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Na+/H+ antiporter plays an important role in maintaining cellular homeostasis by regulating osmotic pressure and intracellular pH. It plays an important role in maintaining cellular homeostasis. InHelicobacter pylori, whole genome sequencing has revealed the presence of two types of Na+/H+ antiporter. A gene (nhaA) homologous to the Na+/H+ antiporter ofEscherichia colihas been investigated and its function has been analyzed. However, another gene homologous to the Na+/H+ antiporter ofEnterococcus hirae(napA) is not yet known in detail. In this study, we investigated the function of this gene (napAinH.pylori). First, to confirm the genetic presence ofnapAin 20H. pyloriclinical isolates, PCR analysis was performed, and thenapAgene was confirmed in all strains. The amount of Na+ extrusion was measured by atomic absorption spectroscopy. The results showed that the Na+ concentration was decreased in the wild-type strain compared to thenapAmutant strain. In addition, there was a significant dose-dependent difference in CFU of Na+ concentration in thenapAmutant strain compared to the wild-type strain. We examined whether thenapAgene is related to motility using both wild-type andnapAmutant strains. As a result, in the motility agar test, the bacterial motility observed in the wild-type strain was not observed in thenapAmutant strain. However, no difference in flagellar proteins was observed by SDS-PAGE analysis. These results suggest that thenapAgene ofH. pylorimay regulate homeostasis by extruding Na+ and may also regulate motility.&nbsp

STUDY AIMS The PillCam patency capsule (PPC) is an Agile tag-less patency capsule used to evaluate gastrointestinal (GI) patency. We determined the appropriate use of PPC to preclude subsequent small bowel capsule endoscopy (SBCE) retention. METHODS This prospective multicenter study consecutively enrolled patients indicated for SBCE with suspected or established small bowel stenosis. Excretion of an intact PPC or its radiologic visualization in the large bowel was considered GI patency. Primary and secondary study endpoints were SBCE retention rates in patients with confirmed patency and identification of factors associated with patency and SBCE retention, respectively. RESULTS Of 1096 patients enrolled in the study, patency was confirmed in 976 (89.1%). PPC excretion occurred in 579 patients. Of the remaining 517 patients, patency was confirmed using imaging modalities in 401 (77.5%). SBCE retention occurred in five (0.51%) of 963 patients who underwent SBCE: 1.0% in established Crohn's disease (CD) patients, 0% in suspected CD, 0% in tumors, and 1.6% in patients with obscure GI bleeding, for which PPC localization had been radiographically misinterpreted. The non-confirmation of patency was associated with established CD, stenosis identified using imaging modalities, abdominal fullness, serum albumin levels

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

Helicobacter pylori(H. pylori) urease generates both ammonia (NH3) and carbon dioxide (CO2) from urea. NH3helpsH. pylorito survive in the stomach in part by neutralizing gastric acid. However, the relationship between CO2andH. pyloriis not completed cleared. We examined the effect of CO2generated by urease on multiplication ofH. pyloriby using isogenicureBmutant andureBcomplemented strain fromH. pyloristrain JP26. Wild-type strain survived in the medium supplement with 1mM urea in room air, however, the urease negative strain did not. To discern whether CO2was incorporated intoH. pylori,14C in bacillus was counted after 6 hours incubation with14C urea in both acidic and neutral medium. Significant more14C uptake was detected in wild-type strain compared toureBmutant strain and this uptake in the wild-type strain was more under acidic condition compared to under neutral condition, but no difference was identified in the mutant strain. These results suggest that CO2generated by urease plays a role in multiplication ofH. pylori.

Colorectal endoscopic submucosal dissection (ESD) is considered one of the most challenging endoscopic procedures for novice endoscopists. When compared with the stomach, the colon and rectum have a narrower tubular lumen, greater angulation at the flexures, and a thinner muscle layer. These factors make endoscopic control and maneuverability difficult. ESD of the colorectum was considered more difficult than gastric and esophageal ESD. However, with learning from the experts, practicing, and selecting an appropriate technique, most of colorectal ESD could be performed successfully. Nevertheless, some colorectal locations are extremely specialized either from unique anatomy or given unstable scope position. Accordingly, the objective of this review was to provide endoscopists with an overview of the techniques and outcomes associated with ESD at these special colorectal locations. ESD at the discussed special locations of the ileo-colo-rectum was found to be feasible, and outcomes were comparable to those of ESD performed in non-special locations of the ileo-colo-rectum. Practice for skill improvement and awareness of the unique characteristics of each special location is the key to performing successful ESD.

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: 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.

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.

The effect of skeletal muscle fat deposition on the prognosis of patients with chronic liver disease remains unclear. Skeletal muscle fat deposition can be estimated by attenuation of skeletal muscle in Hounsfield units (HU) on computed tomography (CT). The aim of this retrospective cohort study was to investigate the association between skeletal muscle fat deposition assessed by skeletal muscle attenuation (SMA), and hepatocellular carcinoma (HCC).We enrolled 288 patients with chronic liver disease (139 men, 149 women; mean age 67.5 ± 10.4 y; hepatitis C virus, 239; hepatitis B virus, 17; without viral infection, 32; chronic hepatitis, 227; and cirrhosis, 61) who underwent liver biopsy and CT scanning between January 2013 and February 2017. The patients were divided into two groups based on SMA levels, with the cutoff value of 31 HU. We analyzed the effect of SMA on HCC development.During the study follow-up period (median, 2.50 y; range, 0.5-4.7 y), HCC was identified in 19 patients (7%). The cumulative incidence of HCC in patients with lower SMA (31 HU) was significantly higher than in patients with SMA ≥31 HU (P = 0.007). Cox proportional hazards regression analysis confirmed cirrhosis (hazard ratio [HR], 6.626; 95% confidence interval [CI], 2.57-17.12; P 0.001) and lower SMA (HR, 3.502; 95% CI, 1.25-9.83; P = 0.017) as significant independent factors associated with HCC development in patients with chronic liver disease.Patients with cirrhosis and skeletal muscle fat deposition assessed by SMA had a higher risk for developing HCC.

BACKGROUND AND AIM Video capsule endoscopy (VCE) is a first-line procedure for the diagnosis of obscure gastrointestinal bleeding (OGIB). The opinions on the timing for such diagnostic evaluation remain unclear. We aimed to explore the role of early VCE in OGIB patients. METHODS A total of 997 patients that underwent VCE at Renji Hospital and Nagoya University from May 15, 2002, to December 28, 2016, were included in this study. We matched patients that underwent early VCE within 14 days of bleeding (early group, n = 678) to patients that did not (late group, n = 319) via 1:1 propensity score matching (PSM). We then compared VCE diagnostic rates and the prevalence of post-VCE rebleeding in patients with initial negative VCE findings within 1 year between these groups before and after PSM. RESULTS Following PSM, early VCE was associated with a significantly higher rate of OGIB diagnosis (56.4% vs 45.5%, P = 0.001) and with a significantly lower incidence of rebleeding within 1 year following treatment (24.7% vs 36.7%, P = 0.041). In univariate and multivariate analyses, VCE timing (odds ratio 0.648; 95% confidence interval 0.496-0.847, P = 0.001 and odds ratio 0.666; 95% confidence interval 0.496-0.894, P = 0.007, respectively) was found to be linked with a higher rate of positive findings. CONCLUSION Early VCE can improve the reliability of OGIB diagnosis while also reducing rates of post-VCE rebleeding. This suggests that timely and accurate diagnosis can help to improve OGIB patient treatment and prognosis.

The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was identified in 2019; thereafter, the COVID-19 outbreak became a health emergency of international concern. The impact of COVID-19 on liver-transplant recipients is unclear. Thus, it is currently unknown whether liver-transplant recipients are at a higher risk of developing complications related to COVID-19. Here, we report the case of liver-transplant recipients who were infected with SARS-CoV-2. A 20-year-old man who had undergone living-donor liver transplantation from his father at 5 years of age because of congenital biliary atresia was referred to our hospital for SARS-CoV-2 infection. Chest computed tomography did not show any abnormalities; however, laboratory results revealed liver dysfunction. He received tacrolimus as maintenance therapy that was continued at the same dose. He has not developed severe pulmonary disease and was discharged after 10 days of hospitalization. Limited data are available on post-transplant patients with COVID-19, and this case of a young patient without metabolic comorbidities did not show any association of severe COVID-19 under tacrolimus treatment. The progression of COVID-19 in liver-transplant recipients is complex, and COVID-19 risk should be evaluated in each patient until the establishment of optimal guidelines.

Although the majority of gastrointestinal stromal tumors (GISTs) possess KIT mutations that induce constitutive signal transduction, the clinical outcomes are variable. The ETS translocation variant 1 (ETV1) gene encodes a transcription factor that is reported to cooperate with KIT in GISTs. However, the clinical role of ETV1 is largely unknown. The aim of this study was to examine ETV1 expression and its associations with clinical features in GISTs. We conducted a cohort study involving 64 patients with GISTs who underwent surgical resection between October 2008 and February 2015. ETV1 mRNA expression was compared with that in non-GISTs and was analyzed among risk classifications or clinical outcomes. The GIST samples exhibited significantly higher ETV1 mRNA expression than the non-GIST samples (P P = 0.025). Our study revealed that low ETV1 expression is an independent factor of recurrence after surgery in patients with GISTs, and thus, low ETV1 expression might be a marker of more aggressive malignant GISTs.

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

Pruritus is one of the complications with chronic liver disease and markedly worsens quality of life. However, the current status of pruritus in chronic hepatitis C patients who have achieved a sustained virological response (SVR) has not been clarified sufficiently. The aim of this study was to investigate the predictors of pruritus in post-SVR patients treated with direct-acting antivirals (DAA).In this retrospective study, we enrolled 110 hepatitis C patients with SVR who underwent serial shear wave elastography before DAA therapy and at the end of treatment. The severity of pruritus was evaluated using Kawashima's pruritus scores and a visual analog scale.The prevalence of pruritus before treatment and after SVR was 28.2 and 25.5%. Multivariate logistic regression analysis confirmed that a history of hepatocellular carcinoma [odds ratio (OR): 9.72; 95% confidence interval (CI): 2.05-46.15; P=0.004], high γ-glutamyl transpeptidase levels at baseline (OR: 5.77; 95% CI: 1.83-18.21; P=0.003), low serum albumin at the end of treatment (OR: 4.85; 95% CI: 1.31-17.99; P=0.018), and high liver stiffness measurement assessed by shear wave elastography at the end of treatment (OR: 3.16; 95% CI: 1.19-11.01; P=0.024) were significant independent factors associated with pruritus in patients who had achieved an SVR following DAA therapy.In chronic hepatitis C patients with SVR after DAA therapy, the incidence of pruritus is not uncommon. Liver stiffness measurement is useful for predicting the incidence of pruritus. Thus, even if SVR is achieved, patients with higher liver stiffness at the end of treatment must be monitored carefully for pruritus.

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.

The optimal term of follow-up for patients who achieve sustained virological responses (SVR) is an important topic because of the widespread use of direct-acting antivirals (DAA), which achieve a high SVR rate. Investigations of long-term follow-up among patients with SVR after interferon (IFN) therapy have reported that approximately 80%-100% of patients maintained SVR. However, the long-term durability of SVR to DAA treatment is unknown. The aim of this study was to evaluate the incidence of late relapse in patients who achieved SVR with daclatasvir (DCV) and asunaprevir (ASV). Four hundred and thirteen patients infected with hepatitis C virus (HCV) genotype 1b who completed ASV and DCV treatment and achieved SVR were selected. Patients who were persistently negative for serum HCV RNA at 24 weeks after withdrawal of DCV and ASV were considered to have SVR24. Mean follow-up period was 21.5 months (range, 4.8-30.3 months) after SVR24. Four patients redeveloped HCV RNA in serum at 6, 12, 12 and 26 months, respectively, after achieving SVR24. Results of molecular analysis by phylogenetic tree of HCV nonstructural protein 3 and 5A regions from late relapse indicated that the same strain was present at pretreatment and late relapse. In conclusion, late relapse by the original HCV strain was confirmed by direct sequencing in 4 of 413 patients with SVR to ASV and DCV. Although a few patients may develop late relapse, SVR achieved with all oral DAA therapy is as durable as that with IFN therapy.

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 Aspartate transaminase–to–platelet ratio index (APRI) and fibrosis-4 (FIB-4) are well known as representative indirect serum biomarkers related to liver fibrosis. The usefulness of these markers for the diagnosis of liver fibrosis after liver transplantation (LT) in hepatitis C virus (HCV)–infected patients and the influence of splenectomy were investigated. Methods From June 2003 to May 2014, 31 HCV-infected patients who underwent LT and postoperative follow-up liver biopsies were included in this study. The association between liver fibrosis and serum biomarkers and the influence of splenectomy on APRI and FIB-4 were also investigated. Results A total of 195 biopsy specimens were collected, and liver fibrosis was identified as: F0, 59.7%; F1, 34.1%; and F2, 6.3%. Both APRI and FIB-4 were significantly higher in patients who showed F1 and F2 in liver biopsy specimen than F0 (P values, .009 and .022, respectively); sensitivity and specificity of APRI were, respectively, 63.4% and 66.7%, and those of FIB-4 were 57.7% and 69.6%. In 11 patients (35.5%) who underwent splenectomy at the time of LT, the cutoff values for APRI and FIB-4 were 0.61 and 1.41, which were significantly lower than the corresponding values (1.00 and 3.64) of patients without splenectomy. Conclusions APRI and FIB-4 could effectively estimate liver fibrosis after LT for HCV-related liver disease. For LT patients with splenectomy, APRI and FIB-4 were also useful to estimate liver fibrosis, but the standard values should be adjusted lower than those for patients without splenectomy.

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.

BACKGROUND AND AIM Severe muscle volume loss is a recognized negative prognostic factor in patients with chronic liver disease. However, the effect of skeletal muscle fat deposition, referred to as myosteatosis on muscle volume loss remains unclear. The aim of this study was to investigate the relationships between myosteatosis and skeletal muscle volume loss. METHODS We enrolled 362 patients with chronic liver disease (186 men, 176 women; mean age 68.4 ± 10.0 years, 94 with cirrhosis) who underwent liver biopsy and computed tomography scanning between January 2013 and February 2017. A transverse computed tomography image of each scan at the third lumbar vertebra was used to evaluate skeletal muscle tissues. RESULTS Prevalence of skeletal muscle volume loss and myosteatosis were 36% and 82%, respectively. Of those with skeletal muscle volume loss, 93% have concomitant myosteatosis. Univariate analysis revealed that higher age, female, lower body mass index (BMI), higher serum albumin, lower alanine aminotransferase (ALT), lower gamma-glutamyl transpeptidase, lower total bilirubin, lower α-fetoprotein, lower skeletal muscle attenuation, and liver steatosis were significantly associated with skeletal muscle volume loss. Multivariate logistic regression analysis confirmed that lower BMI (odds ratio [OR] 5.26, 95% confidence interval [CI], 3.21-8.54; P

BACKGROUND AND AIM Chronic pancreatitis (CP) is sometimes diagnosed at the progressed stage. For the early diagnosis of CP, Endoscopic ultrasonography (EUS) may be a useful method, but its diagnostic criteria are based on subjective judgement. Shear wave elastography (SW-EG) using transabdominal ultrasonography, which quantifies tissue elasticity as an absolute value, may be an objective and non-invasive method for the diagnosis of CP. METHODS Eighty-five patients with known or suspected CP who underwent both EUS and SW-EG from October 2012 to July 2016 were included in this study. Patients were categorized into 4 stages using Rosemont classification (RC) and into 3 stages using Japan Pancreas Society (JPS) clinical diagnostic criteria 2009 that was EUS-based criteria for the diagnosis of CP. SW-EG was measured five times in the pancreatic parenchyma, and the median value was defined as the pancreatic elastic modulus (PEM). RESULTS PEM was significantly positively correlated with RC stage (rs = 0.54), JPS stage (rs = 0.41), and the number of EUS features (rs = 0.47). Area under the receiver operating characteristic curve for the accuracy of SW-EG (consistent with CP and suggestive of CP vs. normal and indeterminate for CP) was 0.77 (sensitivity 77.1%, specificity 64.9%). In a multivariate linear regression analysis including various EUS features related to PEM, hyperechoic foci with shadowing and lobularity with honeycombing were independent features related to PEM. CONCLUSIONS CP may be diagnosed non-invasively and objectively using SW-EG without performing EUS.

Background and Aim Virologic failure of interferon-free therapy has been associated with Y93H mutation in the non-structure 5A region in hepatitis C virus (HCV) genotype 1b, and screening is recommended. A simple assay based on Q-Invader technology was developed for Y93H mutant screening to reduce cost and effort. The present study sought to compare two methods of detection of Y93H mutation and to evaluate the effect of Y93H mutation on response to interferon-free therapy. Methods Y93H mutation was examined in 258 patients with HCV genotype 1b using both direct sequencing analysis and the polymerase chain reaction (PCR)-Invader assay. Daclatasvir and asunaprevir or ledipasvir and sofosbuvir therapy was administered to 205 patients whose sustained virological responses (SVR) were checked. Results Hepatitis C virus was detected in 232 of 258 patients by direct sequencing and in 236 of 258 patients by the PCR-Invader assay. Forty of 231 cases were defined as Y93 mutation by direct sequencing, and 46 of 236 cases were defined as Y93 mutation by the PCR-Invader assay. SVR of patients who were Y93H by direct sequencing, Y93H by the PCR-Invader assay, and Y93H by both methods was 62.5%, 82.4%, and 50%, respectively. Conclusions The sensitivity of the PCR-Invader assay was similar to that of direct sequencing analysis; however, the PCR-Invader assay had a better ability to detect minor strains. Combination of the two assays would improve prediction of the response to daclatasvir and asunaprevir, but Y93H mutation had little effect on SVR in ledipasvir and sofosbuvir therapy.

Background Small bowel capsule endoscopy (SBCE) is the recommended first-line procedure for obscure gastrointestinal bleeding (OGIB). However, a method for predicting the necessity of subsequent double-balloon endoscopy (DBE) has not been established. Aims We aimed to develop a new scoring system that predicts the necessity of DBE in OGIB. Methods A retrospective study was performed in 330 patients who underwent SBCE for OGIB at Nagoya University Hospital. The enrolled patients were randomly assigned to either a development or a validation dataset. The former was used to construct a prediction scoring system to assess the necessity of DBE using independent predictors selected by logistic regression. The diagnostic yield of the prediction model was assessed using the validation dataset. Results Multivariate logistic regression analysis of the development dataset identified OGIB type, blood transfusion, and SBCE findings as independent predictors of the necessity of DBE. A prediction score gave an area under the receiver operating characteristics curve of 0.77. The sensitivity, specificity, positive predictive value, and negative predictive value at a cutoff ≥2.5 points were 72.5%, 74.6%, 72.6%, and 74.5%, respectively. Conclusion Our scoring system may aid clinicians in deciding when to recommend DBE for patients with OGIB.

Background and Aim In this study, we investigated the real-world data of the first approved interferon-free regimen in Japan: daclatasvir and asunaprevir in chronic hepatitis C patients with severe fibrosis. Methods Among 924 patients registered in our multicenter study, 535 patients were defined as having severe fibrosis with Fib-4 index ≧ 3.25 and were included in this study. We investigated antiviral effect and factors associated with sustained viral response 12 (SVR12), and the additional effects on serum α-fetoprotein and albumin levels by eradicating virus in patients who attained SVR were investigated. In statistical analysis, P

Aim To examine usefulness of virtual biopsy using endocytoscopy by comparing the in vivo endocytoscopic and histopathological images of gastric cancers. Methods Endocytoscopy was performed in 30 patients with early gastric cancer. Of these, 26 patients showed well differentiated adenocarcinomas, while 4 patients showed poorly differentiated adenocarcinomas (including one signet ring cell carcinoma). Cancerous and non-cancerous areas were observed after double staining with 0.05% crystal violet and 0.1% methylene blue. The endocytoscopic images obtained were evaluated by an expert endoscopist and an expert pathologist without knowledge of patient clinical data, and endocytoscopic and histopathological diagnoses were compared. Results The endocytoscopic images of the cancerous area were assessed as evaluable in 25 (83.3%) and 27 (90%) patients by endoscopist A and pathologist B, respectively, and those of the non-cancerous area as evaluable in 28 (93.3%) and 23 (76.7%) patients by the endoscopist and pathologist, respectively. The sensitivity, specificity, and diagnostic accuracy of gastric cancer diagnosis using evaluable endocytoscopic images were 88.0% and 92.9%, and 90.6% by endoscopist A, and 88.9% and 91.3%, and 90.0% by pathologist B, respectively. Evaluation of the diagnostic concordance rate between the endoscopist and the pathologist by inter-observer agreement calculation revealed no significant difference between the two observers. The inter-observer agreement (κ-value) for endocytoscopic diagnosis was 0.745. Conclusion Endocytoscopy is useful for the differentiation of cancerous from non-cancerous gastric mucosa, making it a promising tool for virtual biopsy.

Background and Aim Predictive factors for hepatocarcinogenesis following eradication of hepatitis C virus by direct-acting antivirals (DAAs) are unknown. The aim of the study was to investigate the relationships between liver stiffness (LS) using acoustic radiation force impulse (ARFI) erastograghy and the development of hepatocellular carcinoma (HCC) in patients who achieved sustained virological response (SVR) treated with DAA. Methods In this prospective study, we enrolled 263 hepatitis C patients with SVR who underwent ARFI before DAA treatment. Thirty patients had previous HCC. Results The median LS value according to ARFI measurements was 1.34 m/s (range: 0.67–4.35). During the follow-up period (median: 18.1 months), development of HCC occurred in 19 patients (7.2%; HCC occurrence in 7 patients and HCC recurrence in 12 patients). By multivariate Cox regression analysis, HCC history (hazard ratio [HR]: 10.634; 95% confidence interval [CI]: 4.13–27.37; P = 0.001), older age (HR: 4.638; 95% CI: 1.63–13.61; P = 0.004) and higher total bilirubin levels (HR: 4.189; 95% CI: 1.66–10.60; P = 0.002) were independent predictors for the development of HCC, and higher LS value (≥1.73 m/s) at baseline was an independent predictor for HCC occurrence (HR: 8.350; 95% CI: 1.62–43.09; P = 0.011). The cumulative recurrence of HCC was statistically similar according to the degree of LS in patients who were previously treated for HCC. Conclusion The LS value at baseline is useful for predicting HCC occurrence. Thus, even if SVR is achieved, patients with higher LS at baseline must be followed carefully for HCC occurrence.

A new classification of magnifying endoscopy with narrow band imaging (ME-NBI) for diagnosing and staging superficial esophageal squamous cell carcinoma (SESCC) was proposed by the Japan Esophageal Society in 2011. This study aimed to compare the new classification with the conventional classifications (Inoue's classification and Arima's classification). This was a prospective analysis of data from a single cancer center involving 151 consecutive patients with 156 SESCCs that were endoscopically or surgically resected. Initially, only ME-NBI images were selected and reviewed independently by three experienced endoscopists. White light imaging (WLI) was then evaluated separately after an interval. The diagnostic performance of each classification and interobserver agreement were assessed, and the WLI findings that affect the diagnosis by the new classification were identified. The specificity for classifying invasive depth as epithelium (EP)/lamina propria mucosae (LPM) confined was higher with the new classification than with Inoue's classification (0.512 vs. 0.349; P = 0.02) and Arima's classification (0.512 vs. 0.279; P < 0.01). However, the sensitivity was lower (0.902 vs. 1.000; P < 0.01) compared with Arima's classification. The concordance rates of three evaluators (κ values) were 0.52 for the new classification, 0.50 for Inoue's classification, and 0.23 for Arima's classification. On multivariate analysis, thickness on WLI independently affected the accuracy of diagnosis with the new classification (OR 3.23; 95%CI, 1.30-8.03). The new classification is superior to conventional classifications with respect to specificity for diagnosing SESCC with depth EP/LPM. Thickness on WLI was a factor negatively affecting the diagnostic performance of the new classification.

Background and Aims We investigated the correlation between histological characteristics and changes in liver stiffness in patients with sustained virological response using acoustic radiation force impulse elastography. Methods In this prospective study, we enrolled 176 Hepatitis C patients with sustained virological response who underwent acoustic radiation force impulse elastography and liver biopsy before antiviral treatment, and serial acoustic radiation force impulse elastography at the end of treatment and at 24 weeks after the end of treatment. To compare the long-term changes in liver stiffness in patients with sustained virological response using acoustic radiation force impulse elastography, another group of 140 patients who had undergone paired biopsy after achieving sustained virological response were included. Results Mean liver stiffness values were 1.60±0.63 m/s, 1.48±0.56 m/s and 1.37±0.62 m/s at baseline, end of treatment, and 24 weeks after end of treatment, respectively, P < 0.001. Higher inflammatory activity at baseline was associated with an improvement in liver stiffness at the end of treatment, with an odds ratio of 1.940. Significant fibrosis at baseline was associated with an improvement in liver stiffness at 24 weeks after the end of treatment, with an odds ratio of 2.617. Among patients in the paired biopsy group with baseline fibrosis stage identical to the acoustic radiation force impulse group, liver stiffness values at 24weeks after the end of treatment did not show any difference with values at 5 years after end of treatment. Conclusions Pre-treatment histological characteristics influence liver stiffness reduction after sustained virological response is achieved. This article is protected by copyright. All rights reserved.

To evaluate the efficacy and safety of gemcitabine plus cisplatin in Japanese patients with unresectable gallbladder cancer (GBC). Chemo-naive patients with histologically proven unresectable GBC were enrolled in this study. The patients received gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) on days 1 and 8, every 21 days. A response assessment was done by CT scan every 4 weeks. The primary end points were to determine the response rates [RR; complete response (CR) + partial response (PR)] and the disease control rate [DCR; CR + PR + stable disease (SD)]. The secondary end points were to evaluate toxicity, progression-free survival (PFS), and overall survival (OS). From March 2012 to February 2015, 14 patients from seven different institutions were enrolled in the study, and 13 cases were evaluable for assessment. Eleven cases (84.6%) had distant metastases, and 8 cases (61.5%) had obstructive jaundice. There was no CR, 1 PR (7.7%), 11 SD (84.6%), and 1 progressive disease (PD) (7.7%). The RR was 7.7%, whereas the DCR was 92.3%. The median PFS was 3.1 months, the median OS was 6.2 months, and the one-year survival rate was 0%. Grade 3 hematologic toxicity was observed in three cases (23%), but all of them recovered upon drug withdrawal, and there was no treatment-related death. Although gemcitabine plus cisplatin has a high DCR (92.3%) and relatively low toxicity, the RR is less than 10%, and development of new therapies is desired for the treatment of unresectable GBC.

As endoscopic ultrasound-guided tissue acquisition techniques evolve, there is increasing interest in obtaining optimal histological samples to improve diagnostic accuracy. In this study, we aimed to assess the tissue acquisition success rate and test performance characteristics of a novel endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) system. We performed a retrospective review of consecutive patients undergoing EUS-guided tissue sampling of solid lesions using the SharkCore fine needle system in a tertiary referral facility. At least two passes were submitted for histology and diagnostic accuracy was evaluated. Comparison standard was based on final surgical pathology or minimum six-month clinical follow-up. Seventy-nine patients underwent 85 EUS-FNB procedures. Of the 85 histology specimens, 78 (91.7%) were adequate for diagnostic examination (includes six atypical/suspicious for adenocarcinoma). The sensitivity, specificity, and accuracy for diagnosis of malignancy with FNB were 87.1, 100, and 90.6%, respectively. Cytology was simultaneously sent in 43 cases with the same needle in addition to histology. Out of the 14 cases that were atypical/suspicious for adenocarcinoma or non-diagnostic on cytology, 11 cases (78.6%) achieved definite diagnoses on histology. The overall sensitivity, specificity, and accuracy for diagnosis of malignancy combining histology and cytology were 90.3, 100, and 92.9%, respectively. No complications were reported after the procedures. In this initial experience with a new EUS-guided FNB system, obtaining small cores to submit for histological analysis was safe, technically feasible, and highly accurate. Most of the histological cores obtained via FNB yielded a definite diagnosis including in cases with equivocal cytomorphology. Further study is required to confirm these findings.

Liver compartment syndrome is a life-threatening complication of hepatic subcapsular hematoma; diagnosis and assessment of treatment effects are therefore important. We report a rare case of liver compartment syndrome due to spontaneous hepatic subcapsular hematoma without any underlying conditions, in which Doppler ultrasonography (US) proved useful in both diagnosis and assessment of treatment effects. A 32-year-old woman experienced sudden epigastralgia and was diagnosed with hepatic subcapsular hematoma in the right lobe, based on contrast-enhanced computed tomography. Hepatic arteriography showed active hemorrhage and Doppler US showed retrograde flow in the right portal vein. From these findings, we diagnosed hepatic subcapsular hematoma complicated with liver compartment syndrome, and performed embolization of the bleeding point and percutaneous hematoma drainage. After these medical procedures, normalized antegrade flow in the right portal vein was observed on Doppler US. No underlying conditions contributing to hematoma were identified. In this case, Doppler US was useful for both diagnosis and assessment of treatment effects in liver compartment syndrome. When we examine patients with hepatic subcapsular hematoma, Doppler US should be used to diagnose the presence of liver compartment syndrome and assess treatment effects.

For successful treatment for nonalcoholic steatohepatitis (NASH), it may be important to treat the individual causative factors. At present, however, there is no established treatment for this disease. Branched-chain amino acids (BCAAs) have been used to treat patients with decompensated cirrhosis.In order to elucidate the mechanisms responsible for the effects of BCAAs on hepatic steatosis and disease progression, we investigated the effects of BCAA supplementation in mice fed a choline-deficient high-fat diet (CDHF), which induces NASH.Male mice were divided into four groups that received (1) choline-sufficient high fat (HF) diet (HF-control), (2) HF plus 2% BCAA in drinking water (HF-BCAA), (3) CDHF diet (CDHF-control), or (4) CDHF-BCAA for 8weeks. We monitored liver injury, hepatic steatosis and cholesterol, gene expression related to lipid metabolism, and hepatic fat accumulation.Serum alanine aminotransferase (ALT) levels and hepatic triglyceride (TG) were significantly elevated in CDHF-control relative to HF-control. Liver histopathology revealed severe steatosis, inflammation, and pericellular fibrosis in CDHF-control, confirming the NASH findings. Serum ALT levels and hepatic TG and lipid droplet areas were significantly lower in CDHF-BCAA than in CDHF-control. Gene expression and protein level of fatty acid synthase (FAS), which catalyzes the final step in fatty acid biosynthesis, was significantly decreased in CDHF-BCAA than in CDHF-control (P0.05). Moreover, hepatic total and free cholesterol of CDHF-BCAA was significantly lower than those of CDHF-control.BCAA can alleviate hepatic steatosis and liver injury associated with NASH by suppressing FAS gene expression and protein levels.

Aims Epstein-Barr virus-positive (EBV+) intestinal T/NK-cell lymphoma (ITNKL) is an uncommon tumour with an extremely aggressive clinical behavior. However, the clinicopathological characteristics of this tumour, including T-cell receptor (TCR) phenotype and the patient's background, remain unknown. The aim of this study was to elucidate the detailed clinicopathological profile of EBV+ ITNKL. Methods and results We enrolled 12 patients with EBV+ ITNKL without nasal involvement in the study. All patients were characterized by involvement of the small intestine, with concurrent lesions of the large intestine in 2 patients. Seven patients (58%) had Lugano stage IIE/IV disease, and 8 (67%) were categorized as high-intermediate/high-risk according to the Prognostic Index for PTCL (PIT). Three patients (25%) with an age of onset of less than 50 years had chronic active EBV infection (CAEBV). Five CD56-positive patients (42%) had a poorer prognosis than those without CD56 expression (P=0.008). NK-cell-type lymphoma defined by the absence of any TCR expression or clonal TCR-γ rearrangement was found in 6 patients (50%). Interestingly, EBV+ intraepithelial lymphocytosis was observed in one case with a background of CAEBV. Conclusions This study is the first to shed light on the significant heterogeneity of EBV+ ITNKL and its relationship with CAEBV, especially in patients younger than 50 years of age. These observations will provide a guide for diagnostic and therapeutic approaches in routine practice. This article is protected by copyright. All rights reserved.

AIM To evaluate the feasibility of chemotherapy including fluoropyrimidine, platinum and taxane with modified dosages for unresectable gastric cancer in Japanese patients. METHODS We performed a feasibility study of a modified docetaxel, cisplatin and capecitabine (DCX) regimen for stage IV gastric cancer. In particular, 30 or 40 mg/m2 of docetaxel on day 1, 60 mg/m2 of cisplatin on day 1, and 2000 mg/m2 of capecitabine for 2 wk were administered every three weeks. RESULTS Three patients were treated with modified DCX (mDCX) with 30 mg/m2 docetaxel, and five patients were treated with this regimen with 40 mg/m2 docetaxel. Grade 3 or 4 neutropenia was observed in six of the eight patients; no patients exhibited febrile neutropenia. Partial response was achieved in four of the eight patients. Three patients underwent gastrectomy, which achieved R0 resection without residual tumors in dissected lymph nodes. In one of these three patients, resected specimens revealed pathological complete response in the primary lesion and in lymph nodes. CONCLUSION mDCX was well tolerated by Japanese patients with stage IV gastric cancer. This regimen might be useful for allowing gastric cancer patients with distant lymph node metastasis to undergo conversion surgery.

Background and Aims: Cloning of ATP7B provided evidence that Wilson’s disease is a hepatic copper toxicosis with a variety of extrahepatic complications. Affected siblings with the same genetic background and exposure to similar environmental factors may be a good model for the study of genotype-phenotype correlation. Methods: Twenty-three affected siblings in 11 families were selected from a database. The first phenotypes were determined according to the international proposal. The final types of chronic organ damage were re-evaluated for life-long management. Results: Phenotypes were identical in 5 of the families and different in 6 of the families. The acute hepatic phenotype H1 was found in 3 younger siblings and 1 older sibling. All survived an acute episode of hemolysis with underlying chronic liver disease. One also presented complication with neurological disease. The neurological phenotype N1 with neuropsychiatric symptoms and hepatic disease was found in 2 aged siblings of 1 family, in an older sibling in 3 families and in the oldest sibling in 1 family. Phenotypes in siblings were mainly split by either H1 occurring in random order or age-dependent N1. Types of chronic organ damage were identical in 8 of the families and different in 3 of the families. The same combination of chronic liver disease was found in 6 families and chronic liver disease complicated with neurological disease in 2 families. Split organ damage in siblings was found when an older sibling was complicated by neurological disease. There was no reverse combination of a younger sibling being complicated by neurological disease in any of the families. Conclusion: Phenotype combinations of siblings were mainly modified by externally-induced hemolytic episodes, while chronic organ damage in siblings was split by age-dependent neurological complications.

We report a case of a 70-year-old man who presented with abdominal pain and weight loss, with initial imaging showing simultaneous mass lesions in the pancreas and lungs along with extensive lymphadenopathy in the thorax up to the left supraclavicular region. Core biopsies of the left supraclavicular lymph node showed squamous cell carcinoma, which required differentiation between secondary and primary pancreatic neoplasms. Endoscopic ultrasound-guided sampling using a novel fine needle biopsy system was key to making a definite histological diagnosis and determining the best treatment plan.

Background and study aims Diagnosis of Meckel’s diverticulum (MD) before surgery may be challenging; double-balloon endoscopy (DBE) facilitates identification of MD in the setting of a gastrointestinal bleeding; however, MD can be found incidentally without this condition. The purpose of this research was to determine specific characteristic of hemorrhagic MD and incidental MD at DBE. Patients and methods Ectopic gastric mucosa enclosed in the MD and/or ulceration were defined as “major findings”; ring-like scar surrounding the MD was defined as “minor finding”. We retrospectively reviewed the medical records of patients affected by MD and analyzed the findings that significantly affected the characterization of MD. Results MD was diagnosed in 33 patients. The axis of the diverticulum was longer in hemorrhagic MD compared to incidental MD (P = 0.031). The amount of transfusion was significantly higher (P = 0.018) in the hemorrhagic MD group. Hemorrhagic MD was significantly more correlated with major findings (P = 0.01) and minor findings (P Conclusions The combination of major and minor findings appears to improve the diagnostic ability of hemorrhagic MD avoiding unnecessary diverticulectomy.