Pancreatobiliary Maljunction-associated Gallbladder Cancer Is as Common in the West, Shows Distinct Clinicopathologic Characteristics and Offers an Invaluable Model for Anatomy-induced Reflux-associated Physio-chemical Carcinogenesis.

OBJECTIVE: To determine the associations of pancreatobiliary maljunction (PBM) in the West. BACKGROUND: PBM (anomalous union of common bile duct and pancreatic duct) is mostly regarded as an Asian-only disorder, with 200X risk of gallbladder cancer (GBc), attributed to reflux of pancreatic enzymes. Methods: Radiologic images of 840 patients in the US who underwent pancreatobiliary resections were reviewed for PBM and contrasted with 171 GBC cases from Japan. RESULTS: Eight % of the US GBCs (24/300) had PBM (similar to Japan; 15/ 171, 8.8%), in addition to 1/42 bile duct carcinomas and 5/33 choledochal cysts. None of the 30 PBM cases from the US had been diagnosed as PBM in the original work-up. PBM was not found in other pancreatobiliary disorders. Clinicopathologic features of the 39 PBM-associated GBCs (US:24, Japan:15) were similar; however, comparison with non-PBM GBCs revealed that they occurred predominantly in females (F/M = 3); at younger (<50-year-old) age (21% vs 6.5% in non-PBM GBCs; P = 0.01); were uncommonly associated with gallstones (14% vs 58%; P < 0.001); had higher rate of tumor-infiltrating lymphocytes (69% vs 44%; P = 0.04); arose more often through adenoma-carcinoma sequence (31% vs 12%; P = 0.02); and had a higher proportion of nonconventional carcinomas (21% vs 7%; P = 0.03). Conclusions: PBM accounts for 8% of GBCs also in the West but is typically undiagnosed. PBM-GBCs tend to manifest in younger age and often through adenoma-carcinoma sequence, leading to unusual carcinoma types. If PBM is encountered, cholecystectomy and surveillance of bile ducts is warranted. PBM-associated GBCs offer an invaluable model for variant anatomy-induced chemical (reflux-related) carcinogenesis.

A proposed feasible classification of common bile duct duplications based on a newly described variant and review of existing literature.

BACKGROUND: Duplication of the common bile duct (CBD) is extremely rare among the anatomical variations in the biliary tract system, which presents a septum within the CBD or an accessory CBD. In our study, we report a rare case of duplication of the common bile duct combined congenital biliary dilatation.we present a rare case of a septum in the dilated biliary tract. CASE PRESENTATION: We reported a 5-year-old Asian girl who had history of repeated abdominal pain for 4 days and aggravated for 1 day. Magnetic resonance cholangiopancreatography (MRCP) examination revealed duplicated common bile duct (DCBD) malformation with congenital biliary dilatation and distal cholelithiasis. The patient underwent choledochal cyst resection and biliary tract reconstruction and abdominal cavity irrigation and drainage under general anesthesia. A septum was found within the common bile duct during the operation. The septum divided the extrahepatic bile duct into two parts connected to the left and right hepatic ducts respectively and the gallbladder is attached to the repeated right bile duct which was not previously reported in the literature. CONCLUSIONS: We complement and adjust the classification of common bile duct duplication by reviewing the literature.

Pancreaticobiliary maljunction and pancreas divisum accompanied with intestinal malrotation: a case report.

BACKGROUND: Pancreaticobiliary maljunction is a congenital anatomical abnorma l junction of the pancreatic duct and bile duct into a common channel outside the duodenal wall. Pancreas divisum is also a congenital anatomical abnormality characterized by unfused pancreatic ducts. Intestinal malrotation is caused by the failure of bowel rotation and fixation. We reported an optimal surgical intervention for the rare case of pancreaticobiliary maljunction and pancreas divisum accompanied intestinal malrotation. CASE PRESENTATION: A 2-year-old female presented with fever and jaundice. Abdominal ultrasound showed dilated common bile duct and intrahepatic bile ducts; MRCP showed pancreaticobiliary maljunction, pancreas divisum, and dilated biliary system; Abdominal contrast-enhanced CT showed a reversed relationship between the superior mesenteric artery and the superior mesenteric vein. An operation of laparoscopic resection of the extrahepatic bile duct, Roux-en-Y hepaticojejunostomy, and Ladd's procedure was performed after the inflammation of the biliary system was treated. The post-operative follow-up period was uneventful. CONCLUSIONS: The management of pancreas divisum can be conservative. We present an optimal pattern of Roux-en-Y hepaticojejunostomy to deal with pancreaticobiliary maljunction associated with intestinal malrotation.

[Surgical treatment of common bile duct malformations in children]. / Khirurgicheskoe lechenie mal'formatsii obshchego zhelchnogo protoka u detei.

The review is devoted to the current classifications of common bile duct malformations, authors' opinion regarding surgical approach and reconstruction of the bile ducts. The authors describe the modern modifications of bile duct reconstructions and estimate their effectiveness. PubMed database, Google Scholar and National Scientific Electronic Library eLIBRARY.ru databases were used. We analyzed the complications in children depending on various reconstructions, anatomical form, timing of reconstructive surgery and early diagnosis of this pathology.

IL-33 overexpression in gallbladder cancers associated with pancreatobiliary maljunction.

AIMS: To investigate whether genetic or inflammatory pro-oncogenic factors are relevant to the increased risk of gallbladder cancers in patients with pancreaticobiliary maljunction (PBM). METHODS AND RESULTS: Mutations in KRAS exon 2 were examined by a highly sensitive, droplet digital PCR platform using surgically resected specimens of PBM-associated (n = 31) and non-associated gallbladder cancers (n = 49). The tissue expression of IL-6 and IL-33, which are suspected to promote biliary carcinogenesis, was analysed by quantitative real-time PCR and in-situ hybridisation. The incidence of KRAS mutations was similarly low in PBM-associated (five of 32 cases; 16%) and non-associated cancers (four of 49 cases; 8%) (P = 0.272). The tissue expression of IL-33 mRNA, but not IL-6 mRNA, was significantly higher in PBM-associated gallbladder cancers than in gallbladder cancers without PBM (P = 0.004). A similar degree of IL-33 overexpression was also observed in the background non-cancerous mucosa in cases of PBM-associated gallbladder cancers, and was significantly greater than that in PBM cases with cholecystitis alone (P < 0.001). The results of in-situ hybridisation indicated that the source of IL-33 production in PBM-associated carcinomas was the endothelium, cancer cells and non-neoplastic biliary epithelium. In a combined PBM-associated and non-associated cohort, IL-33 overexpression in gallbladder cancers correlated with less aggressive features (e.g. a lower pT stage and longer overall survival), similar to recently reported findings on large-duct cholangiocarcinomas. CONCLUSIONS: KRAS mutations do not appear to be associated with a high risk of malignancy in PBM, while IL-33 overexpression may provide a pro-oncogenic microenvironment in the gallbladder mucosa of patients with PBM.

Choledochal malformations: global research, scientific advances and key controversies.

Choledochal malformations (CMs) represent a spectrum of relatively rare and complex congenital anomalies, characterized by abnormal dilatation of the biliary tract in the absence of any acute obstruction. Today, almost 20% of CMs can be detected in-utero using maternal ultrasonography. Formal scientometric analysis was used to identify where modern CM research is taking place and perhaps where our attention should be directed in the future. Thus, this article offers a comprehensive review of recent scientific advances relating to CMs including the current understanding of etiology and classification, whilst also discussing key controversies such as risk of malignant transformation and the role of newer modalities of surgical treatment. Although laparoscopic excision of CMs and biliary reconstruction is nowadays feasible and safe, care should be taken before dispensing with standard open techniques, which have minimal complication rates and proven long-term benefit.

Intraductal papillary mucinous neoplasm of the main duct in a patient with pancreas divisum.

Pancreas divisum is a congenital anomaly present in 5-10% of the population and is usually asymptomatic. Pancreatic intraductal papillary mucinous neoplasms (IPMN) are mucinous cystic tumors that have malignant potential and are classified according to their location as IPMN of the main duct, branch duct or mixed type. Larger lesions and those originating in the main duct have an increased risk of malignancy. The real incidence is unknown as most lesions are asymptomatic.

Todani Ic cystic dilatation of the bile duct.

The congenital dilation of the bile duct is an infrequent pathology in western countries and is associated with the female sex. It is usually diagnosed clinically with complementary tests and evaluated at an early age and also appears frequently in adults. These dilatations are grouped into five types according to Todani's classification, including type Ic (Figure 1). The treatment of choice for dilatations of the biliary duct Todani type I is the complete excision of the biliary tract due to the susceptibility of malignant degeneration. A reconstruction is performed via a hepaticojejunostomy with a Roux-en-Y loop. Although in non-malignant cases, a papillotomy with prophylactic stent placement using ERCP can be performed as an alternative. We present the case of a 54-year-old female with a history of high blood pressure, she was examined due to generalized abdominal pain which was unrelated to food intake. The blood test did not identify any alterations of interest. Ultrasound identified a fusiform dilation of the common bile duct occupied by lithiasis. ERCP was attempted due to choledocholithiasis, but the procedure was abandoned as it was not feasible to channel the duodenal papilla. The study was completed with NMR cholangiography (transverse plane [Figure 2] and coronal plane [Figure 3]), identifying a diffuse fusiform dilatation of the common bile duct and common hepatic duct, compatible with congenital cystic lesion Todani type Ic. Finally, the patient underwent a hepaticojejunostomy after sectioning of the main bile duct and extraction of choledocholithiasis.

Meta-analysis of risk of developing malignancy in congenital choledochal malformation.

BACKGROUND: Choledochal malformations comprise various congenital cystic dilatations of the extrahepatic and/or intrahepatic biliary tree. Choledochal malformation is generally considered a premalignant condition, but reliable data on the risk of malignancy and optimal surgical treatment are lacking. The objective of this systematic review was to assess the prevalence of malignancy in patients with choledochal malformation and to differentiate between subtypes. In addition, the risk of malignancy following cystic drainage versus complete cyst excision was assessed. METHODS: A systematic review of PubMed and Embase databases was performed in accordance with the PRISMA statement. A meta-analysis of the risk of malignancy following cystic drainage versus complete cyst excision was undertaken in line with MOOSE guidelines. Prevalence of malignancy was defined as the rate of biliary cancer before resection, and malignant transformation as new-onset biliary cancer after surgery. RESULTS: Eighteen observational studies were included, reporting a total of 2904 patients with a median age of 36 years. Of these, 312 in total developed a malignancy (10·7 per cent); the prevalence of malignancy was 7·3 per cent and the rate of malignant transformation was 3·4 per cent. Patients with types I and IV choledochal malformation had an increased risk of malignancy (P = 0·016). Patients who underwent cystic drainage had an increased risk of developing biliary malignancy compared with those who had complete cyst excision, with an odds ratio of 3·97 (95 per cent c.i. 2·40 to 6·55). CONCLUSION: The risk of developing malignancy among patients with choledochal malformation was almost 11 per cent. The malignancy risk following cystic drainage surgery was four times higher than that after complete cyst excision. Complete surgical resection is recommended in patients with choledochal malformation.

Embryological etiology of pancreaticobiliary system predicted from pancreaticobiliary maljunction with incomplete pancreatic divisum: a case report.

BACKGROUND: The genesis of the "complex type" classification of pancreaticobiliary maljunction (PBM) is unclear, and the pancreaticobiliary anatomy is also varied according to each case. We encountered a patient with PBM and incomplete pancreatic divisum (PD). We herein discussed about the embryological etiology of pancreaticobiliary system predicted from PBM with incomplete PD. CASE PRESENTATION: A 67-year-old man was found to have a dilatation of the common bile duct (CBD) during a medical examination at 62 years of age. The dilatation of the CBD subsequently progressed, and he was admitted to our hospital for surgical treatment. Magnetic resonance cholangiopancreatography revealed a dilatation from the common hepatic duct to the middle bile duct with PBM. Endoscopic retrograde cholangiopancreatography from the papilla of Vater revealed the pancreatic main duct via the pancreatic branch duct, and PBM with dilatation of the CBD and incomplete PD were revealed. We performed an extrahepatic bile duct resection and hepaticojejunostomy because of high risk of malignant transformation. Taping and transection of the bile duct without dilatation on the pancreatic side were performed, and thereafter, two orifices of the common channel and ventral pancreatic duct were ligated. The level of amylase in the bile was 7217 IU/L, and a histological examination of the CBD showed an inflammatory change of CBD, not a malignant transformation. CONCLUSION: It is somewhat easy to identify the pancreatobiliary anatomy when the cause of embryology of both PBM and PD is thought to be an abnormal embryology of the ventral pancreas.

Pancreaticobiliary Maljunctions in European Patients with Bile Duct Cysts: Results of the Multicenter Study of the French Surgical Association (AFC).

BACKGROUND: Pancreaticobiliary maljunctions (PBMs) are congenital anomalies of the junction between pancreatic and bile ducts, frequently associated with bile duct cyst (BDC). BDC is congenital biliary tree diseases that are characterized by distinctive dilatation types of the extra- and/or intrahepatic bile ducts. Todani's types I and IVa, in which dilatation involves principally the main bile duct, are the most frequent. PBM induces pancreatic juice reflux into the biliary tract that is supposed to be one of the main factors of biliary cancer degeneration, although the diagnostic criteria of PBM that can be either morphological and/or functional are not well defined especially in Western series. OBJECTIVE: The aim of this study was to assess the relative prevalence of PBM in BDC in a large European multicenter study, to analyze the characteristics of PBM and try to propose diagnostic criteria of PBMs based on morphological and/or functional criteria and define the positive, negative predictive values, sensibility and specificity of either criteria. RESULTS: From 1975 to 2012, 263 patients with BDC were analyzed. Among them, 190 (72.2 %) were considered to present PBM. Types I and IVa had a similar rate of PBM association. According to the "AFC classification," 57.2 % had a C-P type, 34.5 % a P-C type and 8.3 % a complex type ("anse-de-seau"). The median length of the common channel in patients with PBM was 15.8 ± 6.8 mm (range 5-40 mm). The median intrabiliary amylase and lipase levels were 65,249 and 172,104 UI/L, respectively. For the diagnostic of PBM, a common channel length of more than 8 mm and an intrabiliary amylase level superior to 8000 UI/L were associated with a predictive positive value and a specificity of more than 90 %. Synchronous biliary cancer had an incidence of 8.7 % in all patients with BDC and PBM 11.1 % in adults. Compared to type IV, the type I BDC was associated with statistically more cancer patients in the presence of PBM. CONCLUSIONS: Characteristics of PBM associated with BDC in Western population are quite close to reported Eastern series. The results suggest considering both the intrabiliary value of amylase >8000 UI/L and a length of a common channel >8 mm as appropriate values for positive diagnosis of PBM.

Double common bile duct with choledochal cyst and cholelithiasis: report of a case.

Double common bile duct (DCBD) is a rare congenital anomaly of the biliary system, often associated with biliary lithiasis, choledochal cyst, pancreaticobiliary maljunction (PBM), and upper gastrointestinal tract malignancies. We report a case of type I DCBD with choledochal cyst and cholelithiasis in a 52-year-old Chinese man. We also reviewed 24 cases of DCBD reported in the Chinese literature between 1965 and 2012. Most (58.3%) of these cases were classified as type I DCBD, with accompanying choledocholithiasis in 79.2%, cholecystolithiasis in 37.5%, choledochal cyst in 33.3%, and PBM in 8.3%. There was no case of concomitant cancer. The type and coexistence of PBM with DCBD are clinically important because of its close implications with concomitant pathology. Most Chinese people with DCBD have type I. Moreover, the high incidences of choledochal cyst and biliary lithiasis and the extremely low incidences of PBM and biliary cancer are the major clinical characteristics of DCBD in China.

Anatomical and congenital anomalies of extra hepatic biliary system encountered during cholecystectomy.

Anomalous biliary anatomy is frequently encountered by surgeons during cholecystectomy. Importance of its recognition lies in avoiding serious biliary injuries. This study was carried out to assess the frequency of anatomical and congenital anomalies of extrahepatic biliary system in patients undergoing cholecystectomy. This is an observational study performed in the Department of Surgery, Combined Military Hospital (CMH) Momenshahi, CMH Ghatail and Mymensingh Medical College Hospital for a period of five years from June 2007 to June 2012. Two hundred and fifty diagnosed patients of cholelithiasis undergoing routine cholecystectomy were assessed for anatomical and congenital anomalies of extra hepatic biliary system as well as vascular anomalies. Structures mainly assessed for anomalies were gall bladder, cystic duct, supraduodenal part of Common Bile Duct (CBD), cystic artery and hepatic artery which are routinely handled during cholecystectomy. However, assessment of variations and anomalies, of hepatic ducts, portal vein, retroduodenal and pancreatic parts of CBD were not done due to possibility of iatrogenic injuries. Two hundred and fifty cases of cholelithiasis comprising 216(86.4%) females and 34(13.6%) males with mean age of 39.15 years were included in the study. Clinical presentation includes mainly pain in right hypochondrium (74.8%), pain in right hypochondrium and epigastrium (18.8%) and pain in epigastrium alone (7.6%). Laparoscopic cholecystectomy was done in 157 patients and 93 patients were treated by open procedure including conversion cases. Operative findings revealed variations in 38 cases (15.2%) mainly involving cystic artery (8%), cystic duct (4.4%) and gall bladder (1.6%). Postoperative complications includes bleeding 3.6%, biliary leak from drain 1.6% and CBD injury 0.8% giving rise to 0.8% morbidity, however, no mortality was seen in this series. Anatomical and congenital anomalies of biliary tree, are not common but may be significant during surgery as failure to recognize them leads to iatrogenic injuries and can increase morbidity and mortality.

Ectopic Opening of Common Bile Duct to Duodenal Bulb: A Single Tertiary Center Experience.

BACKGROUND: The ectopic opening of the common bile duct(CBD) into the duodenal bulb is a rare biliary anomaly. The study aimed to reveal the experience with clinical and endoscopic outcomes in these patients. MATERIALS AND METHODS: This study was conducted on 57 consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for ectopic opening of the CBD into the duodenal bulb at our institution between 2010 and 2020. RESULTS: The median age was 59 years (49 males). A total of 146 ERCP procedures were performed (once in 26 patients and 2 or more times in 31 patients). Ten patients had a history of unsuccessful ERCP in an external center. The median follow-up time was 14.6 months. All patients had a slit-like opening of the CBD into the duodenal bulb, apical stenosis, and hook-shaped distal CBD. ERCP findings were CBD stone or dilatation in 55 patients and post-cholecystectomy biliary leakage in 2 patients. Balloon dilatation was performed for apical stenosis in 7 patients and distal CBD stenosis in 26 patients. During the first ERCP session, biliary stent/nasobiliary drainage was placed in 37 patients, and CBD stones were extracted in 19 patients without stenting. Biliodigestive anastomosis was applied to 13 patients, 5 of whom had recurrent cholangitis, 7 required recurrent ERCP, and one was due to the technical difficulty of ERCP. CONCLUSIONS: Ectopic biliary opening should be remembered if the papilla cannot be seen in its usual place in a patient with apical stenosis. ERCP should be performed in experienced hands, and surgery should be considered in the need for recurrent ERCP.