Search

Acute pancreatitis is an acute inflammatory process of the pancreas that is becoming an increasingly common clinical issue. The most frequent underlying etiologies include gallstones and chronic alcohol use, which account for more than two-thirds of cases. We recently experienced a rare case of acute myeloid leukemia (AML) presenting with recurrent acute pancreatitis, which we later discovered was caused by diffusely infiltrating extramedullary sarcoma in the pancreas. Comprehensive analysis of previous cases of AML presenting as acute pancreatitis suggested involvement of cytogenetic alterations in chromosome 16 in its pathogenesis. Further improvement in management of acute pancreatitis is needed, and clinicians should note that this occasionally fatal condition can be the initial and only manifestation of AML. In practice, prompt initiation of intensive chemotherapy is critical for treating such cases of AML-induced acute pancreatitis.

Background and aims: There is a lack of biliary epithelial molecular markers for primary sclerosing cholangitis (PSC). We analyzed candidates from disease susceptibility genes identified in recent genome-wide association studies. Methods: Expression was quantified using immunohistochemistry in biliary epithelia in liver biopsy samples from patients with PSC (N = 45) and controls (N = 12). Samples from patients with primary biliary cholangitis (PBC) were used as disease controls (N = 20). Results: The levels of hepatic expression of ATXN2, HHEX, PRDX5, MST1, and TNFRSF14 were significantly altered in the PSC group. We focused on the immune-related receptor, TNFRSF14. Immunohistochemistry revealed that TNFRSF14 positivity was significantly higher in biliary epithelia in the PSC group (96 %) than in the control (42 %) and PBC (55 %) groups. High expression of TNFRSF14 was observed only in patients with PSC. Moreover, the expression of LIGHT, which encodes a TNFRSF14-activating ligand, was increased in PSC liver. Immunohistochemistry showed that high expression of LIGHT was more common in PSC biliary epithelia (53 %) than in the PBC (15 %) or control (0 %) groups; moreover, it was positively associated with fibrotic progression. Conclusions: TNFRSF14 and LIGHT are attractive candidate markers for PSC.

Aim: To determine the significance of the portal venous blood flow and portosystemic shunts in patients with decompensated cirrhosis due to HCV infection following SVR achievement. Methods: Portal hypertension-related events and liver function were evaluated in 27 patients during and after sofosbuvir/velpatasvir therapy. Results: SVR was achieved in 25 patients, and the outcome was evaluated in 24 patients. Serum albumin level (median; g/dL) increased from 2.9 at baseline to 3.5 at 12 weeks after EOT, while liver volumes (cm3) decreased from 1,260 to 1,150. The cumulative occurrence rates of portal hypertension-related events after EOT were 29.2%, 33.3%, and 46.1% at 24, 48, and 96 weeks, respectively. Multivariate logistic regression analysis revealed that the maximal diameter of the shunts was associated with the event development, with a cutoff value of 8.3 mm. Multiple linear regression analysis revealed that portal venous blood flow, liver volume, serum albumin and bilirubin levels at baseline were associated with serum albumin levels at 12 weeks after EOT. Conclusion: In patients with decompensated cirrhosis caused by HCV, the baseline portal venous blood flow and liver volume and function were predictive of liver function following SVR, while the size of portosystemic shunts predicted the portal hypertension-related event occurrence.

Background The clinical characteristics of IgG4-related sclerosing cholangitis (IgG4-SC) especially without autoimmune pancreatitis (AIP) have not been investigated in a large cohort. Aims To clarify the clinical characteristics of IgG4-SC and IgG4-SC without AIP. Methods We retrospectively reviewed imaging, serology, other organ involvement (OOI) and histology of 872 patients with IgG4-SC who participated in a Japanese nationwide survey in 2019, and compared these items between IgG4-SC with and without AIP. Results AIP was present in 83.7% (730/872) of IgG4-SC. In IgG4-SC, bile duct wall thickening was observed on ultrasound (528/650; 81.2%), computed tomography (375/525; 71.4%) and magnetic resonance imaging or cholangiopancreatography (290/440; 65.9%). An elevated serum IgG4 level (≥ 135 mg/dL) was found in 88.0% (322/366). IgG4-related OOI other than AIP was observed in 25.2% (211/836). The proportion of females was significantly higher in IgG4-SC without AIP (28.9% vs. 20.1%; p = 0.025). Hilar stricture was the most common cholangiographic type in IgG4-SC without AIP (39/107; 36.4%).There were no significant differences between IgG4-SC with and without AIP in the rates of bile duct wall thickening, elevated serum IgG4 level, or IgG4-related OOI. Conclusions The clinical characteristics of IgG4-SC was similar between IgG4-SC with and without AIP in a large cohort.

Background Liver failure and biliary tract cancer (BTC) are major life-threatening events in the clinical course of primary sclerosing cholangitis (PSC). Although these are competing events, they are typically evaluated as a composite prognostic endpoint. In Japan, the clinical characteristics and prognosis of PSC reportedly differ according to age of onset. We compared the prognosis of younger- versus older-onset PSC by competing risk analysis. Methods This was a retrospective analysis of 144 patients with PSC who were followed up for a median of 6.7 years. The patients were divided into two groups according to a cutoff age of onset of 44 years. We compared the prognosis of younger-onset PSC (n = 91) and older-onset PSC (n = 53) by competing risk analysis, incorporating mortality related and that unrelated to BTC as competing events. Results There was no difference in BTC-related mortality between patients with younger-onset and those with older-onset PSC (subdistribution hazard ratio [SHR], 0.89; 95% confidence interval [CI], 0.17-4.56, P = 0.888). The cumulative incidence of mortality due to other causes, including liver transplantation and liver failure, was non-significantly higher in patients with older-onset PSC (SHR, 1.58; 95% CI, 0.88-2.84; P = 0.129). Conclusions Although we did not find a significant difference in prognosis by onset age, patients with older-onset PSC had worse liver-transplantation-free survival than those with younger-onset PSC. A large cohort study is needed to evaluate the clinical outcomes of older- and younger-onset PSC.

Background/Aims Endoscopic ultrasound (EUS)-guided tissue acquisition is widely utilized as a diagnostic modality for intra-abdominal masses, but there remains debate regarding which suction technique, slow pull (SP) or conventional suction (CS), is better. A meta-analysis of reported studies was conducted to compare the diagnostic yields of SP and CS during EUS-guided tissue acquisition. Methods We conducted a systematic electronic search using MEDLINE/PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials to identify clinical studies comparing SP and CS. We meta-analyzed accuracy, sensitivity, blood contamination and cellularity using the random-effects model. Results A total of 17 studies (seven randomized controlled trials, four prospective studies, and six retrospective studies) with 1,616 cases were included in the analysis. Compared to CS, there was a trend toward better accuracy (odds ratio [OR], 1.48; 95% confidence interval [CI], 0.97 to 2.27; p=0.07) and sensitivity (OR, 1.67; 95% CI, 0.95 to 2.93; p=0.08) with SP and a significantly lower rate of blood contamination (OR, 0.48; 95% CI, 0.33 to 0.69; p

Proton pump inhibitors (PPIs) are widely prescribed medications for gastric acid-induced diseases. Despite the effectiveness of PPIs, recent evidence suggested an increased risk of various bacterial infections in PPI users. The current study was conducted to evaluate the risk of biliary infection after endoscopic biliary stent placement in regular users of PPIs.Consecutive patients with a native papilla who underwent endoscopic retrograde cholangiopancreatography and stent placement for biliary stricture between January 2010 and August 2019 were included in this retrospective study. The cumulative incidences of biliary infection were compared between regular and non-regular PPI users.During the study period, 270 regular PPI users and 146 non-regular PPI users were included in the analyses. Age, gender, and indication of endoscopic retrograde cholangiopancreatography were not different between the two groups. The incidences of biliary infection were 43% in regular PPI users and 36% in non-regular PPI users but the time to biliary infection was significantly shorter in regular PPI users than in non-regular users (28 vs. 87 days,Regular PPI use was associated with a higher risk of biliary infection after endoscopic biliary drainage. Inappropriate PPI use should be avoided.

Background/Aims Recently, a three-plane symmetric needle with Franseen geometry was developed for endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). In this retrospective study, tissue acquisition per pass was compared between 22-gauge Franseen FNB and standard fine needle aspiration (FNA) needles in patients with solid pancreatic lesions. Methods Consecutive patients who underwent EUS-FNA or EUS-FNB for solid pancreatic lesions between October 2014 and March 2018 were retrospectively studied. The tissue acquisition rate and the diagnostic performance per session, per pass, and at first pass were compared. Results A total of 663 passes (300 by the FNB needle and 363 by the standard FNA needle) were performed in 154 patients (71 FNB and 83 FNA). The tissue acquisition rate per session and at first pass in the FNB and FNA groups was 100% and 95% (p=0.13) and 87% and 69% (p=0.007), respectively. The multivariate analysis revealed that among the patients, EUS-FNB (odds ratio, 3.07; p=0.01) was associated with a higher first-pass tissue acquisition rate. While the tissue acquisition rate reached a plateau after the 4th pass with FNA, it reached a plateau after the 2nd pass with FNB. Among the 129 malignant cases, the histological tissue acquisition rate per session was similar (100% and 94%), but the sensitivity by histology alone per session was higher for FNB than for FNA (93% and 73%, p

Purpose: The aim of this study was to evaluate the efficacy and tolerability of S-IROX and modified FOLFIRINOX (mFFX) after gemcitabine plus nab-paclitaxel for advanced pancreatic cancer (PC) in the real world setting. Methods: Consecutive patients receiving S-IROX or mFFX as a second-line chemotherapy for advanced PC refractory to gemcitabine plus nab-paclitaxel were retrospectively studied. Patients were treated every 2 weeks: S-1 40 mg/m2 was administered orally twice daily on days 1 to 7 in S-IROX and 5-fluorouracil 2400 mg/m2 was intravenously administered for 46 h without bolus infusion in mFFX, in addition to intravenous oxaliplatin 85 mg/m2 and irinotecan 150 mg/m2 on day 1 in both regimens. Results: Fifty-four patients with advanced PC who received S-IROX (n = 19) or mFFX (n = 35) were retrospectively studied. The disease control rate and response rate were 73.7% and 10.5% in the S-IROX group and 62.2% and 2.7% in the mFFX group, respectively. The median progression free survival (PFS) was 7.8 and 5.7 months in the S-IROX and mFFX groups (p = 0.24). The median overall survival (OS) was 14.2 and 11.5 months in the S-IROX and mFFX groups (p = 0.34). There were no significant differences in the incidences of grade 3–4 adverse effects. The subgroup analyses suggested S-IROX demonstrated favorable OS in patients with PFS ≥6 months of first-line gemcitabine plus nab-paclitaxel (p for interaction = 0.02). Conclusions: S-IROX and mFFX were similarly tolerable and effective as a second-line chemotherapy in patients with PC refractory to gemcitabine plus nab-paclitaxel.

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) for patients with surgically altered anatomy is challenging. Recently, balloon endoscopy has been shown to facilitate ERCP for this population with a high technical success rate, but adverse events (AEs) are not uncommon. Compared to non-elderly patients, elderly patients may be at higher risk of AEs due to underlying comorbidities. The current study aimed to evaluate the feasibility of balloon endoscope-assisted ERCP (BE-ERCP) for the elderly. Patients and methods We retrospectively identified patients who underwent BE-ERCP between January 2010 and September 2019. For patients who underwent multiple procedures during the study period, the first session was analyzed. Early AEs associated with BE-ERCP were compared between elderly (≥ 75 years) and non-elderly patients. Results A total of 1,363 BE-ERCP procedures were performed, and 568 patients (211 elderly and 357 non-elderly) were included for the analyses. Technical success rates were high in both the elderly and non-elderly groups (80 % vs. 80 %, respectively). The rates of early AEs were similar between the groups (12 % vs. 9.0 % in the elderly and non-elderly group, respectively; P = 0.31). The mltivariable-adjusted odds ratio for early AEs comparing elderly to non-elderly patients was 1.36 (95 % confidence interval, 0.74–2.51; P = 0.32). Specifically, we did not observe between-group differences in rates of gastrointestinal perforation (2.4 % vs. 2.8 % in elderly and non-elderly groups, respectively; P = 0.99) and aspiration pneumonia (1.9 % vs. 0.6 %, P = 0.20). Conclusions BE-ERCP is a feasible procedure for elderly individuals with surgically altered anatomy.

Purpose. A phase I study of intraperitoneal paclitaxel (ip PTX) combined with gemcitabine (GEM) plus nab-paclitaxel (nab-PTX) (GnP) was conducted to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in pancreatic cancer patients with peritoneal metastasis in first-line setting. Methods. Based on the 3 + 3 dose-escalation model, ip PTX, GEM and nab-PTX were administered at doses of 20 or 30 mg/m2, 800 or 1000 mg/m2 and 100 or 125 mg/m2 (level 1, 2 and 3, respectively) on days 1, 8 and 15 in 4-week cycles. Dose-limiting toxicity (DLT) defined as severe adverse events was evaluated during the first cycle of the treatment. Safety and preliminary efficacy were also investigated. Results. In total, 12 patients were enrolled. While 2 of the first 6 patients enrolled at level 1 experienced DLTs (grade 3 ip port dysfunction and grade 3 pneumonia), no DLT was observed in the next 6 patients enrolled at level 2 and 3. Therefore, we did not reach the MTD and the RD was determined to be level 3 (ip PTX of 30 mg/m2, GEM of 1000 mg/m2, and nab-PTX of 125 mg/m2). The major grade 3/4 adverse events included neutropenia (58%), anemia (33%), and ip port dysfunction (25%). The response rate was 25% and the median PFS was 5.4 (95% confidence interval; 2.4–16.0). The cytological status in peritoneal lavage turned negative in 8 patients (67%). Conclusions. Ip PTX combined with GnP was feasible and potentially effective in pancreatic cancer with peritoneal metastasis as a first-line treatment deserved further evaluations.

Endoscopic ultrasonography (EUS)-guided interventions are often performed using a single guidewire (SGW), but there are a few reports on the use of double guidewire (DGW) technique to facilitate multiple drainage placement during EUS-guided drainage of pancreatic fluid collections. This DGW technique may have advantages other than multiple drainage placement during EUS-guided interventions such as scope stabilization, support for stone extraction and device insertion. Consecutive patients who underwent EUS-guided interventions between Feb 2012 and Apr 2019 were retrospectively reviewed. The rate and reasons of DGW technique, and clinical outcomes were evaluated. DGW technique was performed, using an uneven double lumen cannula (UDLC), which facilitates insertion of 0.025-in. and 0.035-in. guidewires. A total of 249 EUS-guided interventions were analyzed, and DGW technique was utilized primarily in 65 cases (25.7%) and as a salvage after failed SGW technique in 18 cases (7.1%). The reasons for DGW technique were 60 multiple drainage placement, 10 scope stabilization, 7 device insertion, 5 safety guidewire, and 4 antegrade stone removal. Insertion of UDLC and DGW was successful in 100%. Technical success rate of preplanned interventions was 92.7% (96.9% in primary DGW and 77.8% in salvage DGW technique). Adverse events were observed in 19.5% after DGW but were not related to DGW technique. DGW technique using UDLC during EUS-guided interventions was technically feasible and safe. In addition to multiple drainage insertion, it can potentially support complex EUS-guided interventions.

BACKGROUND AND AIM Limited data are available on age and comorbidity assessment in patients with biliary tract cancer (BTC). This study aimed to evaluate the association of age and comorbidity burden with clinical outcomes of chemotherapy for BTC. METHODS Consecutive 197 BTC patients undergoing first-line chemotherapy between 2007 and 2017 were retrospectively studied. Patients were classified to three groups according to the age-adjusted Charlson comorbidity index (ACCI) excluding the score about BTC and progression-free survival, overall survival (OS), and safety were compared. RESULTS Fifty-one patients (26%) were elderly (≥ 75 years), and ACCI was 0-2 in 73 patients (37%), 3-4 in 98 (50%), and ≥ 5 in 26 (13%). ACCI was associated with the administration of first-line combination chemotherapy (89% in 0-2, 80% in 3-4, and 64% in ≥ 5, P

The patient was a 67-year-old man with advanced hepatocellular carcinoma (HCC) due to chronic hepatitis B. Due to refractoriness to radiofrequency ablation and transcatheter arterial chemoembolization, lenvatinib, a new oral mutikinase inhibitor, was started with a daily dose of 12 mg. However, on day 6 the patient developed acute-onset, right upper quadrant pain associated with fever; laboratory tests revealed leukocytosis and liver dysfunction. CT scan showed the swollen gallbladder with wall thickening with no evidence of gallstones, and the diagnosis of acute acalculous cholecystitis was made. After the resolution of cholecystitis by antibiotics and endoscopic nasogallbladder drainage placement, lenvatinib was resumed at a reduced daily dose of 4 mg. However, acute acalculous cholecystitis recurred, supporting lenvatinib as a cause of acute acalculous cholecystitis. Using the Naranjo adverse drug reaction probability scale, a score of 6 was derived, which indicates that this adverse event was probably caused by lenvatinib. In summary, we present a patient with advanced HCC who underwent repeated episodes of acute acalculous cholecystitis as a rare adverse event associated with lenvatinib.

In patients with unresectable hilar malignant biliary obstruction (MBO), bilateral metal stent placement is recommended. However, treatment selection between partially stent-in-stent (SIS) and side-by-side (SBS) methods is still controversial. Clinical outcomes of bilateral metal stent placement by SBS and SIS methods for hilar MBO were retrospectively studied in four Japanese centers. While large-cell-type uncovered metal stents were placed above the papilla in SIS, braided-type uncovered metal stents were placed across the papilla in SBS. A total of 64 patients with hilar MBO (40 SIS and 24 SBS) were included in the analysis. Technical success rate was 100% in SIS and 96% in SBS. Functional success rate was 93% in SIS and 96% in SBS. Early adverse event rates were higher in SBS (46%) than in SIS (23%), though not statistically significant (P = 0.09). Post-procedure pancreatitis was exclusively observed in SBS group (29%). Recurrent biliary obstruction rates were 48% and 43%, and the median time to recurrent biliary obstruction was 169 and 205 days in SIS and SBS, respectively. Other than a trend to higher adverse event rates including post-procedure pancreatitis in SBS, clinical outcomes of SIS and SBS methods were comparable in patients with unresectable hilar MBO.

Background While endoscopic management of benign biliary strictures (BBSs) is the standard of care, long-term treatment remains the issue in refractory cases, especially for anastomotic strictures after living-donor liver transplantation (LDLT) and hepaticojejunostomy anastomotic strictures (HJAS). The aim of this prospective study was to evaluate the safety and effectiveness of a fully covered self-expandable metal stent (FCSEMS) for patients with refractory BBSs. Methods Patients with BBSs that were unamenable to endoscopic plastic stent placement with a treatment period of more than 6 months were eligible. An FCSEMS was placed endoscopically and removed after 90 days. In patients with surgically altered anatomy, an FCSEMS was placed using a double-balloon endoscope. The primary outcome was stricture resolution at FCSEMS removal. The secondary outcomes included stricture recurrence and adverse events. Results A total of 30 patients were enrolled: the causes of their BBSs were anastomotic stricture after LDLT in 13, HJAS in 12, post-cholecystectomy in two, chronic pancreatitis in two, and post-hepatectomy in one. The technical success rate of FCSEMS placement was 100 % and all FCSEMSs were successfully removed. The rate of stricture resolution at FCSEMS removal was 96.6 % (91.7 % in the post-LDLT group and 100 % in the HJAS group). Stricture recurrence occurred in three HJAS patients (10.7 %) during a median follow-up period of 15.6 months. Adverse events were observed in 12.1 %: five cholangitis, one pancreatitis, and one perforation. Conclusion Temporary placement of an FCSEMS was a feasible and effective treatment option for refractory BBSs, especially for post-LDLT strictures and HJAS.

Covered self-expandable metal stent (cSEMS) for gastric outlet obstruction (GOO) has been developed to overcome tumor ingrowth but is prone to be associated with an increased risk of migration. Clinical impact of the novel large-bore cSEMS for malignant GOO remains unclear.A total of 117 patients undergoing endoscopic cSEMS placement for malignant GOO were enrolled in this multicenter retrospective study. Technical and clinical success, adverse events, recurrent GOO, and survival after stent placement were compared between 24 mm-cSEMS (n = 49) and 20 mm-cSEMS (n = 68).Patient characteristics were well-balanced and thus similar survival was observed between the two groups (136 days vs. 89 days, P = 0.60). Technical success rate of 100% and clinical success rate of 96% were achieved both in 24 mm-cSEMS and 20 mm-cSEMS, respectively. The median cumulative time to recurrent GOO was significantly longer in 24 mm-cSEMS than in 20 mm-cSEMS (380 days vs. 138 days, P = 0.01). The incidence of adverse events and recurrent GOO was comparable: 12% vs. 15% (P = 0.91), and 16% vs. 31% (P = 0.11); however, no stent migration was observed in 24 mm-cSEMS. In a subgroup analysis, the superiority of 24 mm-cSEMS to 20 mm-cSEMS was demonstrated in extrinsic cancers (380 days vs. 121 days, P = 0.01) but not in intrinsic cancers (151 days vs. not reached, P = 0.47).The 24 mm-cSEMS may improve time to recurrent GOO with ensuring acceptable safety in patients with malignant GOO.

Endoscopic ultrasonography-guided tissue acquisition (EUS-TA) is now an established technique to obtain the pathological diagnosis of solid pancreatic lesions (SPLs), but the diagnosis of small SPLS by EUS-TA can still be difficult. We conducted a literature review and a meta-analysis on the diagnostic yield of EUS-TA according to the tumor size. In a meta-analysis of 33 studies with 6883 cases, a pooled odds ratio (OR) of sensitivity was significantly higher in SPLs of20 mm (OR 1.64

Background/Aims: We aimed to investigate incidence, characteristics, and possible risk factors of pancreatic cancer in patients under observation for hepatocellular carcinoma (HCC) because the association of hepatitis virus B infection and pancreatic cancer has been reported. Patients and Methods: We performed a retrospective cohort study in the Gastroenterology Department of a University Hospital in Japan between 2004 and 2012. A total of 1848 patients who underwent treatment for HCC were included at the initiation of treatment for HCC (mean follow-up period, 33.6 months). The patients received trimonthly radiological follow-ups. Newly developed cases of pancreatic cancer during follow-up for HCC were compared with that of an age- and sex-matched theoretical cohort from national statistics. Possible predisposing factors for pancreatic cancer related to HCC were assessed. Cumulative probabilities of developing a pancreatic cancer were compared using log-rank test. Results: About 13 of 1848 patients developed pancreatic cancer (mean follow-up period, 45.2 months). The risk ratio for all patients was 3.02 (log-rank test: P =0.01). Statistical analyses showed no effects of the following factors on the development of pancreatic cancer: age, sex, follow-up period, alcohol intake, laboratory data, presence of hepatitis virus, characteristics of HCC, type of treatment, number of radiological examinations, and cumulative effective dose. Conclusions: Increased incidence of pancreatic cancer was found in patients under observation for HCC in a relatively small cohort. HCC or other common underlying conditions might be a risk factor for development of pancreatic cancer.

Background and aims The anastomotic biliary stricture is a clinically important complication after living donor liver transplantation (LDLT) with a duct-to-duct anastomosis. Although endoscopic management of post-LDLT biliary strictures using balloon dilation (BD) and plastic stents (PSs) has provided acceptable short-term outcomes, long-term outcomes and prognostic factors for treatment success remain unclear. Methods We included 96 patients with post-LDLT biliary strictures who were endoscopically managed between 2003 and 2016. BD was utilized as a first-line treatment strategy, and PS placement was carried out for refractory cases. Potential prognostic factors for biliary stricture resolution were analysed using logistic regression analyses. Results Endoscopic treatment was technically successful in 84 patients (87.5%). The overall rate of biliary stricture resolution was 44.8% (43 of 96 patients) with a median follow-up duration of 90.9 months (interquartile range, 30.9-122.3 months). Bile duct kinking was associated with a lower rate of biliary stricture resolution (odds ratio, 0.33; 95% confidence interval, 0.13-0.87). After successful endoscopic treatment, biliary strictures recurred in 22 patients (57.9%) after BD, and in one patient (4%) after PS treatment. Conclusions Despite a high technical success rate, endoscopic treatment only provided a low rate of resolution of anastomotic biliary strictures among LDLT patients and required prolonged treatment duration. Alternative strategies including the use of a covered metal stent should be evaluated to further improve the treatment outcomes of post-LDLT biliary strictures, particularly in those accompanied by the bile duct kinking.

Due to increasing opportunities for abdominal imaging studies, bile duct stones are occasionally diagnosed without any symptoms. However, there has been no consensus on the management of asymptomatic bile duct stones. We conducted a retrospective longitudinal cohort study to investigate the natural history of asymptomatic bile duct stones and clinical outcomes according to the timing of endoscopic removal. We identified consecutive patients who were diagnosed with asymptomatic common bile duct stones and categorized into those who were followed up with stones in situ (wait-and-see group) and those who received early endoscopic stone removal (intervention group). Cumulative incidence functions of biliary complications were estimated and compared between the groups. We included 191 patients (114 patients in the wait-and-see group and 77 patients in the intervention group). In the wait-and-see group, the cumulative incidence of biliary complications was 6.1% at 1 year, 11% at 3 years, and 17% at 5 years. Asymptomatic disappearance of stones was observed in 22 patients (19%). Procedure-related adverse events of early endoscopic stone removal of asymptomatic stones were observed in 25 (32%) patients including 4 (5.2%) with severe pancreatitis. The cumulative incidence function of biliary complications did not differ by treatment strategies (P = 0.55). Biliary complications occurred in a substantial proportion of patients with asymptomatic bile duct stones, but early endoscopic removal appeared to have little effect on the prevention of further biliary complications. Given the risk of procedure-related pancreatitis, the wait-and-see strategy may become a management option of asymptomatic stones.

Autoimmune pancreatitis (AIP) is frequently complicated by diabetes mellitus (DM), but DM associated with AIP is reported to improve after steroid therapy. The aim of this study is to investigate glucose intolerance during steroid therapy according to the onset of DM. Sixty-one patients who underwent steroid therapy for AIP were included into this study. We evaluated C peptide index (CPI), homeostasis model assessment for insulin resistance (HOMA-R), and the pancreatic diameter at AIP diagnosis and after 4 weeks, 1 year, and 2 years of steroid therapy. Patients were categorized into three groups according to DM onset: Pre-existing DM (pDM), concurrent DM (cDM), and non-DM (nDM). Forty-three patients (71%) had DM: 15 pDM and 28 cDM. At AIP diagnosis, CPI was lower in patients with pDM (0.7, P = 0.007) and cDM (0.9, P = 0.018) than nDM (1.3). After 4 weeks of steroid therapy, CPI improved in cDM (P < 0.001) and in nDM (P = 0.021). After 2 years of steroid therapy, HOMA-R increased (2.1–3.0, P = 0.007) but CPI gradually improved (1.0–2.1, P = 0.004). DM improved in 23% of cDM, and 55% of insulin users in cDM discontinued using insulin. Pancreatic atrophy was seen in 30%, and was associated with DM. DM in patients with AIP was associated with impaired insulin secretion rather than insulin resistance. Insulin secretion improved during steroid therapy for AIP in patients with concurrent DM. Thus, glucose intolerance can be an indication for AIP treatment.

Although surgical or endoscopic treatment is effective for pain control in symptomatic calcified chronic pancreatitis, it is still unknown whether early intervention in mild symptomatic pancreatic stones would reduce the frequency of acute exacerbation and improve long-term outcomes. The aim of this randomized-controlled trial was to explore the efficacy of early endotherapy for mild symptomatic pancreatic stones in comparison with the wait-and-see policy.Patients with mild symptoms because of pancreatic stones were assigned randomly to the endotherapy or the wait-and-see group. The wait-and-see group received endotherapy only when they developed refractory exacerbation or intractable pain. The primary outcome was the cumulative incidence of intolerable pain attacks and acute exacerbation. The secondary outcomes were the development of pancreatic insufficiency and the progression of pancreatic atrophy.A total of 20 patients were enrolled between March 2008 and March 2011. The study was terminated prematurely because of the poor patient enrollment. Early endotherapy tended to reduce the cumulative incidence of pain attacks and exacerbation, (P=0.17) with the composite incidence of pain attacks and exacerbation of 30% in the endotherapy group and 60% in the wait-and-see group. There were no significant differences in terms of diabetic status and the presence of steatorrhea. The thickness of the pancreas decreased significantly in the wait-and-see group (9.2-6.8 mm, P=0.041), but not in the endotherapy group (8.7-9.0 mm, P=0.60).In a small group of patients, early endotherapy in mild symptomatic chronic pancreatitis was associated with a trend toward a minor number of acute attacks and atrophy progression of the pancreas.

Objectives A multivariate index calculated using plasma free amino acids (PFAA index) was reported as a diagnostic biomarker for pancreatic cancer (PaC). Although diabetes mellitus (DM) is expected to be an early diagnostic indicator of PaC, identifying the high-risk individuals among patients with DM is warranted. We evaluated the diagnostic yield of the PFAA index for PaC in patients with DM. Methods We compared the diagnostic yield of the PFAA index between individuals with and those without DM. Cases and controls were recruited prospectively, and controls were matched to cases at a 1:1 ratio for age, sex, and DM status. Results A total of 180 case–control pairs were included in the analysis. The prevalence of DM was 53.3%. The sensitivity of the PFAA index was 66.7% in cases with DM and 56.0% in those without DM (P = 0.14), and the specificity was 92.7% in controls with DM and 94.0% in those without DM (P = 0.95). Conclusions This matched case-control study revealed a comparable diagnostic yield of the PFAA index for PaC in individuals with and those without DM. The PFAA index can be used as a biomarker for further diagnostic imaging in selected patients with DM.

Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial sho...

Background/Aims: Endoscopic management by endoscopic sphincterotomy with or without plastic stents or fully covered self-expandable metallic stents (FCSEMSs) is widely accepted as the current standard of care for postoperative bile leaks. Biliary stents are placed across the papilla, not above the papilla. We investigated the safety and effectiveness of the bridge-and-seal technique for bile leaks by the placement of FCSEMS above the papilla. Methods: This was a retrospective study of FCSEMS placement above the papilla for bile leaks between October 2016 and July 2021. FCSEMS was placed above the papilla to bridge and seal the leak. The main outcome measures were the resolution of bile leaks and adverse events. Results: Seven patients with postoperative bile leaks underwent FCSEMS above the papilla. The locations of bile leaks were 1 cystic duct remnant; 2 intrahepatic bile duct; 1 hepatic duct; 2 common bile duct and 1 anastomosis. The technical success rate of FCSEMS placement was 100%, and resolution of bile leaks was achieved in five patients (71.4%). All the adverse events were observed after FCSEMS removal; as follows: 1 moderate cholangitis; 2 mild post-ERCP pancreatitis; and 1 mild remnant cholecystitis. Conclusions: FCSEMS placement above the papilla can be a treatment option for postoperative bile leaks.

BACKGROUND Multidrug-resistant bacteria (MDRB) has rapidly spread worldwide and become a serious problem. Proton pump inhibitors (PPIs) are a class of commonly prescribed medications, but recent studies have suggested the increased risk of infection with MDRB in PPI users. We evaluated the association between PPI use and incidence of cholangitis with MDRB. METHODS Consecutive patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) between January 2010 and August 2019 were included in this retrospective study. The incidence of cholangitis with MDRB was compared between regular and non-regular PPI users. RESULTS A total of 1224 regular PPI users and 1528 non-regular PPI users were identified. There was no clinically significant difference in age and sex between the groups. Indication of ERCP was different between the groups. The number of ERCP sessions during the study periods was higher in regular PPI users. The incidence of cholangitis with MDRB was significantly higher in regular PPI users (3.0% vs 1.1%; P