-17 induce producerea multor altor citokine (cum ar fi IL-6, GM-CSF, IL-1, TGF-, TNF-), chemokine (inclusiv IL-8, GRO-, i MCP-1) i prostaglandine din multe alte tipuri de celule (fibroblati, celule endoteliale, celule epiteliale, keratinocite i macrofage). Funcia IL-17 este de asemenea esenial pentru un subset de celule T CD4+ i anume celule T helper 17 (Th17). Ca urmare a acestor funcii, familia IL-17 a fost asociat cu multe boli imune/autoimune conexe i cu imunitatea anti-tumoral [40-41]. TNF- este considerat un factor rspunztor de caexia neoplazic, fiind produs de macrofage, monocite, fibroblaste, keratinocite precum i alte celule. Este implicat n inflamaia sistemic, stimulnd reacia de faz acut. TNF- este liantul receptorului factorului de cretere epidermic. Aceasta poate funciona printr-un mecanism autocrin sau paracrin i contribuie la supravieuirea tumorii prin stimularea expresiei genelor anti-apoptotice. Pe de alt parte, este un mediator pro-apoptotic atunci cnd este combinat cu interferon. TNF- este utilizat clinic n asociere cu melfalan n perfuzia regional hipertermic n tratamentul melanomului membrelor [42-44]. GM-CSF are efecte anti-tumorale, prin generarea de celule prezentatoare de antigen (APC) eficiente n prelucrarea celulele apoptotice i inducerea imunitii celulare i umorale. GM-CSF prezint un interes special deoarece se administreaz clinic ca tratament adjuvant pentru inducerea APC n vaccinurile mpotriva melanomului. Celulele dendritice i macrofagele sunt eficiente n captarea celulelor tumorale moarte, in inducia celular i imunitatea umoral. Pe de alt parte, s-a remarcat c doze mari de GM-CSF administrat n vaccinuri poate avea un efect imunosupresor. Prin urmare, prezena sa n esutul melanomului poate indica imunosupresia local a celulelor tumorale sau ar putea s induc celulele dendritice i macrofagele sa curee resturile de celule tumorale moarte [45-46]. CONCLUZII Rezultatele noastre au artat c nivelurile plasmatice a ase citokine inflamatorii, i anume - IL-1, IL-10, IL-17, IFN-, TNF- i GM-CSF - au fost semnificativ crescute la pacienii cu melanom, n timp ce alte citokine (IL-1, IL-2, IL-4, IL-6, IL-8 i IL-12), dei au fost crescute la pacieni, diferenele nu au prezentat valori semnificative fa de lotul de control. n concluzie, o reea complex de citokine pare a fi declanat n cazul invaziei melanomului primar, acest rspuns citokinic fiind implicat n reglarea creterii i evoluiei celulelor melanice. Diferenele n ceea ce privete profilul citokinelor ntre pacienii cu melanom si subiecii sntoi au permis o discriminare robust ntre aceste dou grupuri. De asemenea, prin acest studiu am evideniat avantajul analizei multiplexate pentru descoperirea de noi biomarkeri plasmatici i am creat premisele unei mai bune nelegeri a patobiologiei melanomului.
Mulumiri: Aceast lucrare a fost susinut prin CNCSIS UEFISCSU, numr proiect 1197/2009, PN II IDEI, PCE, cod 1750/2008. BIBLIOGRAFIE Pidhorecky I, Lee RJ, Proulx G, Kollmorgen DR, Jia C, Driscoll DL, Kraybill WG, Gibbs JF. Risk factors for nodal recurrence after lymphadenectomy for melanoma. Ann Surg Oncol 2001; 8(2): 109-115. Kim SH, Garcia C, Rodriguez J, Coit DG. Prognosis of thick cutaneous, melanoma. J Am Coll Surg 1999; 188(3): 241- 247.
1. 2.
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Articole originale
3. 4. 5. 6.
7.
8. 9. 10.
11. 12. 13. 14. 15.
16. 17. 18. 19. 20. 21. 22.
Clary BM, Brady MS, Lewis JJ, Coit DG. Sentinel lymph node biopsy in the management of patients with primary cutaneous melanoma: review of a large single-institutional experience with an emphasis on recurrence. Ann Surg 2001; 233(2): 250-258. Barth A,Wanek LA,MortonDL. Prognostic factors in 1,521melanoma patients with distant metastases. J Am Coll Surg 1995; 181(3): 193-201. Manola J, Atkins M, Ibrahim J, Kirkwood J. Prognostic factors in metastatic melanoma: a pooled analysis of Eastern Cooperative Oncology Group trials. J Clin Oncol 2000; 18(22): 3782-3793. Balch CM, Soong SJ, Smith T, Ross MI, Urist MM, Karakousis CP, Temple WJ, Mihm MC, Barnhill RL, Jewell WR, Wanebo HJ, Desmond R; Investigators from the Intergroup Melanoma Surgical Trial. Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas. Ann Surg Oncol 2001; 8(2):101-108. Altekruse SF, Kosary CL, Krapcho M, Neyman N, Aminou R, Waldron W, Ruhl J, Howlader N, Tatalovich Z, Cho H, Mariotto A, Eisner MP, Lewis DR, Cronin K, Chen HS, Feuer EJ, Stinchcomb DG, Edwards BK. SEER Cancer Statistics Review, 1975-2007, National Cancer Institute. Bethesda. http://seer.cancer.gov/csr/1975_2007/. Yurkovetsky ZR, Kirkwood JM, Edington HD, Marrangoni AM, Velikokhatnaya L, Winans MT, Gorelik E, Lokshin AE. Multiplex Analysis of Serum Cytokines in Melanoma Patients Treated with Interferon-alpha2b. Clin Cancer Res 2007;13(8): 2422-2422. Ciotti P, Rainero ML, Nicol G, Spina B, Garr C, Casabona F, Santi PL, Bianchi-Scarr G. Cytokine expression in human primary and metastatic melanoma cells: analysis in fresh bioptic specimens. Melanoma Res 1995; 5(1): 41-47. Westphal JR, Van't Hullenaar R, Peek R, Willems RW, Crickard K, Crickard U, Askaa J, Clemmensen I, Ruiter DJ, De Waal RM. Angiogenic balance in human melanoma: expression of VEGF, bFGF, IL-8, PDGF and angiostatin in relation to vascular density of xenografts in vivo. Int J Cancer 2000; 86(6):768-776. Lazar-Molnar E, Hegyesi H, Toth S, Falus A. Autocrine and paracrine regulation by cytokines and growth factors in melanoma. Cytokine 2000; 12(6): 547-554. Colombo MP, Maccalli C, Mattei S, Melani C, Radrizzani M, Parmiani G. Expression of cytokine genes, including IL-6, in human malignant melanoma cell lines. Melanoma Res 1992; 2(3): 181-189. Mattei S, Colombo MP, Melani C, Silvani A, Parmiani G, Herlyn M. Expression of cytokine/growth factors and their receptors in human melanoma and melanocytes. Int J Cancer 1994; 56(6): 853-857. Tartour E, Dorval T, Mosseri V, Deneux L, Mathiot C, Brailly H, Montero F, Joyeux I, Pouillart P, Fridman WH. Serum interleukin 6 and C-reactive protein levels correlate with resistance to IL-2 therapy and poor survival in melanoma patients. Br J Cancer 1994; 69(5): 911-913. Soubrane C, Rixe O, Meric JB, Khayat D, Mouawad R. Pretreatment serum interleukin-6 concentration as a prognostic factor ofoverall survival in metastatic malignant melanoma patients treated with biochemotherapy: a retrospective study. Melanoma Res 2005; 15(3): 199-204. Dummer W, Becker JC, Schwaaf A, Leverkus M, Moll T, Brcker EB. Elevated serum levels of interleukin-10 in patients with metastatic malignant melanoma. Melanoma Res 1995; 5(1): 67-68. Vihinen P.P., Pyrhonen S.O., Kahari V.M. New prognostic factors and developing therapy of cutaneous melanoma. Ann Med 2003; 35(2): 66-78. Houghton AN. Cancer antigens: immune recognition of self and altered self. J Exp Med 1994; 180(1): 17. Elias EG, Hasskamp JH, Sharma BK. Cytokines and Growth Factors Expressed by Human Cutaneous Melanoma. Cancers 2010, 2(2): 794-808. Cruse JM, Lewis RE, Wang H. Cytokines and chemokines. In Cruse JM, Lewis RE, Wang H. eds. Immunology Guidebook. Amsterdam, The Netherlands, Elsevier Science & Technology Books. 2004; p. 339392. Rodeck U. Growth factor independence and growth regulatory pathways in human melanoma development. Cancer Metastasis Rev. 1993, 12(3-4): 219226. Krasagakis K, Garbe C, Orfanos CE. Cytokines in human melanoma cells: synthesis, autocrine stimulation and regulatory functions-an overview. Melanoma Res. 1993, 3(6): 425433.
61
Articole originale
23. Gray-Schopfer V, Wellbrock C, Marais R. Melanoma biology and new targeted therapy. Nature 2007; 445(7130): 851867. 24. Tyler DS, Francis GM, Frederick M, Tran AH, Ordez NG, Smith JL, Eton O, Ross M, Grimm EA. Interleukin-1 production in tumor cells of human melanoma surgical specimens. J. Interferon Cytokine Res. 1995, 15(4): 331340. 25. Moschos SJ, Edington HD, Land SR, Rao UN, Jukic D, Shipe-Spotloe J, Kirkwood JM. Neoadjuvant treatment of regional stage IIIB melanoma with high-dose interferon a-2b induces objective tumor regression in association with modulation of tumor infiltrating host cellular immune responses. J Clin Oncol 2006; 24(19): 3164 -3171. 26. Kirkwood JM, Ibrahim JG, Sondak VK, Richards J, Flaherty LE, Ernstoff MS, Smith TJ, Rao U, Steele M, Blum RH. High and low-dose interferon alfa-2b in high-risk melanoma: first analysis of intergroup trial E1690/S9111/ C9190. J Clin Oncol 2000; 18(12):2444-2458. 27. Kirkwood JM, Richards T, Zarour HM, Sosman J, Ernstoff M, Whiteside TL, Ibrahim J, Blum R, Wieand S, Mascari R. Immunomodulatory effects of high-dose and low-dose interferon alpha-2b in patients with high- risk resected melanoma: the E2690 laboratory corollary of intergroup adjuvant trialE1690. Cancer 2002; 95(5):1101-1012. 28. Kirkwood JM, Manola J, Ibrahim J, Sondak V, Ernstoff MS, Rao U; Eastern Cooperative Oncology Group. A pooled analysis of Eastern Cooperative Oncology Group and intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res 2004; 10(5): 1670-1677. 29. Akira, S., Taga T., Kishimoto T. Interleukin-6 in biology and medicine. Adv. Immunol. 1993, 54: 178. 30. Leong SR, Lowman HB, Liu J, Shire S, Deforge LE, Gillece-Castro BL, McDowell R, Hbert CA. IL-8 single chain homodimers and heterodimers: interactions with chemokine receptors CXCR-1, CXCR-2 and DARC. Protein Sci. 1997, 6(3): 609617. 31. Gabellini C, Trisciuoglio D, Desideri M, Candiloro A, Ragazzoni Y, Orlandi A, Zupi G, Del Bufalo D. Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. Eur. J. Cancer 2009, 45: 26182627. 32. Varney ML, Johansson SL, Singh RK. Distinct expression of CXCL8 and its receptors CXCR1 and CXCR2 and their association with vessel density and aggressiveness in malignant melanoma. Am. J. Clin. Pathol. 2006, 125(2): 209216. 33. Singh S, Sadanandam A, Nannuru KC, Varney ML, Mayer-Ezell R, Bond R, Singh RK. Smallmolecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival and angiogenesis. Clin. Cancer Res. 2009, 15(7): 23802386. 34. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol. 2004; 22: 929-979. 35. Dummer W, Becker JC, Schwaaf A, Leverkus M, Moll T, Brcker EB. Elevated serum level of interleukin-10 in patients with metastatic malignant melanoma. Melanoma Res. 1995, 5(1): 6768. 36. Tan J, Newton CA, Djeu JY, Gutsch DE, Chang AE, Yang NS, Klein TW, Hua Y. Injection of complementary DNA encoding interleukin-12 inhibits tumor establishment at a distant site in a murine renal carcinoma model. Cancer Res 1996; 56(15): 33993403. 37. Tahara H, Zeh HJ 3rd, Storkus WJ, Pappo I, Watkins SC, Gubler U, Wolf SF, Robbins PD, Lotze MT. Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res 1994; 54(1): 182189. 38. Windhagen A, Anderson DE, Carrizosa A, Williams RE, Hafler DA. IL-12 induces human T cells secreting IL-10 and IFN-. J Immunol 1996; 157(3): 11271131. 39. Sun Y, Jurgovsky K, Mller P, Alijagic S, Dorbic T, Georgieva J, Wittig B, Schadendorf D. Vaccination with IL-12 gene-modified autologous melanoma cells: preclinical results and a first clinical phase I study. Gene Therapy 1998; 5(4): 481490 40. Murugaiyan G, Saha B. Protumor vs antitumor functions of IL-17. J. Immunol. 2009, 183(7): 41694175. 41. Baldwin AS. Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappaB. J. Clin. Invest. 2001, 107(3): 241246. 42. Hayes AJ, Neuhaus SJ, Clark MA, Thomas JM. Isolated limb perfusion with melphalan and tumor necrosis factor for advanced melanoma and soft-tissue sarcoma. Ann. Surg. Oncol. 2007, 14(1): 230238.
62
Articole originale
43. Manna SK, Mukhopadhyay A, Aggarwal BB. IFN-alpha suppresses activation of nuclear transcription factors NF-Kappa and activation protein 1 and potentiates TNF-induced apoptosis. J. Immunol. 2000, 165(9): 49274934. 44. Rossi CR, Russano F, Mocellin S, Chiarion-Sileni V, Foletto M, Pilati P, Campana LG, Zanon A, Picchi GF, Lise M, Nitti D. TNF-based isolated limb perfusion followed by consolidation biotherapy with systemic low-dose interferon alpha 2b in patients with in-transit melanoma metastases: a pilot trial. Ann. Surg. Oncol. 2008, 15(4): 12181223. 45. Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I. High-dose granulocytemacrophage colony- stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res. 2004, 64(17): 63376343. 46. Filipazzi P, Valenti R, Huber V, Pilla L, Canese P, Iero M, Castelli C, Mariani L, Parmiani G, Rivoltini L. Identification of a new subset of myeloid suppressor cells in the peripheral blood of melanoma patients with modulation by granulocyte-macrophage colony-stimulating factor-based antitumor vaccine. J. Clin. Oncol. 2007, 25(18): 25462553.
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IMPORTANA AUTOGREFELOR N RECONSTRUCIA LANULUI OSICULAR N OTITA MEDIE SUPURAT CRONIC

A. Vlase, V. Costinescu, T.Ghindaru Disciplina ORL, Facultatea De Medicina, Universitatea de Medicina i Farmacie Gr.T.Popa Iai
THE IMPORTANCE OF AUTOGRAFTS IN THE RECONSTRUCTIONS OF OSSICULAR CHAIN IN CHRONIC SUPPURATIVE OTITIS MEDIA (ABSTRACT): Improvement of hearing in ossiculoplasty depends on the efficiency of the methods to reestablish the ossicular continuity and the connection with the tympanic membrane. While various prosthesis have been used to bridge the ossicular defect, we have used autogenous bone (incus remnant and cortical bone) and autogenous cartilage ( tragal and concal) for the reconstruction of ossicular continuity. The study was performed on a lot of 86 patients suffering of chronic suppurative otitis media, with good cochlear reserve and good eustachian tube function, admitted in the C.F. Hospital in Iasi during a period of four years. Patiens with atico-antral disease and cholesteatoma were excluded from the study and all these procedures were intact canal wall procedures. The operations were done in local or general anesthesia by post-aural or endaural route. After raising the tympanomeatal flap, it was insured that there was no other disease in the middle ear. The status of the ossicular chain was assessed. Mastoid antrum was opened in most cases to look for any disease there. The patency of the aditus was also checked. Ossicular reconstructive procedure was planned according to the status of the ossicular chain. Temporalis fascia or tragal perichondrum was used to close the perforation. In this stady, we have included only the cases where autogenous cartilage (tragal or choncal) or autogenous bone (incus remnant or cortical bone) was used between1) malleus & head of stapes (malleus-stapes assembly), 2) beetwin malleus & footplate (malleus footplate assembly), 3) stapes head & newly constructed tympanic membrane(short collumela), 4) footplate & newly constructed tympanic membrane (long collumela). Hearing results at 18 months follow up have been fairly good, for example 84% patients had closures of air bone gap within 20 dB and 16% had closure of air bone gap within 10 dB. The study has revealed fairy good hearing results in patients implanted with autogenous cartilage and bone autografts. The functional results were better when using bone grafts in favour of cartilage, these are easily available and cost effective, moreover, they are stable, easily accepted by the body and never extruded out. KEY WORDS: OSSICULOPLASTY, AUTOGRAFTS, TYMPANOPLASTY, MIDDLE EAR. Coresponden: Dr. Alex Vlase, medic specialist ORL, Clinica ORL, Sp. Universitar C.F. Iasi, str. G.Ibraileanu, nr.1, Iai, e-mail: alex_vlase@yahoo.com*.
INTRODUCERE Reconstrucia lanului osicular este o provocare ce se ateapt s dea ca rezultate mbuntirea funciei auditive. Muli factori afecteaz rezultatele osiculoplastiei. Disfuncia trompei lui Eustache, leziunile fibroadezive i starea lanului osicular sunt doar civa factori intrinseci, n timp ce factorii extrinseci sunt tehnica chirurgical i alctuirea i compoziia protezei folosite. Lund n considerare diferitele defecte de continuitate ale lanului osicular asociate cu otita medie supurat cronic, urmtoarele anomalii sunt importante: - afectarea articulaiei incudostapediale;
*
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liza sau absena nicovalei; liza sau absena suprastructurii scriei; liza sau absena ciocanului; combinaii ale celor de mai sus.
MATERIAL SI METOD n funcie de leziunea existent se aleg tehnica chirurgical i materialul de protezare pentru a avea rezultate funcionale auditive postoperatorii optime. Autogrefele, homogrefele i protezele sintetice au fost folosite de-a lungul timpului pentru a suplini defectul osicular. Pennington [1] a prezentat prima mare propunere pentru utilizarea de materiale de autogref lanul osicular. Remodelarea elementelor osiculare i realizarea unor noi suprafee articulare au fost continuate de chirurgii care au ncercat s obin o mai bun stabilitate a lanului osicular nou format i o mai bun eficien acustic. Hough 1977 [2]. Dei nu exist nici o diferen semnificativ ntre autogrefe i homogrefe osiculare transplantabile n ceea ce privete rezultatele, posibilitatea transmiterii bolilor infecioase n cazul utilizrii homogrefelor a fcut ca acestea s nu mai fie utilizate, locul lor fiind luat de proteze sintetice. Materiale sintetice diferite precum plasticul, ceramica, titanul, hidroxiapatita au fost utilizate. De multe ori, n folosirea unora dintre aceste materiale au aprut complicaii precum necroz osicular, respingerea corpului strin, precum i costuri crescute ale materialelor sintetice [3]. Simplitatea utilizrii autogrefelor n reconstrucia lanului osicular a continuat s menin atenia otologilor de-a lungul anilor. Aceste autogrefe pot fi folosite din cartilaj tragal, concal sau ciocan, nicoval sau cortical temporal autogen remodelat. Uurina preparrii, excelenta biocompatibilitate, costurile sczute i rezultatele funcionale auditive sunt marile avantaje ale acestor tipuri de proteze. S-au efectuat 86 de osiculoplastii de-a lungul a 4 ani la spitalul Universitar C. F. Iasi. Au fost selectai pacienii cu otite supurate cronice simple, cu o rezerv cohlear i o bun funcie a trompei lui Eustache. Pacienii cu otite supurate cronice propriu-zise i cu colesteatom au fost exclui din acest studiu. Toate interveniile au fost fcute prin tehnic nchis cu pstrarea peretelui posterior al conductului auditiv extern. REZULTATE Aspectele operatorii de prelevare i remodelare a materialului autolog sunt prezentate n Fig. 1-3. Operaia a fost realizat cu anestezie local sau general, pe cale retro sau endaural (Fig. 4). Dup ridicarea lamboului timpanomeatal, ne-am asigurat de fiecare dat c nu sunt identificate i alte afeciuni ale urechii medii. Starea lanului osicular a fost evaluat, antrul mastoidian a fost deschis n majoritatea cazurilor, pentru a vedea dac nu se ascunde o leziune la acest nivel. Permeabilitatea aditusului a fost de asemenea verificat, procedura de reconstrucie a lanului osicular a fost planificat n funcie de integritatea acestuia. Fascia temporal sau pericondrul tragal au fost folosite pentru nchiderea perforaiei (Fig. 5). n acest studiu, am inclus doar cazurile cu autogref de cartilaj (tragal sau concal) sau autogrefe osoase : nicoval (Fig. 1-3) sau osul cortical care au fost interpuse ntre : 1. ciocan i capul scriei (ansamblul ciocan-cap scri), 2. ciocan i platina scriei (ansamblul ciocan-platin scri), 3. capul scriei i membrana timpanic nou
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construit (columel scurt), 4. platina scriei i membrana timpanic nou construit (columel lung).
Fig.1 Prelevarea nicovalei
Fig.2 Remodelarea nicovalei timpul 1
Fig. 3 Remodelarea nicovalei timpul 2
Fig.4 Introducerea nicovalei in casa timpanului
Fig. 5 Repoziionarea lamboului timpanal
Distribuia pacienilor n funcie de tipul de reconstrucie este detaliat n tabelul 1.
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Tabel 1. Distribuia cazurilor n funcie de tipul de reconstrucie Tipul de reconstrucie Nr. de pacieni ansamblul ciocan-cap scri 28 ansamblul ciocan-platin scri 18 columel scurt 24 columel lung 16
La toi pacienii osiculoplastia a fost realizat cu cartilaj sau os autolog, dup cum se poate observa n tabelul 2.
Tabel 2. Distribuia cazurilor n funcie de tipul autogrefei Material folosit Nr. de pacieni Cartilaj tragal sau concal 23 Nicoval remodelat 36 Cortical temporal remodelat 27
Reconstrucia membranei timpanice, unde a fost necesar, s-a realizat cu pericondrul tragal sau fascie temporal (Fig. 5). Toi pacienii au fost supui la o audiogram nainte de operaie i post operator la 6, 12 i 18 luni. Au fost comparate frecvenele de 500, 1000 i 2000 de heri ntre rezultatele pre i post operatorii. Ctigul auditiv care reiese din rezultatele auditive este bazat pe comparaia mediei pre i post operatorii a celor trei frecvene conversaionale amintite mai sus. n acest studiu, am inclus pacieni care au fost urmrii i testai auditiv cel puin 2 ani post operator. n studiul nostru am observat c 91% din pacieni prezentau un Rine audiometric preoperator de mai mult de 30 dB. Rine-ul audiometric a fost obinut scznd din curba de conducere aerian, curba de conducere osoas. Rezultatele operaiilor au fost evaluate n funcie de ctigul auditiv obinut i au variat n funcie de tipul de reconstrucie (Tabel 3). n cazul folosirii interpoziiei nicovalei ntre ciocan i capul scriei s-a obinut n 87 % din cazuri un ctig audiometric de peste 20 de dB i n 13% din pacieni un ctig audiometric de peste 10 db. Rezultatele pentru ansamblul ciocan-platin scri i pentru columel scurt au fost comparabile.
Tabel 3. Rezultate n funcie de tipul de reconstrucie Ctig audiometric > 10 dB Ctig audiometric > 20 dB Reconstrucie Ansamblul ciocan-cap scri Ansamblul ciocan-platin scri Columel scurt Columel lung Nr. pacieni 4 3 5 6 Procentaj 13% 16% 42% 35% Nr. pacieni 24 15 19 10 Procentaj 87% 84% 79% 65%
Cnd au fost evaluate rezultatele n funcie de materialul de gref folosit, s-a descoperit un ctig audiometric postoperator a fost comparabil la pacienii la care s-a folosit nicovala sau corticala temporal. Rezultatele auditive au fost mai bune la 67
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pacienii la care s-a folosit o autogref osoas fa de cei la care s-a utilizat autogref cartilaginoas (Tabel 4).
Tabel 4. Rezultate n funcie de tipul autogrefei Ctig audiometric > 10 dB Ctig audiometric > 20 dB Tipul autogrefei Nicoval remodelat Os cortical temporal Cartilaj Nr. pacieni 6 5 7 Procentaj 16% 41% 28% Nr. pacieni 30 22 16 Procentaj 84% 82% 72%
DISCUII Autogrefa de nicoval a fost folosit pentru reconstrucia osicular de Hall i Rytzner [4], iar osul cortical de ctre Hough [5] i Zollner [6]. Dei s-a dovedit c rezultatele pe termen lung sunt slabe datorit atrofiei, Mills [7] i Bauer [8] au raportat o experien favorabil i o stabilitate histologic. Guildford [9] a recomandat folosirea protezelor de os autolog (temporal cortical, nicoval i ciocan) atta timp ct ansamblul format este stabil n urechea medie. Ei au oferit o bun meninere a rezultatelor auditive i nu au fost asociate niciodat cu respingerea. Austin [10], Fisch [11] i Pennington [12] au raportat o bun stabilitate i rezultate auditive bune prin folosirea autogrefelor de-a lungul timpului, urmrind cazurile timp de doi, trei, pn la zece ani. Luetje et al [13] au folosit pericondru ataat la cartilajul tragal pentru reconstrucie i au descoperit c este mai sigur, de ncredere i poate fi folosit n chirurgia primar a otitelor cronice. Rezultatele auditive raportate de ei au fost c 79% dintre pacieni au artat un ctig audiometric de 20 de dB i la 21% din pacieni de 10dB. Black [14] a comparat rezultatele interpoziiei dintre ciocan i capul scriei cu ciocan i platina scriei i a obinut un ctig audiometric de 20 de dB la 86% din pacieni la prima situaie i 14% din pacieni n a doua situaie. McGee i Hough [15] au raportat rezultate excelente cu un Rine audiometric postoperator pn n 10 dB folosind ca material autolog elemente ale lanului osicular (nicoval, ciocan). Conform celor raportate de ei, tipul leziunii osiculare influeneaz succesul operaiei. Prezena suprastructurii scriei are rezultzate funcionale cu un ctig audiometric de peste 20 de dB n 85% din cazuri; n absena suprastructurii scriei se obine un ctig de 20 de dB n doar 73% din cazuri. Bauer [8] a analizat n cei 34 de ani de experien folosirea autogrefelor de nicoval i os cortical prin care a format o columel ntre capul scriei i membrana timpanic. n studiul su 85% din pacieni au prezentat un ctig de peste 20 de dB i 15% din pacieni un ctig de 10 dB la care membrana timpanic era integr.[16,17]. Kartush [18] a descoperit c rezultatele obinute n folosirea autogrefelor realizate din modelarea nicovalei i a osului cortical sunt comparabile. A observat, de asemenea, c autogrefele obinute din material osos realizeaz o transmitere mai bun dect cele din cartilaj, avnd ca rezultat un ctig auditiv mai bun.[19,20].
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CONCLUZII n studiul nostru rezultatele generale au artat un ctig audiometric de peste 20 de dB n 84% din cazuri i un ctig audiometric de 10 dB n 37% din cazuri. Am analizat rezultatele noastre n funcie de tipul de reconstrucie i am descoperit c autogrefa interpus ntre ciocan i capul scriei a dat rezultatele cele mai bune, 87% din pacieni au avut un ctig audiometric de peste 20 de dB, urmat de interpoziia autogrefei ntre ciocan i platina scriei i de cei cu columel scurt, adic 84%, respectiv 79% cu ctig auditiv de peste 20 de dB. Rezultate funcionale mai bune au fost obinute n cazul utilizrii nicovalei sau a osului cortical remodalat fa de utilizarea numai a cartilajului tragal sau concal. ntr-o epoc n care o mare varietate de materiale protetice sunt folosite pentru a reconstrui i nlocui lanul osicular, autogrefele joac nc un rol important prezentnd urmtoarele avantaje: uor disponibile, mult mai accesibile din punct de vedere al costurilor dect protezele sintetice , stabile i uor acceptate de organism fiind bine tolerate n urechea medie i nu n ultimul rnd cu rezultate funcionale marcabile.
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. BIBLIOGRAFIE Pennington CL. Incus Interposition Techniques. Annals of Otology, Rhinology and Laryngology. 1973; 82(4): 568-570. Hough JVD. Ossicular Malformations and their Correction. In proceedings of fifth Shambough International Workshop on otomicro surgery and third Shea Fluctuant hearing loss Symposium, Hunts Ville Alabama. 1977; 5(3): 186-194. Glassock III ME, Gulya AJ. Tympanoplasty In Aristides Sysmanis, editor. Surgery of the ear. 5th edition, Hamilton Ontario: Ed. BC Decker Inc; 2003. p. 463-486. Hall A, Rytzner C. Stapedectomy and autotransplantation of Ossicles. Acta OtoLaryngol. 1957; 47(4): 318-324. Hough JVD. Incudo-stapedial joint separation: etiology, treatment and significance. Laryngoscope 1959; 69(6): 644-664. Zollner F. Technik der forming einer Columella aus Knochen, Z. Laryngol Rhinol Otol. 1960; 39(5): 536-540. Mills RF, Cree LA. Histological Fate of Cortical Bone Autograft in Middle Ear. Clinical Otolaryngology 1995; 20(4): 365-367. Bauer M. Ossiculoplasty: Autogenous Bone Grafts, 34 year experience. Clinical Otolaryngology 2000; 25(4): 257-263. Guildford FR. Reposition of Incus. Laryngoscope 1965; 75(2): 236-242. Austin DF. Ossicular Recontruction. Otolaryngologic Clinics of North America, 1982; 18(5): 145-160. Fisch U, May JS, Linder T. Ossiculoplasty In Fisch U. editor. Tympanoplasty, mastoidectomy and stapes surgery, New York; Ed. Thieme Medical Publishers; 2008. p. 313-324. Pennington CL. Incus Interposition a 15 years report . Annals of Otology, Rhinology and Laryngology. 1983; 92(3): 568-570. Luetje CM, Denninghoff JS. Perichondrial Attached Double Cartilage Block: a Better Alternative to PORP. Laryngoscope 1987; 97(9): 1106-1108. Black B. Spanner Malleus stapes-footplate assembly. Laryngoscope 1994; 104(6): 775-778. McGee M, Hough JVD. Ossiculoplasty. Otolaryngologic Clinics of North America 1999; 32(3): 471-487. Haberman RS. Ossiculoplsty In Bojrab DI, Babu SC. editor. Middle ear and mastoid surgery. New York; Ed. Thieme. 2004; p. 151-158. Lesser Th. Mechanics and material in middle ear reconstruction. Clinical Otolaryngology 1991; 16(1): 29-32. Kartush JM. Ossicular Chain Reconstruction. Otolaryngologic Clinics of North America 1994; 27(4): 689-715. Dornhoffer J. Cartilage Tympanoplasty: indications technics and outcomes in 1000- pacient series. Laryngoscope 2003; 113(11): 1844-1856
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20. Bone RT., Gardner EK., Dornhoffer JL. Succes of cartilage grafting in revision tympanoplsty without mastoidectomy. Otol Neurotol. 2004; 25(5): 678-681Kartush JM: Ossicular Chain Reconstruction. Otolaryngologic Clinics of North America 27, 1994; 689-715
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HISTEROSCOPIA, METOD MINIM INVAZIV DE DIAGNOSTIC I TRATAMENT N INFERTILITATEA DE CAUZ UTERIN

Nora (Dumitriu) Miron, Ivona Anghelache-Lupacu, Demetra Socolov, Cristina David, R.Socolov Catedra de Obstetric i Ginecologie Universitatea de Medicin i Farmacie Gr. T. Popa Iai, Romnia
HYSTEROSCOPY, A MINIMALLY INVASIVE METHOD FOR DIAGNOSIS AND TREATMENT OF UTERINE INFERTILITY (ABSTRACT): Hysteroscopy is an endoscopic procedure which consists of introducing a telescope connected to a camera through the dilated cervical canal into the uterine cavity for the visualisation of the cervical canal, uterine cavity and tubal ostiums. It is a minimally invasive method that allows diagnosis and / or treatment of a wide variety of pathologies affecting the proper functionality of internal female genitalia (menstrual and reproductive function). Objectives: It seeks to examine both the frequency and types of endouterine pathology involved in female infertility (intrauterine adhesions, fibroids, polyps, endometritis, adenomiosis). .Material and methods: The study was conducted on 161 infertile patients admitted in "Cuza Voda" Hospital, Iasi, between January 2008 - March 2010. Results: We have investigated patients aged 21-41 years (mean 31 years) with primary infertility - 66 cases (40.99%) and secondary infertility - 95 cases (59.01%). All patients were examined by hysteroscopy combined with laparoscopy for an infertility investigation protocol under general anaesthesia. There was no recorded incident or complication. Conclusions: Hysteroscopy proved to be a useful and relatively easy to perform manoeuvre in the diagnosis and treatment of endouterine pathology. It is important to note that one can identify diseases not diagnosed by ultrasound or hysterosalpingography (endometriosis and filmy adhesions). KEYWORDS: PATHOLOGY. FEMALE UTERINE INFERTILITY; HYSTEROSCPY; ENDOMETRIAL
Coresponden: Nora (Dumitriu) Miron, doctorand Universitatea de Medicin i Farmacie Gr. T. Popa, Iai Tel: 0722299940, e-mail: nora.miron@yahoo.com*.
INTRODUCERE Afeciunile endouterine care au implicaii n fertilitatea feminin se constituie ntr-o patologie complex care pune probleme de diagnostic i tratament. Dintre acestea, cel mai frecvent ntlnite sunt sinechia uterin, polipii endometriali, fibroamele intracavitare, malformaiile i corpii strini (dispozitivele intrauterine sau fire de sutur). Factorul uterin reprezint 2-3% din cauzele de infertilitate, dar leziunile intrauterine sunt mult mai frecvente la femeile infertile (40-50%), pentru toate aceste patologii relaia de cauzalitate cu infertilitatea nefiind foarte clar. Histeroscopia este considerat standardul de aur n evaluarea cavitii uterine [1]. Totui, OMS recomand histerosalpingografia ca procedeu de prim intenie n explorarea cavitii uterine, deoarece n acelai timp se poate evalua i starea trompelor Falloppe. Histeroscopia diagnostic este recomandat de OMS doar dac ecografia transvaginal sau histerosalpingografia indica un aspect patologic [1] sau dup un eec fertilizare in vitro [1].
*
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i totui, n ultimii ani tot mai muli practicieni recomand histeroscopia de ambulator de rutin, ca metod iniial de explorare a cavitii uterine, din cauza frecvenei crescute a patologiei uterine la pacientele infertile. Acest fapt se datoreaz att acurateei crescute a metodei, ct i miniaturizrii echipamentului de histeroscopie, care permit efectuarea tehnicii n ambulator, chiar fr anestezie. Acest studiu retrospectiv i propune ca obiective, evaluarea patologiei endouterine ntr-un lot de paciente infertile care au efectuat histeroscopie, analiznd urmtoarele aspecte: frecvena, principalele tipuri de patologii ntlnite, repartiia lor pe vrste, corelaia cu rezultatele ecografiei transvaginale, histerosonografiei i ale histerosalpingografiei pentru cazurile la care toate aceste date au putut fi obinute. MATERIAL I METOD Am efectuat un studiu retrospectiv pe 159 paciente, internate n Clinica a II-a Ginecologie a Maternitii Cuza-Vod i n Clinica Ginecologie a Maternitii ElenaDoamna din Iai, n perioada ianuarie 2008 - martie 2010, care au efectuat o histeroscopie n cadrul unui bilan de infertilitate. Investigaia a fost efectuat n cadrul unui protocol mai complex pentru depistarea cauzelor de infertilitate. Acest protocol iniial, cuprindea verificarea permeabilitii tubare (prin histerosalpingografie i ultrasonografie cu ser fiziologic barbotat cu aer), urmate de o laparoscopie diagnostic cu Dye test cuplat cu o histeroscopie; evaluarea rezervei ovariene prin dozri hormonale (FSH, LH, Estradiol-n ziua 2-3 de ciclu menstrual), monitorizarea ecografic a ovulaiei, analize de microbiologie (pentru depistarea infeciilor cu Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum i Neisseria Gonorrhoeae), precum i verificarea factorului masculin (spermogram si spermocultur). Att histeroscopia, ct i laparoscopia au fost efectuate cu aparatura Karl Storz Endoskope, Germania, 2008. Pentru histeroscopie s-a folosit histeroscopul rigid cu canal de lucru cu dublu flux (telescop de 2,7 mm. i vedere la 30 cu teaca extern cu diametrul de 6,5 mm. i canal operator de 5 FR). Presiunea s-a realizat cu ajutorul endomatului Hammou, iar ca mediu de distensie s-a folosit serul fiziologic. Pentru toate cazurile s-a efectuat anestezie general. Histeroscopiile s-au efectuat conform unui protocol de lucru, ce cuprinde: inspecia canalului cervical; inspecia cavitii uterine; verificarea celor dou orificii tubare; prelevarea unei biopsii de endometru; tratamentul leziunilor existente (dac situaia impune). REZULTATE Pacientele din studiu au avut o vrste cuprinse ntre 21-41 ani (mediana - 31 ani), fiind investigate pentru infertilitate primar 66 cazuri (40,99 %) i infertilitate secundar 95 cazuri (59,01%) cu durata de peste 1 an. La 46 de paciente (28,57%) histeroscopia a fost normal, iar la 115 paciente (71,43%) s-au decelat diverse patologii dup cum urmeaz: sinechie uterin 63 cazuri (54,78%); fibrom intracavitar - 4 cazuri (3,47%); polipi intracavitari - 12 cazuri (10,43%); hiperplazie simpla de endometru - 3 cazuri (2,6%); stenoza orificiului intern al colului uterin - 2 cazuri (1,74%); malformatii uterine - 14 cazuri (12,17%); corpi strini intrauterini - 1 caz (0,87%); endometru hipotrofic neconcordant cu faza ciclului menstrual (endometrul cu stimul estrogenic insuficient) - 8 cazuri (6,95%); endometrit cronic - 8 cazuri (6,95%) (Fig. 1).
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n 46 cazuri endometrul a fost de aspect normal, corespunztor cu faza ciclului menstrual declarat de pacient.
60 50
polipi intracavitari sinechie uterin fibrom intracavitar
40 30 20 10 0 Patologie intrauterin
hiperplazie simpla de endometru stenoza orificiului intern al colului uterin malformatii uterine corpi strini intrauterini endometru hipotrofic endometrit cronic
Fig.1 Distribuia procentual a patologiei endouterine diagnosticat histeroscopic
Dintre cazurile diagnosticate cu sinechie uterin (Fig. 2), 48 cazuri au prezentat aderene velamentoase (gradul 1 dup Wansteker) care au fost desfcute cu histeroscopul n momentul ptrunderii n cavitatea uterin, iar sinechiile vechi, fibroase (10 cazuri gradul 2; 3 cazuri gradul 3; 2 cazuri gradul 4 dup Wansteker), au fost desfcute cu foarfecul sau cu pensa prin trocarul de lucru al histeroscopului (Fig. 3,4).
Fig.2 Sinechie uterin
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n aceste din urm cazuri, dupa liza sinechiei a fost montat un dispozitiv intrauterin (DIU) temporar, pentru a menine deprtai pereii cavitii uterine i pentru a permite endometrului s se refac corespunztor.
Fig.3 Sinechie uterin desfcut cu foarfecele prin canalul de lucru al histeroscopului
Fig.4 Sinechie uterin desfcut cu pensa prin canalul de lucru al histeroscopului
Polipii intracavitari diagnosticai histeroscopic (12 cazuri), au fost n majoritate unici (10 cazuri), iar n 2 cazuri s-au evideniat polipi multipli. Cei mai muli au fost polipi pediculai (11 cazuri), iar localizarea n ordinea frecvenei a fost urmtoarea: istmic - 58,33%; n coarnele uterine - 25%; fundic - 8,33%; cervical - 8,33%. Polipii intracavitari pediculai (Fig. 5) au fost extrai cu pensa prin torsiune (Fig.6), apoi s-a efectuat chiuretajul cavitii uterine i rezultatul s-a reverificat histeroscopic. Produsul s-a trimis la examen anatomo-patologic.
Fig.5 Polip pediculat ce ocup intreaga cavitate uterin
Fig.6 Polip uterin
Fibroamele intracavitare (Fig. 7) au fost iniial vizualizate ecografic i s-a constatat ca volumul lor este intre 1 i 3 cm, iar localizarea este predominant submucoas (condiia ca ele s poat fi rezecate histeroscopic este ca raportul ecografic s fie 2/3 intracavitar i 1/3 intramural).
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n toate cele 4 cazuri s-a practicat extracia nodulilor fibromatoi cu foarfecele i chiureta, cu rezultate satisfctoare.
Fig.7 Fibrom intracavitar (perete anterior uterin)
Malformaiile uterine diagnosticate histeroscopic au fost: sept complet de la fundul uterului pn la orificiul intern al colului 1 caz; sept incomplet 5 cazuri; fund uterin arcuat 2 cazuri (sept < 2 cm. msurat ecografic); cavitate uterin cilindric (cu diametrul transvers ngustat) 3 cazuri; cavitate uterin hipoplazic grad I 2 cazuri (diametrul transvers < 3 cm. msurat ecografic); cavitate uterin asimetric, cu hipoplazia cornului stng uterin 1 caz. Dintre acestea, cazurile diagnosticate cu sept complet sau incomplet au fost rezolvate pe cale histeroscopic, efectundu-se rezecia septurilor cu foarfecele; celelalte cazuri au beneficiat doar de diagnostic. Am diagnosticat un caz cu corp strin intrauterin, respectiv fire neresorbabile de nylon chirurgical restante dup operaie cezarian efectuat n urm cu 10 ani. S-a practicat extragerea firelor cu pensa prin canalul de lucru al histeroscopului, apoi s-a efectuat chiuretaj uterin biopsic. DISCUII Utilizarea histeroscopiei n investigarea infertilitii de cauz uterin, intr din ce n ce mai mult n practica ginecologic. Avantajele tehnicii sunt reprezentate de posibilitatea diagnosticului direct macroscopic, eventual suplimentat de examenul microscopic, i de opiunile terapeutice conservatoare accesibile tehnicii endoscopice. Caracterul invaziv al metodei, cndva un impediment major, devine tot mai puin important datorit miniaturizrii echipamentului i pregtirii adecvate a specialitilor. n ceea ce privete principalele etiologii ale infertilitii de cauz uterin, remarcm c la cele la care histeroscopia a decelat o patologie, ea a fost cel mai frecvent legata de sinechii (54,78% din total). Aceasta este o particularitate a situaiei de la noi, n care endometrul este traumatizat prin chiuretaje, agresiuni perinatale sau inflamaii persistente, n timp ce n alte ri, ponderea sinechiilor ntre cazurile de infertilitate este
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mai mica [2-5] i se datoreaz mai mult unor gesturi terapeutice intrauterine (miomectomie, polipectomie). Sinechia reprezint o problem major de infertilitate i prin posibilitile limitate terapeutice. Liza histeroscopic este o manevr dificil, cu risc de complicaii, iar rata de recidiv este mare att n experiena noastr cat si n literatur [6,7]. De civa ani, plasarea unui dispozitiv intrauterin n cavitatea uterin dup liza sinechiei i meninerea acestuia timp de 3 luni, este considerat metoda standard de prevenie a aderenelor intrauterine [5,8]. Restul patologiilor uterine determinnd infertilitate s-au ntlnit n cazurile noastre cu o frecven apropiat de cea din literatur [9-11]. Fibroamele intracavitare au fost rezolvate de asemenea pe cale histeroscopic, sub control pre i postoperator ecografic, iar polipii prin torsiune cu pensa histeroscopic. Malformaiile uterine au fost reprezentate n mai mult de jumtate din cazuri de utere septate, suspectate premergtor interveniei i confirmate intraoperator i la care septurile incomplete au fost rezecate la rece cu foarfecele histeroscopic, metoda recomandat de altfel n literatur ca avnd un risc mai mic de perforaii [9,12]. Rezecia histeroscopic a septurilor uterine ajut la creterea ratei de obinere a sarcinilor i de asemenea la reducerea ratei avorturilor spontane i a naterilor premature [6,13]. Analiznd sensibilitatea, specificitatea, valoarea predictiv pozitiv i valoarea predictiv negativ a histerosalpingografiei, a histerosonografiei cu ser fiziologic barbotat i a ecografiei transvaginale, constatm c, prin neefectuarea histeroscopiei n cadrul bilanului iniial, rmn nediagnosticate un numr mare de leziuni cu o implicare potenial n infertilitate. Acest fapt ne permite s propunem histeroscopia diagnostic n bilanul iniial al unei infertiliti. CONCLUZII Frecvena crescut a patologiei endouterine la pacientele infertile, ct i acurateea diagnostic a histeroscopiei, neegalat de celelalte metode de explorare a cavitii uterine (histerosalpingografia, histerosonografia cu ser fiziologic barbotat i ecografia transvaginal) ne permit s o propunem ca metod de rutin n bilanul iniial al unui cuplu infertil. n acest studiu, toate histeroscopiile au fost efectuate sub anestezie general, datorit protocolului de investigare particular adoptat de clinica noastr (n majoritatea cazurilor histeroscopia a fost efectuat concomitent cu laparoscopia diagnostic). Miniaturizarea instrumentarului de histeroscopie, ne ofer posibilitatea practicrii tehnicilor minim invazive n condiii de ambulator, chiar cu anestezie local. n acest fel, ar putea fi introdus ca metod de rutin pentru investigarea infertilitii feminine. BIBLIOGRAFIE
1. 2. 3. 4. Koskas M, Mergui JL, Yazbeck C, Uzan S, Nizard J. Office histeroscopy for infertility: a series of 557 consecutive cases. Obstet Gynecol Int. 2010; 2010: 168096. Fedele L, Vercellini P, Viezzoli T, Ricciardiello O, Zamberletti D. Intrauterine adhesions: current diagnostic and therapeutic trends. Acta Eur Fertil 1986; 17(1): 3137. Feng ZC, Huang YL, Sun JF, Yang BY, Xue BR, Zhuang LQ. Diagnostic and therapeutic hysteroscopy for traumatic intrauterine adhesion. Clinical analysis of 70 patients. Chin Med J (Engl). 1989; 102(7): 553-558. Friedler S, Margalioth EJ, Kafka I, Yaffe H. Incidence of post-abortion intra-uterine adhesions evaluated by hysteroscopy: a prospective study. Hum Reprod 1993; 8(3): 442444.
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5. 6. 7. 8. 9. 10. 11. 12. 13.
Valle RF, Sciarra JJ. Intrauterine adhesions: hysteroscopic diagnosis, classification, treatment, and reprodactive outcome. Am J Obstet Gynecol 1988; 158(6 Pt 1): 1459-1470. Weiss A, Shalev E, Romano S. Hysteroscopy may be justified after two miscarriages. Hum Reprod 2005; 20(9): 26282631. Pabucu R, Atay V, Orhon E, Urman B, Ergun A. Hysteroscopic treatment of intrauterine adhesions is safe and effective in the restoration of normal menstruation and fertility. Fertil Steril 1997; 68(6): 11411143. Nappi C, Di Spiezio Sardo A, Greco E, Guida M, Bettocchi S, Bifulco G. Prevention of adhesions in gynaecological endoscopy. Hum Reprod Update 2007; 13(4): 379394. Heinonen PK, Pystynen PP. Primary infertility and uterine anomalies. Fertil Steril 1983; 40(3): 311316. Pritts EA, Parker WH, Olive DL. Fibroids and infertility: an updated systematic review of the evidence. Fertil Steril 2009; 91(4): 12151223. Spiewankiewicz B, Stelmachow J, Sawicki W, Cendrowski K, Wypych P, Swiderska K. The effectiveness of hysteroscopic polypectomy in cases of female infertility. Clin Exp Obstet Gynecol 2003; 30(1): 2325. Letterie GS. Structural abnormalities and reproductive failure: Effective techniques of diagnosis and management. New York. Blackwell Science. 1998; p. 98-32. Homer HA, Li TC, Cooke ID. The septate uterus: a rewiew of managment and reproductive outcome. Fertil Steril 2000; 73(1): 114.
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TRATAMENTUL CHIRURGICAL RADICAL AL COLANGIOCARCINOMULUI HILAR - PREZENTARE DE CAZ

V. Gavrilovici, F. Grecu, A. Lpuneanu, D. Ferariu Cr. Dragomir 1. Spitalul Sf. Ioan cel Nou Suceava, Secia Chirurgie general, doctorand Universitatea de Medicin i Farmacie Gr.T.Popa Iai 2. Clinica III Chirurgie, Universitatea de Medicin i Farmacie Gr.T.Popa Iai 3. Departamentul de Anatomie Patologic, Sp. Sf Spiridon, Iai
RADICAL SURGICAL TREATMENT FOR HILAR CHOLANGIOCARCINOMA. CASE REPORT (ABSTRACT): The surgical approach to hilar cholangiocarcinoma has changed during last decades from local and non-radical resection to aggressive surgery, including extended liver resections, with low morbidity and mortality rate and better survival. We present the case of a patient with hilar cholangiocarcinoma (classified type IIIb Bismuth-Corlette) treated by left hepatectomy and segment I resection, en bloc with extrahepatic bile duct and periarterial lymphadenectomy. Patient received postoperatively partial adjuvant treatment and is alive three years later. KEY WORDS: HILAR CHOLANGIOCARCINOMA, HEPATECTOMY, SEGMENT I RESECTION AGGRESSIVE SURGERY, LEFT
Coresponden: Dr. Valeriu Gavrilovici, Secia Chirurgie general, Spitalul Sf. Ioan cel Nou Suceava, B-dul 1 Decembrie 1918, nr.21, Suceava*.
INTRODUCERE Colangiocarcinoamele sunt tumori dezvoltate din epiteliul ductal biliar. Ele pot aprea n orice segment al ductelor intrahepatice (colangiocarcinoame intrahepatice, CCI) sau extrahepatice, de la ficat pn la ampula Vater. Colangiocarcinoamele hilare (CCH) sunt cele care intereseaz confluena biliar i au fost descrise de Gerald Klatskin n 1965 [1]. nainte de anii aptezeci majoritatea pacienilor nu erau supui interveniilor chirurgicale cu viz curativ iar n rarele cazuri de excizie tumoral local, aceasta se fcea cu radicalitate redus i supravieuire precar [2]. Ulterior rata de rezecabilitate n CCH a crescut prin adoptarea unei atitudini mai agresive n rezecia convergenei biliare, cu sau fr rezecie hepatic asociat. [3,4], chirurgii hepatobiliari cu experien n acest tip de patologie demonstrnd c o abordare agresiv n rezecarea CCH este posibil, cu rate de mortalitate sczut i cu anse curative mai mari [5-7]. PREZENTARE DE CAZ Pacientul B.G. n vrst de 49 de ani, fr antecedente personale semnificative a fost internat n Clinica III Chirurgie a Universitii de Medicin i Farmacie Gr. T. Popa Iai n noiembrie 2008 pentru icter sclero-tegumentar cu debut insidios,
*
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relativ recent i evoluie progresiv, indolor, afebril, nsoit de prurit i semne de impregnare neoplazic - astenie fizic i scdere ponderal (aproximativ 5 kg n dou sptmni), scaune acolice. Examenul clinic a evideniat icter sclerotegumentar intens, abdomen uor mrit de volum pe seama panicului adipos, dureros difuz la palparea profund la nivelul etajului abdominal superior, cu maximum de intensitate n hipocondrul drept, fr semne de iritaie peritoneal. Bilanul biochimic i hematologic au relevat sindrom anemic (hemoglobin 12,5 g/dl, hematocrit 36,9%), trombocitoz (467000/mm3), sindrom de colestaz (bilirubin total 5,2 mg/dl, bilirubin direct 3,54 %, fosfataz alcalin 1279 UI/L) i transaminaze mrite (TGO 234 UI/L; TGP 365 UI/L), fr modificari ale probelor de coagulare. Examenul ecografic abdominal a artat colecist cu dimensiuni obinuite, coninut lichidian, fr calculi, cile biliare intrahepatice dilatate, convergena canalelor hepatice nevizualizat, calea biliar principal de 4 mm, ficat cu structura omogen, vena port normal ca dimensiuni, permeabil. Examinarea colangiografic prin rezonan magnetic (MRCP) a depistat o formaiune expansiv n 1/3 proximal a coledocului, cu invazia canalului hepatic drept i stng i dilataia cilor biliare intrahepatice, adenopatii n hilul hepatic, cu diametrul maxim de 10 mm (Fig.1).
Fig. 1 MRCP A. aspect lacunar la nivelul confluentului biliar superior; B. absenta metastazelor hepatice; C., D. dilatatia cailor biliare intrahepatice predominant la nivelul lobului hepatic stang.
Diagnosticul stabilit fiind de tumor de convergen (tumor Klatskin) s-a decis realizarea unei intervenii chirurgicale cu intenie radical.
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S-a efectuat laparotomie subcostal dreapt, branat la stnga i cranial ctre apendicele xifoid. Dup colecistectomie, explorarea intraoperatorie a pediculului hepatic i a ficatului a identificat tumora la nivelul convergenei canalelor hepatice drept i stng, avnd dimensiuni de aproximativ 3/4 cm, de consisten dur, cu extensie nivelul canalului hepatic stng. S-a practicat decolare duodenopancreatic pentru explorare limfogaglionar, constatndu-se adenopatii pediculare. Examenul histopatologic extemporaneu a doi ganglioni pericoledocieni (distal i retroduodenopancreatic) nu a evideniat diseminare tumoral. n urma inventarului lezional locoregional i general care nu atest diseminare la distan, s-a decis efectuarea unei rezecii cu viz radical. Dup mobilizarea ficatului stng, prin seciunea ligamentelor de susinere, s-a efectuat ecografie intraoperatorie (Doppler) care a apreciat rapoartele tumorii cu ramurile portale i canalele biliare la nivelul plcii hilare. Tumora obstrua cvasicomplet canalul hepatic stng determinnd dilatarea important a cilor biliare intrahepatice pe partea stng, fr invazia venei porte. S-a continuat cu disecia pediculului hepatic, evideniindu-se o distribuie vascular arterial modal cu bifurcaia arterei hepatice proprii la distan de tumora hilar, procesul tumoral nglobnd doar ramul stng al acesteia (Fig. 2A).
B
Fig. 2 Aspect intraoperator A. Disecia elementelor hilului hepatic B. Trana de rezecie dup hepatectomie stang
Ramul stng al venei porte nu prezenta invazie tumoral. Dupa ligatura ramului stng al arterei hepatice i secionarea distal n segmentul retroduodenal al coledocului, s-a reclinat cranial calea biliar i s-a continuat disecia i separarea acesteia de planul venei porte i ramurilor drept si stng, la nivelul plcii hilare. S-a clampat i secionat ramul stng al venei porte, urmnd sutura bontului portal. Disecia canalului hepatic drept s-a efectuat la distan de convergen i de limita macroscopic a tumorii, n grosimea parenchimului hepatic; s-a identificat astfel un canal hepatic drept cu traiect scurt (aproximativ 5 mm) cu o convergen a canalelor sectoriale paramedian (anterior) i lateral (posterior) apropiat de limita macroscopic a tumorii. Intervenia a continuat cu transecia parenchimului hepatic prin abord anterior la nivelul marginii stngi a fosetei veziculare (Fig. 2B), viznd o rezecie a segmentelor hepatice IV, III, II i I (nomenclatura Couinaud) [8]. Planul de transecie a parenchimului hepatic trece pe flancul stng al venei hepatice medii. Abordul mixt al pediculului glissonian drept, prin disecia iniial 80
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intraglissoniana, i apoi abordul transparenchimatos permit identificarea nivelului optim de seciune a cii biliare pentru ficatul drept la nivelul canalelor sectoriale. Pe trana de rezecie ramn dou canale cu diametrul de aproximativ 2-3 mm fiecare, situate la o distan de aproximativ 10 mm unul de cellalt. Intervenia a continuat cu disecia, ligatura i secionarea ramurilor arteriale i portale ale lobului Spiegel aflate n relaie cu ramul drept al arterei hepatice i al venei porte. S-au ligaturat i secionat venele spiegeliene, ligamentul venos Arantius i ligamentul hepatocav stng, acordndu-se atenie deosebit flancului drept al venei cave pentru conservarea a dou vene accesorii ale segmentului VII. Acest gest ncheie tehnica rezeciei lobului stng anatomic suprimat n bloc cu calea biliar extrahepatic pan la nivel retroduodenal.
B
Fig. 3 Aspect macroscopic al piesei de rezecie i pe seciune
In completarea rezectiei hepatice s-a efectuat limfadenectomie la nivelul arterei hepatice comune pan la nivelul trifurcaiei trunchiului celiac. Tratarea tranei restante dup rezecie s-a realizat prin tehnici combinate de coagulare bipolar i sigilare vascular (Ligasure), completate de hemostaz cu fir sprijinit. Etapa reconstructiv a constat n confecionarea unei anse jejunale n Y la Roux cu capt nchis. Dupa ascensiunea ansei transmezocolic, s-a procedat la adosarea ansei la trana hepatic n plan posterior, secionarea planului seros i muscular corespunztor bonturilor canalelor biliare segmentare i deschiderea punctiform a mucoasei jejunale. A urmat anastomoza colangiojejunal cu fire separate 5/0, a fiecarui canal biliar sectorial cu mucoasa jejunal i plasarea de stenturi anastomotice (6 French) cu capatul distal pierdut n ansa jejunal. Colangiojejunoanstomoza s-a incheiat cu adosarea unui plan anterior al seroasei ansei jejunale la trana hepatic. Plasarea tuburilor de dren juxtaanastomotic, subfrenic stng i n fundul de sacDouglas a ncheiat intervenia chirurgical. Disecia piesei confirm stadiul tumoral IIIb dup clasificarea Bismuth-Corlette [9] (Fig. 3A). Canalul hepatic comun, confluentul biliar superior i canalul hepatic stng sunt incluse ntr-o mas de esut galben sidefiu, de consisten crescut (Fig. 3B).
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Fragmente din canalul hepatic comun i canalul hepatic stng examinate microscopic au evideniat infiltrare de adenocarcinom moderat difereniat, cu abundent strom sclero-hialin abundent i infiltrat inflamator i infiltrarea tecii unor filete nervoase. Rezultatul final al examinarii ganglionilor limfatici a relevat arhitectur pastrat, fr metastaze (pT3N0MxG2). Evoluia postoperatorie a fost favorabil, cu reluarea progresiv a tranzitului intestinal si alimentatiei orale i cu toleran digestiv bun, pacientul fiind externat la 13 zile dup operaie. Pacientul a urmat 3 cure de chimioterapie sistemic cu Gemcitabin, cu toleran scazut datorit toxicitaii digestive i hematologice care au determinat refuzul pacientului de a continua terapia adjuvant. La aproximativ un an de la intervenie s-a evideniat icter moderat. Ecografia hepatic i examinarea computer-tomografic au evideniat absena unuia din stenturile biliare plasate intraoperator, fara a identifica recidiv tumoral. S-a observat dilatarea cilor biliare ale segmentelor VI i VII i stenoza acestora la nivelul tranei hepatice. Sa recurs la plasarea unui drenaj biliar transparietohepatic care s depaeasc zona stenotic la nivelul tranei, avnd captul pierdut n ansa jejunal. Pacientul s-a prezentat ulterior la control n stare general bun i aparent fr semne de recidiv tumoral. DISCUII Tratamentul chirurgical al CCH are trei obiective [10,11]: excizia tumoral complet cu margini histologice negative, nlturarea simptomatologiei legat de obstrucia biliar i refacerea continuitii bilioenterale. Opiunile chirurgicale curative n tratamentul CCH sunt urmtoarele: rezecia cii biliare; rezecie de ficat i de cale biliar, rezecie combinat de ficat i vascular; hepatopancreatoduodenectomie; transplant hepatic [5]. DAngelica a artat c la toi pacienii cu CCH potenial rezecabil chirurgul trebuie s fie totdeauna pregtit pentru a realiza o hepatectomie parial [12]. Cteva studii au raportat supravieuiri semnificativ mai bune dup rezeciile hepatice asociate. n 1990 Boerma constata ntr-o revist a rezultatelor pe 581 de pacieni din literatur o supravieuire mai mic la 5 ani pentru cei supui doar rezeciei locale dect cei cu operaii extinse: 7% versus 17% [13]. Un studiu publicat n 2000 a prezentat diferenele de abordare i rezultatele din dou centre, unul american - Lahey Clinic Medical Center, Burlington, Massachusetts i cellalt din Japonia - Nagoya University School of Medicine, pe baza schimburilor de experien ntre colectivele celor dou clinici i vizitelor reciproce [14]. Cele dou cohorte au fost similare n privina numrului pacienilor tratai pe an per perioada de studiu, datelor demografice, tipului tumoral i expertizei chirurgicale. Astfel, cohorta Lahey a cuprins 100 de pacieni tratai n clinica respectiv ntre 1980 i 1995 (62 de brbai, 38 de femei) n timp ce cohorta de la Nagoya a cuprins 155 de pacieni (100 brbai, 55 femei) tratai ntre 1977 i 1995. Diferene semnificative au existat n privina criteriilor de rezecabilitate, stagingul preoperator, extensia rezeciei, rata marginilor negative i supravieuirea pe termen lung. Criteriile de rezecabilitate la Lahey Clinic au fost: 1)absena adenopatiilor, metastazelor peritoneale i hepatice discontigue, 2) absena invaziei vasculare (portale sau arteriale hepatice) i 3) absena invaziei organelor extrahepatice adiacente.
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Pentru chirurgii de la Nagoya criteriile au fost mult mai liberale, singura contraindicaie absolut pentru rezecie fiind invazia arterial hepatic bilateral sau invazia portal bilateral, detectate preoperator prin angiografie. Rata rezecabilitii a fost de 25% n cohorta Lahey n timp ce pentru cohorta japonez a fost de 79% [14]. n 2001 Jarnagin, analiznd rezultatele a 80 de pacieni consecutivi, gsete supravieuire la 5 ani de 37% la pacienii cu rezecie hepatic i 0% la cei fr astfel de rezecii. Pentru a exclude posibilitatea ca diferenele de supravieuire s se datoreze ratei de radicalitate, analiza a fost repetat incluznd numai pacienii R0 i rezultatele au fost confirmate [15]. n studiul publicat de Kondo n 2004 pe 40 de pacieni consecutivi cu rezecie R0, cei 9 pacieni cu rezecie izolat de cale biliar au avut o supravieuire semnificativ redus comparativ cu cei 17 pacieni la care s-a asociat hepatectomie dreapt [16] iar Launois a artat c rezecabilitatea crete proporional cu rata hepatectomiei [17]. Cancerul convergenei hepatice se extinde nu numai ctre canalele hepatice drept i stng dar i de-a lungul canaliculilor biliari mici de la nivelul hilului, n direcie cranial i dorsal, Seyama i Makuuchi artnd c exist dou puncte-cheie pentru a putea obine rezecia radical a CCH [18]. Primul const n ndeprtarea parenchimului hepatic adiacent hilului hepatic mpreun cu placa hilar iar hepatectomia dreapt extins sau hepatectomia stng sunt preferabile pentru a ndeprta infiltrarea neoplazic a canalelor hepatice. Al doilea punct-cheie este rezecia lobului caudat (segmentul I din nomenclatura Couinaud) i rezecia prii inferioare a segmentului 4 pentru a reui extirparea infiltrrii neoplazice a canalelor biliare mici perihilare [18]. Prima descriere a unei rezecii de lob caudat a fost fcut de Blumgart n 1979 [19], acesta efectund o rezecie hepatic unui brbat de 51 de ani cu CCH. Lobul caudat, hemificatul stng i un segment al hemificatului drept au fost rezecate en-bloc. Necesitatea rezeciei lobului caudat a fost descris de autorii japonezi [20,21], Nimura fiind primul dintre acetia. Astfel, n 1983 Tsuzuki [20] a raportat 16 cazuri de rezecie hepatic pentru cancer al cii biliare proximale, lobul caudat fiind rezecat mpreun cu hemificatul stng la 8 pacieni i cu hemificatul drept la 1 pacient. Mizumoto [22] a raportat n 1986 8 cazuri de rezecie de lob caudat la 13 cazuri de hepatectomie pentru CCH. Iwasaki [23] a descris rezecii pariale de lob caudat n 9 hepatectomii. Nimura [21] a gsit invazie neoplazic microscopic a canaliculelor biliare ale lobului caudat la 44 din 46 de pacieni care au avut rezecie curativ de lob caudat. Eficacitatea rezeciei lobului caudat a fost publicat pentru prima dat de Sugiura [24], rata de supravieuire la 5 ani fiind n studiul lor retrospectiv de 46% cu lobectomie de caudat i de 12% fr rezecia segmentului 1. Rezecia lobului caudat n timpul hepatectomiilor pentru CCH presupune o bun cunoatere a anatomiei i relaiilor dintre vascularizaia hepatic i sistemul ductal biliar. Lobul caudat este divizat n trei subsegmente. La dreapta venei cave inferioare i structurilor portale se situeaz procesul caudat n timp ce la stnga acestora i frecvent vizibil prin micul epiploon se afl lobul Spiegel sau procesul papilar al lobului caudat. Poriunea paracaval se afl ntre cele dou subsegmente menionate i acoper vena cav [25]. Este recomandat ca rezecia procesului caudat i lobului paracaval s fie realizat n toate hepatectomiile pentru CCH ntruct acestea sunt n strnsa proximitate a convergenei hepatice.
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Kosuge consider lobectomia caudat drept o component esenial a chirurgiei radicale pentru CCH i o consider responsabil pentru bunele rezultate pe termen lung obinute la pacienii tratai prin chirurgie rezecional, fiind ncorporat n 92,6% din rezeciile hepatice majore [26-28] . CONCLUZII Tratamentul chirurgical al colangiocarcinomului hilar a cunoscut modificri semnificative n cursul ultimelor decenii. Indicaiile pentru rezecie au sporit progresiv i rezeciile hepatice au fost asociate rezeciei cii biliare pentru a se mri radicalitatea i a obine rezultate mai bune n privina supravieuirii. Rezecia radical reprezint singura ans curativ i pare s ofere singura ans pentru supravieuire ndelungat pacienilor cu colangiocarcinoame hilare. BIBLIOGRAFIE
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. Klatskin G. Adenocarcinoma of the hepatic duct at its bifurcation within the porta hepatic. An unusual tumor with distinctive clinical and pathological feature. Am J Med 1965; 32: 241-256. Launois B, Campion JP, Brissot P, Gosselin M. Carcinoma of the hepatic hilus: surgical management and the case for resection. Ann Surg 1979; 190(2): 151-157. Longmire WP, MacArthur MS, Bastounis EA, Hiatt J. Carcinoma of the extrahepatic biliary duct. Ann Surg 1973; 178(3): 333-345. Blumgart LH, Drury JK, Wood CB. Hepatic resection for trauma, tumor and biliary obstruction. Br J Surg 1979; 66(11): 762-769. Nimura Y, Kamiya J, Nagino M, Kanai M, Uesaka K, Kondo S, Hayakawa N. Aggressive surgical treatment of hilar cholangiocarcinoma. J Hep Bil Pancr Surg 1998; 5(1): 52-61. Hadjis NS, Blenkharn JI, Alexander N, Benjamin IS, Blumgart LH. Outcome of radical surgery in hilar cholangiocarcinoma . Surgery 1990; 107(6): 597-604. Su CH, Tsay SH, Wu CC, Shyr YM, King KL, Lee CH, Lui WY, Liu TJ, P'eng FK. Factors influencing postoperative morbidity, mortality and survival after liver resection for hilar cholangiocarcinoma. Ann Surg 1996; 223(4):384-394. Couinaud C. Le foie: Etudes anatomiques et chirurgicales. Paris, Ed. Masson; 1957. p.13-33. Bismuth H, Corlette MB. Intrahepatic cholangioenteric anastomosis in carcinoma of the hilus of the liver. Surg Gynecol Obstet 1975; 140(2): 170-178. Chamberlain RS, Blumgart LH. Hilar cholangiocarcinoma: a review and a comentary. Ann Surg Oncol 2000; 7(1): 55-66. Parikh AA, Abdalla EK, Vauthey JN. Operative considerations in resection of hilar cholangiocarcinoma. HPB (Oxford) 2005; 7(4):254-258. DAngelica MI, Jarnagin WR, Blumgart LH. Resectable hilar cholangiocarcinoma: surgical treatment and long-term outcome. Surg Today 2004; 34(11): 885-890. Boerma, EJ. Research into the results of resection of hilar bile duct cancer. Surgery 1990; 108(3): 572580. Tsao JI, Nimura Y, Kamiya J, Hayakawa N, Kondo S, Nagino M, Miyachi M, Kanai M, Uesaka K, Oda K, Rossi RL, Braasch JW, Dugan JM. Management of hilar cholangiocarcinoma: comparison of an American and a Japanese experience. Ann Surg. 2000; 232(2): 166174. Jarnagin WR, Fong Y, DeMatteo RP, Gonen M, Burke EC, Bodniewicz J, Zoussef M, Klimstra D, Blumgart LH. Staging, resectability and outcome in 225 patients with hilar cholangiocarcinoma. Ann Surg 2001; 234(4): 507-517. Kondo S, Hirano S, Ambo Y, Tanaka E, Okushiba S, Morikawa T, Katoh H. Forty consecutive resections of hilar cholangiocarcinoma with no postoperative mortality and no positive ductal margins: results of a prospective study. Ann Surg 2004; 240(1): 95-101. Launois B, Terblanche J, Lakehal M, Catheline JM, Bardaxoglou E, Landen S, Campion JP, Sutherland F, Meunier B. Proximal bile duct cancer: high resectability rate and 5-year survival. Ann Surg 1999; 230(2): 266275. SeyamaY, Makuuchi M. Current surgical treatment for bile duct cancer. World J Gastroenterol 2007; 13(10): 1505-1515.
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19. Blumgart LH, Drury JK, Wood CB. Hepatic resection for trauma, tumor and biliary obstruction. Br J Surg 1979; 66(11): 762-769. 20. Tsuzuki T, Ogata Y, Iida S, Nakanishi I, Takenaka Y. Carcinoma of the bifurcation of the hepatic ducts. Arch Surg 1983; 118(10): 1147-1151. 21. Nimura Y, Hayakawa N, Kamiya J, Kondo S, Shionoya S. Hepatic segmentectomy with caudate lobe resection for bile duct carcinoma of the hepatic hilus. World J Surg 1990; 14(4): 535-544. 22. Mizumoto R, Kawarada Y, Suzuki H. Surgical treatment of hilar carcinoma of the bile duct. Surg Gynecol Obstet 1986; 162:153-158. 23. Iwasaki Y, Okamura T, Ozaki A, Todoroki T, Takase Y et al. Surgical treatment for carcinoma at the confluence of the major hepatic ducts: Surg Gynecol Obstet 1986; 162(2): 457-464. 24. Sugiura Y, Nakamura S, Iida S, Hosoda Y, Ikeuchi S, Mori S, Sugioka A, Tsuzuki T. Extensive resection of the bile ducts combined with liver resection for cancer of the main hepatic duct junction: a cooperative study of the Keio Bile Duct cancer Group. Surgery 1994; 115(4): 445-451. 25. Blumgart LH, Hadjis NS, Benjamin IS, Beazley RM. Surgical approaches to cholangiocarcinoma at the confluence of the hepatic ducts. Lancet 1984; 1(8368):66-70. 26. Kosuge T, Yamamoto J, Shimada K, Yamasaki S, Makuuchi M. Improved surgical results for hilar cholangiocarcinoma with procedures including major hepatic resection. Ann Surg. 1999; 230(5): 663671. 27. Silva MA, Tekin K, Aytekin F, Bramhall SR, Buckels JAC, Mirza DF. Surgery for hilar cholangiocarcinoma: a 10 year experience of a tertiary referral centre in the UK. Eur J Surg Oncol 2005; 31(5):533-539. 28. Capussotti L, Vigano A, Ferrero A, Muratore A. Local surgical resection of hilar cholangiocarcinoma: is there still a place? HPB, 2008; 10(3):174-178.
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PSEUDOMYXOMA PERITONEI OF APPENDICEAL ORIGIN AN UNUSUAL CAUSE OF ABDOMINAL COMPARTMENT SYNDROME: CASE REPORT.
I. Mishin, G. Ghidirim, G. Zastavnitsky, M. Vozian First Department of Surgery N. Anestiadi N. Testemitsanu University of Medicine, Kishinev, Moldova.
PSEUDOMYXOMA PERITONEI OF APPENDICEAL ORIGIN AN UNUSUAL CAUSE OF ABDOMINAL COMPARTMENT SYNDROME: CASE REPORT (ABSTRACT): A 75-year old male patient was admitted with clinical features of tensioned ascites, dyspnea for the last two weeks. He had a history of appendectomy four years previously. During the first 24 hours in the intensive care unit (ICU) the patient required high volume of i/v infusion and vasopressors for correction of hypotension and oliguria. Computed tomography revealed characteristic signs for pseudomyxoma peritonei. Grade III Abdominal Compartment Syndrome (ACS) was detected by measuring the intra-abdominal pressure via the bladder and the patient was scheduled for decompressive laparotomy. During decompressive laparotomy surgical debulking, peritoneal stripping combined with intraoperative hyperthermic intraperitoneal chemotherapy with 5-FU were performed. After surgical decompression the patients condition improved, the postoperative period was uneventful. During a 14 month follow-up period the patient was free of disease recurrence. To the best of our knowledge this is the first case of pseudomyxoma peritonei (PMP) induced intraabdominal hypertension and ACS successfully treated by surgical debulking, peritoneal stripping combined with intraoperative hyperthermic intraperitoneal chemotherapy with 5-FU. KEY WORDS: PSEUDOMYXOMA PERITONEI ABDOMINAL COMPARTMENT SYNDROME Correspondence to: Igor Mishin M.D., Ph.D. str. Muncheshty 52, ap.60, 2001, Kishinev, Moldova. Tel: (+ 37322) 83-24-65. Fax: (+ 37322) 52-20-08; e-mail: mishin_igor@mail.ru*
INTRODUCTION Intra-abdominal hypertension (IAH) is defined as sustained or repeated pathologic elevation of abdominal pressure over 12 mmHg [1]. Abdominal compartment syndrome (ACS) is defined as the adverse physiologic effect of increased intraabdominal pressure (IAP) [2]. Elevated IAP can be induced by increased intra-abdominal volume (ascites, blood, tumors, and pregnancy) or conditions that limit the expansion of the abdominal wall (burns); the development of IAH-induced multiple organ dysfunction and failure appears when abdominal pressure is over 10 - 15 mmHg [1, 2]. Abdominal compartment syndrome in patients with malignancy such as large ovarian cystadenoma [3,4], massive neoplastic ascites [5], ovarian tumor (granulosa cell tumor) [6] and pseudo-Meigs syndrome [7] were recently published. The authors present an additional case of ACS due to malignancy and the first Pseudomyxoma peritonei (PMP)-induced ACS case.
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CASE REPORT In February 2008, a 75-year old male patient was admitted with clinical features of tensioned ascites, dyspnea for the last two weeks. He had a history of appendectomy in 2004 for mucinous cystadenoma. On physical examination, the abdomen was largely distended with a significant amount of ascites (Fig. 1).
Fig. 1 Largely distended abdomen with a significant amount of ascites.
During the first 24 h in the ICU the patient required 5300 ml infusion and vasopressors for oliguria (the urine output was 20.8 ml/h) and hypotension (systolic blood pressure 100 mm Hg). The ultrasound (US) and computed tomography (CT) revealed characteristic signs for pseudomyxoma peritonei [8]: low-attenuation mucinous ascites (10 HU) and associated scalloping of the liver margins and hypodense peritoneal implants with bowel implants (Fig. 2).
Fig. 2 Abdominal CT-scan demonstrating mucinous ascites and scalloping of the liver margins.
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The IAP measured using a Foley catheter (according to the technique described by Kron IL. et al) [1, 9] was 40 cm H2O or 29 mm Hg. With the diagnosis of pseudomyxoma peritonei complicated with ACS the patient was taken for decompressive laparotomy. During surgical debulking, peritoneal stripping combined with intraoperative hyperthermic intraperitoneal chemotherapy with 5-FU 750 mg/m2 at 43C was performed. Fifteen liters of mucinous component and 5 kg of solid component were removed from the peritoneal cavity (Fig. 3).
Fig. 3 Solid component removed from the peritoneal cavity (left) and mucinous component removed from the peritoneal cavity (right).
Immediately after surgery the urine output increased from 20.8 ml/h to 110 ml/h and dyspnea resolved. Since our patient developed ACS, we considered the extension of surgery to the Sugarbaker procedure unnecessary [10, 11]. Intraperitoneal hyperthermic chemotherapy with 5-FU 750 mg/m2 was administrated until the 5th postoperative day. Histologically, the benign form of disseminated peritoneal adenomucinosis was diagnosed (Fig. 4) [12]. The postoperative period was uneventful and the patient discharged on the 15th postoperative day, the patient being scheduled for close followup. DISCUSSION Abnormally elevated intraabdominal pressure (over 12 mm Hg) is defined as intraabdominal hypertension; if unrecognized or untreated, it can lead to abdominal compartment syndrome a condition defined as adverse physiologic consequence of acutely increased intraabdominal pressure [1,13,14]. Prolonged, unrelieved elevated intraabdominal pressure over 20 mmHg can induce cardiopulmonary dysfunction, renal failure, visceral ischemia, shock and death [13,14]. Under these circumstances urgent surgical decompression is recommended. Intra-abdominal hypertension and abdominal compartment syndrome is frequently diagnosed in critically-ill patients following severe abdominal trauma, major abdominal surgery, ruptured abdominal aortic aneurysms, intra- or retroperitoneal hemorrhage, and thermal injury; less common causes include abdominal neoplasm, tensioned ascites, and pancreatitis or massive fluid resuscitation for sepsis [15-17].
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Recently a few case reports of abdominal compartment syndrome associated with different malignancies were published [3-7].
Fig. 4 Histology: disseminated peritoneal adenomucinosis (HEX40).
A PubMed search using pseudomyxoma peritonei, intraabdominal hypertension, abdominal compartment syndrome revealed no published cases of PMP-induced IAH and ACS. To the best of our knowledge this is the first case described of PMP-induced ACS. In the present case, the excessive IAP induced oliguria, dyspnea and hypotension with rapid improvement in the patients condition after decompression indicated the existence of ACS. Pseudomyxoma peritonei is a poorly understood disease. Literarily translated PMP means false mucinous tumor. Mucocele of the appendix was recognized as a pathologic entity by Rokitansky in 1842 and was formally named by Feren in 1876 [18], but it was R. Werth [19] to use the term pseudomyxoma peritonei for the first time in 1884 when he described its occurrence in association with a mucinous carcinoma of the ovary. The incidence of PMP is approximately two in 10,000 laparotomies, and about 75% of patients are female with an average age of 53 years [20]. The unifying diagnostic feature of PMP is the presence of extracellular mucin in the peritoneal cavity. Patients with PMP develop a characteristic mucinous ascites associated with mucinous and cellular implants on the peritoneum [21]. The mucinous tumors accumulate at anatomic sites such as the pelvis, right retrohepatic space, the greater and lesser omentum and the abdominal gutters. Tumor implants on the small bowel are extremely rare, most likely because peristaltic movements prevent the adherence and implantation of tumor cells on the bowel surface [10]. This large accumulation of mucinous ascites can theoretically induce IAH and ACS. Any increase in the volume of the abdominal or retroperitoneal contents increases IAP, thus it is only logical to presume that PMP associated with large accumulations of mucinous ascites could induce IAH and ACS.
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In a large majority of patients (80%), PMP arises from appendicular disease and not ovarian disease [22]. According to the data published by Seidman et al. in 90% of female patients diagnosed with PMP, the ovarian seeding is observed [23]. The most common sites of origin are considered the appendix and the ovary, although other sites, such as the gallbladder, stomach, pancreas, colon, uterus, fallopian tubes, urinary bladder, breast and lung, have been described [24, 25]. The recent advances in the immunohistochemistry and molecular biology have greatly contributed to the debate concerning the appendicular or ovarian origin of PMP, thus the molecular profiles generally exhibit a colorectal rather than an ovarian pattern [26]. Up-to-date the origin of the disease is identified by immunohistochemical techniques [26]. Because of the rarity of this condition, the diagnosis of PMP is often difficult. Ultrasonographic findings are echogenic ascites with multiple semi-solid tumors and scalloping of the hepatic and splenic margins from external pressure of adjacent peritoneal implants [27]. On CT, PMP is characterized by low-attenuation mucinous ascites, associated scalloping of the liver margins and hypodense peritoneal implants with bowel implants [8]. Histology is always required and should be achieved by laparotomy. A laparoscopic approach should be avoided since all laparoscopic port sites develop tumor infiltration through the entire thickness of the abdominal wall [28]. Ronnett et al. histologically described three main diagnostic categories of PMP: (1) the benign form of disseminated peritoneal adenomucinosis (DPAM); (2) the malignant form of peritoneal mucinous carcinomatosis (PMCA), and (3) the intermediate form with features between DPAM and PMCA [12]. This classification has an important prognostic significance, because patients with DPAM have a significantly better prognosis than those with PMCA [29]. The therapeutic recommendations are controversial due to the rarity of PMP, the lack of randomized studies, and its complex biology. Certain features such as low biological aggressiveness, rare metastasis to lymph nodes and liver, and accumulation in anatomically resectable sites (pelvis, right retrohepatic space, the greater and lesser omentum and the abdominal gutter) make the disease amenable to curative surgery [10]. Up to date, the standard treatment includes cytoreductive surgery, inclusively peritoneal stripping procedures and appendectomy, in combination with intraoperative/postoperative intraperitoneal chemotherapy [10] in our case, due to the poor patients condition we performed surgical debulking, peritoneal stripping combined with intraoperative hyperthermic intraperitoneal chemotherapy with 5-FU 750 mg/m2 at 43C. In summary, ACS is a surgical emergency frequently diagnosed in critically-ill patients and usually requires immediate decompression. We described the first PMPinduced ACS successfully treated by surgical decompression. Abdominal hypertension and compartment syndrome must be considered in all the patients with PMP and if recognized immediate abdominal decompression by surgical debulking, peritoneal stripping combined with intraoperative hyperthermic intraperitoneal chemotherapy should be considered.
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1.
2.
3. 4.
5. 6. 7. 8. 9. 10.
11. 12.
13. 14.
15. 16. 17. 18. 19. 20. 21.
22. 23.
24.
REFERENCES Malbrain ML, Cheatham ML, Kirkpatrick A, Sugrue M, Parr M, De Waele J, et al. Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. I. Definitions. Intensive Care Med. 2006; 32(11): 1722-1732. Schein M, Wittmann DH, Aprahamian CC, Condon RE. The abdominal compartment syndrome: the physiological and clinical consequences of elevated intra-abdominal pressure. J Am Coll Surg 1995; 180(6): 745-753. Chao A, Chao A, Yen YS, Huang CH. Abdominal compartment syndrome secondary to ovarian mucinous cystadenoma. Obstet Gynecol. 2004; 104(5 Pt 2): 1180-1182. Giuliani A, Basso L, Demoro M, Scimo' M, Galati F, Galati G. Bilateral ovarian mucinous cystadenoma in an adolescent presenting as abdominal compartment syndrome. Eur J Obstet Gynecol Reprod Biol. 2008; 140(2): 278-279. Etzion Y, Barski L, Almog Y. Malignant ascites presenting as abdominal compartment syndrome. Am J Emerg Med. 2004; 22(5): 430-431. Haan J, Johnson SB, Scalea T. Ovarian Tumor Causing Abdominal Compartment Syndrome. J Trauma. 2007; 62(3): 768769. Peparini N, Di Matteo FM, Silvestri A, Caronna R, Chirletti P. Abdominal hypertension in Meigs' syndrome. Eur J Surg Oncol. 2008; 34(8): 938-942. Sulkin TV, ONeill H, Amin AI, Moran B. CT in pseudomyxoma peritonei: a review of 17 cases. Clin Radiol. 2002; 57(7): 608613. Kron IL, Harman PK, Nolan SP. The measurement of intra-abdominal pressure as a criterion for abdominal re-exploration. Ann Surg. 1984; 199(1): 28-30. Sugarbaker PH. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome. Eur J Surg Oncol. 2001; 27(3): 239-243. Sugarbaker PH. Cytoreduction including total gastrectomy for pseudomyxoma peritonei. Br J Surg. 2002; 89(2): 208212. Ronnett BM, Yan H, Kurman RJ, Shmookler BM, Wu L, Sugarbaker PH. Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis. Cancer. 2001; 92(1): 85-91. Burch JM, Moore EE, Moore FA, FrancioseR. The abdominal compartment syndrome. Surg Clin North Am. 1996; 76(4): 833-842. Meldrum DR, Moore FA, Moore EE, Franciose RJ, Sauaia A, Burch JM. Prospective characterization and selective management of the abdominal compartment syndrome. Am J Surg. 1997; 174(6): 667-673. Schein M, Ivatury R. Intra-abdominal hypertension and the abdominal compartment syndrome. Br J Surg. 1998; 85(8): 1027-1028. Saggi BH, Sugerman HJ, Ivatury RR, Bloomfield GL. Abdominal compartment syndrome. J Trauma. 1998; 45(3): 597-609. Bailey J, Shapiro MJ. Abdominal compartment syndrome. Crit Care. 2000; 4(1): 23-29. de Rezende Pereira JC, Trugilho JC, Sarmat AA. Mucocele of the appendix. Surgery. 2004; 136(5): 1096-1097. Hinson FL, Ambrose NS. Pseudomyxoma peritonei. Br J Surg. 1998; 85(10): 1332-1339. Mann WJ, Jr., Wagner J, Chumas J, Chalas E. The management of pseudomyxoma peritonei. Cancer. 1990; 66(7): 16361640. Elias D. Laurent S. Antoun S. Duvillard P. Durceux M. Pocard M. Lasser P. Pseudomyxoma peritonei treated with complete resection and immediate intraperitoneal chemotherapy. Gastroenterol Clin Biol. 2003; 27(4): 407-412. Elias D, Sabourin JC. Les pseudomyxomes pritonaux. Mise au point. J Chir (Paris). 1999; 136(6): 341-347. Seidman JD, Elsayed AM, Sobin LH, Tavassoli FA. Association of mucinous tumors of the ovary and appendix. A clinicopathologic study of 25 cases. Am J Surg Pathol. 1993; 17(1): 22-34. Sherer DM, Abulafia O, Eliakim R. Pseudomyxoma peritonei: a review of current literature. Gynecol Obstet Invest. 2001; 51(2): 7380.
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25. Shimoyama S, Kuramoto S, Kawahara M, Yamasaki K, Endo H, Murakami T, et al. A rare case of pseudomyxoma peritonei presenting an unusual inguinal hernia and splenic metastasis. J Gastroenterol Hepatol. 2001; 16(7): 825829. 26. Ronnett BM, Shmookler BM, Diener-West M, Sugarbaker PH, Kurman RJ. Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women. Int J Gynecol Pathol. 1997; 16(1): 1-9. 27. Lersch C, Frimberger E, Ott R, Classen M. Gray-scale sonographic findings in a patient with pseudomyxoma peritonei. J Clin Ultrasound. 2001; 29(3): 186191. 28. Esquivel J, Sugarbaker PH Pseudomyxoma peritonei in a hernia sac: analysis of 20 patients in whom mucoid fluid was found during a hernia repair. Eur J Surg Oncol. 2001; 27(1): 5458. 29. Ronnett BM, Zahn CM, Kurman RJ, Kass ME, Sugarbaker PH, Shmookler BM. Disseminated peritoneal adenomucinosis and peritoneal mucinous carcinomatosis. A clinicopathologic analysis of 109 cases with emphasis on distinguishing pathologic features, site of origin, prognosis, and relationship to pseudomyxoma peritonei. Am J Surg Pathol. 1995; 19(12): 13901408.
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LARGE SPLENIC CYSTS AT THE UPPER POLE OF THE SPLEEN LAPAROSCOPIC MANAGEMENT
V. urlin1, E. Georgescu1, S. Rmboiu1, Cristiana Dumitrescu2, T. Bratiloveanu1, I. Georgescu1 1. First Clinic of Surgery, County Emergency Hospital of Craiova, Romania 2. Department of Internal Medicine, CORDIS Medical Center University of Medicine and Pharmacy of Craiova
LARGE SPLENIC CYSTS AT THE UPPER POLE OF THE SPLEEN LAPAROSCOPIC MANAGEMENT (ABSTRACT): Splenic cysts represent a rather rare pathology. The traditional management consisted in splenectomy and it is performed more and more frequently by laparoscopy. However, with the recognition of the important immunological function of the spleen, new techniques to preserve splenic function as fenestration, cystectomy or partial splenectomy may be considered. The authors present the cases of 2 women of 17 and 23 years old in whom dynamic enhanced intravenous contrast computed tomography revealed 2 cystic lesions located in the upper pole of the spleen, measuring 7 and 10 cm in diameter with thin walls and homogenous low-density fluid content. Serology for hydatic cyst was negative. The patients were approached by laparoscopy in a right lateral decubitus position. In the first case, only a small area from the upper part of the cyst was visible, outside the spleen parenchyma, needle aspiration removing clear, yellowish fluid. A partial cystectomy was possible after posterior and superior mobilization of spleen attachments, removing almost two-thirds of the cystic wall with spleen parenchyma around it, to avoid recurrence. In the second case, the cyst was not visible, being completely surrounded by parenchyma. Splenectomy was decided and performed. Both cases evolved uneventfully. Histopathology report indicated epithelial cysts in both cases. The conservative laparoscopic management of large splenic cysts is more difficult when located in the upper pole and almost entirely surrounded by parenchyma. Splenectomy is safer for the patient if the true nature of the cyst could not be established before or during the intervention. KEYWORDS: SPLENIC CYST, CYSTECTOMY, LAPAROSCOPY Correspondence to: Dr. Valeriu urlin, Address: Calea Bucureti A8b 3/10, 200484, Craiova, Dolj, Romania, Tel: 0040740182346, e-mail: vsurlin@gmail.com*
INTRODUCTION Splenic cysts represent a rather rare pathology. They are of different origins, may have different size and may be located in all areas of the splenic parenchyma. Their classic management consists of laparotomy and splenectomy. However, due to important immunologic functions of the spleen and to the advent of laparoscopic splenectomy the approach has become less invasive and their management more conservative, aiming to preserve enough splenic parenchyma to ensure protection against overwhelming infection with encapsulated germs. Correct assessment of the nature of the splenic cyst during preoperative diagnosis and intraoperative exploration is also mandatory to choose the adequate surgical approach for the safety of the patient.
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Our purpose is to present two cases of splenic cysts located in the upper pole of the spleen, managed successfully by laparoscopic approach, aiming to identify the most important issues related to the location, preoperative and intraoperative diagnosis and options for laparoscopic management. CASES PRESENT Case 1 A 17 years old female sex patient was admitted to our surgical unit complaining from pain in the left hypochondria and plenitude for a couple of weeks. There was no particular history of personal and familial diseases. There was no recall of an abdominal trauma or fall. An ambulatory abdominal ultrasonography prior to the admission showed a 7 cm hypoechoic, homogenous cyst in the upper pole of the spleen and no other abnormality. Upon admission, the physical examination was normal, with a BMI of 25. Serum levels of hemoglobin, urea, glycemia were normal, the coagulation profile was also normal, serology for hydatidosis was negative. Pulmonary x-ray didnt show any abnormality. A CT-scan was performed that confirmed the cyst with thin welldefined walls but couldnt distinguish the nature of the cyst. No other visceral anomaly was detected. The patient was considered ASA II and approach by laparoscopy in the right lateral decubitus with the table broken at the level of the flank to increase the space between the ribs and the iliac crest. The optical trocar was placed 2-3 cm left from the umbilicus, on a horizontal line, and a 300 laparoscope was inserted. Peritoneal cavity was inspected and then other trocars were inserted along the inferior margin of the costal ridge a 5 mm trocar in the epigastrium, 10 mm trocar on the anterior axillary line and a 5 mm trocar on the posterior axillary line. Inspection of the spleen revealed at its upper pole a cystic formation with transparent walls with clear yellowish fluid. A puncture using a fine needle introduced percutaneously removed a serous fluid. The diagnosis of a simple serous cyst was made and the decision of a partial cystectomy was made. Using the Ligasure AtlasTM system the cystic wall was incised, the fluid aspirated and much of the cyst removed (Fig. 1). As only 1/3 of it was visible outside the splenic parenchyma it necessitated mobilization of the upper pole of the spleen from its attachments to the diaphragm and removal of some part of the surrounding splenic parenchyma that was in fact reduced to a thin layer (Fig. 1).
Fig. 1 Intraoperative view: incision of the cyst after puncture and eviction of fluid (left); partial pericystectomy including a part of the splenic parenchyma (yellow arrow) using Ligasure AtlasTM (right)
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The postoperative course was simple. The patient was discharged in the 6th postoperative day with recommendation of surveillance of platelet count and vaccination against encapsulated germs. Case 2 A 23 years old female sex patient, complaining from unspecific abdominal pain, plenitude, left lumbar pain was admitted to our surgical unit. She was under antibiotic treatment from her physician for an urinary tract infection. An ambulatory ultrasonography discovered a voluminous splenic cyst of 12 cm located in the upper pole and the patient was immediately referred to surgery. There was no recall of an abdominal trauma or fall or any history of personal or familial diseases. Upon admission there was no peculiar finding in her physical examination, a BMI of 26. Laboratory tests indicated normal levels of the hemoglobin, glycemia, blood urea, normal white blood cell and platelet counts. Serology for hydatidosis was negative. Pulmonary X-ray was normal. A CT-scan was performed showing a 12 cm splenic cyst located in the upper part of the spleen, homogenous, low density content, thin walls. There was no other cystic lesion to detect in the liver or kidneys and no other abnormality. The patient was considered ASA II and approach by laparoscopy using the same setup as in the first case. The exploration of the peritoneal cavity didnt find any other associated disease. The spleen was enlarged, especially at the level of its superior pole but there was no visible cyst (Fig. 2).
Fig.2 Intraoperative view: extraction of the resected cyst (yellow arrow)with a part of the splenic parenchyma (blue arrow)
A posterior mobilization of the spleen was performed but there wasnt any part of the cyst that we could saw and appreciate. As it was impossible to establish the nature of the cyst, the splenectomy was decided. This was performed by step by step sealing and dividing of the splenic vessels in the hilum using the Ligasure AtlasTM. The spleen was extracted into a plastic bag by a 5 cm horizontal incision in the left hypocondrium. Upon morcellation and extraction it became evident that the cyst was again a simple serous cyst with no vegetations inside.
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The postoperative course was uneventful and the patient was discharged in the 7th postoperative day with the same recommendations of vaccinations and surveillance of her platelet count. DISCUSSIONS Splenic cysts classify are classified as: parasitic and non-parasitic that can be primary (epithelial:epidermoid, dermoid, mezothelial; endothelial: hemangioma, lymphangioma) or secondary (pseudocyst: post-traumatic, hemorrhagic;infectious, degenerative) [1-4]. Splenic cysts represent a rather rare disease with around 800 cases reported in the literature [5,6]. Most of those cases are parasitic cyst, non-parasitic cyst representing thus only 300 cases [6]. The majority (50-75%) are pseudocysts, secondary to trauma [7,8]. The rest, representing 30% to 40%, are primary splenic cysts [9,10]. From them, true non-parasitic cysts (with an epithelial lining) account for no more than 10% [7,8]. Splenic cysts may remain asymptomatic in 30-60% of the cases and their discovery may be incidental on radiographs if calcifications are present and on abdominal ultrasonography or CT-scan. They may induce local or referred pain, often postural. In case of large cyst, the patient may present abdominal distension, early satiety, vomiting, dysphagia, atelectasis or left lower lobe pneumonia [11]. In both our cases, the patients presented unspecific abdominal pain in the left hypocondria, early satiety and fullness that imposed imagistic investigation that ended up in the discovery of the cyst. The true nature of the cyst is generally difficult to establish preoperatively. In developing countries, like ours, the most frequent is the parasitic aetiology. Differential diagnosis should include cystic lesions of adjacent organs, as pancreas, liver and omentum, intrasplenic aneurysm and benign and malignant splenic tumors [11]. Patient history (age, gender, and history of trauma, acute or chronic pancreatitis) could be of some help but is not very reliable. Both our patients excluded trauma and pancreatitis but both came from the countryside and stated having domestic animals at home, situation that expose her to risk of contamination with echinococcus granulosis. Both our cases had complete abdominal and thoracic plain radiographs, abdominal ultrasonography and CT-scan. Ultrasound or CT scan may help in determining the cyst type but they cannot be 100% precise. Parasitic cysts have some radiographic and sonographic characteristics but preoperative differentiation between epithelial-lined and pseudocysts is not reliable [12]. Ultrasonographic and CT appearances of splenic hydatidosis are not specific, similar aspects being seen in other splenic cystic lesions, such as an epidermoid cyst, splenic abscess, pseudocyst, or cystic neoplasm of the spleen. Splenic cysts are usually located entirely within the spleen, contrary to hepatic or renal cysts which may have a consistent part outside the parenchyma. Calcifications in the walls are more related to a pseudocyst, that could have also debris and echoic contents due to infection or hemorrhage. Internal septation is more frequent in true cysts [13]. The presence of daughter cysts in a large cystic lesion or concomitant cystic lesions in the liver or other organs is highly suggestive of hydatic cyst. In patients with negative serology and determinant US and CT examinations, recent publications advocate the role of MRI. It seems that this diagnostic tool may help differentiate between parasitic, non-parasitic, traumatic or other unilocular cysts. Newer application
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of functional MRI could be even more effective in differentiating parasitic from nonparasitic cysts [14] but it wasnt performed. Serology for hydatidosis was negative in both cases but this not a reliable test to exclude because of its low sensibility and specificity [15]. The final diagnosis was postponed for intraoperative exploration. Generally, more informations could be obtained intraoperatively when we can assess the macroscopic aspect of the cyst, we can obtain cyst fluid to analyse and samples from the cyst wall to perform a frozen section. The most exact diagnosis can be established only postoperatively, when pathologic examination of the entire cyst wall can be performed [16]. Indications for therapy are not very precise in the literature, but are grounded on symptoms and dimensions. Most of the authors consider that a symptomatic splenic cyst presents a high risk for rupture and therefore an absolute indication for therapy [9]. A cyst larger > 5cm is considered at risk for rupture and hemoperitoneum [5] and less suitable for spontaneous resolution [8] and therefore constitutes an indication for therapy. Others consider that a minimum of 4 cm in the greater diameter should mandate immediate therapy [17]. However, there is a contradictive report in the literature by a congenital epithelial cyst of the spleen of 3x6 cm that underwent progressive regression in a period of 10 years of follow-up [18]. Formal objectives of the therapy are eradication of the cyst and the prevention of the recurrence. Modalities of the treatment are represented by traditional laparotomy, laparoscopy and percutaneous aspiration guided by the US/CT scans. Simple percutaneous aspiration guided by US/CT-scans has a relapse risk rate of 100% [19]. Lopez Cano et al [20] report percutaneous aspiration of an epithelial splenic cyst and sclerosing with alcohol with no recurrence at 4 years follow-up. Anon et al [21], using also alcohol, obtain no recurrence at 1 year follow-up. Shimanuki et al [22] report no recurrence at 1 year follow up using minocycline chloride. In a review, percutaneous aspiration and sclerosing with alcohol or tetracycline did not result in long term control [23]. The reference in the elective treatment of any splenic cyst, including epithelial cysts, was considered laparotomy + splenectomy [9,24]. The alternative are conservative methods [10,24] consisting in partial splenectomy, cystectomy or fenestration of minimal 3 cm diameter [25], that are indicated in children and young adults because avoid the risk of fulminant sepsis. Both splenectomy and the conservative procedures could be applied through laparoscopy, whether is pure laparoscopy or hand-assisted. The advantage of laparoscopy is already known and generally accepted in better cosmetic, quicker recovery, reduced postoperative pain and immune depression, lower parietal morbidity. Kum et al [26] in 1993 reported a laparoscopically assisted splenectomy for a wandering splenic cyst. Decapsulation or deroofing of the splenic cyst is by far the simplest method to treat the splenic cysts. Its feasibility and safety was shown in many reports. Posta et al [27] in 1994 reported on a splenic cyst treated laparoscopically with aspiration of the cyst contents and excision of a portion of external cyst wall. In 1995, Targarona et al [28] reported on a similar laparoscopic approach to treatment of a splenic cyst. In 2010, the same author published a similar technique using single incision laparoscopic surgery with access through the umbilicus [29]. Seshadri et al [30] reported the decapsulation of a symptomatic 10-cm epithelial cyst by needlescopic instruments (3 mm or smaller).
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Three trocars were used: one 12-mm umbilical and two 3-mm subcostal ports. The cyst was punctured by a Veress needle, and after drainage of straw-colored fluid, circumferential decapsulation with 5-mm laparoscopic shears through the umbilical port site was done. In those reports the decapsulation was done with monopolar scissors, bipolar or harmonic scalpel [31]. Sellers et al [8] report on using a laparoscopic GIA device. He stated that the use of such device reduces the risk of intraoperative and postoperative bleeding from the resected cyst wall, especially in a vascularized epithelial lined cyst. In our experience this was easily and safely done by using Ligasure Atlas of 10 cm. It was possible to go even through a part of the splenic parenchyma to resect more of the cystic wall. There is no exact evidence about how much to resect from the cystic wall to prevent recurrence. Morgenstern et al [7] did not differentiate between a near-total cystectomy and decapsulation, and the message seems to be that as much of the cystic wall as possible should be resected to prevent reclosure. There is also less evidence about what should be done in case of important remnant cavity. Some authors advocate plication [32] but this is difficult and dangerous in laparoscopy. In a study by Mertens et al [16] decapsulation (resection of the cystic wall outside the splenic parenchyma) with omental flap packing of the remnant cavity performed by laparotomy was followed by recurrence in 4 patients of 7 in a long termfollow up 37,5 months. Only one needed treatment the other 3 with a diameter of less than 3 cm and asymptomatic were not considered for therapy. Partial splenectomy preserves more than 25% of splenic parenchyma, which is the minimal splenic tissue to preserve immunologic protection without increasing the risk of recurrence. Partial splenectomy can be performed safely with the laparoscopic approach [2,31,33]. In the first case we were able to establish the true nature of the cyst intraoperatively based on the aspect of the cysts walls and cysts fluid. Almost one third of it was located outside the splenic parenchyma but near half of it was resected after mobilising the upper pole of the spleen and cutting through the parenchyma. In the second case we couldnt see the cyst, not even after posterior mobilization of the splin, because it was completely surrounded by the splenic parenchyma. In this case we decided that the safest attitude for the patient was the splenectomy. This is supported by the following arguments: - suspicion of a hydatid cyst incompletely excluded; increased use of laparoscopic techniques and spillage of cystic fluid during carelessly-performed operations results in the increase in the recurrence of hydatic disease. - if the cyst was to be a hydatid cyst, Ahmad et al [34] maintain that splenectomy remains the procedure of choice in cases of splenic hydatidosis and Durgun et al [35] sustain that splenectomy without the puncture of the cyst is preferable. any type of conservative procedure is difficult to perform, if the cyst is very large, or is covered completely by the splenic parenchyma (intrasplenic cyst). In these cases, Macheras et al [6] recommend complete splenectomy. CONCLUSIONS Non-parasitic splenic cysts are a rare pathology. Choice between laparoscopic conservative procedures or splenectomy is made upon reliable preoperative and intraoperative diagnosis of the true nature of the cyst.
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Aknowledgments: this paper was presented as a poster (P459) at the E.A.E.S. Congress in Geneva 16-19 June 2010.
REFERENCES 1. Reddi MK, Srinivas B, Sekhar CC, Ramesh O. Mesothelial splenic cyst-a case report. Ann Acad Med Singapore 1998; 27(6): 880-882. 2. Heidenreich A, Canero A, di Pasquo A. Laparoscopic approach for treatment of a primary splenic cyst. Surg Laparosc Endosc 1996, 6(3): 243-246. 3. Trompetas V Panagopoulos E, Priovolou-Papaevangelou M, Ramantanis G. Giant benign true cyst of the spleen with high serum level of CA 19-9. Eur J Gastroenterol Hepatol 2002; 14(1): 85-88. 4. Labruzzo C, Haritopoulos KN, Tayar AR, Hakim NS. Posttraumatic cyst of the spleen: A case report and the review of the litterature, Int Surg 2002; 87(3): 152-156. 5. Geraghty M, Khan IZ, Conlon KC. Large primary splenic cyst a laparoscopic technique, Journal of Minimal Access Surgery 2009, 5(1): 14-16. 6. Macheras A, Misiakos EP, Liakakos T, Mpistarakis D, Fotiadis C, Karatzas G. Non-parasitic splenic cysts: A report of three cases. World J Gastroenterol 2005; 11(43): 6884-6888. 7. Morgenstern L. Nonparasitic splenic cysts: pathogenesis, classification and treatment. J Am Coll Surg 2002; 194(3): 306314. 8. Sellers GJ, Starker PM. Laparoscopic treatment of a benign splenic cyst, Surg Endosc 1997; 11(7): 766-768. 9. Hansen M, Moller A. Splenic cysts. Surg Laparosc Endosc Percutan Tech 2004, 14(6): 316-322. 10. Ough YD, Nash HR, Wood DA. Mesothelial cysts of the spleen with squamous metaplasia. Am J Clin Pathol 1981; 76(5): 666-669. 11. Williams RJLI, Glazer G. Splenic cysts: changes in diagnosis, treatment and aetiological concepts. Ann R Coll Surg Engl. 1993; 75(2): 87-89. 12. Dachman AH, Ros PR, Murari PJ, Olmsted WW, Lichtenstein JE. Nonparasitic splenic cysts: a report of 52 cases with radiologic pathologic correlation. Am J Roentgenol 1986; 147: 537542. 13. Chen MJ, Huang MJ, Chang WH, Wang TE, Wang HY, Chu CH, Lin SC, Shih SC. Ultrasonography of splenic abnormalities. World J Gastroenterol 2005; 11(26): 4061-4066 14. Polat P, Kantarci M, Alper F, Suma S, Koruyucu MB, Okur A. Hydatid disease from head to toe Radiographics. 2003, 23(2):475-94. 15. Milicevici MN. Hydatid disease In Blumgart LH, Fong Y. eds. Surgery of the Liver and Biliary Tract, London, WB Saunders. 2000; p.116. 16. Mertens J, Penninckx F, DeWever I, Topal B. Long-term outcome after surgical treatment of non-parasitic splenic cysts, Surg Endosc 2007; 21(2): 206-208. 17. Pampaloni F, Valeri A, Mattei R, Presenti L, Noccioli B, Tozzini S, Di Lollo S, Pampaloni A. Laparoscopic decapsulation of a large epidermoid splenic cyst in a child using the UltraCision LaparoSonic Coagulating Shears. Pediatr Med Chir. 2002; 24(1): 59-62. 18. Stoidis CN, Spyropoulos BG, Misiakos EP, Fountzilas CK, Paraskeva PP, Fotiadis CI. Spontaneous regression of a true splenic cyst: a case report and review of the litterature, Cases Journal 2009, 2: 8730 19. Wu H, Kortbeek J. Management of splenic pseudocyst following trauma: A retrospective case series. Am J Surg 2006;191(5): 631-634. 20. Lpez Cano A, Muoz Benvenuty A, Mndez Prez C, Herrera M, Ortiz Acero I, Benvenuty Espejo R. Treatment of non-parasitic splenic cyst with percutaneous injection of alcohol. Gastroenterol Hepatol. 2001; 24(4): 199-201. 21. Aon R, Guijarro J, Amoros C, Gil J, Bosca MM, Palmero J, Benages A. Congenital splenic cyst treated with percutaneous sclerosis using alcohol. Cardiovasc Intervent Radiol. 2006; 29(4): 691-693. 22. Shimanuki K, Satake M. Non-surgical treatment of splenic cyst, using with installation of minocycline chloride. Fukushima J Med Sci. 1996; 42(1-2): 23-30. 23. Moir C, Guttman F, Jequier S, Sonnino R, Youssef S. Splenic cysts: aspiration, sclerosis, or resection. J Pediatr Surg 1989; 24: 646648. 24. Smith ST, Scott DJ, Burdick JS, Rege RV, Jones DB. Laparoscopic marsupialization and hemisplenectomy for splenic cysts. Journal of Laparoendosc Adv Surg Tech 2001, 11(4): 243-249.
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25. Salky B, Zimmerman M, Bauer J, Gelernt I, Kreel I. Splenic cystdefinitive treatment by laparoscopy. Gastrointest Endosc 1985; 31(3): 213215. 26. Kum CK, Ngoi SS, Goh P, Lee YS, Gopalan R. A rare wandering splenic cyst removed with laparoscopic assistance. Singapore Med J 1993; 34: 179180. 27. Posta CG. Laparoscopic management of a splenic cyst. J Laparoendosc Surg 1994; 4(5): 347354. 28. Targarona EM, Martinez J, Ramos C, Becerra JA, Trias M. Conservative laparoscopic treatment of a posttraumatic splenic cyst. Surg Endosc 1995; 9(1): 7172. 29. Targarona EM, Pallares JL, Balague C, Luppi CR, Marinello F, Hernndez P, Martnez C, Trias M. Single incision approach for splenic diseases: a preliminary report on a series of 8 cases. Surg Endosc. 2010; 24(9): 2236-2240. 30. Seshadri PA, Poulin EC, Mamazza J, Schlachta CM. Needlescopic decapsulation of a splenic epithelial cyst. Can J Surg. 2000; 43(4): 303-305. 31. Till H, Schaarschmidt K. Partial laparoscopic decapsulation of congenital splenic cysts A medium-term evaluation proves the efficiency in children Surg Endosc 2004; 18(4): 626628. 32. Palanivelu C, Rangarajan M, Madankumar MV, John SJ. Laparoscopic internal marsupialization for large nonparasitic splenic cysts: effective organ preserving technique. World J Surg 2008; 32(1): 20-25. 33. Tomulescu V, Stnciulea O, Blescu I, Vasile S, Tudor S, Gheorghe C, Vasilescu C, Popescu I. First year experience of robotic-assisted laparoscopic surgery with 153 cases in a general surgery department: indications, technique and results. Chirurgia 2009; 104(2): 141-150. 34. Dar MA, Shah OJ, Wani NA, Khan FA, Shah P. Surgical Management of Splenic Hydatidosis. Surg Today 2002; 32(3): 224-229. 35. Durgun V, Kapan S, Kapan M, Karabiak I, Aydogan F, Goksoy E. Primary splenic hydatidosis. Dig Surg 2003; 20(1): 38-41.
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BECKWITH-WIEDEMANN SYNDROME WITH CLEFT PALATE

S. Dey1, B. Kharga1, B. Dhar2, V.K. Singh1, R. Dey3 1. Department of Surgery, Sikkim Manipal Institute of Medical Sciences, India. 2. Department of Surgery, The Mission Hospital, Durgapur, West Bengal, India. 3. Department of Physiology, Sikkim Manipal Institute of Medical Sciences, India.
BECKWITH-WIEDEMANN SYNDROME WITH CLEFT PALATE (ABSTRACT): BeckwithWiedemann syndrome is a rare congenital disorder. Early diagnosis, proper counselling of parents is essential because of significant risk of subsequent development of malignant tumours, associated with this syndrome. Association of cleft palate in this syndrome is extremely rare. Specific difficulties and risks posed by the craniofacial abnormalities like macroglossia and cleft palate are highlighted and discussed along with the management options. The literature is reviewed and discussed. KEY WORDS: BECKWITH-WIEDEMANN SYNDROME, CLEFT PALATE, OMPHALOCELE Correspondence to: Dr. Subhajeet Dey. MBBS, MS. Department of Surgery, Sikkim Manipal Institute of Medical Sciences. 5th Mile, Tadong, Gangtok-737102. Sikkim. India. Phone-00913592271060. 00919434755078. Email: subhajeetd@gmail.com*.
INTRODUCTION Beckwith Wiedemann Syndrome (BWS) is a rare congenital disease of low prevalence independently recognised by Beckwith in 1963 and Wiedemann in 1964. Association of this syndrome with cleft palate is even rarer. Surgical corrections of the craniofacial abnormalities pose significant and specific challenges. CASE REPORT A term, large for gestational age female baby was born to 29 years old primi, which had undergone antenatal checkups outside and was referred to this hospital for non progress of labour, through Caesarian section on 04/09/2007. The baby weighed 4500 grams (>95th centile), with head circumference of 36 cm. (>75th centile) and length of 55 cm. (>95th centile). The APGAR score was 5 at 1 minute and 10 at 5 minutes. The notable congenital anomalies were omphalocele with intact sac, macroglossia with protruding tongue (Fig. 1), short neck and linear indentations of ear lobule with posterior helical pits (Fig. 2), nevus flammeus and cleft palate (Fig. 3). The baby had an episode of generalized tonic clonic convulsion; blood sugar estimated at that time was 45 mg%. Euglycemia was attained and subsequently maintained by intravenous dextrose infusion. A clinical diagnosis of Beckwith-Wiedmann syndrome was made on the basis of these clinical features. Omphalocele was dressed with sterile vaseline gauze and pads and baby started on parenteral antibiotics, put on IV fluid and nasogastic decompression. The baby passed meconium within 24 hours of birth.
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Subsequent investigations included haematology, renal function tests, serum electrolytes including calcium, liver function tests, CRP, blood culture and all were within normal limits. Ultrasonography of whole abdomen, CT scan of cranium and brain and echocardiography did not reveal any abnormality.
Fig. 1 Omphalocele with macroglossia
Fig. 2 Indentations of ear lobule with posterior helical pits
Fig. 3 Cleft palate
Parents did not have any feature of the syndrome. Both the parents were counselled and educated about the syndrome, regarding hypoglycaemia with possible risks of neurological consequences and its prevention, subsequent risk of tumours of solid organs. They were also counselled regarding the small risk during the subsequent pregnancies. The child underwent a successful primary fascial repair of the omphalocele under general anaesthesia with endotracheal intubation and intraoperative plasma glucose monitoring, two days after admission. 102
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The post operative period was uneventful and was discharged on the 20th post operative day once parents were confident about the feeding techniques for the child. The child underwent repair of the cleft palate and release of ankyloglossia under general anaesthesia at the age of 11 months. The follow up of the child till age of two and half years with serial ultrasound examinations of the abdomen did not reveal any evidence of solid tumours. The child has difficulty in articulation and is under speech therapy. DISCUSSION Beckwith-Wiedemann syndrome is a clinical diagnosis, criteria for diagnosis being presence of three major findings (macroglossia, pre- or post natal growth greater than 90th percentile and abdominal wall defects) or two major plus minor manifestations (ear creases or pits, facial neavus flammeus, hypoglycemia, nephromegaly, hemihypertrophy) [1]. Association of cleft palate as a part of the syndrome is extremely rare and very few cases have been reported [2,3]. The genetics of this syndrome is complex, imprinted genes of chromosome 11p15 have been implicated in both familial and sporadic varieties. Paternally derived duplications of chromosome 11p15 and maternally inherited inversions or balanced translocations may be associated this syndrome [4]. The children with this syndrome have increased risk of developing subsequent neoplasia like Wilms tumour, hepatoblastoma, neuroblastoma, rhabdomyosarcoma, adrenocortical carcinoma, estimated to be around 7.5% in the first eight years of life, rarely after 10 years of age [5]. Airway management with craniofacial abnormalities like macroglossia compounded by presence of cleft palate in Beckwith-Weidemann syndrome poses serious challenges. The normal bony and soft tissue anatomy is altered; the anaesthesiologist must be aware and familiar with it [6]. Difficulty in bag/mask ventilation and endotracheal intubation following the induction of anaesthesia and muscle paralysis is to be anticipated, so preparations for a difficult airway management need to be considered before induction [7]. Surgical correction of cleft palate in a patient of Beckwith-Weidemann syndrome is advisable after the age of six months before the speech development process starts [2]. The enlarged tongue has both functional and cosmetic deformity, which may affect the oral airway, speech, and the development of the jaws. Tongue reduction surgery is advocated, preferably to precede the cleft palate repair or may be combined with the palate surgery to reduce the repeated anaesthetic procedural risk. Articulation errors have been reported by various investigators due to the craniofacial abnormalities in Beckwith-Weidemann syndrome. However data are limited as to define the nature of the articulation problems. In a study of 40 patients of Beckwith-Weidemann syndrome with macroglossia, 29 of them had articulation errors, and it persisted in some after corrective surgery [8]. A phonetic analysis of patients of Beckwith-Wiedemann syndrome with macroglossia revealed the affection of consonants with an anterior place of articulation, related to inappropriate tongue and lip postures. An observer experiment conducted, in which naive and expert observers rated speech samples from three modes of presentation (auditory-only, visual-only, and audiovisual), showed that the subjects' speech was more disturbed visually than auditorily [9].
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Phonetic and articulation errors are also known to occur after a cleft palate repair. Hypernasality, weak pressure consonants, nasal escape may indicate incompetent nasopharyngeal sphincter. Dental malocclusion with repaired clefts involving the alveolar ridge will distort the sounds s z ch j, sh, zh. Good improvement is usually noticeable after about three months of regular weekly sessions of speech therapy with a young child of average intelligence [10]. The value of tongue volume reduction surgery for improvement of speech needs prospective assessment and that the adequacy of direct articulation therapy in Beckwith-Wiedemann Syndrome needs to be evaluated [9]. It is also suggested that social environment can also be a contributing factor for development of phonation and articulation [2]. CONCLUSIONS Beckwith-Wiedemann syndrome is a rare congenital disorder. Early diagnosis is essential because of the significant risk of subsequent development of malignant tumours, associated with this syndrome. Association of cleft palate in this syndrome is extremely rare. The treatment of patients with cleft palate and Beckwith-Wiedemann syndrome are difficult and represents a challenge for surgeon.
REFERENCES 1. Elliot M, Bayly R, Cole T, Temple IK, Maher ER. Clinical features and natural history of Beckwith- Wiedemann syndrome: presentation of 74 new cases. Clin Genet.1994; 46(2): 168-174. 2. Laroche C, Testelin S, Devauchelle B. Cleft palate with Beckwith-Wiedemann syndrome. Cleft Palate Cranifac J. 2005; 42(2): 212-217. 3. Takato T, Kamei M, Kato K, Kitano I. Cleft palate in Beckwith- Wiedemann syndrome. Ann Plast Surg. 1989; 22(4): 347-349. 4. Brown KW, Gardner A, Williams JC, Mott MG, McDermott A, Maitland NJ. Paternal origin of 11p15 duplication in Beckwith Wiedemann syndrome. A new case and review of literature. Cancer Genet Cytogenet. 1992; 58(1): 66-70. 5. Wiedemann HR. Frequency of Wiedemann-Beckwith syndrome in Germany; rate of hemihyperplasia and of tumours in affected children. Eur J Pediatr. 1997; 156(3): 251. 6. Nargozian C. Airway in patients with craniofacial abnormalities. Paediatr Anaesth. 2004; 14(1): 53-59. 7. Kim Y, Shibutani T, Hirota Y, Mahbub SF, Matsuura H. Anesthetic considerations of two sisters with Beckwith-Wiedemann syndrome. Anesth Prog. 1996; 43(1): 24-28. 8. Van Borsel J. Notes and Discussion Macroglossia and speech in Beckwith-Wiedemann syndrome: a sample survey study. International Journal of Language & Communication Disorders 1999; 34(2): 209-221. 9. Van Borsel J, Morlion B, Van Snick K, Leroy SJ. Articulation in Beckwith-Wiedemann syndrome: Two case studies. Am J Speech Lang Pathol. 2000; 9: 202-213. 10. Renfrew EC. The role of speech therapists with cleft palate patients. Proc R Soc Med. 1976; 69(1): 3132.
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POLIPOZA HAMARTOMATOAS ENTERAL DEGENERAT MALIGN - PREZENTARE DE CAZ

N. Al Hajjar, Terezia Murean, L. Vlad, C. Iancu, Raluca Bodea, P. Boruah, Angela Pru, A. Coe, Roxana Olteanu Clinica Chirurgie III UMF Iuliu Haieganu, Cluj-Napoca, Romnia
MALIGNANT DEGENERATION OF HAMARTOMATOUS ENTERAL POLYPOSIS A CASE REPORT (ABSTRACT): Intestinal hamartomatous polyps represent a rare cause of proximal bowl obstruction and hemorrage in adults. Till 2009, there were cited less than 15 cases in the literature. Here we present the clinical observation of a patient, admitted in our clinic with the clinical diagnosis of proximal bowl obstruction, accompanied by upper digestive hemorrhage exteriorized through hematemesis, where the surgical intervention performed had showed the presence of an intestinal invagination developed upon an enteral polypod mass, along with some other enteral intraluminal polypoid masses, having different sizes, and were distributed upon a distance of 60 cm from the ligament of Treitz. A segmental eneterectomy keeping in view of the oncologicaly safety margins was performed, along with an end-to-end enetero-enteral anastomosis to restore the bowel continuity. The histopathological exam of the specimen revealed the presence of some hamartomatous polyps, along with the development of a tubular adenocarcinoma at the level of one of these polyps. Association of enteral hamartomatous polyps with enteral carcinoma and the possibility of their malignant transformation is a matter of debate in the literature, where there can be found debates supporting as well as debates negating this theory. KEY WORDS: INTESTINAL HAMARTOMATOUS POLYPS, MALIGNANT TRANSFORMATION, ENTERAL ADENOCARCINOMA. Coresponden: Dr. Nadim Al Hajjar. Clinica Chirurgie III. Str. Croitorilor, nr. 19-23, 400162, ClujNapoca. Tel. 0264-431.759. e-mail: na_hajjar@yahoo.com*.
INTRODUCERE Polipii hamartomatoi enterali reprezint cauze rare de ocluzie intestinal nalt i hemoragie digestiv superioar la adult. n 1982 Fernando i McGroven au definit polipii hamartomatoi enterali din punct de vedere histologic ca fiind proliferri hiperplazice ale elementelor structurale ale peretelui intestinului subire (musculatur neted, filete nervoase periferice nemielinizate, vase sangvine, ganglioni limfatici) [1]. Pn n anul 2009 au fost citate n literatura de specialitate mai puin de 15 cazuri de polipi hamartomatoi enterali [2]. Depistarea acestor entiti anatomo-clinice se face n marea majoritate a cazurilor intraoperator, deoarece examenul clinic i examinrile paraclinice nu furnizeaz date specifice. Diagnosticul de polipoz enteral se pune intraoperator, examenul histopatologic fiind cel care confirm existena polipozei hamartomatoase. Transformarea malign a polipilor hamartomatoi enterali este un subiect de disput n literatura de specialitate. Unii autori contest aceast posibilitate, pe cnd alii susin c ar fi posibil, cu o frecven redus de pn la 3 % [3].
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PREZENTARE DE CAZ Prezentm cazul unei paciente n vrst de 50 de ani, fr antecedente personale patologice semnificative, care a fost internat de urgen n serviciul Clinicii Chirurgie III, Cluj-Napoca, cu urmtoarele simptome: dureri intense n etajul abdominal superior, greuri, vrsturi bilioase i poracee, urmate de hematemez, distensie abdominal marcat. Analizele de laborator au relevat anemie (Hb=10,1g/dL), diselectrolitemie marcat (Na seric 129 mEq/L i K seric 2.7 mEq/L) i leucocitoz. S-a iniiat un program de reechilibrare hidroelectrolitic i acidobazic. Ecografia abdominal a decelat o mas tumoral stenozant la nivel enteral. Endoscopia digestiv superioar efectuat n urgen a relevat hernie hiatal axial, esofagit clasa A Los Angeles, gastrit de reflux. S-a decis efectuarea unui examen computer-tomografic cu substan de contrast al abdomenului i pelvisului, care a evideniat o mas tumoral cu diametru de aproximativ 7 cm diametru, care se umple dup administrarea oral a substanei de contrast. Avnd n vedere examenul clinic i datele paraclinice, s-a decis efectuarea unei laparotomii exploratorii. Intraoperator s-a decelat o invaginaie intestinal pe o formaiune polipoid enteral conopidiform i multiple alte formaiuni polipoide enterale, de diferite dimensiuni, ntinse pe o distan de 60 cm de la unghiul Treiz (Fig. 1). S-a luat decizia efecturii unei enterectomii extinse cu anastomoz enteroenteral termino-terminal.
Fig. 1 Aspecte intraoperatorii - zona de invaginaie intestinal
Evoluia postoperatorie a pacientei a fost marcat de apariia unei supuraii a plgii postoperatorii, cu evoluie favorabil sub tratament conservator. Pacienta a fost externat ameliorat din punct de vedere chirurgical la 11 zile dup intervenia chirurgical.
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Examenul histopatologic al piesei de rezecie a relevat un aspect corespunztor unei polipoze hamartomatoase enterale, cu polipi de 1-4 mm, dispersai pe ntreaga suprafa a intestinului rezecat (Fig. 2), cu aspect tipic de proliferare hamartomatoas (fascicule musculare din musculara mucoasei, fibre nervoase nemielinizate cu celule ganglionare, vase cu aspect de hemangiom). La nivelul zonei de invaginaie s-a evidentiat un polip hamartomatos enteral care prezenta zone de degenerare malign sub forma unui adenocarcinom tubular bine difereniat, pT2NxMxG1L0V0.
Fig. 2 Aspectul pe seciune al piesei de rezecie
Pacienta s-a prezentat n serviciul nostru la o lun postoperator i a fost ndrumat spre un serviciul de oncologie unde a urmat 6 cicluri de chimioterapie cu 5fluorouracil i mitomicina C. La controalele clinice i imagistice efectuate la 3 i 6 luni postoperator pacienta nu prezenta semne de recidiv tumoral sau diseminare la distan. DISCUII Cazul prezentat readuce n discuie o patologie rar, polipoza hamartomatoas enteral. Dei Fernando i McGroven au definit histologic polipii hamartomatoi enterali ca fiind prolioferri hiperplazice ale esuturilor normale ale peretelui enteral (hamartoame neuromusculare i vasculare), exist autori care susin c aceste proliferri aparin spectrului de manifestri al bolii Crohn [3]. Astfel, hiperplazia fibrelor muscular netede i a filetelor nervoase, precum i vasele cu aspect de hemangiom, pot s apar i n boala Crohn, ns aceasta este caracterizat de prezena unor aspecte patognomonice: inflamaie transmural, prezena granuloamelor i a ulcerelor liniare, aspecte care lipsesc cu desvrire la nivelul polipilor hamartomatoi enterali. Exist autori care susin c polipii hamartomatoi enterali sunt leziuni premaligne, dei aceast transformare survine foarte rar (n sub 3% din cazuri). Polipii hamartomatoi enterali reprezint de fapt zone de proliferare celular intens, la nivelul crora pot surveni la un moment dat mutaii, iar transformarea malign s survin trecnd printr-o etap intermediar de displazie [4,5].
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CONCLUZII Dei diagnosticarea polipilor hamartomatoi enterali este cel mai frecvent fcut postoperator, atunci cnd intraoperator se ridic suspiciunea unei polipoze hamartomatoase enterale, susinem c este de preferat o atitudine chirurgical radical, n limite de siguran oncologic, avnd n vedere c transformarea lor malign poate surveni la un moment dat.
1. 2. 3. 4. BIBLIOGRAFIE Fernando SS, McGovern VJ. Neuromuscular and vascular hamartoma of small bowel. Gut. 1982; 23(11): 1008-1012. Theodosiou E, Voulalas G, Salveridis N, Pouggouras K, Manafis K, Christodoulidis K. Neuromesenchymal hamartoma of small bowel .- an extremely rare entity: a case report. World J Surg Oncol. 2009; 7: 92. 3.Shepherd NA, Jass JR. Neuromuscular and vascular hamartoma of the small intestine: is it Crohns disease? Gut. 1987; 28(12): 1663-1668. Aneiros J, Matamala M, Garcia del Moral R, Lopez JJ, Aguilar D, Camara M. Hamartomatous solitary polyp with malignant progression in the jejunum. A histochemical and immunohistochemical study by light and electron microscopy. Acta Pathol Jpn. 1988; 38(8): 1031-1040. Perzin KH, Bridge MF. Adenomatous and carcinomatous changes in hamartomatous polyps of the small intestine (Peutz-Jeghers syndrome): report of a case and review of the literature. Cancer 1982; 49(5): 971983.
5.
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CARBAPENEM-RESISTANT ACINETOBACTER BAUMANNII POSTOPERATIVE MENINGITIS

Laura Ghibu, Egidia Miftode, Olivia Dorneanu, Carmen Dorobat Clinic of Infectious Diseases Gr. T. Popa University of Medicine and Pharmacy Iasi
CARBAPENEM-RESISTANT ACINETOBACTER BAUMANII POSTOPERATIVE MENINGITIS (ABSTRACT): Acinetobacter baumannii is an opportunistic pathogen of increasing relevance in hospital infections during the last 15 years.This organism causes a wide range of infection .Extensive use of antibiotics within hospitals has contribute to the emergence of multidrug-resistent A.baumannii strains that exhibit resistance to a wide range of antibiotics ,including carbapenems.We report the case of an 37 years old man diagnosed with Acinetobacter multidrug-resistant post-neurosurgical meningitis with fatal outcome. KEY WORDS: POSTOPERATIVE MENINGITIS, MULTIDRUG-RESISTANT ACINETOBACTER BAUMANNII. Correspondence to: Laura Ghibu MD, Clinic of Infectious Diseases, Iasi, e-mail: ghibulaura@yahoo.com*
INTRODUCTION Acinetobacter baumannii is an opportunistic germ of clinical importance in continuous boost for the last 15 years, which can determine a big number of infections: sepsis, pneumonias, plague infections, urinary tract infections and post-operation meningitis, especially in the patients of the intensive care units [1]. The emergence of resistance of Acinetobacter to a wide range of antibiotics makes these infections almost impossible to treat. CASE PRESENTATION We would like to present the case of a patient of 37 years old, hospitalized twice in our clinic through transfer from the Neurosurgery Hospital in February and April 2005. This youngster was the victim of a labor accident in February 2005, which resulted into craniocerebral injury, right frontal and orbital sinus, for which it was preceded surgically. Postoperative, after 24 hours, the patient presents fever, the lumbar puncture showing pleiocitosis thus being transferred to the Clinic of Infectious Diseases, with the suspicion of bacterial meningitis. At his first hospitalization (in February 2005): patient was in vegetative status, tube fed. The lumbar puncture presents milky cephalorachidian liquid, with 1500 elements/mmc, with PN prevalence. The fever occurrence immediately after the surgery indicates the suspicion of post-traumatic meningitis and not a nozocomial meningitis and it was initiated a treatment in association with 3rd generation Cefalosporine and Ciprofloxacin. In his 8th day of hospitalization the patient presents convulsions at the level of his right hemicorpus.
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He is evaluated again in the Neurosurgical Clinic and a new surgical intervention is done to solve the cranionasal fistula and in order to evacuate a left parietal hematoma. The evolution is aggravated by incidence of a stercoral peritonitis through the rectum rupture for which it was surgically performed a temporary colostomy. During all this time he received treatment with 3rd generation Cefalosporine, Fluoroquinolone and Metronidazol. The patient becomes feverish, the lumbar puncture presents milky cephalorachidian liquid (LCR), and the cerebral CT examination indicates: bilateral hemispheric diffuse edema, contrast clutch with aspect of epidural and epicranial biconvex lens at the level of the left frontal craniotomy area (aspect of meningo-encefalitis and non-surgical epiduritis at that specific moment). The patient returns to our clinic for further investigations and treatment. At the moment of the hospitalization the patient was in a serious general condition, with obstruction in the tracheo-bronchial area, requires oxygen and frequent aspiration of the tracheo-bronchial areas. The lumbar puncture presents milky purulent cephalorachidian liquid (LCR), with intense inflammatory reaction. At the direct examination there was observed Gram-negative diplococci and coco bacillus. Given the patient status, the multiple surgical interventions and the anterior prolonged treatment with antibiotics it was supposed the implications of several germs with multiple resistance to antibiotics and it was proceeded to the treatment with Vancomycin 1g/day and Meropeneme 3g/day The cultures obtained from the cephalorachidian liquid were positive for Acinetobacter baumannii and the resistance profile of the stem had raised serious problems when choosing the accurate treatment. Acinetobacter baumannii provided resistance to ampicilline, amoxicilline-clavulanic acid , ticarcilline, ticarcilline- clavulanic acid , 3rd generation cephalosporin ,quinolones, trimethoprimsulfamethoxazole , aminoglycozides ,imipenem,meropenem, and cefoxitin. The thoracic radiography proves the aspect of bronchopneumonia (Table 1). The biological analysis emphasizes an important inflammatory syndrome and severe anemia (Table 2).
Table 1 Results of imagistic exploration IMAGISTIC EXPLORATION RESULTS intense and homogenous opacity with retractile character, Thoracic radiography (11.04) left hemithorax Abdominal ultrasonography kidneys with extended sinus areas Cerebral CT cerebral edema, contrast clutch at the right frontal level Table 2 Biological probes Haematocrit Hemoglobin Leucocytes Segmented neutrophils Eosinophils Lymphocytes Monocyte Basophils Trombocytes Fibrinogen VSH 11.04 3.300.000 10 30.000. 90% 5% 5% 305.000. 408 mg% 120 mm/1h 18.04 2.290.000. 6,9 17.300. 88% 1% 7% 4% 246.000.
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In the light of the new information, the choice for an association of efficient antibiotics had proven to be impossible. It was chosen for the association of Vancomycin and Pefloxacine but the evolution was unfavorable and the pleiocytosis persisted in the cephalorachidian liquid (LCR) (Table 3).
Table 3 Examination of the cephalorachidian liquid Cephalorachidian liquid aspect Elements blur uncountable blur uncountable blur uncountable
11.04 14.04 18.04
Sediment PN 95%, L 5% PN 90%, L 7% PN 71%, L 25%
In the 8th day of hospitalization the patient presents troubles of respiratory rhythm with desaturation, needing the transfer into the Neurosurgery Intensive Care Unit for ventilation support where he later deceases. DISCUSSIONS Acinetobacter baumannii is an opportunistic germ of clinical importance in continuous boost for the last 15 years, which can determine a big number of infections: sepsis, pneumonias, plague infections, urinary tract infections and post-operation meningitis, especially in the patients of the intensive care units [1]. The excessive utilization of the antibiotics in the hospitals had lead to an increase of A.baumannii stems with extended resistance to antibiotics, including to the new generations of extended-spectrum of Betalactamine, Aminoglycoside and Fluoroquinolone [2]. The Carbapenemes were, until recently, elective antibiotics for the treatment of the infections determined by the stems of A.baumannii multidrugresistant. However Acinetobacter can develop a resistance to Carbapenemes through different mechanisms: decreasing the membrane permeability, supra expressing the efflux pumps and the Carbanemases production [3]. During the last years the resistance to Carbapenemes was especially attributed to the production of D class Carbapenemases (Carbapenem-hydrolysing oxacillinases) OXA -24, OXA-24, OXA- 58 and the enzymes OXA -51like and less frequent to B class metallo-betalactamases of (MBLs) type IMP, VIP and SIM [3]. Acinetobacter baumannii multidrug-resistant can trigger epidemics in the hospital departments [4,5] (as described in hospitals from Greece and Poland) where it can survive for longer periods of time. The Carbapenemes have constituted for a long time the only hope in the treatment of the infections with Acinetobacter multidrug resistant and continues to be, in many areas, still active. Evidences about the resistance to Carbapenemes were mentioned all over the world [6,7]. Recently, it has been proven the increase of the infection incidence with these stems in the hospitals from USA and Europe, after the return of the militaries from Iraq and in Romania as well [8]. According to a MART-T study accomplished in four university center (Iasi, Constanta, Timisoara and the Institute ,,Matei Bals from Bucharest) during July 2008 December 2009, it was noticed that the volume of Acinetobacter stems sensible to Carbapenemes has largely decreased as compared to the year 2007: p < 0,0001 being identified in approximately 28% of the cases [9]. For these situations we have only a few therapeutic options and
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the circumstances of central nervous system infections are more dramatic as the therapeutic arsenal is somehow reduced. The risk factors for the infections with Acinetobacter multidrug resistant to antibiotics are: prolonged hospitalization - especially in the intensive care units, invasive devices, immune depression and anterior treatment with antibiotics, including Carbapenemes. The patient presented in this case study was hospitalized post-operation in the intensive care unit (The Neurosurgical Hospital, the Clinic of Infectious Diseases) for a period of approximately 50 days. Prolonged hospitalization - especially in the intensive care units, during wich he received multiple antimicrobials, includig 3rd generation Cefalosporine, Fluoroquinolone and carbapenems ,multiples invasive devices , result in high risk of infection with MDR Acinetobacter. During the first period episode of meningitis occurred within 24 hours after the operation, there was no suspicion for a nozocomial etiology of the infection (reason for which it was initiated the treatment with Ceftazidime and Ciprofloxacin, which are proven to cover the etiology of a posttraumatic meningitis). During the second round of hospitalization, after several surgical interventions and hospitalizations in intensive care units, it was emphasized the possible implication of the Meticilline-resistant Staphylococcus Aureus of the resistant nonfermentative Gram-negative bacillus. It was initiated the associated treatment with Vancomycin and Meropeneme. The cultures obtained from the cephalorachidian liquid (LCR) have isolated Acinetobacter baumannii with intermediate resistance to Ofloxacine and Pefloxacine and resistant to Cephalosporin, Ciprofloxacin and Carbapenemes.These strains of Acinetobacter could infect a patient ,,per primam,, or, become resistant because of antimicrobial pressure. The main characteristic of A. baumannii is the capability of surviving for prolonged periods in the environment, thus contributing to the transmission of the organism during outbreaks. The intestinal tract provides also, an important reservoir for antibiotic-resistant gram-negative bacilli,including Enetrobacteriacee species, Pseudomonas aeruginosa, and Acinetobacter baumannii.Selected pressure exerted by antibiotics play a crucial role in emergence and dissemination of these pathogens [10]. In this particular case, intestinal colonization was possible during his prolonged hospitalization and antimicrobial treatments.The incidence of a stercoral peritonitis through the rectum rupture resulted in translocation of MDR Acinetobacter ,as a second possible source of infection. The antibiogram gives us no possibility to treat such an infection. The subsequent treatment of meningitis with Vancomycin and Pefloxacine was inefficient. In the 8th day of hospitalization the patient presents troubles of respiratory rhythm with desaturation and died. This case is an example of worse outcome in a serious ill patient when an antibiotic therapy is no more available. Colistin seems to be the break away solution of the moment, according to the studies proceeded in areas where there have been registered real epidemic infections with Acinetobacter multidrug/pan drug resistant. The microbiological studies have compared the efficiency of Colistin in mono therapy vs. associations, identifying a synergic effect for Colistin - Rifampicin, Colistin Carbapenemes [11]. The reduced permeability of the Colistin in the cephalorachidian liquid (LCR) represents the main disadvantage for treating the infections of the central nervous system (SNC). However,
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there are studies according to which these patients could beneficiate of intrathecal or intraventricular administration of Colistin, with more than 80% success rate [12]. CONCLUSIONS Meningitis with resistant non-fermentative Gram-negative bacillus represents a permanent provocation due to treatment difficulties in the conditions of a reduced arsenal of antibiotics. The amount of Acinetobacter baumannii stems resistant to Carbapenemes reaches disturbing limits in Europe (Poland, Greece) but in Romania as well (where approximately 28% of the stems are sensible to Carbapenemes). The risk factors for the infections with Acinetobacter with multiple resistances to antibiotics are: prolonged hospitalization - especially in intensive care units, invasive devices, immune depression and anterior treatment with antibiotics, including Carbapenemes. The new options for all these infections are the synergic associations such as Colistin Rifampicin, Colistin - Carbapenemes. REFERENCES
Tsakris A, Iconomidis A,Poulou A,.Spanakis A, Vrizas A, Diomidous M, Pournaras S, Markou F. Clusters of imipenem resistant Acinetobacter baumannii clones producing different carbapenemase in an intensive care unit. Clin.Microbiol Infect 2008; 14(6): 588-594. 2. Perez F, Hujer AM, Hujer KM, Decker BK, Rather PN, Bonomo RA. Global challenge of multidrug-resistant Acinetobacter baumannii. Antimicrob Agents Chemother 2007; 51(10): 34713484. 3. Towner JK, Levi K, Vlassiadi M; ARPAC Steering Group. Genetic diversity of carbapenemresistant isolates of Acinetobacter baumannii in Europe. Clin Microbiol Infect 2008; 14(2): 161 167. 4. Falagas ME, Karveli EA. The changing global epidemiology of Acinetobacter baumannii infections: a development with major public health implications. Clin Microbiol Infect 2007; 13(2): 117119. 5. Webster C, Towner KJ, Humphreys H. Survival of Acinetobacter on three clinically related inanimate surfaces. Infect Control Hosp Epidemiol 2000; 21(4): 246. 6. Van Looveren M, Goossens H; ARPAC SteeringGroup. Antimicrobial resistance of Acinetobacter spp. in Europe. Clin Microbiol Infect 2004; 10(8): 684704. 7. Poirel L, Nordmann P. Carbapenem resistance in Acinetobacter baumannii: mechanisms and mechanisms and epidemiology. Clin Microbiol Infect 2006; 12(9): 826836. 8. Miftode E, Leca D, Teodor D, Dorneanu O, Luca V. Meningita postoperatorie cu Acinetobacter baumanii rezistent la carbapeneme; un nou motiv de ingrijorare pentru clinician. Infectio.ro 2005; 3: 50-52. 9. Popescu GA, Gavriliu L, Popescu C, Nicoara E, Miftode E, Rugina S, Dumitru I. Evolutia rezistentei bacililor gram negativi la antibiotice rezultatele studiului MAR-T. Infectio.ro 2010; 22: 36-42. 10. Donskey CJ. Antibiotic regimen and intestinal colonization with antibiotic resistant gramnegative bacilli. Clinical Infectious Diseases 2006; 43(suppl 2): S62-9. 11. Petrosillo N, Ioannidou E, Falagas ME. Colistin monotherapy vs. combination therapy: evidence from microbiological, animal and clinical studies Clin Microbiol Infect 2008; 14(9): 816827. 12. Khawcharoenporn T, Apisarnthanarak A, Mundy L M. Intrathecal colistin for drug-resistant Acinetobacter baumannii central nervous system infection: a case series and systematic review Clin Microbiol Infect 2010; 16(7): 888894. 1.
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Anatomie i tehnici chirurgicale
EARLY RETROPANCREATIC DISSECTION DURING PANCREATICODUODENECTOMY - TECHNICAL NOTES

C. Lupascu1, D. Andronic1, R. Moldovanu1, Corina Ursulescu2, C. Vasiluta1, E. Tarcoveanu1 1. I Tnsescu Vl. Buureanu First Surgical Clinic 2. St. Spiridon Hospital Radiological Clinic Gr. T. Popa University of Medicine and Pharmacy Iai
EARLY RETROPANCREATIC DISSECTION DURING PANCREATICO-DUODENECTOMY TECHNICAL NOTES (ABSTRACT): Background: Pancreaticoduodenectomy (PD) is the procedure of choice for malignant tumors of the pancreatic head and periampullary region. During PD, early pancreatic neck division may be inadequate, especially in cases of hepatic artery (HA) anatomic variants, when invasion of the superior mesenteric artery (SMA) is suspected, or in cases of intraductal papillary mucinous neoplasms (IPMN). Methods: We perform an early approach of the retroportal lamina (RPL) from behind the pancreatic head, before pancreatic transection. This is accomplished after lymphadenectomy and adequate mobilisation of the specimen from the vessels, on either the neck or the body, according to the tumor extension. Results: We successfully used this approach during 28 PD. There were 21 patients to whom we detected anatomic variants of right hepatic artery (RHA), which was spared in 19 cases; arterial reconstruction was required in one case. We also used this technique in 5 patients with IPMN - 3 PD extented to the body and 2 total pancreatectomies, and in other 2 patients with adenocarcinoma involving the porto-mesenteric jonction, requiring limited venous resection and reconstruction. Conclusions: Retropancreatic approach with early RPL dissection is an useful technical variant of pancreaticoduodenectomy which we recommend in selective indications. KEYWORDS: PANCREATICODUODENECTOMY, POSTERIOR APPROACH, RIGHT HEPATIC ARTERY, SUPERIOR MESENTERIC ARTERY, INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM. List of abbreviations: CBD- common bile duct; Ct- celiac trunk; IPMN- intraductal papillary mucinous neoplasm; HA- hepatic artery; MDCT- multidetector computed tomography; PDpancreaticoduodenectomy; PH- porta hepatis; PV- portal vein; RPL- retropancreatic lamina; RHA- right heparic artery; RCHA- replaced common hepatic artery; SMA- superior mesenteric artery; SMVsuperior mesenteric vein. Correspondence to: Associate Professor Cristian Lupascu, MD, PhD. I Tnsescu Vl. Buureanu First Surgical Clinic, St. Spiridon Hospital, Independentei street, no 1, 700111; e-mail: cristian_lupascu@yahoo.com*.
INTRODUCTION Pancreaticoduodenectomy (PD) is still considered nowadays a challenging operation with a postoperative mortality rate of less than 5% but a high morbidity rate of close to 40%, even in recent series [1,2]. It is mostly indicated for malignant tumors of the pancreatic head, uncinate process and periampullary region [3], for some benign pancreatic tumors [4,5], but also recommended for advanced gallbladder carcinoma or mid-to-distal common bile duct (CBD) cancers, (either in hepatoduodenopancreatectomy operation or for removal of retro pancreatic lymph nodes) [6,7].
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Since the first PD performed by Whipple in 1937, more than 65 improvements of the technique were made, concerning mainly pylorus preservation or reconstruction of pancreaticodigestive continuity [1,8]. Durind resection, PD is usually performed backward, with transsection of the pancreatic neck before division of the RPL close to the SMA [9-13]. Recently, indications of PD have extended to IPMN [14,15] and periampullary tumors invading the mesenterico-portal vein [16,17]. In these last two conditions, division of the pancreatic neck may be impossible or inappropriate so that division of the pancreatic body can be preferred. Moreover, the latter indication carries a high risk for palliative resection owing to involvement of the RPL [18]. For these reasons, we perform in such cases a retropancreatic approach PD, with early division of the retroportal tissue close to the origin of SMA, to assess radicality of resection, variant pattern of the arterial blood supply to the liver , to properly mobilize the specimen before pancreatic division, and, if necessary, to safely perform venous clamping [5]. This technical variant was firstly suggested by Leach and then reported by Machado and Pessaux [12, 19-21]. The purpose of the current study is to describe how, when and why we perform this approach during PD, with pancreatic transection as the last step of resection. METHODS Incision and exploration. We routinely use an upper abdominal midline incision as a standard approach. The surgical exploration is completed by intraoperative ultrasonography to confirm preoperative imaging data. The pancreas head exposure is obtained by the Kocher maneuver and opening the lesser sac by separating the greater omentum from the transverse colon. Dorsal to the pancreatic head, the dissection must pass beyond the aorta, to get full posterior mobilisation of the duodenopancreas to the patient`s left, in order to render evident the plane between the superior mesenteric vein (SMV) and the SMA. Liver and peritoneal exploration is performed as well as the palpation of the mesenteric root and biopsy examination of aortocaval nodes with frozen section. Dissection of porta hepatis (PH) (Fig 1). After cholecystectomy we perform dissection and exposure of the CBD, portal vein (PV) and HA.
Fig. 1 Dissection of porta hepatis
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The common and proper HA, when they exist as such, are first identified, dissected and put on tapes. We divide the right gastric vessels and then to identify and clamp the gastroduodenal artery to make sure that arterial flow either in hepatic and gastric arteries remains normal and there is no unrecognized celiac trunk (Ct) stenosis. The gastroduodenal artery is then divided, as well as the the CBD above the entry of the cystic duct. These two last maneuvers improve the exposure on the PV. Care must be taken during dissection and lymphadenectomy on the right side of the PV, because this area may contain an accessory or replaced RHA originating from the SMA, aorta or even the Ct, but also a replaced common hepatic artery (RCHA) arising from the SMA or aorta. This aberrant vessel is usually running upwards behind the PV and CBD, within the hepatic pedicle. We usually dissect and isolate it on a tape, formerly in its segment belonging to PH (Fig. 2).
Fig. 2 Replaced common hepatic artery (RCHA) arising from the SMA
We carry on downwards the retropancreatic dissection, revealing the inferior vena cava and its left side, the left renal vein with its upper margin, and in between, the origin of the SMA (Fig 3).
Fig. 3 Disection of the SMA
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Disection of the SMA and RPL. The key of the intervention is to reveal the SMA origin, by dissecting and removing the RPL, which is inserted on the right aspect of the SMA. We dissect all soft tissues and lymph nodes located in this retropancreatic plane from the origin of the SMA, along 4 cm towards its entry into the mesentery, after progressive exposure and gentle medial retraction of the PV (Fig. 3). This step allows safe exposure and dissection of an accessory or replaced RHA, or RCHA arising from the SMA, aorta or Ct. We dissect and set free the aberrant vessel from the RPL , from its origin, upwards the PH. However, RHA or RCHA originating SMA can course behind, within the pancreatic head, or rarely along the ventral side of the pancreas (Fig. 4). Care must be taken also in case of accessory or replaced RHA, arising from the Ct, because this vessel usually courses behind the upper border of the pancreatic head, crosses the posterior aspect of the PV, to gain a dorsolateral position within PH (Fig 5). For certain, before dissecting and preserving the aberant RHA, we could not confirm its course. To facilitate the SMA and aberrant RHA or RCHA dissection, the pancreatic head and duodenum are retracted en bloc ventrally and to the left (Fig 2). With this exposure, the SMA and an accessory, replaced RHA or RCHA, originating in SMA, aorta or Ct, are easily identified and carefully dissected. We advocate to limit the dissection along the right side of the SMA, in order to avoid an extensive removal of perivascular nervous plexus, resulting in postoperative intestinal motility troubles (diarrhoea).
Fig. 4 CT exam RHA arising from SMA
Fig. 5 CT exam RHA arising from Ct
The SMV dissection and uncinate exposure. The SMV then is entirely dissected at the inferior margin of the pancreas. The right gastroepiploic vein and all veins drainining the uncinate process into SMV, are ligated and divided. The uncinate is exposed up to the the right side of the SMA. Mobilisation of the duodenojejunal jonction. The division of the Treitz ligament, equally by a posterior approach, allows full mobilisation of the duodenojejunal jonction and retraction of the first jejunal loop under the superior mesenteric vessels, so that the specimen to be removed reaches the right side of the mesenteric root. The inferior pancreaticoduodenal artery, wich usually originates from the first jejunal artery, is identified and ligated. When the SMA is supposed to be involved by the tumor,
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according to preoperative imaging, SMA dissection with tissue sampling for frozen section can be performed, without any previous section of the digestive tract or pancreatic continuity, thus avoiding the risk for nonradical resection. As the SMA involvement is proven, the arterial and venous vascular structures of the duodenopancreas are preserved and both a hepatojejunostomy and gastroenterostomy still can be performed. Jejunal and gastric division. Once radicality of PD is established, the proximal jejunum is divided, 10 to 15 cm from the duodenojejunal jonction, by a GIA stapling device. The mesentery is divided from jejunal division towards the SMA , sparing the first jejunal vessels. The uncinate is mobilised from the SMA with lymph node dissection, performing successive ligations af all retropancreatic tissue and vessels situated on the posterior and right sides of the SMA. The distal stomach is then divided using a GIA stapler. Pancreas division The last step of the resection phase is the transection of the pancreatic neck, when adequate, just in front of the portal vein. When we must perform the pancreatic division on the body, owing to the intrapancreatic extension of an IPMN, division of both the dorsal pancreatic artery (originating usually from the Ct or the proximal splenic artery) and collaterals of both the SMA and the SMV (from the inferior edge of the pancreas), are required. In case of pancreatic head tumor involving the portomesenteric confluence, we performe en bloc mobilisation and the splenic vein can be controlled behind the body. Adequate mobilization of the mesentery and of the right colon is necessary to perform safely ,,en bloc resection and reconstruction after segmental resection of the vein. We estimated this mobilization as useful in case of isolated and limited portomesenteric invasion, for avoiding vein grafting during venous reconstruction. In case of PMN, the retro-pancreatic mobilization is carried on towards the left and can be prolonged by dissection of splenic vessels with successive ligation of their collaterals. When the pancreatic body is mobilized enough from splenic vessels, we can divide the pancreas at any level, or even entirely remove it if necessary. Anyway, frozen section analysis can be performed on the cut surface of the specimen, to assess the malignant status of the remnant pancreas. Intraoperative methods to assist in determining the extent of the resection were not routinely used: frozen section analysis in 3 cases. As about the reconstruction phase after the PD, we always perform a pancreaticojejunal end-to-side duct-to- mucosa temporary stented anastomosis with 60 PDS sutures. Standard hepatico-jejunostomy and gastro-jejunostomy are the final steps of the procedure. Drains placement and postoperative care were similar to those from standard PD. RESULTS In our surgical department, the early posterior approach PD has become since 2007 the standard in patients with RHA anatomic variants. RHA anomalies were detected in 21 patients, 18 of them having malignant tumors of the pancreatic head or periampullary region and 3 patients having neuroendocrine tumors of the inferior pancreatic head. Fifteen cases had accessory or replaced RHA arising from SMA [13] or from the Ct (two cases of replaced RHA). Six cases had a RCHA originating in SMA. The HA anatomy was preoperatively assessed in all patients by multidetector computed tomography (MDCT) with angiography, which showed the aberrant HA in 20 cases.
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In one case, despite preoperative MDCT findings of normal HA anatomy, we intraoperatively found out an inadvertent division of a 2-mm diameter accessory RHA. As the patient had also a proper HA with a good backflow from the stump of the accessory RHA, we decided to ligate the latter with no postoperative problem. In another case, a RCHA originating from the SMA was involved by an enlarged lymph nodes mass, located behind the pancreatic head. A segmental resection of the involved RCHA had to be performed. Whereas after the RCHA clamping, an inadequate blood flow in the liver was registered (by Doppler ultrasound intraoperative examination), a vascular reconstruction was decided. The proximal stump of the RCHA was ligated and the arterial reconstruction was made using the gastroduodenal artery stump which was sutured to the distal stump of the RCHA. We also used this posterior approach in 2 patients with ductal adenocarcinoma involving the portomesenteric confluence which required en bloc-vascular resection, mobilization of the right colon and the root of mesentery followed by mesentericoportal end to end anastomosis. The postoperative course was uneventful. In the patients requiring vascular reconstruction, the Doppler ultrasound examination revealed a good arterial supply to the liver and a good portal flow as well. For these 3 patients, clamping time did not exceed 20 minutes. We additionally used this posterior approach in 5 patients with IPMN (3 PD extented to the body - IPMN in the head, neck or uncinate process, and 2 total pancreatectomy- IPMN diffusely involving the pancreatic duct). In patients with IPMN, preoperative imaging consisted in abdominal MDCT and endoscopic ultrasound with guided fine needle aspiration. No postoperative complication was noted, particularly related to this approach. DISCUSSION Because of recent decrease in mortality rate, PD is now performed in case of malignant tumors of the pancreatic head and periampullary region, but also for IPMN, or periampullary tumors invading the mesentericoportal vein. We have described herein our technique of early RPL during PD, with the division of the retroperitoneal soft tissue on the right side of the SMA, before the digestive and pancreatic continuity should be interrupted. We believe that this technique is the best option particularly during PD in case of: (1) HA anatomic variant, with RHA (accessory or replaced) or RCHA arising from the SMA or Ct; (2) suspected involvement of the SMA; (3) IPMN extended from the head to the body; (4) tumoral involvement of the portomesenteric confluent by a head or neck tumor, the last two conditions requiring en bloc resection and pancreatic division of the body. Classically, PD includes the creation of a tunnel between the pancreatic neck and and the underlying portomesenteric confluent, followed by the neck transsection. Thus, pancreatic continuity is interrupted before radicality of the resection could be assessed close to the SMA. Even in some recent series, nonradical PD still represents 9 to 25 % cases [22,23]. Moreover, in the standard PD, dissection of an accessory or replaced RHA or of a RCHA , is usually performed late, when bleeding from the resection specimen decreases the exposure of the SMA and of an aberrant RHA origin. Early neck transsection is not suitable when the neck is involved by the tumor, as in pancreatic head ductal cancer involving the portomesenteric confluence [16,17] or in IPMN extended from the pancreatic head to the body [15].
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One of the difficulties of PD is variability of peripancreatic vessel anatomy. Assessment of variant pattern of the arterial blood supply to the liver in patients who are about to undergo a PD is a challenging but mandatory procedure, that can lead to avoid or minimize unnecessary complications, as fatal hepatic injury [24,25]. Accidental ligation of aberrant HA may result in hepatic necrosis, ischemic biliary injury or anastomotic complications [26]. However, the importance of sparing this artery during PD lies not so much in preventing hepatic ischemia, but in preventing a breakdown of bilioenteric anastomosis, because the blood supply to the cranial part of the bile duct is entirely dependent on the RHA after PD [25,27]. Preoperative assessment of celiomesenteric vascular pattern (variants, strictures) by imaging methods is of the upmost importance for the surgeon. MDCT with angiography is the method of choice, since enables rapid acquisition of thin- slice-high-resolution images of the abdominal arteries, as well as 3D reconstructions. The most likely aberrant HA expected during planning or performing PD is replaced or accessory RHA originating in SMA (9,82-11%) followed by RCHA arising from SMA (1,5-2,8 %) [28-30]. RHA or RCHA from SMA may course behind, within, or along the ventral side of the pancreas [31,32]. Michels [33] found that half of the RHA actually coursed through the pancreatic parenchyma, whereas the other half passed posterior to the pancreas. If RHA or RCHA courses in the pancreas head parenchyma, this artery can be preserved by dividing the parenchyma. However, RHA or RCHA coursing along the posterior side of the pancreas can be dissected and spared formerly on its origin from the SMA and then along its retropancreatic course, under direct vision, up to PH. Before dissecting and preserving the aberrant RHA, we could not confirm its course. If an accessory RHA can usually be ligated with no adverse effects, ligation of a predominant replaced RHA can result in definitive ischemic damage of the liver and biliary tree [27]. Ductal carcinoma with venous limited involvement can be safely resected with a long-term survival similar to that observed after radical resection without venous involvement [16,19,34,35]. In this situation, venous resection is best performed en bloc to obtain disease-free margins. Another advantage of this technique is that it results in the tumor being attached only to the involved veins, so clamping of the portomesenteric confluence may be easier and shorter [36]. Mobilisation of the right colon and the root of mesentery is useful for avoiding vein grafting during reconstruction of the PV [36]. It is expected that, because pancreatic transection is performed at the end, congestion and bleeding are less likely whereas venous drainage of both the specimen and bowel are compromised minimally during most of the procedure. Another new indication for performing a PD is IPMN. The most frequent localization is the pancreatic head, but involvement of the body can occur to some patients as well [14,15]. In this setting and particularly in malignant tumors, en bloc resection requires a PD with pancreatic division located to the body. In these cases, final transection of the pancreas, instead of neck transection followed by additional body resection, can be performed at the desired place if enough mobilized from the splenic vessels, preventing the tumor from opening, which might disseminate cancer into the abdomen. Furthermore, dissection along the splenic vessels can be extended up to the splenic hilum and allows splenic preservation if the whole pancreas must be resected, which is encountered in 2% to 15 % of patients with IPMN [14,15].
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CONCLUSION Early retropancreatic dissection is an useful approach to better expose the retropancreatic mesenteric vasculature during PD. We advocate this approach in selective situations, such as: HA anatomic variants with RHA or RCHA arising from the SMA or Ct, suspected SMA involvement, limited invasion of the mesentericoportal confluence and IPMN. Moreover, by adequate retropancreatic mobilization from right to left towards the body, pancreatic transection can be performed at any level. This approach improves both the safety and radicality of PD, by an early vascular control and enlarged lymphadenectomy. REFERENCES
1. Yeo CJ, Cameron JL, Sohn TA, Lillemoe KD, Pitt HA, Talamini MA, Hruban RH, Ord SE, Sauter PK, Coleman J, Zahurak ML, Grochow LB, Abrams RA. Six hundred fifty consecutive pancreaticoduodenectomies in the 1990s: Pathology, complications, and outcomes. Ann Surg 1997; 226(3): 248-260. Balcom JH 4th, Rattner DW, Warshaw AL, Chang Y, Fernandez-del Castillo C. Ten year experience with 733 pancreatic resections. Arch Surg 2001; 136(4): 391-398. Yeo CJ, Cameron JL, Maher MM, Sauter PK, Zahurak ML, Talamini MA, Lillemoe KD, Pitt HA. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg 1995; 222(4): 580-592. Jagad RB, Koshariya M, Kawamoto J, Papastratis P, Kefalourous H, Patris V, Porfiris T, Gevrielidis P, Tzouma C, Lygidakis NJ. Pancreatic neuroendocrine tumors: our approach. Hepatogastroenterology 2008; 55(81): 274-281. Gao C, Fu X, Pan Y, Li Q. Surgical treatment of pancreatic neuroendocrine tumors: report of 112 cases. Dig Surg. 2010; 27(3): 197-204. Gagner M, Rossi RL. Radical operations for carcinoma of the gallbladder: present status in North America. World J Surg 1991; 15(3): 344-347. Shirai Y, Ohtani T, Tsukada K, Hatakeyama K. Combined pancreaticoduodenectomy and hepatectomy in patients with locally advanced gallbladder carcinoma. Cancer 1997; 80(10): 1904-1909. van Berge Henegouwen MI, Moojen TM, van Gulik TM, Rauws EA, Obertop H, Gouma DJ. Postoperative gain after standard Wipple`s procedure versus pyloruspreserving pancreaticoduodenectomy: The influence of tumor status. Br J Surg 1998; 85(7): 922-926. Carey LC. Pancreaticoduodenectomy. Am J Surg 1992; 16: 153-162. Farnell MB, Nagorney DM, Sarr MG. The Mayo Clinic approach in the surgical treatment of adenocarcinoma of the pancreas. Surg Clin North Am 2001; 81(3): 611-623. Richelme H, Birtwisle Y, Michetti C, Bourgeon A. Posterior attachments of the pancreas. Surgical significance of the right retropancreatic lamina. Chirurgie 1984; 110(2): 150-157. Pessaux P, Regunet N, Arnaud JP. Resection of the retroportal pancreatic lamina during pancreaticoduodenectomy: first dissection of the superior mesenteric artery. Ann Chir 2003; 128(9): 633-636. Pissas A. Essai d`anatomie Clinique et chirurgicale sur la circulation lymphatique du pancreas. J Chir 1984; 121: 557-571. Traverso LW, Peralta EA, Ryan JA Jr, Kozarek RA. Intraductal neoplasms of the pancreas. Am J Surg 1998; 175(5): 426-432. Paye F, Sauvanet A, Terris B, Ponsot P, Vilgrain V, Hammel P, Bernades P, Ruszniewski P, Belghiti J. Intraductal and papillary mucinous tumors of the pancreas: Pancreatic resections guided by preoperative morphological assessment and intraoperative extemporaneous examination. Surgery 2000; 127(5): 536-544. Bachellier P, Nakano H, Oussoultzoglou PD, Weber JC, Boudjema K, Wolf PD, Jaeck D. Is pancreaticoduodenectomy with mesentericoportal venous resection worthwile? Am J Surg 2001; 182(2): 120-129. Bold RJ, Charnsangavej C, Cleary KR, Jennings M, Madray A, Leach SD, Abbruzzese JL, Pisters PW, Lee JE, Evans DB. Major vascular resection as part of pancreaticoduodenectomy for cancer: Radiologic, introperative, and pathologic analysis. J Gastroint Surg 1999; 3(3): 233-243.
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POT FI PREVENITE EVENTRAIILE PARASTOMALE?

E. Trcoveanu, Elena Cotea, A. Vasilescu, Cr. Lupacu, N. Dnil, N. Vlad, Delia Rusu Clinica I Chirurgie I. Tnsescu Vl. Buureanu, Universitatea de Medicin i Farmacie Gr. T. Popa Iai PARASTOMAL HERNIAS CAN BE PREVENTED?(ABSTRACT): Parastomal hernias, although rarely encountered, make special therapeutic problems. The increase in incidence is related to increased life expectancy of patients with rectal cancer. In First Surgical Clinic, between 1993 to 2010 were treated 1465 incisional hernias, of which there were 37 parastomal hernias at 28 patients (2.5%), 9 of which are recurrent parastomal hernia. Clinical examination, intraoperative exploration and CT exam stated the following subtypes of parastomal hernia: interstitial (sac within layers of the abdominal wall) - 10 cases; subcutaneous (hernia sac in the subcutaneous plane) - 12 cases; intrastomal (sac penetrates into stomy) 7 cases; peristomal (sac is within prolapsing stoma) 8 cases. Only in one case, parastomal hernia appeared after loop colostomy, the rest came after end colostomy. The most parastomal hernias were asymptomatic; only six cases with parastomal hernias required emergency surgical treatment for obstruction (3 cases) or strangulation (3 cases). Two patients had associated median incisional hernia. We performed: local tissue repair in 22 cases (8 cases with recurrent parastomal hernia; stoma relocation in one case); sublay mesh repair in 15 cases (one case with recurrent parastomal hernia; stoma relocation in 5 cases). Associated surgery were practiced: viscerolysis, colic resection (6 cases), small bowel resection (2 cases). Postoperative morbidity registered were 5 wound infections (one case after mesh repair which required surgical reintervention) and stoma necrosis in one case with strangulation parastomal hernia with severe postoperative evolution and death. After local tissue repair recurrences were seen in 7 cases, after mesh repair we registered recurrence only in one case, that helped a parietal suppuration and no relapse after the relocation of the stoma. Because the our study and literature review have demonstrated a mesh repair is a safe procedure in the treatment of parastomal hernia, in 2010 we have initiated a prospective prospective randomized trial where prophylactic use of mesh at the time of stoma formation to reduce the risk of parastomal hernia. We describe a surgical techniques sublay mesh placement. So far have been enrolled in the study 10 patients with mesh implanted at the primary operation and 12 patients no mesh. The inclusion criteria are: patients with lower rectal cancer, stage II-III, irradiated, obese, with a history of hernias, patients who do physical work. We use polypropylene mesh. The patients were followed for a median of 9 months (range 3 to 12 months) by clinical examination every 3 months. We registered 3 recurrences, all in the no mesh cohort. We have not seen any morbidity to patients from mesh group. The study will be completed in 2012 after they enroll at least 20 patients in each group and after longer follow up needed to confirm results. Conclusions: Parastomal hernia is a relatively rare disease reported in number of incisional hernia. With increasing life expectancy stands we noted and increased incidence of parastomal hernia. Prophylactic use of mesh during the primary operation is a safe procedure and reduces the risk of parastomal hernia. KEY WORDS: PARASTOMAL HERNIA, MESH REPAIR, PROPHYLACTIC MESH. Coresponden: Prof. Dr. Eugen Tarcoveanu, Clinica I Chirurgie, Spitalul Sf. Spiridon, Str. Independentei nr. 1, 700111, Iasi, e-mail: Page 2 etarcov@yahoo.com.
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eventraii 98%
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Istorie
WILLIAM STEWART HALSTED SI MODERNIZAREA CHIRURGIEI N S.U.A

Liliana Strat Catedra Obstetric Ginecologie Universitatea de Medicin i Farmacie Gr. T. Popa Iai
Rar o via de chirurg i om de tiin care s fi atras mai mult interesul de a o cunoate cum a fost cea a lui Halsted, printele chirurgiei moderne, tiinifice n S.U.A. i cel care a creat un sistem de instruire al tinerilor chirurgi devenit azi clasic. O perioad grea s-a interpus n viaa i activitatea acestuia ameninnd s-i compromit definitiv cariera. Depind greaua ncercare, Halsted a ctigat o mare lupt cu sine ajungnd ca pn la sfritul vieii s-i aplice din plin marile capaciti i concepii inovatoare. S-a nscut n 1852 la New York dintr-o familie venit de peste dou secole din Anglia. ntre 1870-1874 urmeaz Colegiul Yale (New Haven), unde nu se arat prea studios. ncepnd s-l intereseze medicina se nscrie la Colegiul de Medici i Chirurgi al Universitii Columbia din New York; de aceast dat se distinge ca un student eminent nct la absolvire se claseaz ntre primii zece. nainte de absolvire reuete prin concurs s intre intern la Spitalul Bellevue. Dup terminarea Colegiului n 1877 i avnd un an de internat este numit n 1877 medic de domiciliu la Spitalul din New York. Aici l cunoate pe dr. William Welch, patolog, de care l va lega pe via o strns prietenie. Tot aici, Halsted are o prim contribuie ntocmind foaia de nregistrare a temperaturii, pulsului i respiraiei. Pentru a-i completa studiile Halsted se decide ca n toamna anului 1878 s viziteze n Europa cele mai renumite centre universitare din Austria i Germania. A stat mai mult la Viena unde a studiat patologia cu Chiari, anatomia cu Zuckerkandl, embriologia cu von Schneck; a frecventat clinicile de chirurgie ale lui Billroth i Braun legnd strnse relaii cu Welfler i von Mikulicz, reputai asisteni ai lui Billroth. n primvara lui 1879, Halsted vine la Wrzburg pentru a studia embriologia cu Kollicker i osteologia cu Stoehr; frecventeaz i aici clinicile lui von Bergmann, iar la Halle pe cele ale lui Volkmann. La Leipzig l vede pe Tirsch, la Hamburg pe Schede, la Kiel pe Esmarch. Toi acetia i las o profund impresie. Prin studiile efectuate i contactele avute n clinicile de chirurgie, Halsted i completeaz multe cunotine, nsuindu-i noi metode i tehnici operatorii. Apreciaz varietatea mare de instrumente folosite la operaii, mai ales n scop de hemostaz. Ia parte la aplicarea nc de dat recent, a anesteziei generale, precum i la implementarea n slile de operaii a principiilor
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chirurgiei antiseptice formulate de Lister. Este marcat mai ales de sistemul german de pregtire a chirurgilor, mult mai riguros, mai exigent i mai metodic dect n S.U.A. l impresioneaz coala pe care i-o formeaz n jurul lor profesorii de chirurgie, precum i importana corelrii activitii chirurgicale cu cercetarea tiinific i chirurgia experimental. Mult mai pregtit, n toama anului 1880, Halsted se ntoarce la New York. Primii 4 ani din perioada 1880-1886, petrecui de Halsted la New York, l arat deosebit de activ. Bun anatomist, lucreaz ca asistent demonstrator de anatomie la Colegiul de Medici i Chirurgi; este cooptat n staff-ul Spitalului Roosevelt unde organizeaz cu rezultate foarte bune un Dispensar; este i medic de domiciliu la Spitalul Bellevue, iar n unele perioade lucreaz i la alte spitale. Programul foarte ncrcat l face s opereze uneori aici i noaptea. Reuete chiar s i se constuiasc o sal de operaie proprie n care aplic noile metode de antisepsie, care la Spitalul Bellevue nc nu fuseser introduse. ntr-o perioad n care lucra la Spitalul Chambers Street din New York, Halsted a aplicat pentru prima dat autotransfuzia la intoxicaii cu monoxid de carbon; dup sngerare, sngele acestora era ventilat i reperfuzat. Lundu-i o serie de colaboratori, printre care pe Welch ca patolog, Halsted organizeaz pentru viitorii absolveni de la Colegiul de Medici i Chirurgi un gen de pregtire sub form de concurs cu ntrebri. Cercul su cu 65 de studeni devine cel mai cutat. n jurul lui Halsted se creeaz renumele de chirurg bun i ndrzne dar i de dascl nzestrat, mai ales, dup ce n vara lui 1880 este nevoit s-i opereze propria mam, noaptea, la ea acas, pe o simpl mas, fiind n stare grav datorit unui piocolecist calculos cu icter; a efectuat o colecistostomie dup care pacienta a mai trit doi ani, dar cu icter. nc din 1882 interesat de cancerul de sn Halsted ncepe s evideze sistematic axila dup ridicarea marelui pectoral. Iniial, acesta era rezecat doar parial, iar micul pectoral doar secionat. Tegumentele, larg excizate printr-o incizie care se prelungea pe bra, fcea necesar de regul grefa. Ulterior i-a limitat incizia pn n anul deltopectoral. Pentru o scurt perioad a ridicat i ganglionii supraclaviculari. Scopul urmrit era ndeprtarea larg a snului tumoral pn n esut sntos. El susinea c esutul suspect trebuie ridicat monobloc mpreun cu axila, deoarece altfel, plaga se contamineaz cu esut tumoral fie prin seciunea tumorii, fie prin limfaticele care conin celule canceroase. Prima descriere a tehnicii sale o va publica n 1890, iar ulterior rezultatele le va prezenta n alte 4 articole (1894, 1898, 1907, 1912). n aceeai perioad, Halsted elaboreaz i prezint la Societatea de Chirurgie din New York un numr de peste 20 articole. Duce deasemenea i o via social activ. Totul prea s decurg normal, pn n noiembrie 1884, cnd Halsted afl c la Congresul de Oftalmologie de la Heidelberg s-a demonstrat efectul anestezic al cocainei 2% aplicat direct pe cornee. ntrevznd posibilitatea de a extinde efectul i asupra altor esuturi, Halsted i procur cocain i ncepe o serie de experimentri att pe el nsui ct i pe unii colegi. Constat c injectarea unui nerv periferic cu cocain realizeaz anestezia ntregului teritoriu de distribuie i deci posibilitatea efecturii n condiii de insesibilitate a unei intervenii chirurgicale. Rezultatele acestor experiene au fost publicate de Halsted n 1885 ntr-un singur articol i acesta destul de confuz i incoerent datorit faptului c ntre timp att el ct i colegi ai si au devenit dependeni de cocain. Cei mai muli dintre ei au pltit-o chiar cu viaa. Printr-un efort de voin, Halsted ncearc s se elibereze de drog efectund n februarie-martie 1886 o cltorie pe mare spre insulele Windland, nsoit de dr. Welsch. ncercarea eueaz, Halsted devenind n plus dependent de morfin.
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Dup mari insistene, n mai 1886 Halsted accept s fie internat pentru dezintoxicare la Spitalul Butler din Rhode Island. Este externat n acelai an cu rezultatul de a fi rmas dependent doar la morfin. Deprimat, nemaifiind capabil s-i exercite atribuiile, cariera lui Halsted la New York prea definitiv compromis. n aceste condiii, prietenul su Welsch care i cunotea potenialul i capacitile, l invit n decembrie 1886 s vin s lucreaze n Laboratorul su experimental din Baltimore. Aici, Halsted va colabora cu ali tineri cercettori. Prelund ideea c ptura submucoas a intestinului reprezint o structur de rezisten oferind o mai mare siguran unei suturi care s o traverseze, Halsted efectueaz o serie de experimente artnd c pentru a fi sigur i mai funcional, orice anastomoz intestinal trebuie efectuat cu fire trecute prin submucoas. Rezultatele au fost prezentate n aprilie 1887 la coala Medical Harvard. Este nevoit ns s se interneze pentru continuarea tratamentului la Spitalul Butler de unde iese n decembrie 1887, fiind considerat vindecat n ce privete dependena de cocain. n ianuarie 1888 revine la Baltimore unde i reia studiile experimentale de laborator; multe din ele se refer la glanda tiroid. n acelai timp examineaz pacieni i opereaz. Cnd, n 1889, se deschide Spitalul Johns Hopkins, pe baza contribuiilor de pn atunci i fiind considerat recuperat, Halsted este numit Profesor Asociat, Chirurg activ al Spitalului i ef de Dispensar. Peste un an devine Chirurg ef n Spital, iar din 1892 Profesor de chirurgie. De atunci, timp de 3 decenii, pn la moarte, Halsted a fost eful chirurgiei de la Spitalul John Hopkins, Profesor i ef al Departamentului de chirurgie. Pentru dezvoltarea modern a chirurgie n S.U.A. Halsted a avut un rol esenial. n chirurgie, numele lui Halsted rmne legat de numeroase realizri n care de foarte multe ori a fost un pionier. Astfel: a fost primul care a introdus antisepsia n S.U.A.; n 1889 a introdus folosirea mnuilor de cauciuc la operaii; experienele sale cu cocaina au stat la baza dezvoltrii de mai trziu a anesteziei locale i regionale; a fost primul care a recurs la autotransfuzie. Numeroase procedee i tehnici chirurgicale au fost elaborate i aplicate de Halsted, de multe ori cu prioritate. Cea mai reprezentativ i care l-a fcut celebru o constituie tehnica mastectomiei radicale n cancerul de sn, tehnic ce s-a dovedit cea mai semnificativ mbuntire privind supravieuirea pacientelor cu cancer mamar, precum i n posibilitatea de control local al bolii. Acest fapt a dus la adoptarea rapid i larga rspndire ca metod standard de tratament timp de aproape un secol. Halsted a elaborat (1889) i o tehnic de cur a herniei inghinale n care cordonul spermatic este transpus deasupra aponevrozei marelui oblic. n chirurgia biliar a efectuat primele coledocotomii n S.U.A. A fost primul chirurg care n 1898 a efectuat rezecia unui adenocarcinom de ampul a lui Vater cu reimplantarea coledocului n sutura duodenal. mpreun cu Opel, a adus contribuii la patogenia pancreatitei acute de cauz biliar (1901); n pancreatita acut hemoragic, a descris un semn clinic ce-i poart numele. n chirurgia intestinului a subliniat importana efecturii anastomozelor cu fire de sutur trecute prin submucoas ca element de rezisten (1887). A descris i o modalitate proprie de sutur invaginant a intestinului. n chirurgia vascular a fost de asemenea primul care n 1892 a efectuat cu succes ligatura arterei subclaviculare stngi n prima sa poriune. n 1909 a recurs pentru ocluzia unui anevrism arterial la aplicarea unor benzi metalice n loc de ligatur. Pentru a proteja anevrisme de aort abdominal a efectuat bandingul proximal. L-a interesat mult fistulele arterio-venoase; a fost primul care a folosit n SUA firul de mtase pentru
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suturi arteriale; a creat i un tip de pens hemostatic de mare finee; n sindromul de compresiune scalenic a descris un semn care ii poart numele. n chirurgia tiroidian, mpreun cu A. Kocher de la Berna, a adus contribuii la tratamentul guei, elabornd o tehnic de tiroidectomie de mare meticulozitate. n acest domeniu a descris mpreun cu Evans o arcad anastomotic realizat pe faa posterioar a celor doi lobi tiroidieni, ntre artera tiroidian superioar i cea inferioar. A realizat cu succes experimente cu auto i alogrefe de paratiroid (1909). n chirurgia osoas a fost primul care a folosit plcile metalice nurubate aplicndu-le n tratamentul fracturilor oaselor lungi. A elaborat i o tehnic proprie de rahisintez cu grefon tibial. O contribuie dintre cele mai importante adus de Halsted const n introducerea conceptului de chirurgie sigur efectuat cu mult grij i meticulozitate, fr pierderi de snge, cu blndee fa de esuturi i cu refacerea complet a planurilor fr a lsa spaii libere. n domeniul grefelor de esuturi a creat o lege privind condiia de a le asigura integrarea. Dintre toate contribuiile lui Halsted n chirurgie, poate cea mai important a fost introducerea la Spitalul Johns Hopkins a unui sistem integrat de instruire a viitorilor chirurgi sub form de rezideniat. Este primul sistem de acest gen n S.U.A. i care de la Baltimore, s-a generalizat n ntreaga ar. Procesul de instruire se desfura pe o perioad de mai muli ani, responsabilitatea crescnd de la rezident asistent la rezident ef care ajunge s se bucure de o independen aproape total. n concepia lui Halsted atenia era pus cu precdere pe student sau rezident, pe munca, calitile i perspectivele sale i mai puin pe dascl sau profesor. Scopul final era de a crea o coal de clinicieni oameni de tiin, care s ajung elemente model, o elit reprezentativ de profesori i chirurgi efi de spitale, care s asigure procesul de modernizare a chirurgiei n SUA. Rezultatele s-au artat de excepie. Din cei 17 rezideni efi alei s fie instruii de Halsted, apte au devenit profesori la universiti de mare prestigiu, ntre care i Harvey Cushing. Cei 55 asistent rezideni instruii la Spitalul John Hopkins n spiritul colii lui Halsted, care n marea lor majoritate au devenit profesori, profesori asociai, specialiti de mare prestigiu, au constituit un nucleu de cadre a cror rspndire larg a influenat n mod determinat progresul chirurgiei n S.U.A. Spre sfritul vieii, Halsted a dus o existen mai retras. A avut multe relaii de prietenie, n special cu W. Welch i R. Matas precum i cu Th. Kocher. Ca o recunoatere a meritelor sale, Halsted a fost ales membru de onoare i preedinte a unor prestigioase societi tiinifice din ar i strintate. A fost membru al Academiei de tiine din S.U.A. n 1922, n vrst de 70 ani, Halsted moare n urmrile unei reintervenii pentru calcul coledocian restant dup o mai veche colecistectomie i coledocotomie. Aa cum i-a dorit, a avut o nmormntare din cele mai simple, la cimitirul Greenwood din Brooklyn, la care a participat doar Welch, iar din familie un frate i dou surori. Necrologul i l-a fcut Cushing. Personalitatea covritoare a lui Halsted a creat premisele uriaului avnt pe care chirurgia american l-a realizat pn n prezent. Motenirea lsat de el att n chirurgie ct i n procesul de pregtire a multor generaii de chirurgi, face, ca n memoria acestora, numele lui Halsted s rmn cu aureola unui mare precursor, exemplu de munc i perseveren.
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1. 2. 3. 4.
BIBLIOGRAFIE MacCallum WG. William Stewart Halsted, surgeon. Baltimore. Johns Hopkins Press. 1930 Cameron, J. Williams Stewart Halsted: Our Surgical Heritage. Annals of Surgery 1997; 225(5): 445458. Rutkow MI. Surgery: An ilustrated history. St Louis, Missouri. Mosby-Year Book, 1993. Rutkow MI. American surgery: an illustrated history. Philadelphia, Lippincott-Raven, 1998.
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ELEMENTE DE ANATOMIE CHIRURGICAL GHID PENTRU EXAMENUL DE SPECIALITATE

R. Moldovanu, V. Filip, N. Vlad Editura Tehnopress, Iai 2010 ntreaga activitate chirurgical se bazeaz pe cunotinele de anatomie; acestea sunt absolut necesare att pentru promovarea unui examen sau concurs ct, mai ales, pentru a face fa provocrilor zilnice ale activitii medicale, de la interpretarea corect a unei computer tomografii i pn la recunoaterea unui element anatomic n timpul actului chirurgical. Nu ntmpltor toi marii notri profesori de chirurgie au fost i anatomiti, i, a vrea s menionez un singur nume, Thoma Ionescu, ntemeietorul chirurgiei romneti moderne, care a fost profesor de anatomie la Paris i a scris capitolul Aparatul digestiv n Tratatul de anatomie al lui Poirier (1894). Lucrarea ELEMENTE DE ANATOMIE CHIRURGICAL GHID PENTRU EXAMENUL DE SPECIALITATE este binevenit n peisajul publicistic medical i nu este doar un simplu ghid pentru examenul de specialitate, ci va fi sigur util n activitatea medico-chirurgical zilnic. Monografia prezint att datele de anatomie clasice, ct i pe cele moderne, dar i diferitele discuii din literatur privind interpretarea elementelor de anatomie. Subiectele de anatomie sunt prezentate n succesiunea cunoscut: definiie, proiecii scheletotopice, limite, traiect, raporturi, morfologie, vascularizaie i inervaie; autorii insist asupra raporturilor i variantelor anatomice, ceea ce reflect att o intens activitate de documentare, ct i experiena lor personal. Monografia este tehnoredactat oarecum neobinuit pentru o astfel de lucrare, sub form de paragrafe; aceast structurare reflect ns experiena autorilor n activitatea didactic i asigur pentru tinerii medici un suport de lucru extrem de facil, iar chirurgilor formai un mijloc rapid de a revedea anumite particulariti anatomice nainte de o intervenie chirurgical. Ultimul capitol, Subiecte de anatomie n cadrul probelor de examen/concurs este un foarte util ndreptar pentru modul corect de tratare al subiectelor de anatomie n timpul diferitelor examene i concursuri. Interpretarea examinrilor moderne, de tipul computer tomografiei sau imagisticii prin rezonan magnetic, este actualmente absolut necesar n practica medicochirurgical; astfel, n patologia tumoral a esofagului, ficatului, pancreasului, rectului, interpretarea cupelor computer tomografice este esenial att pentru stabilirea diagnosticului, ct, mai ales, pentru stadializare i conduita terapeutic. Sunt deosebit de 135
Recenzii
binevenite i imaginile intraoperatorii, att din chirurgia clasic ct i din cea laparoscopic. Bibliografia cuprinde att lucrrile clasice de anatomie ct i tratate i articole moderne. Indicii bibliografici sunt inclui n text, n ordinea apariiei, iar citarea surselor s-a realizat n conformitate cu normele internaionale. n ncheiere, consider c aceast lucrare poate fi util fiecrui chirurg care practic chirurgia abdominal. E. Tarcoveanu
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Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr.

1 [ISSN 1584 9341]

Mircea Beuran (Bucuresti)

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

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Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

PRIORITI N TRATAMENTUL POLITRAUMATISMELOR CRANIO-CEREBRALE I ABDOMINALE

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

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EPIDEMIOLOGIA, ETIOPATOGENIA I DIAGNOSTICUL HEPATOCARCINOMULUI

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Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

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Fig.2 Aspectul ecografic al unui CHC termonecrozat.

Fig. 3 Tromboza venei porte la un pacient cu CHC multicentric.

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

Fig. 4 Aspectul CT al unui hepatocarcinom multicentric la o examinare multifazic.

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CANCERUL GASTRIC LOCAL AVANSAT SAU METASTAZAT ACTUALITI EPIDEMIOLOGICE I DIAGNOSTICE

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

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GREFONUL SINTETIC N TRATAMENTUL CHIRURGICAL AL EVENTRAIILOR. STUDIU EXPERIMENTAL

received date: 24.09.2010 accepted date: 15.12.2010

Jurnalul de Chirurgie, Iai, 2011, Vol. 7, Nr. 1 [ISSN 1584 9341]

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FACTORII DE RISC N APARIIA STAZEI GASTRICE POST DUODENOPANCREATECTOMIE CEFALIC

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Staz gastric Total 128 Absent - 106 Prezent - 22 P

Pierdere de snge <400 >400 ml ml 46 42 4(9%) 82 64 18(22%)

Complicaii Absente 74 74 0(0%) Prezente 54 32 22(41%)

GLOBAL p=0.374 0 VS 1 p=0.298 0 VS 2 p=0.448 1 VS 2 p=0.854

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11. 12. 13. 14. 15.

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TRAUMATISMELE ABDOMINALE - ATITUDINE TERAPEUTIC

received date: 28.09.2010 accepted date: 25.11.2010

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Fig. 1 Incidena anual a traumatismelor abdominale