Left pneumonectomy for rapidly growing lung metastasis from phyllodes tumor

Distant metastases occur in 10-25% of malignant phyllodes tumors of the breast, heralding fatal outcome within few months. Only four cases of successful resection of solitary pulmonary metastases from phyllodes tumor are described in the literature. We report the case of a 67-year-old woman who developed rapidly growing metastases (volume doubling time: 25 days) in the left lung, two years after mastectomy for malignant phyllodes tumor. The left lung was the only site of 18-FDG uptake at total-body PET scan and the patient was successfully treated by left pneumonectomy

Self-selection effects in smokers attending lung cancer screening: a 9.5-year population-based cohort study in Varese, Italy.

BACKGROUND:: We hypothesize that mortality risk profile of participants and nonparticipants in nonrandomized lung cancer (LC) screening of smokers may be different. METHODS:: In 1997, a population-based cohort of 5815 smokers of Varese Province was invited to nonrandomized LC screening by annual chest x-ray examination for 4 years. LC risk factors and screening participation rate were recorded. Except for screening, the whole cohort received usual care. After 9.5-year observation, we compared mortality of participants versus nonparticipants by assessing age-standardized all-cause mortality rate ratio (MRR) and disease group-specific MRR with 95% confidence intervals (95% CI). RESULTS:: Self-selected screening participants were 21% of cohort. Participants were younger (p < 0.001), were more frequently current smokers (p = 0.019), had more pack-years of smoking (p < 0.0001), and had higher rate of LC family history (p < 0.0001) and of occupational LC risk (p < 0.0001) relative to nonparticipants. In logistic regression analysis familial LC, occupational risk and pack-years smoked were significant predictors of participation in screening and of developing LC. Participants displayed a healthy effect, as shown by all-cause MRR = 0.67 (95% CI, 0.53-0.84), all cancers except LC MRR = 0.61 (95% CI, 0.41-0.91), cardiovascular diseases MRR = 0.38 (95% CI, 0.22-0.63), and noncancer disease other than cardiovascular or respiratory MRR = 0.57 (95% CI, 0.34-0.92). The LC mortality (MRR = 1.40; 95% CI, 1.03-1.91) was higher in participants relative to nonparticipants (p = 0.031). CONCLUSION:: The selection effect in LC screening participants was dual: healthy effect and higher LC mortality. In assessing the overall effectiveness of LC screening on a population level, a higher LC mortality risk in participants should be considered

Farnesyltransferase inhibitors and human malignant pleural mesothelioma: a first-step comparative translational study.

It is known that the potential clinical use of farnesyltransferase inhibitors (FTI) could be expanded to include cancers harboring activated receptor tyrosine kinases. Approximately 70% of malignant pleural mesotheliomas (MPM) overexpress epidermal growth factor receptors (EGFR) and a subset express both EGFR and transforming growth factor A (TGF-A), suggesting an autocrine role for EGFR in MPM. We checked on MPM cells (10 human cell lines, 11 primary cultures obtained by human biopsies, and 7 short-term normal mesothelial cell cultures) concerning the following: (a) the relative overexpression of EGFR (Western blotting, flow cytometry, immunohistochemistry), (b) the relative expression of EGFR ligands (EGF, amphiregulin, TGF-A, ELISA), (c) the relative increase of the activated form of Ras (Ras-bound GTP) after EGF stimulation (Ras activation assay), (d) the efficacy of five different FTIs (HDJ2 prenylation, cell cytotoxicity, and apoptosis using ApopTag and gel ladder). EGFR was overexpressed in MPM cells compared with normal pleural mesothelial cells in equivalent levels as in non\u2013small cell lung cancer cells A549. MPM cells constitutively expressed EGFR ligands; however, Ras activation was attenuated at high EGF concentrations (100 ng/mL). Growth of MPM cells was substantially not affected by treatment with different FTIs (SCH66336, BMS- 214662, R115777, RPR-115135, and Manumycin). Among these, BMS-214662 was the only one moderately active. BMS-214662 triggered apoptosis in a small fraction of cells (not higher than 30%) that was paralleled by a slight decrease in the levels of TGF-A secreted by treated MPM cells. Our data highlighted the concept that the same signaling pathway can be regulated in different ways and these regulations can differ between different cells of different origin

Cost of a population-based programme of chest x-ray screening for lung cancer.

Background. After the implementation of a population- based programme of chest x-ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was significantly reduced. Analysis of the incremental costs due to this type of screening programme is needed to evaluate its economic impact on the healthcare system. Methods. In July 1997 a population-based cohort, consisting of all high-risk smokers (n=5,815) identified among 60,000 adult residents from the Varese province, was invited to a LC screening programme (an annual CXR for five years) in a general practice setting, and was observed through 2006. Invitees received National Health Service (NHS) usual care, with the addition of CXRs in screening participants. At the end of observation, among the 245 LCs diagnosed in the entire screening-invited cohort the observed LC deaths were 38 fewer than expected. To estimate the incremental direct cost due to screening in the invited cohort for the period July 1997-2006, we compared the direct cost of screening administration, CXR screens and LC management in the invited cohort and in the uninvited and unscreened controls in NHS usual care setting. Results. Over the 9.5 years, the total incremental direct healthcare costs (including screening organization/administration, CXR screens, additional procedures prompted by false-positive tests, overdiagnosed LCs) were estimated to range from \u20ac 607,440 to \u20ac 618,370 (in euros as of 2012), equating to between \u20ac 15,985- \u20ac 16,273 per patient out of the 38 LC deaths averted. Conclusions. In a general practice setting, the incremental cost for a CXR screening programme targeted at all high-risk smokers in a population of 60,000 adults was estimated to be about \u20ac65,000 per annum, approx. \u20ac16,000 for each LC death averted

Comparison of multiple techniques for endobronchial ultrasound-transbronchial needle aspiration specimen preparation in a single institution experience.

The optimal method for specimen preparation of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) is still controversial. This study aims to compare several techniques available for EBUS-TBNA specimen acquisition and processing, in order to identify the best performing technique. We retrospectively reviewed the data of 199 consecutive patients [male, 73%; median age, 64 years (IQR: 52-74 years)] undergoing EBUS-TBNA at our institution from 2012 through 2014 for diagnosis of hilar-mediastinal lymph node enlargement suspect of neoplastic (n=139) or granulomatous (n=60) disease. All procedures were performed by two experienced bronchoscopists, under conscious sedation and local anaesthesia, using 21/22-Gauge (G) needle, without rapid on-site evaluation (ROSE). Five specimen-processing techniques were used: cytology slides in 42 cases (21%); cell-block in 25 (13%); core-tissue in 60 (30%); combination of cytology slides and core-tissue in 51 (26%); combination of cytology slides and cell-block in 21 (10%). To assess the diagnostic accuracy of each tissue-processing technique we compared the EBUS-TBNA results to those obtained with surgical lymphadenectomy, or 1-year follow-up in non-operated patients. Diagnostic yield, accuracy and area under the curve (AUC) were as follows. Cytology slides: 81%, 80%, 0.90; cell-block: 48%, 33%, 0.67; core-tissue: 87%, 99%, 0.96; cytology slides + core-tissue: 80%, 100%, 1.00; cytology slides + cell-block: 86%, 100%, 1.00. Cytology slides and core-tissue method showed non-significantly different diagnostic yield (P=0.435) and AUC (P=0.152). In our single-institution experience, cytology slides and core-tissue preparations demonstrated high and similar diagnostic performance. Cytology slides combination with core-tissue or cell-block showed the highest performance, however these combination methods were more resource-consuming

ACTH-producing tumorlets and carcinoids of the lung: clinico-pathologic study of 63 cases and review of the literature.

Adrenocorticotropic hormone (ACTH)-secreting lung carcinoids represent the principal cause of ectopic Cushing syndrome, but the prevalence of ACTH expression and the association between ACTH production and Cushing syndrome in lung carcinoids have scarcely been investigated. In addition, available information on the prognostic meaning of ACTH production is controversial. The aims of this multicentric retrospective study, also including a review of the literature, were to describe the clinico-pathologic features of ACTH-producing lung carcinoids, to assess recurrence and specific survival rates, and to evaluate potential prognostic factors. To identify ACTH production in 254 unselected and radically resected lung carcinoids, we used a double approach including RT-PCR (mRNA encoding for pro-opiomelanocortin) and immunohistochemistry (antibodies against ACTH and β-endorphin). Sixty-three (24.8%) tumors produced ACTH and 11 of them (17.4%), representing 4.3% of the whole series, were associated with Cushing syndrome. The median follow-up time was 71 months. The 10-year overall and specific survival rates were 88.5% and 98.2%, respectively, with difference neither between functioning and nonfunctioning tumors nor between ACTH-positive and ACTH-negative carcinoids. At univariate analysis, histological type (typical or atypical) and Ki67 index significantly correlated with tumor recurrence. The literature review identified 172 previously reported patients with functioning ACTH-secreting lung carcinoids, and the meta-analysis of survival showed that 92% of them were alive after a mean follow-up time of 50 months. Our results demonstrate that ACTH-producing lung carcinoids are not rare, are not always associated with Cushing syndrome, and do not represent an aggressive variant of lung carcinoid

Cost of a population-based programme of chest x-ray screening for lung cancer

Background. After the implementation of a population- based programme of chest x-ray (CXR) screening on smokers in Varese, Italy, lung cancer (LC) mortality was significantly reduced. Analysis of the incremental costs due to this type of screening programme is needed to evaluate its economic impact on the healthcare system. Methods. In July 1997 a population-based cohort, consisting of all high-risk smokers (n=5,815) identified among 60,000 adult residents from the Varese province, was invited to a LC screening programme (an annual CXR for five years) in a general practice setting, and was observed through 2006. Invitees received National Health Service (NHS) usual care, with the addition of CXRs in screening participants. At the end of observation, among the 245 LCs diagnosed in the entire screening-invited cohort the observed LC deaths were 38 fewer than expected. To estimate the incremental direct cost due to screening in the invited cohort for the period July 1997-2006, we compared the direct cost of screening administration, CXR screens and LC management in the invited cohort and in the uninvited and unscreened controls in NHS usual care setting. Results. Over the 9.5 years, the total incremental direct healthcare costs (including screening organization/administration, CXR screens, additional procedures prompted by false-positive tests, overdiagnosed LCs) were estimated to range from € 607,440 to € 618,370 (in euros as of 2012), equating to between € 15,985- € 16,273 per patient out of the 38 LC deaths averted. Conclusions. In a general practice setting, the incremental cost for a CXR screening programme targeted at all high-risk smokers in a population of 60,000 adults was estimated to be about €65,000 per annum, approx. €16,000 for each LC death averted

Exploring the uncertainties of early detection results: model-based interpretation of mayo lung project

Background: The Mayo Lung Project (MLP), a randomized controlled clinical trial of lung cancer screening conducted between 1971 and 1986 among male smokers aged 45 or above, demonstrated an increase in lung cancer survival since the time of diagnosis, but no reduction in lung cancer mortality. Whether this result necessarily indicates a lack of mortality benefit for screening remains controversial. A number of hypotheses have been proposed to explain the observed outcome, including over-diagnosis, screening sensitivity, and population heterogeneity (initial difference in lung cancer risks between the two trial arms). This study is intended to provide model-based testing for some of these important arguments.Method: Using a micro-simulation model, the MISCAN-lung model, we explore the possible influence of screening sensitivity, systematic error, over-diagnosis and population heterogeneity.Results: Calibrating screening sensitivity, systematic error, or over-diagnosis does not noticeably improve the fit of the model, whereas calibrating population heterogeneity helps the model predict lung cancer incidence better.Conclusions: Our conclusion is that the hypothesized imperfection in screening sensitivity, systematic error, and over-diagnosis do not in themselves explain the observed trial results. Model fit improvement achieved by accounting for population heterogeneity suggests a higher risk of cancer incidence in the intervention group as compared with the control group