Is there an oncological interest in the combination of CRS/HIPEC for peritoneal carcinomatosis of HCC? Results of a multicenter international study

Introduction

Peritoneal metastasis (PM) of hepatocellular carcinoma (HCC) without distant spread are rare. The related prognosis is poor without standard treatment available. The role of cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is poorly documented.

Mesothelin and osteopontin as circulating markers of diffuse malignant peritoneal mesothelioma: A preliminary study

Background

The differential diagnosis between diffuse malignant peritoneal mesothelioma (DMPM) and other peritoneal surface malignancies (PSM) is still challenging. Serum mesothelin and osteopontin are increasingly used as markers of pleural mesothelioma, but their role in DMPM is unclear. We assessed the diagnostic and prognostic values of mesothelin, osteopontin, CEA, CA19.9, CA125, and CA15.3 in DMPM patients.

Vitamin K Antagonist Therapy Is a Risk Factor for Ulcer Development and Death Among Dialyzed Patients

Peripheral artery disease is a common complication among dialyzed patients. Since Vitamin K antagonists promote metastatic calcifications and these are the main determinants of vascular damage, we investigated their role in the development of lower limb ulcers in dialyzed patients. We retrospectively enrolled 316 dialyzed patients, aged 68 ± 15 years, 65% male, 32% diabetic, 43% with ischemic heart disease and followed them for 36 ± 25 months. 60 patients assumed Vitamin K antagonists: they were older, with a higher prevalence of heart disease, at greater risk of death and they developed more ulcers and underwent more lower limb amputations compared to the rest of our cohort. Peripheral artery disease, Vitamin K antagonists and diabetes were independent risk factors for foot lesions. In addition, Vitamin K antagonists were also an independent risk factor for death. Vitamin K antagonists are a potent independent risk factor for the development of the uremic foot syndrome and death.     

A de novo 15q13.2q13.3 deletion in a boy with an Angelman syndrome like phenotype

We report on a 11-year-old boy investigated for a clinical suspicion of Angelman syndrome (AS) (OMIM 105830) who was found to carry a de novo interstitial deletion of chromosome 15q13.2q13.3. The deletion overlaps the critical region for the newly recognized recurrent 15q13.3 deletion syndrome. This is the first report of a patient with 15q13.3 deletion syndrome with clinical features similar to that of AS, thus broadening the phenotypic spectrum associated with the 15q13.3 microdeletion syndrome.     

Receptor tyrosine kinase and downstream signalling analysis in diffuse malignant peritoneal mesothelioma

Our aim was to assess the activation profile of EGFR, PDGFRB and PDGFRA receptor tyrosine kinases (RTK) and their downstream effectors in a series of cryopreserved diffuse malignant peritoneal mesothelioma (DMPM) surgical specimens to discover the targets for drug inhibition. We also made a complementary analysis of the cytotoxic effects of some kinase inhibitors on the proliferation of the human peritoneal mesothelioma STO cell line.We found the expression/phosphorylation of EGFR and PDGFRB in most of the tumours, and PDGFRA activation in half. The expression of the cognate ligands TGF-α, PDGFB and PDGFA in the absence of RTK mutation and amplification suggested the presence of an autocrine/paracrine loop. There was also evidence of EGFR and PDGFRB co-activation. RTK downstream signalling analysis demonstrated the activation/expression of ERK1/2, AKT and mTOR, together with S6 and 4EBP1, in almost all the DMPMs. No KRAS/BRAF mutations, PI3KCA mutations/amplifications or PTEN inactivation were observed. Real-time polymerase chain reaction revealed the decreased expression of TSC1 c-DNA in half of the tumours. In vitro cytotoxicity studies showed the STO cell line to be resistant to gefitinib and sensitive to sequential treatment with RAD001 and sorafenib; these findings were consistent with the presence of the KRAS mutation G12D in these cells although it was not detectable in the original tumour.Our results highlight the ligand-dependent activation and co-activation of EGFR and PDGFRB, as well as a connection between these activated RTKs and the downstream mTOR pathway, thus supporting the role of combined treatment with RTK and mTOR inhibitors in DMPM.     

Impact of influenza-like illness and effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy

In order to evaluate the impact of influenza-like illness and the effectiveness of influenza vaccination in children with oncohematological disease who have completed cancer therapy, 182 children with a diagnosis of oncohematological disease were divided into two subgroups on the basis of the length of time off therapy (<6 months or 6–24 months) and randomised 1:1 to receive influenza vaccination or not. The controls were 91 otherwise healthy children unvaccinated against influenza. The results show that the clinical and socioeconomic impact of influenza-like illnesses and the effectiveness of influenza vaccination in oncohematological children who have completed cancer therapy are related to the length of the off therapy period, and seem to be significantly greater in those who have been off therapy for less than 6 months in comparison with healthy controls. This suggests that the administration of influenza vaccination should be strongly recommended only among oncohematological children who have been off therapy for less than 6 months.