TOKYO criteria 2024 for the assessment of clinical outcomes of endoscopic biliary drainage.

The consensus-based TOKYO criteria were proposed as a standardized reporting system for endoscopic transpapillary biliary drainage. The primary objective was to address issues arising from the inconsistent reporting of stent outcomes across studies, which has complicated the comparability and interpretation of study results. However, the original TOKYO criteria were not readily applicable to recent modalities of endoscopic biliary drainage such as biliary drainage based on endoscopic ultrasound or device-assisted endoscopy. There are increasing opportunities for managing hilar biliary obstruction and benign biliary strictures through endoscopic drainage. Biliary ablation has been introduced to manage benign and malignant biliary strictures. In addition, the prolonged survival times of cancer patients have increased the importance of evaluating overall outcomes during the period requiring endoscopic biliary drainage rather than solely focusing on the patency of the initial stent. Recognizing these unmet needs, a committee has been established within the Japan Gastroenterological Endoscopy Society to revise the TOKYO criteria for current clinical practice. The revised criteria propose not only common reporting items for endoscopic biliary drainage overall, but also items specific to various conditions and interventions. The term "stent-demanding time" has been defined to encompass the entire duration of endoscopic biliary drainage, during which the overall stent-related outcomes are evaluated. The revised TOKYO criteria 2024 are expected to facilitate the design and reporting of clinical studies, providing a goal-oriented approach to the evaluation of endoscopic biliary drainage.

A Predictive Strategy for Nonsurgical Management of Pancreatic Stones.

OBJECTIVES: We set out to predict whether nonsurgical treatment is likely to succeed in removing pancreatic stones in a given patient and also to determine an optimal maximal number of extracorporeal shock wave lithotripsy (ESWL) sessions for treatment of pancreatolithiasis in that patient. MATERIALS AND METHODS: We ascertained the number of ESWL sessions for each of 164 patients undergoing that treatment for pancreatolithiasis between 1992 and 2020. Median follow-up duration was 31 months (range, 0-239), median age was 58 years (22-83), and the male to female ratio was 5.1:1.0. Patients were divided into 2 groups based upon an optimal maximal number of ESWL sessions determined by receiver operating characteristic analysis. RESULTS: Total stone clearance was achieved in 130 of 164 patients (79%). The median number of ESWL sessions was 3 (1-61). Receiver operating characteristic analysis determined 7 to be the optimal maximal number of sessions. Complete clearance was more frequent (87%) among the 131 patients requiring 7 or fewer ESWL sessions than among the 33 undergoing more (48%, P < 0.001). Seventeen patients (52%) undergoing 8 or more sessions still had residual stones. CONCLUSIONS: If any pancreatic stones persist after 7 ESWL sessions, we recommend transition to medical or surgical treatments.

Evidence-based clinical practice guidelines for cholelithiasis 2021.

The Japanese Society of Gastroenterology first published evidence-based clinical practice guidelines for cholelithiasis in 2010, followed by a revision in 2016. Currently, the revised third edition was published to reflect recent evidence on the diagnosis, treatment, and prognosis of cholelithiasis conforming to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Following this revision, the present English version of the guidelines was updated and published herein. The clinical questions (CQ) in the previous version were reviewed and rearranged into three newly divided categories: background questions (BQ) dealing with basic background knowledge, CQ, and future research questions (FRQ), which refer to issues that require further accumulation of evidence. Finally, 52 questions (29 BQs, 19 CQs, and 4 FRQs) were adopted to cover the epidemiology, pathogenesis, diagnosis, treatment, complications, and prognosis. Based on a literature search using MEDLINE, Cochrane Library, and Igaku Chuo Zasshi databases for the period between 1983 and August 2019, along with a manual search of new information reported over the past 5 years, the level of evidence was evaluated for each CQ. The strengths of recommendations were determined using the Delphi method by the committee members considering the body of evidence, including benefits and harms, patient preference, and cost-benefit balance. A comprehensive flowchart was prepared for the diagnosis and treatment of gallbladder stones, common bile duct stones, and intrahepatic stones, respectively. The current revised guidelines are expected to be of great assistance to gastroenterologists and general physicians in making decisions on contemporary clinical management for cholelithiasis patients.

Primary sclerosing cholangitis with partial steroid responsiveness: a case report.

A 69-year-old woman suspected to have IgG4-related sclerosing cholangitis causing bile duct stenosis was transferred from another hospital after diarrhea, eosinophilia, and eosinophilic infiltration were detected and prednisolone was prescribed. Additional biliary imaging suggested primary sclerosing cholangitis, but the IgG4 level and inferior bile duct stenosis were alleviated by steroid therapy, suggesting IgG4-related sclerosing cholangitis. Therefore, prednisolone was continued. Bile duct biopsy findings suggesting adenocarcinoma led to a diagnosis of pancreatoduodenectomy. The latter specimen only displayed evidence of primary sclerosing cholangitis, and prednisolone was discontinued. Intractable cholangitis necessitated left hepatectomy, after which serum alkaline phosphatase levels increased and eosinophilic colitis recurred. The reintroduction of prednisolone effectively managed the diarrhea but only temporarily reversed the alkaline phosphatase elevation. When histologic sections from resection specimens were compared, the hepatectomy specimen exhibited greater eosinophil infiltration than the earlier pancreatoduodenectomy specimen, suggesting eosinophilic cholangiopathy superimposed on primary sclerosing cholangitis.

Large or multiple pseudocysts can impede or complicate the nonsurgical treatment of pancreatolithiasis.

Objectives: We aimed to determine when a coexisting pseudocyst was likely to complicate the nonsurgical treatment of pancreatolithiasis. Methods: We treated 165 patients with pancreatolithiasis nonsurgically between 1992 and 2020, including 21 with pseudocysts. Twelve patients had a single pseudocyst less than 60 mm in diameter. Pseudocysts in the other nine patients had diameters of at least 60 mm or were multiple. The locations of pseudocysts along the length of the pancreas varied from the area with stone involvement to the pancreatic tail. We compared the outcomes in these groups. Results: We found no significant differences in pain relief, stone clearance, stone recurrence, or the likelihood of adverse events between pseudocyst groups or between patients with vs without pseudocysts. However, 4 of 9 patients with large or multiple pseudocysts required transition to surgical treatment (44%) compared with 13 of 144 patients with pancreatolithiasis and no pseudocyst (9.0%) (P=0.006). Conclusions: Patients with smaller pseudocysts typically underwent nonsurgical stone clearance successfully with few adverse events, similar to findings in patients with pancreatolithiasis and no pseudocysts. Pancreatolithiasis complicated by large or multiple pseudocysts did not cause more adverse events but was more likely to require transition to surgery compared with pancreatolithiasis without pseudocysts. In patients with large or multiple pseudocysts, early transition to surgery should be considered when nonsurgical treatment is ineffective.

Clinical characteristics and long-term prognosis of type 1 gastric neuroendocrine tumors in a large Japanese national cohort.

OBJECTIVES: Optimal management of type 1 gastric neuroendocrine tumors (T1-GNETs) remains unknown, with few reports on their long-term prognosis. This study investigated the clinical characteristics and long-term prognosis of T1-GNETs. METHODS: We reviewed the medical records of patients diagnosed with T1-GNET during 1991-2019 at 40 institutions in Japan. RESULTS: Among 172 patients, endoscopic resection (ER), endoscopic surveillance, and surgery were performed in 84, 61, and 27, respectively, including 27, 77, and 2 patients with pT1a-M, pT1b-SM, and pT2 tumors, respectively. The median tumor diameter was 5 (range 0.8-55) mm. Four (2.9%) patients had lymph node metastasis (LNM); none had liver metastasis. LNM rates were significantly higher in tumors with lymphovascular invasion (LVI) (15.8%; 3/19) than in those without (1.1%; 1/92) (P = 0.016). For tumors <10 mm, LVI and LNM rates were 18.4% (14/76) and 2.2% (2/90), respectively, which were not significantly different from those of tumors 10-20 mm (LVI 13.3%; 2/15, P = 0.211; and LNM 0%; 0/17, P = 1.0). However, these rates were significantly lower than those of tumors >20 mm (LVI 60%; 3/5, P = 0.021; and LNM 40%; 2/5, P = 0.039). No tumor recurrence or cause-specific death occurred during the median follow-up of 10.1 (1-25) years. The 10-year overall survival rate was 97%. CONCLUSIONS: Type 1 gastric neuroendocrine tumors showed indolent nature and favorable long-term prognoses. LVI could be useful in indicating the need for additional treatments. ER for risk prediction of LNM should be considered for tumors <10 mm and may be feasible for tumors 10-20 mm. TRIAL REGISTRATION: The study protocol was registered in the University Hospital Medical Information Network (UMIN) under the identifier UMIN000029927.

Steroid therapy has an acceptable role as the initial treatment in autoimmune pancreatitis patients with pancreatic cyst formation: Based on a Japanese nationwide study.

BACKGROUND: We attempted to determine the indications and limitations of steroid therapy as the first-line therapy in patients with autoimmune pancreatitis (AIP) with cyst formation (ACF). METHODS: This Japanese multicenter survey was conducted to examine the merits/demerits of steroid treatment as the initial therapy for ACF. RESULTS: Data of a total of 115 patients with ACF were analyzed. Complete remission was achieved in 86% (86/100) of patients who had received steroid treatment, but only 33.3% (5/15) of patients who had not received steroids. Relapse after the remission (n = 86) occurred in 7.6% (6/86) of patients who had received steroid therapy, but 40% (2/5) of patients who had not received steroid therapy. Multivariate analysis identified adoption of the wait and watch approach without steroid treatment (odds ratio = 0.126, P < .001) as a significant and independent negative predictor of remission of ACF. As for predictors of relapse, the presence of varix (odds ratio = 5.83, P = .036) was identified as an independent risk factor. CONCLUSION: Steroid therapy plays an important role as first-line therapy in AIP patients with pancreatic cyst formation, however, varix formation, besides the diameter of the cyst(s), is a risk factor for refractoriness to steroid therapy.

Nonsurgical treatment for asymptomatic pancreatolithiasis is meaning: A case report.

BACKGROUND: Many guidelines for nonsurgical treatment of pancreatolithiasis suggest little guidance for patients with pancreatolithiasis who do not have abdominal pain. Some patients with pancreatolithiasis whom we have treated nonsurgically with extracorporeal shock-wave lithotripsy did not have abdominal pain, and we describe one of them here. METHODS AND RESULTS: A 42-year-old man complaining of an 8-kg weight loss over 6 months was admitted to a nearby hospital, where fasting blood sugar and hemoglobin A1c values were 500 mg/dL and 11.8%. Computed tomography showed stones in the head of the pancreas and dilation of the main pancreatic duct. He was referred to our hospital to be considered for nonsurgical treatment of pancreatolithiasis. His height and weight were 160 cm and 52 kg (body mass index, 20.31). No tenderness or other abdominal findings were evident. After obtaining informed consent for nonsurgical treatment despite absence of abdominal pain, we performed extracorporeal shock wave lithotripsy. Computed tomography showed disappearance of stones from the pancreatic head. At discharge, his weight had increased to 62 kg and hemoglobin A1c was 6.8%, though antidiabetic medication has since become necessary. CONCLUSION: We believe that nonsurgical treatment of pancreatolithiasis was helpful for this patient, and could improve exocrine and endocrine function in other patients without abdominal pain.

Benefit From Nonsurgical Treatment for Asymptomatic Pancreatolithiasis.

OBJECTIVE: Clinical guidelines consider abdominal pain an indication for nonsurgical treatment of pancreatolithiasis. We examined benefit from nonsurgically treating asymptomatic pancreatolithiasis. METHODS: We retrospectively reviewed 165 patients with pancreatolithiasis who underwent nonsurgical treatment between 1992 and 2020. Symptoms were absent in 41, while 124 had abdominal pain. In the asymptomatic group, the median follow-up duration was 8 months (range, 0-166 months), and the median age was 61 years (range, 32-80 years). In patients with pain, the median follow-up duration was 43 months (range, 0-293 months), while the median age was 57 years (range, 22-80 years). The male:female ratio was 3.6:1 for asymptomatic patients and 5.9:1 for those with pain. We compared treatment outcome, stone recurrence rate, and changes in pancreatic exocrine function (bentiromide- p -aminobenzoic acid test results) between groups. RESULTS: Nonsurgical treatment for patients with asymptomatic pancreatolithiasis had a 63% stone clearance rate, lower than 84% for symptomatic pancreatolithiasis but comparable to outcomes at other institutions. Pancreatic exocrine function values during the year after treatment were mean, 52% (standard deviation, 16%) in the asymptomatic group, similar to mean, 57% (standard deviation, 17%) in the symptomatic group. CONCLUSIONS: Nonsurgical treatment in asymptomatic pancreatolithiasis may preserve pancreatic exocrine function as well as in symptomatic pancreatolithiasis.

Pancreatic Stones: Clinical Outcomes With Nonsurgical Treatment in a Japanese Single-Center Study.

OBJECTIVES: While chronic pancreatitis associated with pancreatolithiasis presents with pain, exocrine and endocrine pancreatic functions worsen with time. We examined outcomes of nonsurgical treatment. METHODS: Between 1992 and 2020, we treated pancreatolithiasis nonsurgically in 165 patients with chronic pancreatitis using extracorporeal shock wave lithotripsy alone or followed by endoscopic procedures. The mean follow-up duration was 49 months (standard deviation, 56 months) and the age was 56 years (standard deviation, 13 years). The male:female ratio was 5.1:1 (138 men, 27 women). We followed treatment results including relief of abdominal pain, stone clearance and recurrence, and pancreatic exocrine function (bentiromide-p-aminobenzoic acid testing). RESULTS: Treatment relieved pain in 117 of 124 patients (94%). The overall stone clearance was achieved in 130 of 165 patients (79%). Stones recurred during follow-up in 50 of 130 patients (38%). One fifth of recurrences were early, often involving stricture of the main pancreatic duct. After 1 year, 65% of the patients had improved or stable exocrine function. CONCLUSIONS: Nonsurgical stone removal usually improved symptoms and preserved pancreatic exocrine function. Nonsurgical treatment with extracorporeal shock wave lithotripsy followed by endoscopic treatment if needed is useful as initial management for pancreatolithiasis.

Amendment of the Japanese consensus guidelines for autoimmune pancreatitis, 2020.

In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.

Clinical practice guidelines for endoscopic papillectomy.

The Japan Gastroenterological Endoscopy Society has developed the "Clinical Practice Guidelines for Endoscopic Papillectomy (EP)" as a fundamental guideline using scientific approach. EP is a recently spreading therapeutic modality for ampullary tumors ranked as high risk endoscopic technique. Because of the paucity of high level of evidence, strength of recommendations had to be determined by a consensus among specialists. These guidelines, shed light on the following five issues: Indications, Preoperative/intraoperative preparations and techniques, Early adverse events, Therapeutic outcomes and remnants/recurrences, and Follow-up and late adverse events, to guide current clinical practice on EP.

B-mode ultrasonographic diagnosis in gallbladder wall thickening.

Diseases associated with gallbladder wall thickening include benign entities such as adenomyomatosis of the gallbladder, acute and chronic cholecystitis, and hyperplasia associated with pancreaticobiliary maljunction, and also cancer. Unique conditions such as sclerosing cholecystitis and cholecystitis associated with immune checkpoint inhibitor treatment can also manifest as wall thickening, as in some systemic inflammatory conditions. Gallbladder cancer, the most serious disease that can show wall thickening, can be difficult to diagnose early and to distinguish from benign causes of wall thickening, contributing to a poor prognosis. Differentiating between xanthogranulomatous cholecystitis and gallbladder cancer with wall thickening can be particularly problematic. Cancers that thicken the wall while coexisting with benign lesions that cause wall thickening represent another potential pitfall. In contrast, some benign gallbladder lesions that can cause wall thickening, such as adenomyomatosis and acute cholecystitis, typically show characteristic ultrasonographic features that, together with clinical findings, permit easier diagnosis. In this review of the literature, we describe B-mode abdominal ultrasonographic diagnosis of gallbladder lesions showing wall thickening.

Clinicopathological characteristics of intraductal papillary neoplasm of the bile duct: a Japan-Korea collaborative study.

BACKGROUND: The prevalent location and incidence of intraductal papillary neoplasm of the bile duct (IPNB) and invasive carcinoma associated with them have varied markedly among studies due to differences in diagnostic criteria and tumor location. METHODS: IPNBs were classified into two types: Type 1 IPNB, being histologically similar to intraductal papillary mucinous neoplasm of the pancreas, and Type 2 IPNB, having a more complex histological architecture with irregular papillary branching or foci of solid-tubular components. Medical data were evaluated. RESULTS: Among 694 IPNB patients, 520 and 174 had Type 1 and Type 2, respectively. The levels of AST, ALT, ALP, T. Bil, and CEA were significantly higher in patients with Type 2 than in those with Type 1. Type 1 IPNB was more frequently located in the intrahepatic bile duct than Type 2, whereas Type 2 was more frequently located in the distal bile duct than Type 1 IPNB (P < 0.001). There were significant differences in 5-year cumulative survival rates (75.2% vs 50.9%; P < 0.0001) and 5-year cumulative disease-free survival rates (64.1% vs 35.3%; P < 0.0001) between the two groups. CONCLUSION: Type 1 and Type 2 IPNBs differ in their clinicopathological features and prognosis. This classification may help to further understand IPNB.

International Consensus Guidelines for Risk Factors in Chronic Pancreatitis. Recommendations from the working group for the international consensus guidelines for chronic pancreatitis in collaboration with the International Association of Pancreatology, the American Pancreatic Association, the Japan Pancreas Society, and European Pancreatic Club.

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disease with remarkably impaired quality of life and permanent damage of the pancreas. This paper is part of the international consensus guidelines on CP and presents the consensus on factors elevating the risk for CP. METHODS: An international working group with 20 experts on CP from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 14 statements generated from evidence on four questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available per statement. To determine the level of agreement, the working group voted on the 14 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus and agreement were obtained for the following statements: Alcohol, smoking, and certain genetic alterations are risk factors for CP. Past history, family history, onset of symptoms, and life-style factors including alcohol intake and smoking history should be determined. Alcohol consumption dose-dependently elevates the risk of CP up to 4-fold. Ever smokers, even smoking less than a pack of cigarettes per day, have an increased risk for CP, as compared to never smokers. CONCLUSIONS: Both genetic and environmental factors can markedly elevate the risk for CP. Therefore, health-promoting lifestyle education and in certain cases genetic counselling should be employed to reduce the incidence of CP.

Clinical Questions and Answers on Gastrointestinal Endoscopy during the Novel Coronavirus Disease 2019 pandemic.

Some situations may require endoscopy during the COVID-19 (Coronavirus Disease 2019) pandemic. Here, we describe the necessary precautions in the form of clinical questions and answers (Q&A) regarding the safe deployment of gastrointestinal endoscopy in such situations while protecting endoscopy staff and patients from infection. Non-urgent endoscopy should be postponed. The risk of infection in patients should be evaluated in advance by questionnaire and body temperature. The health of staff must be checked every day. Decisions to employ endoscopy should be based on the institutional conditions and aims of endoscopy. All endoscopic staff need to wear appropriate personal protective equipment (PPE). The endoscope and other devices should be cleaned and disinfected after procedures in accordance with the relevant guidelines. Optimal management of the endoscopy unit is required. Endoscopy for infected patients or those with suspected infection demands exceptional caution. When a patient who undergoes endoscopy is later found to have COVID-19, the members of staff involved are considered exposed to the virus and must not work for at least 14 days if their PPE is considered insufficient. When PPE resources are limited, some equipment may be used continuously throughout a shift as long as it is not contaminated. Details of the aforementioned protective measures are described.

Gastrointestinal endoscopy in the era of the acute pandemic of coronavirus disease 2019: Recommendations by Japan Gastroenterological Endoscopy Society (Issued on April 9th, 2020).

All gastrointestinal endoscopic procedures have a high risk of aerosol contamination of the coronavirus disease 2019 (COVID-19) to endoscopists, nurses, and healthcare assistants. Given the current pandemic situation of COVID-19, the Japan Gastroenterological Endoscopy Society issued the recommendation for gastrointestinal (GI) endoscopy based on the status of COVID-19 as of April 9, 2020, in Japan: (i) indications for GI endoscopy in the pandemic of COVID-19; (ii) practical protective equipment for medical personnel depending on the risk for COVID-19; (iii) preprocedural management, such as pharyngeal local anesthesia using lidocaine spray which has a potential to generate the aerosols; (iv) ideal settings of the endoscopy room including the numbers of the staff and the patients; (v) postprocedural management, such as undressing and follow-up of the patients, as well as the involved staff, were documented to fit the practical scenarios in GI endoscopy, with the available data in Japan and the world. We believe that certain measures will prevent further spread of COVID-19.

Recent innovations in therapeutic endoscopy for pancreatobiliary diseases.

The development of endoscopic treatment for pancreatobiliary diseases in recent years is remarkable. In addition to conventional transpapillary treatments under endoscopic retrograde cholangiopancreatography (ERCP), new endoscopic ultrasound-guided therapy is being developed and implemented. On the other hand, due to the development/improvement of various devices such as new metal stents, a new therapeutic strategy under ERCP is also advocated. The present review focuses on recent advances in the endoscopic treatment of pancreatic pseudocysts, walled-off necrosis, malignant biliary strictures, and benign biliary/pancreatic duct strictures.