Hiroshi Yasuda

Background/Aims: Vedolizumab (VDZ), a gut-selective monoclonal antibody for ulcerative colitis (UC) treatment, has no established biomarkers or clinical features that predict long-term remission. Week 2 remission, a potential predictor of long-term remission, could inform maintenance treatment strategy. Methods: This retrospective, observational chart review included patients with UC in Japan who initiated VDZ between December 2018 and February 2020. Outcome measures included 14- and 54-week remission rates in patients with week 2 and non-week 2 remission (remission by week 14), 54-week remission rates in patients with week 14 remission and primary nonresponse, and predictive factors of week 2 and week 54 remission (logistic regression). Results: Overall, 332 patients with UC (176 biologic-naïve and 156 biologic-non-naïve) were included. Significantly more biologic-naïve than biologic-non-naïve patients achieved week 2 remission (36.9% vs. 28.2%; odds ratio [OR], 1.43; 95% confidence interval [CI], 1.05–1.94; P= 0.0224). Week 54 remission rates were significantly different between week 14 remission and primary nonresponse (both groups: P< 0.0001), and between week 2 and non-week 2 remission (all patients: OR, 2.41; 95% CI, 1.30–4.48; P= 0.0052; biologic-naïve patients: OR, 2.40; 95% CI, 1.10–5.24; P= 0.0280). Week 2 remission predictors were male sex, no anti-tumor necrosis factor alpha exposure, and normal/mild endoscopic findings. Week 54 remission was significantly associated with week 2 remission and no tacrolimus use. Conclusions: Week 2 remission with VDZ is a predictor of week 54 remission in patients with UC. Week 2 may be used as an evaluation point for UC treatment decisions. (Japanese Registry of Clinical Trials: jRCT-1080225363)

Background/Aims: Previous literature suggests that the response of patients with ulcerative colitis to vedolizumab may be affected by previous biologic therapy exposure. This real-world study evaluated vedolizumab treatment effectiveness in biologicnon-naïve patients. Methods: This was a multicenter, retrospective, observational chart review of records from 16 hospitals in Japan (December 1, 2018, to February 29, 2020). Included patients who had ulcerative colitis, were aged ≥ 20 years, and received at least 1 dose of vedolizumab. Outcomes included clinical remission rates from weeks 2 to 54 according to prior biologic exposure status and factors associated with clinical remission up to week 54. Results: A total of 370 eligible patients were included. Clinical remission rates were significantly higher in biologic-naïve (n=197) than in biologic-non-naïve (n=173) patients for weeks 2 to 54 of vedolizumab treatment. Higher clinical remission rates up to week 54 were significantly associated with lower disease severity (partial Mayo score ≤ 4, P= 0.001; albumin ≥ 3.0, P= 0.019) and the duration of prior anti-tumor necrosis factor α (anti-TNFα) therapy (P= 0.026). Patients with anti-TNFα therapy durations of < 3 months, 3 to < 12 months, and ≥ 12 months had clinical remission rates of 28.1%, 32.7%, and 60.0%, respectively (P= 0.001 across groups). Conclusions: The effectiveness of vedolizumab in biologic-non-naïve patients was significantly influenced by duration of prior anti-TNFα therapy. (Japanese Registry of Clinical Trials: jRCT-1080225363)

Background/Aims: The objectives of this real-world study were to determine 1-year persistence with vedolizumab in patients with ulcerative colitis and to evaluate factors contributing to loss of response. Methods: In this multicenter, retrospective, observational chart review, patients with moderately to severely active ulcerative colitis who received ≥ 1 dose of vedolizumab in clinical practice at 16 tertiary hospitals in Japan (from December 2018 through February 2020) were enrolled. Results: Persistence with vedolizumab was 64.5% (n = 370); the median follow-up time was 53.2 weeks. Discontinuation due to loss of response among initial clinical remitters was reported in 12.5% (35/281) of patients. Multivariate analysis showed that concomitant use of tacrolimus (odds ratio [OR], 2.76; 95% confidence interval [CI], 1.00–7.62; P= 0.050) and shorter disease duration (OR for median duration ≥ 7.8 years vs. < 7.8 years, 0.33; 95% CI, 0.13–0.82; P= 0.017) were associated with discontinuation due to loss of response. Loss of response was not associated with prior use of anti-tumor necrosis factor alpha therapy, age at the time of treatment, disease severity, or concomitant corticosteroids or immunomodulators. Of the 25 patients with disease duration < 1 year, 32.0% discontinued due to loss of response. Conclusions: Persistence with vedolizumab was consistent with previous reports. Use of tacrolimus and shorter disease duration were the main predictors of decreased persistence.

5-Aminosalicylate (5-ASA) intolerance complicates ulcerative colitis (UC) management, often necessitating alternative treatment approaches. Granulocyte and monocyte adsorptive apheresis (GMA) has been recognized as a safe treatment option for patients with UC who are refractory or intolerant to conventional drugs, including steroids; however, its effectiveness and safety in patients with 5-ASA intolerance remain unclear. This study aimed to investigate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. We conducted a retrospective observational study to evaluate the effectiveness and safety of GMA in patients with UC and 5-ASA intolerance. Eighty-five patients with UC who underwent GMA were assessed, including 21 with 5-ASA intolerance and 64 with 5-ASA tolerance. This study compared the patient characteristics, treatment outcomes, concomitant drugs, and adverse events between the 2 groups. The remission rate was 28.6% (6/21) in the 5-ASA-intolerant group and 31.3% (20/64) in the 5-ASA-tolerant group, with no significant difference between the groups (P = .967). Both groups showed significant reductions in the dose of oral prednisolone and Lichtiger clinical activity index scores following the GMA. Our study suggests that GMA is equally effective and safe in 5-ASA-intolerant and 5-ASA-tolerant patients, offering an alternative treatment option in this challenging clinical scenario.

Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City, a major urban area with a growing aging population and relatively high screening participation rates. Methods: Between December 2012 and 2021, a total of 337,842 citizens in Kawasaki City underwent population-based GC screening, leading to the detection of 1087 GC cases. Esophageal cancer (EC) has been recorded since 2016, with 236 cases detected. To evaluate the short- and long-term clinical outcomes of screening-detected GC and EC, we conducted a retrospective study using the electronic medical records of patients treated at our hospital, a high-volume institution for GC and EC treatment in the city. As a control group, we included 34 GC and EC cases diagnosed based on symptoms at our hospital in 2018. Results: Among the 1087 GC cases detected through population-based screening, 102 cases treated at our hospital were included in the analysis. Of them, 91 patients (89%) were diagnosed with early-stage GC. All screening-detected GC cases underwent either surgery (27 cases) or endoscopic submucosal dissection (75 cases). The five-year survival rates for GC were 90% in males and 86% in females. Eighteen EC cases were also included in the study. The five-year survival rate for screening-detected advanced GC was 70.0%, while for screening-detected EC, it was 100%. Both survival rates were significantly higher than those for symptom-diagnosed GC (30.0%) and EC (40.8%). Conclusions: The prognosis of GC and EC detected through population-based endoscopic screening is significantly better than that of cancers diagnosed based on symptoms. This underscores the effectiveness of endoscopic screening as a valuable tool for the early detection of upper gastrointestinal tract cancers.

Objectives: To investigate the real-world outcomes of a population-based gastric cancer (GC) screening program in Kawasaki City. Methods: A total of 337,842 citizens underwent population-based GC screening in Kawasaki City between December 2012 and 2021, resulting in the detection of 1,087 GC cases. Esophageal cancer (EC) has been recorded since 2016, with 236 cases detected. To evaluate the short- and long-term clinical outcomes of screening-detected GC and EC, we conducted a retrospective study using electronic medical records of patients treated at our hospital which is a high-volume institution for GC and EC treatment in the city. As a control group, we included 34 GC and EC cases diagnosed based on symptoms at our hospital in 2018. Results: Among the 1,087 GC cases detected through population-based screening, 102 cases treated at our hospital were included in the analysis. Of these, 91 patients (89%) were diagnosed with early-stage GC. All screening-detected GC cases underwent either surgery (27 cases) or endoscopic submucosal dissection (75 cases). The five-year survival rates for GC were 90% in males and 86% in females. Eighteen EC cases were also included in our study. The five-year survival rate for screening-detected advanced GC was 70.0%, and for screening-detected EC was 100%, both significantly higher than those for symptom-diagnosed GC (30.0%) and EC (40.8%). Conclusions: The prognosis of GC and EC detected through population-based endoscopic screening is significantly better than that of cancers diagnosed based on symptoms, underscoring the effectiveness of endoscopic screening as a tool for early detection of upper gastrointestinal tract cancers. Keywords: gastric cancer; esophageal cancer; endoscopy; population-based screening

Background and Aim: Vedolizumab (VDZ) is often used in older patients with ulcerative colitis (UC) in clinical practice; however, real‐world evidence is still limited, including in those with late‐onset UC.Methods: This post hoc analysis of a multicenter, retrospective, observational chart review, enrolling 370 patients with UC receiving VDZ between December 2018 and February 2020, compared effectiveness and safety of VDZ among patients ≥ 70 (n = 40) versus < 70 years (n = 330), and among patients ≥ 70 years with and without late‐onset UC (age at disease onset: ≥ 70 [n = 13] versus < 70 years [n = 26]).Results: There were no differences between patients ≥ 70 and < 70 years in clinical remission rates (week 6: 57.5% vs. 47.6%, p = 0.9174; week 14: 62.5% vs. 54.8%, p = 0.1317; week 54: 47.5% vs. 46.4%, p = 0.8149), primary nonresponse (10.0% vs. 15.5%, p = 0.6248), loss of response (12.5% vs. 9.4%, p = 0.5675), or overall safety. Among patients ≥ 70 years, the incidence of adverse drug reactions was numerically greater in those with concomitant corticosteroids than in those without. For older patients with and without late‐onset UC, week 54 remission rates were 23.1% versus 57.7% (p = 0.0544); surgery was reported in 3/13 versus 2/26 patients and hospitalization in 5/13 versus 6/26 patients. One death was reported in patients with late‐onset UC.Conclusions: VDZ effectiveness and safety were similar in patients ≥ 70 and < 70 years; VDZ may be a suitable treatment option for patients ≥ 70 years with UC. Patients with late‐onset UC tended to have more frequent surgery/hospitalization and lower effectiveness than those without, possibly necessitating greater caution when using VDZ.Trial Registration: Japanese Registry of Clinical Trials registration number: jRCT‐1080225363

Submucosal endoscopy (third-space endoscopy) can be defined as an endoscopic procedure performed in the submucosal space. This procedure is novel and has been utilized for delivery to the submucosal space in a variety of gastrointestinal diseases, such as a tumor, achalasia, gastroparesis, and subepithelial tumors. The main submucosal endoscopy includes peroral endoscopic myotomy, gastric peroral endoscopic myotomy, Zenker peroral endoscopic myotomy, submucosal tunneling for endoscopic resection, and endoscopic submucosal tunnel dissection. Submucosal endoscopy has been used as a viable alternative to surgical techniques because it is minimally invasive in the treatment and diagnosis of gastrointestinal diseases and disorders. However, there is limited evidence to prove this. This article reviews the current applications and evidence regarding submucosal endoscopy while exploring the possible future clinical applications in this field. As our understanding of these procedures improves, the future of submucosal endoscopy could be promising in the fields of diagnostic and therapeutic endoscopy.

Background and Aim: The aim of this study was to identify the factors associated with liver‐related and non‐liver‐related mortality of patients with hepatitis C virus (HCV) after sustained virologic response (SVR) to direct‐acting antiviral agents (DAAs).Methods: We conducted a retrospective, single‐center cohort study of HCV patients cured by DAAs.Results: A total of 330 patients with SVR to DAAs were eligible. The median follow‐up period was 3.38 years (inter‐quartile range: 2.03–4.58). The cumulative liver‐related or non‐liver‐related mortality rates at 1, 3, and 5 years were 0.00 or 1.29%, 2.87 or 3.60%, and 5.10 or 9.46, respectively. Among the liver‐related deaths, 9 of the 10 were from liver cancer. Among the non‐liver‐related deaths, the most common cause was malignancy. Through multivariate analysis using the Cox proportional hazard model, diabetes mellitus (DM, hazard ratio 13.1, 95% confidence interval 2.81–61.3) and a history of hepatocellular carcinoma (HCC, 12.8, 2.76–59.2), independently predicted liver‐related death. No variables were associated with non‐liver‐related death.Conclusion: Our findings suggest that DM and a history of HCC are risk factors for liver‐related mortality of HCV patients cured by DAAs. These results indicate that early management of HCV and HCC surveillance of diabetic patients after SVR are important to increase the chance of survival. Further studies are needed to confirm the association of DM and HCC history with survival.

The patient was a 32-year-old woman who had a 20-year history of intestinal Behçet's disease without ocular involvement. At the age of 12, she developed oral aphthosis, genital ulcers, erythema nodosum on the lower limbs, and soon developed lower abdominal pain. Colonoscopic examination revealed a round punched-out ulceration in the ileocecal region. Human leukocyte antigen (HLA)-B51 (B5) antigen was negative. Drug therapies with salazosufapyridine and prednisolone was started. When prednisolone was reduced to 15 mg/d, the ileocecal lesion recurred and in addition, diabetes mellitus developed. The patient had been suffered corticosteroid dependence with severe side effects. Since the induction of thalidomide at the age of 14, partial remission that allowed for outpatient visits was maintained for more than 10 years, but negative C-reactive protein (CRP) and endoscopically mucosal healing of the ileocecal ulcer on colonoscopy were not achieved. Switch from thalidomide to adalimumab (ADA) was introduced at the age of 26 because of reproductive concern. Since introduction of ADA, no recurrence of genital ulcer or skin lesions had been observed. Negative inflammatory reaction was maintained. Colonoscopy performed after the switch to ADA revealed sustained endoscopic mucosal healing in ileocecal ulcer. ADA may have a more specific anti-inflammatory effect on intestinal BD than thalidomide.