Background: Since inflammation and the immune system contribute to the development and progression of malignancies, parameters that reflect a host’s immune-inflammatory status may be useful prognostic indicators of gastric cancer (GC). The present study examined the clinical significance of a preoperative systemic immune-inflammation index (SII) for predicting postoperative survival outcomes in GC.Methods: A total of 447 patients who underwent curative gastrectomy for GC were included in the present study. SII was calculated as platelet count × neutrophil count/lymphocyte count. The prognostic impact of preoperative SII was examined using univariate and multivariate analyses.Results: Preoperative SII ranged between 105 and 4455 (median 474), and the optimal cutoff value for predicting overall survival (OS) was 395 based on a receiver operating characteristic curve. The 5-year OS rate of the SII ≥ 395 group was 80.0%, which was significantly worse than that (92.7%) of the SII < 395 group (p< 0.001). The multivariate analysis identified SII ≥ 395 (hazard ratio [HR] 2.95; 95% confidence interval [CI] 1.49–6.39;p= 0.001), heart disease (HR 2.14, 95% CI 1.07–4.07), C-reactive protein ≥ 0.5 (HR 2.45, 95% CI 1.15–4.94), pT4 (HR 4.46, 95% CI 2.44–8.14), and pN+ (HR 4.02, 95% CI 2.10–7.93) as independent predictors of worse OS. Peritoneal recurrence was more frequent in the high SII group than in the low SII group (p= 0.028).Conclusion: Preoperative SII may be a useful predictor of postoperative survival outcomes in GC. The meticulous surveillance of GC relapse, particularly peritoneal dissemination, is necessary for patients with SII ≥ 395 even after curative gastrectomy.

Early gastric cancer (EGC) has excellent postoperative survival outcomes; thus, one of the recent keywords in the treatment of EGC is “function‐preserving gastrectomy (FPG).” FPG reduces the extent of lymphadenectomy and gastric resection without compromising the long‐term prognosis. Proximal gastrectomy (PG) is an alternative to total gastrectomy (TG) for EGC in the upper‐third of the stomach, in which the gastric reservoir, gastric acid secretion, and intrinsic factors are maintained. Distal gastrectomy (DG) with a small remnant stomach, namely subtotal gastrectomy (STG), is another option for upper EGC, where the function of the cardia and fundus is preserved. Pylorus‐preserving gastrectomy (PPG) is a good alternative to DG for EGC in the middle‐third of the stomach, where pyloric function is preserved. Following elucidation of the markedly low incidences of possible metastasis to lymph node stations where dissection is omitted, the oncological safety of these FPG procedures was clarified. Nutritional advantages of PG or STG over TG have been reported; however, the standardized reconstruction methods after PG are yet to be established, and it is important to devise methods to prevent postoperative gastroesophageal reflux and anastomotic complications regardless of the reconstruction method. Nutritional benefits of PPG compared with DG have also been clarified, in which reducing postoperative gastric stasis is important. For the further spread of these FPG procedures, several issues, such as precise evaluation of preserved function, confirmation of oncological safety, and standardization of the technique, should be addressed in future prospective randomized controlled trials.

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

Circular RNA is a novel endogenous non‐coding RNA that can serve as a biomarker because of its stable loop structure. We investigated and examined the utility of plasma circERBB2 as a prognostic biomarker in 70 patients with gastric cancer who underwent gastrectomy. We investigated by real‐time quantitative PCR the circERBB2 concentrations in the preoperative and postoperative plasma and the circERBB2 expression in the resected tumors. The relationships between circERBB2 concentration in plasma and the clinicopathological features and prognosis were analyzed. circERBB2 was detected in the preoperative plasma samples of 37 patients. The presence of circERBB2 in preoperative plasma (high group) was significantly correlated with lymph node metastasis (P = .035) and tended to be correlated with men (P = .069). Both relapse‐free and overall survival were significantly poor in the high group (P = .001 and P = .009, respectively). The Cox proportional‐hazard model revealed that the high group was an independent prognostic factor of relapse‐free survival (P = .038). Among 16 patients of the high group, 13 patients did not show circERBB2 in the postoperative plasma. The concentration of circERBB2 in plasma was significantly higher in patients with recurrent cancer than those recurrence‐free patients (P < .001). In 2 patients with recurrent cancer, plasma circERBB2 concentrations were increased, whereas, in 2 recurrence‐free patients, these concentrations hardly changed during the treatment progress. The circERBB2 concentrations in preoperative plasma samples can be considered as a noninvasive prognostic biomarker for gastric cancer. Furthermore, monitoring the postoperative plasma circERBB2 concentrations may be useful for detecting gastric cancer recurrences.

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy. However, there are few useful markers for diagnosis and treatment. Glutathione S‐transferase Pi 1 (GSTP1) has been reported as a predictor of malignancy or anticancer drug resistance in some cancers. We investigated the association of GSTP1 expression with the malignancy or drug resistance in ESCC cell lines and clinical tissue samples. Proliferation and apoptosis assays regarding GSTP1 expression were examined in ESCC cell lines. Proliferation of GSTP1 knockdown cells was significantly decreased (P < .01), and the frequency of early apoptosis was increased (P < .05). Invasion capacity of GSTP1 knockdown cells was slightly decreased in transwell assay. These results suggest that GSTP1 plays an important role in malignant potential. To examine the effects of GSTP1 on drug resistance, chemosensitivity assay and apoptosis assay under cisplatin exposure were carried out. Viability of GSTP1 knockdown cells treated with cisplatin was lower than that of control cells (P < .01). Moreover, the frequency of early and late apoptosis in GSTP1 knockdown cells was markedly increased over that of control cells by cisplatin exposure (P < .01). In immunohistochemistry assay of resected tissue samples, GSTP1 expression was significantly associated with clinical downstaging (P = .04) in 72 ESCC patients with neoadjuvant chemotherapy. Furthermore, there was a significant association between GSTP1 expression in resected tissue and biopsy samples in 34 ESCC patients without neoadjuvant chemotherapy (P = .02). In summary, GSTP1 was related to malignant potential and may be a predictive marker of drug resistance in ESCC patients.