Cost-effectiveness of selective decontamination of the digestive tract to decrease infectious complications in colorectal cancer surgery: An analysis of the SELECT trial.

INTRODUCTION: Selective decontamination of the digestive tract (SDD) is effective in reducing infectious complications in elective colorectal cancer (CRC) surgery. However, it is unclear whether SDD is cost-effective compared to standard antibiotic prophylaxis. MATERIAL & METHODS: Economic evaluation alongside multicenter randomized controlled trial, the SELECT-trial, from a healthcare perspective. Patients included underwent elective surgery for non-metastatic CRC. The intervention group received oral non-absorbable colistin, tobramycin and amphotericin B (SDD) next to standard antibiotic prophylaxis. Both groups received a single shot intravenous cefazolin and metronidazole preoperatively as standard prophylaxis. Occurrence of postoperative infectious complication in the first 30 postoperative days was extracted from medical records, Quality-Adjusted Life-Years (QALYs) based on the ED-5D-3L, and healthcare costs collected from the hospital's financial administration. RESULTS: Of the 455 patients, 228 were randomly assigned to intervention group and 227 patients to the control group. SDD significantly reduced the number of infectious complications compared to control (difference = -0.13, 95 % CI -0.05 to -0.20). No difference was found for QALYs (difference = 0.002, 95 % CI -0.002 to 0.005). Healthcare costs were statistically significantly lower in the intervention group (difference = -€1258, 95 % CI -2751 to -166). The ICER was -9872 €/infectious complication prevented and -820,380 €/QALY gained. For all willingness-to-pay thresholds, the probability that prophylactic SDD was cost-effective compared to standard prophylactic practice alone was 1.0. CONCLUSION: The addition of SDD to the standard preoperative intravenous antibiotic prophylaxis is cost-effective compared to standard prophylactic practice from a healthcare perspective and should be considered as the standard of care.

Selective Decontamination with Oral Antibiotics in Colorectal Surgery: 90-day Reintervention Rates and Long-term Oncological Follow-up.

BACKGROUND: Oral antibiotics (OAB) in colorectal surgery have been shown to reduce surgical site infections (SSIs) and possibly anastomotic leakage. However, evidence on long-term follow-up, reintervention rates and 5-year oncological follow-up is lacking. The current study aims at elucidating this knowledge gap. METHODS: This study evaluated the long-term effectiveness of perioperative 'Selective decontamination of the digestive tract' (SDD) in colorectal cancer surgery. The primary outcome was anastomotic leakage within 90 days, secondary outcomes included infectious complications, reinterventions, readmission, hospital stay, and 5-year overall and disease-free-survival. Statistical analysis including univariate and multivariate analysis was performed to identify predictors of 90-day outcomes, and Kaplan-Meier survival analysis was used for the 5-year survival outcomes. RESULTS: In total 455 patients were analyzed, 228 participants in the SDD group and 227 in the control group. Anastomotic leakage rate was not statistically different between the SDD and control group (6.6% versus 9.7%). One or more infectious complications occurred in 15.4% of patients in the SDD group and in 28.2% in the control group (OR 0.46, 95% C.I. 0.29 - 0.73). In the SDD group 8,8% of patients required a reintervention compared to 16,3% of patients in the control group (OR 0.47, 95% C.I. 0.26 - 0.84). After multivariable analysis SDD remained significant in reducing both infectious complications and reinterventions after 90-days follow-up. There was no difference between SDD and control group in 5-year overall survival and disease-free-survival. CONCLUSION: SDD as OAB is effective in reducing 90-days postoperative infectious complications and reinterventions. As such, SDD as standard OAB in elective colorectal surgery is highly recommended.

The effect of selective decontamination on the intestinal microbiota as measured with IS-pro: a taxonomic classification tool applicable for direct evaluation of intestinal microbiota in clinical routine.

Selective decontamination of the digestive tract (SDD) is aimed at elimination of potential pathogenic microorganisms. In this study, the effect of SDD on gut microbiota was evaluated in a large homogenous group of elective colorectal cancer surgery patients. Rectal swabs were taken from 118 patients undergoing colorectal surgery. These patients were randomly assigned to receive perioperative SDD or to the control group (no SDD). Rectal swabs were taken prior to surgery, 3 days after commencing administration of SDD. Gut microbial profiles were obtained with the IS-pro technique, a standardized microbiota profiling assay applicable in clinical routine. Differences in abundance for different taxonomical groups and diversity between the groups were assessed. Unsupervised and supervised classification techniques were used to assess microbial signatures, differentiating between the SDD group and the control group. Patients in the SDD group had different gut microbial signatures than in the control group, also in phyla that are not a target for SDD. Escherichia coli, Sutterella spp., Faecalibacterium prausnitzii, and Streptococcus spp. were the species that differed the most between the two groups. The SDD group showed clustering into two subgroups. In one subgroup, a decrease in Proteobacteria was observed, whereas the other subgroup showed a shift in Proteobacteria species. This study shows that SDD not only decreases colonization of the gastrointestinal tract with potential pathogenic Gram-negative microorganisms, but also reduces the abundance of normal colonizers of our gastrointestinal system and leads to a shift in total microbiota composition.

Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial).

BACKGROUND: Infectious complications and anastomotic leakage affect approximately 30 per cent of patients after colorectal cancer surgery. The aim of this multicentre randomized trial was to investigate whether selective decontamination of the digestive tract (SDD) reduces these complications of elective colorectal cancer surgery. METHODS: The effectiveness of SDD was evaluated in a multicentre, open-label RCT in six centres in the Netherlands. Patients with colorectal cancer scheduled for elective curative surgery with a primary anastomosis were eligible. Oral colistin, tobramycin and amphotericin B were administered to patients in the SDD group to decontaminate the digestive tract. Both treatment and control group received intravenous cefazolin and metronidazole for perioperative prophylaxis. Mechanical bowel preparation was given for left-sided colectomies, sigmoid and anterior resections. Anastomotic leakage was the primary outcome; infectious complications and mortality were secondary outcomes. RESULTS: The outcomes for 228 patients randomized to the SDD group and 227 randomized to the control group were analysed. The trial was stopped after interim analysis demonstrated that superiority was no longer attainable. Effective SDD was confirmed by interspace DNA profiling analysis of rectal swabs. Anastomotic leakage was observed in 14 patients (6·1 per cent) in the SDD group and in 22 patients (9·7 per cent) in the control group (odds ratio (OR) 0·61, 95 per cent c.i. 0·30 to 1·22). Fewer patients in the SDD group had one or more infectious complications than patients in the control group (14·9 versus 26·9 per cent respectively; OR 0·48, 0·30 to 0·76). Multivariable analysis indicated that SDD reduced the rate of infectious complications (OR 0·47, 0·29 to 0·76). CONCLUSION: SDD reduces infectious complications after colorectal cancer resection but did not significantly reduce anastomotic leakage in this trial. Registration number: NCT01740947 ( https://www.clinicaltrials.gov).

Peri-operative bowel perforation in early stage colon cancer is associated with an adverse oncological outcome.

BACKGROUND: The presence of an inflammatory response resulting from bowel perforation or anastomotic leakage has been suggested to enhance recurrence rates in colorectal cancer patients. Currently, it is unknown if bowel perforation or anastomotic leakage has prognostic significance in early stage colon cancer patients. In this study, the impact of peri-operative bowel perforation including anastomotic leakage on disease-free survival of stage I/II colon cancer patients was investigated. METHODS: Prospective follow up data of 448 patients with stages I/II colon cancer that underwent resection were included. Patients who died within 3 months after initial surgery were excluded. RESULTS: Median follow up was 56.0 months. Patients with peri-operative bowel perforation (n = 25) had a higher recurrence rate compared to patients without perforation (n = 423), 36.0 % vs. 16.1 % (p = 0.01). Disease-free survival was significantly worse for the perforation group compared to patients without perforation (p = 0.004). Multivariate analysis including T-stage, histological grade, and adjuvant chemotherapy showed peri-operative bowel perforation to be an independent factor significantly associated with disease recurrence (odds ratio, 2.7; 95 % CI, 1.1-6.7). CONCLUSION: Peri-operative bowel perforation is associated with increased recurrence rates and impaired disease-free survival in early-stage colon cancer patients.