Double cancers of the gallbladder and bile duct associated with anomalous choledochopancreatic duct junction

A rare case of double cancers of the gallbladder and bile duct associated with anomalous choledo-chopancreatic duct junction (ACPDJ) is reported. The patient was a 61-year-old Japanese woman who with presented right upper quadrant abdominal pain. Liver function tests results were normal. Computed tomography showed a polypoid lesion in the gallbladder, and endoscopic retrograde cholangiopancreatography (ERCP) demonstrated ACPDJ and irregular wall of the inferior bile duct. A diagnosis of double cancers of the gallbladder and bile duct was made and a pancreaticoduodenectomy and liver bed resection was performed. His topathological examination showed papillary adenocarcinoma of the gallbladder and mucosal adenocarcinoma of the bile duct. The patient is in good health 15 months after the operation and shows no signs of recurrence. A review of the literature is presented.     

Multiple carcinoid tumors of the gallbladder and cystic duct

A very rare case of multiple carcinoid tumors of the gallbladder and cystic duct is reported in a 77-year-old woman. Cholecystectomy and resection of the common bile duct, with regional lymph node dissection, were performed. The tumors consisted of a large mass (30×20×15mm) in the neck of the gallbladder and three small lesions in the cystic duct. Histologically, the tumor cells were arranged in solid nests, and showed many mitoses. Histochemical studies revealed argyrophilic and argentaffinic staining. Immunohistochemically, the tumor cells were positive for serotonin, chromogranin A, Leu 7, synaptophysin, and neuron-specific enolase. Thus, the present case was diagnosed as midguttype carcinoids.     

Anomalous junction of the pancreaticobiliary duct accompanied by gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels

We report a case of anomalous junction of the pan creaticobiliary duct (AJPBD) associated with gallbladder cancer and obstructive jaundice in a patient with high serum and bile cytokine levels. The patient was a 63-year-old woman who complained of right hypochondralgia. Ultrasound, computed tomography, percutaneous transhepatic cholangiography, and endoscopic retrograde cholangio-pancreatatography revealed dilation of the bile ducts, an elevated lesion of the gallbladder, and AJPBD. She underwent percutaneous transhepatic cholangio-drainage (PTCD) for obstructive jaundice. However, the total bilirubin concentration remained high 7 days after PTCD. Her serum interleukin 6 level was 57 359 pg/ml before PTCD, and gradually decreased to 10 pg/ml after PTCD. Bile interleukin 6 level was 10 pg/ml before PTCD, 8997 pg/ml 3 h after PTCD and gradually decreased there after. Serum and bile levels of tumor necrosis factor α and hepatocyte growth factor were high before and after PTCD. The patient underwent an extended cholecystectomy and resection of the extrahepatic bile duct. The resected specimen showed two elevated lesions of the gallbladder which, microscopically, revealed moderately differentiated tubular adenocarcinoma. These findings suggest that pre-existing inconspicuous inflammation of the biliary tract due to reflux of pancreatic juice is involved in elevation of serum and bile cytokines, and that cytokines may participate in gallbladder carcinogenesis associated with AJPBD. (Received July 24, 1997; accepted Jan. 23, 1998)     

Clinical and pathological features of primary carcinoma of the cystic duct

Background

According to Farrar’s criteria, a tumor restricted to the cystic duct is defined as cystic duct carcinoma, but this definition excludes advanced carcinoma originating from the cystic duct.

Patients and methods

For the purpose of this study, primary cystic duct carcinoma was defined as a tumor originating from the cystic duct. We investigated the clinicopathological features of 15 cystic duct carcinomas, including 13 that did not fit Farrar’s criteria, and compared them with those of 52 cases of gallbladder carcinoma and 161 cases of extrahepatic bile duct carcinoma.

Results

The incidence of primary cystic duct carcinoma was 6.6% among all malignant biliary tumors. The main symptom was jaundice in 67% of cases. The operative procedures employed ranged from cholecystectomy to hepatopancreatoduodenectomy. The cases of cystic duct carcinoma and bile duct carcinoma showed a high frequency of perineural infiltration. The overall 5-year survival rate of the 15 patients was 40%.

Conclusion

Patients with advanced cystic duct carcinoma show a high frequency of jaundice and perineural infiltration. Our data suggest that cystic duct carcinoma may be considered a distinct subgroup of gallbladder carcinoma. Radical surgery is necessary for potentially curative resection in patients with advanced cystic duct carcinoma.     

Metachronous double cancer of the gallbladder and common bile duct

We report a rare case of metachronous double cancer of the biliary tract. At age 59 years, a man had undergone a cholecystectomy and resection of the liver bed for gallbladder cancer pathologically diagnosed as papillary adenocarcinoma, in 1997. Four years later, he was admitted to our hospital with jaundice. At first, we suspected lymph node metastasis of the gallbladder cancer along the common bile duct. But abdominal computed tomography demonstrated circular wall thickness of the common bile duct, so primary bile duct cancer was strongly suspected. Thus, extended right hepatectomy and pancreaticoduodenectomy were performed after right portal vein embolization. The pathological diagnosis of the resected specimen was well-differentiated tubular adenocarcinoma, and this case was clarified to be metachronous double cancer. A review of the literature regarding double cancer of the biliary tract is presented following this case report. We showed that half of 30 cases of double cancer of the biliary tract were not associated with pancreaticobiliary maljunction, including all 6 metachronous cases.     

胆囊管癌伴右副肝管直接汇入胆囊管1例报告

正胆道变异的类型繁多,包括胆囊管与肝总管并行低位汇合,胆囊管汇入右肝管、副肝管等~([1])。其中副肝管又叫Luschka胆管或迷走胆管,是胚胎期肝十二指肠发育不全的常见畸形,直接连接胆囊和肝内胆管通道,常开口于胆总管,其次是右肝管和胆囊管~([2])。本文报道1例较大右副肝管直接汇入胆囊管,并伴有胆囊管癌的罕见病例。1病例资料患者男性,63岁,因"间断性上腹部胀痛不适2年,加重伴     

Carcinoma of the cystic duct associated with pancreaticobiliary maljunction

Received: February 4, 2000 / Accepted: May 26, 2000     

Hepatopancreatoduodenectomy: its suitability for bile duct cancer versus gallbladder cancer

Background/Purpose

We aimed to determine whether bile duct cancer (BDC) or gallbladder cancer (GBC) was a better candidate for hepatopancreatoduodenectomy (HPD).

Methods

Ten patients with BDC and ten with GBC were treated by HPD with major hepatectomy between 1994 and 2004 and compared, in terms of surgical outcome and survival.

Results

In the BDC patients, the International Union Against Cancer (UICC) stage was I in three patients; II in four; III in one; and IV in two; of the GBC patients, one was stage II; four were stage III; and five were stage IV. The reasons for choosing HPD for BDC were: superficial spreading, in three patients; intramural wide invasion, in five; and hepatoduodenal ligament (HDL) invasion, in two; and for GBC, extrahepatic bile duct invasion, in seven; and HDL invasion, in three. The morbidity and mortality rates for BDC and GBC were 40% and 60%, and 0% and 30%, respectively. All three of the GBC patients who died in hospital had undergone a right trisectionectomy with caudate lobectomy. The cumulative 5-year survival rate of the BDC patients was 64%; the 1-year survival rate for the GBC patients was only 20%, and none survived for over 2 years (P < 0.001). Of the patterns of BDC cancer invasion, the superficial-spreading type appeared to have a better prognosis than the others, but the difference was not statistically significant.

Conclusions

HPD is indicated for any type of BDC, but HPD did not show any survival benefits in treating patients with GBC with obstructive jaundice.

     

Endoscopic biliary imaging and clinicopathological features of cystic duct cancer

Background Cystic duct cancer fulfilling Farrar’s criteria is relatively rare, but tumors whose origin is estimated to be in the cystic duct exist. The clinical features of such “broadly defined” cystic duct cancer have not been clarified. Methods The endoscopic retrograde cholangiography (ERC) findings, intraductal ultrasonography (IDUS) findings, histological findings, and prognoses of 11 cases of cystic duct cancers resected at our institution (group C) were retrospectively analyzed. As a control group, 55 cases of middle or lower bile duct cancer (group B) were used (in 20 of the 55 cases of group B, tumors extended to the cystic duct intraluminally (group B-C (+)). Results (1) ERC findings of group C as compared with those of group B-C (+) were as follows: (a) unilateral bile duct narrowing (spoon-like appearance): 55% versus 5% (P < 0.01); (b) bilateral bile duct narrowing (apple-core-like appearance): 27% versus 95% (P < 0.001). (2) IDUS was unable to visualize the cysticocholedochal junction (negative “confluence sign”) more often in group C (67%) than in group B-C (+) (13%) (P < 0.01). (3) Histologically, tumors extended to the gallbladder and the bile duct in 36% and 91% of the cases in group C, respectively. (4) The median survival time of the two groups was 21 and 28 months, respectively. Conclusions Cystic duct cancers frequently extended to the bile duct. The spoon-like appearance by ERC and the negative confluence sign by IDUS were characteristic findings.     

Mucosal cell proliferation activity of the gallbladder in children with anomalous arrangement of the pancreaticobiliary duct

Anomalous arrangement of the pancreaticobiliary duct (AAPBD) is an anatomical maljunction of the bile duct and the pancreatic duct that is frequently associated with gallbladder carcinoma. In patients with AAPBD, it has been postulated that pancreatic juice regurgitates into the biliary tree, and the mixture of refluxed pancreatic juice and stagnant bile juice acts as an irritant factor to the biliary tract epithelium, leading to chronic inflammation and metaplasia. Eventually these mucosal changes may progress to invasive carcinoma. We reviewed clinicopathologic studies on epithelial changes of the gallbladder in patients with AAPBD to clarify the implications relevant to carcinogenesis. Conventional histological studies have shown that the most characteristic change observed in the gallbladder of children with this anomaly was epithelial hyperplasia. Furthermore, the incidence of mucosal hyperplasia was significantly increased in the gallbladder of children in whom the pancreatic duct joined the common bile duct (P-C type) compared with the incidence in children in whom the common bile duct joined the pancreatic duct (C-P type). In addition, cell kinetic studies have demonstrated increased cellular proliferative activity of the gallbladder in children with AAPBD. Cell proliferative activity was significantly elevated in children with the P-C type of AAPBD compared with that in children with the C-P type of anomaly. In conclusion, AAPBD may yield increased cell proliferation in the gallbladder of patients with this anomaly in early childhood, resulting in epithelial hyperplasia. Although it remains unknown which agents are responsible for promoting the activation of cellular function, it seems that bile acids and refluxed pancreatic proteases are likely play a role in such promotion. Further investigations are needed to elucidate the mechanism of increased cellular function.     

Extracystic biliary carcinoma associated with anomalous pancreaticobiliary junction and cysts

Anomalous pancreaticobiliary junction with cystic dilatation of the biliary tract is usually associated with carcinoma arising from the cyst wall. We report an extracystic location of biliary carcinoma in the presence of anomalous pancreaticobiliary junction and cysts in a patient with obstruction of the origin of the left hepatic duct who underwent hepatobiliary resection. Cholangiocarcinoma was found to have arisen in a noncystic left hepatic duct, in conjunction with cystic dilatation involving both the cystic and common bile ducts. The present case supports a relationship between anomalous pancreaticobiliary junction and biliary carcinogenesis that may affect the extracystic biliary tree.     

Epithelial cyst of the gallbladder associated with adenocarcinoma

Epithelial cyst of the gallbladder associated with papillary adenoma and adenocarcinoma is presented herein. A 70‐year‐old male patient with general malaise was admitted to our hospital during the follow‐up of an elevated mucosal lesion in the fundus of the gallbladder. Endoscopic ultrasonography revealed a cystic lesion adjacent to the elevated lesion, and interruption of the hyperechoic third layer of the gallbladder wall next to the gallbladder bed of the liver. He was diagnosed as having an epithelial cyst of the gallbladder associated with gallbladder carcinoma that directly invaded the gallbladder bed. He underwent resection of the gallbladder with partial resection of the liver and regional lymph node dissection. The resected specimen, which showed multiple cysts with septum formation, measured 1.9–cm in size and was located in the subserosal layer of the gallbladder wall. The wall of the cyst was lined with columnar epithelium and papillary adenoma, and adenocarcinoma was scattered in some portions of the cyst wall. Furthermore, papillary adenoma associated with adenocarcinoma was independently identified in the luminal surface of the gallbladder epithelium covering the cysts. These histological findings were compatible with epithelial cyst of the gallbladder associated with papillary adenoma and adenocarcinoma. The tumor was diagnosed as T1bN0M0, stage I, in the TNM clinical classification. To our knowledge, this is the first report of an epithelial cyst of the gallbladder associated with papillary adenoma and adenocarcinoma, and provides some insight into the relationship between epithelial cyst and adenoma or cystadenocarcinoma of the gallbladder.     

Choledochocele associated with superficial spreading cancer with cholesterolosis of the bile duct

A 74-year-old woman, who had suffered from acute cholangitis, was referred to our department for further evaluation of the biliary tree. A diagnosis of choledochocele was made by endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography. A small flat elevation with cholesterolosis was observed in the lower bile duct, and circumferential wall thickening was apparent in some parts of the upper and middle bile duct by intraductal ultrasonography and peroral cholangioscopy. With the diagnosis of choledochocele associated with superficial spreading cancer and cholesterolosis of the bile duct, pylorus-preserving pancreaticoduodenectomy was carried out. Microscopically, the tumor had spread extensively from the lower to the upper bile duct. Its invasion was limited to the mucosa for the most part, with microinvasion of the subserosa in the upper bile duct. In the lower bile duct, foamy cells were located beneath the neoplastic epithelium of the elevation. The number of cases of choledochocele associated with biliary cancer is becoming higher than previously reported. This anomaly may play some role in the development of biliary malignancy. Histological examination seems to be mandatory before making a diagnosis of cholesterolosis of the bile duct, since this condition may occasionally accompany cancer.     

Carcinoma in adenoma of the gallbladder in a patient with anomalous pancreaticobiliary ductal junction

We present a case of carcinoma in adenoma of the gallbladder with anomalous pancreaticobiliary ductal junction (APBDJ) in a 60-year-old Japanese woman. The patient had no abdominal symptoms. Serum levels of carcinoembryonic antigen, carbohydrate antigen 19-9, elastase 1, and α-fetoprotein were all within normal limits. Ultrasonography demonstrated two irregular hyperechoic lesions of the gallbladder. Computed tomography showed two soft-tissue density masses in the gallbladder. Endoscopic retrograde cholangiopancreatography showed APBDJ and two protruding lesions in the gallbladder. Angiography displayed a hypervascular lesion fed by the cystic artery. The patient underwent total cholecystectomy; the diagnosis of the intraoperative frozen section was well differentiated adenocarcinoma with possible mucosal invasion. Amylase level in the gallbladder bile was 90600 IU/l. Macroscopically, there were two polyps in the gallbladder. The larger one, 3.5 cm in diameter, was adenocarcinoma in adenoma, and the smaller one, an inflammatory polyp. We briefly discuss the relationship among adenoma, adenocarcinoma of the gallbladder, and APBDJ.     

Cancer cells spread through lymph vessels in the submucosal layer of the common bile duct in gallbladder carcinoma

Introduction

In the present study, we performed immunohistochemical staining with a lymphatic epithelium-specific marker, D2-40, to analyze the status of lymphatic spreading in the hepatoduodenal ligament in T2 gallbladder carcinoma (GC).

Methods

One hundred and eighty-six paraffin-embedded specimens from 15 T2 GC patients were reviewed.

Results

Lymph vessels lined with D2-40 were visualized in the submucosal layer of the common bile duct in all cases. In 3 of 15 patients, clusters of cancer cells were identified in the submucosal lymph vessels of the extrahepatic bile duct, and this lymphatic invasion of cancer cells failed to be detected with only conventional hematoxylin–eosin staining. The frequency of the invasion to the submucosal lymph vessels in T2 GC correlated with presence of microscopic invasion to hepatoduodenal ligament and perineural invasion.

Conclusion

There were lymph vessels in the submucosal layer of the common bile duct, and cancer cells can spread through these channels in addition to the large lymph vessels in subserosal layer around the extrahepatic bile duct in GC. The present results would support the concept of en bloc resection of the extrahepatic bile duct in curative resection for T2 GC.     

Recurrent carcinoma of cystic duct remnant with subcutaneous implantation in abdominal wall

A case of recurrent carcinoma of the cystic duct remnant invading the common bile duct and portal vein with subcutaneous implantation of the abdominal wall is presented. The patient was a 55-year-old woman with an abdominal wall tumor at the site of the surgical scar of a cholecystectomy, performed at a local hospital 5 years ago for symptomatic cholelithiasis. The diagnosis was made by incisional biopsy of the tumor, computed tomography, percutaneous transhepatic cholangiography, and angiography. She underwent extended right hepatic lobectomy with en bloc resection of the caudate lobe, extrahepatic bile duct, and portal vein. The abdominal wall tumor was resected concomitantly. Histological examination showed that both the recurrent carcinoma of the cystic duct remnant and the abdominal wall implantation were moderately differentiated adenocarcinoma. This recurrence probably could have been prevented if both the macroscopic and microscopic examinations of the resected specimen had been precisely carried out after the previous cholecystectomy and the primary carcinoma identified and treated at that time.     

Double cancer of gallbladder and bile duct associated with anomalous junction of the pancreaticobiliary ductal system

We report a case of double cancer of the gallbladder and the common bile duct associated with anomalous junction of the pancreaticobiliary ductal system, and review the literature of similar case reports. A 66-year-old woman was admitted to an associated hospital complaining of upper abdominal pain, and was diagnosed as having pancreatitis. Abdominal imaging revealed an irregularly protruding mass at the body of the gallbladder and an intraluminal protrusion at the lower third of the common bile duct. Endoscopic retrograde cholangiopancreatography also revealed anomalous junction of the pancreaticobiliary ductal system with congenital biliary dilatation of 14 mm in the largest diameter. She underwent surgical resection of the gallbladder, the extrahepatic bile duct and the gallbladder bed of the liver with a dissection of the regional lymph nodes for double cancer of the gallbladder and the bile duct associated with anomalous junction of the pancreaticobiliary ductal system. She is still alive 33 months after surgery without any signs of recurrence. There were 12 patients (including our case) reported in the literature who had double cancer of the gallbladder and the extrahepatic bile duct associated with anomalous junction of the pancreaticobiliary ductal system. Only 33% of these 12 patients had jaundice. Tumors of the 12 patients were commonly early-stage cancer both in the gallbladder (36%) and in the extrahepatic bile duct (73%). Therefore, we concluded that precise preoperative imaging of the total biliary tract should be required in order to detect early-stage cancer in patients with anomalous junction of the pancreaticobiliary ductal system before planning surgical procedures, and consideration should be given to the possibility of multiple occurrences of biliary tract cancers.     

Metachronous double cancer of the gallbladder and pancreas associated with pancreaticobiliary maljunction

A 50-year-old Japanese woman complained of abdominal and back pain. Ten years previously she had undergone cholecystectomy, choledochectomy, and Roux-en-Y choledochojejunostomy for gallbladder cancer associated with pancreaticobiliary maljunction without bile duct dilatation. On the present admission, ultrasonography (US) and computed tomography (CT) demonstrated a large mass, 60 mm in size, in the pancreatic tail. Endoscopic retrograde cholangiopancreatography (ERCP) showed obstruction of the main pancreatic duct in the tail of the pancreas and revealed that the pancreatic duct was joined to the bile duct 25 mm above the papilla of Vater. The patient underwent distal pancreatectomy, splenectomy, left adrenalectomy, and partial gastrectomy. Histological examination revealed moderately differentiated ductal adenocarcinoma that had invaded to the proper muscle of the stomach. Double cancer of the gallbladder and pancreas in a patient with pancreaticobiliary maljunction is rare. Although the etiology of cancer of the pancreas associated with pancreaticobiliary maljunction is unclear, we should pay close attention to the pancreas as well as the biliary tract during the long-term follow-up of patients with pancreaticobiliary maljunction after they have undergone a choledochojejunostomy.     

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.     

Carcinoma and polyps of the gallbladder associated with Peutz-Jeghers syndrome

Summary Peutz-Jeghers syndrome is a genetic condition characterized by mucocutaneous pigmentation and gastrointestinal polyposis. A variety of neoplasms have been found in the alimentary tract or else-where in patients with this entity. A 39-year-old female patient who had carcinoma and two polyps in the gallbladder in association with Peutz-Jeghers syndrome is described. Since the polyps consisted of the normal lining epithelium of the gallbladder and pseudopyloric gland-type metaplastic cells and obviously lacked cellular atypism, the authors would consider them hamartomatous. The carcinoma partly showing submucosal invasion existed in an area other than the polyps. This is the first documented case of the syndrome having gallbladder carcinoma.