Etiology and Mechanisms of Peritoneal Carcinomatosis

Primary Cancer Origins and Pathophysiologic Mechanisms

Gastrointestinal cancers are the predominant source of peritoneal carcinomatosis, with gastric cancer accounting for peritoneal metastases in nearly one-third of patients at diagnosis 3
Gynecological malignancies, particularly ovarian cancer, demonstrate high propensity for peritoneal spread 4
Lobular breast cancer represents a unique entity with peritoneal metastatic patterns similar to gastric cancer, driven by specific molecular characteristics 4, 1

Epithelial-mesenchymal transition (EMT) is the critical initial process enabling peritoneal carcinomatosis, transforming epithelial cells into a mesenchymal phenotype with increased migratory capacity, invasive capability, and resistance to anoikis (detachment-induced cell death) 4, 1, 2
Downregulation of E-cadherin and other intercellular adhesion molecules facilitates tumor cell detachment from the primary site 4, 1
CDH1 mutations occur more frequently in peritoneal metastases, particularly in diffuse-type gastric cancers 4, 2
TP53 mutations are present at similar rates in peritoneal metastases as primary tumors 4, 2

The peritoneum provides a unique microenvironment that facilitates tumor implantation, consisting of basement membrane, mesothelial cells, and connective tissue (hyaluron, collagen, proteoglycans) that tumor cells exploit for adhesion 4, 1
Malignant ascites creates a tumorigenic environment through soluble factors, including growth factors, cytokines (IL-6, IL-8), and chemokines (CXCL1/CXCR1, CCL2/CCR4) that promote tumor cell survival and proliferation 4, 2
TGF-β pathway activation increases collagen and fibronectin deposition, facilitating tumor cell adhesion to peritoneal surfaces 1

Synchronous peritoneal carcinomatosis occurs simultaneously with primary cancer diagnosis, with increasing incidence (18% to 26.5% over 2008-2017 in gastric cancer) 7, 8
Metachronous peritoneal carcinomatosis develops 7-32% of the time after curative gastrectomy, typically within 8.5-26 months post-surgery, accounting for one-fifth to three-fifths of all metastatic recurrences 7, 2
CT sensitivity for peritoneal metastases is only 28-51% despite 97-99% specificity, and diagnostic laparoscopy with peritoneal washings should be strongly considered before initiating systemic chemotherapy in all patients with proven gastric cancer to detect occult peritoneal disease 8, 7