Does Congenital Biliary Dilatation Todani Type II (Diverticular Type) Really Exist?

AIM OF THE STUDY: The aim of the study is to clarify the clinicopathological and biliary morphological characteristics in reported cases of diverticular congenital biliary dilatation (CBD). METHOD: Using PubMed and the Japan Medical Abstracts Society, articles on possible diverticular CBD were extracted and the clinical pictures examined. We also sought evidence for definitions of diverticular CBD and the associated condition of pancreaticobiliary maljunction (PBM) using the original articles by Alonso-Lej and Todani. The characteristic biliary morphologies of cases with images were also investigated. RESULTS: Analyses of 211 possible cases superficially demonstrated multiple diverticula in 12 (12%) and single diverticulum in 89 (88%), with diverticula located in the upper (n = 38, 38%), middle (n = 32, 32%), or lower (n = 26, 26%) biliary tract in and presence of intra-diverticular stones, PBM, and biliary carcinoma in 23% (n = 18), 39% (n = 25), and 11% (n = 14), respectively. However, evidence defining diverticular CBD or justifying the lack of associated PBM was not demonstrated even in the original articles. Scrutiny of the biliary anatomy in 59 cases with images showed incorrect inclusions of types I or IV-A with an irregular biliary duct wall or dilated cystic duct, periampullary choledochal diverticula, or even solitary biliary cysts. Authentic diverticular CBD, representing the diverticulum connected to the middle of the common bile duct via a thin, patent stalk was seen in only 6 cases. CONCLUSION: Real diverticular CBD appears extremely rare. The lack of an objective definition allows wide interpretations of clinical pictures, creating inconsistencies in the diagnosis and treatment of CBD and raising questions regarding the utility of conventional classifications. LEVEL OF EVIDENCE: Level III.

Modified Socratic Method (planned and executed by Takada) for medical education: Grade II Acute Cholecystitis of Tokyo Guidelines 2018 as an example case.

BACKGROUND: Socratic method, which is an educational method to promote critical thinking through a dialogue, has never been practiced in a large number of people at the academic societies. METHODS: Modified Socratic method was performed for the first time as an educational seminar using an example case of moderate acute cholecystitis based on the evidence described in Tokyo Guidelines 2018. We adopted a method that Takada had been modifying for many years: the instructor first knows the degree of recognition of the audience, then the instructor gives a lecture in an easy-to-understand manner and receives questions from the audience, followed by repeated questions and answers toward a common recognition. RESULTS: Using slides, video, and an answer pad, 281 participants including the audience, instructors and moderators came together to repeatedly ask and answer questions in the five sessions related to the case scenario. The recognition rate of the topic of Critical View of Safety increased significantly before vs after this method (53.0% vs 90.3%). The seminar had been successfully performed by receiving a lot of praise from the participants. CONCLUSION: This educational method is considered to be adopted by many academic societies in the future as an effective educational method.

Anatomical patterns of biliary atresia including hepatic radicles at the porta hepatis influence short- and long-term prognoses.

BACKGROUND/PURPOSE: The biliary atresia (BA) inflammatory process leads to various obstructive patterns of extrahepatic biliary trees. The significance of the various BA obstructive patterns is unclear. This study aimed to determine the relationship between the anatomical patterns of the biliary tract and short- and long-term prognoses in BA. METHODS: Between 1989 and 2018, 3483 patients were registered in the Japanese Biliary Atresia Registry. For this study, we selected 2649 patients who underwent Kasai portoenterostomy (KP) between the ages of 31 and 90 days to eliminate the influence of age at KP as much as possible. RESULTS: Regarding the main type, there were significant differences in the jaundice clearance rate (JCR; Type I: 67.9%, Type I-cyst: 79.4%, Type II: 74.5%, Type III: 60.9%; P < .0001) and the native liver survival rate (NLSR; P < .0001). In subgroups with hepatic radicles in Types I, II, and I-cyst, there was a significant difference in JCR (P = .0004) and NLSR (P = .0026). In subgroups with hepatic radicles in Type III, there was a significant difference in JCR (P = .0148) and NLSR (P = .0421). CONCLUSIONS: Anatomical patterns of obstruction influenced short- and long-term prognoses in BA. These patterns were suggested to be prognostic factors following KP.

Clinical practice guidelines for biliary atresia in Japan: A secondary publication of the abbreviated version translated into English.

The purpose of this study was to prepare clinical practice guidelines for biliary atresia according to the Medical Information Network Distribution Service (MINDS) Handbook for Clinical Practice Guideline Development 2014. The guideline drafting group determined 25 clinical questions (CQs) essential for daily clinical practice. These CQs were grouped into the following four major categories: diagnosis, treatment, complications, and prognosis. A systematic literature search was performed by the systematic review team, and medical evidence was extracted from articles published until July 2014 on PubMed and the Japan Medical Abstracts Society. To reach a consensus, majority voting (>70%) of the panel of the guideline drafting group was adopted according to the Delphi technique. Recommendations for 21 CQs were appropriately provided. However, for four CQs (CQ2, stool color; CQ9, steroid administration; and CQ24 and CQ25, liver transplantation), recommendations could not be determined due to a scarcity of evidence. The first clinical practice guidelines for biliary atresia were successfully created using procedures recommended by the MINDS. It is expected that these guidelines will be used worldwide, and that the standardization of biliary atresia treatment will improve treatment outcomes.

Pancreaticobiliary maljunction and congenital biliary dilatation.

Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join outside the duodenal wall, usually forming a long common channel. Because the action of the sphincter of Oddi does not regulate the function of the pancreaticobiliary junction in patients with pancreaticobiliary maljunction, two-way regurgitation occurs. Reflux of pancreatic juice into the biliary tract is associated with a high incidence of biliary cancer. Biliary carcinogenesis in patients with pancreaticobiliary maljunction is thought to follow the hyperplasia, dysplasia, then carcinoma sequence due to chronic inflammation caused by pancreatobiliary reflux. Pancreaticobiliary maljunction is diagnosed when an abnormally long common channel is evident on imaging studies. Congenital biliary dilatation involves both local dilatation of the extrahepatic bile duct, including the common bile duct, and pancreaticobiliary maljunction. Extrahepatic bile duct resection is the standard surgery for congenital biliary dilatation. However, complete excision of the intrapancreatic bile duct and removal of stenoses of the hepatic ducts are necessary to prevent serious complications after surgery.

Classification of pancreaticobiliary maljunction and clinical features in children.

BACKGROUND: In 2015, the Committee on Diagnostic Criteria of the Japanese Study Group on Pancreaticobiliary Maljunction (PBM) proposed a classification of PBM into four types: (A) stenotic type, (B) non-stenotic type, (C) dilated channel type, and (D) complex type. To validate this classification and clarify the clinical features of the four types of PBM, a retrospective multicenter study was conducted. METHODS: The study group of 317 children with PBM was divided into the four types of PBM. Clinical features, preoperative complications, operations, and postoperative pancreatic complications were evaluated. RESULTS: All patients underwent excision of the extrahepatic bile duct. In type A, the age was younger and there was a higher incidence of cystic dilatation. Non-dilatation of the common bile duct was frequently seen in type B. Abdominal pain with hyperamylasemia was frequently seen in types B and C. In particular, the incidence of protein plugs and biliary perforation was high in type C (56.1% and 14.3%, respectively). The overall incidence of acute pancreatitis was 7.3%. Pancreatitis after excisional surgery was rare in the children in this study. Two patients with type D (0.6%) developed chronic pancreatitis postoperatively. CONCLUSIONS: This proposed classification is simple and correlates well with clinical features.

Japanese clinical practice guidelines for congenital biliary dilatation.

Until now, there have been no practical clinical guidelines for congenital biliary dilatation (CBD). In this review article, the Japanese Study Group on Congenital Biliary Dilatation (JSCBD) propose to establish clinical practice guidelines for CBD. Because the evidence-based literature is relatively small, we decided to create guidelines based on the consensus of experts, using the medical literature for reference. A total of 20 clinical questions (CQs) were considered by the members of the editorial committee responsible for the guidelines. The CQs included the distinct aspects of CBD: (1) Concepts and Pathology (three CQs); (2) Diagnosis (six CQs); (3) Pancreaticobiliary Complications (three CQs); Treatments and Prognosis (eight CQs). Each statements and comments for CQs were made by the guidelines committee members. CQs were finally approved after review by members of the editorial committee and the guidelines evaluation board of CBD. These guidelines were created to provide assistance in the clinical practice of CBD management; their contents focus on clinical utility, and they include general information on CBD to make this disease more widely recognized.

Long-term outcomes after revision of Kasai portoenterostomy for biliary atresia.

BACKGROUND: The indications for and efficacy of revision of portoenterostomy (PE) for biliary atresia (BA) needs to be reassessed in an era of liver transplantation. We therefore reviewed the long-term outcomes following revision of PE. METHODS: This was a retrospective study of the medical records of patients with BA who underwent PE and revision of PE. We investigated the role of revision on outcomes of jaundice-free native liver survival (approval number: 2015-0094). RESULTS: Portoenterostomy was performed in 76 patients, among whom 22 underwent revision. Revision for recurrent jaundice was performed for four of 51 patients, who were transiently jaundice free after initial PE, but only one achieved native liver survival. Revision for repeated cholangitis in two patients achieved native liver survival over 10 years. Revision was performed in 16 of the 25 patients in whom initial PE failed; of these, four survived with their native liver (ages 3, 12, 12, and 14 years). The PE revision did not significantly affect liver transplantation duration and survival outcome. CONCLUSIONS: Revision of PE was suitable for repeated cholangitis. Revision for recurrent jaundice, regardless of whether the initial PE was successful, could have a limited but positive effect in preventing long-term progressive liver failure.

Diagnostic criteria for congenital biliary dilatation 2015.

BACKGROUND: The Diagnostic Criteria for Pancreaticobiliary Maljunction 2013 were published by the Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) in 2014. The committee of JSGPM for diagnostic criteria for pancreaticobiliary maljunction has established the standard diameter of the bile duct, and a definition of dilatation of the bile duct was proposed in 2014. METHODS: The committee of JSGPM prepared the diagnostic criteria for congenital biliary dilatation in 2014, and a final revised version was approved in 2015. RESULTS: Congenital biliary dilatation is defined as a congenital malformation involving both local dilatation of the extrahepatic bile duct, including the common bile duct, and pancreaticobiliary maljunction. However, cases associated with intrahepatic bile duct dilatation can also be included. Various kinds of pathological conditions can occur on hepatobiliary systems and pancreas by bile duct dilatation and pancreaticobiliary maljunction. For a diagnosis of congenital biliary dilatation, both abnormal dilatation of the bile duct and pancreaticobiliary maljunction must be evident by either imaging test or anatomical examination. Acquired or secondary dilatation of the bile duct by obstruction due to biliary stones or malignancy should be strictly excluded. CONCLUSION: Diagnostic criteria for congenital biliary dilatation 2015 were established from Japan representing a world first.

Usefulness and safety of endoscopic retrograde cholangiopancreatography in children with pancreaticobiliary maljunction.

BACKGROUND: To assess the diagnostic ability and safety of endoscopic retrograde cholangiopancreatography (ERCP) in in-depth preoperative examination of children patients with pancreaticobiliary maljunction (PBM). METHODS: In 63 patients with a definite diagnosis of PBM, the ability to visualize the bile and main pancreatic ducts was compared between ERCP, which was performed in 63 patients with a definite diagnosis of PBM, and magnetic resonance cholangiopancreatography (MRCP), which was performed before ERCP in 29 patients. For ERCP, its complications were also evaluated. RESULTS: The intrahepatic bile ducts could be visualized using ERCP in 44 patients (69.8%) and using MRCP in 18 (62.1%). The extrahepatic bile ducts could be visualized using ERCP in 59 patients (93.7%) and using MRCP in 29 (100%). The rates of the visualization of the main pancreatic duct and pancreaticobiliary ductal union were significantly higher in using ERCP than in using MRCP (96.8 vs. 41.4% and 90.5 vs. 37.9%, respectively; P<0.0001). As complications, hyperamylasemia developed in 12 patients (19%), but no other severe complications such as pancreatitis were observed. CONCLUSIONS: ERCP as part of an in-depth preoperative examination of children with PBM is useful and safe.

Exploring the length of the common channel of pancreaticobiliary maljunction on magnetic resonance cholangiopancreatography.

BACKGROUND: In the revised diagnostic criteria for pancreaticobiliary maljunction (PBM), PBM can be diagnosed from a long common channel by magnetic resonance cholangiopancreatography (MRCP). However, it is necessary to differentiate from high confluence of pancreaticobiliary ducts (HCPBD) with a relatively long common channel (≥6 mm) and effect of the sphincter in the pancreaticobiliary junction. This multicenter study aimed to explore definite value of the length of an abnormally long common channel, which enables to distinguish PBM from HCPBD on MRCP. METHODS: In 184 PBM patients and 22 HCPBD patients who were diagnosed by direct cholangiography and underwent MRCP, the length of the common channel was measured. RESULTS: The length of the common channel was 16.2 ± 6.9 mm on direct cholangiography and 13.9 ± 6.2 mm on MRCP in PBM patients, and 7.7 ± 1.5 mm and 6.6 ± 1.4 mm in HCPBD patients. The optimal cut off value of the length of the common channel to distinguish PBM from HCPBD was identified to be 9 mm. CONCLUSIONS: Pancreaticobiliary maljunction can be diagnosed from an abnormally long common channel on MRCP, but in cases of the common channel ≤9 mm on MRCP, direct cholangiography is needed to confirm PBM.

Diagnostic criteria for pancreaticobiliary maljunction 2013.

Pancreaticobiliary maljunction is a congenital malformation in which the pancreatic and bile ducts join anatomically outside the duodenal wall. The diagnostic criteria for pancreaticobiliary maljunction were proposed in 1987. The committee of The Japanese Study Group on Pancreaticobiliary Maljunction (JSGPM) for diagnostic criteria for pancreaticobiliary maljunction began to revise the diagnostic criteria from 2011 taking recently advanced diagnostic imaging techniques into consideration, and the final revised version was approved in the 36(th) Annual Meeting of JSPBM. For diagnosis of pancreaticobiliary maljunction, an abnormally long common channel and/or an abnormal union between the pancreatic and bile ducts must be evident on direct cholangiography, such as endoscopic retrograde cholangiopancreatography, percutaneous transpehatic cholangiography, or intraoperative cholangiography; magnetic resonance cholangiopancreatography; or three-dimensional drip infusion cholangiography computed tomography. However, in cases with a relatively short common channel, it is necessary to confirm that the effect of the papillary sphincter does not extend to the junction by direct cholangiography. Pancreaticobiliary maljunction can be diagnosed also by endoscopic ultrasonography or multi-planar reconstruction images provided by multi-detector row computed tomography. Elevated amylase levels in bile and extrahepatic bile duct dilatation strongly suggest the existence of pancreaticobiliary maljunction.

Pancreatobiliary reflux in individuals with a normal pancreaticobiliary junction: a prospective multicenter study.

BACKGROUND: Pancreatobiliary reflux (PBR) can occur in individuals without pancreaticobiliary maljunction. The aim of this study was to elucidate the incidence of PBR in individuals with a normal pancreaticobiliary junction and its impact on the biliary tree. METHODS: Data were prospectively collected from 15 centers on 420 patients with a morphologically normal pancreaticobiliary junction who had undergone bile sampling and measurement of the biliary amylase level. We investigated the incidence and predictive factors for high biliary amylase levels (HBAL), as well as the relationship of HBAL with biliary malignancy. RESULTS: Twenty-three patients (5.5%) showed HBAL (≥10,000 IU/L). Univariate analysis showed that risk factors for the elevation of biliary amylase levels were the existence of a relatively long common channel (≥5 mm), acute pancreatitis, and papillitis. Multivariate analysis revealed that only the existence of a relatively long common channel was a significant factor for PBR. Biliary amylase levels in patients with a relatively long common channel were significantly higher than in patients without a long common channel (12,333 vs. 2,070 IU/L, P = 0.001). The incidence of HBAL (P < 0.001), as well as the overall biliary amylase levels (P = 0.007) were significantly higher in patients with gallbladder cancer than in those without gallbladder cancer. CONCLUSIONS: The PBR was frequently observed in individuals with a relatively long common channel. Patients showing HBAL with normal pancreaticobiliary junction are at high risk for gallbladder cancer.

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.

Immunogenicity of inactivated seasonal influenza vaccine in adult and pediatric liver transplant recipients over two seasons.

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

Endoscopic biliary drainage for children with persistent or exacerbated symptoms of choledochal cysts.

BACKGROUND: Symptoms of choledochal cysts sometimes persist or become exacerbated. As preoperative management for patients with these cysts, we prospectively employed endoscopic drainage, based on the theory that protein plugs cause symptoms by obstructing the pancreatobiliary ducts. METHODS: Children with choledochal cysts underwent endoscopic retrograde cholangiopancreatography (ERCP). When ERCP showed compaction with filling defects in patients with persistent or worsening symptoms (study patients), the placement of a short biliary stent tube was attempted for drainage. The clinical and ERCP findings of the study patients were compared with those of patients who were asymptomatic at ERCP (asymptomatic patients). RESULTS: There were 13 study patients (median age 2.9 years) and 41 asymptomatic patients (4.7 years) enrolled in the study between August 2005 and February 2011. Study patients more frequently had jaundice and elevated transaminase levels. ERCP showed that all study patients had obstruction or compacted filling defects in the common channel or the narrow segment distal to the cyst. Insertion of a stent tube was successful in 11 patients. Symptoms were relieved soon after biliary drainage. Surgery revealed that the obstructing materials were protein plugs, except in one case, which involved fatty acid calcium stones. CONCLUSIONS: These results support the protein plug theory. Endoscopic short-tube stenting is adequate and effective as preoperative management.

Extrahepatic bile duct measurement by using transabdominal ultrasound in Japanese adults: multi-center prospective study.

BACKGROUND: In adults, less than 10-mm bile duct has idiomatically been recognized as "non-dilated bile duct" though there was no obvious evidence. The aim of this study was to prospectively examine the maximum inner diameter of extrahepatic bile duct (MDEBD) in consecutive adults. METHODS: Transabdominal ultrasound (US) was performed to measure the MDEBD of 8840 cases (4420 male) in five institutions. The frequency of ultrasound probe ranged from 3.5 to 5 MHz. RESULTS: The mean diameter of MDEBD was 4.5 ± 1.4 mm (range 1-14 mm). The relationship between the MDEBD and age was shown as follows: MDEBD = 2.83 + 0.03 × age. Multiple regression analysis was analyzed between 6 groups and significant α level is 0.008 in this analysis. In all age groups but 20s and 30s, there was statistically significant MDEBD among each age group (p < 0.0001). Mean, mode value and median MDEBD is increasing according to the age as follows: 20s: 3.9 ± 1.0 mm, 30s: 3.9 ± 1.2 mm, 40s: 4.3 ± 1.2 mm, 50s: 4.6 ± 1.3 mm, 60s: 4.9 ± 1.4 mm, >70s: 5.3 ± 1.6 mm. CONCLUSION: The present study revealed that MDEBD positively correlates with age. Therefore, when we examine the presence of dilation of the bile duct, our calculating formula appears to be suitable for accurate evaluation.