PubMed HealthSearch

Biomedical subjects

U Pastorino

Publications and source records attributed to U Pastorino.

At least 19 recordsLinked to original sources

Systematic nodal dissection in the intrathoracic staging of patients with non-small cell lung cancer.

OBJECTIVE: Although systematic nodal dissection is accepted as an important component of the intrathoracic staging of disease in patients undergoing thoracotomy for lung cancer, many surgeons still do not routinely perform it. We reviewed our practice to assess the information provided by its routine application even when lymph node metastases are considered unlikely. METHODS: The records of 240 patients undergoing thoracotomy for clinically staged cT1-3 N0-1 non-small cell lung cancer were reviewed. In 5 cases (2%) mediastinal dissection was not performed because of specific contraindications and in 8 cases (3%) exploratory thoracotomy was performed. The pathologic findings in the 227 patients who underwent pulmonary resection with systematic nodal dissection were analyzed. RESULTS: The median number of nodal stations, including N1 and N2, examined and submitted separately for histologic assessment was 7 per patient (range 3-13). N2 disease was disclosed in 46 patients overall (20%), including 41 of the 227 patients undergoing pulmonary resection (18%) and 5 of those undergoing exploratory thoracotomy (62.5%). No subgroup had a 0% incidence of N2 metastases. Multivariate analysis showed that younger age, increasing tumor size, left lower lobe origin, and bronchial origin were significant independent variables for prediction of lymph node metastases at the N1 level, the N2 level, or both. CONCLUSIONS: Because no clinical or pathologic subset of patients with a negligible incidence of N2 disease could be discriminated, systematic nodal dissection must be routinely employed for accurate intrathoracic staging of non-small cell lung cancer.

Adenocarcinoma

Endobronchial stenting for extrinsic compression caused by pulsatile pulmonary artery in a 4-week-old infant.

Respiratory compromise secondary to external vascular compression may complicate the course of infants and neonates undergoing repair of congeni tal heart disease. Management of such complications usually involves prolonged ventilatory support and even additional high-risk surgical procedures. In recent years, endobronchial placement of self-expanding stents became a realistic treatment option, although there is controversy as to which of the many stents available today give the best results. We report the first successful endobronchial placement of a self-expanding stent in a 4-week-old infant. This conservative treatment for extrinsic airway compression led to the rapid extubation and recovery of the patient.

Bronchial Diseases

Loss of FHIT function in lung cancer and preinvasive bronchial lesions.

We previously cloned and characterized the tumor suppressor gene FHIT (fragile histidine triad) at chromosome 3p14.2 and found that this gene is altered by deletions in human tumors, including lung cancer. To assess the frequency and specificity of inactivation and its relevance in a clinical setting, we have produced antibodies against the Fhit protein and studied its expression in a series of non-small cell lung cancers and normal bronchial mucosa and a spectrum of preinvasive lesions by immunohistochemistry. The data indicate that the loss of Fhit protein is the most frequent alteration in non-small cell lung cancer (73%) and precancerous lesions (93%), is significantly higher in the tumors of smokers (75%) than in those of nonsmokers (39%; P < 0.0005), and is an independent and more frequent event than p53 overexpression in tumors and precancerous lesions (73 versus 46%). The percentage of cases lacking Fhit expression was higher in the squamous type compared to adenocarcinoma (87 versus 57%; P < 0.00001), whereas other histotypes (large cell, mucoepidermal) showed an intermediate value (69%). Loss of Fhit expression in a very high percentage of primary lung carcinomas and precancerous lesions supports the notion that FHIT alterations play an important role in the growth control of bronchial cells. FHIT inactivation is particularly important in squamous cell carcinomas that are often associated with precursor dysplastic lesions. The overall high frequency and precocity of Fhit loss in lung carcinogenesis and the development of the presently described immunohistochemical approach suggest a potential use of this gene in the early detection of lung cancer and in chemopreventive studies as an intermediate biomarker.

Acid Anhydride Hydrolases

Prognostic value of loss of heterozygosity and KRAS2 mutations in lung adenocarcinoma.

The prognostic values of loss of heterozygosity (LOH) at loci frequently involved in non-small cell lung cancer and of KRAS2 gene mutations were studied in lung adenocarcinoma patients. LOHs were relatively common, ranging from 24% at chromosome 10p to 55% at chromosome 17p13. KRAS2 mutations at codon 12 were present in 26% of cases, were more common in male than in female patients and were associated with a smoking habit. No association between LOH at any site and clinical stage or survival rate was found. On the other hand, we observed a trend between the presence of any type of KRAS2 mutations and poor survival. Analysis of specific KRAS2 mutations showed a strong effect of Asp (GAT) and Val (GTT) mutations, resulting in a very poor survival compared with wild type group, whereas the most common mutation (Cys, TGT) was not associated with prognosis. Our results indicate the importance of specific activating mutations of the KRAS2 gene as genetic markers of clinical outcome for patients with lung adenocarcinoma.

Adenocarcinoma

Selective use of PET scan in the preoperative staging of NSCLC.

Positron emission tomography (PET) is a imaging technique which identifies abnormalities by utilising their metabolic properties rather than their anatomical density. In this study, we evaluated the place of PET scanning for the characterisation of additional abnormalities discovered on routine, preoperative CT evaluation of patients with proven NSCLC. A total of 21 patients underwent PET scanning using fluorodeoxyglucose (FDG). In these patients, routine CT scans had found 26 concomitant lesions which were in lung, adrenal gland, liver, kidney, spleen and pleura. FDG uptake was positive at the primary site in all patients. FDG uptake in 13 of the concomitant lesions suggested malignancy. Malignancy was confirmed at all of these foci by histology in eight (six at thoracotomy, fine needle aspiration biopsy (FNAB) and open biopsy) and by clinical and radiological follow-up for 1-15 months in five. In 13 lesions, PET suggested benign disease. Histology reported no evidence of malignancy in five and the six foci followed on clinical and radiographic follow-up for 2-16 months had no evidence of malignancy. PET was falsely negative in only one site where malignancy was proven by thoracotomy. PET failed to detect the remaining lesion which was an unassociated primary kidney tumour in a patient with Li-Fraumeni syndrome. The accuracy of PET scanning in the assessment of those additional lesions found on CT evaluation of otherwise operable NSCLC was found to be 96% with a sensitivity of 93% and specificity of 100%. These results indicate that PET is useful to characterise additional lesions found on CT scan of patients with NSCLC.

Adult

Thoracic metastasectomy for germ cell tumours: long term survival and prognostic factors.

BACKGROUND: This study evaluated the results of thoracic metastasectomy for germ cell tumours to assess long term survival and identify prognostic factors. PATIENTS AND METHODS: A series of 141 consecutive patients who underwent resection of thoracic metastases at Royal Brompton Hospital were retrospectively reviewed. Kaplan-Meier estimates of survival were calculated for clinical variables related to primary tumour and thoracic metastases, using the Cox model for multivariate analysis. RESULTS: Complete resection was achieved in 123 cases (87%); pathology showed viable malignant elements in 46 (32%), necrosis or fibrosis in 32, differentiated teratoma in 63. The overall survival was 77% at five years and 65% at 15 years, being significantly shorter in patients with malignant teratomatous elements (51% at five years, P = 0.0001) or incomplete resection (64% at five years, P = 0.019). At multivariate analysis these factors retained their prognostic value, with a relative risk of death of 5.7 for malignant teratomatous elements and 4.0 for incomplete resection. In addition, the Cox model revealed a 3.2 times higher risk of relapse in patients with malignant teratomatuos elements at the time of thoracic metastasectomy. CONCLUSIONS: These data confirm the value of thoracic metastasectomy to asses pathological response and achieve permanent cure of chemoresistant disease.

Adult

Suppression of tumour development by substances derived from the diet--mechanisms and clinical implications.

The concept that cancer can be prevented, or its onset postponed, by certain diet-derived substances is currently eliciting considerable interest. Agents which interfere with tumour development at the stage of promotion and progression in particular are of potential clinical value. As chemopreventive agents have to be administered over a long period of time in order to establish whether they possess efficacy in humans, it is of paramount importance to establish their lack of toxicity. The desire to select the best chemopreventive drug candidates for clinical trial, and the necessity to monitor efficacy in the short and intermediate term, render the identification of specific mechanism-based in vivo markers of biological activity a high priority. Antioxidation, inhibition of arachidonic acid metabolism, modulation of cellular signal transduction pathways, inhibition of hormone and growth factor activity and inhibition of oncogene activity are discussed as mechanisms by which the soya constituent genistein, the curry ingredient curcumin and the vitamin A analogue 13-cis retinoic acid exert tumour suppression. A better understanding of these mechanisms will help the establishment of screens for the discovery of new and better chemopreventive agents and the identification of surrogate markers to assess the outcome of clinical chemoprevention trials.

Anticarcinogenic Agents

Multiple synchronous lung cancers and atypical adenomatous hyperplasia in Li-Fraumeni syndrome.

AIM: We report a patient with Li-Fraumeni syndrome who developed multiple synchronous primary lung cancers together with atypical adenomatous hyperplasia, and discuss the pathogenesis of the lesions. CASE DETAILS: A 57-year-old woman with Li-Fraumeni syndrome and a history of smoking was diagnosed as having multiple synchronous primary lung tumours, all of which were treated by surgical excision. Histological examination showed three separate well-differentiated adenocarcinomas and a single focus of atypical adenomatous hyperplasia. A constitutional mutation of the p53 gene had been identified, both in this patient and other members of her family. CONCLUSION: Multiple synchronous primary lung tumours have not been reported before in association with this syndrome. With both smoking and Li-Fraumeni syndrome known to be associated with mutations in the p53 gene, a cumulative effect is suggested in this patient.

Adenocarcinoma

A new staging proposal for pulmonary metastases. The results of analysis of 5206 cases of resected pulmonary metastases.

In 1991, the International Registry of Lung Metastases was formed by 18 thoracic surgery departments in Europe and North America. Statistical analysis of combined data from the Registry revealed significant variables in patient selection, which helped to guide treatment modalities for specific patients. A simple system of stage classification is presented in this article as a basis for discussions on future results and for clinical trial design.

Actuarial Analysis

Absence of Fhit protein in primary lung tumors and cell lines with FHIT gene abnormalities.

Genomic alterations and abnormal expression of the FHIT gene at 3p14.2 have been observed in cell lines and primary tumors of the lung. To correlate FHIT locus DNA and RNA lesions with effects on Fhit protein expression, we have analyzed 11 lung cancer cell lines, 15 small cell lung carcinomas, and 38 pairs of non-small cell primary tumors and bronchial mucosa specimens by molecular genetic and immunocytochemical methods. Using specific antibodies against the Fhit protein, we observed concordance between RNA abnormalities and lack of Fhit protein expression in lung tumors and cell lines. In addition, absence of Fhit protein in some precancerous dysplastic lesions suggested that FHIT inactivation may occur at an early phase of lung carcinogenesis.

Acid Anhydride Hydrolases

Association between cigarette smoking and FHIT gene alterations in lung cancer.

Epidemiologic data have strongly indicated that cigarette smoking is linked to the development of lung cancer. However, little is known of the molecular targets of carcinogens contained in tobacco smoke. To identify genetic lesions characteristic of tobacco damage, we undertook a molecular analysis of microsatellite alterations within the FHIT gene and FRA3B, as well as at an independent locus on chromosome 10, D10S197, in lung tumors from heavy smokers and in tumors from never smokers. Loss of heterozygosity affecting at least one locus of the FHIT gene was observed in 41 of 51 tumors in the smokers group (80%) but in only 9 of 40 tumors in nonsmokers (22%). The comparison between the frequency of losses in FHIT in smokers and nonsmokers was statistically significant (P = 0.0001), whereas no difference in loss of heterozygosity rate was observed at D10S197 locus. These findings suggest that FHIT is a candidate molecular target of carcinogens contained in tobacco smoke.

Acid Anhydride Hydrolases

Suppression of retinoic acid receptor beta in non-small-cell lung cancer in vivo: implications for lung cancer development.

BACKGROUND: Retinoids, analogues of vitamin A, are required for the normal growth and differentiation of human bronchial epithelium. They are also able to reverse premalignant lesions and prevent second primary tumors in some patients with non-small-cell lung cancer (NSCLC). These effects are thought to result from modulation of cell growth, differentiation, or apoptosis (programmed cell death). When certain retinoid receptors in the cell nucleus (i.e., retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which mediate most retinoid actions, are suppressed, abnormal activity may result that could enhance cancer development. PURPOSE: This study was designed to determine whether there are abnormalities in the expression of retinoid receptors in surgical specimens from patients with NSCLC. METHODS: Transcripts of nuclear retinoid receptors were detected in formalin-fixed, paraffin-embedded specimens by use of digoxigenin-labeled riboprobes specific for RAR alpha, RAR beta, RAR gamma, RXR alpha, RXR beta, and RXR gamma for in situ hybridization to histologic specimens from 79 patients with NSCLC and as control from 17 patients with non-lung cancer. The quality and specificity of the digoxigenin-labeled probes were determined by northern blotting, and the specificity of the binding of antisense riboprobes was verified by use of sense probes as controls. RESULTS: All receptors were expressed in at least 89% of control normal bronchial tissue specimens from 17 patients without a primary lung cancer and in distant normal bronchus specimens from patients with NSCLC. RAR alpha, RXR alpha, and RXR gamma were expressed in more than 95% of the NSCLC specimens. In contrast, RAR beta, RAR gamma, and RXR beta expression was detected in only 42%, 72%, and 76% of NSCLC, respectively. CONCLUSIONS: These data suggest that the expression of RAR alpha, RXR alpha, and RXR gamma is not altered in NSCLC; however, expression of RAR beta and possibly also of RAR gamma and RXR beta is suppressed in a large percentage of patients with lung cancer. IMPLICATIONS: The loss of expression of one or more of these nuclear retinoid receptors may be associated with lung carcinogenesis.

Adenocarcinoma

Full thickness eosinophilia in oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis. A common allergic inflammatory profile?

Oesophageal leiomyomatosis and idiopathic eosinophilic oesophagitis are both extremely rare. The former is a diffuse proliferation of smooth muscle in the muscularis propria, whilst the latter is an idiopathic inflammatory condition, thought to be associated with background atopy and characterized by an infiltrate of eosinophils throughout the full thickness of the oesophagus. However, two recent cases of oesophageal leiomyomatosis showed similar full thickness infiltration of the oesophageal wall by eosinophils and this inflammatory cell infiltrate was investigated in conjunction with one case of idiopathic eosinophilic oesophagitis. All three had a similar allergic profile characterized by CD45RO-positive primed T-lymphocytes, EG2-positive (i.e., activated) eosinophils, and tryptasepositive mast cells, together with gene expression for interleukin 4. Previous descriptions of leiomyomatosis describe an association with systemic mastocytosis and urticaria and the possibility that there is a common underlying allergic component to both disorders is raised.

Adult

Sternal resection for primary or secondary tumors.

METHODS: From January 1980 to December 1993, 52 patients underwent surgical-resection for tumors involving the sternum. The series included 20 primary malignant tumors, 4 desmoid tumors, 2 malignant tumors infiltrating the sternum from adjacent organs, 19 local recurrences or metastases of breast tumors, and 7 metastases of other tumors. Total sternectomy was performed in 5 patients, subtotal sternal resection in 19, and partial resection (less than 50% of the sternum) in 28. Concurrent en bloc resection included anterior ribs in 37 patients, clavicle in 11, lung in 12 patients, pericardium in 7, and diaphragm in 2. The chest was reconstructed with prosthetic material and a myocutaneous flap in 26 patients (50%), prosthetic material only in 12 patients (23%), a myocutaneous flap in 5 patients (10%), and other techniques in the remaining patients. In 47 patients (90%) the resection was radical, and in the remaining 5 patients it was palliative. RESULTS: No perioperative deaths occurred. After a median follow-up of 39 months, the overall 3-year survival was 58% and the 5-year survival 46%, with a median survival of 50 months. In 24 patients with primary tumor the 5-year survival after radical resection was 63%, and in 23 patients with secondary invasion (direct extension or metastasis) the 5-year survival was 38% (median 35 months). In recurrent breast cancer the 5-year survival was 48% in patients with direct extension to the chest wall and 60% in patients with distant bone metastasis. CONCLUSIONS: Our experience demonstrates that sternal resection is a safe and effective treatment, which may improve the patient's quality of life and achieve a long-term survival not only in primary tumors but also in selected secondary malignant tumors of the sternum.

Actuarial Analysis

Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases.

OBJECTIVES: The International Registry of Lung Metastases was established in 1991 to assess the long-term results of pulmonary metastasectomy. METHODS: The Registry has accrued 5206 cases of lung metastasectomy, from 18 departments of thoracic surgery in Europe (n = 13), the United States (n = 4) and Canada (n = 1). Of these patients, 4572 (88%) underwent complete surgical resection. The primary tumor was epithelial in 2260 cases, sarcoma in 2173, germ cell in 363, and melanoma in 328. The disease-free interval was 0 to 11 months in 2199 cases, 12 to 35 months in 1857, and more than 36 months in 1620. Single metastases accounted for 2383 cases and multiple lesions for 2726. Mean follow-up was 46 months. Analysis was performed by Kaplan-Meier estimates of survival, relative risks of death, and multivariate Cox model. RESULTS: The actuarial survival after complete metastasectomy was 36% at 5 years, 26% at 10 years, and 22% at 15 years (median 35 months); the corresponding values for incomplete resection were 13% at 5 years and 7% at 10 years (median 15 months). Among complete resections, the 5-year survival was 33% for patients with a disease-free interval of 0 to 11 months and 45% for those with a disease-free interval of more than 36 months; 43% for single lesions and 27% for four or more lesions. Multivariate analysis showed a better prognosis for patients with germ cell tumors, disease-free intervals of 36 months or more, and single metastases. CONCLUSIONS: These results confirm that lung metastasectomy is a safe and potentially curative procedure. Resectability, disease-free interval, and number of metastases enabled us to design a simple system of classification valid for different tumor types.

Adolescent