The role of brachytherapy in the 21st century for prostate cancer.

Men presenting with clinically confined prostate cancer have a variety of established treatment options, among them brachytherapy is gaining increased acceptance, even in the absence of randomized comparative data between brachytherapy, surgery and external radiotherapy. This review summarizes the results of low dose rate transrectal-guided transperineal permanent seed implantation brachytherapy. We present the evolution of the different treatment planning techniques and a comprehensive review of published mature data on 10-year or longer of biochemical and survival outcome for brachytherapy alone, and brachytherapy combined with supplemental external beam radiation therapy with emphasis on its impact on quality of life.

Are consecutive nightly recordings required for valid evaluation of sleep-associated erections?

We questioned the need for more than one RigiScan recording for accurate assessment of sleep-associated penile erections and determine the necessity of consecutive nightly recordings for valid evaluation of sleep-associated erections. Men complaining of erectile dysfunction (ED) and referred to RigiScan evaluation for the first time participated. Recordings were performed at the patient's home during two consecutive nights, and data on test time, number of erections, erection duration, minimal and maximal base and tip tumescence and rigidity were retrieved for both nights. Normal erectile function was defined with the recording of at least one erection (70 out of 100% tip rigidity lasting for at least 10 min during either night). The main outcome measures were RigiScan recordings. Group 1 consisted of 29 men (mean age 42.4+/-13.8 years, range 22-71) who had normal erections, all during the first night. Group 2 consisted of 26 men (mean age 48.6+/-13.5 years, range 25-70) who failed to fulfill both criteria for normal erection. In Group 2, only the values for penile base rigidity and erection duration were normal during the first night: the parameters of maximal base tumescence, tip rigidity, number of effective erections and duration of effective erections that were impaired during the first night were significantly worse (P<0.01) during the second night. The required information for the diagnosis of psychogenic ED was obtained during the first night in >50% of the participants. Men with normal erections during the first night can be spared the inconvenience and cost of re-testing. Consecutive night recording should be reserved for patients whose recorded data during the first night did not fulfill the criteria for normal erection.

Age, comorbidity and hypertensive co-medication do not affect cardiovascular tolerability of 10 mg alfuzosin once daily.

PURPOSE: We assessed in real-life practice the impact of age, cardiovascular comorbidity and co-medication on the tolerability and efficacy of 10 mg alfuzosin OD in men with lower urinary tract symptoms suggestive of benign prostatic obstruction. MATERIALS AND METHODS: A total of 6,523 men with a mean age of 64.7 years were enrolled in a 6-month open label study of 10 mg alfuzosin OD. They were stratified by age quartile (younger than 60, 60 to 64, 65 to 70 and older than 70 years), comorbidity (hypertension, ischemic heart disease and diabetes) and antihypertensive co-medication (diuretics, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II inhibitors and calcium channel antagonists). RESULTS: Alfuzosin was effective and well tolerated. Despite an increased prevalence of cardiovascular comorbidity and antihypertensive co-medication with age changes in blood pressure did not significantly differ among age groups. In controls, ie those with no cardiovascular comorbidity or co-medication, alfuzosin produced minimal decreases in sitting systolic (mean -2.6 to -2.8 mm Hg) and diastolic (mean -1.7 to -1.8 mm Hg) blood pressure. In men with cardiovascular comorbidity mean decreases in systolic (-3.5 to 5.8 mm Hg) and diastolic (-2.0 to -3.3 mm Hg) blood pressure remained marginal. Of the 6,523 exposed patients 19.3% withdrew from the study, mainly for adverse events (6.4%) or a lack of efficacy (5.3%), while 229 (3.5%) experienced serious adverse events and 1,558 (23.9%) reported at least 1 treatment emergent adverse event. The most commonly reported adverse event was dizziness/postural dizziness (4.8%). Hypotension/postural hypotension was uncommon (0.7%). Age, cardiovascular comorbidity and antihypertensive co-medication had no impact on the safety profile of 10 mg alfuzosin OD. CONCLUSIONS: Alfuzosin (10 mg) OD is effective and well tolerated, and it has marginal effects on blood pressure, including in elderly patients and those with hypertension, ischemic heart disease or diabetes and those receiving antihypertensive agents.

Sexual dysfunction in women partners of men with erectile dysfunction.

We evaluated 113 female partners of men with erectile dysfunction (ED) attending a sexual dysfunction clinic in order to define sexual dysfunction among these women. In all, 51 (45%) women denied having any sexual dysfunction. The other 62 (55%) responded to questions classifying their complaint(s) according to the international classification of female sexual dysfunction (FSD) in the following topics (40/62, 65%, reported having more than one problem): decreased sexual desire (n=35, 56%), sexual aversion (none), arousal (n=23, 37%) and orgasmic disorders (n=39, 63%), dyspareunia (n=19, 31%), vaginismus (n=3, 5%), and noncoital sexual pain (none). Many female partners of men with ED report having some form of sexual disorder, mostly orgasmic problems and decreased sexual desire. Therefore, for optimal outcome of ED treatment, evaluation and treatment of male and FSD should be addressed as one unit within the context of the couple, and be incorporated into one clinic of sexual medicine.

Combination therapy-permanent interstitial brachytherapy and external beam radiotherapy for patients with localized prostate cancer.

BACKGROUND: Combination of permanent interstitial brachytherapy based on radioactive iodine with external beam radiotherapy is an alternative to other treatment modalities, such as radical prostatectomy or external beam radiotherapy alone in patients with intermediate-risk localized prostate cancer. In this article we report our experience with this combination modality. METHODS: Among patients who were treated in our institute with brachytherapy, there were 64 patients who received combination therapy for the above indication. Combination therapy enables administration of 110 Gy as brachytherapy and thereafter 45 Gy as external beam radiation. All patients received adjuvant androgen deprivation therapy for 6 months. The prospective follow-up was done with the aid of validated evaluation instruments (questionnaires). RESULTS: Combination therapy was administered without additional urinary (IPSS-based) or sexual (IIEF-based) side effects above those with brachytherapy alone. No severe perianal and lower intestinal tract side effects were observed. Short-to-moderate-term results based on serum PSA levels are encouraging, and are not inferior to what is accepted by the literature for other radical therapies. CONCLUSION: Combination of permanent interstitial brachytherapy and external beam radiotherapy in the appropriate patients does not cause any additional morbidity, and its biochemical results justify its application. This modality should be offered as an accepted and good alternative to other radical treatment options, to men with prostate cancer with moderate risk factors.

Sexual function after permanent 125I-brachytherapy for prostate cancer.

We prospectively assessed patients' erectile function (EF) using the International Index of Erectile Function (IIEF) and a global assessment questionnaire (GAQ) following permanent 125I-brachytherapy for localized prostate cancer. Of 378 treated patients, 220 had a minimal 2-y follow-up and 131/220 were sexually active prior to brachytherapy, with an EF domain score of > or = 11 (study group). Patients were allowed sildenafil at any time of the study. The patients' mean EF score, without excluding patients who used sildenafil, dropped within 3 months after brachytherapy, recovered at the end of the first year and remained unchanged for at least up to 2 y after treatment regardless of the addition of neoadjuvant hormone therapy to 125I-brachytherapy. Analysis of the GAQ revealed that 80% of the patients were satisfied with their sexual function up to 3 y after treatment. Any detrimental effect of permanent brachytherapy with or without the addition of hormone therapy on EF is reversible, and recovery is expected at 1 y after treatment in most patients.

Per urethra insertion of a through-and-through safety guide wire using a dual-lumen ureteral catheter during percutaneous nephrolithotripsy.

BACKGROUND: The second ("safety") of two guide wires is commonly inserted antegradely in percutaneous nephrolithotripsy (PCNL). We describe the retrograde insertion of a through-and-through safety guide wire during PCNL. METHODS: After inserting a percutaneous nephrostomy 1 day earlier, a guide wire was introduced through the nephrostomy tube to the bladder and pulled out through the urethral meatus via a cystoscope and grasper. The tube was removed, leaving the wire positioned from the flank to the meatus. A dual-lumen catheter was introduced retrogradely through the urethra over the wire, up to the nephrostomy incision. The safety guide wire was introduced retrogradely through the catheter's other port. RESULTS: This procedure succeeded in 9 of 10 patients: the exception was very obese and the catheter was too short to reach the incision in the flank. CONCLUSION: Using a dual-lumen catheter allows quick and simple retrograde insertion of a safety guide wire during PCNL.

Melatonin elicits nuclear exclusion of the human androgen receptor and attenuates its activity.

BACKGROUND: The androgen receptor (AR) promotes growth and functionality of androgen sensitive benign and cancer tissues. The pineal hormone melatonin is an androgen protagonist in vivo and in vitro. The interference of melatonin in the AR cascade was explored. METHODS: The effects of melatonin on AR expression, level, agonist and androgen-response element (ARE) binding, reporter gene activity and intracellular localization were explored in prostate cancer LNCaP cell line. RESULTS: Melatonin increased immunoreactive AR cells in the absence and presence of dihydrotestosterone. Despite this increase and maintenance of AR agonist binding capacity, the androgen-induced reporter gene activity and suppression of AR-mRNA were attenuated. Immunocytochemical analysis and subcellular fractionation studies revealed nuclear exclusion of AR by melatonin. CONCLUSIONS: The melatonin-mediated nuclear exclusion of the AR may explain the attenuation of AR activity in the prostate cancer cells. This is the first demonstration of a hormone-induced mislocalization of the AR in prostate epithelial cells and may represent a novel route for regulating AR activity.

[I125 prostate brachytherapy--short-term results of the first 150 patients in Israel].

UNLABELLED: Prostate cancer is the most common malignancy among adult men. The treatment of locally confined prostate cancer is either surgical or radiation therapy. In the last decade or so a renewed method has gained popularity among patients and physicians, the use of implantable I125 seeds into the prostate--named brachytherapy. METHOD: We describe our first 150 cases treated with I125 brachytherapy with a follow-up after 3-24 months, median of 15 months. Twenty patients had a combination of external beam radiation and brachytherapy. RESULTS: Nadir PSA values of < 0.5 ng/ml were noted in 89%. This is accepted as evidence of cure. In 6 men elevation of PSA was noted and interpreted as a recurrence of disease. Associated morbidity was mild to moderate focusing on lower urinary tract symptoms, for about 3 months. IPSS values, measuring urinary symptoms after 3 months, resembled baseline levels. Impotence developed in 1/3 of men as a result of treatment. This was assessed using a self-completed IIEF questionnaire. No major complications (WHO grade III-IV) were noted in either urinary system or lower gastro-intestinal tract. IN CONCLUSION: We describe initial experience with Brachytherapy for the treatment of prostate cancer in Israel. Our results compare favourably with those published in American literature and profess moderate impact on quality of life as well as transient effects on lower urinary tract symptoms, and a minimal impotence rate (1/3) developing as a result of treatment. These results compare favourably with morbidity rates cited for radical surgery or external beam radiotherapy.

Hydronephrosis associated with colorectal carcinoma: treatment and outcome.

AIM: Obstruction of the upper urinary tract, hydronephrosis, is not uncommon in the context of primary or recurrent colorectal cancer (CRC). Its presence poses a therapeutic dilemma. This study focuses on the significance of hydronephrosis as a prognostic marker for CRC by analysing the resectability and survival rates of patients affected. PATIENTS AND METHODS: Retrospective data of 52 patients with hydronephrosis were analysed. Ten had primary CRC at different sites and 42 developed hydronephrosis 1-84 months following resection of a primary CRC. Twenty eight had unilateral and 24 bilateral hydronephrosis. RESULTS: In 10 patients with primary CRC and in 38 of those with a history of CRC, hydronephrosis was secondary to malignant obstruction. In four it was related to iatrogenic injury to the urinary tract. Complete surgical resection was possible in five patients (10%) with malignant obstruction. The remaining 90% underwent palliative or no surgical treatment due to diffuse metastasis or extensive local disease. No difference in survival was found between these two groups (6 vs 8 months) nor when comparing CEA levels, Duke's staging, or unilateral vs bilateral hydronephrosis. Patients with benign obstruction were treated by a ureteric stent, leading to resolution of hydronephrosis. All four are alive. CONCLUSIONS: Malignant hydronephrosis, secondary to primary or recurrent CRC, represents local manifestation of a disseminated disease with almost no probability of long-term survival and cure. It would seem that patients with such disease do not benefit from aggressive operations.

The effect of methylene blue on histological damage after spermatic cord torsion in a rat model.

OBJECTIVE: To investigate, in a rat model, whether methylene blue (a free-radical scavenger) is effective in alleviating the histological testicular damage caused by reperfusion after spermatic cord torsion. MATERIALS AND METHODS: Male Wistar rats underwent a clockwise 720 degrees left spermatic cord torsion lasting 3 h; they were then randomly assigned to treatment and control groups. In the treated group, 2 mg/kg methylene blue was injected intraperitoneally 20 min before the cord was untwisted, and an additional 1 mg/kg injected into the penile vein 1--2 min beforehand. After 14 days, the left testicle was removed and assessed histologically. The control group was not treated. RESULTS: Thirty-three rats in the treatment group and 35 untreated controls were suitable for evaluation. Treatment with methylene blue was not significantly predictive of histological damage; the colour of the testis before detorsion was not correlated with histological damage. CONCLUSION: Anti-oxidant treatment with methylene blue had no palliative effect on the histological changes after torsion and detorsion of the spermatic cord in this rat model.

Clinical efficacy of sildenafil in patients on chronic dialysis.

PURPOSE: We evaluate the clinical efficacy of sildenafil citrate for patients who are on chronic dialysis and who have concomitant erectile dysfunction. MATERIALS AND METHODS: A total of 35 men (mean age 60.7 years) on dialysis and with erectile dysfunction of various etiologies were administered 25 to 100 mg sildenafil for at least 6 months. The International Index of Erectile Function questionnaire (IIEF), a global assessment question and partner satisfaction question were used to evaluate sildenafil efficacy. Patients also reported any adverse events that occurred during treatment. RESULTS: Treatment was effective for 28 of the 35 (80%) patients according to the results of the IIEF and global assessment questions. Partner satisfaction correlated with the IIEF overall response (0.79) and global assessment question results (0.86). No correlation was found between sildenafil failure and patient age, the etiology of erectile dysfunction, duration of erectile dysfunction, prior treatments, testosterone and prolactin blood levels, and the duration and etiology of renal failure. Of the 35 patients sildenafil was stopped due to intolerable headaches in 3 and because of lack of efficacy in 7. CONCLUSIONS: Sildenafil is an effective and safe treatment for erectile dysfunction in most patients on chronic dialysis.

Pudendal nerve conduction to evaluate organic erectile dysfunction.

OBJECTIVE: This study aimed to evaluate the value of testing pudendal nerve conduction in men with erectile dysfunction. DESIGN: This open prospective study was conducted on 150 men with documented erectile dysfunction of at least 6 mo of duration, all of whom underwent pudendal nerve conduction by the same investigator. RESULTS: Only patients with erectile dysfunction and low back pain (n = 9) showed statistically significant prolonged pathologic pudendal nerve conduction latency of 43.1 msec/div (SD +/- 11.3 msec/div, P < 0.05). There were no correlations between the pudendal nerve conduction latency in patients suffering from erectile dysfunction associated with diabetes mellitus, local trauma, pelvic surgery, or antihypertensive drugs. CONCLUSIONS: Pudendal nerve conduction may contribute valuable information to the evaluation of patients with erectile dysfunction caused by neurologic deficits as manifested by low back pain.

The value of testing pudendal nerve conduction in evaluating erectile dysfunction in diabetics.

We conducted an open prospective study on the value of testing pudendal nerve conduction (PNC) in 45 diabetic and 32 nondiabetic men with documented erectile dysfunction (ED) of at least six months duration. All subjects underwent PNC by the same investigator using the Medcelec/TECA Sapphire device with calibration parameters of sweep 10 ms/div an amplitude of 200 microV/div. No statistically significant differences was found in the mean bulbocavernosus reflex (BCR) latencies between the nondiabetics (33.6 ms/div +/- 4.1) and the diabetics (37.5 ms/div +/- 9.1) (P > 0.05). Our results show that electrophysiological measurement of the BCR in diabetics is not a useful diagnostic test and emphasize the importance of a multifactorial evaluation of diabetic ED.

Is a second injection of vasoactive medication necessary during color duplex doppler evaluation of young patients with veno-occlusive erectile dysfunction?

OBJECTIVES: To assess the contribution of a second injection of vasoactive medication into the corpus cavernosum during the duplex Doppler study for evaluation of young patients with vasculogenic erectile dysfunction (ED). METHODS: Thirty-five patients, 23 to 50 years old (median age 43), clinically diagnosed as having veno-occlusive ED underwent a color duplex Doppler study. The peak systolic velocity, end-diastolic velocity, resistance index, and arterial diameter measurements were obtained from both cavernosal arteries before and 2, 5, 10, and 20 minutes after an intracavernous injection of a vasoactive drug. All patients were reinjected with similar doses of the same medication, and all measurements were repeated. The erection quality was estimated 20 minutes after each injection. RESULTS: The peak systolic velocity after the second injection was significantly higher statistically than after the first injection (P <0.02). No differences in end-diastolic velocity, resistance index, arterial diameter, or the evaluated side between the first and second injections were found. CONCLUSIONS: A single injection of vasoactive drugs can provide sufficient information on the arterial and veno-occlusive mechanism during color duplex Doppler evaluation of young patients with vasculogenic ED without compromising the quality of the evaluation. Limiting the number of injections to only one may prevent adverse reactions caused by the second injection and reduce the cost and duration of this test.

Clinical significance of gross hematuria and its evaluation in patients receiving anticoagulant and aspirin treatment.

OBJECTIVES: To investigate the results of evaluations in patients presenting with gross hematuria while receiving anticoagulant or aspirin treatment and to compare the source of bleeding in these respective groups. METHODS: We retrospectively studied all patients admitted because of gross hematuria while receiving warfarin or aspirin treatment between 1990 and 1998. The degree of anticoagulation was evaluated in patients taking anticoagulation medication. Almost all patients were evaluated by cystoscopy and either excretory urography or ultrasound. RESULTS: Patients taking warfarin had a normal evaluation almost twice as often as those taking aspirin: 38% versus 22%, respectively. The leading pathologic findings in both groups were a bleeding benign prostate and a tumor in the urinary tract, in similar proportions. Overall, a tumor was diagnosed in one quarter of patients, and other treatable pathologic findings were diagnosed about half the time. In the 11 patients receiving excessive anticoagulation medication, two tumors were found (18%). Hemorrhagic cystitis was diagnosed in 12 patients. All 12 were taking aspirin. CONCLUSIONS: A normal evaluation was more prevalent in the warfarin group. A tumor was diagnosed in about one quarter of the patients. The prevalence of hemorrhagic cystitis in patients taking aspirin may point to a specific bleeding diathesis in the urothelium of these patients. In light of these findings, a full evaluation is warranted in patients receiving aspirin or warfarin therapy, and the presence of excessive anticoagulation should not impede a full evaluation.