Immunosuppressive therapy after solid organ transplantation leads to the development of cancer in many recipients. Analysis of the occurrence of different types of de novo carcinomas in relation to specific immunosuppressive drugs may give insight into their carcinogenic process and carcinogenesis in general. Therefore, a systematic search was performed in Embase and PubMed. Studies describing over five de novo carcinomas in patients using immunosuppressive drugs after solid organ transplantation were included. Incidence per 1000 person-years was calculated with DerSimonian–Laird random effects model and odds ratio for developing carcinomas with the Mantel–Haenszel test. Following review of 5606 papers by title and abstract, a meta-analysis was conducted of 82 studies. The incidence rate of de novo carcinomas was 8.41. Patients receiving cyclosporine developed more de novo carcinomas compared to tacrolimus (OR1.56, 95%CI 1.00–2.44) and mycophenolate (OR1.26, 95%CI 1.03–1.56). Patients receiving azathioprine had higher odds to develop de novo carcinomas compared to mycophenolate (OR3.34, 95%CI 1.29–8.65) and head and neck carcinoma compared to tacrolimus (OR3.78, 95%CI 1.11–12.83). To conclude, patients receiving immunosuppressive drugs after solid organ transplantation have almost a 20-fold increased likelihood of developing carcinomas, with the highest likelihood for patients receiving cyclosporine A and azathioprine. Looking into altered immune pathways affected by immunosuppressive drugs might lead to better understanding of carcinogenesis in general.

Background Preoperative prehabilitation programmes for patients with colorectal cancer have been shown to reduce complications and hospital length of stay. However, supervised weekly physiotherapy is expensive and timeconsuming for both healthcare professionals and patients, leading to suboptimal implementation of prehabilitation programmes. A previous study demonstrated that offering home-based prehabilitation through an app is feasible and leads to outcomes comparable to supervised prehabilitation programmes. This study was conducted at a single hospital. To expand this promising modality nationwide, it is essential to identify key implementation determinants. We therefore initiated this multicentre study involving a more diverse and heterogeneous patient population. The findings of this study will provide valuable input for scaling strategies for prehabilitation programmes in the Netherlands and beyond. Methods In this prospective multicentre cohort study, approximately 300 patients with colorectal cancer scheduled for curative surgery will be enrolled over 12 months. The study adopts a hybrid type 3 design, reporting clinical outcomes while exploring implementation-related factors. Five hospitals with varied profiles (academic, non-academic teaching and general hospitals) and geographical locations (urban and rural, high and low socioeconomic areas) are participating. The primary endpoint is the identification of barriers and facilitators, using both qualitative (interviews) and quantitative (user statistics, questionnaires) data from stakeholders. Secondary endpoints include fitness and clinical outcomes such as complications and mortality. Ethics and dissemination This study was approved by the METC (Medisch Ethische Toetsings Commissie / Dutch Medical Ethics Committee) and was established not to apply to the Medical Research Involving Human Subjects Act (WMO / Wet Medisch Wetenschappelijk Onderzoek met mensen); submission was 21 April 2025. The app is proven safe and feasible in earlier studies and is CE certified (Conformité Européenne). Informed consent will be obtained from all patients (Supplement 1). Adverse events will be monitored and reported. Only researchers will have access to the final dataset. Results will be disseminated through publications, patient group briefings and implementation feedback to healthcare workers. Plans for sharing deidentified individual clinical trial participant-level data consist of quotes from interviews held on stakeholders. This study protocol adheres to the SPIRIT guidelines.