Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for resectable peritoneal metastases is feasible in elderly patients.

The aim is to evaluate the feasibility and the prognosis of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for resectable peritoneal metastases (RPM) in elderly patients. Patients who underwent CRS with HIPEC for RPM between 2012 and 2018 in one tertiary reference center were retrospectively included and divided according to the age: Group A (< 65 years) and Group B (≥ 65 years). Postoperative outcomes and survivals were compared. Ninety-five patients were included in Groups A (n = 65) and B (n = 30). The incidence of comorbidities was significantly higher in elderly patients (65 vs 90%, p = 0.01), but RPM characteristics were similar between groups. There was no difference between groups in terms of postoperative results: 30-day major morbidity (33 vs 23%, p = 0.4), 30-day mortality (0 vs 3%, p = 0.3), mean length of stay (26.7 ± 19.4 vs 22.4 ± 10.3 days, p = 0.3) and readmission's rate (15 vs 33%, p = 0.06). The only one significant difference was the 90-day mortality which never occurred before 65 years but in 10% of elderly patients (p = 0.03). There was no difference regarding recurrence's rate (56 vs 37%, p = 0.1), neither 1-, 3- and 5-year overall survival rates (86, 64 and 52% vs 85, 74% and not reached, p = 0.8) and disease-free survival rates (61, 28 and 28% vs 56, 45% and not reached, p = 0.6). CRS with HIPEC is feasible in elderly patients. Since the 90-day mortality appeared to be higher in elderly patients, additional criteria are necessary to improve the selection of elderly patients for this major surgery.

The Interaction of Platelets with Colorectal Cancer Cells Inhibits Tumor Growth but Promotes Metastasis.

Platelets promote metastasis, however, their role in tumor growth remains controversial. Here, we investigated the effect of platelet interactions with colorectal tumor cells. Platelets extravasated into the tumor microenvironment and interacted with tumor cells in a cadherin-6-dependent manner. The interaction induced platelet spreading, release of their granule content, and the generation of three types of microparticles (iMP) that expressed platelet markers, tumor markers, or both. The presence of iMPs was confirmed in colorectal cancer tissue specimens. Platelets significantly reduced tumor growth and increased intratumoral macrophages. This was mediated by iMP recruitment of macrophages via the chemoattractants RANTES, MIF, CCL2, and CXCL12 and activation of their tumor cell killing capacity through IFNγ and IL4, which led to cell-cycle arrest of tumor cells in a p21-dependent manner. In contrast, in the bloodstream, iMPs activated endothelial cells and platelets and induced epithelial-to-mesenchymal transition of tumor cells, promoting metastasis. Altogether, these results indicate that depending on the environment, local or bloodstream, the consequences of the interactions between platelets and a tumor may promote or prevent cancer progression. SIGNIFICANCE: Tumor cell interaction with platelets produces chimeric extracellular vesicles that suppress primary tumor growth by activating tumor-eliminating macrophages, while promoting metastasis through EMT and endothelial activation.

Endoscopic perforations: what are the indications for surgery?

BACKGROUND: Despite their low occurrence, endoscopic perforations (EPs) are concerning. Some predictive factors have been identified, and EP management is debated, whether non-surgical (medical and/or endoscopic) or surgical. The objective was to elaborate a predictive score for surgical management of EP. METHODS: All the patients addressed for upper and lower EP, except oesophageal EP, were retrospectively included (2004-2015). Demographic data, endoscopic features (indication, location, type), clinical, biological and radiological presentations of EP were reviewed. Management of EP and outcomes were recorded. A predictive score was constructed by multiple linear regression and a cut-off value for surgical management was identified. Additional subgroup analysis was performed according to the location of EP (upper and lower). RESULTS: Among 41150 endoscopic procedures, 44 patients (22 males, median age = 65 years [22-87]) presenting with EP were included (0.09%). Lower gastrointestinal (GI) endoscopy was mostly performed (66%). EP diagnosis was immediate in 73% of the cases (n = 32). Non-surgical management was efficient in 2/3 cases treated medically alone, and 18/20 cases treated by endoscopy. Surgical management was always successful (n = 24/24). In case of peritonitis, surgery was systematically required, whereas easily required in case of delayed diagnostic of EP. The EP score was based on the presence of previous abdominal surgery, lower GI endoscopy and diagnostic endoscopy. A cut-off EP score of 22.8% for surgery was chosen; it was associated with a specificity and sensitivity of 40 and 100%, respectively. When subgroups were analysed according to EP location, the EP score was still based on the presence of previous abdominal surgery and diagnostic endoscopy. The cut-off was 6.3 and 73.3% for upper (specificity: 73%, sensitivity: 100%) and lower (89 and 45%) locations, respectively. CONCLUSION: The predictive EP score may avoid inappropriate surgical management, as well as delayed surgery after non-surgical management failure. Forthcoming study should prospectively validate this score.