早野 康一

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.

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.

PURPOSE: To investigate the treatment outcomes of patients with non-occlusive mesenteric ischemia (NOMI) at our institution, we focused on their post-treatment return to social activities. METHODS: This study included patients with suspected NOMI who were referred to our department between 2011 and 2023. In-hospital mortality was also investigated as a prognostic factor. The Glasgow-Pittsburgh Outcome Categories (GPOC) score was used to evaluate the return to social activities. The relationship between in-hospital mortality and GPOC scores and patient background and treatment factors was examined. RESULTS: Eighty-two patients were included in the study. Among them, 54 (65.9%) died during hospitalization. Only 9 patients (11%) returned to their social activities. In the multivariate analysis, non-surgical management was found to be the only independent factor for in-hospital mortality. Positive portal venous gas on computed tomography, no open abdomen, no pre-onset catecholamine administration, platelet count < 100,000/µL, lactate level < 5 mmol/L, APTT < 46 s, and Sequential Organ Failure Assessment score < 11 were factors significantly associated with an increased likelihood of return to social activities. CONCLUSION: This is the first study to assess the post-treatment return to social activities among patients with NOMI. Our findings highlight the concerning reality that survivors may face prolonged dependence on medical care.

Esophageal squamous cell carcinoma (ESCC) is an intractable type of cancer that requires novel therapeutic modalities, since the therapeutic outcomes are often inadequate, even in response to multidisciplinary treatment. The antitumor effect of metformin, an antidiabetic drug, has been reported in esophageal cancer; however, its effects are diverse. Since various multidisciplinary therapies are used in ESCC, the antitumor effect of metformin is expected to be synergistic in some treatment strategies. The present review summarizes the antitumor effects of metformin and discusses its use in combination with existing therapies. The present study reviewed relevant studies where the molecular targets of metformin (AMPK and inflammatory system signals) were described, followed by the classification and organization of its antitumor effects, and subsequently summarized the current research on its antitumor effects, especially in ESCC. A number of studies have reported that metformin prevents the development of ESCC and exerts its antitumor effects through various pathways. In addition, metformin has been shown to inhibit tumor growth, induce apoptosis, inhibit cancer cell invasion, migration and angiogenesis into the tumor, and decrease tumor malignancy, such as metastasis. Furthermore, it may modulate host tumor immunity in a tumor-suppressive manner and is expected to improve prognosis following treatment for ESCC. Notably, metformin may be beneficial in combination with chemotherapy, such as cisplatin, and radiation. By contrast, it has been shown to potentially induce resistance to 5-fluorouracil. Finally, the effects of metformin in combination with other therapies are discussed in the present study, and perspectives on the potential benefits of metformin for future ESCC treatment are presented. In conclusion, the present review may be useful in improving the understanding of the wide range of antitumor effects of metformin. Although some concerning points remain, using metformin in ESCC treatment could be promising. Notably, more knowledge needs to be accumulated regarding the effects of metformin on ESCC.