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.

Canadian taTME expert collaboration (CaTaCO) position statement.

INTRODUCTION: Transanal total mesorectal excision (taTME) is a novel approach to surgery for rectal cancer. The technique has gained significant popularity in the surgical community due to the promising ability to overcome technical difficulties related to the access of the distal pelvis. Recently, Norwegian surgeons issued a local moratorium related to potential issues with the safety of the procedure. Early adopters of taTME in Canada have recognized the need to create guidelines for its adoption and supervision. The objective of the statement is to provide expert opinion based on the best available evidence and authors' experience. METHODS: The procedure has been performed in Canada since 2014 at different institutions. In 2016, the first Canadian taTME congress was held in the city of Toronto, organized by two of the authors. In early 2019, a multicentric collaborative was established [The Canadian taTME expert Collaboration] which aimed at ensuring safe performance and adoption of taTME in Canada. Recently surgeons from 8 major Canadian rectal cancer centers met in the city of Toronto on December 7 of 2019, to discuss and develop a position statement. There in person, meeting was followed by 4 rounds of Delphi methodology. RESULTS: The generated document focused on the need to ensure a unified approach among rectal cancer surgeons across the country considering its technical complexity and potential morbidity. The position statement addressed four domains: surgical setting, surgeons' requirements, patient selection, and quality assurance. CONCLUSIONS: Authors agree transanal total mesorectal excision is technically demanding and has a significant risk for morbidity. As of now, there is uncertainty for some of the outcomes. We consider it is possible to safely adopt this operation and obtain adequate results, however for this purpose it is necessary to meet specific requirements in different domains.

Safety and Feasibility of Using Magnetic Resonance Imaging Criteria to Identify Patients With "Good Prognosis" Rectal Cancer Eligible for Primary Surgery: The Phase 2 Nonrandomized QuickSilver Clinical Trial.

IMPORTANCE: Chemoradiotherapy (CRT), followed by surgery, is the recommended approach for stage II and III rectal cancer. While CRT decreases the risk of local recurrence, it does not improve survival and leads to poorer functional outcomes than surgery alone. Therefore, new approaches to better select patients for CRT are important. OBJECTIVE: To conduct a phase 2 study to evaluate the safety and feasibility of using magnetic resonance imaging (MRI) criteria to select patients with "good prognosis" rectal tumors for primary surgery. DESIGN, SETTING, AND PARTICIPANTS: Prospective nonrandomized phase 2 study at 12 high-volume colorectal surgery centers across Canada. From September 30, 2014, to October 21, 2016, a total of 82 patients were recruited for the study. Participants were patients newly diagnosed as having rectal cancer with MRI-predicted good prognosis rectal cancer. The MRI criteria for good prognosis tumors included distance to the mesorectal fascia greater than 1 mm; definite T2, T2/early T3, or definite T3 with less than 5 mm of extramural depth of invasion; and absent or equivocal extramural venous invasion. INTERVENTIONS: Patients with rectal cancer with MRI-predicted good prognosis tumors underwent primary surgery. MAIN OUTCOMES AND MEASURES: The primary outcome was the proportion of patients with a positive circumferential resection margin (CRM) rate. Assuming a 10% baseline probability of a positive CRM, a sample size of 75 was estimated to yield a 95% CI of ±6.7%. RESULTS: Eighty-two patients (74% male) participated in the study. The median age at the time of surgery was 66 years (range, 37-89 years). Based on MRI, most tumors were midrectal (65% [n = 53]), T2/early T3 (60% [n = 49]), with no suspicious lymph nodes (63% [n = 52]). On final pathology, 91% (n = 75) of tumors were T2 or greater, 29% (n = 24) were node positive, and 59% (n = 48) were stage II or III. The positive CRM rate was 4 of 82 (4.9%; 95% CI, 0.2%-9.6%). CONCLUSIONS AND RELEVANCE: The use of MRI criteria to select patients with good prognosis rectal cancer for primary surgery results in a low rate of positive CRM and suggests that CRT may not be necessary for all patients with stage II and III rectal cancer. TRIAL REGISTRATION: ISRCTN.com identifier: ISRCTN05107772.

Technical Performance as a Predictor of Clinical Outcomes in Laparoscopic Gastric Cancer Surgery.

OBJECTIVE: The purpose of this study was to evaluate the relationship between technical performance and patient outcomes in laparoscopic gastric cancer surgery. BACKGROUND: Laparoscopic gastrectomy for cancer is an advanced procedure with high rate of postoperative morbidity and mortality. Many variables including patient, disease, and perioperative management factors have been shown to impact postoperative outcomes; however, the role of surgical performance is insufficiently investigated. METHODS: A retrospective review was performed for all patients who had undergone laparoscopic gastrectomy for cancer at 3 teaching institutions between 2009 and 2015. Patients with available, unedited video-recording of their procedure were included in the study. Video files were rated for technical performance, using Objective Structured Assessments of Technical Skills (OSATS) and Generic Error Rating Tool instruments. The main outcome variable was major short-term complications. The effect of technical performance on patient outcomes was assessed using logistic regression analysis with backward selection strategy. RESULTS: Sixty-one patients with available video recordings were included in the study. The overall complication rate was 29.5%. The mean Charlson comorbidity index, type of procedure, and the global OSATS score were included in the final predictive model. Lower performance score (OSATS ≤29) remained an independent predictor for major short-term outcomes (odds ratio 6.49), while adjusting for comorbidities and type of procedure. CONCLUSIONS: Intraoperative technical performance predicts major short-term outcomes in laparoscopic gastrectomy for cancer. Ongoing assessment and enhancement of surgical skills using modern, evidence-based strategies might improve short-term patient outcomes. Future work should focus on developing and studying the effectiveness of such interventions in laparoscopic gastric cancer surgery.

Urologic complications of composite resection following combined modality treatment of colorectal cancer.

BACKGROUND: It is a common perception that preoperative radiation increases the incidence of urologic complications following composite resection, but there is little evidence to support or refute this claim. METHODS: Patients who underwent ureteric reconstruction as a component of en bloc resection for locally advanced or recurrent colorectal cancer were identified from a multicenter institutional database (1982-2007). Charts were reviewed to determine the incidence, nature, management, and predictors of serious urologic complications. RESULTS: 126 patients (34 female, 92 male) met the inclusion criteria: (1) division of one or both ureters; and (2) ureteric reconstruction involving anastomosis to ureter, bladder, small bowel or colon. Urologic complications requiring intervention occurred in 30 (24%) patients, including: anastomotic leak (n = 11), anastomotic stricture (n = 10), fistula (n = 5), conduit/stoma problem (n = 5), and other (n = 3). Eight patients required surgical revision. The rate of urologic complications was similar in patients who had received radiation at some time prior to the index surgery and those who had not (25% and 19%, respectively, P = 0.61). There was a trend towards a higher complication rate with more complex compared with simpler reconstructive procedures (38% versus 20%, P = 0.069). CONCLUSION: 24% of patients who underwent ureteric reconstruction following composite resection developed a urologic complication that required intervention. Preoperative radiotherapy did not appear to predispose patients to urologic complications. Optimization of surgical technique at the time of en bloc resection may obviate the need for subsequent revision.

Safe implementation of laparoscopic gastrectomy in a community-based general surgery practice.

BACKGROUND: This study reviewed a 3-year experience with the implementation of laparoscopic gastrectomy at a community hospital. METHODS: A retrospective chart review identified all patients that underwent laparoscopic gastrectomy between January 2004 and March 2007. Patient demographics, tumor characteristics, length of stay, operative time, and short-term outcomes (postoperative complications and death) were examined. RESULTS: A total of 49 patients were identified; 25 (51%) were male. Median age was 68 years (range 31-90 years). Thirty-five (71%) and seven (14%) patients presented with adenocarcinoma and gastrointestinal stromal tumor (GIST), respectively. Median operative time was 169 min (range 23-387 min). Conversion to open laparotomy was necessary in six cases (12%). Median length of stay was 5 days (range 0-48 days). There were four (8.2%) postoperative deaths, and eight major complications, which included: myocardial infarction, pulmonary embolism, duodenal stump leak, bleeding, dehiscence, anastomotic leak, and obstruction. Of patients undergoing laparoscopic gastrectomy with curative intent, 36/38 (95%) underwent R0 resection. Median number of lymph nodes that were pathologically evaluated was 11 (range 1-27). CONCLUSION: To our knowledge, this is the first study to report on the implementation of laparoscopic gastrectomy in a community hospital setting. Laparoscopic gastrectomy can be performed safely in a community hospital setting with operative times and length of stay that are comparable to open cases. Our short-term outcomes are comparable with existing studies from academic/university centers.

Results of an aggressive approach to resection of locally recurrent rectal cancer.

BACKGROUND: The value of resection for locally recurrent rectal cancer (LRRC) remains controversial. We analyzed outcomes of an aggressive approach to resection of LRRC. METHODS: We conducted a retrospective chart review of 52 consecutive patients who underwent resection of LRRC from September 1997 through August 2005. Overall and disease-free survival (OS, DFS) curves were constructed by the Kaplan-Meier method, and compared by log-rank analysis. Median follow-up time was 29 months (range 3-72). RESULTS: Thirty-one patients (60%) were male. Median age was 60 years (range 36-88). Forty-six of the 52 patients were resected with curative intent, while 6 had known distant metastases at the time of resection. All 52 patients underwent grossly complete resection of local disease, and 41 (79%) had microscopically clear resection margins. An en bloc sacrectomy was performed in 28 (54%) patients. Postoperative mortality was nil; significant complications developed in 42% of patients. The complication rate was higher in patients with sacrectomy than without (50 vs. 33%, P = 0.017, Chi square). For the entire cohort of 52 patients, median OS and DFS were 40 and 24 months, respectively. Survival was equivalent in patients with and without sacrectomy. In the 46 patients who had resection with curative intent, 4-year OS was 48%. Median OS in the six patients with distant metastases at the time of resection was 21 months. OS was predicted by the presence of metastases (P = 0.01), and margin status (P < 0.0001). DFS was predicted by margin status (P = 0.0001). CONCLUSIONS: In this series of patients who underwent resection of LRRC, microscopic margin status was the most significant predictor of OS and DFS. Requirement for en bloc sacrectomy was not associated with inferior survival. Carefully selected patients with distant metastases may benefit from resection of LRRC.

Influence of gender and interleukin-10 deficiency on the inflammatory response during lung infection with Pseudomonas aeruginosa in mice.

Cystic fibrosis females have a worse prognosis compared to male patients. Furthermore, cystic fibrosis patients infected with Pseudomonas aeruginosa have been shown to have dysregulated cytokine profiles, as higher levels of tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-8, and lower levels of IL-10 are found in the bronchoalveolar lavage fluid compared to healthy controls. The present study was aimed at investigating the importance of gender and IL-10 in the susceptibility of C57BL/6 mice to pulmonary infection with Pseudomonas aeruginosa. We found that wildtype females were more susceptible than males to infection, as we observed greater weight loss, higher bacterial load, and inflammatory mediators in their lungs. IL-10 knockout mice, both females and males, had higher levels of TNF-alpha in the lungs compared to wildtype mice and maintained higher levels of polymorphonuclear cells and lower levels of macrophages for a longer period of time. Our results demonstrate that the number of bacteria recovered from the lungs of IL-10 knockout male mice was significantly higher than that observed in their wildtype male counterparts and we show that neutralization of IL-10 in infected female mice for a prolonged period of time leads to increased susceptibility to infection. Results reported in this study clearly demonstrate that females, both wildtype and IL-10 knockout mice are more susceptible to Pseudomonas aeruginosa infection than males, and that they mount a stronger inflammatory response in the lungs.