Natural orifice specimen extraction surgeries (NOSES) have been applied to colorectal cancer (CRC). Different types of NOSES have been proposed. Traditional laparoscopic CRC surgeries (non-NOSES) have been widely adopted in clinical practice. Therefore, the safety and feasibility of NOSES could be clarified by comparing with non-NOSES.Consecutive cases who underwent NOSE or non-NOSE rectal surgeries were retrospectively collected at the Second Affiliated Hospital of Harbin Medical University between 1 January 2013 and 31 December 2018. Other inclusion criteria included patients with adenocarcinoma of the rectum within 15 cm of the anal verge, over the age of 18 and undergoing primary laparoscopic rectal resection. Patients who were lost to follow-up or had incomplete information were excluded. Basic characteristics including gender, tumor location, age, staging, treatment, and Body Mass Index (BMI) were analyzed. Short-term outcomes including comorbidities, intra-operative blood loss, hospital stay, gas exhaust time were compared between different NOSES and non-NOSES groups. Long-term outcomes including overall survival (OS) and disease-free survival (DFS) were also analyzed. Patients were followed-up during the inpatient period, at an outpatient clinic, or by phone call.A total of 196 NOSES cases and 243 non-NOSES cases were included. There was a sex difference between the two groups and other factors were comparable. Cases were divided into NOSES groups [including extra-abdominal resection (EVER), specimen extraction and extra-abdominal resection (EXER), and intra-abdominal resection and specimen extraction (IREX)] and non-NOSES groups. Differences in sex (P=0.016), BMI (with mean of 22.08, 22.00, 22.53, and 23.26 kg/m2, P=0.003), and staging (P=0.008) were observed between the four groups. There was a difference in the intra-operative blood loss between NOSES and non-NOSES groups (57.05±62.78, 52.65±68.19, 36.52±43.99 76.12±90.11 mL, P=0.002), in which NOSES groups had less blood loss. Furthermore, NOSES groups showed a better post-operative gas exhaust time (54.68±37.80, 45.06±24.69, 47.91±28.93 56.94±27.69 hours, P=0.012). NOSES groups also had fewer ileostomies (17 37, P=0.003). There was no difference in the long-term DFS and OS between the two groups.NOSES in rectal cancer showed better short-term outcomes and had comparable long-term outcomes compared with non-NOSE surgeries.2022 Annals of Translational Medicine. All rights reserved.

The tumor microenvironment contributes to the survival and development of tumor cells and is therefore a key target for cancer therapy. The tumor microenvironment has unique physical and chemical properties and is associated with inflammation and immunity. To examine the correlation between tumor microenvironment-associated factors and the efficacy and prognosis of neoadjuvant therapy for rectal cancer, and to compare the differences between two treatments [neoadjuvant chemotherapy (NAC) vs. neoadjuvant chemoradiotherapy (NACR)], an immunohistochemical method was used to measure the expression levels of CD4 tumor-infiltrating lymphocytes (TILs), cluster of differentiation (CD)8TILs, forkhead box P3 (FOXP3)TILs, cytotoxic T lymphocyte-associated antigen-4TILs and programmed death ligand-1 (PD-L1)TILs in 109 patients with rectal cancer, pre- and post-neoadjuvant therapy. The significance of these protein expression patterns was also analyzed using tissue microarrays, and the prognostic significance of these findings evaluated. The results indicated that high levels of CD4TILs, CD8TILs and PD-L1TILs may be associated with favorable responses to neoadjuvant therapy, whereas high levels of FOXP3TILs were associated with poor therapeutic responses. Expression levels of CD8TILs and FOXP3TILs following neoadjuvant therapy were independent prognostic factors and affected the total survival of patients subjected to neoadjuvant therapy for the treatment of rectal cancer. Moreover, the effects of NAC and NACR on the tumor microenvironment may be different.

Neoadjuvant chemoradiotherapy followed by surgery is the mainstay treatment for locally advanced rectal cancer, leading to significant decrease in tumor size (downsizing) and a shift towards earlier disease stage (downstaging). Extensive histopathological work-up of the tumor specimen after surgery including tumor regression grading and lymph node status helped to visualize individual tumor sensitivity to chemoradiotherapy, retrospectively. As the response to neoadjuvant chemoradiotherapy is heterogeneous, however, valid biomarkers are needed to monitor tumor response. A relevant number of studies aimed to identify molecular markers retrieved from tumor tissue while the relevance of blood-based biomarkers is less stringent assessed. MicroRNAs are currently under investigation to serve as blood-based biomarkers. To date, no screening approach to identify relevant miRNAs as biomarkers in blood of patients with rectal cancer was undertaken. The aim of the study is to investigate the role of circulating miRNAs as biomarkers in those patients included in the TiMiSNAR Trial (NCT03465982). This is a biomolecular substudy of TiMiSNAR Trial (NCT03962088).All included patients in the TiMiSNAR Trial are supposed to undergo blood collection at the time of diagnosis, after neoadjuvant treatment, after 1 month from surgery, and after adjuvant chemotherapy whenever indicated.TiMiSNAR-MIRNA will evaluate the association of variation between preneoadjuvant and postneoadjuvant expression levels of miRNA with pathological complete response. Moreover, the study will evaluate the role of liquid biopsies in the monitoring of treatment, correlate changes in expression levels of miRNA following complete surgical resection with disease-free survival, and evaluate the relation between changes in miRNA during surveillance and tumor relapse.Clinicaltrials.gov NCT03962088. Registered on 23 May 2019.

To develop a radiomics model based on pretreatment whole-liver portal venous phase (PVP) contrast-enhanced CT (CE-CT) images for predicting metachronous liver metastases (MLM) within 24 months after rectal cancer (RC) surgery.This study retrospectively analyzed 112 RC patients without preoperative liver metastases who underwent rectal surgery between January 2015 and December 2017 at our institution. Volume of interest (VOI) segmentation of the whole-liver was performed on the PVP CE-CT images. All 1316 radiomics features were extracted automatically. The maximum-relevance and minimum-redundancy and least absolute shrinkage and selection operator methods were used for features selection and radiomics signature constructing. Three models based on radiomics features (radiomics model), clinical features (clinical model), and radiomics combined with clinical features (combined model) were built by multivariable logistic regression analysis. Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of models, and calibration curve and the decision curve analysis were performed to evaluate the clinical application value.In total, 52 patients in the MLM group and 60 patients in the non-MLM group were enrolled in this study. The radscore was built using 16 selected features and the corresponding coefficients. Both the radiomics model and the combined model showed higher diagnostic performance than clinical model (AUCs of training set: radiomics model 0.84 (95% CI, 0.76-0.93), clinical model 0.65 (95% CI, 0.55-0.75), combined model 0.85 (95% CI, 0.77-0.94); AUCs of validation set: radiomics model 0.84 (95% CI, 0.70-0.98), clinical model 0.58 (95% CI, 0.40-0.76), combined model 0.85 (95% CI, 0.71-0.99)). The calibration curves showed great consistency between the predicted value and actual event probability. The DCA showed that both the radiomics and combined models could add a net benefit on a large scale.The radiomics model based on preoperative whole-liver PVP CE-CT could predict MLM within 24 months after RC surgery. Clinical features could not significantly improve the prediction efficiency of the radiomics model.© 2022. The Author(s).

We aimed to develop and validate a nomogram model, which could predict metachronous liver metastasis in colorectal cancer within two years after diagnosis.A retrospective study was performed on colorectal cancer patients who were admitted to Beijing Shijitan Hospital from January 1, 2016 to June 30, 2019. The least absolute shrinkage and selection operator (LASSO) regression model was used to optimize feature selection for susceptibility to metachronous liver metastasis in colorectal cancer. Multivariable logistic regression analysis was applied to establish a predictive model through incorporating features selected in the LASSO regression model. C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis (DCA) were employed to assess discrimination, distinctiveness, consistency with actual occurrence risk, and clinical utility of candidate predictive model. Internal validation was assessed with bootstrapping method.Predictors contained in candidate prediction nomogram included age, CEA, vascular invasion, T stage, N stage, family history of cancer, and KRAS mutation. This model displayed good discrimination with a C-index of 0.787 (95% confidence interval: 0.728-0.846) and good calibration, whereas area under the ROC curve (AUC) of 0.786. Internal validation obtained C-index of 0.786, and AUC of validation cohort is 0.784. Based on DCA, with threshold probability range from 1 to 60%; this predictive model might identify colorectal cancer metachronous liver metastasis to achieve a net clinical benefit.We have developed and validated a prognostic nomogram with good discriminative and high accuracy to predict metachronous liver metastasis in CRC patients.© 2022. The Author(s).

Our previous study showed that adhesion molecule with immunoglobulin like domain 2 (AMIGO2) is a pivotal driver gene of liver metastasis via regulating tumor cell adhesion to liver endothelial cells in mouse models. The aim of the present study was to clarify the role of AMIGO2 in liver metastasis in patients the colorectal cancer (CRC). Two human CRC cell lines, Caco-2 (AMIGO2-low) and HCT116 (AMIGO2-high), were used in this study. AMIGO2-overexpressing Caco-2 and AMIGO2-knockdown HCT116 cells were generated by transfection with an AMIGO2 expression vector or AMIGO2 small interfering RNA, respectively. Cell proliferation, invasion and adhesion to human liver endothelial cells were examined in studies. Immunohistochemical analysis was also performed to evaluate the association between AMIGO2 expression and liver metastasis in patients with CRC. studies revealed that cell proliferation, invasion and adhesion to liver endothelial cells were accelerated by upregulation of AMIGO2 expression, but suppressed by downregulation of AMIGO2 expression in human CRC cells. Immunohistochemical analysis using clinical CRC specimens revealed that AMIGO2 expression was associated with the frequency of liver metastasis (P<0.01), but not that of pulmonary metastasis (P=0.611) and peritoneal dissemination (P=0.909). In addition, AMIGO2 expression levels in tumor cells were significantly higher in liver metastatic foci than primary lesions (P=0.012). In conclusion, the present results indicated that AMIGO2 expression may contribute to the formation of liver metastasis in CRC.Copyright: © Tanio et al.

Colorectal cancer (CRC) is one of the most common malignancies in Western countries. Over the last 20 years, and the last decade in particular, the clinical outcome for patients with metastatic CRC (mCRC) has improved greatly due not only to an increase in the number of patients being referred for and undergoing surgical resection of their localised metastatic disease but also to a more strategic approach to the delivery of systemic therapy and an expansion in the use of ablative techniques. This reflects the increase in the number of patients that are being managed within a multidisciplinary team environment and specialist cancer centres, and the emergence over the same time period not only of improved imaging techniques but also prognostic and predictive molecular markers. Treatment decisions for patients with mCRC must be evidence-based. Thus, these ESMO consensus guidelines have been developed based on the current available evidence to provide a series of evidence-based recommendations to assist in the treatment and management of patients with mCRC in this rapidly evolving treatment setting.© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Metachronous liver metastasis (MLM) occurs in 20–40% of colorectal cancer (CRC) patients following surgical treatment. The aim of the present study was to determine the risk factors affecting the development of MLM in CRC patients following curative resection.

Whole-block imaging (WBI) using micro-computed tomography (micro-CT) allows the nondestructive reconstruction of a three-dimensional view of tissues, implying that WBI may be used for accurate pathological evaluation of patients with rectal cancer. HOWEVER, the clinical impact of this approach is unclear. We aimed to clarify the efficacy of WBI in the whole-mount specimens of locally advanced rectal cancer. A total of 237 whole-mount formalin-fixed paraffin-embedded blocks from 13 patients with rectal cancer who underwent surgical treatment were enrolled and scanned with micro-CT to generate three-dimensional images. WBI was evaluated following the conventional pathological review of the corresponding whole-slide imaging (WSI). WBI identified all tumor sites detected using WSI. Furthermore, WBI revealed one additional tumor site, which was not detected using WSI. Tumor resection margin was significantly closer to the soft-tissue edge when measured using WBI (7.7 mm vs. 6.6 mm, p < 0.01). Seventy-six percent of tumor deposits on WSI were changed according to the evidence of tumor interaction with the surrounding tissues confirmed using WBI. Furthermore, WBI revealed 25 additional lymph nodes, six of which were metastatic. The combination of conventional hematoxylin and eosin-stained imaging and WBI may contribute to an accurate pathological assessment.

This study aimed to investigate the predictive value of pre-/postneoadjuvant chemoradiotherapy (nCRT) magnetic resonance imaging (MRI) characteristics for the long-term survival outcomes in patients with locally advanced rectal cancer (LARC).We retrospectively evaluated pre- and post-nCRT MRI and clinicopathologic characteristics of LARC patients. The 3-year disease-free survival (DFS) was estimated using the Kaplan-Meier product-limit method. Associations between MRI variabilities and survival outcomes were assessed using Cox proportional hazards model.In total, 171 LARC patients (112 men and 59 women) with a median age of 55 years (range, 27-82 years) treated with nCRT were evaluated. The median follow-up was 47.6 months, and the 3-, 4-, and 5-year DFS in the overall cohort was 76.6%, 74.5%, and 73.7%, respectively. MRI assessment of extramural venous invasion (mrEMVI) positivity was a significant independent adverse factor of long-term survival (hazard ratio [HR] = 2.589, 95% confidence interval [CI] = 1.398-4.794, p = 0.002) on multivariate analysis. Patients with positive mrEMVI had significantly lower 3-year DFS than those with negative mrEMVI (52.6 months vs 65.1 months; p = 0.003). Moreover, the tumor regression grade on MRI (mrTRG) also significantly correlated with survival outcomes in patients with LARC. Patients with partial response on post-nCRT MRI (mrPR) showed short DFS than those with complete response (mrCR; HR = 4.914, 95% CI = 1.176-20.533, p = 0.029). The 3-year DFS of mrCR and mrPR patients were 74.3 months and 58.9 months, respectively (p = 0.011).The pre-/post-nCRT MRI characteristics may be used to long-term survival stratification in LARC patients. mrEMVI positivity was an independent adverse prognostic indicator for 3-year DFS. Further, mrTRG may also be a predictive factor for the prognosis of LARC patients. The pre-/post-nCRT MR imaging may offer more information for providing individualized treatment.Copyright © 2019 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.