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Background: LLND in cases with suspected lateral lymph node (LLN) metastasis has been focused on as a novel treatment strategy in recent years. However, the optimal indication for LLND in rectal cancer patients has not been determined. This study aimed to establish the optimal indication for lateral lymph node dissection (LLND) in patients with rectal cancer using magnetic resonance imaging (MRI). Methods: A total of 209 patients with rectal adenocarcinoma who underwent total mesorectal excision and LLND in 13 hospitals were prospectively registered. By matching the sizes of the harvested LNs and those in magnetic resonance imaging (MRI), the pathological outcome of each LN was confirmed one-by-one. Using parameters of the LLNs in MRI, the optimal diagnostic criteria for LLND were established. Results: Of 3241 harvested LLNs, including 83 metastatic nodes, 1010 (31.1%) were visualized on MRI. Although all parameters assessed showed strong correlations with the presence of metastasis, none of these parameters could discriminate metastatic LLNs from non-metastatic nodes with sufficient sensitivity. However, by using the combination of long axis and short/long ratio in pretreatment MRI, we could establish optimal criteria for LLND. The sensitivity and specificity of the criteria for LLN metastasis were 94.3% and 40.2%, respectively. Conclusions: In conclusion, we established novel criteria for LLND in rectal cancer patients using MRI. Our criteria will be of great clinical use in determining indications for LLND. [ABSTRACT FROM AUTHOR]

Immunogenic neoantigens derived from somatic mutations in cancer have been identified through clinical studies with the cloning of tumor-infiltrating T cells, and cancer driver gene mutation-derived epitopes have been reported; however, these are rare. At present, the validation of epitopes predicted in silico is difficult as human T-cell clonal diversity cannot be reproduced in vitro or in experimental animal models. To confirm the epitope peptides presented by human leukocyte antigen (HLA) class I molecules predicted in silico, biochemical methods such as major histocompatibility complex (MHC) stabilization assays and mass spectrometry-mediated identification have been developed based on HLA-A*02:01 monoallelic T2 cells and HLA-C*01:02 monoallelic LCL721.221 cells. Therefore, in the present study, to prevent confusion due to peptide cross-presentation among HLA molecules, HLA class I monoallelic B-cell clones were generated from the TISI cell line by knocking out HLA-ABC and TAP2, and knocking in HLA alleles. To explore cancer driver mutations as potential targets for immunotherapy, exome sequencing data from 5,143 patients with cancer enrolled in a comprehensive genome analysis project at the Shizuoka Cancer Center were used to identify somatic amino acid substituted mutations and the 50 most frequent mutations in five genes, TP53, EGFR, PIK3CA, KRAS and BRAF, were identified. Using NetMHC4.1, the present study predicted whether epitopes derived from these mutations are presented on major HLA-ABC alleles in Japanese individuals and synthesized 138 peptides for MHC stabilization assays. The authors also attempted to examine the candidate epitopes at physiological temperatures by using antibody clone G46-2.6, which can detect HLA-ABC, independent of ß2-microglobulin association. In the assays, although the peptide-induced HLA expression levels were associated with the predicted affinities, the respective HLA alleles exhibited varying degrees of responsiveness, and unexpectedly, p53-mutant epitopes with predicted weak affinities exhibited strong responses. These results suggested that MHC stabilization assays using completely monoallelic HLA-expressing B-cell lines are useful for evaluating the presentation of neoantigen epitopes. [ABSTRACT FROM AUTHOR]

Background: Small intestine carcinoma (SIC) cases in Japan have recently been treated with chemotherapy according to colorectal carcinoma classification, while papilla of Vater carcinoma (PVC) cases according to cholangiocarcinoma (CHC) classification. However, few research reports support the molecular genetic validity of these therapeutic choices. Patients and methods: Here, we investigated the clinicopathological and molecular genetic factors of SIC and PVC. We used the data from the Japanese version of The Cancer Genome Atlas. Additionally, molecular genetic data on gastric adenocarcinoma (GAD), colorectal adenocarcinoma (CRAD), pancreatic ductal adenocarcinoma (PDAC), and CHC were also referred to. Results: This study consisted of tumor samples from 12 patients of SIC and three patients of PVC treated from January 2014 to March 2019. Among them, six patients had pancreatic invasion. t-Distributed stochastic neighbor embedding analysis showed that the gene expression pattern of SIC was similar not only to those of GAD and CRAD, but also to that of PDAC in the pancreatic invasion patients. In addition, PVC resembled the GAD, CRAD, and PDAC, rather than the CHC. The molecular genetic characteristics of the six patients with pancreatic invasion were: one had high microsatellite instability, two had a TP53 driver mutation, and three had tumor mutation burden values <1 mutation/Mb with no driver mutation. Conclusions: In this study, the extensive gene expression profiling of organ carcinomas newly suggests that SIC or PVC may resemble GAD, CRAD, and PDAC. In addition, the data demonstrate that pancreatic invasive patients may be classified into several subtypes using molecular genetic factors. [ABSTRACT FROM AUTHOR]

Abstract Purpose  Total pelvic exenteration (TPE) is the standard procedure for locally advanced rectal cancer involving the prostate and seminal vesicles. We evaluated the feasibility of bladder-sparing surgery as an alternative to TPE. Methods  Eleven patients with advanced primary or recurrent rectal cancer involving the prostate or seminal vesicles, or both, underwent bladder-sparing extended colorectal resection with radical prostatectomy. The procedures performed were abdominoperineal resection (APR) with prostatectomy (n = 6), colorectal resection using intersphincteric resection combined with prostatectomy (n = 4), and abdominoperineal tumor resection with prostatectomy (n = 1). Local control and urinary and anal function were evaluated postoperatively. Results  Cysto-urethral anastomosis (CUA) was performed in seven patients and catheter-cystostomy was performed in four patients. Coloanal or colo-anal canal anastomosis was also performed in four patients. There was no mortality, and the morbidity rate was 38%. All patients underwent complete resection with negative surgical margins. After a median follow-up period of 26 months there was no sign of local recurrence, and ten patients were alive without disease, although distant metastases were found in three patients. Five patients had satisfactory voiding function after CUA, and three had satisfactory evacuation after intersphincteric resection (ISR). Conclusion  These bladder-sparing procedures allow conservative surgery to be performed in selected patients with advanced rectal cancer involving the prostate or seminal vesicles, without compromising local control. [ABSTRACT FROM AUTHOR]