DTR after LPG is a feasible, simple, and novel reconstruction method with excellent postoperative outcomes in terms of preventing reflux symptoms. Its clinical applicability must be validated by prospective randomized trials.

Objective The aim of this study was to evaluate the prognostic significance of the intratumor stromal proportion in gastric signet ring cell (SRC) carcinomas. Background Cancer stroma, as exemplified by cancer-associated fibroblasts (CAFs), plays critical roles in cancer proliferation, invasion, and metastasis. Methods One hundred seventy-five SRC carcinoma cases were classified according to the intratumor desmoplastic stromal proportion to then analyze the clinicopathologic characteristics of stroma-rich cases. We also investigated the impact of CAFs on the migration as well as on the phenotypic changes of gastric SRC carcinomas in vitro.Furthermore, we performed RNA sequencing of a pair of CAFs and normal-tissue-associated fibroblasts. Results Stroma-rich SRC carcinomas (64 of 175 cases, 36.5%) were associated with female patients (P = 0.045), large tumor size (P = 0.007), higher T category (P \ 0.001), and the presence of perineural invasion (P = 0.018). Patients with stroma-rich SRC carcinomas had a significantly shorter disease-free survival (P \ 0.001) and overall survival (P \ 0.001). However, in a subgroup analysis, the prognostic significance of the stromal proportion correlated only with patients with T3/4 disease. From multivariate analysis, the high stromal proportion is an independent prognostic factor to predict worse disease-free survival (hazard ratio 2.288; P = 0.001) and overall survival (hazard ratio 2.503; P = 0.001). We found that CAFs enhanced the migratory abilities of cancer cells through the epithelial-mesenchymal transition, and RNA sequencing results confirmed these findings. Conclusions The intratumor stromal proportion could be a useful prognostic biomarker and a potential therapeutic target in gastric SRC carcinomas.

Purpose: Histologic features of diffuse-type gastric cancer indicate that the tumor microenvironment (TME) may substantially impact tumor invasiveness. However, cellular components and molecular features associated with cancer invasiveness in the TME of diffuse-type gastric cancers are poorly understood. Experimental Design: We performed single-cell RNA-sequencing (scRNA-seq) using tissue samples from superficial and deep invasive layers of cancerous and paired normal tissues freshly harvested from five patients with diffuse-type gastric cancer. The scRNA-seq results were validated by immunohistochemistry (IHC) and duplex in situ hybridization (ISH) in formalin-fixed paraffin-embedded tissues. Results: Seven major cell types were identified. Fibroblasts, endothelial cells, and myeloid cells were categorized as being enriched in the deep layers. Cell type–specific clustering further revealed that the superficial-to-deep layer transition is associated with enrichment in inflammatory endothelial cells and fibroblasts with upregulated CCL2 transcripts. IHC and duplex ISH revealed the distribution of the major cell types and CCL2-expressing endothelial cells and fibroblasts, indicating tumor invasion. Elevation of CCL2 levels along the superficial-to-deep layer axis revealed the immunosuppressive immune cell subtypes that may contribute to tumor cell aggressiveness in the deep invasive layers of diffuse-type gastric cancer. The analyses of public datasets revealed the high-level coexpression of stromal cell–specific genes and that CCL2 correlated with poor survival outcomes in patients with gastric cancer. Conclusions: This study reveals the spatial reprogramming of the TME that may underlie invasive tumor potential in diffuse-type gastric cancer. This TME profiling across tumor layers suggests new targets, such as CCL2, that can modify the TME to inhibit tumor progression in diffuse-type gastric cancer. See related commentary by Huang and Brekken, p. 6284

Background Although the frequency of laparoscopic total gastrectomy (LTG) has been increasing, the procedure requires considerable experience because of its technical difficulty and the concern for oncological safety. This study intended to define the learning curve associated with the procedure. Methods All 256 cases of LTG performed from June 2003 to December 2012 were enrolled. The cases were divided into ten groups of 25 cases based on when they occurred. The learning curve was defined using the moving average method. LTG, performed in the absence of other procedures (pure-LTG, 132 cases), was extracted from the ten groups, and the mean operative time and estimated blood loss (EBL) were compared to define the learning curve. Retrieved lymph nodes, hospital stay, and complications were compared across the phases of the learning curve. LTG with spleen resection, performed in the absence of other procedures (pure-srLTG, 53 cases), was also analyzed by the same method. Results A three-phase learning curve of LTG was defined: the first two groups, the following two groups, and the final six groups (mean operative time: 223.0, 244.8, and 207.8 min, respectively, p = 0.003; mean EBL: 94.6, 237.0, and 116.5 ml, respectively, p \ 0.001). The rates of complications and open conversions were similar across the three phases. There were no significant differences in mean operative time, EBL, retrieved LNs, hospital stay, or complication rates between pure-LTG and pure-srLTG, after completing the respective learning curves. Conclusions Experience with approximately 100 LTG cases was required to complete learning of the procedure.