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Aim: Immune checkpoint inhibitors (ICIs) are less effective in mismatch repair (MMR)‐proficient (pMMR) colorectal cancers (CRCs) than in MMR‐deficient CRCs. Here, we investigated changes in the tumor microenvironment after neoadjuvant chemotherapy (NAC) without radiotherapy in locally advanced rectal cancer (LARC) and the potential of ICIs as therapeutic agents for pMMR CRCs. Methods: This was an ad hoc analysis of a KSCC1301 randomized phase II trial in which patients with untreated resectable LARC were randomly assigned to receive S‐1 and oxaliplatin or folinic acid, 5‐fluorouracil, and oxaliplatin as NAC. Forty‐nine patients were studied in this ad hoc analysis. As a reference cohort, we assessed 25 rectal cancer patients who underwent surgery without NAC outside the randomized trial. Immune checkpoint molecules (ICMs; PD‐1, PD‐L1, CTLA‐4, LAG3), tumor‐infiltrating lymphocytes (TILs; CD8, FOXP3), and other related proteins were evaluated by immunohistochemistry. Next‐generation sequencing (NGS) using Oncomine™ Comprehensive Assay version 3 was conducted in 23 patients. Results: The expression levels of PD‐1, CTLA‐4, and LAG3 in the NAC group were significantly higher than in reference patients (p < 0.001). Additionally, the infiltration of CD8+ and FOXP3+ T cells, and the CD8/FOXP3 ratio were significantly higher in the NAC group than in reference patients (p < 0.0001). NGS analysis revealed no specific gene alteration related to TILs or ICMs. Conclusion: We demonstrated changes in the tumor immune microenvironment after NAC in pMMR rectal cancer. NAC was associated with increased expression of ICMs and TILs. Rectal cancer could be susceptible to combined immunotherapy with chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to identify biomarkers that predict efficacy of preoperative therapy and survival for esophageal squamous cell carcinoma (ESCC). Background: It is essential to improve the accuracy of preoperative molecular diagnostics to identify specific patients who will benefit from the treatment; thus, this issue should be resolved with a large-cohort, retrospective observational study. Methods: A total of 656 patients with ESCC who received surgery after preoperative CDDP + 5-FU therapy, docetaxel + CDDP + 5-FU therapy or chemoradiotherapy (CRT) were enrolled. Immunohistochemical analysis of TP53, CDKN1A, RAD51, MutT-homolog 1, and programmed death-ligand 1 was performed with biopsy samples obtained before preoperative therapy, and expression was measured by immunohistochemistry. Results: In all therapy groups, overall survival was statistically separated by pathological effect (grade 3 > grade 2 > grade 0, 1, P < 0.0001). There was no correlation between TP53, CDKN1A, MutT-homolog 1, programmed death-ligand 1 expression, and pathological effect, whereas the proportion of positive RAD51 expression (>=50%) in cases with grade 3 was lower than that with grade 0, 1, and 2 (P = 0.022). In the CRT group, the survival of patients with RAD51-positive tumor was significantly worse than RAD51-negative expressors (P = 0.0119). Subgroup analysis of overall survival with respect to positive RAD51 expression indicated preoperative chemotherapy (CDDP + 5-FU or docetaxel + CDDP + 5-FU) was superior to CRT. Conclusions: In ESCC, positive RAD51 expression was identified as a useful biomarker to predict resistance to preoperative therapy and poor prognosis in patients who received preoperative CRT. Administration of preoperative chemotherapy may be warranted for patients with positive RAD51 expression. [ABSTRACT FROM AUTHOR]

Background and Aim: The C‐reactive protein (CRP)/albumin (Alb) ratio has been reported as a novel prognostic marker in several cancers. The objective of this study was to investigate the prognostic value of the CRP/Alb ratio in patients who underwent surgery for adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC). Methods: Data for 144 patients who underwent surgery for AEG and UGC were reviewed. The CRP/Alb ratio, neutrophil–lymphocyte ratio, platelet–lymphocyte ratio, Glasgow Prognostic Score, and controlling nutritional status score were calculated, and the relationship between these biomarkers and postoperative prognosis was analyzed. Results: The optimal cutoff value of the CRP/Alb ratio was determined to be 0.1. According to the cutoff value of CRP/Alb ratio, patients were divided into two groups (CRP/Alb < 0.1, n = 124; CRP/Alb ≥ 0.1, n = 20). The 5‐year recurrence‐free survival and overall survival (OS) rates were significantly lower in the patients with the CRP/Alb ratio ≥ 0.1 than in those with the CRP/Alb ratio < 0.1 (recurrence‐free survival: 44.9% vs 77.9%, P = 0.0011; OS: 43.4% vs 82.0%, P < 0.0001). In the multivariate analyses, the N‐stage, and CRP/Alb ratio ≥ 0.1 were identified as independent predictive factors for OS in patients with AEG and UGC (P = 0.0061 and P = 0.0439, respectively). Conclusions: The CRP/Alb ratio was strongly associated with poor prognosis in patients who underwent surgery for AEG and UGC. [ABSTRACT FROM AUTHOR]

Background and Aim: The C-reactive protein (CRP)/albumin (Alb) ratio has been reported as a novel prognostic marker in several cancers. The objective of this study was to investigate the prognostic value of the CRP/Alb ratio in patients who underwent surgery for adenocarcinoma of the esophagogastric junction (AEG) and upper gastric cancer (UGC)., Methods: Data for 144 patients who underwent surgery for AEG and UGC were reviewed. The CRP/Alb ratio, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, Glasgow Prognostic Score, and controlling nutritional status score were calculated, and the relationship between these biomarkers and postoperative prognosis was analyzed., Results: The optimal cutoff value of the CRP/Alb ratio was determined to be 0.1. According to the cutoff value of CRP/Alb ratio, patients were divided into two groups (CRP/Alb < 0.1, n = 124; CRP/Alb ≥ 0.1, n = 20). The 5-year recurrence-free survival and overall survival (OS) rates were significantly lower in the patients with the CRP/Alb ratio ≥ 0.1 than in those with the CRP/Alb ratio < 0.1 (recurrence-free survival: 44.9% vs 77.9%, P = 0.0011; OS: 43.4% vs 82.0%, P < 0.0001). In the multivariate analyses, the N-stage, and CRP/Alb ratio ≥ 0.1 were identified as independent predictive factors for OS in patients with AEG and UGC (P = 0.0061 and P = 0.0439, respectively)., Conclusions: The CRP/Alb ratio was strongly associated with poor prognosis in patients who underwent surgery for AEG and UGC., (© 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)