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The preS1 region of the large hepatitis B virus (HBV) surface protein is a crucial component in HBV infection; however, its impact on the development of hepatocellular carcinoma (HCC) remains unknown. This study investigated the relationship between serum preS1 levels and hepatocarcinogenesis in patients with chronic hepatitis B (CHB). The preS1 levels were measured in 531 patients with CHB without a history of HCC. Among the patients, 293 HBV carriers who had never received nucleotide/nucleoside analog (NA) therapy had their preS1 levels measured at their first visit (non-NA group), and 238 patients who had received NA therapy had their preS1 levels measured at the start of NA administration (NA group). The two groups had no significant differences in hepatitis B surface antigen (HBsAg) levels; however, the NA group’s preS1/HBsAg ratio was significantly higher. The preS1/HBsAg ratio was significantly different between patients with CHB not meeting the NA treatment criteria and patients with chronic hepatitis and cirrhosis who were eligible for NA treatment. The predictors of HCC development were analyzed, and the preS1/HBsAg ratio was identified in both groups. The preS1/HBsAg ratio could predict hepatocarcinogenesis in patients with CHB with or without NA administration.

Abstract Background Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. Methods This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23–87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. Results Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P

To clarify the risk factors for the aggravation of esophagogastric varices (EGVs) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGVs were aggravated in 42 (25%) patients despite SVR. The cumulative 1-, 3-, 5-, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified a platelet count < 11.0 × 104/μL, LSM ≥ 18.0 kPa, total bile acid ≥ 33.0 μmol/L, and a diameter of left gastric vein (LGV) ≥ 5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that met all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGVs tend to worsen as two or more of these risk factors increase.

Introduction: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is frequently associated with various gastrointestinal symptoms, including abdominal pain, vomiting, and diarrhea. Moreover, several cases of refractory diarrhea have been reported after COVID-19 recovery. Herein, we present a case of severe refractory diarrhea associated with COVID-19. Case Presentation: A 50-year-old man with no comorbidities was admitted to our hospital with SARS-CoV-2 pneumonia. His respiratory status deteriorated, and ventilatory management, including extracorporeal membrane oxygenation, was needed. The patient’s respiratory condition improved, resulting in a transfer to another hospital for rehabilitation. However, the patient developed diarrhea that worsened to 6,000–7,000 mL/day, and he was transferred to our hospital. We diagnosed the patient with enterocolitis caused by cytomegalovirus infection and treated him with ganciclovir on day 5 after transfer to our hospital. The diarrhea did not improve. We suspected enterocolitis associated with COVID-19 and administered a methylprednisolone pulse (intravenous injection, 1,000 mg/day for 3 days) on day 10 after transfer, resulting in a marked improvement in his symptoms. The prednisolone dose was tapered, and no recurrence of diarrhea was observed thereafter. Conclusion: The prevalence of COVID-19-associated enterocolitis is low, and the pathogenesis of the disease remains unclear. Prednisolone administration should be considered in cases of post-COVID-19 symptoms of severe diarrhea due to a possible abnormal immune response related to COVID-19.

Recent studies indicate that treatment of chronic hepatitis D virus (HDV) with either pegylated interferon (IFN)λ or pegylated IFNα monotherapy leads to a dramatic decline in HDV RNA. Herein, we investigated the innate antiviral efficacy of IFNλ and IFNα in humanized mice that lack an adaptive immune response. Humanized mice were either co-infected with hepatitis B virus (HBV) and HDV simultaneously, or HDV infection was performed subsequent to HBV infection (i.e., superinfected). After steady viral replication was achieved, mice received either IFNλ (n = 6) or IFNα (n = 7) for 12 (or 13) weeks. Pretreatment median levels of serum HBV DNA (8.8 [IQR:0.2] log IU/ml), HDV RNA (9.8 [0.5] log IU/ml), HBsAg (4.0 [0.4] log IU/ml) and human albumin, hAlb (6.9 [0.1] log ng/mL) were similar between mice treated with IFNα or IFNλ and between those coinfected versus superinfected. Compared to mice treated with IFNλ, mice treated with IFNα had a significantly greater decline in HBV, HDV, and HBsAg levels. In conclusion, IFNα induces stronger inhibition of HBV and HDV than IFNλ in humanized mice that lack an adaptive immune response. Further studies are needed to assess the respective role of the combined innate-and adaptive-immune systems in the treatment of HBV and HDV with IFNα and IFNλ.

BackgroundAdditional surgery with lymph node (LN) dissection is recommended for pT1 colorectal carcinoma (CRC) resected by endoscopy, based on pathological risk factors for LN metastasis (LNM), according to guidelines by the Japanese Society for Cancer of the Colon and Rectum (JSCCR), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO).MethodsWe retrospectively analyzed 560 consecutive patients with T1 CRC who underwent endoscopic resection alone (n=190) or initial or additional surgery with LN dissection (n=370) between 1992 and 2017 at Hiroshima University Hospital. Patients were classified into LNM low- and high-risk groups according to guidelines by the JSCCR, NCCN, and ESMO as follows. Patients without any specified pathological LNM risk factor were included in the LNM low-risk group, while the high-risk group comprised all other patients. We analyzed the LNM predictive ability of each guideline.ResultsThe LNM high-risk rate, sensitivity, specificity, positive and negative predictive values, accuracy of LNM risk, and AUC for LNM predictive ability were 82%, 100%, 19%, 9%, 100%, 26% and 0.596 in the JSCCR guidelines; 52%, 98%, 52%, 15%, 99%, 56%, and 0.749 in the NCCN; and 54%, 98%, 50%, 15%, 99%, 54%, and 0.743 in the ESMO, respectively.ConclusionsThe JSCCR guidelines could diagnose LNM in all cases but had the highest false-positive rate. It is important to reduce unnecessary additional surgeries for pT1 CRCs after ER.

Introduction: Familial adenomatous polyposis (FAP), a hereditary disorder of the gastrointestinal tract, is an autosomal dominant inherited condition caused by germline mutations in the adenomatous polyposis coli (APC) gene. It is characterized by the development of hundreds to thousands of colorectal adenomatous polyps, which, if left untreated, can eventually develop into colorectal carcinomas. Representative extracolonic tumors in FAP include multiple duodenal adenomas and desmoid tumors. Moreover, multiple fundic gland polyps are frequently identified in the stomachs of patients with FAP. Case Presentation: Herein, we report the two cases. A 52-year-old woman who underwent total colectomy for FAP, and pancreatoduodenectomy was initiated on esomeprazole for the treatment of anastomotic erosion. Esophagogastroduodenoscopy performed 42 months later showed an increased number and size of gastric fundic gland polyps, which subsequently decreased after replacing esomeprazole with ranitidine. Similarly, a 39-year-old woman with FAP was initiated on vonoprazan for the treatment of reflux symptoms. Esophagogastroduodenoscopy and colonoscopy performed 14 months later indicated an increase in the number of gastric fundic gland polyps and colorectal polyps, which subsequently decreased after vonoprazan discontinuation. In these two cases, the increase and decrease in the number and size of fundic gland polyps and colon adenoma were associated with serum gastrin levels. Conclusion: Gastric fundic gland polyps and colon polyps may rapidly increase in number and size due to increased gastrin levels induced by proton pump inhibitor/potassium-competitive acid blocker use. Hence, these drugs should be prescribed with caution.

Abstract Background The validity of endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma (ESCC) in older individuals with comorbidities remains unclear. Therefore, this study evaluated the safety and efficacy of ESD and additional treatment for ESCC in older adult patients. Methods The clinicopathological characteristics and clinical outcomes of 398 consecutive older adult patients (≥ 65 years) with 505 lesions who underwent ESD for ESCC at the Hiroshima University Hospital between September 2007 and December 2019 were retrospectively evaluated. Additionally, the prognoses of 381 patients who were followed up for > 3 years were assessed. Results The mean patient age and procedure time were 73.1 ± 5.8 years and 77.1 ± 43.5 min, respectively. The histological en bloc resection rate was 98% (496/505). Postoperative stenosis, perforation, pneumonia, and delayed bleeding were conservatively treated in 82 (16%), 19 (4%), 15 (3%), and 5 (1%) patients, respectively. The 5-year overall and disease-specific survival rates were 78.9% and 98.0%, respectively (mean follow-up time: 71.1 ± 37.3 months). Multivariate analysis showed that age and the American Society of Anesthesiologists classification of physical status class ≥III (hazard ratio: 1.27; 95% confidence interval: 1.01–1.59, p = 0.0392) were independently associated with overall survival. A significantly lower overall survival rate was observed in the high-risk follow-up group than in the low-risk follow-up and high-risk additional treatment groups (p

Abstract Accurate 3D shape measurement is crucial for surgical support and alignment in robotic surgery systems. Stereo cameras in laparoscopes offer a potential solution; however, their accuracy in stereo image matching diminishes when the target image has few textures. Although stereo matching with deep learning has gained significant attention, supervised learning requires a large dataset of images with depth annotations, which are scarce for laparoscopes. Thus, there is a strong demand to explore alternative methods for depth reconstruction or annotation for laparoscopes. Active stereo techniques are a promising approach for achieving 3D reconstruction without textures. In this study, a 3D shape reconstruction method is proposed using an ultra‐small patterned projector attached to a laparoscopic arm to address these issues. The pattern projector emits a structured light with a grid‐like pattern that features node‐wise modulation for positional encoding. To scan the target object, multiple images are taken while the projector is in motion, and the relative poses of the projector and a camera are auto‐calibrated using a differential rendering technique. In the experiment, the proposed method is evaluated by performing 3D reconstruction using images obtained from a surgical robot and comparing the results with a ground‐truth shape obtained from X‐ray CT.

Abstract This study investigated whether the progression of liver fibrosis affects the prevalence of sarcopenia and incidence of decreased gait speed in older patients with chronic liver disease (CLD). Patients with CLD aged ≥ 60 years were classified into low, intermediate, and high fibrosis 4 (FIB-4) index groups according to the degree of liver fibrosis. The prevalence of sarcopenia and incidence of decreased gait speed (

Abstract We developed a fatty liver mouse model using human hepatocyte chimeric mice. As transplanted human hepatocytes do not respond to mouse growth hormone (GH) and tend to accumulate fat, we hypothesized that addition of human GH would alter lipid metabolism and reduce accumulation of fat in the liver even when fed a high-fat diet. Six uPA/SCID chimeric mice were fed a high-fat GAN diet to induce fatty liver while six were fed a normal CRF1 diet, and GH was administered to three mice in each group. The mice were euthanized at 8 weeks, and human hepatocytes were extracted for RNA-Seq, DIA proteomics, and metabolomics analysis. Abdominal echocardiography revealed that the degree of fatty liver increased significantly in mice fed GAN diet (p

Abstract Background Endoscopic resection is widely accepted as a local treatment for rectal neuroendocrine tumors sized ≤ 10 mm. However, there is no consensus on the best method for the endoscopic resection of rectal neuroendocrine tumors. As a simplified endoscopic procedure, endoscopic submucosal resection with a ligation device (ESMR-L) indicates a histologically complete resection rate comparable to that of endoscopic submucosal dissection (ESD). We hypothesized that ESMR-L than ESD would be preferred for rectal neuroendocrine tumors. Hence, this trial aimed to verify whether ESMR-L is non-inferior to ESD in terms of histologically complete resection rate. Methods This is a prospective, open-label, multicenter, non-inferiority, randomized controlled trial of two parallel groups, conducted at the Shizuoka Cancer Center and 31 other institutions in Japan. Patients with a lesion endoscopically diagnosed as a rectal neuroendocrine tumor ≤ 10 mm are eligible for inclusion. A total of 266 patients will be recruited and randomized to undergo either ESD or ESMR-L. The primary endpoint is the rate of en bloc resection with histologically tumor-free margins (R0 resection). Secondary endpoints include en bloc resection rate, procedure time, adverse events, hospitalization days, total devices and agents cost, adverse event rate between groups with and without resection site closure, outcomes between expert and non-expert endoscopists, and factors associated with R0 resection failure. The sample size is determined based on the assumption that the R0 resection rate will be 95.2% in the ESD group and 95.3% in the ESMR-L group, with a non-inferiority margin of 8%. With a one-sided significance level of 0.05 and a power of 80%, 226 participants are required. Assuming a dropout rate of 15%, 266 patients will be included in this study. Discussion This is the first multicenter randomized controlled trial comparing ESD and ESMR-L for the R0 resection of rectal neuroendocrine tumors ≤ 10 mm. This will provide valuable information for standardizing endoscopic resection methods for rectal neuroendocrine tumors. Trial registration Japan Registry of Clinical Trials, jRCTs042210124. Registered on Jan 6, 2022.

Abstract Background/Aims Chronic constipation (CC) is one of the most common gastrointestinal disorders in the general population. Although there are many treatment options, achieving a stable treatment for CC remains one of the challenges in clinical practice. This study aimed to evaluate the clinical factors associated with stable treatment for CC in Japanese patients. Methods A retrospective, cross-sectional, and multicenter study was carried out. Patients were eligible for inclusion if they fulfilled the Rome IV criteria for diagnosing CC and had been treated for at least one and a half years. Patients with up to two prescription modifications for CC in one year were defined as the stable treatment group, whereas those with three or more prescription changes were defined as the unstable treatment group. Univariate and multivariate analyses were carried out to identify factors associated with CC. Results A total of 114 patients have been recruited. There were 82 patients (77.0%) in the stable treatment group and 32 patients (23.0%) in the unstable treatment group. Based on multivariate likelihood analysis, only using acid-suppressive drugs contributed to stability treatment in CC patients (odds ratio: 2.81, 95% confidence interval: 1.12–7.08, p = 0.03). Conclusion Administration of acid-suppressive drugs was the only factor related to the stability of CC treatment. Further studies are needed to validate the results as well as clarify the causes.

Objectives: Bowel preparation is burdensome because of long cleansing times and large dose volumes of conventional polyethylene glycol (PEG) lavage solution NiflecⓇ (Nif). MoviPrep (Mov)Ⓡ is a hyperosmolar preparation of PEG, electrolytes, and ascorbic acid; despite the smaller dose volume of 2 L, it can be challenging for many patients. We examined a more effective and acceptable bowel preparation method without compromising cleanliness and effectiveness, combining low-residue diet and laxative (Modified Brown Method) in Mov administered 1 day pre-colonoscopy. Methods: This multicenter, randomized, open-label, parallel-group comparative study, conducted at Hiroshima University Hospital and 7 affiliated hospitals in May 2015-March 2016, evaluated adherence to and effectiveness of Mov in bowel preparation. Participants (n=380) were allocated to receive 1 of 3 pre-colonoscopy regimens: Nif+Modified Brown Method (Group A), Mov+Modified Brown Method (Group B), or Mov+Laxative (Group C). Results: Total intake volume showed no significant difference among the groups. Bowel preparation time was significantly shorter in Group B (112.4±44.8 min, n=118) than in Groups A (131.3±59 min, n=105) and C (122.6±48.1 min, n=115). Sleep disturbance (37%) was significantly higher in Group B than Group A; distension (11%) was significantly lower in Group C than in Groups A and B (p

Abstract Background Methods to prevent esophageal stenosis (ES) after endoscopic submucosal dissection (ESD) for superficial esophageal squamous cell carcinoma (ESCC) have received increasing attention. Although steroid administration is a prophylactic treatment, the risk factors for ES during prophylactic steroid therapy remain unknown. Therefore, this study aimed to retrospectively evaluate the risk factors for refractory ES in patients administered prophylactic steroids after ESD for ESCC. Methods Among 795 patients with ESCC (854 lesions), 180 patients (211 lesions) administered local triamcinolone acetonide (TrA) and/or oral prednisolone were recruited for this study. We compared the total number of endoscopic balloon dilatation (EBD) procedures performed for post-ESD ES and clinical findings (tumor size, ESD history or chemoradiation therapy [CRT], entire circumferential resection, muscle layer damage, supplemental oral prednisolone administration, EBD with TrA injection, and additional CRT) between patients with refractory and non-refractory ES. EBD was continued until dysphagia resolved. We categorized cases requiring ≥ 8 EBD procedures as refractory postoperative stenosis and divided the lesions into two groups. Results Multivariate logistic regression analysis revealed that factors such as ESD history, CRT history, tumor size, and entire circumferential resection were independently associated with the development of refractory ES. The withdrawal rates of EBD at 3 years were 96.1% (52/53) and 58.5% (39/59) in the non-refractory and refractory groups, respectively. Conclusions Our data suggest that entire circumferential resection and CRT history are risk factors for refractory post-ESD ES in ESCC, even with prophylactic steroid administration.

Abstract Objectives Endoscopic submucosal dissection (ESD) for colorectal tumors with positive muscle‐retracting (MR) sign often results in incomplete resection or discontinuation owing to the difficulty of submucosal dissection. The present study aimed to evaluate the usefulness of endoscopic ultrasonography (EUS) in diagnosing the MR sign and performing ESD using the pocket‐creation method (PCM). Methods Thirty‐six cases of colorectal tumors with positive MR sign during ESD between January 2015 and December 2021 were retrospectively reviewed. Cases were divided into two groups: 1) the conventional method (CM) group, comprising 29 cases, and 2) the PCM group with seven cases, in which preoperative EUS and ESD using PCM were performed. Treatment outcomes were compared between the groups. The diagnostic yield of EUS for the MR sign was evaluated among large sessile tumors >20 mm in which preoperative EUS was performed. Results Histologic diagnosis was adenoma or Tis carcinoma in 12 cases (33%), T1 carcinoma in 18 cases (50%), T2 carcinoma in four cases (11%), and unevaluable in two cases (6%). The sensitivity and specificity of the EUS‐MR sign for large sessile tumors were 87.5% and 83.3%, respectively. ESD was achieved in all cases in the PCM group, although it was discontinued in eight cases (28%) in the CM group. There were significant differences between the PCM and CM groups in en bloc resection (100% vs. 48%, p = 0.013) and R0 resection rates (71% vs. 31%, p = 0.049). Conclusion The MR sign can be predicted by preoperative EUS, and ESD using PCM allows en bloc resection.

Abstract Colorectal adenomas with squamoid morules are rare; however, colorectal adenocarcinomas are even rarer. Herein, we present a case of colorectal adenocarcinoma with squamoid morules arising from the transverse colon. A 60‐year‐old Japanese man underwent a colonoscopy, and a Type 0‐Is polyp was detected in the transverse colon. The endoscopic findings suggested a high possibility of carcinoma invasion into the deep submucosa. However, endoscopic mucosal resection was performed due to the patient's preference. Histopathologically, the tumor cells mostly formed atypical glandular structures corresponding to adenocarcinomas. Solid nests were observed in parts of the tumor, composed of round, small to short spindles. Immunohistochemically, p63 was positive in some areas, CK20 was negative, and the Ki‐67 positive cell rate was almost zero, suggesting a squamoid morule. Based on the above findings, colorectal adenocarcinoma with a squamoid morule was diagnosed; only the fifth case was reported worldwide. Squamoid morules should be carefully differentiated from squamous components of adenosquamous carcinomas.

Abstract Objectives Complete en‐bloc resection of pedunculated colorectal carcinoma is necessary for a proper pathological diagnosis. However, due to poor visibility, large pedunculated colorectal carcinomas are difficult to snare and resect en‐bloc using endoscopic resection or polypectomy. Additionally, the bleeding risk of large pedunculated colorectal carcinomas is relatively high. We aimed to assess the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas. Methods We conducted a retrospective multicenter cohort study to assess 36 consecutive patients with 36 large pedunculated colorectal carcinomas who underwent endoscopic submucosal dissection and evaluated the outcomes of endoscopic submucosal dissection. Furthermore, patients were divided into two groups according to the procedure time, and the factors related to the procedure time were assessed. Results The mean tumor size was 34.1 ± 9.9 mm. The en‐bloc, complete en‐bloc, and curative resection rates were 97% (35/36), 97% (35/36), and 81% (29/36), respectively. The rate of severe bleeding during the procedure was 11% (4/36); however, it could be controlled endoscopically in all patients. The rate of intraoperative perforation and delayed bleeding was 0% (0/36). Delayed perforations occurred in one patient that required surgery. A long procedure time was correlated with the location of the flexure and poor endoscope operability. No recurrence was observed in any patient. None of the patients died of colorectal carcinoma. Conclusions Our results showed the feasibility and safety of endoscopic submucosal dissection for large pedunculated colorectal carcinomas.

Abstract Objectives Underwater endoscopic mucosal resection (UEMR) is a simpler procedure for superficial non‐ampullary duodenal epithelial tumors (SNADET) than conventional endoscopic mucosal resection (cEMR). This study aimed to evaluate whether cEMR can be substituted by UEMR for SNADET in terms of effectiveness, safety, and learning curve. Methods A total of 157 consecutive patients with 203 SNADETs ≤20 mm in diameter, including 107 lesions resected by cEMR and 96 lesions resected by UEMR, between January 2019 and May 2023, were retrospectively recruited. The treatment outcomes were compared between the cEMR and UEMR groups. The risk factors for incomplete resection by UEMR were analyzed using univariate and multivariate analyses. Lesions in the UEMR group were divided chronologically into five periods; thereafter, the en bloc resection rate and procedure time were compared. Results No significant differences existed between the cEMR and UEMR groups in the mean procedure time (3.9 min vs. 3.6 min, p = 0.1380) or en bloc resection rate (91% vs. 94%, p = 0.4138). No perforation was observed in either group. Tumor size was an independent risk factor for incomplete resection using UEMR (p

Abstract Aim Atezolizumab plus bevacizumab combination therapy (Atezo + Beva) is used as the first‐line therapy for unresectable hepatocellular carcinoma (u‐HCC). Serious adverse events (AEs), including rupture of esophagogastric varices, have been seen during treatment. Therefore, the relationships of efficacy, safety, and portal hypertension (PH) were analyzed. Methods A total of 146 patients with u‐HCC and Child‐Pugh Scores of 5–7 received Atezo + Beva. Prophylactic treatment for varices was performed for patients with the risk of rupture of varices before the start of Atezo + Beva. A propensity score‐matched cohort was created to minimize the risk of potential confounders. Efficacy was assessed in 41 propensity score‐matched pairs. AEs were assessed between patients without PH (n = 80) and with PH (n = 66). Results In patients without PH and with PH, median overall survival was 18.4 months and 18.8 months (p = 0.71), and median progression‐free survival was 8.6 months and 5.8 months (p = 0.92), respectively. On the best radiological response evaluation for Response Evaluation Criteria in Solid Tumors, the objective response rate was 31.7% and 26.8% (p = 0.81), respectively. Variceal rupture occurred in three patients with PH, but there were no significant differences in the occurrence of variceal rupture (p = 0.090) and Grade 3–4 AEs between patients without and with PH. Conclusions No significant differences in efficacy and safety were observed with PH. Prophylactic treatment for varices before the start of Atezo + Beva would allow treatment to continue relatively safely.

Abstract A 62‐year‐old man presented with a 7‐cm cystic lesion with irregularly thickened cyst wall in contact with the pancreatic tail. The pancreatic tail was described as hypoechoic on endoscopic ultrasonography. The cyst subsequently increased rapidly to 13 cm, and surgery was performed. This revealed adenosquamous carcinoma in the pancreatic tail to have invaded the stomach and transverse colon along the cyst wall. The cyst was diagnosed as a retention cyst due to pancreatic tail tumor. Invasion of nearby organs by a pancreatic cancer via the retention cyst wall is very rare, but it is necessary to keep the potential for such progress in mind.

Abstract Background Lenvatinib, a multiple receptor tyrosine kinase inhibitor, might exert antitumor effects via tumor immune modulation. However, changes in the tumor immune microenvironment induced by lenvatinib are poorly understood. We investigated the effect of lenvatinib on immune features in clinical samples from patients with hepatocellular carcinoma. Methods Fifty-one patients with advanced hepatocellular carcinoma who received lenvatinib monotherapy as first-line treatment were enrolled. We collected blood sample (n = 51) and tumor tissue (n, baseline/four weeks after treatment initiation/post-progression = 50/8/12). DNA, RNA, and proteins extracted from the tissues were subjected to multi-omics analysis, and patients were classified into two groups according to baseline immune status. Each group was investigated in terms of the dynamics of tumor signaling. We also longitudinally analyzed circulating immune proteins and chemokines in peripheral blood. Results Here we show that lenvatinib has similar anti-tumor efficacy with objective response rate and progression-free survival in both Immune-Hot and Immune-Cold subtypes. Immune signatures associated with T-cell functions and interferon responses are enriched in the early phase of treatment, while signatures associated with immunoinhibitory cells are downregulated along with efficient vascular endothelial growth factor receptor and fibroblast growth factor receptor blockades. These findings are supported by imaging mass cytometry, T-cell receptor repertoire analysis and kinetics of circulating proteins. We also identify interleukin-8 and angiopoietin-2 as possible targets of intervention to overcome resistance to existing immunotherapies. Conclusions Our findings show the ability of lenvatinib to modulate tumor immunity in clinical samples of hepatocellular carcinoma.

Cowden syndrome (CS)/PTEN hamartoma tumor syndrome (PHTS) is a rare autosomal dominantly inherited condition caused by germline pathogenesis. It is associated with multiple hamartomatous lesions occurring in various organs and tissues, including the gastrointestinal tract, skin, mucous membranes, breast, thyroid, endometrium, and brain. Macrocephaly or multiple characteristic mucocutaneous lesions commonly develop in individuals in their 20s. This syndrome is occasionally diagnosed in childhood due to the occurrence of multiple gastrointestinal polyps, autism spectrum disorders, and intellectual disability. CS/PHTS can be diagnosed taking the opportunity of multigene panel testing in patients with cancer. Appropriate surveillance for early diagnosis of associated cancers is required because patients have a high risk of cancers including breast, thyroid, colorectal, endometrial, and renal cancers. Under these circumstances, there is growing concern regarding the management of CS/PHTS in Japan, but there are no available practice guidelines. To address this situation, the guideline committee, which included specialists from multiple academic societies, was organized by the Research Group on Rare and Intractable Diseases granted by the Ministry of Health, Labour, and Welfare, Japan. The present clinical guidelines explain the principles in the diagnosis and management of CS/PHTS, together with four clinical questions and the corresponding recommendations, incorporating the concept of the Grading of Recommendations Assessment, Development, and Evaluation system. Herein, we present an English version of the guideline, some of which have been updated, to promote seamless implementation of accurate diagnosis and appropriate management of pediatric, adolescent, and adult patients with CS/PHTS.

Abstract Background Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. Methods We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (

Background/Purpose: Differential diagnosis of isolated immunoglobin (Ig)G4-related sclerosing cholangitis (IgG4-SC) and cholangiocarcinoma is challenging. We aimed to clarify the role of endoscopic retrograde cholangiography (ERCP)-related procedures in the differential diagnosis of isolated IgG4-SC and perihilar cholangiocarcinoma (PHCC). Methods: Seven patients with hilar-type isolated IgG4-SC diagnosed at Hiroshima University Hospital and sixty-five patients with surgically resected invasive PHCC were enrolled, and the diagnostic yields of intraductal ultrasonography (IDUS), peroral cholangioscopy (POCS), and pathological examinations were determined. Results: In six of seven (86%) patients with isolated IgG4-SC, the stricture was in the perihilar bile duct. IDUS showed that symmetrical wall thickening (40% vs. 5%, p = 0.04), homogeneous internal echo (80% vs. 5%, p < 0.001), and smooth outer margins (80% vs. 6%, p < 0.001) were more frequent in isolated IgG4-SC than in PHCC. POCS showed a smooth mucosal surface more frequent in isolated IgG4-SC (75% vs. 7%, p = 0.006). Only one patient had two pathological findings characteristic of IgG4-SC. The sensitivity for diagnosing PHCC was 81% using two or more combined sampling methods. Conclusions: Pathological examinations have limitations in the differential diagnosis of isolated-IgG4-SC and PHCC, and a diagnostic strategy that combines multiple ERCP-related procedures, including IDUS and POCS, is recommended.

Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.

Abstract Background Metabolic dysfunction-associated fatty liver disease (MAFLD) represents a new classification system for fatty liver disease. In this study, we investigated the clinical characteristics of patients with MAFLD-hepatocellular carcinoma (HCC) in comparison with those with nonalcoholic fatty liver disease (NAFLD) and considered the validity and challenges of the new criteria. Methods This study included 237 untreated non-B, non-C HCC patients with hepatic steatosis. We examined the profile and laboratory findings of patients with MAFLD-HCC and NAFLD-HCC. We also classified MAFLD-HCC patients according to the factors on which the diagnosis was based and compared their clinical characteristics. Results A total of 222 (94%) and 101 (43%) patients were diagnosed with MAFLD and NAFLD, respectively. MAFLD-HCC patients were more likely to be male than NAFLD-HCC, but there were no significant differences in metabolic indices, noninvasive liver fibrosis score or HCC status. In a study of MAFLD-HCC patients by diagnostic factor, those with overweight only were younger and had advanced liver fibrosis histologically, and when limited to patients younger than 70 years, the majority were overweight. Redefinition of overweight as BMI ≥ 25 reduced the number of MAFLD-HCC patients by only 5, from 222 to 217. Conclusions MAFLD accounted for the majority of non-B, non-C HCC cases with hepatic steatosis. Examination of additional cases and revision of the detailed criteria is needed so that it can be used to efficiently select patients with fatty liver who are at high risk of developing HCC.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is sometimes detected in non‐drinker and non‐smoker females who are considered to have very low risk of ESCC development in daily practice. This study examined the clinicopathological and genomic characteristics of ESCCs in females with no history of drinking and smoking. Methods The sample comprised 118 ESCC lesions occurring in 95 female patients who underwent endoscopic submucosal dissection at our department between January 2008 and December 2019. The patients were categorized into two groups: 51 lesions in 49 patients with no history of drinking and smoking (nondrinker/nonsmoker [NDNS] group) and 69 lesions in 45 patients with a history of drinking or smoking (drinker/smoker [DS] group). We analyzed the differences in clinicopathological and cancerous genomic characteristics between the groups. Significant genomic alterations were validated using immunohistochemistry. Results Multiple logistic regression revealed that older age, fewer multiple Lugol‐voiding lesions (LVLs), and reflux esophagitis (RE) were independently associated with the occurrence of ESCCs in the NDNS group. ESCC lesions in the NDNS group were predominantly located in the mid‐thoracic esophagus, posterior wall side, with 0‐IIa, the aspect ratio of the lesion >2 (vertical/horizontal), and endoscopic keratinization. Genetic analysis showed that CDKN2A driver alterations were significantly more frequent and KMT2D alterations were significantly less frequent in the NDNS group than in the DS group. KMT2D alterations were strongly correlated with immunostaining. Conclusion Older nondrinker, nonsmoker females with RE and fewer multiple LVLs may develop longitudinal 0‐IIa ESCC with keratinization of the posterior wall of the mid‐thoracic esophagus. ESCCs in nondrinker, nonsmoker females had fewer KMT2D alterations and more CDKN2A alterations, which may be a biomarker for treatment.

PURPOSELimited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA.METHODSThis retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests.RESULTSData from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively.CONCLUSIONPatients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.

BackgroundChronic constipation (CC) is one of the most frequently reported gastrointestinal disorders in the general population and a prominent problem among university students. The study aimed to evaluate the prevalence and the associated factors of CC among Japanese university students.MethodsThis cross-sectional study was conducted among university students at Hiroshima University, Japan. Students answered the web questionnaire when making a web reservation for the health checkup (April 1 to May 31, 2023). The web questionnaire consisted of four sections, including baseline characteristics, lifestyle factors, family history of CC, and three scales to assess depression and eating disorders: the Beck Depression Inventory (BDI), Eating Attitudes Test (EAT)-26 and Bulimic Investigatory Test (BITE). CC was diagnosed using Rome IV criteria. The multivariate logistic regression model was used to determine CC-related factors.ResultsOut of 10,500 individuals who participated in the annual health checkup, 7,496 participants answered the web questionnaire, of whom 5,386 answered all the survey questions. The mean age of the students was 21.1 ± 4.1 years. The male-to-female ratio was 1:1.17. The prevalence of CC was 13.7%. Factors significantly associated with CC in the multivariate model were first-degree family members with CC [Odd ratio (OR): 2.77, 95% confidence interval (CI): 2.31–3.31], severe depression according to BDI scale (OR: 2.59, 95% CI: 1.96–3.43), female sex (OR: 2.00, 95% CI: 1.69–2.36), and short sleep duration of 6 hours or less per day (OR: 1.28, 95% CI: 1.09–1.50). Lack of physical exercise tended to be associated with CC (OR: 1.19, 95% CI: 1.00–1.40).ConclusionsCC is prevalent among Japanese university students. Significant risk factors for CC included the first-degree family history of CC, severe depression, female sex, and short sleep duration. Lack of physical exercise tended to be associated with CC. This may contribute to implementing suitable education health programs, health care professionals, and public health policies to identify individuals at risk for CC to prevent and treat CC effectively.

Abstract Background The ABC method, which combines the pepsinogen method and anti-Helicobacter pylori antibody titers, has been used for risk screening for gastric cancer in Japan. However, it has been reported that there are cases of gastritis and carcinogenesis risk even in group A, which is considered to be a low-risk group based on the ABC method. Currently, in group A, endoscopic examination is needed to strictly discriminate “patients without gastritis” (defined as true A patients) from those “with gastritis.” A simple and minimally invasive diagnostic criterion for gastritis using serological markers is desirable. In this study, we aimed to identify the normal serum gastrin concentrations in normal stomach cases based on pathological diagnosis and investigate the usefulness of serum gastrin concentrations in diagnosing gastritis. Methods Patients who underwent endoscopy and blood tests at Hiroshima University Hospital were enrolled in the study and categorized into the “pathologically-evaluated group” and “endoscopically-evaluated group,” according to the evaluation method of atrophic gastritis. Initially, we measured serum gastrin concentrations in the normal stomach cases in the pathologically-evaluated group and calculated the normal range of serum gastrin concentrations. We used the upper limit of this normal range of serum gastrin concentrations and performed a validation study to determine its usefulness as a diagnostic marker for distinguishing between cases of gastritis and true A in the endoscopically-evaluated group. Results The 95th percentile of serum gastrin concentrations in pathologically-evaluated normal stomach cases was 34.12–126.03 pg/mL. Using the upper limit of this normal range of serum gastrin concentrations, the sensitivity, specificity, positive predictive value, and negative predictive value for gastritis were 52.8%, 92.6%, 97.0%, and 31.0%, respectively. Additionally, the receiver operating characteristic (ROC) curve for the endoscopically-evaluated group showed an area under the ROC curve of 0.80. Conclusion The gastrin cut-off value of 126 pg/mL has a good positive predictive value (97.0%) for detecting gastritis positing its use as a marker for cases requiring endoscopy. However, the identification of patients with gastritis having normal serum gastrin concentrations due to insufficient sensitivity remains a challenge for the future.

Abstract Background Balloon-occluded retrograde transvenous obliteration (BRTO) is a treatment option for patients with gastric varices (GVs). This study aimed to clarify the clinical significance of portal hypertension estimated by the hepatic venous pressure gradient (HVPG), subsequent exacerbation of esophageal varices (EVs), and prognosis of patients who underwent BRTO for GVs. Methods Thirty-six patients with GVs treated with BRTO were enrolled in this study, and their HVPG was measured before (pre-HVPG) and on the day after BRTO (post-HVPG). After BRTO, patients were followed-up for a median interval of 24.5 (3–140) months. Clinical factors related to EVs exacerbation and prognosis after BRTO were retrospectively analyzed. Results Post-HVPG increased compared to pre-HVPG in 21 out of 36 patients (58%), and post-HVPG was overall significantly higher compared to pre-HVPG (P = 0.009). During the observation period, 19 patients (53%) developed EVs exacerbation, and the cumulative EVs exacerbation rates at 1, 3 and 5 years after BRTO were 27%, 67%, and 73%, respectively. Pre-HVPG was not related to EVs exacerbation, although elevation of post-HVPG to ≥ 13 mmHg (P

Abstract Early diagnosis of articular cartilage damage and repeated evaluation of treatment efficacy are essential for osteoarthritis treatment. In this study, we established a simple ultrasound grading system for early degenerative articular cartilage and investigated its relationship with cartilage biological characteristics. The ultrasound grading system were based on surface integrity (S1a: continuous high-echo lines, S1b: discontinuous or weak high-echo lines, S2: surface irregular) and cartilage echogenicity (E1: with > 50%, E2:

Abstract Meniscal degeneration is defined by semi-quantitative assessment of multiple histological findings and has been implicated in biomechanical dysfunction, yet little is known about its relationship with biological properties. This paper aimed to quantitatively evaluate degenerative findings in human meniscus to examine their relationship with gene expression and biomechanical properties, and to extract histological findings that reflect biological properties like gene expression and cytokine secretion. This study included lateral menisci of 29 patients who underwent total knee arthroplasty. The menisci were divided into six samples. For each sample, Pauli's histological evaluation and corresponding quantitative assessment (surface roughness, DNA content, collagen orientation, and GAG content) were performed, with surface roughness showing the highest correlation with the histological evaluation in a single correlation analysis (r = 0.66, p

Abstract Background Gastric cancer remains a severe public health problem worldwide, particularly in Japan. Recent studies have demonstrated that serum markers are beneficial for risk stratification in gastric cancer development. We aimed to evaluate the usefulness of serum markers either alone or in combination (serum markers plus endoscopy) for effective risk stratification of gastric cancer development. Methods We enrolled 22,736 patients aged 20–95 years who underwent blood sampling and endoscopic examination at Hiroshima University Hospital in Japan between 1990 and 2014. The serum pepsinogen (PG) levels and anti-Helicobacter pylori antibody (Hp-Ab) titers were evaluated in each patient. The enrolled patients were matched with the database of the Hiroshima Prefecture Regional Cancer Registry. We processed the medical records and excluded patients with possible confounding factors for PG levels, such as proton pump inhibitor use, prior successful eradication therapy, post-gastrectomy, severe hepatorenal dysfunction, Zollinger–Ellison syndrome, and autoimmune gastritis. Among the remaining 5131 patients, we reviewed records of endoscopic examinations and selected 1507 patients (mean age, 62.5 years; 985 men and 522 women) who underwent endoscopic examination more than three months after blood sampling. First, based on the ABC method, patients were classified as follows: High PG levels and negative Hp-Ab, group A, high PG levels and positive Hp-Ab, group B, low PG levels and positive Hp-Ab, group C, and low PG levels and negative Hp-Ab, group D. Group A was further classified into two subgroups using endoscopic findings: true A without atrophic gastritis and pseudo A with atrophic gastritis. All patients underwent annual endoscopy follow-up. Results Among the 1,507 patients (mean age, 62.5 years; 985 men), 24 were diagnosed with newly developed gastric cancer. No significant difference in cancer development was found between group A (PG negative and Hp-Ab negative) and the other groups. Remarkably, no true A group subjects developed gastric cancer. Conclusions The combination of serum markers and endoscopic findings is essential for the risk evaluation of gastric cancer.

Abstract Objectives 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. Methods 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). Results 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%, p

Background and study aims Prevention of bleeding and perforation during gastric endoscopic submucosal dissection (ESD) is important. Scissor-type knives can accurately grasp and incise the targeted tissue using electrosurgical currents, thereby eliminating unexpected incisions. The SB Knife GX, a scissor-type knife specialized for gastric ESD, was released in June 2016 in Japan. The aim of the present study was to evaluate the efficacy and safety of gastric ESD using the SB Knife GX. Patients and methods A total of 716 patients who underwent gastric ESD at Hiroshima University Hospital between July 2016 and December 2020 were retrospectively reviewed. From these, 671 patients underwent ESD using the IT Knife 2 (IT-2 group), while 45 underwent ESD using an SB Knife GX (SB-GX group). After propensity score matching, the procedure time, specimen size, en bloc and complete resection rates, and intraoperative bleeding, delayed bleeding, and perforation rates were evaluated. Results No significant differences were observed in mean procedure time (SB-GX group: 115 ± 165 min; IT-2 group: 95 ± 61 min; P = 0.82) and en bloc and complete resection rates between the two groups. Intraoperative bleeding rates were significantly lower in the SB-GX group than in the IT-2 group (18 % vs. 40 %; P = 0.01), and there were no differences in delayed bleeding (4 % vs. 4 %) or perforation (0 % vs. 4 %) between the two groups. Conclusions The SB Knife GX was proven to be useful for control of intraoperative bleeding during gastric ESD, although the procedure time tended to be longer.

The risk of malignant tumor progression has been a concern associated with the use of anti-tumor necrosis factor-alpha monoclonal antibody (anti-TNFα mAb). On the contrary, recent observational studies have reported negatively on this risk and instead suggested that anti-TNFα mAb acts as a tumor suppressor in inflammatory carcinogenesis models and subcutaneous transplant models of colorectal cancer. However, no consensus has been established regarding the actual effects of anti-TNFα mAb on malignant tumors. Here, we aimed to evaluate, for the first time, the effect of anti-TNFα mAb on the tumor microenvironment in the absence of intestinal inflammation in a colorectal cancer orthotopic transplant mouse model suitable for tumor microenvironment assessment. The orthotopic transplantation model was developed by transplanting CT26 cells into the cecum of BALB/c mice. Changes in tumor size and weight were recorded 3 weeks after transplantation, and the tumor microenvironment was assessed via RNA sequencing and immunohistological staining. In the orthotopic transplant model, the administration of anti-TNFα mAb led to a reduction in colorectal cancer. The RNA sequencing analysis showed upregulation of immune-related pathways and apoptosis and suppression of stromal- and tumor growth-related pathways. Additionally, Gene Ontology analysis showed inhibition of angiogenesis. Immunohistochemical staining showed inhibition of tumor growth, increase in apoptosis, suppression of stromal response, suppression of angiogenesis, enhancement of tumor immunity, and reduction in the number of tumor-associated macrophages. Anti-TNFα mAb acts as an inhibitor of tumor progression in the tumor microenvironment of a colorectal cancer orthotopic transplant mouse model.

Abstract Systemic sclerosis (SSc) is characterized by fibrosis of the skin and various internal organs. However, there is limited knowledge concerning small-bowel lesions. We evaluated the clinical state of patients with SSc according to the capsule endoscopy (CE) findings. Sixty-five consecutive patients with SSc (61 females; mean age, 64.3 years) underwent CE at Hiroshima University Hospital between April 2012 and December 2019. SSc was subclassified into diffuse and limited cutaneous SSc. Among the 65 patients, 55 (51 females; mean age, 64.5 years; diffuse cutaneous SSc, 27 patients) were evaluated for the presence of fibrosis in the gastrointestinal tract by biopsy. Small-bowel lesions were detected in 27 (42%) patients with SSc. Type 1b angioectasia (Yano-Yamamoto classification) was more frequent in limited cutaneous SSc patients (p = 0.0071). The average capsule transit time of the esophagus was significantly longer in diffuse cutaneous SSc patients (p = 0.0418). There were more cases of Type 1a angioectasia in SSc patients without fibrosis. The average capsule transit time of the esophagus was significantly longer in SSc patients with fibrosis. Thus, this study revealed that the frequency of small-bowel angioectasia and gastrointestinal motility in patients with SSc differed depending on SSc subclassification and the presence of fibrosis.

Pathological examination is essential for the diagnosis and treatment of pancreatic ductal adenocarcinoma (PDAC). Moreover, a reliable pathological diagnosis is extremely important for improving prognosis, especially in early-stage PDAC. This study prospectively evaluated the usefulness of repeated pancreatic juice cytology (PJC) using an endoscopic nasopancreatic drainage (ENPD) catheter for the diagnosis of PDAC. We enrolled 82 patients suspected of having resectable PDAC, based on imaging studies, and judged the necessity for cytology. The diagnostic yield of up to six repeated PJCs and the incidence of complications, such as pancreatitis, was evaluated. A total of 60 patients were diagnosed with PDAC. The overall sensitivity and specificity were 46.7% and 95.5%, respectively. The cumulative positivity rate increased with the number of sampling sessions, reaching 58.3% in the sixth session. The sensitivity was significantly higher in the pancreatic head than in the pancreatic tail (p = 0.043). Additionally, it was 100% in four patients with a tumor size ≤10 mm. Pancreatitis occurred in six patients (7.3%), all of whom were treated conservatively. In the diagnosis of PDAC, repeated PJC using an ENPD catheter revealed a cumulative effect of sensitivity up to six times and an excellent diagnostic yield for small PDAC.

Abstract Background In Japan, endoscopic submucosal dissection (ESD) is standardized for large colorectal tumors. However, its validity in the elderly population is unclear. We aimed to evaluate the safety and efficacy of ESD for colorectal tumors in elderly patients aged over 80 years. Methods ESD was performed on 178 tumors in 165 consecutive patients aged over 80 years between December 2008 and December 2018. We retrospectively evaluated the clinicopathological characteristics and clinical outcomes of ESD. We also assessed the prognosis of 160 patients followed up for more than 12 months. Results The mean patient age was 83.7 ± 3.1 years. The number of patients with comorbidities was 100 (62.5%). Among all patients, 106 (64.2%) were categorized as class 1 or 2 according to the American Society of Anesthesiologists classification of physical status (ASA-PS), and 59 (35.8%) were classified as class 3. The mean procedure time was 97.7 ± 79.3 min. The rate of histological en bloc resection was 93.8% (167/178). Delayed bleeding in 11 cases (6.2%) and perforation in 7 cases (3.9%) were treated conservatively. The 5-year survival rate was 89.9%. No deaths from primary disease (mean follow-up time: 35.3 ± 27.5 months) were observed. Overall survival rates were significantly lower in the non-curative resection group that did not undergo additional surgery than in the curative resection group (P = 0.0152) and non-curative group that underwent additional surgery (P = 0.0259). Overall survival rates were higher for ASA-PS class 1 or 2 patients than class 3 patients (P = 0.0105). Metachronous tumors (> 5 mm) developed in 9.4% of patients. Conclusions ESD for colorectal tumors in patients aged over 80 years is safe. Colorectal cancer-associated deaths were prevented although comorbidities pose a high risk of poor prognosis.

Abstract 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.

Abstract Background An educational and training program is required for generalization of Japan NBI Expert Team (JNET) classification. However, there is no detailed report on the learning curve of the diagnostic accuracy of endoscopists using JNET classification. We examined the effect of an educational lecture on beginners and less experienced endoscopists for improving their diagnostic accuracy of colorectal lesions by JNET classification. Methods Seven beginners with no endoscopy experience (NEE group), 7 less experienced endoscopists (LEE group), and 3 highly experienced endoscopists (HEE group) performed diagnosis using JNET classification for randomized NBI images of colorectal lesions from 180 cases (Type 1: 22 cases, Type 2A: 105 cases, Type 2B: 33 cases, and Type 3: 20 cases). Next, the NEE and LEE groups received a lecture on JNET classification, and all 3 groups repeated the diagnostic process. We compared the correct diagnosis rate and interobserver agreement before and after the lecture comprehensively and for each JNET type. Results In the HEE group, the correct diagnosis rate was more than 90% with good interobserver agreements (kappa value: 0.78–0.85). In the NEE and LEE groups, the correct diagnosis rate (NEE: 60.2 → 68.0%, P

Abstract Submucosal deep invasion of gastric cancer (T1b2; depth of submucosal invasion ≥ 500 μm) is a risk factor for lymph node metastasis and, thus, is one of the criteria for curative treatment. Our aim was to evaluate the specific influence of endoscopic submucosal dissection (ESD) on the prognosis of patients with T1b2 gastric cancer. This was a retrospective analysis of 248 consecutive patients, with 252 pT1b2 gastric cancer lesions, who underwent ESD prior to additional surgery (Group A, n = 101) or surgery only (Group B, n = 147). After propensity score-matching (for sex, age, tumor diameter and gross type), we compared pathological characteristics between the 2 groups and the prognosis over a follow-up period ≥ 60 months. Compared to Group B, patients in Group A were older, with a higher proportion of men. The proportion of depressed and undifferentiated type tumors was greater in Group B than A, with larger tumor size and depth of submucosal invasion as well. There was no incidence of local recurrence, but distant metastasis was identified in 5% of cases in Group A and 3% in Group B. After propensity score-matching, there were no difference in the 5-year overall survival rate between Group A and B (87.5% vs. 91.2%, respectively), nor in the 5-year disease-specific survival rate (96.3% vs. 96.4%, respectively). ESD prior to surgery for T1b2 gastric cancer did not adversely affect clinical outcomes after additional surgery.

Abstract Objectives There are some endoscopic resection (ER) methods for neuroendocrine tumors (NETs), however, which method is most useful remains unclear. This study aimed to compare the outcomes of different ER techniques, such as conventional endoscopic mucosal resection (cEMR), endoscopic submucosal dissection (ESD), and endoscopic submucosal resection with a ligation device (ESMR‐L) for rectal NETs. Methods We retrospectively analyzed 96 consecutive patients with 102 rectal NETs of less than 10 mm in diameter who underwent ER between January 2001 and December 2019 at Hiroshima University Hospital. We compared the clinical outcomes of each ER method (cEMR 60 lesions, ESD 21 lesions, and ESMR‐L 21 lesions), divided according to the treatment periods, and evaluated the risk factors for vertical margin (VM) positivity in relation to clinicopathological and endoscopic characteristics. Results As for the mean procedure time, ESD took significantly longer to perform than the other methods. The histological complete resection rate was 80% (48/60) for cEMR, 85.7% (18/21) for ESD, and 100% (21/21) for ESMR‐L, and the VM positive rate was 20% (12/60) for cEMR, 14.3% (3/21) for ESD, and 0% (0/21) for ESMR‐L, with no significant difference. However, the tumor‐front‐to‐VM distance was significantly longer in the ESMR‐L group than in the cEMR and ESD groups. cEMR and ESD were both significant risk factors for VM positivity. No perforation or local recurrence was observed in all methods. Conclusions ESMR‐L is the most useful ER method for small rectal NETs.

Abstract Objectives A single‐balloon overtube (SBO) can improve poor scope operability during colonic endoscopic submucosal dissection (ESD). We aimed to evaluate the clinical usefulness of SBO for ESD in the proximal colon and the predictive factors for cases in which SBO is useful. Methods A total of 88 tumors located in the proximal colon resected by balloon‐assisted ESD (BA‐ESD) using SBO and 461 tumors resected by conventional ESD (C‐ESD) between June 2015 and November 2020 were considered. Seventy‐eight tumors each in the BA‐ESD and C‐ESD groups were matched by propensity score matching. ESD outcomes were compared between the groups, and a decision tree analysis was performed to explore the predictive factors for cases in which SBO is useful. Results There were no significant differences between the groups in the major outcomes such as en bloc resection rate (95% vs. 99%, p = 0.17), R0 resection rate (92% vs. 96%, p = 0.30), mean dissection speed (16 mm2/min vs. 16 mm2/min, p = 0.53), and intraoperative perforation rate (5% vs. 6%, p = 0.73). Even when considering cases with poor preoperative scope operability, there were no significant differences between the groups. Comparison of tumors ≥40 mm in diameter between the groups confirmed that the intraoperative perforation rate was significantly lower in the BA‐ESD group than in the C‐ESD group (0% vs. 24%, p = 0.0188). Conclusion SBO is useful for ESD of tumors ≥40 mm in diameter in the proximal colon to prevent intraoperative perforation, which usually has a long procedure time.

Abstract Background Gastric cancer develops even in Helicobacter pylori(H. pylori)-uninfected patients and its typical histological feature is signet ring cell carcinoma (SRCC) within the mucosal layer. However, the biological characteristics of SRCC remain unclear. We aimed to clarify the pathological and genetic features of SRCC in H. pylori-uninfected patients. Methods Seventeen H. pylori-uninfected patients with mucosal SRCCs were enrolled and their clinicopathological characteristics were compared with those of H. pylori-infected patients with mucosal SRCCs. Seven SRCCs without H. pylori-infected, including two invasive SRCCs, and seven H. pylori-infected SRCCs were subjected to a genetic analysis using next-generation sequencing. Results H. pylori-uninfected patients with mucosal SRCCs revealed male dominancy and a significantly higher prevalence of smokers among them as compared with the H. pylori-infected patients with SRCC. A CDH1 mutation (frame shift indel) was detected in one H. pylori-uninfected cancer not only in the mucosal SRCC but also in the invasive portion. A TP53 mutation was detected in one SRCC without H. pylori-infected. In the control group, ARID1A and TP53 mutations were detected in one SRCC each. The C to A mutation, which is a characteristic smoking-induced mutation, was not found in any of the samples. Conclusions Some SRCCs in H. pylori-uninfected patients may have a malignant potential similar to that of SRCCs in H. pylori-infected patients. Smoking may not be the main carcinogenic factor for the development of SRCCs among the H. pylori-uninfected patients.

Abstract Background Endoscopic resection is widely used as an effective treatment for superficial esophageal cancer. However, the risk of lymph node metastasis increases in cases of muscularis mucosae or deeper invasion, for which additional treatment such as radiotherapy or surgery is required. Accordingly, the current study investigated the efficacy and toxicity of salvage radiotherapy after non-curative endoscopic resection as an organ preservation strategy. Methods We retrospectively reviewed 37 esophageal cancer patients who received salvage radiotherapy after non-curative endoscopic resection. The pathological invasion depths were the muscularis mucosae, submucosal layer, and muscularis propria in 14, 22, and one patient, respectively. All patients received external beam radiotherapy. Among them, eight received intraluminal brachytherapy following external beam radiotherapy. Elective nodal irradiation was administered to all patients. Twenty-five patients received concurrent platinum and fluorouracil-based chemotherapy. Results The median follow-up time was 74 months (range: 3–212). The 5-year progression-free survival and overall survival rates were 64 and 78%, respectively. No local or regional lymph node recurrence was observed. The causes of death included esophageal cancer in one patient, metachronous esophageal cancer in one patient, other malignancies in eight patients, and other causes in six patients. Late cardiac toxicities ≥ grade 3 were observed in six patients, one of whom died of arrhythmia. Conclusions Salvage radiotherapy after non-curative esophageal endoscopic resection is an effective treatment as an organ preservation strategy. Although muscularis mucosae and submucosal cancer have a high risk of lymph node metastasis, our results suggest that elective nodal irradiation contributes to reduced regional node metastases.