Rivaroxaban vs placebo for extended antithrombotic prophylaxis after laparoscopic surgery for colorectal cancer

The clinical benefit of extended prophylaxis for venous thromboembolism (VTE) after laparoscopic surgery for cancer is undear. The efficacy and safety of direct oral anticoagulants for this indication are unexplored. PROphylaxis of venous thromboembolism after LAParoscopic Surgery for colorectal cancer Study II (PROLAPS II) was a randomized, double-blind, placebo-controlled, investigator-initiated, superiority study aimed at assessing the efficacy and safety of extended prophylaxis with rivaroxaban after laparoscopic surgery for colorectal cancer. Consecutive patients who had laparoscopic surgery for colorectal cancer were randomized to receive rivaroxaban (10 mg once daily) or a placebo to be started at 7 +/- 2 days after surgery and given for the subsequent 3 weeks. All patients received antithrombotic prophylaxis with low-molecular-weight heparin from surgery to randomization. The primary study outcome was the composite of symptomatic objectively confirmed VTE, asymptomatic ultrasonography-detected deep vein thrombosis (DVT), or VTE-related death at 28 +/- 2 days after surgery. The primary safety outcome was major bleeding. Patient recruitment was prematurely closed due to study drug expiry after the inclusion of 582 of the 646 planned patients. A primary study outcome event occurred in 11 of 282 patients in the placebo group compared with 3 of 287 in the rivaroxaban group (3.9 vs 1.0%; odds ratio, 0.26; 95% confidence interval [CI], 0.07-0.94; log-rank P = .032). Major bleeding occurred in none of the patients in the placebo group and 2 patients in the rivaroxaban group (incidence rate 0.7%; 95% CI, 0-1.0). Oral rivaroxaban was more effective than placebo for extended prevention of VTE after laparoscopic surgery for colorectal cancer without an increase in major bleeding

Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort

Objective:To develop and validate a prediction model (STOMA score) for 1-year stoma-free survival in patients with rectal cancer (RC) with anastomotic leakage (AL).Background:AL after RC resection often results in a permanent stoma.Methods:This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres and included patients who developed AL after RC surgery between 2014 and 2018. Clinically relevant predictors for 1-year stoma-free survival were included in uni and multivariable logistic regression models. The STOMA score was developed and internally validated in a cohort of patients operated between 2014 and 2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated.Results:This study included 2499 patients with AL, 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA score: sex, age, American Society of Anestesiologist classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction, and reactivation leakage. The STOMA score showed good discrimination and calibration (c-index: 0.71, 95% CI: 0.66-0.76).Conclusions:The STOMA score consists of 18 clinically relevant factors and estimates the individual risk for 1-year stoma-free survival in patients with AL after RC surgery, which may improve patient counseling and give guidance when analyzing the efficacy of different treatment strategies in future studies

30-day Morbidity and Mortality after Cholecystectomy for Benign Gallbladder Disease (AMBROSE): A Prospective, International Collaborative Cohort Study

Objective: This study aimed to assess 30-day morbidity and mortality rates following cholecystectomy for benign gallbladder disease and identify the factors associated with complications. Summary background data: Although cholecystectomy is common for benign gallbladder disease, there is a gap in the knowledge of the current practice and variations on a global level. Methods: A prospective, international, observational collaborative cohort study of consecutive patients undergoing cholecystectomy for benign gallbladder disease from participating hospitals in 57 countries between January 1 and June 30, 2022, was performed. Univariate and multivariate logistic regression models were used to identify preoperative and operative variables associated with 30-day postoperative outcomes. Results: Data of 21,706 surgical patients from 57 countries were included in the analysis. A total of 10,821 (49.9%), 4,263 (19.7%), and 6,622 (30.5%) cholecystectomies were performed in the elective, emergency, and delayed settings, respectively. Thirty-day postoperative complications were observed in 1,738 patients (8.0%), including mortality in 83 patients (0.4%). Bile leaks (Strasberg grade A) were reported in 278 (1.3%) patients and severe bile duct injuries (Strasberg grades B-E) were reported in 48 (0.2%) patients. Patient age, ASA physical status class, surgical setting, operative approach and Nassar operative difficulty grade were identified as the five predictors demonstrating the highest relative importance in predicting postoperative complications. Conclusion: This multinational observational collaborative cohort study presents a comprehensive report of the current practices and outcomes of cholecystectomy for benign gallbladder disease. Ongoing global collaborative evaluations and initiatives are needed to promote quality assurance and improvement in cholecystectomy

Early outcomes from the Minimally Invasive Right Colectomy Anastomosis study (MIRCAST)

Background: The impact of method of anastomosis and minimally invasive surgical technique on surgical and clinical outcomes after right hemicolectomy is uncertain. The aim of the MIRCAST study was to compare intracorporeal and extracorporeal anastomosis (ICA and ECA respectively), each using either a laparoscopic approach or robot-assisted surgery during right hemicolectomies for benign or malignant tumours. Methods: This was an international, multicentre, prospective, observational, monitored, non-randomized, parallel, four-cohort study (laparoscopic ECA; laparoscopic ICA; robot-assisted ECA; robot-assisted ICA). High-volume surgeons (at least 30 minimally invasive right colectomy procedures/year) from 59 hospitals across 12 European countries treated patients over a 3-year interval The primary composite endpoint was 30-day success, defined by two measures of efficacy-absence of surgical wound infection and of any major complication within the first 30 days after surgery. Secondary outcomes were: overall complications, conversion rate, duration of operation, and number of lymph nodes harvested. Propensity score analysis was used for comparison of ICA with ECA, and robot-assisted surgery with laparoscopy. Results: Some 1320 patients were included in an intention-to-treat analysis (laparoscopic ECA, 555; laparoscopic ICA, 356; robot-assisted ECA, 88; robot-assisted ICA, 321). No differences in the co-primary endpoint at 30 days after surgery were observed between cohorts (7.2 and 7.6 per cent in ECA and ICA groups respectively; 7.8 and 6.6 per cent in laparoscopic and robot-assisted groups). Lower overall complication rates were observed after ICA, specifically less ileus, and nausea and vomiting after robot-assisted procedures. Conclusion: No difference in the composite outcome of surgical wound infections and severe postoperative complications was found between intracorporeal versus extracorporeal anastomosis or laparoscopy versus robot-assisted surgery

A critical appraisal of epidemiological studies comes from basic knowledge: a reader's guide to assess potential for biases

: Scientific literature may be biased because of the internal validity of studies being compromised by different forms of measurement error, and/or because of the selective reporting of positive and 'statistically significant' results. While the first source of bias might be prevented, and in some cases corrected to a degree, the second represents a pervasive problem afflicting the medical literature; a situation that can only be 'corrected' by a change in the mindset of authors, reviewers, and editors. This review focuses on the concepts of confounding, selection bias and information bias, utilising explanatory examples and simple rules to recognise and, when possible, to correct for them. Confounding is a mixing of effects resulting from an imbalance of some of the causes of disease across the compared groups. It can be prevented by randomization and restriction, and controlled by stratification, standardization or by using multivariable techniques. Selection bias stems from an absence of comparability among the groups being studied, while information bias arises from distorted information collection techniques. Publication bias of medical research results can invalidate evidence-based medicine, when a researcher attempting to collect all the published studies on a specific topic actually gathers only a proportion of them, usually the ones reporting 'positive' results. The selective publication of 'statistically significant' results represents a problem that researchers and readers have to be aware of in order to face the entire body of published medical evidence with a degree of scepticism

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group

Aim Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. Methods The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. Results A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. Conclusions While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Background The optimal treatment of anastomotic leak after rectal cancer resection is unclear. This worldwide cohort study aimed to provide an overview of four treatment strategies applied.Methods Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. Treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1).Results Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. One-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. Propensity score matching resulted in 556 patients with passive and 278 with active drainage. There was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. After active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days).Conclusion Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding.The optimal treatment strategy for anastomotic leakage after restorative rectal cancer surgery remains unknown. This large, international collaborative study investigated various outcomes after four predefined treatment strategies for anastomotic leakage. Substantial differences were observed in patient and leakage characteristics, as well as outcomes following the four treatment strategies. However, no statistically significant differences were reported in stoma-free survival rates between active (vacuum) drainage and passive drainage

3D pelvimetry and biometric measurements: a surgical perspective for colorectal resections

Purpose Male sex, high BMI, narrow pelvis, and bulky mesorectum were acknowledged as clinical variables correlated with a difficult pelvic dissection in colorectal surgery. This paper aimed at comparing pelvic biometric measurements in female and male patients and at providing a perspective on how pelvimetry segmentation may help in visualizing mesorectal distribution. Methods A 3D software was used for segmentation of DICOM data of consecutive patients aged 60 years, who underwent elective abdominal CT scan. The following measurements were estimated: pelvic inlet, outlet, and depth; pubic tubercle height; distances from the promontory to the coccyx and to S3/S4; distance from S3/S4 to coccyx's tip; ischial spines distance; pelvic tilt; offset angle; pelvic inlet angle; angle between the inlet/sacral promontory/coccyx; angle between the promontory/coccyx/pelvic outlet; S3 angle; and pelvic inlet to pelvic depth ratio. The measurements were compared in males and females using statistical analyses. Results Two-hundred patients (M/F 1:1) were analyzed. Out of 21 pelvimetry measurements, 19 of them documented a significant mean difference between groups. Specifically, female patients had a significantly wider pelvic inlet and outlet but a shorter pelvic depth, and promontory/sacral/coccyx distances, resulting in an augmented inlet/depth ratio when comparing with males (p < 0.0001). The sole exceptions were the straight conjugate (p = 0.06) and S3 angle (p = 0.17). 3D segmentation provided a perspective of the mesorectum distribution according to the pelvic shape. Conclusion Significant differences in the structure of pelvis exist in males and females. Surgeons must be aware of the pelvic shape when approaching the rectum

The Use of Indocyanine Green (ICG) and Near-Infrared (NIR) Fluorescence-Guided Imaging in Gastric Cancer Surgery: A Narrative Review

Near-infrared fluorescence imaging with indocyanine green is an emerging technology gaining clinical relevance in the field of oncosurgery. In recent decades, it has also been applied in gastric cancer surgery, spreading among surgeons thanks to the diffusion of minimally invasive approaches and the related development of new optic tools. Its most relevant uses in gastric cancer surgery are sentinel node navigation surgery, lymph node mapping during lymphadenectomy, assessment of vascular anatomy, and assessment of anastomotic perfusion. There is still debate regarding the most effective application, but with relatively no collateral effects and without compromising the operative time, indocyanine green fluorescence imaging carved out a role for itself in gastric resections. This review aims to summarize the current indications and evidence for the use of this tool, including the relevant practical details such as dosages and times of administration

Polymorphisms in metabolic genes, their combination and interaction with tobacco smoke and alcohol consumption and risk of gastric cancer: a case-control study in an Italian population

Background: The distribution and the potential gene-gene and gene-environment interaction of selected metabolic genetic polymorphisms was investigated in relation to gastric cancer risk in an Italian population. Methods: One hundred and seven cases and 254 hospital controls, matched by age and gender, were genotyped for CYP1A1, CYP2E1, mEH, GSTM1, GSTT1, NAT2 and SULT1A1 polymorphisms. Haplotype analysis was performed for EPHX1 exons 3 and 4, as well as CYP2E1 RsaI (* 5 alleles) and CYP2E1 DraI (* 5A or * 6 alleles). The effect modification by alcohol and cigarette smoking was tested with the heterogeneity test, while the attributable proportion ( AP) was used to measure the biological interaction from the gene-gene interaction analysis. Results: Gastric cancer risk was found to be associated with the inheritance of GSTT1 null genotype ( OR = 2.10, 95% CI: 1.27 - 3.44) and the SULT1A1 His/ His genotype ( OR = 2.46, 95% CI: 1.03 - 5.90). No differences were observed for the haplotype distributions among cases and controls. For the first time an increased risk was detected among individuals carrying the * 6 variant allele of CYP2E1 if ever-drinkers ( OR = 3.70; 95% CI: 1.45 - 9.37) with respect to never-drinkers ( OR = 0.18; 95% CI: 0.22 - 1.46) ( p value of heterogeneity among the two estimates = 0.001). Similarly, the effect of SULT1A1 variant genotype resulted restricted to ever-smokers, with an OR of 2.58 ( 95% CI: 1.27 - 5.25) for the carriers of His allele among smokers, and an OR of 0.86 ( 95% CI: 0.45 1.64) among never-smokers ( p value of heterogeneity among the two estimates = 0.03). The genegene interaction analyses demonstrated that individuals with combined GSTT1 null and NAT2 slow acetylators had an additional increased risk of gastric cancer, with an OR of 3.00 ( 95% CI: 1.52 - 5.93) and an AP of 52%. Conclusion: GSTT1, SULT1A1 and NAT2 polymorphisms appear to modulate individual's susceptibility to gastric cancer in this Italian population, particularly when more than one unfavourable genotype is present, or when combined with cigarette smoke. The increased risk for the carriers of CYP2E1* 5A or * 6 alleles among drinkers need to be confirmed by larger prospective studies