Accumulating evidence indicates that alterations of gut microbiota are associated with colorectal cancer (CRC). Therefore, the use of gut microbiota for the diagnosis of CRC has received attention. Recently, several studies have been conducted to detect the differences in the gut microbiota between healthy individuals and CRC patients using machine learning‐based gut bacterial DNA meta‐sequencing analysis, and to use this information for the development of CRC diagnostic model. However, to date, most studies had small sample sizes and/or only cross‐validated using the training dataset that was used to create the diagnostic model, rather than validated using an independent test dataset. Since machine learning‐based diagnostic models cause overfitting if the sample size is small and/or an independent test dataset is not used for validation, the reliability of these diagnostic models needs to be interpreted with caution. To circumvent these problems, here we have established a new machine learning‐based CRC diagnostic model using the gut microbiota as an indicator. Validation using independent test datasets showed that the true positive rate of our CRC diagnostic model increased substantially as CRC progressed from Stage I to more than 60% for CRC patients more advanced than Stage II when the false positive rate was set around 8%. Moreover, there was no statistically significant difference in the true positive rate between samples collected in different cities or in any part of the colorectum. These results reveal the possibility of the practical application of gut microbiota‐based CRC screening tests.
Background Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status. However, recent investigations have demonstrated that intratumoral fibrosis is important as a factor affecting the infiltration of TILs. This study investigated the organ specificities of TIL infiltration and intratumoral fibrosis in primary colorectal cancer and distant metastases, as well as the relationship between the distribution of TILs and intratumoral fibrosis. Methods Patients who underwent resection of primary tumors or distant metastases for colorectal cancer with distant metastases were enrolled. We evaluated the TIL infiltration by immunohistochemical staining with CD3&CD8 and intratumoral fibrosis by immunohistochemical staining with α-SMA positive cancer-associated fibroblasts and Masson’s trichrome staining against collagen fibers. The "ImageJ" was used to evaluate fibrosis, and the density of TILs in the dense and sparse areas of fibrosis was calculated. The Immunoscore (IS) was obtained based on the density of CD3+/CD8+TILs in the tumor center and invasive margin of the primary tumor. Results The degree of CD3+/CD8+TIL infiltration in peritoneal metastases was significantly lower than that in liver and lung metastases. The area ratio of α-SMA positive cancer-associated fibroblasts and collagen fibers in peritoneal metastases was significantly higher than that of liver and lung metastases. Furthermore, the density of TILs in the high-fibrosis area was significantly lower than that in the low-fibrosis area. In the high-IS group of primary tumors, the degree of TIL infiltration in distant metastases was significantly higher than that in the low-IS group. Conclusion The infiltration of T lymphocytes into tumors is prevented in peritoneal metastases of colorectal cancer due to the high intratumoral fibrosis, which may lead to treatment resistance and a poor prognosis.
Background/Aim: The efficacy of trifluridine/ thymidine phosphorylase inhibitor (FTD/TPI) plus bevacizumab as later-line treatment for metastatic colorectal cancer (mCRC) has been demonstrated. However, little is known about the impact of a usage history of bevacizumab in front-line treatment on the clinical benefit of combining bevacizumab with FTD/TPI. Patients and Methods: A total of 62 patients with mCRC treated with FTD/TPI±bevacizumab was enrolled and assessed for chemotherapeutic efficacy and adverse events. Results: Regardless of the usage history of bevacizumab in front-line treatment, the FTD/TPI plus bevacizumab group had a significantly better progression-free survival rate than the FTD/TPI monotherapy group, and no significant differences in the safety profile were observed between the two groups. Conclusion: Combining bevacizumab with FTD/TPI improves the survival outcomes with manageable toxicity, regardless of the usage history of bevacizumab in front-line treatment, in patients with mCRC.The phase III RECOURSE trial has demonstrated a survival benefit of trifluridine/thymidine phosphorylase inhibitor (FTD/TPI) compared with placebo in patients with chemorefractory metastatic colorectal cancer (mCRC) (1), and FTD/TPI is recommended as a later-line treatment in the NCCN and ESMO guidelines (2, 3). Furthermore, as the efficacy of bevacizumab in combination with FTD/TPI has been demonstrated in some previous studies, including the C-TASK FORCE (4-9), the application of FTD/TPI plus bevacizumab therapy is gradually spreading in clinical practice.Bevacizumab is a recombinant, humanized monoclonal antibody that suppresses angiogenesis by inhibiting vascular endothelial growth factor (VEGF) (10). Combining bevacizumab with cytotoxic anti-cancer agents has been reported to improve the survival outcomes in the first-line and/or second-line treatment for mCRC (11,12). In clinical practice, almost all patients are treated with the antiangiogenic inhibitor in front-line treatment. In particular, patients treated with bevacizumab beyond progression (BBP) receive bevacizumab for a long period.However, in some basic research using experimental animal models, it was reported that persistent suppression of VEGF may cause acquired resistance of cancer cells to the anti-angiogenic inhibitor (13). Therefore, the effect of combining bevacizumab with FTD/TPI in later-line treatment may be influenced by the usage history of bevacizumab in front-line treatment. However, there have been no reports focusing on the impact of the usage history of bevacizumab in front-line treatment on the clinical benefit of combining bevacizumab with FTD/TPI in later-line treatment.The present study examined whether or not the clinical benefit and tolerance of the addition of bevacizumab to FTD/TPI in later-line treatment was influenced by the usage history of bevacizumab in front-line treatment. Patients and MethodsPatients. We retrospectively reviewed the medical records of 62 patients with mCRC who were treated with FTD/
Background Due to the development of surgical techniques and devices, the incidence of anastomosis leakage in rectal surgery has decreased. However, anastomotic leakage in rectal surgery remains a serious postoperative complication. The present study examined whether or not a polyglycolic acid (PGA) sheet is effective for reinforcing rectal anastomosis. Material and methods Fifteen patients who underwent double-stapling technique (DST) anastomosis during rectal surgery were enrolled in this study. The PGA sheet was used as the reinforcing material. DST anastomosis was performed with the PGA sheet sandwiched, and a strip of the PGA sheet was wrapped around the anastomosis. Results No patients had anastomotic leakage. Conclusion A PGA sheet may be effective for preventing anastomotic leakage in DST anastomosis for rectal surgery.
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