Periampullary carcinoma

obstructive jaundice

a long case discussion

Dr Ramdip Ray

MS, MRCS ( Eng)

Assistant Professor Medical College, Kolkata

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My dear boy !
you said that the Gall bladder is firm This is a classic case of a

hard

gall bladder.

Sir !

I . felt that it is firm .

Are you sure ?

I think so

Okay go on

obstructive jaundice

Obstructive Jaundice

yellow sclera, skin, mucosa dark urine clay coloured stools itching

why itching ?
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the itch

accumulation of bile salts in blood/ tissues

sometimes precedes jaundice

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where to look for mild jaundice ?

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early jaundice

examine posterior hard palate

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why periampullary ?
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Periampullary CA

elderly male not known patient of gallstones

progressive jaundice
anorexia

Courvoisiers law

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Courvoisier's law : 1890

If in the presence of jaundice the gallbladder is palpable, then the jaundice is unlikely to be due to a stone
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Courvoisier's law : 1890

With obstruction of the common bile duct by stone, dilatation of gallbladder is rare. The organ is usually shrunken. With obstruction of other kinds, on the contrary, distention is the rule, shrinking occurs in only one twelfth of these cases 16

exceptions ?
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Exceptions to Courvoisier

pancreatic calculus at ampulla double impaction Oriental cholangiohepatitis

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Exceptions to Courvoisier

pancreatic calculus at ampulla double impaction Oriental cholangiohepatitis ( long standing stones in CBD + Clonorchis sinensis from freshwater fish )

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Exceptions to Courvoisier

NOT mucocele GB

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define periampullary CA
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Periampullary CA
within 2 cm of ampulla
1 2 3 4 pancreatic head / CA intrapancreatic CBD ampullary duodenal

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differential diagnoses ?
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Differential diagnoses

pancreatic head CA distal cholangioCA CA Gall bladder HCC CBD stone

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Other differential diagnoses

chronic pancreatitis
enlarged pericholedochal lymph nodes

sclerosing cholangitis
oriental cholangiohepatitis hydatid cyst choledochal cyst
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Which type of periampullary ?

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Which type of periampullary ?

difficult to say

typical ampullary :
intermittent / waxing & waning jaundice

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confirm obstructive jaundice

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confirm obstructive jaundice

hyperbilirubinemia, mainly conjugated elevated ALP & GGT

normal or mildly elevated ALT/AST

low albumin

prolongation of P time

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normal LFT values ?

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normal values

Albumin
ALP

: 3.5 5 mg / dL
: 30 300 IU / L ( adults )

ALT
AST

: 3 35 IU / L
: 3 35 IU / L

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Why does ALP rise ?

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Why ALP / GGT rise

ALP & GGT : bile duct epithelial damage ALT & AST : hepatocyte damage
Albumin & P time : hepatic synthetic function

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other causes of high ALP ?

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ALP rise

Obstructive Jaundice
Hepatocellular Jaundice Malignant infiltration Pagets disease Pregnancy Childhood

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elevated P time

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P time

Inj Vitamin K ( Vit K dependent II, VII, IX, X ) prefer I.V. to avoid risk of intramuscular haematoma FFP

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after LFT ?
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Ultrasonography

organ of origin GB
hepatomegaly, any liver SOL distented GB / absence of gallstones

dilated IHBR, CHD & CBD

dilated MPD any periampullary SOL any enlarged LN, ascites
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spleen just palpable ?

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Splenomegaly

just palpable.. One & a half times L sided portal hypertension splenic vein thrombosis

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father had an abdominal cancer

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familial / hereditary ?

HNPCC
Familial Breast Cancer ( BRCA2 mutation )

Peutz Jeghers
Ataxia telangiectasia FAMMM ( Familial Atypical Multiple Mole Melanoma )

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other risk factors ?

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Risk factors Pancreatic CA

age : strongest
smoking : N nitroso compounds hereditary / chronic pancreatitis cystic fibrosis carcinogens : DDT

diabetes mellitus ??
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diabetes mellitus

diabetes or abnormal GTT in 80 % of pancreatic CA

increased insulin, but reduced peripheral sensitivity

glucagon, somatostatin & amylin increased

amylin from peritumour tissue in response to a factor produced by the tumour. Surgical resection may improve !

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molecular genetics

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molecular genetics
The molecular genetics of pancreatic adenocarcinoma have been well studied. Of these tumors, 80-95% have mutations in the KRAS2 gene, and 85-98% have mutations, deletions, or hypermethylation in the CDKN2 gene. Of these cancers, 50% have mutations in TP53 and about 55% have homozygous deletions or mutations of Smad4. Some of these mutations can also be found in high-risk precursors of pancreatic cancer. For example, in chronic pancreatitis, 30% of patients have detectable mutations in TP16 and 10% have K-ras mutations. Although studies are underway, the genetic mutations associated with pancreatic adenocarcinoma are not yet clinically useful in screening for or diagnosing the disease.

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molecular genetics
The molecular genetics of pancreatic adenocarcinoma have been well studied. Of these tumors, 80-95% have mutations in the KRAS 2 gene, and 85-98% have mutations, deletions, or hypermethylation in the CDKN2 gene. Of these cancers, 50% have mutations in T P53 and about 55% have homozygous deletions or mutations of Smad4. Some of these mutations can also be found in high-risk precursors of pancreatic cancer. For example, in chronic pancreatitis, 30% of patients have detectable mutations in TP16 and 10% have K-ras mutations. Although studies are underway, the genetic mutations associated with pancreatic adenocarcinoma are not or diagnosing the disease.
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yet clinically useful in screening for

after USG ?
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CECT

confirm USG findings

liver mets, LN, distant mets hypodense mass on venous phase abutment, encasement or occlusion of portal vein / SMV / SMA or coeliac axis

vascular anomalies
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best imaging ?
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Current standard

helical CECT with 3D reconstruction

further imaging in equivocal cases

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other imaging options

MRCP MR Angiography

EUS PET

Laparoscopy
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role of EUS
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EUS

more sensitive for lesions < 2cm better for L N mets guided FNAC : esp for Neoadjuvant Issues : availibility, expertise, cost, invasive

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role of ERCP
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ERCP
to visualise / biopsy ampullary / duodenal brush cytology & delineation of cholangioCA for stenting : plastic or metallic

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pre operative stenting

unresolved debate

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pre operative stenting

biliary tract sepsis elderly / comorbidities

very high bilirubin levels

( as per institutional policy )

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pre op biopsy
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pre operative biopsy

non issue not required in good risk patient with double duct sign

negative bx will not change plan

positive bx may help in counselling if neo adjuvant planned 10 % benign after Whipples
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diagnostic laparoscopy
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diagnostic laparoscopy

very large tumours

no need of palliative surgery ( stent in place ) body / tail tumours

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Pathological dilemma

abundant desmoplastic stroma

widely scattered neoplastic glands

few cancer cells in FNAC / Bx specimens !

more host tissue than cancer cells

atypia often in chronic pancreatitis

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differential behaviour

similar perioperative M & M

post operative diabetes rare .. In all

long-term survival different

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differential behaviour

pancreatic most clinically aggressive

K ras mutations for codon 12 specific for pancreatic Jaundice more common in cholangio & ampullary

Waxing & waning in ampullary

But none present at earlier stage
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differential behaviour
Location Median survival 11 18 mo 22 33 mo 38 49 mo 86 mo 5 yr survival L N mets Perineural invasion Most 86 % 5 17 % -

Pancreatic Cholangio Ampullary Duodenal

6 26 % 13 43 % 33 48 % 32 67 %

56 79 %

56 69 % 30 50 % 36 47 %

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ampullary & duodenal

no ampulla in two-thirds
pathological distinction difficult

similar presentation / outcome

proposal : classified as one !

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Assessment of fitness

Hb, TLC, DLC Sugar, Urea, Creatinine CXR PA, ECG Echo, Stress Echo, TMT in some centres

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Informed consent

discuss diagnosis with patient natural course & treatment options the surgical procedure

chances of inoperability / surgical bypass

Risk of death ( < 4 % ) Risk of morbidities ( 30 50 % ) Residual disease / Recurrent disease
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pre operative preparation

adequate hydration : urine output

mannitol / diuretics : unproven role Inj Vit K 10 mg I.m. / I.v. 3 5 days FFP if required prophylactic I.v. antibiotics at induction stenting if indicated
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Complications of obstructive jaundice ?

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Obstructive jaundice

Cholangitis : pain, fever & jaundice

Toxic cholangitis : also shock, confusion

Infective complication
Coagulopathy Hepatorenal syndrome Impaired immune function
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plan

Whipples operation in good risk

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signs of inoperability

liver / distant metastases

peritoneal metastases SMV portal vein / SMA fixity

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palliative bypass

hepaticojejunostomy
NOT cholecystojejunostomy unless

laparoscopic palliation

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margins

pancreatic parenchymal
CBD

G I mucosal
retroperitoneal / uncinate / mesenteric vascular margin : most important

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controversies

pre op biopsy : resolved pre op stenting pre-op mannitol / diuretics prophylactic octreotide PP-PDR vs Classic PDR Classic vs extended PDR

Adjuvant therapy
Prophylactic G J : resolved
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thank you
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