Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Imaging-based prostate cancer screening among BRCA mutation carriers-results from the first round of screening.

BACKGROUND: Male-carriers of BRCA1/2 gene mutations have an increased risk of prostate cancer (PCa) with a more aggressive phenotype. Current screening-guidelines suggest the use of prostate-specific antigen (PSA) only among BRCA2 carriers. Female carriers have extensive guidelines that include imaging. Our objective was to test the prevalence of PCa among BRCA carriers and examine screening strategies, using PSA and multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: We recruited men aged 40-70 years with BRCA1/2 germline mutations and no prior history of prostate biopsy. All men underwent an initial round of screening which included PSA, and prostate mpMRI. PSA was considered elevated using an age-stratified threshold of ≥1 ng/ml for 40-50 years of age, ≥2 ng/ml for 50-60 years of age, and 2.5 ng/ml for 60-70 years of age. Men with elevated PSA and/or suspicious lesion on mpMRI were offered a prostate biopsy. PSA levels, MRI findings, PCa incidence, and tumor characteristics were evaluated. Decision curve analysis was used to compare screening strategies. RESULTS: We recruited 188 men (108 BRCA1, 80 BRCA2), mean age 54 years (9.8). One hundred and ten (57%) had either elevated age-stratified PSA (75; 40%), a suspicious MRI lesion (67; 36%), or both (32; 17%). Of these, 92 (85%) agreed to perform a prostate biopsy. Sixteen (8.5%) were diagnosed with PCa; 44% of the tumors were classified as intermediate- or high-risk disease. mpMRI-based screening missed only one of the cancers (6%), while age-stratified PSA would have missed five (31%). Decision curve analysis showed that mpMRI screening, regardless of PSA, had the highest net benefit for PCa diagnosis, especially among men younger than 55 years of age. We found no difference in the risk of PCa between BRCA1 and BRCA2 (8.3% versus 8.7%, P = 0.91). Ninety percent had a Jewish founder mutation, thus the results cannot be generalized to all ethnic groups. CONCLUSIONS: PCa is prevalent among BRCA carriers. Age may affect screening strategy for PCa in this population. Young carriers could benefit from initial MRI screening. BRCA carriers aged older than 55 years should use PSA and be referred to mpMRI if elevated. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT02053805.

Ureteric stent versus percutaneous nephrostomy for acute ureteral obstruction - clinical outcome and quality of life: a bi-center prospective study.

BACKGROUND: To compare quality of life (QoL) indices between ureteral stent (DJS) and nephrostomy tube (PCN) inserted in the setting of acute ureteral obstruction. METHODS: Prospective bi-centered study. Over the span of 2 years, 45 DJS and 30 PCN patients were recruited. Quality of life was assessed by 2 questionnaires, EuroQol EQ-5D and 'Tube symptoms' questionnaire, at 2 time points (at discharge after drainage and before definitive treatment). RESULTS: Patients' demographics and pre-drainage data were similar. There were no clinically significant differences in patient's recovery between the groups, including post procedural pain, defeverence, returning to baseline renal function, and septic shock complications. More DJS patients presented to the emergency room with complaints related to their procedure compared to PCN patients. At first, DJS patients complained more of urinary discomfort while PCN patients had worse symptoms relating to mobility and personal hygiene, with both groups achieving similar overall QoL score. At second time point, PCN patients' symptoms ameliorated while symptoms in the DJS group remained similar, translating to higher overall QoL score in the PCN group. CONCLUSIONS: The two techniques had a distinct and significantly different impact on quality of life. Over time, PCN patients' symptoms relieve and their QoL improve, while DJS patients' symptoms persist. Specific tube related symptoms, and their dynamics over time, should be a major determinant in choosing the appropriate drainage method, especially when definitive treatment is not imminent.

Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

Early initiation of aspirin after prostate and transurethral bladder surgeries is not associated with increased incidence of postoperative bleeding: a prospective, randomized trial.

PURPOSE: Lower urinary tract operations are being increasingly performed in elderly patients, in whom aspirin intake is common for preventing cardiovascular disease. We determined the safety of early aspirin re-initiation after lower urinary tract surgeries. MATERIALS AND METHODS: A randomized, open label clinical trial was done. The study cohort included patients referred for transurethral prostatectomy, open prostatectomy and transurethral resection of bladder tumor while receiving aspirin prophylaxis. After controlling for surgical modality patients were randomized into 2 arms, including aspirin treatment initiation 24 hours after discontinuing of bladder irrigation (early treatment group) and aspirin treatment initiation 3 weeks after surgery (late treatment group). Primary end points were pre-discharge hematuria necessitating the restoration of bladder irrigation or the cessation of aspirin treatment and late hematuria treated in an urgent care setting, requiring hospital admission or compelling the cessation of aspirin treatment. RESULTS: A total of 120 patients were enrolled, including 60 per treatment group. There were no significant differences between the groups in surgery related factors that could have affected postoperative bleeding. Primary end points were attained by 16 of the 120 patients (13.6%), including 10 of the 60 (16.7%) in the early treatment group and 6 (10%) in the late treatment group (p = 0.28). Time to catheter removal and persistent hematuria duration were similar in the 2 groups. Cardiovascular morbidity was noted in 3 of 120 patients, of whom all were assigned to the early treatment group. CONCLUSIONS: Early aspirin initiation after lower urinary tract surgeries does not appear to carry an increased risk of postoperative bleeding. Thus, it may be considered in patients at high risk for cardiovascular morbidity.

Preliminary European results of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma of the bladder.

INTRODUCTION: Superficial bladder cancer can be treated by transurethral resection (TUR) and adjuvant intravesical therapy. Intravesical bacillus Calmette-Guérin (BCG) has been proven to be more efficacious with respect to recurrence prevention than intravesical chemotherapy, although at the cost of more severe side effects. There is a need for a new treatment modality with higher efficacy and less toxicity. The subject of this study is the efficacy of local microwave hyperthermia and chemotherapy treatment in intermediate or high risk superficial transitional cell carcinoma (TCC) of the bladder. PATIENTS AND METHODS: Ninety eligible patients received adjuvant treatment with a combination of mitomycin-C (MMC) and local microwave hyperthermia. All patients had multiple or recurrent Ta or T1 TCC of the bladder and were classified as intermediate or high risk according to EAU criteria. In total, 41 patients were BCG failures. The treatment regimen included 6 to 8 weekly sessions followed by 4 to 6 monthly sessions. Follow-up consisted of video-cystoscopy and urine cytology every 3 months. All patients were observed for 2 years. RESULTS: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed. CONCLUSION: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.

Intracavernous injections for erectile dysfunction in patients with cardiovascular diseases and failure or contraindications for sildenafil citrate.

The aim of this study was to evaluate the effectiveness of a progressive program for the treatment of erectile dysfunction in patients with cardiovascular disease in whom sildenafil citrate (Viagra) was not an option. The study population included 106 patients selected from 267 with cardiovascular disease. The intracavernous injection program consisted of three protocols of increasingly complex combinations of vasoactive drugs, papaverine, phentolamine, prostaglandin E1 and atropine sulfate. Patients who failed the first protocol were switched to the second, and those who failed the second were switched to the third. A positive response was defined as an erection sufficient for vaginal penetration. A positive response was achieved on protocol I in 61 of the 106 patients (57.5%); protocol II in 32 of the remaining 45 patients (71.1%); and protocol III in seven of the remaining 13 patients (53.8%); the total success rate was 94.3%. These 100 patients were included in the 1-year follow-up, and 90 reported successful coitus at the end of that period: 79 patients (87.8%) with intracavernous injection and 11 (12.2%) without injection. The remaining 10 patients (10%) dropped out of the program, seven (7.0%) for health or marital reasons and three (3.0%) because of treatment failure. We conclude that a progressive program of intracavernous injections of vasoactive drugs may be a good alternative for the treatment of erectile dysfunction in patients with cardiovascular disease.

Light chain amyloidosis of the urinary bladder. A site restricted deposition of an externally produced immunoglobulin.

AIMS: To identify the amyloid protein in a patient with amyloidosis localised to the urinary bladder, and to see whether subtyping of the protein by sequence analysis increases the understanding of the selection of the urinary bladder as the site of amyloid deposition. METHODS: A patient with gross haematuria and a congophilic mass in his urinary bladder was evaluated further. Characterisation of the amyloid protein was performed using conventional histological and immunohistochemical methods. Determination of the N-terminal amino acid sequence of the amyloid protein was performed using protein sequencers. RESULTS: The patient's history, physical examination, and laboratory evaluation excluded the involvement of other organs, justifying a diagnosis of amyloidosis localised to the urinary bladder. Histological and immunological studies showed that the amyloid protein deposited in the urinary bladder of the patient was probably of the amyloid light chain type. No plasma cells or lymphocytes were seen in sections of the urinary bladder and lower ureter adjacent to the amyloid deposits. Molecular analysis showed the sequence NFMLTQPHSISGSPG, which assigned the amyloid protein to either the Vlambda(I) or the Vlambda(VI) immunoglobulin (Ig) light chain families. CONCLUSIONS: The findings suggest that the amyloid protein in this patient originated outside the urinary bladder. The heterogeneity of the Ig proteins in known cases of amyloidosis of the lower urinary tract suggests that the amino acid residues, which determine the Vlambda subtyping, have no major role in restricting the deposited protein to the urinary bladder.

Predicting the success of retrograde stenting for managing ureteral obstruction.

PURPOSE: Retrograde ureteral stenting is often considered the first line option for relieving ureteral obstruction when temporary drainage is indicated. Several retrospective studies have implied that in cases of extrinsic obstruction retrograde ureteral stenting may fail and, therefore, percutaneous nephrostomy drainage is required. We examined the efficacy of retrograde ureteral stenting for resolving ureteral obstruction and identified clinical and radiological parameters predicting failure. MATERIALS AND METHODS: Enrolled in our prospective study were 92 consecutive patients with ureteral obstruction, which was bilateral in 8. Retrograde ureteral stenting was attempted in all cases by the urologist on call. When stent insertion failed, drainage was achieved by percutaneous nephrostomy. Patients were followed at 3-week intervals for 3 months. Each followup visit included a medical interview, blood evaluation, urine culture and ultrasound. Stent malfunction was defined as continuous flank pain manifesting as recurrent episodes of acute renal colic, 1 or more episodes of pyelonephritis, persistent hydronephrosis or elevated creatinine. Preoperative data and outcomes were compared in cases of intrinsic and extrinsic obstruction. Univariate and multivariate analysis was done to identify predictors of the failure of ureteral stent insertion and long-term function. RESULTS: The etiology of obstruction was intrinsic in 61% of patients and extrinsic in 39%. Extrinsic obstruction, which was associated with a greater degree of hydronephrosis, was located more distal. Retrograde ureteral stenting was successful in 94% and 73% of patients with intrinsic and extrinsic obstruction, respectively. At the 3-month followup stent function was maintained in all patients with intrinsic obstruction but in only 56.4% with extrinsic obstruction. On multivariate logistic regression the type of obstruction, level of obstruction and degree of hydronephrosis were the only predictors of stent function at 3 months. Stent diameter and preoperative creatinine had no predictive value. CONCLUSIONS: Retrograde ureteral stenting is a good solution for most acutely obstructed ureters. In patients with extrinsic ureteral obstruction a more distal level of obstruction and higher degree of hydronephrosis are associated with a greater likelihood of stent failure. These patients may be better served by percutaneous drainage.

Comparative evaluation of treatments for erectile dysfunction in patients with prostate cancer after radical retropubic prostatectomy.

OBJECTIVE: To assess the effectiveness of a progressive local treatment protocol for erectile dysfunction (ED) in patients after undergoing radical retropubic prostatectomy (RRP) for prostate cancer. PATIENTS AND METHODS: The study included 85 patients (mean age 59.5 years, range 50--75) with ED after RRP. Treatment was offered in four progressive phases, with patients passing to the next phase only if they failed the previous one: in phase I patients used a vacuum erection device; in phase II, sildenafil; in phase III, intracorporal injection; and in phase IV, intracorporal injection plus the vacuum erection device. The patients were followed for 1 year. RESULTS: Of the 85 patients, 78 (92%) responded to the vacuum erection device (with an erection sufficient for vaginal penetration), but only 11 (14%) agreed to continue with it at home. Of the remaining 74 patients, 69 with no contraindications were given sildenafil and 14 (20%) had a positive response. Sixty patients were then treated with intracorporal injection and 51 (85%) had a positive response; four of the nine failures in phase III responded to intracorporal injection plus vacuum therapy. Five patients failed all four protocols. After 1 year of follow-up, 76 of the 80 patients were successfully continuing treatment at home; seven (9%) used the vacuum erection device, 11 (14%) sildenafil, 54 (71%) intracorporal injection and four (5%) intracorporal injection plus the vacuum erection device. CONCLUSION: Overall, this progressive treatment method gave a positive response in 80 of the 85 patients (94%). After 1 year of follow-up, 76 of the 80 patients (95%) continued to respond well. Of all the methods used, intracorporal injection was the most effective for ED after RRP.

The effect of cholinergic enhancement during filling cystometry: can edrophonium chloride be used as a provocative test for overactive bladder?

PURPOSE: Overactive bladder, a highly prevalent disorder, is suspected of having a low detection rate due to the lack of sensitive diagnostic tools. Recent studies imply the involvement of the cholinergic system in the pathophysiological mechanism underlying overactive bladder. We determined whether in vivo enhancement of cholinergic activity with edrophonium chloride, a potent cholinesterase inhibitor, would serve as a provocative maneuver to increase the sensitivity of filling cystometry. MATERIALS AND METHODS: A total of 27 patients underwent a multichannel video urodynamic evaluation, followed by filling cystometry with the intravenous administration of 10 mg. edrophonium chloride. The response to edrophonium was defined as a significant change in sensation and decreased bladder capacity, the induction or amplification of involuntary detrusor contractions, or significantly decreased detrusor compliance. Findings were compared in responders and nonresponders. RESULTS: We identified 11 responders and 16 nonresponders. A response was noted in 78% of the patients with the symptomatology of overactive bladder but in none with no specific complaints suggesting bladder overactivity. In 7 of the 12 responders (64%) baseline cystometry was interpreted as normal. In 6 of the 11 responders (54%) uninhibited urinary leakage was observed in response to edrophonium. There were no serious adverse reactions to the drug. CONCLUSIONS: This preliminary study implies that edrophonium may serve as a novel, practical and safe drug for provocative cystometry. By significantly increasing cystometry sensitivity the drug would facilitate the identification of the subset of patients with overactive bladder who are currently classified with sensory urgency.

Sperm extraction at orchiectomy for testis cancer.

OBJECTIVE: To evaluate the value of aspirating sperm from the vas and epididymis at orchiectomy in azoospermic patients. DESIGN: Retrospective clinical study. SETTING: Tertiary care academic hospital. PATIENT(S): Three patients with known azoospermia who presented with testicular masses suspected to be cancerous. INTERVENTION(S): At orchiectomy, immediately after ligation of the spermatic cord, the contents of the epididymis and vas deferens were extracted into preserving media. MAIN OUTCOME MEASURE(S): Fertility rate. RESULT(S): Sperm retrieval was successful in all three patients. The mean total sperm count was 2.3 x 10(6)/mL with 20% motility. Intracytoplasmic injection of sperm harvested by using this method was successful in two couples, one of which delivered a healthy infant. CONCLUSION(S): Sperm can be aspirated from the vas deferens and epididymis at orchiectomy for preservation. In azoospermic patients, this procedure may salvage enough sperm for successful use in micromanipulation techniques. It may be worthwhile to perform sperm aspiration during orchiectomy for testis cancer in any patient with known or suspected infertility.

Three-year outcome of a progressive treatment program for erectile dysfunction with intracavernous injections of vasoactive drugs.

OBJECTIVES: To perform a comparative evaluation and follow-up of patients with erectile dysfunction (ED) who were treated with intracavernous injection of vasoactive drugs, starting with simple drugs and advancing to complex combinations. METHODS: The study included 625 patients, 26 to 85 years old, with ED. Four intracavernous injection protocols were used: protocol 1, papaverine plus phentolamine; protocol 2, prostaglandin E(1); protocol 3, papaverine, phentolamine, and prostaglandin E(1); and protocol 4, atropine sulfate, papaverine, phentolamine, and prostaglandin E(1). A positive response was defined as an erection sufficient for penetration. Patients for whom the basic protocol failed were successively switched to the more advanced protocols until a positive response was achieved. RESULTS: A positive response was achieved by 415 (66.4%) of the 625 patients given protocol 1; 75 (36%) of the remaining 210 patients given protocol 2; 98 (72.6%) of the 135 patients given protocol 3; and 22 (59.5%) of 37 patients given protocol 4. All four protocols failed in only 15 patients (2. 4%). At the 3-year follow-up visit (n = 610), 349 had achieved coitus, 65 (10.6%) without an injection and 202 (33.1%) with an injection. Eighty-two patients sometimes performed coitus without an injection. Sixty-three patients (10.3%) abandoned the program because of marital or health problems; 198 asked to be switched to Viagra during the follow-up period, and 120 returned to the program. CONCLUSIONS: Overall, our progressive treatment yielded a high positive response rate (97.6%), with 57.2% achieving successful coitus on follow-up. The main advantage of the program is that it spares patients who are responsive earlier from using more complex, painful, and costly drugs.

Bladder neck involvement at radical prostatectomy: positive margins or advanced T4 disease?

OBJECTIVES: To assess the prognosis of patients with bladder neck (BN) involvement in radical prostatectomy specimens and compare it with patients with seminal vesicle invasion (SVI) presumed to have an inferior stage according to the TNM classification. METHODS: Two hundred eighty-six case files of consecutive radical prostatectomies were reviewed. The records of patients with pathologic BN involvement (pT4a) or SVI (pT3c) were thoroughly analyzed and compared. The mean and median follow-up periods were 30.8 and 35.5 months (range 9 to 40), respectively, for the patients with Stage pT4a and 40.8 and 44.1 months (range 8 to 86), respectively, for the patients with Stage pT3c. Particular attention was paid to the preoperative clinical and pathologic evaluation, the pathologic analysis of the prostatectomy specimen, and the postoperative follow-up data. Progression was defined as a prostate-specific antigen level of 0.2 ng/mL and rising. Adjuvant therapy was not initiated unless prostate-specific antigen failure had occurred. RESULTS: BN involvement was identified in 25 patients (8.7%) and SVI was found in 26 patients (9.1%). In 7 patients (2.4%), the BN was the only site of positive margins. Thirty-six percent of patients with BN involvement and 62% of patients with SVI demonstrated biochemical progression. Disease-free survival and metastasis-free survival rates were significantly better for the patients with Stage pT4a than for the patients with Stage pT3c at 24 and 36 months after surgery. Univariate analysis identified the prostate-specific antigen nadir to be the most significant predictor of prognosis. CONCLUSIONS: In this study, BN involvement in the surgical specimen carried a lower risk of progression than SVI. On the basis of our preliminary results and those in other studies, a conceivable downstaging of BN involvement in the TNM staging system should be considered. Possibly, additional modification of the TNM staging system should be contemplated on the basis of the results of pathologic analysis and prognosis. The significance of BN involvement and the role of adjuvant therapy in this group of patients need further evaluation.

The rate of the founder Jewish mutations in BRCA1 and BRCA2 in prostate cancer patients in Israel.

Inherited predisposition occurs in 5-10% of all prostate cancer (CaP) patients, but the genes involved in conferring genetic susceptibility remain largely unknown. Several lines of evidence indicate that germline mutations in BRCA1 and BRCA2 might be associated with an increased risk for CaP. Three mutations in these two genes (185delAG and 5382InsC (BRCA1) and 6174delT (BRCA2) occur in about 2.5% of the general Ashkenazi population, and the 185delAG BRCA1 mutation, in up to 1% of non-Ashkenazi Jews. In order to assess the contribution of these germline mutations to prostate cancer in Jewish Israeli patients, we tested 174 unselected prostate cancer patients (95 of Ashkenazi origin) for these mutations by PCR amplification and modified restriction enzyme digests. Patient's age range was 45-81 years (median 66), and in 24 (14.4%) the disease was diagnosed prior to 55 years of age. Nineteen (11%) and 12 (6.9%) patients had a first or second degree relative with CaP or breast cancer, respectively. Overall, five mutation carriers were detected: 2/152 (1.3%) 185delAG, 2/104 (2%) 5382InsC, and 1/158 (0.6%) 6174delT. In all carriers, the disease was diagnosed after the age of 55, and only one of them had a family history of breast and CaP. In addition, no allelic losses at the BRCA1 locus were demonstrated in 17 patients with a family history of CaP, using seven microsatellite markers. We conclude that the rate of the predominant Jewish BRCA1 and BRCA2 mutations in CaP patients does not significantly differ from that of the general population, and that mutational inactivation of the BRCA1 is rare in familial CaP. Thus, germline BRCA1 and BRCA2 mutations probably contribute little to CaP occurrence, to inherited predisposition, and to early onset disease in Jewish individuals.

Low PSA metastatic androgen- independent prostate cancer.

OBJECTIVES: To describe the clinical parameters of low PSA, progressive metastatic androgen-independent prostate cancer. METHODS: From April 1995 to May 1999, we selected 18 patients with clinically progressive androgen-independent prostate cancer and low PSA (

Combination chemotherapy following adrenal suppression in androgen- independent prostate cancer.

OBJECTIVES: Recent trials with modern chemotherapy have demonstrated activity in androgen-independent prostate cancer, but all focused on patients with progression following androgen suppression or antiandrogen withdrawal. Limited data are available on the activity of chemotherapy in androgen-independent, hormone-refractory (progressing following adrenal suppression) prostate cancer. We evaluated the activity of estramustine combined with vinblastine in this subset of androgen-independent prostate cancer. METHODS: From January 1995 until April 1999, 19 patients with hormone-refractory prostate cancer received estramustine 140 mg p.o., three times daily along with weekly vinblastine 5 mg/m(2). RESULTS: A decrease in prostate-specific antigen of 50% or more was noted in 12 patients (63.1%, 95% CI 38.3-83.7%). The median decrease in prostate-specific antigen was 71.2% (range 50.5-85.2%). None of the 7 patients with measurable soft-tissue disease showed an objective response. The median survival from onset of chemotherapy was 6 (range 1.4-27.7) months and from initiation of adrenal suppression 16.9 (range 3.8-40. 5) months. CONCLUSIONS: The combination of estramustine and vinblastine is capable of inducing activity in androgen-independent prostate cancer progressing after adrenal suppression. In our small sample, the survival rate was low, and we obtained no response in soft-tissue sites. Future prospective trials are needed to determine the benefit of sequential versus simultaneous incorporation of adrenal suppression with chemotherapy in the management of androgen-independent prostate cancer.

Sexual function in 131 patients with benign prostatic hyperplasia before prostatectomy.

OBJECTIVE: The aim of the present study was to ascertain the frequency of sexual dysfunction in patients with benign prostatic hyperplasia (BPH) before prostatectomy. METHODS: The study population included 131 patients aged 55-74 years (mean 61.4+/-2.7) with BPH. The patients had been complaining of daytime urgency and nocturia for the last 1-14 years (average 4.5+/-1.5 years). The diagnosis of BPH was based on the anamnestic data, the International Prostate Symptom Score (IPSS(0-35)) and quality of life assessment (L(0-6)), and results of digital rectal examination, transrectal ultrasound, and uroflowmetry. Sexual dysfunction was determined by retrospective analysis of the psychosexual history (with and separately from the spouse), penile brachial index (PBI), nocturnal penile tumescence (NPT), and blood hormone levels (testosterone). RESULTS: The patients were divided into two groups by severity of the urinary disorder: group I, severe (IPSS(0-35)-L(6); n = 70); and group II, mild relative to group I (IPSS(32-34)-L(4-5); n = 61). In group I, 15 patients (21.4%) performed normal coitus, 24 (34.2%) had weak coitus with incomplete penetration, and 21 (44.2%) had unsuccessful coitus because of a weak erection. In group II, 28 patients (45.9%) had normal coitus, 25 (40.9%) incomplete penetration, and 8 (13.1%) unsuccessful coitus. There was no significant correlation between sexual function and the patients' general health condition. The quantitative assessment of sexual dysfunction yielded the following results in groups 1 and 2, respectively: negative NPT in 32.4+/-1.8 and 24.4+/-2.1% (p<0.05); PBI <0.6 in 33.4+/-1.7 and 22.3+/-1.2% (p<0.001); and testosterone decrease to <12 nmol/l in 36.4+/-1.2 and 28.5+/-1.2% (p<0.05), respectively. The differences between the groups were significant (p<0.05) for all three parameters. CONCLUSIONS: Considering the 44. 2% rate of unsuccessful coitus in the patients with a severe urinary dysfunction compared to only 13.1% in those with a milder dysfunction and the significant correlation between severe urinary dysfunction and measures of sexual dysfunction, we suggest that BPH may be a risk factor for sexual dysfunction.

Complications of retroperitoneal lymph node dissection in testicular cancer: primary and post-chemotherapy.

Retroperitoneal lymph node dissection (RPLND) is utilized in low-stage testis cancer as a primary diagnostic and therapeutic procedure. In the post-chemotherapy setting, it serves as an adjuvant procedure to resect residual tumor. Primary RPLND entails minimal resection of lymphatic tissue in the retroperitoneum; the complications are minor and insignificant. Wound infection is the main complication, affecting less than 5% of patients. Atelectasis and small bowel obstruction may occur in less than 2% of patients. In post-chemotherapy RPLND, the template and the surgical challenge are much larger. Extensive tumor size, difficult location, adherence to major vessels, and vital structures, together with inferior pre-operative status, are probably the main reasons for complications. The overall complication rate is 20% to 35% and mortality is 0.8% to 1%. Pulmonary insufficiency secondary to bleomycin-induced interstitial fibrosis is the cause of the most severe side effects and mortality in these operations. Chylous ascites may occur, especially where resection of the inferior vena cava is necessary. Other complications occur to a lesser extent. A summary of all complications is presented and measures to avoid or manage them are depicted.