Precancerous conditions of biliary tract cancer in patients with pancreaticobiliary maljunction: reappraisal of nationwide survey in Japan

It is widely known that pancreaticobiliary maljunction (PBM), an anomalous arrangement of the pancreaticobiliary ductal system, is frequently associated with biliary tract cancer in patients with or without bile duct dilatation. In 1985, we surveyed patients with PBM who had been operated on at 133 Japanese institutions. A close relationship was shown between biliary tract carcinogenesis and PBM, according to the type of maljunction and age distribution: PBM patients with cystic dilatation had a high risk of bile duct cancer, even in those who were young (aged less than 20 years); the incidence of gallbladder cancer increased markedly in PBM patients over 40 years old with cystic dilatation, while it gradually increased with age in the PBM patients without cystic dilatation. Therefore, we recommend surgical treatment for patients with PBM even if they have no symptoms.     

Clinical problems in the surgical treatment of pancreaticobiliary maljunction

The results of surgical treatment of pancreaticobiliary maljunction at our department are described. The 67 patients who underwent surgery for this disease were divided by age into an adult group (45 patients, aged 16 years and over) and a pediatric group (22 patients, aged less than 16 years). The incidence of concomitant carcinoma before surgery and the incidence and severity of postoperative cholangitis were compared between these two groups. In addition, the cell proliferating activity of the biliary tract epithelium in cancer-free patients was compared between the two groups, using the proliferating cell nuclear antigen labeling index (PCNA LI). Ten patients (all adults) were diagnosed with cancer (gallbladder carcinoma in 7 and bile duct carcinoma in 3) before surgery. The surgical techniques used for reconstruction in the cancer-free patients were: in the adult group, hepaticoduodenostomy in 9 patients, Roux-en-Y hepaticojejunostomy in 17, jejunal interposition in 8, and another technique in 1. In the pediatric group, hepatico-duodenostomy was performed in 17 patients. Roux-en-Y hepaticojejunostomy in 3, and jejunal interposition in 2. Postoperative cholangitis occurred in 6 adults (including 2 with severe form) and 1 child (mild case). The PCNA LI of the biliary tract epithelium was high compared to control findings in the biliary tract epithelium of 10 adult patients without pancreaticobiliary maljunction. In the adult group with dilated extrahepatic bile ducts (n=10 examined) this index was 11.4% for the bile duct epithelium (control, 1.5%) and 12.7% for the gallbladder epithelium (control, 1.4%). In the adult group with non-dilated extrahepatic bile ducts (n=5 examined) it was 5.9% for the bile duct epithelium and 13.1% for the gallbladder epithelium. In the pediatric group (n=10 with extrahepatic bile duct dilatation) it was 7.5% for the bile duct and 9.7% for the gallbladder epithelium. (Differences from control values were all significant.) These results suggest that surgery for this disease should be performed as early as possible and that extrahepatic bile duct excision and biliary reconstruction should be performed whether or not extrahepatic bile ducts are dilated.     

Congenital choledochal cyst: Occurrence of primary intrahepatic stones and prevention of carcinogenesis

Intrahepatic biliary stones and carcinogenesis are two major complications seen after corrective surgery for congenital choledochal cyst. The incidence of these two complications was reviewed in patients seen at out-patient clinics at a mean follow-up time of 13 years and 6 months. Intrahepatic biliary stones developed in 5 of 56 patients who had undergone a standard excisional operation; in 4 of the 5 patients, the stones were found in the preexisting intrahepatic biliary dilatation (with or without a downstream stenosis), 7–15 years postoperatively. Biliary stricture with dilatation is a putative cause of intrahepatic bile duct stones, and this hypothesis was supported here, since stones developed in all 3 of the patients who had the peculiar configuration of intrahepatic biliary dilatation and stenosis. Biliary carcinoma was not observed in any of the 56 patients who had undergone standard excision of a choledochal cyst followed by hepatico-jejunostomy, but developed in 1 of 12 patients in whom complete excisional resection of the dilated extrahepatic bile duct had not been performed. The occurrence of carcinoma in choledochal cysts is reviewed.     

Primary choledochoduodenostomy for benign obstructive biliary tract disease

Repeated surgical interventions on the biliary ductal system increase morbidity and mortality, particularly in the geriatric patient. In an attempt to prevent these complications, side-to-side choledochoduodenostomy was performed as the primary operative procedure in 54 patients, age 72 +/- 13 years. This was the patients' first surgical intervention for benign obstructive lesions of the biliary tract system. Indications for choledochoduodenostomy were: multiple or irremovable common or hepatic duct stones, doubtfulness of complete clearing of the duct, primary common bile duct stones or mud and sludge, a grossly dilated biliary duct system, and ampullary stenosis. We encountered no operative or hospital mortality among this group of 54 patients. The mean postoperative hospital stay for this aged and relatively sick group of patients was 12.3 +/- 6.2 days. Twenty-three minor postoperative complications occurred in 18 patients, none of them requiring reoperation. The patients were followed for 2-16 years. Thirteen patients (24%) were lost to follow-up. Of the 41 patients available for follow-up, 14 died, none from biliary tract associated causes--mostly from cerebrocardiovascular disease. Twenty-seven patients still alive were found to be free of biliary tract associated abdominal complaints or recurrent cholangitis for a mean period of 7.8 +/- 3.7 years. The data indicate a zero reoperation rate during long-term follow-up, zero mortality rate, and low morbidity in a group of elderly, mostly poor risk patients. This leads us to conclude that a side-to-side choledochoduodenostomy is both the best therapy as well as prophylaxis against common duct stones. This, even in this era of endoscopic papillotomy and biliary lithotripsy.     

Clinical aspects of congenital cystic dilatation of the common bile duct in adults

We reviewed the data for 155 patients with congenital cystic dilatation of the common bile duct (CCDB; Alonso-Lej Type I) treated at our institute in the past 12 years. Our definition of CCDB was segmental enlargement of the common bile duct or enlargement involving the proximal bile duct, visualized on cholangiograms. CCDB was subclassified as infant or adult type cyst, based on the extent of the enlargement and the clinicopathologic findings. The former is typically an enlargement of the common bile duct or an enlargement involving the common hepatic duct, while the latter is an enlargement of the entirety of the extrahepatic ducts or involves the intrahepatic bile ducts. Of the 155 patients, 5 (including 1 child) had infant type cysts and 150 (including 1 child) had adult type cysts; 125 patients had benign CCDB (3 with infant type cyst) and 30 exhibited CCDB biliary malignancy (2 with infant type). Anomalous arrangement of the pancreaticobiliary ductal system (AAPB) and congenital biliary stricture were frequently associated with CCDB and these features played an important role in the presenting symptoms of CCDB: AAPB was detected in 100 of the 155 patients, and stricture in 51. AAPB caused disturbance of the passage of bile from the terminal bile duct to the duodenum and cholestasis in the enlargement, with reciprocal regurgitation of bile into the pancreas and pancreatic juice into the bile duct, and the AAPB appeared to precede obstructive jaundice, acute pancreatitis, or biliary malignancies. Stricture was observed at one to all of six sites in the hepatic hilum. Intrahepatic stones were seen in 30 patients, and intrahepatic bile duct cancer was seen in 8 patients; in all these 8 patients, the cancer was associated with primary intrahepatic stones.     

Embryogenesis of pancreaticobiliary maljunction inferred from development of duodenal atresia

The embryogenesis of pancreaticobiliary maljunction is inferred from the embryogenesis of duodenal atresia. The epithelial cells of the duodenum begin to proliferate and completely plug the lumen, but a process of vacuolation recanalizes the duodenum. Recanalization of the common duct frequently appears with two lumina and openings into the duodenum with two orifices. These two major canals create a narrow segment of the duodenum and this narrow zone is the area in the duodenum that is most prone to faulty recanalization and atresia formation. A bifid biliary system inserts at blind upper and lower pouches of the duodenum, and the common bile duct inserts in a Y fashion. The common bile duct inserts at the stenotic segment, and the end result is a T-shaped formation in patients with duodenal stenosis. During the development of the bile duct, abnormal fusion may occur between the bile duct and branches of the right ventral pancreatic duct. The site in the bile duct where a branch of the pancreatic duct joins is likely to develop atresia due to disturbance of the recanalization process, as seen in duodenal atresia. Severe impairment of vacuolation causes divided atretic bile duct at the site where the pancreatic duct inserts in a Y-fashion into the upper and lower bile duct. Moderate impairment of vacuolation causes a stenosis at the site where the pancreatic duct inserts in a T-shape, with a moderate dilatation of the bile duct.     

Endoscopic Biliary Drainage for Acute Obstructive Cholangitis: Analysis of 100 Consecutive Patients

Abstract: Acute obstructive suppurative cholangitis is a life-threatening condition and prompt biliary decompression is essential if the patient is to survive. One hundred patients with acute obstructive (suppurative) cholangitis were treated by simple endoscopic cannulation for biliary drainage. Forty-eight patients had common duct stones alone, 33 patients had additional stones in the gallbladder, and 18 patients had stones in the intrahepatic ducts. Another patient had a confluence stone. Twenty-six patients had undergone endoscopic sphincterotomy. Bile duct dilatation was present in only 25 of 47 patients (53%) studied by ultrasound tomography. Biliary decompression was achieved in 98 patients. One tortuous distal bile duct and one oversized stone were the causes of failure in two patients. Forty-seven patients proved to have suppurative cholangitis. Most patients felt instant and dramatic relief of their syniptoms. Bleeding at sphinctetomy was the only complication associated with the decompression ocurring in 2 patients. Bending (2 patients) and withdrawal (2 patients) of a nasobiliary catheter, and nasal bleeding (1 patient) were the complications related to nasobiliary drainage. Two patients with suppurative cholangitis died despite successful decompression performed 3 and 5 days after the onset of cholangitis. This delay seemed responsible for their deaths. Thus the mortality rate was 2.0% for all the patients arid 4.3% for those with suppurative cholangitis. These results suggest that endoscopic cannulation, which is feasible even in the absence of bile duct dilatation, is a prompt, safe, and effective procedure for emergency biliary decompression for the treatment of acute obstructive (suppurative) cholangitis.     

Recent advances and problems in the management of pancreaticobiliary maljunction: feedback from the guidelines committee

Clinical practice guidelines on how to deal with pancreaticobiliary maljunction (PBM) were made in Japan in 2012, representing a world first. Using a narrow definition, congenital biliary dilatation involves only Todani type I (except type Ib) and type IV‐A, both of which are accompanied by PBM in almost all cases. Prospective ultrasonographic study revealed that the maximum diameter of the common bile duct increased with age. Pathophysiological conditions due to pancreatobiliary reflux occur in patients with high confluence of the pancreaticobiliary ducts, a common channel ≥6 mm long and occlusion of communication during contraction of the sphincter of Oddi. Since PBM can be diagnosed by magnetic resonance cholangiopancreatography, multi‐planar reconstruction multi‐detector row computed tomography and endoscopic ultrasonography, the current diagnostic criteria should be revised to take these diagnostic imaging modalities into consideration. According to a nationwide survey, biliary cancer occurred in 21.6% of adult patients with PBM with biliary dilatation and 42.2% of patients with PBM without biliary dilatation. In biliary cancer associated with PBM without biliary dilatation, 88.1% were gallbladder cancer. Treatment for PBM with biliary dilatation is prophylactic flow‐diversion surgery, but further investigations and surveillance studies are needed to clarify the appropriate surgical strategy for PBM without biliary dilatation.     

Risk factors of choledocholithiasis formation after liver transplantation

Systematic study of risk factors for biliary stone post-liver transplantation is rarely performed. To investigate the risk factor of choledocholithiasis formation after liver transplantation, we c onducted a case-control study. Fourteen patients were selected into a study group. The stones of the bile duct of the patients were confirmed and treated successfully by endoscopic retrograde cholangiopancreatography. For univariate analysis, we selected carefully some potential risk factors such as cold ischemia time, warm ischemia time, and biliary stricture. The results revealed that cold ischemia time and biliary stenosis were significant predictors. But multivariate analysis revealed that only biliary stenosis was a significant risk factor. In conclusion, biliary stenosis is a risk factor of bile duct stones formation after liver transplantation. Endoscopic retrograde cholangiopancreatography is effective and safe in the diagnosis or treatment of bile duct stones after liver transplantation.     

Surgical treatment for congenital biliary dilatation, with or without intrahepatic bile duct dilatation.

BACKGROUND/AIMS: The incidence of postoperative cholangitis differs between patients with and those without congenital intrahepatic bile duct dilatation. The aim of this study was to evaluate comparatively the treatment results in these two patients groups. METHODOLOGY: Forty-eight patients were classified into those with (dilated type) and those without (nondilated type) intrahepatic bile duct dilatation. The surgical procedure used, clinical manifestation, and cell kinetics (proliferating cell nuclear antigen labeling index, PCNALI) of bile duct epithelium were examined with respect to the incidence and course of postoperative cholangitis. RESULTS: Nineteen patients were classified as the dilated type, and the other 29 patients were the nondilated type. In the dilated-type group, hepaticoduodenostomy was performed on five patients, hepaticojejunostomy (Roux-en-Y method) on eight and jejunal interposition on six. Among the 29 nondilated-type patient, hepaticoduodenostomy was performed on 19 patients, hepaticojejunostomy (Roux-en-Y method) on seven, and jejunal interposition on three. Hepatectomy was performed in one dilated-type adult patient with marked cholangiectasia in the left hepatic lobe. The incidence of postoperative cholangitis was 26.3% (5/19) in the dilated-type group and 6.9% (2/29) in the nondilated-type group. The clinical manifestation was generally mild in the nondilated-type patients. However, among the adult dilated-type patients, on whom jejunal interposition had been performed, there were two patients who required additional surgery for the treatment of cholangitis that occurred postoperatively. The PCNALI in the bile duct epithelium was 13.9% for the dilated-type and 8.8% for the nondilated-type groups, respectively. CONCLUSIONS: Jejunal interposition for biliary reconstruction seems a contraindicated maneuver for adult dilated-type patients, because of the possible development of postoperative cholangitis. The cellular proliferating activity in the bile duct epithelium of the patients of both the dilated and nondilated type was significantly increased compared to that of a control group. Consequently, the extrahepatic bile duct might have to be removed in patients with pancreaticobiliary maljunction regardless of the presence or absence of biliary dilatation.     

Studies on biliary tract carcinoma in the case with pancreaticobiliary maljunction

BACKGROUND/AIMS: The purpose of this study was to clarify the clinicopathological features of pancreaticobiliary maljunction and to determine the appropriate surgical approach for biliary tract with pancreaticobiliary maljunction. METHODOLOGY: The data of 77 patients with pancreaticobiliary maljunction including 13, who had been treated for biliary tract cancer, were reviewed retrospectively. We assessed the clinical features, biological characteristics of the cancer, methods of surgical treatment, postoperative outcome and cell proliferating activity of the biliary epithelium, evaluated by the PCNALI (proliferating cell nuclear antigen-labeling index). RESULTS: The incidence of cancer development in the case with pancreaticobiliary maljunction was 13.4% in the bile duct dilatation group (n = 67) and 40.0% in the non-dilatation group (n = 10). Dissection of lymphadenectomy was performed in 10 (76.9%) of 13 patients, and curative resection was feasible in 9 of the 10 patients. Two (20.0%) of the 10 patients had lymph node involvement noted at surgery and died of recurrence. In the other eight patients without lymph node involvement at surgery, six patients underwent curative resection and are alive at 7 months to 11 years and 6 months after surgery. PCNALI of the biliary epithelium of the patients with pancreaticobiliary maljunction was significantly higher than that of the control group. CONCLUSIONS: For patients with pancreaticobiliary maljunction, it should be stressed that the extrahepatic bile duct be prophylactically removed, even when there are no neoplasmatic changes because of high prevalence of cancer development, presumably predicted by the increase of cell proliferative activity in the biliary epithelium. For patients with biliary cancer, early detection at the stage with no lymph node involvement is essential to secure for long-term survival.     

Current status of endoscopic ultrasound-guided antegrade intervention for biliary diseases in patients with surgically altered anatomy

Endoscopic management of biliary diseases in patients with surgically altered anatomy can be challenging because the altered anatomy makes it difficult to insert an endoscope into the biliary orifice. Even if insertion is feasible, the worse maneuverability of the endoscope and the restriction in available devices and techniques could complicate the procedure. Recently, endoscopic ultrasound-guided antegrade intervention (EUS-AG) has been reported as a useful management method for biliary diseases, especially in patients with surgically altered anatomy. In EUS-AG, the biliary disease is managed in an antegrade fashion through a temporal fistula created under EUS guidance between the intrahepatic biliary duct and upper intestine. In this article, we reviewed the current status of EUS-AG for each biliary diseases, malignant biliary obstruction, bile duct stones, and benign biliary stricture in patients with surgically altered anatomy.     

A case of groove pancreatitis (segmental form) presented with obstructive jaundice associated with pancreatobiliary maljunction

A 52-year-old-man was admitted to our hospital for obstructive jaundice. Percutaneous transhepatic cholangio drainage (PTCD) and endscopic retrograde cholangiopancreatography (ERCP) were performed, and pointed out stenosis of lower common bile duct (CBD) and pancreatobiliary maljunction. Brushing cytology of this lesion was negative for malignancy. CT and MRI revealed chronic inflammatory change in groove lesion with no mass formation suggesting tumor. So we diagnosed groove pancreatitis (segmental form) associated with pancreatobiliary maljunction, and operation (resection of the bile duct and biliary reconstruction by Roux-en-Y) was done. Resected specimen was revealed stenosis of the bile duct formed by fibrous tissue with no malignancy compatible to groove pancreatitis pathologically. This is first reported case of groove pancreatits associated with pancreatobiliary maljunction.     

Surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction should include excision of the extrahepatic bile duct

BACKGROUND/AIMS: The authors evaluated the surgical treatment for non-dilated biliary tract with pancreaticobiliary maljunction. METHODOLOGY: Sixty-nine patients with pancreaticobiliary maljunction were divided into 61 patients with the dilated biliary tract and 8 with the non-dilated biliary tract. The levels of amylase activity in the bile in the gallbladder and the bile duct, the incidence and severity of postoperative cholangitis, and cell proliferating activity of the biliary tract epithelium, examined the proliferating cell nuclear antigen labeling index (PCNALI), were examined. RESULTS: Of the 61 dilated type patients, 12 were of Ia, 1 was of Ib, 22 were of Ic, 25 were of IV-A, and 1 was of IV-B according to Todani's classification. Cancer was detected in 7 dilated type patients and in 3 non-dilated type patients. A high level of amylase activity was measured in the bile juice in both the gallbladder and bile duct in all of the patients with pancreaticobiliary maljunction. PCNALI of the biliary tract epithelium of the patients without cancer (dilated type: bile duct 11.4%, gallbladder 12.7%; non-dilated type: bile duct 5.9%, gallbladder 13.8%) was higher than that of the patients without pancreaticobiliary maljunction (bile duct 1.5%, gallbladder 1.4%). CONCLUSIONS: In a non-dilated type, as well as in a dilated type, a high level of amylase activity and increase of cell proliferative activity of the biliary tract epithelium were observed. Therefore, these results suggest that the extrahepatic bile duct should be prophylactically removed in patients with non-dilated type as well as in those with dilated type pancreaticobiliary maljunction.     

ENDOSCOPIC TREATMENT FOR THE BENIGN BILIARY STRICTURE IN THE PATIENT WITH CHRONIC PANCREATITIS

In some patients with chronic pancreatitis (CP), strictures are observed in the intrapancreatic bile ducts due to fibrosis and inflammation in the pancreas. Normally, even when biliary strictures exist, obstructive jaundice is rarely observed. It seemed that obstructive jaundice was brought about by temporary pancreatitis due to immoderate alcohol ingestion, followed by the aggravation of the intrapancreatic biliary stricture. When immoderate alcohol ingestion is incriminated for the pancreatic disorder, the patient should be strictly instructed to abstain from alcohol, but failure to observe this instruction seems to render endoscopic biliary stenting ineffective. When CP is complicated with pancreatolithiasis, stone fragmentation using extracorporeal shock wave lithotripsy (ESWL) is effective, and combination with endoscopic lithotomy makes it possible to remove pancreatic stones in the main pancreatic duct (MPD). To treat the beside dilating stricture of the MPD, balloon dilation and pancreatic duct stenting are performed. We obtained good results with 10 Fr pancreatic duct stents, but biliary strictures are better treated with a combination of these methods. When 10 Fr or larger straight biliary stents are used, they may be dislodged or stray if the bile duct is sharply curved. To prevent this accident we have used 10 Fr double layer stents and obtained good results. In patients with benign biliary strictures, stents are temporarily placed and should be removable. Some cases have been reported where Wallstent gave good results in a short period, but the stents were occluded due to hyperplastic proliferation of the biliary epithelium. Metal stents are not considered desirable for benign biliary strictures. Our results seem to support the assumption that benign biliary strictures are improved with 10 Fr or larger biliary stents while exercizing care to keep the patient abstinent from alcohol and performing ESWL and endoscopic treatment for CP.     

SPECIFIC DIAGNOSIS OF BILIARY STRICTURES BY QUANTITATIVE ASSESSMENT USING A CHOLANGIOSCOPICALLY DERIVED HEMOGLOBIN INDEX

Background: We used percutaneous transhepatic cholangioscopy for detailed assessment of biliary tumors. Among the most important endoscopic findings is greater mucosal vascularity in malignant than in benign biliary strictures. Development of digital image processing now permits measurement of mucosal hemoglobin volume as a hemoglobin index. We studied the clinical usefulness of this hemoglobin index for differentiating malignant from benign biliary strictures. Methods: From 2000 to 2002 we determined the hemoglobin index in 22 patients with biliary stricture (8 with bile duct carcinoma; 1 with carcinoma of the duodenum; 5 with pancreatic carcinoma and 8 with benign stricture). Eight patients with malignant stricture were diagnosed by the histological examinations of resected specimens; six with malignant stricture and eight with benign stricture were diagnosed by examination of biopsy specimens. The ratio of hemoglobin indices in a given patient of lesional and uninvolved mucosa was determined from cholangioscopic imaging data. Results: The mean hemoglobin index ratio for bile duct carcinoma was 1.83; for carcinoma of the duodenum 1.98; and for pancreatic carcinoma, 1.35. For benign strictures, the ratio was only 1.09. The mean hemoglobin index ratio in patients with bile duct or pancreatic carcinoma was significantly higher than in patients with benign stricture (P < 0.05, paired t‐test). Conclusions: An image‐derived hemoglobin index is useful for diagnostic assessment of biliary stricture.     

Cholangiocarcinoma after flow diversion surgery for congenital biliary dilatation: A case report and review of literature

BACKGROUND Pancreaticobiliary maljunction(PBM) can be classified into two categories, PBM with congenital biliary dilatation(CBD) or PBM without biliary dilatation, and the management of PBM is often controversial. The treatment for PBM with CBD is prophylactic flow diversion surgery, and some authors have reported that the incidence of cancer after extrahepatic bile duct excision is less than 1%. A very rare case of intrahepatic cholangiocarcinoma 6 years after flow diversion surgery for PBM with CBD is reported.CASE SUMMARY A 30-year-old man was diagnosed as having PBM with CBD, Todani classification type IVA, because of abnormal liver enzyme profiles. He underwent flow diversion surgery and cholecystectomy, and the specimen showed adenocarcinoma foci, p T1, p Stage IA. Five and a half years passed without any recurrence of bile duct cancer. However, 6 years after his operation, computed tomography showed a gradually growing nodule in the bile duct.Fluorodeoxyglucose positron emission tomography showed high uptake, and magnetic resonance imaging showed restricted diffusion signals. On double balloon enteroscopy, the nodule at the posterior bile duct-jejunum anastomosis was directly visualized, and its biopsy specimen showed adenocarcinoma. The patient underwent right lobectomy and biliary reconstruction. The pathological diagnosis was intraductal papillary neoplasm with high-grade intraepithelial neoplasia, p Tis, p N0, p Stage 0. The patient's postoperative course was uneventful, and he has had no recurrence up to the present time.CONCLUSION This case suggests the necessity of careful observation after flow diversion surgery, especially when PBM with CBD is detected in adulthood.     

Temporary endosonography-guided biliary drainage for transgastrointestinal deployment of a self-expandable metallic stent

Endosonography-guided biliary drainage (ESBD) is now gaining acceptance as a useful alternative for the management of obstructive jaundice.(1) At present, ESBD is used mainly to establish an anastomosis between the biliary tree and the duodenum, stomach, jejunum, or esophagus by placing a stent so as to bridge the bile duct and alimentary tract. We herein report a new application of ESBD, that is, its temporary use for gaining access to the bile duct in order to deploy a self-expandable metallic stent (SEMS) via the transhepatic route. In a patient with pylorus stenosis due to advanced gastric cancer with extrahepatic bile duct obstruction caused by nodal metastasis, a plastic stent was placed temporarily by ESBD to bridge the esophagus and the left hepatic duct. Ten days later, the stent was retrieved, leaving a guidewire in the bile duct, and a delivery unit of a SEMS was introduced into the bile duct over the guidewire via the sinus tract. The SEMS was then successfully deployed through the stenosis. No stent was left in the sinus tract. This procedure yields a mature fistula through which a delivery unit can be safely introduced into the bile duct followed by uneventful deployment of a SEMS.     

p53 gene mutation and p53 protein overexpression in a patient with simultaneous double cancer of the gallbladder and bile duct associated with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. We present a case of simultaneous double cancer of the gallbladder and bile duct. A 77-year-old woman who had jaundice, intra- and extra-hepatic biliary ductal dilatation and a space-occupying lesion in the gallbladder and lower bile duct underwent pancreatoduodenectomy. The gallbladder cancer showed papillary carcinoma without mutation of the K-ras gene and with p53 non-sense mutation of CCA (Pro) to CA (Stop) on codon 301 in exon 8. The bile duct cancer revealed a well-differentiated adenocarcinoma without mutation of the K-ras gene and with p53 miss-sense mutation of GTG (Val) to GAG (Glu) on codon 272 in exon 8. There were no mutations of either the K-ras or p53 gene in non-cancerous epithelia. In contrast, only the mucosa of the common channel had p53 protein accumulation and high cell proliferation activity. Therefore, the genetic pathway might be the same in both the gallbladder and bile duct cancer, and a high potential for carcinogenesis might be present in the epithelium of the common channel in patients with PBM.     

Cancer of the gallbladder associated with pancreaticobiliary maljunction without bile duct dilatation in a European patient

A rare case of pancreaticobiliary maljunction (PBM) without dilatation of the biliary tract (DBT) associated with gallbladder carcinoma is described herein. A 62‐year‐old European woman with a long history of right upper abdominal pain was diagnosed as having PBM without DBT by endoscopic retrograde cholangiopancreatography and other examinations. Excision of the gallbladder and biliary duct with a Roux‐en‐Y hepaticojejunostomy was performed, and subsequent pathological examination of the surgical specimen showed a well differentiated adenocarcinoma of the gallbladder. She had no clinical symptoms for 58 months postoperatively. PBM allows reflux of pancreatic juice into the biliary tract. Recent findings support the idea that epithelial hyperplasia plays an important role in gallbladder carcinogenesis with PBM, and also support the concept that gene mutations are involved in the carcinogenesis of biliary epithelium in patients with PBM. For these reasons, we advocate that resection of the extrahepatic biliary tract in PBM patients without bile duct dilatation, rather than cholecystectomy alone, is the treatment of choice for preventing bile duct carcinoma.