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Marco Lucchi

Publications and source records attributed to Marco Lucchi.

14 recordsLinked to original sources
PubMed2006

A phase II study of intrapleural immuno-chemotherapy, pleurectomy/decortication, radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II-III malignant pleural mesothelioma.

OBJECTIVE: From therapeutic nihilism to extremely aggressive management, there is a wide range of possibilities in the treatment of malignant pleural mesothelioma (MPM). Unfortunately, there is little evidence as regards the best treatment to offer to the MPM patients. In 1999, we started a phase II study based on the multimodality treatment of stage II-III MPM, the results of which have been analysed and reported. METHODS: From 1999 to 2004, 49 patients with IMIG stage II-III MPM underwent a multimodality treatment including: intrapleural pre-operative interleukin 2 (IL-2, 18x10(6) UI/day per 3 days), pleurectomy/decortication, intrapleural post-operative epidoxorubicin (25mg/m2 per 3 days), IL-2 (18x10(6) UI/day per 3 days), adjuvant radiotherapy (30Gy), systemic chemotherapy (cisplatin 80 mg/m2 day 1, gemcitabine 1250 mg/m2 day 1 and 8 up to 6 courses) and long-term sub-cutaneous IL-2 (3x10(6) UI/day 3 days per week). RESULTS: There were 41 males and 8 females with a median age of 61 years (range 41-77). All the patients had a diagnosis of MPM by thoracoscopy before inclusion. We did not experience any post-operative mortality. The histology was: 39 epitheliomorf, 6 bifasic and 4 sarcomatous. According to the IMIG the post-operative staging was III in 40 cases and II in 9 cases. With a median follow-up of 59 months (range 14-81) 13 patients are still alive and the median actuarial survival is 26 months (31 and 21 months for stage II and III, respectively). Only the Performance Status at the diagnosis affected survival significantly. CONCLUSIONS: The multimodality treatment we adopted for stage II-III MPM was feasible, well tolerated by most of the patients and produced a favourable outcome. New targeted therapies are awaited for further improvements in the treatment of this disease.

Adult↗
PubMed2006

Percutaneous radiofrequency ablation of lung tumours: results in the mid-term.

INTRODUCTION: Radiofrequency ablation (RFA) of lung tumours has recently received much attention for the promising results achieved. Herein, we report the 5 years experience of a single referral centre in Europe, with particular reference to the mid-term results. METHODS: Between October 2001 and June 2005, we performed 88 RFAs of lung tumours, 9 of which were followed by surgical resection. The remaining 79 RFAs, the object of this paper, were performed to treat 64 lesions in 54 patients: 39 males and 15 females with a mean age of 71.7 years (range of 51-89). All patients had clinical or pathological evidence of the neoplastic lesion, which was non-small cell lung cancer (NSCLC) in 40 cases and a metastasis in 24 cases. The mean size of the lesions was 2.4 cm (range of 1-5). Ten lesions were re-treated from one to as many as four times. The procedure was always performed under local anaesthesia and conscious sedation. A generator of RF with max power output of 200W was utilised together with a needle with nine deployable electrodes, to achieve a target temperature of 90 degrees C that was maintained for 15-27 min according to the size of the lesions. RESULTS: In all cases, except two, the procedure was technically successful. Morbidity consisted in 10 cases (12.7%) of partial pneumothorax, 1 haematoma of the chest wall and 1 pleural effusion. At a mean follow-up of 23.7 months (range of 6-50) we recorded a 61.9% of complete responses, with a higher rate in the metastatic lesions (70.8%) and in those smaller than 3 cm (69.7%). Mean (median) overall survival and local progression-free interval were 17.3 (28.9) months and 12.9 (24.1) months, respectively. CONCLUSIONS: Efficacy of RFA in the mid-term seems to settle at a promising level, with better results for metastatic lesions and, above all, for lesions smaller than 3 cm. Notwithstanding these encouraging results, RFA remains an alternative local therapy only when surgery cannot be performed, especially in NSCLC.

Aged↗
PubMed2006

Tumour necrosis factor-alpha: prognostic role and relationship with interleukin-8 and endothelin-1 in non-small cell lung cancer.

Cytokines mediate numerous physiological and immune reactions, which are manifested in various biological effects, including tumouricidal activity. We evaluated the expression of the pleiotropic cytokine, tumour necrosis factor-alpha (TNF-alpha), by competitive PCR technique in 47 non-small cell lung cancer (NSCLC) cases and the impact of TNF-alpha on their clinical behaviour. Using univariate analysis, our study demonstrated a positive correlation between high TNF-alpha expression and favourable prognosis in NSCLC in terms of overall survival and disease free interval (p=0.03 and 0.04, respectively) and TNF-alpha maintained its independent role in multivariate analysis. TNF-alpha can stimulate the expression of many molecules, including interleukin-8 (IL-8) and endothelin-1 (ET-1); in our study, the expression of TNF-alpha was significantly associated with high IL-8 mRNA levels (p=0.008) and ET-1 mRNA positivity (p=0.03). We suggested that TNF-alpha can induce ET-1 mRNA expression in NSCLC, similarly to IL-8 expression. Our study may also contribute to advancing the knowledge of the molecular relationship between cytokines and endothelial functions in NSCLC.

Adult↗
PubMed2005

Expression of endothelin-1 is related to poor prognosis in non-small cell lung carcinoma.

The endothelin (ET) system influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. The aim of this study was to determine whether the expression of endothelin-1 (ET-1) is related to the angiogenic phenomenon in lung cancer and whether it could be involved in its clinical behaviour. Expression of ET-1, endothelin-converting enzyme-1 (ECE-1) and endothelin-receptors ETA and ETB was examined in 201 non-small cell lung carcinoma (NSCLC) and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Forty NSCLC were also analysed for vascular endothelial growth factor (VEGF) expression by a competitive-PCR approach to assess whether ET-1 expression was related to this angiogenic factor. A higher number of cases with ET-1, ECE-1 and ETA mRNA expression was observed in malignant lung tumours compared with normal lung tissues (45.7% versus 33% for ET-1 (P < 0.0001); 38.3% versus 16.5% for ECE-1 (P = 0.004); and 42.8% versus 28.5% for ETA (P < 0.0001)). On the other hand, ETB mRNA was higher in normal lung tissues than in tumour samples (58.5% versus 52.8% (P < 0.0001)). Immunohistochemical analysis was also performed in 78 cases, selected from among those with high ET-1 mRNA, to confirm the presence of ET-1 protein and to determine its distribution and localisation. Moreover, an interesting relationship was observed between ET-1 and VEGF mRNA levels (P = 0.02). At univariate analysis, clinical-pathological parameters, such as sex, nodal metastatic involvement and stage, and ET-1 expression were seen to be significant predictors of worse prognosis regarding both overall survival (P = 0.001, P = 0.0003, P = 0.001 and P = 0.03, respectively) and disease-free interval (P = 0.0005, P = 0.0007, P = 0.001 and P = 0.04, respectively). We conclude that ET-1 could be involved in angiogenic phenomena in NSCLC and may represent a further indicator of progression and poor prognosis in this type of cancer, with interesting therapeutic implications.

Adult↗
PubMed2005

Osteopontin expression and prognostic significance in non-small cell lung cancer.

PURPOSE: The survival rate of non-small cell lung cancer patients is very low, and knowledge of predictors of outcome is inadequate. To improve the curability of lung cancer, we need to identify new specific molecules involved in tumorigenesis and progression. The purpose of this study was to better define the role of osteopontin in non-small cell lung cancer biology by determining its prognostic significance. EXPERIMENTAL DESIGN: Osteopontin expression was evaluated by immunohistochemistry, as percentage of neoplastic cells with cytoplasmic immunoreactivity, in a wide series of patients with stage I-IIIA non-small cell lung cancer (207 cases). The median value of this series (20% of positive cells) was used as the cutoff value to distinguish tumors with low (<20%) from tumors with high (> or =20%) osteopontin expression. RESULTS: Taking the series of patients as a whole (207 cases), osteopontin expression was associated with neither overall survival (P = 0.14) nor disease-free survival (P = 0.074). However, among patients with at least 6 years of follow-up (163 cases), 6-year overall survival and disease-free survival were significantly reduced if osteopontin expression was high (P = 0.0085 for overall survival, P = 0.0023 for disease-free survival). Moreover, a statistically significant correlation between high levels of osteopontin and shorter overall survival (P = 0.034) and disease-free survival (P = 0.011) in patients with stage I tumors (136 cases) was shown. CONCLUSIONS: Our results support the hypothesis of an association between high osteopontin expression and poor survival of patients with stage I non-small cell lung cancer, suggesting that osteopontin could be a candidate target for cancer therapy.

Adult↗
PubMed2005

Interleukin-8 in non-small cell lung carcinoma: relation with angiogenic pattern and p53 alterations.

Progression of solid tumors, including NSCLC, is associated with increase in MVC (microvessel count), as a measure of tumor angiogenesis resulting from an imbalance between angiogenic factors and inhibitors. However, since tumor angiogenesis is a multi-step process under the control of various molecules, the mechanism of angiogenesis has not been fully clarified. Interleukin (IL)-8 has been shown to have a potential angiogenic effect in vitro and in vivo, and is overexpressed in several human solid cancers. Among the various angiogenic factors, vascular endothelial growth factor (VEGF) has been shown to correlate with a high MVC and with adverse prognosis in several human cancers, including NSCLC. Alterations of p53 suppressor gene are the most common genetic changes found in malignant tumors; several studies examined the link between aberrant p53 and angiogenesis in lung cancer, but only a few studies report data regarding a relation between p53 mutations and IL-8 expression. In this study we observed a correlation between IL-8 mRNA expression, intratumoral MVC and VEGF mRNA expression levels; furthermore, an aberrant p53 status was related to IL-8 expression. However, in our samples IL-8 levels did not significantly affect prognosis of NSCLC; more studies are required to elucidate the precise role of IL-8 in a large series of patients with non-small cell lung carcinoma.

Adenocarcinoma↗
PubMed2005

Advanced stage thymomas and thymic carcinomas: results of multimodality treatments.

BACKGROUND: With the aim of evaluating the results of multidisciplinary approaches, we reviewed our experience in multimodality treatment of advanced stage (III and IVA) thymic tumors. METHODS: From 1976 to 2003, 56 patients with Masaoka stage III and IVA thymic tumors underwent a multimodality treatment. Thirty-six patients underwent neoadjuvant chemotherapy, surgery, and postoperative radiotherapy; 20 patients were treated by primary surgery and postoperative radiotherapy (n = 12), chemotherapy (n = 1) or chemoradiotherapy (n = 7). The neoadjuvant or adjuvant chemotherapy consisted of three courses of cisplatin, epidoxorubicin, and etoposide every 3 weeks. Adjuvant radiotherapy consisted of 45 Gy for complete resections or 60 Gy for incomplete resections. RESULTS: The preoperative diagnosis of invasive thymomas was performed in a total of 29 cases: 15 by mediastinotomy, 6 by video-assisted thoracoscopic surgery, and 8 by fine-needle aspiration. In 27 cases no diagnosis was available, but in most of them a thymus-related syndrome was present. Thirty-four patients are still alive (31 disease-free), and 22 have died (2 disease-free). Ten-year survival was 48% and 45.7% for stage III and IVA thymomas, respectively. The presence of myasthenia gravis (p = 0.04) and neoadjuvant chemotherapy (p = 0.004) affected survival significantly. CONCLUSIONS: The multimodality treatment of stage III and IVA thymic tumors allows a good long-term outcome; the neoadjuvant chemotherapy improves the resectability rate and the survival of both stages of the disease.

Adult↗
PubMed2005

Metachronous adrenal masses in resected non-small cell lung cancer patients: therapeutic implications of laparoscopic adrenalectomy.

OBJECTIVE: In literature only few reports focused on the resection of solitary adrenal gland metastasis in patients operated on for non-small cell lung cancer (NSCLC). We report our experience on laparoscopic adrenalectomy for suspected or confirmed metachronous solitary adrenal metastasis from NSCLC and discuss its therapeutic role. METHODS: From June 1993 to March 2003, 14 patients (pts), who had been undergone lung resection for NSCLC, with suspected or confirmed solitary adrenal gland metastasis at the follow-up, underwent 15 laparoscopic adrenalectomy (in 1 patient it was bilateral). All the patients had enlarged adrenal glands at the abdominal ultrasound or CT. All but 2 pts underwent at least 1 adrenal fine needle aspiration. All the patients underwent a careful staging to exclude other sites of metastasis. The adrenal gland was in 6 cases the right, in 9 cases the left. RESULTS: In 7 cases we had a preoperative cytological diagnosis of metastasis. In 1 case adrenalectomy was not performed because of infiltration of vena cava and in 1 case it was necessary to perform a small laparotomy because of bleeding. The pathologic examination confirmed in 11 cases a NSCLC metastasis while in 4 cases it was a cortical adenoma. Regarding the 10 patients with NSCLC metastases, 3 are still alive and well at 37-80 months from the lung resection. One patient (who underwent bilateral adrenalectomy) is still alive at 44 months with local relapse. Two patients died 5 and 6 months after the adrenalectomy for other causes, 1 died at 14 months for local and systemic relapse and the remaining 3 patients died at 12 to 38 months for systemic relapse. CONCLUSIONS: Laparoscopic adrenalectomy in patients resected for NSCLC is a safe mini-invasive procedure. Even though this series is still too small, laparoscopic adrenalectomy should be considered an effective therapeutic tool in case of progressive adrenal gland enlargement, also with negative cytological examinations. A bigger series and other institution experiences will clarify its oncological value.

Adrenal Gland Neoplasms↗
PubMed2004

Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance.

PURPOSE: The c-kit protein, also known as CD117, is a member of the type III receptor tyrosine kinase family. Kinase activity has been implicated in the pathophysiology of many tumors, including small-cell lung carcinoma (SCLC). Autocrine or paracrine activation of c-kit by its ligand has been postulated for lung cancer, but this receptor can also be activated by mutations of the c-kit gene. We examined c-kit expression and mutational status in SCLC to verify its putative expression and genetic alterations, as well as its eventual prognostic impact. EXPERIMENTAL DESIGN: We studied 60 SCLC samples to determine the mutations of the coding region of the gene; the exons 9 and 11 were analyzed by PCR-single-strand conformational polymorphism and automated sequencing. Moreover, c-kit expression was evaluated in 55 samples by immunohistochemical method. RESULTS: Expression of c-kit was demonstrated in about 40% of SCLC samples. Two mutations in exon 9 and three mutations in exon 11 were found. Kaplan-Meier analysis revealed no prognostic significance of c-kit expression for survival. CONCLUSIONS: In our series, the expression of c-kit and its mutational status failed to appear relevant or to have a significant impact on survival; this makes the therapeutic approach with an inhibitor of tyrosine kinase more difficult in SCLC until a sure demonstration of c-kit implication is obtained for this tumor.

Adult↗
PubMed2004

Applications of tissue microarray technology in immunohistochemistry: a study on c-kit expression in small cell lung cancer.

Tissue microarray technology allows the immediate evaluation of molecular profiles of numerous different tissues, with savings of money and time. It was created for rapid, large-scale molecular studies, and the main concern regarding its possible broad acceptance is that the analysis of tissue microarrays instead of whole tissue sections may lead to false negative or positive results because of tissue heterogeneity. In the present study, we analyzed in 54 small cell lung cancers, by immunohistochemistry, the expression of the antigen c-kit, which seems to be important in these neoplasms' tumorigenesis, and compared the staining obtained on whole sections with that of the corresponding tissue microarrays. Although c-kit expression of the whole sections agreed with that of the corresponding biopsies in many cases, the correlation between whole sections and all the companion nonlost single cores or their mean value turned out to be highly significant only if the 36 double negatives (ie, both whole sections and companion tissue microarrays negative) were included (P <0.0001). In fact, if only cases positive to at least 1 of the tests (i.e. whole sections or corresponding tissue microarrays positive) were considered, the correlation was not significant (P=0.055). Tissue microarrays showed a good specificity (94.2% for all single cores and 92.3% for their mean value) but a rather poor sensitivity (respectively, 69.4% and 71.4%). Moreover, a high percentage (13.4%) of cores was lost, and this loss was not random. To sum up, in our experience, tissue microarray technology cannot be a substitute for whole sections in clinical diagnosis of individual cases.

Adult↗
PubMed2004

A reappraisal of the indications for laparoscopic treatment of adrenal metastases.

BACKGROUND: Laparoscopic adrenalectomy (LA) is unanimously recognized as the gold standard for the surgical treatment of adrenal lesions, but when to remove malignant lesions by this approach still remains controversial. STUDY DESIGN: We reviewed all cases of LA for suspected adrenal metastases carried out in our hospital, trying to focus on what should be the ideal preoperative workup, so as to avoid unnecessary operations. The possible role of fine needle aspiration biopsy (FNAB) in selecting patients was evaluated. RESULTS: Twenty-two patients underwent LA for suspected adrenal metastases from May 1994 to March 2003. Primary tumors were from lung in 14 cases, colon in 2 cases, kidney in 3 cases, thyroid in 2 cases, and breast in 1 case. LA was successfully performed in all but three cases. In 13 patients, 14 FNAB were performed: 8 cases proved to be true positive, 4 true negative, and 2 false negative. Final histology showed 6 cortical adenomas. Local relapse was present only in one patient, who died after 14 months. Of the metastatic patients, 8 are alive and free of disease after a mean followup of 39 months. CONCLUSIONS: The most accurate workup is of the greatest importance in order to avoid unnecessary surgery for suspected adrenal metastases. The absence of false positives (FP) and the fairly high number of true positives (TP) does not justify the effort of performing FNAB routinely. Indeed, laparoscopic exploration, being simple and quick, allows optimal diagnosis at a low cost, even when histological definition cannot be obtained.

Adrenal Gland Neoplasms↗
PubMed2002

Small cell lung carcinoma (SCLC): the angiogenic phenomenon.

OBJECTIVES: Tumor angiogenesis, expressed by the microvessel count (MVC), and its mediators (i.e. vascular endothelial growth factor) significantly correlate with metastases in surgically treated non-small cell lung carcinoma/cancer (NSCLC). SCLC is rarely treated by surgery, as a consequence, few specimens are available to perform a biological characterization. We reviewed our experience in the surgical treatment of SCLC with particular reference to the angiogenetic expression and its correlation to the stage of disease and prognosis. METHODS: We retrospectively investigated a homogenous cohort of 87 patients with SCLC, who were primarily operated on and then underwent adjuvant chemotherapy between 1980 and 1998. Their median age was 62 years (range 34-73). All the patients were completely staged. The surgical procedures included: 32 pneumonectomies and 55 lobectomies. There were 46 N0, 17 N1 and 24 N2-disease. The adjuvant chemotherapy consisted of four to six courses of cyclophosphamide, epidoxorubicine and etoposide. The MVC was determined highlighting the microvessels with anti-CD34 monoclonal antibodies. Immunostaining for VEGF was performed using the ABC method with anti-VEGF monoclonal antibodies. The p53 protein expression was assessed by NCL-DO7 anti-p53 monoclonal antibody. RESULTS: With a median follow-up of 109.6 months (range 25-238), 37 patients are alive and well, two are alive with systemic metastases. Forty-four patients died of local (n=5) or systemic (n=39) relapse, while four patients died from other causes. The median MVC was 59 (range 18-145). Among the clinico-pathological parameters, metastatic nodal-involvement (P=0.002) and advanced stage of disease (P=0.005) were associated with a worse overall survival (OS). MVC and VEGF protein expression significantly affected the survival (P<0.001 and P=0.0008, respectively). No statistical association was found between p53 alterations and OS as well as no association was found among p53 alterations, MVC and VEGF expression. On multivariate analysis only the VEGF expression (P=0.003) was an independent prognostic factor. CONCLUSIONS: Angiogenesis plays a role in the metastatic process of the SCLC as well as NSCLC. SCLC has a higher vascularization than NSCLC as results from the higher number of microvessels; however, tumor angiogenesis tested by the MVC and the VEGF protein expression correlates with the prognosis also in SCLC. SCLC may be an ideal field to test new antiangiogenic drugs associated to chemotherapy.

Adult↗