BACKGROUND Most of colorectal cancer diagnosed are candidates for surgical resection with curative intent, although colorectal surgery is associated with some complications that could be life-threatening. Antibiotic prophylaxis is commonly used for the prevention of infectious postoperative complications. However, this intervention can change the composition of intestinal microbiota and promote adverse inflammatory outcomes in colorectal cancer patients. It seems that the combination of different fungal extracts could be beneficial because of their role in gut microbiota modulation and their anti-inflammatory activity. OBJECTIVE Based on this hypothesis, we have designed a double-bind randomized clinical trial to evaluate the effect of the nutraceutical fungal extract MICODIGEST 2.0 on the complications of surgery for colorectal cancer resection. METHODS Colorectal cancer candidates for surgery will be considered for inclusion in the study. After evaluation in the multidisciplinary tumor board, patients who fulfill criteria will be screened, stratified according to the tumor location and randomly allocated to be treated with MICODIGEST 2.0 or placebo. Treatment will be continued until admission for surgery (4-6 weeks). Participants will also undergo a medical and clinical evaluation, which will include baseline and before admission quality of life, microbiome composition, inflammatory and nutritional status, adverse events and adherence. The main endpoint of the study is the surgery complication rate. We will evaluate them using the Clavien-Dindo classification. It would be necessary to recruit a total of 144 patients to find a relevant clinical difference. We will also evaluate the effect of the nutraceutical on microbiome composition, inflammatory response, nutritional status and quality of life, as well as the effect of these variables on the surgical complications. RESULTS This study was funded in 2020 by the Center for Industrial Technology Development. The recruitment started in September 2021 and is expected to be completed in September 2022. Data will be analyzed and the results will be disseminated in 2023. CONCLUSIONS The results of this protocol study could help to reduce the surgery complications in patients with colorectal cancer using the new treatment MICODIGEST. Apart from this treatment, this study could also identify new features associated with colorectal surgery complications. In summary, this study trial could improve the management of colorectal cancer patients. CLINICALTRIAL Clinical Trials.gov. Identifier: NCT04821258. Registered on March 29, 2021.

Background Both vedolizumab and ustekinumab are approved for the management of Crohn’s disease (CD). Data on which one would be the most beneficial option when anti-TNF agents fail are limited. Aims To compare the durability, effectiveness and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. Methods CD patients from ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated both in the short and the long term. Effectiveness was defined according to Harvey-Bradshaw index (HBI). Safety profile was compared between both treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. Results A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab (vs. ustekinumab) was associated with higher risk of treatment discontinuation [Hazard ratio (HR) 2.55, 95%CI:2-02-3.21], adjusted by corticosteroids at baseline (HR 1.27; 95%CI:1.00-1.62), moderate-severe activity in HBI (HR 1.79; 95%CI:1.20-2.48) and high levels of C-reactive protein at baseline (HR 1.06; 95%CI:1.02-1.10). The inverse probability weighting method confirmed these results. Clinical response, remission and corticosteroid-free clinical remission were higher with ustekinumab than vedolizumab. Both drugs had low risk of adverse events with no differences between them. Conclusion In CD patients who have failed to anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Background Most colorectal cancer patients diagnosed are candidates for surgical resection with curative intent, although colorectal surgery is associated with some complications that could be life-threatening. Antibiotic prophylaxis is commonly used for the prevention of infectious postoperative complications. However, this intervention can change the composition of intestinal microbiota and promote adverse inflammatory outcomes in colorectal cancer patients. The combination of different fungal extracts could be beneficial because of their role in gut microbiota modulation and their anti-inflammatory activity. Objective Based on this hypothesis, we have designed a double-bind, randomized clinical trial to evaluate the effect of the nutraceutical fungal extract Micodigest 2.0 on complications of surgery for colorectal cancer resection. Methods Colorectal cancer candidates for surgery will be considered for inclusion in the study. After evaluation by the multidisciplinary tumor board, patients who meet selection criteria will be screened, stratified according to tumor location, and randomly allocated to be treated with Micodigest 2.0 or placebo. Treatment will be continued until admission for surgery (4-6 weeks). Participants will undergo a medical and clinical evaluation including baseline and preadmission quality of life, microbiome composition, inflammatory and nutritional status, adverse events, and adherence assessments. The main end point of the study is the surgery complication rate. We will evaluate complications using the Clavien-Dindo classification. It will be necessary to recruit 144 patients to find a relevant clinical difference. We will also evaluate the effect of the nutraceutical on microbiome composition, inflammatory response, nutritional status, and quality of life, as well as the effect of these variables on surgical complications. Results This study was funded in 2020 by the Center for Industrial Technology Development. Recruitment began in September 2021 and is expected to be completed in September 2022. Data will be analyzed and the results will be disseminated in 2023. Conclusions The results of this protocol study could help to reduce surgery complications in patients with colorectal cancer using the new treatment Micodigest. This study could also identify new features associated with colorectal surgery complications. In summary, this study trial could improve the management of colorectal cancer patients. Trial Registration Clinical Trials.gov NCT04821258; https://clinicaltrials.gov/ct2/show/NCT04821258 International Registered Report Identifier (IRRID) DERR1-10.2196/34292