Search

The appropriate method of preoperative endoscopic biliary drainage (EBD) for cholangiocarcinoma with hilar biliary obstruction remains controversial. The inside-stent technique is a method of placing plastic stents entirely inside the bile duct. Several studies of patients with unresectable stage have reported longer stent patency compared with conventional endoscopic biliary stenting (EBS). Inside-stent techniques have been introduced as a bridge-to-surgery option and as an alternative to conventional EBS.We aimed to evaluate the clinical outcomes of inside stent use and conventional EBS.During this retrospective multicenter study, we reviewed consecutive patients with cholangiocarcinoma who underwent radical surgery after conventional EBS or inside-stent insertion. Adverse event (AE) rates after EBD and post-surgical AEs were compared. A multivariable analysis was performed to identify factors affecting cholangitis after EBD.Conventional EBS and inside-stent procedures were performed for 56 and 73 patients, respectively. Patient backgrounds were similar between groups, except for percutaneous transhepatic portal vein embolization. The waiting time before surgery was similar between groups (28.5 days vs. 30 days). There were no significant differences in the cholangitis rate (21.4% vs. 26.0%; P = 0.68) and all AEs (25.0% vs. 30.1%; P = 0.56) between groups. The post-surgical AE rate was similar between the groups. The multivariable analysis found that preprocedural cholangitis was a risk factor for cholangitis after EBD (odds ratio: 5.67; 95% confidence interval: 1.61-19.9).The outcomes of inside-stent techniques and conventional EBS for the management of preoperative EBD are comparable for patients with cholangiocarcinoma.

Interventional endoscopic ultrasonography is performed for various situations that require drainage, after which stent migration is the most severe adverse event. Several lumen-apposing metal stents (LAMS) and covered self-expandable metal stents (CSEMS) provide antimigration systems; however, their anchoring ability has not been studied well. Therefore, we measured and compared the anchoring force (ACF) of commercially available LAMS and CSEMS.Anchoring force was measured for five types of LAMS (NAGI, SPAXUS, Plumber, and AXIOS 8 and 10 mm) and seven types of CSEMS (BCL, SHCL, BCG, BPD [four types of HANAROSTENT], HILZO, Niti-S [Spring Stopper], and Wallflex). We created a phantom model for inducing stent migration. It has a rotatable part as a curved fixture, and we measured ACF at angles between 0° and 40°.The mean ACF at 0° and 20° were NAGI 1.50, 1.84 N, SPAXUS 1.73, 1.72 N, Plumber 2.64, 2.03 N, and AXIOS 3.96, 3.61 N, respectively; and BCL 0.48, 0.53 N, Wallflex 0.53, 0.48 N, SHCL 0.64, 0.73 N, HILZO 1.09, 1.09 N, BCG 1.22, 1.20 N, BPD 1.78, 1.67 N, and Spring Stopper 2.29, 2.51 N.We measured ACF in LAMS and CSEMS with a new phantom model. The highest value among the LAMS was for the AXIOS and among the CSEMS was for the Spring Stopper. Some of the ACF values varied with the direction of pull. These findings may have a significant impact on stent selection for interventional endoscopic ultrasonography, and this model can be used to evaluate newly developed stents.

Video 1The duct was cannulated with a modified MTW catheter using the hitch-and-ride method. A duodenal flap of the 5F, 7-cm pancreatic plastic stent was cut with a surgical scalpel and tied to the duodenal edge of the stent with a 0.3-mm silk suture. The suture tied to the stent was ligated at the center. The sutured stent was inserted into the pancreatic duct above the minor duodenal papilla. The tumor and silk suture were held together by a 25-mm oval polypectomy snare and were resected. The suture tied to the pancreatic plastic stent was grasped by biopsy forceps and pulled into the duodenum.

Predictive factors for intrahepatic cholangiocarcinoma in long-term follow-up of hepatolithiasis are unknown. We thus conducted a cohort study to investigate the predictive factors for developing intrahepatic cholangiocarcinoma in hepatolithiasis.This cohort is comprised of 401 patients registered in a nationwide survey of hepatolithiasis for 18 years of follow-up. Cox regression analysis was used to elucidate predictive factors for developing intrahepatic cholangiocarcinoma.The median follow-up period of patients was 134 months. Twenty-two patients developed intrahepatic cholangiocarcinoma and all died. Identified independent significant factors were as follows: age 63 years or older (hazard ratio [HR] 3.344), residual stones at the end of treatment (HR 2.445), and biliary stricture during follow-up (HR 4.350). The incidence of intrahepatic cholangiocarcinoma in patients with three factors was significantly higher than that in patients with one or two factors. The incidence in the groups with one or two predictive factors was not different. In 88.9% of patients with both biliary stricture and intrahepatic cholangiocarcinoma, the duration between the diagnoses of biliary stricture and intrahepatic cholangiocarcinoma was ≥ 5 years. However, once intrahepatic cholangiocarcinoma developed, 77.8% of patients died within 1 year. Of 24 patients with no symptoms, no previous choledocoenterostomy, no signs of malignancy, no biliary stricture, and no treatment for hepatolithiasis during follow-up, only one developed intrahepatic cholangiocarcinoma.Regarding carcinogenesis, complete stone clearance and releasing biliary stricture can prevent the development of intrahepatic cholangiocarcinoma and improve the prognosis of hepatolithiasis.

The role of a covered vs. an uncovered self-expandable metal stent (SEMS) for malignant distal biliary obstruction (MDBO) is not clear. This meta-analysis compared the efficacy of covered vs. uncovered SEMS for patients with MDBO after endoscopic insertion.A systematic meta-analysis of all relevant articles listed in PubMed, the Cochrane Library, and Google Scholar databases was performed. Fixed effects or random effects models were used to investigate pooled effects with 95% confidence intervals (CIs).The meta-analysis included 2358 patients from 12 eligible studies. Time to recurrent biliary obstruction (RBO) was significantly longer for covered SEMS (mean difference, 45.51 days; 95% CI 11.79-79.24). Although there was no significant difference in the RBO rate, subgroup analysis in pancreatic cancer occupying more than 90% (PC) revealed that the RBO rates were significantly lower for covered SEMS (odds ratio [OR] 0.43, 95% CI 0.25-0.74). Stent migration, sludge formation, and overgrowth were significantly more common with a covered SEMS (OR 7.92, 95% CI 4.01-15.64; OR 3.25, 95% CI 1.89-5.59; OR 2.03, 95% CI 1.20-3.43, respectively). The rate of ingrowth was significantly lower for covered SEMS. There was no significant difference in total procedure-related adverse events between the two types of SEMS.A covered SEMS is superior to an uncovered SEMS with respect to prevention of RBO in patients with MDBO, particularly those caused by PC.

Background Indeterminate strictures pose a therapeutic dilemma. In recent years, cholangioscopy has evolved and the availability of cholangioscopy has increased. However, the position of cholangioscopy in the diagnostic algorithm to diagnose malignancy have not been well established. We aim to develop a consensus statement regarding the clinical role of cholangioscopy in the diagnosis of indeterminate biliary strictures. Methods The international experts reviewed the evidence and modified the statements using a three-step modified Delphi method. Each statement achieves consensus when it has at least 80% agreement. Results Nine final statements were formulated. An indeterminate biliary stricture is defined as that of uncertain etiology under imaging or tissue diagnosis. When available, cholangioscopic assessment and guided biopsy during the first round of ERCP may reduce the need to perform multiple procedures. Cholangioscopy are helpful in diagnosing malignant biliary strictures by both direct visualization and targeted biopsy. The absence of disease progression for at least 6 months is supportive of non-malignant etiology. Direct per-oral cholangioscopy provides the largest accessory channel, better image definition, with image enhancement but is technically demanding. Image enhancement during cholangioscopy may increase the diagnostic sensitivity of visual impression of malignant biliary strictures. Cholangioscopic imaging characteristics including tumor vessels, papillary projection, nodular or polypoid mass, and infiltrative lesions are highly suggestive for neoplastic/malignant biliary disease. The risk of cholangioscopy related cholangitis is higher than in standard ERCP, necessitating prophylactic antibiotics and ensuring adequate biliary drainage. Per-oral cholangioscopy may not be the modality of choice in the evaluation of distal biliary strictures due to inherent technical difficulties. Conclusion Evidence supports that cholangioscopy has an adjunct role to abdominal imaging and ERCP tissue acquisition in order to evaluate and diagnose indeterminate biliary strictures.

AIM Anti-ribosomal P protein antibodies (anti-ribo P) have been reported as one of the specific autoantibodies in patients with systemic lupus erythematosus (SLE) and has been demonstrated to bind and activate macrophages in vitro. Clinically, hyperferritinemia has been known to be a biomarker for macrophage activation. The aim of this study is to clarify the relationship of anti-ribo P and clinical characteristics and biomarkers including serum ferritin in patients with SLE. METHODS Clinical parameters and laboratory data were measured in patients with active SLE (N = 127) in our university hospital. The risk factors affected by anti-ribo P were retrospectively calculated by logistic regression analysis, and the correlation of anti-ribo P and clinical factors was demonstrated. RESULTS Anti-ribo P was significantly elevated in active SLE compared to non-SLE diseases (P

Background: Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is a devastating and life-threatening condition during its clinical course. Biomarkers for precisely anticipating the prognosis of AE-IPF remain to be fully established. The objective of this study was to clarify whether S100A8 and S100A9, which are calcium-binding proteins mainly produced by activated neutrophils, are significant prognostic biomarkers in AE-IPF.Methods: Thirty-seven patients with AE-IPF who were diagnosed and treated at our hospital were retrospectively evaluated. The serum levels of S100A8 and S100A9 were measured using enzyme-linked immunosorbent assay, and the relationships between these levels and clinical parameters or prognosis were evaluated.Results: The serum levels of S100A8 (median 386.5ng/mL) and S100A9 (median 60.2ng/mL) in patients with AE-IPF were significantly higher than those in age-matched healthy controls and in patients at IPF diagnosis (p

BACKGROUND Disconnected pancreatic duct syndrome (DPDS) frequently occurs in patients with acute necrotizing pancreatitis and resultant pancreatic fluid collection (PFC). We performed a systematic review and meta-analysis to evaluate outcomes of endoscopic ultrasound-guided treatment of PFCs according to the presence of DPDS. METHODS Using PubMed, Embase, and the Cochrane database, we identified clinical studies published until January 2021 with data comparing outcomes of endoscopic ultrasound-guided drainage of PFCs between DPDS and non-DPDS patients. We pooled data on technical and clinical success rates, PFC recurrence, and adverse events using the random-effects model. RESULTS We identified five eligible articles including 941 PFC patients treated with endoscopic ultrasound-guided interventions. Clinical success, defined as resolution of the PFC and symptoms, was achieved in a majority of the cases irrespective of DPDS (pooled odds ratio [OR] comparing DPDS to non-DPDS patients, 0.77; 95% confidence interval [CI] 0.33-1.81). Compared to patients without DPDS, patients with DPDS were more likely to undergo PFC recurrence (pooled OR 6.72; 95% CI 2.72-16.6) after clinical resolution of PFC. Prolonged plastic stent placement following the clinical resolution was more frequently performed in DPDS patients than in non-DPDS patients (pooled OR 15.9; 95% CI 2.76-91.9). No statistically significant difference was observed between the groups in terms of the rate of technical success, adverse events, or mortality. CONCLUSION Disconnected pancreatic duct syndrome was associated with higher rate of PFC recurrence after successful endoscopic treatment of PFCs. Future studies should evaluate effectiveness and optimal duration of long-term placement of transmural plastic stents for PFCs with DPDS.

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.

Objectives The oncological outcomes, especially high recurrence rate, of bridge-to-surgery (BTS) self-expandable metallic stent (SEMS) placement remain concerning, emphasizing the necessity of standardized SEMS placement. However, its impact on long-term BTS outcomes is unknown. We investigated the long-term outcomes of BTS colonic stenting using standardized SEMS placement. Methods This prospective, multicenter cohort study conducted at 46 hospitals in Japan (March 2012-October 2013) included consecutive patients with stage II and III obstructive colorectal cancer managed with BTS SEMS placement. The SEMS placement technique was standardized by information dissemination among the participating hospitals. The primary outcome was overall survival (OS) after SEMS placement, and the secondary outcomes were relapse-free survival (RFS), recurrence, and short-term outcomes of SEMS placement and surgery. Results The 1-, 3-, and 5-year OS rates were 94.1%, 77.4%, and 67.4%(Kaplan-Meier), respectively, with high technical success (99.0%, 206/208) and low perforation (1.9%, 4/208) rates. The 1-, 3-, and 5-year RFS rates were 81.6%, 65.6%, and 57.9% (Kaplan-Meier), respectively, and the overall recurrence rate was 31.0% (62/200). The RFS rate was significantly poorer in patients with perforation (n = 4) than in those without perforation (n = 196) (log-rank p = 0.017); moreover, perforation was identified as an independent factor affecting RFS (hazard ratio: 3.31; 95% confidence interval: 1.03-10.71, multivariate Cox regression). Conclusions This large, prospective, multicenter study revealed satisfactory long-term outcomes of BTS colonic stenting using a standardized SEMS insertion method, which might be specifically due to reduced perforation rate. (UMIN000007953).

Pancreatic fluid collections (PFCs) commonly develop as complications of acute pancreatitis and ductal disruption due to chronic pancreatitis. In the revised Atlanta classification, PFCs were classified based on the presence of necrosis and duration following the onset of acute pancreatitis. Interventions are required in cases of symptomatic pancreatic pseudocysts or walled-off necrosis (WON). In the management of these PFCs, endoscopic ultrasound-guided transluminal drainage and subsequent direct endoscopic necrosectomy for WON are increasingly utilized as less invasive treatment modalities compared to surgical debridement. To date, researchers have focused predominantly on the technical aspects of endoscopic therapy for symptomatic PFCs. Given the poor physical condition of patients receiving endoscopic treatment for PFCs, systemic support may have a substantial impact on the short- and long-term outcomes of these patients. A multidisciplinary approach is required to improve the clinical outcomes of patients with infected PFCs and their associated comorbidities. However, non-interventional support during the periprocedural period of endoscopic treatment of PFCs has not been fully discussed, and there have been considerable variations in the selection of treatment options between endoscopists and centers. To address these unmet needs in the clinical management of PFCs and promote future research to improve the clinical outcomes, we conducted a review of the literature within a multicenter consortium of expert endoscopists with specific expertise in the endoscopic treatment of PFCs. In this review, we summarize the current evidence on non-interventional supportive care (e.g., continuous lavage, medications, nutritional support, and antimicrobials) and propose potential topics for future research.

Background: To investigate patient characteristics and the risk of post endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in association with fluid volume and type during ERCP. Methods: Two hundred and forty seven of 480 patients with naïve papilla undergoing therapeutic ERCP between April 2013 and March 2018 were enrolled for the study. The following patient characteristics were investigated: age, sex, body mass index, previous diseases (heart disease, renal failure, cerebrovascular disorders, coexisting malignancy and pulmonary disease), history of PEP, common bile duct diameter, diverticula and volume of fluid infused 24 hours after the procedure. All ERCP cases had naïve papilla and had undergone treatment. Results: The incidence of PEP was 8.5%. Significant differences were observed in the volume of fluid infused between patients without and with a history of heart disease (1,380 vs. 1,755 mL). The mean volume of the infused fluid was significantly lower in the PEP than non-PEP group (1,483 vs. 1,688 mL, P = 0.02). Moreover, PEP incidence differed according to a fluid infusion cutoff of 1,000 mL (7 vs. 11 cases of PEP in those with ≦1,000 mL and >1,000 mL fluid volume, respectively, P < 0.001). Conclusion: Restricted fluid volume was a newly identified risk factor for PEP, particularly in patients with heart and renal diseases as comorbidities.

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 and study aim Management of bile duct stones (BDSs) in patients with surgically altered anatomies (SAAs) remains challenging. An endoscopic ultrasound-guided antegrade (EUS-AG) procedure and double-balloon enteroscopy-assisted endoscopic retrograde cholangiography (DB-ERC) have been used to remove BDSs from patients with SAAs. However, few comparative data have been reported. Therefore, we compared the efficacy and safety of the techniques. Methods This was a single-center retrospective study. Patients with SAA who underwent the EUS-AG procedure or DB-ERC to remove intra- or extra-BDSs between November 2010 and March 2020 were included. The primary outcome was the technical success rate, defined as stent insertion or stone removal during the initial session. The secondary outcomes were the procedure time, incidence of adverse events (AEs), and complete stone removal rate. Results Of the 54 patients enrolled, 23 underwent the EUS-AG procedure and 31 DB-ERC. The technical success rates of EUS-AG and DB-ERC were 87.0% and 64.5%, respectively (P = 0.11). The procedure time was significantly shorter in the EUS-AG group than in the DB-ERC group (51.9 ± 15.4 vs 72.6 ± 32.2 min; P = 0.01), and the early AE rates were 26.1% and 12.9%, respectively (P = 0.71). The complete stone removal rates in patients who underwent previous stone removal were 94.1% in the EUS-AG group and 85.7% in the DB-ERC group (P = 0.61). Conclusion The EUS-AG afforded technical success and complete stone removal rates comparable with those of DB-ERC, but the former procedure was shorter. The AE rate was acceptable.

Acute recurrent pancreatitis (ARP) is defined as two distinct episodes of acute pancreatitis (AP), whereas chronic pancreatitis (CP) is caused by persistent inflammation of the pancreas. In children they are caused by genetic mutations, autoimmune pancreatitis, congenital pancreatic abnormalities, and other conditions. Acute recurrent pancreatitis is frequently a precursor to CP, and both are thought to be on the same disease continuum. In particular, genetic factors are associated with early progression of ARP to CP. The diagnosis of CP, as in AP, is based on clinical findings, biochemical tests, and imaging studies. Findings of exocrine pancreatic dysfunction are also important in the diagnosis of CP. A step-up strategy has become increasingly standard for the treatment of patients with CP. This strategy starts with endoscopic treatment, such as pancreatic sphincterotomy and stenting, and progresses to surgery should endoscopic therapy fail or prove technically impossible. Non-opioid (e.g. ibuprofen / naproxen) and opioid (e.g. oxycodone) forms of analgesia are widely used in pediatric patients with AP or CP, whereas pancreatic enzyme replacement therapy may be beneficial for patients with abdominal pain, steatorrhea, and malnutrition. Despite the disparity in the age of onset, pediatric CP patients display some similarities to adults in terms of disease progress. To reduce the risk of developing pancreatic exocrine inefficiency, diabetes and pancreatic cancer in the future, clinicians need to be aware of the current diagnostic approach and treatment methods for ARP and CP and refer them to a pediatric gastroenterologist in a timely manner.

Background and aims Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is used for the histopathological diagnosis of any type of gastrointestinal disease. Few adverse events are experienced with this procedure; however, the actual rate of adverse events remains unclear. This study aimed to clarify the current status of cases that experienced adverse events related to the EUS-FNA procedure used for histopathologic diagnoses. Methods A retrospective analysis of cases with EUS-FNA-related adverse events in Japanese tertiary centers was conducted by assessing the following clinical data: basic case information, FNA technique, type of procedural adverse events, and prognosis. Results Of the 13,566 EUS-FNA cases overall, the total number of cases in which adverse events related to EUS-FNA occurred was 234. The incidence of EUS-FNA-related adverse events was ~1.7%. Bleeding and pancreatitis cases accounted for ~49.1% and 26.5% of all adverse events, respectively. Bleeding was the most common adverse event with only seven cases requiring blood transfusion. In cases with neuroendocrine tumors, pancreatitis was the most frequent adverse event. Needle tract seeding because of EUS-FNA was observed during the follow-up period in only ~0.1% of cases with pancreatic cancer. There was no mortality because of adverse events caused by EUS-FNA. Conclusions This study revealed that the adverse events-related EUS-FNA for histopathologic diagnoses were not severe conditions, and had low incidence.

Background Interventional endoscopic ultrasound-guided procedures (I-EUS) are widely accepted as salvage procedures in ERCP-failed cases, and to drain fluid collected in the abdominal cavity. Although I-EUS has a relatively high incidence of complications and is severe/fatal in some cases, no follow-up strategy has been established. In our institution, plain computed tomography (P-CT) is performed routinely the day after I-EUS. In this study, we evaluated the usefulness of routine P-CT the day after I-EUS, as a follow-up method, and propose an algorithm. Methods We retrospectively reviewed 81 patients who underwent I-EUS and evaluated the usefulness of P-CT, abdominal X-ray, laboratory data, and symptoms as a follow-up method. An adverse event (AE) was defined as an event requiring any treatment. Results Technical success, clinical success, and AE rates were 96.3%, 90.1%, and 18.9%, respectively. In total, 30 patients had abnormal findings among the follow-up methods: 6 cases underwent additional procedures, 8 underwent medical treatments, and 16 were observed. The sensitivity, specificity, and accuracy for detecting AEs were assessed based on P-CT (85.7%, 100%, and 97.5%), X-ray (7.1%, 100%, and 83.5%), laboratory data (71.4%, 83.0%, and 81.0%), and symptoms (92.9%, 86.2%, and 87.3%). The sensitivity and accuracy of the latter two items were as high as those for X-ray, but specificity was lower than those for X-ray and P-CT. Conclusions Routine P-CT the day after I-EUS was useful for detecting complications and deciding to perform an invasive salvage procedure. Symptoms and laboratory data were useful to supplement routine P-CT.

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

To clarify whether there were any significant differences in clinical symptoms and eating patterns between functional dyspepsia (FD) patients and FD with pancreatic enzyme abnormalities (FD-P) patients as refractory FD, we compared these factors in multicenter studies in Singapore and Japan.One hundred ninety-eight consecutive patients presenting with FD (n = 88), FD-P patients (n = 81) based on Rome III classification and controlled group (n = 39) recruited from six institutions in Singapore and Japan. Clinical characteristics, clinical symptoms for dietary fat intake, and eating behaviors were estimated using questionnaires. Anxiety and health-related quality of life were determined by STAI-state/-trait and SF-8, respectively.There were no significant differences in age, sex, BMI, smoking, alcohol intake, past medical history, and history of allergy in FD and FD-P patients between Singapore and Japan. There were no significant differences in FD subtypes, gastrointestinal symptom rating scale score, severity of FD symptoms, and eating pattern in Singapore and Japan. Moreover, there were significant differences in certain eating behaviors between FD and FD-P patients in Singapore and Japan. Interestingly, epigastric pain and early satiety following fat meals in FD-P patients were significantly (P = 0.003 and P = 0.008, respectively) higher compared with those in FD patients in Japan. Physical component score in FD-P patients was significantly (P = 0.019) disturbed compared with those in FD patients in Japan.Epigastric pain and early satiety following fat meals in FD-P patients may be useful tools to differentiate FD-P patients from FD patients in Japan.

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.

OBJECTIVES Colorectal stenting is widely performed using self-expandable metallic stents (SEMSs), but the mechanical properties have not been evaluated. Therefore, we conducted an in vitro study to evaluate the mechanical properties of colorectal SEMSs. METHODS Eighteen individual types and sizes of uncovered SEMSs were evaluated for their mechanical properties. Radial force was measured using a measurement machine. Axial force (AF) was measured by two methods: a conventional manual method and a new method using a measurement machine. The correlation of these two methods was evaluated. We also proposed an "AF zero border" that was defined as the angle at which the torque force disappeared. RESULTS Radial force versus diameter curves and AF versus angle curves were influenced by the structure and the size of each stent. There was excellent correlation of AFs measured by the new and conventional manual method (y = 21.434x, R = 0.881, P

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

Background/Aims: The aim of this study was to evaluate the safety and efficacy of partially covered self-expandable metallic stents (PCSEMS) in patients undergoing neoadjuvant chemo (radio) therapy (NAC) for pancreatic cancer (PC). Methods: This was a prospective multicenter study to evaluate the safety and efficacy of PC-SEMS in patients receiving NAC for resectable and borderline resectable PC. The primary endpoint was the rate of recurrent biliary obstruction (RBO). Results: Twenty-six patients with PC (three with resectable PC and 23 with borderline resectable PC) who underwent NAC at seven Japanese centers were included in the analysis. Both the technical and functional success rates of PCSEMS placement were 100%. Early stent-related complications were observed in three patients (11.5%): mild pancreatitis (n=2) and mild liver abscess (n=1). The median time to surgery or palliation was 4.0 months. Surgical resection was eventually performed in 73.1% of patients, and stent removal during surgery was successful in all patients. RBO was observed in nine patients (34.6%): seven with stent occlusion, one with kinking and one with migration. The RBO rates in resected cases and nonresected cases were 36.8% and 28.6%, respectively. Conclusions: Biliary drainage by PCSEMS was safe and feasible in patients undergoing NAC for resectable and borderline resectable PC. (Gut Liver 2021;15:135-141)

Objectives To clarify the significance of ultrasonographically recorded pancreatic duct dilatation. Methods Various parameters predicting pancreatic disease were evaluated in relation to pancreatic duct dilatation using data from medical checkups of healthy examinees. Results Records of 281,384 subjects were analyzed. Pancreatic duct dilatation (≥3 mm) was determined ultrasonographically in 524 patients (0.19%). Subsequent detailed examinations revealed the presence of pancreatic disease in 24.8% of these patients, including pancreatic cysts (15.6%) and chronic pancreatitis (4.9%). Pancreatic cancer was found in 6 cases (1.3%). Predictive factors of pancreatic diseases in examinees with pancreatic duct dilatation were investigated, and the diameter of the pancreatic duct (p

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.

OBJECTIVE The aim of the study was to develop a formula for predicting the probability of malignancy of mucinous cystic neoplasm (MCN) of the pancreas with ovarian-type stroma. METHODS A total of 364 patients were enrolled. A total score was calculated as the sum of the approximate integers of the odds ratios of the predictive factors identified by multivariate analysis. The relationship between the total score and pathological results was assessed. RESULTS A total of 321 patients had benign MCN and 43 had malignant MCN. Five possible predictive factors were analyzed: 56 years or older, high serum carcinoembryonic antigen level, high carbohydrate antigen 19-9 level, tumor size of 51 mm or greater, and the presence of mural nodules. The total score was significantly higher in patients with malignant MCN (median, 24; range, 0-37) compared with benign MCN (median, 5; range, 0-33; P < 0.001). Receiver operating characteristic curve analysis demonstrated that the area under the curve was 0.86, and the sensitivity and specificity of the total score for discriminating malignant MCNs were 72% and 83%, respectively, using a cut-off value of 22. CONCLUSIONS The current simple formula can predict the malignancy of MCN and may thus contribute to the adequate management of patients with MCN.

Background/Aim: A sufficiently open papilla is needed to remove common bile duct stones (CBDS) but endoscopic sphincterotomy (EST) requires a high level of skill and is difficult with endoscopic papillary balloon dilation (EPBD). The main adverse event of EST is bleeding and perforation and that of EPBD is post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. To reduce these adverse events we employed minimal EST followed by papillary dilation (ESBD), and retrospectively evaluated its efficacy and safety compared with EST. Patients and Methods: CBDS patients who underwent EST (n = 114) or ESBD (n = 321) at Juntendo University Hospital from January 2009 to December 2018 were consecutively enrolled, retrospectively. The exclusion criteria were large-balloon dilation (≥ 12 mm), large CBDS (>12 mm), and previous EST/EPBD. We compared the overall stone removal rate, incidence of adverse event, procedure time, number of ERCP procedures, and rate of mechanical lithotripsy (ML) between the two groups. Results: Complete stone removal was successful in both ESBD and EST group. However, the rate of multiple ERCP sessions was significantly lower (35.1% vs. 12.8%, P < 0.001), procedure time was shorter (31.6 vs. 25.8 min, P = 0.01), and rate of ML was lower (16.7% vs. 7.8%, P = 0.01) in ESBD group. Bleeding was significantly more frequent in the EST group (9.6% vs. 1.2%, P < 0.001), particularly acute bleeding (7.9% vs. 0.9%, P < 0.001). Conclusions: ESBD is more efficient and safer in the management of CBD stones than EST. A prospective randomized study comparing ESBD with EST is needed to establish this combination technique.

Endoscopic ultrasound-guided tissue acquisition (EUS-TA) plays a crucial role in the diagnosis of pancreatic tumors. The present study aimed to investigate the current status of needle tract seeding (NTS) after EUS-TA of pancreatic tumors based on a nationwide survey in Japan.Patients who underwent surgical resection of primary pancreatic tumors after EUS-TA performed between April 2010 and March 2018 were surveyed. The incidence rates of NTS were determined, and compared in patients with pancreatic ductal adenocarcinomas (PDACs) and other tumors, and in patients who underwent transgastric and transduodenal EUS-TA of PDACs. The detailed features and prognosis of patients with NTS were also assessed.A total of 12,109 patients underwent surgical resection of primary pancreatic tumors after EUS-TA. The overall incidence rate of NTS was 0.330%, and the NTS rate was significantly higher in patients with PDAC than in those with other tumors (0.409% vs. 0.071%, P=0.004). NTS was observed in 0.857% of patients who underwent transgastric EUS-TA, but in none of those who underwent transduodenal EUS-TA. Of the patients with NTS of PDACs, the median time from EUS-TA to occurrence of NTS and median patient survival were 19.3 and 44.7 months, respectively, with 97.4% of NTS located in the gastric wall and 65.8% of NTS resected. The patient survival was significantly longer in patients who underwent NTS resection than in those without NTS resection (P=0.037).NTS appeared only after transgastric not after transduodenal EUS-TA. Careful follow-up provides an opportunity to remove localized NTS lesions by gastrectomy.

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.

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.

Benign esophageal strictures (BES) cause dysphagia and decrease patients' quality of life. Although mechanical dilation is the standard of care for BES, in some patients, dysphagia is unrelieved despite repeated procedures. The biodegradable stent was developed to resolve refractory BES, with reported favorable outcomes, but it is unapproved in Japan. Thus, we evaluated the safety and efficacy of the biodegradable stent (BDS) for patients with refractory BES for regulatory approval.This was a nonrandomized single-arm prospective trial conducted at eight institutions. We included patients with BES after ≥ 5 times of dilation or ≥ one time of radial incision and cutting whose dysphagia score (DS) was 2 or worse and an endoscope could not admit. The primary endpoint was the proportion of patients whose DS improvement of ≤ 1 was maintained at 3 months.Thirty patients (median age: 69 years, male/female: 27:3) were enrolled and treated; BDS placement failed in 1 patient. Fourteen patients maintained their DS improvement until 3 months after placement (proportion of DS improvement at 3 months 46.7% [95% CI: 28.3-65.7]), and the median dysphagia-free survival was 98 days [95% CI: 68-123]. Most adverse events could be managed conservatively; however, a patient with BES after chemoradiotherapy (CRT) developed an esophago-left atrium fistula and died approximately 4 months after stent placement.The BDS was effective for refractory BES and the safety was acceptable. However, the indication for this procedure in patients RECEIVING CRT for esophageal cancer should be carefully considered.

A decrease in carbohydrate antigen (CA) 19-9 levels has been proposed as a prognostic marker for survival and recurrence in patients with pancreatic cancer. We evaluated the association between duration of reduced CA 19-9 levels during 6 months after treatment and long-term survival for 79 patients with unresectable locally advanced pancreatic cancer (LAPC). We calculated the differences between pretreatment and monthly CA19-9 levels. We categorized 71 patients with decreases in CA19-9 levels into three groups based on the duration of these reduced levels (&gt, 2, &gt, 3, and &gt, 4 months). The cut-off level for long-term (more than 2 years) survival was identified as a 44% reduction from the baseline, using a ROC curve. A reduction duration &gt, 2 months was not associated with overall survival (p = 0.1), while &gt, 3 months was significantly associated with survival (p =.04). In multivariate analysis, a reduction duration &gt, 3 months predicted a good long-term prognosis (odds ratio = 5.75, 95% confidence interval = 1.47–22.36, p &lt, 0.01). In patients with unresectable LAPC, the duration of reduced CA19-9 levels for more than 3 months, rather than the rate of reduction in CA19-9 levels, during 6 months after treatment was significantly associated with good prognosis.

Video Video 1 Percutaneous cholangioscopy was performed to confirm complete closure of the choledochojejunostomy. Percutaneous cholangioscopy revealed complete closure of the anastomosis. Our attempt to pass a guidewire through the anastomosis failed accordingly.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with a poor prognosis. There are no established serum biomarkers for predicting the outcomes of IPF. S100 calcium-binding protein A4 (S100A4) is considered as a marker of fibroblasts; however, its clinical application remains to be investigated. We evaluated the clinical relevance of S100A4 in IPF patients.Serum S100A4 levels in 95 consecutive IPF patients and 50 healthy controls (HC) were measured using enzyme-linked immunosorbent assay. S100A4 expression in lung tissues was determined using immunohistochemistry/immunofluorescence and its association with disease progression (defined as deterioration in lung function or death) and mortality was assessed using Kaplan-Meier method and Cox hazards analysis.Serum S100A4 levels were undetectable in all HC but were detectable in 26 (27.3%) of the 95 IPF patients (P 0.01). Immunostaining of lung tissues from IPF patients showed aggregation of numerous S100A4-expressing cells around the fibroblastic foci and mature fibrotic regions. IPF patients with higher serum S100A4 levels had a significantly worse prognosis than those with low serum levels (2-year cumulative survival rate: 41.7% vs 77.0%, respectively, P 0.01). On multivariate analyses, baseline serum S100A4 levels (per 10 ng/mL increase) were independently associated with higher disease progression rate (odds ratio: 1.06, P = 0.01) and higher mortality (hazard ratio: 1.18, P = 0.03).S100A4 is a promising serum biomarker that may help predict disease progression/mortality. Our findings may help establish treatment strategies for IPF.

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.