Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis.

BACKGROUND: Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. METHODS: Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. RESULTS: Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). CONCLUSIONS: All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

Risk factors for non-closure of an intended temporary defunctioning stoma after emergency resection of left-sided obstructive colon cancer.

PURPOSE: A substantial part (21-35%) of defunctioning stomas created during resection for colorectal cancer will never be reversed. Known risk factors for non-closure are age, peri- or postoperative complications, comorbidity, and tumor stage. However, studies performed to identify these risk factors mostly focus on rectal cancer and include both preoperative and postoperative factors. This study aims to identify preoperative risk factors for non-reversal of intended temporary stomas created during acute resection of left-sided obstructive colon cancer (LSOCC) with primary anastomosis. METHODS: All patients who underwent emergency resection for LSOCC with primary anastomosis and a defunctioning stoma between 2009 and 2016 were selected from the Dutch ColoRectal Audit, and additional data were collected in the local centers. Multivariable analysis was performed to identify independent preoperative factors for non-closure of the stoma. RESULTS: A total of 155 patients underwent acute resection for LSOCC with primary anastomosis and a defunctioning stoma. Of these, 51 patients (32.9%) did not have their stoma reversed after a median of 53 (range 7-104) months of follow-up. In multivariable analysis, hemoglobin < 7.5 mmol/L (odds ratio (OR) 4.79, 95% confidence interval (95% CI) 1.60-14.38, p = 0.005), estimated glomerular filtration rate (eGFR) ≤ 45 mL/min/1.73 m2 (OR 4.64, 95% CI 1.41-15.10, p = 0.011), and metastatic disease (OR 6.12, 95% CI 2.35-15.94, p < 0.001) revealed to be independent predictors of non-closure. CONCLUSIONS: Anemia, impaired renal function, and metastatic disease at presentation were found to be independent predictors for non-reversal of intended temporary stomas in patients who underwent acute resection for LSOCC. In patients who have an increased risk of non-reversal, the surgeon should consider a Hartmann's procedure.

Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research.

BACKGROUND: Systematic evaluation and validation of new prognostic and predictive markers, technologies and interventions for colorectal cancer (CRC) is crucial for optimizing patients' outcomes. With only 5-15% of patients participating in clinical trials, generalizability of results is poor. Moreover, current trials often lack the capacity for post-hoc subgroup analyses. For this purpose, a large observational cohort study, serving as a multiple trial and biobanking facility, was set up by the Dutch Colorectal Cancer Group (DCCG). METHODS/DESIGN: The Prospective Dutch ColoRectal Cancer cohort is a prospective multidisciplinary nationwide observational cohort study in the Netherlands (yearly CRC incidence of 15 500). All CRC patients (stage I-IV) are eligible for inclusion, and longitudinal clinical data are registered. Patients give separate consent for the collection of blood and tumor tissue, filling out questionnaires, and broad randomization for studies according to the innovative cohort multiple randomized controlled trial design (cmRCT), serving as an alternative study design for the classic RCT. Objectives of the study include: 1) systematically collected long-term clinical data, patient-reported outcomes and biomaterials from daily CRC practice; and 2) to facilitate future basic, translational and clinical research including interventional and cost-effectiveness studies for both national and international research groups with short inclusion periods, even for studies with stringent inclusion criteria. RESULTS: Seven months after initiation 650 patients have been enrolled, eight centers participate, 15 centers await IRB approval and nine embedded cohort- or cmRCT-designed studies are currently recruiting patients. CONCLUSION: This cohort provides a unique multidisciplinary data, biobank, and patient-reported outcomes collection initiative, serving as an infrastructure for various kinds of research aiming to improve treatment outcomes in CRC patients. This comprehensive design may serve as an example for other tumor types.

Vacuum-assisted closure therapy for infected perineal wounds after abdominoperineal resection. A retrospective cohort study.

INTRODUCTION: Perineal wound complications are a main problem after abdominoperineal resection (APR). There is little evidence concerning perineal wound management. This study describes and evaluates the role of vacuum-assisted closure (VAC) therapy in wound management strategies of perineal wound infections after APR. METHODS: Patients undergoing APR for malignant disease between January 2007 and January 2013 were identified retrospectively. Data regarding occurrence and management of perineal wound complications were collected. Perineal wound infections were classified into minor or major complications and time to wound healing was measured. Time to wound healing was compared between patients receiving routine care or with additional VAC therapy. RESULTS: Of 171 included patients, 76 (44.4%) had minor and 36 (21.1%) major perineal wound infections. Management of major infected perineal wounds consisted of drainage (n = 16), debridement (n = 4), drainage combined with debridement (n = 4), VAC therapy alone (n = 5), or VAC therapy combined with other treatments (n = 7). Median duration of perineal wound healing in major infected wounds was 141 days (range 17-739). Median time to wound healing was not different in patients treated with (172 days, range 23-368) or without VAC therapy (131 days, range 17-739). DISCUSSION AND CONCLUSION: In this study, VAC therapy did not shorten time to wound healing. However, prospective studies are required to investigate the role of VAC therapy in management of infected perineal wounds after APR. Up to then, wound management will remain to be based on clinical perception and 'gut-feeling'.