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Surgical Treatment for Anomalous Arrangement ofthe Pancreaticobiliary Duct With Nondilatation

of the Common Bile DuctBy Naomi Iwai, Shigehisa Fumino, Tomoki Tsuda, Shigeru Ono, Osamu Kimura, and Eiichi Deguchi

Kyoto, Japan

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ackground/Purpose: For anomalous arrangement of theancreaticobiliary duct (AAPBD) with nondilatation of theommon bile duct (CBD), the optimal surgical procedureemains controversial. The authors investigated which pro-edure would be most effective for AAPBD with nondilata-ion of the CBD.

ethods: The authors encountered 60 children with AAPBDn our institution between 1979 and 2002. Six of the 60 werelassified as the nondilated type (CBD diameter; less than 8m), whereas the other 54 were classified as the dilated type

CBD diameter; more than 9 mm). Amylase levels in serum,BD, and gallbladder were examined. Cellular activity of theesected gallbladder was examined for the incidence of hy-erplasia and Ki-67 labeling index (Ki-67 LI).

esults: The amylase level in the nondilated type was ele-

ated as in the dilated type. Epithelial hyperplasia of the o

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allbladder was present in 4 of the 6 with the nondilated type67%). 10 of the 20 with the dilated type (50%), and none ofhe 6 controls (0%). The Ki-67 LI of the dilated type wasignificantly higher than that of control.

onclusions: A free reflux of pancreatic juice into the biliaryystem was found regardless of dilatation, and cellular pro-iferative activity of the gallbladder mucosa was increased inoth the nondilated and dilated type. Therefore, excision ofhe extrahepatic bile duct including cholecystectomy is rec-mmended for AAPBD with nondilatation of the CBD.Pediatr Surg 39:1794-1796. © 2004 Elsevier Inc. All rights

eserved.

NDEX WORDS: Anomalous arrangement of the pancreatico-iliary duct, choledochal cyst, common channel, hyperplasia

f gallbladder.

NOMALOUS ARRANGEMENT of the pancreati-cobiliary duct (AAPBD) often is associated with

holedochal cyst. Excision of the extrahepatic bile ductas been accepted as a standard procedure for chole-ochal cyst.1,2 Therefore, excision of the extrahepaticile duct is recommended for AAPBD with dilatation ofhe common bile duct (CBD). Recently, reports ofAPBD with nondilatation of the CBD have in-

reased.3,4 For those with nondilatation of the CBD,owever, the optimal surgical procedure remainsontroversial.

From the perspective of pathophysiology of the bileuct, we investigated which procedure was most effec-ive for AAPBD with nondilatation of the CBD. We alsoiscuss the definition of nondilatation of the CBD inediatric patients with AAPBD.

From the Division of Surgery, Children’s Research Hospital, Kyotorefectural University of Medicine, Kyoto, Japan.Presented at the 37th Annual Meeting of the Pacific Association of

ediatric Surgeons, Seoul, Korea, May 16-20, 2004.Address reprint requests to Professor Naomi Iwai, Division of

urgery, Children’s Research Hospital, Kyoto Prefectural Universityf Medicine, Kyoto, 602-8566, Japan.© 2004 Elsevier Inc. All rights reserved.0022-3468/04/3912-0014$30.00/0

MATERIALS AND METHODS

Between 1979 and 2002, 60 children with AAPBD aged 5 months to7 years were treated in the Division of Surgery, Children’s Researchospital, Kyoto Prefectural University of Medicine. All 60 underwent

xcision of the extrahepatic bile duct with Roux-en-Y hepaticojejunos-omy. Endoscopic retrograde cholangiopancreatography (ERCP) orntraoperative cholangiography was performed to confirm the diagno-is. Six of the 60, aged 1 year, 7 months to 13 years, who complainedf jaundice or abdominal pain with hyperamylasemia, were classifieds having the nondilated type by ERCP (diameter of the CBD; less thanmm). The remaining 54, aged 5 months to 17 years, were classified

s having the dilated type (diameter of the CBD; more than 9 mm;able 1). The AAPBD was classified into the P-C type, in which theajor pancreatic duct joined the CBD, and C-P type, in which the CBD

oined the major pancreatic duct.5

Amylase level in serum, CBD, and gallbladder were examined.ellular activity of the resected gallbladder was examined for the

ncidence of hyperplasia and Ki-67 labeling index (Ki-67 LI). Ki-67 LIas calculated by counting the number of Ki-67 positive cells per 1,000allbladder epithelial cells.6

Statistical analysis was performed using Welch’s t test as the vari-nces differed significantly, and Fisher’s Exact probability test (�2

est). A P value less than .05 was considered significant.

RESULTS

Clinical symptoms and cholangiopancreatography in 6atients with the nondilated type AAPBD are shown inable 2. There were 4 girls (aged 1 year, 7 months to 3ears), and 2 boys (aged 2 years and 13 years). Four ofhe 6 complained of abdominal pain accompanied by

omiting, and 2 of the 6 presented with jaundice. All of

of Pediatric Surgery, Vol 39, No 12 (December), 2004: pp 1794-1796

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1795ANOMALOUS ARRANGEMENT OF PANCREATICOBILIARY DUCTS

he 6 showed the P-C type of anomalous junction. Theiameter of the CBD ranged from 4 mm to 8 mm, and theength of common channel ranged from 6 mm to 25mmFig 1).

In these 6 patients with the nondilated type AAPBD,he mean amylase levels in serum, CBD, and gallbladderere 1,062 � 420 IU/L, 36,200 � 12,800 IU/L, and2,975 � 19,800 IU/L, respectively. In 54 patients withhe dilated type, the mean amylase levels in serum, CBD,nd gallbladder were 435 � 87 IU/L, 50,648 � 10,420U/L, and 82,640 � 14,982 IU/L, respectively. In chil-ren with AAPBD, serum and biliary amylase levelsere the same regardless of whether the bile duct wasilated.As shown in Table 3, epithelial hyperplasia of the

allbladder was present in 4 of the 6 children with theondilated type (67%), 10 of 20 with the dilated type50%), and none of 6 controls (0%). There was a signif-cant difference in the incidence of hyperplasia in theallbladder mucosa between the nondilated type andontrol patients (P � .02) and also between the nondi-ated type and control patients (P � .05).

The Ki-67 LI of the nondilated type was 6.02 � 1.91,hat of the dilated type was 14.46 � 3.17, and that ofontrols was 4.93 � 1.35. There was a significant dif-erence between the dilated type and controls (P � .02).

DISCUSSION

The precise definition of a dilated CBD in children hasot been fully established.7 In adult patients, however, it

Table 1. Patients with Anomalous Ar

No. of Patients

Common bile duct � 8 mm 6Common bile duct � 9 mm 54Control Patients 6

Table 2. Clinical Symptoms and Cholangiopancreatograp

CaseNo. Sex Age Clinical Symptom

1 F 2 yr JaundiceAcholic stool

2 F 3 yr Abdominal painVomiting

3 M 13 yr Abdominal painVomiting

4 F 3 yr Abdominal painVomiting

5 F 1 yr, 7 mo JaundiceVomiting

6 M 2 yr Abdominal pain

Vomiting

eems that there is a consensus definition of CBD diam-ter greater than 10 mm.8 Miyano et al9 defined aondilated type CBD as less than 8 mm (patients aged 1o 7 years), whereas Ando et al10 defined a nondilatedBD as less than 6 mm (patients aged 1 to 6 years). Wesed Miyano’s definition of less than 8 mm.All 6 of our patients with the nondilated AAPBD had

he P-C type, not the C-P type. Ono et al6 reported thatAPBD patients with P-C type showed higher incidencef epithelial hyperplasia of the gallbladder, which mightrogress to metaplasia or precancerous lesion11 com-ared with those with the C-P type. We found thatpithelial hyperplasia of gallbladder was increased inAPBD patients with a nondilated CBD. However, thealue of Ki-67 LI in the nondilated type, which has beensed as a good marker of cellular proliferation of tumorsnd precancerous lesions,12 was not significantly higherhan that in control patients.

A free reflux of pancreatic juice into the biliary systemhrough the anomalous junction occurs in patients withAPBD.13 This was confirmed in the current study,hich showed high amylase levels in serum, CBD, andallbladder in patients with both the dilated and nondi-ated type of AAPBD. Longstanding inflammation of theiliary tract might be caused by reflux of pancreaticuice, which becomes one of the factors promoting car-inogenesis in the biliary tract.14

Surgical indications in AAPBD in the absence ofiliary dilatation are controversial. Some investiga-ors15,16 have insisted that prophylactic cholecystectomy

ment of the Pancreaticobiliary Duct

x (M / F) Mean Age (Range)

2/4 4 yr, 2 mo (1 yr, 7 mo-13 yr)17/37 4 yr, 11 mo (5 mo-17 yr)3/3 3 yr, 2 mo (3 mo-12 yr)

dings in 6 Patients With the Nondilated Type of AAPBD

Type ofJunction

Diameter ofCBD (mm)

Length of CommonChannel (mm)

P-C 8 10

P-C 6 11

P-C 8 6

P-C 5 20

P-C 7 10

P-C 4 25

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1796 IWAI ET AL

s sufficient, especially in adult patients. Although thencidence of bile duct cancer was low, gallbladder canceras often observed. Furthermore, cholecystectomy is

ess invasive than excision of the extrahepatic bile duct.

Fig 1. Intraoperative cholangiopancreatography Case 6. AAPBD

ith nondilatation of the CBD was observed. The diameter of the

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BD was 4 mm. The length of common channel was 25 mm.

oth Miyano and Ando have argued that simple chole-ystectomy is not sufficient for pediatric patients with theondilated type. Because they feel that the goal ofurgery should be prevention of both bile stasis andeflux of pancreatic juice into the bile duct, they advocatexcision of the CBD in addition to cholecystectomy. Byhowing clear evidence of elevated amylase and epithe-ial hyperplasia in AAPBD patients with nondilateducts, the current study supports the belief that CBDxcision may be indicated. Furthermore, we previouslyeported cholangiocarcinoma in a child with choledochalyst and AAPBD.7 Based on these results, it was sug-ested that the extrahepatic bile duct should be excised inediatric patients with the nondilated type of AAPBD as

Table 3. Epithelial Hyperplasia and Ki-67 LI in the Gallbladder

of Patients with Anomalous Arrangement

of the Pancreaticobiliary Duct

No. of Patients

Presence ofEpithelial

Hyperplasia (%) Ki-67 LI

Nondilated type 6 4 (67%)* 6.02 � 1.91Dilated type 20 10 (50%)† 14.46 � 3.17‡Control patients 6 0 (0%)*† 4.93 � 1.35‡

NOTE. Values expressed as mean � SD.*P � .02.†P � .05.‡P � .02.

ell as in those with the dilated type.17

REFE

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ilatation with emphasis on pathophysiology of the biliary tract. Annurg 215:27-30, 19923. Ohta T, Nakagawa T, Ueno K, et al: Clinical experience of biliary

ract carcinoma associated with anomalous union of the pancreatico-iliary ductal system. Jpn J Surg 20:36-43, 19904. Todani T, Watanabe Y, Urushihara N, et al: Choledochal cyst,

ancreatobiliary malunion and cancer. J Hep Bil Pancr Surg 1:247-251,9945. Tokiwa K, Iwai N: Early mucosal changes of the gallbladder in

atients with anomalous arrangement of the pancreaticobiliary duct.astroenterology 110:1614-1618, 19966. Ono S, Tokiwa K, Iwai N: Cellular activity in the gallbladder of

hildren with anomalous arrangement of the pancreaticobiliary duct.Pediatr Surg 34:962-966, 19997. Witcombe JB, Cremin BJ: The width of the common bile duct in

hildhood. Pediatr Radiol 7:147-149, 19788. Hara H, Morita S, Ishibashi T, et al: Surgical treatment for

on-dilated biliary tract with pancreaticobiliary maljunction shouldnclude excision of the extrahepatic bile duct. Hepatogastroenterology8:984-987, 20019. Miyano T, Ando K, Yamataka A, et al: Pancreaticobiliary mal

unction associated with nondilatation or minimal dilatation of theommon bile duct in children: Diagnosis and treatment. Eur J Pediatr

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11. Duarte I, Llanos O, Domke H, et al: Metaplasia and precursoresions of gallbladder carcinoma. Frequency, distribution, and proba-ility of detection in routine histologic samples. Cancer 72:1878-1884,993

12. Porschen R, Lohe B, Hengels KJ, et al: Assessment of cellroliferation in colorectal carcinomas using the monoclonal antibodyi-67. Correlation with pathohistologic criteria and influence of irra-iation. Cancer 64:2501-2505, 1989

13. Iwai N, Tokiwa K, Tsuto T, et al: Biliary manometry in chole-ochal cyst with abnormal choledochopancreatico ductal junction.Pediatr Surg 21:873-876, 1986

14. Imazu M, Iwai N, Tokiwa K, et al: Factors of biliary carcino-enesis in choledochal cysts. Eur J Pediatr Surg 11:24-27, 2001

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16. Tanaka K, Nishimura A, Yamada K, et al: Cancer of theallbladder associated with anomalous junction of the pancreatobiliaryuct system without bile duct dilatation. Br J Surg 80:622-624, 1993

17. Iwai N, Deguchi E, Yanagihara J, et al: Cancer arising in aholedochal cyst in a 12-year-old girl. J Pediatr Surg 25:1261-1263,

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