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Biomedical subjects

P Granone

Publications and source records attributed to P Granone.

At least 19 recordsLinked to original sources

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

Adult↗

Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells.

The effects of different marine derived agents were studied in A549 cell growth. These drugs induced cell cycle arrest at the G2-M phase associated with the up-regulation of GADD45alpha-gamma and down-regulation of c-Myc. In treated cells, GADD45alpha-gamma and c-Myc were up- and down-regulated, respectively. A cascade of events leading to apoptotic mitochondrial 'intrinsic' pathway was observed in treated cells: (1) dephosphorylation of BAD serine136; (2) BAD dissociation from 14-3-3 followed by its association with BCL-XL; (3) cytochrome c release; (4) caspase-3 activation, and (5) cleavage of vimentin. Caspase(s) inhibitor prevented the formation of cleavage products and, in turn, apoptosis was inhibited through a p53-independent mechanism. Moreover, these compounds did not activate NF-kappaB. Our findings may offer new insights into the mechanisms of action of these agents in A549 cells. The better understanding of their effects might be important to fully exploit the potential of these new drugs.

14-3-3 Proteins↗

Chemo-radiotherapy in non-small cell lung cancer: the role of gemcitabine.

Gemcitabine (2'-2'-difluorodeoxycytidine) is a well-known cytotoxic drug and a potent radio-enhancer. We herein report the in vitro evidence of its activity, and the clinical experiences when this drug is administered concurrently with radiation. The phase I-II trials are analyzed, focusing on the recent ability to deliver irradiation with low incidence of side effects.

Antineoplastic Combined Chemotherapy Protocols↗

Critical presentation of pleuropulmonary blastoma.

We report two cases of critical presentation of a quite rare lung neoplasm of childhood. Presentation findings were at the extremes of the clinical pattern of this polymorphous neoplasm, ranging from an enormous solid mass causing airway compression and dislocation to an apparently benign cystic lesion discovered because of a tension pneumothorax. Both children were discharged from the pediatric intensive care unit and underwent appropriate surgical removal and oncological management. Congenital lung cysts, even asymptomatic, should not be underestimated and need elective surgical excision and histologic examination.

Biopsy↗

Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging.

BACKGROUND: To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. PATIENTS AND METHODS: Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. RESULTS: In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0-I (DS 0-I) showed a statistically significant improved disease-free survival (26.2 months pStage 0-I versus 11.2 months pStage II-III; P=0.0116) and overall survival (median 32.5 months pStage 0-I versus 18.3 months pStage II-III; P=0.025). Patients with DS 0-I had a significantly lower probability (P=0.0353) of developing distant metastases estimated in 0.2963 odds ratio. CONCLUSION: Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.

Adult↗

Thymoma in patients with MG: characteristics and long-term outcome.

OBJECTIVE: To examine the characteristics of thymoma when associated with MG and to evaluate those conditions that can complicate management and affect survival. METHODS: The study includes 207 myasthenic patients who were operated on for thymoma, with at least 1-year follow-up from surgery. MG severity and response to treatment, the occurrence of paraneoplastic diseases and extrathymic malignancies, thymoma histologic types and stages, adjuvant therapy, tumor recurrences, and causes of death were recorded. RESULTS: MG-associated thymoma was predominantly of B type and was invasive in the majority of patients. MG was generally severe, and most patients remained dependent on immunosuppressive therapy. Other paraneoplastic disorders and extrathymic malignancies were found in 9.66 and 11.11% of patients. Thymoma recurrences occurred in 18 of 115 patients with invasive tumors (15.65%) and were often associated with the onset/aggravation of autoimmune diseases. On completion of the study, MG and thymoma accounted for a similar mortality rate. CONCLUSIONS: Thymoma should be considered as a potentially malignant tumor requiring prolonged follow-up. The presence of myasthenic weakness can still complicate its management. Thymoma-related deaths are bound to outnumber those due to MG in the future.

Adolescent↗

Vascular phenotype in angiogenic and non-angiogenic lung non-small cell carcinomas.

We have previously described a group of non-small cell lung carcinomas without morphological evidence of neo-angiogenesis. In these tumours neoplastic cells fill up the alveoli and the only vessels present appear to belong to the trapped alveolar septa. In the present study we have characterised the phenotype of the vessels present in these non-angiogenic tumours, in normal lung and in angiogenic non-small cell lung carcinomas. The vessels, identified by the expression of CD31, were scored as mature when expressing the epitope LH39 in the basal membrane and as newly formed when expressing alphaVbeta3 on the endothelial cells and/or lacking LH39 expression. In the nine putative non-angiogenic cases examined, the vascular phenotype of all the vessels was the same as that of alveolar vessels in normal lung: LH39 positive and alphaVbeta3 variable or negative. Instead in 104 angiogenic tumours examined, only a minority of vessels (mean 13.1%; range 0--60%) expressed LH39, while alphaVbeta3 (in 45 cases) was strongly expressed on many vessels (mean 55.5%; range 5--90%). We conclude that in putative non-angiogenic tumours the vascular phenotype is that of normal vessels and there is no neo-angiogenesis. This type of cancer may be resistant to some anti-angiogenic therapy and different strategies need to be developed.

Carcinoma, Non-Small-Cell Lung↗

Ten year experience with induction therapy in locally advanced non-small cell lung cancer (NSCLC): is clinical re-staging predictive of pathological staging?

OBJECTIVE: To verify if in our experience with 'induction therapy' in non-small cell lung cancer (NSCLC) the clinical re-staging is really predictive of pathological staging. MATERIALS AND METHODS: From January 1990 to February 2000, 136 patients with locally advanced NSCLC underwent a protocol of induction therapy according to three different treatment plans: Carboplatin + radiotherapy--study A; Cisplatin + 5-Fluorouracil + radiotherapy--study B; Gemcitabine + radiotherapy--study C. RESULTS: Clinical re-staging showed in the patients enrolled in study A a clinical Complete Response rate (cCR) of 2.3%; a clinical Partial Response rate (cPR) of 50%; a clinical Stable Disease (cSD) rate of 44.3%; a clinical Disease Progression (cDP) rate of 3.4%. In study B, cCR was 0%; cPR: 71.4%; cSD 10.7%; cDP: 17.9%. In study C, cCR was 0%; cPR: 23.5%; cSD: 11.8%; cDP: 64.7%. After clinical re-staging, 76 patients (47 group A; 23 group B; 6 group C) were judged to be resectable and underwent a surgical operation. Pathological staging showed no tumour in eight patients (10.5%; 8/76) (three in study A, four in study B, one in study C) and microscopic neoplastic remnants in seven (9.2%; 7/76). Thirty-nine patients were pN0. Overall downstaging rate in the operated patients was 51%. No precise correlation was found among clinical re-staging and pathological staging. We had two cCRs and eight pCRs, and all of these pCRs had been re-staged as cPR except in one case (cSD). In seven cases, where only microscopic remnants have been found, six had been clinically restaged as cPR and one as cSD. CONCLUSIONS: Our experience confirmed how often the clinical re-staging data are unreal. Accordingly surgery should be indicated in any case where an induction therapy has been administered, if it is reasonably possible.

Adult↗

Non-small cell lung cancer with single brain metastasis: the role of surgical treatment.

OBJECTIVE: The prognosis of non-small cell lung cancer (NSCLC) with brain metastasis is very poor, with median survival rate below 6 months, even if treated with palliative radio and/or chemotherapy. To assess the effectiveness of surgical treatment for this kind of patients we reviewed our experience. METHODS: From January 1989 to October 1999, 30 patients (26 males and four females; mean age: 58.7 years) with NSCLC and single brain metastasis underwent surgical treatment of both primary lung cancer and secondary cerebral lesion. Patients (pts) were divided into two major groups. In group 1 (G1) 20 pts (18 males and two females) presented a synchronous brain metastasis. In group 2 (G2) 10 pts (eight males and two females) presented a metachronous brain metastasis during the follow-up period (range 3-24 months since the primary tumor). Patients selected in G1 had T1-2, N0-1 clinical staging, good 'performance status' (ECOG:0--1; Karnofsky index > 70%), age < 75 years. Craniotomy has always been the first approach. In G2 also patients with locally advanced tumors (T3 and/or N2) were included. Whole brain radiotherapy and/or chemotherapy was the post-operative choice treatment. RESULTS: Histologic findings have shown: adenocarcinoma in 17 cases (12 in G1; five in G2), squamous cell carcinoma in 10 cases (six in G1; four in G2), large cell carcinoma in 2 (one in G1; one in G2) and large cell neuroendocrine carcinoma in one (G1). Survival analysis (Kaplan--Meier method) has shown an overall value of 80% at 1 year (95% in G1; 50% in G2), 41% at 2 years (47% in G1; 30% in G2) and 17% at 3 years (14% in G1; 20% in G2). Overall median survival is 23 months (23 in G1; 11 in G2); mean survival 27.8 months (30.3 months in G1; 22.8 months in G2). According to univariate analysis prognosis is definitively better in N0 tumors compared to N1-2 tumors and in adenocarcinoma cases compared to other histotypes (P < 0.05). CONCLUSIONS: We can conclude that combined surgical therapy is, nowadays, the choice treatment for this kind of patients, even though restricted to selected cases. The knowledge of prognostic factors may optimize indications for surgery.

Adenocarcinoma↗

Radiotherapy versus follow-up in the treatment of pathological stage Ia and Ib non-small cell lung cancer. Early stopped analysis of a randomized controlled study.

OBJECTIVE: This is an analysis of a randomized controlled clinical trial planned to evaluate the effects of adjuvant radiotherapy (AR) on the local recurrence rate in patients with non-small cell lung cancer (NSCLC) with pathological stage (pStage) Ia (pT1N0) and Ib (pT2N0). The effects of AR on the long-term survival have also been marginally evaluated. MATERIALS AND METHODS: This clinical trial was planned with the hypothesis that AR on pStage Ia and Ib, R0 NSCLCs was effective on local recurrence rate. From July 1989 through March 1997, 104 patients with NSCLC who presented with pStage Ia and Ib have been observed and treated and entered the study. Male/female ratio was 91:13; the mean age was 62 years (range 41-75 years). All patients underwent major pulmonary resection and homolateral standard hilar and mediastinal lymph node dissection. pStage was T1N0 in 29 and T2N0 in 75 cases. Patients have been randomized 'by chance' into two groups (G1 and G2). G1 received radiotherapy, G2 did not receive any adjuvant treatment. Fifty-two patients entered G1 and 52 entered G2. RESULTS: Post-operative mortality was nil. Seven patients have been excluded from the study (four in G1 and three in G2), due to incomplete follow-up data. We do not report any radiotherapy-related complication or deterioration of lung function. The treatment effect on the local recurrence rate demonstrated a clearly significant protective effect of the AR. No statistically significant difference was found from the comparison of the 5-year survival rate of the treated (83%) versus untreated (70%) patients. No detrimental effect of the radiotherapy has been assessed. CONCLUSIONS: AR in the treatment of pStage Ia and Ib NSCLC has been well tolerated and had a significant relative effect on the local recurrence rate but did not significantly modify overall survival even if a positive trend in the group of treated patients is reported.

Adult↗

[Evaluation of the "N" factor in nonsmall cell lung cancer. Correlation between computerized tomography and pathologic anatomy].

PURPOSE: To evaluate the role of CT in identifying other morphological signs of metastatic lymph node involvement from non small cell bronchogenic carcinoma. This is done to improve N staging, a critical step in this disease. In fact, since diameter is the only criterion used to distinguish normal form abnormal lymph nodes, medistinal CT only has 80% diagnostic accuracy. MATERIAL AND METHODS: 137 patients with known or suspected lung cancer were examined with Helical CT during early and late arterial phases (2 min delay, 3 mm thickness, 5 mm interslice gap) to depict node characteristics. Mediastinal lymph nodes, located according to the American Thoracic Society mapping, were considered normal when they were not visible or, if visible, less than 1 cm in diameter and of homogeneous density; lymph nodes over 1 cm in diameter and homogeneous density were considered reactive. A lymph node was considered metastatic when, independent of size, the following signs were found: central hypodensity; hyperdense thin/thick rim, with nodules within; hyperdense strands or diffuse hyperdensity in perinodal adipose tissue. The tumor site was also considered. RESULTS: Seventy patients were excluded because they were inoperable. Sixty-five of the remaining 67 patients were operated on, 1 underwent mediastinoscopy and another one mediastinoscopy followed by surgery. Based on the above CT signs, 46 patients were staged as N0, 61 as N1 and 15 as N2. In 44/46 N0 patients there was agreement between anatomical and pathologic findings; 3 of the 44 patients had lymph nodes over 1 cm in diameter and with homogeneous density. Micrometastases to mediastinal lymph nodes (N2) were found at histology in 2/46 patients (CT false negatives). In the 6 N1 and the 15 N2 patients there was complete agreement between anatomical and pathologic findings; in particular, 9 N2 patients had lymph nodes less than 1 cm in diameter with signs of metastasis and 4 had lymph nodes over 1 cm in diameter with signs of metastasis and 2 had lymph nodes either over or less than 1 cm. In all N2 patients the tumor histotype and the mediastinal location were also considered relative to the lesion site. DISCUSSION: A closer correlation was found with node morphology and density than with size. Indeed, CT sensitivity, specificity and diagnostic accuracy were 97, 100 and 97%, respectively, for the former versus 52, 93 and 77% for the latter. Adenocarcinoma was the predominant histotype (70.5%) in N2 patients. Metastases to node region 4 were predominant in right upper lobe carcinomas while node region 5 was predominant in left upper lobe lesions. CONCLUSIONS: Other criteria can be associated with size to improve CT diagnostic accuracy in N staging. Technique optimization plays a major role particularly in the late, thin slice, examination phase.

Adenocarcinoma↗

Thymectomy in myasthenia gravis via video-assisted infra-mammary cosmetic incision.

We describe the technique, the benefits and the drawbacks of an original video-assisted thymectomy (VAT), performed through an inframammary cosmetic incision and median sternotomy in myasthenia gravis (MG) patients. This procedure is clinically valuable and cosmetically satisfactory so as to be very well accepted by patients, especially by young women. We report a review of 71 MG patients treated between 1993 and 1997. A clinical remission was obtained in 48 (80%) out of 60 patients who had been followed for at least 12 months from surgery. Fifty-three of these patients (93%) judged their cosmetic results to be excellent or good.

Esthetics↗