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Biomedical subjects

F Rea

Publications and source records attributed to F Rea.

At least 19 recordsLinked to original sources

Transforming growth factor-beta type II receptor in pulmonary arteries of patients with very severe COPD.

A mild-to-moderate increase in pulmonary arterial pressure is often associated with severe chronic obstructive pulmonary disease (COPD). Transforming growth factor (TGF)-beta is a cytokine involved in the maintenance of integrity of vasculature. The aim of the study was to investigate whether the TGF-beta pathway might be involved in the development of pulmonary hypertension associated with COPD. Surgical specimens from 14 patients undergoing lung transplantation for very severe COPD (forced expiratory volume in one second 17 +/- 2% of the predicted value) and from seven donors were examined. The expression of TGF-beta1 and TGF-beta type II receptor (TGF-betaRII), cell proliferation index and structural changes in pulmonary arteries were quantified immunohistochemically. In severe COPD patients, increased expression of TGF-betaRII was observed in both the tunica media and intima, which was associated with a normal proliferation index in both layers. Conversely, significant thickening of the tunica intima, which was not present in the tunica media, was observed, suggesting that mechanisms other than cell proliferation may be involved in intimal thickening. In conclusion, in the pulmonary arteries of patients with severe chronic obstructive pulmonary disease, there is upregulation of transforming growth factor-beta type II receptor expression associated with a normal proliferation index. These findings suggest the activation of an antiproliferative pathway, which might explain the relatively low degree of pulmonary hypertension observed in these subjects.

Female↗

Long-term results of surgical management of pulmonary metastases from renal cell carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (RCC) has a poor prognosis and conventional treatments such as chemoradiotherapy show little efficacy. Surgical resection of pulmonary metastases from RCC is a widely accepted treatment, even if selection criteria based on prognostic factors have still not been defined. The aim of this study was to determine the long-term survival, clinical outcome and prognostic factors after surgery. METHODS: Between 1988 and 2004, 59 patients underwent resection of pulmonary metastases from RCC. Univariate and multivariate analysis of prognostic factors was carried out. RESULTS: Complete resection was achieved in 54 (91.5 %) patients. No intra- or postoperative mortality occurred, 5 (8.5 %) patients experienced postoperative complications. Overall, the 1-, 3-, and 5-year survival rates were 86.5 %, 63 % and 53 %, respectively. Age at the time of pulmonary resection was found to be the only independent factor influencing prognosis. CONCLUSION: Pulmonary resection of metastases from RCC is a safe and effective treatment associated with a low morbidity and mortality and with high long-term survival. The lack of other effective therapies suggests use of the surgical approach whenever possible.

Adult↗

Surgical outcome of combined pulmonary and atrial resection for lung cancer.

OBJECTIVES: The study was carried out to assess the short and long-term outcome of patients with non-small cell lung cancer infiltrating the left atrium treated by surgery. METHODS: We retrospectively collected the hospital files of twenty-three consecutive patients operated on between 1982 and 2001 in two units of Thoracic Surgery. Four patients received an induction regimen. Fourteen right pneumonectomies, 8 left pneumonectomies and 1 right inferior lobectomy were performed. No cardiopulmonary bypass was employed. RESULTS: In all patients the diagnosis of T4 atrial invasion was confirmed by pathological examination. A complete resection was achieved in nineteen patients (83%). With respect to nodal staging, there were 13 N0, 5 N1 and 4 N2 cases, respectively. Two deaths occurred during the one month postoperative period (9%). Three patients had postoperative atrial fibrillation. Two other patients had postpneumonectomy empyema without bronchopleural fistula and recovered, one after thoracoscopic debridement and the second after open window thoracostomy. Follow-up was completed on September 2002; only one patient was lost to follow-up. Median survival, excluding the perioperative mortality, was 20 months (range 4 - 62 months). The survival rate, calculated with the Kaplan-Meier method, was estimated as 63% at 1 year, 2 % at 3 years and 10% at 5 years. Using a Cox model analysis, lymph node stage and completeness of resection were not independent prognostic factors. CONCLUSIONS: In cases of NSCLC with left atrial invasion complete resection is technically feasible in most instances without cardiopulmonary bypass. The acceptable operative risk and the encouraging long-term survival observed in this series suggest that NSCLC invading the left atrium should not be systematically considered as a definitive contraindication to surgery.

Adult↗

Mediastinitis due to cryptococcal infection: a new clinical entity in the HAART era.

OBJECTIVES: Highly active antiretroviral therapy (HAART) produces a rapid decline in plasma HIV-1 RNA levels with concomitant immune reconstitution. Probably due to the enhanced immune function, shortly after starting HAART, some latent opportunistic infections precipitated. The aim of this study was to illustrate the results of a survey on Cryptococcus associated mediastinitis occurring after HAART introduction, carried out at a referral centre of Infectious Diseases in the north-east of Italy, between October 1999 and October 2000. METHODS: All consecutive HIV-positive patients, naive to HIV-protease inhibitor therapy, and diagnosed with culture-proven cryptococcal infection were included in the study. Clinical and immuno-virological parameters before HAART and subsequently for 12 months were evaluated. RESULTS: Three of five patients were diagnosed with cryptococcal mediastinitis within a median time of 90 days (range, 60-150) after commencing HAART and fluconazole prophylaxis. Diagnosis was established by lymph node biopsy alone. Clinical improvement was documented when systemic anti-fungal therapy was combined with surgical drainage of the suppurative lesions. The role of immune restoration was confirmed by the significant increase in CD4 cell count, the reduction of HIV-RNA to undetectable levels and the prominent inflammatory reactions of lymph nodes. CONCLUSIONS: Our report suggests that HIV-positive patients with prior cryptococcal systemic infection may present a re-exacerbation of atypical cryptococcosis as a manifestation of immune restoration, even when fluconazole prophylaxis is ongoing.

AIDS-Related Opportunistic Infections↗

Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers.

BACKGROUND: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. METHODS: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. RESULTS: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9-5.8) and 1.4 (1.07-3.4) respectively); glands (33.3 (18.2-43.8) and 16.2 (11.5-22.2), respectively); and bronchial vessels (54.2 (48.7-56.8) and 40.0 (36-40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p<0.005) only for bronchial vessels. CONCLUSIONS: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.

Aged↗

Cxcr3 and its ligand CXCL10 are expressed by inflammatory cells infiltrating lung allografts and mediate chemotaxis of T cells at sites of rejection.

The attraction of T lymphocytes into the pulmonary parenchyma represents an essential step in mechanisms ultimately leading to lung allograft rejection. In this study we evaluated whether IP-10 (CXCL10), a chemokine that is induced by interferon-gamma and stimulates the directional migration of activated T cells, plays a role in regulating the trafficking of effector T cells during lung allograft rejection episodes. Immunohistochemical examination showed that areas characterized by acute cellular rejection (grades 1 to 4) and active obliterative bronchiolitis (chronic rejection, Ca) were infiltrated by T cells expressing CXCR3, i.e., the specific receptor for CXCL10. In parallel, T cells accumulating in the bronchoalveolar lavage of lung transplant recipients with rejection episodes were CXCR3+ and exhibited a strong in vitro migratory capability in response to CXCL10. In lung biopsies, CXCL10 was abundantly expressed by graft-infiltrating macrophages and occasionally by epithelial cells. Alveolar macrophages expressed and secreted definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3+ T-cell line 300-19; the secretory capability of alveolar macrophages was up-regulated by preincubation with interferon-gamma. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the bronchoalveolar lavage in individuals with rejection episodes. These data indicate the role of the CXCR3/CXCL10 interactions in the recruitment of lymphocytes at sites of lung rejection and provide a rationale for the use of agents that block the CXCR3/CXCL10 axis in the treatment of lung allograft rejection.

Bronchiolitis Obliterans↗

Surgical results for multiple primary lung cancers.

OBJECTIVE: The development of a multiple primary lung cancer (MPLC) is not rare in long-term survivors after curative resections. We analysed our experience in order to verify surgical results and long-term survival in our patients. METHODS: From 1971 to 1999, 80 patients with MPLC (two tumours each, total 160) were treated at the Division of Thoracic Surgery of the University of Padua. Our criteria for the definition of a synchronous or metachronous cancer are those proposed by Martini and Melamed. We had 19 patients with a synchronous tumour and 61 patients with a metachronous tumour. We performed 95 lobectomies, 5 completion pneumonectomies and 53 segmentectomies. Of 160 MPLCs, 60 were squamous carcinomas, 78 adenocarcinomas, 8 small cell lung cancers, 9 large cell lung cancers and 5 other tumours. Of 160 MPLCs, 140 were N0 disease (87.5%) and 20 were N1 or N2 disease (12.5%). RESULTS: The overall 30-day mortality was 2.5% (2 patients). Eighteen patients (22.5%) had postoperative complications. Survival at 5 and 10 years for all patients was 72% and 58%, respectively. Five-year survival for patients with metachronous and synchronous disease from the time of initial diagnosis of cancer was 85% and 20% (P=0.001), and 10-year survival was 58% and 0% (P=0.001), respectively. Survival after the development of a metachronous lesion was 51% at 5 years and 20% at 10 years. The 5-year survival of patients with metachronous tumours undergoing standard surgical procedures of the second tumour was 52%; the 5-year survival of patients undergoing atypical or segmental resections was 55%. CONCLUSIONS: Careful follow-up is recommended in all patients surviving curative resection. More accurate selection criteria for MPLC is required. An aggressive surgical approach is justified in patients with MPLC and offers the greatest chance for long-term survival even in the case of limited resection.

Adult↗

Follicular dendritic cell tumor of the mediastinum.

Follicular dendritic cell tumor (FDT) is a rare neoplasm usually occurring in the laterocervical lymph nodes, but presentations elsewhere are also well documented. We report a case of FDT in a 48-year-old man with myasthenia gravis, in whom a slow-growing mediastinal mass that had been surgically excised manifested after 3 years with a local recurrence in the same site. The lesion was aspirated and cytology showed a tumor composed of groups of oval or elongated cells intermingled with several mature small lymphocytes. On histology, the tumor was highly cellular with abundant perivascular lymphocytic infiltration; large cells with pale, eosinophilic cytoplasm and round nuclei, arranged in fascicles often showed a storiform pattern. Occasional binucleated cells were also present. A panel of antibodies showed positivity only for CD21 and CD35, and a weak response to S-100. Electron microscopy showed that the layer cells had convoluted nuclei and elongated interdigitating processes with desmosome-like junctions. The definitive diagnosis of FDT can be concluded only with positive immunostaining for CD21 and CD35. However, in the presence of a mixed population of lymphocytes and larger eosinophilic cells the hypothesis of FDT should always be considered.

Biomarkers, Tumor↗

An unusual presentation of invasive aspergillosis after lung transplantation.

Aspergillus infections in lung transplant patients are frequently reported with a large pattern of manifestations varying from simple colonization of the lungs to complicated infections. Pulmonary invasive aspergillosis and disseminated aspergillosis often result in death. The majority of cases occur during the first months after transplantation with pulmonary involvement and have been described as the first clinical localization of the disease. Here we present the first reported case of an endophthalmitis caused by Aspergillus fumigatus developing 18 months after lung transplantation, and presenting as a manifestation of invasive aspergillosis.

Aspergillosis↗

The role of surgery in integrated therapies for non-small-cell lung cancer.

Surgery represents the best treatment for early-stage non-small-cell lung cancer (NSCLC). In selected cases, even locally-advanced cancers may be suitable for surgical treatment. The combination of chemotherapy (with or without radiotherapy) and surgery has proved potentially useful in improving survival, but pre-operative treatment may represent a risk factor for the onset of post-operative complications. Studies performed to date indicate the need for further multidisciplinary research with a view to identifying more advantageous treatment modalities, particularly for locally-advanced NSCLC.

Carcinoma, Non-Small-Cell Lung↗

CD8+ve cells in the lungs of smokers with chronic obstructive pulmonary disease.

Previous studies have shown an increased number of inflammatory cells and, in particular, CD8+ve cells in the airways of smokers with chronic obstructive pulmonary disease (COPD). In this study we investigated whether a similar inflammatory process is also present in the lungs, and particularly in lung parenchyma and pulmonary arteries. We examined surgical specimens from three groups of subjects undergoing lung resection for localized pulmonary lesions: nonsmokers (n = 8), asymptomatic smokers with normal lung function (n = 6), and smokers with COPD (n = 10). Alveolar walls and pulmonary arteries were examined with immunohistochemical methods to identify neutrophils, eosinophils, mast cells, macrophages, and CD4+ve and CD8+ve cells. Smokers with COPD had an increased number of CD8+ve cells in both lung parenchyma (p < 0.05) and pulmonary arteries (p < 0.001) as compared with nonsmokers. CD8+ve cells were also increased in pulmonary arteries of smokers with COPD as compared with smokers with normal lung function (p < 0.01). Other inflammatory cells were no different among the three groups. The number of CD8+ve cells in both lung parenchyma and pulmonary arteries was significantly correlated with the degree of airflow limitation in smokers. These results show that an inflammatory process similar to that present in the conducting airways is also present in lung parenchyma and pulmonary arteries of smokers with COPD.

Airway Resistance↗

Long term results of surgery and chemotherapy in small cell lung cancer.

OBJECTIVE: The aim of the study is to analyse long-term results of patients with small cell lung cancer (SCLC) treated at the same institution according to a prospective study including surgery, chemotherapy, and radiotherapy. METHODS: From 1981 to 1995, 104 patients with a proven histology of SCLC underwent surgery, chemotherapy, and radiotherapy. Fifty-one patients with operable stage I or II lesion received surgical resection followed by adjuvant chemotherapy and radiotherapy. Fifty-three patients with proved SCLC and clinical stage III received induction chemotherapy followed by surgery and radiotherapy. All patients received from four to six courses of chemotherapy and 36 had prophylactic cranial irradiation (PCI). All patients had follow-up for at least 1 year, and survival time was calculated from the date of the diagnosis until death or most recent follow-up. RESULTS: Ninety-six patients were male and eight female. We performed 29 pneumonectomies, eight bilobectomies, 66 lobectomies and one no resection. Regarding the clinical stage, 35 patients (33.6%) had stage I, 16 patients (15.4%) had stage II and 53 (51%) had stage III. Post-operative pathologic staging revealed stage I in 37 patients (35.6%), stage II in nine patients (8.6%), stage III in 45 patients (43.3%), and in 13 patients (12.5%) there was no more tumor. The 30-day mortality was 2% (two patients). Fourteen patients (13.4%) had post-operative complications. Fifty-one patients (49%) had a relapse. The median follow-up was 55 months. Twenty-six patients remain alive and 78 patients have died. The overall 5-year survival rate was 32%, with an estimate median survival time of 28 months; according to the pathologic stage, the survival data were 52.2%, 30% and 15.3% for stage I, II and III, respectively (P < 0.001). The 5-year survival was 41% in patients without SCLC after chemotherapy. CONCLUSION: As with non-small cell lung cancer, survival following surgery and chemotherapy clearly correlates with the stage. At present, it is not clear whether surgery is truly effective for patients with SCLC. In our experience, the complete elimination of small cell lung cancer is associated with an improvement in survival (41% at 5 years).

Adult↗

Ultrarapid high-dose course of prophylactic cranial irradiation in small-cell lung cancer: evaluation of late neurologic morbidity in 16 long-term survivors.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Adult↗

Morbidity, mortality, and survival after bronchoplastic procedures for lung cancer.

OBJECTIVE: Bronchoplastic procedures represent an effective surgical therapy for benign lesions, tumors of low-grade malignancy and also bronchogenic carcinoma in patients with a limited pulmonary function. We analyzed our experience in order to verify the mortality, morbidity, and long term survival in our patients. METHODS: From 1980 to 1994, 217 patients underwent bronchoplastic procedures. We performed 92 bronchoplasties, 94 bronchial sleeves, and 31 tracheo-bronchial sleeves. Histologic examination revealed 133 epidermoid carcinomas, 28 adenocarcinomas, 11 small cells lung cancers, 5 large cells carcinomas, 2 adenosquamous carcinomas, 29 bronchial carcinoids, 6 adenoidocistic carcinomas, and 3 mucoepidermoid tumors. Regarding nodal status, 99 patients had N0 disease, 64 patients had N1 disease, and 54 patients had N2 disease. Thirty-six patients had preoperative irradiation and 181 patients had no preoperative irradiation. In 63 patients we used a perianastomotic pedicled flap; in 154 we did not use it. We considered all the 217 patients for the analysis of 30-day mortality and morbidity; of the 217 patients we analyzed long-term survival only in 179 because we excluded 38 patients with low grade malignant neoplasm. RESULTS: Twenty-seven patients (12.5%) had postoperative complications. The 30-day mortality was 6.2% (14 patients). Survival at 5 and 10 years for all patients but those with low grade malignant neoplasm was 49 and 38%, respectively. For patients with N0 status 5- and 10-year survival was 72.4 and 59.4%; for patients with N1 status these rates were 35.7 and 26.8%; for patients with N2 status, 5- and 10-year survival was 22 and 14.4%. Postoperative complication rates for patients with or without pedicled flap are not significantly different; however, the rates for patients with or without preoperative irradiation are significantly different. CONCLUSIONS: Bronchoplastic procedures are a safe and effective therapy for selected patients with pulmonary malignancy. Tracheo-bronchial sleeves are associated with high postoperative mortality and complication rates and these procedures should be limited to patients without N2 disease. Preoperative irradiation increases significantly the mortality and morbidity. A multivariate analysis shows that only the nodal status affects long-term survival (P = 0.0002).

Adult↗