Antonio Carlos Lima Pompeo

Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: a systematic review and meta-analysis

The objective of this study was to clarify the role of bisphosphonates in the treatment of osteoporosis in patients with prostate adenocarcinoma under androgen deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American Society of Clinical Oncology abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer (PC) under ADT. The outcomes assessed were fracture, osteoporosis, incidence of adverse events and changes in bone mineral density (BMD) during treatment. A total of 15 articles (2634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (risk ratio (RR), 0.80; P=0.005) and osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number needed to treat (NTT), compared with placebo, in relation to fractures and osteoporosis (NNT=14.9 and NNT=2.68, respectively). The between-group difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD were 5.18±3.38% and 2.35±1.16%, respectively. This benefit of bone loss prevention could be reached without major side effects (cardiovascular or gastrointestinal events). Bisphosphonates are effective in preventing bone loss in patients with PC who are under ADT.

Prospective Randomized Study of Treatment of Large Proximal Ureteral Stones: Extracorporeal Shock Wave Lithotripsy Versus Ureterolithotripsy Versus Laparoscopy

PURPOSE The best treatment modalities for large proximal ureteral stones are controversial, and include extracorporeal shock wave lithotripsy, ureterolithotripsy, percutaneous nephrolithotripsy, laparoscopic ureterolithotomy and open surgery. To the best of our knowledge extracorporeal shock wave lithotripsy, semirigid ureterolithotripsy and laparoscopic ureterolithotomy have not been previously compared for the treatment of large proximal ureteral stones. Therefore, we compared these modalities for the treatment of large proximal ureteral stones. MATERIALS AND METHODS A total of 48 patients with large proximal ureteral stones (greater than 1 cm) were prospectively randomized and enrolled in the study at a single institution between 2008 and 2010. Eligible patients were assigned to extracorporeal shock wave lithotripsy, semirigid ureterolithotripsy or laparoscopic ureterolithotomy. RESULTS Extracorporeal shock wave lithotripsy had a 35.7% success rate, semirigid ureterolithotripsy 62.5% and laparoscopic ureterolithotomy 93.3%. Stone-free rates showed a statistically significant difference among the groups (p = 0.005). Patients treated with laparoscopic ureterolithotomy vs semirigid ureterolithotripsy vs extracorporeal shock wave lithotripsy required fewer treatment sessions (mean ± SD 1.9 ± 0.3 vs 2.2 ± 0.6 vs 2.9 ± 1.4, p = 0.027). Neither major nor long-term complications were observed. CONCLUSIONS Proximal ureteral stone treatment requires multiple procedures until complete stone-free status is achieved. Laparoscopic ureterolithotomy is associated with higher success rates and fewer surgical procedures, but with more postoperative pain, longer procedures and a longer hospital stay. Although it is associated with the highest success rates for large proximal ureteral calculi, laparoscopic ureterolithotomy remains a salvage, second line procedure, and it seems more advantageous than open ureterolithotomy. At less well equipped centers, where semirigid ureterolithotripsy or extracorporeal shock wave lithotripsy is not available, it remains a good treatment option.

Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

BackgroundProstate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all randomized controlled trials that compared the efficacy and adverse events profile of intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic hormone-sensitive prostate cancer.MethodsSeveral databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS), cancer-specific survival (CSS), time to progression (TTP) and adverse events. We performed a meta-analysis (MA) of the published data. The results were expressed as Hazard Ratio (HR) or Risk Ratio (RR), with their corresponding 95% Confidence Intervals (CI 95%).ResultsThe final analysis included 13 trials comprising 6,419 patients with hormone-sensitive prostate cancer. TTP was similar in patients who received intermittent androgen deprivation (IAD) or continuous androgen deprivation (CAD) (fixed effect: HR = 1.04; CI 95% = 0.96 to 1.14; p = 0.3). OS and CSS were also similar in patients treated with IAD or CAD (OS: fixed effect: HR = 1.02; CI 95% = 0.95 to 1.09; p = 0.56 and CSS: fixed effect: HR = 1.06; CI 95% = 0.96 to 1.18; p = 0.26).ConclusionOverall survival was similar between IAD and CAD in patients with locally advanced, recurrent or metastatic hormone-sensitive prostate cancer. Data on CSS are weak and the benefits of IAD on this outcome remain uncertain. Impact in QoL was similar for both groups, however, sexual activity scores were higher and the incidence of hot flushes was lower in patients treated with IAD.

Methylenetetrahydrofolate reductase polymorphisms are related to male infertility in Brazilian men.

OBJECTIVE The objective of this study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic infertile Brazilian patients with nonobstructive azoospermia (NOA) or severe oligozoospermia and fertile Brazilian men as controls to explore the possible association of these polymorphisms and male infertility. METHODS A case-control study was carried out, including 156 idiopathic infertile Brazilian patients with NOA (n=49) or severe oligozoospermia (n=107) and 233 fertile men as controls. Polymorphisms C677T and A1298C were studied by quantitative polymerase chain reaction and the results were statistically analyzed. RESULTS The frequency of genotypes MTHFR 677CC, 677CT, and 677TT in idiopathic infertile men with NOA were 55.1%, 30.6%, and 14.3% (p=0.0305); 50.6%, 42.0%, and 7.5% (p=0.0006) regarding the severe oligozoospermic men; and 71.7%, 53.0%, and 5.6% in the control group. As for polymorphism A1298C, regarding the NOA group, the frequencies of the 1298AA, 1298AC, and 1298CC genotypes were 53.0%, 28.6%, and 18.4% (p=0.0132); 42.0%, 44.9%, and 13.1% (p=0.0188) among the severe oligozoospermic group; and 55.8%, 38.2%, and 6.0% (14/233) in the control group. CONCLUSION The data suggest that MTHFR C677T and A1298C could be important genetic factors predisposing to infertility in Brazilian infertile men.

Dynamic Sentinel Node Biopsy for Inguinal Lymph Node Staging in Patients with Penile Cancer: A Systematic Review and Cumulative Analysis of the Literature

BackgroundDynamic sentinel node biopsy (DSNB) is used to evaluate the nodal status of patients with clinically node-negative penile carcinoma. Its use is not widespread, and the majority of patients with clinically node-negative disease undergo an elective inguinal lymph node dissection (ILND). However, a prophylactic bilateral ILND is a procedure with approximately 50% of morbidity. The purpose of this review is to evaluate the accuracy of DSNB in penile cancer.MethodsThis is a systematic review and cumulative analysis of studies published between 1966 and 2010. The Medline, Embase, Cancerlit, and American Society of Clinical Oncology abstract databases were searched for published studies on penile cancer and DSNB. The outcomes assessed were: sensitivity, specificity, likelihood ratios, and summary receiver operating characteristics (ROC) curves.ResultsTen articles covering 519 participants were included in the cumulative analysis. The pooled sensitivities and specificities for sentinel node biopsy for detection of metastasis were 77.1 and 100% versus ILND and 87.9 and 100% versus wait and see program. The false-negative rate founded was 3.1% in the ILND group and 3.5% in the wait and see group.ConclusionsThe use of dynamic sentinel lymph node biopsy to detect lymph node metastasis in specialized centers appears to be justified. Addiction of other techniques to DSNB to reduce false-negative results is awaited and must be confirmed by future studies.

Diagnosis and Staging of Penile Cancer

A comprehensive literature study was conducted to evaluate the levels of evidence (LEs) in publications on the diagnosis and staging of penile cancer. Recommendations from the available evidence were formulated and discussed by the full panel of the International Consultation on Penile Cancer in November 2008. The final grades of recommendation (GRs) were assigned according to the LEs of the relevant publications. The following consensus recommendations were accepted: physical examination of the primary penile lesion is mandatory, evaluating the morphologic and physical characteristics of the lesion (GR A). Evaluation of the primary lesion with ultrasonography is of limited value for local tumor staging (GR C); however, evaluation of the primary tumor with magnetic resonance (MRI) imaging during artificial erection induced by intracavernosal injection of prostaglandin might be more useful (GR B). Histologic or cytologic diagnosis of the primary lesion is mandatory (GR A). For accurate histologic grading and staging, a resected specimen is preferable to a biopsy specimen alone (GR B). Penile cancer should be staged according to the TNM system; however, the 1987/2002 TNM staging system requires revision using data from larger patient cohorts to validate the recently proposed modifications (GR B). The histopathology report should provide information on all prognostic parameters, including the tumor size, histologic type, grade, growth pattern, depth of invasion, tumor thickness, resection margins, and lymphovascular and perineural invasion (GR B). Physical examination of the inguinal and pelvic areas to assess the lymph nodes is mandatory (GR B). Ultrasound-guided fine needle aspiration cytology is indicated for both palpable and nonpalpable inguinal nodes. If the findings confirm lymph node metastasis (LNM), complete inguinal lymph node dissection is indicated (GR B). In patients with nonpalpable inguinal nodes, if the ultrasound-guided fine needle aspiration cytology findings are negative for tumor, dynamic sentinel node biopsy can be performed if the equipment and technical expertise are available (GR C). In patients at high risk of inguinal LNM according to the available guidelines and nomograms, surgical staging can be performed by complete, bilateral inguinal lymph node dissection, which might also be curative (GR B). In patients at intermediate risk of LNM, sentinel node biopsy or modified (limited) inguinal lymph node dissection might be performed (GR B). In patients with nonpalpable inguinal nodes, imaging with computed tomography (CT) or MRI is not indicated, because they are not useful in detecting small-volume LNM. Also, it is very unlikely that large-volume LNM (detectable by CT/MRI) would be present in the pelvic nodes (GR B). In patients with confirmed inguinal LNM, CT of the pelvis is indicated to detect iliac LNMs (GR B). Abdominal CT and chest radiography are advisable if the pelvic CT findings are positive (GR B).

Granulosa cell tumor of the adult testis: report of a case and review of the literature

A 59-year-old man, referred to us with a 2-year historyof a painless growing mass in the left testis without pasthistory of trauma, infection, or lower urinary tract symp-toms. Physical exams revealed a normal right epididymisand testis, and a 13-cm mass and hydrocele in the left tes-tis, without hernia. Ultrasonography showed a 15 x 11 x12 cm mass with solid and cystic components and a largehydrocele. Serum levels of alpha-fetoprotein, beta-hCG,and LDH were within normal ranges. He underwent in-guinal surgical exploration of the left testis in October2000, when a large testicular mass was found. A radicalorchiectomy was performed, and the hydrocele fluid wasanalyzed. No frozen section biopsy was performed. His-topathological examination showed a 9-cm yellow tumor,with a small degenerated cystic area. Final analysis revealeda granulosa cell tumor with oval nuclei having a longitu-dinal nuclear groove (coffee bean appearance – Figure 1),focal invasion of the tunica albuginea and rete testis, nomitotic figures, and no invasion of surgical margins, sper-matic cord, or epididymis. Cytological analysis of the hy-drocele fluid was negative for tumor cells. Immunohisto-chemical tests were positive for vimentin, actin HFN 35,desmin, and cytokeratin AE-1/AE-3, but negative for epi-thelial membrane antigen. These findings strongly suggestthe diagnosis of a granulosa cell tumor.Follow-up was carried out with determinations of se-rum levels of alpha-fetoprotein, beta-hCG, and LDH, aswell as computerized tomography of the abdomen and chestx-ray every 6 months for 4 years, with no clinical recur-rence or exam abnormalities.Described for the first time in 1952,

Polymorphisms in Folate-Related Enzyme Genes in Idiopathic Infertile Brazilian Men

The aim of the study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) polymorphisms in idiopathic infertile Brazilian men and fertile men. Case–control study comprising 133 idiopathic infertile Brazilian men with nonobstructive azoospermia ([NOA] n = 55) or severe oligozoospermia ([SO] n = 78) and 173 fertile men as controls. MTHFR C677T, A1298C, and G1793A; MTRR A66G; and MTR A2756G polymorphisms were studied by quantitative polymerase chain reaction (qPCR). The results were analyzed statistically and a P value <.05 was considered significant. Single-marker analysis revealed a significant association among MTHFR C677T polymorphism and both NOA group (P = .018) and SO group (P < .001). Considering the MTHFR A1298C, MTHFR G1793A, and MTRR A66G polymorphisms, no difference was found between NOA group and SO group. Regarding the MTR A2756G polymorphism, a significant difference was found between NOA and controls, P = .017. However, statistical analysis revealed no association between SO group and controls. Combined genotypes of 3 MTHFR polymorphisms did not identify a haplotype associated with idiopathic infertility. The combinatory analysis of the 3 polymorphisms MTHFR, MTRR, and MTR did not show difference between cases and controls. The findings suggest the MTHFR C677T and MTR A2756G polymorphisms could be an important genetic factor predisposing to idiopathic infertility in Brazilian men.

Quality of Life, Behavioral Problems, and Marital Adjustment in the First Year After Radical Prostatectomy

UNLABELLED Patients submitted for prostatectomy were evaluated regarding their quality of life, behavioral problems, and marital adjustment. Thirty-two patients aged 54-76 years old were included. The results indicated that prostatectomy does not prevent normal psychological functioning, although there is a relationship between smoking and lower quality of life in these patients. INTRODUCTION Different types of monotherapy for prostate cancer leads to impairment in urinary and sexual functions, but prostatectomy seems to have worse results in physical functioning when compared with other treatments. Nevertheless, patients report high quality of life (QOL) levels, even when there are comments about the impact of sexual dysfunction on psychological health. The objectives of this work were to analyze levels of QOL, marital adjustment (MA), and behavioral problems (BP) of patients submitted to prostatectomy. METHODS Thirty-two patients from 54 to 76 years of age who underwent radical prostatectomy were evaluated during their follow-up appointments with the medical staff at the urology department of a private medical school. QOL scores were obtained from the World Health Organization Quality of Life instrument, short version. BP scores of patients younger than 60 years of age were assessed through the Adult Self-Report, whereas patients older than 60 years were assessed through the Older Adult Self-Report. MA scores were obtained by using the Locke-Wallace Marital Adjustment Test. RESULTS The patients reported relatively high levels of QOL and MA, along with low BPs. Marital support was associated with higher levels of QOL. BPs were associated with lower physical and total QOL scores. Smoking habits were associated with lower levels of MA, psychological health, and QOL. Erectile dysfunction was related to lower MA levels and lower QOL scores. CONCLUSIONS Overall, the patients had high self-reported QOL levels, which indicated that physical impairments related to surgery did not prevent patients to return to normal functioning.

Molecular oncogenesis of prostate adenocarcinoma: role of the human epidermal growth factor receptor 2 (HER-2/ neu )

The potential mechanisms involving the genesis and growth of androgen-independent prostate cancer include super-expression of the androgen receptor (AR), in an attempt to compensate for the low androgenic plasma levels and mutations of this specific receptor, which could determine resistance to anti-androgenic therapy. However, most advanced prostate tumors have no mutations or amplifications of the AR, suggesting a potential role of non-androgenic growth factors, including epidermal growth factor (EGF), transforming growth factor α, insulin-like growth factor (IGF-1) and fibroblast growth factor. More specifically, these factors, and their receptors like EGFR (HER-1) and HER-2/neu, through paracrine and autocrine mechanisms, may contribute to the proliferation and growth of prostate cancer. Free full text available at www.tumorionline.it