Kim TH, et al. J Gastric Cancer. 2023 Jan;23:e11. https://doi.org/10.5230/jgc.2023.23.e11

Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC. To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues. Secretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy. Our data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.

The purpose of this study was to show the feasibility and safety of pure single-port laparoscopic distal gastrectomy (SDG) by comparing its short-term outcomes with those of conventional multiport totally laparoscopic distal gastrectomy (TLDG). Prospectively collected data of 50 gastric cancer patients who underwent pure SDG from November 2011 through October 2013 were compared with the matched data of 50 TLDG patients. Mean operation time (144.5 vs 140.3 minutes; p = 0.561) and number of harvested lymph nodes (51.7 ± 16.3 vs 52.4 ± 17.9; p = 0.836) were comparable. Estimated blood loss was lower in the SDG patients (50.5 ± 31.5 mL vs 87.5 ± 79.6 mL; p = 0.007). Postoperative recovery was faster in the SDG patients in terms of lower maximum pain score on the operative day (6.1 ± 1.4 vs 6.9 ± 1.5; p = 0.015) and postoperative day 1 (4.6 ± 1.0 vs 5.5 ± 1.4; p < 0.001), less use of parenteral analgesics (0.8 ± 1.0 vs 1.4 ± 1.0; p = 0.020), and less increase in C-reactive protein level on postoperative day 5 (4.57 ± 6.26 mg/L vs 8.51 ± 5.25 mg/L; p = 0.008). Postoperative morbidity occurred in 6 (12%) and 5 (10%) patients in the SDG and TLDG group, respectively. This study showed that pure SDG is both safe and feasible for early gastric cancer, with similar operation time and better short-term outcomes than TLDG in terms of postoperative pain, estimated blood loss, inflammatory reaction, and cosmetic result.