Efficacy and safety of extended duration to perioperative thromboprophylaxis with low molecular weight heparin on disease-free survival after surgical resection of colorectal cancer (PERIOP-01): multicentre, open label, randomised controlled trial.

OBJECTIVE: To determine the efficacy and safety of extended duration perioperative thromboprophylaxis by low molecular weight heparin when assessing disease-free survival in patients undergoing resection for colorectal cancer. DESIGN: Multicentre, open label, randomised controlled trial. SETTINGS: 12 hospitals in Quebec and Ontario, Canada, between 25 October 2011 and 31 December 2020. PARTICIPANTS: 614 adults (age ≥18 years) were eligible with pathologically confirmed invasive adenocarcinoma of the colon or rectum, no evidence of metastatic disease, a haemoglobin concentration of ≥8 g/dL, and were scheduled to undergo surgical resection. INTERVENTIONS: Random assignment to extended duration thromboprophylaxis using daily subcutaneous tinzaparin at 4500 IU, beginning at decision to operate and continuing for 56 days postoperatively, compared with in-patient postoperative thromboprophylaxis only. MAIN OUTCOME MEASURES: Primary outcome was disease-free survival at three years, defined as survival without locoregional recurrence, distant metastases, second primary (same cancer), second primary (other cancer), or death. Secondary outcomes included venous thromboembolism, postoperative major bleeding complications, and five year overall survival. Analyses were done in the intention-to-treat population. RESULTS: The trial stopped recruitment prematurely after the interim analysis for futility. The primary outcome occurred in 235 (77%) of 307 patients in the extended duration group and in 243 (79%) of 307 patients in the in-hospital thromboprophylaxis group (hazard ratio 1.1, 95% confidence interval 0.90 to 1.33; P=0.4). Postoperative venous thromboembolism occurred in five patients (2%) in the extended duration group and in four patients (1%) in the in-hospital thromboprophylaxis group (P=0.8). Major surgery related bleeding in the first postoperative week was reported in one person (<1%) in the extended duration and in six people (2%) in the in-hospital thromboprophylaxis group (P=0.1). No difference was noted for overall survival at five years in 272 (89%) patients in the extended duration group and 280 (91%) patients in the in-hospital thromboprophylaxis group (hazard ratio 1.12; 95% confidence interval 0.72 to 1.76; P=0.1). CONCLUSIONS: Extended duration to perioperative anticoagulation with tinzaparin did not improve disease-free survival or overall survival in patients with colorectal cancer undergoing surgical resection compared with in-patient postoperative thromboprophylaxis alone. The incidences of venous thromboembolism and postoperative major bleeding were low and similar between groups. TRIAL REGISTRATION: ClinicalTrials.gov NCT01455831.

Laparoscopic translevator approach to abdominoperineal resection for rectal adenocarcinoma: feasibility and short-term oncologic outcomes.

BACKGROUND: The extra-levator approach to abdominal perineal resection (APR) was developed in order to reduce the rates of positive circumferential resection margin. This approach, however, is associated with significant morbidity. We postulate that a less radical resection of the levators done laparoscopically could significantly decrease the rate of perineal complications while ensuring an oncologically adequate specimen. To date, to our knowledge, there are no reports in the literature describing a laparoscopic translevator approach for APR. The purpose of this study is to describe our initial experience with this approach and assess our short-term oncologic and clinical outcomes. METHODS: This is a retrospective study of patients who underwent laparoscopic APR with intra-abdominal levator transection for rectal cancer from 2012 to 2014 at a single tertiary care institution. Main outcome measures include: perineal flap rates, post-operative complications, length of stay, distance from tumour to circumferential resection margin, R0 status, and disease recurrence. Data are presented as median (interquartile range) unless otherwise noted. RESULTS: Seventeen cases were identified. Patient age was 61 (range 34-75), and 59 % were male. Pre-operative distance of the tumour from the anal verge was 2.6 cm (0.4-3.9). Post-operative length of stay was 4 (4-6) days. One patient required a perineal flap for reconstruction. Four patients (22 %) had perineal complications (three wound infections and one hernia). No patients reported sexual dysfunction, and one (5 %) developed urinary retention. Five (29 %) patients had a complete pathological response. The circumferential resection margin was 1.5 (0.8-2.5) cm, with no positive margins reported. The number of retrieved lymph nodes was 12 (range 2-30). Follow-up was 9.7 months (range 20 days-23 months), during which one patient developed recurrent disease. CONCLUSIONS: This study describes a novel surgical approach to APR that has the potential to both decrease perineal complications and provide excellent oncologic results.