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Colorectal cancer (CRC) is the third highest incidence cancer and a leading cause of cancer mortality worldwide. To date, chemotherapeutic treatment of advanced CRC that has metastasized has a dismayed success rate of less than 30%. Further, most (80%) sporadic CRCs are microsatellite-stable and are refractory to immune checkpoint blockade therapy. KRAS is a gatekeeper gene in colorectal tumorigenesis. Nevertheless, KRAS is 'undruggable' due to its structure. Thus, focus has been diverted to develop small molecule inhibitors for its downstream effector such as ERK/MAPK. Despite intense research efforts for the past few decades, no small molecule inhibitor has been in clinical use for CRC. Antibody targeting KRAS itself is an attractive alternative. We developed a transient ex vivo patient-derived matched mucosa-tumor primary culture to assess whether anti-KRAS antibody can be internalized to bind and inactivate KRAS. We showed that anti-KRAS antibody can enter live mucosa-tumor cells and specifically aggregate KRAS in the cytoplasm, thus hindering its translocation to the inner plasma membrane. The mis-localization of KRAS reduces KRAS dwelling time at the site where it tethers to activate downstream effectors. We previously showed that expression of SOX9 was KRAS-mutation-dependent and possibly a better effector than ERK in CRC. Herein, we showed that anti-KRAS antibody treated tumor cells have less intense SOX9 cytoplasmic and nuclear staining compared to untreated cells. Our results demonstrated that internalized anti-KRAS antibody inhibits KRAS function in tumor. With an efficient intracellular antibody delivery system, this can be further developed as combinatorial therapeutics for CRC and other KRAS-driven cancers. [ABSTRACT FROM AUTHOR]

Purpose: Prehabilitation (PH) is purported to improve patients' preoperative functional status. This systematic review and meta-analysis sought to compare short-term postoperative outcomes between patients who underwent a protocolized PH program and the existing standard of care among colorectal cancer patients awaiting surgery., Methods: A search in MEDLINE/PubMed, the Cochrane Library, Embase, Scopus, and CINAHL was conducted to identify relevant articles. Repetitive and exhaustive combinations of MeSH search terms ("prehabilitation," "colorectal cancer," "colon cancer," and "rectal cancer") were used to identify randomized and nonrandomized studies comparing PH versus standard of care for colorectal cancer patients awaiting surgery. The primary outcomes included postoperative morbidity, length of hospital stay, and readmission rates., Results: Seven studies including 1,042 colorectal cancer patients (PH, 382) were included. No significant differences were found in intraoperative outcomes. The postoperative complication rates were comparable between groups (Clavien-Dindo grades I and II: risk ratio, 0.82; 95% confidence interval, 0.62-1.07; P=0.15; Clavien-Dindo grades ≥III: risk ratio, 1.02; 95% confidence interval, 0.72-1.44; P=0.92). There were also no significant differences in length of hospital stay (P=0.21) or the risk of 30-day readmission (P=0.68)., Conclusion: Although PH does not appear to improve short-term postoperative outcomes following colorectal cancer surgery, the quality of evidence is impaired by the limited trials and heterogeneity. Thus, further large-scale trials are warranted to draw definitive conclusions and establish the long-term effects of PH.

Purpose: We compared the incidence of venous thromboembolism (VTE) among Asian populations with localized colorectal cancer undergoing curative resection with and without the use of pharmacological thromboprophylaxis (PTP)., Methods: A comprehensive literature search was undertaken to identify relevant studies published from January 1, 1980 to February 28, 2022. The inclusion criteria were patients who underwent primary tumor resection for localized nonmetastatic colorectal cancer; an Asian population or studies conducted in an Asian country; randomized controlled trials, case-control studies, or cohort studies; and the incidence of symptomatic VTE, deep vein thrombosis, and/or pulmonary embolism as the primary study outcomes. Data were pooled using a random-effects model. This study was registered in PROSPERO on October 11, 2020 (No. CRD42020206793)., Results: Seven studies (2 randomized controlled trials and 5 observational cohort studies) were included, encompassing 5,302 patients. The overall incidence of VTE was 1.4%. The use of PTP did not significantly reduce overall VTE incidence: 1.1% (95% confidence interval [CI], 0%-3.1%) versus 1.9% (95% CI, 0.3%-4.4%; P = 0.55). Similarly, PTP was not associated with significantly lower rates of symptomatic VTE, proximal deep vein thrombosis, or pulmonary embolism., Conclusion: The benefit of PTP in reducing VTE incidence among Asian patients undergoing curative resection for localized colorectal cancer has not been clearly established. The decision to administer PTP should be evaluated on a case-bycase basis and with consideration of associated bleeding risks.

This study aims to assess the quality and performance of predictive models for colorectal cancer liver metastasis (CRCLM). A systematic review was performed to identify relevant studies from various databases. Studies that described or validated predictive models for CRCLM were included. The methodological quality of the predictive models was assessed. Model performance was evaluated by the reported area under the receiver operating characteristic curve (AUC). Of the 117 articles screened, seven studies comprising 14 predictive models were included. The distribution of included predictive models was as follows: radiomics (n = 3), logistic regression (n = 3), Cox regression (n = 2), nomogram (n = 3), support vector machine (SVM, n = 2), random forest (n = 2), and convolutional neural network (CNN, n = 2). Age, sex, carcinoembryonic antigen, and tumor staging (T and N stage) were the most frequently used clinicopathological predictors for CRCLM. The mean AUCs ranged from 0.697 to 0.870, with 86% of the models demonstrating clear discriminative ability (AUC > 0.70). A hybrid approach combining clinical and radiomic features with SVM provided the best performance, achieving an AUC of 0.870. The overall risk of bias was identified as high in 71% of the included studies. This review highlights the potential of predictive modeling to accurately predict the occurrence of CRCLM. Integrating clinicopathological and radiomic features with machine learning algorithms demonstrates superior predictive capabilities.

Rectal cancer response to neoadjuvant long-course chemoradiotherapy (LCCRT) is assessed by magnetic resonance tumour regression grade (mrTRG) and this has an impact on surgical management. However, there is limited data on the correlation between mrTRG and pathological tumour regression grade (pTRG). This study aims to evaluate the correlation between mrTRG and pTRG and the prognostic value of mrTRG on survival., Methods: Between 2011 and 2016, patients with rectal cancer who underwent LCCRT and had post-LCCRT MRI were included in the study. Both mrTRG and pTRG were dichotomised into good responders (mrTRG 1-3 and pTRG 0-1) and poor responders (mrTRG 4-5 and pTRG 2-3). Correlation between mrTRG and pTRG was assessed with Cohen κ analysis. Survival analysis was performed with Kaplan-Meier test and Cox proportional hazard models., Results: There were 59 patients included in this study. There were significant reductions in anal sphincter and circumferential resection margin involvement in post-LCCRT MRI. Fair agreement was found between mrTRG and pTRG (κ=0.345). Sensitivity, specificity and accuracy of mrTRG 1-3 to predict good pathological response were 100%, 46.3% and 62.7%, respectively. On survival analysis, mrTRG 1-3 was not associated with improved overall survival and recurrence-free survival., Conclusions: While there is fair agreement in correlation between mrTRG and pTRG, MRI remains an objective, noninvasive assessment of tumour response. Further studies are required to improve the ability of mrTRG to predict good responders to LCCRT and evaluate its role as a prognostic marker for survival., Competing Interests: The authors declare that they have no financial conflict of interest with regard to the content of this report.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Natural orifice specimen extraction (NOSE) via the anus or vagina replaces conventional transabdominal specimen retrieval via the transabdominal route through a limited mid-line laparotomy or Pfannenstiel incision. Reducing the number of laparoscopic ports further decreases operative abdominal wall trauma. These techniques reduce the surgical wound size as well as the risk of incision-related morbidity., Aim: To compare short-term outcomes following 3-port NOSE surgery with a matched cohort of conventional non-NOSE colorectal cancer surgery., Methods: Patients who underwent elective 3-port laparoscopic colorectal NOSE surgery between February to October 2021 were identified. Selection criteria for NOSE surgery was adapted from the 2019 International Consensus on Natural Orifice Specimen Extraction Surgery for colorectal cancer. Patients with clinical T4 or N2 tumors on staging computed tomography were also excluded. The propensity score-matched cohort was identified amongst patients who underwent conventional laparoscopic colorectal surgery from January 2019 to December 2020. Matching was performed in the ratio of 1:4 based on age, gender, type of resection, and p - tumor node metastasis staging., Results: Over the eight-month study duration, 14 consecutive cases (nine female, five male) of elective 3-port laparoscopic surgery with NOSE were performed for colorectal cancer. Median age and body mass index were 70 (range 43-82) years and 24.1 (range 20.0-31.7) kg/m 2 respectively. Six patients underwent transanal NOSE and eight had transvaginal NOSE. Median operative time, intraoperative blood loss and postoperative length of stay were 208 (range 165-365) min, 30 (range 10-150) mL and 3 (range 2-6) d respectively. Two (14%) suffered minor postoperative compilations not attributable to the NOSE procedure. Median follow-up duration was 12 (range 8-15) mo. No instances of mortality, local or distant disease recurrence were recorded in this cohort. Compared to the conventional surgery cohort of 56 patients, the 3-port NOSE cohort had significantly quicker mean return of bowel function (2.6 vs 1.2 d, P < 0.001), reduced postoperative pain and patient-controlled analgesia use, and decreased length of hospital stay (6.4 vs 3.4 d, P < 0.001). There were no statistical differences in surgical duration and perioperative complication rates between the NOSE and non-NOSE cohorts., Conclusion: 3-port laparoscopic colorectal surgery with NOSE is a feasible technique, augmenting the minimally invasive nature of surgery and producing good outcomes. Appropriate patient selection and expertise in conventional laparoscopy are required., Competing Interests: Conflict-of-interest statement: All authors declare no conflict-of-interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)