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Background/Aims The optimal length of the uncovered portion of partially covered self-expandable metal stents (PCSEMSs) used in endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) remains unclear. This study investigated the safety and efficacy of PCSEMSs with different uncovered lengths, with a focus on stent migration and time to recurrent biliary obstruction (RBO). Methods Outcomes of patients undergoing EUS-HGS using PCSEMSs with 5-mm and 20-mm uncovered portions at our institution from January 2016 to December 2021 were compared. Results Sixty-two patients underwent EUS-HGS using PCSEMS (5/20-mm uncovered portions: 32/30). Stent migration occurred only in the 5-mm group. There were no differences in RBO rates (28.1% vs. 40.0%) or median time to RBO (6.8 vs. 7.1 months) between the two groups. Median overall survival (OS) was longer in the 20-mm group (3.1 vs. 4.9 months, p=0.037) due to the higher number of patients that resumed chemotherapy after EUS-HGS (56.7% vs. 28.1%, p=0.029). Good performance status, absence of hepatic metastases, and chemotherapy after EUS-HGS were independent predictors of longer OS. Conclusions No migration was observed in patients treated with PCSEMS with 20-mm uncovered portions. Patients treated with PCSEMS with 20-mm uncovered portions performed at least as well as those treated with 5-mm uncovered portions in all material respects.

Background/Aims Hepaticojejunostomy anastomotic stricture (HJAS) is a feared adverse event associated with hepatopancreatobiliary surgery. Although balloon dilation for benign HJAS during endoscopic retrograde cholangiopancreatography with balloon-assisted enteroscopy has been reported to be useful, the treatment strategy remains controversial. Therefore, we evaluated the outcomes and risk factors of recurrent stenosis after balloon dilation alone for benign HJAS. Methods We retrospectively analyzed consecutive patients who underwent balloon-assisted enteroscopy–endoscopic retrograde cholangiopancreatography for benign HJAS at our institution between July 2014 and December 2020. Results Forty-six patients were included, 16 of whom had recurrent HJAS after balloon dilation. The patency rates at 1 and 2 years after balloon dilation were 76.8% and 64.2%, respectively. Presence of a residual balloon notch during balloon dilation was an independent predictor of recurrence (hazard ratio, 2.80; 95% confidence interval, 1.01–7.78; p=0.048), whereas HJAS within postoperative 1 year tended to be associated with recurrence (hazard ratio, 2.43; 95% confidence interval, 0.85–6.89; p=0.096). The patency rates in patients without a residual balloon notch were 82.1% and 73.1% after 1 and 2 years, respectively. Conclusions Balloon dilation alone may be a viable option for patients with benign HJAS without residual balloon notches on fluoroscopy.

Background/Aims Selective bile duct or pancreatic duct cannulation remains a significant initial hurdle in endoscopic retrograde cholangiopancreatography (ERCP) despite advances in endoscopy and accessories. This study evaluated our experience with a rotatable sphincterotome in cases of difficult cannulation. Methods We retrospectively reviewed ERCP cases using TRUEtome, a rotatable sphincterotome, as a rescue device for cannulation at a cancer institute in Japan from October 2014 to December 2021. Results TRUEtome was used in 88 patients. Duodenoscopes were used for 51 patients, while single-balloon enteroscopes (SBE) were used for 37 patients. TRUEtome was used for biliary and pancreatic duct cannulation (84.1%), intrahepatic bile duct selection (12.5%), and strictures of the afferent limb (3.4%). Cannulation success rates were similar in the duodenoscope and SBE groups (86.3% vs. 75.7%, p=0.213). TRUEtome was more commonly used in cases with steep cannulation angles in the duodenoscope group and in cases requiring cannulation in different directions in the SBE group. There were no significant differences in adverse events between the two groups. Conclusions The cannulation sphincterotome was useful for difficult cannulations in both unaltered and surgically altered anatomies. It may be an option to consider before high-risk procedures such as precut and endoscopic ultrasound-guided rendezvous techniques.

Abstract Objectives Hepaticojejunostomy anastomotic stricture (HJAS) is a serious adverse event of pancreaticoduodenectomy. Preoperative biliary drainage with a self‐expandable metal stent (SEMS) is often performed before pancreaticoduodenectomy. The purpose of this study is to evaluate the risk factors and impact of preoperative SEMS placement on developing benign HJAS after pancreaticoduodenectomy. Methods We retrospectively analyzed consecutive patients who underwent pancreatoduodenectomy at our institution between July 2014 and June 2020. Risk factors for benign HJAS were identified using univariate and multivariate logistic regression analysis. We also compared outcomes of preoperative biliary drainage using SEMS and non‐SEMS. Results Of the 626 included patients, benign HJAS occurred in 36 patients (5.8%). The median follow‐up time was 36.7 months (interquartile range, 25.4–57.4 months). Multivariate logistic regression analysis revealed that lack of preoperative biliary drainage, preoperative bile duct diameter

Abstract Background 10‐mm self‐expandable metal stents (SEMSs) are commonly used for preoperative biliary drainage in pancreatic cancer. However, smaller diameter SEMSs have attracted attention with the attempt to reduce stent‐related adverse events (AEs). Methods We retrospectively analyzed consecutive borderline resectable pancreatic cancer patients who underwent neoadjuvant therapy and fully covered SEMS (FCSEMS) placement from April 2015 to May 2023. The primary outcome was stent‐related non‐event rate (NER), which was defined as the rate of completion of surgery without developing any preoperative events (recurrent biliary obstruction [RBO] or stent‐related AEs). Secondary outcomes included stent‐related AEs, causes of RBO, and cumulative incidence of RBO. Risk factors for pancreatitis, RBO, and stent migration were also examined. Results A total of 76 patients were included (6‐mm group: 23; 10‐mm group: 53). Stent‐related NER (57% vs. 64%, p = 0.610), stent‐related AEs (4% vs. 15%, p = 0.263), overall RBO rates (39% vs. 23%, p = 0.168), cumulative incidence of RBO (hazard ratio, 2.24; 95% confidence interval, 0.95–5.25; p = 0.065) were not significantly different between the two groups. Tumor involvement of the pancreatic duct was identified as a risk‐reducing factor for pancreatitis, while an FCSEMS diameter of 6 mm was not identified as a risk factor for RBO and stent migration. Conclusions Stent‐related NER was not significantly affected by FCSEMS diameter. Further studies are needed to confirm the usefulness of 6‐mm diameter FCSEMS for preoperative biliary drainage in patients with borderline resectable pancreatic cancer.

Abstract We report a case of ruptured cystic artery pseudoaneurysm after self‐expandable metal stent placement for malignant biliary obstruction. A 78‐year‐old woman on palliative care after chemotherapy for unresectable pancreatic head cancer presented with obstructive jaundice. Imaging revealed a dilated common bile duct and an enlarged gallbladder with cystic wall thickening. Endoscopic retrograde cholangiopancreatography was performed and a fully‐covered self‐expandable metal stent was placed in the bile duct, leading to resolution of jaundice. She presented with hematochezia 7 days later. Contrast‐enhanced computed tomography revealed a cystic artery pseudoaneurysm with extravasation of contrast into a blood‐filled gallbladder. Hemostasis was achieved after emergent transcatheter arterial embolization. Rupture of cystic artery pseudoaneurysm should be raised as a differential diagnosis for hemobilia after self‐expandable metal stent placement, particularly in cases accompanied by inflamed gallbladders.

Background/Aims Mechanical properties (MPs) and axial and radial force (AF and RF) may influence the efficacy and complications of self-expandable metallic stent (SEMS) placement. We measured the MPs of various SEMSs and examined their influence on the SEMS clinical ability. Methods We evaluated the MPs of 29 types of 10-mm SEMSs. RF was measured using a conventional measurement device. AF was measured using the conventional and new methods, and the correlation between the methods was evaluated. Results A high correlation in AFs was observed, as measured by the new and conventional manual methods. AF and RF scatterplots divided the SEMSs into three subgroups according to structure: hook-and-cross-type (low AF and RF), cross-type (high AF and low RF), and laser-cut-type (intermediate AF and high RF). The hook-and-cross-type had the largest axial force zero border (>20°), followed by the laser-cut and cross types. Conclusions MPs were related to stent structure. Hook-and-cross-type SEMSs had a low AF and high axial force zero border and were considered safest because they caused minimal stress on the biliary wall. However, the increase in RF must be overcome.

Abstract Alterations in KRAS, CDKN2A (p16), TP53, and SMAD4 genes have been major drivers of pancreatic carcinogenesis. The clinical course of patients with pancreatic cancer in relation to these driver alterations has not been fully characterised in large populations. We hypothesised that pancreatic carcinomas with different combinations of KRAS mutation and aberrant expression of CDKN2A, p53, and SMAD4 might show distinctive recurrence patterns and post‐operative survival outcomes. To test this hypothesis, we utilised a multi‐institutional cohort of 1,146 resected pancreatic carcinomas and assessed KRAS mutations by droplet digital polymerase chain reaction and CDKN2A, p53, and SMAD4 expression by immunohistochemistry. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for disease‐free survival (DFS) and overall survival (OS) were computed according to each molecular alteration and the number of altered genes using the Cox regression models. Multivariable competing risks regression analyses were conducted to assess the associations of the number of altered genes with specific patterns of recurrence. Loss of SMAD4 expression was associated with short DFS (multivariable HR, 1.24; 95% CI, 1.09–1.43) and OS times (multivariable HR, 1.27; 95% CI, 1.10–1.46). Compared to cases with 0–2 altered genes, cases with three and four altered genes had multivariable HRs for OS of 1.28 (95% CI, 1.09–1.51) and 1.47 (95% CI, 1.22–1.78), respectively (ptrend

The safety and effectiveness of chemotherapy in elderly patients with biliary tract cancer (BTC) remain unclear. Therefore, we retrospectively reviewed patients who underwent chemotherapy for locally advanced, metastatic, or recurrent BTC at our institution from January 2016 to December 2021. Of the 283 included patients, 91 (32.5%) were aged 75 years or older when initiating chemotherapy. Elderly patients were more likely than non-elderly patients to receive monotherapy with gemcitabine or S-1 (58.7% vs. 9.4%, p < 0.001) and were less likely to experience grade 3–4 toxicities (55.4% vs. 70.2%, p = 0.015). The rates of termination due to intolerance (6.5% vs. 5.8%, p = 0.800) and transition to second-line chemotherapy (39.1% vs. 40.3%, p = 0.849) were similar between groups. In the overall cohort, age was not an independent predictor of overall survival (OS). Within the elderly cohort, there were no differences in severe adverse events between patients receiving monotherapy and combination therapy (50.0% vs. 63.2%, p = 0.211). Median OS was longer in the combination therapy group (10.4 vs. 14.1 months; p = 0.010); however, choice of monotherapy was not an independent predictor of overall survival. Monotherapy appears to be a viable alternative in selected elderly BTC patients.

Background/Aims Digital single-operator cholangioscopy (DSOC)-guided mapping biopsy (DMB) and tube-assisted mapping biopsy (TMB) are two techniques used for preoperative evaluation of biliary tract cancer (BTC). However, data regarding the diagnostic performance of these techniques are limited. Methods We retrospectively examined consecutive patients with BTC who underwent either technique at our institution between 2018 and 2020. We evaluated the technical success rate, adequate tissue acquisition rate, and diagnostic performance of these techniques for the evaluation of lateral spread of BTC. Results A total of 54 patients were included in the study. The technical success rate of reaching the target sites was 95% for DMB and 100% for TMB. The adequate tissue acquisition rate was 61% for DMB and 69% for TMB. The adequate tissue acquisition rate was low, especially for target sites beyond the secondary biliary radicles. The sensitivity of DMB alone was 39%, which improved to 65% when combined with visual impression. Experts demonstrated a higher negative predictive value and diagnostic accuracy with respect to both DSOC visual impression and DMB for the evaluation of lateral spread of BTC compared to trainees. Conclusions Adequate tissue acquisition rates were similar between the two techniques. Since DMB requires expertise, TMB may be an acceptable option when DSOC is unavailable or when DSOC expertise is limited.

Abstract Objectives Duckbill‐type metal stent (DMS) was the first laser‐cut biliary metal stent with an anti‐reflux valve. Removal of DMS is believed to be difficult and relevant reports are scarce. This study aims to investigate the feasibility of DMS removal. Methods We retrospectively analyzed patients who underwent DMS removal between June 2019 and March 2022 to evaluate success rates and factors affecting outcomes. In addition, six different methods of DMS removal were reproduced in vitro, varying removal devices, angle of applied force, and grasped location. Extraction resistance, the distance of forceps stroke, and stent length after removal were compared. Results Forty patients were enrolled, and DMS removal was successful in 31 cases (78%). No adverse events were observed. Tumor ingrowth was evident in 78% (7/9) of failed cases. Patients receiving biliary metal stents for the first time (naïve cases), long indwelling time, longer stent, and stent tearing during removal were associated with unsuccessful stent removal. In the in vitro study, a larger force was required to remove the stent at an extraction angle of 120° than at 0°. Among cases in which force was applied at 120°, the load tended to be lower when rat‐tooth forceps were applied horizontally across the stent. Conclusions Stent removal was possible in a majority of cases. Deployment of additional stents inside DMS may be preferable to forceful removal in the presence of factors associated with difficult stent removals, such as tumor ingrowth, naïve cases, longer stents, long indwelling time, and stent tearing during removal.

Abstract Background The usefulness of duckbill‐type anti‐reflux metal stent (DMS) in self‐expandable metal stent‐naïve pancreatic cancer (PC) patients has not been well‐studied. This study aimed to evaluate the efficacy and safety of DMS in such patients. Methods We analyzed consecutive patients with unresectable PC who received a covered metal stent (CMS) as the initial self‐expandable metal stent at our institution. Technical success, functional success, causes of recurrent biliary obstruction (RBO), time to RBO (TRBO), adverse events (AEs), and reintervention rates were compared between DMS and conventional CMS (c‐CMS). Results A total of 69 patients were included (DMS: 28, c‐CMS: 41). Technical success, functional success, and AEs were similar between groups. Tumor ingrowth was more common in the DMS group (18% vs. 0%, p = 0.009), while non‐occlusion cholangitis tended to be more common in the c‐CMS group (0% vs. 15%, p = 0.074). Median time to RBO was similar between groups (276 vs. 273 days, p = 0.915). The anti‐reflux valve of DMS was found torn in 56% of patients. Endoscopic reintervention was successful in all cases, despite failed stent removal in 88% of patients in the DMS group. Conclusions DMS was not associated with longer time to RBO compared to c‐CMS in self‐expandable metal stent‐naïve patients.

BackgroundLenvatinib is an oral anticancer medication used to treat radioiodine-refractory thyroid cancer and unresectable hepatocellular carcinoma. The purpose of this study is to evaluate lenvatinib adherence by patients and to identify factors associated with decreased lenvatinib adherence.MethodsAmong 153 patients who started treatment with lenvatinib for unresectable thyroid cancer or unresectable hepatocellular carcinoma between May 1, 2015 and August 31 2021 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 102 were eligible for this study (55 thyroid cancer, 47 hepatocellular carcinoma). The lenvatinib adherence rate in a treatment cycle was defined as the number of times a patient took lenvatinib in a 28-day cycle divided by the prescribed 28 doses. The rate was determined by pill counting and self-reporting at the pharmaceutical outpatient clinic. Reasons for non-adherence were established by interview and analyzed.ResultsThe median adherence rate of lenvatinib in the first cycle was 90.1% (n = 55) in thyroid cancer and 94.9% (n = 47) in hepatocellular carcinoma. In thyroid cancer, there were 255 incidents of lenvatinib non-adherence. Non-adherence was mainly associated with bleeding events (18.6%), followed by hand-foot skin reactions (10.6%). In hepatocellular carcinoma, there were 97 incidents of non-adherence. Hypertension accounted for 20.6%, followed by hoarseness (18.6%) and diarrhea (17.5%).ConclusionThe adherence rate for lenvatinib in Japanese patients with thyroid and hepatocellular carcinoma in real-world clinical practice was more than 90% in this study. Hypertension was a major reason for non-adherence, followed by hand-foot skin reactions and diarrhea.

Abstract In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).

Background/Aims Several fine-needle biopsy (FNB) needles are available for endoscopic ultrasound (EUS)-guided tissue acquisition. However, there is disagreement on which type of needle has the best diagnostic yield. The aim of this study was to compare the performance and safety of two commonly used EUS-FNB needles. Methods We retrospectively analyzed consecutive patients who underwent EUS-FNB between June 2016 and March 2020 in our hospital. Two types of needles were evaluated: a 20-gauge Menghini needle with a lateral forward bevel and a 22-gauge Franseen needle. Rapid on-site evaluation was performed in all the cases. A multivariate analysis was performed to clarify the negative predictive factors for obtaining a histological diagnosis. Propensity score matching was performed to compare the diagnostic yields of these two needles. Results We analyzed 666 patients and 690 lesions. The overall diagnostic rate of histology alone was 88.8%, and the overall adverse event rate was 1.5%. Transduodenal access and small lesions (≤2 cm) were identified as negative predictive factors for obtaining a histological diagnosis. After propensity score matching, 482 lesions were analyzed. The diagnostic accuracy rates of histology in the M and F needle groups were 89.2% and 88.8%, respectively (p=1.00). Conclusions Both the needles showed high diagnostic yield, and no significant difference in performance was observed between the two.

Previous genome-wide association studies have identified risk loci for pancreatic cancer but were centered on individuals of European ancestry. Here the authors identify GP2 gene variants associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

Abstract Background There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival. Methods From 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m2, intravenous irinotecan 150 mg/m2, and continuous infusion of 5-fluorouracil 2400 mg/m2 for 46 h without bolus infusion). Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2–9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8–5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5–100%), 77.2% (range 38.1–100%), and 85.9% (range 36.9–100%), respectively. Grade 3–4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6–16.3) and 7.6 months (95% CI 4.1–10.5) for the good prognostic factors, 6.5 (95% CI 5.5–10.0) and 3.6 months (95% CI 2.7–4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9–6.6) and 1.7 months (95% CI 0.9–4.3) for the poor prognostic factors, respectively. Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

AimCombination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (nab-paclitaxel), known as GnP therapy, significantly prolongs the survival of pancreatic cancer patients compared with gemcitabine monotherapy. However, it may cause severe neutropenia, requiring discontinuation of treatment. This study aimed to clarify the risk factors for Grade 3/4 neutropenia during GnP therapy.MethodsClinical data of pancreatic cancer patients who underwent GnP therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from December 2014 to December 2016 were retrospectively collected. The relationship of Grade 3/4 neutropenia onset to laboratory values and patient background factors was investigated by multivariate logistic regression analysis.ResultsClinical data of 222 patients were analyzed. Grade 3/4 neutropenia occurred in 118 patients (53.2%) in the first cycle of GnP therapy. Multivariate analysis identified low absolute neutrophil count (ANC), high total bilirubin (T-Bil), and low C-reactive protein (CRP) as risk factors for Grade 3/4 neutropenia. Age was not a risk factor. The incidence of neutropenia was 85.7% in patients with all three risk factors, but only 27.7% in patients with none of them.ConclusionLow ANC, high T-Bil, and low CRP may be risk factors for Grade 3/4 neutropenia in patients receiving GnP therapy, even if these laboratory values are within normal reference ranges. Patients with these risk factors should be carefully monitored for adverse events.

Background and study aims Self-expandable metallic stents (SEMS) are now widely used even for patients with borderline resectable (BR) pancreatic cancer (PC), as neoadjuvant therapy has become common. Therefore, we conducted this study to evaluate safety of SEMS placement in the population including BR PC and to explore risk factors for recurrent biliary obstruction (RBO), pancreatitis, and cholecystitis. Patients and methods We retrospectively investigated consecutive patients with PC who received initial SEMS between January 2015 and March 2019. We compared time to RBO (TRBO), causes of RBO, and stent-related adverse events (AEs) according to resectability status. Univariate and multivariate analyses were performed to explore risk factors for TRBO, pancreatitis, and cholecystitis. Results A total of 135 patients were included (BR 31 and unresectable [UR] 104). Stent-related AEs occurred in 39 patients: pancreatitis 14 (mild/moderate/severe 1/6/7), cholecystitis 12, and non-occluding cholangitis 13. TRBO, causes of RBO, and stent-related AEs were not significantly different according to resectability status. Overall rate of RBO was higher in UR PC due to the longer follow-up period. Sharp common bile duct (CBD) angulation was an independent risk factor for short duration of TRBO. High pancreatic volume index and SEMS of high axial force were independent risk factors for pancreatitis, whereas tumor involvement to orifice of cystic duct was the only risk factor for cholecystitis. Conclusions We demonstrated that SEMS can be safely deployed even in patients with BR PC. Sharp CBD angulation and high pancreatic volume index were identified as novel risk factors for RBO and pancreatitis, respectively, after SEMS placement.

Background and study aims Endoscopic ultrasound (EUS)-guided tissue acquisition is sometimes required to diagnose small solid pancreatic lesions. The aim of this study was to evaluate the diagnostic yield of EUS-guided tissue acquisition for small solid pancreatic lesions and the differences in diagnostic yield among different needles. Patients and method We retrospectively analyzed consecutive patients who had undergone EUS-guided tissue acquisition for solid pancreatic lesions less than 2 cm between November 2012 and June 2019. Three types of needles were evaluated in this study: a 22-gauge fine-needle aspiration (FNA) Lancet needle, a 20-gauge fine-needle biopsy (FNB) Menghini needle with a lateral forward bevel, and a 22-gauge FNB Franseen needle. We evaluated the diagnostic yield and safety of the procedure using these needles. Results We analyzed 160 patients with 163 lesions. The overall sensitivity, specificity, and accuracy were 92.0 %, 100 %, and 92.6 %, respectively. In the histological plus cytological diagnosis, accuracies of the Lancet, Menghini, and Franseen needles were 92.7 %, 97.0 %, and 85.7 %, respectively (P = 0.10). In the histological diagnosis alone, the negative predictive values (NPVs) of the Lancet, Menghini, and Franseen needles were 13.3 %, 53.3 %, and 27.3 %, respectively (P = 0.08). Adverse events occurred in four cases (2.5 %): one postprocedural bleeding, two cases of pancreatitis, and one pancreatic abscess. Conclusions EUS-guided tissue acquisition for small solid pancreatic lesions has a high diagnostic yield and safety. This study suggested a difference in the diagnostic yield of each needle for small solid pancreatic lesions.

Pancreatic cancer is an aggressive, solid tumor, with a grave prognosis. Despite surgical treatment in patients with pancreatic cancer, the rate of recurrence is high. In addition, although tumor biomarkers are frequently used to confirm advanced pancreatic cancer, this is not accurate and the biomarkers currently used cannot indicate prognosis. This study sought to evaluate circulating tumor DNA as a tumor biomarker to prognosticate pancreatic cancer. Patients with advanced pancreatic cancer and liver metastasis (N = 104) were included, and blood samples were collected from all patients. The mutant allele frequency was measured using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with > 240 hot spots. In patients with advanced pancreatic cancer, 50% (N = 52) had detectable ctDNA levels, with TP53 (45%, N = 47) and KRAS (42.3%, N = 44) mutations the most common. Patients with detectable circulating tumor DNA levels also had significantly worse overall survival and progression free survival than ctDNA negative patients (8.4 vs 16 months, P

Hereditary pancreatic cancers are caused by several inherited genes. Familial pancreatic cancer is defined as pancreatic cancer arising in a patient with at least two first-degree relatives with pancreatic cancer in the absence of an identified genetic cause. Hereditary pancreatic cancer syndromes and familial pancreatic cancers account for about 10% of pancreatic cancer cases. Germline mutations in BRCA1, BRCA2, ATM, PALB2, CDKN2A, STK11, and TP53 and mismatch repair genes (MLH1, MSH2, MSH6, PMS2, and EPCAM) are among the well-known inherited susceptibility genes. Currently available targeted medications include poly (ADP-ribose) polymerase inhibitors (PARP) for cases with mutant BRCA and immune checkpoint inhibitors for cases with mismatch repair deficiency. Loss of heterozygosity of hereditary pancreatic cancer susceptibility genes such as BRCA1/2 plays a key role in carcinogenesis and sensitivity to PARP inhibitors. Signature 3 identified by whole genome sequencing is also associated with homologous recombination deficiency and sensitivity to targeted therapies. In this review, we summarize molecular features and treatments of hereditary pancreatic cancer syndromes and surveillance procedures for unaffected high-risk cases. We also review transgenic murine models to gain a better understanding of carcinogenesis in hereditary pancreatic cancer.

Background and study aims: Temporary placement of a fully covered self-expandable metal stent (FCSEMS) has recently emerged as a treatment option for pancreatic duct strictures due to chronic pancreatitis refractory to conventional plastic stenting. However, there are no data about long-term outcomes with this therapeutic option. The aims of the current study were to estimate the feasibility, safety, efficacy, and long-term outcomes of temporary FCSEMS placement for refractory pancreatic duct strictures. Patients and methods: This was a prospective, single-center feasibility study. Ten patients with refractory pancreatic duct strictures due to chronic pancreatitis underwent FCSEMS placement for 3 months. We evaluated the rate of recurrent symptoms after stent removal during long-term follow-up, as well as adverse events (AEs). Results: Two patients required early (within 1 week) stent removal because of intolerable pain or pancreatitis. In the remaining 8 patients, the recurrence rate of any symptoms after FCSEMS removal was 63% during 35 months of follow up. The causes of recurrent symptoms were as follows: recurrence of stricture in 2; stent-induced stricture in 1; impaction of pancreatic stones in 1; and development of a pseudocyst in 1. When limited to stricture, the recurrence rate was 38%. Additional endoscopic treatments were required in 4 patients: a second FCSEMS placement in 1; plastic stent (PS) placement in 1; stone extraction in 1; and endoscopic ultrasound–guided pseudocyst drainage in 1. Asymptomatic stent migration occurred in 2 patients. Suppurative pancreatic ductitis due to food impaction in the FCSEMS occurred in 2 patients, and endoscopic pancreatic duct drainage was performed. Stent-induced ductal changes developed in 2 patients and PS treatment was required in 1 patient for pain relief. Conclusion: The FCSEMS appears to be a feasible and potentially effective option for the management of refractory pancreatic duct strictures due to chronic pancreatitis during long-term follow-up. AEs including post-procedure pain, stent-induced ductal changes, migration, and ductitis are issues that need to be resolved.

Background and study aims A short-type single-balloon enteroscope with a 3.2-mm working channel makes it possible to insert an enteral stent by the through-the-scope technique in patients with malignant afferent loop obstruction. Here, we report five cases of malignant afferent loop obstruction treated with endoscopic enteral stenting. We also propose a new classification for three types of malignant afferent loop obstruction. Type 1: The obstruction site is located distal to the papilla or the bilioenteric anastomosis. Type 2: The obstruction site is located at the papilla or the bilioenteric anastomosis. Type 3: The obstruction site is located between the bilioenteric and pancreaticoenteric anastomosis. The patients with type 1 and 3 were simply treated by inserting an enteral stent endoscopically. The patient with type 2 was treated with an endoscopic enteral stent for malignant afferent loop obstruction and with percutaneous transhepatic biliary stenting for malignant biliary obstruction. Although double stenting for type 2 remains a difficult endoscopic procedure, the endoscopic approach has become the standard approach for malignant afferent loop obstruction.

Background and study aims Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is widely performed to obtain pathological evidence from several parts of the body. Major complications of EUS-FNA are bleeding, pancreatitis, and abdominal pain. Needle fracture is a rare complication of EUS-FNA and only a few relevant reports are available. Here, we report a case of needle fracture during EUS-FNA using a needle with a side hole. A 61-year-old man underwent EUS-FNA of the uncinate process of the pancreas to confirm malignancy. A 20-gauge needle with a side hole was used to puncture the mass from the first part of the duodenum. The needle fracture occurred at the side hole during the third passage, and the fragment remained in the pancreas. Fortunately, the patient did not exhibit any symptoms due to the needle fragment. This case indicates that repeated puncture using the same needle with a side hole might increase risk of needle fracture during EUS-FNA. It is important to inform clinicians about the potential risk of needle fracture, particularly given the increasing number of EUS-FNAs being performed.

Genome-wide association studies (GWASs) have identified many single nucleotide polymorphisms (SNPs) that are significantly associated with pancreatic cancer susceptibility. We sought to replicate the associations of 61 GWAS-identified SNPs at 42 loci with pancreatic cancer in Japanese and to develop a risk model for the identification of individuals at high risk for pancreatic cancer development in the general Japanese population. The model was based on data including directly determined or imputed SNP genotypes for 664 pancreatic cancer case and 664 age- and sex-matched control subjects. Stepwise logistic regression uncovered five GWAS-identified SNPs at five loci that also showed significant associations in our case-control cohort. These five SNPs were included in the risk model and also applied to calculation of the polygenic risk score (PRS). The area under the curve determined with the leave-one-out cross-validation method was 0.63 (95% confidence interval, 0.60-0.66) or 0.61 (0.58-0.64) for versions of the model that did or did not include cigarette smoking and family history of pancreatic cancer in addition to the five SNPs, respectively. Individuals in the lowest and highest quintiles for the PRS had odds ratios of 0.62 (0.42-0.91) and 1.98 (1.42-2.76), respectively, for pancreatic cancer development compared with those in the middle quintile. We have thus developed a risk model for pancreatic cancer that showed moderately good discriminatory ability with regard to differentiation of pancreatic cancer patients from control individuals. Our findings suggest the potential utility of a risk model that incorporates replicated GWAS-identified SNPs and established demographic or environmental factors for the identification of individuals at increased risk for pancreatic cancer development.

Background/Aims: Endoscopic papillary balloon dilation (EPBD) is a possible alternative to endoscopic sphincterotomy (EST) for common bile duct (CBD) stones. To date, 10- and 8-mm EPBD have not been fully compared. Patients and Methods: Patients who underwent EPBD for CBD stones at two Japanese tertiary care centers between May 1994 and January 2014 were identified. Matched pairs with 10- and 8-mm EPBD were generated. Short- and long-term outcomes were compared between the two groups. Results: A total of 869 patients were identified (61 and 808 patients for 10- and 8-mm EPBD, respectively), and 61 well-balanced pairs were generated. The rate of complete stone removal within a single session was higher in the 10-mm EPBD group than in the 8-mm EPBD group (69% vs. 44%, P < 0.001), and use of lithotripsy was less frequent in the 10-mm EPBD group (23% vs. 56%, P < 0.001). The rates of post-ERCP pancreatitis were similar between the 10- and 8-mm EPBD groups (11% vs. 8%). Cumulative biliary complication-free rates were not statistically different between the two groups: 88% [95% confidence interval (CI): 79–97%] and 94% (95% CI: 88–100%) at 1 year and 69% (95% CI: 56–85%) and 80% (95% CI: 69–93%) at 2 years in the 10- and 8-mm EPBD groups, respectively. In the 10-mm EPBD group, ascending cholangitis was not observed, and pneumobilia was found in 5% of cases during the follow-up period. Conclusions: EPBD using a 10-mm balloon for CBD stones is safe and more effective than 8-mm EPBD. The sphincter function is highly preserved after 10-mm EPBD.

Background and study aims: Background and study aims: Temporary placement of a fully covered self-expandable metal stent (FCSEMS) has recently emerged as a treatment option for pancreatic duct strictures due to chronic pancreatitis refractory to conventional plastic stenting. However, there are no data about long-term outcomes with this therapeutic option. The aims of the current study were to estimate the feasibility, safety, efficacy, and long-term outcomes of temporary FCSEMS placement for refractory pancreatic duct strictures. Patients and methods: This was a prospective, single-center feasibility study. Ten patients with refractory pancreatic duct strictures due to chronic pancreatitis underwent FCSEMS placement for 3 months. We evaluated the rate of recurrent symptoms after stent removal during long-term follow-up, as well as adverse events (AEs). Results: Two patients required early (within 1 week) stent removal because of intolerable pain or pancreatitis. In the remaining 8 patients, the recurrence rate of any symptoms after FCSEMS removal was 63% during 35 months of follow up. The causes of recurrent symptoms were as follows: recurrence of stricture in 2; stent-induced stricture in 1; impaction of pancreatic stones in 1; and development of a pseudocyst in 1. When limited to stricture, the recurrence rate was 38%. Additional endoscopic treatments were required in 4 patients: a second FCSEMS placement in 1; plastic stent (PS) placement in 1; stone extraction in 1; and endoscopic ultrasound–guided pseudocyst drainage in 1. Asymptomatic stent migration occurred in 2 patients. Suppurative pancreatic ductitis due to food impaction in the FCSEMS occurred in 2 patients, and endoscopic pancreatic duct drainage was performed. Stent-induced ductal changes developed in 2 patients and PS treatment was required in 1 patient for pain relief. Conclusion: The FCSEMS appears to be a feasible and potentially effective option for the management of refractory pancreatic duct strictures due to chronic pancreatitis during long-term follow-up. AEs including post-procedure pain, stent-induced ductal changes, migration, and ductitis are issues that need to be resolved.