Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study).

BACKGROUND: This randomized phase II study explored the superiority of trastuzumab plus S-1 plus cisplatin (SP) over SP alone as neoadjuvant chemotherapy (NAC) for HER2-positive resectable gastric cancer with extensive lymph node metastasis. METHODS: Eligible patients with HER2-positive gastric or esophagogastric junction cancer and extensive lymph node metastasis were randomized to receive three or four courses of preoperative chemotherapy with SP (arm A) or SP plus trastuzumab (arm B). Following gastrectomy, adjuvant chemotherapy with S-1 was administered for 1 year in both arms. The primary endpoint was overall survival, and the sample size was 130 patients in total. The trial is registered with the Japan Registry of Clinical Trials, jRCTs031180006. RESULTS: This report elucidates the early endpoints, including pathological findings and safety. The study was terminated early due to slow patient accruals. In total, 46 patients were allocated to arm A (n = 22) and arm B (n = 24). NAC was completed in 20 patients (91%) in arm A and 23 patients (96%) in arm B, with similar incidences of grade 3-4 hematological and non-hematological adverse events. Objective response rates were 50% in arm A and 84% in arm B (p = 0·065). %R0 resection rates were 91% and 92%, and pathological response rates (≥ grade 1b in Japanese classification) were 23% and 50% (p = 0·072) in resected patients, respectively. CONCLUSIONS: Trastuzumab can be safely added to platinum-containing doublet chemotherapy as NAC, and it has the potential to contribute to higher antitumor activity against locally advanced, HER2-positive gastric or esophagogastric junction cancer with extensive nodal metastasis.

Feasibility of laparoscopic/robot-assisted surgery for Borrmann type 4 gastric cancer: a comparison study with conventional open surgery.

BACKGROUND: Laparoscopic surgery for early gastric cancer is regarded as a standard of care because of robust evidences obtained by several phase-III trials. Furthermore, the efficacy of laparoscopic radical surgery for advanced gastric cancer has been also reported. Meanwhile, the feasibility of laparoscopic surgery for Bormann type 4 gastric cancer, special type with unfavorable prognosis, remains unclear since excluded from eligibility of these trials. METHODS: This study included 100 patients with type 4 gastric cancer who underwent laparoscopic/robot-assisted (minimally invasive surgery (MIS) group; n = 32) or open (Open group; n = 68) curative surgery between 2008 and 2021. After propensity score matching, 30 patients in each group were extracted for analysis. Clinical data, including surgical and midterm survival outcomes, were retrospectively compared between the two groups. RESULTS: Incidences of postoperative complication (≥ Clavien-Dindo grade III) were recorded in 23.3% in the MIS group and 13.3% in the Open group, but no statistical significance was demonstrated (P = 0.50). The 3-year overall survival rate in the MIS group was better than that in the Open group (80.2% vs. 53.5%, log-rank, P = 0.03). The trend of recurrence site was similar. Multivariate analysis showed that adjuvant chemotherapy was an independent favorable prognostic factor (hazard ratio, 0.33, 95% confidence interval 0.11-0.93) for overall survival. MIS was indicated as a favorable prognostic factor (hazard ratio, 0.39, 95% confidence interval 0.39-1.07), but without statistical difference. CONCLUSION: While multidisciplinary treatment is mainstay of treatment because of the poor prognosis of this disease, minimally invasive surgery may play an important role in treatment if appropriate patient selection is done. Further analyses with larger sample size are necessary to reach a final conclusion regarding oncological efficacy.

Surgical step recognition in laparoscopic distal gastrectomy using artificial intelligence: a proof-of-concept study.

PURPOSE: Laparoscopic distal gastrectomy (LDG) is a difficult procedure for early career surgeons. Artificial intelligence (AI)-based surgical step recognition is crucial for establishing context-aware computer-aided surgery systems. In this study, we aimed to develop an automatic recognition model for LDG using AI and evaluate its performance. METHODS: Patients who underwent LDG at our institution in 2019 were included in this study. Surgical video data were classified into the following nine steps: (1) Port insertion; (2) Lymphadenectomy on the left side of the greater curvature; (3) Lymphadenectomy on the right side of the greater curvature; (4) Division of the duodenum; (5) Lymphadenectomy of the suprapancreatic area; (6) Lymphadenectomy on the lesser curvature; (7) Division of the stomach; (8) Reconstruction; and (9) From reconstruction to completion of surgery. Two gastric surgeons manually assigned all annotation labels. Convolutional neural network (CNN)-based image classification was further employed to identify surgical steps. RESULTS: The dataset comprised 40 LDG videos. Over 1,000,000 frames with annotated labels of the LDG steps were used to train the deep-learning model, with 30 and 10 surgical videos for training and validation, respectively. The classification accuracies of the developed models were precision, 0.88; recall, 0.87; F1 score, 0.88; and overall accuracy, 0.89. The inference speed of the proposed model was 32 ps. CONCLUSION: The developed CNN model automatically recognized the LDG surgical process with relatively high accuracy. Adding more data to this model could provide a fundamental technology that could be used in the development of future surgical instruments.

Failure mechanisms data analysis during tension of additively manufactured Ti-6Al-4V alloy reinforced with nano-zirconia particles: Investigations of the crack path.

The data presented here aim to show how to analyze crack propagation of a novel metallic matrix composite of Ti-6Al-4V reinforced with 1 wt.% nano-yttria-stabilized zirconia processed by laser powder bed fusion technology. The data was acquired via microstructural observations and electron backscatter diffraction (EBSD) analyses after the quasistatic tensile tests at room temperature. The overall crack path configuration based on the fracture surface observation by scanning electron microscopy (SEM) was first operated, presenting two main regions: (i) local inclined planes (hereafter denoted as "stair-like"), and (ii) region in accordance with the theoretical mode I fracture plane. Thereafter, a series of EBSD data set on a surface obtained after longitudinal cut off operation on one failed piece was conducted at three distinct positions: (i) in the stair-like configuration region, (ii) in the mode I fracture region, and (iii) in the region where the crack path made his transition between these two mechanisms. Since the EBSD data sets were not prone to any post-processing filtering operation, comparison of the observed mechanism with other Ti-6Al-4V alloy processed by additive manufacturing (AM) technology can be easily carried out.

Comparison of the survival outcomes between retrocolic and antecolic Roux-en-Y reconstruction after gastrectomy for gastric cancer.

Background: There are two methods of Roux-en-Y (RY) reconstruction after gastrectomy: the antecolic route (ACR) and retrocolic route (RCR). There is no evidence to support that the ACR achieves comparable long-term survival. Methods: This was a multi-center historical cohort study. Patients diagnosed with clinical T3/4a and any N stage who underwent open gastrectomy and R0 resection for gastric adenocarcinoma between January 2006 and December 2012 were enrolled. The primary outcome was the hazard ratio of ACR for overall survival, with adjustment for confounding factors by propensity score matching, and a Cox proportional hazards model. Results: A total of 1758 eligible patients were identified from the database. After matching, 410 patients in the ACR and RCR groups were included in the final analysis. The adjusted hazard ratio (95% CI) for ACR was 1.148 (0.870-1.492). The five-year survival rates in the ACR and RCR groups were 74.3% (69.5-78.4) and 77.3% (72.3-81.2), respectively. The short-term surgical outcomes of the two groups did not differ to a statistically significant extent. Conclusion: The route used to lift the jejunum in RY reconstruction did not affect the incidence of long-term survival or postoperative complications. The ACR and RCR are both acceptable options for RY reconstruction during gastric cancer surgery.

Definitive chemoradiotherapy induces T-cell-inflamed tumor microenvironment in unresectable locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Chemoradiotherapy (CRT) modulates the tumor immune microenvironment of multiple cancer types, including esophageal cancer, which potentially induces both immunogenicity and immunosuppression by upregulating the presentation of tumor-specific antigens and immune checkpoint molecules in tumors, respectively. The prognostic effects of immune modification by CRT in esophageal squamous cell carcinoma (ESCC) remain controversial because of the lack of detailed immunological analyses using paired clinical specimens before and after CRT. We aimed to clarify the immunological changes in the tumor microenvironment caused by CRT and elucidate the predictive importance of clinical response and prognosis and the rationale for the necessity of subsequent programmed cell death protein 1 (PD-1) inhibitor treatment. METHODS: In this study, we performed a comprehensive immunological analysis of paired biopsy specimens using multiplex immunohistochemistry before and after CRT in patients with unresectable locally advanced ESCC. RESULTS: CRT significantly increased the intra-tumoral infiltration and PD-1 expression of CD8+ T cells and conventional CD4+ T cells but decreased those of regulatory T cells and the accumulation of tumor-associated macrophages. Multivariate analysis of tumor-infiltrating T-cell phenotypes revealed that the density of PD-1+CD8+ T cells in the tumor after CRT could predict a confirmed complete response and favorable survival. CONCLUSIONS: This study showed that CRT improved the immunological characteristics of unresectable locally advanced ESCC and identified the density of PD-1+CD8+ T cells as a predictive factor for prognosis. This finding supports the rationale for the necessity of subsequent PD-1 inhibitor treatment.