Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: −1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.

Although artificial ulcers generally heal faster than Helicobacter pylori-related or nonsteroidal anti-inflammatory drug-related peptic ulcers, endoscopic submucosal dissection (ESD)-induced gastric ulcers are usually treated with a proton pump inhibitor (PPI) for 4–8 weeks. The effect of oral administration of a PPI for 1 week on ESD-induced gastric ulcers has not yet been evaluated. In the present study, we evaluated the efficacy of oral PPI for 1 week in patients with ESD-induced ulcers. We selected 45 patients who underwent ESD for gastric mucosal tumors between June 2005 and July 2006 at Toyama University Hospital, and who met our inclusion criteria. All patients received omeprazole intravenously for 2 days after ESD and then orally for 1 week to prevent bleeding. Twenty two patients received no further omeprazole therapy (1-week group) and the rest received omeprazole orally for 7 more weeks (8-week group). Follow-up endoscopy was performed at 1 day, 4 weeks, and 8 weeks after ESD. We compared the ulcer healing rates between both groups. There were no significant differences between the groups in the ulcer-healing rate, because ulcers healed in 22 (96%) and 20 (91%) patients from the 8-week and 1-week groups, respectively. In our study, oral administration of omeprazole for 1 week was sufficient to achieve healing of ESD-induced artificial gastric ulcers. A larger prospective trial will be required to confirm these findings.

Objectives: To date, no second-line chemotherapy regimen for esophageal squamous cell carcinoma (SCC) has been established. This clinical trial aimed to assess the optimum dose of docetaxel plus nedaplatin (cis-diammine-glycolate platinum) as second-line chemotherapy. Methods: Patients with metastatic or recurrent esophageal SCC after treatment with cisplatin plus 5-fluorouracil received docetaxel (50 or 60 mg/m²) plus nedaplatin (70 mg/m²) on day 1 every 4 weeks. The recommended dose was based on dose-limiting toxicities defined during the first cycle. Results: From February 2009 to November 2011, 9 patients were enrolled in the study. Their median age was 62 years (range, 58 to 72 y). Six patients had undergone radiotherapy and 4 had undergone surgical resection of primary lesions. Dose-limiting toxicities were observed in 2 patients at dose level 1 (60 mg/m² docetaxel, 70 mg/m² nedaplatin) but not at dose level 0 (50 mg/m² docetaxel, 70 mg/m² nedaplatin). Thus, the maximum tolerated dose was established at dose level 1. No severe nonhematological toxicity was observed. No patient achieved complete response, but 2 (22%; 95% confidence interval, 0%-49%) achieved partial response and 3 had stable disease. Median progression-free and overall survival times were 2.1 and 9.5 months, respectively. Conclusions: Docetaxel plus nedaplatin chemotherapy seems to be a safe and feasible second-line regimen for the treatment of esophageal SCC. We recommend the administration of 50 mg/m² docetaxel (day 1) plus 70 mg/m² nedaplatin (day 1) every 4 weeks in a phase II study.

Introduction: The efficacy of immune checkpoint inhibitors (ICIs) is heterogeneous at each metastatic site, and tumor progression pattern is associated with survival; however, it remains unclear in gastric cancer (GC). Therefore, we aimed to clarify the progression pattern in response to ICIs in patients with GC, and we analyzed its mechanism focusing on the intratumoral immune cells.Methods: Patients who received ICIs were retrospectively classified into non-systemic and systemic progression groups based on their radiological assessments. Moreover, the best percentage change in target lesions from each organ was compared.Results: Among 148 patients, the non-systemic progression group showed a significant improvement in overall survival (OS) compared with the systemic progression group (median, 5.6 months vs. 3.3 months; HR, 0.53; 95%CI, 0.32–0.89; p = 0.012). Poor performance status (HR, 1.73, 95%CI, 1.00–2.87) and systemic progression (HR, 3.09, 95%CI, 1.95–4.82) were associated with OS. Of all metastatic sites, the liver showed the poorest percentage change, and liver metastasis (OR, 2.99, 95%CI, 1.04–8.58) was associated with systemic progression. Hence, intratumoral CD8+ T-cell density was lower in patients with liver metastasis than in those without liver metastasis after ICIs, although the density of CD4+ T-cells (Th1, Th17, and Treg) and CD163+ cells (TAM) were not significantly different.Conclusion: The new progression pattern was associated with OS in GC. Liver metastasis may be a predictive factor of systemic progression during ICIs by regulating intratumoral CD8+ T-cells.

(1) Background: Nivolumab plus chemotherapy is established as a first-line treatment for advanced gastric cancer (AGC). While mFOLFOX6 is commonly used for AGC with severe peritoneal metastasis, the efficacy of nivolumab combined with it remains uncertain. We evaluated the outcomes of nivolumab plus mFOLFOX6 for AGC with severe peritoneal metastasis in clinical practice. (2) Methods: This multicenter retrospective study was conducted between December 2021 and June 2023. We investigated AGC patients with massive ascites or inadequate oral intake due to severe peritoneal metastasis and who received nivolumab plus mFOLFOX6. (3) Results: Among 106 patients treated with nivolumab plus chemotherapy, 21 (19.8%) had severe peritoneal metastasis, with 14 receiving nivolumab plus mFOLFOX6. The median progression-free survival was 7.4 months (95%CI 1.9-10.1), and the median overall survival was 10.7 months (95%CI 5.3-NA), with four patients (28.5%) surviving more than 12 months. Improved ascites and oral intake were observed in 6/14 patients (42.8%) and 10/11 patients (90.9%), respectively. The major grade 3 or more adverse events included leukopenia (28.5%) and neutropenia (21.4%), with no severe immune-related adverse events reported. (4) Conclusions: The safety and moderate efficacy of nivolumab plus mFOLFOX6 were suggested even in AGC patients with severe peritoneal metastasis.