Predicting the risk of distant metastasis in patients with locally advanced rectal cancer using model based on pre-treatment T2WI-based radiomic features plus postoperative pathological stage.

Objective: To assess the prognostic value of a model based on pre-treatment T2WI-based radiomic features and postoperative pathological staging in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy. Methods: Radiomic features were derived from T2WI, and a radiomic signature (RS) was established and validated for the prediction of distant metastases (DM). Subsequently, we designed and validated a nomogram model that combined the radiomic signature and postoperative pathological staging for enhanced DM prediction. Performance measures such as the concordance index (C-index) and area under the curve (AUC) were computed to assess the predictive accuracy of the models. Results: A total of 260 patients participated in this study, of whom 197 (75.8%) were male, and the mean age was 57.2 years with a standard deviation of 11.2 years. 15 radiomic features were selected to define the radiomic signature. Patients with a high-risk radiomic signature demonstrated significantly shorter distant metastasis-free survival (DMFS) in both the development and validation cohorts. A nomogram, incorporating the radiomic signature, pathological T stage, and N stage, achieved an area under the curve (AUC) value of 0.72 (95% CI, 0.60-0.83) in the development cohort and 0.83 (95% CI, 0.73-0.92) in the validation cohort. Conclusion: A radiomic signature derived from T2WI-based radiomic features can effectively distinguish patients with varying risks of DM. Furthermore, a nomogram integrating the radiomic signature and postoperative pathological stage proves to be a robust predictor of DMFS.

Integrated proteomic and phosphoproteomic data-independent acquisition data evaluate the personalized drug responses of primary and metastatic tumors in colorectal cancer.

Mass spectrometry (MS)-based proteomics and phosphoproteomics are powerful methods to study the biological mechanisms, diagnostic biomarkers, prognostic analysis, and drug therapy of tumors. Data-independent acquisition (DIA) mode is considered to perform better than data-dependent acquisition (DDA) mode in terms of quantitative reproducibility, specificity, accuracy, and identification of low-abundance proteins. Mini patient derived xenograft (MiniPDX) model is an effective model to assess the response to antineoplastic drugs in vivo and is helpful for the precise treatment of cancer patients. Kinases are favorable spots for tumor-targeted drugs, and their functional completion relies on signaling pathways through phosphorylating downstream substrates. Kinase-phosphorylation networks or edge interactions are considered more credible and permanent for characterizing complex diseases. Here, we provide a workflow for personalized drug response assessment in primary and metastatic colorectal cancer (CRC) tumors using DIA proteomic data, DIA phosphoproteomic data, and MiniPDX models. Three kinase inhibitors, afatinib, gefitinib, and regorafenib, are tested pharmacologically. The process mainly includes the following steps: clinical tissue collection, sample preparation, hybrid spectral libraries establishment, MS data acquisition, kinase-substrate network construction, in vivo drug test, and elastic regression modeling. Our protocol gives a more direct data basis for individual drug responses, and will improve the selection of treatment strategies for patients without the druggable mutation.

Comparison of functional and oncological outcome of conformal sphincter preservation operation, low anterior resection, and abdominoperineal resection in very low rectal cancer: a retrospective comparative cohort study with propensity score matching.

PURPOSE: Conformal sphincter preservation operation (CSPO) procedure is a sphincter preservation procedure for preserving the anal canal function for very low rectal cancers. This study investigated the functional and oncological outcome of conformal sphincter preservation operation by comparing with low anterior resection (LAR) and abdominoperineal resection (APR). METHODS: This is a retrospective comparative study. Patients who received conformal sphincter preservation operation (n = 52), low anterior resection (n = 54), or abdominoperineal resection (n = 69) were included between 2011 and 2016 in a tertiary referral hospital. Propensity score matching was applied to adjust the baseline characteristics which may influence the choice of the surgical procedure. RESULTS: Twenty-one pairs of conformal sphincter preservation operation vs. low anterior resection and 29 pairs of conformal sphincter preservation operation vs. abdominoperineal resection were selected. The first group had a higher tumor location than the second group. Compared with the low anterior resection group, the conformal sphincter preservation operation group had shorter distal resection margins; however, no significant differences were identified in daily stool frequency, Wexner incontinence score, local recurrence, distant metastasis, overall survival, and disease-free survival between both groups. Compared with the abdominoperineal resection group, the conformal sphincter preservation operation group had shorter operative time and shorter postoperative hospital stay. No significant differences were identified in local recurrence, distant metastasis, overall survival, and disease-free survival. CONCLUSION: Conformal sphincter preservation operation is oncologically safe compared to APR and LAR, and has similar functional findings to LAR. Studies comparing CSPO with intersphincteric resection should be performed.

DSTN Hypomethylation Promotes Radiotherapy Resistance of Rectal Cancer by Activating the Wnt/ß-Catenin Signaling Pathway.

PURPOSE: Although surgical resection combined with neoadjuvant radiation therapy can reduce the local recurrence rate of rectal cancer, not all patients benefit from neoadjuvant radiation therapy. Therefore, screening for patients with rectal cancer who are sensitive or resistant to radiation therapy has great clinical significance. METHODS AND MATERIALS: Patients with rectal cancer were selected according to postoperative tumor regression grade, and tumor samples were taken for detection. Differential genes between radiation-resistant and radiation-sensitive tissues were screened and validated by Illumina Infinium MethylationEPIC BeadChip, proteomics, Agena MassARRAY methylation, reverse transcription quantitative real-time polymerase chain reaction, and immunohistochemistry. In vitro and in vivo functional experiments verified the role of DSTN. Protein coimmunoprecipitation, western blot, and immunofluorescence were used to investigate the mechanisms of DSTN-related radiation resistance. RESULTS: DSTN was found to be highly expressed (P < .05) and hypomethylated (P < .01) in rectal cancer tissues resistant to neoadjuvant radiation therapy. Follow-up data confirmed that patients with high expression of DSTN in neoadjuvant radiation therapy-resistant rectal cancer tissues had shorter disease-free survival (P < .05). DSTN expression increased after methyltransferase inhibitor inhibition of DNA methylation in colorectal cancer cells (P < .05). In vitro and in vivo experiments showed that knockdown of DSTN promoted the sensitivity of colorectal cancer cells to radiation therapy, and overexpression of DSTN promoted the resistance of colorectal cancer cells to radiation (P < .05). The Wnt/ß-catenin signaling pathway was activated in colorectal cancer cells overexpressing DSTN. ß-catenin was highly expressed in radiation therapy-resistant tissues, and there was a linear correlation between the expression of DSTN and ß-catenin (P < .0001). Further studies showed that DSTN can bind to ß-catenin and increase its stability. CONCLUSIONS: The degree of DNA methylation and the expression level of DSTN can be used as biomarkers to predict the sensitivity of neoadjuvant radiation therapy for rectal cancer. DSTN and ß-catenin are also expected to become a reference for the selection of neoadjuvant radiation therapy.

Predictive value of modified MRI-based split scar sign (mrSSS) score for pathological complete response after neoadjuvant chemoradiotherapy for patients with rectal cancer.

PURPOSE: To measure the diagnostic performance of modified MRI-based split scar sign (mrSSS) score for the prediction of pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for patients with rectal cancer. METHODS: The modified MRI-based split scar sign (mrSSS) score, which consists of T2-weighted images (T2WI)-based score and diffusion-weighted images (DWI)-based score. The sensitivity, specificity, and accuracy of modified mrSSS score, endoscopic gross type, and MRI-based tumor regression grading (mrTRG) score, in the prediction of pCR, were compared. The prognostic value of the modified mrSSS score was also studied. RESULTS: A total of 189 patients were included in the study. The Kendall's coefficient of interobserver concordance of modified mrSSS score, T2WI -based score, and DWI-based score were 0.899, 0.890, and 0.789 respectively. And the maximum and minimum k value of the modified mrSSS score was 0.797 (0.742-0.853) and 0.562 (0.490-0.634). The sensitivity, specificity, and accuracy of prediction of pCR were 0.66, 0.97, and 0.90 for modified mrSSS score; 0.37, 0.89, and 0.78 for endoscopic gross type (scar); and 0.24, 0.92, and 0.77 for mrTRG score (mrTRG = 1). The modified mrSSS score had significantly higher sensitivity than the endoscopic gross type and the mrTRG score in predicting pCR. Patients with lower modified mrSSS scores had significantly longer disease-free survival (P < 0.05). CONCLUSION: The modified mrSSS score showed satisfactory interobserver agreement and higher sensitivity in predicting pCR after nCRT in patients with rectal cancer. The modified mrSSS score is also a predictor of disease-free survival.

Multiregion single cell analysis reveals a novel subtype of cancer-associated fibroblasts located in the hypoxic tumor microenvironment in colorectal cancer.

BACKGROUND: The tumor microenvironment (TME) plays a critical role in shaping tumor progression and determining the outcome of the therapeutic response. In this study, we aimed to generate a comprehensive cellular landscape of the colorectal cancer (CRC) TME. METHODS: We generated a comprehensive single-cell atlas by collecting CRC cases that have been uploaded to the online database and conducting an in-depth secondary analysis. We then carried out spatial transcriptomic sequencing and multiple immunohistochemical analyses to verify the results of the single-cell analysis. Moreover, we applied our findings to the TCGA database and used tissue microarray (TMA) on CRC tissue specimens to validate clinical prognosis. FINDINGS: We re-analyzed the transcriptomes of 23785 cells, revealing a pattern of cell heterogeneity in the tumor region, leading-edge region, and non-tumor region. A subtype of COL11A1+INHBA+ tumor-resident cancer-associated fibroblasts (CAFs) was identified, and marker genes, transcription factors, and tissue-specific expression differences were noted and suggested to have potential roles in promoting cancer. We further confirmed that COL11A1+INHBA+ tumor-resident CAFs are mainly located in the hypoxic TME and we propose that they interact with CD44+ CRC cells via INHBA. Elevation of INHBA in CRC is associated with a poor prognosis. INTERPRETATION: Our results demonstrated a single cell landscape of CRC in different regions and identified in hypoxic TME a special subtype of CAFs producing INHBA, which promotes CRC development and correlates with poor prognosis. This special subtype of CAFs is a candidate target for translational research.

Trends of sphincter-preserving surgeries for low lying rectal cancer: A 20-year experience in China.

Background: Over the last 2 decades, patients with low rectal cancer have had better outcomes from improvements in surgical techniques in sphincter preservation. We aimed to quantify the trends in sphincter-preserving surgeries for low rectal cancer over 20 years in a top tertiary hospital in China. Methods: Between 1999 and 2021, a cohort of patients with primary malignant rectal tumor ≤5cm from the anal verge and who received elective surgeries at Changhai Hospital, Shanghai, China, was identified. Data were extracted from electronic medical records. A Joinpoint Regression Model was used to analyze trends in surgical procedures by average annual percentage change (AAPC). Adjusted Cox proportional hazards regression model was used to assess overall survival. Results: Among a total of 4,172 patients during the study period, 3,111 (74.6%) underwent a sphincter-preserving surgery and 1,061 (25.4%) received APR. Sphincter-preserving surgery increased 3.6% per year (95%CI, 2.3-4.9). Low anterior resection was the most performed procedure (86.3%) and maintained a steady trend, while intersphincteric resection increased 49.4% annually (95%CI, 19.5-86.7) after initiation. Laparoscopic techniques increased 15.1% per year (95%CI, 8.4-43.4) after initiation. Sphincter-preserving surgery increased annually for tumors ≤2cm, 2-≤3cm and 3-≤4cm from the anal verge (AAPC 7.1, 4.5-9.8; 4.7, 3.1-6.3; 2.7, 1.7-3.6, respectively). Furthermore, patients with sphincter-preserving surgery had a better overall survival than abdominoperineal resection (APR) patients (adjusted HR 0.78, 95% CI, 0.65-0.93, p=.01). Conclusions: Utilization of sphincter-preserving surgeries increased significantly over the last 20 years. Patients with low rectal cancer who underwent sphincter preservation had better survival than similar patients who underwent APR.

Measurement of distal intramural spread and the optimal distal resection by naked eyes after neoadjuvant radiation for rectal cancers.

BACKGROUND: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. METHODS: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. RESULTS: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was - 0.3 (95%CI - 4.0 ~ 3.4) mm, - 0.9 (95%CI - 3.4 ~ 1.7) mm, and - 0.4 (95%CI - 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. CONCLUSIONS: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety.

High expression of phosphorylated focal adhesion kinase predicts a poor prognosis in human colorectal cancer.

Background: Phosphorylated Focal adhesion kinase (FAK) has been reported to be intimately involved in various malignant tumors. The effect of p-FAK on colorectal cancer (CRC) is still disputable. The purpose of this study is to investigate the role of p-FAK in the prognosis of colorectal cancer. Methods: The clinical significance of p-FAK expression in CRC was evaluated by immunohistochemistry in a large cohort, including carcinoma and para-carcinoma tissues from 908 patients, and normal tissues, adenoma, and metastasis tissues. The correlation between p-FAK expression and CRC occurrence was investigated in tumor and other tissues. Factors contributing to prognosis were evaluated using Kaplan-Meier survival analysis and Cox regression model. Results: p-FAK is apparently overexpressed in CRC and metastasis tissues. Compared with low p-FAK expression, patients with high p-FAK expression had shorter overall survival [hazard ratio (HR), 2.200; 95% confidence interval (CI), 1.265-3.452; p < 0.01] and disease-free survival (HR, 2.004; 95% CI 1.262-3.382; p < 0.01) in multivariate Cox analysis after adjusting other prognostic factors. High p-FAK expression was also related to a worse chemotherapeutic response in patients who achieved adjuvant chemotherapy (p < 0.01). Conclusion: Expression level of p-FAK is an independent risk factor and can serve as a prognostic biomarker for CRC. High p-FAK expression predicts an unfavorable prognosis of CRC as well as poor chemotherapeutic response.

Trends, clinicopathological features, surgical treatment patterns and prognoses of early-onset versus late-onset colorectal cancer: A retrospective cohort study on 34067 patients managed from 2000 to 2021 in a Chinese tertiary center.

BACKGROUND: In recent decades, the incidence of early-onset colorectal cancer (EOCRC) has reportedly increased in several developed countries, whereas that of late-onset colorectal cancer (LOCRC) has decreased continuously. The trends, clinicopathological features, surgical treatment patterns, and prognoses of EOCRC and LOCRC in China remain unclear. MATERIALS AND METHODS: This retrospective cohort study was performed in China using data from our pathology registry collected in 2000-2021. Pathologically confirmed cases of colorectal cancer (CRC) were analyzed. The average annual percentage change (AAPC) was estimated to quantify the secular trends. Clinicopathological features, surgical treatment patterns, and prognoses were compared between the two groups. Multivariate Cox regression analyses were performed for disease-free survival and overall survival. RESULTS: A total of 34,067 cases of CRC were included, with 6,369 cases of EOCRC and 27,698 cases of LOCRC. Overall, the numbers of EOCRC (AAPC = 8.4%), LOCRC (AAPC = 11.6%), and CRC (AAPC = 11.0%) cases increased significantly from 2000 to 2021. Compared to the LOCRC group, the EOCRC group had fewer men, comorbidities, concomitant cancers, polyps, and KRAS mutations; more symptoms, rectal cancers, multiple primary CRCs, deficient mismatch repair tumors, poorly differentiated, mucinous adenocarcinoma or signet ring cell carcinoma, advanced TNM stage, vascular invasion, perineural invasion; less laparoscopic surgery and sphincter-preserving surgery; more extended radical resection, perioperative chemoradiotherapy and targeted therapy; and similar disease-free and overall survival rates. CONCLUSION: The numbers of EOCRC and LOCRC cases have continuously increased over the last two decades. The EOCRC group has more aggressive features, advanced TNM stage, intensified surgical treatment and perioperative treatment than the LOCRC group, but similar disease-free and overall survival rates. More CRC screening programs are recommended for younger adults to combat the rapidly increasing trend of EOCRC.

Development and Validation of an 8-Gene Signature to Improve Survival Prediction of Colorectal Cancer.

Background: Most prognostic signatures for colorectal cancer (CRC) are developed to predict overall survival (OS). Gene signatures predicting recurrence-free survival (RFS) are rarely reported, and postoperative recurrence results in a poor outcome. Thus, we aim to construct a robust, individualized gene signature that can predict both OS and RFS of CRC patients. Methods: Prognostic genes that were significantly associated with both OS and RFS in GSE39582 and TCGA cohorts were screened via univariate Cox regression analysis and Venn diagram. These genes were then submitted to least absolute shrinkage and selection operator (LASSO) regression analysis and followed by multivariate Cox regression analysis to obtain an optimal gene signature. Kaplan-Meier (K-M), calibration curves and receiver operating characteristic (ROC) curves were used to evaluate the predictive performance of this signature. A nomogram integrating prognostic factors was constructed to predict 1-, 3-, and 5-year survival probabilities. Function annotation and pathway enrichment analyses were used to elucidate the biological implications of this model. Results: A total of 186 genes significantly associated with both OS and RFS were identified. Based on these genes, LASSO and multivariate Cox regression analyses determined an 8-gene signature that contained ATOH1, CACNB1, CEBPA, EPPHB2, HIST1H2BJ, INHBB, LYPD6, and ZBED3. Signature high-risk cases had worse OS in the GSE39582 training cohort (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.42 to 1.67) and the TCGA validation cohort (HR = 1.39, 95% CI = 1.24 to 1.56) and worse RFS in both cohorts (GSE39582: HR = 1.49, 95% CI = 1.35 to 1.64; TCGA: HR = 1.39, 95% CI = 1.25 to 1.56). The area under the curves (AUCs) of this model in the training and validation cohorts were all around 0.7, which were higher or no less than several previous models, suggesting that this signature could improve OS and RFS prediction of CRC patients. The risk score was related to multiple oncological pathways. CACNB1, HIST1H2BJ, and INHBB were significantly upregulated in CRC tissues. Conclusion: A credible OS and RFS prediction signature with multi-cohort and cross-platform compatibility was constructed in CRC. This signature might facilitate personalized treatment and improve the survival of CRC patients.

Role of Perirectal Fat in the Carcinogenesis and Development of Early-Onset Rectal Cancer.

Purpose: The incidence of early-onset rectal cancer (EORC) has been increasing since the past decade, while its underlying cause remained unknown. This study was aimed at clarifying the relationship between perirectal fat area (PFA) and EORC. Patients and Methods. All patients with rectal cancer who received radical excision between January 2016 and December 2017 at our hospital were included. The fat series images of pelvic magnetic resonance imaging scans were obtained and PFA at the ischial spine level was calculated using the ImageJ software. Results: A total of 303 patients were finally included and divided into two groups according to the median PFA: Group 1 (<20.2 cm2, n = 151) and Group 2 (≥20.2 cm2, n = 152). PFA positively correlated with body weight and body mass index. PFA increased with invasion depth, lymph node metastasis, TNM stage, tumor deposits, and vascular invasion. Patients with EORC had higher PFA than those with late-onset rectal cancer (LORC; P = 0.009). Among patients with stage I-III rectal cancers, those in Group 2 had significantly shorter disease-free survival (P = 0.010) and overall survival (P = 0.034) than those in Group 1, and PFA was an independent predictor of disease-free survival (OR: 1.683 [1.126-3.015], P = 0.035) and overall survival (OR: 1.678 [1.022-2.639], P = 0.046). Conclusions: Patients with EORC had significantly higher PFA than those with LORC. PFA is positively correlated with T stage, N stage, TNM stage, tumor deposit, and vascular invasion and is an independent predictor of disease-free survival and overall survival. Therefore, perirectal fat may be involved in the carcinogenesis and development of EORC.

Evaluation of the learning curve for conformal sphincter preservation operation in the treatment of ultralow rectal cancer.

BACKGROUND: To investigate the learning curve of conformal sphincter preservation operation (CSPO) in the treatment of ultralow rectal cancer and to further explore the influencing factors of operation time. METHODS: From August 2011 to April 2020, 108 consecutive patients with ultralow rectal cancer underwent CSPO by the same surgeon in the Department of Colorectal Surgery of Changhai Hospital. The moving average and cumulative sum control chart (CUSUM) curve were used to analyze the learning curve. The preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data were compared before and after the completion of learning curve. The influencing factors of CSPO operation time were analyzed by univariate and multivariate analysis. RESULTS: According to the results of moving average and CUSUM method, CSPO learning curve was divided into learning period (1-45 cases) and learning completion period (46-108 cases). There was no significant difference in preoperative clinical baseline data, postoperative pathological data, postoperative complications, and survival data between the two stages. Compared with the learning period, the operation time (P < 0.05), blood loss (P < 0.05), postoperative flatus and defecation time (P < 0.05), liquid diet time (P < 0.05), and postoperative hospital stay (P < 0.05) in the learning completion period were significantly reduced, and the difference was statistically significant. Univariate and multivariate analysis showed that distance of tumor from anal verge (≥ 4cm vs. < 4cm, P = 0.039) and T stage (T3 vs. T1-2, P = 0.022) was independent risk factors for prolonging the operation time of CSPO. CONCLUSIONS: For surgeons with laparoscopic surgery experience, about 45 cases of CSPO are needed to cross the learning curve. At the initial stage of CSPO, beginners are recommended to select patients with ultralow rectal cancer whose distance of tumor from anal verge is less than 4 cm and tumor stage is less than T3 for practice, which can enable beginners to reduce the operation time, accumulate experience, build self-confidence, and shorten the learning curve on the premise of safety.

Machine learning-based random forest predicts anastomotic leakage after anterior resection for rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is one of the commonest and most serious complications after rectal cancer surgery. The previous analyses on predictors for AL included small-scale patients, and their prediction models performed unsatisfactorily. METHODS: Clinical data of 5,220 patients who underwent anterior resection for rectal cancer were scrutinized to create a prediction model via random forest classifier. Additionally, data of 836 patients served as the test dataset. Patients diagnosed with AL within 6 months' follow-up were recorded. A total of 20 candidate factors were included. Receiver operating characteristic (ROC) curve was conducted to determine the clinical efficacy of our model, and compare the predictive performance of different models. RESULTS: The incidence of AL was 6.2% (326/5,220). A multivariate logistic regression analysis and the random forest classifier indicated that sex, distance of tumor from the anal verge, bowel stenosis or obstruction, preoperative hemoglobin, surgeon volume, diabetes, neoadjuvant chemoradiotherapy, and surgical approach were significantly associated with AL. After propensity score matching, the temporary stoma was not identified as a protective factor for AL (P=0.58). Contrastingly, the first year of performing laparoscopic surgery was a predictor (P=0.009). We created a predictive random forest classifier based on the above predictors that demonstrated satisfactory prediction efficacy. The area under the curve (AUC) showed that the random forest had higher efficiency (AUC =0.87) than the nomogram (AUC =0.724). CONCLUSIONS: Our findings suggest that eight factors may affect the incidence of AL. Our random forest classifier is an innovative and practical model to effectively predict AL, and could provide rational advice on whether to perform a temporary stoma, which might reduce the rate of stoma and avoid the ensuing complications.

Prognostic factors in patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy and radical resection of rectal cancer.

BACKGROUND: There are only a few studies on the prognosis of patients with complete response of the tumour (ypT0) after neoadjuvant chemoradiotherapy (NCRT) and radical resection of rectal cancer. The aim of the study was to identify prognostic factors with regard to oncological outcome in ypT0 patients after NCRT and radical resection. METHODS: All ypT0 patients with rectal cancer after NCRT and radical resection between January 2010 and June 2019 were included. Cox univariate and multivariate regression analyses were used to determine the prognostic factors of these patients. RESULTS: Seventy-six patients with ypT0 rectal cancer were included. In nine patients (11.8%), lymph node metastasis was identified. Age, gender, elevated carcinoembryonic antigen (CEA) and ypN+ were risk factors associated with a worse 5-year disease-free survival (DFS) rate in univariate analysis (P = 0.08, 0.14, 0.007 and 0.003, respectively). In multivariate analysis, ypN+ and elevated CEA before NCRT were independent risk factors for worse 5-year DFS (P = 0.005 and 0.021, respectively). Elevated CEA before NCRT, post-operative chemotherapy and ypN+ were risk factors associated with worse overall survival in univariate analysis (P = 0.14, 0.002 and 0.17, respectively). However, in multivariate analysis, none of these three factors were independent risk factors for worse overall survival (P = 0.20, 0.34 and 0.06, respectively). CONCLUSION: ypN+ and elevated CEA before NCRT were found to be independent risk factors for an unfavourable DFS in ypT0 patients with complete response of the tumour after neoadjuvant chemoradiotherapy for rectal cancer.

Corrigendum to "The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery".

[This corrects the article DOI: 10.1155/2020/2052561.].

Integrated Omics of Metastatic Colorectal Cancer.

We integrate the genomics, proteomics, and phosphoproteomics of 480 clinical tissues from 146 patients in a Chinese colorectal cancer (CRC) cohort, among which 70 had metastatic CRC (mCRC). Proteomic profiling differentiates three CRC subtypes characterized by distinct clinical prognosis and molecular signatures. Proteomic and phosphoproteomic profiling of primary tumors alone successfully distinguishes cases with metastasis. Metastatic tissues exhibit high similarities with primary tumors at the genetic but not the proteomic level, and kinase network analysis reveals significant heterogeneity between primary colorectal tumors and their liver metastases. In vivo xenograft-based drug tests using 31 primary and metastatic tumors show personalized responses, which could also be predicted by kinase-substrate network analysis no matter whether tumors carry mutations in the drug-targeted genes. Our study provides a valuable resource for better understanding of mCRC and has potential for clinical application.

Rectal cancer patients with downstaging after neoadjuvant chemoradiotherapy and radical resection do not benefit from adjuvant chemotherapy.

BACKGROUND: Whether adjuvant chemotherapy is beneficial for rectal cancer patients who respond well to neoadjuvant chemoradiotherapy (NCRT) and undergo radical resection is controversial. This study aimed to assess the effect of adjuvant chemotherapy on the oncological outcomes of ypT0-2N0 rectal cancer patients after NCRT and radical resection, and identify the prognostic factors. METHODS: The clinical and pathological data of rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection between January, 2010 and June, 2018 were collected and retrospectively analyzed. The oncological outcomes of the chemotherapy (chemo) group and the non-chemotherapy (non-chemo) group were compared. Multivariate analysis, using a Cox proportional hazard model, was performed to identify independent predictors of oncological outcome. RESULTS: Of the 121 rectal cancer patients enrolled, 90 patients received postoperative adjuvant chemotherapy with no fewer than 3 cycles (the chemo group), and the other 31 patients with fewer than 3 cycles (the non-chemo group). There was no significant difference in the 5-year disease-free survival (DFS) or overall survival (OS) rates between the two groups (DFS: 79.1% vs. 82.9%, P=0.442; OS: 87.5% vs. 78.2%, P=0.667). cT4 is an independent risk factor for OS (HR =4.227, 95% CI: 1.128-15.838, P=0.02) and DFS (HR =4.878, 95% CI: 1.752-13.578). Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT significantly improved the DFS rate (HR =0.212, 95% CI: 0.058-0.776, P=0.019). CONCLUSIONS: Rectal cancer patients with ypT0-2N0 who underwent NCRT and radical resection did not benefit significantly from postoperative adjuvant chemotherapy. For these patients, cT4 was an independent risk factor for OS and DFS. Preoperative consolidation chemotherapy with Capeox or FOLFOX after NCRT can significantly improve DFS.

The Prognostic Significance of Tumor Deposit Count for Colorectal Cancer Patients after Radical Surgery.

BACKGROUND: The prognostic value of tumor deposit (TD) count in colorectal cancer (CRC) patients has been rarely evaluated. This study is aimed at exploring the prognostic value of TD count and finding out the optimal cutoff point of TD count to differentiate the prognoses of TD-positive CRC patients. METHOD: Patients diagnosed with CRC from Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2010, to December 31, 2012, were analyzed. X-tile program was used to identify the optimal cutoff point of TD count in training cohort, and a validation cohort was used to test this cutoff point after propensity score matching (PSM). Univariate and multivariate Cox proportional hazard models were used to assess the risk factors of survival. RESULTS: X-tile plots identified 3 (P < 0.001) as the optimal cutoff point of TD count to divide the patients of training cohort into high and low risk subsets in terms of disease-specific survival (DSS). This cutoff point was validated in validation cohort before and after PSM (P < 0.001, P = 0.002). More TD count, which was defined as more than 3, was validated as an independent risk prognostic factor in univariate and multivariate analysis (P < 0.001). CONCLUSION: More TD count (TD count ≥ 4) was significantly associated with poor disease-specific survival in CRC patients.

Impact of Smoking Status on Stroke Recurrence.

Background Smoking is a well-established risk factor of stroke and smoking cessation has been recommended for stroke prevention; however, the impact of smoking status on stroke recurrence has not been well studied to date. Methods and Results Patients with first-ever stroke were enrolled and followed in the NSRP (Nanjing Stroke Registry Program). Smoking status was assessed at baseline and reassessed at the first follow-up. The primary end point was defined as fatal or nonfatal recurrent stroke after 3 months of the index stroke. The association between smoking and the risk of stroke recurrence was analyzed with multivariate Cox regression model. At baseline, among 3069 patients included, 1331 (43.4%) were nonsmokers, 263 (8.6%) were former smokers, and 1475 (48.0%) were current smokers. At the first follow-up, 908 (61.6%) patients quit smoking. After a mean follow-up of 2.4±1.2 years, 293 (9.5%) patients had stroke recurrence. With nonsmokers as the reference, the adjusted hazard ratios for stroke recurrence were 1.16 (95% CI , 0.75-1.79) in former smokers, 1.31 (95% CI , 0.99-1.75) in quitters, and 1.93 (95% CI , 1.43-2.61) in persistent smokers. Among persistent smokers, hazard ratios for stroke recurrence ranged from 1.68 (95% CI , 1.14-2.48) in those who smoked 1 to 20 cigarettes daily to 2.72 (95% CI , 1.36-5.43) in those who smoked more than 40 cigarettes daily ( P for trend <0.001). Conclusions After an initial stroke, persistent smoking increases the risk of stroke recurrence. There exists a dose-response relationship between smoking quantity and the risk of stroke recurrence.