The CHAMP-study: the CHemopreventive effect of lithium in familial AdenoMatous Polyposis; study protocol of a phase II trial

Background: Familial adenomatous polyposis (FAP) is a rare autosomal dominant disease characterized by germline mutations in the Adenomatous Polyposis Coli (APC) gene, resulting in the development of numerous colorectal adenomas. As these patients have a high risk of developing colorectal cancer (CRC), guidelines suggest prophylactic colectomy during early adulthood, however, adenoma development is still observed in the remaining intestinal tract. Therefore, FAP patients would benefit from chemoprevention strategies reducing the development of adenomas. Recent work in mice reveals a chemopreventive effect of lithium on the development of adenomas by inhibiting the expansion of Apc mutated intestinal stem cells (ISCs) within the crypts of normal intestinal mucosa. Here, we aim to investigate the effect of lithium on the spread of APC mutant cells within the human intestinal epithelium. Methods: This prospective phase II single arm trial has a duration of 18 months. FAP patients (18–35 years) with a genetically confirmed APC mutation who did not undergo colectomy will be treated with lithium carbonate orally achieving a serum level of 0.2–0.4 mmol/l between month 6 and 12. Colonoscopy with biopsies of normal intestinal mucosa will be performed at baseline and every six months. The primary endpoint is the effect of lithium on the spread of APC mutant cells within intestinal crypts over time by using APC specific marker NOTUM in situ hybridization. Secondary endpoints include change in adenoma burden, patient reported side effects and safety-outcomes. Total sample size is 12 patients and recruitment will take place in the Amsterdam UMC, location AMC in the Netherlands. Discussion: The outcome of this study will function as a proof-of-concept for the development of novel chemoprevention approaches that interfere with the competition between normal and mutant ISCs. Trial registration: ClinicalTrials.gov (https://clinicaltrials.gov/): NCT05402891 (June 1, 2022) and the EU Clinical Trials Register: EuraCT 2022-000240-30 (January 1, 2022)

Renal and Bladder Cancer During Pregnancy: A Review of 47 Cases and Literature-based Recommendations for Management

Objective: To provide contemporary gestational age-specific recommendations for management, a retrospective series of patients with renal or bladder cancer during pregnancy is reported. Methods: Obstetric and oncological data of pregnant patients with a diagnosis of renal or bladder cancer were selected from the worldwide registry of the International Network of Cancer, Infertility and Pregnancy. In addition, the literature was reviewed for recent case reports since last reviews in 2014 for renal cancer and 2004 for bladder cancer. Results: International Network of Cancer, Infertility and Pregnancy registered 22 cases (14 renal cancer and 8 bladder cancer), diagnosed between 1999 and 2017, and the literature reported 15 cases with renal cancer and 10 cases with bladder cancer between 2004 and 2019. Most common symptoms for renal and bladder cancer were pain (28%) and hematuria (66%), respectively. In more than half of the patients, surgical treatment was performed during pregnancy. Preterm deliveries were mostly medically induced (12 of 17, 71%) and all patients with a planned delivery before 34 weeks had advanced cancer. For renal and bladder cancer respectively, 79% and 87% of patients obtained complete remission. Advanced cancer stages had worse prognosis; 3 of 7 patients with known follow-up deceased within 15 months after diagnosis. Conclusion: Gestational age at diagnosis determines further management of renal and bladder cancers during pregnancy. Advanced stages challenge decision-making. The maternal needs for immediate treatment, and the neonatal risks including the impact of a preterm delivery should be discussed in a multidisciplinary setting while respecting the patient's autonomy

Annual Report 2023 and Phase-I Closeout

This report summarises the activities of the CERN strategic R&D programme on technologies for future experiments during the year 2023, and highlights the achievements of the programme during its first phase 2020-2023