A multicentre cohort study of serum and peritoneal biomarkers to predict anastomotic leakage after rectal cancer resection.

AIM: Anastomotic leakage (AL) is one of the most feared complications after rectal resection. This study aimed to assess a combination of biomarkers for early detection of AL after rectal cancer resection. METHOD: This study was an international multicentre prospective cohort study. All patients received a pelvic drain after rectal cancer resection. On the first three postoperative days drain fluid was collected daily and C-reactive protein (CRP) was measured. Matrix metalloproteinase-2 (MMP2), MMP9, glucose, lactate, interleukin 1-beta (IL1ß), IL6, IL10, tumour necrosis factor alpha (TNFα), Escherichia coli, Enterococcus faecalis, lipopolysaccharide-binding protein and amylase were measured in the drain fluid. Prediction models for AL were built for each postoperative day using multivariate penalized logistic regression. Model performance was estimated by the c-index for discrimination. The model with the best performance was visualized with a nomogram and calibration was plotted. RESULTS: A total of 292 patients were analysed; 38 (13.0%) patients suffered from AL, with a median interval to diagnosis of 6.0 (interquartile ratio 4.0-14.8) days. AL occurred less often after partial than after total mesorectal excision (4.9% vs 15.2%, P = 0.035). Of all patients with AL, 26 (68.4%) required reoperation. AL was more often treated by reoperation in patients without a diverting ileostomy (18/20 vs 8/18, P = 0.03). The prediction model for postoperative day 1 included MMP9, TNFα, diverting ileostomy and surgical technique (c-index = 0.71). The prediction model for postoperative day 2 only included CRP (c-index = 0.69). The prediction model for postoperative day 3 included CRP and MMP9 and obtained the best model performance (c-index = 0.78). CONCLUSION: The combination of serum CRP and peritoneal MMP9 may be useful for earlier prediction of AL after rectal cancer resection. In clinical practice, this combination of biomarkers should be interpreted in the clinical context as with any other diagnostic tool.

Transanal total mesorectal excision: how are we doing so far?

AIM: This subgroup analysis of a prospective multicentre cohort study aims to compare postoperative morbidity between transanal total mesorectal excision (TaTME) and laparoscopic total mesorectal excision (LaTME). METHOD: The study was designed as a subgroup analysis of a prospective multicentre cohort study. Patients undergoing TaTME or LaTME for rectal cancer were selected. All patients were followed up until the first visit to the outpatient clinic after hospital discharge. Postoperative complications were classified according to the Clavien-Dindo classification and the comprehensive complication index (CCI). Propensity score matching was performed. RESULTS: In total, 220 patients were selected from the overall prospective multicentre cohort study. After propensity score matching, 48 patients from each group were compared. The median tumour height for TaTME was 10.0 cm (6.0-10.8) and for LaTME was 9.5 cm (7.0-12.0) (P = 0.459). The duration of surgery and anaesthesia were both significantly longer for TaTME (221 vs 180 min, P < 0.001, and 264 vs 217 min, P < 0.001). TaTME was not converted to laparotomy whilst surgery in five patients undergoing LaTME was converted to laparotomy (0.0% vs 10.4%, P = 0.056). No statistically significant differences were observed for Clavien-Dindo classification, CCI, readmissions, reoperations and mortality. CONCLUSION: The study showed that TaTME is a safe and feasible approach for rectal cancer resection. This new technique obtained similar postoperative morbidity to LaTME.

A preoperative prediction model for anastomotic leakage after rectal cancer resection based on 13.175 patients.

INTRODUCTION: This study aims to develop a robust preoperative prediction model for anastomotic leakage (AL) after surgical resection for rectal cancer, based on established risk factors and with the power of a large prospective nation-wide population-based study cohort. MATERIALS AND METHODS: A development cohort was formed by using the DCRA (Dutch ColoRectal Audit), a mandatory population-based repository of all patients who undergo colorectal cancer resection in the Netherlands. Patients aged 18 years or older were included who underwent surgical resection for rectal cancer with primary anastomosis (with or without deviating ileostomy) between 2011 and 2019. Anastomotic leakage was defined as clinically relevant leakage requiring reintervention. Multivariable logistic regression was used to build a prediction model and cross-validation was used to validate the model. RESULTS: A total of 13.175 patients were included for analysis. AL was diagnosed in 1319 patients (10%). A deviating stoma was constructed in 6853 patients (52%). The following variables were identified as significant risk factors and included in the prediction model: gender, age, BMI, ASA classification, neo-adjuvant (chemo)radiotherapy, cT stage, distance of the tumor from anal verge, and deviating ileostomy. The model had a concordance-index of 0.664, which remained 0.658 after cross-validation. In addition, a nomogram was developed. CONCLUSION: The present study generated a discriminative prediction model based on preoperatively available variables. The proposed score can be used for patient counselling and risk-stratification before undergoing rectal resection for cancer.

The effect of neoadjuvant short-course radiotherapy and delayed surgery versus chemoradiation on postoperative outcomes in locally advanced rectal cancer patients - A propensity score matched nationwide audit-based study.

OBJECTIVE: To investigate differences in postoperative outcomes between short-course radiotherapy and delayed surgery (SCRT-delay) and chemoradiation (CRT) in patients with locally advanced rectal cancer (LARC). BACKGROUND: Previous trials suggest that SCRT-delay could serve as an adequate neoadjuvant treatment for LARC. Therefore, in frail LARC patients SCRT-delay is recommended as an alternative to CRT. However, data on postoperative outcomes after SCRT-delay in comparison to CRT is scarce. METHODS: This was an observational study with data from the Dutch ColoRectal Audit (DCRA). LARC patients who underwent surgery (2014-2017) after an interval of ≥6 weeks were included. Missing values were replaced by multiple imputation. Propensity score matching (PSM), using age, Charlson Comorbidity Index, cT-stage and surgical procedure, was applied to create comparable groups. Differences in postoperative outcomes were analyzed using Chi-square test for categorical variables, independent sample t-test for continuous variables and Mann-Whitney U test for non-parametric data. RESULTS: 2926 patients were included. In total, 288 patients received SCRT-delay and 2638 patients underwent CRT. Patients in the SCRT-delay group were older and had more comorbidities. Also, ICU-admissions and permanent colostomies were more common, as well as pulmonic, cardiologic, infectious and neurologic complications. After PSM, both groups comprised 246 patients with equivalent age, comorbidities and tumor stage. There were no differences in postoperative complications. CONCLUSION: Postoperative complications were not increased in LARC patients undergoing SCRT-delay as neoadjuvant treatment. Regarding treatment-related complications, SCRT-delay is a safe alternative neoadjuvant treatment option for frail LARC patients.