The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

AIM: Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. METHOD: This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. RESULTS: Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. CONCLUSION: Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

Peritoneal nebulizer: a novel technique for delivering intraperitoneal therapeutics in laparoscopic surgery to prevent locoregional recurrence.

BACKGROUND: Peritoneal involvement is a significant issue in the treatment of gastrointestinal malignancies. Current statistics indicate that after surgical intervention, up to 20% of patients will present with locoregional metastasis. The ability to inhibit initial tumor adhesion to the mesothelial lining of the peritoneum may be considered critical in the inhibition of tumor development. This article describes, the use of a novel nebulizer system capable of delivering high-concentration, low-dose therapeutics to the peritoneal cavity. METHODS: For this study, 30 male WAG rats were inoculated with CC531 colorectal tumor cells. The rats were randomized into three groups: control group (n = 10), heparin-treated group (n = 10), and high-molecular-weight hyaluronan-treated group (n = 10). A peritoneal cancer index was used to determine tumor burden at 15 days. Analysis of variance (ANOVA) was used to compare multiple group means. RESULTS: Nebulization therapy was performed without any complication in the cohort. Heparin inhibited macroscopic intraperitoneal tumor growth completely (p = 0.0001) without affecting tumor cell viability. The introduction of hyaluronan attenuated both tumor size and distribution, was compared with the control group (p = 0.002). CONCLUSION: Nebulized heparin and hyaluronic acid using a novel nebulization technique attenuates peritoneal tumor growth after laparoscopic surgery. The technique itself is easy to use and safe.