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Biomedical subjects

Lorenzo Spaggiari

Publications and source records attributed to Lorenzo Spaggiari.

At least 37 records · Page 2Linked to original sources
PubMed2005

Alteration of the E-cadherin/beta-catenin cell adhesion system is common in pulmonary neuroendocrine tumors and is an independent predictor of lymph node metastasis in atypical carcinoids.

BACKGROUND: To the authors' knowledge, little is known regarding the role of E-cadherin/beta-catenin system dysregulation in pulmonary neuroendocrine tumors. METHODS: E-cadherin and beta-catenin immunoreactivity was evaluated in 10 hyperplastic neuroendocrine tumorlets and 210 neuroendocrine tumors, including 96 typical carcinoids (CTs), 35 atypical carcinoids (ACTs), 49 large cell neuroendocrine carcinomas (LCNECs), and 30 small cell lung carcinomas (SCLCs). RESULTS: Normal and hyperplastic bronchial neuroendocrine cells expressed E-cadherin/beta-catenin with an orderly distribution along the cell membrane. Neuroendocrine tumors retained beta-catenin expression in all tumors and E-cadherin in most tumors, with the exception of 2% of LCNECs, 3% of SCLCs and 9% of ACTs. E-cadherin showed a prevalent membrane-associated, linear immunoreactivity in CTs, whereas membrane-disarrayed and cytoplasmic staining was seen in most ACTs, LCNECs, and SCLCs (P < 0.001). beta-Catenin exhibited similar immunoreactivity patterns according to tumor type and a close association with E-cadherin subcellular distribution (P < 0.001). Nuclear accumulation of beta-catenin was found only in seven LCNECs and in two SCLCs. In ACTs, disarrayed immunoreactivity for E-cadherin and/or beta-catenin was associated with a nontrabecular growth pattern, altered expression of the cell-motility marker fascin, and lymph node metastases. Furthermore, a disarrayed E-cadherin distribution pattern was associated with the pathologic lymph node classification and the number of involved lymph nodes. Multivariate analysis confirmed that a disarrayed E-cadherin or beta-catenin pattern was an independent predictor of lymph node metastases in patients with ACT. CONCLUSIONS: The subcellular compartmentalization of the E-cadherin/beta-catenin complex was altered in pulmonary neuroendocrine tumors. This likely affects the tumor growth pattern and cell motility of ACT and was correlated with the occurrence of lymph node metastases.

Adult↗
PubMed2005

Lack of prognostic implications of HER-2/neu abnormalities in 345 stage I non-small cell carcinomas (NSCLC) and 207 stage I-III neuroendocrine tumours (NET) of the lung.

HER-2/neu oncogene activation by either gene amplification and/or protein overexpression has been documented in several human malignancies. Irrespective of protein overexpression, HER-2/neu gene amplification is rare in lung cancer and studies on its prevalence and clinicopathological implications in early stage non-small cell lung cancer (NCSLC) and neuroendocrine tumours (NET) of the lung are lacking. We evaluated HER-2/neu abnormalities in 345 Stage I NSCLC and 207 Stage I-III NET of the lung of all the diverse histological types, by using immunohistochemistry and fluorescent in situ hybridization in selected cases. Overall, HER-2/neu immunoreactivity was detected in 23% of 345 NSCLC and in 7% of 207 NET. Gene amplification was seen in only 7 (7.4%) of the immunoreactive tumours, with high-level amplification (HER-2/neu gene to chromosome 17 ratio > 4.0) in 3 adenocarcinomas, 1 squamous-cell carcinoma and 1 large-cell neuroendocrine carcinoma (LCNEC), and low-level amplification (HER-2/neu gene to chromosome 17 ratio from 2.0 to 4.0) in 1 squamous-cell carcinoma and 1 LCNEC. None of tested carcinoids and SCLC showed gene amplification. All but 1 gene amplified case exhibited 2+ or 3+ membrane labeling. No relationship was found between gene amplification or protein overexpression and patients' survival or other clinicopathological variables. HER-2/neu gene amplification and protein overexpression are not closely correlated in lung carcinomas and do not bear any prognostic implication. Among neuroendocrine tumours, LCNEC show a slightly higher prevalence of either HER-2/neu gene amplification or protein overexpression.

Adenocarcinoma↗
PubMed2005

Three-times-daily radiotherapy with induction chemotherapy in locally advanced non-small cell lung cancer. Feasibility and toxicity study.

PURPOSE: To evaluate the feasibility and toxicity of three-times-daily radiotherapy (3tdRT), preceded by induction chemotherapy (iCT), in stage IIIA-IIIB non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: iCT consisted of three cycles of cisplatin and gemcitabine. Surgery was considered for stage IIIA patients responsive to iCT; definitive or postoperative 3tdRT was planned. Doses of 54.4 Gy and 64.6 Gy in postoperative and definitive treatments, respectively, were delivered in three daily fractions. RESULTS: From February 1998 to October 2000, 37 patients received 3tdRT as definitive (n = 18) or postoperative treatment (n = 19). Toxicity was limited to RTOG grade 2 (25 patients, 67.6%) and grade 3 (four patients, 10.8%) acute esophagitis; no grade 3 late esophagitis occurred. Late lung toxicity was represented by one grade 3 pneumonitis. No correlation emerged between acute esophageal toxicity and irradiated esophageal volume or disease- and treatment-related factors. A significant correlation was found for stage (IIIA vs. IIIB; p = 0.03) and a trend for the N-class (N2 vs. N3; p = 0.08). CONCLUSION: In this experience of 3tdRT preceded by iCT, the low toxicity profile confirmed the feasibility of this combination. The limited statistical power does not permit a definition of predictors for radiation-induced esophagitis incidence and severity; additional studies are required to clarify the impact of volumetric and dosimetric parameters. Failure patterns and survival results are warranted to confirm the efficacy of this approach in locally advanced NSCLC.

Antineoplastic Agents↗
PubMed2005

Two-year survival after multiple bilateral lung metastasectomies for cranial meningioma.

The lung represents a common site of metastases from extrathoracic malignancies, and several studies have strengthened the evidence that complete resection of pulmonary metastases is a useful therapeutic treatment for prolonged survival in selected patients. However, fewer data are available in the literature regarding the role of lung metastasectomy in rare malignancy. We present a case of extensive bilateral lung metastases due to recurrent cranial meningioma, which was successfully treated by aggressive, staged metastasectomies.

Aged↗
PubMed2005

Extended pneumonectomy with partial resection of the left atrium, without cardiopulmonary bypass, for lung cancer.

BACKGROUND: Extended pneumonectomy with partial resection of the left atrium for lung cancer is not frequently performed; therefore, its results remain controversial. The present study analyzed a single center's experience with this extended surgery, highlighting the surgery's technical aspects, postoperative outcomes, and oncologic results. METHODS: From November 1996 to December 2003, 15 patients underwent extended pneumonectomy with partial resection of the left atrium for lung cancer, without cardiopulmonary bypass. RESULTS: Of the 15 patients (median age of 63 years, range 35 to 74 years), 11 were men (73%) and 4 were women. Six patients (40%) underwent preoperative invasive mediastinal staging. Nine patients (60%) underwent induction chemotherapy. Nine patients (60%) underwent right pneumonectomy. Pathologic analysis of the specimens identified 8 patients (53%) with N2 disease, 5 patients (33%) with N1 disease, and 2 patients with N0 disease. The T status was T4 in 10 patients, pT3 in 3 patients, and T0 in the remaining 2 patients. The were 10 squamous cell carcinomas (60%), 2 adenocarcinomas, 1 adenosquamous carcinoma, 1 mucoepidermoid carcinoma, and 1 atypical carcinoid tumor. The median intensive care unit and hospital stay were 1 day and 6.4 days, respectively. There were only two (15.3%) minor postoperative complications (atrial arrhythmias), which were successfully treated medically. There was no postoperative mortality. At completion of the study, 9 patients (60%) were still alive, with 8 showing no evidence of disease. The remaining 6 patients died because of systemic recurrences. The 3-year probability of survival was 39%. CONCLUSIONS: Extended pneumonectomy with partial resection of the left atrium for advanced lung cancer is a feasible procedure, with low postoperative morbidity and mortality. In fact, it can lead to excellent local control of the disease, if not to a permanent cure in select patients.

Adenocarcinoma↗
PubMed2005

Resection for tumors with carinal involvement: technical aspects, results, and prognostic factors.

BACKGROUND: Resection of tumors with carinal involvement remains a challenge because of specific problems of operative technique and airway management. We reviewed our experience with carinal resection and studied factors influencing postoperative course and long-term survival. METHODS: Between 1983 and 2002, 65 patients underwent a carinal resection for non-small-cell lung cancers involving the carina (54 squamous cell carcinomas and 11 adenocarcinomas). RESULTS: Fifty-eight right sleeve pneumonectomies and 2 left sleeve pneumonectomies were performed. In addition, five tracheocarinal resections with double bronchial reimplantation (no lung resection) were also performed. The intraoperative airway management consisted of high-frequency jet ventilation in 83% of patients and intermittent conventional ventilation through the operative field in the remaining 17% of patients. Operative mortality was 7.7%. Resection was complete in 61 patients. The overall 5-year and 10-year survival rates were 26.5% and 10.6%, respectively. Patients with N0 or N1 disease had a 5-year survival of 38% compared with 5.3% for those with N2 disease (p < 0.01). At multivariate analysis only nodal status (N0, N1 versus N2; p = 0.0046) had a significant impact on long-term survival. CONCLUSIONS: Carinal resection provides acceptable results in terms of operative mortality and long-term survival rates. Patients should be carefully selected and probably enrolled in a multimodality treatment program in case of anticipated mediastinal lymph node involvement.

Adult↗
PubMed2004

Tumour CEA as predictor of better outcome in squamous cell carcinoma of the lung.

High levels of serum carcinoembryonic antigen (S-CEA) are considered a negative prognostic factor in non-small-cell lung cancer (NSCLC), while the prognostic value of tumour CEA (T-CEA) is unknown. We investigated the prognostic role of T-CEA in radically resected early stage NSCLC. We measured preoperative S-CEA levels and T-CEA in 146 patients with stage 1-2 NSCLC, and analysed their influence on survival. In patients positive for T-CEA, 3-year survival was 80%, compared to 65% in T-CEA-negative patients (p=0.03). After stratification by histology, T-CEA positivity was prognostic of better survival in squamous cell carcinoma (SCC) (p=0.024) but not in adenocarcinomas (ADK) (p=0.87). Multiple Cox regression analysis showed that T-CEA positivity was an independent predictor of better survival in patients with early stage NSCLC (p=0.02). In SCC patients, the magnitude of the hazard ratio was confirmed even if the precision of the estimate is decreased (p=0.06). In conclusion, T-CEA expression appears to be an important prognostic factor in early stage SSC of the lung.

Adult↗
PubMed2004

Modulation of epidermal growth factor receptor status by chemotherapy in patients with locally advanced non-small-cell lung cancer is rare.

PURPOSE: To determine whether epidermal growth factor receptor (EGFR) expression in non-small-cell lung cancer (NSCLC) is modulated by chemotherapy and to assess the agreement of EGFR status between mediastinal nodes and the primary tumor after chemotherapy. PATIENTS AND METHODS: Patients with NSCLC stage IIIa/b pN2/3 confirmed by mediastinoscopy or mediastinostomy were treated with at least three cycles of chemotherapy before undergoing surgery. EGFR expression was evaluated on mediastinal nodes at the time of initial diagnosis and on both the primary tumor and residual metastatic nodes after treatment. RESULTS: EGFR expression determined on 138 of 164 patients who underwent mediastinoscopy or mediastinostomy was 0 (22 patients), 1+ (27 patients), 2+ (28 patients), and 3+ (61 patients). Fifty-four patients of 164 received chemotherapy followed by surgery. Of the 89 of 138 patients with EGFR score of 2+/3+ at the time of diagnosis, 34 patients underwent surgery after induction chemotherapy. None changed to zero EGFR immunoreactivity, with 29 patients (88%) maintaining a score of 2+/3+. Of the 22 of 138 patients with no EGFR expression at the time of diagnosis, six underwent surgical resection after induction chemotherapy. Of these six patients, four changed their EGFR expression from an EGFR score of 0 to 2+/3+. After treatment, the agreement of EGFR status between tumor and nodes in the subgroup of patients with EGFR score 2+/3+ was 89% to 92%. CONCLUSION: Our data suggest a very good agreement of EGFR status before and after chemotherapy in EGFR-positive NSCLC. Induction chemotherapy can induce EGFR expression in occasional EGFR-negative tumors.

Adolescent↗
PubMed2004

CD117 immunoreactivity in high-grade neuroendocrine tumors of the lung: a comparative study of 39 large-cell neuroendocrine carcinomas and 27 surgically resected small-cell carcinomas.

Little is known about CD117 prevalence and clinicopathological implications in pulmonary large-cell neuroendocrine carcinoma. We studied CD117 immunoreactivity in surgical specimens from 39 large-cell neuroendocrine carcinomas of stages I-III and 27 limited-disease small-cell carcinomas, 56 typical and atypical carcinoids of the lung, and 10 neuroendocrine tumorlets, including the membrane and cytoplasmic immunostaining patterns. Membrane CD117 immunoreactivity in 5% or more tumor cells was documented in 30 (77%) large-cell neuroendocrine carcinomas and 18 (67%) small-cell carcinomas and 4 (7%) carcinoids, whereas cytoplasmic labeling was seen in 17 (44%) large-cell neuroendocrine carcinomas, 19 (70%) small-cell carcinomas, and 3 (5%) carcinoids. None of the neuroendocrine cells of the normal bronchial epithelium and of 10 tumorlets showed any CD117 immunoreactivity. Cytoplasmic immunostaining was more prevalent in small-cell carcinomas, whereas membrane labeling did not differ between the two types of high-grade carcinomas. Downregulation of CD117 by neoadjuvant chemotherapy was seen in large-cell neuroendocrine carcinomas but not small-cell carcinomas. Multiple linear regression analysis demonstrated a marginal association between cytoplasmic CD117 immunoreactivity and regional lymph node metastasis in small-cell carcinomas but not large-cell neuroendocrine carcinomas. There was no association between CD117 immunoreactivity and survival in either small-cell carcinoma or large-cell neuroendocrine carcinoma patients.

Aged↗
PubMed2004

Optimization of the schedule of gemcitabine-cisplatin combination as induction regimen for patients with biopsy-proven stage IIIa N2 - stage IIIb non-small-cell lung cancer: a prospective phase-II study.

Aim of this study was to define the optimal schedule of gemcitabine (GCB)\cisplatin (CDDP) combination as induction chemotherapy (CHT) in patients with stage IIIa pN2-IIIb non - small-cell lung cancer (NSCLC). Fifty patients with mediastinoscopically-proven stage-IIIa pN2 -IIIb NSCLC were treated with 3 cycles of induction CHT followed by surgery (if staged IIIa) and three-time-daily accelerated radiotherapy. Chemotherapy initially consisted of 3 courses of CDDP 100 mg\m(2) d1 plus GCB 1000 mg\m(2) dd 1,8,15 repeated every 4 weeks, than was modified in CDDP 80 mg\m(2) d1 plus GCB 1250 mg\m(2) dd 1,8 repeated every 3 weeks. Twenty-nine four-week scheduled treatment cycles were firstly administered to 10 patients (pts): treatment-related toxicity, mainly hematological, caused a dose-reduction or treatment omission on day 15 in 65% of cycles. After the protocol was amended, 119 three-week scheduled treatment cycles were administered to 40 pts. Treatment-related toxicity of the new schedule caused a dose-reduction or treatment omission in only 10% of cycles, no patients requiring chemotherapy discontinuation. Thirty-seven out of fifty patients (74%, 95% CI: 60-85%) achieved a partial response, 7 had stable disease and 6 had disease progression. Similar activity was seen with both schedules. One nodal pathological complete remission was observed among the 24 pts who underwent surgery. At present, with a median follow-up of 13 months (mos), 2-year (y) survival of all the 50 pts and of the 24 pts staged IIIa who underwent surgery is estimated as 37% (95% CI: 24-58%) and 47% (95%CI: 27-80%), respectively. When given as induction chemotherapy, a three-week schedule of CDDP plus GCB combination appeared to be effective, with lower toxicity and better compliance than a four-week schedule.

Adult↗
PubMed2004

Superior vena cava reconstruction using heterologous pericardial tube after extended resection for lung cancer.

Superior vena cava (SVC) resection for lung cancer is feasible in selected patients, but the type of vessel reconstruction is still object of debate. We report a case of SVC revascularization successfully performed with heterologous 'custom-made' pericardial tube. This type of revascularization may improve the reconstruction of large mediastinal veins after their resection for malignancies.

Animals↗
PubMed2004

Results of superior vena cava resection for lung cancer. Analysis of prognostic factors.

AIMS: The benefits of superior vena cava (SVC) resection for lung cancer remain controversial. Data obtained in four international centers were analyzed in order to identify prognostic factors and thus guide in future patient selection. MATERIALS AND METHODS: Retrospective study. Prognostic factors were examined by logistic regression for postoperative morbidity/mortality using the Kaplan-Meier method (log rank test) and the Cox proportional-hazard model for survival. RESULTS: From 1963 to 2000, 109 patients underwent SVC resection. Induction treatment was given to 23 (21%) patients. The SVC was resected for T involvement in 78 (72%) cases and for N involvement in 31 (28%) cases. Fifty-five (50.5%) patients underwent pneumonectomy (20 with carinal resection), while the remaining underwent lobar resections. Prosthetic SVC replacement was performed in 28 (26%) patients; partial resection with running suture (53%), vascular stapler (13%), or patch (7%) was performed in 80 patients; 1 patient did not undergo reconstruction. Pathological examination identified direct involvement (T4) in 66 (60%) patients and N2 disease in 55 (50%) patients. Major postoperative morbidity and mortality were 30 and 12%, respectively. Median intensive care unit stay was 3 days, while median hospital stay was 16 days. Five-year survival was at 21%, with median survival at 11 months. In multiple regression analysis, induction treatment was associated with an increased risk of major complications (P = 0.016). None of the factors assessed demonstrated an association with postoperative death. In multivariate survival analysis, both pneumonectomy and complete resection of the SVC with prosthetic replacement were associated with a significant increased risk of death (P = 0.0013 and 0.014, respectively). CONCLUSIONS: The radical resection of lung cancer involving the SVC may result in a permanent cure in carefully selected patients. The type of pulmonary resection (i.e., pneumonectomy) and the type of SVC resection (i.e., complete resection with prosthetic replacement) are the prognostic factors with the greatest adverse effect on survival.

Adult↗