PubMed Health⌕ Search

Biomedical subjects

F Pagano

Publications and source records attributed to F Pagano.

At least 19 recordsLinked to original sources

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Aged↗

Tumor-like multiple sclerosis (MS) lesions: neuropathological clues.

The neuroradiological evidence of a single, large white matter lesion with mass effect, clinically revealed by signs of endocranial hypertension, is highly suspicious for central nervous system neoplasm. In rare cases, a demyelinating disorder can start with atypical features suggestive of a brain tumor; in these cases a brain biopsy is often carried out. We report our experience regarding cases of multiple sclerosis (MS) with atypical tumor-like presentation. None of our patients underwent biopsy. Serial magnetic resonance imaging performed during steroid treatment, together with other paraclinical data, were sufficient for the final diagnosis of MS. These cases are characterized by a severe clinical course and a rapid clinical deterioration, only partially modified by medical treatments. Atypical severe cases, misdiagnosed as MS, can be indeed due to primary CNS vasculitis.

Adult↗

Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study.

OBJECTIVES: To compare the pathologic stage and surgical margin status in patients undergoing either immediate radical prostatectomy or surgery preceded by 3 or 6 months of neoadjuvant hormonal treatment (NHT) in a prospective, randomized study. METHODS: Four hundred thirty-one men with prostate cancer were enrolled in the Italian randomized prospective PROSIT study. The whole-mount sectioning technique was used. By May 1999, the reviewing pathologist had evaluated 303 specimens. One hundred seven patients were untreated before radical prostatectomy was performed, and 114 and 82 patients had been treated for 3 and 6 months, respectively, with complete androgen blockade. RESULTS: Pathologic organ-confined disease was found in 63.1% of patients with clinical Stage B disease treated with 6 months of NHT versus 61.0% after 3 months of NHT and 37.5% after immediate surgery. Among patients with clinical Stage C tumors, pathologic staging found organ-confined disease in 62.5%, 32.1%, and 11.1% of patients after 6 months of NHT, 3 months of NHT, and immediate surgery, respectively. Three months of NHT produced a significant increase in negative margins both in patients with clinical Stage B and C disease, but the addition of another 3 months of treatment did not significantly improve this result. A lower degree of benefit was observed in patients with clinical Stage C tumors. CONCLUSIONS: This study shows that complete androgen blockade before surgery is beneficial in men with clinical Stage B disease. The effects are more pronounced after 6 months of NHT than after 3 months.

Aged↗

Arachidonic acid causes cell death through the mitochondrial permeability transition. Implications for tumor necrosis factor-alpha aopototic signaling.

We have investigated the effects of arachidonic and palmitic acids in isolated rat liver mitochondria and in rat hepatoma MH1C1 cells. We show that both compounds induce the mitochondrial permeability transition (PT). At variance from palmitic acid, however, arachidonic acid causes a PT at concentrations that do not cause PT-independent depolarization or respiratory inhibition, suggesting a specific effect on the PT pore. When added to intact MH1C1 cells, arachidonic acid but not palmitic acid caused a mitochondrial PT in situ that was accompanied by cytochrome c release and rapidly followed by cell death. All these effects of arachidonic acid could be prevented by cyclosporin A but not by the phospholipase A(2) inhibitor aristolochic acid. In contrast, tumor necrosis factor alpha caused phospholipid hydrolysis, induction of the PT, cytochrome c release, and cell death that could be inhibited by both cyclosporin A and aristolochic acid. These findings suggest that arachidonic acid produced by cytosolic phospholipase A(2) may be a mediator of tumor necrosis factor alpha cytotoxicity in situ through induction of the mitochondrial PT.

Animals↗

Loss of FHIT expression in transitional cell carcinoma of the urinary bladder.

Cytogenetic and loss of heterozygosity (LOH) studies demonstrated chromosome 3p deletions in transitional cell carcinoma (TCC). We recently cloned the tumor suppressor gene FHIT (fragile histidine triad) at 3p14.2, one of the most frequently deleted chromosomal regions in TCC of the bladder, and showed that it is the target of environmental carcinogens. Abnormalities at the FHIT locus have been found in tumors of the lung, breast, cervix, head and neck, stomach, pancreas, and clear cell carcinoma of the kidney. We examined six TCC derived cell lines (SW780, T24, Hs228T, CRL7930, CRL7833, and HTB9) and 30 primary TCC of the bladder for the integrity of the FHIT transcript, using reverse transcriptase-polymerase chain reaction (RT-PCR) to investigate a potential role of the FHIT gene in TCC of the bladder. In addition, we tested expression of the Fhit protein in the six TCC-derived cell lines by Western blot analysis and in 85 specimens of primary TCCs by immunohistochemistry. Three of the six cell lines (50%) did not show the wild-type FHIT transcript, and Fhit protein was not detected in four of the six cell lines (67%) tested. Fhit expression also was correlated with pathological and clinical status. A significant correlation was observed between reduced Fhit expression and advanced stage of the tumors. Overall, 26 of 30 (87%) primary TCCs showed abnormal transcripts. Fhit protein was absent or greatly reduced in 61% of the TCCs analyzed by immunohistochemistry. These results suggested that loss of Fhit expression may be as important in the development of bladder cancer as it is for other neoplasms caused by environmental carcinogens.

Acid Anhydride Hydrolases↗

Total PSA, free PSA/total PSA ratio, and molecular PSA detection in prostate cancer: which is clinically effective and when?

OBJECTIVES: To ascertain when the serum determination of the free prostate-specific antigen (PSA)/total PSA (fPSA/tPSA) ratio is clinically useful, and whether the identification of PSA or prostate-specific membrane antigen (PSM) mRNA in circulating cells has diagnostic advantages over the determination of their protein product. METHODS: fPSA, tPSA, and the fPSA/tPSA ratio were determined in the sera of 50 men with benign nonprostatic urologic diseases (EPD), 112 patients with prostate cancer (PCa), and 218 with benign prostatic hyperplasia (BPH). mRNA was extracted from the circulating mononuclear cells of 13 EPD samples, 25 PCa samples, and 38 BPH samples. PSA and PSM mRNA signals were identified in these samples by means of reverse transcriptase-polymerase chain reaction. RESULTS: Overall, at a fixed specificity of 95%, the sensitivity of tPSA was 19% and that of the fPSA/tPSA ratio was 40% in distinguishing PCa from BPH. The fPSA/tPSA ratio allowed the discrimination of PCa from BPH with satisfactory sensitivity and specificity when considering patients less than 60 years of age (100% and 95%, respectively). PSA and PSM mRNA were positive in 1 and 7 of 13 EPD samples, 6 and 13 of 25 PCa samples, and 6 and 17 of 38 BPH samples. The Gleason score did not correlate with tPSA, the fPSA/tPSA ratio, PSA mRNA, or PSM mRNA. CONCLUSIONS: The serum determination of the fPSA/tPSA ratio is an excellent index of PCa for subjects younger than 60 years of age; the clinical utility of PSA mRNA identification in circulating cells needs to be validated by large follow-up studies, and the analysis of PSM mRNA seems to be of no clinical interest.

Aged↗

Quality of life after radical cystectomy and orthotopic bladder substitution: a comparison between Italian and Swedish men.

OBJECTIVE: To investigate possible differences between Italian and Swedish men in health-related quality of life (HRQL) after cystectomy and orthotopic bladder substitution for bladder cancer. PATIENTS AND METHODS: Thirty-three men in Padua, Italy and 33 in Lund, Sweden were assessed after respective mean postoperative periods of 42 and 52 months. Three questionnaires were used: (i) dealing with view-of-life issues; (ii) the core questionnaire QLQ-C30(+3) from the European Organization for Research and Treatment of Cancer, with added questions on urinary symptoms and sexuality; and (iii) one focusing on postoperative psychosocial and sexual adjustment. RESULTS: While Italian and Swedish men did not differ in their central values, they differed significantly in belief-related values, such as religion. Urinary problems and erectile dysfunction were common in both groups, the former possibly commoner in the Swedish men and the latter in the Italians. Changes in mood and self-esteem were common in both groups. On a visual analogue scale, the Italian men reported a worse present mood than the Swedish men, but expressed a more favourable outlook on their future. CONCLUSION: Despite differences in philosophical attitudes between Italian and Swedish men, there were no major differences in HRQL. Caution is required in interpreting these findings because there were few participants and the possible inadequacy of the methods used to evaluate the complex concept of quality of life.

Adult↗

Correlates of osteoporosis in chronic obstructive pulmonary disease.

The aim of this study was to analyse the correlates of reduced bone mineral density in patients with chronic obstructive pulmonary disease (COPD), with special regard to a possible protective role of hypercapnia. One hundred and four consecutive COPD inpatients in stabilized respiratory conditions underwent a comprehensive assessment of their health status. Bone mineral density was measured by X-ray absorptiometry at the lumbar site and at the femoral neck site. Differences in health-related variables between patients with (group O, n=62) and without (group N, n=42) lumbar and/or femoral neck osteoporosis were assessed first by univariate analysis and then by logistic regression analysis aimed to identify independent correlates of osteoporosis. Group O was characterized by worse nutritional status, as reflected by indices exploring either lean or fat mass, and by a trend towards lower forced expiratory volume in 1 sec/forced vital capacity ratio. Arterial tension of carbon dioxide lacked any correlation with bone mineral density. According to the logistic regression analysis, body mass index < or = 22 kg m(-2) qualified as the only and positive independent correlate of osteoporosis (odds ratio=4.18; 95% confidence intervals=1.19-14.71). In conclusion, malnutrition characterizes COPD patients with osteoporosis, while mild to moderate hypercapnia lacks either a positive or negative effect on bone mineral density. Longitudinal studies are needed to identify predictors rather than correlates of bone mineral density.

Absorptiometry, Photon↗

Modified induction course: a solution to side-effects?

Side-effects are commonly manifested during intravesical Bacillus Calmette-Guérin (BCG) immunotherapy of superficial bladder cancer. This often causes delays or interruptions of the instillations and consequently reduces the efficacy of treatment. Treatment strategies aimed at reducing the side-effects of BCG immunotherapy while maintaining efficacy are currently being considered in the search for an optimal treatment regimen. The following two approaches to BCG immunotherapy were investigated at the Department of Urology of Padova University by specific Phase II and III trials designed to evaluate the possibility of reducing BCG-related side-effects without compromising therapeutic efficacy: (1) by reducing the dose of BCG per instillation 'low-dose' regimen, (2) by delaying the interval of the instillations 'slow-rate' regimen.

Administration, Intravesical↗

[Traditional ultrasonography, directional Doppler power, and levovist in the morphological and functional evaluation of single kidney].

Either the color and the power Doppler have given important information on renal haemodynamics, but these methods are limited. The power directional Doppler (pdD) surpasses such limits; again, administration of Levovist increases the intensity of vascular signal. The aim of this study is the evaluation, in subjects with a solitary kidney, but without evident nephropathies, the morphology, the cortical vascularization and the functional status of the kidney. We studied 21 patients divided into three groups. Group A: subjects with normal renal function; group B: patients with caliceal and pielic dilation; group C: patient with chronic renal failure (CRF). In all subjects, a pdD was effected. Only in three patients it was necessary to administer Levovist, in order to emphasize the parenchymal vascularization. The A group subjects, on echographic B-mode examination, presented a normal morphology and volume of the kidney; on pdD exam, a regular intense and homogeneous parenchymal vascularization, with resistance index (RI) = 0.53 divided by 0.66. In B group, pdD showed an irregular vascularization, with RI > 0.7; also the glomerular filtration rate (GFR) was reduced (70 ml/min). In C group, at the pdD it was relevant a reduced and irregular vascularization in whole renal tissue. If possible, the echographic B-mode examination must be completed with the pdD, with or without Levovist, in order to identify unknown renal pathologies, moreover in subjects with a single kidney.

Adult↗

Effect of total androgen ablation on pathologic stage and resection limit status of prostate cancer. Initial results of the Italian PROSIT study.

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%, respectively). The initial results of this study suggest that total androgen ablation before RP is beneficial in men with clinical stage B because of the significant pathological downstaging and decrease in the number of positive margins in the RP specimens. These two effects are more pronounced after six months of NHT than after three months of therapy. The same degree of beneficial effects are not observed in clinical C tumours.

Adenocarcinoma↗

Body mass index and mortality among older people living in the community.

OBJECTIVES: To determine if body mass index (BMI = weight/height2), predictive of mortality in seriously ill hospitalized and institutionalized patients, is also predictive of mortality in a longitudinal epidemiologic study. DESIGN: A prospective cohort study. SETTING: Rovereto, a town in northern Italy. PARTICIPANTS: A consecutive sample of 214 patients aged 81.2 +/- 7.3 years receiving community care services. MAIN OUTCOME MEASURES: Malnutrition and mortality. RESULTS: According to logistic regression analysis, malnutrition status, expressed by a BMI < 22 Kg/m2, was correlated with dependency in Activity of Daily Living (odds ratio 1.21; 95% confidence interval (CI) 1.01-1.45). Only a low BMI was associated with 1-year survival in Cox regression analysis, after adjusting for potential confounders (relative risk 0.85; 95%CI, 0.74-0.97). A high BMI (>27 Kg/m2) was not significantly related to risk of mortality. CONCLUSIONS: Nutrition variables are a cardinal component of comprehensive geriatric assessment. Our results suggest that BMI, a simple anthropometric measure of nutritional status, is an important predictor of mortality among older people living in the community. Even when controlling for clinical and functional variables, a low BMI remained a significant and independent predictor of shortened survival.

Activities of Daily Living↗

Comparison of the BTA stat test with voided urine cytology and bladder wash cytology in the diagnosis and monitoring of bladder cancer.

OBJECTIVE: To compare the BTA stat test (BTA stat), a new one-step immunochromatographic assay that can be performed in the urologist's office or in the laboratory, to voided urine cytology and bladder wash cytology (cytology) in the diagnosis and monitoring of cancer of the bladder (BC). METHODS: BTA stat and cytology were performed in a double-blinded, prospective, clinical study on specimens from 240 subjects (68 females; mean age of subjects: 64 years) suspected of having BC. RESULTS: In 107 subjects with final diagnoses of BC confirmed by cystoscopy or cystoscopy and biopsy, the overall sensitivities of BTA stat and cytology were 65 and 33%, respectively. For tumor grades I, II, and III, the sensitivities of BTA stat were 39, 67 and 83%, respectively. Those of cytology were 4, 20 and 69%. Nine subjects had a diagnosis of 'suspicious for bladder cancer'. The specificities of BTA stat and cytology in the 124 subjects without BC were 64 and 99%, respectively. In the subjects with a history of BC (n = 74), the specificities of BTA stat and cytology were 72 and 99%, respectively. The specificity of BTA stat was lower in subjects with benign or malignant genitourinary disease other than BC (46%) than in subjects without genitourinary disease (71%). CONCLUSIONS: The BTA stat test is considerably more sensitive than cytology in the detection of BC and can replace cytology as an adjunct to cystoscopy in the diagnosis and follow-up of patients with BC. However, due to low specificity, BTA stat should not be used without first ruling out potential interferences such as infections, renal disease and cancer, or genitourinary trauma.

Adult↗

Abnormal patterns of mucin secretion in ileal neobladder mucosa: evidence of preneoplastic lesion?

In gastric and colonic mucosa the abnormal pattern of mucin secretion has been related to an increased risk of malignant changes. The short- and long-term histologic and histochemical changes in the mucin content of the ileal mucosa have been studied in 180 biopsies from 90 male patients 6-96 months after radical cystectomy and urinary diversion via an orthotopic neobladder. Up to 3 years after surgery, histologic changes comprise a shortening of the villi and an increase in the number of goblet cells. Concomitantly, an abnormal pattern of mucin secretion, with a predominant secretion of sulfomucins, is demonstrable. After 3 years of follow-up, the mucosa progressively flattens and mucin production reduces; after 6 years, the prevalent finding is a flat, avillous epithelium without evidence of mucin secretion. There was no dysplasia or malignancies in any of the patients. The changes in the pattern of mucin production are not potential preneoplastic lesions, but represent a transient defence mechanism of the ileal mucosa exposed to urine.

Aged↗

Multicenter trial of the quantitative BTA TRAK assay in the detection of bladder cancer.

BACKGROUND: Human complement factor H-related protein (hCFHrp) is produced by several bladder cancer cell lines and may be useful as a cancer marker. The aim of this study was to compare urinary hCFHrp and cytology for the detection of bladder cancer found by cystoscopy in patients with suggestive signs, symptoms, or preliminary test results. METHODS: The BTA TRAK assay, a quantitative enzyme immunoassay for the bladder tumor-associated antigen in urine, was compared with exfoliative cytology in 220 patients (155 men, 65 women; mean age, 64.2 years) presenting with signs, symptoms, or preliminary diagnostic results suggestive of this disease. Cystoscopy was the standard of detection. RESULTS: In the 100 patients found to have bladder cancer, the overall sensitivities of the BTA TRAK assay (at a previously determined decision threshold of 14 kilounits/L) and cytology were 66% (66 of 100) and 33% (33 of 100), respectively (P <0.001). The BTA TRAK assay proved to be statistically more sensitive than cytology for tumor grades I and II and for stage Ta and T1 tumors. In contrast, the overall specificity of the BTA TRAK assay in the 120 patients without cystoscopically confirmed bladder cancer was 69% (83 of 120) and that of cytology was 99% (119 of 120; P <0.001). The specificity of the BTA TRAK assay was higher in patients without benign or malignant genitourinary disease other than bladder cancer (76%; n = 89) than in patients with these conditions. When the BTA TRAK assay and cytology were used together such that a positive result in either test was scored as positive and the results compared with those of the BTA TRAK assay alone, increases in overall sensitivity and equivalent specificity were observed. CONCLUSION: Because of its relatively high sensitivity, the BTA TRAK assay could complement cytology as an adjunct to cystoscopy in the diagnosis and follow-up of most patients with bladder cancer.

Adult↗

Prognostic factors of outcome after radical cystectomy for bladder cancer: a retrospective study of a homogeneous patient cohort.

PURPOSE: Pathological predictors of outcome for patients undergoing radical cystectomy for bladder cancer are needed as few data are available in the literature. We retrospectively analyzed a homogeneous and contemporary series of patients treated with radical surgery as monotherapy for bladder cancer to identify the independent predictors of survival. MATERIALS AND METHODS: We evaluated 369 of 535 patients with bladder cancer treated with radical cystectomy, pelvic node dissection and urinary diversion by the same staff at a single institution between February 1982 and February 1994. Patients treated with radiation therapy and/or chemotherapy, and those who did not undergo formal pelvic node dissection were excluded from study. The end point of univariate and multivariate analyses was the overall 5-year survival. RESULTS: Univariate analysis revealed that tumor stage, nodal involvement, ureteral obstruction, and vascular, lymphatic and perineural invasion were prognostic predictors of survival (p <0.05). However, only tumor stage (p <0.0000) and nodal involvement (p <0.0000) were independent prognostic variables of survival on multivariate analysis. CONCLUSIONS: Tumor stage and nodal involvement are the only independent predictors of survival to be used to select the optimal therapy after radical cystectomy, stratify patients in controlled trials and evaluate new prognostic factors.

Adult↗

[Synchronous and metachronous bilateral tumors of the testis: a single institution experience of 11 cases and review of the literature].

Bilateral testicular tumors represent a very rare event and account for 2.7% of all testicular neoplasms. 15% of bilateral testicular tumors occurs simultaneously in both testicles, but in 85% of cases the second neoplasia appears in the remaining testicles of patients affected by unilateral testicular tumor after a very variable period of time. The aim of this work was to value our experience on 11 cases of bilateral testis tumors: six arised simultaneously in both gonads (five germ cell tumors and one Leydig cell tumor) and five with metachronous appearance (all germ cell tumors). A comprehensive valuation has been made considering other cases reported in literature until 1996, in order to identify predisposing conditions to bilateral disease. Examining separately synchronous and metachronous neoplasms, as far as we know, only 218 cases of simultaneous bilateral testicular tumors are reported in literature, and most of them are pure seminomas; however, after 1988 this result has been reversed in favour of neoplasms with non-seminomatous elements: this data suggests inadequate classification in the past. Moreover, considering 243 cases of metachronous neoplasms, 126 of them (51.9%) began as non-seminomatous tumors: this disagrees with an old belief that patients affected by seminoma are more prone to develop a second tumor in the remaining testicle. It has been also possible to confirm that testis sparing surgery allows to maintain both fertility and endocrinous function. This technique can be used in any potentially benign neoplasms (as Leydig cell tumors) while the same treatment modality, although already reported in literature, needs more experience to be considered as a successful therapy for germinal tumors.

Adolescent↗