Paying the price for standing tall: Fluid mechanics of prostate pathology.

BACKGROUND: Age-dependent increase in the incidence of benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are both related to cell proliferation and survival controlled by intraprostatic free testosterone (FT) concentration. Paradoxically, BPH and PCa occur as circulating testosterone levels decrease, so any possible relationship between testosterone levels and development of BPH and PCa remains obscure. RESULTS: In BPH the enlarging prostate is exposed to high testosterone levels arriving directly from the testes at concentrations about hundredfold higher than systemic FT. This occurs because venous blood from the testes is diverted into the prostate due to the elevated hydrostatic pressure of blood in the internal spermatic veins (ISVs). Elevated pressure is caused by the destruction of one-way valves (clinically detected as varicocele), a unique phenomenon related to human erect posture. While standing, human males are ISVs vertically oriented, resulting in high intraluminal hydrostatic pressures-a phenomenon not found in quadrupeds. In this communication, we demonstrate the fluid mechanics' phenomena at the basis of varicocele leading to prostate pathology. CONCLUSIONS: So far, varicocele has been studied mostly for its etiologic role in male infertility and, thus, for its effects on the testes. It is becoming clear that varicocele is a major etiologic factor in BPH and likely also in PCa. Restoring normal testicular venous pressure by treatment of the abnormal ISV's in varicocele has been shown to avert the flow from the prostate with the effect of reducing prostate volume, alleviating symptoms of BPH, and increasing concentrations of circulating FT.

Azoospermia and Sertoli-cell-only syndrome: hypoxia in the sperm production site due to impairment in venous drainage of male reproductive system.

Sertoli-cell-only (SCO) syndrome, or germ cell aplasia, is diagnosed on testicular biopsy when germ cells are seen to be absent without histological impairment of Sertoli or Leydig cells. It is considered a situation of irreversible infertility. Recent studies have shown that varicocele, a bilateral disease, causes hypoxia in the testicular microcirculation. Destruction of one-way valves in the internal spermatic veins (ISV) elevates hydrostatic pressure in the testicular venules, exceeding the pressure in the arteriolar system. The positive pressure gradient between arterial and venous system is reversed, causing hypoxia in the sperm production site. Sperm production deteriorates gradually, progressing to azoospermia. Our prediction was that, if genetic problems are excluded, SCO may be the final stage of longstanding hypoxia which deteriorates sperm production in a progressive process over time. This would indicate that SCO is not always an independent disease entity, but may represent deterioration of the testicular parenchyma beyond azoospermia. Our prediction is confirmed by histology of the seminiferous tubules demonstrating that SCO is associated with extensive degenerative ischaemic changes and destruction of the normal architecture of the sperm production site. Adequate treatment of bilateral varicocele by microsurgery or by selective sclerotherapy of the ISV resumes, at least partially, the flow of oxygenated blood to the sperm production site and restored sperm production in 4 out of 10 patients. Based on our findings the following statements can be made: (i) SCO may be related in part of the cases to persistent, longstanding testicular parenchymal hypoxia; (ii) germ cells may still exist in other areas of the testicular parenchyma; and (iii) if genetic problems are excluded, adequate correction of the hypoxia may restore very limited sperm production in some patients.

Right varicocele and hypoxia, crucial factors in male infertility: fluid mechanics analysis of the impaired testicular drainage system.

Varicocele is considered a predominantly unilateral left-sided disease. However, since male fertility is preserved with only one healthy testis, infertility perforce represents bilateral testicular dysfunction. It was hypothesized that: (i) right varicocele cannot be diagnosed by palpation and therefore has not been treated in the past by the traditional treatment, and (ii) right varicocele causes impaired oxygen supply in the right testicular microcirculation, leading to germ cell degeneration. This study performed venographies of both right and left internal spermatic veins during the treatment of 840 infertile men with varicocele and analysed the results using tools of fluid mechanics. Histopathology of the right testis revealed stagnation of blood flow and degenerative changes attributed to lack of adequate oxygenation in all testicular cell types. Right varicocele was found in the vast majority of the patients. We found that due to the destruction of one-way valves, pathologic hydrostatic pressure is produced in the testicular venous microcirculatory system about five times higher than normal, exceeding arteriolar pressure. The pressure gradient between the arterioles and venules in the testicular tissue is therefore reversed, leading to persistent hypoxia. Right varicocele, although undetected, is prevalent in infertile men with varicocele, hence only bilateral occlusion of the internal spermatic veins, including the associated bypasses, eliminating the pathologic hydrostatic pressure will lead to resumption of arterial blood flow in the testicular microcirculation.

A proposed anatomic typing of the right internal spermatic vein: importance for percutaneous sclerotherapy of varicocele.

PURPOSE: To classify the anatomic types of the right internal spermatic vein (ISV). METHODS: We evaluated venograms obtained in 150 consecutive patients with idiopathic varicocele referred for transfemoral sclerotherapy. RESULTS: Six anatomic types of the right internal spermatic vein (ISV) were recognized. These were classified by the location of their orifices and the tributary venous patterns. In roughly half the patients (53%), the ISV appeared as a simple vein with no remarkable retroperitoneal interconnections. In the remainder, complex retroperitoneal anastomoses were encountered. CONCLUSION: By understanding these anatomic variations, the angiographer can approach treatment of right-sided varicocele with foreknowledge of the nature of these types and the presence of valves and collaterals.

Varicocele, hypoxia and male infertility. Fluid Mechanics analysis of the impaired testicular venous drainage system.

BACKGROUND: Varicocele is a bilateral vascular disease, involving a network of collaterals and small, retroperitoneal bypasses. The right and the left testicular venous drainage systems are complex and not identical to each other. It was considered a predominantly unilateral (left-sided) disease. Its pathophysiology has not been clearly delineated and the treatments offered do not seem to be effective. The medical literature is replete with articles demonstrating inconsistent and even contradictory results which have led clinicians to dissociate varicocele from male infertility. Since male fertility is preserved with only one healthy testis, male infertility perforce represents bilateral testicular dysfunction. This poses an enigma to clinicians: How can left-sided varicocele causes bilateral testicular dysfunction? METHODS: We investigated the internal spermatic veins by venography to understand testicular damage due to varicocele. A total of 740 venographies of the internal spermatic veins (ISVs) were performed, with sclerotherapy of the ISV as treatment for varicocele. Epon-embedded testicular tissue sections were used to identify blood stagnation in the testis. RESULTS: Varicocele is predominantly a bilateral disease in 84% of cases, associated with collaterals and retroperitoneal venous bypasses in 70% in the left side and 75% in the right side. Histopathology demonstrate stagnation in the testicular microcirculation and hypoxic-ischaemic degenerative changes in all cells' types in the sperms' production site. CONCLUSION: Based on our findings (i) varicocele is a bilateral disease; (ii) the disease is expressed earlier in the left side and is more intense because the blood column is longer in the left side than the right; (iii) partial treatment to the left side only and ignoring bypasses is not adequate to correct the problem; (iv) hypoxia leading to ischaemic damage to both testes is the effect of varicocele due to hydrostatic pressures in the impaired venous drainage system, which exceeds the pressures in the testicular arterial microcirculation due to blood columns produced in the disease; (v) hydrostatic pressure does not depend on vein diameter but on blood column height, only; and (vi) thermography alone or combined with ultrasonography with special attention to the bilaterality of the disease are the best non-invasive tools for its detection.

Uterine artery embolization: a pilot study in a rabbit model.

Eight female adult ex-breeder New Zealand white rabbits underwent bilateral, unilateral, or superselective unilateral uterine artery embolization. The histopathologic changes after embolization in New Zealand white rabbits resemble those in humans, making rabbits an appropriate model for experimental uterine artery embolization.

Induction of spermatogenesis in azoospermic men after internal spermatic vein embolization for the treatment of varicocele.

BACKGROUND: To evaluate the improvement in semen quality and pregnancy rate after internal spermatic vein (ISV) embolization in men with nonobstructive azoospermia virtual azoospermia, or extremely severe oligoteratoasthenoazoospermia (OTA). METHODS: A prospective cohort of 101 azoospermic or severe oligoteratoasthenospermic men of mean (+/-SD) age 34.1+/-7.7 years who underwent ISV between September 1998 and June 2003 were evaluated for semen characteristics, endocrinology profile, and conception rate. RESULTS: Significant improvement was noted in mean sperm concentration, motility, and morphology in 83 men (82%). Mean sperm concentration increased from 0.22+/-0.30 x 10(6)/ml total sperm in the ejaculate to 9.28+/-1.2 x 10(6)/ml after embolization (P < 0.001); mean sperm motility rose from 8.78+/-1.59 to 29.56+/-2.0% (P < 0.001), and mean sperm morphology rose from 3.79+/-0.74 to 13.72+/-1.37% (P < 0.005). Pregnancy was achieved in 34 cases (34%), 20 (20%) unassisted and 14 (14%) assisted. CONCLUSIONS: Based on our findings, the following statements can be made: (i) Varicocele may cause any variation of severity in OTA, including azoospermia. (ii) Since male fertility is preserved with only one testis, OTA, azoospermia or virtual azoospermia represent bilateral testicular dysfunction. (iii) Treatment of bilateral varicocele may reverse testicular dysfunction and improve spermatognesis and testosterone production in men with extremely severe OTA and induce sperm production in men with azoospermia and virtual azoospermia. (iv) If azoospermia is not too long-standing, the treatment of varicocele may significantly improve spermatogenesis and renew sperm production. (v) Adequate treatment may spare in > 50% of azoospermic patients the need for testicular sperm extraction as preparation for ICSI. (vi) Since achievement of pregnancy in IVF units is higher when spermatogenesis is better, the treatment of varicocele (bilateral) is an effective medical adjunct for the IVF units prior to the treatment. We recommend that infertile men with azoospermia or virtual azoospermia or extremely severe OTA be evaluated for varicocele, with special attention to its bilateral nature.

Physical examination may miss the diagnosis of bilateral varicocele: a comparative study of 4 diagnostic modalities.

PURPOSE: We evaluated the sensitivity of 3 noninvasive methods for detecting left and right varicoceles. MATERIALS AND METHODS: Three noninvasive methods for the detection of varicocele in the left and right internal spermatic veins were evaluated in 214 infertile men, namely, physical examination, scrotal contact thermography and ultrasound Doppler. Venography was used as the reference diagnosis. RESULTS: Varicocele was detected in 195 patients (91.1%), on the left side in 37 (19%), on the right side in 3 (1.5%) and bilaterally in 155 (79.5%). Scrotal contact thermography using varicoscreen proved to be the most accurate method. Sensitivity, specificity, accuracy and positive predictive value were 98.9%, 66.6%, 98.5% and 100%, respectively, for left varicocele, and 95.6%, 91.6%, 94.9% and 98%, respectively, for right varicocele. Doppler sonography was associated with the highest number of false-positive results. Accuracy in evaluating retrograde flow was lowest for both sides for physical examination and highest for the combination of Doppler sonography and contact thermography, with a sensitivity, specificity, accuracy and positive predictive value of 100%, 33.3%, 99.0% and 98.9%, respectively, for the left side, and 97.4%, 58.3%, 90.3% and 91.1%, respectively, for the right side. In 165 (85%) of the 195 patients who underwent internal spermatic vein embolization sperm parameters were improved. CONCLUSIONS: The present study yielded 2 major findings. Thermography is more sensitive and accurate for the detection of varicocele than Doppler ultrasound and physical examination, and it can be used for screening as a single modality in infertile men. Doppler ultrasound and thermography are complementary and their combined use yields the highest sensitivity and accuracy.

Elevation of serum testosterone and free testosterone after embolization of the internal spermatic vein for the treatment of varicocele in infertile men.

BACKGROUND: To evaluate the effect of internal spermatic vein (ISV) embolization on levels of serum testosterone and free testosterone and on spermatogenesis. METHODS: The files of 83 infertile men treated for varicocele were reviewed for changes in serum testosterone, free testosterone and spermatogenesis after ISV embolization. RESULTS: Mean serum testosterone concentration rose after embolization by 43%, from 12.07 +/- 6.07 nmol/l to 17.22 +/- 8.43 nmol/l (P<0.001). Mean serum free testosterone concentration rose by 72%, from 5.93 +/- 2.44 nmol/l to 10.21 +/- 7.69 nmol/l (P<0.001). Mean sperm concentration increased from 7.49 +/- 1.73 x 10(6)/ml to 18.14 +/- 2.36 x 10(6)/ml (P<0.001); mean sperm motility increased from 21.74 +/- 2.47 to 34.47 +/- 2.27% (P<0.001); and mean sperm morphology increased from 6.63 +/- 1.07 to 13.08 +/- 1.44% (P<0.001). CONCLUSIONS: ISV embolization apparently induces an increase in both serum testosterone and free testosterone concentrations and in sperm parameters in infertile patient with varicocele, regardless of the size of the varicocele.

Varicocele: a bilateral disease.

OBJECTIVE: To evaluate the prevalence of varicocele in the left and right spermatic veins in infertile men by several methods of examination. DESIGN: Prospective study. SETTING: Andrology unit of a department of obstetrics and gynecology, and interventional radiology unit of the radiology department at a tertiary care facility. PATIENT(S): Two hundred eighty-six infertile men evaluated for varicocele. INTERVENTION(S): Patients underwent evaluation for infertility. Physical examination was followed by contact thermography, Doppler sonography, and venography of both testes. MAIN OUTCOME MEASURE(S): We measured the prevalence of varicocele in the left and right spermatic veins in infertile men, and the response of semen parameters after embolization of internal spermatic vein. RESULT(S): Varicocele was detected by one of the noninvasive methods and confirmed by venography in 255 patients (89.2%): the left site in 45 (17.6%), the right side in 4 (1.5%), and bilaterally in 206 (80.8%). All patients were treated by embolization. Mean sperm concentration increased from 6.12 +/- 1.02 to 21.3 +/- 1.69 million/mL; mean sperm motility from 16.81 +/- 1.51 to 35.90 +/- 1.41%; and mean sperm morphology from 9.75 +/- 0.85 to 16.92 +/- 1.17%. Pregnancy rate was 43.5%. CONCLUSION(S): The present study finds that what was traditionally considered a predominantly unilateral anatomical abnormality apparently has a strikingly high bilateral prevalence (80.7%). This may suggest that we should consider varicocele a bilateral disease. The second finding is the high rate of varicocele detected by venography, thermography, and sonography when compared with physical examination results. Our study may have important implications for treatment, indicating that patients with clinical evidence of unilateral left varicocele should be carefully evaluated for bilateral varicocele.

Initial experience with ovarian vein embolization for the treatment of chronic pelvic pain syndrome.

BACKGROUND: Ovarian vein embolization was recently suggested as the preferred treatment for chronic pelvic pain syndrome. OBJECTIVE: To evaluate the technical feasibility, complications and early clinical and radiographic results of ovarian vein embolization in women with pelvic pain syndrome. METHODS: Percutaneous transcatheter ovarian vein embolization with coils was performed in six patients aged 27-53 years who presented with pelvic pain syndrome. All had lower abdominal pain, and pelvic varicosities were found on Doppler ultrasound and retrograde ovarian vein venography. Embolization was done unilaterally in three patients (on the left side) and bilaterally in three. Mean follow-up by telephone questionnaire was 7.3 months. RESULTS: The procedure was technically successful in all patients. Two patients reported partial relief of symptoms (33.3%) and three had complete relief (50%), for a total of 5 patients (83.3%) with some measure of improvement. There were no complications following the procedure. CONCLUSIONS: Percutaneous transcatheter ovarian vein embolization seems to be safe and feasible for the treatment of pelvic pain syndrome. The procedure is performed on an outpatient basis and is well tolerated by patients.

Adolescent varicocele: is it a unilateral disease?

OBJECTIVES: To evaluate the incidence of left and right varicocele in adolescents. METHODS: The study group consisted of 28 adolescents who underwent evaluation for varicocele at our clinic. In 19 patients, varicocele was detected on routine physical examination, and 9 patients presented with scrotal pain or discomfort. All patients were evaluated by three methods. Physical examination was followed in all cases by contact thermography and venography studies of both testes. RESULTS: The rate of left and right retrograde flow in the spermatic veins by the three methods used was as follows: physical examination 92.8% and 10.7%; contact thermography 100% and 89%; and venography 100% and 85.7%, respectively. Varicocele was not detected by physical examination in 2 (7.2%) of the 28 patients on the left side and in 21 (87.5%) of 24 on the right side. CONCLUSIONS: The main finding of this study was that varicocele is a bilateral disease in 85.7% of adolescents. The high percentage of bilateral varicocele in our sample may explain the pathophysiologic mechanism whereby what has traditionally been considered a unilateral disease can produce bilateral testicular dysfunction. The high incidence of subclinical bilateral varicocele may indicate that we should consider varicocele a bilateral disease. The second finding was that only 10% of patients with right varicocele were diagnosed by physical examination and more than 85% were diagnosed by thermography, with confirmation by venography. Therefore, we suggest that thermography and venography should play a major role in the diagnosis of varicocele.