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.

Pre-treatment neutrophil-to-lymphocyte ratio may be associated with the outcome in patients treated with everolimus for metastatic renal cell carcinoma.

BACKGROUND: Everolimus is a mammalian target of rapamycin inhibitor approved for the treatment of metastatic renal cell carcinoma (mRCC). We aimed to assess the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the outcome of patients treated with everolimus for mRCC. METHODS: Ninety-seven patients with mRCC were treated with everolimus till April 2013 in our institutions. Patients were stratified in two groups with NLR >3 (Group A) vs <3 (Group B). Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier method. Gender, age, Motzer prognostic group, PFS on first-line therapy, neutrophilia and NLR were included in the Cox analysis to investigate their prognostic relevance. RESULTS: Median OS and PFS were 10.6 and 5.3 months, respectively. Median OS was 12.2 months in Group A and 24.4 months in Group B (P=0.001). Median PFS was 3.4 months in Group A and 9.9 months in Group B (P<0.001). At multivariate analysis, only Motzer prognostic group and NLR were independent prognostic factors for OS and PFS. CONCLUSION: Pre-treatment NLR is an independent prognostic factor for patients with mRCC treated with second- or third-line everolimus. This should be investigated and validated in prospective studies.

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.

Expression of basic fibroblast growth factor, its receptors and syndecans in bladder cancer.

Basic fibroblast growth factor (bFGF) is a heparin-binding cationic protein involved in a variety of pathological conditions including angiogenesis and solid tumour growth. The basic fibroblast growth factor receptor (FGFR) family comprises at least 4 high affinity tyrosine kinase receptors that require syndecans for their function. Mounting evidence indicates that syndecans, that bind both bFGF and their FGFRs, will act as stimulators, whereas syndecans that only bind bFGF will act as inhibitors of signaling by sequestering the growth factor. Recent findings have highlighted the importance of syndecans in urological cancers. The aim of this study is to investigate the expression of bFGF, its receptors (R1 and R2) and syndecans (1-4) in invasive urothelial carcinoma and normal-looking urothelium by Western blotting, RT-PCR, and immunohistochemistry analyses. Interestingly, bFGF, FGFR1 and FGFR2 protein levels statistically increased in bladder cancer tissues. mRNA of FGFR1 and syndecans (1-4), showed a statistically significant increase while an mRNA increase in the other molecules analysed was not significant. bFGF, its receptors and syndecan immunostaining were mainly present in the urothelium both in normal-looking tissues and urothelial neoplastic cells. In conclusion, our data report that the bFGF, FGFR and syndecan expressions are altered in bladder tumours.

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.

Neutrophil-to-lymphocyte ratio may be associated with the outcome in patients with prostate cancer.

PURPOSE: Evidences have shown that neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with cancer. We wanted to test the prognostic significance of NLR in prostatic cancer of patients who are candidate to radical prostatectomy. METHODS: We have considered 731 patients. Complete demographic data including age, tumor stage, Gleason score, complete blood count and serum biochemical profile were collected. Pre-treatment percentage of neutrophils and NLR were considered, and correlated with patients data and recurrence free survival. RESULTS: 389 patients were evaluated, mean age 65 years, mean follow-up 51.5 months, mean recurrence free survival 51.3 months. Total neutrophil count does not correlate with biochemical recurrence and disease free survival. Patients with a value higher of 60% of neutrophils are more likely to have a recurrence. Patients with a total lymphocyte count <1,500 have a higher rate of relapse. NLR was not correlated with baseline total PSA, with Gleason score and with pathological stage; patients with a NLR >3 has a higher incidence of recurrence. In multivariate analysis including age, total PSA and NLR, NLR is the most important factor able to predict recurrence. There are some limitations to this study; first, this is a retrospective study, and the total number of patients analyzed is relatively small. CONCLUSIONS: Our study suggests that pre-treatment NLR may be associated with disease free survival in patients with prostate cancer, and could be introduced in clinical practice. NLR has the advantage of low economic cost and wide availability.

Effects of combination endocrine treatment on normal prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma.

AIMS: To investigate the effect of combination endocrine treatment (CET) or luteinising hormone releasing hormone agonist and flutamide on non-neoplastic prostate, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma. METHODS: The morphology, including the mitotic activity, of 12 radical prostatectomies from patients with prostatic adenocarcinoma pretreated for three months with CET was evaluated in haematoxylin and eosin stained sections and compared with an untreated age and stage matched control group. RESULTS: A differential effect on the non-neoplastic prostate was observed. In fact, the transition zone of the treated prostate showed simplification of the glandular lobules: the ducts and acini were small without undulations of the epithelial border and with a prominent basal cell layer. Within the peripheral zone there was inconspicuous branching of the ducts and acini which looked dilatated and lined by flattened atrophic epithelium. Prostatic intraepithelial neoplasia occurred in scattered ducts and acini in the peripheral zone of 10 of the 12 patients. The epithelial cell lining showed a prominent basal cell layer. A certain degree of secretory cell type stratification was always present. However, crowding was less evident than in the untreated prostate because of cytoplasmic clearing and enlargement as a result of coalescence of vacuoles. The treated adenocarcinomas had neoplastic acini which looked small and shrunken, and areas of individual infiltrating tumour cells separated by abundant interglandular connective tissue. The secretory cells of the nonneoplastic, prostatic intraepithelial neoplasia, and prostatic adenocarcinoma lesions had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation, and cytoplasmic clearing. Apoptotic bodies were easily identifiable in all the cell layers. The lumina were rich in macrophages, sloughed secretory cells with degenerative features, and apoptotic bodies. Mitoses were not observed in any of the treated non-neoplastic prostate, prostatic intraepithelial neoplasia, or prostatic adenocarcinomas, whereas the mitotic frequency increased from non-neoplastic prostate through prostatic intraepithelial neoplasia up to prostatic adenocarcinomas in the untreated specimens. CONCLUSIONS: CET before radical prostatectomy causes regressive epithelial changes together with enhanced apoptosis and blocked mitotic activity.

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".

Prostatic invasive adenocarcinoma. Effect of combination endocrine therapy (LHRH agonist and flutamide) on the expression and location of proliferating cell nuclear antigen (PCNA).

Expression and location of Proliferating Cell Nuclear Antigen immunostaining in epithelial nuclei were assessed on histological sections from 32 cases of invasive adenocarcinoma of the prostate gland: 20 untreated and 12 treated with combination endocrine therapy or CET. The PCNA-positive nuclei showed homogeneous or granular types of staining or a mixture of both, and a gradation in the intensity of staining. Nuclei with homogeneous patterns appeared darker brown than the lighter granular and mixed patterns. Darker nuclei were more frequently noted, mainly among the epithelial cells adjacent to the stroma, in the untreated cases. In contrast, nuclei with pyknotic chromatin, unstained and corresponding to apoptotic bodies, were more frequently seen in the treated patients. For the untreated invasive adenocarcinomas, the mean proportion of PCNA-stained epithelial nuclei in the 10 cases with an acinar pattern (small and large) was 8.86% (SE 0.23%). The mean value in the 5 cases with a cribriform pattern was 11.76% (SE 0.52%), that is, greater than in the acinar pattern, and decreased from the nuclei in the basal position, or adjacent to the stroma, toward the lumen: 14.40% (SE 0.61%) in the basal position, 11.84% (SE 1.30%) in the intermediate and 9.26% (SE 0.66%) in the lumenal. In the 5 cases with a solid/trabecular pattern, the proportion of PCNA-positive nuclei was 15.74% (SE 2.30%), that is, higher than in all the other patterns, and decreased from the cell layer adjacent to the stroma (17.60%, SE 2.92%) toward the other layers (13.88%, SE 1.71%).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

[Endoscopic treatment of vesicoureteral reflux in adults with bovine collagen]. / Il trattamento endoscopico del reflusso vescico-ureterale nell'adulto mediante collagene bovino.

Endoscopic subureteral collagen injection has become widely accepted a practiced method for the treatment of vesico-ureteral reflux in children. The aim of this study was to evaluate the efficacy of the treatment in adult patients affected by vesico-ureteral reflux. We have selected 45 patients with primary e 10 patients with secondary reflux (tot. 76 ureters) treated by endoscopic subureteric injection of collagen. The success rate after one injection in primary reflux was 74%. 13 ureters required a 2nd or 3rd injection to achieves success. The minimum follow-up time for the successfully treated patients was 12 months; we did not observe no reflux in 92% of ureters. Endoscopic injection of collagen is a reliable alternative to open surgery.

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.

[Fragments of prostatic biopsy: characteristics, dimensions, and number]. / I frammenti di biopsia prostatica: caratteristiche, dimensioni e numero.

Prostate needle biopsy can give important clinical information on tumor extension and grading, useful prognostic parameters for the therapeutic choice and prognostic definition. Currently about the 25% of positive biopsies for carcinoma contain only small foci of cancer that makes histopathological evaluation often the difficult and less reliable. We reviewed the literature about different methods to perform needle biopsies and methods to improve histologic yield of prostatic biopsies in order to obtain more histopathological information on the specimens to improve diagnostic accuracy on core biopsy. We report our initial experience using the preembedding methods proposed by Rogatsch. The best method to perform a prostate biopsy includes the use of using 18-gauges needles, single specimen identification and subsequent orientation of every bioptic fragment by inking its proximal end. We performed the preembedding technique of the fragments, proposed by Rogatsch et al., stretching the fragment between two nylon meshes enclosed in a tissue cassette in formalin. The full length of the biopsy is within the section plane. This technique partially modified in our preliminary experience with the employment of two sponges containing 10% buffered formalin placed in a tissue cassette (2.8 x 3.3 cm). This "sandwich" technique has furnished evident advantages for the pathologist, optimizing the visible area for section plane in comparison to that obtainable from free floating core biopsies. In conclusion, routinely application of the preembedding prostatic core biopsies could improve the accuracy of the histopathological examination and therefore provide more reliable data on tumor extension and grade.

[Intraprostatic spread of prostatic carcinoma: stereographic representation based on ultrasonography and biopsy findings]. / Diffusione ghiandolare del carcinoma prostatico: schema di rappresentazione steroegrafica su reperti ecografici e bioptici.

The aim of this study is to identify and evaluate a scheme of graphic representation of the prostate, that allows the reconstruction of cancer diffusion based on ultrasound findings and on histological biopsy findings. A graphical representation of the prostate using transversal and longitudinal sections is represented by the US-operator, who write severy single performed biopsies (site, directions, and angle) and draws the US relieves. Biopsy specimens are separately prepared on a paper-support and marked at one extremity with china ink. The histopathological examination on every single specimen allows to identify the tumor extent, Gleason grading and the percentage occupied by the neoplasia. Were performed 50 transrectal echo-guided mapping biopsies. Comparing biopsy results with the pathological analysis on 13 whole-mount radical prostatectomy: pathological stage was predicted in 6 of 7 cases, Gleason grading was predicted in 85% of cases. In 5 cases in which the core biopsy histological analysis showed only atypical glands suspicious for cancer it has been possible to repeat new biopsies in the same site of the gland. Tumor was this time diagnosed in 3 of 5 cases (60%). The proposed approach can be useful to reduce variables linked to operator, technique, and single clinical situation, but it needs an employment on a higher number of cases and a verification on more surgical specimens. The scheme proposed has been of easy complication and immediate interpretation by clinicians and pathologists.

[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.