Flávio Hering

Comparative study of the protective effect of different intravenous bisphosphonates on the decrease in bone mineral density in patients submitted to radical prostatectomy undergoing androgen deprivation therapy. A prospective open-label controlled study

Objectives:  To establish whether androgen deprivation therapy (ADT) promotes osteoporosis and osteopenia

CLODRONATE FOR TREATMENT OF BONE METASTASES IN HORMONE REFRACTORY PROSTATE CANCER

INTRODUCTION Approximately 85% of patients who die from prostate cancer have bone metastases. Even though the radiological aspect of such metastases is osteoblastic, we currently know that these lesions are mixed, with coexisting blastic and lytic lesions, always beginning with bone lysis by osteoclast proliferation. Treatment options are palliative and have poor response, and when there is an improvement it is usually short-lived. This work intends to study the effect of clodronate in the treatment of skeletal complications of prostate cancer. MATERIALS AND METHODS In an open prospective study 32 patients with hormone refractory prostate cancer with metastases to bones were assessed, in the period between November 2000 and September 2002. Mean age was 69 years (51 to 83 years). Patients were previously assessed by a pain scale and Karnofsky index. They underwent bone scintigraphy, X-ray, dosage of prostate specific antigen (PSA) and biochemical tests before and following treatment (administration of intravenous clodronate every 28 days). The Students t-test was used for statistical analysis. RESULTS Twenty-nine patients (90.6%) showed improvement after the first and the 2nd cycles, which persisted for at least 4 months. Average on the pain scale improved from 7.7 to 2.1 and Karnofsky index raised from 42 to 71. Radiological aspect of the metastases improved in 15 patients (46.8%) and side effects were low (only 2 patients - 6.2%). CONCLUSION Bisphosphonate was effective in the treatment of skeletal complications of prostate cancer, presenting an objective response in 90.6% of treated patients, with a marked improvement in the pain scale, Karnofsky index and consequently in the quality of life of patients, and with low side effects.

Comparison of positivity frequency of bcl-2 expression in prostate adenocarcinoma with low and high Gleason score

CONTEXT Multiple genetic and epigenetic factors have been implicated in the oncogenesis and progression of prostate cancer. The major difficulty is in that the clinical management stems from the reality that reliable and accurate prognostic biomarkers are not available and that effective treatment regimens forming hormone-resistant prostate cancers are yet to be developed. Among the most important regulators of apoptosis and programmed cell death is the bcl-2 gene and its related proteins. Elevated levels of bcl-2 protein may contribute to the progression of prostate cancers to a metastatic and hormone-insensitive state characterized by poor responses to chemotherapy. OBJECTIVE To characterize the expression of bcl-2 proteins as a prognostic factor in humans. DESIGN A retrospective approach. SETTING Urology section, Federal University of São Paulo. DIAGNOSTIC TEST USED: Immunohistochemical analysis using bcl-2 protein antibody and normal staining by hematoxylin-eosin. MAIN MEASUREMENTS Prognostic relations and protein expression were evaluated considering the total sample (28) divided into two groups, high (8 to 10) and low (2 to 4), separated according to the histological differentiation grade (Gleason score) with 10 and 18 samples, respectively. RESULTS The differentiation of grade into two groups separated according to the Gleason score in low and high types presented different bcl-2 expression (P < 0.001). CONCLUSION The higher frequency of bcl-2 immunostaining in tumor samples was observed in association with more advanced Gleason scores and suggests that an increase in the ratio of this anti-apoptotic protein often occurs during progression of prostate cancers.

PERFORATION OF SIGMOID COLON AFTER EXTRACORPOREAL LITHOTRIPSY

A 32-year-old white man presented with an 8 mm. renoureteral calculus on the left side. He was placed in the ventral decubitus position and underwent ESWL with 3,000, 7 kV. shock waves. The patient had symptoms of nephritic colic on the left side and on day 5 after ESWL he complained of indistinct pain in the left iliac fossa along with 6 episodes of diarrhea in 24 hours. Symptoms improved after receiving analgesics but on day 7 significant clinical worsening was characterized by signs of septicemia and an acute abdomen. An x-ray of the abdomen revealed pneumoperitoneum with the right diaphragmatic cupula and bilateral disappearance of the psoas muscle line (fig. 1). With the diagnostic hypothesis of perforative acute abdomen due to the use of antiinflammatory drugs the patient underwent laparotomy. The surgical finding was diffise pustular peritonitis and a blocked 1 cm. perforation in the distal sigmoid colon in the mesocolic margin. No diverticulum or foreign body was identified in the colon or in the cavity. In the distal urethral projection an intense organized inflammatory process was identified. The patient elected resection of the perforated intestinal segment following terminal colostomy of the sigmoid, rectal stump closure, washing of the abdominal cavity and broad-spectrum antibiotic therapy (fig. 2). On pathological examination a perforative process was observed in a segment of the sigmoid with infiltrating polymor

A randomized and prospective study on the value of antibiotic prophylaxis administration in transurethral resection of the prostate.

CONTEXT Antibiotic prophylaxis in transurethral resection of the prostate is a regular practice in urology. However, its prophylactic effect can be questioned when the antiseptic surgical technique is used. Nonetheless, urine culture-oriented antibiotic therapy is the gold standard for avoiding improper medication usage and bacterial resistance. OBJECTIVE To study the efficacy of antibiotic usage in patients with negative urine cultures, who were submitted to transurethral resection of the prostate. TYPE OF STUDY Prospective open labeled study. SETTING Tertiary care referral hospital. PARTICIPANTS 124 consecutive patients, who were randomly divided into two groups to receive antibiotic prophylaxis or not. MAIN MEASUREMENTS Cultures from meatus, urine, irrigation and antiseptic fluid, and prostate tissue chips, were compared and analyzed for bacterial sensitivity to the antibiotic used, according to the surgeons personal criteria. McLennans test was used for statistical analysis. RESULTS No statistically significant difference regarding clinical evolution was found between the groups that received or antibiotics or not. Statistical significance was found regarding the occurrence of positive urine cultures during the postoperative period for those not receiving antibiotics, but not in relation to fever, prostate chip culture or bacteremic episodes. Sixty-eight subjects (57.1%) presented positive prostatic tissue culture. There was no specific correlation between the recovered bacteria from the meatus, prostatic tissue chip and urine and the spectrum of the administered antibiotic. Six cases showed the same bacteria in the urine and prostatic tissue chip. Only fifteen cases (25%) in the antibiotic group showed the desired sensitivity directed to the collected bacteria. CONCLUSIONS Antibiotic prophylaxis for patients whose urine is sterile is debatable in patients who are candidates for transurethral resection of the prostate. Most of the time, the antibiotic agent used is not specific for any of the bacteria recovered from the various sources analyzed.

Carcinoma de células renais incidentais e sintomáticos: fatores patológicos e sobrevida

BACKGROUND: Patients with early diagnosis of renal cell carcinoma (CCR) have higher chance of cure following surgical treatment. This study was set to compare the pathological characteristics between the surgical specimens and the survival of the patients with incidental and symptomatic CCR. METHODS: One hundred and fifteen patients with sporadic CCR were studied retrospectively following nephrectomy and divided into two groups. Group 1; 59 patients with incidental diagnosis and Group 2; 56 symptomatic patients. The mean age of the patients was 59 years, with 86 men and 29 women. Radical nephrectomy was performed in 96 patients and the conservative surgery was performed in the remaining 19. Comparison parameters included pathological outcome, specifically nuclear grade, pathological stage, size of the tumor and presence of microvascular invasion intratumoral and patients survival. RESULTS: Comparison between the two groups confirmed that the incidental tumors have smaller nuclear grade (p=0,003), smaller size (p=0,001) smaller incidence of micro vascular invasion (p< 0,001) and lower stage (p<0,001). Disease specific survival and recurrence free survival of the incidental group were statistically higher than the symptomatic group (p<0,001). CONCLUSION: Incidentally discovered CCR have more favorable pathological characteristics; the patients have disease free survival when compared to symptomatic CCR.

Adjuvant Effect of IV Clodronate on the Delay of Bone Metastasis in High-Risk Prostate Cancer Patients: A Prospective Study

Purpose High-risk prostate cancer patients undergoing treatment often experience biochemical recurrence. The use of bisphosphonates as an adjuvant treatment delays skeletal events, yet whether or not bisphosphonates also delay metastastic development remains to be determined. Materials and Methods A total of 140 high-risk prostate cancer patients who were undergoing definitive treatment and who had clinically organ-confined disease and who suffered from biochemical recurrence were administered intravenous (IV) clodronate. The patients were treated with a radical retropubic prostatectomy (RP) or curative radiotherapy (RTx). Upon androgen deprivation therapy initiation, tri-monthly IV clodronate was added to the treatment to prevent bone demineralization. Twenty-six out of 60 operated cases and 45 out of 80 irradiated cases received bisphosphonate. The length of time until the first bone metastasis was recorded and analyzed. Results No statistical difference was found for the type of primary treatment (RP or RTx) on the time to the first bone metastasis (95% confidence interval [CI], 0.40 to 2.43; p=0.98). However, there was a clear advantage favoring the group that received bisphosphonate (p<0.001). The addition of bisphosphonate delayed the appearance of the first bone metastasis by seven-fold (95% CI, 3.1 to 15.4; p<0.001). Conclusion Treatment with tri-monthly IV clodronate delayed the time to the first bone metastasis in high-risk prostate cancer patients who were experiencing an increase in the prostate specific antigen level after definitive treatment.

Involuntary Detrusor Contraction Is a Frequent Finding in Patients with Recurrent Urinary Tract Infections

Objective: To check whether subtle voiding dysfunction is related to recurrent urinary tract infection (rUTI). Methods: 254 consecutive patients with at least four episodes of urinary tract infection (UTI) were studied. At least three repeat urodynamic evaluations with an additional ice water test to maximize the detection of involuntary detrusor contraction (IDC) were used. Stress urinary incontinence cases were used as controls. Nonparametric univariate and multivariate analyses were used for statistics. Results: IDC was detected in 83.6% of patients in the rUTI group and in 31.7% in the control group. IDC was <15 cm H2O in 54.7% whereas high-amplitude (>50 cm H2O) IDC was observed in 6.8% in the rUTI group. Female urinary tract obstruction was diagnosed in 16.8% of patients in the rUTI group and in 7.9% in the control group. Residual volume, PdetQmax and Qmax were not predictive of UTI recurrence. Symptoms were similar in both groups. Conclusions: Patients with rUTI present with covert bladder dysfunctions represented by detrusor overactivity.

Incidental and symptomatic renal tumors: impact on patient survival

CONTEXT Renal cell carcinoma is the third most frequent genitourinary neoplasia, and there is currently an increase in the incidental diagnosis of tumors confined to the kidneys. OBJECTIVE To study the survival of patients with incidental and symptomatic renal tumors who have undergone nephrectomy. DESIGN Retrospective. SETTING Hospital Sírio Libanês and Hospital Beneficência Portuguesa de São Paulo. PARTICIPANTS 115 patients with diagnosis of renal cell carcinoma, operated on by the same group of surgeons and evaluated by a single pathologist. MAIN MEASUREMENTS Sex, age and diagnosis method, analyzed in two groups, according to the tumor diagnosis: Group 1 with incidental diagnosis and Group 2 with symptomatic tumors. The anatomopathological characteristics and patient survival in both groups were evaluated. A statistical analysis was performed using the Student t, chi-squared, log rank and Kaplan-Meyer tests. RESULTS Among the studied patients, 59(51%) had an incidental diagnosis, with 78% diagnosed by ultrasonography, 20% by computerized tomography scan and 2% during surgeries; 56 patients (49%) were symptomatic. Tumor locations were equally distributed between the two kidneys, and the surgery was conservative for 24% of the incidental and 9% of the symptomatic group. In the incidental group only one patient had tumor progression and there was no death, while in the symptomatic group there were 5 progressions and 10 deaths. The 5-year specific cancer-free survival was 100% in the incidental and 80% in the symptomatic group (p = 0.001) while the disease-free rate was 98% in the incidental and 62% in the symptomatic group (p < 0001). CONCLUSION Incidental renal tumor diagnosis offers better prognosis, providing longer disease-free survival.

Valsalva Leak Point Pressure to Determine Internal Sphincter Deficiency in Stress Urinary Incontinence

Introduction: Valsalva leak point pressure (VLPP) represents the global competence of the conjunctive forces around the urethra to support increased pressure from the abdominal cavity with transmission to the bladder. Assessment of VLPP has prognostic meaning, but measurement techniques are still subject to controversy. Patients and Methods: One hundred and eight consecutive women with no genital prolapse or bladder hyperactivity exclusively presenting with urinary stress incontinence were submitted to VLPP determination during urodynamic evaluation using a rectal and urethral catheter. Rectal pressure measurement served as the landmark in the determination of Valsalva’s maneuver. After determining the rectal pressure, the urethral probe was pulled out and the maneuver repeated. Results: Eighty-four cases (group I) presented leakage during Valsalva’s maneuver with the urethral catheter being in place. Group Ia (66.6%) had a reduction of 44.5 cm H2O in the rectal pressure after catheter removal. In group Ib, rectal leakage pressure increased after catheter removal from 76.5 ± 18.7 to 79.5 ± 24.7 cm H2O. Eight patients did not demonstrate urine leakage after catheter removal. In group II, 24 cases showed a rise in rectal leakage pressure to 76.2 ± 22 cm H2O, but urinary leakage was only observed after catheter removal. In group IIa (19 cases), the VLPP decreased by 12.6 ± 15 cm H2O, while in group IIb (5 cases) leakage occurred only in patients showing an increase of 22.2 ± 7 cm H2O in the rectal pressure after the second maneuver with the urethral catheter in position. Conclusions: Precise determination of the abdominal leak point pressure through Valsalva’s maneuver may be critical. The different techniques used for VLPP determination may render comparisons difficult. Rectal pressure measurement with no urethral catheter in place to monitor abdominal leak pressure seems to be more appropriate because it resembles clinical practice. Although lower abdominal leakage pressures may be found, this is not a uniform finding, and a higher incidence of type III incontinence may be expected, and critical analysis or painstaking repetition may be required in the case of lack of demonstration of urinary loss.