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Background: Asporin (ASPN), a member of the proteoglycan family, has been shown to have a close correlation with cancer progression. It is not known whether ASPN is an oncogenic driver or a tumor suppressor in human gastric cancer. We sought herein to determine the relationship between ASPN expression and clinicopathological features of gastric cancer. Patients and Methods: A total of 296 gastric cancer patients (diffuse type, n = 144; intestinal type, n = 152) were enrolled. The ASPN expression level in each case was analyzed by immunohistochemistry. Results: ASPN was mainly found on stromal cells, especially on fibroblasts in tumor stroma, i.e., cancer-associated fibroblasts. The ASPN expression on either cancer cells or stromal cells was significantly high in macroscopic scirrhous-type tumors (p < 0.001) and histologically abundant stroma-type tumors (p < 0.001). Interestingly, a Kaplan-Meier survival curve of the 144 cases of diffuse-type gastric cancer revealed a significantly poorer prognosis in patients with ASPN-positive expression (p = 0.043; log rank) compared to those with ASPN-negative expression, but the prognoses were not significantly different in these subgroups of the 152 cases of intestinal-type gastric cancer. A multivariate analysis with respect to overall survival showed that ASPN expression on stromal cells and/or cancer cells was significantly correlated with overall survival in patients with diffuse-type gastric cancer (p = 0.041). Conclusion: In gastric cancer, ASPN was expressed mainly on stromal cells and partially on cancer cells. ASPN expression on stromal cells and/or cancer cells might be a useful prognostic marker in patients with diffuse-type gastric cancer. [ABSTRACT FROM AUTHOR]

Introduction: Cancer cachexia occurs in cancer patients more frequently as the cancer progresses, with a negative impact on treatment outcomes. In this study, we sought to clarify the clinical impact of a cancer cachexia index (CXI) in patients with gastric cancer (GC) undergoing gastrectomy. Methods: Between January 2013 and December 2018, we reviewed data from 556 patients treated for GC at our hospital. CXI was calculated using skeletal muscle index (SMI), serum albumin, and neutrophil-lymphocyte ratios (NLR). Patients were divided into high (n = 414) or low CXI (n = 142) groups. We investigated the clinical impact of CXI in patients with GC undergoing gastrectomy. Results: Multivariate analyses of 5-year overall survival (OS) and cancer-specific survival (CSS) rates indicated that a low CXI was independently associated with unfavorable outcomes for patients with GC. In multivariate analyses, SMI was independent predictor of OS but not CSS. NLR was not an independent predictor of either OS or CSS. Complication incidences (≥ Clavien Dindo 3) were non-significantly higher in the low (vs. high) CXI group. Conclusion: CXI was a more valuable prognostic biomarker when compared with SMI or NLR in GC patients undergoing gastrectomy. We suggest that patients with low CXI values should be given more comprehensive treatment, including exercise and nutritional therapy to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to clarify the risk of loss of independence (LOI) following gastrectomy in elderly patients with gastric cancer (GC). Methods: In this prospective study, frailty was assessed preoperatively by a frailty index (FI) in 243 patients aged ≥ 65 years who underwent gastrectomy for GC between August 2016 and December 2020. Patients were assigned into two groups (high FI vs. low FI) to investigate frailty and the risk of LOI after gastrectomy for GC. Results: Overall and minor (Clavien–Dindo classification [CD] 1, 2) complication rates were significantly higher in the high FI group, but the two groups had similar rates of major (CD ≥ 3) complications. The frequency of pneumonia was significantly higher in the high FI group. In univariate and multivariate analyses for LOI after surgery, high FI, older age (≥ 75 years), and major (CD ≥ 3) complications were independent risk factors. A risk score assigning 1 point for each of these variables was useful in predicting postoperative LOI (LOI: score 0, 7.4%; score 1, 18.2%; score 2, 43.9%; score 3, 100%; area under the curve [AUC] = 0.765.) Conclusions: LOI after gastrectomy was independently associated with high FI, older age (≥ 75 years), and major (CD ≥ 3) complications. A simple risk score assigning points for these factors was an accurate predictor of postoperative LOI. We propose that frailty screening should be applied for all elderly GC patients before surgery. [ABSTRACT FROM AUTHOR]

Background: This study investigated the impact and short-term surgical outcomes of two different main energy devices for robotic gastrectomy for gastric cancer. The outcomes of robotic gastrectomy with ultrasonic shears and those of robotic gastrectomy with conventional forceps were compared.Methods: We retrospectively evaluated 171 patients who underwent robotic distal gastrectomy or total gastrectomy for gastric cancer. We classified patients into the ultrasonic shears (US) and Maryland bipolar (MB) forceps groups according to the main energy device used for robotic gastrectomy.Results: We extracted 58 patients from the US group and 58 patients from the MB forceps groups using propensity score matching. The total console time (310 min [interquartile range (IQR), 253-369 min] and 332 min, [IQR, 294-429 min]; p = 0.022) and the console time to gastrectomy (222 min [IQR, 177-266 min] and 247 min [IQR, 208-321 min]; p = 0.004) were significantly shorter in the US group than in the MB forceps group. Less blood loss occurred in the US group than in the MB forceps group (20 mL [IQR, 10-40 mL] and 30 mL [IQR, 16-80 mL]; p = 0.014). The postoperative complication rate and postoperative hospital stay length were similar between groups. A multivariate multiple linear regression analysis demonstrated that the use of an ultrasonically activated device was one an independent factor that reduced the operative time of robotic gastrectomy.Conclusion: Using ultrasonic shears as the main energy device may contribute to better surgical outcomes after robotic gastrectomy for gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: The mesentery of the jejunum (MJ) of the Roux limb is conventionally divided when Roux-en-Y reconstruction is performed after total gastrectomy for gastric cancer (GC). However, the impact of dividing or preserving the MJ on anastomotic leakage (AL) at the esophagojejunostomy (EJS) site after minimally invasive total gastrectomy for GC is unclear.Methods: This retrospective cohort study enrolled 226 patients with GC who underwent EJS after laparoscopic or robotic total gastrectomy, including preservation of the MJ (n = 87) and division of the MJ (n = 137). The prevalence of anastomotic complications at the EJS and short-term outcomes were compared between groups using propensity score (PS) matching.Results: After PS matching, 69 patients were selected for the preserving and dividing MJ groups. There were no significant intergroup differences in patient backgrounds, including oncological stage, body mass index, and gender ratio. After PS matching, overall and severe complications after surgery were compared between the preserving and dividing MJ groups (21.7% vs. 27.5%, p = 0.554 and 8.7% vs. 13.8%, p = 0.137, respectively). However, the rate of AL at the EJS was significantly lower in the preserving than that in the dividing MJ group (1.4% vs. 13.0%, p = 0.017). In addition, the median postoperative hospital stay was significantly shorter in the preserving than that in the dividing MJ group (13.0 days vs. 16.0 days, p = 0.005).Conclusions: Preserving the MJ significantly reduced AL at the EJS after minimally invasive total gastrectomy for GC. [ABSTRACT FROM AUTHOR]

Background/Aims: Lysyl oxidase (LOX) family members play a key role in modifying the primary tumor microenvironment by crosslinking collagens and elastin in the extracellular matrix. The aim of this study was to analyze the LOX-like (LOXL)1, LOXL3, and LOXL4 expressions in gastric cancer tissue by immunohistochemical staining. Methods: The correlations between the clinicopathological features of 597 primary gastric carcinomas and LOX family members – LOXL1, LOXL3, and LOXL4 – were investigated by immunohistochemical studies. The effect of the transforming growth -factor β1 (TGFβ1) on the expressions of LOXL1, LOXL3, and LOXL4 in gastric cancer was examined using diffuse-type gastric cancer cell lines in vitro. Results: The expressions of LOXL1, LOXL3, and LOXL4 were correlated with T invasion, lymph node metastasis, and lymphatic and venous invasion. LOXL1 expression was associated with histological intestinal-type and expanding growth patterns. The overall survival of patients with LOXL1-, LOXL3-, or LOXL4-positive cancer was poorer than those with negative cancer. LOXL3 and LOXL4 mRNA expressions were significantly high in diffuse-type gastric cancer cells with high invasion ability. TGFβ decreased the LOXL1 expression and increased LOXL3 and LOXL4 expression. Conclusion: LOXL1, LOXL3, and LOXL4 expressions are associated with distant metastasis of gastric cancer. [ABSTRACT FROM AUTHOR]

Purpose: It was reported that the chemokine (C-X-C motif) ligand 1 (CXCL1) from cancer cells stimulated the recruitment of bone marrow-derived mesenchymal cells (BM-MCs) into tumor stroma via chemokine (C-X-C motif) receptor 2 (CXCR2) signaling. We conducted this retrospective study to determine the clinicopathologic significance of the CXCL1-CXCR2 axis in human gastric cancer. Methods: The correlations between the clinicopathological features of 270 primary gastric carcinomas and CXCL1 in cancer cells and CXCR2 in stromal cells were analyzed in immunohistochemical studies. The effect of gastric cancer cells on the expression of CXCR2 in BM-MCs was examined using diffuse-type gastric cancer cell lines in vitro. Results: The expression of CXCL1 in cancer cells was correlated with T invasion (T2–T4), lymph node metastasis, lymphatic invasion, venous invasion, peritoneal cytology, peritoneal metastasis and CXCR2 expression in stromal cells. The expression of CXCR2 in stromal cells was correlated with macroscopic type-4 cancers, histological type, T invasion (T2–T4), lymph node metastasis, lymphatic invasion, infiltration, peritoneal cytology, peritoneal metastasis and CD271 expression in stromal cells. The overall survival of patients with CXCL1 and CXCR2-positive cancer was poorer than that of the patients with negative cancer. Both CXCL1 expression in cancer cells and CXCR2 expression in stromal cells were independent prognostic factors for gastric cancer patients. Conclusion: The expressions of CXCL1 in cancer cells and CXCR2 in stromal cells are useful prognostic factors for gastric cancer patients. [ABSTRACT FROM AUTHOR]

Epithelial mesenchymal transition (EMT) is considered to be correlated with malignancy of cancer cells and responsible for cancer invasion and metastasis. We previously reported that distant metastasis was associated with hypoxia in gastric cancer. We therefore investigated the effect of hypoxic condition on EMT of gastric cancer cells. Gastric cancer cells were cultured in normoxia (21% O2) or hypoxia (1% O2) for 24 h. EMT was evaluated as the percentage of spindle-shaped cells in total cells. Effect of transforming growth factor β1 (TGFβ1) or tyrosine kinase inhibitors on the EMT was evaluated. The expression level of TGFβ1 and TGFβR was evaluated by real time RT-PCR. The TGFβ1 production from cancer cells was measured by ELISA. Hypoxia stimulated EMT of OCUM-2MD3 and OCUM-12 cells, but not that of OCUM-2M cells. The expression level of TGFβ1 mRNA under hypoxia was significantly higher than that under normoxia in all of three cell lines. The expression level of TGFβR mRNA was significantly increased by hypoxia in OCUM-2MD3 cells, but not in OCUM-2M cells. TGFβR inhibitor, SB431542 or Ki26894, significantly suppressed EMT of OCUM-2MD3 and OCUM-12. TGFβ1 production from OCUM-2MD3 and OCUM-12 cells was significantly increased under hypoxia in comparison with that under normoxia. These findings might suggest that hypoxia stimulates the EMT of gastric cancer cells via autocrine TGFβ/TGFβR signaling. [ABSTRACT FROM AUTHOR]