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Biomedical subjects

Marco Carini

Publications and source records attributed to Marco Carini.

At least 19 recordsLinked to original sources

Physical activity of men with chronic prostatitis/chronic pelvic pain syndrome not satisfied with conventional treatments--could it represent a valid option? The physical activity and male pelvic pain trial: a double-blind, randomized study.

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome is a major healthcare burden. Affected patient quality of life is poor and currently no investigated treatments have significant long-term benefit. We performed a preliminary investigation of the role of physical activity and its effects on select patients with chronic prostatitis/chronic pelvic pain syndrome. MATERIALS AND METHODS: Between 2002 and 2004 we recruited a volunteer sample of 231 eligible males 20 to 50 years old with chronic prostatitis/chronic pelvic pain syndrome who were unresponsive to conventional treatments and free of any contraindication for moderate intensity physical exercise. This group was screened and, if in accordance with study inclusion/exclusion criteria, patients were randomized into 2 groups. Participants were randomly assigned to the aerobic exercise group (52) and the placebo/stretching and motion exercises group (51). Main outcome measures were the Italian version of the National Institutes of Health Chronic Prostatitis Symptom Index, Beck Depression Inventory, State Anxiety Inventory-Y and a pain intensity visual analog scale administered at baseline, and 6 and 18 weeks. RESULTS: At 18 weeks 36 subjects (75%) in the aerobic exercise group vs 40 (81.63%) in the placebo/stretching and motion exercises group completed the 18-week program and evaluation. Differences between the 2 groups were found in total National Institutes of Health Chronic Prostatitis Symptom Index, pain and quality life impact subscales, and pain visual analog score (ANCOVA p = 0.006, 0.0009, 0.02 and 0.003, respectively). CONCLUSIONS: Improvements in the aerobic exercise group were significantly superior compared to those in the placebo/stretching and motion exercises group. Aerobic exercise represents a valid treatment option and it should be further investigated in a larger study with longer followup.

Adult↗

Characterization and functional role of androgen-dependent PDE5 activity in the bladder.

Benign prostate hyperplasia is the most common disease in the aging male, often comorbid with erectile dysfunction. Phosphodiesterase type 5 (PDE5) inhibitors (sildenafil, tadalafil, and vardenafil) decrease lower urinary tract symptoms in patients with erectile dysfunction and BPH. We studied PDE5 expression and activity in the human bladder and PDE5i effects both in vitro (human and rat) and in vivo (rat). PDE5 is highly expressed in rat and human bladder and immunolocalized in vascular endothelium and muscle fibers. Sildenafil, tadalafil, and vardenafil blocked 70% of the total cGMP-catabolizing activity; vardenafil was the most potent (IC(50) = 0.3 nm). In human bladder cells and in rat strips, a PDE-resistant cGMP analog, SP-8-Br-PET-cGMPS, induced, respectively, a consistent antiproliferative and relaxant effect. In contrast, the nitric oxide donor sodium nitroprusside (SNP) was almost ineffective. However, blocking PDE5 with vardenafil increased SNP antiproliferative and relaxant activity up to the level observed with SP-8-Br-PET-cGMPS. We also found that castration decreased, and T supplementation restored, PDE5 gene expression in rat bladder. Accordingly, bladder strips from castrated rats were more sensitive to SNP-induced relaxation than strips from control or T-replaced rats, whereas in the presence of vardenafil, all groups showed the same SNP sensitivity. To discover whether vardenafil affects bladder activity in vivo, the rat bladder outlet obstruction model was used. Chronic treatment with 10 mg/kg.d vardenafil significantly reduced nonvoiding contractions (47%, P < 0.05 vs. placebo) up to tamsulosin level (51%). Overall, these results demonstrate that PDE5 regulates bladder smooth muscle tone, strongly limiting the nitric oxide/cGMP signaling, and that vardenafil, by blocking PDE5, may be a possible therapeutic option for bladder dysfunction by ameliorating irritative lower urinary tract symptoms.

3',5'-Cyclic-GMP Phosphodiesterases↗

Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

AC133 Antigen↗

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia.

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.

Adult↗

Alfuzosin (10 mg) does not affect blood pressure in young healthy men.

OBJECTIVES: Alfuzosin 10mg is a uroselective alpha(1)-adrenoceptor antagonist used to treat lower urinary tract symptoms suggestive of benign prostatic hyperplasia. Recent studies have suggested the potential efficacy of alfuzosin in the treatment of distal ureteral stones and prostatitis syndrome, two conditions frequently encountered in young patients. The objective of this study was to evaluate the effect of 10mg alfuzosin on blood pressure (BP) and heart rate (HR) in young healthy volunteers. MATERIALS AND METHODS: In a randomized, double-blind, placebo-controlled, crossover study, the effect of alfuzosin 10mg on BP and HR was evaluated in 14 male volunteers (mean age: 28 yr; range: 24-30). BP<135/85 obtained in two separated measurements was a main inclusion criterion. Patients were then randomized to alfuzosin (10mg once a day) or placebo for 1 wk, followed by a washout week, and then crossed over to the other treatment. Patients were instructed to self-measure systolic (SBP) and diastolic (DBP) blood pressure and HR every hour between 8am and 8pm during the first and the last day of each cycle treatment. RESULTS: All 14 enrolled volunteers completed the study. No significant difference in either SBP, DBP, or HR was observed between the placebo and alfuzosin groups at baseline. Alfuzosin did not affect SBP, DBP, or HR. No hypotensive episode (SBP reduction >10%) was recorded during each treatment. CONCLUSIONS: This study shows that alfuzosin 10mg is well tolerated by young healthy subjects and may therefore be safely administered to young normotensive patients affected by distal ureteral stones and prostatitis.

Adrenergic alpha-Antagonists↗

Simple enucleation for the treatment of PT1a renal cell carcinoma: our 20-year experience.

OBJECTIVES: To evaluate the safety and efficacy of simple enucleation as a conservative treatment for pT1a RCC, and to report on the incidence of major complications, local recurrence, and progression-free and disease-specific survival rates. METHODS: We retrospectively reviewed the data of 232 patients who had nephron-sparing surgery (NSS) by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed pT1a RCC. The patients' status was evaluated last in September 2005. The mean (median, range) follow-up was 76 (61, 12-225) months. RESULTS: The mean (SD, median, range) tumor greatest dimension was 2.8 (0.78, 2.85, 0.6-4) cm. The histopathologic review according to the International Union Against Cancer and American Joint Commission for Cancer (1997) classification revealed 198 clear cell (85.3%), 18 papillary (7.8%), 15 chromophobe (6.5%) and one (0.4%) collecting duct RCCs. There were no major complications, such as prolonged acute tubular necrosis/chronic renal insufficiency and bleeding requiring open reoperation. One patient developed postoperative late retroperitoneal fluid collection consistent with urinoma, which required aspiration, drainage position and JJ stenting for 3 weeks. The 5- and 10-year cancer-specific survival were 96.7% and 94.7%, respectively. The 5- and 10-year progression-free survival were 96% and 94%, respectively. Overall, 13 (6.4%) patients had disease progression, three of whom had local recurrences alone (1.5%) elsewhere in the kidney; none had local recurrence at the level of the enucleation bed. CONCLUSIONS: Simple tumor enucleation is a safe and acceptable nephron-sparing treatment that provides excellent long-term local control and cancer-specific survival rates.

Adult↗

Cancer progression after anterograde radical prostatectomy for pathologic Gleason score 8 to 10 and influence of concomitant variables.

OBJECTIVES: To evaluate the outcome in patients with clinically localized prostate cancer and pathologic Gleason score 8 to 10 disease treated by anterograde radical prostatectomy, either alone for node-negative disease or with early hormonal therapy for node-positive disease, and to characterize the prognostic significance of other pathologic variables. METHODS: A total of 729 patients underwent radical prostatectomy for clinically localized prostate cancer between 1989 and 2003. We identified 116 patients (15.9%) with specimen Gleason score 8 or greater. The mean follow-up was 48 months (range 6 to 145). RESULTS: The 5-year biochemical-free survival rate for those with pT2, pT3a, and pT3b diseases was 100%, 65.1%, and 10.5%, respectively (P < or =0.05). The 5-year biochemical-free survival rate for those with specimen Gleason score 8 and 9 was 72.1% and 38.2%, respectively (P < or =0.05). The incidence of positive surgical margins was 14.6% and led to a high pT3a specimen-confined detection rate. The preoperative prostate-specific antigen level, primary Gleason pattern, and surgical margin status had no statistically significant impact on biochemical recurrence-free survival. The multivariate Cox model showed seminal vesicle invasion to be the only independent prognostic factor. The 3 and 5-year progression-free survival rate of the 45 node-positive patients was 72.6% and 60.5%, respectively. CONCLUSIONS: Our findings emphasize the need for early diagnosis, which can make this disease curable by radical prostatectomy alone, and show that poorly differentiated prostate cancer that has invaded the capsule can be cured by surgery. Biochemical recurrence represented a common event in pT3b and Gleason score 9 disease, suggesting a possible role for early adjuvant treatment.

Aged↗

Simple enucleation for the treatment of renal cell carcinoma between 4 and 7 cm in greatest dimension: progression and long-term survival.

PURPOSE: We present our findings in a series of patients treated with simple enucleation for RCC 4 to 7 cm in greatest dimension. We specifically report the incidence of local and systemic recurrence, and the disease specific survival rate. MATERIALS AND METHODS: We retrospectively reviewed clinical and pathological data on 71 patients who underwent nephron sparing surgery by simple enucleation between 1986 and 2004 for sporadic, unilateral, pathologically confirmed, 4 to 7 cm RCC. Patients with a solitary kidney due to previous RCC treated with radical nephrectomy were excluded from study. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free of distant metastases before surgery (M0). Patient status was last evaluated in May 2005. Mean followup was 74 months (median 51, range 12 to 225). RESULTS: Pathological review according to the 2002 TNM classification showed that 42% of the tumors (30 of 71) were pT1a, 44% (31 of 71) were pT1b and 14% (10 of 71) were pT3a. Mean tumor greatest dimension +/- SD was 4.7 +/- 0.81 cm (median 4.5, range 4.0 to 7.0) cm. None of the patients died within the first 30 days of surgery. There were no major complications requiring open reoperation, such as bleeding and urinary leakage/urinoma. Five and 8-year cancer specific survival was 85.1% and 81.6%, respectively. Five-year cancer specific survival in patients with pT1a (4 cm), pT1b and pT3a disease was 95.7%, 83.3% and 58.3%, respectively (pT1a vs pT1b p = 0.254, pT1a vs pT3a p = 0.006 and pT1b vs pT3a p = 0.143). Overall 10 patients experienced progressive disease (14.9%), of whom 3 had local recurrence (4.5%) alone or local recurrence associated with distant metastases. CONCLUSIONS: Simple tumor enucleation is a useful and acceptable approach to nephron sparing surgery for 4 to 7 cm RCC. It provides long-term cancer specific survival rates similar to those of radical nephrectomy and is not associated with a greater risk of local recurrence than partial nephrectomy for RCC less than 4 cm in greatest dimension.

Adult↗

Enterogenous cyst of the testis.

Enterogenous cyst is a rare congenital lesion generally located in the mediastinum or the abdominal cavity. We reported the first case of testicular enterogenous cyst in a 55-year-old white male presented with testicular pain and a gradually enlarging left scrotal mass with a 2-week duration.

Cysts↗

Intravesical gemcitabine in BCG-refractory T1G3 transitional cell carcinoma of the bladder: a pilot study.

OBJECTIVE: The aim of this pilot study is to analyze the safety and short-term efficacy of gemcitabine (GEM) as salvage intravesical therapy in a very selected population of bacille Calmette-Guérin (BCG)-resistant T1G3 patients. METHODS: 9 recurrent BCG-refractory pT1G3 patients, unsuitable for radical treatment, were treated with GEM, and compared with 10 pT1G3 patients previously treated with at least two courses of transurethral resection plus BGC, with further conservative endovesical BCG administration. RESULTS: Both intravesical administrations of GEM and BCG were generally well tolerated: no severe adverse events were reported. Of the 9 patients treated with GEM, 3 were recurrence-free after 13, 17 and 21 months and 7 kept an intact bladder, with an overall survival rate of 9 of 9. Among 10 patients treated with BCG instillation, 1 was recurrence-free after 27 months and 6 kept their bladders, with a survival rate of 8 of 10. CONCLUSIONS: Our experience confirms the high risk of tumor recurrence and progression of BCG-refractory pT1G3 transitional cell carcinoma. In this case, further BCG courses seem to be unsuitable, resulting in a high risk of tumor progression and mortality. The use of GEM in BCG-refractory pT1G3 patients has to be considered experimental until multicentric randomized studies with adequate follow-up are able to confirm the preliminary results of this pilot study.

Adjuvants, Immunologic↗

Pre and postoperative quantitative detection of fragments of cytokeratins 8 and 18 (UBC IRMA) as markers of early recurrence of superficial bladder tumor.

OBJECTIVES: The Urinary Bladder Cancer (UBC) test is a marker that detects urinary fragments of cytokeratin 8 and 18. The aim of this study is to evaluate the usefulness of the pre and post operative UBC test to detect early recurrences of a bladder tumor in the first year after the transurethral resection of a bladder tumor. MATERIALS AND METHODS: A multicentric perspective study on 36 patients with superficial bladder cancer (pTa-pT1) treated with transurethral resection (TUR) was performed. Each patient underwent 4 specific urine collections: 1) preoperatively, 2) 3 days after TUR, 3) 7 days after TUR, 4) 30 days after TUR. UBC was analysed on urine with the IRMA method and the cut off value of 12 mg/L was used. Cystoscopy was performed after 3, 6, 9, and 12 months after TUR, with the aim of identifying all cancer recurrences in the first year postoperatively. Statistical analyses to identify differences between patients with or without early recurrence were performed in accordance with Fisher's exact test and Chi-square analysis. RESULTS: Of the 36 patients included in the study 15 showed early recurrence and 21 were recurrence free 1 year after surgery. UBC levels measured in recurrence free patients 30 days after TUR showed normal values, values decreasing as compared with preoperative levels or both circumstances, even if a statistically significant difference was not found between the two groups. CONCLUSIONS: In this study we reported an insignificant correlation between the postoperative modifications of UBC levels and the risk of tumor recurrence during the first year of follow-up. A larger study group with longer follow-ups will probably allow better evaluation of the real power of UBC tests in clinical practice.

Aged↗

Progression and long-term survival after simple enucleation for the elective treatment of renal cell carcinoma: experience in 107 patients.

PURPOSE: We present our findings in a series of T1a renal cell carcinoma treated with elective simple enucleation, specifically reporting the incidence of local recurrence, and progression-free and disease specific survival rates. MATERIALS AND METHODS: A total of 107 patients who underwent elective nephron sparing surgery performed with simple enucleation from January 1989 to December 2000 were studied retrospectively. None of the patients had preoperative or intraoperative suspicion of positive nodes. All patients were free from distant metastases before surgery (M0). Patient status was last evaluated in July 2004. Mean (median, range) followup was 88.3 (84, 44 to 175) months. RESULTS: Pathological review according to the 2002 TNM classification showed that 95% (102 of 107) of tumors were pT1a, 4% (4 of 107) pT1b and 1% (1 of 107) pT3a. Mean (SD, median, range) tumor greatest dimension was 2.7 (0.93, 2.5, 0.6 to 5) cm. None of the patients died in the immediate postoperative period (within the first 30 days). There were no major complications such as bleeding and urinary leakage/urinoma requiring reoperation. The 5 and 10-year cancer specific survival was 99% and 97.8%, respectively. The 5 and 10-year progression-free survival was 98.1% and 94.7%, respectively. Overall 3 patients had disease progression (2.8%) of whom 2 (1.9%) were local recurrence, 1 alone and 1 associated with distant metastases diagnosed 12 months earlier. CONCLUSIONS: Simple tumor enucleation is a safe and acceptable approach for elective nephron sparing surgery. It provides excellent long-term progression-free and cancer specific survival rates, and is not associated with an increased risk of local recurrence compared with partial nephrectomy.

Aged↗