Adjuvant chemotherapy is superior to chemoradiation after D2 surgery for gastric cancer in the per-protocol analysis of the randomized CRITICS trial

Background: The Intergroup 0116 and the MAGIC trials changed clinical practice for resectable gastric cancer in the Western world. In these trials, overall survival improved with post-operative chemoradiotherapy (CRT) and perioperative chemotherapy (CT). Intention-to-treat analysis in the CRITICS trial of post-operative CT or post-operative CRT did not show a survival difference. The current study reports on the per-protocol (PP) analysis of the CRITICS trial.Patients and methods: The CRITICS trial was a randomized, controlled trial in which 788 patients with stage Ib-Iva resectable gastric or esophagogastric adenocarcinoma were included. Before start of preoperative CT, patients from the Netherlands, Sweden and Denmark were randomly assigned to receive post-operative CT or CRT. For the current analysis, only patients who started their allocated post-operative treatment were included. Since it is uncertain that the two treatment arms are balanced in such PP analysis, adjusted proportional hazards regression analysis and inverse probability weighted analysis were used to minimize the risk of selection bias and to estimate and compare overall and event-free survival.Results: Of the 788 patients, 478 started post-operative treatment according to protocol, 233 (59%) patients in the CT group and 245 (62%) patients in the CRT group. Patient and tumor characteristics between the groups before start of the post-operative treatment were not different. After a median follow-up of 6.7 years since the start of post-operative treatment, the 5-year overall survival was 57.9% (95% confidence interval: 51.4% to 64.3%) in the CT group versus 45.5% (95% confidence interval: 39.2% to 51.8%) in the CRT group (adjusted hazard ratio CRT versus CT: 1.62 (1.24-2.12), P = 0.0004). Inverse probability weighted analysis resulted in similar hazard ratios.Conclusion: After adjustment for all known confounding factors, the PP analysis of patients who started the allocated post-operative treatment in the CRITICS trial showed that the CT group had a significantly better 5-year overall survival than the CRT group (NCT00407186).Surgical oncolog

Study protocol PROMETHEUS: prospective multicenter study to evaluate the correlation between safety margin and local recurrence after thermal ablation using image co-registration in patients with hepatocellular carcinoma

Purpose The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions = 10% for patients with a minimal ablation margin >= 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan-Meier estimates are used to assess local and overall recurrence, disease-free and overall survival.Discussion It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Pelvic floor physical therapy in the treatment of chronic anal fissure (PAF trial): quality of life outcome

Background Chronic anal fissure is one of the most common anorectal diseases and is associated with reduced quality of life. The aim of this study was to investigate the effects of pelvic floor physical therapy on quality of life in patients with chronic anal fissure using the Short-Form 36 Health Survey (RAND-36). Methods Adult patients, with chronic anal fissure and concomitant pelvic floor dysfunction, such as dyssynergia and increased pelvic floor muscle tone, were recruited at the Proctos Clinic in the Netherlands, between December 2018 and July 2021 and randomly assigned to an intervention group, receiving 8 weeks of pelvic floor physical therapy or assigned to a control group receiving postponed pelvic floor physical therapy (PAF trial). Quality of life and pain ratings were outcomes of the study and were measured at 8- and 20-week follow-up. Results One hundred patients (50 women and 50 men, median age 44.6 years [range 19-68 years]), completed the RAND-36 questionnaire and visual analog (VAS) pain scale score at admission. A significant improvement was found at 20-week follow-up in all domains of the RAND-36; physical functioning, pain, health change (p < 0.001); physical role, vitality, general health, social functioning, emotional role, mental health (p < 0.05). VAS pain was significantly reduced at 8 weeks (mean estimated difference 1.98; 95% CI 1.55-2.42, p < 0.001) and remained significant at 20-week follow-up (p < 0.001). The difference between the groups as regards change in the mean pain intensity scores at 8 weeks was 2.48 (95% CI - 3.20 to - 1.75; p < 0.001). Compared to the reference values of the general Dutch population, the patients in our study with a chronic anal fissure and pelvic floor dysfunction reported an impaired quality of life in 8 of 9 domains of the RAND-36. After treatment, significant lower scores were found in 2 out of 9 domains. Conclusions The results of this study provide evidence that treatment by pelvic floor physical therapy improves quality of life and reduces pain, making it an important tool in management of chronic anal fissure and concomitant pelvic floor dysfunction

AVOID; a phase III, randomised controlled trial using indocyanine green for the prevention of anastomotic leakage in colorectal surgery

Introduction: Anastomotic leakage (AL) is one of the major complications after colorectal surgery. Compromised tissue perfusion at the anastomosis site increases the risk of AL. Several cohort studies have shown that indocyanine green (ICG) combined with fluorescent nearinfrared imaging is a feasible and reproducible technique for real-time intraoperative imaging of tissue perfusion, leading to reduced leakage rates after colorectal resection. Unfortunately, these studies were not randomised. Therefore, we propose a randomised controlled trial to assess the value of ICG-guided surgery in reducing AL after colorectal surgery. Methods and analysis: A multicentre, randomised controlled clinical trial will be conducted to assess the benefit of ICG-guided surgery in preventing AL. A total of 978 patients scheduled for colorectal surgery will be included. Patients will be randomised between the Fluorescence Guided Bowel Anastomosis group and the Conventional Bowel Anastomosis group. The primary endpoint is clinically relevant AL (defined as requiring active therapeutic intervention or reoperation) within 90 days after surgery. Among the secondary endpoints are 30-day clinically relevant AL, all-cause postoperative complications, all-cause and AL-related mortality, surgical and non-surgical reinterventions, total surgical time, length of hospital stay and all-cause and AL-related readmittance. Ethics and dissemination: This protocol has been approved by the Medical Ethical Committee Leiden-Den Haag-Delft (METC-LDD) and is registered at ClinicalTrials. gov and trialregister.nl . The results of this study will be reported through peer-reviewed publications and conference presentations.Surgical oncolog

The association analysis for number of affected vessels using rs1333049 as predictors in a linear regression model in CAD patients and subgroups.

<p>The correlation was shown with adjustment for age, sex, SBP, DBP, BMI, TC, TG, HDL-C, LDL-C, glucose, smoking, DM, and hypertension status. The rs1333049 GG genotype was as reference.</p