Maurizio Mezzetti

Assessment of outcomes in typical and atypical carcinoids according to latest WHO classification

BACKGROUND Pulmonary carcinoid tumors represent a group of malignant neoplasms comprised of neuroendocrine cells. In 1999, the World Health Organization (W.H.O.) proposed the definitive classification of neuroendocrine tumors based on the criteria from Travis and associates. The W.H.O. described two different groups of carcinoid tumors: typical carcinoids (TC) and atypical carcinoids (AC). Few reports have reviewed their data according to the current classification, and therefore, prognosis and standard therapy for TC and AC are still uncertain. METHODS From 1980 to 2001, 98 pulmonary resections have been performed for primary bronchial carcinoid tumors in our Thoracic Department of the University of Milan. We reviewed original histology using the current W.H.O. criteria and identified 88 patients with TC and 10 with AC. We reviewed the outcomes in each group. RESULTS The 5 year-overall survival rate was 91.9% for TC and 71% for AC. The 10-year overall survival rate was 89.7% for TC and 60% for AC. The 5-year TNM-related survival rates in the TC group were: IA-B, 100%; IIA-B, 75%; and IIIA, 50%. At 10 years, they were: IA-B, 100%; IIA-B, 75%; and IIIA, 0%. The 5-year survival rates in the AC group were: IA-B, 100%; IIA-B, 100%; and IIIA, 0%. At 10 years, they were: IA-B, 100%; IIA-B, 66%; and IIIA, 0%. CONCLUSIONS Prognosis is favorable for both subtypes in the early stage. Advanced stages are related to better prognosis in TC. Recurrences rate is worse in the AC subtype. Our data suggest avoiding limited resections when feasible in AC. Parenchyma-sparing resections should be encouraged in TC.

Intraoperative ultrasound during thoracoscopic procedures for solitary pulmonary nodules

BACKGROUND Traditional nonoperative diagnostic approaches to the solitary pulmonary nodule (bronchoscopy and percutaneous needle biopsy) can be inconclusive. Video-assisted thoracic surgery (VATS) provides a minimally invasive way to diagnose and treat these nodules. We evaluated the use of a dedicated intraoperative ultrasound probe as an aid in localization of small pulmonary nodules during VATS. METHODS An intraoperative ultrasound examination during a thoracoscopic procedure was performed on 18 patients to localize deep pulmonary nodules less than 20 mm in diameter without a definitive diagnosis by preoperative imaging techniques. RESULTS In the 18 patients, all nodules were successfully identified by intraoperative ultrasound. A definitive pathologic diagnosis was obtained from thoracoscopic biopsy or resection. The final diagnoses were primary lung cancer in 5 patients, metastatic lesions in 4 patients, hamartoma or chondroma in 4, granuloma in 3, and interstitial fibrosis in 2 patients. CONCLUSIONS In our experience, intraoperative ultrasound can safely and effectively localize invisible or nonpalpable pulmonary nodules at the time of thoracoscopy. This may help surgeons perform minimally invasive lung resections with clear surgical margins.

Atrial fibrillation after operation for lung cancer: clinical and prognostic significance

BACKGROUND Atrial fibrillation is a common complication of early postoperative period in lung cancer thoracotomy. Its clinical incidence and short- and long-term impact on overall mortality has never been definitely assessed; moreover, it is unclear whether the arrhythmia represents an independent cardiac risk factor. METHODS We prospectively studied 233 consecutive patients undergoing operation for lung cancer (170 with non-small-cell lung cancer). Postoperative atrial fibrillation incidence was related to different clinical factors possibly involved in its occurrence and to both short- and long-term survival. RESULTS Atrial fibrillation occurred in 28 patients (12%) (same percentage in non-small-cell lung cancer); a strong relationship was observed between arrhythmia and age, history of hypertension and associated lymph node resection. The mean hospitalization time was 14 +/- 4 days in patients developing atrial fibrillation and 13 +/- 4 days in those who did not (p = not significant). No difference was observed between the two groups with regard to short- or long-term mortality or to long-term atrial fibrillation recurrences, also when considering the entire population and only non-small-cell lung cancer, separately. CONCLUSIONS At our institution, early atrial fibrillation occurrence after operation for lung cancer does not show any negative impact on short- and long-term mortality or on recurrence rate.

Human bronchial epithelial cells modulate CD3 and mitogen-induced DNA synthesis in T cells but function poorly as antigen-presenting cells compared to pulmonary macrophages

This study was undertaken to investigate the ability of bronchial epithelial cells (ECs) to function as accessory cells. Pulmonary monocytes were our reference cells. ECs and pulmonary monocytes were isolated from the bronchial mucosa and pulmonary parenchyma of subjects undergoing lobectomy for standard clinical reasons. Circulating autologous T cells were rigorously depleted of accessory cells to the extent that they lost the capacity to respond to mitogenic lectins alone. ECs restored mitogen-induced DNA synthesis and DNA synthesis triggered by CD3 cross-linking in T cells, as did pulmonary macrophages, and this was unrelated to HLA-DR expression. The ability of promoting T cell proliferation after CD3 cross-linking was, in part, due to the secretory products of ECs, since their supernatants were also effective. Interferon-gamma-treated ECs were capable of presenting antigens to autologous T cells. This was an HLA-DR-restricted phenomenon, but EC efficiency in this system was less than 40% of efficiency demonstrated by pulmonary monocytes. However, ECs greatly upregulated antigen-specific responses supported by pulmonary monocytes.

Personal experience in lung cancer sleeve lobectomy and sleeve pneumonectomy.

BACKGROUND Sleeve lobectomy (SL) and tracheal sleeve pneumonectomy (TSP) represent valuable alternative techniques to standard resections in the treatment of benign and malignant conditions of the airway and allow preservation of lung parenchyma. METHODS Eighty-three sleeve lobectomies and 27 tracheal sleeve pneumonectomies have been performed for nonsmall cell lung cancer in the thoracic department of the University of Milan from 1979 to 1999. There were 46 upper right lobectomies, 11 upper and middle lobectomies, 18 upper left lobectomies, 8 lower left lobectomies, and 27 right pneumonectomies. RESULTS Mortality rate was 3.6% in SL and 7.4% in TSP. Complications were 10.8% of all SLs and 15% of all TSPs. The overall 5-year survival rate was 43% for SL and 20% for TSP; the 10-year survival rate was 34% and 14%, respectively. There was a highly significant difference in survival between patients with N0 and N1-N2 disease. CONCLUSIONS Sleeve lobectomy is an appropriate surgical procedure and an alternative to pneumonectomy in patients with limited respiratory reserve whenever the situation permits. Trachael sleeve pneumonectomy is associated with more complications and poor survival.

Nedocromil Sodium Prevents the Release of 15-Hydroxyeicosatetraenoic Acid from Human Bronchial Epithelial Cells Exposed to Toluene Diisocyanate in vitro

The in vivo exposure to an asthmogenic stimulus, toluene diisocyanate (TDI), causes airway epithelial damage associated with inflammation and increased bronchial hyperresponsiveness. The latter mechanisms might partly be mediated by the release of eicosanoids from bronchial epithelial cells. We have previously demonstrated that the in vitro exposure of bronchial epithelial cells to TDI results in the release of immunoreactive 15-hydroxyeicosatetraenoic acid (15-HETE), a product of activation of the 15-lipoxygenase pathway with inflammatory properties. In the present study we show that TDI-induced release of 15-HETE from epithelial cells can be prevented by nedocromil sodium, an anti-asthmatic drug with anti-inflammatory properties. This mode of action of the compound may explain its clinical effectiveness in asthma.

Heterogeneity of binding sites for ICI 198,615 in human lung parenchyma

We have identified and characterized two different subclasses of binding site for the novel peptido-leukotriene (LT) antagonist, [3H]ICI 198,615, in membranes from human lung parenchyma using a receptor-ligand assay. This novel compound is representative of a new class of LT receptor antagonists and it has been demonstrated to be several orders of magnitude more potent and selective than most other LT antagonists described to date. The binding of [3H]ICI 198,615 is rapid, specific and saturable. Equilibrium was reached within 5-10 min. Non linear fitting of dissociation time courses has revealed the presence of two different components (K(off)1 = 8.3 +/- 6.8 x 10(-4) sec-1 and K(off)2 = 0.79 +/- 1.66 x 10(-3) sec-1) of the kinetic curves, suggesting heterogeneity of the binding sites. Computer analysis of equilibrium binding data obtained at 25 degrees results in a model with two classes of binding sites, a high affinity-low capacity class with Kd1 = 0.024 +/- 0.014 nM and Bmax1 = 0.015 +/- 0.004 pmol/mg protein and a low affinity-high capacity class with Kd2 = 6326 +/- 3859 nM and Bmax2 = 473 +/- 383 pmol/mg protein. In competition studies, LTD4 was also found to interact with two classes of binding site (Kd1 = 0.016 +/- 0.008 nM and Kd2 = 15195 +/- 8965 nM). On the contrary, LTE4 and LTC4 were found to interact with a homogeneous class of sites only with Kd = 7466 +/- 4629 nM and Kd = 428 +/- 73 nM, respectively. Furthermore, we have evaluated the effect of a number of LT antagonists on the binding of [3H]ICI 198,615. Ro 24-5913 (Kd = 3.0 +/- 2.1 nM), FPL55712 (Kd = 4945 +/- 2868 nM), LY171883 (Kd = 19628 +/- 12365 nM), SKF 104353 (Kd = 74.2 +/- 46 nM) and its enantiomer SKF 104373 (Kd = 13627 +/- 6813 nM) were found to interact with a single class of binding sites. The present studies indicate a heterogeneity of binding sites for ICI 198,615 in membranes from human lung parenchyma and that ICI 198,615 is a very potent and selective antagonist of LTD4 receptors in this tissue.

Surgical experience of 15 solitary benign fibrous tumor of the pleura

OBJECTIVE The localized benign fibrous tumor of the pleura represents 8% of all benign pathologies of the chest and 10% of neoplasms of the pleura. The authors review the literature, and report on 15 cases of localized benign fibrous tumors of the pleura surgically treated over a period of 15 years to further knowledge of this pathology, its therapy and prognosis. METHODS With respect to the well-known diffuse malignant mesothelioma, different etiopathogenesis, prognosis, and therapeutic approaches characterize the localized benign fibrous tumor of the pleura. In our experience, 15 patients underwent thoracotomy with excision of a pathological endothoracic mass, then histologically proved to be a localized benign tumor of the pleura. The whole group underwent pre-operative evaluation and, when clinic suggested, stadiation and post-operative frequent follow-up. RESULTS The whole group of 15 patients underwent surgical approach well tolerated the surgical treatment with perfect recovery of post-operative respiratory function. There was no relapse of disease in any patients. At the moment all patients are still alive except one dead of heart failure. CONCLUSION The differential diagnosis of benign fibrous tumor of the pleura and lung and pleural malignancy depends upon immunohistochemistry of the surgical specimen so that prognosis could be formulated only after surgery. We consider surgery as the treatment of choice in this pathology.

Eicosanoid release and mepyramine, LTC4 and LTD4 binding in passively sensitized human lung parenchyma in vitro

In vitro passive sensitization of human lung parenchyma with hyper-immune serum did not affect the release of prostaglandin D2 (PGD2) or leukotriene (LT)-like activity upon challenge with anti-IgE antibody with respect to control lung, despite a marked difference in IgE levels between control (C) and sensitized (S) tissue. Binding studies with [3H]LTC4, [3H]LTD4 and [3H]mepyramine (a histamine H1 antagonist) showed a statistically significant increase in the amount bound in sensitized vs control lung for [3H]mepyramine only. Contractile response to 5 x 10(-5) M histamine (H) in C and S lung parenchymal strips did not correlate with binding data. It is concluded that in vitro elevated IgE levels do not affect the interaction of sulfidopeptide leukotrienes with their putative receptors. As for the observed increase in [3H]mepyramine binding, this might not represent a true increase in histamine receptors on lung smooth muscle cells.

Elevaciones de la troponina I cardiaca tras la cirugía torácica. Incidencia y correlaciones con las características clínicas basales, la proteína C reactiva y los parámetros perioperatorios

Resumen Introduccion y objetivos La incidencia real de las elevaciones de la troponina I cardiaca tras la cirugia toracica y su correlacion con otros parametros clinicos no esta plenamente definida. El objetivo de este estudio fue evaluar la frecuencia de las elevaciones postoperatorias de la troponina I cardiaca despues de cirugia pulmonar o pleural por sospecha de cancer e investigar las correlaciones con los perfiles clinicos basales, con la proteina C reactiva y los parametros perioperatorios. Metodos Se registro a 50 pacientes consecutivos y se midieron los siguientes parametros en cada paciente: variables clinicas basales y concentracion de la proteina C reactiva, concentracion de troponina I cardiaca en los dias 1, 3 y 5 del postoperatorio, electrocardiograma, presion arterial, y frecuencia cardiaca diarias desde el dia de la operacion hasta el dia 5 del postoperatorio. Resultados Se produjeron elevaciones postoperatorias de la troponina I cardiaca en el 20% de los pacientes y estas estaban significativamente asociadas con los antecedentes de coronariopatia o mas de 2 factores de riesgo coronario (el 80 frente al 32,5%; p = 0,011), los antecedentes de tratamiento antiagregante plaquetario cronico (el 50 frente al 17,5%; p = 0,046), la neumonectomia comparada con los procedimientos menos invasivos (el 40 frente al 10%; p = 0,041), la pericardiotomia (el 30 frente al 2,5%; p = 0,022) y las modificaciones transitorias del segmento ST en el electrocardiograma perioperatorio (el 60 frente al 20%; p = 0,02). No se observo correlacion significativa entre las elevaciones de la troponina I cardiaca y la proteina C reactiva basal. Conclusiones Las elevaciones de la troponina I cardiaca despues de la cirugia toracica son frecuentes y estan asociadas con marcadores clinicos de coronariopatia, procedimientos quirurgicos extensos y cambios isquemicos en el electrocardiograma perioperatorio.