Rectal neuroendocrine neoplasms (NENs) are rare neoplasms with limited understanding of its genomic alterations and molecular typing.

There are only a few epidemiological reports available for reference. The clinicopathological features are not clear, so there is no consensus on treating rectal multiple neuroendocrine neoplasms. This study aims to summarize the clinicopathological characteristics and preliminarily discuss the clinical diagnosis and treatment of rectal multiple neuroendocrine neoplasms.

Radiotherapy is a common treatment for rectal cancer, yet the risk of second gynecological malignant neoplasms (SGMNs) in patients with rectal cancer undergoing radiotherapy have not been adequately studied.

Microbial ecosystems that inhabit the human gut form central component of our physiology and metabolism, regulating and modulating both health and disease. Changes or disturbances in the composition and activity of this gut microbiota can result in altered immunity, inflammation, and even cancer.

Background. Limited research is available regarding colorectal NENs and the prognostic factors remain controversial. Materials and Methods. A total of 68 patients with colorectal NENs were studied retrospectively. Clinical characteristics and prognosis between colonic and rectal NENs were compared. The Cox regression models were used to evaluate the predictive capacity. Results. Of the 68 colorectal NENs patients, 43 (63.2%) had rectal NENs, and 25 (36.8%) had colonic NENs. Compared with rectal NENs, colonic NENs more frequently exhibited larger tumor size (P < 0.0001) and distant metastasis (P < 0.0001). Colonic NENs had a worse prognosis (P = 0.027), with 5-year overall survival rates of 66.7% versus 88.1%. NET, NEC, and MANEC were noted in 61.8%, 23.5%, and 14.7% of patients, respectively. Multivariate analyses revealed that tumor location was not an independent prognostic factor (P = 0.081), but tumor size (P = 0.037) and pathological classification (P = 0.012) were independent prognostic factors. Conclusion. Significant differences exist between colonic and rectal NENs. Multivariate analysis indicated that tumor size and pathological classification were associated with prognosis. Tumor location was not an independent factor. The worse outcome of colonic NENs observed in clinical practice might be due not only to the biological differences, but also to larger tumor size in colonic NENs caused by the delayed diagnosis.

High-grade (HG) gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are rare but have a very poor prognosis and represent a severely understudied class of tumours. Molecular data for HG GEP-NEN are limited, and treatment strategies for the carcinoma subgroup (HG GEP-NEC) are extrapolated from small-cell lung cancer (SCLC). After pathological re-evaluation, we analysed DNA from tumours and matched blood samples from 181 HG GEP-NEN patients; 152 neuroendocrine carcinomas (NEC) and 29 neuroendocrine tumours (NET G3). Based on the sequencing of 360 cancer-related genes, we assessed mutations and copy number alterations (CNA). For NEC, frequently mutated genes were TP53 (64%), APC (28%), KRAS (22%) and BRAF (20%). RB1 was only mutated in 14%, but CNAs affecting RB1 were seen in 34%. Other frequent copy number losses were ARID1A (35%), ESR1 (25%) and ATM (31%). Frequent amplifications/gains were found in MYC (51%) and KDM5A (45%). While these molecular features had limited similarities with SCLC, we found potentially targetable alterations in 66% of the NEC samples. Mutations and CNA varied according to primary tumour site with BRAF mutations mainly seen in colon (49%), and FBXW7 mutations mainly seen in rectal cancers (25%). Eight out of 152 (5.3%) NEC were microsatellite instable (MSI). NET G3 had frequent mutations in MEN1 (21%), ATRX (17%), DAXX, SETD2 and TP53 (each 14%). We show molecular differences in HG GEP-NEN, related to morphological differentiation and site of origin. Limited similarities to SCLC and a high fraction of targetable alterations indicate a high potential for better-personalized treatments.

Several approaches have been suggested to be useful in the early detection of colorectal neoplasms. Since metabolites are closely related to the phenotype and are available from different human bio-fluids, metabolomics are candidates for non-invasive early detection of colorectal neoplasms.

Rectal mucosal melanoma (RMM) is a rare and highly aggressive disease with a poor prognosis. Due to the rarity of RMM, there are few studies focusing on its genetic mechanism. This retrospective study aimed to analyze the genetic spectrum and prognosis of RMM in China and lay a foundation for targeted therapy.

Protective ileostomy is always applied to avoid clinically significant anastomotic leakage and other postoperative complications for patients receiving laparoscopic rectal cancer surgery. However, whether it is necessary to perform the ileostomy is still controversial. This meta-analysis aims to analyze the efficacy of ileostomy on laparoscopic rectal cancer surgery.

Rectal neuroendocrine neoplasms can induce liver metastasis. However, few reports exist on the associated long-term recurrence rates. We report a case of liver metastasis identified 15 years after rectal neuroendocrine neoplasm resection.

To assess the efficacy of total neoadjuvant therapy (TNT) for rectal carcinoma in comparison with conventional chemoradiotherapy (CRT).

Colorectal cancer is a heterogeneous group of malignancies with complex molecular subtypes. While colon cancer has been widely investigated, studies on rectal cancer are very limited. Here, we performed multi-region whole-exome sequencing and single-cell whole-genome sequencing to examine the genomic intratumor heterogeneity (ITH) of rectal tumors.

A meta-analysis was carried out to compare the efficacy and safety of capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical Literature Database between January 1998 and October 2014. Trials of capecitabine compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for inclusion. RevMan software was used to analyze these data. Nine trials were included in this meta-analysis, which covered a total of 3141 patients. The meta-analysis showed that capecitabine group had statistically significant better pCR rates (OR, 1.34; 95% CI, 1.10-1.64; P = 0.003), T downstaging rates (OR, 1.58; 95% CI, 1.22-2.06; P = 0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34-3.16; P = 0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44-0.88; P = 0.007), and lowered leucocytes (OR, 0.25; 95% CI, 0.11-0.54; P = 0.0005), but with higher incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59-12.33; P = 0.004). Capecitabine was more efficient than 5-FU in terms of tumor response in neoadjuvant treatment for patients with LARC and favourably low toxicity with the exception of HFS.

Neoadjuvant chemoradiotherapy (nCRT) following surgery significantly improves the survival rate of patients with rectal cancer. However, nCRT is associated with significant adverse symptoms and high medical costs. Therefore, it is important to investigate potential biomarkers for the prediction of the response to nCRT in patients with rectal cancer. The present study identified candidate biomarkers for predicting a complete response (CR) to nCRT in patients with rectal cancer and investigated the associated mechanisms. Microarray data (accession no. GSE29298) was downloaded from the Gene Expression Omnibus database. Differentially expressed microRNAs (miRNAs/miR) were screened between the pathological CR (pCR) group and no pCR (incomplete response) group. miRNA target genes were predicted using the miRWalk 2.0 online tool and subjected to Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Furthermore, a miRNA co‑regulatory network was constructed and disease‑associated genes were predicted. The results demonstrated that a total of 36 upregulated and 5 downregulated miRNAs were identified between the two groups. Among these differentially expressed miRNAs, miR‑548c‑5p, miR‑548d‑5p and miR‑663a were significantly associated with a CR to nCRT. The co‑regulatory network and pathway analysis indicated that miR‑548c‑5p and miR‑548d‑5p may function together through stem cell pluripotency and ubiquitin‑mediated proteolysis signaling pathways. Furthermore, the prediction of disease‑associated genes demonstrated that miR‑548c‑5p/miR‑548d‑5p and miR‑663a may regulate genes associated with rectal cancer, including mutated in colorectal cancers (MCC) and adenomatous polyposis coli (APC), and colorectal neoplasms, including interleukin‑6 signal transducer (IL6ST), cell cycle checkpoint kinase 2 (CHEK2), marker of proliferation Ki‑67 (MKI67), cadherin 7 (CDH7), calreticulin (CALR) and transforming growth factor β1 (TGFB1). Therefore, miR‑548c‑5p, miR‑548d‑5p and miR‑663a are promising candidate biomarkers for predicting a CR to nCRT. miR‑548c‑5p/miR‑548d‑5p may be associated with a CR by regulating IL6ST, CHEK2, MKI67 and MCC. In addition, it may function through the pluripotency of stem cells and ubiquitin‑mediated proteolysis signaling pathways. miR‑663a may be associated with a CR to nCRT by targeting CDH7, CALR, APC and TGFβ1. Thus, the miRNA biomarkers investigated in the present study may represent novel therapeutic targets for the prediction and eventual improvement of the response to nCRT in patients with rectal cancer.

Practice of neuroendocrine neoplasms (NENs) of the digestive tract, which comprise of a highly diverse group of tumors with a rising incidence, faces multiple biological, diagnostic, and therapeutic issues. Part of these issues is due to misuse and misinterpretation of the classification and terminology of NENs of the digestive tract, which make it increasingly challenging to evaluate and compare the literature. For instance, grade 3 neuroendocrine tumors (NETs) are frequently referred to as neuroendocrine carcinomas (NECs) and vice versa, while NECs are, by definition, high grade and therefore constitute a separate entity from NETs. Moreover, the term NET is regularly misused to describe NENs in general, and NETs are frequently referred to as benign, while they should always be considered malignancies as they do have metastatic potential. To prevent misconceptions in future NEN-related research, we reviewed the most recent terminology used to classify NENs of the digestive tract and created an overview that combines the classification of these NENs according to the World Health Organization (WHO) with location- and functionality-based classifications. This overview may help clinicians and researchers in understanding the current literature and could serve as a guide in the clinic as well as for writing future studies on NENs of the digestive tract. In this way, we aim for the universal use of terminology, thereby providing an efficient foundation for future NEN-related research.

Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT), followed by surgical resection. However, >70% of patients do not achieve a complete pathological response and have higher rates of relapse and death. There are no validated pre- or on-treatment factors that predict response to NACRT besides tumour stage and size. We characterised the response of 33 LARC patients to NACRT, collected tumour samples from patients prior to, during and after NACRT, and performed whole exome, transcriptome and high-depth targeted sequencing. The pre-treatment LARC genome was not predictive of response to NACRT. However, in line with the increasing recognition of microbial influence in cancer, RNA analysis of pre-treatment tumours suggested a greater abundance of Fusobacteria in intermediate and poor responders. In addition, we investigated tumour heterogeneity and evolution in response to NACRT. While matched pre-treatment, on-treatment and post-treatment tumours revealed minimal genome evolution overall, we identified cases in which microsatellite instability developed or was selected for during NACRT. Recent research has suggested a role for adaptive mutability to targeted therapy in colorectal cancer cells. We provide preliminary evidence of selection for mismatch repair deficiency in response to NACRT. Furthermore, pre-NACRT genomic landscapes do not predict treatment response but pre-NACRT microbiome characteristics may be informative.

Rectal cancer is the second leading cause of cancer-related death in the Western world. Preoperative neoadjuvant chemoradiotherapy (nCRT) has been widely performed in the treatment of rectal cancer patients. However, there is no consensus on the length of waiting interval between the end of preoperative nCRT and surgery. Present network meta-analysis (NMA) aims to compare the differences of effect between all available interval to surgery after nCRT in rectal cancer in improving overall survival, disease-free survival and pathologic complete response (pCR) rate, and to rate the certainty of evidence from present NMA.

The aim of this study was to analyse the landscape of publications on rectal cancer (RC) over the past 25 years by machine learning and semantic analysis.

Distant metastasis has been the major concern of prognosis in patients with locally advanced rectal cancer (LARC). The purpose of this study was to investigate the prognostic value of TMB in blood (bTMB) in LARC patients after receiving neoadjuvant chemoradiotherapy (nCRT) and surgery. Using targeted ctDNA sequencing, we revealed that bTMB level at baseline was positively correlated with recurrence-free survival (RFS). Following nCRT, the patients with decreasing TMB tends to have a longer median RFS. bTMB level after surgery was negatively correlated with RFS. The serum cytokines including IFNγ, IFNα2, IL-1β, IL-2 and MIP-1β were significantly higher in pre-nCRT serum with higher bTMB group than that of lower bTMB group. Clonal evolution analysis showed that the pre- and post-nCRT ctDNAs of most cases had shared mutations. In conclusion, we presume that bTMB could potentially improve pre- and post-treatment risk assessment and facilitate individualized therapy for patients with LARC.

Under the South Korea's unique health insurance structure, any new surgical technology must be evaluated first by the government in order to consider whether that particular technology can be applied to patients for further clinical trials as categorized as 'New Health Technology,' then potentially covered by the insurance sometime later. The aim of this meta-analysis was to assess the safety and efficacy of transanal total mesorectal excision (TaTME) for rectal cancer, activated by the National Evidence-based Healthcare Collaborating Agency (NECA) TaTME committee.