Congenital Choledochal Cysts in Adults

PAPER Congenital Choledochal Cysts in Adults

Brendan C. Visser, MD; Insoo Suh, BS; Lawrence W. Way, MD; Sang-Mo Kang, MD

Hypothesis: Excision of the extrahepatic portion of con- (1patient). In none of the patients with cancer was sur- genital choledochal cysts (CCs) avoids the risk of can- gery not curative. Nine patients had previously under- cer. The standard classification scheme is out of date. gone a cystoduodenostomy and/or cystojejunostomy as children. Four of them had cancer on presentation as Design: Retrospective case series and literature review. adults. There were no postoperative deaths. Cancer sub- sequently developed in no patient whose benign extra- Setting: Tertiary care university hospital. hepatic cyst was excised, regardless of the extent of en- largement of the intrahepatic bile duct. Patients: Thirty-eight adult patients diagnosed as having CC from 1990 to 2004 . Conclusions: Congenital CCs consist principally of congenital dilation of the extrahepatic bile duct with a vari- Main Outcome Measures: Clinical and radio- able amount of intrahepatic involvement. We believe that graphic imaging findings, operative treatment, patho- the standard classification scheme is confusing, unsup- logic features, and clinical outcome. ported by evidence, misleading, and serves no purpose. The distinction between type I and type IV CCs has to be ar- Results: Thirty-nine adult patients were treated for CCs bitrary, for the intrahepatic ducts were never completely (mean [SD] age at diagnosis, 31 [17] years, and mean normal. Although Caroli disease may resemble CCs mor- [SD] age at surgery 37 [14] years). The primary report phologically, with respect to cause and clinical course, the was abdominal pain (36 of 39 patients). Eight patients 2 are unrelated. The other rare anomalies (gallbladderlike had cholangitis, 5 had jaundice, and 6 had pancreatitis. diverticula; choledochocele) are also unrelated to CC. There- Radiographic imaging studies and operative findings fore, the term “congential choledochal cyst” should be ex- showed that the abnormality predominantly involved the clusively reserved for congenital dilation of the extrahe- extrahepatic bile duct in 30 patients, the intrahepatic and patic and intrahepatic bile ducts apart from Caroli disease, extrahepatic bile ducts in 7 patients; and 2 were diver- and the other conditions should be referred to by their ticula attached to the common bile duct. Surgical treat- names, for example, choledochocele, and should no longer ment in 29 (90%) of 31 patients with benign cysts (re- be thought of as subtypes of CC. Our data demonstrate once gardless of intrahepatic changes) consisted of resection again a persistent tendency to recommend expectant treat- of the enlarged extrahepatic bile duct and gallbladder and ment in patients without symptoms and the extreme risk Roux-en-Y hepaticojejunostomy. Eight patients (21%) of nonexcisional treatment. The entire extrahepatic bil- were initially seen with associated cancer (cholangiocar- iary tree should be removed when CC is diagnosed whether cinoma of the extrahepatic duct in 6; gallbladder cancer or not symptoms are present. The outcome of that ap- in 2). Seven of 8 patients had a prior diagnosis of CC but proach was excellent. had undergone a drainage operation (3 patients), expectant treatment (3 patients), or incomplete excision Arch Surg. 2004;139:855-862

ESCRIBED INITIALLY IN fication system, which has been widely 1852,1 congenital chole- adopted, includes no less than 8 separate dochal cysts (CCs) were alphanumeric subtypes (Figure 1).5 separated into 3 types by Though the diagnosis of CC is most Alonso-Lej et al 2 in 1959. often made in childhood, 25% of patients TodaniD and colleagues3 modified this clas- are initially seen as adults.6,7 In the past, CCs sification in 1977 adding types IV and V, were often treated using drainage proce- 4 From the Department of and more recently Todani revised it fur- dures (cystoduodenostomy or cystojejun- Surgery, University of ther to reflect the presence of pancreati- ostomy),8-10 but it has since become clear California, San Francisco. cobiliary maljunction. The Todani classi- that these operations have not only an unac-

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 855

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 pancreatitis, 5 (13%) jaundice or impaired liver function, and 4 (11%) weight loss. Three of 5 patients pre- senting with jaundice and 3 of 4 patients reporting weight Ib loss were found to have cancer, which had arisen within Ia the abnormal extrahepatic biliary tree. Nonspecific mild to moderate elevations of preoperative liver function test Ic I II III results and amylase levels were observed. The laboratory findings in patients with cancer did not differ from those with benign disease. Imaging studies were performed with the following frequency: endoscopic retrograde cholangiopancreaticography, 79%; computed tomography, 68%; ultrasonography, 65%; percutaneous IV-A IV-B V transhepatic cholangiography, 18%; magnetic reso- nance imaging, 9%; oral cholecystogram, 3%; and hepato- iminodiacetic acid (lidofenin) scan, 3%. Each patient un- Figure 1. Todani classification of choledochal cysts (reprinted with permission from Todani et al5). derwent a mean of 2.4 (0.9) preoperative imaging tests. In 30 patients (74%) the abnormality consisted prima- rily of dilation of the extrahepatic bile duct with less ceptable rate of long-term complications, most particu- prominent dilation of the intrahepatic ducts (Todani type larly malignant transformation, but also anastomotic stric- I); in 7 patients (18%) dilation of the extrahepatic bile ture formation, cholangitis, pancreatitis, and biliary ducts was accompanied by equally prominent dilation of calculi.11-14 To prevent these long-term complications, cyst the intrahepatic ducts (Todani type IVa); and 2 patients excision has been recommended for all patients, includ- (5%) had lesions consisting of a polypoid diverticulum ing those who have previously undergone drainage pro- (similar in appearance to a gallbladder) attached to an cedures.6,7,15,16 Our experience, however, indicates that the otherwise normal bile duct (Todani type II). Deciding risks of temporizing are still underappreciated. In addi- whether to call the disease type I or type IVa was arbi- tion, confusion persists regarding the appropriate proxi- trary, because the intrahepatic ducts were never en- mal and distal extent of cyst excision, particularly with re- tirely normal in any patient with congenital dilation of gard to the treatment of intrahepatic disease. Our analysis the extrahepatic bile duct. The presence or absence of of a large group of adult patients with this condition leads pancreaticobiliary maljunction was poorly documented us to challenge the validity of the accepted classification in the patients who had undergone endoscopic retro- system and to reemphasize the critical need for complete grade cholangiopancreaticography. removal of the extrahepatic biliary tree. Among the 31 patients with benign disease, 28 patients (90%) were treated by excision of the extrahe- METHODS patic bile duct and gallbladder and reconstruction with The clinical and laboratory findings of 39 adult patients who were a Roux-en-Y hepaticojejunostomy. One patient had ex- treated for CCs at the University of California, San Francisco, from cision of the duct and end-to-side hepaticoduodenos- 1990 to 2004 were analyzed for demographic and clinical infor- tomy, 1 underwent a Whipple pancreaticoduodenec- mation. The preoperative data included the patient’s age at diag- tomy, and 1 underwent excision of a large distal remnant nosis, manifesting symptoms, and the results of diagnostic tests. of a cyst that remained after partial resection and hepati- Preoperative radiographic imaging findings were reviewed to verify cojejunostomy at another hospital. No patient under- the morphologic condition of the biliary abnormalities. Ten pa- went liver resection for intrahepatic involvement. tients had previously undergone 1 or more operations on the bil- Eight patients (21%), whose mean age was 52 (15) iary tree (ie, cystoduodenostomy or cystojejunostomy) at other years, presented with an invasive cancer. Six had cho- institutions. Details of the operations conducted at University of langiocarcinoma and 2 had gallbladder cancer. The pres- California, San Francisco were determined, including the extent of excision, technique of biliary reconstruction, perioperative ence of the CC had been known for many years in 7 of 8 course, complications, and outcome. Data are given as mean (SD) patients, whose earlier treatment had been limited to values unless otherwise noted. This study was reviewed and ap- drainage (3 patients), expectant treatment (3 patients), proved by the University of California, San Francisco Commit- or partial excision (1 patient). These patients and their tee on Human Research. operations are summarized in Table 1. In none of the patients with cancer was surgery not curative. One pa- RESULTS tient with carcinoma in situ in the excised cyst has had no evidence of further disease after 31 months. Thirty-nine adults, 7 men (18%) and 32 women (82%), Ten patients had undergone previous operations on with congential CCs were treated between 1990 and 2004. their biliary tree at other hospitals (Table 2). Four (40%) Ten patients (26%) were Asian and 29 patients (74%) were of 10 patients were found to have cancer on evaluation white or Hispanic. The patient’s mean age at initial di- at our institution. The mean interval between the first agnosis of CCs was 31 (17) years. The patient’s mean age operation and the diagnosis of cancer in these patients at the time of treatment at the University of California, was 26 years. San Francisco was 37 (14) years. The primary present- Postoperative complications, most of which were mi- ing symptom in 36 patients (92%) was abdominal pain. nor, developed in 11 (29%) of 38 patients who under- Eight patients (21%) had episodes of cholangitis, 6 (16%) went surgery. One patient required a second operation

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 856

Patient No./ Age at Age at Initial Diagnosis of Choledochal Diagnosis, y Prior Operation Cancer, y Manifestation Cyst Type* Operation at UCSF Pathologic Features 1/5 Cystoduodenostomy and 40 Pain I Excision of cyst and T3 cholangiocarcinoma at cystojejunostomy hepaticojejunostomy prior anastomosis in cyst 2/15 Cystojejunostomy 35 Pain I Excision of cyst and T4 cholangiocarcinoma in cyst hepaticojejunostomy 3/62 None 62 Jaundice and IVa Excision of extrahepatic BD T3 cholangiocarcinoma from weight loss and R-sided R hepatic duct trisegmentectomy 4/5 Cystoduodenostomy 33 Pain, jaundice, I None; CT revealed tumor in FNA of liver metastasis: and weight choledochal cyst and liver cholangiocarcinoma loss metastasis; underwent PTBD 5/52 None (“observed” after 58 Pain I Excision of cyst, radical T3N1 gallbladder cancer diagnosis because cholecystectomy, and symptoms improved) hepaticojejunostomy 6/68 None (planned excision 73 Pain, jaundice, I Palliative cholecystectomy and T2N2 gallbladder cancer but preoperative workup and weight choledochoduodenostomy revealed CAD required loss CABG; then lost to follow-up) 7/50 None (‘observed’ after 53 Pain and I Excision of cyst and T3 cholangiocarcinoma in cyst diagnosis because weight loss hepaticojejunostomy symptoms improved) 8/23 Cholecystectomy; partial 45 Pain I Whipple operation T2 cholangiocarcinoma in cyst excision and remnant choledochojejunostomy

Abbreviations: BD, bile duct; CAD, coronary artery disease; CABG, coronary artery bypass graft; CT, computed tomography; FNA, fine-needle aspiration; PTBD, percutaneous transhepatic biliary drain; UCSF, University of California, San Francisco. *Todani choledochal cyst classification type I indicates dilation of the extrahepatic bile duct with less prominent dilation of the intrahepatic ducts; type IVa, dilation of the extrahepatic ducts with accompanying equally prominent dilation of the intrahepatic ducts.

to revise a stricture at the hepaticojejunostomy anasto- Others have postulated that partial distal obstruction, mosis. One patient died of gastrointestinal hemorrhage whether due to a stricture, web, or sphincter of Oddi dys- from an arteriobiliary fistula after percutaneous tran- function, might have a causative role.15,21,22 These theo- shepatic dilation of an anastomotic stricture. ries are interesting but supported by sparse evidence. At most, they could only partially explain the pathogen- COMMENT esis since CCs occur without an anomalous biliary- pancreatic junction, anomalous junction is common in the As now used, the term choledochal cyst is unfaithful to absence of biliary disease, and pancreatic enzymes are not the usual meaning of these words. Choledoch, a word that universally found within congenital CCs. refers to the common bile duct, comes from the Greek The first classification system for CCs was proposed words chole (bile) and dechomai (to receive). The word by Alonso-Lej et al,2 but the most widely used one, au- cyst, from the Greek kystis (sac, bladder), is convention- thored by Todani and colleagues,3,4 includes 8 separate al- ally defined as a closed cavity or sac lined by epithe- phanumeric subtypes (Figure 1). Types I and IVa, which lium. Choledochal cyst, however, has escaped from this are variations of a single disease, account for more than etymology and is used to cover the entire spectrum of 90% of the patients. 6,23,24 Type III cysts are better known congenital dilation throughout the biliary tree. Further- as choledochoceles, and type V refers to Caroli disease. more, the lesions are not really cysts The type II lesions appear as a diverticulum of the com- The cause of CCs is uncertain. Most patients with mon bile duct. Some such cases closely resemble gallblad- types I and IV lesions also have an anomalous pancreati- der duplication while others are more rudimentary diver- cobiliary junction, in which the pancreatic duct joins the ticular structures. There is no reason to believe that these bile duct 1 to 2 cm proximal to the sphincter of Oddi.15,17,18 choledochal diverticula are related to the more common This results in a common channel of 15 mm or more, which congenital ductal dilation. In choledochoceles, the duct has been thought to allow reflux of pancreatic enzymes terminates in a small intramural cystic lesion lined by into the bile duct, increasing ductal pressure, and caus- duodenal mucosa. Choledochocele has no clinical, patho- ing it to dilate.19 Experimental diversion of pancreatic juice logic, or etiologic relationship to CC, and most observers into the bile duct produces progressive dilation in dogs.20 consider it to be a variant of duodenal duplication. Caroli Nevertheless, a high junction is seen in about 9% of en- disease is thought to arise from ductal plate malforma- doscopic retrograde cholangiopancreaticograms per- tion and is often associated with congenital hepatic fibro- formed in patients without congenital choledochal cysts.18 sis (with cirrhosis and portal hypertension).25 It is an au-

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 857

Symptoms Patient No./Age at at Second Age at UCSF Diagnosis, y Prior Operation Presentation Operation, y Operation at UCSF Cancer 1/21 Laparoscopic exploratory Pain 21 Excision, Roux-en-Y No surgery (planned hepaticojejunostomy cholecystectomy but aborted when found cyst) 2/5 Cholecystectomy, Pain 40 Excision, Roux-en-Y Cholangiocarcinoma cystoduodenostomy, and hepaticojejunostomy cystojejunostomy 3/Child Cystoduodenostomy and Pain and weight 66 Excision, Roux-en-Y No cystojejunostomy loss hepaticojejunostomy 4/57 Cystojejunostomy Cholangitis 60 Excision, Roux-en-Y No (intrahepatic hepaticojejunostomy, stones) and gastrojejunostomy 5/3 Cystojejunostomy and Pain 29 Excision of cyst remnant No excision with hepaticojejunostomy 6/5 Cystoduodenostomy Pain, jaundice, and 33 None, unresectable Cholangiocarcinoma weight loss cholangiocarcinoma required PTBD 7/2 Cystoduodenostomy Pain 35 Excision, Roux-en-Y No hepaticojejunostomy 8/15 Cystojejunostomy Pain 35 Excision, Roux-en-Y Cholangiocarcinoma hepaticojejunostomy 9/15 Cystoduodenostomy Pain and 37 Excision, Roux-en-Y No cholangitis hepaticojejunostomy 10/23 Cholecystectomy and partial Pain 43 Whipple operation Cholangiocarcinoma excision with choledochojejunostomy

Abbreviation: PTBD, percutaneous transhepatic biliary drain.

cer. In the Japanese registry of 1353 patients, 16% overall had coincident cancer, increasing with each age of life de- cade from 2% for patients in their 20s, to 43% for those in their 60s.30 Type I and IV cysts have the highest risk of cancer,31 while cancer is rare in choledochoceles and gallbladder duplications.32,33 Caroli disease carries a small (about 7%) risk of cholangiocarcinoma,34,35 but most patients with Caroli disease require treatment for cholangitis or compromised liver function well before cancer appears.36 While most of the reported cases of cancer arising in CCs are cholangiocarcinoma within dilated extrahepatic bile ducts, 10% are gallbladder cancers.29 The overall survival following the diagnosis of cancer is poor, regardless of treatment. Few patients survive beyond 2 years.7,28,37,38 Thus, the pathogenesis, risk of malignancy, natural history, and treatment of CCs vary with each of the Todani subtypes except I and IV, which are the same condition. We believe the current classification system is a Figure 2. Endoscopic retrograde cholangiopancreaticogram showing Todani cause of confusion and has no discernible purpose. First, type I choledochal cyst (arrowhead), although the intrahepatic biliary tree is it incorporates 4 distinct diseases, and by grouping them also abnormally dilated (arrows). together incorrectly suggests that they are related. Sec- ond, by separating types I and IV into different sub- tosomal recessive inherited condition with specific types, a distinction is made that is artificial or at least chromosomal abnormalities26,27 and clinically is associ- greatly exaggerated. The intrahepatic ducts are almost al- ated with intrahepatic gallstone formation and a high in- ways abnormal; just the magnitude varies (Figure 2). cidence of renal disease. Although the radiologic findings Furthermore, the intrahepatic dilation could either re- in Caroli disease may resemble a CC, the other features flect congenital ectasia or stasis from the extrahepatic dis- show it to be a distinct, unrelated entity. ease, and the contribution of each may be impossible to In the current series as well as in other reports,7,28,29 judge. We think discussions of these anomalies would many patients with CC presented with concomitant can- be simplified and made more understandable by aban-

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 858

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 doning the numerical designations altogether and just re ferring to them according to the descriptive terms already in common use: CC, choledochal diverticulum, choledochocele, and Caroli disease (Figure 3). The term congenital CC should be reserved for the single condition made up of Todani types Ia through Ic and IVa. It would then be unnecessary to include cases of the un- Choledochal Cysts related anomalies in articles on congenital CCs. It has been suggested that cystenterostomy, by ex- posing the mucosa of the abnormal duct to pancreatic juice, may hasten the development of cancer in a choledochal cyst.24 But as mentioned earlier, time seems to be the domi-

nant factor. Thus, the principal risk of a drainage proce- Choledochal Diverticulum Choledochocele Caroli Disease dure may be to render the patient asymptomatic until cancer appears many years later. Although for 30 years the Figure 3. Proposed new nomenclature of biliary lesions formerly all termed literature on the surgical treatment of congenital CCs has “choledochal cysts.” The choledolchal cysts depicted are not meant to stressed the superiority of cyst excision over a drainage represent distinct subtypes, but merely to depict the spectrum of intrahepatic procedure, drainage procedures may still be required un- involvement. der circumstances in which a more aggressive operation is too risky for technical or clinical reasons. What needs emphasis at this point is the importance of electively ex- developing in the remaining ductal system is small. In cising the abnormal bile duct later after the patient has re- fact, malignant degeneration in the intrahepatic ducts may covered from the palliative bypass. Even some recent au- be related to the enteric anastomosis itself rather than to thors have equivocated on the indications for surgery in any intrinsic quality of the biliary epithelium associated patients who have had a bypass. Two people in our series with CC disease.50 Therefore, more radical procedures— who had cystoduodenostomies in childhood had been told hepatic resection and transplantation—are unwar- that they might some day need another operation but that ranted as prophylaxis against cancer, regardless of the they could wait until symptoms developed. The first symp- extent of dilation of the intrahepatic ducts. toms, several decades later turned out to be from incurable cancer in the cyst. Three (30%) of 10 patients in the CONCLUSIONS current series who had previously undergone cystenterostomy were found to have cancer on presentation at our This series, one of the largest in North America, dem- institution. We recommend that any patient with a con- onstrated the extreme risk of nonexcisional treatment of genital CC who had had a bypass operation in childhood CCs. The standard classification scheme for CCs is con- have the cyst excised before the age of 30 years whether fusing and inaccurate. The distinction between Todani or not symptoms are present. type I and type IV cysts is arbitrary because the intrahe- Despite near universal recognition of the impor- patic ducts are never completely normal. We believe that tance of excision, the specific surgical technique remains the numbered system of types should be abandoned, the controversial, particularly with regard to the proximal and term congenital CC should be reserved for the anomaly distal extent of resection 6,39,40 and the conduit for recon- consisting of extrahepatic and variable degrees of intra- struction (ie, hepaticojejunostomy7,41 vs hepaticojejuno- hepatic dilation, and the other conditions should be called duodenostomy 42,43 vs appendicoduodenostomy44). The ap- choledochocele, choledochal diverticulum, and Caroli dis- propriate treatment for most patients with benign types I ease. Patients whose cyst was bypassed in childhood and IV cysts (regardless of any intrahepatic changes) is re- should have the lesion excised before the age of 30 years. section of the extrahepatic biliary tree and Roux-en-Y he- Patients diagnosed as having CCs as adults, regardless paticojejunostomy. This procedure, performed in 28 (90%) of symptoms, should undergo complete excision of the of our 31 patients with benign disease, eliminates the mu- extrahepatic duct, cholecystectomy, and Roux-en-Y he- cosa at highest risk for malignant degeneration. The re- paticojejunostomy. The outcome of that approach was section should extend from the bifurcation of the lobar he- excellent. patic ducts into the parenchyma of the pancreas to a point just short of where the duct abruptly narrows to a 1- to Accepted for publication April 9, 2004. 3-mm diameter. For the rare patient with extensive intra- This paper was presented at the 75th Annual Meeting hepatic biliary dilation complicated by gallstone forma- of the Pacific Coast Surgical Association; February 14, 2004; tion, cholangitis, or biliary cirrhosis, liver resection (for Maui, Hawaii; and is published after peer review and revi- unilobar disease)2,45 or transplantation (for bilobar dis- sion. The discussions that follow this article are based on ease)46 may be indicated. But we did not see such a case. the originally submitted manuscript and not the revised Several recent reports have described cases of cho- manuscript. langiocarcinoma that developed after excision of CCs.47-49 We thank Jeanne Koelling for the illustrations. Cancer after excision is rare (Ͻ1%),30 with fewer than Correspondence: Lawrence W. Way, MD, University 30 cases reported to date. In most such cases the previ- of California, San Francisco, 505 Parnassus Ave, Room ous excision has been found to be incomplete.30,47 After S-550, San Francisco, CA 94143-0470 (wayl@surgery complete cyst removal, the risk of cholangiocarcinoma .ucsf.edu).

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 859

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 33. Pisano G, Donlon JB, Platell C, Hall JC. Cholangiocarcinoma in a type III chole- REFERENCES dochal cyst. Aust N Z J Surg. 1991;61:855-857. 34. Dayton MT, Longmire WP Jr, Tompkins RK. Caroli’s disease: a premalignant con- 1. Douglas A. Case of dilation of the common bile duct. Mon J Med. 1852;14:97- dition? Am J Surg. 1983;145:41-48. 100. 35. Shimonishi T, Sasaki M, Nakanuma Y. Precancerous lesions of intrahepatic cho- 2. Alonso-Lej F, Rever WB Jr, Pessagno DJ. Congenital choledochal cyst, with a langiocarcinoma. J Hepatobiliary Pancreat Surg. 2000;7:542-550. report of 2, and an analysis of 94, cases. Int Abstr Surg. 1959;108:1-30. 36. Dagli U, Atalay F, Sasmaz N, et al. Caroli’s disease: 1977-1995 experiences. Eur 3. Todani T, Watanabe Y, Narusue M, et al. Congenital bile duct cysts: classifica- J Gastroenterol Hepatol. 1998;10:109-112. tion, operative procedures, and review of thirty-seven cases including cancer aris- 37. Tsuchiya R, Harada N, Ito T, et al. Malignant tumors in choledochal cysts. Ann ing from choledochal cyst. Am J Surg. 1977;134:263-269. Surg. 1977;186:22-28. 4. Todani T. Congenital choledochal dilatation: classification, clinical features, and 38. Flanigan DP. Biliary carcinoma associated with biliary cysts. Cancer. 1977;40: long-term results. J Hepatobiliary Pancreat Surg. 1997;4:276-282. 880-883. 5. Todani T, Watanabe Y, Toki A, Morotomi Y. Classification of congenital biliary 39. Ohi R, Yaoita S, Kamiyama T, et al. Surgical treatment of congenital dilatation of cystic disease: special reference to type Ic and IVA cysts with primary ductal stric- the bile duct with special reference to late complications after total excisional ture. J Hepatobiliary Pancreat Surg. 2003;10:340-344. operation. J Pediatr Surg. 1990;25:613-617. 6. Stain SC, Guthrie CR, Yellin AE, Donovan AJ. Choledochal cyst in the adult. Ann 40. Todani T, Watanabe Y, Toki A, et al. Reoperation for congenital choledochal cyst. Surg. 1995;222:128-133. Ann Surg. 1988;207:142-147. 7. Liu CL, Fan ST, Lo CM, et al. Choledochal cysts in adults. Arch Surg. 2002;137: 41. Shi LB, Peng SY, Meng XK, et al. Diagnosis and treatment of congenital chole- 465-468. dochal cyst: 20 years’ experience in China. World J Gastroenterol. 2001;7:732- 8. O’Neill JA Jr, Clatworthy HW Jr. Management of choledochal cysts: a fourteen- 734. year follow-up. Am Surg. 1971;37:230-237. 42. Oweida SW, Ricketts RR. Hepatico-jejuno-duodenostomy reconstruction follow- 9. Trout HH III, Longmire WP Jr. Long-term follow-up study of patients with con- ing excision of choledochal cysts in children. Am Surg. 1989;55:2-6. genital cystic dilatation of the common bile duct. Am J Surg. 1971;121:68-86. 43. Henne-Bruns D, Kremer B, Thonke F, et al. “Endoscopy friendly” resection tech- 10. Fonkalsrud EW, Boles ET Jr. Choledochal cysts in infancy and childhood. Surg nique of choledochal cysts. Endoscopy. 1993;25:176-178. Gynecol Obstet. 1965;121:733-742. 44. Wei MF, Qi BQ, Xia GL, et al. Use of the appendix to replace the choledochus. 11. Nagorney DM, McIlrath DC, Adson MA. Choledochal cysts in adults: clinical man- Pediatr Surg Int. 1998;13:494-496. agement. Surgery. 1984;96:656-663. 45. Kanoh K, Shimura T, Tsutsumi S, et al. Left hepatectomy for the choledochal 12. Kouraklis G, Misiakos E, Glinavou A, et al. Cystic dilatations of the common bile cyst (type IV-A) with intrahepatic stenosis: report of a case. Hepatogastroenter- duct in adults. HPB Surg. 1996;10:91-95. ology. 2002;49:144-147. 13. Takiff H, Stone M, Fonkalsrud EW. Choledochal cysts: results of primary sur- 46. Magid MS, Emre S, Norton KI, et al. A 7-month-old male infant with extra- and gery and need for reoperation in young patients. Am J Surg. 1985;150:141-146. intrahepatic biliary cysts. Semin Liver Dis. 2000;20:385-390. 14. Powell CS, Sawyers JL, Reynolds VH. Management of adult choledochal cysts. 47. Koike M, Yasui K, Shimizu Y, et al. Carcinoma of the hepatic hilus developing 21 Ann Surg. 1981;193:666-676. years after biliary diversion for choledochal cyst: a case report. Hepatogastro- 15. Metcalfe MS, Wemyss-Holden SA, Maddern GJ. Management dilemmas with cho- enterology. 2002;49:1216-1220. ledochal cysts. Arch Surg. 2003;138:333-339. 48. Fujisaki S, Akiyama T, Miyake H, et al. A case of carcinoma associated with the 16. de Vries JS, de Vries S, Aronson DC, et al. Choledochal cysts: age of presenta- remained intrapancreatic biliary tract 17 years after the primary excision of a cho- tion, symptoms, and late complications related to Todani’s classification. J Pe- ledochal cyst. Hepatogastroenterology. 1999;46:1655-1659. diatr Surg. 2002;37:1568-1573. 49. Goto N, Yasuda I, Uematsu T, et al. Intrahepatic cholangiocarcinoma arising 10 17. Babbitt DP. Congenital choledochal cysts: new etiological concept based on anoma- years after the excision of congenital extrahepatic biliary dilation. J Gastroen- lous relationships of the common bile duct and pancreatic bulb [in French]. Ann terol. 2001;36:856-862. Radiol (Paris). 1969;12:231-240. 50. Strong RW. Late bile duct cancer complicating biliary-enteric anastomosis for 18. Matsumoto Y, Fujii H, Itakura J, et al. Pancreaticobiliary maljunction: pathophysi- benign disease. Am J Surg. 1999;177:472-474. ological and clinical aspects and the impact on biliary carcinogenesis. Langen- becks Arch Surg. 2003;388:122-131. DISCUSSION 19. Iwai N, Yanagihara J, Tokiwa K, et al. Congenital choledochal dilatation with emphasis on pathophysiology of the biliary tract. Ann Surg. 1992;215:27-30. Clifford W. Deveney, MD, Portland, Ore: The authors have 20. Ohkawa H, Sawaguchi S, Yamazaki Y, et al. Experimental analysis of the ill effect described their experience with CCs and make the point that of anomalous pancreaticobiliary ductal union. J Pediatr Surg. 1982;17:7-13. 21. Ponce J, Garrigues V, Sala T, et al. Endoscopic biliary manometry in patients the cysts of concern are types I and IV of the 1959 Classifica- with suspected sphincter of Oddi dysfunction and in patients with cystic dilatation of Alonso-Lej as modified by Todani and colleagues in the tion of the bile ducts. Dig Dis Sci. 1989;34:367-371. 1970s. The authors correctly point out that types II, III, and V 22. Tsang TM, Tam PK, Chamberlain P. Obliteration of the distal bile duct in the de- are different entities with different treatments and that they velopment of congenital choledochal cyst. J Pediatr Surg. 1994;29:1582-1583. should not be called CCs. The authors advocate abandoning 23. Hara H, Morita S, Ishibashi T, et al. Surgical treatment for congenital biliary di- the Alonso-Lej classification and simply calling these biliary ab- latation, with or without intrahepatic bile duct dilatation. Hepatogastroenterol- normalities by what they are (ie, types I and IV CCs, type II ogy. 2001;48:638-641. choledochal diverticulum, type III choledochocele, and type 24. Kobayashi S, Asano T, Yamasaki M, et al. Risk of bile duct carcinogenesis after V Caroli disease). This would certainly make things simpler. excision of extrahepatic bile ducts in pancreaticobiliary maljunction. Surgery. 1999; 126:939-944. Because of the risk of cancer developing in the CCs (types I 25. Desmet VJ. Ludwig symposium on biliary disorders, part I: pathogenesis of duc- and IV), the authors recommend excision of the entire extra- tal plate abnormalities. Mayo Clin Proc. 1998;73:80-89. hepatic biliary tree and Roux-en-Y hepaticojejunostomy for re- 26. Parada LA, Hallen M, Hagerstrand I, et al. Clonal chromosomal abnormalities in construction when the diagnosis is made regardless of symp- congenital bile duct dilatation (Caroli’s disease). Gut. 1999;45:780-782. toms. 27. Wu KL, Changchien CS, Kuo CM, et al. Caroli’s disease: a report of two siblings. In this series, the patients had a variety of preoperative stud- Eur J Gastroenterol Hepatol. 2002;14:1397-1399. ies of the biliary tract (eg, computed tomography scan, ERCP 28. Ishibashi T, Kasahara K, Yasuda Y, et al. Malignant change in the biliary tract [endoscopic retrograde cholangiopancreaticogram], percuta- after excision of choledochal cyst. Br J Surg. 1997;84:1687-1691. neous transhepatic cholangiogram, and others). It appears the 29. Fieber SS, Nance FC. Choledochal cyst and neoplasm: a comprehensive review of authors would recommend a biliary tract imaging study and a 106 cases and presentation of two original cases. Am Surg. 1997;63:982-987. computed tomographic scan preoperatively. Is this correct? Is 30. Watanabe Y, Toki A, Todani T. Bile duct cancer developed after cyst excision for choledochal cyst. J Hepatobiliary Pancreat Surg. 1999;6:207-212. it ever difficult to distinguish a choledochal diverticulum from 31. Todani T, Tabuchi K, Watanabe Y, Kobayashi T. Carcinoma arising in the wall of a CC since the treatment is different? You have included 2 pa- congenital bile duct cysts. Cancer. 1979;44:1134-1141. tients with choledochal diverticula in this study (type II). Was 32. Coyle KA, Bradley EL III. Cholangiocarcinoma developing after simple excision your treatment of these patients simple removal of the diver- of a type II choledochal cyst. South Med J. 1992;85:540-544. ticulum?

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 860

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Cancer developed in the cyst in several of your patients, know that they have developed a carcinoma because the drain- but 2 of your patients had gallbladder cancer. Is gallbladder can- age is already there so they do not get early obstruction and, cer associated with types I and IV CCs? thus, early treatment. Some technical questions. Do you ever have any diffi- But one of the questions that I had was the large amount culty distinguishing where the duct becomes normal as it goes of Asian patients that were presented. That certainly is not most into the pancreas for your distal margin? people’s experience unless you are operating in China or Ja- Do you ever use hepatic stents? For example, in patients pan, but certainly not in the United States, although this may with intrahepatic ductal dilation who have had a preoperative be the experience in San Francisco. Especially the ones that were percutaneous transhepatic cholangiogram and there is a stric- not diagnosed previously, did not have a previous drainage pro- ture. What do you think the risk of cancer is in those patients cedure, and were diagnosed in their 50s and 60s—how many with intrahepatic ductal dilation. Is there an increased risk of of those patients were Asian? Do they have rather than a con- cancer in any of the remaining ducts (ie, in the pancreas)? You genital CC, the biliary dilation that you see in Asians, cholan- have addressed this somewhat in your paper. Your follow-up giohepatitis type, an acquired biliary dilation, secondary to para- on your patients is rather short to really determine if you have sites or other unknown reasons? avoided the development of cancer, but you might comment The second question is to echo what Dr Deveney said. As on that from the literature. far as I know, there is no real association between gallbladder I would commend the authors, Drs Visser, Suh, Way, and cancers and CCs. Which were the patients in whom gallbladder Kang, for simplifying a confusing classification of biliary duc- cancer developed in this series and was it in patients who were tal abnormalities and for reemphasizing the need for excision older, with biliary dilation rather than a strict congenital CC? of all extrahepatic bile ducts when CCs (type I and IV) are The third question is that the authors come out strongly present. recommending a Roux-en-Y hepaticojejunostomy, and al- Susan Orloff, MD, Portland: That was a very nice and im- though I think that is acceptable, have they considered doing portant series. I am wondering what you suggest based on your a hepaticoduodenostomy? That is much more physiologic, sur- study as to the follow-up of patients in whom you perform ex- veil the duct that remains, and in case stenosis develops, you cision and hepaticojejunostomy, especially those patients who have access to your anastomosis to dilate it. In fact, in one case have intrahepatic or suspected intrahepatic ductal involve- they actually did an excision with a choledochoduodenos- ment in terms of the risk for cancer. What do you suggest is tomy. What was the occasion that they did that type of opera- the best screening imaging and how often should these pa- tion? Why did they choose that operation that one time? tients be followed up given that you had a 16-year interval as a Yeu-Tsu M. Lee, MD, Honolulu, Hawaii: I had a chance mean for recurrence of cancer or development of cancer? to go to China and Taiwan and just like Dr Ted O’Connell said, Eric W. Fonkalsrud, MD, Los Angeles, Calif: I congratu- the Asians have a much higher rate of CCs. They also have a late Dr Visser and his colleagues on using their data with this higher rate of CC with associated cancer too. So I have 2 ques- large number of adult patients with CCs to revise the classifi- tions. (1) Since you are reporting the largest series in America, cation and to emphasize the high frequency of virulent carci- I like to see a racial breakdown, specifically how many were noma when less than complete cyst excision is performed, even Asians and maybe their associated age distributions. (2) Now in children. In fact, one wonders since the average age of your with all the human genetic research in patients with cancer, patients was 50 years, are these truly congenital CCs or are they whether the authors know of any genetic studies because I do occasionally developmental? I wonder if the authors could specu- know there are a few cases with positive family histories in Chi- late why there is such a great propensity to develop carcinoma nese. in the common bile duct wall even when the cyst is drained Kimberly S. Kirkwood, MD, San Francisco, Calif: I want adequately into the jejunum. In other types of biliary surgery, the authors to speculate on the pathogenesis of the develop- this rarely occurs. How many of your patients having carci- ment of cancer in these patients. You implied that excision of noma were actually diagnosed preoperatively, or was this a find- the extrahepatic duct was adequate and that you had not seen ing that you made at operation? Should we consider all of those development of cancer within the intrahepatic ducts. Dr patients who have had drainage procedures in previous years Fonkalsrud’s question implied that biliary stasis might not be for callback—to have total cyst excision now even though they the cause since even patients who had adequate drainage of cho- are asymptomatic? ledochal cysts were still at risk for development of carcinoma. There are several patients we see in the pediatric age group So what is the hypothesis that explains the lack of develop- that have a fusiform dilation of only 1 to 2 cm in diameter. Do ment of carcinoma in the residual dilated intrahepatic ducts these patients have the same risk of developing carcinoma as and what is known about the genetics of this disease? those large giant CCs that you have shown so nicely? Or should Bruce E. Stabile, MD, Torrance, Calif: An observation that these patients with fusiform dilations not even be considered has been made is that there is an anomaly of the pancreatico- as CCs in your new proposed classification? biliary system associated with CC and that is a long common Since patients with Caroli disease have an increased risk channel or a more proximal than normal insertion of the pan- of developing carcinoma, and we are unsure if drainage actu- creatic duct into the bile duct. This has been thought to per- ally lowers the risk in these patients, what should we do with haps cause abnormal reflux of pancreatic juice into the biliary all of those patients that have intrahepatic ductal dilation with system. This particular anomaly has been observed in cases of CC? Do they have a lower risk of developing carcinoma than both CC, at least of the type I and IV varieties, and has also those with Caroli disease? been observed in cases of gallbladder cancer. Do the authors Lastly, I wonder if the authors could speculate on the re- have any information on this large patient experience as to any lationship between sclerosing cholangitis and the frequency and anatomical information related to the long common channel type of ductal carcinoma compared with the CC and the car- in the patients with CC and gallbladder cancer? cinoma, which develops there? Dr Way: I want to thank all of the discussants. It is re- Theodore X. O’Connell, MD, Los Angeles: I certainly agree warding to see that your paper has titillated a lot of interest like that CCs should be completely excised and patients who had that. I will try to answer the questions. Some of the questions them drained in the past should be called back to have them I do not have answers to. I think Dr Deveney and others asked excised because when they develop carcinoma it is really dev- whether the gallbladder cancer is associated with congenital astating. Once CCs have been previously drained, you do not CC and, in fact, that has been reported from all of the series.

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 861

©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 The gallbladder is abnormal just as the rest of the extrahepatic had something other than just cholangitis in an otherwise healthy biliary tree. The reason why cancer develops in this lesion is person and so we were quite concerned in a many of these pa- really unknown. There is a variety of things that have been tient although we might not have had complete proof preop- pointed out as being associated with the condition, and Dr Sta- eratively. bile just mentioned one of them and that is a high junction of About the risk of the patients and the drainage proce- the pancreatic duct and the bile duct that people have said is dure, you see in this study and in many studies that these people probably pancreatic juice reflux and maybe that causes the cyst are returning in their 30s, 40s, and 50s with cancer. As some- in the first place and in the second place gives rise to cancer. body mentioned, the drainage procedure takes away early the But we have a lot of situations in which there is reflux of pan- development of the early symptoms of obstruction and then creatic juice and it does not cause much trouble and there are the cancer is incurable. So I recall a young woman in her late a lot of abnormal junctions that have been shown on endo- 30s who was a nurse in the surgical unit and she had had a drain- scopic retrograde cholangiopancreaticograms performed in age procedure as a child and was told, well, as long as you are people who do not have CCs and in addition to that pancre- asymptomatic, you might need that out some day but as long atic enzymes are not universally found within these cysts. So I as you are asymptomatic you might as well wait. Our conclu- think that is an interesting and enticing observation, that there sion from our observations is that all of these cancers ap- is such a high incidence of this maljunction but whether you peared in patients in their 30s. None appeared in patients in can just have a full-blown satisfying theory on the causation their 20s, and if it were me, I would want to have the thing out from that alone I think is not yet there. But it is an important of there while I was in my 20s and then you know that the risk observation that still needs to be considered. really is as low as possible. The patients are adults. The opera- As far as the development of cancer, one thing not brought tion is not particularly difficult at that time, so that is our pro- out in the presentation and really not discussed much in the posal. We put it out there. We do not know all of the answers, paper is the fact that the biliary epithelium tends to be abnor- but it certainly would have saved a few of these patients if that mal when you see it. Whether this is owing to reflux or stasis had been done. or whatever, there is quite a bit of abnormality within the epi- Dr Fonkalsrud, I do not know about all of the experi- thelium, signs of chronic inflammation, and this gives rise, prob- ences of pediatric surgeons and the fusiform dilation and what ably is a steppingstone on the way to the development of can- the natural history of this disease is. Certainly, there is not much cer, and it also is responsible for the many times anastomoses in the way of observations of the untreated patient so I cannot to this abnormal dilated bile duct tends to stricture down. I re- answer your question in that regard. call a case about 5 or 6 years ago of a young woman who sev- Caroli’s disease—we are pretty sure that is a separate en- eral years previously underwent a choledochojejunostomy with tity. Cancer develops in some of these patients but they have a nice big anastomosis and when we reoperated on her, it had congenital hepatic fibrosis. They have intrahepatic gallstone dis- completed healed over so there is something peculiar about this ease that is pretty uncommon except in patients who have had epithelium in general and the risk does seem to be concen- a lot of cholangitis in the ordinary form of congenital CC, so trated in the extrahepatic biliary tree because not only in our most of these people have serious liver disease before cancer series which is a short-term follow-up but throughout the lit- ever has the chance to develop in them. I do not think there is erature the appearance of cancer within the liver, in the abnor- any relationship in my mind between sclerosing cholangitis and mal bile ducts there, is really uncommon. So that is why we CC on the one hand and the development of cancer on the other, think a good thorough job in the extrahepatic biliary tree is im- but I think that we would have to admit that we do not know portant in this respect. It is important to get all of that lower the steps leading to cancer in either condition. into the bile duct because there are quite a few cases of cancer Dr O’Connell, what about the large number of Asians? Well, developing in an incompletely resected lower end, and that is we had 9 Asians and for San Francisco that might not be an the result of surgeons being a little bit timid about taking that inappropriate balance. That may very well represent the de- lower end because the lower end really is inside the pancreas. mography of our community. This disease is not easily con- Surgeons are a little bit frightened about getting that high junc- fused with the recurrent pyogenic cholangitis or what used to tion of the pancreatic duct and the bile duct. So there are a couple be called “Oriental cholangiohepatitis “which begins as a pri- of reasons why you might, if you are new to this, be a little shy mary gallstone formation in the bile ducts, not in the gallblad- of a thorough operation at that level. If you stay right on the der but in the bile ducts, and is very early associated with a lot surface of that bile duct, cut it across right at the surface of the of intrahepatic gallstone formation. Those patients do not un- pancreas, stick your thumb or your finger down, and then stay dergo a high junction of the pancreatic duct and the bile duct right on the external surface using little clips. You can take that and they can generally in the early stages be treated by an en- out, stop short about a centimeter of where that duct comes to doscopic sphincterotomy which I believe is the most common an abrupt halt, and you can remove just about all of it. treatment in Hong Kong. It is only the more advanced cases So Dr Orloff, I do not know the answer to your question that require complex things like hepatic lobectomy. But I do about the follow-up of these patients because the risk of de- not think that there is any relationship between these 2 con- veloping cancer is so low and the period would be so great. I ditions, nor do I think we have any patients in this series who just do not know the answer. It is sort of a statistical question have cholangiohepatitis. We know what that is because we have on whether you would be doing repeated studies on these people seen quite a bit of it. over the years. You think of all of the morbidity involved with I think I answered your questions about cancer and you these follow-up studies, frightening people periodically, so I asked me, well, why not hook the bile duct up to the duode- do not know the answer to that. num. Well, I do not know. I suppose that could be done. There Dr Fonkalsrud, the diagnosis of cancer was suspected pre- is some concern about reflux of duodenal juices and in some operatively in many of these patients because they had weight cases it will be something of a stretch. But I do not otherwise loss and the pain was more unremitting and boring and they have any objections to that.

(REPRINTED) ARCH SURG/ VOL 139, AUG 2004 WWW.ARCHSURG.COM 862