Technical review of endoscopic ultrasound-guided drainage/anastomosis and trans-endosonographically created route procedures for the treatment of pancreatic diseases.

Endoscopic ultrasound (EUS)-guided pancreatic duct drainage includes two procedures: EUS-guided drainage/anastomosis (EUS-D/A) and trans-papillary drainage with EUS-assisted pancreatic rendezvous. EUS-guided pancreatogastrostomy is the most common EUS-D/A procedure and is recommended as a salvage procedure in cases in which endoscopic retrograde cholangiopancreatography fails or is difficult. However, initial EUS-D/A is performed in patients with surgically altered anatomy at our institution. It is one of the most difficult interventional EUS procedures and has a high incidence of adverse events. The technical difficulties differ according to etiology, and the incidence of adverse events varies between initial EUS-D/A and subsequent trans-endosonographically/EUS-guided created route procedures. Hence, it is important to meticulously prepare a procedure based on the patient's condition and the available devices. The technical difficulties in EUS-D/A include: (1) determination of the puncture point, (2) selection of a puncture needle and guidewire, (3) guidewire manipulation, and (4) dilation of the puncture route and stenting. Proper technical procedures are important to increase the success rate and reduce the incidence and severity of adverse events. The complexity of EUS-D/A is also contingent on the severity of pancreatic fibrosis and stricture. In post-pancreatectomy cases, determination of the puncture site is important for success because of the remnant pancreas. Trans-endosonographically/EUS-guided created route procedures following initial EUS-D/A are also important for achieving the treatment goal. This article focuses on effective strategies for initial EUS-D/A, based on the etiology and condition of the pancreas. We mainly discuss EUS-D/A, including its indications, techniques, and success-enhancing strategies.

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.

Computed tomography-based prediction of pancreatitis following biliary metal stent placement with the convolutional neural network.

Background and study aims Pancreatitis is a potentially lethal adverse event of endoscopic transpapillary placement of a self-expandable metal stent (SEMS) for malignant biliary obstruction (MBO). Deep learning-based image recognition has not been investigated in predicting pancreatitis in this setting. Patients and methods We included 70 patients who underwent endoscopic placement of a SEMS for nonresectable distal MBO. We constructed a convolutional neural network (CNN) model for pancreatitis prediction using a series of pre-procedure computed tomography images covering the whole pancreas (≥ 120,960 augmented images in total). We examined the additional effects of the CNN-based probabilities on the following machine learning models based on clinical parameters: logistic regression, support vector machine with a linear or RBF kernel, random forest classifier, and gradient boosting classifier. Model performance was assessed based on the area under the curve (AUC) in the receiver operating characteristic analysis, positive predictive value (PPV), accuracy, and specificity. Results The CNN model was associated with moderate levels of performance metrics: AUC, 0.67; PPV, 0.45; accuracy, 0.66; and specificity, 0.63. When added to the machine learning models, the CNN-based probabilities increased the performance metrics. The logistic regression model with the CNN-based probabilities had an AUC of 0.74, PPV of 0.85, accuracy of 0.83, and specificity of 0.96, compared with 0.72, 0.78, 0.77, and 0.96, respectively, without the probabilities. Conclusions The CNN-based model may increase predictability for pancreatitis following endoscopic placement of a biliary SEMS. Our findings support the potential of deep learning technology to improve prognostic models in pancreatobiliary therapeutic endoscopy.

Controversies in endoscopic ultrasonography-guided management of walled-off necrosis.

Walled-off necrosis (WON) develops as local complications after acute necrotizing pancreatitis. Although less invasive interventions such as endoscopic ultrasonography (EUS)-guided drainage and endoscopic necrosectomy are selected over surgical interventions, delayed and step-up interventions are still preferred to avoid procedure-related adverse events. However, there is a controversy about the appropriate timing of drainage and subsequent necrosectomy. The advent of large-caliber lumen-apposing metal stents has also brought about potential advantages of proactive interventions, which still needs investigation in future trials. When step-up interventions of necrosectomy and additional drainage are necessary, a structured or protocoled approach for WON has been reported to improve safety and effectiveness of endoscopic and/or percutaneous treatment, but has not been standardized yet. Finally, long-term outcomes such as recurrence of WON, pancreatic endocrine, and exocrine function are increasingly investigated in association with disconnected pancreatic duct syndrome. In this review we discuss current evidence and controversy on EUS-guided management of WON.

Drainage for fluid collections post pancreatic surgery and acute pancreatitis: similar but different?

Postoperative pancreatic fistulas (POPFs) are common adverse events that occur after pancreatic surgery. Endoscopic ultrasonography (EUS)-guided drainage (EUS-D) is a first-line treatment, similar to that for pancreatic fluid collection (PFCs) after acute pancreatitis. However, some POPFs do not develop fluid collections depending on the presence or location of the surgical drain, whereas others develop fluid collections, such as postoperative fluid collections (POPFCs). Although POPFCs are similar to PFCs, the strategy and modality for POPF management need to be modified according to the presence of fluid collections, surgical drains, and surgical type. As discussed for PFCs, the indications, timing, and selection of interventions or stents for EUS-D have not been fully elucidated for POPFs. In this review, we discuss the management of POPFs and POPFCs in comparison with PFCs due to acute pancreatitis and summarize the topics that should be addressed in future studies.

Dedicated Echoendoscope for Interventional Endoscopic Ultrasound: Comparison with a Conventional Echoendoscope.

Background/Objective: Interventional endoscopic ultrasound (I-EUS) is technically difficult and has risks of severe adverse events due to the scarcity of dedicated endoscopes and tools. A new EUS scope was developed for I-EUS and was modified to increase the puncture range, reduce the blind area, and overcome guidewire difficulties. We evaluated the usefulness and safety of a new EUS scope compared to a conventional EUS scope. Methods: All I-EUS procedures were performed at Juntendo University Hospital from April 2020 to April 2022. The primary outcomes included the procedure time and fluoroscopy time. The secondary outcomes included the technical success rate and the rates of procedure-related adverse events. Clinical data were retrospectively reviewed and statistically analyzed between the new and conventional EUS scopes. Results: In total, 143 procedures in 120 patients were analyzed. The procedure time was significantly shorter with the new EUS scope, but the fluoroscopy time was not different. Among the patients only undergoing EUS-guided biliary drainage (EUS-BD), 79 procedures in 74 patients were analyzed. Both the procedure time and fluoroscopy time were significantly shorter with the new EUS scope. Multivariate analysis revealed that a new EUS scope and use of covered metal stents could reduce the fluoroscopy time. The technical success rate and the adverse event rate were not significantly different between the total I-EUS and the EUS-BD only groups. However, the conventional scope showed stent deviation during stent placement, which did not happen with the new scope. Conclusions: The new EUS scope reduced procedure time for total I-EUS and fluoroscopy time for EUS-BD compared to a conventional EUS scope because of the improvement suitable for I-EUS.

Role of advanced endoscopy in the management of inflammatory digestive diseases (pancreas and biliary tract).

The progress of endoscopic diagnosis and treatment for inflammatory diseases of the biliary tract and pancreas have been remarkable. Endoscopic ultrasonography (EUS) and EUS-elastography are used for the diagnosis of early chronic pancreatitis and evaluation of endocrine and exocrine function in chronic pancreatitis. Notably, extracorporeal shock wave lithotripsy and electrohydraulic shock wave lithotripsy have improved the endoscopic stone removal rate in patients for whom pancreatic stone removal is difficult. Studies have reported the use of self-expanding metal stents for stent placement for pancreatic duct stenosis and EUS-guided pancreatic drainage for refractory pancreatic duct strictures. Furthermore, EUS-guided drainage using a double-pigtailed plastic stent has been performed for the management of symptomatic pancreatic fluid collection after acute pancreatitis. Recently, lumen-apposing metal stents have led to advances in the treatment of walled-off necrosis after acute pancreatitis. EUS-guided biliary drainage is an alternative to refractory endoscopic biliary drainage and percutaneous transhepatic biliary drainage for the treatment of acute cholangitis. The placement of an inside stent followed by switching to uncovered self-expanding metal stents in difficult-to-treat cases has been proposed for acute cholangitis by malignant biliary obstruction. Endoscopic transpapillary gallbladder drainage is an alternative to percutaneous transhepatic gallbladder drainage for severe and some cases of moderate acute cholecystitis. EUS-guided gallbladder drainage has been reported as an alternative to percutaneous transhepatic gallbladder drainage and endoscopic transpapillary gallbladder drainage. However, it is important to understand the advantages and disadvantages of each drainage method and select the optimal drainage method for each case.

Risk of recurrence with or without plastic stent after EUS-guided treatment of peripancreatic fluid collections: A systematic review and meta-analysis.

Background and study aims Recent advances in endoscopic transmural treatment have improved the clinical outcomes of patients with pancreatic fluid collections (PFCs). However, there is still a debate about the preventive effect of long-term placement of a transmural plastic stent (PS) on recurrence after successful endoscopic ultrasound (EUS)-guided treatment of PFCs. We conducted a systematic review and meta-analysis to evaluate PFC recurrence rates with and without a transmural PS after EUS-guided treatment. Patients and methods A systematic literature search of PubMed, Embase, and the Cochrane database was conducted to identify clinical studies comparing outcomes with and without transmural PS published until September 2022. Data on PFC recurrence and adverse events (AEs) were pooled using a random-effects model. Results Nine studies including 380 patients with long-term transmural PS and 289 patients without PS were identified. The rate of PFC recurrence was significantly lower in patients with transmural PS (pooled odds ratio [OR] = 0.23, 95% confidence interval [CI] [0.08-0.65], P = 0.005). In a subgroup analysis limited to studies focusing on patients with disconnected pancreatic duct syndrome, which has been reported to be a risk factor for PFC recurrence, the OR was numerically lower than that for the entire cohort (OR = 0.14, 95% CI [0.04-0.46]). The rate of AEs was significantly higher with long-term transmural PS (OR = 14.77, 95% CI [4.21-51.83]). Conclusions In this meta-analysis, long-term PS placement reduced the risk of PFC recurrence. Given the potential AEs of indwelling PS, further research is required to evaluate the overall benefits of long-term PS placement.

Safety and effectiveness of SARS-CoV-2 vaccines for patients with intractable hepatobiliary diseases: A multicenter, questionnaire-based, cross-sectional study.

AIM: There are few data regarding the safety and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with intractable hepatobiliary diseases. We conducted a multicenter, questionnaire-based, cross-sectional study to determine the safety and effectiveness of the SARS-CoV-2 vaccines in Japanese patients with intractable hepatobiliary disease. METHODS: Patients aged ≥18 years with autoimmune hepatitis (AIH), primary biliary cholangitis, primary sclerosing cholangitis, Budd-Chiari syndrome, idiopathic portal hypertension, and extrahepatic portal vein obstruction at each center were consecutively invited to join the study. Participants were asked to complete a questionnaire regarding their characteristics, vaccination status, post-vaccination adverse effects, and SARS-CoV-2 infection. Additionally, liver disease status, treatment regimens, and liver function test values pre- and post-vaccination were collected. RESULTS: The survey was conducted from September 2021 to May 2022, and 528 patients (220 AIH, 251 primary biliary cholangitis, 6 AIH- primary biliary cholangitis/primary sclerosing cholangitis overlap, 39 primary sclerosing cholangitis, 4 Budd-Chiari syndrome, 5 idiopathic portal hypertension, and 3 extrahepatic portal vein obstruction) participated in the study. Post-vaccination adverse effects were comparable to those observed in the general population. Post-vaccination liver injuries classified as grade 1 or higher were observed in 83 cases (16%), whereas grades 2 and 3 were observed in only six cases (1.1%); AIH-like liver injury requiring treatment was not observed. Overall, 12 patients (2.3%) were infected with SARS-CoV-2, and only one patient was infected 6 months after the second vaccination. CONCLUSION: SARS-CoV-2 vaccines demonstrated satisfactory safety and effectiveness in Japanese patients with intractable hepatobiliary diseases.

Maintenance steroid therapy is associated with decreased risk of malignancy and better prognosis of patients with autoimmune pancreatitis: A multicenter cohort study in Japan.

BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.

Early versus delayed EUS-guided drainage for postoperative pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Postoperative pancreatic fluid collections (POPFCs) are common adverse events (AEs) after pancreatic surgery and may need interventions. Endoscopic ultrasound (EUS)-guided drainage for POPFCs is increasingly reported, but its appropriate timing has not been fully elucidated. The aim of this meta-analysis was to evaluate treatment outcomes of POPFCs according to the timing of EUS-guided drainage. METHODS: Using PubMed, Embase, Web of Science, and the Cochrane database, we identified clinical studies published until December 2022 with data comparing outcomes of early and delayed EUS-guided drainage for POPFCs. We pooled data on AEs, mortality, and technical and clinical success rates, using the random-effects model. RESULTS: From 1415 papers identified in the initial literature search, we identified 6 retrospective studies, including 128 and 107 patients undergoing early and delayed EUS-guided drainage for POPFCs. The threshold of early and delayed drainage ranged from 14 to 30 days. Distal pancreatectomy was the major cause of POPFCs, ranging from 44 to 100%. The pooled odds ratio (OR) for AEs was 0.81 (95% confidence interval [CI] 0.40-1.64, P = 0.55) comparing early to delayed drainage. There was no procedure-related mortality. Technical success was achieved in all cases and a pooled OR of clinical success was 0.60 (95% CI 0.20-1.83, P = 0.37). CONCLUSION: POPFCs can be managed by early EUS-guided drainage without an increase in AEs.

Increased expression of TNFRSF14 and LIGHT in biliary epithelial cells of patients with primary sclerosing cholangitis.

BACKGROUND AND AIMS: There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies (GWAS). METHODS: Expression levels of GWAS genes were analyzed in archival liver tissues of patients with PSC and controls. Immunohistochemical analysis was performed to evaluate expression levels in the biliary epithelia of PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20). RESULTS: Hepatic expression levels of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that high expression of TNFRSF14 in biliary epithelial cells was observed only in the PSC group. In addition, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53%) than in the PBC (15%) or control (0%) groups; moreover, it was positively associated with fibrotic progression, although it was not an independent prognostic factor. CONCLUSIONS: TNFRSF14 and LIGHT are promising candidate markers for PSC.

Endoscopic nasobiliary drainage versus endoscopic biliary stenting for preoperative biliary drainage in patients with malignant hilar biliary obstruction: Propensity score-matched multicenter comparative study.

OBJECTIVES: For preoperative biliary drainage (PBD) of malignant hilar biliary obstruction (MHBO), current guidelines recommend endoscopic nasobiliary drainage (ENBD) due to the higher risk of cholangitis after endoscopic biliary stenting (EBS) during the waiting period before surgery. However, few studies have supported this finding. Therefore, we aimed to compare the outcomes of preoperative ENBD and EBS in patients with MHBO. METHODS: Patients with MHBO who underwent laparotomy for radical surgery after ENBD or EBS were included from retrospectively collected data from 13 centers (January 2014 to December 2018). We performed a 1:1 propensity score matching between the ENBD and EBS groups. These patients were compared for the following: cholangitis and all adverse events (AEs) after endoscopic biliary drainage (EBD) until surgery, time to cholangitis development after EBD, postsurgical AEs, and in-hospital death after surgery. RESULTS: Of the 414 patients identified, 355 were analyzed in this study (226 for ENBD and 129 for EBS). The matched cohort included 63 patients from each group. The proportion of cholangitis after EBD was similar between the two groups (20.6% vs. 25.4%, P = 0.67), and no significant difference was observed in the time to cholangitis development. The proportions of surgical site infections, bile leaks, and in-hospital mortality rates were similar between the groups. CONCLUSION: For PBD of MHBO, the proportion of AEs, including cholangitis, after EBD until surgery was similar when either ENBD or EBS was used.

Current Situation and Problems in Diagnosis of Early Chronic Pancreatitis.

OBJECTIVES: The Japan Pancreas Society introduced the concept of early chronic pancreatitis (ECP) in 2009, but its epidemiology remains unclear. This study investigated challenges in ECP diagnosis. METHODS: Early chronic pancreatitis was diagnosed in 4 cohorts between April 2019 and November 2021 using the Clinical Diagnostic Criteria for Chronic Pancreatitis 2019. These cohorts included patients with abdominal/back pain, abnormal pancreatic enzyme levels, ECP suspected due to other reasons, and those who underwent endoscopic ultrasonography for other diseases. RESULTS: A total of 2502 cases were analyzed and 150 (40 alcoholic and 110 nonalcoholic) cases with ECP findings on endoscopic ultrasonography were included. Early chronic pancreatitis was confirmed in 14 cases (9%), including 9 (22.5%) alcoholic and 5 (4.5%) nonalcoholic cases. Early chronic pancreatitis was confirmed in 15%, 0%, 2.2%, and 0.13% cases in the 4 cohorts, respectively. Early chronic pancreatitis was confirmed in 10 (48%) of the 21 (14%) cases with pancreatic pain. CONCLUSIONS: Early chronic pancreatitis diagnostic rate was low, particularly in nonalcoholic cases, but was slightly higher in cases with pancreatic pain. The diagnostic rate was highest in the abdominal/back pain group. Further studies are required to establish appropriate diagnostic criteria for ECP.