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Michele Gallucci

Publications and source records attributed to Michele Gallucci.

12 recordsLinked to original sources

Adjuvant chemotherapy in muscle-invasive bladder carcinoma: a pooled analysis from phase III studies.

BACKGROUND: The treatment of muscle-invasive bladder carcinoma should include both the eradication of local disease and the elimination of potential micrometastases. To date, the 'gold standard' treatment for muscle invasive bladder carcinoma has been recognized to be radical cystectomy. Adjuvant chemotherapy (AC) has the advantage of being administered to patients with known prognostic factors of recurrence. A pooled analysis was used to verify whether AC is able to increase the disease-free survival (DFS) and overall survival (OS) of patients with muscle-invasive bladder carcinoma who had undergone radical cystectomy. METHODS: All published randomized Phase III studies were considered eligible and a literature-based pooled analysis was accomplished. DFS and OS were the endpoints. Event-based relative risk ratio (RR) and 95% confidence intervals (95% CI) were derived. Combined effect estimation was computed with a fixed- and a random-effect model. A heterogeneity test was applied as well. RESULTS: Five trials were collected. All were evaluable for OS (350 patients) and four of these also were evaluable for DFS (273 patients). A significant benefit from AC was noted both in OS (RR, 0.74; 95% CI, 0.62-0.88 [P = 0.001]) and DFS (RR, 0.65; CI 0.54-0.78, [P < 0.001]). No significant heterogeneity was found. CONCLUSIONS: Although the results of the analysis favor the use of AC, larger studies are needed to identify the role of AC in the treatment of muscle-invasive bladder carcinoma. Ongoing trials (European Organization for Research and Treatment of Cancer [EORTC]/Southwest Oncology Group [SWOG] and the Italian Multicentric Study) can help to better identify patients who can benefit from this approach.

Adult↗

Epithelial-restricted gene profile of primary cultures from human prostate tumors: a molecular approach to predict clinical behavior of prostate cancer.

The histopathologic and molecular heterogeneity of prostate cancer and the limited availability of human tumor tissue make unraveling the mechanisms of prostate carcinogenesis a challenging task. Our goal was to develop an ex vivo model that could be reliably used to define a prognostic signature based on gene expression profiling of cell cultures that maintained the tumor phenotype. To this end, we derived epithelial cultures from tissue explanted from 59 patients undergoing radical prostatectomy or cistoprostatectomy because of prostate benign hyperplasia/prostate cancer or bladder carcinoma. Patient selection criteria were absence of hormonal neoadjuvant treatment before surgery and diagnosis of clinically localized disease. Using this unique experimental material, we analyzed expression of 22,500 transcripts on the Affymetrix Human U133A GeneChip platform (Affymetrix, Inc., High Wycombe, United Kingdom). Cultures from normal/hyperplastic tissues with a prevalent luminal phenotype and from normal prostate epithelial tissue with basal phenotype (PrEC) served as controls. We have established a large number of prostate primary cultures highly enriched in the secretory phenotype. From them, we derived an epithelial-restricted transcriptional signature that (a) differentiated normal from tumor cells and (b) clearly separated cancer-derived lines into two distinct groups, which correlated with indolent or aggressive clinical behavior of the disease. Our findings provide (a) a method to expand human primary prostate carcinoma cells with a luminal phenotype, (b) a powerful experimental model to study primary prostate cancer biology, and (c) a novel means to characterize these tumors from a molecular genetic standpoint for prognostic and/or predictive purposes.

Aged↗

Cytogenetic profiles as additional markers to pathological features in clinically localized prostate carcinoma.

Fluorescence in situ hybridization analysis for evaluation of 7, 8, X chromosomes and EGFR, LPL, MYC, AR genes in 79 neoplastic foci from 56 patients with clinically localized prostate cancer was performed. We found aneusomy for chromosome 7, 8 and X in 74/77 (96.1%), 56/76 (73.7%), 26/70 (37.1%) of examined foci respectively. No specimen was amplified for EGFR and AR genes, only 2/71 (2.8%) specimens showed MYC gene amplified. LPL deletion was present in 52/76 (68.4%) specimens. Statistically association between Gleason score and both chromosome 7 aneusomy and 8p21 deletion was present. The frequency of chromosome 7 aneusomy was statistically higher in T3-4 cases than T2c and T2a-T2b ones. We considered as unfavorable a genetic set if aneusomy for at least two chromosomes and one altered gene were present. The percentage of tumors, with unfavorable genetic pattern, increased from 36.4 to 75.0% in those with Gleason >7 and from 40.0 to 73.7% in those with stage T3 or more. These alterations could be considered potent genetic markers adjunctive to conventional prognostic parameters. Our objective was to establish specific genetic profiles which may discriminate favorable and unfavorable genetic prognosis tumors.

Biomarkers, Tumor↗

Laparoscopic nephrectomy using Ligasure system: preliminary experience.

BACKGROUND AND PURPOSE: The advent of laparoscopic surgery has created new technical challenges and problems. Recently, a new commercially available vessel-sealing technology, the Ligasure system, was introduced. The aim of our study was to compare the effectiveness of this new system with earlier methods in a group of patients affected by renal-cell carcinoma. PATIENTS AND METHODS: A series of 30 patients underwent laparoscopic radical nephrectomy for clinically localized renal-cell carcinoma. We always used a transperitoneal approach with a three-trocar technique. Patients were randomly divided in two groups: 15 underwent conventional laparoscopic radical nephrectomy, while 15 underwent laparoscopic nephrectomy using the Ligasure system, which is a bipolar radiofrequency generator. Information analyzed included intraoperative blood loss, operative time, conversion rate, and postoperative course. Statistical analysis was performed with commercially available software. The two groups were compared in term of clinical and pathologic variables using Student's t-test. Differences were considered significant at p < 0.05. RESULTS: No statistically significant differences were observed between the two groups for baseline characteristics. No conversion occurred in either group. Statistically significant differences were observed between conventional and Ligasure nephrectomy regarding mean intraoperative blood loss (485 mL and 100 mL, respectively; p < 0.05) and mean operative time (164 minutes and 68 minutes, respectively p < 0.05). No statistically difference was observed in the postoperative discharge time. CONCLUSION: The Ligasure vessel-sealing system seems to produce a consistent, reliable, permanent seal of veins, arteries, and tissue bundles by fusing the collagen in vessel walls. By reducing sutures and the number of instrument exchanges in the operating theatre, the Ligasure decreases operating time and blood loss. This new energy-based vessel-ligation device appears to be effective in advanced laparoscopic procedures.

Blood Loss, Surgical↗

Predicting survival in terminal cancer patients: clinical observation or quality-of-life evaluation?

INTRODUCTION: This study compares the relative prognostic power of clinical variables and quality-of-life (QoL) measures in a population of terminal cancer patients. METHODS: A prospective cohort study in 58 Italian Palliative Care Units. Of the 601 randomly selected terminal cancer patients, 574 were followed until death in order to compare clinical and QoL variables (using the Therapy Impact Questionnaire (TIQ) as predictors of survival, and assess whether their combined implementation makes prediction more accurate. RESULTS: The clinical variables most strongly associated with survival were dyspnoea, cachexia, Katz's ADL, oliguria, dysphagia, dehydration, liver and acute kidney failure and delirium (hazard ratios (HR) ranging from 2.10 to 3.01). Only the first four kept their strength once introduced in the Cox model (HRs ranging from 1.95 to 2.22). In the TIQ primary scale the strongest predictors were physical wellbeing, fatigue, functional status and cognitive status (HRs ranging from 1.42 to 1.71), but only fatigue showed an independent prognostic relevance (90% of selection). In the TIQ global scales, the Physical Symptom Index showed a stronger association with survival (HR 1.71) than the Therapy Impact Index (HR 1.47). The former marginally improved the prognostic power of the model when added to clinical variables. Internal validation confirmed that the results were not spurious. CONCLUSIONS: In terminal cancer patients, clinical variables are better predictors of survival than QoL. The large residual variability not accounted for by the model (approximately 70%) suggests that survival is also influenced by factors unlikely to be identified in a survey.

Aged↗

Liver harvesting surgical technique for the treatment of retro-hepatic caval thrombosis concomitant to renal cell carcinoma: perioperative and long-term results in 15 patients without mortality.

OBJECTIVE: Radical surgical treatment improves the prognosis of patients affected by Inferior Vena Cava (IVC) thrombosis concomitant to renal carcinoma. However, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable haemorrhages and tumor fragmentation. We report the results of an innovative surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. In the presence of retro-hepatic IVC thrombosis, this technique improves vascular control and allows to perform a large cavotomy with an en-bloc removal of the thrombus and the tumor. METHODS: From January 1995 through June 2003, 15 patients with renal cancer and caval thrombosis were treated at our Institution. Four, ten and one patients were respectively affected by an infrahepatic (Level I), retro-hepatic (Level II) and atrial (Level III) IVC thrombosis. RESULTS: All patients underwent radical surgical treatment. In presence of Level II caval thrombosis, the patients underwent the above reported surgical technique. Perioperative mortality was absent; major morbidity occurred in one patient (6.7%). The thrombus was radically removed in all cases. After a mean follow-up of 53.9 months (5-100 months) all patients but one are still alive. One patient died 9 months after surgery with multiple bilateral pulmonary metastases. CONCLUSIONS: Isolation of the retro-hepatic IVC is a safe and effective manoeuvre to significantly reduce perioperative mortality and morbidity in patients affected by Level II caval thrombosis concomitant to renal carcinoma.

Aged↗

Mutations of the D310 mitochondrial mononucleotide repeat in primary tumors and cytological specimens.

A mononucleotide repeat (D310) in mitochondrial DNA has been recently identified as a mutational hot spot in primary tumors. We analyzed 56 tumors for insertion/deletion mutations in the D310 repeat. A total of 13 mutations were detected. The highest frequency of mutations was found for cervical cancer, followed by bladder tumors, breast cancer and endometrial neoplasia. No alterations were observed in four patients suspected of malignancy but without evidence of malignant tumor. We detected identical changes in four of four urine sediments from patients with bladder cancer and in three of three fine needle aspirates of patients with breast cancer. Our results indicate that D310 abnormalities are detectable in cytology specimens from patients with cancer and support the notion that D310 analysis may represent a new molecular tool for cancer detection.

Breast Neoplasms↗

Comparison between SLC3A1 and SLC7A9 cystinuria patients and carriers: a need for a new classification.

Recent developments in the genetics and physiology of cystinuria do not support the traditional classification, which is based on the excretion of cystine and dibasic amino acids in obligate heterozygotes. Mutations of only two genes (SLC3A1 and SLC7A9), identified by the International Cystinuria Consortium (ICC), have been found to be responsible for all three types of the disease. The ICC set up a multinational database and collected genetic and clinical data from 224 patients affected by cystinuria, 125 with full genotype definition. Amino acid urinary excretion patterns of 189 heterozygotes with genetic definition and of 83 healthy controls were also included. All SLC3A1 carriers and 14% of SLC7A9 carriers showed a normal amino acid urinary pattern (i.e., type I phenotype). The rest of the SLC7A9 carriers showed phenotype non-I (type III, 80.5%; type II, 5.5%). This makes the traditional classification imprecise. A new classification is needed: type A, due to two mutations of SLC3A1 (rBAT) on chromosome 2 (45.2% in our database); type B, due to two mutations of SLC7A9 on chromosome 19 (53.2% in this series); and a possible third type, AB (1.6%), with one mutation on each of the above-mentioned genes. Clinical data show that cystinuria is more severe in males than in females. The two types of cystinuria (A and B) had a similar outcome in this retrospective study, but the effect of the treatment could not be analyzed. Stone events do not correlate with amino acid urinary excretion. Renal function was clearly impaired in 17% of the patients.

Adolescent↗