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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 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. Materials and methods 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. Results 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. Conclusion 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.

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.

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.

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

Upper gastrointestinal endoscopy is widely performed to detect early gastric cancers. As an automated detection method for early gastric cancer from endoscopic images, a method involving an object detection model, which is a deep learning technique, was proposed. However, there were challenges regarding the reduction in false positives in the detected results. In this study, we proposed a novel object detection model, U-Net R-CNN, based on a semantic segmentation technique that extracts target objects by performing a local analysis of the images. U-Net was introduced as a semantic segmentation method to detect early candidates for gastric cancer. These candidates were classified as gastric cancer cases or false positives based on box classification using a convolutional neural network. In the experiments, the detection performance was evaluated via the 5-fold cross-validation method using 1208 images of healthy subjects and 533 images of gastric cancer patients. When DenseNet169 was used as the convolutional neural network for box classification, the detection sensitivity and the number of false positives evaluated on a lesion basis were 98% and 0.01 per image, respectively, which improved the detection performance compared to the previous method. These results indicate that the proposed method will be useful for the automated detection of early gastric cancer from endoscopic images.

Gallbladder (GB) diseases represent various lesions including gallstones, cholesterol polyps, adenomyomatosis, and GB carcinoma. This review aims to summarize the role of endoscopic ultrasound (EUS) in the diagnosis of GB lesions. EUS provides high-resolution images that can improve the diagnosis of GB polypoid lesions, GB wall thickness, and GB carcinoma staging. Contrast-enhancing agents may be useful for the differential diagnosis of GB lesions, but the evidence of their effectiveness is still limited. Thus, further studies are required in this area to establish its usefulness. EUS combined with fine-needle aspiration has played an increasing role in providing a histological diagnosis of GB tumors in addition to GB wall thickness.

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.

Previous therapeutic attempts to deplete cancer-associated fibroblasts (CAFs) or inhibit their proliferation in pancreatic ductal adenocarcinoma (PDAC) were not successful in mice or patients. Thus, CAFs may be tumor suppressive or heterogeneous, with distinct cancer-restraining and -promoting CAFs (rCAFs and pCAFs, respectively). Here, we show that induced expression of the glycosylphosphatidylinositol-anchored protein Meflin, a rCAF-specific marker, in CAFs by genetic and pharmacological approaches improved the chemosensitivity of mouse PDAC. A chemical library screen identified Am80, a synthetic, non-natural retinoid, as a reagent that effectively induced Meflin expression in CAFs. Am80 administration improved the sensitivity of PDAC to chemotherapeutics, accompanied by increases in tumor vessel area and intratumoral drug delivery. Mechanistically, Meflin was involved in the suppression of tissue stiffening by interacting with lysyl oxidase to inhibit its collagen crosslinking activity. These data suggested that modulation of CAF heterogeneity may represent a strategy for PDAC treatment.

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

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.

Aim Esophagogastric variceal hemorrhage is a cause of poor prognosis in patients with biliary atresia (BA). To prevent variceal hemorrhage, simple and reliable screening methods for high-risk esophagogastric varices (HR-EGV) are needed. We evaluated the efficacy of liver stiffness (LS) and spleen stiffness (SS) as measured by 2-D shear wave elastography (2D-SWE), which was reported to be more accurate than transient elastography, for detecting HR-EGV in children with BA. Methods Thirty-four children with BA were enrolled. Both LS and SS were measured by 2D-SWE. The presence of large esophageal varices or esophageal varices of any size with red wale marking and/or the presence of gastric varices along the cardia were defined as HR-EGV. Clinical data were collected and previously reported prediction indices for varices were calculated. Results Liver stiffness and SS were obtained from all patients. Fourteen patients showed HR-EGV. Significantly different variables between patients with and without HR-EGV were as follows: spleen diameter (116 mm vs. 95 mm), clinical prediction rule (104.7 vs. 124.7), King's variceal prediction score (78.8 vs. 99.4), aspartic aminotransferase-to-platelet ratio index (2.03 vs. 0.98), LS (2.63 m/s vs. 1.87 m/s), and SS (4.44 m/s vs. 3.69 m/s). The highest area under the receiver operating characteristic curve for detecting HR-EGV was that for SS (0.900), and the cut-off SS of 4.12 m/s yielded 92.9% sensitivity and 90% specificity. The intraclass correlation coefficient for intra-observer reproducibility was 0.828. Conclusions Spleen stiffness from 2D-SWE offered the most accurate predictor of HR-EGV in BA children.

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.

Postmenopausal women have a higher risk of nonalcoholic steatohepatitis (NASH) along with an increase in age, and vitamin D deficiency occurs in some patients with NASH. We performed ovariectomy (OVX) surgery on female mice to mimic menopause, fed them a choline-deficient high-fat (CDHF) diet to induce NASH, and then investigated the effects of treatment with 1,25(OH)2D3. Seven-week-old C57BL/6J female mice were separated into five experimental groups: SHAM, OVX, and OVX + intraperitoneal (i.p.) injection of 1,25(OH)2D3 (0.0008, 0.004, and 0.02 μg/kg). All groups were fed a CDHF diet for 8 weeks. Injections took place twice per week throughout the experimental period. Blood samples and liver tissue were collected for analyzing liver histological changes, serum biochemical indicators of hepatic function, and hepatic genes associated with fibrosis. Supplementation of 1,25(OH)2D3 in CDHF-diet mice showed decreased serum levels of ALT, AST, indicating the improvement in overall liver function, and suppressed histological NASH regarding fibrosis stage, lobular inflammation, and steatosis compared to the OVX group. Primary fibrotic markers of TGF-β, TIMP-1, α-SMA, and COL1A1 were significantly lower in the 1,25(OH)2D3 groups than in the OVX group. Furthermore, down-regulated levels of SMAD2 and SMAD3 were also observed in 1,25(OH)2D3 groups. Supplementation of 1,25(OH)2D3 may ameliorate liver fibrosis and improve liver function in OVX mice with NASH induced by a CDHF diet, suggesting the therapeutic effects on postmenopause with NASH.

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/Aim: The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice. Patients and Methods: Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated. Results: The incidence of grade 3 adverse events was low, at 13.0%. Albumin–bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively. Conclusion: Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.

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

Sound speed correction (SSC) is a non-invasive modality that quantifies the hardness of neoplasms. The aim of our study was to evaluate the usefulness of SSC for the diagnostic accuracy of colorectal neoplasms and to differentiate the depth of invasion. Forty colorectal neoplasms, contributed by 40 patients, were included in the analysis. The primary outcome was the diagnostic ability of SSC for the depth of invasion of colorectal neoplasms, with the secondary endpoint being the clinical efficacy of SSC to distinguish between a neoplasm and normal mucosa. The median sound speeds for colorectal neoplasms and normal mucosa were 1580 m/s and 1515 m/s, respectively (p < 0.001), with a median sound speed of 1583 m/s for lesions with a depth shallower than that of the muscularis propria and 1610 m/s for depths deeper than that of the muscularis propria (p = 0.002). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 80.0%, 100%, 100%, 83.3%, 90.0%, and 100%, respectively, for the diagnosis of neoplasms (using a cut-off sound speed of 1557 m/s) and 100%, 77.8%, 33.3%, 100%, 80.0%, respectively, for the diagnosis of the depth of invasion (using a cut-off of 1590 m/s). We identified absolute sound speeds for colorectal neoplasms and the depth of invasion of neoplasms which yielded a good diagnostic performance. SSC provides an objective evaluation of colorectal neoplasms and the depth of invasion of neoplasms and, thus, might be a useful modality in practice. UMIN000038235 , Date of registration; October 8, 2019

OBJECTIVES There are few reports on the long-term prognosis of papillary tumors after endoscopic papillectomy. Here, we report a retrospective study of the therapeutic effects, long-term prognosis, and affecting factors. METHODS The inclusion criteria were papillary adenoma with/without an adenocarcinoma component on biopsy results and ≤10 mm intraductal extension, and the exclusion criteria were moderate to poorly differentiated adenocarcinoma on biopsy results. If no residual lesion was confirmed ≥6 months after the last endoscopic treatment, remission was defined. Subsequently, follow-up endoscopy was scheduled once a year. Surgery was required in the case of adenocarcinoma recurrence or intraductal lesions >10 mm. The rates of adverse events, remission, recurrence, and need for surgery were examined. The affecting factors were calculated. RESULTS There were a total of 253 subjects, including 65 with adenocarcinoma. Pancreatitis (7.5%), bleeding (9.1%) and perforation (2.8%) were observed as adverse events. Among 221 subjects with ≥6 months of follow-up, 212 (95.9%) were in remission. The cumulative recurrence rate using the Kaplan-Meier analysis at 5 years was 16.9% (22 cases), with the need for surgery in 5.9% (5 cases). Intraductal extension on preoperative diagnosis was the only significant risk factor for both recurrence (P

Intraductal papillary mucinous neoplasm (IPMN) is reported as a high-risk factor for pancreatic cancer (PC) that includes IPMN-derived cancers (IPMC) and the development of invasive pancreatic ductal adenocarcinoma (PDAC) concomitant with IPMN. Since invasive IPMC and PDAC exhibit different oncological behaviors, their differentiation is clinically important. We aimed to investigate the use of contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) for the differential diagnosis between invasive IPMC and PDAC.This study involved 183 consecutive patients with PC (invasive IPMC: 42, PDAC concomitant with IPMN: 9, without IPMN: 132) who underwent CEH-EUS preoperatively. While investigating the patterns, enhanced effects in the solid part of the tumor were compared with those in the surrounding pancreatic parenchyma after administration of Sonazoid® and evaluated as hyperenhanced, isoenhanced, or hypoenhanced. We retrospectively compared the enhanced pattern of CEH-EUS by using multiphasic analysis and clinicopathological factors between invasive IPMC and PDAC.In multiphase evaluations at 20, 40 and 60 s in CEH-EUS, 75.2% (106/141) of PDACs were hypoenhanced (-) at ≥2 of the 3 time points, with significant differences from those of invasive IPMC (P 0.001). The solid tumor diameter was significantly larger in PDAC than in invasive IPMC, and the tumor stage and preoperative serum carbohydrate antigen 19-9 level were higher. After propensity score matching of stage and solid tumor diameter, contrast enhancement patterns were significantly more persistent in invasive IPMC than in PDAC (P = 0.0013).Multiphase evaluation using CEH-EUS is a useful method for differentiating between invasive IPMC and PDAC.

Introduction: We aimed to compare the efficacy of endoscopic ultrasound elastography (EUS-EG) with that of magnifying chromoendoscopy (MCE) and endoscopic ultrasonography (EUS) for the diagnosis of the depth of invasion in colorectal neoplasms. This is an important clinical issue as the depth of invasion is associated with the risk of metastasis. Methods: Consecutive patients with suspected superficial colorectal neoplasms, evaluated by MCE, EUS, and EUS-EG, for whom endoscopic submucosal dissection was considered, were enrolled in 2018 (derivation study) and in 2019–2020 (validation study). The primary clinical endpoint was the diagnostic yield differentiating intramucosal and shallow submucosal neoplasms from deep submucosal (dSM) and advanced colorectal cancers. In addition, inter- and intra-observer agreements of the elastic score of colorectal neoplasm (ES-CRN) were evaluated by 2 expert and 2 non-expert endoscopists. Results: Thirty-one (33 lesions) and 50 (55 lesions) patients were enrolled in the derivation and validation studies, respectively. Sensitivity, specificity, positive, and negative predictive values, and accuracy of assessment of the depth of submucosal or deeper invasion in the derivation and validation groups were as follows: EUS-EG, 100/88.2/86.7/100/93.3% and 77.8/86.1/73.7/88.6/83.3%; MCE, 66.7/94.4/90.9/77.3/81.8% and 84.2/91.4/84.2/91.4/88.9%; and EUS, 93.3/77.8/77.8/93.3/84.8% and 89.5/65.7/58.6/92.0/74.1%, respectively. For the 2 expert endoscopists, interobserver agreement for the ES-CRN (first and second assessments) in the derivation group was 0.84 and 0.78, respectively; these values were 0.73 and 0.49, respectively, for the 2 non-expert endoscopists. Discussion/Conclusion: All 3 modalities presented similar diagnostic yield. Inter- and intra-observer agreements of the ES-CRN were substantial, even for non-expert endoscopists. Therefore, EUS-EG may be a useful modality in determining the depth of invasion in colorectal neoplasms.

BackgroundVascular invasion is an important criterion for resectability and deciding the therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC), but imaging diagnosis is currently difficult. Endoscopic ultrasound (EUS) elastography (EG) images have band-like artifacts on the border between tumor and vessel due to different movement if the tumor is not connected to the vessel, i.e., no invasion. Based on this phenomenon, we assessed the usefulness of EUS-EG in the diagnosis of vascular invasion in PDAC.MethodsThe subjects were 44 out of 313 patients with PDAC who underwent EUS between January 2015 and November 2018, followed by surgery, no chemotherapy or radiotherapy, and pathological evaluation. Diagnostic accuracies of vascular invasion using dynamic computed tomography (CT), EUS B-mode and EUS-EG were compared with histopathological diagnosis.ResultsIn 44 subjects (48 sites) who underwent both dynamic CT and EUS-B mode, the sensitivity, specificity and accuracy were 0.733, 0.697 and 0.708 on dynamic CT (48 sites); 0.733, 0.606 and 0.646 in EUS B-mode (48 sites); and 0.917, 0.900 and 0.906 in EUS-EG (32 sites). In 27 subjects (29 sites) with a tumor contacting a vessel with no vascular obstruction or stenosis on dynamic CT, the sensitivity, specificity and accuracy were 0.556, 0.750 and 0.690 on dynamic CT; 0.667, 0.700 and 0.690 in EUS B-mode; and 0.889, 0.850 and 0.862 in EUS-EG.ConclusionsThese results suggest that EUS combined with EG improves diagnostic performance of vascular invasion in PDAC, especially in cases of which vascular invasion cannot be clearly assessed by dynamic CT.

Introduction: Quality measures for colonoscopy such as adenoma detection rate (ADR) have been proposed to be surveilled for ensuring minimum standards. However, its direct measurement is time consuming and often neglected. Extrapolating ADR and other quality measures from polyp detection rate (PDR) can be a pragmatic alternative. Objective: To determine quotients for estimating ADR and sessile serrated adenoma/polyp detection rate (SSA/P-DR) from PDR in an Australian cohort. Methods: Consecutive adult patient colonoscopies during a 1-year period were retrospectively assessed in a single Australian tertiary endoscopy center. Adenoma detection quotient (ADQ) and SSA/P detection quotient (SSA/P-DQ) were defined as the division of ADR and SSA/P-DR by PDR, respectively. The primary outcome was the number of procedures to achieve a stable cumulative ADQ and SSA/P-DQ. Secondary outcomes included evaluation of ADQ and SSA/P-DQ in different subsets. Results: In total, 2,657 colonoscopies were performed by 15 endoscopists in 2016. The ADR, SSA/P-DR, and PDR found were 32.2, 6.7, and 47.3%, respectively. The ADQ and SSA/P-DQ values found were 0.68 and 0.14, respectively. After approximately 500 procedures, both ADQ and SSA/P-DQ became stable. Interclass correlation coefficient (ICC) for the prediction of ADR from ADQ was excellent for all endoscopists that performed >177 procedures in that year (ICC 0.84). Conclusions: ADQ and SSA/P-DQ values were consistent when over 500 procedures were analyzed. ADQ had an excellent correlation with ADR when >177 procedures per endoscopist were evaluated.

Strategies for early detection of gallbladder cancer are not always easy. Symptoms reported in gallbladder cancer patients include abdominal pain, jaundice, nausea, vomiting, and weight loss. However, these symptoms rarely occur in early gallbladder cancer, and many of the symptoms are found in advanced gallbladder cancer. Risk factors for the development of gallbladder cancer include pancreaticobiliary maljunction (PBM), gallbladder stone, porcelain gallbladder, infection, and adenomyomatosis. In particular, PBM without bile duct dilatation is considered a risk factor for the development of gallbladder cancer, and diagnosing PBM can be an important strategy for early detection of gallbladder cancer. Diagnosis of uniform gallbladder wall thickness by TUS (transabdominal ultrasonography) makes it possible to directly depict PBM in some cases. Also, measurement of arterial blood flow velocity along the gallbladder wall by color Doppler flow imaging analysis can contribute to early diagnosis of gallbladder cancer and diagnosis of PBM. In Japan, in view of the risk of dissemination, biopsy using EUS-FNA is not recommended for patients with operable gallbladder cancer. Tumor markers capable of diagnosing early gallbladder cancer have not been developed at present and appearance of useful biomarkers for early detection of gallbladder cancer is eagerly awaited.

Background Primary intestinal diffuse large B‐cell lymphoma (iDLBCL) is rare. In this study, we investigated the clinicopathological features of this disease to further understand the prognostic value of CD5, programmed cell death ligand 1 (PD‐L1), and Epstein‐Barr virus (EBV) on tumor cells. Methods Tumor specimens from 62 patients consecutively diagnosed with primary iDLBCL at a single institution were analyzed. Results Our series consisted of EBV‐positive (EBV+) iDLBCL (n = 10), de novo CD5+ iDLBCL (n = 4), and DLBCL, not otherwise specified (DLBCL‐NOS; n = 48). Notably, seven of 10 EBV+ cases had treated lymphoma‐associated (n = 4) or iatrogenic immunodeficiency (n = 3). Two of 10 EBV+ cases expressed PD‐L1 on tumor cells, whereas the remaining eight were positive for PD‐L1 on microenvironment immune cells. Only one DLBCL‐NOS case had neoplastic PD‐L1 expression with a giant cell‐rich appearance. Both EBV‐harboring and PD‐L1 expression on tumor cells, but not CD5, were associated with worse overall survival (OS) in iDLBCL patients receiving rituximab‐containing chemotherapy (P = 0.0354, P = 0.0092, and P = 0.1097, respectively). Multivariate analysis identified PD‐L1 positivity on tumor cells (P = 0.0106), PD‐L1 negativity on microenvironment immune cells (P = 0.0193), and EBV positivity (P = 0.0324) as poor independent prognostic factors for OS. Among iDLBCL cases without any EBV association, CD5 positivity, or neoplastic PD‐L1 expression, high PD‐L1 expression (≥40%) on microenvironment immune cells predicted an extremely favorable outcome. Conclusion EBV+ iDLBCL mainly comprised immunodeficiency‐associated patients, which may highlight the specificity of the intestine. PD‐L1 expression on tumor cells or microenvironment immune cells was found to have an opposite prognostic impact in iDLBCL.

Objective: To evaluate the efficacy and safety of alternate-day administration of S-1 as second-line chemotherapy for unresectable pancreatic cancer in a multicenter, randomized, phase II study. Methods: Patients with histologically proven, unresectable pancreatic cancer treated with chemotherapy not including S-1 as first-line therapy were randomly assigned to receive either daily or alternate-day treatment with S-1. The primary end point was overall survival (OS), and the secondary end points were progression-free survival (PFS), time to treatment failure (TTF), response rate, and adverse events. Results: A total of 77 patients were enrolled, of which 75 were included in the final analysis. The median OS was 4.5 months in the daily group and 4.4 months in the alternate-day group (HR 1.178; 95% CI 0.741–1.875), with no significance in PFS and TTF. The response rate was 2.8% in the daily group and 0% in the alternate-day group. Grade 3 or higher adverse events occurred with significantly higher incidence in the daily group (47.2 vs. 25.6%, p = 0.044). Conclusion: As a second-line chemotherapy for unresectable pancreatic cancer, although the efficacy in both groups was comparable and we can expect fewer toxicities with alternate-day administration of S-1, the noninferiority of alternate-day treatment to daily treatment with S-1 was not verified.

BACKGROUND AND AIM The fibrosis stage of non-alcoholic fatty liver disease (NAFLD) is closely associated with long-term prognosis, including liver-related mortality. However, it is not yet clear whether noninvasive fibrosis markers can predict the incidence of non-liver-related complications in Japanese NAFLD. In this study, we clarified the prognosis of NAFLD patients, including non-liver-related diseases, based on hepatic pathology and noninvasive fibrosis markers. METHODS A total of 246 Japanese patients with NAFLD diagnosed by liver biopsy were enrolled. We investigated their prognosis based on hepatic pathology and noninvasive fibrosis markers. RESULTS When these patients were categorized based on the severity of liver fibrosis as F0-2 (n = 196) and F3-4 (n = 50), the patients with F3-4 had significantly poorer prognosis in overall survival rates and all complications (P

There have been reports that a vitamin K2 (VK2) analog is beneficial for the prevention of recurrence in hepatocellular carcinoma (HCC) patients after curative therapy. However, the VK2 analogs in current use do not appear to show dramatic antitumor effects when given alone. Here, we report the case of a 67-year-old male patient with sorafenib-failure advanced HCC who achieved complete response (CR) after VK2 analog monotherapy. At the time of sorafenib failure confirmation, the patient had multiple intrahepatic tumors, multiple lung metastases, and Vp3 portal vein tumor thrombosis. He had poor liver function (Child-Pugh score of 9, Child-Pugh class B) and poor performance status (Eastern Cooperative Oncology Group performance status 2). Both serum α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels were elevated (558 900 ng/mL and 917 300 mAU/mL, respectively). Treatment with VK2 analog was initiated at 45 mg/day. Five months later, both tumor markers had decreased to normal levels (AFP 8 ng/mL and DCP 10 mAU/mL). Contrast-enhanced computed tomography showed that all intrahepatic tumors had shrunk, there was no enhancement of tumor staining in the arterial phase, and all lung metastases and portal vein tumor thromboses had disappeared. We considered that CR was achieved according to the modified Response Evaluation Criteria in Solid Tumors. Eighteen months after the start of VK2 analog administration, the patient continues to receive treatment and has remained in CR without adverse events. Here, we report a rare case of sorafenib-failure advanced HCC in which sustained CR was achieved by VK2 analog monotherapy.

Major aortopulmonary collateral arteries (MAPCAs) are unique vessels associated with hypoxia induced by congenital heart disease (CHD). Although MAPCAs are essential to supply blood to the lungs, their development and proliferation can induce life-threatening complications, such as rupture into the lung. Here, we describe a rare case of esophageal bleeding from MAPCAs in a CHD patient, which was successfully treated by transcatheter arterial embolization (TAE). A 16-year-old male with CHD experienced a hematemesis and melena after the Bentall procedure to treat valvular heart disease. Emergent esophagogastroduodenoscopy revealed spurting bleeding from the middle esophageal vessels; accordingly, endoscopic variceal ligation (EVL) was performed. However, he had a hematemesis again after 2 weeks of EVL. The arterial phase of dynamic computed tomography indicated that a MAPCA associated with CHD was the origin of bleeding. Hence, TAE of this MAPCA with a mixture of n-butyl-2-cyanoacrylate and ethiodized oil was performed to prevent re-bleeding. Color Doppler mode in endoscopic ultrasonography via the esophagus revealed mosaic-like signals in MAPCAs located in the esophageal wall. This finding was consistent with tortuous MAPCAs accompanied by turbulent blood flow. When clinicians encounter CHD patients with unexpected massive esophageal bleeding, bleeding related to MAPCAs should be considered.

BACKGROUND AND AIM Amino-acid substitutions in the interferon sensitivity-determining region (ISDR) within the NS5A region are known to be associated with responsiveness to interferon (IFN)-based therapy. Additionally, previous studies reported that the ISDR was related to the development of hepatocellular carcinoma (HCC) in patients infected with hepatitis C virus (HCV). However, the association between substitutions in the ISDR and the development of HCC in patients who achieved sustained virological response (SVR) is unclear. The aim of this study was to clarify the association between amino-acid substitutions in the ISDR and development of HCC after SVR. METHODS One thousand five hundred eighty-eight patients infected with HCV who were treated with IFN-based therapy were enrolled, and 475 patients who achieved SVR and underwent complete virological analysis at pretreatment were investigated. HCV genotypes consisted of 1a (n = 10), 1b (n = 307), 2a (n = 110), 2b (n = 41), and 3a (n = 7), and the ISDR in each genotype was examined by direct sequencing. RESULTS Nineteen patients developed HCC after SVR. The cumulative incidence of HCC was 2.1% and 15.9% at 5 and 10 years after SVR, respectively. Multivariate analysis indicated older age (≥ 60 years: hazard ratio [HR], 3.23; P = 0.014), higher γ-glutamyl transpeptidase level (≥ 50 IU/L: HR, 8.42; P

EBV‐positive diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS), often affects the gastrointestinal tract. However, the prognostic significance of EBV associated with primary gastric DLBCL (gDLBCL) has not been established. This retrospective study included 240 patients with primary gDLBCL, diagnosed between 1995 and 2015. Tumor specimens were analyzed with EBER in situ hybridization. In 25 (10%) cases, tumor cells harbored EBV. The EBV + group more frequently exhibited programmed death‐ligand 1 (PD‐L1) expression in microenvironment immune cells, but not tumor cells, compared to the EBV − group (86% vs 43%, P = .006). Among 156 patients that received rituximab‐containing chemotherapy, the EBV + group had a significantly worse overall survival (OS) than the EBV − group (P = .0029). Multivariate analyses identified 3 independent adverse prognostic factors of OS: multiple gastric lesions (P = .002), EBER positivity (P = .003), and B symptoms (P = .018). These factors were combined to develop a gDLBCL prognostic (gDLP) model that significantly stratified the patients into 3 distinct risk groups (Scores: good = 0, intermediate = 1, and poor = 2/3, P

Background Prognosis of pancreatic cancer is poor with a 5-year survival rate of only 7%. Although several new chemotherapy treatments have shown promising results, all patients will eventually progress, and we need to develop newer chemotherapy treatments to improve response rates and overall survival (OS). HF10 is a spontaneously mutated oncolytic virus derived from a herpes simplex virus-1, and it has potential to show strong antitumor effect against malignancies without damaging normal tissue. We aimed to evaluate the safety and anti-tumor effectiveness in phase I dose-escalation trial of direct injection of HF10 into unresectable locally advanced pancreatic cancer under endoscopic ultrasound (EUS)-guidance in combination with erlotinib and gemcitabine administration. The mid-term results have been previously reported and here we report the final results of our study. Methods This was a single arm, open-label Phase I trial. HF10 was injected once every 2 weeks and continued up to four times in total unless dose-limiting toxicity (DLT) appears. A total of nine subjects in three Cohorts with dose-escalation were planned to be enrolled in this trial. The primary endpoint was the safety assessment and the secondary endpoint was the efficacy assessment. Results Twelve patients enrolled in this clinical trial, and ten subjects received this therapy. Five patients showed Grade III myelosuppression and two patients developed serious adverse events (AEs) (perforation of duodenum, hepatic dysfunction). However, all of these events were judged as AEs unrelated to HF10. Tumor responses were three partial responses (PR), four stable diseases (SD), and two progressive diseases (PD) out of nine subjects who completed the treatment. Target lesion responses were three PRs and six SDs. The median progression free survival (PFS) was 6.3 months, whereas the median OS was 15.5 months. Two subjects from Cohort 1 and 2 showed downstaging and finally achieved surgical complete response (CR). Conclusions HF10 direct injection under EUS-guidance in combination with erlotinib and gemcitabine was a safe treatment for locally advanced pancreatic cancer. Combination therapy of HF10 and chemotherapy should be explored further in large prospective studies. Trial registration: This study was prospectively registered in UMIN-CTR (UMIN000010150) on March 4th, 2013. Electronic supplementary material The online version of this article (10.1186/s12885-018-4453-z) contains supplementary material, which is available to authorized users.

OBJECTIVES The aim of this study is to evaluate a functional correlation between the pancreas and the small intestine and the association of this relationship with nutritional status, using magnifying enteroscopy. METHODS The subjects were adults aged 20 years or older who underwent upper gastrointestinal endoscopy. An endoscope was inserted into the jejunum, and 10% glucose was sprayed under magnifying observation to evaluate changes in blood flow in the villous capillary network. Mucosal biopsy was performed before and after spraying to evaluate the incretin response in the jejunal mucosa. RESULTS A total of 124 patients participated in the study. There was a positive correlation between villous blood flow change and exocrine pancreas function (R = 0.4337, P < 0.0001). Changes of gastric inhibitory polypeptide and glucagon-like peptide messenger RNAs in biopsy samples were positively correlated with endocrine pancreas function in 88 patients without treatment for diabetes (R = 0.4314, P = 0.0012; R = 0.4112, P = 0.0081). In patients with lower villous blood flow change and decreased pancreatic exocrine function, the prognostic nutritional index were significantly lower (P = 0.0098), compared with other patients. CONCLUSIONS This study provides the first evidence of a close functional correlation between the pancreas and the small intestine.

Small bowel capsule endoscopy (SBCE) and balloon-assisted endoscopy (BAE) have revolutionized the diagnosis and treatment of small bowel bleeding (SBB), allowing access to the small bowel and identification of specific bleeding lesions. However, some patients experience rebleeding after small bowel investigation, and there are no definitive algorithms for determining the most appropriate follow-up strategy in SBB patients. We developed and validated a nomogram that can predict rebleeding risk and be used to develop a risk-stratified follow-up strategy in SBB patients. A retrospective study was performed using data from 401 SBB patients who underwent SBCE at Nagoya University Hospital. We developed and internally validated a predictive model for rebleeding in the form of a nomogram using Cox regression models and a bootstrap resampling procedure. Optimal risk factors were selected according to the least absolute shrinkage and selection operator (LASSO). The LASSO method identified 8 independent predictors of rebleeding that could be assessed to obtain a ‘predicting rebleeding in SBB’, or ‘PRSBB’ score: age, sex, SBB type, transfusion requirement, cardiovascular disease, liver cirrhosis, SBCE findings, and treatment. The c-statistic for the predictive model was 0.681. In conclusion, our PRSBB score can help clinicians devise appropriate follow-up plans.

Background/Objectives Time-intensity curve (TIC) under contrast-enhanced EUS (CE-EUS) allows continuous and quantitative evaluation of targeted area in the pancreas. However, TIC is not always available and the procedure is complicated. We aimed to propose a simplified method by evaluating multiple phases of CE-EUS in the diagnosis of pancreatic solid lesions. Methods We retrospectively reviewed 210 patients with pancreatic solid lesions including 142 with pancreatic ductal cancer (PDAC), 31 with pancreatic neuroendocrine neoplasm, 13 with solid pseudopapillary neoplasm and 24 with mass-forming pancreatitis who underwent CE-EUS and achieved final diagnoses. The CE-EUS images were continuously recorded for 60 s, and each image at 20, 40 and 60 s was used for the evaluation. The images were classified into three patterns as hypoechoic, hyperechoic and isoechoic vascular patterns compared with the surrounding pancreas, and the relevance between the multiphase evaluation of CE-EUS and each disease group was investigated. Results In PDAC group, majority of the lesions showed hypovascular pattern at 20 or 40 s after injection of contrast medium following early enhancement. The sensitivity, specificity and accuracy of PDAC pattern in the differentiation of PDAC from other lesions was 83.1%, 86.8% and 84.3%, respectively. On histopathological analysis, significant differences were seen in histologic types, infiltration (INF), and neural invasion (ne) between those who showed PDAC pattern and those who didn't. Conclusions Multiphase evaluation of CE-EUS is convenient and useful method for the differentiation of pancreatic solid lesions which can be alternatively used for TIC.