Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997), pp.

2045± 2051

Is Biliary Lithogenesis Affected by Length

and Implantation of Cystic Duct?
Study of 270 Patients with Endoscopic Retrograde
Cholangiopancreatography
FRANCOIS-XAV IER CAROLI-BO SC, MD, JEAN-FRANC
Ë OIS DEMARQ UAY, MD,
MASSIMO CO NIO, MD, CHRISTIANE DEV EAU, MD, PATRICK HASTIER, MD,
ALAN HARRIS, MD, REMY DUMAS, MD, and JEAN-PIERRE DELMO NT, PhD

The gallbladde r se ems to play an important role in lithoge ne sis. Moreover, the morphology
and the implantation of the cystic duct may also in¯ ue nce this process. O ur purpose was to
e valuate if the le ngth and the implantation of the cystic duct may affe ct the formation of
gallstone s. Be twee n April 1992 and March 1994, 270 patie nts who unde rwent e ndoscopic
re trograde cholangiopancr eatography were include d in the study, and the radiological le ngth
of the cystic duct was carefully re corde d. Patie nts were divide d into two groups: I, abse nce of
lithiasis: 113 patie nts (65 men, 48 women); and II, gallbladde r lithiasis or lithiasis in the
common bile duct with or without gallbladde r lithiasis: 157 patie nts (73 men, 84 women). A
statistically signi® cant diffe rence was obse rved among the two groups regarding the inse rtion
of the cystic duct: implantation on the left side of the common bile duct re pre sented a risk
factor of lithiasis. The le ngth of the cystic duct was not dire ctly implicate d. Hypokine sis of the
gallbladde r is curre ntly re cognize d as be ing a major factor in the initial ste ps of lithoge ne sis,
but the implantation of the cystic duct can play an important role by incre asing cystic duct
re sistance and causing a reduce d washout e ffe ct of the gallbladde r conte nts, including
chole ste rol crystals.

KEY WORDS: lithogenesis; gallbladde r lithiasis; cystic duct implantation; cystic duct length.

During routine analysis of re trograde cholangiopan-
creatography x-rays, it was obse rve d that the diame te r
and le ngth of the cystic duct see med gre ate r in pa-
tients with gallstone s than in those without the m. In
orde r to verify this, a systematic study was made and
a ® rst pape r was publishe d on the diame te r of the
Manuscript receive d February 5, 1997; re vised manuscript re -
ce ived June 11, 1997; accepte d June 30, 1997.
From the De partment of Gastroe nterology, Arche t II Hospital,
Unive rsity of Nice, Nice , France.
Addre ss for re print re que sts: F.X. Caroli-B osc, Se rvice
d’He pato-Gastroente rologie, Ho
à pital Universitaire de l’Archet II,
151 route Saint-Antoine de GinestieÁ re , 06202 Nice Ce de x 3,
France .
cystic duct (1). The pre sent study conce rns the length
and implantation of the cystic duct.
The cystic duct, which is 0.5± 8 cm, conne cts the
ne ck of the gallbladde r to the common bile duct.
Most anatomists agre e on an ave rage le ngth of 3 cm
(2± 4). The course of the cystic duct and its entrance
to the hepatic duct are variable (5). The cystic duct
usually e nte rs the common he patic duct dire ctly
(about 70% of cases), but some time s it runs paralle l
to it, or spirals around it before e nte ring. The cystic
duct usually e nte rs the right side of the common bile
duct, but it can also run dorsally and e nte r the pos-
te rior left side (about 10% of time s). A long cystic
duct may run paralle l to the common bile duct for as

Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997) 2045
0163-2116/97/1000-2045$12.50/0 Ñ 1997 Plenum Publishing Corporation
 CAROLI-BOSC ET AL

T ABLE 1. COMPARISON OF CLINICOPATHOLOGICAL FEATURES IN T HREE G ROUPS OF P ATIENTS

G roup I (N 5 113) G roup II (N 5 73) G roup III (N 5 84)

Param eter N % N % N % P

Se x 0.09
Male 65 57.5 38 52.1 35 41.7
Fe male 48 42.5 35 47.9 49 58.3
Implantation* , 0.0001
RM 102 90.3 51 69.9 55 65.5
LM 11 9.7 22 30.1 29 34.5
Age (yr)² , 0.0001
Me an 6 SEM 57.2 6 14.8 65.4 6 17 68.7 6 19.5
# 64 77 68.1 31 42.5 28 33.3
. 64 36 31.9 42 57.5 56 66.7
Length (cm)² , 0.05
Me an 6 SEM 3.5 6 1.3 4.2 6 1.9 4.7 6 2.1
# 3 56 49.6 29 39.7 27 32.1
. 3 57 50.4 44 60.3 57 67.9

* RM, right margin; LM, left margin.

² The data are expressed as me an 6 SEM.

long as 3 cm, closely adhe re nt to it, and may e nte r it
afte r passing be hind the ® rst portion of the duode -
num. We think that the se variations in le ngth and
implantation may partially explain the formation of
gallstone s.
MATERIALS AND METHODS
In the De partme nt of Gastroe nte rology of the Unive r-
sity of Nice , be twe e n April 1, 1992, and March 31, 1994,
1540 e ndoscopic retrograde cholangiopancreatogr aphie s
(E RCP) we re pe rforme d, afte r simple pre me dication
with diazepam (V alium) and pe thidine (Dolosal), or
unde r ge neral ane sthesia with propofol (Diprivan) and
bromide of N-butylhyoscine (Buscopan). The e ndoscopes
used we re a Pe ntax E D 3410 and an O lympus JF1T10.
The E RCPs we re performe d for diagnostic, the rapeutic,
or both purposes.
Patients e xcluded from the study we re those with previ-
ous cholecystectomy, carcinoma of the pancreas or biliary
tract, benign stenoses of the sphincter of Oddi, periampul-
lary diverticula, lack of visualization of the e ntire cystic
duct, and biliary endoprotheses. We also excluded ERCPs
aime d at visualizing only the pancreas and ® lms where the
failure of the cannulation of the common bile duct oc-
curred.
The ® nal number of patie nts included in this study was
270. Pe rsonal data on e ach patie nt consisted of age , sex, and
implantation and length of the cystic duct. The length was
me asured by means of a string that was the n placed on a
grade d ruler, the e ndoscope diame te r (11 mm) was used to
make corrections for magni® cation (Table 1). Four types of
common bile duct (CBD) we re considered: (1) short cystic
duct placed on the right side of the CBD; (2) short cystic
duct placed on the left side of the CBD; (3) long cystic duct
placed on the right side of the CBD; and (4) long cystic duct
placed on the left side of the CBD. The cystic duct was
considered ª longº when its length was greate r than 3 cm.
The data were obtained from the ERCP x-ray ® lms of the
patie nts in the prone position. The presence or absence of
gallstones was ascertained on the same x-ray ® lms, as well as
by one or seve ral abdominal ultrasonographies taken before
or afte r the ERCPs.
The patie nts we re the n divide d into three groups (Ta-
ble 1) : group IÐ absence of lithiasis in the biliary tract
and gallbladde r; group IIÐ prese nce of lithiasis in the
gallbladder but not in the CBD; and group IIIÐ lithiasis
in the CBD with or without gallbladde r lithiasis. Groups
II and III we re comparable for all parame te rs described
in this study. To achieve the analysis, we compared two
groups: one without lithiasis (WL) and one with lithiasis
(L) (Table 2) .
Statistical analysis was performed using the chi-square
test and logistic regre ssion (BMDP) (6) .
RESULTS
Grou p IÐ Patien ts With ou t Lith ias is. O ne hun-
dre d thirte e n patie nts were include d, of the se 42.5%
were female s. The male /fe male se x ratio was 1.2,
mean age : 57.2 (range : 25± 86 ye ars). Among the se, 11
le ft-side implantations were found (9.7% ): this result
ove rlaps with data already re porte d in the literature
(5). A cystic duct longe r than 3 cm was de te cted in
50.4% of patie nts. The lower insertion was always on
the le ft side. The uppe r inse rtion was always on the
right side.
Grou p IIÐ Gallb lad d er Lith ias is. Seve nty-thre e
patie nts were include d, 47.9% of whom were wome n.
The male /female sex ratio was 1, mean age : 65.4
(range : 21± 94 years). Among them, 22 left-side im-
plantations were found (30.1% ). A cystic duct longe r
than 3 cm was observe d in 60.3% of patie nts. The
lower inse rtion was always on the le ft side .
Grou p IIIÐ CBD Lith ias is with or With ou t Gall-
blad der Lith ias is. Eighty-four patie nts were include d;
58.3% were women. The male/fe male sex ratio was

2046 Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997)
BILIARY LITHOGENESIS

T ABLE 2. COMPARISON OF C LINICOPATHOLOGICAL C HARACTERISTICS OF P ATIENTS

WITH (L) AND W ITHOUT (WL) L ITHIASIS*

G roup WL (N 5 113) G roup L (N 5 157)

Param eter N % N % P

Se x
Male 65 57.5 73 46.5 0.07
Fe male 48 42.5 84 53.5
Age (yr)
# 64 77 68.1 59 37.6 , 0.0001
. 64 36 31.9 98 62.4
Implantation
RM 102 90.3 106 67.5 , 0.0001
LM 11 9.7 51 32.5
Length (cm)
# 3 56 49.6 56 35.7 0.02
. 3 57 50.4 101 64.3

*As groups II and III showed similar characteristics, the patie nts we re pooled in two
groups: with (L) and without (WL) lithiasis.

0.7, me an age : 68.7 ye ars (range : 20 ± 97 ye ars) .
Among the m, 29 long left-side implantations were
found (34.5% ). The lower insertion was observe d four
times on the right side and 29 times on the le ft side.
All patie nts in this study with a cystic duct shorte r
than 3 cm showe d an inse rtion of the duct on the right
side of the CBD (N 5 112). In orde r to analyze the
role playe d by the inse rtion, we se le cted those pa-
tients with a cystic duct longe r than 3 cm (N 5 158)
(Table 3). Similarly, in orde r to evaluate the role of
the le ngth of this duct, we conside re d those patie nts
having an insertion of the cystic duct on the right side
of the CBD (N 5 208) (Table 4).
The le ngth of the cystic duct was not a risk factor
for lithiasis (Table 5). O n the contrary, the insertion
of the duct on the le ft margin of the CBD (Figure 1),

T ABLE 3. A NALYSIS OF P ATIENTS SHOWING A C YSTIC D UCT LONGER THAN 3 cm

(N 5 158)

G roup WL (N 5 57) G roup L (N 5 101)

Param eter N % N % P

Se x
Male 35 61.4 49 48.5 0.12
Fe male 22 38.6 52 51.5
Age (yr)
# 64 37 64.9 38 37.6 0.001
. 64 20 35.1 63 62.4
Implantation
RM 46 80.7 50 49.5 , 0.0001
LM 11 19.3 51 50.5

T ABLE 4. A NALYSIS OF P ATIENTS WITH C YSTIC D UCT ON THE R IGHT S IDE OF THE
CBD (N 5 208)

G roup WL (N 5 102) G roup L (N 5 106)

Param eter N % N % P

Se x
Male 59 57.8 50 47.2
0.12
Fe male 43 42.2 56 52.8
Age (yr)
# 64 70 68.6 37 34.9 , 0.0001
. 64 32 31.4 69 65.1
Length (cm)
# 3 56 54.9 56 52.8
0.76
. 3 46 45.1 50 47.2

Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997) 2047

T ABLE 5. E VALUATION OF I NFLUENCE OF A GE AND LENGTH
C YSTIC D UCT L ONGER THAN 3 cm*
Param eter Crude OR P Adjusted OR
Se x (F/M) 1.54 0.12
Age ( . 64/ # 64) 4.08 , 0.0001
Length ( . 3/# 3) 1.09 0.76
*Univariate and multivariate analysis.
which is always associate d with a length gre ate r than
3 cm, acts as a risk factor for lithiasis (O R 5 4.58; P ,
0.0001) (Table 6).
DISCUSSION
From our study, we conclude that our initial im-
pre ssion is valid, ie , implantation of the cystic duct on
the left side of the common bile duct is more freque nt
in patie nts with lithiasis than in those without it. In
this case, the length of the cystic duct was always ove r
3 cm. The patie nts with stone s were olde r and more
like ly to be female . Howeve r, in multivariate analysis
including age and se x, implantation was an inde pen-
de nt risk factor of lithiasis, whate ve r the group.
How are the se two facts re late d: is lithiasis a cause
or a conse que nce ? In our pre vious pape r on the size
of the cystic duct (1), we refute d the idea that large r
size may affe ct the incide nce of lithiasis. In fact, the
gallbladde r se e ms to play an increasingly important
role in lithoge ne sis (7± 9). It is well known that the
® rst ste p of lithoge nesis occurs in the gallbladde r.
This ste p is characte rize d by chole ste rol crystals and
sludge (10) when the following three factors combine :
incre ase in the inde x of chole ste rol solubility, balance
of nucle ation and antinucle ation factors (the secre-
tion of mucus by the gallbladde r se e ms to be signi® -
cant) , and hypokine sis of the gallbladde r.
The initial elements of gallstone s (groups of crys-
tals, microgallstone s , 2 mm not dete ctable by ultra-
sonography) are ¯ ushe d into the CBD during normal
gallbladde r contractions (11, 12) . A cystic duct con-
ge nitally large r than normal facilitate s the evacuation
of the se e le me nts and is the re fore a prote ction
against lithiasis. Accordingly, in our previous pape r,
we conclude d that an incre ase in the diame te r of the
cystic duct was not a cause but a conse que nce of
gallstone s and the ir migration.
In the pre sent pape r, the discussion is diffe re nt: in
no way is the position of the cystic duct on CBD a
conse que nce of gallstone s and the ir migration. Two
hypothe se s may be conside re d:
1. Infection . Whe n the cystic duct is implante d on
2048
CAROLI-BOSC ET AL
IN P ATIENTS WITH
Con® dence
interval P
1.37 0.76± 2.46 0.29
3.96 2.20± 7.12 , 0.0001
1.03 0.57± 1.85 0.93
the le ft side of the CBD (Figure 1), its position is very
low and the re is often only 1± 3 cm of true CBD. The
proximity of the two ori® ces (O ddi and cystic junc-
tion) have the same e ffect on uppe r migrating infe c-
tions. Some authors are of opinion that periampullary
dive rticula may affect gallbladde r or CBD lithiasis
(13± 15) . Howeve r, whe n there is no dif® culty in ¯ ush-
ing bile into the duode num, the bile of the CBD is
ste rile (16) . Furthe rmore, bacte ria that lack bilirubin
conjugation favors pigme ntary lithoge nesis (17) . Re-
cent unpublishe d data from our group con® rms that
lithiasis in our are a is chole sterolic in nature in more
than 80% of case s.
2. Sp iral Morphology an d In crease in Cystic Dead
Sp ace. This se cond hypothe sis see ms more re alistic. It
implie s dif® culty in ¯ ushing the primary e le ments of
lithiasis (crystals, microgallstone s, etc) from the gall-
bladde r. The work of Ivy and O ldbe rg (18) and Boy-
de n (19) in the 1920s on the function of the biliary
ducts is no longe r valid. The ir theory was base d on the
contractions of the sphincte r of O ddi (closing tone of
the sphincte r of O ddi) (20), which allow inte rprandial
® lling and postprandial e mptying of the gallbladde r
by ope ning unde r the in¯ ue nce of CCK.
Se veral re cent article s show that the gallbladde r is
not ine rt during the inte rprandial pe riod and that bile
¯ ow is adjuste d by the migrating motor comple x
(MMC) (21± 25) . More over, the gallbladde r acts like a
pair of bellows, with succe ssive e mptying and ® lling
phase s cause d by the chole re tic he patic ¯ ow, which is
incre ase d by meals. This is cle arly shown by the work
of Lanzini et al (26) . Final con® rmation is provide d by
more recent work of Howard et al (27) . It can the re -
fore be assume d that if microgallstone s and chole s-
te rol crystals appe ar in the gallbladde r, they are more
easily ¯ ushe d in the case of a right-side d implantation
of the cystic duct. The spiral morphology of the cystic
duct, due to its insertion on the left margin, incre ase s
the re sistance of the bile ¯ ow into the duode num, and
the bile stasis could promote the appe arance of cho-
le ste rol crystals.
The cystic duct represe nts a de ad space comparable
Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997)
BILIARY LITHOGENESIS

Fig 1. Endoscopic retrograde cholangiogram showing a cystic duct implanted on

the left side of the common bile duct.

to the de ad air space re late d to re spiratory physiology we faile d to obse rve any statistically signi® cant in¯ u-
(28) . A left implantation of the cystic duct is always ence of the le ngth of the duct, there is undoubte dly an
associate d with a le ngth gre ate r than 3 cm. Although incre ase of the dead space as mentione d above .

T ABLE 6. E VALUATION OF I NFLUENCE OF A GE AND I MPLANTATION IN P ATIENTS WITH CYSTIC D UCT

L ONGER THAN 3 cm*

Con® dence
Param eter Crude OR P Adjusted OR interval P

Se x (F/M) 1.69 0.12 1.37 0.66± 2.84 0.39

Age ( . 64/ # 64) 3.07 0.001 3.33 1.60± 6.91 0.001
Implantation (LM/RM) 4.27 0.0001 4.58 2.04± 10.3 0.0001

*Univariate and multivariate analysis.

Digestive Diseases and Sciences, Vol. 42, No. 10 (October 1997) 2049

As one of the ® rst stage s of e xpe rime ntal litho-
ge ne sis appe ars to be gallbladd e r hypokine sis ( 29 ±
31) , e xplaine d by a de cre ase in the e ndoge nous
se cretion of CCK ( 32, 33) , it is assum e d that crys-
tals or microgallstone s ¯ ushe d into the cystic duct
cannot re ach the CBD and are drawn bac k ( be llows
contractions) or re turne d ( biliary he patic ¯ ow) to
the gallbladd e r.
This mechanism may allow an incre ase in the size
of gallstone s, due to the succe ssive deve lopme nt of
chole sterol crystals and of a glycoprote in matrix re-
sulting from the mucus produce d by the gallbladde r
epithe lium (34) , until gallstone s become too large to
be e liminate d through a narrow cystic duct. It would
be inte resting to know if, in othe r e pide miological
surve ys, a right implantation of the cystic duct was
pre sent in patie nts from whom gallstone s disappe are d
( 35) . Similarly, it would be important to know
whether it was also pre se nt in the 9% of subje cts in
the control group of a randomize d study in whom
gallstone s disappe are d, as re porte d by Schoe n® eld et
al on gallstone dissolution (36) . O f course , this ana-
tomic factor would be insuf® cient, as gallbladde r con-
tractions are of major importance (37) , but it is as-
sume d that a spiral anatomical structure and an
exce ssive le ngth of the cystic duct enhance the e ffects
of hypokine sis.
If our second hypothe sis could be ve ri® ed, it would
explain why that, after medical treatment [dissolution
by bile acids with or without e xtracorpore al shock-
wave lithotripsy (ESWL) ], two groups see m to e xist
(38, 39) : one showing a 10% re lapse rate pe r ye ar and
the othe r no relapse . It would be extre mely inte re st-
ing to determine if, in the second group, a right-side
implante d, large r than normal cystic duct is pre sent
(1). In conclusion, we think that, in the study of biliary
lithiasis, the e xtrahe patic bile ducts de se rve greate r
atte ntion.
Hypokine sis of the gallbladde r is currently re cog-
nize d as be ing a major factor in the initial ste ps of
lithoge ne sis, but also the diame te r and the implanta-
tion of the cystic duct can play important role s. This
hypothe sis is corroborate d by a report of Pitt et al
(40) who sugge st that be fore gallstone formation,
stasis re sults from both increased cystic duct re sis-
tance and alte re d gallbladde r compliance . Recently,
Jazrawi e t al (41) propose d a mode l that shows the
turnove r of bile is marke dly re duced in chole lithiasis,
causing a reduce d washout effe ct of the gallbladde r
conte nts, including chole ste rol crystals. Others have
studie d the re lationship betwe en cystic duct anatomy
and gallstone s. When the cystic duct e nte red the
2050
CAROLI-BOSC ET AL
he patic duct at a very low position, complications
such as gallstone s, pancre atitis, or Mirizzi syndrome
occurred more fre que ntly (42). Bornman e t al (43)
have shown that stone s in the bile duct are commonly
associate d with a low, and ofte n, le ft-side d e ntry of
the cystic duct into the bile duct. Finally, Kubota e t al
(44) showe d recently that low e ntry of the cystic duct
was observe d freque ntly in patie nts with chole cysto-
lithiasis (15.7% vs 2.1% in controls, P , 0.01), which
correlate s our re sults.
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