A restrictive stoma policy after colorectal anastomosis in ovarian cancer based on ghost ileostomy use.

BACKGROUND: The incidence of anastomotic leak after colorectal anastomosis in ovarian cancer has been reported to be much lower than that in colorectal cancer patients. Regarding the use of protective manoeuvres (diverting ileostomy) as suggested by clinical guidelines, the goal should be the implementation of a restrictive stoma policy for ovarian cancer patients, given the low rate of anastomotic leakage in this population. MATERIAL AND METHODS: Patients who underwent cytoreduction surgery in a single centre (University Hospital La Fe, Valencia Spain) due to ovarian cancer between January 2010 and June 2023 were classified according to two groups: a non-restrictive stoma policy group (Group A) and a restrictive stoma policy group (Group B). RESULTS: A total of 256 patients were included in the analysis (group A 52 % vs group B 48 %). The use of protective diverting ileostomy was lower in the restrictive stoma policy group (14 % vs 6.6 %), and the use of ghost ileostomy was 32 % vs 87 % in groups A and B, respectively (p < 0.00001). No differences were found in the anastomotic leak rate, which was 5.2 % in the non-restrictive group and 3.2 % in the restrictive stoma policy group (p = 0.54). CONCLUSION: The use of a restrictive stoma policy based on the use of ghost ileostomy reduces the rate of diverting ileostomy in patients with ovarian cancer after colorectal resection and anastomosis. Furthermore, this policy is not associated with an increased rate of anastomotic leakage nor with an increased rate of morbi-mortality related to the leak.

Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia.

Neonatal platelets are hypo-reactive to the tyrosine kinase-linked receptor agonist collagen. Here, we have investigated whether the hypo-responsiveness is related to altered levels of glycoprotein VI (GPVI) and integrin α2ß1, or to defects in downstream signalling events by comparison to platelet activation by C-type lectin-like receptor 2 (CLEC-2). GPVI and CLEC-2 activate a Src- and Syk-dependent signalling pathway upstream of phospholipase C (PLC) γ2. Phosphorylation of a conserved YxxL sequence known as a (hemi) immunotyrosine-based-activation-motif (ITAM) in both receptors is critical for Syk activation. Platelets from human pre-term and full-term neonates display mildly reduced expression of GPVI and CLEC-2, as well as integrin αIIbß3, accounted for at the transcriptional level. They are also hypo-responsive to the two ITAM receptors, as shown by measurement of integrin αIIbß3 activation, P-selectin expression and Syk and PLCγ2 phosphorylation. Mouse platelets are also hypo-responsive to GPVI and CLEC-2 from late gestation to 2 weeks of age, as determined by measurement of integrin αIIbß3 activation. In contrast, the response to G protein-coupled receptor agonists was only mildly reduced and in some cases not altered in neonatal platelets of both species. A reduction in response to GPVI and CLEC-2, but not protease-activated receptor 4 (PAR-4) peptide, was also observed in adult mouse platelets following immune thrombocytopenia, whereas receptor expression was not impaired. Our results demonstrate developmental differences in platelet responsiveness to GPVI and CLEC-2, and also following immune platelet depletion leading to reduced Syk activation. The rapid generation of platelets during development or following platelet depletion is achieved at the expense of signalling by ITAM-coupled receptors.