Munenori Honda

Aim: Statins contribute to the preservation of hepatic function and reduce the risk of hepatocellular carcinoma (HCC) in patients with chronic liver disease; however, their clinical significance during systemic therapy for unresectable HCC remains unclear. Therefore, we investigated whether baseline statin use influences clinical outcomes in patients with unresectable HCC treated with atezolizumab plus bevacizumab. Methods: We conducted a multicenter, retrospective cohort study of patients with unresectable HCC treated with atezolizumab–bevacizumab. Patients were classified as statin users or non‐users at treatment initiation. The primary outcome was overall survival (OS), and secondary outcomes included progression‐free survival (PFS) and post‐progression survival (PPS). To adjust for baseline imbalances, inverse probability of treatment weighting (IPTW) was applied, and propensity score (PS) matching was performed as a sensitivity analysis. Results: A total of 284 patients were included, of whom 50 received statins. In the unadjusted cohort, OS was significantly longer in statin users than in non‐users ( p = 0.026). After IPTW adjustment, this OS benefit remained significant ( p = 0.031). In contrast, PFS did not differ significantly between groups in either the unadjusted ( p = 0.291) or IPTW‐adjusted cohorts ( p = 0.117). PPS was significantly prolonged in the statin group ( p = 0.006), with consistent findings after IPTW adjustment ( p = 0.018). In addition, deterioration in ALBI score was attenuated in statin users, suggesting better preservation of hepatic functional reserve. Conclusions: Statin use was associated with significantly improved OS and PPS without affecting PFS, likely reflecting host‐related benefits through preservation of hepatic function.

Purpose: Observational studies have repeatedly reported lower cancer incidence among metformin users than nonusers, but findings are inconsistent and often affected by issues such as immortal time, unclear comparators, and use of total cancer as a composite outcome, which precludes adequate adjustment for site‐specific confounding. These limitations can be mitigated by explicitly emulating a target trial with a suitable active comparator. Methods: We emulated a target trial using a Japanese claims database (April 2014–March 2024) to assess whether metformin reduces colorectal cancer (CRC) risk compared with dipeptidyl peptidase‐4 inhibitors (DPP‐4is) in patients with type 2 diabetes. DPP‐4is served as an active comparator because they are widely used as first‐line alternatives in Japan and have no clear evidence of affecting CRC risk. We estimated the observational analogue of the per‐protocol effect using pooled logistic regression with inverse probability weighting to adjust for baseline and time‐varying confounders. Results: Among 26 273 metformin users and 108 299 DPP‐4i users, the 5‐year risk of CRC was 1.55% (95% confidence interval, 1.16 to 2.04) versus 1.26% (1.13 to 1.41), yielding a risk difference of 0.29% (−0.12 to 0.79) and a risk ratio of 1.23 (0.91 to 1.66). Conclusions: Metformin use did not reduce the 5‐year risk of CRC compared with DPP‐4is. This finding is consistent with meta‐analyses of randomized trials and contrasts with earlier observational reports of substantial benefit, which were likely inflated by methodological flaws. Explicitly emulating a target trial minimized design‐related biases and provided estimates that support causal interpretation.

Background Hepatitis B virus (HBV) reactivation is a critical complication in patients receiving systemic chemotherapy. While current guidelines recommend screening, whether appropriate preventive measures are implemented based on screening results remains unclear. This study aimed to evaluate the implementation of HBV screening and subsequent preventive measures according to hepatitis B surface antigen (HBsAg) status in patients undergoing chemotherapy in Japan. Methods This retrospective cohort study utilized Japan’s largest electronic medical record database to evaluate HBV management in adults (≥ 20 years) who initiated anticancer therapy between 2006 and 2020. Patients with prior HBV treatment were excluded. We assessed the implementation proportions of key steps in HBV management, including initial HBsAg screening, subsequent antibody and DNA testing based on results, and prophylactic antiviral therapy initiation. Results Of 162,040 eligible patients, 93,801 (57.9%) underwent HBV screening. Among HBsAg-negative patients, only 29.4% received subsequent hepatitis B core antibody (anti-HBc) and hepatitis B surface antibody (anti-HBs) testing. HBV DNA testing was performed in 56.0% of patients positive for anti-HBc or anti-HBs. Only 18.3% of HBsAg-positive patients eligible for prophylaxis received nucleoside analogs. Screening and prophylaxis proportions improved over time, with the proportion receiving prophylactic administration reaching 27.1% in 2020. Screening was most frequent in patients with hematologic malignancies (58.3%) and in those receiving anti-CD20 antibodies (65.6%). Conclusion Despite suboptimal initial HBV screening proportions in Japan, a substantial gap remains in implementing subsequent preventive measures, particularly prophylactic therapy for HBsAg-positive patients. This highlights the critical need to improve adherence to guidelines to prevent HBV reactivation.

Background and Aim: Colonoscopy can reduce colorectal cancer mortality. Although guidelines recommend surveillance intervals, clinical practice often varies according to physician discretion and patient factors. Inappropriate shortening of intervals results in unnecessary procedures and increased healthcare costs. This study aimed to examine the real‐world practice of colonoscopy intervals and identify the factors that influence shorter surveillance intervals to optimize surveillance strategies. Methods: We conducted a retrospective cohort study using a claims database of patients aged ≥ 40 years who underwent initial colonoscopy between April 2012 and December 2019. Based on the findings from the index colonoscopy, patients were categorized into four groups: diagnostic, endoscopic resection of polyps < 2 cm (ER < 2 cm), ER ≥ 2 cm, and endoscopic submucosal dissection (ESD). Colonoscopy intervals were estimated as time ratios (TRs) using an accelerated failure time model. Results: Among 147 390 patients (diagnostic: 97 621; ER < 2 cm: 47 303; ER ≥ 2 cm: 2190; and ESD: 276), the surveillance intervals were significantly shorter in the ER < 2 cm (TR = 0.56), ER ≥ 2 cm (TR = 0.33), and ESD (TR = 0.17) groups than in the diagnostic group (all p < 0.001). Older age, male sex, higher body mass index, nonsmoking status, regular alcohol consumption, and smaller facility size were independently associated with shorter intervals ( p < 0.05). Conclusions: This study revealed substantial variation in surveillance colonoscopy intervals in Japan, influenced by procedural, patient, and institutional factors. Shorter intervals observed in smaller facilities and specific subgroups may indicate inefficient use of medical resources and unequal access to care.

INTRODUCTION: Index colonoscopy findings can affect surveillance decisions that have an impact on the future risk of colorectal cancer (CRC). However, the effectiveness of surveillance colonoscopy in reducing CRC risk remains unclear. The aim of this study was to evaluate whether the timing of the first surveillance colonoscopy affected CRC incidence rates. METHODS: We conducted a retrospective cohort study at 2 community endoscopy clinics between 2005 and 2021, including 20,397 individuals. Based on the findings at index colonoscopy, we categorized into 4 groups: advanced adenoma (AA), ≥3 non-AAs, 1–2 non-AAs, and no adenoma. We compared the cumulative incidence of CRC among these groups, focusing on whether the first surveillance interval was less than or greater than 3 years after index colonoscopy. RESULTS: Index colonoscopy findings identified 11,601 subjects with no adenoma, 5,288 with 1–2 non-AA, 1,484 with ≥3 non-AA, and 2,024 with AA. There were 50 cases of CRC: 23 in the no adenoma, 10 in the 1–2 non-AA, 6 in the ≥3 non-AA, and 11 in the AA group. First surveillance after 3 years was associated with a higher incidence of subsequent CRC in the AA group (hazard ratio 3.49, 95% confidence interval 1.06–11.46, P = 0.04). DISCUSSION: In the AA group, surveillance colonoscopy within 3 years was associated with a lower risk of CRC. These findings suggest that a first surveillance within 3 years is particularly effective in subjects with AA.

Background: To characterize real‐world pharmacotherapy patterns among Japanese children with chronic functional constipation (CFC), with particular attention to changes after the market introduction of polyethylene glycol (PEG) 4000 in 2019. Methods: This longitudinal descriptive study was conducted using a Japanese health insurance claims database. We identified children aged 0–14 years who had an outpatient claim with a constipation diagnosis and received an initial prescription for laxatives lasting ≥5 days at the same visit between 2012 and 2022. We described baseline characteristics and laxative treatment trajectories throughout a 12‐month follow‐up. Subgroup analyses were performed by sex, age, and institution type. Results: Among 166,808 eligible children, 64.1% entered the cohort after 2019. Mean age was 4.0 years and 56.6% were female. Magnesium oxide was the most commonly used laxative (31.0%), followed by PEG 4000 (19.9%). Introduction of PEG 4000 in 2019 was accompanied by a decline in prescriptions for other conventional agents. Medication choices varied by age: magnesium oxide was predominant across all age groups; PEG 4000, malt extract, and lactulose were more commonly used in younger children; and traditional Japanese Kampo medicine was favored in older children. Conclusions: Magnesium oxide remains the most frequently prescribed laxative for pediatric CFC in Japan, with PEG 4000 now ranking second. The introduction of PEG 4000 in 2019 reduced reliance on other conventional laxatives. These findings may help clinicians tailor pharmacotherapy for childhood constipation.

Cronkhite‐Canada syndrome (CCS) is a rare disease characterized by gastrointestinal polyposis, skin pigmentation, alopecia, and abnormal nailfolds. Although colorectal cancer has been reported in patients with CCS, reports are limited regarding the effectiveness of the usage of image‐enhanced endoscopy in CCS lesions. Here, we report a case of CCS in which narrow‐band imaging (NBI) magnifying endoscopy was applied to detect an adenomatous component in multiple hamartomatous polyps. A 79‐year‐old female complained of taste disorder, anorexia, and weight loss over several months. Endoscopic examination revealed multiple reddened polyps in the stomach and colon, leading to a diagnosis of CCS. Narrow‐band imaging magnification showed sparse and dilated round pits on the CCS polyps. Furthermore, 12 out of the numerous colorectal CCS polyps had a coexisting light reddish elevated component with a regular distribution of microvessels and a regular reticular pattern. This pattern satisfied the criteria for Type 2A of the Japan Narrow‐band‐imaging Expert Team classification, indicating adenoma. After resection, these twelve polyps were subject to pathological analysis, which confirmed they were all hamartomatous polyps with low‐grade adenoma on the superficial layer. Immunohistochemical analysis revealed a significant increase in the Ki‐67 index and p53 staining only in the adenomatous lesions. We conclude that narrow‐band imaging magnifying endoscopy would be useful in differentiating adenoma from CCS‐related polyps, which thereby facilitates early detection and treatment of precancerous lesions.