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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)., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Aims: Pancreatic juice cytology is useful for diagnosing pancreatic duct strictures and cystic lesions. However, some cases cannot be diagnosed using cytology. This study aimed to evaluate the utility of the overnight-stored pancreatic juice cell block (CB) method for diagnosing pancreatic disease., Methods: This retrospective study included 32 patients who presented with pancreatic duct strictures or cystic lesions between 2018 and 2024. The sensitivity, specificity, and accuracy of the CB method and single/multiple pancreatic juice cytology were compared to evaluate the utility of the CB., Result: An endoscopic nasopancreatic drainage tube was placed in the main pancreatic duct, and pancreatic juice was collected to create a CB specimen. The median amount of pancreatic juice collected was 180(30-200) mL, and the median number of cytological examinations was three(2-8). Of the 32 cases, 13 were malignant, and 19 were benign (non-malignant). The sensitivity was significantly higher for the CB method (62 %) than for single cytology(15 %, P = 0.0414), and there was no significant difference between CB and multiple cytology(54 %, P = 1.0). The specificity and accuracy were not significantly different between the CB method and single or multiple cytology. When multiple cytology and CB were combined, sensitivity improved to 77 %. The pathological findings of the CB specimens were similar to the surgical specimens, including immunohistochemistry., Conclusion: The overnight-stored pancreatic juice CB method was more effective than single cytology, with similar sensitivities to multiple cytology and can also be used for immunohistochemistry. The pancreatic juice CB method is useful for pancreatic juice assessment., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX are widely used as first-line regimens for unresectable pancreatic cancer (PC). When GnP therapy is selected, considering patient age or condition, second-line FOLFIRINOX is sometimes difficult to administer owing to its toxicity. This study aimed to determine the recommended dose (RD) of S-IROX (S-1, oxaliplatin, and irinotecan combination) regimens in patients with unresectable PC after first-line GnP failure. This phase-I study used the "3 + 3" dose-escalation design with two dose levels. Patients who failed first-line GnP therapy for unresectable PC were enrolled. Oxaliplatin and irinotecan were administered on day 1, and S-1 was administered orally twice daily on days 1-7, followed by 7 days of rest. The primary endpoints were dose-limiting toxicities (DLTs) and determination of RD. The secondary endpoint was the evaluation of potential antitumor activity. Nine patients received the second-line S-IROX regimen. In level-0 (S-1, 80 mg/m 2 ; oxaliplatin, 85 mg/m 2 ; and irinotecan, 120 mg/m 2 ), no patient experienced DLT; however, one patient experienced grade 3 neutropenia. At level-1 (irinotecan increased to 150 mg/m 2 ), one of six patients experienced DLTs, including G3 diarrhea. The RD was confirmed at the level-1 dose. The response rate, disease control rate, median progression-free survival, and median overall survival were 33.3%, 77.8%, 172 (range:77-422) days, and 414 (101-685) days, respectively. One patient underwent surgery after the second-line S-IROX therapy. Second-line S-IROX treatment was deemed acceptable. The RD was set at level-1 dose (S-1, 80 mg/m 2 ; oxaliplatin, 85 mg/m 2 ; and irinotecan, 150 mg/m 2 )., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The identification of anticancer therapies using next-generation sequencing (NGS) is necessary for the treatment of cholangiocarcinoma. NGS can be easily performed when cell blocks (CB) are obtained from bile stored overnight. We compared NGS results of paired CB and surgically resected specimens (SRS) from the same cholangiocarcinoma cases. Of the prospectively collected 64 bile CBs from 2018 to 2023, NGS was performed for three cases of cholangiocarcinoma that could be compared with the SRS results. The median numbers of DNA and RNA reads were 95,077,806 [CB] vs. 93,161,788 [SRS] and 22,101,328 [CB] vs. 24,806,180 [SRS], respectively. We evaluated 588 genes and found that almost all genetic alterations were attributed to single-nucleotide variants, insertions/deletions, and multi-nucleotide variants. The coverage rate of variants in SRS by those found in CB was 97.9-99.2%, and the coverage rate of SRS genes by CB genes was 99.6-99.7%. The NGS results of CB fully covered the variants and genetic alterations observed in paired SRS samples. As bile CB is easy to prepare in general hospitals, our results suggest the potential use of bile CB as a novel method for NGS-based evaluation of cholangiocarcinoma.

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.

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., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background and Aims: Covered self-expandable metallic stents have longer patency than uncovered self-expandable metallic stents for unresectable malignant distal biliary obstruction because of the prevention of tumor ingrowth, and they are removable during reintervention. One main cause of recurrent biliary obstruction in covered self-expandable metallic stents is sludge formation, which can be prevented by using large-bore stents. We evaluated the treatment results of 12-mm and 10-mm covered self-expandable metallic stents for unresectable malignant distal biliary obstructions using a randomized controlled trial., Methods: This study was conducted between May 2016 and January 2019 and included 81 consecutive patients with unresectable malignant distal biliary obstruction. The primary endpoint was the rate of nonrecurrent biliary obstruction at 6 months after stent placement., Results: The primary endpoint in the 12-mm group was significantly higher than that in the 10-mm group (P = .0369). Therefore, the median time to recurrent biliary obstruction was 172 days in the 12-mm group and 120 days in the 10-mm group. The median time to recurrent biliary obstruction in the 12-mm group was significantly longer than that in the 10-mm group (P = .0168). Using the 12-mm covered self-expandable metallic stents and receiving chemotherapy were factors affecting the rate of recurrent biliary obstruction in the multivariate analysis., Conclusions: The 12-mm covered self-expandable metallic stents provide a longer time to recurrent biliary obstruction than do 10-mm covered self-expandable metallic stents for managing unresectable malignant distal biliary obstruction. (Clinical trial registration number: UMIN000016911.)., Competing Interests: Disclosure All authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background/aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) using a 19-gauge needle is an efficient sampling method for the diagnosis of lymphadenopathy. This study compared 19-gauge conventional and Franseen needles for the diagnosis of lymphadenopathy and classification of malignant lymphoma (ML)., Methods: Patient characteristics, number of needle passes, puncture route, sensitivity, specificity, and accuracy of cytology/histology for lymphadenopathy were analyzed in patients diagnosed with lymphadenopathy by EUS-FNA using conventional or Franseen needles., Results: Between 2012 and 2022, 146 patients met the inclusion criteria (conventional [n=70] and Franseen [n=76]). The median number of needle passes was significantly lower in the conventional group than in the Franseen group (3 [1-6] vs. 4 [1-6], p=0.023). There were no significant differences in cytological/histological diagnoses between the two groups. For ML, the immunohistochemical evaluation rate, sensitivity of flow cytometry, and cytogenetic assessment were not significantly different in either group. Bleeding as adverse events (AEs) were observed in three patients in the Franseen group., Conclusions: Both the 19-gauge conventional and Franseen needles showed high accuracy in lymphadenopathy and ML classification. Considering sufficient tissue collection and the avoidance of AEs, the use of 19-gauge conventional needles seems to be a good option for the diagnosis of lymphadenopathy.

Background: Extracorporeal shock wave lithotripsy (ESWL) is a common treatment for pancreatic stones in chronic pancreatitis. In contrast, peroral pancreatoscopy-guided lithotripsy (POPS-L) remains underexplored, with limited comparative studies to ESWL. This study compared the treatment outcomes of disposable POPS-L tools and ESWL for pancreatic stones., Methods: A retrospective analysis was conducted on 66 patients who had undergone pancreatic stone treatment at three institutions between 2006 and 2022. The treatment outcomes of POPS-L and ESWL were compared., Results: This study included 19 and 47 patients who had undergone POPS-L and ESWL, respectively. In a comparison between POPS-L and ESWL, the stone clearance rates were 78.9% vs. 70.2% ( p = 0.55), while the procedure-related complication rates were 21% vs. 6.3% ( p = 0.09). The median total session counts were 1 vs. 5 ( p < 0.01). The cumulative stone recurrence rates were comparable in both groups. Multivariate analysis revealed no significant factors influencing the stone clearance rates, and the choice between POPS-L and ESWL did not affect the stone clearance rates., Conclusions: POPS-L and ESWL exhibited comparable treatment outcomes in terms of stone clearance, complications, and recurrence rates. Furthermore, POPS-L is advantageous due to the need for fewer sessions to achieve pancreatic stone clearance.

Background: Although intraductal plastic stent (IS) placement is an effective treatment for unresectable malignant hilar biliary obstruction (UMHBO), the effectiveness of unilateral and bilateral IS drainage remains controversial. This retrospective study investigated the effectiveness of bilateral IS placement for UMHBO using the propensity score matching method., Methods: Patients who underwent transpapillary endoscopic stenting for UMHBO were analyzed for technical and clinical success, adverse events, and time to recurrent biliary obstruction (TRBO)., Results: A total of 321 patients were enrolled in the study with 27 patients in each unilateral and bilateral IS group in the propensity score-based cohort. Technical success was 100%, while clinical success was 93% and 96% in the unilateral and bilateral IS groups, respectively (p = 1.0). Cholecystitis occurred in 4% and 7%, respectively (p = 1.0). The median TRBO was shorter in the unilateral group (129 [5-383] days) than that in the bilateral group (226 [16-563] days) (p = .0281). Bilateral IS placement was an independent long TRBO factor (hazard ratio [HR] 0.46; 95% confidence interval [CI]: 0.21-0.97; p = .041)., Conclusions: Unilateral and bilateral IS placement had high technical and clinical success rates in primary stent placement. However, bilateral IS placement showed a longer TRBO. Bilateral IS placement may be a good option for initial UMHBO drainage., (© 2023 Japanese Society of Hepato‐Biliary‐Pancreatic Surgery.)

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., Competing Interests: Conflict of Interest YN received research grants from Boston Scientific Japan, Fujifilm Corporation, and HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, Olympus Corporation, and Gadelius Medical. HI received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gadelius Medical KK, and Zeon Medical Inc., and honoraria from Boston Scientific Japan, Fujifilm Corporation, Taewoong Medical Devices, Olympus Corporation, Century Medical Inc., and Cook Medical Japan G.K. Other authors have no conflicts of interest to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

A 59-year-old man receiving sunitinib chemotherapy for postoperative recurrence of renal cell carcinoma (RCC) metastases was found to have multiple metastases on contrast-enhanced computed tomography (CECT). CECT revealed a typical hyperdense enhanced nodule in the arterial phase of the stomach and head and tail of the pancreas. However, in the uncinate process of the pancreas, CECT revealed an atypical image and a hypodense enhanced nodule in each phase. Both lesions were finally pathologically diagnosed as clear cell carcinoma. Treatment-modified pancreatic metastases from RCC may present with nonspecific images; therefore, caution is required when deciding on treatment strategies.

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., (© 2023. The Author(s).)

Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Therefore, indicators that can be used for the early prediction of the prognosis of PDAC are needed. Peroxiredoxin (PRDX) 4 is a secretion-type antioxidant enzyme located in the cytoplasmic endoplasmic reticulum. Recent studies have reported that it is closely related to the development and prognosis of many types of cancer. Perilipin (PLIN) 2 is a lipid droplet coating protein. The high expression of PLIN2 is known to be an indicator of some types of cancer and oxidative stress management. It is highly suggestive of the interplay between PRDX4 and PLIN2 to some degree. In this study, we collected 101 patients' clinical data and paraffin-embedded specimens with PDAC and analyzed them with immunohistochemical staining of PRDX4 and PLIN2. We found that the low expression of PRDX4 predicts longer survival and a better clinical condition in PDAC patients. Moreover, when the low expression of PRDX4 is combined with the low expression of PLIN2, the 3-year survival is significantly improved. Univariate and multivariate Cox proportional hazard analyses showed that the PRDX4 expression in PDAC was an independent prognostic factor for survival. Taken together, between PRDX4 and PLIN2, PRDX4 plays a main role in prognosis and has the potential to become a clinical prognostic indicator of PDAC., (©The Author(s) 2023. Open Access. This article is licensed under a Creative Commons CC-BY International License.)

Background and Aims: Intraductal plastic stent (IS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage. However, the effectiveness of bilateral IS placement compared with bilateral self-expandable metal stent (SEMS) placement remains unclear., Methods: Overall, 301 patients with UMHBO were enrolled; 38 patients underwent bilateral IS placement (IS group) and 38 patients underwent SEMS placement (SEMS group) in the propensity score-based cohort. Both groups were compared for technical and clinical success, adverse events (AEs), recurrent biliary obstruction (RBO), time to RBO (TRBO), overall survival (OS), and endoscopic reintervention (ERI)., Results: No significant differences were observed between the groups regarding technical and clinical success, AEs and RBO occurrence rates, TRBO, or OS. The median initial endoscopic procedure time was significantly shorter in the IS group (23 vs 49 minutes, P < .01). ERI was performed on 20 and 19 patients in the IS and SEMS groups, respectively. The median ERI procedure time was significantly shorter in the IS group (22 vs 35 minutes, P = .04). Median TRBO after ERI with plastic stent placement tended to be longer in the IS group (306 vs 56 days, P = .068). A Cox multivariate analysis showed that the IS group was the significant related factor for TRBO after ERI (hazard ratio, .31; 95% confidence interval, .25-.82; P = .035)., Conclusions: Bilateral IS placement can reduce the duration of the endoscopic procedure and provide sufficient stent patency both initially and after ERI stent placement, and the stents are removable. Bilateral IS placement is considered a good option for initial UMHBO drainage. (Clinical trial registration number: UMIN000050546.)., Competing Interests: Disclosure All authors disclosed no financial relationships. This work was supported by JSPS KAKENHI (grant no. JP23K14646, Mitsuru Okuno)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objectives: Bilateral self-expandable metallic stent (SEMS) placement for unresectable malignant hilar biliary obstruction (UMHBO) is an effective option for biliary drainage with long-term stent patency. Laser-cut and braided SEMS can be used for bilateral SEMS placement. This study aimed to clarify any differences in the clinical features and proper use of the laser-cut and braided SEMS placement using the stent-in-stent method for UMHBO., Methods: In this study, 78 patients who underwent bilateral stent-in-stent SEMS placement for UMHBO were included. The patients were divided into the laser-cut (n = 33) and braided groups (n = 45). Both groups were compared for technical and clinical success, adverse events (AEs), time to recurrent biliary obstruction (TRBO), overall survival, and endoscopic reintervention (ERI)., Results: There were no significant differences in technical and clinical success rates (laser-cut vs. braided group, 97% vs. 95.6%, P = 1.0), AEs (21.2% vs. 15.6%. P = 0.56), median TRBO (242 days vs. 140 days, P = 0.36), and median overall survival (654 days vs. 675 days, P = 0.58). ERI was required in 15 patients in the laser-cut group and in 20 patients in the braided group. The technical and clinical success rates of ERI (60% vs. 85%) were not significantly different (P = 0.13); however, the median ERI procedure time was significantly longer in the laser-cut group (38 min) than in the braided group (22 min; P = 0.02)., Conclusion: No significant difference in initial SEMS placement was noted between the laser-cut and braided groups; however, the laser-cut group required a longer ERI procedure time than that required by the braided group. The use of braided SEMS may be a convenient option for ERI., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pancreatic fluid collections (PFCs) typically develop as local complications of acute pancreatitis and complicate the clinical course of patients with acute pancreatitis and potentially fatal clinical outcomes. Interventions are required in cases of symptomatic walled-off necrosis (WON) (matured PFCs with necrosis) and pancreatic pseudocysts (matured PFCs without necrosis). In the management of necrotizing pancreatitis and WON, endoscopic ultrasound-guided transluminal drainage combined with on-demand endoscopic necrosectomy (i.e. the step-up approach) is increasingly used as a less invasive treatment modality compared with a surgical or percutaneous approach. Through the substantial research efforts and development of specific devices and stents (e.g. lumen-apposing metal stents), endoscopic techniques of PFC management have been standardized to some extent. However, there has been no consensus about timing of carrying out each treatment step; for instance, it is uncertain when direct endoscopic necrosectomy should be initiated and finished and when a plastic or metal stent should be removed following clinical treatment success. Despite emerging evidence for the effectiveness of noninterventional supportive treatment (e.g. antibiotics, nutritional support, irrigation of the cavity), there has been only limited data on the timing of starting and stopping the treatment. Large studies are required to optimize the timing of those treatment options and improve clinical outcomes of patients with PFCs. In this review, we summarize the current available evidence on the indications and timing of interventional and supportive treatment modalities for this patient population and discussed clinical unmet needs that should be addressed in future research., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Endoscopic ultrasound-guided antegrade treatment (EUS-AG) and balloon endoscopy-assisted endoscopic retrograde cholangiopancreatography (BE-ERCP) have emerged as useful procedures for managing bile duct stones (BDS) in patients with surgically altered anatomy. However, the comparison between these two procedures has not been well studied. The aim of our study was to compare the clinical outcomes of EUS-AG and BE-ERCP for managing BDS in patients with surgically altered anatomy., Methods: The database was retrospectively evaluated at two tertiary care centers to identify patients with surgically altered anatomy who underwent either EUS-AG or BE-ERCP for BDS. Clinical outcomes were compared between the procedures. The success rate of each procedure was evaluated in three steps: endoscopic approach, biliary access, and stone extraction., Results: Among the 119 identified patients, 23 had EUS-AG, and 96 had BE-ERCP. The overall technical success rates of EUS-AG and BE-ERCP were 65.2% (15/23) and 69.8% (67/96), respectively (P = .80). The comparison of each step between the procedures EUS-AG versus BE-ERCP was as follows: endoscopic approach, 100% (23/23) versus 88.5% (85/96) (P = .11); biliary access, 73.9% (17/23) versus 80.0% (68/85) (P = .57); stone extraction, 88.2% (15/17) versus 98.5% (67/68) (P = .10). The overall adverse event rate was 17.4% (4/23) versus 7.3% (7/96) (P = .22)., Conclusions: Both EUS-AG and BE-ERCP are effective and relatively safe procedures in the management of BDS in patients with surgically altered anatomy. The challenging steps of each procedure might be different, which could help decide which one to use to manage BDS in patients with surgically altered anatomy., (© 2023 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background and Aims: A novel EUS-guided fine-needle biopsy sampling (EUS-FNB) needle enabled physicians to obtain sufficient pathologic samples with fewer to-and-fro movements (TAFs) within the lesion. We compared the diagnostic yields of EUS-FNB with 3 and 12 TAFs at each puncture pass., Methods: The primary endpoint of this multicenter, noninferiority, crossover, randomized controlled trial involving 6 centers was diagnostic sensitivity. Secondary endpoints were diagnostic accuracy and quantity and quality evaluation of EUS-FNB specimens. Length of the macroscopically visible core (MVC) and microscopic histologic quantity were used for quantitative evaluation. Macroscopic visual and microscopic histologic evaluations were performed for qualitative evaluation., Results: Among 110 patients (220 punctures, 110 for 3 TAFs and 12 TAFs each), 105 (210 punctures) had malignant histology. Diagnostic sensitivity for malignancy of 3 TAFs (88.6%) was not inferior to that of 12 TAFs (89.5%; difference, -.9%; 95% confidence interval, -9.81 to 7.86). Diagnostic accuracy for malignancy was 92.7% for 3 TAFs and 94.6% for 12 TAFs. Overall median MVC length was 13.5 mm in both groups. The 3-TAF group had a significantly higher rate of score ≥3 on macroscopic visual quality evaluation than the 12-TAF group (71.8% vs 52.7%, P = .009). No significant intergroup differences existed in microscopic histologic quantity and quality evaluations (quantity evaluation, 88.2% for 3 TAFs vs 83.6% for 12 TAFs; quality evaluation, 90.0% for 3 TAFs vs 89.1% for 12 TAFs)., Conclusions: Diagnostic sensitivity and accuracy of EUS-FNB with 3 TAFs were not inferior to those with 12 TAFs for solid pancreatic lesions. The 3-TAF group showed significantly less blood contamination in sampled tissues than the 12-TAF group. (Clinical trial registration number: UMIN000037309.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Sludge occlusion is a primary reason for recurrent biliary obstruction (RBO) after self-expandable metallic stent (SEMS) placement. However, the efficacy of ursodeoxycholic acid (UDCA) for SEMS occlusion remains unexplored to date. This study aimed to evaluate the efficacy of UDCA after SEMS placement for malignant distal biliary obstruction (MDBO)., Methods: Three hundred fifty-four patients were included, of which 60 received UDCA. Additionally, we conducted a propensity score-matched cohort analysis on 110 patients with SEMS placement for MDBO to reduce selection bias. Patients were categorized into 2 groups of 55 each, based on whether they received UDCA. In the UDCA group, the treatment was administered for more than a month. The primary endpoint was the time to RBO (TRBO) after SEMS placement. The secondary endpoint was to evaluate SEMS occlusion rate and early adverse events (AEs)., Results: The cumulative SEMS occlusion rate was 41.8% and 18.2% in the groups with and without UDCA, respectively (P = .0119). Median TRBO was significantly longer in the control group than in the UDCA group (528 vs 154 days, P = .0381). In the multivariate analysis, UDCA administration was identified as the independent risk factor for reducing TRBO (hazard ratio, 2.28; 95% confidence interval, 1.06-4.88; P = .0348). The overall early AE rate showed insignificant differences between groups., Conclusions: Administering UDCA after SEMS placement was not efficacious for prolonging the TRBO in MDBO. Moreover, administering UDCA beyond a month might increase the risk of stent sludge occlusion. (Clinical trial registration number: UMIN000046862.)., (Copyright © 2023 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Video 1Management of ampullary perforation by endoscopic nasobiliary drainage tube placement through the perforation for suctioning out leaked intestinal juice and indicating the presence of the hepatic portal vein., (© 2022 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Objectives: Interventions for necrotizing pancreatitis are generally postponed until 4 weeks after the onset of acute pancreatitis, but there remains controversy about whether we should always wait >4 weeks or can intervene early when necessary. This meta-analysis was conducted to evaluate treatment outcomes of necrotizing pancreatitis according to the cut-off defined in the revised Atlanta classification (≤4 vs. >4 weeks)., Methods: Using PubMed, Web of Science, and the Cochrane database, we identified clinical studies published until March 2022 with data comparing outcomes of early and delayed interventions of necrotizing pancreatitis. We pooled data on adverse events, mortality, technical and clinical success rates, and needs for necrosectomy and open surgery, using the random-effects model., Results: We identified 11 retrospective studies, including 775 patients with early interventions and 725 patients with delayed interventions. Patients with early interventions tended to be complicated by organ failure. The rate of adverse events was comparable (OR 1.41, 95% CI 0.66-3.01; p  = 0.38) but the rate of mortality was significantly higher (OR 1.70, 95% CI 1.21-2.40; p  < 0.01) in early interventions. Technical success rates were similarly high but clinical success rates tended to be low (OR 0.39, 95% CI 0.15-1.00; p  = 0.05) in early interventions, though not statistically significant. Pooled ORs for necrosectomy and open surgery were 2.14 and 1.23, respectively., Conclusions: Early interventions for necrotizing pancreatitis were associated with higher mortality rates and did not reduce adverse events or improve clinical success. However, our results should be confirmed in prospective studies., Competing Interests: Yousuke Nakai received research grants from Boston Scientific Japan, HOYA Corporation, and honoraria from Boston Scientific Japan, Fujifilm Corporation, and Olympus Corporation. Hiroyuki Isayama received research grants from Boston Scientific Japan, Fujifilm Corporation, Fujifilm Health Care Corporation, Gaderius Medical KK, Zeon Medical Inc., and honoraria from Boston Scientific Japan, Fujifilm Corporation, Taewoong Medical Devices, Olympus Corporation, Century Medical, Inc. and Cook Medical Japan G.K., (© 2022 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: During endoscopic ultrasound-guided biliary drainage (EUS-BD), a combination of a 19-gauge needle and a 0.025-inch guidewire is generally used. However, a 19-gauge needle has poor maneuverability because of their stiffness and rigidity and might have poor penetrability in non-dilated bile ducts because of their large bore. In contrast, the application of a 22-gauge needle is expected to have improved maneuverability. However, only a 0.018-inch guidewire, which has less supportability, is applicable in the subsequent guidewire selection. This study aimed to evaluate the feasibility and safety of a dedicated bougie dilator for a 0.018-inch guidewire., Methods: From September 2019 to May 2020, 26 patients underwent fistula dilation using the dilator after accessing the bile duct using a 22-gauge needle and a 0.018-inch guidewire during EUS-BD. The success and adverse event rates of EUS-BD were evaluated., Results: Biliary access with a combination of a 22-gauge needle and a 0.018-inch guidewire was successful in all with a median bile duct diameter of 5 mm. Dilation of the fistula using the dedicated dilator was also successful in all cases. Subsequently, the dilator was successfully exchanged to an ERCP catheter that allowed for exchange to a 0.025-inch guidewire, except in one case where the catheter did not cross the fistula and a dilation balloon was inserted for an exchange to a 0.025-inch guidewire. The technical success rate of the EUS-BD was 100%. The adverse event rate was 19%., Conclusion: The application of the dedicated dilator for a 0.018-inch guidewire was considered feasible and safe for EUS-BD., (© 2021 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background & Aims: The efficacy of endoscopic sphincterotomy (ES) before endoscopic transpapillary biliary drainage in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) has not been established. The aim of this study was to evaluate the effect of performing ES before biliary stent/tube placement on the occurrence of PEP., Methods: Three hundred seventy patients with biliary stricture requiring endoscopic biliary stenting were enrolled and randomly allocated to the ES group (n = 185) or non-ES group (n = 185). All participants were followed up for 30 days after the procedure. The data and occurrence of adverse events were prospectively collected. The primary outcome measure of this study was the incidence of PEP within 2 days of initial transpapillary biliary drainage. Secondary outcome measures were the incidence of other adverse events related to biliary stent/tube placement., Results: PEP occurred in 36 patients (20.6%) in the non-ES group and in 7 patients (3.9%) in the ES group (P < .001). The difference in the incidence of PEP between the 2 groups in the per-protocol population was 16.7% (95% confidence interval, 10.1%-23.3%), which was not within the noninferiority margin of 6%. Except for bleeding, the incidences of other adverse events were not significantly different between the groups., Conclusion: ES before endoscopic biliary stenting could have the preventive effect on the occurrence of PEP in patients with biliary stricture. University Hospital Medical Information Network Number, UMIN000025727.University Hospital Medical Information Network Clinical Trial Registry URL: https://www.umin.ac.jp/ctr/index.htm., (Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.)

The specimen collection and subsequent pathological diagnosis of malignant biliary stricture (MBS) are difficult. This study aimed to determine whether the cell block (CB) method using overnight-stored bile is useful in the diagnosis of MBS. This trial was a single-arm prospective study involving a total of 59 patients with suspected MBS. The primary endpoint was cancer detectability and accuracy using the CB method, and a comparison with the detectability and accuracy achieved with bile cytology was made. The immunohistochemical sensitivity for maspin and p53 was also investigated in the CB and surgical specimens. We were able to collect bile from all 59 patients, and 45 of these patients were clinically diagnosed with MBS. The cancer detectability using the CB method (62.2%) was significantly higher than that using cytology (37.8%) ( p = 0.0344). When CB was combined with biopsy, the rates of cancer detectability (75.6%) and accuracy (81.4%) increased. In eight patients who received surgical therapy, maspin- and p53-immunohistochemistry was applied to the surgical and CB specimens, and cancer cells in both specimens showed positive cytoplasmic and nuclear staining for maspin and nuclear staining for p53. The CB method is, thus, useful for detecting malignancy (UMIN000034707).

After an abdominal injury, a woman in her 20s presented to our hospital with abdominal pain. Pancreatic trauma was discovered on computed tomography, along with a pancreatic duct injury and pancreatic juice leakage. Endoscopic retrograde pancreatography revealed a 10-mm rupture of the pancreatic body's main pancreatic duct (MPD) and intraperitoneal leakage of contrast enzyme from the MPD. The pancreatic injury was treated with the placement of a 5-Fr endoscopic nasopancreatic drainage tube in the ruptured distal side of the pancreatic duct;however, 3 months later, the MPD stenosis occurred. The MPD stenosis was improved using a 7-Fr pancreatic stent, and finally, placement of the pancreatic stent was not required for MPD drainage.

Video 1After insertion of the cholangioscope into the common bile duct, electrohydraulic lithotripsy was performed. All common bile duct stones were shattered and successfully removed using a basket and balloon catheter., (© 2021 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc.)

Background: Intestinal perforation is a severe adverse event during pancreaticobiliary endoscopy. The use of over-the-scope clip (OTSC) has recently increased; however, the efficacy of OTSC during pancreaticobiliary endoscopy has not been well studied., Aims: To evaluate the efficacy of OTSC for the closure of gastrointestinal iatrogenic perforation during pancreaticobiliary endoscopy., Patients and Methods: This was a retrospective multicenter cohort study conducted at 3 tertiary care centers. The inclusion criteria were patients who had gastrointestinal perforation during endoscopic procedures for pancreaticobiliary diseases and underwent perforation closure using OTSC. The primary outcome was the clinical success rate. Secondary outcomes were technical success rates, adverse event rates, and the duration until the start of oral intake after OTSC., Results: Ten patients were treated by OTSC from January 2013 to December 2017. In 2 out of 10, the perforations could not be closed completely. In the remaining 8, perforations were closed completely, but intestinal obstruction caused by OTSC occurred in 1 patient. The clinical success rate was 80% (8/10). The technical and adverse event rates were 80% (8/10) and 10% (1/10), respectively. A median resumption timing of oral intake was 5 days (range, 3 to 10 d)., Conclusion: OTSC is considered as effective management for perforations during pancreaticobiliary endoscopy, although careful consideration is required for the indication of OTSC.

Background and Aims: Contrast-enhanced EUS (CE-EUS) allows qualitative and quantitative evaluation based on real-time perfusion imaging and may improve the diagnostic capability. The aim of this study was to evaluate the efficacy of CE-EUS in differentiating malignant from benign lymphadenopathy., Methods: Patients undergoing EUS-FNA for abdominal or mediastinal lymphadenopathy were prospectively enrolled. The echofeatures on B-mode EUS and the vascular and enhancement patterns in CE-EUS were qualitatively evaluated. The echo intensity change during 60 seconds in the lymphadenopathy was quantitatively evaluated by time intensity curve (TIC) analysis., Results: One hundred consecutive patients with 70 malignant and 30 benign lesions were enrolled. The sensitivity, specificity, and accuracy of the qualitative assessment in B-mode EUS were 77%, 17%, and 59%, respectively. When the heterogeneous enhancement was defined as malignancy, the sensitivity, specificity, and accuracy of the qualitative assessment in CE-EUS were 67%, 87%, and 73%, respectively. In TIC analysis, the velocity of reduction for homogeneous lesions showed a significant difference between malignant and benign lesions (P = .0011), and the receiver operating characteristic analysis showed an optimal cut-off value of .149 dB/s. The sensitivity, specificity, and diagnostic capabilities of CE-EUS for malignancy were improved to 89%, 77%, and 85%, respectively, on combining the qualitative and quantitative analyses. With regard to diagnostic accuracy, CE-EUS with combined qualitative and quantitative analyses was significantly higher than those of B-mode EUS or qualitative assessment of CE-EUS., Conclusions: CE-EUS with the combined qualitative and quantitative analyses for lymphadenopathy might be useful to complement regular EUS and EUS-FNA. (Clinical trial registration number: UMIN000024298.)., (Copyright © 2019 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Malignant gastric outlet obstruction (GOO) often develops in patients with advanced pancreatic cancer (APC). It is not clear whether endoscopic duodenal stenting (DS) or surgical gastrojejunostomy (GJJ) is preferable as palliative treatment., Aims: To compare the efficacy and safety of GJJ and DS for GOO with APC., Methods: Consecutive 99 patients who underwent DS or GJJ for GOO with APC were evaluated. We compared the technical and clinical success rates, the incidence of adverse event (AE), the time to start chemotherapy and discharge and survival durations between DS and GJJ. Prognostic factors for overall survival (OS) were investigated on the multivariate analysis., Results: GOO was managed with GJJ in 35 and DS in 64. The technical and clinical success rates were comparable. DS was associated with shorter time to start oral intake and earlier chemotherapy start and discharge. No difference was seen in the early and late AE rates. Multivariate analyses of prognostic factors for OS showed that performance status ≧2, administration of chemotherapy, and presence of obstructive jaundice to be significant factors. There were no significant differences in survival durations between the groups, regardless of the PS., Conclusions: There were no significant differences in the technical and clinical success and AE rates and survival duration between DS and GJJ in management of GOO by APC. DS may be a preferable option over GJJ given that it will lead to an earlier return to oral intake, a shortened length of hospital stay, and finally an earlier referral for chemotherapy., (Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Objectives: The aim of this study was to assess prevailing treatment of pancreatolithiasis in Japan., Methods: We surveyed clinical data from 1834 patients (1479 men and 355 women) at 125 hospitals., Results: Extracorporeal shock-wave lithotripsy (ESWL) was performed alone in 103 patients (5.6%), ESWL plus an endoscopic procedure in 446 (24.3%), endoscopic treatment alone in 261 (14.2%), and surgery in 167 (9.1%). Other treatments were given to 358 (19.5%), whereas 499 (27.2%) received no treatment. Symptoms were relieved in 85.7% after ESWL, 80.8% after endoscopic treatment alone, and 92.8% after surgery. Early complication rates within 3 months after ESWL, endoscopic treatment alone, and surgery were 8%, 4.5%, and 27.1%, respectively. Late complications after ESWL, endoscopic procedures alone, and surgery were 1.7%, 2.5%, and 8.2%, respectively. Symptom relief but also early and late complications were greater after surgery than after ESWL and endoscopic treatment. Among 417 patients undergoing ESWL, 61 (14.6%) required surgery, as did 32 (16%) of 200 patients treated endoscopically. Surgery was required less frequently following initial operative treatment (11/164 patients [6.7%]). Nonsurgical initial treatments were chosen more frequently., Conclusions: First-line treatment of pancreatolithiasis should be ESWL with or without endoscopy because of minimal invasiveness and fewer complications.

Background/aim: The aim of the present study was to further develop our previous study on c-Met expression in colorectal cancer and epithelial-mesenchymal transition (EMT) induced by hepatocyte growth factor (HGF), to investigate EMT in the process of liver metastases, and evaluate the effects of chemotherapy on EMT cells as a therapeutic strategy for colorectal liver metastasis., Materials and Methods: CT26 colon cancer cells were treated with 5-FU and oxaliplatin with or without HGF. The signaling pathway was evaluated by western blotting analysis, and drug resistance was evaluated by the MTT (3-(4,5-dimethyl-2-tetrazolyl)-2,5-diphenyl-2H tetrazolium bromide) assay., Results: Under pretreatment with HGF for 96 h, 5 μM and 10 μM of 5-FU mediated significant growth inhibition by 72.5±3.9% and 76.2±2.4%, respectively, compared to HGF alone, and by 105.1±2.8% and 103.5±2.9%, respectively, without HGF. The expression of E2F1 was decreased significantly to 50.5±3.8% after 24 hours by HGF with a reduction of both cyclin D1 to 52.1±7.0% and E to 73.7±3.8%. Thymidylate synthase was also decreased in a time-dependent manner to 80.6±2.0% after 24 h and to 52.7±1.5% after 96 h., Conclusion: The presence of HGF was found to increase the 5-FU-induced death signal, JNK pathway, and inhibition of cell growth. As its mechanism, HGF was shown to decrease E2F-1 by reducing cyclin D or E by cell-cycle activation, resulting in inactivation of thymidylate synthase. The chemotherapeutic effect of 5-FU was increased in HGF- but not TGF-β-induced EMT., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Aim: In patients with unresectable malignant distal biliary obstruction, covered self-expandable metallic stents (CSEMS) may remain patent longer than uncovered self-expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large-bore stent. Therefore, we developed a novel, 12-mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events., Methods: This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non-RBO rate 6 months after placement., Results: Technical and functional success rates of the procedures were 100%. Six-month non-RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at <30 days) developed in six patients (16%; cholecystitis, one; pancreatitis, one; hyperamylasemia, one; pancreatic ductitis, one; abdominal pain, two). Stent removal for reintervention was successfully completed in eight patients., Conclusion: Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events., (© 2016 Japan Gastroenterological Endoscopy Society.)

Aim: To evaluate the differences in the treatment outcomes between the unresectable and recurrent biliary tract cancer patients who received chemotherapy., Methods: Patients who were treated with gemcitabine and S-1 combination therapy in the previous prospective studies were divided into groups of unresectable and recurrent cases. The tumor response, time-to-progression, overall survival, toxicity, and dose intensity were compared between these two groups., Results: Response rate of the recurrent group was higher than that of the unresectable group (40.0% vs 25.5%; P = 0.34). Median time-to-progression of the recurrent and unresectable groups were 8.7 mo (95%CI), 1.2 mo, not reached) and 5.7 mo (95%CI: 4.0-7.0 mo), respectively (P = 0.14). Median overall survival of the recurrent and the unresectable groups were 16.1 mo (95%CI: 2.0 mo-not reached) and 9.6 mo (95%CI: 7.1-11.7 mo), respectively (P = 0.10). Dose intensities were significantly lower in the recurrent groups (gemcitabine: recurrent group 83.5% vs unresectable group 96.8%; P < 0.01, S-1: Recurrent group 75.9% vs unresectable group 91.8%; P < 0.01). Neutropenia occurred more frequently in recurrent group (recurrent group 90% vs unresectable group 55%; P = 0.04)., Conclusion: Not only the efficacy but also the toxicity and dose intensity were significantly different between unresectable and recurrent biliary tract cancer.

Background: Endoscopic biliary stenting is a well-established palliative treatment for unresectable malignant biliary strictures, for which plastic tube stents (PSs) and self-expandable metallic stents (SEMSs) are most commonly used. The efficacy of these stents has been extensively described in distal biliary strictures, but not in hilar biliary strictures. The present study aimed to compare the efficacy of PSs and SEMSs for unresectable malignant hilar biliary strictures., Methods: From June 2004 to November 2008, 60 patients were enrolled and prospectively randomized into the PS or SEMS group., Results: The 6-month patency rate was significantly higher in the SEMS group than in the PS group (81 vs. 20%; p = 0.0012). Kaplan-Meier analysis showed significantly longer patency in the SEMS group than in the PS group (p = 0.0002); the 50% patency period was 359 days in the SEMS group and 112 days in the PS group. There was no significant difference in the overall survival period between the PS and SEMS groups (p = 0.2834). The mean number of reinterventions for stent failures was significantly lower in the SEMS group (0.63 times/patient) than in the PS group (1.80 times/patient) (p = 0.0008). The overall total cost for the treatment was significantly lower in the SEMS group than in the PS group (p = 0.0222)., Conclusions: SEMSs were associated with a longer patency than PSs in patients with unresectable hilar biliary stricture. SEMSs were also more advantageous in reducing the number of reintervention sessions and the overall treatment cost.

Background: Covered self-expandable metal stents (CSEMSs) were developed to prevent tumor ingrowth, but stent migration is one of the problems with CSEMSs., Objective: To evaluate a new, commercially available CSEMS with flared ends and low axial force compared with a commercially available CSEMS without the anti-migration system and high axial force., Design: Multicenter, prospective study with a historical cohort., Setting: Twenty Japanese referral centers., Patients: This study involved patients with unresectable distal malignant biliary obstruction., Intervention: Placement of a new, commercially available, partially covered SEMS., Main Outcome Measurements: Recurrent biliary obstruction rate, time to recurrent biliary obstruction, stent-related complications, survival., Results: Between April 2009 and March 2010, 141 patients underwent partially covered nitinol stent placement, and between May 2001 and January 2007, 138 patients underwent placement of partially covered stainless stents as a historical control. The silicone cover of the partially covered nitinol stents prevented tumor ingrowth. There were no significant differences in survival (229 vs 219 days; P = .250) or the rate of recurrent biliary obstruction (33% vs 38%; P = .385) between partially covered nitinol stents and partially covered stainless stents. Stent migration was less frequent (8% vs 17%; P = .019), and time to recurrent biliary obstruction was significantly longer (373 vs 285 days; P = .007) with partially covered nitinol stents. Stent removal was successful in 26 of 27 patients (96%)., Limitations: Nonrandomized, controlled trial., Conclusion: Partially covered nitinol stents with an anti-migration system and less axial force demonstrated longer time to recurrent biliary obstruction with no tumor ingrowth and less stent migration., (Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.)

Background & Aims: Histologic techniques are used to distinguish autoimmune pancreatitis (AIP) from pancreatic malignancies and to confirm the etiology of pancreatitis. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is a well-established technique used in the diagnosis of pancreatic cancer. However, it is unclear whether specimens obtained from pancreatic lesions by EUS-FNA are adequate for the histologic diagnosis of AIP, because the evaluation of tissue architecture and immunostaining assays usually require larger samples., Methods: We evaluated samples collected by EUS-FNA with a conventional 19-gauge needle by histologic analysis, looking for features of AIP. We analyzed data from 44 patients who were diagnosed with AIP and underwent EUS-FNA with a 19-gauge needle from January 2004 to September 2010. The FNA specimens were reviewed by histologic analysis; AIP was diagnosed based on the presence of lymphoplasmacytic sclerosing pancreatitis or immunoglobulin (Ig)G4-positive plasma cells in the infiltrate., Results: The specimen amount was inadequate from 3 patients. Among the remaining 41 patients, histopathologic analysis revealed lymphoplasmacytic sclerosing pancreatitis in 17 samples and IgG4-positive plasma cells in 5 (3 samples were positive for both); no samples had granulocytic epithelial lesions. Therefore, 19 patients (43%) were diagnosed with AIP based on histologic analysis. One patient had temporary abdominal pain., Conclusions: EUS-FNA, with a 19-gauge needle, is a safe and reliable procedure for obtaining pancreatic samples for the histologic analysis of AIP. Although it does not have a high diagnostic yield, it might be useful in patients without typical features of AIP because it would allow patients to avoid surgery., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Pancreatitis is the most common and potentially serious complication of post-endoscopic retrograde cholangiopancreatography (ERCP). Post-ERCP pancreatitis (PEP) is caused mostly by postprocedural papillary edema and retention of pancreatic juice. We conducted a randomized controlled trial to determine whether placement of a temporary-type, pancreatic duct stent prevents PEP and to identify risk factors for PEP., Methods: We analyzed data from 426 consecutive patients who underwent ERCP-related procedures at 37 endoscopic units. The patients were assigned randomly to groups that received stents (S group, n = 213) or did not (nS group, n = 213). The stent used was temporary, 5F in diameter, 3 cm long, and straight with an unflanged inner end., Results: The overall frequency of PEP was 11.3%. The frequencies of PEP in the S and nS groups were 7.9% and 15.2%, respectively; the lower incidence of PEP in the S group was statistically significant based on the full analysis set (P = .021), although there was no statistically significant differences in an intention-to-treat analysis (P = .076). There were significant differences in PEP incidence between groups in multivariate analysis for the following risk factors: pancreatography first, nonplacement of a pancreatic duct stent after ERCP, procedure time of 30 minutes or more, sampling of pancreatic tissue by any method, intraductal ultrasonography, and difficulty of cannulation (≥15 min). Patients with more than 3 risk factors had a significantly greater incidence of pancreatitis., Conclusions: Placement of a pancreatic duct stent reduces the incidence of PEP. Several risk factors are associated with PEP., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background/aims: Nonobese diabetic (NOD) mice, a model of type I diabetes mellitus, harbor certain unique defects in their immune system. The aim of this study was to investigate how NOD mice show hepatic injury and subsequent fibrogenic responses., Methods: Hepatic fibrosis was induced by intraperitoneal injections of dimethylnitrosamine (DMN), and assessed biochemically and histologically. Expressions of cytokine messenger RNA (mRNA) in the liver were determined., Results: In a model of liver cirrhosis induced by dimethylnitrosamine (DMN), we found that NOD mice had lower levels of hepatic fibrosis and better survival than control ICR mice. The resistance to DMN-induced lethality in NOD mice was independent of apoptosis and necrosis of hepatocytes, but apparently due to the prevention of hepatic fibrosis. We also found increased inductions of interferon-gamma (IFN-gamma) mRNA in the liver of NOD mice and of intracellular IFN-gamma from intrahepatic T cells following DMN administration. Treatment with neutralizing anti-IFN-gamma-antibody cancelled the inhibition of hepatic fibrosis in NOD mice., Conclusions: These results suggest that IFN-gamma is effective for inhibiting hepatic fibrosis and that genetic host factors may be important in determining differential responses to injury.

Recently, the treatment using biliary stents play an important role to improve the quality of life (QOL) in patients with inoperable malignant biliary obstruction. Long-term patency is preferable, but the convenience of treatment for stent obstruction should also be considered. In this study, we investigated which stent is currently the most appropriate in hilar and extrahepatic bile duct obstruction. In hilar obstruction, metallic stents (MS) had significantly longer patency than plastic tube stents (TS). As for extrahepatic bile duct obstruction, covered MS (CMS) and MS had significantly longer patency than TS. On the other hand, many difficulties occurred when the MS was obstructed. In some of these patients, it was difficult to place the internal drainage again and their QOL was severely impaired. CMS was more convenient because it could be removed when it was obstructed. These results may suggest that MS should be used carefully in the hilar obstruction and that CMS is the best for the treatment of extrahepatic bile duct obstruction.