Fatty liver and mortality: a cohort population study in South Italy.

OBJECTIVE: Alcoholic fatty liver (AFLD) and non-alcoholic fatty liver (NAFLD) are two common conditions. However, if they can increase the risk of death is poorly explored. We therefore aimed to investigate the potential association between the presence and severity of liver steatosis and mortality in a large sample of older people. DESIGN: Prospective. SETTING: Community. PARTICIPANTS: Women and men randomly sampled from the electoral rolls of the population of Castellana Grotte, a town in Southern Italy (Apulia region) between 2005 and 2006. Among 1942 initially contacted, 1708 (=87.9%) participated to the baseline survey (Multicentrica Colelitiasi III (MICOL III)). This specific study included 1445 older participants (mean age=65.2 years, females=44.2%). EXPOSURE: NAFLD or AFLD. PRIMARY AND SECONDARY OUTCOMES: Mortality (all-cause and specific-cause). RESULTS: After a median of 12 years, 312 participants (=21.6%) died. After adjusting for nine potential confounders, the presence of steatosis was not associated with any increased risk of death in both NAFLD and AFLD. The severity of liver steatosis was not associated with any increased risk of mortality in NAFLD, while in AFLD, the presence of moderate steatosis significantly increased the risk of overall (HR=2.16; 95% CI 1.19 to 3.91) and cancer-specific (HR=3.54; 95% CI 1.16 to 10.87) death. CONCLUSIONS: Liver steatosis is not associated with any increased risk of death in NAFLD, while moderate steatosis could be a risk factor for mortality (particularly due to cancer) in people affected by AFLD.

Use of nivolumab in elderly patients with advanced squamous non-small-cell lung cancer: results from the Italian cohort of an expanded access programme.

AIM: This analysis evaluated the efficacy and safety of nivolumab, an immune checkpoint inhibitor, in elderly patients with stage IIIB or IV squamous non-small-cell lung cancer (NSCLC) enrolled in the expanded access programme (EAP) in Italy. METHODS: Nivolumab was available on physician request. Safety data included adverse events (AEs). Efficacy data included investigator-assessed tumour response, progression date and survival information. Results were analysed for patients aged <65, 65-<75 and ≥75 years and for the overall population. RESULTS: A total of 371 patients with squamous NSCLC were enrolled at 96 centres between April 2015 and September 2015; 34% (n = 126), 47% (n = 175) and 19% (n = 70) were aged <65, 65-<75 and ≥75 years, respectively. Efficacy was similar among patients aged <65, 65-<75 and ≥75 years and the overall population (objective response rates: 18%, 18%, 19% and 18%, respectively; disease control rates: 49%, 47%, 43% and 47%, respectively). Median overall survival was reduced in patients aged ≥75 years (5.8 months) versus patients aged <65; years (8.6 months), patients aged 65-<75 years (8.0 months) and the overall population (7.9 months). The incidence of grade 3-4 treatment-related AEs was low in patients aged 65, 65-<75 and ≥75 years and the overall population (3%, 9%, 3%, 6%, respectively). Discontinuation rates due to treatment-related AEs were low irrespective of age (4-5%). CONCLUSIONS: These EAP results suggest that elderly patients with advanced squamous NSCLC benefit from nivolumab, with tolerability similar to that in the overall population.

Metachronous primary uterine cancer surgically resected during Crizotinib treatment in a ALK-rearranged advanced lung adenocarcinoma.

Rearrangements of the anaplastic lymphoma kinase (ALK) gene are present in 3% to 7% of non-small-cell lung cancers (NSCLCs). Patients harboring ALK rearrangements show very favourable outcomes if treated with targeted agents, among which crizotinib is the first and best studied. Crizotinib, an oral small-molecule tyrosine kinase inhibitor of ALK, MET, and ROS1 kinases, is a very active and well tolerated drug. Nevertheless, the optimal therapy management with this new drug is still partially unknown, especially with regard to the safety of combined treatments. Recently, the integration of locoregional treatments has been proposed as a feasible multimodality strategy in selected patients with good clinical conditions and slow-growing or oligoprogressive disease. In this report, a case of advanced lung adenocarcinoma, progressed after first line chemotherapy and re-biopsied detecting ALK rearrangement, is described. During crizotinib treatment the primary lung tumor showed an excellent regression; meanwhile a major surgery for a metachronous uterine cancer was safely and successfully carried out.

Sarcomatoid mesothelioma: future advances in diagnosis, biomolecular assessment, and therapeutic options in a poor-outcome disease.

Malignant pleural mesothelioma (MPM) is the most frequent pleural neoplasm, with asbestos exposure as one of the recognized carcinogen agents, causative in 80% of cases. The prognosis is poor; median survival of untreated cases is 6-9 months, with fewer than 5% of patients surviving 5 years. Sarcomatoid mesothelioma (SM) represents the subtype with the worst outcome and median survival ranging from 3.5 to 8 months. In the last few years, an accurate differentiation between the subtypes of MPM has become a crucial issue, due to differences in chemosensitivity and clinical outcome, and several studies have evaluated different immunohistochemical markers to better define the diagnosis. The different and worse outcome of patients with SM and, in general, nonepithelioid subtypes makes it intriguing to select these cases to better study the biomolecular profile in order to find factors linked to prognosis and/or predictive of therapeutic response. Considering recent studies on miRNA and genetic mapping, further investigation of this rare subtype might represent a field for basic and clinical-translational research providing for more tailored therapies.

Bladder and gastric metastases from lung adenocarcinoma harboring codon 13 KRAS mutation: a case report with unusual clinical outcome.

AIMS AND BACKGROUND: Gastric and bladder metastases are rare in non-small-cell lung cancer (NSCLC) and the differential diagnosis with primary tumors requires an in-depth examination. KRAS gene mutations are the main oncogenic driver of lung adenocarcinoma in Caucasian patients, occurring in 25%-30% of cases, but their prognostic and predictive role is complex and not fully clarified. KRAS mutations in lung adenocarcinoma are considered negatively predictive for epidermal growth factor receptor tyrosine kinase inhibitors therapy as well as for adjuvant chemotherapy. In this report, the authors describe a case of lung adenocarcinoma harboring a codon 13 KRAS mutation detected in all the biopsies performed in unusual metastatic sites during an atypical disease course. CONCLUSIONS: Recently, a different prognostic significance of various KRAS mutations in lung adenocarcinoma has been suggested. Further studies on rare biomolecular alterations to identify subgroups of patients with different prognostic/predictive characteristics are needed.

Cisplatin/Pemetrexed Followed by Maintenance Pemetrexed Versus Carboplatin/Paclitaxel/Bevacizumab Followed by Maintenance Bevacizumab in Advanced Nonsquamous Lung Cancer: The GOIM (Gruppo Oncologico Italia Meridionale) ERACLE Phase III Randomized Trial.

INTRODUCTION: Cisplatin with pemetrexed (CP) and carboplatin with paclitaxel and bevacizumab (CbTB) are standard first-line treatments for patients with advanced nonsquamous (NS) non-small-cell lung cancer (NSCLC). Quality of life (QoL) is a key objective in the management of advanced NSCLC. Thus, effect on QoL could be an additional factor in the choice of treatment. PATIENTS AND METHODS: Patients with untreated stage IIIB/IV NS-NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomized to receive first-line chemotherapy with cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2), every 3 weeks, for 6 cycles followed by maintenance pemetrexed; or carboplatin area under the curve 6, paclitaxel 200 mg/m(2), and bevacizumab 15 mg/kg, every 3 weeks, for 6 cycles followed by maintenance bevacizumab. The primary end point was the difference in QoL between the 2 treatment arms after 12 weeks of maintenance, measured using the EuroQoL 5 Dimensions-Index (EQ5D-I) and EQ5D-visual analogue scale (EQ5D-VAS). RESULTS: One hundred eighteen patients were randomized to CP (n = 60) or CbTB (n = 58). Baseline characteristics were well balanced. The proportion of patients evaluable for the primary end point was lower than planned. After 12 weeks of maintenance, the difference between mean changes in EQ5D-I was 0.137, favoring CP (95% confidence interval [CI], -0.02 to 0.29, Wilcoxon P = .078), although not statistically significant; and the difference between mean changes in EQ5D-VAS was 0.97 (95% CI, -9.37 to 11.31, Wilcoxon P = .41). CONCLUSION: Although the study was underpowered because of a small number of patients evaluable for the primary end point, QoL did not differ between treatment arms. Other factors such as comorbidities and schedule should be used when deciding on first-line treatment.