Importance of early diagnosis of pancreaticobiliary maljunction without biliary dilatation

AIM:To clarify the strategy for early diagnosis of pancreaticobiliary maljunction(PBM) without biliary dilatation and to pathologically examine gallbladder before cancer develops.METHODS:The anatomy of the union of the pancreatic and bile ducts was assessed by using endoscopic retrograde cholangiopancreatography(ERCP).Patients with a long common channel in which communication between the pancreatic and bile ducts was maintained even during sphincter contraction were diagnosed as having PBM.Of these,patients in which the maximal diameter of the bile duct was less than 10 mm were diagnosed with PBM without biliary dilatation.The process of diagnosing 54 patients with PBM without biliary dilatation was retrospectively investigated.Histopathological analysis of resected gallbladder specimens from 8 patients with PBM without biliary dilatation or cancer was conducted.RESULTS:Thirty-six PBM patients without biliary dilatation were diagnosed with gallbladder cancer after showing clinical symptoms such as abdominal or back pain(n = 16) or jaundice(n = 12).Radical surgery for gallbladder cancer was only possible in 11 patients(31%) and only 4 patients(11%) survived for 5 years.Eight patients were suspected as having PBM without biliary dilatation from the finding of gallbladder wall thickening on ultrasound and the diagnosis was confirmed by ERCP and/or magnetic resonance cholangiopancreatography(MRCP).The median age of these 8 patients was younger by a decade than PBM patients with gallbladder cancer.All 8 patients underwent prophylactic cholecystectomy and bile duct cancer has not occurred.Wall thickness and mucosal height of the 8 resected gallbladders were significantly greater than controls,and hyperplastic changes,hypertrophic muscular layer,subserosal fibrosis,and adenomyomatosis were detected in 7(88%),5(63%),7(88%) and 5(63%) patients,respectively.Ki-67 labeling index was high and K-ras mutation was detected in 3 of 6 patients.CONCLUSION:To detect PBM without biliary dilatation before onset of gallbladder cancer,we should perform MRCP for individuals showing increased gallbladder wall thickness on ultrasound.

A case of gallbladder carcinoma associated with pancreatobiliary reflux in the absence of a pancreaticobiliary maljunction:A hint for early diagnosis of gallbladder carcinoma

A 62-year-old man with progressive thickening of the gallbladder wall visited our outpatient clinic. The biliary amylase level in the common bile duct was 19900 IU/L and that of the gallbladder was 127000 IU/L, although endoscopic retrograde cholangiopancreatography revealed no pancreaticobiliary maljunction. Histology demonstrated a moderately differentiated adenocarcinoma of the gallbladder. Pancreatobiliary reflux and associated gallbladder carcinoma were confirmed in the present case, in the absence of a pancreaticobiliary maljunction. Earlier detection of the pancreatobiliary reflux and progressive thickening of the gallbladder wall might have led to an earlier resection of the gallbladder and improved this patient＇s poor prognosis.

Magnetic resonance cholangiopancreatography study of pancreaticobiliary maljunction and pancreaticobiliary diseases

AIM: To discuss the imaging anatomy about pancreaticobiliary ductal union, occurrence rate of pancreaticobiliary maljunction (PBM) and associated diseases in a Chinese population by using magnetic resonance cholangiopancreatography (MRCP).

Relationship between pancreaticobiliary maljunction and gallbladder carcinoma: a meta-analysis

BACKGROUND: Reports on the relationship between pancreaticobiliary maljunction (PBM) and gallbladder carcinoma (GBC) are conflicting. The frequency of PBM in GBC patients and the clinical features of GBC patients with PBM vary in different studies. DATA SOURCES: English-language articles describing the association between PBM and GBC were searched in the PubMed and Web of Science databases. Nine case-control studies fulfilled the inclusion criteria and addressed the relevant clinical questions of this analysis. Data were extracted independently by two reviewers using a predefined spreadsheet. RESULTS: The incidence of PBM was higher in GBC patients than in controls (10.60% vs 1.76%, OR: 7.41, 95% CI: 5.03 to 10.87, P<0.00001). The proportion of female patients with PBM was 1.96-fold higher than in GBC patients without PBM (80.5% vs 62.9%, OR: 1.96, 95% CI: 1.09 to 3.52, P=0.12). GBC patients with PBM were 10 years younger than those without PBM (SMD: -9.90, 95% CI: -11.70 to -8.10, P<0.00001). And a difference in the incidence of associated gallstone was found between GBC patients with and without PBM (10.8% vs 54.3% OR: 0.09, 95% CI: 0.05 to 0.17, P<0.00001). Among the GBC patients with PBM, associated congenital dilatation of the common bile duct was present with a higher incidence ranging from 52.2% to 85.7%, and 70.0%-85.7% of them belonged to the P-C type of PBM (the main pancreatic duct enters the common bile duct). No substantial heterogeneity was found and no evidence of publication bias was observed.CONCLUSIONS: PBM is a high-risk factor for developing GBC, especially the P-C type of PBM without congenital dilatation of the common bile duct. To prevent GBC, laparoscopic cholecystectomy is highly recommended for PBM patients without congenital dilatation of the common bile duct, especially relatively young female patients without gallstones.

Synchronous gallbladder and pancreatic cancer associated with pancreaticobiliary maljunction

We report the case of a 46-year-old woman who presented with chronic intermittent abdominal pain without jaundice; abdominal ultrasonography showed thickening of the gallbladder wall and dilatation of the bile duct. Endoscopic retrograde cholangiopancreaticography showed pancreatobiliary maljunction with proximal common bile duct dilatation. Pancreatobiliary maljunction was diagnosed. A computed tomography scan of the abdomen showed suspected gallbladder cancer and distal common bile duct obstruction. A pancreatic head mass was incidentally found intraoperative. Radical cholecystectomy with pancreatoduodenectomy was performed. The pathological report showed gallbladder cancer that was synchronous with pancreatic head cancer. In the pancreatobiliary maljunction with pancreatobiliary reflux condition, double primary cancer of the pancreatobiliary system should be awared.

Spontaneous necrosis of solid gallbladder adenocarcinoma accompanied with pancreaticobiliary maljunction

A 71-year-old Japanese man with acute cholecystitis and an incarcerated gallbladder （GB） stone was admitted. Plain ultrasonography （US） incidentally detected a mass-like lesion in the fundus. Doppler US revealed that this elevated lesion had no blood flow. Computed tomography showed a relatively low-density mass, measuring 5 cm x 4 cm in diameter, with no positive enhancement. Magnetic resonance imaging showed a mass in the fundus with a slightly low intensity on Tl-weighted images and a slightly high intensity on T2-weighted images. We were agonized in making the qualitative diagnosis of mass-like lesions of the fundus, such as a benign tumor, cancer, or debris. We performed laparoscopic cholecystectomy, because the incarcerated GB stone clearly caused acute cholecystitis. Intra-operative cholangiography clearly revealed pancreaticobiliary maljunction. Amylase levels in the common bile duct and gallbladder were quite high. The elevated lesion in the fundus dearly showed severe necrosis. Although this necrotic nodule included non-viable adenocarcinoma cells, viable cancer cell nests were located in the muscularis propria and subcutaneous layer. Histopathological examination confirmed a solid adenocarcinoma. Thus, we diagnosed it as a gallbladder cancer, based on histopathological analysis of the resected specimen. We therefore undertook radical surgery, including wedge resection of the liver, radical dissection of regional lymph nodes, and resection of the extrahepatic bile duct. Histopathological findings revealed no cancer, hyperplasia or dysplasia in the additionally resected specimens. The patient was finally staged as T2, N0, H0, P0, M（-）, stage Ⅱ. We present the first case of spontaneous necrosis of solid gallbladder adenocarcinoma, with a review of previous studies.

Carcinoma of the papilla of Vater following treatment of pancreaticobiliary maljunction

Pancreaticobiliary maljunction(PBM)is frequently associated with biliary cancer due to reflux of pancreatic enzymes into the choledochus,and even after surgery to correct the PBM such patients still have a risk of residual bile duct cancer.Here,we report the case of a 59-year-old female with carcinoma of the papilla of Vater which developed 2.5 years after choledochoduodenostomy for PBM.During the postoperative follow-up period,computed tomography obtained 2 years after the first operation demonstrated a tumor in the distal end of the choledochus,although she did not have jaundice and laboratory tests showed no abnormalities caused by the previous operation.As a result,carcinoma of the papilla of Vater was diagnosed at an early stage,followed by surgical cure.For early detection of periampullary cancer in patients undergoing surgery for PBM,careful long-term follow-up is needed.

Liver, biliary and pancreatic injuries in pancreaticobiliary maljunction model in cats

BACKGROUND： Pancreaticobiliary maljunction is a high risk factor of pancreatitis and biliary tract cancer. How this maljunction affects the liver remains obscure. This study aimed to examine the effects of pancreaticobiliary maljunction on the liver, pancreas and gallbladder in a cat model.METHODS： A model of choledocho-pancreatic side-to-side ductal anastomosis was created in ten cats. Before the procedure,a small piece of tissue from the liver, pancreas and gallbladder was collected as a control. The common channel formation was checked by cholecystography. The livers, pancreases and gallbladders of these cats were harvested for histological examination. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. RESULTS： Seven of the 10 cats survived for 6 months after surgery. The color of the liver was darker in the PBM model than the control specimen, with nodules on the surface. Histological examination showed ballooning changes and inflammatory infiltrations and the histopathological score increased significantly（P〈0.05）. Also, mitochondria swelling and lipid droplet in cytoplasm were observed under an electron microscope. The pancreas also appeared darker in the PBM model than the control specimen and dilated pancreatic ducts were found in three cats. Histopathological examination revealed vascular proliferation and inflammatory infiltration with numerous neutrophils. Gallbladder epithelial cells were featured by expanded endoplasmic reticulum, increased intercellular space and cellular nucleus deformation. The positive cells ofproliferating cell nuclear antigen were increased significantly（P〈0.05）. CONCLUSION： The present study demonstrated that pancreaticobiliary maljunction can lead to the injuries of the liver, pancreas and gallbladder.

Application of imaging techniques in pancreaticobiliary maljunction

Imaging techniques are useful tools in the diagnosis and treatment of pancreaticobiliary maljunction(PBM).PBM is a precancerous lesion often relative to the disease of the pancreas and biliary tract,for example,cholecystolithiasis,protein plugs,and pancreatitis.For patients with PBM,early diagnosis and timely treatment are highly important,which is largely dependent on imaging techniques.The continuous development of imaging techniques,including endoscopic retrograde cholangiopancreatography,magnetic resonance cholangiopancreatography,computed tomography,ultrasound,and intraoperative cholangiography,has provided appropriate diagnostic and therapeutic tools for PBM.Imaging techniques,including non-invasive and invasive,have distinct advantages and disadvantages.The purpose of this paper is to review the application of various imaging techniques in the diagnosis and treatment of PBM.

Diagnosis and clinical implications of pancreatobiliary reflux

The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. A common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall, as occurs in pancreaticobiliary maljunction （PBM）; in such cases, sphincter action does not functionally affect the junction. As the hydropressure within the pancreatic duct is usually greater than in the bile duct, pancreatic juice frequently refluxes into the biliary duct （pancreatobiliary reflux） in PBM, resulting in carcinogenetic conditions in the biliary tract. Pancreatobiliary reflux can be diagnosed from elevated amylase level in the bile, secretinstimulated dynamic magnetic resonance cholangiop ancreatography, and pancreatography via the minor duodenal papilla. Recently, it has become obvious that pancreatobiliary reflux can occur in individuals without PBM. Pancreatobiliary reflux might be related to biliary carcinogenesis even in some individuals without PBM. Since few systemic studies exist with respect to clinical relevance and implications of the pancreatobiliary reflux in individuals with normal pancreaticobiliary junction, further prospective clinical studies including appropriate management should be performed.

Gallbladder carcinoma associated with pancreatobiliary reflux

AIM: To detect the patients with and without pan-creaticobiliary maljunction who had pancreatobiliary reflux with extremely high biliary amylase levels.METHODS: Ninety-six patients, who had diffuse thickness (> 3 mm) of the gallbladder wall and were suspected of having a pancreaticobiliary maljunction on ultrasonography, were prospectively subjected to endoscopic retrograde cholangiopancreatography, and bile in the common bile duct was sampled. Among them, patients, who had extremely high biliary amylase levels (>10 000 IU/L), underwent cholecystectomy, and the clinicopathological findings of those patients with and without pancreaticobiliary maljunction were examined.RESULTS: Seventeen patients had biliary amylase levels in the common bile duct above 10 000 IU/L, including 11 with pancreaticobiliary maljunction and 6 without pancreaticobiliary maljunction. The occurrence of gallbladder carcinoma was 45.5% (5/11) in patients with pancreaticobiliary maljunction, and 50% (3/6) in those without pancreaticobiliary maljunction.CONCLUSION: Pancreatobiliary reflux with extremely high biliary amylase levels and associated gallbladder carcinoma could be identified in patients with and without pancreaticobiliary maljunction, and those patients might be detected by ultrasonography and bile sampling.

Synchronous double cancers of the common bile duct

We report an extremely rare case of synchronous double cancers of the common bile duct without pancreaticobiliary maljunction.Only two similar cases have been reported in the English literature.Endoscopic retrograde cholangiopancreatography showed a tuberous filling defect in the middle and superior parts of the common bile duct,and mild stenosis in the inferior duct.Computed tomography(CT) showed a well enhanced mass in the middle and superior parts of the common bile duct.A single cancer of the middle and superior bile duct was suspected and extra-hepatic bile duct resection was performed.CT eleven months after surgery revealed enhanced inferior bile duct wall and a slightly enhanced tumor within it.Retrospective review of the CT images taken before first surgery showed enhanced inferior bile duct wall without intrabiliary tumor only on the delayed phase.The inferior bile duct tumor was suspected to have originally co-existed with the middle and superior bile duct tumor.Pancreaticoduodenectomy was performed subsequently.Histopathological examination revealed that the middle and superior bile duct tumor was a moderately differentiated tubular adenocarcinoma while the inferior bile duct tumor was a papillary adenocarcinoma.The two tumors were separated and had different histological findings and growth patterns,further suggesting that they were two primary cancers.