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Capsule endoscopy (CE) has been shown to have poor diagnostic performance when the capsule passes quickly through the small bowel, especially the proximal jejunum. This study aimed to evaluate the diagnostic yield of proximal jejunal lesions with third-generation CE technology.We retrospectively examined 138 consecutive patients, 76 (55.0%) of whom were men. The patients' median age was 70 years, and proximal jejunal lesions were detected by CE and/or double-balloon endoscopy at Hiroshima University Hospital between January 2011 and June 2021. We analyzed the diagnostic accuracy of CE for proximal jejunal lesions and compared the characteristics of the discrepancy between the use of CE and double-balloon endoscopy with Pillcam SB 2 (SB2) and Pillcam SB 3 (SB3).SB2 and SB3 were used in 48 (35%) and 90 (65%) patients, respectively. There was no difference in baseline characteristics between these groups. Small-bowel lesions in the proximal jejunum comprised 75 tumors (54%), 50 vascular lesions (36%), and 13 inflammatory lesions (9%). The diagnostic rate was significantly higher in the SB3 group than in the SB2 group for tumors (91% vs. 72%,SB3 use improved the detection of proximal jejunal tumors and vascular lesions compared with SB2 use.

Background and Aim Gastric antral vascular ectasia (GAVE) causes gastrointestinal bleeding. The initial treatment for GAVE bleeding is endoscopic hemostasis, and currently, the most performed technique to achieve hemostasis is argon plasma coagulation (APC). However, APC is associated with a high recurrence rate. To overcome this limitation, we examined the outcomes of the combination therapy of APC and polidocanol injection (PDI) for treating GAVE. Methods We retrospectively analyzed the outcomes of 15 consecutive GAVE patients treated with PDI + APC at Hiroshima University Hospital between November 2011 and September 2019 with respect to clinical characteristics, hemostatic efficacy, complications related to treatment, and recurrence rate. Results The mean age of patients (4 men and 11 women) was 74 ± 8.4 years. Patients had comorbidities of liver cirrhosis (seven patients, 47%), chronic renal failure (seven patients, 47%), and autoimmune diseases (seven patients, 47%). Endoscopic hemostasis with PDI + APC was performed in all patients (n = 15). The mean number of PDIs attempted to stop bleeding was 1.5 ± 0.8 (1–4), and the mean number of APCs attempted was 2.1 ± 1.2 (1–5). Complications related to treatment occurred in two patients (14%): ulceration in one patient and hematoma in another patient, both of whom were treated conservatively. Two patients (13%) had recurrences during the follow‐up period (average period, 42 months). Both were cured with additional treatment of PDI only. Conclusion The combination therapy of PDI and APC is effective for GAVE with a low recurrence rate., Argon plasma coagulation (APC) is effective for gastric antral vascular ectasia (GAVE) bleeding; however, the high recurrence rate is a problem. GAVE is a condition in which dilatation and proliferation of blood vessels are observed not only in the mucosal layer but also in the submucosal layer, and the high recurrence rate is considered to be because APC only treats vessels in the mucosal layer. We have traditionally treated the mucosal layer with APC and submucosal layer with polidocanol injection (PDI), and this combination therapy with PDI + APC for GAVE has a high hemostatic rate and low recurrence rate based on long‐term prognosis.

A novel large neutral amino acid transporter 1 (LAT1)-specific inhibitor, JPH203, is expected to cause cancer-specific starvation and possess anti-tumor effects; however, its anti-tumor mechanism for colorectal cancer (CRC) remains unclear. We analyzed LAT family gene expressions in public databases using UCSC Xena and evaluated LAT1 protein expression using immunohistochemistry in 154 cases of surgically resected CRC. We also evaluated mRNA expression using polymerase chain reaction in 10 CRC cell lines. Furthermore, JPH203 treatment experiments were conducted in vitro and in vivo using an allogeneic immune-responsive mouse model with abundant stroma created via the orthotopic transplantation of the mouse-derived CRC cell line CT26 and mesenchymal stem cells. The treatment experiments were followed by comprehensive gene expression analyses with RNA sequencing. Database analyses and immunohistochemistry research on clinical specimens revealed that LAT1 expression was cancer-dominant, and its increase was accompanied by tumor progression. In vitro, JPH203 was effective in an LAT1 expression-dependent manner. In vivo, JPH203 treatment considerably reduced tumor size and metastasis, and RNA sequencing-based pathway analysis showed that not only tumor growth and amino acid metabolism pathways, but also stromal activation-related pathways were suppressed. The results of the RNA sequencing were validated in the clinical specimens, as well as both in vitro and in vivo. LAT1 expression in CRC plays an important role in tumor progression. JPH203 may inhibit the progression of CRC and tumor stromal activity.

Although radiotherapy is the standard treatment for Helicobacter pylori (Hp)-negative gastric mucosa-associated lymphoid tissue (MALT) lymphoma, eradication therapy using antibiotics and an acid secretion suppressor can sometimes induce complete remission. We explored predictive markers for the response to eradication therapy for gastric MALT lymphoma that were negative for both API2-MALT1 and Hp infection using comprehensive RNA sequence analysis. Among 164 gastric MALT lymphoma patients who underwent eradication therapy as primary treatment, 36 were negative for both the API2-MALT1 fusion gene and Hp infection. Based on eradication therapy efficacy, two groups were established: complete response (CR) and no change (NC). The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that cancer-related genes and infection-related genes were highly expressed in the NC and CR groups, respectively. Based on this finding and transcription factor, gene ontology enrichment, and protein–protein interaction analyses, we selected 16 candidate genes for predicting eradication therapy efficacy. Real-time PCR validation in 36 Hp-negative patients showed significantly higher expression of olfactomedin-4 (OLFM4) and the Nanog homeobox (NANOG) in the CR and NC groups, respectively. OLFM4 and NANOG could be positive and negative predictive markers, respectively, for eradication therapy efficacy against gastric MALT lymphoma that is negative for both API2-MALT1 and Hp infection.

Objective The Chicago classification using high-resolution manometry (HRM) has been proposed for the diagnosis of esophageal motility disorders. However, HRM is expensive, and few patients are likely to benefit from this method. We established a method using a raised infusion catheter called "esophageal manometry using a trans-nasal endoscope". In this study, we examined the clinical utility of this new method for the assessment of patients with dysphagia. Methods We enrolled 124 consecutive patients who complained of dysphagia and were suspected of having esophageal motility disorders. Patients underwent manometry using a trans-nasal endoscope at Hiroshima University Hospital from September 2008 to December 2018. An esophageal biopsy was performed during the procedure from the thoracic esophagus to detect eosinophilic esophagitis. In addition, we examined the clinical courses of patients diagnosed with achalasia. Results The diagnostic ability of manometry using a trans-nasal endoscope was 98%, and no major complications associated with the procedure were recorded. About 30% of patients were diagnosed with achalasia, and most (77%) were well controlled by medications or balloon dilation. One patient was diagnosed with eosinophilic esophagitis. Conclusion Manometry using a trans-nasal endoscope is beneficial and can be used for the clinical management of patients with dysphagia.

The presence of post-endoscopic submucosal dissection (ESD) scars renders complete metachronous superficial esophageal squamous cell carcinoma resection difficult. We aimed to identify the risk factors for incomplete resection of metachronous esophageal squamous cell carcinoma close to the post-ESD scar by ESD.We enrolled patients who developed post-ESD superficial esophageal squamous cell carcinoma at Hiroshima University Hospital between January 2006 and March 2020. We analyzed the outcomes and risk factors of incomplete resection between patients whose lesions were close to (close-to group) and away from (away-from group) the post-ESD scar.We included 111 patients with 212 lesions. The close-to group had a significantly lower complete resection rate (88.6% [62/70] vs. 98.6% [69/70], p = 0.033), longer procedure time (80.2 ± 47.2 min vs. 60.4 ± 29.3 min, p 0.01), higher proportion of lesions with severe fibrosis (72.9% [51/70] vs. 5.7% [4/70], p 0.01), and higher intraoperative bleeding rate (78.6% [55/70] vs. 60.0% [42/70], p = 0.027) than the away-from group. There was no significant difference in the rate of local recurrence, muscle injury, perforation, and stenosis as well as the pathological tumor depth between the groups. Of the 92 lesions in the close-to group, the proportion of lesions located on the oral side of the post-ESD scar significantly affected the incidence of incomplete resection (91.7% [11/12] vs. 53.8% [43/80], p = 0.013).Complete resection was more difficult for lesions located on the oral side of the post-ESD scar.

In this study, we investigated the in vivo metastasis suppression effects of the platelet-derived growth factor receptor inhibitor dasatinib, which targets cancer-associated fibroblasts (CAFs), in combination with an anti-programmed cell death-1 (PD-1) antibody. We classified clinical CRC cases as inflamed, excluded, or desert using immunohistochemical analysis and evaluated the tumor stroma. The excluded type was the most common, and cases with high-volume stroma in the primary lesions also had a high stromal volume in the liver metastatic lesions. Liver-metastasis mouse models with different stromal volumes were established and treatment-induced changes in the tumor immune microenvironment were evaluated. The anti-PD-1 antibody alone exhibited a therapeutic effect for the liver metastases with low stromal volumes but not for the liver metastases with high stromal volumes. In contrast, antitumor effects were observed with anti-PD-1 antibody/dasatinib combination therapy even in the liver metastases with high stromal volumes. Combination therapy reduced the stromal volume, promoted immune cell infiltration, induced antitumor cytotoxic T-cell responses, activated antitumor immunity, and promoted tumor regression. These results suggest that CAFs play an important role in the immune evasion of CRC and that anti-PD-1 antibody/dasatinib combination therapy has potential as a treatment option for patients with metastatic CRC for whom immunotherapy alone is ineffective.

Objective Systemic sclerosis (SSc) is defined as an autoimmune disease presenting with fibrosis of various organs and vascular endothelial damage. Vascular lesions, including small-bowel angioectasias, are also frequently detected in SSc patients. Polidocanol injection (PDI) is a safe and effective hemostatic treatment for gastrointestinal bleeding. We evaluated the outcomes of PDI for small-bowel angioectasia in SSc patients. Methods We retrospectively evaluated 65 consecutive SSc patients (61 women; mean age, 64.3 years old) who underwent capsule endoscopy (CE) and/or double-balloon endoscopy at Hiroshima University Hospital between April 2012 and December 2019. Patients Patients were stratified according to the presence of small-bowel angioectasia. Among patients who underwent CE during the same period, those with small-bowel angioectasia without concomitant diseases were compared with SSc patients with small-bowel angioectasia. Clinical and endoscopic characteristics, treatment outcomes, and the incidence of metachronous small-bowel angioectasia after PDI were evaluated. Results SSc patients with small-bowel angioectasia exhibited significantly lower hemoglobin levels and a significantly higher incidence of skin telangiectasia than those without small-bowel angioectasia. On a multivariate analysis of the presence of small-bowel angioectasia, anemia and skin telangiectasia were significant independent factors. SSc patients with small-bowel angioectasia included a higher proportion of women and exhibited a significantly higher incidence of metachronous small-bowel angioectasia than X [please define X]. The characteristics of small-bowel angioectasia and outcomes of PDI were not significantly different between the two groups. No post-treatment rebleeding cases or adverse events were noted. Conclusion CE should be performed for SSc patients with anemia and/or skin telangiectasia. PDI is effective for SSc patients with small-bowel angioectasia.

BACKGROUND AND AIM The typical histology of Helicobacter pylori-uninfected gastric cancer is signet ring cell carcinoma (SRCC) localized in the mucosal layer, but the potential of these SRCCs to invade the submucosal layer is unclear. This study aimed to investigate the clinicopathological characteristics of SRCC in H. pylori-uninfected patient and its prevalence in diffuse-type gastric cancer (DGC) within Japan. METHODS We enrolled consecutive pure DGC patients diagnosed with the disease either localized in the mucosal layer or with submucosal invasion. H. pylori infection was investigated, and the patients were divided into three groups according to histological types: pure SRCC, SRCC with poorly differentiated adenocarcinoma (PDA), and pure PDA. RESULTS Of the 345 pure DGC patients, 132 (38%), 127 (37%), and 86 (25%) had pure SRCC, SRCC with PDA, and pure PDA histologies, respectively. The prevalence of H. pylori infection and the SM ratio were significantly lower in the pure SRCC group than other groups (P

BACKGROUND AND AIM To examine the effect on recurrence and survival of treatment by interferon (IFN)-free direct-acting antivirals (DAA) for patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) who underwent primary curative treatment. METHODS This was a retrospective cohort study of 250 patients with HCV who had received curative treatment for primary HCC. As anti-HCV treatment after HCC treatment, 38 patients received IFN-free DAA therapy (DAA patients) and 94 received IFN-based therapy (IFN patients). The recurrence of HCC and overall survival of the patient groups were compared in a case-control study. RESULTS The cumulative HCC recurrence rates at 1, 3, and 5 years were 5%, 39%, and 39% for DAA patients and 0%, 46%, and 62% for IFN patients, respectively (P = 0.370). Multivariate analysis of the HCC recurrence identified treatment responses (sustained virological response [SVR]: hazard ratio [HR] 2.237; P = 0.003) as an independent predictive factor. The cumulative overall survival rates at 3 and 5 years were 96%, 96% for DAA patients and 93%, 73% for IFN patients, respectively ( P = 0.163). Multivariate analysis identified treatment responses (SVR: HR 8.742; P

Background Although pegylated interferon (PEG-IFN) and nucleotide/nucleoside analogue (NA) combination therapy is considered to be optimal for accelerating serum hepatitis B surface antigen (HBsAg) reduction, the effect is limited, and the best approach to PEG-IFN treatment for chronic hepatitis B patients during long-term NA therapy has yet to be determined. Methods A total of 21 hepatitis B e antigen-negative chronic hepatitis B patients whose HBV DNA levels were suppressed to undetectable levels by NA therapy were administrated PEG-IFN-α2a for 48 weeks (sequential therapy: 10, add-on therapy: 11). Factors associated with HBsAg reduction by PEG-IFN therapy were analysed. Results During PEG-IFN treatment, HBsAg levels were reduced by 0.48 log IU/ml. More than 1 log IU/ml of HBsAg reduction was observed in eight patients (sequential therapy: six, add-on therapy: two), and one patient with sequential therapy achieved HBsAg loss. By univariate analysis, sequential therapy was marginally associated with more than 1 log IU/ml HBsAg reduction during PEG-IFN treatment ( P=0.060). After PEG-IFN treatment, only five patients, including the patient with HBsAg loss, achieved more than 0.5 log IU/ml of HBsAg reduction by 1 year after PEG-IFN treatment. By univariate analysis, sequential therapy was significantly associated with HBsAg reduction after PEG-IFN treatment ( P=0.012). In addition, alanine aminotransferase elevation during PEG-IFN therapy and lower serum interleukin-8 level at the end of PEG-IFN treatment were also significantly associated with HBsAg reduction by 1 year after PEG-IFN treatment ( P=0.038, P=0.044, respectively). Conclusions Sequential therapy may be superior to addon therapy in reducing HBsAg levels during long-term NA therapy in chronic hepatitis B patients.

Background: The efficacy of second-generation PillCam ­COLON2 capsule endoscopy (CCE2) in detecting colorectal superficial lesions remains unclear. Objective: We sought to determine the diagnostic yield of CCE2 in the detection of colorectal superficial lesions. Methods: We performed CCE2 in 60 consecutive patients between April 2011 and ­December 2017. Lesions ≥6 mm in size were detected in 34 patients (25 males, average age: 60.5 years). We performed endoscopic resection and histopathological analysis of all resected lesions within 3 months after CCE2. We considered the optical colonoscopy (OC) findings as the gold standard and evaluated CCE2 sensitivity. Results: Sixty-seven lesions (≥6 mm) were detected via OC, with 27 colorectal superficial lesions and 40 protruded lesions. CCE2 sensitivity for ≥6-mm-sized, superficial, and protruded lesions was 84, 78, and 88%, respectively. No significant intergroup differences were observed. CCE2 false-negative colorectal superficial lesions accounted for 31% of right-sided colon lesions and 50% of sessile serrated adenomas/polyps (SSA/Ps). The CCE2 false-negative protruded lesions accounted for 17% of right-sided colon lesions. Conclusion: CCE2 sensitivities for colorectal superficial and protruded lesions were not significantly different. However, flat-type SSA/Ps in the right colon, especially when the transit time is fast, have a risk of demonstrating CCE2 false-negative results.

The clinical course and responsiveness to antiviral treatments differs among hepatitis B virus (HBV) genotypes. However, the cause of these differences is unclear. In the present study, we compared mRNA expression profiles in human hepatocyte chimeric mice infected with HBV genotypes A and C. Fifteen chimeric mice were prepared and divided into the following three groups: uninfected control mice, HBV genotype A-infected mice, and HBV genotype C-infected mice. Human hepatocytes were collected from these mouse livers and gene expression analyses were performed using next-generation RNA sequencing. Although similar pathways were influenced by HBV infection, including inflammation mediated by chemokine and cytokine signaling, p53, and integrin signaling pathways, expression levels of up-regulated genes by HBV genotype A or C infection were quite different. In HBV genotype A-infected hepatocytes, 172 genes, including KRT23 and C10orf54, were significantly more highly expressed than in HBV genotype C-infected cells, whereas 10 genes, including SPX and IER3, were expressed at significantly lower levels. Genes associated with the p53 pathway and the inflammation mediated by chemokine and cytokine signaling pathway were more highly expressed in cells with HBV genotype A infection, whereas genes associated with CCKR signaling map and oxidative stress response were more highly expressed in cells with HBV genotype C infection. Several differences in gene expression with respect to HBV genotype A and C infection were detected in human hepatocytes. These differences might be associated with genotypic difference in the clinical course or responsiveness to treatment.

We report a case of an 86-year-old Japanese woman diagnosed with a food-induced ileus whose condition improved by aspiration with the overtube of a balloon endoscopy. She had undergone a total gastrectomy for gastric cancer and reconstruction by Roux-en Y anastomosis and jejunum pouch 17 years earlier. She complained of constipation and loss of appetite lasting more than 1 wk before admission. Her left abdomen showed gradual fullness, and tenderness was also found at the same site. Contrast computed tomography (CT) of the abdomen showed that the jejunal pouch lumenwas markedly expanded by food residue and was pressed into the intestinal tract of the small intestine. Gastrointestinal endoscopy revealed that the food residue was fluid and flowed back up into the esophagus, and the jejunum pouch was filled with food residue. As the patient was elderly, we attempted to aspirate the food residue with the overtube of a balloon endoscopy device. Food-induced ileus has been improved by surgery in the past; however, in determining treatment for ileus it is always necessary to consider the individual patients’ conditions, including the gastrointestinal contents.