Evidence for trophic transfer of Inodosporus octospora and Ovipleistophora arlo n. sp. (Microsporidia) between crustacean and fish hosts.

Within aquatic habitats, the hyper-abundant Order Crustacea appear to be the predominant host group for members of the Phylum Microsporidia. The musculature, a common site of infection, provides access to biochemical (carbohydrate-rich) and physiological (mitochondria-rich) conditions conducive to prolific parasite replication and maturation. The significant proportion of body plan devoted to skeletal musculature in Crustacea provides the location for a highly efficient intracellular parasite factory. In this study, we utilize histological, ultrastructural and phylogenetic evidence to describe a previously known (Inodosporus octospora) and novel (Ovipleistophora arlo n. sp.) microsporidian parasites infecting the musculature of the common prawn (Palaemon serratus) from the same site, at the same time of year. Despite similar clinical signs of infection, both parasites are otherwise distinct in terms of pathogenesis, morphology and phylogeny. Based upon partial subunit ribosomal RNA (SSU rDNA) sequence, we show that that I. octospora may be identical to a Kabatana sp. previously described infecting two-spot goby (Gobiusculus flavescens) in Europe, or at least that Inodosporus and Kabatana genera are synonyms. In addition, SSU rDNA sequence for O. arlo places it within a distinct clade containing Ovipleistophora mirandellae and Ovipleistophora ovariae, both infecting the oocytes of freshwater fish in Europe. Taken together, our data provide strong evidence for trophic-transfer between crustacean and fish hosts for two different microsporidians within clade 5 of the phylum. Furthermore, it demonstrates that morphologically and phylogenetically distinct microsporidians can infect the same tissues of the same host species to impart clinical signs which mimic infection with the other.

Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes.

VEGF and VEGFR polymorphisms affect clinical outcome in advanced renal cell carcinoma patients receiving first-line sunitinib.

BACKGROUND: Currently, sunitinib represents one of the therapeutic strongholds for renal cell carcinoma, but the criteria for treatment selection are lacking. We assessed the role of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR) polymorphisms in the prediction of the clinical outcome in metastatic renal cell carcinoma (mRCC) patients. METHODS: A total of 84 tumour samples from mRCC patients receiving first-line sunitinib were tested for VEGF and VEGFR single-nucleotide polymorphisms (SNPs). The SNP results were correlated with progression-free survival (PFS) and overall survival (OS). RESULTS: Median PFS was 8.22 months, although whereas median OS was 32.13 months. The VEGF A rs833061 resulted significant in PFS (17 vs 4 months; P<0.0001) and OS (38 vs 10 months; P<0.0001). The VEGF A rs699947 was significant for PFS (18 vs 4 months; P=0.0001) and OS (37 vs 16 months; P<0.0001). The VEGF A rs2010963 was significant in PFS (18 vs 8 vs 2 months; P=0.0001) and OS (31 vs 36 vs 9 months; P=0.0045). The VEGR3 rs6877011 was significant in PFS (12 vs 4 months; P=0.0075) and OS (36 vs 17 months; P=0.0001). At multivariate analysis, rs833061, rs2010963 and rs68877011 were significant in PFS, and rs833061 and rs68877011 were independent factors in OS. CONCLUSIONS: In our analysis, patients with TT polymorphism of rs833061, CC polymorphism of rs699947, CC polymorphism of rs2010963 and CG polymorphism of rs6877011 seem to have a worse PFS and OS when receiving first-line sunitinib.

Do DNA-methylation and histone acetylation play a role in clear cell renal carcinoma? Analysis of radical nephrectomy specimens in a long-term follow-up.

We investigated global methylation and histone acetylation in 50 conventional clear cell renal carcinomas (RCC), treated with radical nephrectomy, to assess their possible role as diagnostic biomarkers. The features considered in this study were patient age, tumor size and grade, percentage and intensity of 5-methylcytosine (5mc) and Acetyl-Histone (Lys 9) expression in tumor tissue. All considered parameters were correlated with patient specific survival. The mean percentage of global cellular methylation in tumoral tissue was significantly higher compared to normal peritumoral tissue (p<0.0001), while the intensity of cellular methylation was significantly higher in normal tissue than in tumoral tissue (p=0.001). The mean percentage of histone cellular acetylation in tumoral tissue was significantly lower compared to normal peritumoral tissue (p=0.0005), while the intensity of mean acetylation in neoplastic tissue was similar to the normal tissue. The percentage of global DNA methylation was significantly higher in grades 3 and 4 tumors (p=0.033). Global DNA methylation and histone acetylation in tumoral tissue did not correlate with survival. Fuhrman grade was statistically significant for prognosis (p=0.031). In conclusion, global hypermethylation and histone hypoacetylation play an important role in RCC carcinogenesis; Fuhrman grade is still considered the most important factor for patient survival; 5mc can have a role as markers of aggressiveness.

Prognostic role of global DNA-methylation and histone acetylation in pT1a clear cell renal carcinoma in partial nephrectomy specimens.

Surgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin-embedded sections, using anti-5-methylcytosine (5mc) and anti-Acetyl-Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P = 0.033), whereas the percentage of histone acetylation was significantly lower (P = 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.

Angiotensin II stimulates and atrial natriuretic peptide inhibits human visceral adipocyte growth.

OBJECTIVE: Cardiovascular peptides such as angiotensin II (Ang II) and atrial natriuretic peptide (ANP) have metabolic effects on adipose cells. These peptides might also regulate adipocyte proliferation and visceral adipose tissue (VAT) expansion. Well-differentiated and stabilized primary cultures of human visceral mature adipocytes (MA) and in vitro-differentiated preadipocytes (DPA) were used as a model to study regulation of VAT expansion. METHODS: Adipocyte differentiation was evaluated by Oil Red O staining and antiperilipin antibodies. MA and DPA from intra- and retro-peritoneal depots were treated with increasing Ang II (with or without valsartan, a highly selective, competitive, 'surmountable' AT1 antagonist devoid of peroxisome proliferator-activated receptor gamma agonistic activity) or ANP concentrations. Cell counts and bromodeoxyuridine incorporation were used to evaluate proliferation. Apoptosis was evaluated by Hoechst 33342 staining. 8-Bromo cyclic guanosine monophosphate (8Br-cGMP) was used to investigate ANP effects, and real-time PCR to evaluate Ang II and ANP receptors' expression. RESULTS: Cell proliferation was progressively stimulated by increasing Ang II concentrations (starting at 10-11 M) and inhibited by ANP (already at 10-13 M) in both MA and DPA. Co-incubation with increasing Ang II concentrations and valsartan indicated that Ang II effects were AT1-mediated. Indeed, AT2 receptors were not expressed. Valsartan alone slightly inhibited basal proliferation indicating an autocrine/paracrine growth factor-like effect of endogenous, adipocyte-derived Ang II. 8Br-cGMP experiments indicated that the effects of ANP were mediated by the guanylyl cyclase type A receptor. CONCLUSION: A cell-culture model to study VAT growth showed stimulation by Ang II and inhibition by ANP at physiological concentrations. Because similar effects are likely to occur in vivo, Ang II and ANP might be important modulators of VAT expansion and associated metabolic and cardiovascular consequences.

Prognostic role of tumor necrosis, microvessel density, vascular endothelial growth factor and hypoxia inducible factor-1alpha in patients with clear cell renal carcinoma after radical nephrectomy in a long term follow-up.

Angiogenesis is a critical step in the growth, invasive progression and metastatic spread of solid tumors. We investigated the importance of tumor necrosis, and microvessel density (MVD), vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1alpha (HIF-1alpha) immunohistochemical expression in a large series of clear cell renal carcinomas treated with radical nephrectomy and assessed the prognostic value of their expression in terms of patient survival at long-term followup. Fifty patients with clear cell RCC were examined. The features considered when evaluating the patients were age, tumor size and grade, intratumoral vascular and renal capsula invasion, histological necrosis, and MVD, vascular and tumoral cell VEGF, and vascular, tumoral cytoplasmic and nuclear HIF-1alpha expression on the histologic specimens. All considered parameters were correlated with patient specific survival. Mean age was 62.06 +/- 6.8 years. Median follow-up was 191.66 months; median survival was 120.86 months. Twenty-one patients developed metastases in the follow-up. Tumor necrosis, microvascular invasion and renal capsula infiltration are more likely to occur in high stage and grade RCC; cytoplasmic HIF-1alpha is highly expressed in high grade RCC. Survival is dependent upon tumor stage and grade, the presence of intratumoral vascular invasion and capsular infiltration, and tumor necrosis; MVD also resulted as being an important prognostic factor. VEGF and HIF-1alpha correlate with prognosis in high stage tumors where VEGF is the most important independent prognostic factor for cancer specific death. The histological and immunohistochemical parameters considered in our study can influence disease recurrence and survival in RCC.

Activity and expression of nitric oxide synthase in rat bladder after sacral neuromodulation.

The aim of our study is to investigate the effects of chronic sacral neuromodulation on Nitric Oxide (NO) metabolism in the rat bladder. 26 female Sprangue-Dawley rats were considered: group I, normal control rats; group II, a sham treatment, in whom catheters for electrical stimulation were placed in the S1 foramen bilaterally and left in place for 21 days, without performing neuromodulation; group III in whom electrical sacral neuromodulation was performed for 21 days. Finally a cystectomy was performed and the bladder biopsy specimens were sent for immunostaining with n-NOS and i-NOS. Morphological and immunohistochemical analysis was carried out, and evaluated in urothelial cells, endothelial cells and muscle fibers of the muscularis propria. Differences between the 3 groups were analyzed by Student Newman-Keuls test. We could observe that urothelial and endothelial i-NOS (37.00+/-4.69 and 59.00+/-7.42 respectively) and urothelial n-NOS (36.80+/-7.85) expression are significantly increased in neuromodulated rats, compared to groups 1 and 2 (p<0.005). In conclusion, the increase of i-NOS expression on endothelial cells after sacral neuromodulation could be in some way related to angiogenetic responses in the microvascular structures; the increase of n-NOS and i-NOS expression on urothelial cells can suggest that NO is able to influence the plasticity of bladder response, inducing the release of messengers within the urothelium. This study can therefore improve our understanding of the mechanisms of sacral neuromodulation on chronic bladder dysfunction; further studies will need to better demonstrate the role of angiogenesis in the bladder after sacral neuromodulation and to investigate the effects of neuromodulation in rats with chronically induced bladder dysfunction.

Cardiovascular effects of sildenafil in hypertensive men with erectile dysfunction and different alleles of the type 5 cGMP-specific phosphodiesterase (PDE5).

Erectile dysfunction (ED) is frequent in patients with essential hypertension (EH); a likely common pathogenetic pathway could be a reduced ability of arteriolar vascular smooth muscle (VSM) to relax. Increasing intracellular levels of cGMP reduce the contractile status of VSM; on the contrary, type 5 cGMP-specific phosphodiesterase (PDE5, codified by PDE5A gene) regulates cGMP levels through its clearance. The PDE5A gene represents a good candidate for the intermediate phenotype EH/ED: genetic variants of the PDE5A may predispose to EH and ED and could affect the local and systemic response to sildenafil administration. Thus, a functionally relevant portion of PDE5 5'-flanking promoter region was analyzed by PCR and direct sequencing in patients with EH and idiopathic ED. The sequences obtained showed a T/G polymorphism at position -1142, near an AP1 regulatory element, that was not apparently associated with the intermediate phenotype. We also studied the relationship between this polymorphism and the effects of oral sildenafil on blood pressure (BP) and heart rate (HR) in men with ED. Sildenafil caused a significant decrease of BP, but had no effects on HR; statistical analysis showed no differences in BP and HR variations among PDE5A genotypes. In conclusion, our data showed no correlations of a novel polymorphism of the PDE5A promoter gene with the intermediate phenotype EH/ED and the BP and HR response to sildenafil administration. Further studies are necessary to define the role of this polymorphism and to study the genetic predisposition for EH with ED.

Detectable serum PSA after radical prostatectomy. Clinical and pathological relevance of perianastomotic biopsies.

BACKGROUND: Few reports have detailed the histopathological results of biopsies of the vesicourethral anastomosis or prostatic bed in patients with a detectable postoperative PSA. PATIENTS AND METHODS: Among a series of 153 patients who underwent radical retropubic prostatectomies, we analyzed the results of 64 perianastomotic biopsies performed in 17 men with a detectable PSA and no evidence of local recurrence or distant metastases. RESULTS: Fourteen of the 17 patients had a relapse of prostatic carcinoma; the results of histology in the three pT2bN0M0 patients revealed the presence of benign prostatic hyperplasia in 2 patients and atypical cribriform proliferation in 1 patient. The first two patients are free from prostatic cancer recurrence 36 months after perianastomotic biopsies; a further biopsy performed 6 months after in the third patient showed the presence of prostatic carcinoma. CONCLUSION: The present study raises the possibility that residual benign tissue, resulting from unintentional disruption of the prostatic capsule during surgery, may be responsible for a detectable postoperative PSA. These cases comprise a histopathological classification described as "intraprostatic surgical margin".

Skin metastases from prostate cancer associated with malignant melanoma.

A 66-year-old man, admitted to the hospital for prostatic carcinoma, presented with a nodular lesion located on the presternal region and a small nodule (0.5 cm in diameter) simulating a scalp sebaceous cyst located on the scalp. Moreover, an irregular darkbrown lesion was observed on the left side of the abdomen, and a brownish macula was also present on the presternal region. Histologic examination of the two nodular lesions revealed cutaneous metastases from prostatic carcinoma. The pigmented lesion, localized on the abdomen, proved to be a superficial spreading melanoma with a maximal depth of 1.36 mm. Histologic examination of the brownish lesion on the presternal region revealed nevus cell nests within the epidermis and in the dermis. We discuss the propensity of developing a secondary cancer in a patient with a primary malignancy.

Cryptorchidism and infertility: retrospective study of 18 post puberal patients affected with monolateral cryptorchidism.

The Authors report their experience on patients with monolateral inguinal cryptorchidism, comparing the clinical picture with the morphological pattern of both the testicular parenchima and the semen. Light and electron microscopic analysis of testicular biopsy and spermatozoa from the ejaculate have been taken into account. 4 patients out of 18 (22.2%) showed a normal spermiogram, while 14 showed a pathological spermiogram. The morphological study of the testicular parenchima showed a spectrum of lesions, most of which advanced, confirming that they are irreversible lesions of the germinal epithelium.

Infections after renal transplantation. Recipient factors affecting their incidence.

We have evaluated the incidence of infection in patients with kidney transplant, their effect on graft function and on patient outcome. Factors important for the development of infections in the post-transplant course in this group of patients have been analyzed, as well as factors affecting graft and patient survival. The prevention of infection is the main aim in this patient population, as every episode of clinical infection requiring treatment carries the potential for lethal consequences, and every effort should be made to assure appropriate screening of the prospective renal recipient.

[Long-term follow up of patients surgically treated for pyelo-ureteral disease by the Anderson-Hynes technique]. / Follow-up a distanza dei pazienti operati di malattia del giunto pielo-ureterale (GPU) secondo Anderson-Hynes.

A series of 48 patients with hydronephrosis (mean age 31 yrs.) underwent on Anderson-Hynes pyeloplasty. Assessment was carried out in 30 pts. after a mean observation time of 90 months, with a minimum 5 years follow-up. Clinical examination, laboratory investigations, renal ultrasonography, urography and renal scan were performed pre-operatively and at follow-up. There was one patient with evidence of stenosis in the ureteropelvic junction; one patient developed urinary leakage post-operatively and required surgical correction. All patients had symptoms pre-operatively and no one had symptoms post-operatively. Four patients had calcolosis associated, postoperatively all pts. were stone free; four years later one patient developed litiasis. We observed that the results of surgical intervention in hydronephrosis are excellent especially in patients aged less than 30 years.

[Gene p53 mutation and prognosis in bladder tumors]. / Mutazione del gene p53 e prognosi nei tumori vescicali.

The choice of treatment for bladder tumors is based on pathological criteria, i.e. staging and grading mainly. It has recently been observed that genetic alterations that involve activation of oncogenes and inactivation of suppressor genes can occur during tumorigenesis. p53 protein is coded for by a genes on chromosome 17, and is able to suppress malignant transformation and proliferation; it can be important in maintaining the integrity of DNA, when damaged during neoplastic disease. We have analyzed samples of transitional cell carcinoma of the bladder of 60 patients managed by conservative treatment; all the specimens have been stained for p53 protein. We could observe that the presence of the protein p53 is correlated with staging and grading and is associated with an increased risk of relapse and progression. Patients with transitional-cell carcinoma confined to the bladder that demonstrates nuclear p53 reactivity should be considered for protocols of adjuvant treatment.

[Ultrasound-guided cryosurgery of the prostate: short- and long-term experience]. / Criochirurgia ecoguidata della prostata: esperienza a breve e medio termine.

We have assessed 24 patients consecutively treated with cryosurgery and chosen according to the guidelines of the European Study Group of Urologic Cryosurgeons. Of the 24 patients (average age about 70, range 61-79), all were not considered candidates for radical prostatectomy, 9 (37%) were clinical stage cT2 N0M0, 15 (63%) cT3 N0M0 who had not received any prior treatment, except 1 patient (61 years old) who was treated with TCT and successive recurrence of the disease (cT2). Of the 24 chosen patients, 13 (55%) were over the age of 71, 11 (45%) had important factors of co-morbidity and an elevated risk of surgery (ASA 3). The average PSA was of 19.3 ng/ml (range 2.2-61). Gleason score was 2-5 in 9 cases, 6-7 in 14 and 8-10 in 1 case. In the follow-up, we evaluated serum PSA every 3 months and transrectal ultrasound and the echoguided prostatic biopsies at 6, 12 and 24 months. Post-operative complications included: ecchymosis and edema of external genitals (16/24), fever > 38 degrees C (1/24), sloughing syndrome (6/24), urinary tract infections (10/24) acute urine retention (1/24). In 2 cases, 6 months after treatment, a transrectal resection was carried out. After a follow-up at 6 months, the PSA was 0.4 ng/ml (range 0.1-0.9), in 1 case. In positive core biopsy out of 6 showed neoplastic cells with fibrous tissue; the patient had a PSA of 0.58 ng/ml. At 12 months there were 11 assessable patients. The average PSA was 0.3 ng/ml (range 0.1-0.9). At 24 months there were 4 assessable patients, 1 of 4 showed serum PSA level of 4 ng/ml and cancer in apical biopsy. Erectile dysfunction was assessed on 8 patients affective before surgery: 1 referred to sufficient erections at penetration (1/8, 12.5%). After removal of the catheter, 4 of the 20 patients suffered stress and urge incontinence with the use of 1 pad a day. In 1 case, 18 months from surgery, slight stress incontinence was found (1 pad/day). Cryoablation is an efficient method and is given to slight post-operative morbidity and no intra-operative mortality, also in patients with high risk for open surgery. Indications may be found in patients with the following conditions: older than 72 years, severe co-morbidity and high risk for surgery, neoplasia at high risk of progression, and disease recurrence after radiotherapy. Our case history is at the moment encouraging and a larger number of cases as well as longer follow-up are needed.

[Role of transrectal ultrasonography in the follow-up of patients treated with prostatic cryosurgery]. / Ruolo dell'ecografia transrettale nel follow-up dei pazienti sottoposti a criochirurgia prostatica.

Cryosurgery of prostate is a minimally invasive treatment for localized cancer. Imaging techniques (transrectal ultrasound (TRUS) or magnetic resonance) have been proposed to evaluate tumor persistence/recurrence after cryosurgical treatment other than serum PSA and prostate biopsies. Actually, criteria to identify cancer after cryosurgical ablation are not well assessed. Aim of this study is to evaluate the clinical significance and role of TRUS in detecting tumor within the former prostate gland after cryoablation. We evaluated ultrasound (US) features and imaging, serum PSA and biopsies in 20 patients treated by cryosurgery at our Hospital with a mean follow-up of 18 months. Twenty patients (mean age 70 years, PSA 25.9 ng/ml, clinical stage: 10 T2 N0M0 and 10 T3 N0M0) were followed up for a mean of 16 months. Ultrasound findings (gland volume, capsule, hypoechoic area, post-voided urine volume, seminal vesicles) were correlated to PSA levels (every 3 months) and prostate biopsies (6, 12 and 24 months). All cases were evaluated by the same ultrasound scanner (Eidos, Hitachi-5-6.5 MHz) and by two operators. Prostate capsule was interrupted by hypo-hyperechoic areas in all cases. Transition zone was no more recognizable. Ultrasound findings showed in all cases hypoechoic areas, but US did not identified tumor recurrence in 2 patients. During follow-up, PSA below 0.5 ng/ml was recorded in 75% of cases. We detected tumor in 2 cases, respectively 12 and 18 months after cryosurgery: in the first case few residual cancer cells within fibrous tissue were found in 1 out of 6 biopsies at 6 months (PSA 0.58 ng/ml), in the second one, tumor with viable normal prostatic glands was found in one biopsy of the apex at 18 months (PSA 4.0 ng/ml). TRUS showed several anaechoic foci with necrotic tissue and coalescence of liquid areas in 2 patients (one developed acute urinary retention). Actually, serum PSA is the best marker in order to detect clinically significant tumor after cryosurgery. Hypoechoic areas and capsule interruptions observed by ultrasound imaging of prostate gland after cryosurgery are not correlated with tumor recurrence or tumor persistence. TRUS is only indicated for ultrasound-guided biopsies during follow-up and to confirm urologic complications.

[Transurethral needle ablation (TUNA) in benign prostatic hypertrophy: 2-year follow-up]. / Trans-urethral needle ablation (TUNA) nell'ipertrofia prostatica benigna: follow up a 2 anni.

In this study we have evaluated the effectiveness, safety and tolerability of TUNA in the long term follow-up. We have evaluated 24 patients, aged between 66 and 81 years (mean age 73, 4 yrs) with a mean prostatic volume of 57 ml (range 33-140 mls). Before treatment, urodynamic investigation (max flow rate), residual volume, PSA, IPSS and quality of life tests have been performed in all patients. After treatment, all the patient have been evaluated at 6, 12 and 24 months by the same parameters. Based on our experience, we can say that the results obtained after 24 months are similar to those observed 12 months after treatment, except a slight increase in IPSS and quality of life tests in patients older than 70 years, with a baseline maximal detrusorial pressure > 60 cm H2O, with a baseline residual urine > 100 cc and with a baseline quality of life = 5.

Renal oncocytoma. Pathological evaluation and clinical implications.

Renal oncocytoma is a benign tumour of renal tubular origin; oncocytes are transformed epithelial cells rich in mitochondria, probably representing senescent degenerative cellular changes. Most of renal oncocytomas usually follow a benign clinical course and partial nephrectomy or enucleation has been advocated as curative. By immunohistological staining of tissue sections using monoclonal antibodies (DBA, SBA, PNA, UEA, Cytocheratine), we can suppose the histogenetic origin of renal oncocytomas from a region other than the proximal tubular epithelium, and in particular from the collecting duct epithelium. We believe that it is most important to perform flow cytometry to study the chromosomal pattern of the tumour, once intra-operative frozen sections have advanced the suspicion of renal oncocytoma; if oncocytic cells show a diploid pattern, and the tumour mass is well circumscribed and has not an excessive diameter, we favour renal sparing surgery.

[Urinary NMP22 as a new marker in patients with transitional cell carcinoma]. / NMP22 urinario come nuovo marcatore tumorale in pazienti con carcinoma uroteliale.

To evaluate urinary NMP22 dosage as a marker of urothelial tumours, we have selected a group of 90 patients (85 males and 5 females, mean age 66 years) with clinical suspicion of transitional cell carcinoma (TCC), with microscopic or macroscopic hematuria, flank pain, urographic abnormalities and dysuria. All the patients have been evaluated by urinary cytology, renal and bladder ultrasound, cystoscopy. When a bladder tumour has been detected, bladder biopsies and, when required, I.V.P., CT or retrograde pyelography have been performed. A urine sample has been collected between midnight and noon; all samples from patients who were undergoing invasive procedures such as cystoscopy, were collected before or at least 5 days after the procedure. The test has been performed according to ELISA NMP22 (Matritech) technique; the test is specific for the nuclear matrix protein/nuclear mitotic apparatus protein expressed by cancer cells. When performing the test, 30 patients presented macroscopic hematuria. 22 patients resulted to have benign urinary tract conditions, 65 patients had TCC and 3 patients had a final evaluation suspicious for TCC. The NMP22 values were respectively 7.1 +/- 4.7 U/ml, 21.9 +/- 21.0 U/ml and 16 +/- 8.0 U/ml. From our study the sensitivity of the test is 67% (with a threshold value of 10 U/ml) and 55% (with a threshold value of 20 U/ml), while the urinary cytology resulted to have a sensitivity of 26% (p < 0.05). The sensitivity of the test in relation to staging was as follow: Tis 66% with a mean NMP22 value of 23.3 U/ml, Ta 26% with a mean NMP22 value of 13.2 U/ml, T1 100% with a mean NMP22 value of 40 U/ml, T2 73% with a mean NMP22 value of 36.4 U/ml. The specificity of the test was 100% with a threshold value of 20 U/ml. When considering a threshold value of 10 U/ml, the NMP22 test has a sensitivity higher than cytology, especially in low stage TCC. Macroscopic hematuria does not affect its sensitivity; the diagnostic efficacy of the test is not increased by the association of urinary cytology. It has an important role in the diagnosis of residual disease after TURB and in the follow-up evaluation of bladder cancer patients, since its dosage is not influenced by inflammatory conditions of the mucosa. We believe therefore that NMP22 is useful in clinical practice.