Ishikawa Prefectural Central Hospital

Correction: Overall survival of palbociclib plus endocrine therapy in Japanese patients with HR+/HER2- advanced breast cancer in the first-or second-line setting: a multicenter observational study (P-BRIDGE study)

The recommendation to discontinue low-dose aspirin (LDA) during the periprocedural period of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) remains controversial in patients at low thrombotic risk. If continuation of LDA does not increase bleeding risk, gastric ESD could be safely performed under sustained antiplatelet effects, benefiting patients. This study aimed to evaluate whether continuation of LDA is noninferior to discontinuation regarding ESD-related bleeding risk in patients with low thrombotic risk. Patients with gastric mucosal neoplasms and low thrombotic risk who were taking LDA were eligible. Participants were randomly assigned to either the discontinuation or continuation group. No prophylaxis was performed except for cauterizing exposed vessels at the ulcer base. The primary end point was the incidence of ESD-related major bleeding. A total of 551 patients were enrolled. In the modified intent-to-treat analysis, the incidence of ESD-related major bleeding (95%) was 7.6% (4.8-11) in the discontinuation group (n = 276) and 10% (6.9-14) in the continuation group (n = 275), yielding a risk difference of 2.5% (-2.3 to 7.4). The upper limit of the 2-sided 90% confidence interval (6.6%) exceeded the predefined noninferiority margin (Δ5%, P = 0.157). The per-protocol analysis supported this negative result, with a risk difference of 4.4% (-0.5 to 9.5). Two patients in the continuation group developed cerebral infarction. The noninferiority of LDA continuation over discontinuation for ESD-related major bleeding in gastric ESD was not demonstrated. Therefore, discontinuation of LDA during the periprocedural period is recommended for patients with low thrombotic risk (UMIN000013177).

Neuroblastoma is the most common extracranial solid tumor in children and often requires complex, multimodal treatment. A major advancement in its treatment has been the development of metaiodobenzylguanidine (MIBG), a norepinephrine analog, for diagnostic imaging and targeted radiotherapy. This review provides a comprehensive overview of the clinical applications and recent advancements of 131I-MIBG in neuroblastoma treatment. The agent has exhibited substantial efficacy in newly diagnosed and relapsed or refractory disease, through strategies such as monotherapy, tandem dosing, and high-dose administration with stem cell transplantation support. Combination regimens incorporating radiosensitizers, chemotherapeutic agents, and novel targeted approaches-including histone deacetylase inhibitors and immunotherapy-have further broadened its therapeutic scope. Challenges remain, including nonavid tumors, radiation-related risks, and logistical constraints. However, with the recent regulatory approval of 131I-MIBG for neuroblastoma treatment in Japan, its role is expected to expand, paving the way for improved outcomes and more personalized, targeted approaches in pediatric oncology.

Anticoagulant effects of direct oral anticoagulants (DOACs) are influenced by their plasma levels and anti-factor Xa (FXa) activity. Delayed bleeding is a major adverse event associated with endoscopic mucosal resection (EMR) of colorectal neoplasms. However, the association between post-EMR bleeding and pharmacodynamics in patients taking DOAC remains unknown. This study investigated the association between pharmacological risk factors and delayed bleeding in patients receiving DOAC. This multicenter prospective trial in Japan evaluated the incidence of post-EMR delayed bleeding in DOAC users between April 2018 and May 2022 and determined the association of post-EMR delayed bleeding with plasma levels and FXa activity. The incidence of post-EMR delayed bleeding was 10.5% (95% confidence interval [CI]: 5.3%-18.0%). There were large individual differences in plasma levels and FXa activity for each DOAC. At the trough and Tmax, plasma DOAC levels and plasma level/dose ratios were significantly correlated with FXa activity. Multivariate analysis showed that high anticoagulant ability was a risk factor for post-EMR delayed bleeding (adjusted OR, 12.211; 95% CI: 1.081-137.922, p = 0.043). DOAC users with high anticoagulant activity may be at higher risk of post-EMR delayed bleeding from colorectal neoplasms.

Double-tract reconstruction is commonly performed after proximal gastrectomy to prevent gastroesophageal reflux and ensure adequate nutrition. We developed a modified double-tract reconstruction intervention, denominated the NI method, in which the anastomosis between the remnant stomach and jejunum was strategically configured to optimize food passage and suppress gastroesophageal reflux. This retrospective study included patients with upper-third gastric cancer and adenocarcinoma of the esophagogastric junction who underwent proximal gastrectomy with either conventional or NI-modified double-tract reconstruction at two institutions. Postoperative outcomes, including body weight loss and incidence of reflux esophagitis, were compared. In total, 115 patients underwent proximal gastrectomy with double-tract reconstruction, including 35 with the NI method and 110 using the conventional method. No significant differences were observed in the baseline characteristics between the two groups. The incidence of reflux esophagitis was significantly lower in the NI group (0% vs. 14.3%, P = 0.032). Although not statistically significant, the NI group showed consistently lower weight loss rates, with approximately 2% less reduction at both 6 and 12months after surgery. The NI-modified double-tract reconstruction is a safe and function-preserving technique for proximal gastrectomy. The unique gastrojejunostomy design may contribute to reduce reflux and achieve better nutritional outcomes by restoring more physiological food passage.

Abstract We analyzed the differences in bacterial composition between 475 Japanese patients with advanced gastric cancer (median age 70 years, median BMI 20.0) and 106 healthy individuals using a comprehensive metagenome shotgun analysis. Among the patients with advanced gastric cancer, 71% were male, 37.% patients had relapsed, and 55.5% previously underwent gastrectomy. Bifidobacterium , Anaerostipes , and Parabacteroides were predominant in healthy individuals, whereas Streptococcus , Lactobacillus , and Odoribacter were predominant in patients with advanced gastric cancer. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that butanoate and pyruvate metabolism was enriched in healthy individuals, whereas factors such as ABC transporters and ribosomes were enriched in patients with advanced gastric cancer. Clustering analysis broadly classified patients with advanced gastric cancer and healthy individuals into two clusters; however, clustering using pathway data enabled a clearer classification of patients with advanced gastric cancer and healthy individuals than clustering using flora analysis. Moreover, healthy individuals showed higher bacterial flora diversity than patients with advanced gastric cancer. Thus, we successfully identified the molecular characteristics of microbial genera and functional pathways in the gut of patients with advanced gastric cancer. Our results suggest that fecal metagenomic shotgun sequencing analysis can be used to detect gastric cancer.

The Nuss procedure is widely applied for the treatment of pectus excavatum (PE); however, postoperative infection remains a significant concern. Herein, we evaluated the postoperative outcomes and risk factors for postoperative infections following the Nuss procedure. This study comprised a retrospective review of 112 cases of PE treated via the Nuss procedure between January 2019 and March 2024. Postoperative infection control measures, including thorough disinfection of the surgical field and perioperative intravenous administration of cefazolin, were ensured in all cases. Patient characteristics, surgical outcomes, and postoperative complications were analyzed, and risk factors for postoperative infection were assessed via multivariate analysis. Postoperative complications were observed in 17 cases (15.2%), including 6 (5.4%) with infection. Atopic dermatitis (AD) was significantly more common in the infection group (4/6, 66.7%) than in the non-infection group (8/106, 7.6%, p < 0.01). Multivariate analysis further identified the use of topical steroid medications for AD as the only independent risk factor for postoperative infection (Odds Ratio: 51.0, 95% CI: 7.12-366.0). Notably, two infections occurred beyond the typical 90-day surveillance period. AD is a significant risk factor for postoperative infection following the Nuss procedure, particularly when managed with topical steroid medications. These results suggest that patients with AD undergoing this procedure require meticulous preoperative management, rigorous infection control measures, and extended follow-up owing to the continued risk of infection throughout the bar placement period.

BackgroundThe real-world efficacy of the P2X3 antagonist gefapixant, a new class of antitussive for refractory chronic cough, is not yet fully understood. This study aimed to evaluate the real-world usage and response to gefapixant in patients with refractory chronic cough.MethodsThis multicentre retrospective study involved patients with refractory chronic cough who visited cough clinics and were prescribed gefapixant. Data collected included baseline demographics, cough characteristics, response to gefapixant, degree of taste disturbance (both assessed by cough specialists), and the course of cough after discontinuation, if applicable.Results272 cases were analysed. The population was predominantly middle-aged females, with most patients having asthmatic cough as a comorbidity, dry cough, and predominantly daytime cough. Half of the patients reported a response rate of ≥5 on a 0–10 scale, with 25% reporting a response rate of ≥8. Among responders (response rate ≥5), improvement was largely seen within 2 weeks. The median treatment duration with gefapixant was 32 days (interquartile range 14–175 days), with longer treatment periods observed in responders. Responders typically had more severe pre-treatment cough, dry cough, asthmatic cough as a comorbidity and specific laryngeal sensations. In patients who discontinued gefapixant, sustained improvement was observed in responders. Taste disturbance was not associated with response to gefapixant and was less frequent in patients with cough triggers such as smoke, dry air, or scents, than in those without these triggers.ConclusionsGefapixant demonstrated a rapid and effective antitussive effect in this multicentre, real-world study.

Clinical trials rarely focus on elder patients with castration-resistant prostate cancer (CRPC), and data on the outcomes of second-generation androgen receptor signaling inhibitors (ARSIs) remain limited. The ENABLE study for prostate cancer was an investigator-initiated, multicenter, randomized controlled trial conducted in Japan to compare enzalutamide (ENZ) and abiraterone plus prednisolone (ABI). This sub-analysis was performed to evaluate the efficacy and the safety profiles between patients aged ≥ 75 (older) and < 75 years (younger), and then between the ENZ and ABI arms in the older and the younger cohort separately. The ENZ arm included 41 younger and 51 older patients, while the ABI arm included 36 younger and 56 older patients. No significant differences in survival endpoints were observed between younger and older patients. Median time to prostate-specific antigen (PSA) progression (TTPP) was 15.2 months for younger and 21.2 months for older patients (HR 0.84, 95% CI 0.53-1.33, p = 0.4647). Median overall survival (OS) was 33.7 months for younger and 37.8 months for older patients (HR 0.80, 95% CI 0.50-1.29, p = 0.3651). Among older patients (n = 107), the ENZ arm had a TTPP of 21.2 months compared to 10.1 months for the ABI arm and an OS of 37.8 months compared to 44.7 months for the ABI arm (p = 0.1506 and p = 0.9321, respectively). Any grade and grade ≥ 3 adverse events were observed in 47 (61%) and 11 (14%) younger patients and 73 (68%) and 18 (17%) older patients, respectively. No significant differences were found in any grade or grade ≥ 3 adverse events between younger and older patients (p = 0.3487 and p = 0.6885, respectively). ARSIs demonstrated similar efficacy and safety in both younger and older patients. ENZ may be a more suitable option for older patients due to its higher PSA response rate. This trial was registered with the University Hospital Medical Information Network (UMIN) Center under identifier UMIN000015529.