早野 康一

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most malignant cancers in the world, which seriously affects the survival and quality of life of patients. Aberrant expression of microRNAs plays an important role in the occurrence and progression of cancer, while exosomes usually act as the transmission of intercellular substances (including miRNAs). The objective of this study was to investigate the relationship between the expression of exosomal miR-148a and ESCC. METHODS: Real Time-quantitative Polymerase Chain Reaction (qRT-PCR) was used to evaluate the expression level of miR-148a. cell counting kit-8(CCK-8) and transwell assays are used to detect the proliferation and invasion of cancer cells. Kaplan-Meier method was used to calculate the survival rate of ESCC patients. RESULTS: The survival rate of ESCC patients was significantly separated by the expression level of exosomal miR-148a, and the overall survival time of patients with high expression of exosomal miR-148a was significantly higher than that of the group with low expression. In the cell function test, the expression of miR-148a in ESCC cell lines was significantly lower than that in normal cell lines. Overexpression of miR-148a significantly reduced the proliferation, migration and invasion of cancer cells compared with the control group. CONCLUSIONS: Conclusions: miR-148a can inhibit the proliferation, migration, and invasion of cancer cells, and patients with high expression of exosome miR-148a in ESCC patients have a longer survival, suggesting that exosome miR-148a can inhibit cancer progression, and may be used as an indicator for the diagnosis and prognosis of ESCC.

INTRODUCTION: Patients with large Stage IV gastric cancer (GC) invading the proximal stomach find it difficult to receive not only bypass surgery but also S-1-based chemotherapy. This study aimed to show our treatment results for those GC patients using elementary diet (ED) tubes, which enabled S-1-based chemotherapy and nutrition support. CASE PRESENTATION: We evaluated 20 patients (13 men and 7 women; median age 70 years) with large Stage IV GCs (8.7-21.9 cm) invading the proximal stomach, who were admitted due to inability to eat, treated with S-1-based chemotherapy using an ED tube. The duration from the initiation of the chemotherapy to the improvement of oral intake, changes in nutritional status, and disease-specific survival (DSS) were retrospectively investigated. Two of the 20 patients failed to complete even one cycle of chemotherapy due to severe nausea or diarrhea. The other 18 patients improved oral liquid intake after 47.5 ± 18.8 days, and 17 patients improved oral solid food intake after 54.5 ± 19.6 days from the start of chemotherapy. In addition, three patients (16.7%) could receive conversion surgery after improvement of oral intake. The median DSS of those 18 patients was 13.1 months. Serum albumin level and prognostic nutritional index (PNI) were significantly improved after about 1 month of the treatment (both P <0.0001). Improvement of serum albumin level and PNI during the first 1 month of the treatment significantly correlated with better DSS (P = 0.006, 0.01, respectively). CONCLUSIONS: Given a high oral intake success rate, S-1-based chemotherapy using an ED tube can be a promising treatment option for large Stage IV GC with poor oral intake.

Abstract Background Recent studies have focused on evaluating the biomarker value of textural features in radiological images. Our study investigated whether or not a texture analysis of computed tomographic colonography (CTC) images could be a novel biomarker for colorectal cancer (CRC). Methods This retrospective study investigated 263 patients with CRC who underwent contrast‐enhanced CTC (CE‐CTC) before curative surgery between January 2014 and December 2017. Multiple texture analyses (fractal, histogram, and gray‐level co‐occurrence matrix [GLCM] texture analyses) were applied to CE‐CTC (portal‐venous phase), and fractal dimension (FD), skewness, kurtosis, entropy, and GLCM texture parameters, including GLCM‐correlation, GLCM‐autocorrelation, GLCM‐entropy, and GLCM‐homogeneity, of the tumor were calculated. These texture parameters were compared with pathological factors (tumor depth, lymph node metastasis, vascular invasion, and lymphatic invasion) and overall survival (OS). Results Tumor depth was significantly associated with FD, kurtosis, entropy, GLCM‐correlation, GLCM‐autocorrelation, GLCM‐entropy, and GLCM‐homogeneity (p = 0.001, 0.001, 0.001, 0.001, 0.018, 0.008, and 0.001, respectively); lymph node metastasis was associated with GLCM‐homogeneity (p = 0.004); lymphatic invasion was associated with GLCM‐correlation and GLCM‐homogeneity (p = 0.001 and 0.012, respectively); and venous invasion was associated with FD, entropy, GLCM‐correlation, GLCM‐autocorrelation, and GLCM‐entropy of the tumor (p = 0.001, 0.033, 0.021, 0.046, respectively). In the Kaplan–Meier analysis, patients with high GLCM‐correlation tumors or high GLCM‐homogeneity tumors showed a significantly worse OS than others (p = 0.001 and 0.04, respectively). Multivariate analyses showed that the GLCM correlation was an independent prognostic factor for the OS (p = 0.021). Conclusion CE‐CTC‐derived texture parameters may be clinically useful biomarkers for managing CRC patients.

BACKGROUND: Tumor cells (TC) participate in tumor progression by altering the immune responses in the tumor microenvironment. However, the clinical relevance and prognostic effect of PD-L1 expression and tumor-infiltrating lymphocytes (TILs) in esophageal squamous cell carcinoma (ESCC) are unknown. The purpose of this study was to investigate the interactions and clinical significance of PD-L1 expression and TILs in ESCC. METHODS: Tissue specimens were collected from 126 patients with ESCC who underwent curative esophagectomy. Immunohistochemical analysis and multiplex immunofluorescence for CD4, CD8, CD25, FOXP3, and PD-L1 in the tumor were used to identify multiple tumor-infiltrating immune cells (TIIC), Tregs, and TC. RESULTS: PD-L1 was expressed in tumor cells (PD-L1 TC). PD-L1 TIIC and PD-L1 TC affected the biological behavior of TC. The positive expression rate of PD-L1 TC and CD8+ TILs was 27.8% (35/126) and 31.7% (40/126), respectively. Kaplan-Meier analysis showed that overall survival (OS) was significantly associated with decreased CD8+ TILs and PD-L1 TC-positive expression, which promote ESCC progression and metastasis. CONCLUSION: Tumor depth, CD8, and PD-L1 TC were independent prognostic factors in ESCC, and a predictive nomogram with these three risk factors improved the accuracy of predicting OS in patients with ESCC after surgical resection. The conjoint analysis of multiple immune-related factors is beneficial for stratifying patient survival risk.