Large-cell neuroendocrine carcinoma of prostate. Case report.

OBJECTIVE: To report a case of a neuroendocrine differentiation in a prostate cancer patient, a rare subtype. METHODS: We describe the case of a patient diagnosed with adenocarcinoma of the prostate initially, who presented hematuria due to disease progression with neuroendocrine differentiation despite androgen-deprivation therapy (ADT ). DISCUSSION: Prostate cancer is the most common tumor in men. Histologically they are diagnosed as adenocarcinomas, which followed by ADT for a long time, develop neuroendocrine differentiation (NED ). CONCLUSIONS: The prognostic significance of NED remains controversial. We must think in neuroendocrine differentiation in ADT-treated patient with disease progression and low PSA.

Paratesticular rhabdomyosarcoma: a case report.

OBJECTIVE: To report a case of paratesticular rhadomyosarcoma and to perform a bibliographic review. METHODS: We report the case of a 16-year-old male referred to our Department because of a left paratesticular hard tumor with progressive growth. Ultrasound examination showed a paratesticular heterogeneous mass with Internal flow on Doppler. RESULTS: The patient underwent left inguinal orchiectomy, with pathological diagnosis of rhabdomyosarcoma. He refused adjuvant chemotherapy. After being disease-free for 13 months, he presented with left colic pain. Ultrasound and CT examinations showed a left paraaortic retroperitoneal mass causing grade III ureterohydronephrosis, and lung metastases. Despite rescue chemotherapy treatment, there was no response and the abdominal mass progressed. A surgical approach was not possible since patient showed a rapid clinical worsening leading to his death a few weeks later. CONCLUSIONS: Paratesticular sarcomas are very uncommon tumors with poor prognosis.

Right hypochondrium pain and giant mass.

OBJECTIVE: To report a case of a right hypochondrium giant mass in a 40-year-old patient. METHODS: We report the case of a 40 year-old male referred to our Department because of right hypochondrium pain and increased abdominal perimeter. Radiological examination showed a 30 × 24 × 20 cm retroperitoneal mass, dependent on the upper pole of the right kidney. RESULTS: We performed radical nephrectomy through a mid line laparotomy. The pathological analysis described it as a clear cell renal carcinoma pT2bN0M0. CONCLUSION: There are few reported cases of renal carcinomas with intraparenchymal bleeding exceeding 20 cm, the largest one exceeding 10 kg, and they usually show a good prognosis.

Impact of benign prostatic hyperplasia surgery on erectile function.

AIM: We evaluate the prevalence of erectile dysfunction (ED) prior to surgery for benign prostatic hyperplasia (BPH) and changes produced after surgical intervention. PATIENTS AND METHODS: This prospective study included 128 patients treated surgically for BPH. The prevalence of ED was determined before and after surgery according to the International Index of Erectile Function (IIEF). The influence of different clinical variables on erectile function (EF) improvement or deterioration after surgery was determined using uni- and multivariate analyses. RESULTS: Mean IIEF score before surgery was 20.5 +/- 7.6. Overall, ED was absent in 32% of patients, mild in 42%, moderate in 13.3%, and severe in 12.5%. Mean IIEF score following surgery was 21.5 +/- 7.4 (p = n.s.). After surgery EF improved in 26.6% (34/128) of patients and worsened in 18.8% (24/128) (p < 0.05). Analysing the subset of patients with presurgical ED, 39% reported improvement and 21.1% reported worsening of EF postoperatively. None of the variables analyzed showed a significant relationship with improvement or worsening of EF. Only age was related to worsening EF in the subgroup of non-ED patients. CONCLUSIONS: There is a high prevalence of ED amongst candidates for BPH surgery. Although the risk of worsening EF exists postsurgically, an important percentage of ED patients will improve.

Impact of different patterns of sperm chromosomal abnormalities on the chromosomal constitution of preimplantation embryos.

OBJECTIVE: To evaluate the effect of sperm chromosome abnormalities--disomy for sex chromosomes and diploidy--in the chromosomal constitution of preimplantation embryos. DESIGN: Retrospective cohort study. SETTING: Infertility clinic. PATIENT(S): Three groups: 46,XY infertile men with increased incidence of sex chromosome disomy in sperm; 46,XY infertile men with increased diploidy rates in sperm; 47,XYY infertile men with increased sex chromosome disomy and diploidy rates in sperm. INTERVENTION(S): Sperm collection for fluorescence in situ hybridization analysis. Embryo biopsy for preimplantation genetic screening. MAIN OUTCOME MEASURE(S): Frequencies of numerical abnormalities in sperm for chromosomes 13, 18, 21, X, and Y, and in embryos for chromosomes 13, 16, 18, 21, 22, X, and Y. RESULT(S): A significant increase of chromosomally abnormal and mosaic embryos was observed in the three study groups compared with controls. Those sperm samples with increased sex chromosome disomy rates produced significantly higher percentages of aneuploid embryos, with a threefold increase for sex chromosomes. Sperm samples with increased diploidy rates were mainly associated to the production of triploid embryos. CONCLUSION(S): A strong correlation between sperm and embryo chromosomal constitution has been shown in infertile men with 46,XY and 47,XYY karyotypes.

[Assymptomatic prostatic infiltration by chronic lymphocytic leukemia]. / Infiltración asintomática de la próstata por leucemia linfática crónica.

OBJECTIVE: Report of a case of leukemic infiltration of the prostate as an incidental CT finding. METHODS: We describe a case of a 60-year-old male suffering from chronic lymphocytic leukemia. A routine-performed CT showed multiple lymphadenopathies and an hypodense area in the left prostatic lobe. The patient was sent to our department to carry out a transrectal ultrasound and prostatic biopsy. He didn't relate any urinary symptoms. RESULTS: By the prostate rectal examination the gland felt hard and with no well defined limits. The transrectal ultrasound showed heterogene parenchyma and several hyperechoic areas by a bad circumscribed prostate. The pathological analysis reported a diffuse infiltration of the gland by chronic lymphocytic leukemia cells. CONCLUSIONS: Although the relapse of hematological tumors to the prostate has been described previously, there is no published case to our knowledge of a leukemic prostate infiltration in an assymptomatic patient as an incidental finding by an imaging procedure.

First report of the absence of viral load in testicular sperm samples obtained from men with hepatitis C and HIV after washing and their subsequent use.

Human immunodeficiency virus and hepatitis C infections are sexually transmitted diseases that require sperm samples to be pretreated to eliminate the viral presence before their safe use in assisted reproduction treatments. In this report we describe our experience with sperm washing protocols applied to sperm cells from testicular biopsies as well as the results obtained in subsequent assisted reproduction treatments on seropositive males that are also azoospermic.

Relationship between the Saint Louis University ADAM questionnaire and sexual hormonal levels in a male outpatient population over 50 years of age.

OBJECTIVES: To determine the relationship between the ADAM questionnaire and the sexual hormonal levels in a male population older than 50 yr, and to know the predictive capacity of this questionnaire with regard to biochemical hypogonadism in the ageing male. METHODS: A prospective study was carried out on 230 Spanish men. Patients were evaluated by clinical history. The ADAM questionnaire and the Yesavage's Geriatric Depression Scale were completed by each patient. Blood tests were performed including total testosterone, SHBG, free testosterone (FT), dehidroepiandrosterone sulfate (DHEA-S), androstenedione, 17-beta-estradiol, FSH, LH, and prolactin. The relationship between positive ADAM questionnaire and age, clinical and sociodemographic backgrounds, and hormone levels was analysed by means of uni- and multivariate tests. The capacity of the ADAM questionnaire to predict biochemical hypogonadism was determined with a chi-square test. RESULTS: ADAM questionnaire (excluding men with positive Yesavage's Scale) was positive in 140 patients (67.9%). With respect to clinical backgrounds, diabetes mellitus and age had a significant relationship with an ADAM-positive questionnaire. With respect to hormones, FT and DHEA-S levels were significantly lower when the ADAM questionnaire was positive. In the multivariate analysis, age, FT, and diabetes were independently related to an ADAM-positive questionnaire. Prevalence of biochemical hypogonadism (FT<0.228 nmol/l) was 24.6%. The ADAM test had a sensitivity of 84.0% and a specificity of 36.6% to detect biochemical hypogonadism. CONCLUSIONS: FT is inversely related to the ADAM-positive questionnaire, independently of age. The ADAM questionnaire is a valid test to detect hypogonadism but has low specificity.

Percentage of cancer in prostate biopsies as prognostic factor for staging and postoperative biochemical failure after radical prostatectomy.

OBJECTIVE: To assess if the percentage of cancer in prostate needle biopsies provides independent prognostic information for predicting pathological stage and/or biochemical relapse after radical prostatectomy. METHODS: One hundred and forty prostate cancer patients who underwent radical prostatectomy were evaluated. Preoperative parameters analyzed were patient age, PSA, clinical stage, and the information obtained from sextant biopsies (Gleason score, maximum percentage of cancer in a core, percentage of tissue with cancer in all biopsies and the number of cores positive for cancer). Univariate and multivariate analyses (logistic regression) for the dependent variables (prostate cancer, organ-confined and biochemical relapse) were performed. RESULTS: The tumor was organ-confined in 73.6% of patients. In those patients studied for disease progression (n = 126), no biochemical recurrence was observed in 76.2%. In the multivariate analysis for organ-confined disease, the total percentage of biopsy tissue with cancer, the preoperative PSA level, the Gleason score and the clinical stage were the most accurate predictive factors of pathological stage. The multivariate analysis for the study of biochemical failure indicated that only the total percentage of biopsy tissue with cancer, the preoperative PSA level and the Gleason score were independent predictive factors. According to the logistic regression analysis for disease recurrence, 3 risk groups could be identified: low risk (less than 10% probability of disease progression), intermediate risk (30%) and high risk (more than 70%). CONCLUSIONS: The percentage of cancer in prostate biopsy provides independent prognostic information for predicting pathological stage and the risk of biochemical failure after radical prostatectomy.

Testosterone levels in men with erectile dysfunction.

OBJECTIVE: To investigate the frequency of hypogonadism in men with erectile dysfunction (ED) and to assess which factors are related with low testosterone levels. PATIENTS AND METHODS: In all, 165 men with ED were assessed; the evaluation included: hormonal profiles, serum total and free testosterone (using Vermeulen's formula) levels, and self-reported questionnaires on erectile function and desire domains of the International Index of Erectile Function. The frequency of hypogonadism was established using total and free testosterone levels as diagnostic criteria. The factors that might influence testosterone levels were evaluated by univariate and multivariate statistical analysis, and a logistic regression was used to determine which factors can predict free testosterone levels below normal limits (biochemical hypogonadism). RESULTS: Using the total testosterone levels, 4.8% of the men were hypogonadal, whereas when using the free testosterone levels, 17.6% were hypogonadal. In the univariate analyses, not smoking and hypertension were associated with lower total and free testosterone levels. Ageing, absence of nocturnal erections and a lower erectile function score were only associated with lower free testosterone serum levels. There was no association between total and free testosterone levels and desire. In the multivariate analysis, only total testosterone levels were related to hypertension, while free testosterone levels were related to age and nocturnal erections. For biochemical hypogonadism, simple logistic regression analysis selected age, erectile function score and aetiological diagnosis of ED as predictors. In the multivariate analysis only the erectile function score had significant independent prognostic value. CONCLUSIONS: The frequency of hypogonadism is higher when free testosterone levels are used for diagnosis. The total and free testosterone levels were not related to the level of sexual desire in men with ED. The free testosterone levels could be related to the quality and frequency of nocturnal erections, and when ED is more severe, it is more probable that free testosterone levels are below the 'normal' limit.

Presence of human papillomavirus DNA in testicular biopsies from nonobstructive azoospermic men.

CONTEXT: Human papillomavirus (HPV) plays a major role in the etiology of many malignancies of diverse localization, such as uterine cervical carcinoma and its precursors. Human papillomavirus sequences have been detected throughout the male lower genitourinary tract, but the role of men as transmitters remains unclear. OBJECTIVE: To investigate the relationship between azoospermia and the presence of HPV DNA in testicular cells. DESIGN: One hundred eighty-five patients with azoospermia undergoing testicular biopsy were studied. Histologic study was done on formalin-fixed, paraffin-embedded samples from testicular biopsies, stained with hematoxylin-eosin. Molecular study to detect HPV sequences was performed on genomic DNA isolated from paraffin sections by standard protocols. Seven cases containing HPV sequences were studied after microdissection with PALM microlaser technology in order to determine the presence of HPV DNA sequences in different cells, as well as from seminal tubules or stromal (Leydig) cells. RESULTS: Human papillomavirus DNA sequences were detected in testicular biopsies of 12 patients (6.48%). Human papillomavirus type 16 was the most common genotype encountered. Among the 92 patients who underwent bilateral testicular biopsy, HPV sequences were detected in 9 patients (9.78%), all of whom showed only unilateral testicular affection, more often in the left testicle (ratio, 2: 1). After microdissection, HPV DNA sequences were seen in Leydig and Sertoli cells; the presence of HPV in germinal cells could not be ruled out. CONCLUSIONS: Leydig cells, Sertoli cells, and probably germinal cells (cases 2, 3, and 4) harbored HPV DNA sequences. Such findings have not been previously described in testicular tissue.

[Spermatic recovery techniques for intracytoplasmic spermatozoid injection (ICSI) in male infertility]. / Técnicas de recuperación espermática para inyección intracitoplasmática de espermatozoides (ICSI) en infertilidad masculina.

The introduction of intracytoplasmic spermatozoid injection (ICSI) not only has improved significantly the prospects of fertility after assisted reproduction by using spermatozoa recovered from the seminal tract, but also has allowed extension of the spectrum of recovery techniques. For obstructive azoospermia, it is currently possible to use not only spermatozoa obtained by microsurgical techniques from the epididymis (MESA), but also spermatozoa obtained from the testicle by means of testicular biopsy (TESE), or spermatozoa percutaneously aspirated from the testicle/epididymis by minimally invasive techniques (TESA, PESA). Minimal requirements in terms of spermatic quality for ICSI have also allowed to successfully criopreserve epididymal and testicular spermatozoa. ICSI results are not influenced by the origin of spermatozoa (epididymis or testicle), neither by the technique of spermatic recovery. Fresh or criopreserved spermatozoa microinjections are not different either. On the other side, 40-60% of patients with secretory azoospermia show small foci with preserved spermatogenesis in their testicles. For ICSI, these scarce spermatozoids may also be extracted from the testicle by multiple open biopsies, percutaneous aspiration, or microsurgical biopsies (micro-TESE). Nevertheless, in secretory azoospermia the yield of percutaneous techniques is lower than open or microsurgical procedures. It is also possible to criopreserve testicular spermatozoa in secretory azoospermia without the process significantly influencing ICSI results. Finally, spermatozoid testicular recovery by biopsy or percutaneous aspiration followed by ICSI has also been employed as a resource in patients with necrozoospermia and anejaculation.

Prognostic value of morphometry in low grade papillary urothelial bladder neoplasms.

OBJECTIVE: To analyze the prognostic value of morphometry in low grade papillary urothelial bladder neoplasms (LGPUBNs). STUDY DESIGN: The primary (most common) and secondary (second most common) histologic grades were considered in accordance with the 1998 World Health Organization/International Society of Urological Pathology and the 1999 World Health Organization classifications. With the primary grade, 54 cases were papillary urothelial neoplasms of low malignant potential (PUNLMPs) and 66 low grade papillary urothelial carcinomas (LGPUCs), whereas the secondary grade consisted of 45 PUNLMPs and 75 LGPUCs. To assess the proliferative index, an immunohistochemical study was performed. Regarding nuclear morphometry, an image analysis system on Feulgen-stained sections was utilized in different tumor zones (Zs): Z 1, 100-150 cells from the outer layers of the papillae; Z 2, 100-150 cells from the inner layers; and Z 3, 10 largest nuclei. In univariate studies, a t test, and Mann-Whitney U test and Kaplan-Meier curves were applied, whereas a Cox regression model was used for multivariate study of the variables: size, multiplicity, maximum Ki-67 index, mean nuclear area (MNA) and SD, mean nuclear perimeter and SD, and roundness factor. RESULTS: All 120 cases were followed for a mean of 76.6 months (range, 36-168). In univariate studies, many variables showed a significant correlation (p < 0.05) with recurrence prediction, relapse-free interval and histologic grade regardless of adjuvant therapy. Otherwise, only the MNA of the 10 largest nuclei (threshold, 52 microm2) and the maximum proliferative index (threshold, 7.9%) appeared as independent prognostic markers in the multivariate study. CONCLUSION: In LGPUBNs, the independent prognostic value of MNA of the 10 largest nuclei as well as the maximum proliferative index indicates the importance of histologic grade assessment based on the secondary (second most common) grade.

Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in hypogonadotropic hypogonadism with persistent azoospermia after hormonal therapy.

PURPOSE: We aimed to retrieve testicular sperm to be employed on intracytoplasmic sperm injection (ICSI) cycles on a male affected of hypogonadotropic hypogonadism (HH) that remained azoospermic after long-time hormonal treatment. METHODS: Design. We initially performed hormonal therapy using gonadotropins to achieve spermatogenesis. After several semen analyses, we weighed the possibility of looking for testicular spermatozoa for ICSI. Setting. A private university-affiliated setting. Patient. A 30-years-old man diagnosed 10 years ago to suffer from idiopathic, prepubertal HH. Interventions. Gonadotrophin treatment was initiated with hCG and follicle stimulating hormone (FSH). Testicular sperm extraction was carried out when repeated spermiograms were negative. Motile testicular spermatozoa were cryopreserved and were subsequently employed for ICSI. Multiple follicular development was stimulated with gonadotropins after a downregulation with gonadotropin-releasing hormone (GnRH) antagonists in the woman. Main Outcome Measures. Seminal analyses were performed after 3, 6, and 12 months of treatment and serum FSH, luteinizing hormone (LH) and testosterone levels were also measured. RESULTS: Seminal analysis showed always azoospermia. Serum FSH was 2.9 mIU/mL, serum LH >1 mIU/mL and serum testosterone 7.9 ng/mL (12 months after treatment). Nine oocytes were collected by ultrasound-guided transvaginal route and eight of them were microinjected with motile, frozen-thawed testicular spermatozoa. Four oocytes were fertilized. Three embryos were transferred without pregnancy. CONCLUSIONS: The case report here presented shows that the currently available assisted reproduction techniques may be of value in patients with HH not responding to conventional hormonal treatments.

[Comparative study of P 53, Bcl-2, and C-erbB-2 expression in low-grade papillary bladder tumors]. / Estudio comparativo de la expresión de p53, Bcl-2 y C-erbB-2 en neoplasias papilares vesicales de bajo grado.

OBJECTIVE: To study the prognostic value of p53, bcl-2 and c-erbB-2 immunoexpression in predicting tumor relapses in low-grade papillary bladder neoplasms. METHODS: In all patients a complete transurethral resection of the lesion was performed. All the material was formalin-fixed and paraffin-embedded. At the immunohistochemical level, the following monoclonal antibodies were utilized: p53 (clone DO7), bcl-2 (clone 124) and c-erbB-2 (clone CB11). In order to predict tumor relapses during follow-up, a study of specificity, sensitivity and predictive positive value (PVP) and negative was designed. In univariate statistical studies, the following tests were utilized: Chi-square, Kaplan-Meier estimates and Cox logistic regression. RESULTS: Mean follow-up was 76.6 months (38 to 168). In recurrence prediction, p53 expression showed a high specificity (99%) as well as a high PPV (96%). Regarding bcl-2 and c-erbB-2 immunoexpression, both specificity (65% and 72%) and PPV (61% and 72%) were also high, although these percentages were lower than those obtained for p53 expression. The combined analysis of p53 and bcl-2 indicated that bcl-2 immunoexpression in non-basal cells of the urothelium could be independent of p53, although the number of cases showing this particular expression pattern is not high enough to perform an accurate statistical analysis. Otherwise, histologic grade demonstrated higher sensitivity (64%) and lower specificity (40%) than the immunohistochemical markers. In univariate studies, p53 showed an intense statistical correlation with relapse-free interval (RFI) and prediction of tumor recurrences during follow-up (p < 0.001), whereas the expression of bcl-2 (p = 0.065) was nearly correlated with RFI (p = 0.065). In contrast, expression of c-erbB-2 did not show statistical correlation (p = 0.112). CONCLUSIONS: In our study, individual and combined analysis of p53 and bcl-2 immunoexpression have demonstrated to be useful in predicting tumor recurrences and RFI in low-grade bladder lesions.

Cytokeratin expression patterns in low-grade papillary urothelial neoplasms of the urinary bladder.

BACKGROUND: The differential expression patterns of cytokeratin 20 (CK20) and 34betaE12 antigen in low-grade papillary urothelial tumors of the bladder are discussed. METHODS: A retrospective study of 120 patients with low-grade papillary bladder tumors (45 neoplasms of low malignant potential and 75 low-grade WHO G1 carcinomas) was performed. All tumors were graded in accordance with the 1998 World Health Organization/International Society of Urological Pathology (WHO/ISUP) and 1999 WHO classifications. The mean follow-up was 76.6 months (range, 36-168 mos), considering for prognostic purposes the time to first recurrence, or relapse-free interval (RFI), and the total number of recurrent patients. Immunohistochemically, normal or abnormal CK20 and 34betaE12 antigen expression patterns were determined for each patient. CK20 (clone IT-Ks) and a high-molecular weight cytokeratin (clone 34betaE12) were the monoclonal antibodies used in the immunohistochemical study. RESULTS: Seventy-seven of 120 patients (64.2%) experienced a recurrence during follow-up. In recurrence prediction, the differential expression pattern of both cytokeratins showed a high sensitivity (76.6% for CK20 and 80.5% for 34betaE12 antigen) and a high positive predictive value (85.5% for CK20 and 75.6% for 34betaE12 antigen), although specificity was higher for CK20 (76.7%) than it was for 34betaE12 antigen (53.4%). Independent of adjuvant intravesical chemotherapy, these 2 markers showed a strong statistical correlation (p < 0.001) in univariate studies with both the prediction of disease recurrences and RFI. CONCLUSIONS: CK20 and 34betaE12 antigen have proved to be strong predictive markers of disease recurrences when considering different topographic expression profiles, and, in the authors' opinion, these profiles could be incorporated into follow-up clinicopathologic strategies.