Pseudomyxoma Peritonei: Diagnostic Pearls, Surgical Decision-making and HIPEC Controversies

Background: Pseudomyxoma peritonei (PMP) is a rare clinical syndrome characterised by progressive intraperitoneal accumulation of mucinous ascites, most commonly arising from appendiceal mucinous neoplasms. Once uniformly fatal, the prognosis has been transformed by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Nevertheless, controversies persist regarding diagnostic strategies, surgical thresholds and the true incremental value of HIPEC. Objective: This review synthesises contemporary evidence on the pathogenesis, diagnostic pearls, surgical decision-making and HIPEC controversies in PMP, while exploring emerging systemic and targeted therapies and future directions in biomarker-driven and AI-assisted management. Methods: A comprehensive literature review of PubMed-indexed studies from 2000 to 2025 was performed, with emphasis on systematic reviews, meta-analyses, randomised controlled trials and multicentre registries. Key themes were integrated under diagnostic evaluation, surgical selection, HIPEC pharmacology, systemic therapy limitations and translational innovations. Seminal historical references were retained selectively for context. Conclusion: PMP exemplifies the convergence of rare disease biology and surgical audacity. CRS remains the cornerstone, with peritoneal cancer index (PCI) and completeness of cytoreduction (CC score) guiding operative decision-making. While HIPEC is widely practised, the absence of randomised data in PMP sustains debate over its necessity, optimal regimens and feasibility in low-resource settings. Systemic therapies remain limited, but novel mucinase strategies, immunotherapy and AI-driven imaging prediction herald a future of personalised care. Global collaboration through registries and consensus frameworks will be critical to resolving controversies and ensuring equitable access to curative strategies worldwide.