Long-term oxygen therapy in chronic respiratory failure: a Multicenter Italian Study on Oxygen Therapy Adherence (MISOTA)

BACKGROUND: The adherence to the prescribed oxygen therapy is difficult to obtain for patients on long-term oxygen therapy (LTOT). There is little information on the modalities of oxygen utilisation for patients on LTOT who are using liquid oxygen in real life. STUDY OBJECTIVE: Evaluation of the behaviour and the knowledge regarding LTOT in a large group of patients mainly using liquid oxygen. DESIGN AND SETTING: Questionnaire administered to consecutive outpatients on domiciliary LTOT for at least 6 months referring to one of 20 clinics throughout Italy. Blinded to this result, the physician who cared for the patient completed another questionnaire. RESULTS: We evaluated 1504 patients (mean age 71.6 years; males 64%; 74% suffering from COPD). Most respondents (93%) used liquid oxygen with mobile device. Fifteen per cent of patients had a prescribed length of oxygen therapy less than 15 h/day; 21% reported to practice oxygen for less than 15 h/day. Patients reported using oxygen for less hours than had been prescribed during the day at rest (P=0.02, k=0.80) during exercise (P=0.002, k=0.72) and at night (P=0.0036, k=0.77). There was no difference between the flow prescribed by the physician and that known and practised by the patient at rest or during sleep; during exercise the flow reported by patients was lower than that prescribed by the physician. Patients used in the night but not at rest or during exercise, a lower level of oxygen flow than what they knew had been prescribed. Fifty-five per cent of patients received indications to modify the oxygen flow in the various situations of life. Liquid oxygen was almost always useful to decrease breathlessness. Most (84%) patients possessed a mobile device, but only 40% declared they used it daily, 'shame' being indicated as the principal barrier. On the physicians' side, we found that the criteria used in prescribing did not always correspond to evidence-based recommendations. CONCLUSION: The widespread use of liquid oxygen did not automatically assure optimal adherence to the prescribed treatment as regards times and modality of oxygen use. A better education of patients, relatives, and the general public, as well as increased self-assessment on the part of health caregivers would improve the practice of LTOT in Italy.     

Circulating CA125 in Patients with Peritoneal Mesothelioma Treated with Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion

Background Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP. Methods Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules ≤ 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined. Results Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy. Conclusions CA125 was elevated in the majority of patients with PM in the present series. Serial maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.     

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.

Clinicopathological features of primary cutaneous B-cell lymphomas from an academic regional hospital in central Italy: no evidence of Borrelia burgdorferi association

We reviewed the clinico-pathological features of 73 primary cutaneous B-cell lymphomas (PCBCLs), diagnosed in 10 years in Marche region in central Italy, which included 16 marginal zone lymphomas (MZL), 33 follicle centre lymphomas (FCL) and 24 diffuse large B cell lymphomas (DLBCL). We also investigated the presence of Borrelia burgdorferi in tissues by polymerase chain reaction. Differences in age, sex, location site, response to therapy, disease recurrence and 5-year disease-specific survival were observed among the 3 histological groups. Specific DNA sequences of Borrelia burgdorferi were not detected in any of the 73 cases of PCBCL. We conclude that PCBCLs in Marche region behave according to the literature data and do not seem to be associated with Borrelia burgdorferi. Additional investigations should be performed on other possible etiologies, at least in our geographical area.     

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.