Masahiro Yura

PURPOSE: Cure of metastatic gastric or gastroesophageal junction cancer (mGC/GEJC) with systemic chemotherapy alone is extremely rare. Although long-term follow-up from previous phase III studies suggest that durable complete response (CR) may occur in a limited number of patients with first-line treatment, clinical characteristics of such cases remain poorly characterized. MATERIALS AND METHODS: We retrospectively reviewed medical records of patients with mGC/GEJC who received systemic chemotherapy at our institute between April 2013 and March 2022. Patients were defined as having a potential cure if they demonstrated a clinical or pathologic CR, maintained progression-free survival for more than 3 years from the treatment initiation, and remained free from disease progression for at least 1 year after treatment discontinuation. Clinicopathologic features, treatment regimens, and biomarker profiles, including human epidermal growth factor receptor 2 (HER2), mismatch repair (MMR), programmed death ligand-1 (PD-L1), and claudin 18.2 (CLDN18.2), were analyzed. RESULTS: Fifty-one patients met the criteria for potential cure. The median age was 67 years and 72.5% of the patients were male and had single-organ metastasis. Among patients with assessable biomarker status, the proportions of positive cases were 23.5% for HER2 (n = 51), 23.3% for deficient MMR (dMMR; n = 43), 16.0% for CLDN18.2 (n = 25), and 30.0% for PD-L1 Combined Positive Score (CPS) ≥10 (n = 30). First-line therapy led to potential cure in 52.9% of patients. Ten patients were potentially cured with cytotoxic chemotherapy alone, while 23 and 26 patients received molecular targeted agents or immunotherapy, respectively. CONCLUSION: The introduction of molecular targeted agents and immunotherapy has expanded the chance of potential cure. The enrichment of dMMR, HER2-positive, and CPS-high tumors among potentially cured cases highlights the urgent need to develop effective therapies for those lacking actionable biomarkers.

PURPOSE: Perioperative fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is a standard treatment for locally advanced gastric/gastroesophageal junction cancer (GC/GEJC). The impact of biomarker status on the efficacy of perioperative FLOT remains unclear. This study evaluated the association between clinicopathological features, including biomarker status, and the efficacy of perioperative FLOT in patients with resectable GC/GEJC. PATIENTS AND METHODS: A retrospective observational study was conducted by reviewing medical records of patients treated with perioperative FLOT between February 2020 and March 2024. Eligible patients had histologically confirmed adenocarcinoma, resectable disease at stages cT2-4a and/or N0-3, M0, and underwent biomarker testing. RESULTS: Among 116 eligible patients, human epidermal growth factor receptor 2 (HER2) positivity was observed in 7.8%, whereas PD-L1 combined positive score (CPS) of ≥1, ≥5, and ≥10 was detected in 90.5%, 44.0%, and 15.5% of patients, respectively. Claudin-18 isoform 2 (CLDN18.2) positivity (2+/3+ in ≥75% of tumor cells) was observed in 30.2% of patients. Major pathological response (MPR) and pathological complete response (pCR) rates were 22.4% (95% CI, 15.3 to 31.0) and 8.6% (95% CI, 4.2 to 15.3), respectively. Diffuse-type histology was a negative indicator for pathological response. CLDN18.2 expression decreased significantly after preoperative FLOT, with the median H-score declining from 285.0 to 187.5 ( P < .001) in patients with CLDN18.2 positivity at initiation. Maintained CLDN18.2 positivity was more frequently observed in patients without MPR compared with those with MPR (53.8% v 12.5%, P = .05). CONCLUSION: HER2, PD-L1, and CLDN18.2 statuses were not linked to pathological response to FLOT in resectable GC/GEJC. CLDN18.2 expression significantly decreased after preoperative FLOT but remained higher in patients without MPR, suggesting that CLDN18.2-targeted therapy may warrant investigation in the perioperative setting.

Background: Innovations in artificial intelligence (AI) are revolutionizing surgical practices, enhancing the analysis and outcomes of complex procedures. Recent advances in AI‐based computer vision have enabled our team to develop a novel artificial intelligence model that can recognize defined steps of robotic distal gastrectomy (RDG). Methods: This study assessed 130 robotic surgical videos from two institutions, 69 and 61 videos, respectively. The AI model used TeCNO, a multi‐stage temporal convolutional network, and was trained using annotated videos with surgical steps defined by qualified surgeons. RDG step recognition predicted by the model was assessed using accuracy, precision, recall, and F‐value metrics, and statistical analysis was assessed. Results: Three data sets were established to train and test the model. AI trained on single institution training sets performs moderately well at predicting RDG surgical steps with accuracies ranging from 56% to 63%, whereas AI trained on the multi‐institutional data yielded a step recognition accuracy of 86%. These results were confirmed with F ‐scores and precision tests. Conclusions: We demonstrated that an AI step recognition model for RDG can predict surgical steps in an external video dataset with moderate accuracy. Furthermore, we conclude that training an AI model on a multi‐institutional dataset significantly increases its step recognition capabilities. These results confirm that our model can be utilized by external institutions, and that a diverse training set of RDG procedures from multiple institutions is valuable to developing an AI model with precise step recognition capabilities in new institutions.

Background Standard surgery for upper advanced gastric cancer without invasion of the greater curvature (UGC-GC) is spleen-preserving D2 total gastrectomy without dissection of the splenic-hilar nodes (#10). However, some patients with nodal metastasis to #10 survive more than 5 years due to nodal dissection of #10. If nodal metastasis to #10 is predictable based on the positivity of other nodes dissected by the current standard surgery without #10 nodal dissection, physicians may be able to consider #10 dissection. Methods This study retrospectively reviewed data from the National Cancer Center Hospital in Japan between 2000 and 2012. We selected cases that met the following criteria: (1) D2 or more total gastrectomy with splenectomy, (2) UGC-GC, and (3) histological type is gastric adenocarcinoma. We performed univariate and multivariate analyses concerning lymph node stations associated with #10 metastasis. Results A total of 366 patients were examined. A multivariate analysis revealed that #10 metastasis was associated with positivity of the nodes along the short gastric arteries (#4sa) and distal nodes along the splenic artery (#11d) (#4sa: p = 0.003, #11d: p = 0.016). When either key node was positive, the metastatic rate of #10 was 24.4%, and the therapeutic value index was 13.3. Conclusions #4sa and #11d were key lymph nodes predicting #10 nodal metastasis in UGC-GC. When these key nodes are positive on computed tomography before surgery or according to a rapid pathological examination during surgery, dissection of #10 should be considered even if upper advanced tumors are not invading the greater curvature.

Background: Advanced gastric cancer sometimes causes macroscopic serosal change (MSC) due to direct invasion or inflammation. However, the prognostic significance of MSC remains unclear. Methods: A total of 1410 patients who had been diagnosed with deeper-than-pathological-T2 gastric cancer and undergone R0 gastrectomy with lymph node dissection at the National Cancer Center Hospital during January 2000 and December 2012 were restrospectively reviewed. Results: MSC was not found in 108 of the 506 patients with pathological T4a (21.3%), whereas it was detected in 250 of the 904 patients with pathological T2-T3 (27.7%). The sensitivity, specificity and accuracy for diagnosing pathological serosa exposed (SE) by MSC were 78.7, 72.3 and 74.6%, respectively. The MSC-positive cases had a worse 5-year overall survival (OS) than the MSC-negative cases in pT3 (72.9% vs. 84.3%, p = 0.001), pT4a (56.2% vs. 73.4%, p = 0.001), pStageIIB (76.0% vs. 88.4%, p = 0.005), pStageIIIA (63.4% vs. 75.6%, p = 0.019), pStageIIIB (53.6% vs. 69.2%, p = 0.029) and pStage IIIC (27.6% vs. 50.0%, p = 0.062). A multivariate analysis showed that MSC was a significant independent predictor for the OS (hazard ratio [HR]: 1.587, 95%CI 1.209–2.083, p = 0.001) along with the tumor depth (HR: 7.742, 95%CI: 2.935–20.421, p < 0.001), nodal status (HR:5.783, 95% CI 3.985–8.391, p < 0.001) and age (HR:2.382, 95%CI: 1.918–2.957, p < 0.001). Peritoneal recurrence rates were higher in the MSC-positive cases than in the MSC-negative cases at each pT stage. Conclusions: In this study, the MSC was one of the independent prognostic factors in patients with resectable locally advanced gastric cancer.

Whether or not surgery alone is sufficient for treating patients with pathological stage T1N2M0 (Stage IIA), T1N3a/bM0 (Stage IIB/IIIB), and T3N0M0 (Stage IIA) gastric cancer who were not indicated for adjuvant treatment according to the Japanese gastric cancer treatment guideline remains unclear.