Venous thromboembolism among Asian populations with localized colorectal cancer undergoing curative resection: is pharmacological thromboprophylaxis required? A systematic review and meta-analysis.

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.

Postoperative outcomes after prehabilitation for colorectal cancer patients undergoing surgery: a systematic review and meta-analysis of randomized and nonrandomized studies.

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.

Stenting as bridge to surgery versus upfront emergency resection for non-metastatic left sided obstructing colorectal cancer: risk of peritoneal recurrence and long-term outcomes.

BACKGROUND: Oncological outcomes of stenting as a bridge to surgery (SBTS) remain a major concern, despite perioperative benefits it offers. This study aims to evaluate the differences in recurrence patterns and survival in patients with non-metastatic, obstructing left sided colon cancers treated by SBTS versus upfront emergency surgery (ES). METHODS: This is a retrospective, single-centre cohort study of 227 consecutive patients with non-metastatic, obstructing left sided colon cancer between 2007 and 2016. Primary outcomes were pattern of recurrence, and survival. Univariate, bivariate and multivariate logistic regression were done to determine relationships between factors and recurrence. Kaplan Meier curves and log rank tests were used to analyse survival outcomes. RESULTS: Of the 227 patients included, 62 underwent SBTS and 165 underwent upfront ES. There was a higher rate of peritoneal recurrence in SBTS group (27.4 vs 15.2% p = 0.034), with no difference observed in overall, liver or lung recurrences. No significant difference in overall survival (p = 0.11), cancer specific survival (p = 0.35), or recurrence free survival (p = 0.107) was observed. Univariate analysis showed that SBTS (OR 2.12, p = 0.036), diabetes mellitus (DM) (OR 2.58, p = 0.013), T4 (OR 2.81, p = 0.001), N + (OR 4.02, p = 0.001), lymphovascular invasion (OR 2.43, p = 0.011) contributed to a higher rate of peritoneal recurrence. Bivariate analysis showed synergistic relationship between T4 tumors and SBTS: in T4 tumors that underwent SBTS, the odds of having peritoneal recurrence was 6.8 times higher when compared to ES (p = 0.004); whilst in T2/3 tumors there was no significant difference observed (OR 1.33, p = 0.55). Multivariable analysis showed SBTS (OR 2.60, p = 0.04), DM (OR 2.88, p = 0.012), N + (OR 2.97, p = 0.026) were significant predictors for peritoneal recurrence. CONCLUSIONS: There are concerns over oncological safety of SBTS even with low rates of stent-related perforation. Higher rates of peritoneal recurrence are seen especially with T4 colon cancers treated with SBTS. SBTS, DM and nodal stage were significant predictors for peritoneal recurrence.

Surgical and short-term oncological safety of total neoadjuvant therapy in high-risk locally advanced rectal cancer.

BACKGROUND: Management for locally advanced rectal cancer (LARC) conventionally comprises long-course chemoradiotherapy (LCCRT), total mesorectal excision (TME), and adjuvant chemotherapy. However, the RAPIDO study published in 2021 showed that total neoadjuvant therapy (TNT) led to better oncological outcomes without increased toxicity. We review the surgical and short-term oncological outcomes of patients with high-risk LARC who underwent TNT or LCCRT before TME. METHODS: Patients with high-risk LARC who underwent TNT or LCCRT before TME between 2021 and 2022 were reviewed. RESULTS: Thirty-five patients (66%) had TNT as per RAPIDO whilst 18 underwent LCCRT. Median follow-up was 16 months (range 5-25). Of the patients who had TNT, median age was 65 years old (range 44-79), 34 (97%) had clinical Stage 3 LARC and median height FAV was 5 cm (range 0.5-14). Nine (26%) required a dose delay/reduction due to treatment toxicity. Seven (50%) showed resolution of previously enlarged lateral nodes. Three (9%) had pathological complete response. Postoperative major morbidity was 23%, of which 4 patients required a reoperation. Six (17%) patients had disease-related treatment failure, with two having disease progression during TNT, two developed local recurrence, and two developed distal metastasis following surgery. Median duration to surgery following completion of chemotherapy was significantly shorter with TNT (36 days versus 74 days) (P < 0.001). There were no other significant differences in outcomes. CONCLUSION: TNT is clinically safe in high-risk LARC patients with no significant difference to surgical and short-term oncological outcomes compared to LCCRT, although a higher incidence of early surgical morbidity was observed.

Patient-reported unmet supportive care needs in long-term colorectal cancer survivors after curative treatment in an Asian population.

OBJECTIVES: Despite an increase in colorectal cancer (CRC) survival, less is known about CRC-specific long-term unmet supportive needs in Asian patients. This study aimed to examine the prevalence of long-term unmet needs and identify clinical and socio-demographic factors associated with increased unmet needs in Asian CRC survivors. DESIGN AND SETTING: We conducted a cross-sectional study that assessed unmet needs using the Cancer Survivors' Unmet Needs scale. CRC survivors of at least two years after undergoing curative surgery were recruited from an outpatient clinic of a large public hospital in Singapore. RESULTS: In total, 400 CRC survivors with a mean age of 64 and a median survival time post-surgery of 78 months participated in the study. Approximately half of patients (52%) reported at least one unmet need. Male gender (RR 1.19, p = 0.01), age greater than 65 years (RR 0.63, p < 0.0001), longer follow up of more than 5 years (RR 0.80, p = 0.009), presence of a permanent stoma (RR 1.78, p < 0.0001), prior radiotherapy in treatment course (RR 1.99, p < 0.0001), higher educational status (RR 1.30, p = 0.0002), currently employed (RR 0.84, p = 0.014), currently married (RR 0.84, p = 0.01) were significant predictors for increased unmet needs. CONCLUSION: There is a high prevalence of unmet needs in long-term Asian CRC survivors, which underscores the importance of screening patients to allow for early detection of unmet needs. Our findings on sociodemographic and clinical predictors can inform the development of targeted interventions tailored to the need domains and improvement of survivorship programmes.

Predictive modeling algorithms for liver metastasis in colorectal cancer: A systematic review of the current literature.

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.

A reduction in hospital length of stay reduces costs for colorectal surgery: an economic evaluation of the National Surgical Quality Improvement Program in Singapore.

PURPOSE: In 2017, the National Surgical Quality Improvement Program (NSQIP) was introduced in the Department of Colorectal Surgery at Singapore General Hospital as a pilot quality improvement initiative. This study aimed to examine the cost-effectiveness of NSQIP by evaluating its effects on surgical outcomes, length of stay (LOS), and costs. METHODS: We retrospectively reviewed patients undergoing colorectal surgery (2017-2020). Patients were divided into two cohorts: pre-NSQIP (2017-2018) and post-NSQIP (2019-2020). Outcomes evaluated were 30-day postoperative complications, LOS, and costs. Total cost-savings from NSQIP intervention's impact on LOS were estimated using a decision model with a one-way sensitivity analysis. Multivariate logistic regression was performed to identify factors for prolonged LOS. RESULTS: 1905 patients underwent colorectal surgery, with 996 in the pre-NSQIP cohort and 909 in the post-NSQIP cohort. A significant reduction in overall postoperative complications of 4.7% was observed in the post-NSQIP cohort (36.5% vs. 31.8%, p = 0.029). Patients in the post-NSQIP cohort had a shorter median LOS (8.0 vs. 6.0 days, p < 0.001). The implementation of NSQIP resulted in an 8.5% decrease in prolonged LOS > 6 days (p < 0.001), saving S$0.31 million on LOS. Total costs per case were reduced by 20.8% following NSQIP (S$39,539.05 vs. S$31,311.93, p < 0.001). CONCLUSION: Implementing NSQIP has significantly reduced overall postoperative complications, LOS, and costs and achieved cost savings following colorectal surgery.

Clinical outcomes and cost comparison of laparoscopic versus open surgery in elderly colorectal cancer patients over 80 years.

PURPOSE: The growth of Singapore's geriatric population, coupled with the rise in colorectal cancer (CRC), has increased the number of colorectal surgeries performed on elderly patients. This study aimed to compare the clinical outcomes and costs of laparoscopic versus open elective colorectal resections in elderly CRC patients over 80 years. METHODS: A retrospective cohort study using data from the American College of Surgeons National Surgery Quality Improvement Program (ACS-NSQIP) identified patients over 80 years undergoing elective colectomy and proctectomy between 2018 and 2021. Patient demographics, length of stay (LOS), 30-day postoperative complications, and mortality rates were analysed. Cost data in Singapore dollars were obtained from the finance database. Univariate and multivariate regression models were used to determine cost drivers. The 5-year overall survival (OS) for the entire octogenarian CRC cohort with and without postoperative complications was estimated using the Kaplan-Meier curves. RESULTS: Of the 192 octogenarian CRC patients undergoing elective colorectal surgery between 2018 and 2021, 114 underwent laparoscopic resection (59.4%), while 78 underwent open surgery (40.6%). The proportion of proctectomy cases was similar between laparoscopic and open groups (24.6% vs. 23.1%, P = 0.949). Baseline characteristics, including Charlson Comorbidity Index, albumin level, and tumour staging, were comparable between both groups. Median operative duration was 52.5 min longer in the laparoscopic group (232.5 vs. 180.0 min, P < 0.001). Both groups had no significant differences in postoperative complications and 30-day and 1-year mortality rates. Median LOS was 6 days in the laparoscopic group compared to 9 days in the open group (P < 0.001). The mean total cost was 11.7% lower in the laparoscopic group (S$25,583.44 vs. S$28,970.85, P = 0.012). Proctectomy (P = 0.024), postoperative pneumonia (P < 0.001) and urinary tract infection (P < 0.001), and prolonged LOS > 6 days (P < 0.001) were factors contributing to increased costs in the entire cohort. The 5-year OS of octogenarians with minor or major postoperative complications was significantly lower than those without complications (P < 0.001). CONCLUSION: Laparoscopic resection is associated with significantly reduced overall hospitalization costs and decreased LOS compared to open resection among octogenarian CRC patients, with comparable postoperative outcomes and 30-day and 1-year mortality rates. The extended operative time and higher consumables costs from laparoscopic resection were mitigated by the decrease in other inpatient hospitalization costs, including ward accommodation, daily treatment fees, investigation costs, and rehabilitation expenditures. Comprehensive perioperative care and optimised surgical approach to mitigate the impact of postoperative complications can improve survival in elderly patients undergoing CRC resection.

Elderly patients over 80 years undergoing colorectal cancer resection: Development and validation of a predictive nomogram for survival.

BACKGROUND: Surgery remains the primary treatment for localized colorectal cancer (CRC). Improving surgical decision-making for elderly CRC patients necessitates an accurate predictive tool. AIM: To build a nomogram to predict the overall survival of elderly patients over 80 years undergoing CRC resection. METHODS: Two hundred and ninety-five elderly CRC patients over 80 years undergoing surgery at Singapore General Hospital between 2018 and 2021 were identified from the American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) database. Prognostic variables were selected using univariate Cox regression, and clinical feature selection was performed by the least absolute shrinkage and selection operator regression. A nomogram for 1- and 3-year overall survival was constructed based on 60% of the study cohort and tested on the remaining 40%. The performance of the nomogram was evaluated using the concordance index (C-index), area under the receiver operating characteristic curve (AUC), and calibration plots. Risk groups were stratified using the total risk points derived from the nomogram and the optimal cut-off point. Survival curves were compared between the high- and low-risk groups. RESULTS: Eight predictors: Age, Charlson comorbidity index, body mass index, serum albumin level, distant metastasis, emergency surgery, postoperative pneumonia, and postoperative myocardial infarction, were included in the nomogram. The AUC values for the 1-year survival were 0.843 and 0.826 for the training and validation cohorts, respectively. The AUC values for the 3-year survival were 0.788 and 0.750 for the training and validation cohorts, respectively. C-index values of the training cohort (0.845) and validation cohort (0.793) suggested the excellent discriminative ability of the nomogram. Calibration curves demonstrated a good consistency between the predictions and actual observations of overall survival in both training and validation cohorts. A significant difference in overall survival was seen between elderly patients stratified into low- and high-risk groups (P < 0.001). CONCLUSION: We constructed and validated a nomogram predicting 1- and 3-year survival probability in elderly patients over 80 years undergoing CRC resection, thereby facilitating holistic and informed decision-making among these patients.

Acute hospital-community hospital care bundle for elderly orthopedic surgery patients: A propensity score-matched economic analysis.

BACKGROUND: While Singapore attains good health outcomes, Singapore's healthcare system is confronted with bed shortages and prolonged stays for elderly people recovering from surgery in acute hospitals. An Acute Hospital-Community Hospital (AH-CH) care bundle has been developed to assist patients in postoperative rehabilitation. The core concept is to transfer patients out of AHs when clinically recommended and into CHs, where they can receive more beneficial dedicated care to aid in their recovery, while freeing up bed capacities in AHs. AIM: To analyze the AH length of stay (LOS), costs, and savings associated with the AH-CH care bundle intervention initiated and implemented in elderly patients aged 75 years and above undergoing elective orthopedic surgery. METHODS: A total of 862 1:1 propensity score-matched patients aged 75 years and above who underwent elective orthopedic surgery in Singapore General Hospital (SGH) before (2017-2018) and after (2019-2021) the care bundle intervention period was analyzed. Outcome measures were AH LOS, CH LOS, hospitalization metrics, postoperative 30-d mortality, and modified Barthel Index (MBI) scores. The costs of AH inpatient hospital stay in the matched cohorts were compared using cost data in Singapore dollars. RESULTS: Of the 862 matched elderly patients undergoing elective orthopedic surgery before and after the care bundle intervention, the age distribution, sex, American Society of Anesthesiologists classification, Charlson Comorbidity Index, and surgical approach were comparable between both groups. Patients transferred to CHs after the surgery had a shorter median AH LOS (7 d vs 9 d, P < 0.001). The mean total AH inpatient cost per patient was 14.9% less for the elderly group transferred to CHs (S$24497.3 vs S$28772.8, P < 0.001). The overall AH U-turn rates for elderly patients within the care bundle were low, with a 0% mortality rate following orthopedic surgery. When elderly patients were discharged from CHs, their MBI scores increased significantly (50.9 vs 71.9, P < 0.001). CONCLUSION: The AH-CH care bundle initiated and implemented in the Department of Orthopedic Surgery appears to be effective and cost-saving for SGH. Our results indicate that transitioning care between acute and community hospitals using this care bundle effectively reduces AH LOS in elderly patients receiving orthopedic surgery. Collaboration between acute and community care providers can assist in closing the care delivery gap and enhancing service quality.

Effect of preoperative oral antibiotics and mechanical bowel preparation on the prevention of surgical site infection in elective colorectal surgery, and does oral antibiotic regime matter? a bayesian network meta-analysis.

PURPOSE: Surgical site infection (SSI) impacts 5-20% of patients after elective colorectal surgery. There are varying reports on the effectiveness of oral antibiotics (OAB) with preoperative mechanical bowel preparation (MBP) in preventing SSI. We aim to determine the role of OAB and MBP in preventing SSI after elective colorectal surgery. We also determine if a specific OAB regimen will be more effective than others. METHODS: This study investigated the impact of OAB and MBP in patients undergoing elective colorectal surgery. PubMed, MEDLINE, Ovid, Cochrane Central Register of Controlled Trials, ACP Journal Club, and Embase databases were searched for randomized clinical trials (RCTs) published by June 2022. All RCTs comparing various preoperative bowel preparation regimens, including pairwise or multi-intervention comparisons, were included. To establish the role of OAB and MBP in preventing SSI, we conducted a Bayesian network meta-analysis on all RCTs. We further performed subgroup analysis to determine the most effective OAB regimen. RESULTS: Among included 46 studies with a total of 12690 patients, patients in the MBP + OAB group were less likely to have SSI than those having MBP-only (OR 0.55, 95% CrI 0.39-0.76), and without MBP and OAB (OR 0.52, 95% CrI 0.32-0.84). OAB regimen C (kanamycin + metronidazole) and A (neomycin + metronidazole) demonstrated a significantly reduced incidence of SSI, compared to regimen B (neomycin + erythromycin) with OR 0.24 (95% CrI 0.07-0.79) and 0.26 (95% CrI 0.07-0.99) respectively. CONCLUSIONS: OAB with MBP reduces the risk of SSI after elective colorectal surgery. Providing adequate aerobic and anaerobic coverage with OAB may confer better protection against SSI.

KRAS-specific antibody binds to KRAS protein inside colorectal adenocarcinoma cells and inhibits its localization to the plasma membrane.

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.

The role of magnetic resonance tumour regression grade in the prediction of regression and survival of rectal adenocarcinoma after long-course chemoradiotherapy: a cohort study.

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.

Cost-effectiveness comparison of minimally invasive, robotic and open approaches in colorectal surgery: a systematic review and bayesian network meta-analysis of randomized clinical trials.

PURPOSE: This study compares the cost-effectiveness of open, laparoscopic (LAP), laparoscopic-assisted (LAPA), hand-assisted laparoscopic (HAL), and robotic colorectal surgery using a network meta-analysis. METHODS: Randomized clinical trials (RCTs) evaluating the cost-effectiveness of comparing the five different approaches in colorectal surgery were included in a literature search until September 2022. Bayesian network meta-analysis was conducted, and surface under cumulative ranking area (SUCRA) values, odds ratio (OR), and 95% credible intervals (CrIs) were reported for total costs, surgical costs, operating time, length of stay (LOS), and postoperative outcomes. Cluster analysis was performed to examine the similarity and classification of surgical approaches into homogeneous clusters. The cophenetic correlation coefficient (cc) was evaluated to identify the most cost-effective clustering method. The primary outcomes assessed were: costs-morbidity, costs-mortality, and costs-efficacy, measuring total costs against postoperative complications, mortality rate, and LOS, respectively. RESULTS: 22 RCTs with 4239 patients were included. Open surgery had the lowest total costs, surgical costs, and operating time but the longest LOS and most postoperative complications. LOS was significantly decreased in LAP compared to open surgery (OR 0.67, 95% CrI 0.46-0.96). Robotic surgery resulted in the highest total costs, surgical costs, and most extended operative duration but the shortest LOS and lowest mortality. LAPA and robotic surgery were superior in the costs-morbidity analysis. HAL was associated with the worst costs-mortality profile. LAP, LAPA, and HAL were better in terms of costs-efficacy. CONCLUSION: Overall, LAP and LAPA are the most cost-effective approaches for colorectal surgery in terms of overall postoperative complications, mortality, and LOS.

Stenting as a bridge to surgery in obstructing colon cancer: Long-term recurrence pattern and competing risk of mortality.

BACKGROUND: Stenting as a bridge to curative surgery (SBTS) for obstructing colon cancer (OCC) has been associated with possibly worse oncological outcomes. AIM: To evaluate the recurrence patterns, survival outcomes, and colorectal cancer (CRC)-specific death in patients undergoing SBTS for OCC. METHODS: Data from 62 patients undergoing SBTS at a single tertiary centre over ten years between 2007 and 2016 were retrospectively examined. Primary outcomes were recurrence patterns, overall survival (OS), cancer-specific survival (CSS), and CRC-specific death. OS and CSS were estimated using the Kaplan-Meier curves. Competing risk analysis with cumulative incidence function (CIF) was used to estimate CRC-specific mortality with other cause-specific death as a competing event. Fine-Gray regressions were performed to determine prognostic factors of CRC-specific death. Univariate and multivariate subdistribution hazard ratios and their corresponding Wald test P values were calculated. RESULTS: 28 patients (45.2%) developed metastases after a median period of 16 mo. Among the 18 patients with single-site metastases: Four had lung-only metastases (14.3%), four had liver-only metastases (14.3%), and 10 had peritoneum-only metastases (35.7%), while 10 patients had two or more sites of metastatic disease (35.7%). The peritoneum was the most prevalent (60.7%) site of metastatic involvement (17/28). The median follow-up duration was 46 mo. 26 (41.9%) of the 62 patients died, of which 16 (61.5%) were CRC-specific deaths and 10 (38.5%) were deaths owing to other causes. The 1-, 3-, and 5-year OS probabilities were 88%, 74%, and 59%; 1-, 3-, and 5-year CSS probabilities were 97%, 83%, and 67%. The highest CIF for CRC-specific death at 60 mo was liver-only recurrence (0.69). Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictive of CRC-specific death. CONCLUSION: The peritoneum was the most common metastatic site among patients undergoing SBTS. Liver-only recurrence, peritoneum-only recurrence, and two or more recurrence sites were predictors of CRC-specific death.

Efficacy of biofeedback therapy for faecal incontinence in an Asian population.

BACKGROUND: Faecal incontinence (FI) is a debilitating condition which reduces quality of life (QOL). Conservative management with education, pelvic floor exercise and pharmacological agents are first-line treatment. Following which, biofeedback therapy (BFT) is recommended. Although well described in the West, existing literature on its efficacy in Asian populations remains sparse. The primary aim of our study is to evaluate the efficacy of BFT in improvement of symptoms, QOL and overall satisfaction in our Asian population. METHODS: Patients with moderate FI in Singapore General Hospital between 2012 and 2016 were enrolled. Rockwood FI quality of life scale (FIQL) and Wexner scale were used to evaluate QOL across four domains, and symptom severity respectively. They were scored at baseline and again after four sessions of BFT, with an additional overall satisfaction score (OSS). RESULTS: A total of 137 patients were included. Mean age was 62 years and 72.3% were female. Majority demonstrated improvement in Wexner score (68.6%) and FIQL (65%). Sixty-five patients (47.4%) reported improvement in both. Positive correlation was found between Wexner score and OSS (r = 0.206), and Wexner score and FIQL across all four domains. Only one FIQL domain-coping/behaviour, showed statistically significant correlation with OSS (r = 0.263). CONCLUSION: BFT is effective in our Asian population in both symptom reduction and improving QOL. Wexner score demonstrated low correlation with FIQL and OSS-suggesting that FI requires a multi-dimensional approach beyond symptom treatment, of which ability to cope appears crucial. BFT, consistent with the biopsychosocial model, shows benefit in this regard.

Survival outcomes of salvage surgery in the watch-and-wait approach for rectal cancer with clinical complete response after neoadjuvant chemoradiotherapy: a systematic review and meta-analysis.

PURPOSE: This systematic review and meta-analysis compared the outcomes of the watch-and-wait (WW) approach versus radical surgery (RS) in rectal cancers with clinical complete response (cCR) after neoadjuvant chemoradiotherapy. METHODS: This study followed the PRISMA guidelines. Major databases were searched to identify relevant articles. WW and RS were compared through meta-analyses of pooled proportions. Primary outcomes included overall survival (OS), disease-free survival (DFS), local recurrence, and distant metastasis rates. Pooled salvage surgery rates and outcomes were also collected. The Newcastle-Ottawa scale was employed to assess the risk of bias. RESULTS: Eleven studies including 1,112 rectal cancer patients showing cCR after neoadjuvant chemoradiation were included. Of these patients, 378 were treated nonoperatively with WW, 663 underwent RS, and 71 underwent local excision. The 2-year OS (risk ratio [RR], 0.95; P = 0.94), 5-year OS (RR, 2.59; P = 0.25), and distant metastasis rates (RR, 1.05; P = 0.80) showed no significant differences between WW and RS. Local recurrence was more frequent in the WW group (RR, 6.93; P < 0.001), and 78.4% of patients later underwent salvage surgery (R0 resection rate, 97.5%). The 2-year DFS (RR, 1.58; P = 0.05) and 5-year DFS (RR, 2.07; P = 0.02) were higher among RS cases. However, after adjustment for R0 salvage surgery, DFS showed no significant between-group difference (RR, 0.82; P = 0.41). CONCLUSION: Local recurrence rates are higher for WW than RS, but complete salvage surgery is often possible with similar long-term outcomes. WW is a viable strategy for rectal cancer with cCR after neoadjuvant chemoradiation, but further research is required to improve patient selection.

The distinct clinical trajectory, metastatic sites, and immunobiology of microsatellite-instability-high cancers.

Microsatellite-instability-high (MSI-H) cancers form a spectrum of solid organ tumors collectively known as Lynch Syndrome cancers, occurring not only in a subset of colorectal, endometrial, small bowel, gastric, pancreatic, and biliary tract cancers but also in prostate, breast, bladder, and thyroid cancers. Patients with Lynch Syndrome harbor germline mutations in mismatch repair genes, with a high degree of genomic instability, leading to somatic hypermutations and, therefore, oncogenesis and cancer progression. MSI-H cancers have unique clinicopathological characteristics compared to their microsatellite-stable (MSS) counterparts, marked by a higher neoantigen load, immune cell infiltration, and a marked clinical response to immune checkpoint blockade. Patients with known Lynch Syndrome may be detected early through surveillance, but some patients present with disseminated metastatic disease. The treatment landscape of MSI-H cancers, especially colorectal cancers, has undergone a paradigm shift and remains to be defined, with immune checkpoint blockade coming to the forefront of treatment strategies in the stage IV setting. We summarize in this review the clinical features of MSI-H cancers with a specific interest in the pattern of spread or recurrence, disease trajectory, and treatment strategies. We also summarize the tumor-immune landscape and genomic profile of MSI-H cancers and potential novel therapeutic strategies.

Heat selection enables highly scalable methylome profiling in cell-free DNA for noninvasive monitoring of cancer patients.

Genome-wide analysis of cell-free DNA methylation profile is a promising approach for sensitive and specific detection of many cancers. However, scaling such assays for clinical translation is impractical because of the high cost of whole-genome bisulfite sequencing. We show that the small fraction of GC-rich genome is highly enriched in CpG sites and disproportionately harbors most of the cancer-specific methylation signature. Here, we report on the simple and effective heat enrichment of CpG-rich regions for bisulfite sequencing (Heatrich-BS) platform that allows for focused methylation profiling in these highly informative regions. Our novel method and bioinformatics algorithm enable accurate tumor burden estimation and quantitative tracking of colorectal cancer patient's response to treatment at much reduced sequencing cost suitable for frequent monitoring. We also show tumor epigenetic subtyping using Heatrich-BS, which could enable patient stratification. Heatrich-BS holds great potential for highly scalable screening and monitoring of cancer using liquid biopsy.

Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.

The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined 'IMF' classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).