Cellularity in low-grade Pseudomyxoma peritonei impacts recurrence-free survival following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

PURPOSE: Documentation of cellularity in Pseudomyxoma peritonei (PMP) is not performed on a regular basis in everyday clinical practice, but is recommended by the PSOGI (Peritoneal Surface Oncology Group International). We investigated the impact of cellularity in PMP following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) on recurrence-free survival. METHODS: Data from 25 patients with low-grade (American Joint Committee on Cancer grade G1) PMP were retrospectively evaluated. Cellularity was categorized as acellular mucin, scant (< 2% cellularity), moderate (2-19% cellularity), or high cellularity (> 20% cellularity). Impact of cellularity, PCI, CC-score, and HIPEC regimen on recurrence-free and overall survival was primarily assessed. RESULTS: Assessment of cellularity showed acellular mucin in ten patients (40%), scant cellularity in 11 (44%) patients, moderate cellularity in one (4%) patient, and high cellularity in three (12%) patients. Median PCI was 15 (range, 1-39). A CC-0 score was achieved in 13 (52%) patients and a CC-1 score was achieved in 12 (48%) patients. After a median follow-up of 25 (range, 2-74) months, all patients were still alive. Overall, four (16%) patients suffered from recurrent disease after a median of 38 (range, 36-60) months. PCI above 17 (p = 0.03) and moderate and high cellularity (p = 0.007) were statistically significantly associated with recurrent disease. CC-score and HIPEC compound used did not impact on recurrence-free survival. CONCLUSIONS: Recurrent disease occurs more often in patients with PCI values above 17 and with moderate and high cellularity in low-grade PMP. Pathological assessment of cellularity is crucial for identification of patients at risk for recurrence.

Phosphorylation of vasodilator-stimulated phosphoprotein (VASP) dampens hepatic ischemia-reperfusion injury.

Recent work has demonstrated that the formation of platelet neutrophil complexes (PNCs) affects inflammatory tissue injury. Vasodilator-stimulated phosphoprotein (VASP) is crucially involved into the control of PNC formation and myocardial reperfusion injury. Given the clinical importance of hepatic IR injury we pursued the role of VASP during hepatic ischemia followed by reperfusion. We report here that VASP(-/-) animals demonstrate reduced hepatic IR injury compared to wildtype (WT) controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate (AST) and alanine (ALT) aminotransferase and the presence of PNCs within ischemic hepatic tissue and could be confirmed using repression of VASP through siRNA. In studies employing bone marrow chimeric mice we identified hematopoietic VASP to be of crucial importance for the extent of hepatic injury. Phosphorylation of VASP on Ser(153) through Prostaglandin E1 or on Ser(235) through atrial natriuretic peptide resulted in a significant reduction of hepatic IR injury. This was associated with a reduced presence of PNCs in ischemic hepatic tissue. Taken together, these studies identified VASP and VASP phosphorylation as crucial target for future hepatoprotective strategies.