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F Pagano

Publications and source records attributed to F Pagano.

At least 37 records · Page 2Linked to original sources

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↗

Double-blind, placebo-controlled trial to assess the efficacy and tolerability of mepartricin in the treatment of BPH.

BACKGROUND: Mepartricin, a semisynthetic polyene derivative with a favorable effect on urethro-prostatic function, was clinically evaluated, adopting the diagnostic and research criteria recommended by the First International Consultation on BPH. METHODS: A multicenter, randomized, double-blind, parallel-group study compared mepartricin 40 mg/daily to placebo in the treatment of 196 patients with newly diagnosed BPH and mild-to-moderate symptomatology. International Prostate Symptom Score (I-PSS), quality of life (QoL) index and maximum urinary flow-rate (Qmax) were determined every 4 weeks for 6 months; postvoiding volume, prostate volume, and prostate-specific antigen (PSA) were assessed after 3 and 6 months of therapy. RESULTS: Mepartricin was shown to determine a statistically significant improvement over placebo in I-PSS and QoL index from month 2 onwards, and a significant linear increase in Qmax over the study period. At month 6, the improvement in the mepartricin and placebo groups in I-PSS, QoL index, and Qmax was 6.3 (standard error (SE) 0.51) and 4.2 (SE 0.60) points (P = 0.003), 0.99 (SE 0.14) and 0.62 (SE 0.12) points (P = 0.036), and 2.7 (SE 0.46) and 1.2 (SE 0.46) ml/sec (P = 0.051), respectively. No significant differences were noted in postvoiding residual volume, prostate volume, or PSA. Mepartricin tolerability was good, showing no adverse events on sexual function. CONCLUSIONS: Mepartricin proved to be an effective treatment of benign prostatic hyperplasia, determining an improvement in symptoms, quality of life, and peak urinary flow.

Aged↗

Duplication and overexpression of the mutant allele of the MET proto-oncogene in multiple hereditary papillary renal cell tumours.

Previous karyotyping showed a combined trisomy of chromosome 7 and 17 in sporadic and hereditary papillary renal cell tumours (RCT). A recent molecular analysis revealed a mutation in the MET tyrosine kinase (chromosome 7q31) in the germline of four out of seven families with hereditary papillary RCT (HPRCT). We have analysed germline cells as well as multiple tumours obtained from HPRCT families and sporadic cases for alteration of the MET tyrosine kinase and for allelic duplication at chromosome 7 and 17. We have detected a germ line mutation in the MET tyrosine kinase in one of the two families with HPRCTs and also found the same mutation in the germ line of one patient with clinically recognized multiple, bilateral papillary RCTs but without family history. The mutant MET allele is consequently duplicated and overexpressed in tumour cells indicating that duplication of the mutant MET allele is necessary before cells enter the tumorigenic pathway. The lack of germline mutation in two members of another HPRT family and duplication of the same parental allele of chromosome 7 in multiple tumours suggests that a germ line event other than mutation of MET tyrosine kinase is involved in the development of these tumours. Duplication of different alleles of chromosome 7 in sporadic and of chromosome 17 in both types of tumours excludes a germline mutation at these chromosomal sites.

Adenoma↗

Changes in nutritional status during the hospital stay: a predictor of long-term survival.

The objectives of this prospective observational study were to assess whether: 1) midarm circumference (MAC), previously shown to predict in-hospital mortality, maintains its prognostic implication after discharge; 2) in-hospital changes in aspecific indicators of the health status are predictors of long-term survival. The study population consisted of 249 patients from the general community [mean age 80 +/- 7 (70-99) years], consecutively discharged from geriatric and medical wards of an acute care hospital. Changes in health status during hospitalization were recorded (dynamic or delta variables) and health-related variables were collected at discharge (discharge variables). The relationship of both sets of variables to survival over a 3-year period was assessed by Cox's proportional hazards regression analysis. The discriminatory efficacy of predictive models was estimated by the Hanley and McNeil method. Survival curves were drawn with the patients alternatively grouped according to the presence or absence of each of the predictive variables. Serum albumin < 3.5 g/dL (hazard rate = 0.57, 95% confidence limits = 0.33-0.96) and dependency in at least one ADL (h.r. = 0.87, c.l. = 0.79-0.98) were found to be associated with increased mortality, and delta MAC (h.r. = 1.03, c.l. = 1.01-1.05), i.e., there was a positive change or no change in MAC from admission to discharge, with increased survival. A slightly weaker predictive model was obtained using only discharge variables. However, Hanley and McNeil's analysis showed that both models were far from achieving the optimal discrimination of high from low risk subjects. Effects on survival of individual variables varied in magnitude and dependency on time. We concluded that measuring in-hospital changes in nutritional status might improve prediction of long-term survival. Attempts should be made to identify variables having the strongest prognostic implications, and to tailor dynamic assessment to the needs of selected categories of patients.

Activities of Daily Living↗

Functional response of cavernosal tissue to distension.

We studied rabbit isolated erectile tissue responses to changes in preload and to active tension development with norepinephrine. The effects of antagonists of endothelin-1, prostaglandins E2 and F2alpha and of nitric oxide were also tested on normal and de-endothelialized preparations. Tissue distension was found to elicit spontaneous rhythmic contractions. Increase in preload diminished the latency of the spontaneous activity and augmented the developed force. Active tension development and the inhibitor of the Na+,K+ pump, ouabain, opposed the spontaneous activity. A marked reduction in the resting tension with abolition of the spontaneous activity was observed on normal, but not on de-endothelialized tissues, following the addition of the specific prostaglandin E2 and F2alpha receptor antagonist, SC-19220. At 3 x 10(-4) M, the highest concentration used, the endothelin-A receptor antagonist BQ-123 failed to change the pattern of the spontaneous activity and the resting tension of normal tissues. The nitric oxide synthesis inhibitor, L-NAME, did not produce reliable effects. These findings point to a causal relation between cavernosal tissue distension and phasic and tonic contractions. Phasic contractions appear to be elicited by smooth muscle cells through the enzyme Na+,K+-ATPase. Increase in the resting tone could be mediated, at least in part, by the endothelium, through the release of prostaglandins E2 and/or F2alpha but not of endothelins. We discuss the hypothesis that, in cavernosal tissue, mechanotransduction of distension to contractile responses is an important determinant of detumescence.

Acetylcholine↗

Morphometric analysis of the fibroadipose tissue of the female pelvis.

PURPOSE: The structure of the retroperitoneal connective tissue of the female pelvis was evaluated to determine whether its spatial arrangement may have a role in supporting the pelvic viscera. MATERIALS AND METHODS: After in situ formalin fixation the pelvic viscera with the surrounding connective tissue were removed together with the pelvic floor from 18 female cadavers 48 to 68 years old. Serial macrosections of the bladder base, cervix, lower rectum and pelvic floor complex, cut in coronal (4 cases) and horizontal (10 cases) planes, were stained with azan-Mallory, and the remaining 4 were cut in the horizontal plane and plastinated using von Hagens E12 technique. Morphometry of the retroperitoneal connective tissue was performed using a computerized system for image analysis connected through a black and white television camera to an optic microscope. The diameters of the adipose lobules and density of the connective tissue were evaluated in the proximity of the visceral adventitia and the parietal pelvic fascia, respectively. RESULTS: The retroperitoneal connective tissue of the female pelvis consists of varying amounts of adipose tissue divided into small lobules by thin connective laminae. These laminae are connected to the visceral and parietal layers of the pelvic fascia, and are closely connected to the vascular and nervous bundle sheaths crossing the pelvis. At the level of the sacrouterine and cardinal ligaments we were unable to find any connective ligamentous structure. Only an areolar tissue was seen, which after removal of the lipids demonstrated a fibrillar structure. The mean area of the adipose lobules was smaller (average of 1.41 mm.2) near the viscera with respect to the lateral retroperitoneal connective tissue (average of 1.73 mm.2) due to greater ramification of the connective laminae. CONCLUSIONS: In the absence of real connective ligaments the retroperitoneal connective tissue forms a 3-dimensional network of thin connective laminae that are connected to the visceral adventitia, parietal layer of the pelvic fascia and neurovascular bundles crossing the pelvis. These connective laminae are bounding adipose lobules of different size (smaller near the viscera, larger at the periphery). Overall, the retroperitoneal connective tissue constitutes an anatomical structure that, beyond the functional limits of any individual ligament, may have supporting properties.

Aged↗

Structural and ultrastructural changes in ileal neobladder mucosa: a 7-year follow-up.

OBJECTIVE: To investigate the long-term morphological changes in the intestinal segment used to create an orthotopic ileal neobladder. MATERIALS AND METHODS: Periodic endoscopy with biopsy of the ileal mucosa was performed in 90 patients 3-84 months after radical cystectomy and urinary diversion via an orthotopic neobladder. Three cold-cup biopsies were taken from each patient and mucosal specimens processed for light and electronic microscopy. RESULTS: Early changes (up to 1 year after surgery) comprised a marked shortening of the villi with loss of microvilli. After 4 years, the prevalent finding was of flat, avillous epithelium that tended to stratify in some areas. The avillous areas were mixed with islets of villous mucosa. There was no dysplasia or malignancy in any of the 90 patients. CONCLUSIONS: Prolonged contact with urine elicited a biphasic response in the ileal mucosa, i.e. an early inflammatory phase, ascribed to the noxious action of urine, followed by a regressive phase in which the epithelium tended to assume a morphology similar to the urothelium. The atrophic changes were almost totally completed after 4 years, although areas with marked modifications alternated with others where the morphology was normal, even many years after surgery. Late changes in the ileal neobladder mucosa appear to be an expression of a functional adaptation of the mucosa to the new environment.

Follow-Up Studies↗

Comparison of LH-RH analogue 1-month depot and 3-month depot by their hormone levels and pharmacokinetic profile in patients with advanced prostate cancer.

In an open, randomized phase II pharmacokinetic study conducted in Germany and Italy, a total of 42 patients with advanced or metastatic prostate cancer (PCa) were treated for 9 months with the luteinizing hormone-releasing hormone analogue (LH-RH-a) leuprorelin acetate depot in two different formulations. Fifteen patients received the 1-month depot and 27 patients received the newly developed 3-month depot, containing 3.75 mg and 11.25 mg, respectively. In both groups, subcutaneous injections of leuprorelin acetate injected monthly or at 3-month intervals produced a complete down-regulation of the pituitary and led to persistent suppression of testosterone and dihydrotestosterone to the castrate range (< or = 50 ng/dl for testosterone) within the first month of treatment, which thereafter could be maintained over the entire observation period of 9 months. In 10 patients, pretreatment with an antiandrogen for the prevention of clinical flare-up resulted in a slightly more profound and earlier drop in serum testosterone. The 3-month depot showed a higher median peak serum concentration (Cmax) of leuprorelin at 20.8 ng/ml than the 1-month depot at 10.7 ng/ml but, conversely, this did not influence the rise in serum testosterone levels. Cmax occurred at 3 h for the 3-month and at 1 h for the 1-month depot formulation. During the steady state, constant release could be detected, starting on day 3 and day 7 for the 1-month and 3-month depot, respectively. A marked decrease in median prostate-specific antigen levels of 97.8% (1-month depot) and 96.6% (3-month depot) compared with baseline was observed, indicating an objective clinical response for more than 80% of all patients in both arms. Based on European Organization for Research and Treatment of Cancer criteria, the best response in terms of complete/partial remissions and stabilization was comparable in the two arms at 86.7% (1-month depot) and 85.2% (3-month depot). 6.7% in the 1-month group and 3% in the 3-month depot group showed progression of the disease. The most common side effects in both treatment groups were related to hormone deprivation. Both formulations of the potent LH-RH-a leuprorelin acetate were highly effective in the treatment of advanced PCa and led to comparable endocrine and clinical effects.

Aged↗

Bone density and skeletal metabolism are altered in idiopathic hypercalciuria.

OBJECTIVE: To study bone density in hypercalciuric patients, when classified according to the main metabolic defect. METHODS: We studied 49 patients, aged 19-60 years with calcium stones and idiopathic hypercalcuria. All subjects underwent an evaluation of mineral metabolism and a spinal and femoral DEXA measurement. Then, patients were classified as having Fasting (FH, 31 subjects) or Absorptive (AH, 18 patients) Hypercalciuria according to a standard oral calcium load. RESULTS: Spinal bone density was lower only in FH patients as compared to controls (p <0.001). Bone alkaline phosphatase and urine hydroxyproline were higher with respect to controls only in patients with FH (p <0.005 and p <0.015, respectively). After low calcium diet, hydroxyproline excretion continued to be higher in FH patients (p <0.05). Although in the normal range, serum and urine uric acid were higher in hypercalciuric subjects (p <0.03 and p <0.005, respectively); blood pH was lower in hypercalciuric patients than in controls (p <0.01). In FH patients urine hydroxyproline negatively correlated with spinal and femoral density (p <0.001 and p <0.005, respectively), and blood pH positively correlated with spinal density. CONCLUSIONS: a disordered bone metabolism and bone loss are present only in patients with fasting hypercalciuria. An excessive acid load, possibly of dietary origin, might be involved as a pathogenetic factor.

Absorptiometry, Photon↗

Neuropsychologic effects of carotid endarterectomy.

This study assessed neuropsychologic changes after internal carotid endarterectomy using a design that limited the confounding effects of surgical and anesthesiological stress. Twenty-eight patients (mean age = 65.9 years, SD = 8.4, range 45-79), underwent extensive neuropsychological assessment before and on the seventh day after carotid endarterectomy for symptomatic carotid stenosis greater than 75%. A similarly assessed control group of 30 patients underwent elective orthopaedic surgery. A third cognitive assessment was performed 4 months postoperatively on a subgroup of the study patients. No significant cognitive change occurred in the control group. The study patients showed significant improvement in verbal memory, constructive abilities, verbal attainment, and visual attention; a trend towards further improvement of verbal functions was evident at the late postoperative assessment. No side-specific cognitive change was observed. In conclusion, carotid endarterectomy performed for currently accepted indications significantly improves several cognitive functions.

Aged↗

Bone density and skeletal metabolism in patients with orthotopic ileal neobladder.

The interposition of a bowel segment as a bladder substitute into the urinary tract may result in impaired calcium metabolism. We studied 25 male patients (aged 45 to 77 yr) who had undergone a Vescica Ileale Padovana (VIP) reconstruction following cystectomy 29 to 75 mo before. Bone mineral density of the spine and femur was measured by dual x-ray absorptiometry. Blood and 24-h urine samples were analyzed for the main parameters of bone metabolism. Sixteen healthy men were enrolled as a control group. Although blood pH did not differ between patients and control subjects, VIP subjects showed lower levels of plasma HCO3- (P < 0.005) and higher serum chloride (P < 0.001). Bone alkaline phosphatase was higher (P < 0.001), and urine calcium, phosphate, and creatinine levels were lower in VIP patients (P < 0.01, P < 0.01, and P < 0.05, respectively). Bone mineral density at the femoral neck (P < 0.03) and Ward's triangle (P < 0.05) was decreased in VIP patients. When subdivided according to time since operation, patients who had the ileal neobladder implanted for a shorter period of time showed lower blood pH (P < 0.03) and urine calcium (P < 0.05) levels and higher urinary hydroxyproline (P < 0.02). Duration of the ileal neobladder was positively correlated with PTH (r = 0.46, P < 0.03) and blood pH (r = 0.47, P < 0.02). Furthermore, pH values were positively correlated with urine calcium (r = 0.48, P < 0.02). In conclusion, in patients with ileal neobladder, a mild metabolic acidosis is responsible for an increased bone turnover and lower bone mass. Moreover, a decrease over time in the absorption capacity of the ileal pouch might result in calcium malabsorption, which represents an additional risk factor for reduced bone mass in these patients.

Aged↗

Time-dependent remodeling of the bladder wall in growing rabbits after partial outlet obstruction.

PURPOSE: We asked whether a urethral constriction gradually developed during growth would give rise to a structural remodeling of the bladder wall distinct from that of the mature rabbits in terms of cellular response. MATERIALS AND METHODS: We examined the serosa and detrusor muscle in immature rabbits whose urethra was obstructed at 30 days postnatal and studied 7 to 30 days after partial outlet obstruction. Morphometry, bromo-deoxyuridine (BrdU) incorporation, Western blotting and immunocytochemical staining with a panel of monoclonal antibodies specific to selected cytoskeletal, cytocontractile and membrane-related proteins unique to non-muscle and smooth muscle cells (SMC) were used to analyze the effects of obstruction on the differentiation pattern. RESULTS: In comparison with results in adult obstructed bladders, we have found that in growing rabbits: (1) the cell conversion from fibroblasts to SMC, occurring within the 'extrinsic' region of serosal thickening, takes place earlier; (2) newly formed SMC are localized exclusively to the thickened serosa, and can group in bundles depending on the density of the regional innervation; (3) the peak level of BrdU incorporation is more elevated than in the adult bladder wall; and (4) change in the phenotypic profile of SMC of detrusor muscle is delayed. CONCLUSION: These data indicate that the basic features of structural remodeling in the two models are similar, though partial outlet obstruction produced in growing animals accelerates the fibroblast conversion to SMC and their spatial, differentiation-specific arrangement in the serosa. The late phenotypic changes in obstructed detrusor muscle correlate with the decline of the DNA synthesis level after an initial burst and strongly suggest that newly formed SMC in the serosa do not derive from pre-existing SMC.

Animals↗