Using heart rate variability to develop a predictive model for post-operative cardiovascular complications following major abdominal surgery: A pilot study.

BACKGROUND: Heart Rate Variability (HRV) is a dynamic reflection of heart rhythm regulation by various physiological inputs. HRV deviations have been found to correlate with clinical outcomes in patients under physiological stresses. Perioperative cardiovascular complications occur in up to 5% of adult patients undergoing abdominal surgery and are associated with significantly increased mortality. This pilot study aimed to develop a predictive model for post-operative cardiovascular complications using HRV parameters for early risk stratification and aid post-operative clinical decision-making. METHODS: Adult patients admitted to High Dependency Units after elective major abdominal surgery were recruited. The primary composite outcome was defined as cardiovascular complications within 7 days post-operatively. ECG monitoring for HRV parameters was conducted at three time points (pre-operative, immediately post-operative, and post-operative day 1) and analyzed based on outcome group and time interactions. Candidate HRV predictors were included in a multivariable logistic regression analysis incorporating a stepwise selection algorithm. RESULTS: 89 patients were included in the analysis, with 8 experiencing cardiovascular complications. Three HRV parameters, when measured immediately post-operatively and composited with patient age, provided the basis for a predictive model with AUC of 0.980 (95% CI: 0.953, 1.00). The negative predictive value was 1.00 at a statistically optimal predicted probability cut-off point of 0.16. CONCLUSION: Our model holds potential for accelerating clinical decision-making and aiding in patient triaging post-operatively, using easily acquired HRV parameters. Risk stratification with our model may enable safe early step-down care in patients assessed to have a low risk profile of post-operative cardiovascular complications.

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.

The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/ß-catenin to RTK/MAPK signaling.

Wnts, cholesterol, and MAPK signaling are essential for development and adult homeostasis. Here, we report that fatty acid hydroxylase domain containing 2 (FAXDC2), a previously uncharacterized enzyme, functions as a methyl sterol oxidase catalyzing C4 demethylation in the Kandutsch-Russell branch of the cholesterol biosynthesis pathway. FAXDC2, a paralog of MSMO1, regulated the abundance of the specific C4-methyl sterols lophenol and dihydro-T-MAS. Highlighting its clinical relevance, FAXDC2 was repressed in Wnt/ß-catenin-high cancer xenografts, in a mouse genetic model of Wnt activation, and in human colorectal cancers. Moreover, in primary human colorectal cancers, the sterol lophenol, regulated by FAXDC2, accumulated in the cancerous tissues and not in adjacent normal tissues. FAXDC2 linked Wnts to RTK/MAPK signaling. Wnt inhibition drove increased recycling of RTKs and activation of the MAPK pathway, and this required FAXDC2. Blocking Wnt signaling in Wnt-high cancers caused both differentiation and senescence; and this was prevented by knockout of FAXDC2. Our data show the integration of 3 ancient pathways, Wnts, cholesterol synthesis, and RTK/MAPK signaling, in cellular proliferation and differentiation.

Intracorporeal antimesenteric ancillary trocar: an anastomotic technique facilitating natural orifice specimen extraction in left-sided colorectal surgery.

AIM: Natural orifice specimen extraction (NOSE) in left-sided colorectal surgery requires application of the circular stapler anvil to the proximal bowel without exteriorization through an additional abdominal incision. We describe an intracorporeal method to secure the stapler anvil, termed the intracorporeal antimesenteric ancillary trocar (IAAT) technique. METHOD: The ancillary trocar is attached to the stapler anvil before introduction into the abdominal cavity through the anal or vaginal orifice. The colon is incised before the trocar spike is brought out through the antimesenteric surface 3-4 cm within the cut edge. A linear stapler is used to seal the bowel end. The ancillary trocar is detached and retrieved via the NOSE conduit. Following the NOSE procedure, a side-to-end colorectal anastomosis is performed with the transanal circular stapler. RESULTS: Ten consecutive patients underwent elective left-sided colorectal resection with IAAT for NOSE (seven transanal, three transvaginal) from January to June 2023. Median age and body mass index were 66 (range 47-74) years and 24.3 (range 17.9-30.8) kg/m2 respectively. Two (20%) patients underwent sigmoid colectomy for sigmoid volvulus while eight (80%) underwent anterior resection for colorectal cancer. Median operating time, operative blood loss and postoperative length of hospital stay were 170 (range 140-240) min, 20 (range 10-40) mL and 1 (range 1-3) day respectively. There were no postoperative complications, readmissions or reoperations. Median follow-up duration was 3 (range 1-6) months. CONCLUSION: The IAAT double-stapling side-to-end anastomotic technique is safe and feasible for patients undergoing left-sided colorectal resection with NOSE, resulting in good outcomes.

Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas.

BACKGROUND: Colorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aimed to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients. METHODS: A case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analysed with the correlation/trend test based on the additive model. SNP variants with association testing -log10 p value ≥5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation. RESULTS: Glycolysis was uncovered as the top hallmark gene set. Transcripts from two of the five genes profiled, hematopoietic substrate 1 associated protein X 1 (HAX1) and hyaluronan-mediatedmotility receptor (HMMR), were significantly upregulated in the metastasis-positive tumours. In contrast to disease-risk variants, HAX1 appeared to act synergistically with HMMR in significantly impacting metastasis-free survival. Examining the subtype datasets with FUMA and Ingenuity Pathway Analysis (IPA) identified distinct pathways demonstrating sexual dimorphism in CRC metastasis. CONCLUSIONS: Combining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of patients with stage I-III CRC.

Transanal Total Mesorectal Excision With Delayed Coloanal Anastomosis (TaTME-DCAA) Versus Laparoscopic Total Mesorectal Excision (LTME) and Robotic Total Mesorectal Excision (RTME) for Low Rectal Cancer: A Propensity Score-Matched Analysis of Short-term Outcomes, Bowel Function, and Cost.

INTRODUCTION: Total mesorectal excision (TME) with delayed coloanal anastomosis (DCAA) is surgical option for low rectal cancer, replacing conventional immediate coloanal anastomosis (ICAA) with bowel diversion. This study aimed to assess the outcomes of transanal TME (TaTME) with DCAA versus laparoscopic TME (LTME) with ICAA versus robotic TME (RTME) with ICAA. METHODS: This was a retrospective propensity score-matched analysis of patients who underwent elective TaTME-DCAA between November 2021 and June 2022. Patients were propensity-score matched in a ratio of 1:3 to patients who underwent LTME-ICAA and RTME-ICAA from January 2019 to December 2020. Outcome measures were histopathologic results, postoperative morbidity, function, and inpatient costs. RESULTS: Twelve patients in the TaTME-DCAA group were compared with 36 patients in the LTME-ICAA and RTME-ICAA groups each after propensity score matching. Histopathologic results and postoperative morbidity rates were statistically similar. Overall stoma-related complication rates in the ICAA groups were 11%. Median total length of hospital stays for TME plus stoma reversal surgery was similar across all techniques (10 vs. 10 vs. 9 days; P =0.532). Despite a significantly shorter duration of follow-up, bowel function after TaTME-DCAA was comparable to that of LTME-ICAA and RTME-ICAA. Overall median inpatient costs of TaTME-DCAA were comparable to LTME-ICAA and significantly cheaper than RTME-ICAA ($31,087 vs. $29,927 vs. $36,750; P =0.002). CONCLUSIONS: TaTME with DCAA is a feasible and safe technique compared with other minimally invasive methods of TME, while avoiding bowel diversion and stoma-related complications, as well as comparing favorably in terms of overall hospitalization costs.

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.

Transvaginal Natural Orifice Specimen Extraction (NOSE) in Laparoscopic Colorectal Cancer Surgery With New Insights on Technique and Patient Selection.

BACKGROUND: Following laparoscopic colorectal surgery, transabdominal specimen extraction requires a mini-laparotomy or Pfannenstiel incision, associated with increased postoperative pain and wound complications. The vagina has several unique properties that make natural orifice specimen extraction (NOSE) ideal. We report our experience with transvaginal NOSE for colorectal cancer surgery. MATERIALS AND METHODS: A transvaginal sizer allows the posterior vagina to be incised under tension. A transverse or cruciate incision is made, followed by the insertion of a double-ring wound protector. The external ring is opened against the perineum to shorten the length of the conduit for specimen delivery. Vaginotomy closure is performed via laparoscopy using a barbed suture. RESULTS: Seventeen consecutive female patients underwent elective colorectal cancer surgery with attempted transvaginal NOSE. Median age and body mass index was 67 (range: 50 to 82) years and 26.5 (range: 19.7 to 35.8) kg/m 2 , respectively. Fourteen patients (82%) underwent left-sided resections and 3 (18%) underwent right-sided resections. Median operating time, blood loss, and length of hospital stay was 245 (range: 155 to 360) minutes, 30 (range: 10 to 500) mL, and 3 (range: 2 to 9) days, respectively. Transvaginal extraction was unsuccessful in 1 (6%) patient. Two (12%) patients experienced early postoperative morbidity, neither attributable to the extraction procedure. Median tumor circumferential diameter was 3.3 (range: 2.2 to 7.0) cm. Median follow-up duration was 17 (range: 8 to 27) months. There was no instance of sexual dysfunction. CONCLUSIONS: Transvaginal NOSE for colorectal cancer surgery is feasible and safe in selected patients. Overall specimen diameter, inclusive of tumor and mesentery, relative to pelvic outlet and conduit diameter is the most important consideration for transvaginal NOSE.

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.

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.