Search PubMed⌕ Search

Biomedical subjects

U Pastorino

Publications and source records attributed to U Pastorino.

At least 19 recordsLinked to original sources

Early detection of cancer: ideas for a debate.

Even if the overall number of cancer is increasing, the mortality has started to decrease in the Western World. The role of early detection in this decrease is a matter of debate. To assess its impact on mortality it is important to distinguish between diagnosis of cancer in symptomatic patients, and early detection in asymptomatic individuals who may self-refer or who may be offered ad hoc or systematic screening. The policies for early detection and screening vary greatly between European countries, despite many similarities in their cancer burden, and this partly reflects the uncertainties surrounding asymptomatic testing for cancer. A Task Force of European expert, held in Azzate (VA), Italy, established to address these issues, acknowledged the need for more research in the field of individual risk assessment since general statistics are more and more perceived as inadequate to design personal early detection plans. The group also recognised that combinations of early detection and screening will enforce the effectiveness of new treatments in curbing mortality curves, although policies will vary with different cancers.

Breast Neoplasms↗

Identification of RASSF8 as a candidate lung tumor suppressor gene.

The RASSF8 gene, which maps close to the KRAS2 gene, contains a RAS-associated domain and encodes a protein that is evolutionarily conserved from fish to humans. Analysis of the RASSF8 transcript revealed a complex expression pattern of 5'-UTR mRNA isoforms in normal lung and in lung adenocarcinomas (ADCAs), with no apparent differences. However, RASSF8 gene transcript levels were approximately seven-fold-lower in lung ADCAs as compared to normal lung tissue. Expression of RASSF8 protein by transfected lung cancer cells led to inhibition of anchorage-independent growth in soft agar in A549 cells and reduction of clonogenic activity in NCI-H520 cells. These results raise the possibility protein encoded by RASSF8 is a novel tumor suppressor for lung cancer.

5' Untranslated Regions↗

Independent prognostic value of fascin immunoreactivity in stage I nonsmall cell lung cancer.

Fascin-1, the most expressed form of fascin in vertebrate tissues, is an actin-bundling protein that induces cell membrane protrusions and increases motility of normal and transformed epithelial cells. Very few data are available on the role of this protein in nonsmall cell lung cancer (NSCLC). Two hundred and twenty patients with stage I NSCLC and long-term follow-up were evaluated immunocytochemically for fascin expression. Overall, variable fascin immunoreactivity was detected in 98% of 116 squamous cell carcinomas, in 78% of 96 adenocarcinomas, in 83% of six large cell carcinomas, and in the two adenosquamous carcinomas under study. Neoplastic emboli were commonly decorated by the antifascin antibody (P<0.001), also when the surrounding invasive carcinoma was unreactive. Fascin immunoreactivity correlated with high tumour grade (P=0.017) and, in adenocarcinomas, with high Ki-67 labelling index (P=0.021). Adenocarcinomas with a prevalent bronchiolo-alveolar in situ component were less commonly immunoreactive for fascin than invasive tumours (P=0.005). Contralateral thoracic or distant metastases were associated significantly with diffuse (>60% immunoreactive tumour cells) fascin expression in adenocarcinomas (P=0.043), and marginally with strong fascin immunostaining in squamous cell carcinomas (P=0.13). No associations were noted with any other clinicopathological variables tested. Patients with tumours showing diffuse (>60% immunoreactive neoplastic cells) and/or strong immunoreactivity for fascin had a shorter survival (P=0.006 for adenocarcinomas and P=0.026 for squamous cell carcinomas), even after multivariate analysis (P=0.014 and 0.050, respectively). The current study documents for the first time that fascin is upregulated in invasive and more aggressive NSCLC, being an independent prognostic predictor of unfavourable clinical course of the disease. Targetting the fascin pathway could be a novel therapeutic strategy of NSCLC.

Adult↗

Fluorodeoxyglucose positron emission tomography improves preoperative staging of resectable lung metastasis.

OBJECTIVE: F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) is now a procedure of proven clinical value in the staging of primary lung cancer. This study evaluated the role of PET in the preoperative assessment of resectable lung metastases. METHODS: Eighty-six patients with previously treated malignancy and proven or suspected lung metastases, deemed resectable at computed tomography scan, were investigated with 89 preoperative PET procedures. Primary tumor sites were: gastrointestinal in 32 cases, sarcoma in 13, urologic in 14, breast in 8, head and neck in 7, gynecologic in 5, thymus in 5, other in 5. Seventy lung resections were performed in 68 patients of whom only 54 proved to be lung metastasis, 7 were primary lung tumors, and 9 were benign lesions. RESULTS: In 19 cases (21%) lung surgery was excluded on the basis of PET scan results due to extrapulmonary metastases (11 cases), primary site recurrence (2), mediastinal adenopathy (2), or benign disease (4). All mediastinal node metastases (7 cases) were detected by PET with a sensitivity, accuracy, and negative predictive value for mediastinal staging of 100%, 96%, and 100%, respectively, versus 71%, 92%, and 95% of the computed tomography scan. In the group of patients who underwent lung resection, PET sensitivity for detection of lung metastasis was 87%. CONCLUSIONS: PET scan proved to be a valuable staging procedure in patients with clinically resectable lung metastasis and changed the therapeutic management in a high proportion of cases.

Female↗

Blood glutathione as a surrogate marker of cancer tissue glutathione S-transferase activity in non-small cell lung cancer and squamous cell carcinoma of the head and neck.

The identification of markers predicting the response to therapy is of the utmost importance in oncology. Several authors have suggested that increased levels of glutathione (GSH) and glutathione S-transferase (GST) activity might be meaningful predictors of poor responsiveness to chemotherapy in several human cancers, but the biological assays have not been standardised and published studies show conflicting evidence. The aim of the present study was to select a validated panel of tests to assess the GST/GSH system in a clinical setting. Matched blood and tissue samples (normal and malignant) from 52 cancer patients with either non-small cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (SCCHN) were investigated. GSH levels and GST activity were higher in cancer tissues than in matched normal tissues in both malignancies. The difference was statistically significant in NSCLC (P=0.0004 and P=0.0002, for GSH and GST, respectively) and borderline in SCCHN (P=0.03 and P=0.02, for GSH and GST, respectively). Moreover a strong correlation was found between the GSH level in whole blood and GST activity in cancer tissue in both malignancies (P=0.003, r=0.53 in NSCLC, P<0.0001, r=0.89 in SCCHN). In conclusion, reliable and robust methods for routine use in tissue extracts and in whole blood have been validated. Our finding regarding the GSH level in blood indicates that circulating GSH could have a clinical relevance as a surrogate marker of GST activity in tumour tissue.

Adult↗

Fluoro-deoxi-glucose uptake and angiogenesis are independent biological features in lung metastases.

Neoangiogenesis and enhanced glucose metabolism in neoplasms are likely to be activated by the same biochemical stimulus; hypoxia. A correlation between these two parameters has been postulated. The objective of this study was to evaluate the relationship between Fluoro-desoxi-glucose uptake at positron emission tomography scan and angiogenesis in lung metastasis. Fluoro-desoxi-glucose activity, expressed as a standard uptake value, and microvessel intratumoural density, were retrospectively calculated in a series of 43 lung metastasis resected in 19 patients. Primary sites were colorectal cancer in 16 metastases, sarcoma in eight, gynaecological in four and other sites in 15. The correlation between the two parameters was tested by logistic regression and multivariate analysis. Positron emission tomography scan was positive in 17 patients (sensitivity 89%). No correlation was observed between standard uptake value and microvessel intratumoural density in this series of lung metastasis. Positron emission tomography negative and positive nodules presented comparable value of microvessel intratumoural density (12.9 vs 11.3). Standard uptake value was significantly correlated with nodules size and was higher in colon cancer metastasis than in sarcoma ones. Microvessel intratumoural density was independent from nodule size but significantly higher in sarcoma than in colon cancer metastasis. The lack of correlation was confirmed by multivariate analysis after adjustment for tumour type and nodules size. The present study demonstrated that positron emission tomography scan is positive in a high proportion of patients regardless of microvessel density. Glucose uptake and angiogenesis appear to be independent biological features in lung metastasis. This observation may have implications for future antiangiogenic therapies.

Adult↗

Low morbidity of bronchoplastic procedures after chemotherapy for lung cancer.

OBJECTIVE: To evaluate if induction chemotherapy, with or without irradiation, represents an additional risk factor for early and late morbidity and perioperative mortality in bronchoplastic procedures for lung cancers. METHODS: From January 1998 to January 2001, 27 patients underwent a bronchial sleeve resection after induction treatment at the European Institute of Oncology in Milan. They represent 7% of lung cancer resections (387) and 27% of those performed after neoadjuvant treatment (100 cases). Histology was: 17 epidermoid carcinoma, 8 adenocarcinoma and 2 SCLC. Twenty-four patients (89%) received a preoperative cisplatin based polichemotherapy, and three cases (11%) a chemo-radiation therapy. A right sleeve lobectomy or bilobectomy was undertaken in 21 patients (78%) and a left lobectomy in 6 (22%). A resection of tracheal carina was associated in three cases and a vascular resection in 10 (five vena cava and five pulmonary artery). Twelve patients (44%) received adjuvant mediastinal irradiation. Perioperative morbidity of the study group (group 1) was compared with that of patients submitted to sleeve resection without neoadjuvant treatment (group 2), or standard pneumonectomy after induction treatment (group 3). RESULTS: There were no postoperative deaths. A major perioperative complication occurred in two patients (7%) of group 1, one patient of group 2 (3.5%), and four in group 3 (17%). Among patients of the study group, no anastomotic dehiscence or pleural empyema were observed. Only one late anastomotic stricture occurred after postoperative radiation treatment. No significant difference in early and late complication rate was found between the three groups of patients. High rate of complete resection was achieved (93%) in patients of the study group and extent of nodal dissection was similar between sleeve resections and pneumonectomy patients. CONCLUSIONS: Preoperative chemotherapy or combination of chemo-radio therapy is not associated with an additional risk of anastomotic complications in bronco and angioplastic procedures. Parenchyma sparing resection is a valid option for selected patients with locally advanced lung cancer after induction treatment. A longer follow up is necessary to evaluate efficacy of the procedure in term of survival and local control.

Adult↗

Postpneumonectomy-like syndrome after chemoradiation therapy for lymphoma.

Postpneumonectomy syndrome (PPS) is a rare complication of pneumonectomy due to an excessive mediastinal shift producing compression of the main bronchus or a lobe bronchus on the aorta or the spine. We report an exceptional case in which an extreme mediastinal shift was due to fibrosis and complete atelectasis of the left lung, as a complication of chemoradiation treatment for recurrent mediastinal Hodgkin's lymphoma. This condition, associated with a further recurrence of the disease, indicated a postpneumonectomy-like syndrome.

Adult↗

Surgical treatment of chest wall tumors.

Chest wall tumors have long represented challenging clinical entities for surgeons. Until recently, incorrect diagnosis, incomplete resection, or inability to perform successful reconstruction of large thoracic wall defects led to high rates of perioperative morbidity and mortality. The latter were primarily associated with infections of the pleural cavity, respiratory failure, and paradoxical breathing. The long-term prognosis was also poor owing to a high percentage of local relapse. During the same operating procedure wide resection and reconstruction of the thoracic wall are performed successfully. Improvement of the prognosis reported in large series of patients with resection leads to surgical treatment being considered the best option for primary tumors and for selected secondary tumors of the chest wall. Because positive margins are the most important risk factor for local recurrence, adequate margins of healthy tissue surrounding the tumors have a considerable impact on disease-free and overall survival. Involvement of ribs, sternum, superior sulcus, or spine is not considered a technical limitation to surgical resection. Nowadays correct management cannot be precluded by tumor size, site, or contiguous structure involvement because concurrent reconstruction with prosthetic materials and myocutaneous flaps is feasible. Surgery provides the best chance of cure in patients with chest wall tumors. Therefore the surgical strategy must be based on the features of the individual's disease.

Breast Neoplasms↗

Double transmanubrial approach and sternotomy for resection of a giant thymic carcinoid tumor.

The transmanubrial approach allows excellent unilateral exposure of the thoracic outlet. However, selected patients may require a bilateral cervicomediastinal exposure to completely resect the neoplasm. We report the use of a "double" transmanubrial approach for the resection of a giant mediastinal mass requiring bilateral vascular dissection and superior vena cava system resection and replacement.

Aged↗

Endoscopic argon plasma coagulation for palliative treatment of malignant airway obstructions: early results in 47 cases.

Argon plasma coagulation (APC) is a new method of non-contact electrocoagulation, using high frequency current by means of ionized argon gas (argon plasma). Recently, this technique has become available for flexible endoscopic delivery through special probes. Aim of this study is to evaluate the efficacy, indications and the possible side effects of APC use in the palliative treatment of malignant airway obstructions and/or bleeding. Over a 24-month period, 47 patients underwent APC treatment for malignant neoplasms of the tracheobronchial system causing obstruction and/or recurrent bleeding. Immediate airway patency and haemostasis were obtained in 91.5% of cases (43/47). No complications or side effects caused by the treatment were observed. In two patients, the treatment allowed a radical surgical approach after induction chemotherapy. In all cases, APC proved to be highly effective and easy to perform. In our experience, APC has proven to be easy to perform, rapidly effective, safe and well tolerated by the patient, even after repeated application. This study highlights the value of endoscopic APC in the palliative management of tracheobronchial neoplasms.

Adult↗

Cardiac dislocation after extended pneumonectomy with pericardioplasty.

Two cases of cardiac dislocation occurred after intrapericardial right pneumonectomy with extended pericardiectomy and radical nodal dissection in spite of proper reconstruction with a pericardial fat flap in one case and with a Gore-tex prosthesis in the other. In the case of major pericardial excision resulting in extensive mobilisation of the SVC a complete reconstruction of pericardium and mediastinal pleura is recommended in order to prevent cardiac dislocation.

Carcinoma, Non-Small-Cell Lung↗