Yamaguchi University Hospital

要旨 【背景】 髄膜炎を主病巣としない侵襲性肺炎球菌感染症において，中枢神経感染症を考慮した対応をどこまで行うべきか明らかではない。今回我々は，侵襲性肺炎球菌感染症に伴う急性感染性電撃性紫斑病の治療中に，髄膜炎・脳室炎が明らかとなり治療変更を要した症例を経験したので報告する。 【症例】 65歳の男性が発熱と四肢の疼痛・紫斑のために救急搬送され，尿中抗原検査・血液培養の結果から肺炎球菌性電撃性紫斑病と診断された。来院時から軽度の意識障害を認めたが，高度の凝固障害のため腰椎穿刺は施行困難であった。高用量のCeftriaxone投与を行ったが，経過中に髄膜刺激症状が顕在化し，髄液検査と頭部MRIの所見から髄膜炎・脳室炎の合併と診断した。Vancomycinの併用を開始した後は速やかに改善が得られ，神経学的後遺症なく退院した。 【結語】 侵襲性肺炎球菌感染症に伴う電撃性紫斑病では，中枢神経感染症を合併することがあるが，初期の臨床所見における非特異性と出血傾向に伴う腰椎穿刺の困難さから，診断が遅れることがある。中枢神経感染症を念頭に置いた経験的治療を速やかに開始したうえで，病状が軽減次第髄液検査やMRIを施行し，その結果と臨床経過に基づき治療方針を再検討することが重要であると考えられた。

Background Urinary C-peptide testing is widely used to evaluate insulin secretion capacity from pancreatic β-cells. We report a case in which urinary C-peptide showed abnormally high levels during treatment with an angiotensin receptor-neprilysin inhibitor (ARNI). Case presentation The patient was a 54-year-old man undergoing treatment for type 2 diabetes mellitus and hypertension. Following an abnormal electrocardiogram during a health check-up, he was diagnosed with aortic valve insufficiency. During admission to the diabetes and endocrinology department for preoperative glycemic control, a clinical laboratory technologist first recognized a marked discrepancy between urinary and serum C-peptide results and reported this to the attending physician, prompting further investigation. A literature review revealed reports suggesting that ARNI administration may suppress C-peptide metabolism, potentially leading to elevation of measured values. Results The patient's excreted urinary C-peptide level decreased markedly after ARNI therapy was discontinued, suggesting that ARNI influences an increase in urinary C-peptide. Conclusions When excreted urinary C-peptide is abnormally elevated and discrepant from the serum C-peptide level, it is important to confirm ARNI use and follow laboratory-driven recommendations for retesting after discontinuation if needed. Prompt reporting of this finding by the clinical laboratory is essential for the accurate assessment of insulin secretion capacity.

Abstract Purpose: Postoperative pancreatic fistula (POPF) is a potentially fatal complication of distal pancreatectomy (DP) but the optimal prevention method is unknown. The standard methodology for DP is to dissect the pancreas using a stapler alone. This pilot study evaluated post-DP remnant closure by stapling plus a PGA felt patch and examined the predictors of POPF. Methods: We prospectively enrolled and analyzed 26 patients scheduled for DP in which the remnants were closed with staples and a PGA felt patch. Results: Primary disease included 17 pancreatic adenocarcinomas, 3 pancreatic neuroendocrine neoplasms, 2 mucinous cystic neoplasms, 2 solid pseudopapillary neoplasms, and 2 other disorders. The mean main pancreatic duct diameter at the excision site was 2.3 mm. The mean pancreatic parenchyma thickness was 12.3 mm. The mean pancreatic dissected line was 0.5 mm to the left from the left edge of the portal vein. We observed nine biochemical leaks and the formation of nine grade B POPFs. We found significant differences in the BMI, pancreatic parenchymal thickness, and pancreatic dissection line between patients with and without POPF. Conclusion: Although stapling and applying PGA felt did not show efficacy in preventing POPF, the pancreatic dissecting line was suggested as a risk factor.

Antigen heterogeneity remains a major obstacle to the effective application of chimeric antigen receptor (CAR)-T cell therapy in solid tumors. We investigated the potential of epitope spreading as a strategy to overcome this limitation and examined whether CAR-T cells concomitantly producing IL-7 and CCL19 (7 × 19 CAR-T cells) could act as potent inducers of epitope spreading, as well as the underlying mechanisms. We used a murine model inoculated with a mixture of cancer cell lines—genetically modified to express the CAR target antigen—and their respective parental lines lacking target expression. Following administration of 7 × 19 CAR-T cells, flow cytometry and peptide stimulation assays were performed to evaluate the induction of tumor antigen-specific T cells and dendritic cells within tumor-draining lymph nodes and tumor tissues. We also evaluated the antitumor efficacy of 7 × 19 CAR-T cells derived from an allogeneic donor and their capacity to induce epitope spreading in vivo and ex vivo. In multiple tumor mixture models, 7 × 19 CAR-T cells demonstrated marked antitumor activity and promoted epitope spreading in murine solid tumor models, enabling endogenous T cells to recognize and target tumor-associated antigens. This response was dependent on cross-presentation by defined dendritic cell subsets in both the tumor microenvironment and tumor-draining lymph nodes within 2 weeks of 7 × 19 CAR-T cell administration. Notably, 7 × 19 CAR-T cells derived from allogeneic donors also induced epitope spreading in tumor-bearing hosts, thereby increasing survival. The 7 × 19 CAR system is a promising strategy for overcoming antigen heterogeneity in solid tumors by promoting epitope spreading.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00262-026-04316-z.

Crohn's-disease-associated colorectal cancer, where chronic inflammation increases the risk of cancer development, is less common than other types of colorectal cancer. Pathological analyses of Crohn's-disease-associated colorectal cancer are limited. Herein, we present a case of Crohn's disease-associated colorectal cancer, suggesting stepwise carcinogenesis from the chronic inflammatory mucosa. A man in his 40s had a 28-year history of Crohn's disease with perianal involvement for over 20years. He visited our hospital due to worsening anal pain and fecal incontinence. Following clinical evaluation, he was diagnosed with anal canal cancer and subsequently underwent surgery. Histopathological examination revealed cancer originating from the chronically inflamed mucosa, suggesting p53-positive dysplasia, well-differentiated adenocarcinoma, and subsequently, mucinous adenocarcinoma. The final diagnosis was Crohn's-disease-associated anal canal cancer. Despite postoperative adjuvant chemotherapy, he exhibited pelvic recurrence and distant metastasis 20months postoperatively. A comprehensive multidisciplinary treatment intervention was implemented; however, he eventually succumbed to cancer progression 3years after surgery. This case suggests inflammation-associated stepwise carcinogenesis, demonstrating tumor heterogeneity and providing insights into dysplasia. Despite improved understanding from recent registry studies, the diagnosis and treatment of CD-CRC remain challenging in clinical practice, as seen in this case.

BackgroundOur Neurosurgery Department started inter-hospital medical collaboration using hotline telephones in 2000 and has been sharing images using videophone and smartphones since 2002. Currently, an image sharing system using Synapse (Fujifilm medical) is deployed at 15 hospitals in and outside of Yamaguchi Prefecture, and about 300 Doctor to Doctor (D2D) consultations are conducted annually. The consultations conducted so far have been D2D telephone consultations for acute diseases, mainly stroke and head trauma.ProblemWhile it is difficult to maintain advanced medical care of brain tumor in depopulated areas, a system is needed to enable consultation on treatment plans and advanced medical care at hospitals in depopulated areas in order to minimize the burden of patient travel. To achieve this, a system that (1) enables easy communication, (2) makes images available to all hospitals, and (3) is low-cost is needed.MethodsTo solve these problems, we established MEDIMONY, the first start-up company from our department, and have been developing the system. The system is based on a zero-touch system that allows hospitals in underpopulated areas to communicate with each other without having to operate the system. The zero-touch system is operated with ordinary tablets and uses LTE for communication, so Wi-Fi is not required for hospitals in depopulated areas. Doctor to Patient (D2P) with D has been in operation since May 2025, using this system to provide chemotherapy at hospitals in underpopulated areas.FutureThe company is also developing a system to share monitor images from electronic medical records without the need for an image sharing system, aiming to enable consultations at all hospitals. The company will continue to develop D2D and D2P with D for brain tumor patients in Yamaguchi Prefecture, aiming to create a model project that will enable equalization of medical care in depopulated areas.

IntroductionFibrates are effective triglyceride-lowering drugs, but they may affect bile acid metabolism, raising concerns about biliary adverse drug events (ADEs).ObjectiveIn this study, we used spontaneous reporting system databases to evaluate the association between fibrates and biliary ADEs. This study has been reported in accordance with the Reporting of a Disproportionality Analysis for Drug Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance guidelines.MethodsWe used data from the Japanese Adverse Drug–Event Report (JADER) and the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) databases. The signal detection metrics employed were reporting odds ratio (ROR), proportional reporting ratio, Bayesian confidence propagation neural network, and Gamma–Poisson Shrinker. We also conducted stratified disproportionality and time-to-onset analyses.ResultsWe identified 58 and 260 unique individual case safety reports from the JADER and FAERS databases, respectively. Primary disproportionality analysis of all fibrates in the JADER dataset revealed an ROR of 3.74 [2.88–4.85]. All other signal detection metrics also exhibited statistically significant associations. In the stratified disproportionality analysis, pemafibrate showed significant signals across all strata, confirming the robustness of the signal. In the Weibull analysis for pemafibrate, the shape parameter (β) was 1.59 [1.17–2.56], indicating an increasing trend in ADE reporting with continued pemafibrate use.ConclusionA significant signal for biliary ADEs was detected for fibrates in both databases, with a particularly consistent association for pemafibrate. Regular hepatobiliary monitoring and individualized patient management are recommended.

Introduction: The prognosis of patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer has improved with the introduction of oral EGFR-tyrosine kinase inhibitor (TKI). Lower adherence to oral anticancer medications is reportedly associated with a poor prognosis. It is important to understand the causes of lower adherence to oral anticancer medications. We aimed to assess the potential risk factors associated with low adherence to EGFR-TKIs in a real-world clinical setting using administrative claims data in Japan. Methods: We identified 10,809 outpatients routinely prescribed EGFR-TKIs between December 2015 and January 2023. Adherence to EGFR-TKIs was assessed based on the medication possession ratio (MPR) during the 12-month follow-up period from the date of first outpatient EGFR-TKI prescription. Multivariable linear regression analysis was performed to identify the potential risk factors associated with lower adherence. Results: The mean (standard deviation) MPR was 94.1% (14.0). Lower adherence was associated with increasing age (per 10-year increase), female sex, dysphagia, and a higher number of concomitant oral medications (per doubling of the count). Conclusion: Adherence to EGFR-TKIs was generally high, but the findings support tailored adherence strategies, especially for older patients and for those with a higher number of concomitant oral medications, including medication review to reduce pill burden and proactive support for swallowing difficulties.