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Cultural, environmental and religious resources are a repository of values participating in the process of recognizing the environmental semantic roots. The presence and use of these resources transform an anonymous place into a place of art, contemplation, meeting and cultural exchange; they contribute to psychological well-being, to the realization of social equity and to the economic development by attracting new investments and strengthening existing ones.

Objective: To evaluate the detection rate of anterior zone (AZ) prostate cancer (PCa) in patients submitted to initial and repeat transperineal prostate biopsy. Methods: From January 2013 to August 2013, 226 patients (median age 64 years) with negative digital rectal examination underwent initial (144 cases) and repeat (82 cases) transperineal prostate biopsy for PSA >10 ng/ml, PSA 4.1-10.0 or 2.6-4.0 ng/ml with free/total PSA ≤25% and ≤20%, respectively. A median of 22 versus 32 cores were performed, including 4 cores of the AZ versus 6 cores (4 anterior plus 2 cores of the transition zone, TZ) at initial versus repeat biopsy, respectively. The detection rate of PCa of the peripheral zone (PZ), AZ and TZ was prospectively evaluated. Results: The median PSA was 7.6 ng/ml; overall, a stage cT1c PCa was found in 104/226 (46%) patients, in 70 (48.6%) and 34 (41.5%) of the men who underwent initial and repeat biopsy, respectively. An AZ PCa was found in 11.5 vs. 8.8% (p = 0.32) of the patients submitted to initial versus repeat biopsy, respectively. AZ cancers demonstrated a number of positive cores (p = 0.03), greatest percentage of cancer (p = 0.001) and total percentage of cancer (p = 0.001) significantly lower in comparison with PZ PCa; moreover, 56.2 vs. 36.5% of AZ versus PZ PCa were characterized by a microfocus of cancer (p = 0.001), respectively. Conclusions: AZ biopsies increase the detection rate of PCa (about 10% of cases) at initial and repeat biopsy, allowing reduction of the biopsy false-negative rate.

Detection rate for prostate cancer (PCa) and complications following transperineal prostate biopsy (TPBx) were reported.From January 1991 to December 2012, 4,000 men underwent TPBx; from 1991 to 2001, the patients underwent biopsy for suspicious DRE or PSA values4 ng/mL; moreover, from 2002, the indications were abnormal DRE, PSA10 ng/mL, PSA values between 4.1 and 10, 2.6 and 4 and2.5 ng/mL with F/T PSA25,2015 %, respectively. In case of initial biopsy, the number of needles cores increased from 6 (1991-1996) to 12 (1997-2012) and 18 cores (2002-2012); in case of repeat biopsy, since 2005 a saturation biopsy (SPBx) with24 cores was performed.Overall, PCa, normal parenchyma, HGPIN and ASAP were found in 1,379 (34.5 %), 2,400 (60 %), 175 (4.4 %) and 46 (1.1 %) patients, respectively; in case of initial TPBx, the scheme at 18 showed a greater PCa detection in comparison with scheme at 6-12 cores (p0.05). In case of repeat biopsy, a higher detection of microfocus of cancer was found performing a SPBx; moreover, 15 % of cancers were localized in the anterior zone. Incidence of hemospermia and urinary retention were correlated with the number of needle cores resulting equal to 30.4 versus 11.1 % in case of SPBx (p0.05); moreover, none developed sepsis.Transperineal prostate biopsy (TPBx) resets the risk of sepsis; moreover, in case of repeat SPBx, the transperineal approach detects a high number of significant PCa localized in the anterior zone (15 % of the cases).

UNLABELLED What's known on the subject? and What does the study add? Immediate surgery for major renal truma has led to a high rate of nephrectomy in comparison with an expectant management. We reviewed our case material on the management of severe blunt renal trauma in adults with emphasis on conservative management. Only shattered kidneys and pedicle avulsion required immediate surgery. OBJECTIVE To review retrospectively the management of major blunt renal truma in adult patients admitted to our level I trauma centre. PATIENTS AND METHODS Among 1460 blunt abdominal trauma cases collected from January 2001 to December 2010, 221 (15%) affected the kidneys. All patients, except seven who needed immediate laparotomy, underwent a computed tomography scan to stage the injuries. Renal injuries were graded according to the American Association for the Surgery of Trauma Grading System; grade 4 and 5 injuries were subclassified based on vascular or parenchymal injury. RESULTS Only 45/221 patients (20%) suffered major blunt renal trauma (21 grade 3, 18 grade 4 and six grade 5); 43% of the patients had associated lesions and 77% had gross haematuria. Nephrectomy rates were 9% for grade 3, 22% for grade 4 and 83% for grade 5 with an exploration rate of 26% for major renal trauma. CONCLUSIONS Conservative management of grade 3-5 blunt renal trauma in haemodynamically stable patients yields more favourable results with high renal salvage rate. Grade 5 injuries still result in a nephrectomy rate of more than 80%. The absence of data on long-term outcomes and a potential inclusion bias due to the retrospective nature of the data represent major limitations of this review.

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; PSA10 ng ml(-1); PSA ≤ 2.5 ng ml(-1), included between 2.6-4 and 4.1-10 ng ml(-1) with %f-PSA15,20 and25%, 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.

Objectives: To evaluate the incidence of indolent prostate cancer (PCa; Methods: From January 2005 to December 2008, 413 patients (median age 61.5 years) underwent SPBx (median 30 cores). A single neoplastic microfocus (5% or less of cancer in a single core) was found in 55 men and all patients underwent retropubic prostatectomy. Median PSA was equal to 8.2 ng/ml, digital rectal examination was negative and GS was 6 in 40 cases and not evaluable in 15 cases. Results: Prostatectomy specimens showed a significant cancer in 48/55 (87.3%) patients with a median GS of 6.2 (range 5–8), presence of extraprostatic extension and positive surgical margins in 15 (27.3%) and 8 (14.5%) cases, respectively. Six patients had an indolent PCa, and in 1 case no tumor was found. Conclusions: Patients with a single microfocal PCa diagnosed on SPBx corresponded to an insignificant cancer in surgical specimens only in 12.7% of cases, but they should be informed that they may harbor more aggressive disease with a risk of non-organ-confined cancer that in our series was 27.3%.

Objectives: To evaluate retrospectively the detection rate of prostate cancer (PCa) located only in the transition zone (TZ) by directed cores at repeated saturation prostate biopsy (SPB). Methods: From July 2001 to December 2009, 380 and 43 patients (median age: 63 years) underwent second and third SPB because they were persistently suspicious for PCa. Indications for biopsy were: prostate-specific antigen (PSA) of >10 ng/ml, and PSA between 4.1 and 10 ng/ml or 2.6 and 4 ng/ml with free/total PSA of ≤25 and ≤20%, respectively. A median of 23 cores were taken in the posterior zone, including 3 (median) cores in the TZ. The median PSA was 12.8 and 19.5 ng/ml and the digital rectal examination was positive in 36 (9.5%) and in no cases at second and third SPB, respectively. In patients with persistent and/or increasing PSA or abnormal free/total PSA values after negative second and third SPB, a transurethral prostate resection (TURP) was suggested to avoid the risk of missing a cancer localized in the TZ. Results: PCa was detected in the TZ only in 2/82 cases (2.5%), and in details in 1/79 (1.2%) and 1/3 (33.3%) of the men diagnosed at second and third SPB, respectively. After TURP, a PCa was found in 18/95 men (18.9%; 14 stage T1a and 4 stage T1b) and in 3/15 men (20%; 2 stage T1a and 1 stage T1b) previously having had negative second and third SPB. Conclusions: Sampling from the prostatic TZ by directed needle biopsies at repeated SPB was associated with a very low incidence of PCa (2.5%), especially if compared to TURP (19% detection rate), and could be omitted.

To evaluate prostate cancer (PCa) detection after repeated negative saturation biopsy, 75 patients, aged 53-78 years, underwent transurethral resection of prostate (TURP) because of persistent suspicion of cancer; median PSA was 11.8 ng ml(-1) and 58 men complained lower urinary tract symptoms (LUTS). In 12 (16%) and 3 (4%) men a T1a and T1b PCa was found with median PSA and Gleason score equal to 14.2 vs 23.6 ng ml(-1) and 5.6 vs 7 ng ml(-1). In case of persistent suspicion of PCa after repeated negative saturation biopsy, TURP may be proposed, aside from the coexistence of LUTS, to rule out a PCa, in younger patients with high PSA values (or =20 ng ml(-1)).

The management of genital lymphedema due to congenital agenesis of the lymphatic ducts is reported. The surgical procedure consisted of the total excision of the affected skin and subcutaneous tissue followed by scrotoplasty and split-thickness skin graft to resurface the penile shaft. The cosmetic and functional results were excellent.

Introduction. Multiparametric pelvic magnetic resonance imaging (mpMRI) accuracy in prostate cancer (PCa) diagnosis was evaluated. Materials and Methods. From June 2011 to December 2013, 168 patients (median 65 years) with negative digital rectal examination underwent repeat transperineal saturation biopsy (SPBx; median 28 cores) for persistently high or increasing PSA values, PSA >10 ng/ml or PSA values between 4.1-10 o r 2.6-4 ng/ml with free/total PSA < 25% and < 20%, respectively. All patients underwent mpMRI using a 3.0 Tesla scanner equipped with surface 16 channels phased-array coil and lesions suspicious for PCa were submitted to additional targeted biopsies. Results. A T1c PCa was found in 66 (39%) cases; SPBx and mpMRI-suspicious targeted biopsy diagnosed 60 (91%) and 52 (78.8%) cancers missing 6 (all of the anterior zone) and 14 cancers (12 and 2 of the lateral margins and anterior zone), respectively; in detail, mpMRI missed 12 (18.1%) PCa charaterized by microfocal (1 positive core with greatest percentage of cancer and Gleason score equal to 5% and 6, respectively) disease at risk for insignificant cancer. The diameter of the suspicious mpMRI lesion was directly correlated to the diagnosis of PCa with poor Gleason score (p < 0.05); detection rate of cancer for each suspicious mpMRI core was 35.3%. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive value of mpMRI in diagnosing PCa was 75.7%, 82.5%, 71.8%, 78.9%, 87.9%, respectively. Conclusion. Multiparametric pMRI improved SPBx accuracy in diagnosing significant anterior PCa; the diameter of mpMRI suspicious lesion resulted significantly predictive of aggressive cancers.

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.

To evaluate if the addition of a renal color-Doppler ultrasonography (CDU) in the setting of acute renal colic improves the sensitivity of conventional sonography.Between July 2002 and June 2003, 100 patients (median 49 years) with renal colic have been evaluated. Within 24 h of the admission, a CDU study of the urinary tract was performed using a sonograph GE Logiq 500 PRO with a multifrequency (3-5 MHz) convex probe. The following parameters were evaluated: ultrasonography (US) of both kidneys, ureters and bladder; resistive index (RI) of the arciform arteries of both kidneys in three different parenchymal areas; ureteric jets in response to hydration. A renal RI0.70 and/or a 10% difference between the kidneys were considered as diagnostic of obstructive uropathy; an asymmetric and/or reduced ureteric jet from the ureteric orifices was an additional indicator of obstruction. All patients underwent a CT scan both with and without the administration of contrast medium.Enhanced helical CT demonstrated an urinary stone in 90 out of the 100 patients (90%): 29 pyelic, 28 at the pyelo-ureteral junction, 23 lumbo-iliac and 10 juxtavesical stones. Among 90 patients with urolithiasis, the stone was undetectable with US in 11 cases (12.2%); in 8 cases (8.9%) pyelocalicectasis was absent, and in 6 patients (6.6%) a non-obstructive hydronephrosis was present. Median RI in obstructed and non-obstructed kidney was 0.73 (range 0.71-0.87) versus 0.62 (0.50-0.68), respectively; in two, obstructed kidneys RI was0.70 but greater than 10% compared with normal side. Sensitivity and specificity of US, CDU (RI+ureteric jet), unenhanced helical CT and CDU in association with unenhanced helical CT were 94.8 and 55.5, 98.9 and 90.9, 100 and 100%, respectively.CDU in patients with renal colic and/or pelvicalicectasis improves the diagnostic accuracy of US in distinguishing between obstructive and non-obstructive dilatation. Combined with unenhanced CT, CDU has a 100% sensitivity and specificity. Moreover, due to the absence of contraindications and side-effects, CDU is indicated for the follow-up of patients after ESWL, pregnant women and children.

As a preliminary approach to define the object of larger case-control studies, the distribution of potential risk factors coming from environmental pollution among patients affected by superficial bladder cancer (TCCB) has been analyzed. Material e Methods. The analysis included only patients affected by medium risk superficial TCCB. Forty Italian urological centres joined the study. Detailed information about age, sex, residency, employment, active and passive cigarette smoking, water resource, hair-dye use were centralized. All patients underwent TUR and early intravesical chemotherapy. The distribution of the above mentioned environmental factors was related to tumor characteristics such as multiplicity and previous natural history. Results. Until today 474 patients have been recruited, 182 (38.4%) with primary tumors and 293 (61.8%) with multiple lesions. Over 80% of the patients lived in urban areas, 20% were employed in industry at risk for bladder cancer and 8% used hair dye. Forty percent of the patients were smokers, with a median smoking period of 30 years. Bottled water was the only water resource in 42% of cases. At multivariate statistical analysis a significant correlation between tumor multiplicity and employment in industry (p

The diagnosis of prostate carcinoma has been monitored in Sicily and Calabria for one year. Material e Methods Twenty-seven urological centres of Sicily and Calabria joined the study. Detailed informations about age, familiarity, PSA, Gleason score and TNM stage at diagnosis were centralized between november 2001 and november 2002. Results 721 patients have been recruited. The median age was 73 years. More than 80% of the patients were older than 65 years. Median PSA was 14 ng/ml. The clinical stage at diagnosis was T1c in 33% of patients and 67% had an organ confined prostate cancer (T1-T2). Familiarity was detected in 8% of cases. Age and PSA at diagnosis in these patients were similar to those of the remaining population. However, only 18% of them had a T1 tumor, emphasizing the delay in diagnosis in these patients. Although only 10% of the patients shows at diagnosis a metastatic tumor, 29% only are fit for radical prostatectomy in according to age, PSA and stage.

Cholecystokinin (CCK) IS a regulatory peptide that acts via two receptor subtypes, CCK1-R and CCK2-R. RT-PCR demonstrated the expression of both CCK1-R and CCK2-R in the zona glomerulosa (ZG), but not zona fasciculata-reticularis cells of the human adrenal cortex. CCK and the CCK2-R agonist pentagastrin enhanced basal aldosterone secretion from ZG cells without affecting cortisol production from zona fasciculata-reticularis cells. The aldosterone response to CCK and pentagastrin was suppressed by a CCK2-R antagonist, but not by a CCK1-R antagonist. Pentagastrin evoked a sizeable cAMP, but not inositol triphosphate, response from ZG cells, whereas CCK plus CCK2-R antagonist was ineffective. The cAMP response to pentagastrin was abrogated by CCK2-R antagonist or the adenylate cyclase inhibitor SQ-22536, and the aldosterone response was abolished by both SQ-22536 and the protein kinase A inhibitor H-89. Both CCK and pentagastrin increased steroidogenic acute regulatory protein mRNA expression in ZG cells; the effect was abrogated by CCK2-R antagonist. We conclude that CCK exerts secretagogue action on human ZG cells, acting through CCK2-Rs coupled to the adenylate cyclase/protein kinase A signaling cascade, which, in turn, stimulates the expression of steroidogenic acute regulatory protein, the rate-limiting step of steroidogenesis.

Renal neuroendocrine tumors (NET) are rare neoplasms of unknown histogenesis. To the best of our knowledge, 40 such cases have been described, 11 of which arising in horseshoe kidneys (HSK). We report an additional case of a NET associated with a HSK occurring in a 45-year-old man. A clinicopathological review of the reported cases together with an updated follow-up of such tumors arising in HSK is provided. The present data show that NET associated with HSK present a better prognosis than those occurring in normal kidneys, even over long-term follow-up periods.

Objectives: To evaluate whether the adjunct of an ultrasound contrast medium improves the detection rate of prostate cancer. Method: In 34 patients, scheduled to undergo a trans-perineal extended prostate biopsy, we carried out a color-Doppler ultrasound (CDU) of the prostate before and after i.v. injection of Levovist®, an ultrasound contrast medium. Further bioptic samples were taken in the areas where a marked increase in vascularization was noticed. Results: The overall diagnostic sensitivity, specificity and efficiency were respectively 72.7, 56.2 and 62.9% for transrectal ultrasound (TRUS); 80, 56.2 and 65.3% for CDU and 88.8, 54.5 and 68% for CDU after Levovist® injection; 66.5, 72.6 and 65.1% for digito-rectal examination (DRE); 100, 51.4 and 65.4% for total PSA; and 100, 88.8 and 94.3% for PSA free/total. In the 16 patients with prostate carcinoma, the sensitivity of CDU after Levovist® was 92.3, 66% for both DRE and TRUS, and 80% for DRE plus TRUS. Conclusions: Considering the cost and the results obtained (high sensitivity and low specificity), a routine use of Levovist® does not seem indicated in patients undergoing prostatic biopsy. An exception may be represented by patients with both negative DRE and TRUS.

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 20 mg continuously (daily group) or the same but with tamoxifen at 20 mg weekly after the first 8 wk of daily treatment (weekly group). Three patients in theweekly group and one in the daily groupwere 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 20 mg/wk is inferior to tamoxifen 20 mg/d in preventing the incidence and severity of bicalutamide-induced breast events. The safety and efficacy of tamoxifen at the common daily dose of 20 mg for the prophylaxis of bicalutamide-induced breast events were confirmed.

The prostate-specific antigen (PSA) nadir and long-term outcome in patients with pT3b prostate cancer were evaluated.From July 2000 to December 2012, in 100 patients (median age=62 years) with pT3b prostate cancer following radical retropubic prostatectomy (RRP) preoperative and pathological findings predictive of PSA nadir (≤0.2 vs.0.2 ng/ml) were retrospectively evaluated; moreover, biochemical recurrence-free survival (bRFS), cancer specific survival (CSS) and overall survival (OS) in patients who underwent watchful waiting (16 cases), adjuvant (84 cases) and salvage (10 cases) therapy were recorded.A PSA nadir0.2 ng/ml was correlated with node involvement, Gleason score ≥9, cT2, PSA20 ng/ml, positive surgical margins and total cancer percentage20%. At a median follow-up of 90 months (range=10-155 months) bRFS, OS and CSS were 92%, 96% and 80%, respectively.Radical retropubic prostatectomy combined with adjuvant and salvage treatments demonstrated a satisfactory outcome for pT3b prostate cancer.

Preoperative findings, pathological stage PSA recurrence in patients with prostate cancer incidentally detected (iPCa) at radical cystectomy (RCP) were prospectively evaluated.From July 2000 to July 2013, 242 men 71 years old (median) underwent RCP; preoperatively, all patients underwent digital rectal examination (DRE), total and free/total PSA. The bladder was totally examined; moreover, the prostate gland was step-sectioned at 4-mm intervals. The incidence of iPCa that fulfilled criteria for clinically significant iPCa was recorded: tumor volume ≥0.5 mL, Gleason grade ≥4, extracapsular extension, seminal vesicle invasion, lymph node metastasis or positive surgical margins. In the presence of iPCa, the patients underwent PSA evaluation during the follow-up and recurrence was defined as two subsequent rises0.2 ng/mL.Among the 50 (20.6%) out of 242 patients submitted to RCP, an iPCa was found and 18 (36%) of them met criteria for insignificant iPCa; moreover, 30% of the patients had apex involvement. Median total PSA and PSA F/T values were not significantly different in the presence versus the absence of iPCa (2.6 vs 2.7 ng/mL and 26 vs 27%; p0.05) and between significant versus insignificant iPCa (p0.05). None of the patients during the follow-up (median 58 months; range 6-102 months) had PSA recurrence.PSA and PSA F/T values are provided for poor accuracy in distinguishing preoperatively significant from insignificant iPCa; however, the life expectancy of the patients is dramatically influenced by bladder cancer pTN (in our series, none developed PSA failure). In younger men in whom a prostate-sparing cystectomy could be proposed, an accurate preoperative evaluation should be mandatory to rule out significant iPCa at the risk of apex involvement (in our series equal to 30% of the cases).

The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

Glucagon-receptor mRNA was detected by reverse transcription-polymerase chain reaction in three human pheochromocytomas, but not in four normal adrenal medullas. Quantitative autoradiography demonstrated the presence of abundant [ 125 I-Thyr 10 ]glucagon binding sites in pheochromocytomas, which were displaced by both cold glucagon and the glucagon receptor antagonist Des-His 1 [Glu 9 ]glucagon amide (GR-A). Adrenal medulla was weakly labeled, and the binding was not displaced by GR-A. Glucagon enhanced epinephrine and norepinephrine release by pheochromocytoma slices, minimal and maximal effective concentrations being 10 −8 M and 10 −6 M. Adrenomedullary slices evidenced a weak catecholamine response only to 10 −5 M glucagon. GR-A abolished the secretory response to glucagon of pheochromocytomas, but not of adrenal medullas. Collectively, these findings indicate that human pheochromocytomas, but not adrenal medulla, express glucagon receptors and possess a marked secretory response to glucagon, thereby providing the rationale to explain the specificity of the glucagon provocative test in the diagnosis of pheochromocytoma.

Background 11β-hydroxysteroid dehydrogenase Type-2 (11β-HSD2) is an unidirectional enzyme that catalyzes the conversion of glucocorticoid hormones cortisol and corticosterone (B) into their corresponding inactive forms, cortisone, and 11-dehydrocorticosterone (DH-B). We have provided evidence that 11β-HSD2 is expressed as messenger RNA (mRNA) and protein in human adrenocortical cells, where its activity is inhibited in vitro by the main glucocorticoid agonists, adrenocorticotropic hormone (ACTH) and angiotensin-II. It seemed worthwhile, therefore, to study the gene expression and activity of 11β-HSD2 in cortisol-secreting adrenocortical adenomas. Methods Three adrenal adenomas that produced Cushing syndrome were recruited. Three normal adrenal glands were obtained from patients who underwent unilateral nephrectomy with ipsilateral adrenalectomy for renal cancer. 11β-HSD2 gene expression was studied by reverse transcription-polymerase chain reaction (RT-PCR) in adenoma and normal adrenocortical tissue. Cortisol, B, cortisone, and DH-B production by adenoma and adrenal slices in vitro was assayed by quantitative high-performance liquid chromatography (HPLC), and the activity of 11β-HSD2 was evaluated by measuring the conversion of [3H]-cortisol to [3H]-cortisone. Results RT-PCR allowed the detection of the 11β-HSD2 mRNA in the three adrenal adenomas and normal adrenal cortices examined. Under basal conditions, adenoma slices secreted higher amounts of cortisol and B, but markedly lower amounts of cortisone and DH-B than adrenal slices. ACTH raised cortisol and B production from both specimens, and it lowered cortisone and DH-B yield. The level basal conversion of [3H]-cortisol to [3H]-cortisone was notably less in adenomas than in adrenals, and ACTH decreased it in both tissues. Conclusions Collectively, our findings indicate that cortisol-secreting adrenal adenomas express the 11β-HSD2 gene, but the activity of the enzyme is suppressed in adenomas when compared with the normal adrenal cortex. We advance the hypothesis that the elevated local concentration of steroid hormones that occur in adenomas down-regulates 11β-HSD2 activity, thereby contributing to their abnormal steroidogenic function.

Orexins A and B are two hypothalamic peptides that increase food intake and body weight and probably play a role in the sleep regulation. They act through two subtypes of G protein-coupled receptors, called OX1-R and OX2-R. OX1-R selectively binds orexin-A, whereas OX2-R is nonselective for both orexins. Orexins did not affect the in vitro secretion of either catecholamine or aldosterone from human adrenals. Conversely, orexin A, but not orexin B, concentration dependently increased basal cortisol secretion from dispersed adrenocortical cells; the maximal effective concentration was 10−8 mol/L. Orexin A (10−8 mol/L) enhanced the cortisol response to maximal effective concentrations (10−9 mol/L) of angiotensin II and endothelin-1, but only to low concentrations of ACTH (10−12/10−11 mol/L). Orexin A (10−8 mol/L) increased basal cAMP release by dispersed adrenocortical cells, and the effect was blocked by the adenylate cyclase inhibitor SQ-22536. The cortisol response to 10−8 mol/L orexin A was unaffected by the ACTH receptor antagonist corticotropin-inhibiting peptide, but was abolished by either SQ-22536 or the protein kinase A inhibitor H-89. RT-PCR demonstrated high levels of OX1-R messenger ribonucleic acid and very low levels of OX2-R messenger ribonucleic acid in human adrenal zona fasciculata-reticularis and adrenal medulla. Collectively, our findings suggest that orexins selectively stimulate glucocorticoid secretion from human adrenocortical cells, acting through OX1-R coupled with the adenylate cyclase-dependent signaling pathway.

Blood samples were collected intraoperatorily from inferior vena cava (VC) and adrenal vein (AV) of 8 male and 9 female consenting adult patients undergoing unilateral nephrectomy with ipsilateral adrenalectomy for kidney cancer, and steroid-hormone concentrations were assayed by quantitative HPLC. Hormonal concentrations were significantly higher in AV than in VC (systemic) blood and did not display significant differences between males and females. Higher levels not only of the main glucocorticoids cortisol and corticosterone, but also of their inactive oxidized forms corticosterone and 11-dehydrocorticosterone (DH-B), respectively, were detected in AV than in VC blood. Highly significant inverse correlations between cortisol and cortisone, and corticosterone and DH-B concentrations were observed in AV, but not in VC blood. Moreover, in AV blood the concentration of the main cortisol precursor 11-deoxycortisol correlated inversely with those of both cortisone and DH-B. Taken together, these findings are in keeping with previous in vitro evidence that human adrenal glands possess 11beta-hydroxysteroid dehydrogenase activity, which is engaged in the inactivation of newly formed glucocorticoids and is probably negatively regulated by the local concentrations of non-11beta-hydroxylated steroid-hormone precursors.

Abstract —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 [ 125 I]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 Ca 2+ 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 Ca 2+ -dependent, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca 2+ 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.

AACOF3 is a trifluomethylketone analog of arachidonic acid, which inhibits phospholipase-A2 (PLA2). AACOCF3 was found to concentration-dependently increase basal aldosterone and corticosterone secretion by dispersed rat zona glomerulosa and zona fasciculata/reticularis cells, respectively, as well as aldosterone and cortisol production by dispersed human adrenocortical cells. Maximal effective concentration was 10(-5) M, and elicited about 2.5-3.0-fold rises in steroid output. 10(-5) M AACOCF3 also enhanced submaximally (10(-15)/10(-12) M), but not maximally (10(-9) M) ACTH-stimulated hormonal secretion. Quantitative HPLC showed that 10(-5) M AACOCF3 evokes similar increases (from 2.0- to 3.0-fold) in the basal release of the entire spectrum of adrenocortical steroids (i.e. both intermediate and definitive products of steroid synthesis), thereby suggesting that AACOCF3 acts on the early steps of steroid synthesis. Accordingly, when pregnenolone metabolism is prevented by cyanoketone, 10(-5) M AACOCF3 increased by about 8-10-fold the production of this steroid. In conclusion, we have demonstrated a side-effect of AACOCF3, which may become relevant in studies where this chemical is used to inhibit PLA2 in tissues able to convert cholesterol to pregnenolone.

The development of a reno-jejunal fistula following a Roux-en-Y cystojejunostomy for an incorrectly diagnosed pancreatic pseudocyst is described. Up to now, this is the second case of iatrogenic reno-jejunal fistula reported in literature. Reno-jejunal fistulas are exceedingly rare and are usually consequences of urologic pathologies of infectious origin. Reno-jejunal fistulas of iatrogenic origin are even rarer, only one case being referred in literature [1]. Herein the second case is reported.

Objective: Measurement of the ethanol concentration in expired breath during transurethral resection of the prostate (TURP). Methods: TURP is a noninvasive method to estimate the amount of irrigant absorbed. The expiratory breath ethanol concentrations (EBEC) were measured with a standard alcohol breath analyzer in 35 patients in the course of TURP. All interventions were performed with a 27-french continuous flow resectoscope using a solution of 1.5% glycine + 1% ethanol as irrigating fluid. Serum sodium and osmolality were measured pre- and postoperatively. No patient developed signs of transurethral resection syndrome; no significant changes in serum sodium, osmolality and EBEC were found throughout the operation. Conclusion: Absorption of irrigant fluid during TURP with continuous low-pressure irrigation seems to be extremely slight (if not absent) as measured by expired breath ethanol method.

The association of seminal vesicle cyst and upper urinary tract malformation is well known in the literature [1]. More rarely, urogenital malformations are associated with vertebral [2] or anorectal anomalies [3]. A 35-year-old infertile man with unilateral renal and deferential agenesis, seminal vesicle cyst and hemivertebra is reported. This complex malformative syndrome has been reported previously by Sheih et al. [4] and, to our knowledge, this is the third case described in the literature.

Magnetic resonance imaging (MRI) accuracy in prostate cancer (PCa) diagnosis in men submitted to saturation prostate biopsy (SPBx) was evaluated.From June 2011 to December 2012, 78 patients (median 63 years) underwent repeat SPBx (median 28 cores). Multiparametric MRI using a 3 Tesla pelvic phased-array coil was performed before SPBx and lesions suspicious for PCa were submitted to additional targeted biopsies.A T1c PCa was found in 32 (41%) cases. SPBx vs. MRI-suspicious targeted biopsy diagnosed 28 (87.5%) vs. 26 (81.2%) PCa missing four (12.5%) and six (18.8%) cancers localized in the anterior zone and in the lateral margin of the prostate, respectively; moreover, MRI diameter lesions correlated with PCa diagnosis and Gleason score (p0.05).Multiparametric MRI improved SPBx accuracy in diagnosing PCa of the anterior zone; moreover, suspicious areas10 mm resulted as highly predictive of cancer (about 70% of the cases).

To evaluate Prostate Cancer Prevention Trial (PCPT) risk calculator versus prostate cancer gene 3 (PCA3) score versus case-finding protocol accuracy in prostate cancer diagnosis in patients with prostate-specific antigen (PSA) below 10 ng/mL submitted to repeat saturation biopsy (SPBx).From December 2010 to December 2011, 100 patients (median 66 years) underwent a SPBx (median 30 cores); the indications for repeat biopsy were those of a case-finding protocol: PSA values between 4.1 ng/mL-10 ng/mL or 2.6 ng/mL-4 ng/mL with F/T PSA ≤ 25% and ≤ 20%, respectively. All patients had negative digital rectal examination (DRE) and median PSA was 7.9 ng/mL. The performance of PCPT risk calculator (alone, combined with PSA free/total ( F/T) or PCA3 score) and PCA3 score in comparison with the case-finding protocol results (alone or combined with PCA3 score) was retrospectively evaluated in terms of detection rate for cancer and number of avoided biopsies.Prostate cancer was found in 28 (28%) patients; in the presence and absence of prostate cancer median PCA3 score was 57 versus 35 (p0.05). Using PCPT risk calculator (cut off probability of 25%) combined with PCA3 score no prostate cancer would be missed avoiding 8% of unnecessary biopsies. PCA3 score20 missed 7.2% of cancer; the case-finding protocol combined with PCA3 score35 would save 22% of avoidable biopsies, missing no cancer if all patients with PSA F/T ≤ 15% would undergo prostate biopsy irrespective of PCA3 values.PCA3 score improves PCPT risk calculator accuracy in prostate cancer diagnosis; moreover, PCA3 score combined with PSA F/T reduce number of unnecessary biopsies (about 20%).

To evaluate PCA3 score accuracy in prostate cancer (PCa) diagnosis in patients undergoing repeat saturation prostate biopsy (SPBx).From January 2010 to March 2012, 177 patients (median 64 years) with primary negative extended biopsy underwent a SPBx (median 28 cores) for persistent suspicion of PCa. The indications for repeat biopsy were: PSA10 ng/mL, PSA values between 4.1-10 or 2.6-4 ng/mL with free/total PSA25% and20%, respectively; moreover, before performing SPBx PCA3 score was evaluated.Median PSA was 9.5 ng/mL (range: 3.7-28 ng/mL): in 74 (41.8%) cases PSA was10 ng/mL, in 99 (56%) and 4 (2.2%) was included between 4-10 and 2.6-4 ng/mL, respectively. Median PCA3 score was equal to 52 (range 3-273); 140 (79%) and 100 (56.5%) patients had a PCA3 score greater than 20 and 35, respectively. A T1c PCa was found in 48 patients (27.1%); PCA3 score was 60 (median; range: 7-208) in the presence of PCa and 34 (median; range: 3-268) in the absence of cancer (p0.05). Diagnostic accuracy, sensitivity, specificity, PPV and NPV of PCA3 score cut-off of 20 vs. 35 in PCa diagnosis were 43.5 vs. 50.2%, 91.7 vs. 73%, 25.6 vs. 41.8%, 31.5 vs. 35% and 89.5 vs. 80.6%, respectively.PCA3 score reduce number of unnecessary repeat SPBx; using a PCA3 cut-off of 20 vs 35 would have avoided 21% vs. 37.8% of biopsies while missing 8.4% (4 cases) vs. 27% (13 cases) of significant PCa, respectively.

Clinical recurrence in the absence of biochemical PSA failure is uncommon and accounts for less than 1%; we report a rare case of solitary lung metastasis in a patient with undetectable PSA level (0.1 ng/mL) after radical prostatectomy (RP) for prostate cancer (PCa). An asymptomatic 75-year-old man nine years after RP showed a solitary lung mass (about 2 cm) at chest radiography; the 18-FDG-PET/CT confirmed the presence of an isolated mass suspicious for primitive pulmonary cancer. The initial histological specimen after RP showed a mixed acinar and ductal PCa (Gleason score 7, pT3aNO stage, negative surgical margins). A segmental pulmonary resection was performed and definitive specimen demonstrated a single ductal PCa metastasis; after six months from surgery the patient was free from recurrence. In conclusion, in patients with atypical PCa variants imaging studies may be considered in the follow up even in presence of undetectable PSA because they could benefit from early salvage therapy.

Carcinosarcoma is a rare malignant tumor with a biphasic morphology characterized by the presence of a malignant epithelial and mesenchymal component. It has been reported in many organs, including the genitourinary tract. We describe a case of a 47-year-old woman admitted to our hospital for history of recurrent urinary tract infection, dysuria and discharge of bloody fluid from the urethra at the end of urination. A tender palpable mass under the anterior vaginal wall was found and pathological examination showed a urethral carcinosarcoma. The histopathogenetic hypothesis and clinical management were considered in this report.

To evaluate clinical complications after transperineal prostate biopsy in patients undergoing 12 vs 18 vs more than 24 cores.From February 2002 to December 2012, 3000 patients (median age, 66 years) underwent transperineal prostate biopsy after an abnormal result on a digital rectal examination, prostate-specific antigen (PSA) level10 ng/mL, PSA values between 4.1 and 10, 2.6 and 4, and 2.5 ng/mL with free/total PSA ≤25%, ≤20%, and ≤15%, respectively. Of these, 915 (30.5%), 1330 (48.5%), and 630 patients (21%) underwent 12, 18, and24 needle cores under antibiotic prophylaxis. Prostate biopsy-related complications were evaluated within 15 to 20 days after the prostate biopsy. The number of patients who needed hospital admission or an emergency department visit (EDV) was recorded.Prostate cancer was found in 1150 (38.3%) patients. Side effects after the biopsy occurred in 40.2% of the patients, and the complications were directly correlated with the number of needle cores: 31.5% with 12 cores, 41.8% with 18 cores, and 57.4% with24 cores (P = .001). Overall hospital admission and EDV were 1.2% and 9.1% and occurred, respectively, in 1% and 6% (12 cores) vs 1.3% and 9.6% (18 cores) vs 1.6% and 14.4% (24 cores) of the patients. The most frequent complication that needed hospital admission vs EDV was urinary tract infection (0.7%) vs acute urinary retention (6.7%), respectively. No patients developed sepsis.Clinical complications after transperineal prostate biopsy occurred in 40.2% of the patients, but only 1.2% required hospital admission. The number of needle cores (12 vs 18 vs24) significantly correlated with increased onset of side effects.

Laparoscopy plays an outstanding role in the diagnosis of non palpable testis. Laparoscopy is as accurate as surgical exploration but, compared with the latter, is less invasive and faster; moreover in cases of testicular absence it makes surgery unnecessary. Concerning laparoscopic surgery in the case of abdominal testis, orchiectomy is an easy procedure which prolongs diagnostic laparoscopy for only a short time. It is indicated in pediatric patients with hypoplasic testis. In adult patients, except for cases of monorchidism and bilateral abdominal testis, orchiectomy is always recommended. At present laparoscopic orchiopexy does not seem to offer sure advantages compared to traditional surgery.