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1-Kestose (kestose) is the smallest fructooligosaccharide component and shows a particularly high prebiotic function. Both kestose and the bile acid metabolite isoallolithocholic acid (isoalloLCA) are known to be beneficial for human health, especially in terms of immune homeostasis in the gastrointestinal system; however, the effect of kestose on the levels of microbial isoalloLCA producers remains to be clarified. IsoalloLCA is known to be produced by several members of the phylum Bacteroidota that carry the 5α-reductase (5AR) gene, a key isoalloLCA biosynthetic gene. Thus, we designed a specific primer set to detect the 5AR gene based on the consensus sequences of the genes from several isoalloLCA producers. Using real-time quantitative PCR with this primer set and fecal DNA samples, we compared the 5AR gene level (5ar-level) in the intestinal microbiota of a kestose-supplemented group (n=20) and a placebo group (n=16) before and after intake for 12 wk. The 5ar-level was significantly increased in the kestose-supplemented group (p=0.015), but not in the placebo group (p=0.379), indicating that kestose supplementation increased the 5ar-level in human intestinal microbiota. Our findings suggest that targeting functional gene levels could potentially be used to predict and understand the beneficial prebiotic effects associated with changes in gut microbiota.

Background and Aims: Parkinson’s disease (PD) is the second most neurodegenerative disease after Alzheimer’s disease. Accumulating knowledge points to the notion that abnormal aggregation of alpha-synuclein (αSyn) starts in the gut and ascends to the substantia nigra via the vagus nerve in about a half of PD patients. Epidemiological studies revealed that ulcerative colitis (UC) increases a risk for PD 1.3 to 1.8-folds. However, it remains unknown whether αSyn is abnormally aggregated in the enteric neurons in UC patients. Methods: We first inspected and optimized the immunostaining protocols with an anti-phosphorylated αSyn antibody, pSyn#64, using the brain and the gut of eight autopsied cases (five with PD and three without PD). Then, we examined abnormal αSyn aggregation in the enteric neurons in 23 and 18 colectomized patients with and without UC, respectively. Five or more sections were stained for αSyn in each of 87 and 25 paraffin- embedded blocks in patients with and without UC, respectively. Results: Ten different protocols of epitope exposure appropriately stained aggregated αSyn in the brain, but only complete lack of epitope exposure stained aggregated αSyn in the colon with low background. Abnormal αSyn aggregates, which was confirmed by co-localization of p62, in the enteric neurons were detected in a single patient with UC but not in any patients without UC. Conclusions: Omission of epitope exposure enabled us to immunostain aggregated αSyn in the colon by pSyn#64 with low nonspecific staining, but the number of 23 UC patients was not high enough to discern whether abnormal αSyn aggregation in the colonic neural plexus was increased in UC or not.

Background: The prognostic nutritional index (PNI) and Charlson comorbidity index (CCI) have been useful for predicting the prognosis based on nutritional condition and comorbidities in surgery and endoscopic mucosal dissection. The age-adjusted CCI (ACCI) has also been reported to be useful in surgery, but it has not been applied to endoscopic treatment. We therefore clarified the prognostic factors associated with ampullary tumors treated with endoscopic papillectomy (EP). Methods: From January 2003 to December 2020, 236 patients who underwent EP for sporadic ampullary tumors at Nagoya University Hospital were included in this study. The 5-year survival and ability to predict the prognosis were evaluated in terms of the sex, PNI, ACCI, final pathological diagnosis, and intraductal extension. Results: During a median follow-up period of 1558 days, 17 patients died. No patient died of the primary disease. The 5-year survival rate was 91.1%. In a univariate analysis, only a high ACCI (≥ 5) was extracted as a significant prognostic factor (Odds ratio, 12.2; 95% confidence interval, 3.81–39.3; p

There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms.

Objectives: We investigated the utility of endoscopic ultrasound (EUS) for differentiating between solid pseudopapillary neoplasm of the pancreas (SPN) and pancreatic neuroendocrine neoplasm (PanNEN). Methods: A retrospective analysis was performed on 29 and 77 consecutive patients with pathologically proven SPN and nonfunctional PanNEN. In patients who underwent contrast-enhanced harmonic EUS (CH-EUS), lesions were classified into 3 vascular patterns (hypoechoic/isoechoic/hyperechoic), and the presence of “the alveolus nest sign,” which we previously reported as a characteristic feature of SPN on CH-EUS, was also assessed. Results: Conventional EUS findings showed that calcification echoes were significantly more frequent in SPN lesions than in PanNEN lesions (19/29 [66%] vs 21/77 [27%], P = 0.001) as was internal isoechogenicity or hyperechogenicity (10/29 [34%] vs 11/77 [14%], P = 0.029). Contrast-enhanced harmonic EUS findings showed that SPN lesions more frequently had the isoechoic or hypoechoic vascular pattern, and significantly more frequently had the alveolus nest sign (18/25 [72%] vs 4/60 [7%], P < 0.001). In a multivariate analysis, the presence of the alveolus nest sign contributed the most to the SPN diagnosis (odds ratio, 70; 95% confidence interval, 6.2–786). Conclusions: Endoscopic ultrasound, particularly the presence of the alveolus nest sign on CH-EUS, is useful for differentiating SPN from PanNEN.

To compare contrast-enhanced transabdominal ultrasonography (CE-US) following contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) with enhanced magnetic resonance imaging using gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (EOB-MRI) in the diagnosis of liver metastases in patients with pancreatic cancer.Patients who underwent contrast-enhanced computed tomography for possible pancreatic cancer and required further evaluation with CH-EUS were enrolled in this study, and the diagnostic performance of CE-US following CH-EUS for liver metastasis was compared with that of EOB-MRI.A total of 228 patients were included in the final analysis. Two hundred thirty-four hepatic lesions were found in 81 patients, and 178 lesions were finally diagnosed as metastases. EOB-MRI had a higher sensitivity (0.837 vs 0.949), while CE-US had a higher specificity and positive predictive value (PPV) (0.982 and 0.993 vs 0.911 and 0.971, respectively) in the diagnosis of liver metastasis. CE-US with defect reperfusion imaging had a higher diagnostic performance than EOB-MRI (0.866 vs 0.667) in the differentiation between liver metastasis and abscess.EOB-MRI had a higher sensitivity than CE-US for diagnosing liver metastasis in patients with pancreatic cancer, but CE-US following CH-EUS demonstrated a higher specificity and PPV than EOB-MRI and was especially useful in the differentiation between liver metastasis and abscess.

The gut microbiota interacts with infectious diseases and affects host immunity. Liver disease is also reportedly associated with changes in the gut microbiota. To elucidate the changes in the gut microbiota before and after hepatitis C virus (HCV) eradication through direct-acting antiviral (DAA) treatment in patients with chronic hepatitis C (CHC), we investigated 42 samples from 14 patients who received DAA therapy for HCV. Fecal samples were obtained before treatment (Pre), when treatment ended (EOT), and 24 weeks after treatment ended (Post24). The target V3–4 region of the 16S rRNA gene from fecal samples was amplified using the Illumina Miseq sequencing platform. The diversity of the gut microbiota did not significantly differ between Pre, EOT, and Post24. Principal coordinates analysis showed that for each patient, the values at Pre, EOT, and Post24 were concentrated within a small area. The linear discriminant analysis of effect size showed that the relative abundances of Faecalibacterium and Bacillus increased at EOT, further increased at Post24, and were significantly increased at Post24 compared to Pre. These suggest that changes in the gut microbiota should be considered as among the various effects observed on living organisms after HCV eradication.

The incidence and mortality rates of pancreatic cancer (PC) are increasing. It is important to discriminate PC from the other pancreatic lesions; however, differential diagnosis based on conventional transabdominal ultrasound (US) remains challenging even though US is often the first examination performed. Transabdominal contrast-enhanced ultrasound (CEUS) has high diagnostic accuracy for PC. This meta-analysis aimed to examine the utility of low-mechanical-index CEUS with enhancement for PC diagnosis. A systematic meta-analysis of all potentially relevant articles was performed. Fixed-effects or random-effects models were used to investigate pooled sensitivity, specificity, positive likelihood ratio (LR) and negative LR. The study enrolled 983 patients from nine eligible studies. The pooled estimates of sensitivity and specificity were 92% (95% confidence interval [CI]: 0.89-0.94) and 76% (95% CI: 0.71-0.81), respectively. The diagnostic odds ratio (DOR) for CEUS was high (53.62). The area under the summary receiver operating characteristic curve was 0.95. Funnel plots revealed no publication bias, and there was no significant relationship between the DORs and study characteristics, including continent, type of contrast agent, contrast agent dosage and scan phase. Only number of patients affected diagnostic ability. This meta-analysis indicates that CEUS with enhancement pattern is useful for diagnosis of PC.

Objectives: Pancreatic metastases from renal cell carcinoma (PRCC) often appear many years after treatment of the primary tumor, and differentiation from pancreatic neuroendocrine neoplasm (PanNEN) can be challenging due to their hypervascularity. Here, we investigated the utility of endoscopic ultrasound (EUS) for differentiation of these conditions. Methods: A retrospective analysis was performed in 17 and 79 consecutive patients with pathologically proven PRCC and non-functional PanNEN who were examined by EUS. In cases examined by EUS elastography or contrast-enhanced harmonic EUS (CH-EUS), the lesions were classified as stiff or soft, or into three vascular patterns as hypoechoic, isoechoic, and hyperechoic. CH-EUS images at 20 s, 40 s, 60 s, 3 min and 5 min were used for evaluation. EUS images were independently reviewed by two readers who were blinded to all clinical information. Results: The patients with PRCC were significantly older than those with PanNEN (median, 71 (range, 45–81) vs. 58 (22–76), P = 0.001) and more often had multiple tumors (6/17 (35%) vs. 7/79 (9%), P = 0.010). In EUS findings, PRCC lesions significantly more frequently had a marginal hypoechoic zone (MHZ) (11/17 (65%) vs. 27/79 (34%), P = 0.028), being classified as soft (12/13 (92%) vs. 26/58 (45%), P = 0.002), and showed sustained hyperechoic vascular patterns at 5 min (7/8 (88%) vs. 4/59 (7%), P < 0.001) compared to PanNEN lesions. Conclusions: The presence of a MHZ, a soft lesion, and a sustained hyperechoic vascular pattern in EUS may be useful for differentiating PRCC from PanNEN.

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.

The management of bleeding during endoscopic submucosal dissection (ESD) is critical and related to the procedure time. We collaborated on a new image enhancement algorithm with parameter optimization for clinical use being developed by FUJIFILM Co. and processed white light image data offline to evaluate the effectiveness of this technology. This study aims to evaluate the clinical usefulness of this technology.Eighteen video scenes of bleeding points from five gastric ESDs were selected and processed by the new image enhancement algorithm. The time until a bleeding point was found, visibility of a bleeding point, and color abnormality of the submucosal layer were evaluated by ESD experts, ESD trainees, and endoscopy trainees. The color differences between the bleeding point and the surroundings in CIE-L*a*b* color space were calculated in the original and enhanced images.The time until a bleeding point was found in the enhanced videos was significantly shorter than that in the original videos (11.10 s vs 13.85 s) (P = 0.017). On a 5-point (-2 to +2) Likert scale of visibility, the enhanced image was slightly superior to the original (+0.45), and the appearance of the submucosa was comparable between images (+0.14). The color difference among the bleeding areas on the enhanced images was significantly larger than that on the original images (10.93 vs 8.36).This novel image enhancement algorithm emphasizes the color difference between a bleeding point and the surrounding area, which would help find bleeding points faster during ESD for the less experienced endoscopists.

Background Endoscopic papillectomy of duodenal papillary tumors (PT) is indicated for adenomas or well-differentiated adenocarcinomas that do not involve the sphincter of Oddi. However, there is currently no reliable pre-operative method to diagnose the infiltration in the sphincter of Oddi.’ Insulin-like growth factor 2 mRNA protein 3 (IMP3) staining is reportedly associated with advanced disease stage and clinical outcomes in many carcinomas. The aim of this retrospective study was to investigate the ability of diagnosing sphincter of Oddi involvement in PT and predicting the prognoses using IMP3 immunohistochemistry. Methods Twenty-five resected specimens from patients with PT and 24 biopsy specimens from the same patients excluding one were immunostained for IMP3. The percentage of positive cells in the tumor was evaluated and compared with the final pathological diagnosis and prognosis. Results The final pathological diagnoses were adenoma in 5 patients and adenocarcinoma in 20 patients (no sphincter of Oddi involvement in 5 and involvement in 15). The ability to diagnose sphincter of Oddi involvement based on the percentage of IMP3-positive cells in resected specimens and tissue biopsies was the area under the curve 0.8 and 0.78, respectively, of the receiver operating characteristic curve, and the accuracies were 80.0% and 75.0% (cutoff value: 10%), respectively. Moreover, patients with an IMP3-positive cell rate of ≥ 10% had a significantly worse prognosis (log-rank test P = 0.01). Conclusion IMP3 immunostaining of resected and biopsy specimens from PT patients enables the diagnosis of sphincter of Oddi involvement objectively and is also effective in predicting the prognosis.

/Objectives: Endoscopic ultrasound elastography (EUS-EG) is useful for diagnosis of small solid pancreatic lesions (SPLs), particularly in excluding pancreatic cancer (PC), but its dependence on main pancreatic duct dilatation (MPDD) has not been examined. We aimed to investigate EUS-EG for diagnosis of small SPLs with and without MPDD.Patients with pathologically diagnosed SPLs of ≤20 mm were included and retrospectively analyzed. Using the blue:green ratio, an EUS-EG image was classified as blue-dominant, equivalent, or green-dominant. Using multiple EUS-EG images per patient, a lesion with a greater number of blue-dominant than green-dominant images was classified as stiff, and the others as soft. EUS-EG images in random order were judged by three raters. Considering stiff SPLs as PC, diagnostic performance of EUS-EG was examined for SPLs with and without MPDD.Of 126 cases analyzed, 65 (52%) were diagnosed as PC, and 63 (50%) had MPDD. A total of 1077 EUS-EG images were examined (kappa coefficient = 0.783). Lesions were classified as stiff in 91 cases and soft in 35 (kappa coefficient = 0.932). The ratio of stiff to soft lesions was significantly higher in PC than in non-PC (62:3 vs. 29:32, P 0.001). The sensitivity, specificity, and negative predictive value of a stiff lesion with vs. without MPDD for diagnosis of PC were 94%, 23%, and 50% vs. 100%, 60%, and 100%, respectively.Using the EUS-EG stiffness classification for small SPLs, PC can be excluded with high confidence and concordance for a soft lesion without MPDD.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014.In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as Grade 1 (strong) or Grade 2 (weak) according to the concepts of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system.The 31 CQs covered the six topics: (a) prophylactic treatment, (b) diagnosis, (c) biliary drainage, (d) surgical treatment, (e) chemotherapy, and (f) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded.This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.

Although black stools are one of the signs of upper gastrointestinal bleeding, not all patients without hematemesis need endoscopic intervention. There is no apparent indicator to select who needs treatment thus far. The aim of this study was to establish a novel score that predicts the need for endoscopic intervention in patients with black stools without hematemesis.We retrospectively enrolled 721 consecutive patients with black stools without hematemesis who underwent emergency endoscopy from two facilities. In the development stage (from January 2016 to December 2018), risk factors that predict the need for endoscopic intervention were determined from the data of 422 patients by multivariate logistic regression analysis, and a novel scoring system, named the modified Nagoya University score (modified N score), was developed. In the validation stage (from January 2019 to September 2020), we evaluated the diagnostic value of the modified N score for 299 patients.Multivariate logistic regression analysis revealed four predictive factors for endoscopic intervention: syncope, the blood urea nitrogen (BUN) level, and the BUN/creatinine ratio as positive indicators and anticoagulant drug use as a negative indicator. In the validation stage, the area under the curve of the modified N score was 0.731, and the modified N score showed a sensitivity of 82.0% and a specificity of 58.8%.Our modified N score, which consists of only four factors, can identify patients who need endoscopic intervention among those with black stools without hematemesis.

AimsThis study aimed to evaluate the feasibility and efficacy of Endoscopic ultrasound elastography-guided fine needle biopsy (EUS-EG-FNB) for the diagnosis of pancreatic mass lesions.MethodsEUS-EG images were classified into heterogeneous and homogeneous groups. For the heterogeneous group, EUS-FNB was separately performed in both hard areas and soft areas. Only samples obtained during the first two passes (hard/soft areas) were used to compare the diagnostic accuracy as well as the quality and quantity of the specimens. We investigated the association of EUS-EG findings using strain histogram analysis with the histological findings.ResultsFifty-five patients were enrolled including 25 patients with heterogeneous group. The homogeneous group had significantly lower mean strain value (hard) lesions. The adequate sampling rates from hard and soft areas were 88% and 92%, respectively (P=0.6374). Comparison of the diagnostic accuracy and the quality and quantity of the histological core between hard and soft areas showed no significant differences. In pancreatic adenocarcinoma cases, the proportion of fibrous stroma in the core tissue was significantly correlated with the elasticity of the region. (R2=0.1226: P=0.0022) ConclusionEUS-EG may reflect tissue composition in pancreatic tumors, however, EUS-EG did not affect either the quality and quantity of the tissues obtained.(Clinical Trial Registry No. UMIN-000033073)

Background and Aims Endoscopy guidelines recommend adhering to policies such as resect and discard only if the optical biopsy is accurate. However, accuracy in predicting histology can vary greatly. Computer-aided diagnosis (CAD) for characterization of colorectal lesions may help with this issue. In this study, CAD software developed at the University of Adelaide (Australia) that includes serrated polyp differentiation was validated with Japanese images on narrow-band imaging (NBI) and blue-laser imaging (BLI). Methods CAD software developed using machine learning and densely connected convolutional neural networks was modeled with NBI colorectal lesion images (Olympus 190 series - Australia) and validated for NBI (Olympus 290 series) and BLI (Fujifilm 700 series) with Japanese datasets. All images were correlated with histology according to the modified Sano classification. The CAD software was trained with Australian NBI images and tested with separate sets of images from Australia (NBI) and Japan (NBI and BLI). Results An Australian dataset of 1235 polyp images was used as training, testing, and internal validation sets. A Japanese dataset of 20 polyp images on NBI and 49 polyp images on BLI was used as external validation sets. The CAD software had a mean area under the curve (AUC) of 94.3% for the internal set and 84.5% and 90.3% for the external sets (NBI and BLI, respectively). Conclusions The CAD achieved AUCs comparable with experts and similar results with NBI and BLI. Accurate CAD prediction was achievable, even when the predicted endoscopy imaging technology was not part of the training set.

Background and aims Endoscopic ultrasound (EUS) elastography (EUS-EG) is a minimally invasive diagnostic method for evaluating tissue elasticity. The aim of this study was to evaluate the feasibility of newly developed EUS shear-wave measurement (EUS-SWM) and to compare diagnostic performance between EUS-SWM and the conventional strain elastography (SE) for the measurement of elasticity of solid pancreatic lesions (SPLs). Methods From December 2017 until August 2019, we retrospectively reviewed 64 consecutive cases with SPLs who underwent both EUS-SWM and SE. EUS-SWM was used to measure the shear-wave velocity, Vs (m/s), and the unique measurement reliability index, VsN (%), in the target lesion. SE images were assessed by strain histogram (SH) analysis, and the mean strain value of the elasticity index was measured. We evaluated the diagnostic performance of EUS-SWM and SE with SH to characterize the SPLs. Results The Vs (m/s) values of SPLs were 2.19 for pancreatic cancer (PC), 1.31 for pancreatic neuroendocrine neoplasm (PanNEN), 2.56 for mass-forming pancreatitis (MFP) and 1.58 for metastatic tumors. Vs showed no significant difference based on the disease. The mean strain values were 45.5 for PC, 47.3 for PanNEN, and 74.5 for MFP. In the comparison of tissue elasticity between PC and MFP, Vs showed no significant difference (P = 0.5687); however, the mean strain value was significantly lower in PC cases (45.4 vs 74.5: P = 0.0007). Conclusion Endoscopic ultrasound SWM tended to be unstable for the measurement of elasticity of SPLs, and conventional SE with SH was superior for their characterization.

Introduction: Dysphagia is a common symptom that occurs in patients with diabetes mellitus (DM). There have been few prospective observational studies on esophageal motility disorders in DM using high-resolution manometry (HRM). This study aimed to clarify the characteristics of esophageal motility disorders using HRM in patients with dysphagia and compare them between DM and non-DM patients. Methods: Patients with dysphagia were prospectively recruited between October 2018 and July 2019. Patients (n = 89) underwent esophagogastroduodenoscopy and HRM and completed the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire. Manometry parameters and motility disorder classifications were compared between DM and non-DM patients. We also investigated the differences in clinical backgrounds and questionnaire scores among DM patients with normal and abnormal manometry results. Results: A higher prevalence of esophageal motility disorder was observed in DM patients (60%, 21/35) compared to non-DM patients (29.6%, 16/54) (p = 0.001). The prevalence of minor disorders such as ineffective esophageal motor disorder and fragmented peristalsis was significantly higher (45 vs. 11%), and the distal contractile integral, integrated relaxation pressure, and contractile front velocity values were lower in the DM group. Among DM patients, those with abnormal esophageal motility had a significantly higher prevalence of neuropathy, retinopathy, and nephropathy, as well as higher reflux or constipation scores on the GSRS, than those with normal results. Conclusions: Among patients with dysphagia, the frequency of minor esophageal motility disorders was higher in DM patients than in non-DM patients. Abnormal esophageal motility related to poor esophageal clearance was associated with higher prevalence of diabetic complications.

Objectives The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society. Methods Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis. Results Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group. Conclusions Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.

Background Main pancreatic duct (MPD) involvement in branch duct-type intraductal papillary mucinous neoplasms (BD-IPMNs) is a high risk finding for malignant IPMNs. However, discrepancies exist in the identification of MPD involvement between imaging findings and pathological diagnosis. The purpose of this study was to evaluate the diagnostic accuracy of preoperative assessment of MPD involvement in IPMNs using contrast-enhanced harmonic endoscopic ultrasound (CH-EUS). Methods This study involved 166 consecutive patients with BD-IPMNs who underwent surgical resection. CH-EUS was used to evaluate the MPD involvement according to the presence of mural nodules (MN) that advanced into the MPD or involved the MPD. The CH-EUS findings were compared with the pathological findings. Additionally, we analyzed the risk factors for malignant BD-IPMNs using multivariate analysis. Results A total of 77, 51, and 38 patients were pathologically diagnosed with low-grade or intermediate-grade dysplasia, high-grade dysplasia and invasive IPMNs, respectively. MPD involvement was diagnosed using CH-EUS (MPD-inv.-EUS) in 90 (54.2%) patients with a sensitivity, specificity and accuracy of 83.5%, 87.0% and 84.9%, respectively. The malignancy rate in patients with MPD-inv.-EUS was 71.6% (63/90). Multivariate logistic regression analysis showed that MPD-inv.-EUS (OR, 3.61; 95% CI:1.45–8.98), age (OR, 5.70; 95% CI: 1.47–22.2), cyst size (OR, 2.45; 95% CI:1.04–5.78) and MN size (OR, 7.05; 95% CI:2.48–20.0) were significant for malignant BD-IPMNs. Conclusions MPD-inv.-EUS accurately represents the pathological involvement of IPMN and may be a useful predictor of malignant BD-IPMNs.

Background Detailed histological evaluation is important in the diagnosis of autoimmune pancreatitis (AIP). However, it remains challenging to obtain adequate tissue from the pancreas. Recently, several reports have suggested the usefulness of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using the new “core” needles for acquiring pancreatic tissue. We aimed to investigate the usefulness of EUS-FNB for diagnosing AIP with one such needle, a 22-gauge Franseen needle. Methods Patients who met the imaging diagnostic criteria for AIP based on the International Consensus Diagnostic Criteria (ICDC) were enrolled in the study. All patients underwent EUS-FNB with a 22-gauge Franseen needle. Histological findings were evaluated based on the ICDC, and the detection rates of level 1 and level 1 or 2 histology were calculated. Results 56 patients from 11 different institutions were enrolled in the final analysis (55 suspected to have type 1 AIP and one with type 2 AIP). Lymphoplasmacytic infiltration, obliterative phlebitis, storiform fibrosis, and > 10 IgG4-positive cells per high-power field were detected in 55 (100 %), 24 (43.6 %), 40 (72.7 %), and 36 (65.5 %) of the 55 patients, respectively. The detection rates of level 1 and level 1 or 2 histology for AIP were 58.2 % (95 % confidence interval [CI] 44.1 % – 71.3 %) and 92.7 % (95 %CI 82.4 % – 98.0 %), respectively, which were apparently higher than our historical results (7.9 % [95 %CI 1.7 % – 21.4 %] and 62.2 % [95 %CI 46.5 % – 76.2 %], respectively) using a conventional needle. Conclusions EUS-FNB with a 22-gauge Franseen needle demonstrated favorable detection rates which would be clinically beneficial for the histological diagnosis of AIP.

INTRODUCTION In laparoscopic gastrectomy, a method to locate the margin of an early-stage cancerous lesion that is invisible from the serosal surface and impalpable during laparoscopic procedures is needed to determine an appropriate transection line. We conducted a prospective study to develop a new marking method using preoperative submucosal injection of indocyanine green (ICG). METHODS Patients undergoing laparoscopic gastrectomy for T1 gastric cancer were recruited. The first 11 patients comprised the learning set and the subsequent 18 patients the validation set. ICG was endoscopically injected in the submucosal layer of the stomach approximately 1 cm away from the tumor edge 1 or 3 days before surgery. The diameters of the visualized ICG were compared with those of a conventional marking method using India ink in 10 historical controls. RESULTS In the learning set, the optimal amount of ICG was determined to be 0.1 mL at a concentration of 0.5 mg/mL. In the validation set, the same procedure was repeated. No technical problems or adverse reactions related to ICG injection were observed. In all cases, ICG was successfully detected, and negative surgical margins were pathologically confirmed. The mean long diameter of the visualized ICG fluorescence measured at the mucosal surface of the stomach was significantly smaller in the current study than in the historical controls in whom India ink was used (21 vs 52 mm, P

BACKGROUND Double-balloon endoscopic retrograde cholangiography (DB-ERC) is widely performed for biliary diseases after reconstruction in gastrointestinal surgery, but there are few reports on DB-ERC after hepatectomy or living donor liver transplantation (LDLT). AIM To examine the success rates and safety of DB-ERC after hepatectomy or LDLT. METHODS The study was performed retrospectively in 26 patients (45 procedures) who underwent hepatectomy or LDLT (liver operation: LO group) and 40 control patients (59 procedures) who underwent pancreatoduodenectomy (control group). The technical success (endoscope reaching the choledochojejunostomy site), diagnostic success (performance of cholangiography), therapeutic success (completed interventions) and overall success rates, insertion and procedure (completion of DB-ERC) time, and adverse events were compared between these groups. RESULTS There were no significant differences between LO and control groups in the technical [93.3% (42/45) vs 96.6% (57/59), P = 0.439], diagnostic [83.3% (35/42) vs 83.6% (46/55), P = 0.968], therapeutic [97.0% (32/33) vs 97.7% (43/44), P = 0.836], and overall [75.6% (34/45) vs 79.7% (47/59), P = 0.617] success rates. The median insertion time (22 vs 14 min, P < 0.001) and procedure time (43.5 vs 30 min, P = 0.033) were significantly longer in the LO group. The incidence of adverse events showed no significant difference [11.1% (5/45) vs 6.8% (4/59), P = 0.670]. CONCLUSION DB-ERC after liver operation is safe and useful but longer time is required, so should be performed with particular care.

The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml.Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline.In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3

Background/Aims. The usefulness of macroscopic on-site evaluation (MOSE) during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) has been reported, but a specific method for MOSE has not been established. We aimed to investigate the usefulness of MOSE using a stereomicroscope (S-MOSE) for the diagnosis of solid pancreatic lesions (SPLs). Methods. We reviewed a total of 60 consecutive patients who underwent both S-MOSE and rapid on-site cytopathological evaluation (ROSE) during EUS-FNB between July 2019 and October 2020, and the usefulness of S-MOSE in comparison with histology was evaluated. A 22-gauge Franseen needle was used to perform EUS-FNB in all patients, and only the specimens obtained by the first pass were evaluated. The final diagnosis was based on the surgical specimen or the clinical course consistent with the EUS-FNB results. Results. The final diagnoses of the 60 patients included 45 patients with pancreatic ductal adenocarcinoma, 6 with autoimmune pancreatitis, 4 with mass-forming pancreatitis, 1 with pancreatic metastasis, 2 with pancreatic neuroendocrine tumor, and 2 with intraductal papillary mucinous carcinoma. The histological diagnostic accuracy of the first pass of EUS-FNB was 83.3% (50/60). The agreement between the S-MOSE and the histological diagnosis was 90% (54/60). The positive predictive value of S-MOSE for histological diagnosis was 90.7%, which can be an indicator of when to stop the EUS-FNB procedure. There were no immediate or delayed adverse events reported after the FNB based on the chart and medical visit history review. Conclusion. In the EUS-FNB of SPLs, S-MOSE can be an alternative to ROSE for specimen evaluation and has the potential to shorten the procedure time.

Helicobacter pylori infection causes atrophic gastritis, which affects the gut microbiome; the gastric acid concentration depends on the degree of atrophic gastritis. Helicobacter pylori eradication also affects gastric acidity. Here, we determined the differences in the post-eradication changes in the gut microbiome in relation to the progression of gastric atrophy.Ten patients were included in the closed group and five in the open group, consisting of patients with non-progressive and progressive atrophy, respectively, diagnosed by endoscopy. The faecal microbiome was analysed and compared among three time-points: before eradication, 8 weeks after eradication, and 6 months after eradication. The microbiome was analysed by targeting 16S rRNA using Illumina Miseq.The relative abundance of 14 genera significantly differed between the closed and open groups before eradication, but only 12 and 6 genera presented a significant difference in the relative abundance at 8 weeks and 6 months after eradication, respectively. Of the 12 genera that differed between the closed and open groups before eradication, 8 genera, namely, Actinomyces, Aggregatibacter, Campylobacter, Granulicatella, Pyramidobacter, Streptococcus, Cardiobacterium, and Haemophilus, were oral-origin bacteria. Longitudinal changes showed that Haemophilus and Catenibacterium were consistently significantly more abundant in the open group than in the closed group during the follow-up period.The gut microbiome substantially differed depending on the progression of gastric atrophy, but this difference was decreased by eradication, especially the differences in the number of oral bacteria in the gut. Eradication therapy may improve dysbiosis that result from gastric atrophy.

In Japan, endoscopic submucosal dissection (ESD) has been widely performed for ESD-adapted gastric cancer, but little is known about the prognostic factors after ESD for gastric cancer in older patients. The psoas muscle index (PMI) is an indicator of sarcopenia calculated from computed tomography images and reportedly related to the prognosis of some diseases. This study aimed to explore factors related to long-term survival after ESD for gastric cancer in patients aged ≥ 80 years.We retrospectively reviewed 88 patients (63 men, 25 women) with early gastric cancer who underwent ESD at ≥ 80 years. Possible factors related to death after gastric ESD were analyzed by univariate and multivariate analyses using a Cox proportional hazards model. The estimated overall survival (OS) was compared between the groups stratified by significant factors.The 5-year OS rate was 73.9% (median follow-up period, 5.4 years). In the multivariate analysis, a low PMI ( 6.36 in men, 3.92 in women) (hazard ratio [HR] 2.89, 95% confidence interval [CI] 1.11-7.54) and high Charlson comorbidity index (CCI) (≥ 3) (HR 1.87, 95% CI 1.14-3.09) were independently related to death after ESD. The 5-year OS rates were significantly higher in the high PMI group (82.3% vs. 70.7%, P = 0.026) and the low CCI group (76.0% vs. 37.9%, P = 0.002).In addition to low CCI, high PMI is a predictor of long-term survival after ESD for gastric cancer in patients aged ≥ 80 years.

Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN.

Introduction: The aim of this study was to investigate the early changes in alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab and to evaluate the relationship between changes in these tumor markers and treatment efficacy. Methods: Of 58 consecutive patients who started atezolizumab plus bevacizumab at our institution, 50 patients with information on antitumor response obtained at 6 weeks after therapy were enrolled in this study and their treatment outcomes were retrospectively evaluated. Results: According to the Response Evaluation Criteria in Solid Tumors at 6 weeks, the objective response (OR) rate was 22.0% and the disease control (DC) rate was 78.0%. In patients who achieved OR at 6 weeks, median AFP and DCP ratios at weeks 1, 2, 3, and 6 were significantly lower than those in patients who did not achieve OR. AFP ratios in patients who did not achieve DC at 6 weeks (Non-6W-DC group) were significantly higher than in those who achieved DC at week 6 (6W-DC group). Median overall survival in the Non-6W-DC group was significantly shorter than in the 6W-DC group (156 days vs. not reached, p = 0.0008). An AFP ratio of 1.4 or higher at 3 weeks had a specificity of 88.0% and a sensitivity of 88.9% for predicting Non-6W-DC. Median progression-free survival was significantly shorter in patients with an AFP ratio of 1.4 or higher at 3 weeks than in those with an AFP ratio of p = 0.0003). Conclusion: Early changes in AFP might be useful for predicting the antitumor efficacy of atezolizumab plus bevacizumab in patients with advanced HCC. An AFP ratio of 1.4 or higher at 3 weeks might be an early predictor of refractoriness to atezolizumab plus bevacizumab therapy.

BACKGROUND AND AIM Microbiota have been associated with several diseases including colorectal cancer (CRC). This study aimed to evaluate the microbiota in early/invasive CRC utilizing stool and cytological brushes to determine differences in relative abundance (RA). METHODS Colonoscopy patients referred for endoscopic submucosal dissection or previous to CRC surgery were prospectively enrolled. Stool was collected pre-bowel preparation; and brush samples were taken during colonoscopy (three regions). DNA extraction, 16S rRNA next generation sequencing, and biostatistics (qiime and stamp software packages) followed. Primary outcome was the difference in RA of the Fusobacterium genus between the groups. Secondary outcomes included analyses of other microbiota. RESULTS Twenty-five patients were included, of which 14 had invasive cancer (≥ 1000 mm into the submucosa). The three major genera for invasive cancer were Bacterioides, Oribacterium, and Fusobacterium, whereas for early cancer were Oribacterium, Bacterioides, and Prevotella (decreasing order of RA). There was a significantly higher RA of Fusobacterium in the invasive cancer group (9.65% vs 0.95%, respectively, P

Cancer-associated fibroblasts (CAF) constitute a major component of the tumor microenvironment. Recent observations in genetically engineered mouse models and clinical studies have suggested that there may exist at least two functionally different populations of CAFs, that is, cancer-promoting CAFs (pCAF) and cancer-restraining CAFs (rCAF). Although various pCAF markers have been identified, the identity of rCAFs remains unknown because of the lack of rCAF-specific marker(s). In this study, we found that Meflin, a glycosylphosphatidylinositol-anchored protein that is a marker of mesenchymal stromal/stem cells and maintains their undifferentiated state, is expressed by pancreatic stellate cells that are a source of CAFs in pancreatic ductal adenocarcinoma (PDAC). In situ hybridization analysis of 71 human PDAC tissues revealed that the infiltration of Meflin-positive CAFs correlated with favorable patient outcome. Consistent herewith, Meflin deficiency led to significant tumor progression with poorly differentiated histology in a PDAC mouse model. Similarly, genetic ablation of Meflin-positive CAFs resulted in poor differentiation of tumors in a syngeneic transplantation model. Conversely, delivery of a Meflin-expressing lentivirus into the tumor stroma or overexpression of Meflin in CAFs suppressed the growth of xenograft tumors. Lineage tracing revealed that Meflin-positive cells gave rise to α-smooth muscle actin-positive CAFs that are positive or negative for Meflin, suggesting a mechanism for generating CAF heterogeneity. Meflin deficiency or low expression resulted in straightened stromal collagen fibers, which represent a signature for aggressive tumors, in mouse or human PDAC tissues, respectively. Together, the data suggest that Meflin is a marker of rCAFs that suppress PDAC progression., ファイル公開：2020/10/01

Endoscopic ultrasonography (EUS) is a modality with high spatial resolution that enables comprehensive observation of the entire pancreas and plays an important role in the diagnosis of pancreatic lesions. Recent advances in diagnostic imaging methods such as ultrasound, computed tomography, and magnetic resonance imaging have increased the incidental detection of pancreatic cystic lesions (PCLs). EUS has been recognized as an essential diagnostic method for the detection and evaluation of PCLs. EUS has two important roles: as a detailed (high-resolution) imaging diagnostic method and as an approach for collecting cyst fluid content by EUS-guided fine needle aspiration for pathological diagnosis or biomarker evaluation. Furthermore, in recent years, the usefulness of contrast-enhanced EUS for the differential diagnosis of PCLs or evaluation of grade of malignancy, and a novel imaging technique called needle-based confocal laser endomicroscopy to observe intraductal structures through a needle, has been reported. An understanding of the morphological characteristics of PCLs depicted by ultrasound imaging and of the benefits and limitations of EUS diagnosis in daily practice is needed.

Objectives Accurate diagnosis of invasion depth is important for reliable treatment of esophageal squamous cell carcinoma (ESCC), but it is limited to the muscularis mucosae to slight submucosal invasion (MM/SM1). The diagnostic accuracy of invasion depth is unsatisfactory and remains to be improved. We aimed to investigate the association between the color of the superficial ESCC and invasion depth using linked color imaging (LCI) under light-emitting diode (LED) light sources. Methods Lesions diagnosed as superficial ESCC were observed using white light imaging and then by LCI. The color values were calculated using Commission Internationale de l'Eclariage - L*a*b* color space, and the color difference was calculated according to invasion depth. The vascular diameters and vascular angles of the intrapapillary capillary loops were pathologically analyzed. Their correlation with mucosal color was also investigated by LCI. Results In all, 52 lesions from 48 patients were analyzed. On the basis of invasion depth, the color difference between the normal mucosa and the lesion was larger in the MM/SM1 or deeper group than in the epithelium and the lamina propria mucosa (EP/LPM) group using LCI (P = 0.025). The vascular diameter was positively correlated with the b* color value (correlation coefficient = 0.302, P = 0.033). Conclusion Observation using LCI under LED light sources may improve the endoscopic diagnosis of the invasion depth of superficial ESCC. Further research is needed to validate its usefulness. (UMIN000024615).

Pancreatic cystic lesions (PCLs) are incidental findings that are being increasingly identified because of recent advancements in abdominal imaging technologies. PCLs include different entities, with each of them having a peculiar biological behavior, and they range from benign to premalignant or malignant neoplasms. Therefore, accurate diagnosis is important to determine the best treatment strategy. As transabdominal ultrasonography (US) is noninvasive, inexpensive, and widely available, it is considered to be the most appropriate imaging modality for the initial evaluation of abdominal diseases, including PCLs, and for follow-up assessment. We present a review of the possibilities and limits of US in the diagnosis of PCLs, the technical development of US, and the ultrasonographic characteristics of PCLs.

Objectives: The time to recurrent biliary obstruction (TRBO) of unresectable distal malignant biliary obstruction is generally thought to be longer when a self‐expandable metal stent (SEMS) with a thicker inner diameter is used for drainage, but the dependence on the inner diameter using a fully covered SEMS (FCSEMS) is uncertain. The objective of this multicenter prospective study was to compare TRBO and adverse events, such as cholecystitis and pancreatitis, in treatment of patients with unresectable malignant biliary obstruction using 8‐ and 10‐mm diameter FCSEMS. Methods: Eighteen tertiary‐care centers participated in the study. Patients were allocated to the 8‐ and 10‐mm diameter groups. TRBO, non‐inferiority of the 8‐mm FCSEMS, overall survival time, frequency and type of adverse events, and non‐recurrent biliary obstruction (RBO) rate at the time of death were compared between the two groups. Results: Median TRBO did not differ significantly between the 8‐mm (n = 102) and 10‐mm (n = 100) groups (275 vs 293 days, P = 0.971). The hazard ratio of the 8‐ to 10‐mm groups was 0.90 (80% confidence interval, 0.77–1.04; upper limit lower than the acceptable hazard ratio [1.33] of the null hypothesis). Based on these findings, the 8‐mm diameter stent was determined to be non‐inferior to the 10‐mm diameter stent. Survival time, incidence of adverse events and non‐RBO rate at the time of death did not differ significantly between the two groups. Conclusions: Time to RBO with an 8‐mm diameter FCSEMS was non‐inferior to that with a 10‐mm diameter FCSEMS. This finding is important for development of future SEMS., ファイル公開：2020-07-01

Purpose To assess the feasibility and the clinical usefulness of a newly developed endoscopic ultrasonography (EUS) shear-wave elastography technique (EUS shear-wave measurement: EUS-SWM) in the diagnosis and treatment of autoimmune pancreatitis (AIP). Methods Tissue elasticity was measured in the pancreas in 160 patients. The success rate of EUS-SWMs, the velocity of the shear wave (Vs, m/s), and the reliability index of the Vs measurement (VsN) were evaluated, and the elasticity (median Vs) was compared between AIP patients (n = 14) and normal controls. Results A total of 3837 EUS-SWMs were performed without adverse events. Overall, 97.6% (3743/3837) were successful. The median VsN was 74%. The median Vs values of the pancreas were as follows: 2.22 m/s in the pancreatic head (push position), 2.36 m/s in the head (pull position), 1.99 m/s in the body, and 2.25 m/s in the tail. The median Vs of the AIP group (2.57 m/s) was significantly higher than that of the normal controls (1.89 m/s) (P = 0.0185). The mean Vs significantly decreased from 3.32 m/s to 2.46 m/s after steroid therapy (n = 6) (P = 0.0234). Conclusion EUS-SWM is feasible and generates credible results. EUS-SWM was a useful method for assessment of the effect of steroid therapy in AIP patients. Electronic supplementary material The online version of this article (10.1007/s10396-019-00944-4) contains supplementary material, which is available to authorized users.

Ultrasonographic imaging techniques have been rapidly developing. The new transesophageal echocardiography (TEE) system made it possible to obtain the real-time three-dimensional (3D) image of the cardiac system through the esophagus, that can be applied to the field of gastroenterology. We herein present a case of 72-year-old woman who was referred for evaluation of an incidentally found cystic lesion in the tail of the pancreas. The real-time 3D imaging with TEE probe clearly demonstrated the internal features of the cyst consistent with MCN, which helped narrow down the differential diagnosis. The patient was proceeded with distal pancreatectomy and a definite diagnosis of MCN was confirmed with the histopathological findings of the resected specimen associated with ovarian-type stroma. This is the first report which showed the real-time 3D image of MCN in the pancreas obtained with TEE. Further investigation is warranted to determine the clinical relevance of 3D ultrasonographic techniques used to evaluate the pancreatic cystic lesions.

Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease. From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child–Turcotte–Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states. Before PSM, Child–Turcotte–Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p

BACKGROUND AND AIM Adenoma detection rate (ADR) is an important quality metric in colonoscopy. However, there is conflicting evidence around factors that influence ADR. This study aims to investigate the effect of time of day and endoscopist background on ADR and sessile serrated adenoma/polyp detection rate (SSA/P-DR) for screening colonoscopies. METHODS Consecutive patients undergoing colonoscopy in 2016 were retrospectively evaluated. Primary outcome was the effect of time of day and endoscopist specialty on screening ADR. Secondary outcomes included evaluation of the same factors on SSA/P-DR and other metrics and collinearity of ADR and SSA/P-DR. Linear regression models were used for association between ADR, time of day, and endoscopist background. Bowel preparation, endoscopist, session, patient age, and gender were adjusted for. Linear regression model was also used for comparing ADR and SSA/P-DR. Chi-square was used for difference of proportions. RESULTS Two thousand six hundred fifty-seven colonoscopies, of which 558 were screening colonoscopies, were performed. The adjusted mean ADR (screening) was 36.8% in the morning compared with 30.5% in the afternoon (P

Autoimmune pancreatitis (AIP) has the potential to transform into chronic pancreatitis with pancreatic stone involvement. This retrospective investigation sought to clarify the risk factors for stone formation in type 1 AIP.Questionnaires on patients with type 1 AIP were sent to 22 high-volume medical centers across Japan to compare the clinical features of patients with and without pancreatic stone formation.Of the completed records on 624 type 1 AIP patients, 31 (5%) had experienced pancreatic stones. Median follow-up duration was 1853 days. Bentiromide test values at diagnosis were significantly lower, and hemoglobin A1c values after corticosteroid treatment were significantly higher in patients with pancreatic stones. Imaging results disclosed that pancreatic atrophy and hilar or intrahepatic bile duct stenosis were significantly more frequent in patients with pancreatic stone formation. Pancreatic head swelling tended to be more frequent in this group as well. On the other hand, a shorter follow-up period was associated with the nonformation of pancreatic stones.The increased frequency of pancreatic head swelling in type 1 AIP patients exhibiting pancreatic stones indicated a propensity for pancreatic juice stasis with subsequent stone development and pancreatic dysfunction occurring over longer periods of disease duration.

Background: The incidence of mixed hepatitis C virus (HCV) genotype infection is variable, and a few reports exist regarding the efficacy of direct-acting antivirals (DAA) therapy for mixed genotype. We aimed to investigate the prevalence of mixed genotype and its impact on the virologic response to DAA therapy. Methods: A total of 365 patients with chronic HCV infection who completed antiviral therapy were recruited. Nested polymerase chain reaction with universal and specific primers of genotypes 1b and 2 and direct sequencing were used for HCV genotyping. Results: Direct sequencing with universal primers defined genotypes 1b (n = 230), 2a (n = 95), and 2b (n = 40). Direct sequencing of genotype 2 was performed in patients with genotype 1b, and direct sequencing of genotype 1b in patients with genotype 2. Four patients with genotype 1b underwent amplification for genotype 2, and direct sequencing identified genotypes 1b (n = 1), 2a (n = 1), and 2b (n = 2). None with genotype 2 underwent amplification for genotype 1b. Three cases were confirmed to have mixed genotype. Conclusions: Mixed genotype was rare, and hence the impact of mixed genotype on treatment outcome with DAA therapy is expected to be minimal.

Chronic pancreatitis (CP) is pathologically characterized by the loss of exocrine pancreatic parenchyma, irregular fibrosis, cellular infiltration, and ductal abnormalities. Diagnosing CP objectively is difficult because standard diagnostic criteria are insufficient. The change of parenchymal hardness is the key factor for the diagnosis and understanding of the severity of CP. The ultrasonography (US) or endoscopic ultrasonography (EUS) elastography have been used to diagnose pancreatic diseases. Both strain elastography (SE) and shear wave elastography are specific diagnostic techniques for measuring tissue hardness. Most previous studies were conducted with SE. There are three methods of interpreting SE; the method of recognizing the patterns in SE distribution images in the region of interest, the method of using strain ratio to compare the hardness of adipose tissue or connective tissue with that of the lesion, and the method of evaluating the hardness distribution of a target by histogram analysis. These former two methods have been used primarily for neoplastic diseases, and histograms analysis has been used to assess hardness distribution in the evaluation of CP. Since the hardness of the pancreas increases with aging, it is necessary to consider the age in the diagnosis of pancreatic disorders using US or EUS elastography.

Background Pancreatic exocrine insufficiency (PEI) is associated with the outcome of pancreatic disease. However, there is no method for assessing PEI that can be used noninvasively and easily for outpatient. It has been reported that changes in intestinal bacteria caused by PEI may increase breath hydrogen concentration (BHC) levels during glucose or lactose loading. We have evaluated the usefulness of fasting breath hydrogen concentration (FBHC) measurement without glucose loading for the evaluation of PEI. Methods Sixty patients underwent FBHC measurement, BT-PABA testing, and microbiome analysis. They were classified into PEI group (PABA excretion rate Results FBHC levels was higher in the PEI group 15.70 (1.4 to 77.0) ppm than in the non-PEI group 2.80 (0.7 to 28.2) ppm (P P P P Clostridium (P Conclusion FBHC shows good potential as a simple and repeatable test for the diagnosis of PEI. The elevated FBHC levels may be caused by hydrogen-producing bacteria such as Clostridium.

The Asian Federation of Societies for Ultrasound in Medicine and Biology aimed to provide information on techniques and indications for contrast-enhanced harmonic endoscopic ultrasound (CH-EUS), and to create statements including the level of recommendation. These statements are based on current scientific evidence reviewed by a Consensus Panel of 15 internationally renowned experts. The reliability of clinical questions was measured by agreement rates after voting. Six statements were made on techniques, including suitable contrast agents for CH-EUS, differences between contrast agents, setting of mechanical index, dual imaging and duration and phases for observation. Thirteen statements were made on indications, including pancreatic solid masses, pancreatic cancer staging, pancreatic cystic lesions and mural nodules, detection of subtle pancreatic lesions, gallbladder sludge and polyps, hepatic lesions, lymph nodes, subepithelial lesions, visceral vascular diseases, guidance of fine needle aspiration and evaluation for local therapy. These international expert consensus guidelines will assist endosonographers in conducting CH-EUS according to evidence-based information.

Autoimmune pancreatitis (AIP) is recognized as the pancreatic manifestation of a systemic IgG4-related disease that can involve various organs, including the kidney. However, renal lesions tend to be overlooked when AIP is diagnosed, and the clinical characteristics and long-term prognosis of AIP with renal lesions are unclear. We retrospectively reviewed 153 patients with AIP diagnosed at our hospital with a median follow-up period of 41 months (interquartile range, 10–86) and classified them into two groups: the KD group (n = 17), with characteristic renal imaging features, and the non-KD group (n = 136). Serum IgG4 levels were significantly higher in the KD group (663 vs. 304.5 mg/dl, P = 0.014). No differences were observed between the two groups in terms of steroid treatment [14/17 (82.4%) vs. 112/136 (82.4%), P = 1] or in the number of patients who exhibited exacerbation of renal function during treatment [1/17 (5.9%) vs. 8/136 (5.9%), P = 1]. However, the cumulative relapse rate was significantly higher in the KD group [61% vs. 21.9% (3 years), P