Francesco Aragona

POLYTETRAFLUOROETHYLENE GIANT GRANULOMA AND ADENOPATHY: LONG-TERM COMPLICATIONS FOLLOWING SUBURETERAL POLYTETRAFLUOROETHYLENE INJECTION FOR THE TREATMENT OF VESICOURETERAL REFLUX IN CHILDREN

PURPOSE The use of polytetrafluoroethylene as bulking agent for the endoscopic treatment of vesicoureteral reflux in children has raised many concerns about the implant histocompatibility and the risk of migration of polytetrafluoroethylene particles. We report on 3 cases of long-term complications following subureteral polytetrafluoroethylene injection (STING) and an extensive review of the literature is presented. MATERIALS AND METHODS Between January 1993 and December 1995, 3 children (2 males, 1 female; 4, 7 and 6 years old), previously submitted to STING, underwent open surgery for recurrent vesicoureteral reflux. RESULTS In 1 case a hard nodular mass, strictly adherent to the ureteral wall, was a foreign body giant granuloma. All patients demonstrated a heavy multinucleated foreign body reaction around polytetrafluoroethylene particles in the pelvic nodes. CONCLUSIONS Many experimental studies and some clinical observations have demonstrated that polytetrafluoroethylene particles elicit a foreign body granulomatous reaction and have the tendency to migrate. Until the long-term effects of their presence are well known, STING should be carefully evaluated in children and young patients.

An Open, Randomised, Multicentre, Phase 3 Trial Comparing the Efficacy of Two Tamoxifen Schedules in Preventing Gynaecomastia Induced by Bicalutamide Monotherapy in Prostate Cancer Patients

BACKGROUND Bicalutamide monotherapy is a valuable option for prostate cancer (PCa) patients who wish to avoid the consequences of androgen deprivation; however, this treatment induces gynaecomastia and mastalgia in most patients. Tamoxifen is safe and effective in preventing breast events induced by bicalutamide monotherapy without affecting antitumor activity, but possible interference between bicalutamide and tamoxifen remains a matter of concern. To reduce the exposure to tamoxifen, we considered the putative advantages of weekly administration. OBJECTIVE To compare the efficacy of two different schedules of tamoxifen in preventing breast events. Toxicity, prostate-specific antigen behaviour, and sexual-functioning scores were also evaluated. DESIGN, SETTING, AND PARTICIPANTS This was a noninferiority trial. From December 2003 to February 2006, 80 patients with localised/locally advanced or biochemically recurrent PCa who were also candidates for bicalutamide single therapy were randomised to receive two different schedules of tamoxifen: daily (n=41) and weekly (n=39). Median follow-up was 24.2 mo. INTERVENTION Daily bicalutamide (150 mg) plus daily tamoxifen 20mg continuously (daily group) or the same but with tamoxifen at 20mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in the weekly group and one in the daily group were discontinued for adverse events. MEASUREMENTS For gynaecomastia, we used ultrasonography. For mastalgia and sexual functioning, we used questionnaires. RESULTS AND LIMITATIONS Gynaecomastia developed in 31.7% of patients in the daily group and in 74.4% of patients in the weekly group (p<0.0001), and it was more severe in patients who switched to weekly tamoxifen (p=0.001). Mastalgia occurred in 12.2% and 46.1% of patients, respectively (p=0.001). There were no major differences among treatment schedules relative to sexual functioning scores and incidence and severity of adverse events. No differences between groups in PSA behaviour and disease progression have been detected so far. CONCLUSIONS This study demonstrated that tamoxifen 20mg/wk is inferior to tamoxifen 20mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20mg for the prophylaxis of bicalutamide-induced breast events were confirmed.

Prostate Needle Biopsy: 12 vs. 18 Cores – Is It Necessary?

Introduction: The aim of this study is to compare the histological results of a prostate needle biopsy scheme of 12 and 18 cores used in 372 consecutive patients submitted to an early stage diagnosis programme for prostate cancer (PCa). Materials and Methods: From February 2002 to July 2003 a transperineal TRUS-guided prostate needle biopsy was performed in 372 patients aged 40–73. Indications for biopsy were: suspected DRE, total PSA (PSAt) >10 ng/ml; PSAt equal to 4–10, 2.6–3.9, ≤2.5 ng/ml and PSA F/T <25%, <20% and <15%, respectively. In 256 patients, we performed 12 cores and in 116 cases 18 cores. Results: 159 (42.7%) patients were diagnosed with PCa, 138 (37%) with BPH, 58 (15.7%) with chronic prostatitis, 15 (4%) with a HGPIN, 2 (0.6%) with ASAP. In patients that underwent 12 and 18 cores the incidence of PCa was 39.8 and 49%; the incidence of PCa in patients with PSA ≤10 and >10 ng/ml submitted to 12 and 18 cores was 35 vs. 47% and 57.8 vs. 52%, respectively. The preponderance of clinical stage T1c was 50% (12 cores) vs. 72% (18 cores). The median bioptic Gleason score in both groups resulted 6.6 (12 cores) and 6 (18 cores). In 110 (12 bioptic cores) and in 30 (18 bioptic cores) patients that underwent a RRP, the pTNM proved a significant clinical neoplasm (Gleason score ≧6 and/or tumoral volume >0.5 cm3) in the first group in all cases, while in the second group in 28/30 (94%) cases. Conclusions: Extended schemes of prostate needle biopsy of 18 or more cores increases the PCa diagnosis in early stage and should be adopted for young patients with a PSA <10 ng/ml, negative DRE and in case of rebiopsies.

Proadrenomedullin N-Terminal 20 Peptide (PAMP), Acting Through PAMP(12–20)-Sensitive Receptors, Inhibits Ca2+-Dependent, Agonist-Stimulated Secretion of Human Adrenal Glands

Proadrenomedullin N-terminal 20 peptide (PAMP) is a 20-amino acid hypotensive peptide expressed in the adrenal medulla. We investigated the localization and function of PAMP receptors in the human adrenal gland. Autoradiography showed the presence of [125I]PAMP-binding sites in both zona glomerulosa and adrenal medulla that were displaced by cold PAMP and PAMP(12-20) but not by other preproadrenomedullin-derived peptides. PAMP, but not PAMP(12-20), counteracted, in a concentration dependent manner, both aldosterone response of zona glomerulosa cells and catecholamine response of adrenal medulla cells to BAYK-8644, the selective agonist of voltage-activated Ca2+ channels, as well as to K+ and angiotensin II. PAMP(12-20) partially reversed this antisecretagogue effect of PAMP. Collectively, these findings suggest (1) that PAMP inhibits Ca2+-dependent, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca2+ influx; and (2) that PAMP(12-20) acts as a weak antagonist of PAMP receptors, thereby suggesting that both C- and N-terminal sequences of the PAMP molecule are required for this peptide to exert its antisecretagogue action on the human adrenal gland.

Incidence of insignificant prostate cancer using free/total PSA: results of a case-finding protocol on 14,453 patients.

To evaluate prostate cancer (PCa) detection and incidence of pathologically insignificant PCa (pIPCa) tumour using percent-free PSA (%f-PSA) in patients with total PSA ⩽10 ng ml−1. From February 2002 to October 2009, 14 453 patients (median 60.5 years) were enrolled in a case-finding protocol for the early diagnosis of PCa. Indications to biopsy were suspicious digital rectal examination; PSA >10 ng ml−1; PSA⩽2.5 ng ml−1, included between 2.6–4 and 4.1–10 ng ml−1 with %f-PSA <15, <20 and <25%, respectively. A median of 18 and 26 cores in case of primary and repeated biopsy were determined; 2123 men underwent prostate biopsy, of whom 1589 (74.8%) had a PSA ⩽10 ng ml−1. A PCa was found in 777 (36.6%) and in 35 (23.3%) patients at primary and repeated biopsy: 459 and 26 men had PSA ⩽10 ng ml−1 and 419 and 26 patients underwent surgery, respectively, 244 (58.3%) and 18 (69.2%) had an organ-confined PCa with a pIPCa incidence equal to 1.4 and 7.7%, respectively. Cancer detection rate of 28.8% in patients with PSA ⩽10 ng ml−1 associated with a low incidence of pIPCa should induce to introduce %f-PSA in screening programmes to reduce the risk of overdiagnosis.

Urinary retention due to a müllerian duct cyst: role of ultrasonically guided fine needle aspiration in the diagnosis and treatment.

Abstract We report a case of urinary retention secondary to a mullerian duct cyst, which was treated successfully by ultrasonically guided transperineal fine needle aspiration

Management of severe blunt renal trauma in adult patients: a 10-year retrospective review from an emergency hospital.

Study Type – Therapy (case series)

Clinical value of pathologic changes after intravesical BCG therapy of superficial bladder cancer

Bladder pathologic features related to intravesical bacillus Calmette-Guerin (BCG) therapy in superficial bladder cancer (Ta, T1, Tis) were evaluated and related to clinical outcome. A total of 105 patients were treated with 75 mg Pasteur BCG weekly for six consecutive weeks. When tumor was not demonstrated a maintenance course was given. An additional six-week course was given when tumor recurrence or persistence, without progression, was observed after the induction course. An inflammatory change in the bladder was the most common pathologic finding. Granuloma was the only specific BCG-related feature and did not appear to be a prognostic factor because of low incidence (24%) and lack of correlation with clinical course. Dysplasia occurred more frequently (57%) in nonresponder patients and (26%) in responder patients, often heralding recurrence of tumor. All patients showing concurrent squamous and/or glandular metaplasia were unresponsive to BCG therapy. Histology and cytology did not correlate perfectly: cytology was ineffective in low-grade tumors and improved diagnostic accuracy, particularly when dysplasia was histologically evident.

Should Men with Serum Prostate-Specific Antigen ≤4 ng/ml and Normal Digital Rectal Examination Undergo a Prostate Biopsy?

The clinical significance of a prostate cancer (PCa) cannot be determined solely by tumor volume (≤0.5 cm3), as small tumors of higher Gleason grade and tumors occurring in younger men may become clinically significant even though the initial volume at diagnosis is small. A certain number of these minimal cancers are likely to remain clinically insignificant; however, it is unpredictable how many can progress beyond the curable stage by the time there is a rise in serum prostate-specific antigen (PSA) values. Compared to clinically detected PCa, PCa detected exclusively by PSA screening (clinical stage T1c) are less likely to be advanced but no more likely to be insignificant in terms of volume, pathologic stage, and Gleason pattern. Only 10–15% of PSA-detected cancers have the features of PCa found at autopsy or in cystoprostatectomy specimens. Actually, 25–30% of PCa are detected with PSA values between 2.5 and 4 ng/ml, and most of these cancers are clinically significant. Evidence from both retrospective and longitudinal studies has shown that the risk of a PCa is dependent on the patient’s age and the initial serum PSA. This allows an individualized approach to PCa screening programs, and PSA cutoff values for biopsy indication may be lowered in selected patients.

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.