和歌山医科大学

With recent advances in chemotherapy for unresectable pancreatic ductal adenocarcinoma (PDAC) with liver metastasis (LM), attempts have been made to resect the primary tumor in patients showing favorable responses to anti-cancer treatment (so-called “conversion surgery”; CS). This study aimed to clarify the outcomes of CS for PDAC with LM in a nationwide multicenter study. This retrospective, multicenter study was conducted as a project study of the Japan Pancreas Society and included patients with PDAC with LM at initial diagnosis, diagnosed radiologically or intraoperatively (occult LM), who underwent CS after at least 4 months of chemotherapy between 2010 and 2022. Survival outcomes and prognostic factors were analyzed. 90 patients were enrolled from 31 Japanese institutions. Median duration of preoperative chemotherapy was 10.4 (range, 4.2–58.5) months, and gemcitabine plus nab-paclitaxel was the most common first-line regimen, followed by folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin. Liver metastasectomy was performed in 27 patients (30

Whether hyperuricemia (HU) independently predicts cardiovascular disease (CVD) remains debated, whereas chronic kidney disease (CKD) is a well-established risk factor. This study assessed the independent and mediated association of HU in CKD on long-term CVD mortality in a 30-year nationwide Japanese cohort. Data from NIPPON DATA90 participants aged ≥ 30 years enrolled in 1990 and followed for up to 30 years were used. HU was defined as serum uric acid ≥ 416.4 µmol/L, and CKD as an estimated glomerular filtration rate < 60 mL/min/1.73 m² or positive proteinuria. Four baseline categories were created (neither, HU-only, CKD-only, both conditions), and analyzed via Cox models to estimate hazard ratios (HR) for CVD mortality, adjusted for age, sex, hypertension, diabetes mellitus, dyslipidemia, BMI, and history of smoking/alcohol. Among 7,336 participants (58.5

Nivolumab plus ipilimumab (NIVO + IPI) is a standard first-line therapy for intermediate-risk and poor-risk metastatic renal cell carcinoma (mRCC), but the long-term prognostic impact of prior primary tumor resection in this setting remains unclear. We retrospectively reviewed patients with mRCC that received NIVO + IPI as first-line therapy at eight Japanese institutions between October 2015 and May 2022. Patients were stratified into groups according to timing of metastasis and prior primary tumor resection (cytoreductive nephrectomy; CN): a metachronous group, a synchronous/CN(+) group, and a synchronous/CN(−) group. Progression-free survival, overall survival, and tumor responses were compared among groups, with a median follow-up of 54 months. Among 135 eligible patients, 40 were classified into the metachronous group (30

Background Reliable biomarkers for prognostication and recurrence surveillance in esophageal squamous cell carcinoma (ESCC) remain limited. The authors therefore investigated the potential clinical utility of exosomal DNA, which has emerged as a promising component of liquid biopsy. Methods This study screened 54 patients with ESCC. After exclusions, 210 blood samples from 21 patients underwent mutation-specific droplet digital polymerase chain reaction assays of plasma exosomal DNA (exoDNA) and circulating tumor DNA (ctDNA) before and after treatment. Kaplan-Meier and receiver operating characteristic analyses were performed to examine associations with overall survival (OS), disease-specific survival (DSS), relapse-free survival (RFS), and recurrence. Results Pretreatment exoDNA positivity was significantly associated with shorter DSS (p = 0.035) and shorter RFS (p = 0.048). Post-treatment exoDNA positivity was significantly associated with shorter OS (p = 0.0008), DSS (p = 0.0001), and RFS (p = 0.0001). Post-treatment ctDNA positivity was associated with shorter DSS (p = 0.038). Conclusions In ESCC, exoDNA demonstrated prognostic and predictive value, supporting its potential role as a complementary biomarker for postoperative surveillance.

Diphenidine (DPD) is a dissociative novel psychoactive substance (NPS) structurally related to phencyclidine and ketamine. Although DPD is legally regulated in Japan and several other countries, analogues sharing the core scaffold are not comprehensively regulated. Therefore, it is possible that analogues with minor scaffold modifications may continue to emerge. This study examined the effects of methoxy or hydroxy substitution at the 4-position of DPD on its blood–brain barrier (BBB) penetration and dopamine release in the synaptic cleft. Using in vivo brain microdialysis in freely moving unanesthetized rats, DPD, 4-methoxydiphenidine (4MeO-DPD), and 4-hydroxydiphenidine (4OH-DPD) (20 mg/kg, i.p. each) were administered, and concentrations in the nucleus accumbens and plasma were quantified by liquid chromatography–mass spectrometry. Extracellular dopamine levels were determined by high-performance liquid chromatography with electrochemical detection. To investigate carrier-mediated BBB transport, verapamil (P-glycoprotein, P-gp, inhibitor) or diphenhydramine (organic cation transporter, OCT, inhibitor) was administered 1 h prior to each compound. DPD and its analogues showed distinct BBB penetration profiles, among which 4OH-DPD showed the highest brain concentrations and dopamine release. Verapamil but not diphenhydramine pretreatment significantly increased brain extracellular concentrations and prolonged elimination half-lives of all compounds, particularly 4MeO-DPD. P-gp inhibition elevated brain-to-plasma concentration ratios, indicating restricted BBB penetration by P-gp. The dopamine concentration profile was consistent with those observed for DPD and its analogues. This study demonstrates that 4MeO-DPD and 4OH-DPD strongly elicit dopamine release compared with DPD. These findings show that P-gp regulates BBB penetration, offering important insights for the toxicological risk assessment for newly emerging NPS.