Prospective multicenter surveillance study of branch-duct intraductal papillary mucinous neoplasm of the pancreas; risk of dual carcinogenesis.

BACKGROUND: The natural history of branch-duct intraductal papillary mucinous cystic neoplasms (BD-IPMNs) in the pancreas remains unclear. This study aimed to answer this clinical question by focusing on the development of concomitant pancreatic ductal adenocarcinomas (cPDAC). METHODS: The Japan Pancreas Society conducted a prospective multicenter surveillance study of BD-IPMN every six months for five years. The primary endpoints were progression of BD-IPMN, progression to high-grade dysplasia/invasive carcinoma (HGD/IC), and cPDAC. Factors predicting the progression of BD-IPMN to HGD/IC and development of cPDAC were also assessed as secondary endpoints. RESULTS: Among the 2104 non-operated patients, 348 (16.5 %) showed progression of primary BD-IPMN. Cumulative incidences of BD-IPMN with HGD/IC and cPDAC during the 5.17-year surveillance period were 1.90 % and 2.11 %, respectively, and standard incidence ratios of BD-IPMN with HGD/IC and cPDAC were 5.28 and 5.73, respectively. Of 38 cPDACs diagnosed during surveillance, 25 (65.8 %) were resectable. The significant predictive characteristics of BD-IPMN for progression to HGD/IC were larger cyst size (p = 0.03), larger main pancreatic duct size (p < 0.01), and mural nodules (p = 0.02). Significant predictive characteristics for the development of cPDAC were male sex (p = 0.03) and older age (p = 0.02), while the size of IPMN was not significant. CONCLUSION: Careful attention should be given to "dual carcinogenesis" during BD-IPMN surveillance, indicating the progression of BD-IPMN to HGD/IC and development of cPDAC distinct from BD-IPMN, although the establishment of risk factors that predict cPDAC development remains a challenge (UMIN000007349).

ERCP using balloon-assisted endoscopes versus EUS-guided treatment for common bile duct stones in Roux-en-Y gastrectomy.

BACKGROUND AND AIMS: We compared ERCP using a balloon-assisted endoscope (BE-ERCP) with EUS-guided antegrade treatment (EUS-AG) for removal of common bile duct (CBD) stones in patients with Roux-en-Y (R-Y) gastrectomy. METHODS: Consecutive patients who had previous R-Y gastrectomy undergoing BE-ERCP or EUS-AG for CBD stones in 16 centers were retrospectively analyzed. RESULTS: BE-ERCP and EUS-AG were performed in 588 and 59 patients, respectively. Baseline characteristics were similar, except for CBD diameter and angle. The technical success rate was 83.7% versus 83.1% (P = .956), complete stone removal rate was 78.1% versus 67.8% (P = .102), and early adverse event rate was 10.2% versus 18.6% (P = .076) in BE-ERCP and EUS-AG, respectively. The mean number of endoscopic sessions was smaller in BE-ERCP (1.5 ± .8 vs 1.9 ± 1.0 sessions, P = .01), whereas the median total treatment time was longer (90 vs 61.5 minutes, P = .001). Among patients with biliary access, the complete stone removal rate was significantly higher in BE-ERCP (93.3% vs 81.6%, P = .009). Negative predictive factors were CBD diameter ≥15 mm (odds ratio [OR], .41) and an angle of CBD <90 degrees (OR, .39) in BE-ERCP and a stone size ≥10 mm (OR, .07) and an angle of CBD <90 degrees (OR, .07) in EUS-AG. The 1-year recurrence rate was 8.3% in both groups. CONCLUSIONS: Effectiveness and safety of BE-ERCP and EUS-AG were comparable in CBD stone removal for patients after R-Y gastrectomy, but complete stone removal after technical success was superior in BE-ERCP.

A comparative study between computed tomography and endoscopic ultrasound in the detection of a mural nodule in intraductal papillary mucinous neoplasm -Multicenter observational study in Japan.

BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.

Prophylactic endoscopic gallbladder stent placement for cholecystitis after covered metal stent placement for distal biliary obstruction (with video).

BACKGROUND AND AIMS: Acute cholecystitis is occasionally observed after biliary drainage using a covered self-expandable metal stent (CSEMS) for distal biliary obstruction (DBO). Gallbladder drainage before CSEMS placement may reduce cholecystitis. This study aimed to examine the preventive effect of endoscopic gallbladder stent placement (EGBS) on cholecystitis with CSEMSs. METHODS: We retrospectively analyzed patients with DBO who underwent CSEMS placement across the orifice of the cystic duct between November 2014 and October 2021 and were negative for cholecystitis on biliary drainage. Prophylactic EGBS was attempted before CSEMS placement. The incidence of cholecystitis was compared between patients with and without EGBS. RESULTS: In total, 286 patients (128 men; median age, 75 years) were included in this study. EGBS was attempted in 32 patients before CSEMS placement, and technical success was achieved in 24 patients (75%). Adverse events were noted in 3 patients (9.4%; penetration of cystic duct in 1 and acute pancreatitis in 2). The cumulative incidence of cholecystitis was significantly lower in patients with EGBS than in those without EGBS (1 [4.2%] vs 56 [21.4%], P = .045). In multivariable analysis, EGBS was a significant protective factor against cholecystitis (hazard ratio, .11; 95% confidence interval, .01-.79; P = .028). CONCLUSIONS: Although the transpapillary approach to the gallbladder is not easy for patients with DBO, EGBS is effective in preventing cholecystitis associated with CSEMS placement.

Efficacy of pancreatic duct stenting to prevent postendoscopic retrograde cholangiopancreatography pancreatitis after covered self-expandable metal stent deployment.

OBJECTIVES: Although covered self-expandable metal stents (CSEMSs) are associated with the risk of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis due to pancreatic duct (PD) orifice obstruction, they are often used for biliary drainage treatment in malignant biliary obstruction (MBO). This study aimed to investigate the efficacy of PD stenting in preventing post-ERCP pancreatitis after CSEMS implantation. METHODS: This retrospective cohort study analyzed 554 patients with transpapillary CSEMS for MBO. Patients with noninitial deployment, benign disease, CSEMS deployment above the papilla, surgically altered anatomy, uncovered self-expandable metal stents, multiple thin self-expandable metal stents, and unavailable procedure videos were excluded. Logistic regression analysis estimated the association between PD stenting and post-ERCP pancreatitis incidence. We adjusted for age, sex, pancreatitis history, prophylactic rectal nonsteroidal anti-inflammatory drug use, naïve papilla, MBO etiology, and prolonged biliary cannulation time. RESULTS: Among 554 patients, 67 (12.1%) experienced post-ERCP pancreatitis. Post-ERCP pancreatitis was recorded in 13.7% of patients in the non-PD stenting and 4.3% in the PD stenting groups. Pancreatic duct stenting was associated with lower risks of post-ERCP pancreatitis (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.099-0.79; P = 0.028). In multivariable analysis, the association between PD stenting and lower post-ERCP pancreatitis incidence was consistent (OR 0.19; 95% CI 0.062-0.58; P = 0.0034). CONCLUSIONS: Pancreatic duct stenting could reduce the risk of post-ERCP pancreatitis after CSEMSs.

Efficacy and factors affecting procedure results of short-type single-balloon enteroscopy-assisted ERCP for altered anatomy: a multicenter cohort in Japan.

BACKGROUND AND AIMS: Although single-balloon enteroscopy (SBE)-assisted or short-type SBE (short SBE)-assisted ERCP has been reported as useful in patients with surgically altered anatomy, most studies had small sample sizes or single-center designs. This study aimed to evaluate the efficacy and factors affecting the procedure results of short SBE-assisted ERCP in patients with surgically altered anatomy. METHODS: This multicenter, retrospective study was conducted at 8 tertiary referral care centers in Japan. The data of patients who underwent ERCP-related procedures using short SBE between September 2011 and August 2019 at each facility were analyzed. RESULTS: Overall, 1318 patients were included in this analysis. The enteroscopy (reaching the target site), cannulation, and total procedural success rates were 87.9% (95% confidence interval [CI], 86.1%-89.6%), 87.0% (95% CI, 84.9%-88.8%), and 74.9% (95% CI, 72.5%-77.2%), respectively. Adverse events occurred in 7.7% of patients (95% CI, 6.4%-9.3%). Multiple logistic regression analysis indicated that age (≥75 years), Roux-en-Y reconstruction, pancreatic indication, and malignancy were factors affecting the total procedural failure. CONCLUSIONS: This large-scale study proved that short SBE-assisted ERCP in patients with surgically altered anatomy was effective. Moreover, it clarified factors affecting procedure results. Proficiency with alternative treatment techniques is required in difficult cases. (Clinical trial registration number: UMIN00004045.).

Feasibility of biliary stenting to distal malignant biliary obstruction using a novel designed metal stent with duckbill-shaped anti-reflux valve.

OBJECTIVES: Anti-reflux metal stent (ARMS) has been used to prevent recurrent biliary obstruction (RBO) due to sludge formation or food impaction. However, the most suitable ARMS remains to be identified. This study aimed to evaluate the feasibility, safety, and efficacy of biliary drainage using duckbill-shaped ARMS (D-ARMS). METHODS: This was a multicenter, retrospective observational study conducted at three Japanese tertiary institutions. Patients with distal malignant biliary obstruction who underwent biliary stenting using D-ARMS were eligible to participate. Technical success, functional success, adverse event (AE), and time to RBO (TRBO) were evaluated. RESULTS: Thirty patients underwent biliary stenting using D-ARMS from December 2018 to October 2019. The technical success rate and functional success rate were 93% and 87%, respectively. However, nonvisibility of the markers at the tip of the metal stent or spontaneous extension was occasionally observed, making biliary stenting using D-ARMS difficult. Early AE occurred in 10% of the patients including cholangitis and pancreatitis. During the median postprocedural observation time of 5.1 months (range, 0.8-22.8), RBO occurred in 33% and the median TRBO was 261 days. As for reintervention, D-ARMS could be extracted in 67% of the patients with RBO. However, the stent was torn off on removal in half of the patients. CONCLUSIONS: Although some modifications are still needed, D-ARMS was feasible and safe for biliary drainage, and sufficient TRBO was achieved. Subsequent multi-institutional studies involving a larger number of patients and a longer follow-up period are warranted to validate the present results.

New Model for Predicting Malignancy in Patients With Intraductal Papillary Mucinous Neoplasm.

OBJECTIVE: To create a simple, objective model to predict the presence of malignancy in patients with intraductal papillary mucinous neoplasm (IPMN), which can be easily applied in daily practice and, importantly, adopted for any lesion types. BACKGROUND: No predictive model for malignant IPMN has been widely applied in clinical practice. METHODS: The clinical details of 466 patients with IPMN who underwent pancreatic resection at 3 hospitals were retrospectively analyzed for model development. Then, the model was validated in 664 surgically resected patients at 8 hospitals in Japan.In the preoperative examination, endoscopic ultrasonography (EUS) was considered to be essential to observe mural nodules in both the model development and external validation sets. Malignant IPMNs were defined as those with high-grade dysplasia and associated invasive carcinoma. RESULTS: Of the 466 patients, 258 (55%) had malignant IPMNs (158 high-grade dysplasia, 100 invasive carcinoma), and 208 (45%) had benign IPMNs. Logistic regression analysis resulted in 3 variables (mural nodule size, main pancreatic duct diameter, and cyst size) being selected to construct the model. The area under the receiver operating characteristic curve (AUC) for the model was 0.763. In external validation sets, the pathological diagnosis was malignant and benign IPMN in 351 (53%) and 313 (47%) cases, respectively. For the external validation, the malignancy prediction ability of the model corresponded to an AUC of 0.725. CONCLUSION: This predictive model provides important information for physicians and patients in assessing an individual's risk for malignancy and may help to identify patients who need surgery.

Metachronous intraductal papillary mucinous neoplasms disseminate via the pancreatic duct following resection.

Metachronous development of intraductal papillary mucinous neoplasms in the remnant pancreas following resection is a significant clinical burden. Our aim was to characterize the clinicopathological and molecular features of the patients with metachronous tumor development to identify predictive factors and the possible route(s) of dissemination. Seventy-four patients who underwent resection of intraductal papillary mucinous neoplasms with no invasive compartment or associated carcinoma were retrospectively analyzed. In patients with metachronous tumor development, targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical detection of four proteins (p53, SMAD4, p16, and ß-catenin) were performed on both primary and metachronous tumors. The distributions of microscopic neoplastic lesions were examined at surgical margins and in apparently normal tissue apart from the primary tumor. During the median follow-up period of 52 months, 9 patients (12%) developed metachronous tumors in the remnant pancreas. Primary tumors located in the body/tail of the pancreas (odds ratio, 15; 95% confidence interval, 1.6-131) and of the pancreatobiliary type (odds ratio, 6.1; 95% confidence interval, 1.1-35.7) were identified as significant risk factors for subsequent metachronous tumor development. Eight of the nine patients shared molecular aberrations between their primary and metachronous tumors, suggesting migrations from the primary tumor to the pancreatic duct as the cause of metachronous tumor development. Our data suggest that these post-resection metachronous tumors develop by skip dissemination of the primary tumor, potentially via the pancreatic duct. The development of strategies to better predict and prevent this form of tumor progression is necessary.

Interventional endoscopic ultrasonography in patients with surgically altered anatomy: Techniques and literature review.

There are various reconstruction techniques that are used after upper gastrointestinal surgery. In recent years, opportunities for endoscopic diagnosis and treatment have been increasing in patients undergoing gastrointestinal surgery. With the advent of interventional endoscopic ultrasound (IV-EUS), various procedures have been developed mainly for patients in whom endoscopic retrograde cholangiopancreatography is difficult to carry out. Indications for such procedures are expanding. IV-EUS for surgically altered anatomy (SAA) includes EUS-guided fine-needle aspiration, biliary interventions (e.g. biliary drainage, treatment of bile duct stricture, removal of bile duct stones, and the rendezvous technique), and pancreatic interventions (e.g. rendezvous technique after Whipple surgery). In addition, there have been reports of various EUS-related procedures using a forward-viewing curved linear-array echoendoscope that are carried out for postoperative intestinal tract reconstruction. Although interventional EUS is a useful therapeutic procedure for SAA, there are still no dedicated devices, and standardization of the procedure is warranted.

Endoscopic ultrasound-guided fine needle aspiration for diagnosing pancreatic mass in patients with surgically altered upper gastrointestinal anatomy.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been established as a safe and accurate method for diagnosing a pancreatic mass; however, EUS-FNA for patients with surgically altered upper gastrointestinal (UGI) anatomy has not yet been investigated sufficiently. Therefore, the feasibility and safety of EUS-FNA in these patients were retrospectively investigated. METHODS: Patients in whom EUS-FNA was performed between March 2008 and April 2017 were retrospectively investigated in terms of EUS-FNA technical success, procedure time, diagnostic accuracies of cytology and histology, and procedure-related adverse events. RESULTS: Twenty-five EUS-FNAs were performed for 15 pancreatic body-to-tail and 10 head lesions. All patients underwent EUS-FNA successfully; however, changing of the echoendoscope to a forward-viewing echoendoscope and preplacement of a nasobiliary catheter by balloon-assisted enteroscopy for guidance were needed in one and two cases, respectively. The median procedure time was 26 min (range, 16-70). The diagnostic accuracies were 76%, 84%, and 88% for cytology, histology, and combined use, respectively. Adverse events were not observed. CONCLUSIONS: Endoscopic ultrasound-guided FNA is a safe and efficient method for diagnosing a pancreatic mass even in patients with surgically altered UGI anatomy. Nevertheless, some sophisticated techniques are required for pancreatic head lesions if reaching the duodenum after passing through the jejunal limb is required for visualization of the pancreatic mass.