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Capodanno A.,University of Pisa | Boldrini L.,University of Pisa | Proietti A.,University of Pisa | Ali G.,Unit of Pathological Anatomy III | And 8 more authors.
International Journal of Oncology | Year: 2013

MicroRNAs (miRNAs) play a key role in cancer pathogenesis and are involved in several human cancers, including non-small cell lung cancer (NSCLC). This study evaluated Let-7g and miR-21 expression by quantitative real-time PCR in 80 NSCLC patients and correlated the results with their main clinicopathological and molecular features. MiR-21 expression was significantly higher in NSCLC tissues compared to non-cancer lung tissues (p<0.0001), while no significant changes in Let-7g expression were observed between the tumor and normal lung tissues. Target prediction analysis led to the identification of 26 miR-21 and 24 Let-7g putative target genes that play important roles in cancer pathogenesis and progression. No significant association was observed between the analysed miRNAs and the main clinicopathological or molecular characteristics of the NSCLC patients, although both miRNAs were downregulated in squamous cell carcinomas compared to adenocarcinomas. Noteworthy, we observed a significant association between low Let-7g expression and metastatic lymph nodes at diagnosis (p=0.046), as well as between high miR-21 expression and K-Ras mutations (p=0.0003). Survival analysis did not show any significant correlation between prognosis and the analysed miRNAs, although the patients with a high Let-7g and miR-21 expression showed a significantly lower short-term progression-free survival (p=0.01 and p=0.0003, respectively) and overall survival (p=0.023 and p=0.0045, respectively). In conclusion, we showed that Let-7g and miR-21 expression was deregulated in NSCLC and we demonstrated a strong relationship between miR-21 overexpression and K-Ras mutations. Our data indicate that Let-7g and miR-21 profiling combined with the determination of K-Ras mutational status may be considered a useful biomarker for a more effective molecular characterization and clinical management of NSCLC patients.


Lococo F.,Unit of Thoracic Surgery | Cesario A.,IRCCS San Raffaele Pisana | Okami J.,Japan National Cardiovascular Center Research Institute | Cardillo G.,Azienda Ospedaliera San Camillo Forlanini | And 5 more authors.
Lung Cancer | Year: 2013

Introduction: To investigate the performance of combined 18F-FDG-PET/CT as a predictor of the WHO-classification based malignancy grade in thymic epithelial tumors. Methods: From 05/06 to 02/12, the data of 47 patients with thymic epithelial tumors assessed by 18F-FDG-PET/CT before being surgically treated were collected in 3 centers and retrospectively reviewed for the purposes of this study. The SUVmax and the SUVmax/T index (the ratio tumor-SUVmax to tumor-size) have been matched with specific subgroups of the WHO-classification: low-risk thymomas (types A-AB-B1), high-risk thymomas (types B2-B3) and thymic carcinomas (type C). Results: There were 22 men and 25 women (age range: 31-84 yrs). Mean tumor size was 44.7 ± 19.0. mm. The WHO-classification was: type-A #2, type-AB #11, type-B1 #9, type-B2 #9, type-B3 #9 and type-C #7. The SUVmax and the SUVmax/T were found to be predictive factors useful to distinguish thymomas from thymic carcinomas (SUVmax: area under ROC-curve: 0.955, p= 0.0045; SUVmax/T-size: area under ROC-curve: 0.927, p= 0.0022). Moreover, both parameters were found to be correlated with the WHO malignancy grade (low-risk thymomas; high-risk thymomas; thymic carcinoma), Spearman correlation coefficients being 0.56 (p< 0.0001) and 0.76 (p< 0.0001), respectively for the SUVmax and for the SUVmax/T index. In addition, the SUVmax is also significantly correlated with Masaoka stage (Spearman correlation coefficient: 0.30, p= 0.0436). Conclusions: A significant relationship was observed between 18F-FDG-PET/CT findings and histologic WHO-classification for this cohort of thymic epithelial tumors. Thus, on the basis of these evidences, we infer that 18F-FDG-PET/CT may be useful to predict histology and the WHO classes of risk. © 2013 Elsevier Ireland Ltd.


Treglia G.,Oncology Institute of Southern Switzerland | Sadeghi R.,Mashhad University of Medical Sciences | Giovanella L.,Oncology Institute of Southern Switzerland | Cafarotti S.,San Giovanni Hospital | And 2 more authors.
Lung Cancer | Year: 2014

Aim: To perform a systematic review and meta-analysis of published data on the role of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG PET) in predicting the WHO grade of malignancy in thymic epithelial tumors (TETs). Methods: A comprehensive literature search of studies published up to March 2014 was performed. Data on maximum standardized uptake value (SUVmax) in patients with low-risk thymomas (A, AB, B1), high-risk thymomas (B2, B3) and thymic carcinomas (C) according to the WHO classification were collected when reported by the retrieved articles. The comparison of mean SUVmax between low-risk thymomas, high-risk thymomas and thymic carcinomas was expressed as weighted mean difference (WMD) and a pooled WMD was calculated including 95% confidence interval (95%CI). Results: Eleven studies were selected for the meta-analysis. The pooled WMD of SUVmax between high-risk and low-risk thymomas was 1.2 (95%CI: 0.4-2.0). The pooled WMD of SUVmax between thymic carcinomas and low-risk thymomas was 4.8 (95%CI: 3.4-6.1). Finally, the pooled WMD of SUVmax between thymic carcinomas and high-risk thymomas was 3.5 (95%CI: 2.7-4.3). Conclusions: 18F-FDG PET may predict the WHO grade of malignancy in TETs. In particular, we demonstrated a statistically significant difference of SUVmax between the different TETs (low-grade thymomas, high-grade thymomas and thymic carcinomas). © 2014 Elsevier Ireland Ltd.


Sandri A.,University of Turin | Cusumano G.,Vittorio Emanuele Hospital | Lococo F.,Unit of Thoracic Surgery | Alifano M.,University of Paris Descartes | And 7 more authors.
Journal of Thoracic Oncology | Year: 2014

Objectives: The treatment for recurrent thymoma remains a very controversial issue. This study aims to investigate the long-term outcomes in patients with relapse according to treatment strategies and clinicopathological features. Methods: We retrospectively analyzed the database of three tertiary centers of thoracic surgery with the aim of reviewing the clinical records of 81 patients who experienced a recurrent thymoma after radical thymectomy, in the period between January 2001 and June 2013. The staging of both primitive and recurrent thymomas were based on the surgical and pathological criteria described by Masaoka. Experienced pathologists reassessed independently the histology of the initial thymoma and its relapse, according to the WHO classification. To the purposes of this study R+ resection or thymic carcinoma were considered as exclusion criteria. The overall outcome for long-term (5 years and 10 years) survival and disease-free survival after initial thymectomy and after treatment of recurrent thymoma were analyzed using standard statistics. Results: The population was gender balanced (41 M, 40 F), mean age: 46.4 ± 12.3 years. Fifty-four patients (66.7%) were affected by myasthenia gravis, while the other 14 by other paraneoplastic conditions. Surgery was performed in 61 patients (75.3%,), and radiotherapy and/or chemotherapy in 14 patients (17.3%). The mean follow-up duration after recurrence onset was 66.3 ± 56.4 months. Adjuvant therapy had no effect on prolonging the disease-free survival: no differences were found when investigating the administration of adjuvant chemotherapy (no CHT = 91.5 ± 76.4 months versus yes CHT=64.0 ± 41.3) and radiotherapy (no RT=86.2 ± 72.8 months versus yes RT= 93.0 ± 62.3; p = 0.8). Relapses were mostly local (mediastinum: 15 cases, pleura: 44 cases); hematogenous distant recurrences were observed in 15 cases (lung: 12; liver: 1; bone: 2 cases). An upgrade in the WHO class (defined as the "migration" of WHO class at initial thymectomy to more aggressive WHO class assigned at thymic recurrence resection) was found in 25/61 cases (40.9%), but this phenomenon apparently did not influence patient's prognosis. Overall, the 5- and 10-year survival rates after the initial thymectomy were 94.8% and 71.7%, respectively, while the 5- and 10-year survival rates after the treatment of the recurrence at the thymic level were 73.6% and 48.3%, respectively (82.4% at 5 years and 65.4% at 10 years when a R0-re-resection was obtained). The analysis on the trends of disease-free survival indicated that the site of recurrence (hematogenous diffusion) seems to be associated to a higher risk of re-relapse (p = 0.01). Conclusions: Even following a thymectomy performed with radical intent, thymoma may recur several years later, usually as a locoregional relapse. A rewarding long-term survival may be expected after treatment, especially when a re-resection (radical) is performed (82.4% at 5 years). An histopathological "WHO upgrade" (from "low-risk" WHO classes at thymectomy to "high-risk classes" at relapse) may be observed in a remarkable percentage of patients (nearly 40% in this series), but this phenomenon seems to be not correlated with any worsening of the prognosis. Copyright © 2014 by the International Association for the Study of Lung Cancer.


Cavazza A.,Unita Operativa di Anatomia Patologica | Rossi G.,Unit of Pathology | Carbonelli C.,Unit of Pulmunology | Spaggiari L.,Unit of Radiology | And 2 more authors.
Respiratory Medicine | Year: 2010

The diagnosis of idiopathic pulmonary fibrosis (IPF) currently requires an integrated clinical-radiological-pathological approach in which the histology plays a different role from in the past. The first reason for this change is that non-invasive diagnostic procedures, particularly pulmonary function tests and high resolution computed tomography, have become increasingly competitive with biopsy in providing prognostic information. The other reason is a better appreciation of the limitations of histology: sampling error and interobserver variation. In this review we analyze the reasons for this change of perspective, provide an update on the practical role of histology in the diagnosis of IPF and discuss some of its complications. © 2010 Elsevier Ltd. All rights reserved.


Lococo F.,Unit of Thoracic Surgery | Treglia G.,Oncology Institute of Southern Switzerland
Hellenic Journal of Nuclear Medicine | Year: 2014

Bronchial carcinoids (BC) are rare well-differentiated neuroendocrine tumours (NET) sub-classified into typical (TC) and atypical carcinoids (AC). A correct pathological identification in the pre-operative setting is a key element for planning the best strategy of care, considering the different biological behavior of TC and AC. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in BC. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (dotanoc, dotatoc or dotatate) labeled with gallium-68 ( 68Ga) in pulmonary NET. Based on information obtained by using different radiopharmaceuticals and different 68Ga labeled somatostatin analogues in PET and PET/CT studies, we are able to diagnose BC. In conclusion, by using somatostatin receptor imaging and 18F-FDG PET/CT scan, we can differentiate BC from benign pulmonary lesions and TC from AC by specific diagnostic patterns. Clinical trials on larger groups of patient would allow for a better and "tailored" therapeutic strategy in NET patients using dual-tracer PET/CT to identify BC and distinguish between TC and AC.


Janssen J.,Canisius Wilhelmina Hospital | Cardillo G.,Unit of Thoracic Surgery
Respiration | Year: 2011

The initial treatment of primary spontaneous pneumothorax is not standardized throughout the world. Although aspiration is less painful and requires less hospitalization than chest tube drainage does, the latter is still frequently used as the initial treatment. After a recurrence or failure of aspiration, chest tube drainage, again, is often the procedure of choice although VATS or thoracoscopy and talc poudrage have been proven to be much more effective. For the surgical treatment of recurrent pneumothorax, the role of routine resection of blebs and nonruptured bullae still needs to be assessed. Pleurodesis (chemical or mechanical) should be the standard treatment in a surgical procedure. © 2011 S. Karger AG, Basel.


Salati M.,Unit of Thoracic Surgery
Journal of Thoracic Disease | Year: 2015

The process of data collection inevitably involves costs at various levels. Nevertheless, this effort is essential to base our knowledge and the consequent decision making on solid foundations. The European Society of Thoracic Surgeons (ESTS) database collects a large amount of data on general thoracic surgery derived from about 60 units representative of 11 nations. Since its beginning in 2001, the ESTS database has contributed to increase the knowledge and the quality of care in our specialty. The present paper illustrates the ultimate finalities and the obtained results of this data collection, providing a broad overview of the motivations to participate to the ESTS database. © Journal of Thoracic Disease.


Stefani A.,Unit of Thoracic Surgery | Nesci J.,Unit of Thoracic Surgery | Casali C.,Unit of Thoracic Surgery | Morandi U.,Unit of Thoracic Surgery
Minerva Chirurgica | Year: 2012

Aim. Advances in imaging techniques and screening protocols can detect more small lung cancers. Controversy exists regarding surgical management of these small tumors. Methods. Records and long-term outcome of all patients with TINO (<2 cm) non-small cell lung cancer undergoing wedge resection with curative intent from 1996 through 2010 were retrospectively reviewed. Those patients were compared with a group of patients treated with lobectomy during the same period and for a disease at the same stage. Sublobar resections were performed in compromised patients in all cases. Results. The study included 206 patients: 82 received wedge resection, 124 lobectomy. Morbidity and mortality were similar between the two groups. Locoregional recurrence rate was significantly higher for wedge resection compared with lobectomy (22% versus 8% respectively), cancer-specific survival and disease-free survival were significantly poorer for wedge resection with respect to lobectomy: 5-year survival of 74% versus 85% respectively, 5-year disease-free survival of 62% versus 77%. The type of operation resulted as an independent prognostic factor of cancer-specific survival. Conclusions. We found poorer outcome for wedge resection compared to lobectomy. We believe that caution should be used when suggesting the use of wedge resection as intentional limited resection for patients with small non-small cell lung cancer who may otherwise tolerate lobectomy. Two randomized trials comparing limited resection and lobectomy are ongoing in Japan and in United States: they will better clarify the role of limited resection, especially segmentectomy, in the treatment of T1aN0 tumors. Wedge resection may remain a valid option for compromised patients.


PubMed | Unit of Pathology, Unit of Thoracic Surgery, Catholic University of the Sacred Heart, Medical Physics Unit and 2 more.
Type: | Journal: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery | Year: 2017

False-negative (FN) uptake of 18F-fluorodeoxyglucose (FDG) can be divided into those cases related to technological limitations of positron emission tomography (PET) and those related to inherent properties of neoplasms. Our goal was to clarify possible factors causing FN PET results in patients with solid-type pulmonary adenocarcinomas (PAs).From January 2007 to December 2014, of the 255 patients with p-stage-1 non-small-cell lung cancer observed and treated (surgically) in our institution, we retrospectively reviewed the PET/computed tomography (CT) records, the clinical information, the preoperative thin-section CT images, and the pathological features [classified by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) subtyping criteria] of 94 consecutive solid-type p-stage-1 PAs. Univariable and multivariable logistic analyses were used to identify and weigh the independent predictors of the PET findings using the following variables: body weight, blood glucose level, tumour size, tumour location, and histological classification.There were 58 men and 36 women (mean age=68.78.9 years, range 42-85). Considering the maximum standardized uptake value (SUVmax) 2.5 as a PET-positive result, 77 lesions (81.9%) proved PET positive and 17 lesions (18.1%), PET negative (with SUVmax<2.5). Overall, the median SUVmax value was 5.7 [interquartile range (IQR) 2.8-10.3]. Higher SUVmax values (P<0.001) were observed in those PAs larger than 2cm in their major axis (median SUVmax=9.0; IQR 4.6-14.6); in PAs<2cm, the median SUVmax was 4.1; IQR 2.2-5.9. When clustering the cohort in two histological classes (class A, colloid/mucinous/lepidic versus class B, micropapillary/solid/acinar/papillary), the radiometabolic patterns were significantly different (median SUVmax=2.8; IQR 1.7-4.9 in class A vs median=7.4 IQR 4.5-13.9 in class B, P<0.001). Significant PET FN rates were reported in (i) PAs measuring <2cm in their major axis (27.9%), (ii) lesions located in the lower zones of the lung (31.0%), and (iii) class A tumours (37.5%). In the multivariable logistic analysis, histological type (IASLC/ATS/ERS aggregated clusters) proved to be the only independent relevant factor for determining whether PET results were negative or positive (OR:7.23, 95% CI: 2.05-25.43, P=0.002).The IASLC/ATS/ERS pattern significantly influences FDG uptake in solid-type p-stage-1 PAs. The fact that colloid/mucinous/lepidic adenocarcinomas have a notable tendency to produce negative findings on PET scans warrants particular attention.

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