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.

Comorbidity burden and outcomes of endoscopic ultrasound-guided treatment of pancreatic fluid collections: Multicenter study with nationwide data-based validation.

OBJECTIVES: The appropriate holistic management is mandatory for successful endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs). However, comorbidity status has not been fully examined in relation to clinical outcomes of this treatment. METHODS: Using a multi-institutional cohort of 406 patients receiving EUS-guided treatment of PFCs in 2010-2020, we examined the associations of Charlson Comorbidity Index (CCI) with in-hospital mortality and other clinical outcomes. Multivariable logistic regression analysis was conducted with adjustment for potential confounders. The findings were validated using a Japanese nationwide inpatient database including 4053 patients treated at 486 hospitals in 2010-2020. RESULTS: In the clinical multi-institutional cohort, CCI was positively associated with the risk of in-hospital mortality (Ptrend < 0.001). Compared to patients with CCI = 0, patients with CCI of 1-2, 3-5, and ≥6 had adjusted odds ratios (95% confidence intervals) of 0.76 (0.22-2.54), 5.39 (1.74-16.7), and 8.77 (2.36-32.6), respectively. In the nationwide validation cohort, a similar positive association was observed; the corresponding odds ratios (95% confidence interval) were 1.21 (0.90-1.64), 1.52 (0.92-2.49), and 4.84 (2.63-8.88), respectively (Ptrend < 0.001). The association of higher CCI with longer length of stay was observed in the nationwide cohort (Ptrend < 0.001), but not in the clinical cohort (Ptrend = 0.18). CCI was not associated with the risk of procedure-related adverse events. CONCLUSIONS: Higher levels of CCI were associated with a higher risk of in-hospital mortality among patients receiving EUS-guided treatment of PFCs, suggesting the potential of CCI in stratifying the periprocedural mortality risk. TRIAL REGISTRATION: The research based on the clinical data from the WONDERFULcohort was registered with UMIN-CTR (registration number UMIN000044130).

Diagnosis of isolated hilar-/extrahepatic-type IgG-4-related sclerosing cholangitis can be increased by improved recognition of this condition-A Japanese multicenter analysis.

BACKGROUND: Patients with isolated IgG4-related sclerosing cholangitis (IgG4-SC) often undergo unnecessary resection. The aim of this study was to validate the revised Japanese diagnostic criteria for isolated IgG-4-SC and to improve awareness about this condition in the population. METHODS: This was a Japanese retrospective multicenter study. We focused on the data and diagnostic yield obtained using the Japanese diagnostic criteria published initially in 2012 and revised later in 2020 for the diagnosis of isolated IgG4-SC. RESULTS: Patients with isolated IgG4-SC could be classified into two groups based on the primary location of the lesion: the hilar type (n = 40) and the extrahepatic type (n = 13). In total, 10 patients with the hilar type had undergone unnecessary resection. The revised 2020 criteria are useful for the diagnosis of extrahepatic lesions, which are not included in the 2012 criteria. The need for a steroid trial was reduced from 37.7% when the diagnosis was based on the 2012 criteria to 7.6% when the diagnosis was based on the revised 2020 criteria. The diagnostic specificity also improved from 58.5% for the 2012 criteria to 88.7% for the revised 2020 criteria. CONCLUSION: Our validation of the 2020 criteria for the diagnosis of IgG4-SC could contribute to avoiding unnecessary resection in patients with isolated IgG4-SC, which can be classified into the hilar and extrahepatic types. The 2020 criteria can enhance the diagnosis rate of isolated IgG4-SC and uncover this tough-to-diagnose entity based on inclusion of the imaging findings and decrease the dependence on a steroid trial.

WONDER-02: plastic stent vs. lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic pseudocysts-study protocol for a multicentre randomised non-inferiority trial.

BACKGROUND: Endoscopic ultrasound (EUS)-guided transluminal drainage has become a first-line treatment modality for symptomatic pancreatic pseudocysts. Despite the increasing popularity of lumen-apposing metal stents (LAMSs), plastic stents may resolve non-necrotic fluid collections effectively with lower costs and no LAMS-specific adverse events. To date, there has been a paucity of data on the appropriate stent type in this setting. This trial aims to assess the non-inferiority of plastic stents to a LAMS for the initial EUS-guided drainage of pseudocysts. METHODS: The WONDER-02 trial is a multicentre, open-label, non-inferiority, randomised controlled trial, which will enrol pancreatic pseudocyst patients requiring EUS-guided treatment in 26 centres in Japan. This trial plans to enrol 80 patients who will be randomised at a 1:1 ratio to receive either plastic stents or a LAMS (40 patients per arm). In the plastic stent group, EUS-guided drainage will be performed using two 7-Fr double pigtail stents. In the LAMS group, the treatment will be performed in the same way except for LAMS use. The step-up treatment will be performed via endoscopic and/or percutaneous procedures at the trial investigator's discretion. The primary endpoint is clinical success, which is defined as a decrease in a pseudocyst size to ≤ 2 cm and an improvement in inflammatory indicators (i.e. body temperature, white blood cell count, and serum C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, pseudocyst recurrence, and medical costs. DISCUSSION: The WONDER-02 trial will investigate the efficacy and safety of plastic stents compared to a LAMS in EUS-guided treatment of symptomatic pancreatic pseudocysts with a particular focus on the non-inferior efficacy of plastic stents. The findings will help establish a new treatment algorithm for this population. TRIAL REGISTRATION: ClinicalTrials.gov NCT06133023 registered on 9 November 2023. UMIN000052647 registered on 30 October 2023. jRCT1032230444 registered on 7 November 2023.

Recent progress and current status of pancreatobiliary interventional endoscopic ultrasound in children.

In recent years, the usefulness of endoscopic ultrasound (EUS) has been recognized in children. A dedicated pediatric EUS scope has not been developed; in our experience, however, an adult EUS scope can be used. The American Society for Gastrointestinal Endoscopy Technical Committee status assessment report on pediatric endoscopy equipment provides some guidance on the feasibility of EUS according to body size. Careful monitoring is required, keeping in mind potential adverse events such as cervical esophageal perforation and unstable breathing due to tracheal compression. Most devices designed for interventional pancreatobiliary endoscopy are also available for children. Sedation or intubated general anesthesia (GA) is mandatory when performing interventional EUS (I-EUS). I-EUS for children is generally performed using GA in the operating room, but sedation in the endoscopy room is also possible under appropriate monitoring by pediatricians. I-EUS in the operating room is sometimes difficult for endoscopists to perform because of the unsuitable fluoroscopic imaging and the lack of familiar equipment and staff. Compared to GA, sedation in the endoscopy room facilitates easier and quicker repetition of procedures when necessary. Adult pancreatobiliary endoscopists perform most I-EUS procedures in the pediatric population because most pediatric endoscopists have few opportunities to perform EUS-related procedures and thus have difficulty maintaining their skills. To popularize I-EUS techniques for children, it will be necessary to establish a training program for developing pediatric endoscopists.

Assessing outcomes and complications of secondary hepatolithiasis after choledochoenterostomy: A nationwide survey in Japan.

BACKGROUND: This study aimed to evaluate the outcomes and complications of secondary hepatolithiasis following choledochoenterostomy to guide suitable management. METHODS: The study analyzed 127 patients from a 2017 national survey conducted by the Ministry of Health, Labor, and Welfare. The 2023 cohort study assessed residual stones, recurrences, cholangitis, cholangiocarcinoma, and prognosis. RESULTS: The median follow-up duration was 48 months. Balloon endoscopy-assisted endoscopic retrograde cholangiography (BE-ERC) was the most common treatment, achieving complete stone clearance in 84.4% of patients. Anatomical hepatectomy was the most common surgery. Predictors of residual stones were stone number ≥10 (odds ratio [OR], 7.480; p = .028) and stone diameter ≥10 mm (OR, 5.280; p = .020). Predictors of stone recurrence during follow-up were biliary strictures (hazard ratio [HR], 3.580; p = .005) and cholangitis (HR, 2.700; p = .037). Predictors of cholangitis during follow-up were biliary stricture (HR, 5.016; p = .006) and dilatation (HR, 3.560; p = .029). Any treatment for hepatolithiasis reduced cholangitis occurrence (HR, 0.168; p = .042). Balloon dilation combined with stenting for ≥3 months improved biliary strictures in 57.1% of patients. CONCLUSION: This study recommends BE-ERC as the first-choice treatment for secondary hepatolithiasis. Stone removal and relief of biliary strictures and dilatation are crucial to prevent stone recurrence and cholangitis after treatment.

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.

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.

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.

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.

Risk factors for adverse outcomes at various phases of endoscopic ultrasound-guided treatment of pancreatic fluid collections: Data from a multi-institutional consortium.

OBJECTIVES: No comprehensive study has examined short- and long-term adverse outcomes of endoscopic ultrasound (EUS)-guided treatment of pancreatic fluid collections (PFCs) including walled-off necrosis (WON) and pseudocysts. METHODS: In a multi-institutional cohort of 357 patients receiving EUS-guided treatment of PFCs (228 with WON and 129 with pseudocysts), we examined PFC type-specific risk factors for procedure-related adverse events (AEs), clinical failure, and recurrence. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were computed using the logistic and Cox regression models, respectively, adjusting for potential confounders. RESULTS: Adverse events were observed predominantly in WON, and risk factors were WON extension to the pelvis (OR 2.49; 95% CI 1.00-6.19) and endoscopic necrosectomy (OR 5.15; 95% CI 1.61-16.5). Risk factors for clinical failure in WON treatment included higher Charlson Comorbidity Index (OR for ≥3 vs. ≤2, 2.58; 95% CI 1.05-6.35), extension to the pelvis (OR 3.63; 95% CI 1.57-8.43), nonuse of a lumen-apposing metal stent (OR 2.88; 95% CI 1.10-7.54), and percutaneous drainage (OR 3.73; 95% CI 1.27-10.9). Patients with pseudocysts extending to the paracolic gutter and the need for more than two endoscopic/percutaneous procedures had ORs for clinical failure of 5.28 (95% CI 1.10-25.3) and 5.52 (95% CI 1.61-18.9), respectively. Pseudocysts requiring the multigateway approach were associated with a high risk of recurrence (HR 4.00; 95% CI 1.11-11.6). CONCLUSION: The adverse outcomes at various phases of EUS-guided PFC treatment may be predictable based on clinical parameters. Further research is warranted to optimize treatment strategies for high-risk patients.

WONDER-01: immediate necrosectomy vs. drainage-oriented step-up approach after endoscopic ultrasound-guided drainage of walled-off necrosis-study protocol for a multicentre randomised controlled trial.

BACKGROUND: With the increasing popularity of endoscopic ultrasound (EUS)-guided transmural interventions, walled-off necrosis (WON) of the pancreas is increasingly managed via non-surgical endoscopic interventions. However, there has been an ongoing debate over the appropriate treatment strategy following the initial EUS-guided drainage. Direct endoscopic necrosectomy (DEN) removes intracavity necrotic tissue, potentially facilitating early resolution of the WON, but may associate with a high rate of adverse events. Given the increasing safety of DEN, we hypothesised that immediate DEN following EUS-guided drainage of WON might shorten the time to WON resolution compared to the drainage-oriented step-up approach. METHODS: The WONDER-01 trial is a multicentre, open-label, superiority, randomised controlled trial, which will enrol WON patients aged ≥ 18 years requiring EUS-guided treatment in 23 centres in Japan. This trial plans to enrol 70 patients who will be randomised at a 1:1 ratio to receive either the immediate DEN or drainage-oriented step-up approach (35 patients per arm). In the immediate DEN group, DEN will be initiated during (or within 72 h of) the EUS-guided drainage session. In the step-up approach group, drainage-based step-up treatment with on-demand DEN will be considered after 72-96 h observation. The primary endpoint is time to clinical success, which is defined as a decrease in a WON size to ≤ 3 cm and an improvement of inflammatory markers (i.e. body temperature, white blood cell count, and C-reactive protein). Secondary endpoints include technical success, adverse events including mortality, and recurrence of the WON. DISCUSSION: The WONDER-01 trial will investigate the efficacy and safety of immediate DEN compared to the step-up approach for WON patients receiving EUS-guided treatment. The findings will help us to establish new treatment standards for patients with symptomatic WON. TRIAL REGISTRATION: ClinicalTrials.gov NCT05451901, registered on 11 July 2022. UMIN000048310, registered on 7 July 2022. jRCT1032220055, registered on 1 May 2022.

A pilot study of Spring Stopper Stents: Novel partially covered self-expandable metallic stents with anti-migration properties for EUS-guided hepaticogastrostomy.

Background and Objectives: EUS-guided hepaticogastrostomy (EUS-HGS) is an effective salvage procedure when conventional endoscopic transpapillary biliary drainage is difficult or fails. However, the risk of stent migration into the abdominal cavity has not been resolved completely. In this study, we evaluated a newly developed partially covered self-expandable metallic stent (PC-SEMS) that has a spring-like anchoring function on the gastric side. Methods: This retrospective pilot study took place at four referral centers in Japan between October 2019 and November 2020. We enrolled 37 cases consecutively who underwent EUS-HGS for unresectable malignant biliary obstruction. Results: The rates of technical and clinical success were 97.3% and 89.2%, respectively. Technical failures included one case in which the stent was dislocated during the removal of the delivery system, requiring additional EUS-HGS on another branch. Early adverse events (AEs) were observed in four patients (10.8%): two with mild peritonitis (5.4%) and one each (2.7%) with fever and bleeding. No late AEs were observed during the mean follow-up period of 5.1 months. All recurrent biliary obstructions (RBOs) were stent occlusions (29.7%). The median cumulative time to RBO was 7.1 months (95% confidence interval, 4.3 to not available). Although stent migration in which the stopper was in contact with the gastric wall on follow-up computed tomography was observed in six patients (16.2%), no migration was observed. Conclusions: The newly developed PC-SEMS is feasible and safe for the EUS-HGS procedure. The spring-like anchoring function on the gastric side is an effective anchor preventing migration.