EUS-guided biopsies versus surgical specimens for establishing patient-derived pancreatic cancer organoids: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Patient-derived tumor organoids (PDTOs) are a promising new disease model in pancreatic cancer for use in personalized medicine. However, the overall success rate (SR) of establishing these cultures from EUS-guided biopsies is unknown. METHODS: We searched relevant database publications reporting SRs of PDTO establishment from pancreatic cancer. The primary outcome was SR stratified on tissue acquisition method (EUS-guided biopsies, percutaneous biopsies, and surgical specimens). RESULTS: Twenty-four studies were identified that included 1053 attempts at establishing PDTOs. Overall SR was 63% (95% confidence interval [CI], 54%-72%). Pooled SRs of PDTO establishment from EUS-guided biopsies, percutaneous biopsies, and surgical specimens were 60% (95% CI, 43%-76%), 36% (95% CI, 14%-61%), and 62% (95% CI, 48%-75%), respectively, and did not differ significantly (P = .1975). CONCLUSION: The SR of PDTO establishment from EUS-guided biopsies is comparable to that from surgical specimens. Both techniques are suitable for tissue acquisition for PDTOs in clinical and research settings. (PROSPERO registration number: CRD42023425121.).

Progress report: Peutz-Jeghers syndrome.

Peutz-Jeghers syndrome is a rare, autosomal dominant polyposis syndrome. Presenting with a remarkable phenotype including development of characteristic gastrointestinal polyps, mucocutaneous pigmentations, and an increased risk of cancer, the syndrome has been subject to many studies concerning the natural course of disease. In most patients, pathogenic germline variants are detected in the STK11 gene including cases of mosaicism and structural variants. Yet, studies assessing the effect of surveillance, understanding of cancer development, as well as clinical studies evaluating chemoprevention are lacking. In addition, the impact of Peutz-Jeghers syndrome on mental health, education, and family planning are insufficiently addressed. In this progress report, we describe current knowledge, clinical phenotype, surveillance strategies, and future areas of research.

Re-evaluating the genotypes of patients with adenomatous polyposis of unknown etiology: a nationwide study.

In the Danish Polyposis Register, patients with over 100 cumulative colorectal adenomas of unknown genetic etiology, named in this study colorectal polyposis (CP), is registered and treated as familial adenomatous polyposis (FAP). In this study, we performed genetic analyses, including whole genome sequencing (WGS), of all Danish patients registered with CP and estimated the detection rate of pathogenic variants (PV). We identified 231 families in the Polyposis Register, 31 of which had CP. A polyposis-associated gene panel was performed and, if negative, patients were offered WGS and screening for mosaicism in blood and/or adenomas. Next-generation sequencing (NGS) was carried out for 27 of the families (four declined). PVs were detected in 11 families, and WGS revealed three additional structural variants in APC. Mosaicism of a PV in APC was detected in two families. As the variant detection rate of eligible families was 60%, 93% of families in the register now have a known genetic etiology.