A prospective european trial comparing laparotomy, laparoscopy, robotic-assisted, and transanal total mesorectal excision procedures in high-risk patients with rectal cancer: the RESET trial

Objective: To compare total mesorectal excision (TME) techniques combined with sphincter-sparing procedure in high-risk patients (HRPs). Background: TME is the standard treatment for rectal cancer, but can be challenging in HRPs. The available surgical approaches must be compared, especially in HRPs. Methods: Prospective, observational, multicenter trial to compare laparotomy (OTME), laparoscopy (LTME), robotic-assisted surgery (RTME), and transanal surgery (TaTME) in HRPs. The composite primary outcome included circumferential radial margin (CRM) 1mm, TME grade II-III, and absence of Clavien-Dindo grade III-IV complications. Three propensity score analyses were performed (LTME vs. RTME, RTME vs. TaTME, LTME vs. TaTME). Results: 1078 HRPs (75% of men, median body mass index of 27 kg/m2, 50% of tumors in the lower third of the rectum) underwent surgery. The RTME and TaTME groups included patients with more advanced and lower tumors and coloanal anastomosis (P<0.001). Operative time was longer for RTME surgery (P<0.001). Conversion rate was similar for minimally invasive procedures (4.5%). The global R0 resection rate was 96% without difference among techniques. The primary outcome rates were 82.4%, 64.3%, 74.7%, and 80.3% for LTME, OTME, RTME, and TaTME, respectively. None achieved the expected success rate (85%), and propensity score analyses found no differences. Operative results were similar between high- and low-volume inclusion centers only for RTME. Conclusions: The RESET trial yielded high-quality results despite focusing on HRPs. Minimally invasive procedures showed similar sphincter-sparing procedure outcomes, but LTME included patients with more favorable tumors. Oncologic and functional outcomes will be evaluated at 2 years (ClinicalTrials.gov, ID: NCT03574493).Conflicts of Interest and Source of Funding: RESET was endorsed by the European Society of Coloproctology (ESCP). Financial support was provided by Intuitive Surgical, Aubonne, Switzerland. RESET was designed and conducted independently at the Montpellier Cancer Institute. The funding institutions had no influence on the design or conduct of the study. PR received research and education grants from Intuitive Surgical. The other authors declare no other conflict of interest

Masked bolus gluten challenge low in FODMAPs implicates nausea and vomiting as key symptoms associated with immune activation in treated coeliac disease

Background In patients with coeliac disease, FODMAPs in gluten-containing foods, and participant anticipation of a harmful ('nocebo') effect, may contribute to acute symptoms after gluten challenge. Aim To establish acute gluten-specific symptoms linked to immune activation in coeliac disease Methods We included 36 coeliac disease patients on a gluten-free diet receiving placebo in the RESET CeD trial. Double-blind, bolus vital wheat gluten (similar to 6-g gluten protein) and sham challenges low in FODMAPs were consumed 2 weeks apart. Assessments included daily Coeliac Disease Patient Reported Outcome (CeD PRO) symptom scores (0-10), adverse events and serum interleukin-2 (baseline and 4 hours). Results Median CeD PRO score for nausea increased most (sham: 0 vs gluten: 5.5; P < .001). Apart from tiredness (1 vs 4, P = .005) and headache (0 vs 2, P = .002), changes in other symptoms were small or absent. Only nausea increased significantly in occurrence with gluten (11% vs 69%, P < .001). Without nausea, only tiredness and flatulence were common after gluten. Nausea (6% vs 61%, P < .001; median onset: 1:34 hours) and vomiting (0% vs 44%, P < .001; 1:51 hours) were the only adverse events more common with gluten than sham. Interleukin-2 was always below the level of quantitation (0.5 pg/mL) at baseline, and after sham. Interleukin-2 was elevated after gluten in 97% of patients (median fold-change: 20), and correlated with severity of nausea (r(s) = .49, P = .0025) and occurrence of vomiting (P = .0005). Conclusions Nausea and vomiting are relatively specific indicators of acute gluten ingestion, and correlate with immune activation. IBS-like symptoms without nausea are unlikely to indicate recent gluten exposure