RESUMEN
Peritoneal carcinomatosis originating from gastric/gastroesophageal junction cancer (GC-PC) occurs in a defined subset of gastric cancer patients with unique clinical, pathologic, molecular and immunologic characteristics that create significant obstacles to effective treatment with modern therapy. Although systemic chemo- and immuno- therapy have yielded disappointing results in GC-PC, recent advances in the characterization of GC-PC and peritoneal immune biology present new opportunities for targeted therapeutics. In this review article, we discuss the distinct properties of GC-PC and the peritoneal immune environment as they pertain to current and investigative treatment strategies. We discuss pre-clinical studies and clinical trials relevant to the modulation of the peritoneal environment as a therapeutic intervention in GC-PC. Finally, we present a road map for future combinatorial strategies based on the conception of the peritoneal cavity as a bioreactor. Within this isolated compartment, prevailing immunosuppressive conditions can be altered through regional interventions toward an adaptive phenotype that would support the effectiveness of regionally delivered cellular therapy products. It is hoped that novel combination strategies would promote efficacy not only in the sequestered peritoneal environment, but also via migration into the circulation of tumor-reactive lymphocytes to produce durable systemic disease control, thereby improving oncologic outcome and quality of life in patients with GC-PC.
RESUMEN
Premature birth in conjunction with extremely low birth weight (<1 kg, ELBW) is associated with insulin resistance and increased cardiometabolic health risk compared to birth at full term with normal birth weight (NBW). However, little is known regarding the biologic mediators of these effects. Abdominal and ectopic lipid accumulation is linked to insulin resistance and metabolic dysfunction, yet whether ELBW survivors are predisposed to aberrant lipid deposition in adulthood is unknown. We used magnetic resonance imaging in a cohort of 16 NBW and 29 ELBW participants to determine if ELBW survivors have differences in pancreatic, hepatic, subcutaneous and visceral fat distribution compared to NBW participants. ELBW individuals had a higher proportion of liver and pancreatic fat compared to NBW subjects (P < 0.05). Abdominal subcutaneous fat, but not visceral fat, area was higher in ELBW survivors compared to NBW individuals. In multivariate analyses, tissue fat measures were most highly related to BMI and sex, but not preterm birth. This work highlights that fat deposition is enhanced in adults born preterm and suggests that ectopic fat accretion driven by their relatively greater adiposity may contribute to the higher rates of metabolic dysfunction seen in ELBW survivors.
