In varicocele, there is venous flow of free testosterone (FT) directly from the testes into the prostate. Intraprostatic FT accelerates prostate cell production and prolongs cell lifespan, leading to the development of BPH. We show that in a large group of patients presenting with BPH, bilateral varicocele is found in all patients. A total of 901 patients being treated for BPH were evaluated for varicocele. Three diagnostic methods were used as follows: physical examination, colour flow Doppler ultrasound and contact liquid crystal thermography. Bilateral varicocele was found in all 901 patients by at least one of three diagnostic methods. Of those subsequently treated by sclerotherapy, prostate volume was reduced in more than 80%, with prostate symptoms improved. A straightforward pathophysiologic connection exists between bilateral varicocele and BPH. The failure of the one-way valves in the internal spermatic veins leads to a cascade of phenomena that are unique to humans, a result of upright posture. The prostate is subjected to an anomalous venous supply of undiluted, bioactive free testosterone. FT, the obligate control hormone of prostate cells, reaches the prostate directly via the venous drainage system in high concentrations, accelerating the rate of cell production and lengthening cell lifespan, resulting in BPH.

The purpose was to examine the results of bilateral percutaneous sclerotherapy of the internal spermatic veins on prostate volume and prostatic symptoms. We previously showed that destruction of one-way valves in the internal spermatic veins (varicocele) elevates hydrostatic pressure in the vertical testicular venous drainage system in the erect human. This diverts free testosterone (FT) flow at high concentrations directly from the testes into the prostate. High intraprostatic FT prolongs prostate cell life and increases cell proliferation rate-synergistic effects resulting in increased cell population (BPH). Treatment by interventional radiology (or microsurgery) techniques eliminates this diversion of FT flow to the prostate and reverses these pathologic processes. A total of 206 BPH patients with varicocele underwent bilateral sclerotherapy of the ISV. Of these, 81.5% exhibited significantly reduced prostate volume and improvement in prostatic symptoms (measured by IPSS scores) during follow-up period of 12 to over 24 months. 8% went on to require surgery despite mild post-treatment improvement (TURP). The use of prostate medications along with the treatment may have a combined positive effect. Very large prostate volume and large residual volume may limit degree of improvement. It is concluded that effective treatment of varicocele restores normal supply of testosterone to the prostate solely via its arterial supply, resulting in significant decrease of prostate volume and prostatic symptoms. The procedure is safe with only minor transient side effects.

AndrologiaVolume 44, Issue 3 p. 145-146 EDITORIAL Erect posture of humans leads to male infertility, BPH and prostate cancer Y. Gat, Y. Gat Andrology and Interventional Radiology, Mayanei Hayeshua medical center, Bnei Brak, Israel Sub-micron research, condensed matter Physics, Weizmann Institute of Science, Rehovot, Israel E-mail: [email protected]Search for more papers by this authorM. Gornish, M. Gornish Andrology and Interventional Radiology, Mayanei Hayeshua medical center, Bnei Brak, IsraelSearch for more papers by this author Y. Gat, Y. Gat Andrology and Interventional Radiology, Mayanei Hayeshua medical center, Bnei Brak, Israel Sub-micron research, condensed matter Physics, Weizmann Institute of Science, Rehovot, Israel E-mail: [email protected]Search for more papers by this authorM. Gornish, M. Gornish Andrology and Interventional Radiology, Mayanei Hayeshua medical center, Bnei Brak, IsraelSearch for more papers by this author First published: 23 April 2012 https://doi.org/10.1111/j.1439-0272.2011.01233.xCitations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume44, Issue3June 2012Pages 145-146 RelatedInformation

Maturation arrest (MA) of spermatogenesis is diagnosed on histology as interruption of spermatogenesis before the final stage without impairment of Sertoli or Leydig cells. It is considered a condition of irreversible or absolute infertility. Varicocele, which represents impairment in the testicular venous drainage system, has been shown to be a bilateral disease. Malfunction of the valves increase the hydrostatic pressure in the testicular venous system that exceeds the pressure in the arterial system leading to hypoxia in the testicular microcirculation and in the seminiferous tubules, the sperm production site. Sperm production deteriorates, and ultimately progresses to azoospermia. Our prediction was that MA, if genetic factors are excluded, is the final stage of long standing hypoxia. This would indicate that MA is not always an independent disease entity, but may represent progressive process of deterioration of the testicular parenchyma beyond azoospermia. By histology and electron microscopy, our prediction confirmed, at least partially, that MA is associated with degenerative ischaemic changes in the seminiferous tubules. Adequate treatment of bilateral varicocele by microsurgery or super-selective sclerotherapy of the internal spermatic veins including associated network of venous bypasses, vertically oriented, may resume the flow of oxygenated blood. If irreversible damages did not occur and ischaemia is not too long standing, limited sperm production may be restored, at least partially.

To evaluate the incidence of pediatric robotic-assisted laparoscopic pyeloplasties (RALPs) and to determine if there were regional or age-related trends associated with the performance of RALP.Using 2005-2010 data from the Nationwide Inpatient Sample (NIS), the incidence of and trends in pyeloplasty in patients less than 18 years of age were assessed. This was broken down by open, laparoscopic, and robotic techniques when possible. Multiple logistic regression determined which characteristics were associated with increased performance of RALP. Population weighting was used to estimate national rates.A total of 15,498 pediatric pyeloplasties were performed between 2005 and 2010. Coding for robotics began at the end of 2008, and, since then, 750 of the 5557 pediatric pyeloplasties were robotic. The rate of RALP remained unchanged from 2008-2010 (odds ratio [OR] 0.93, P = .051); however, there was an overall increase in minimally invasively procedures (RALP or laparoscopic) since 2005 (OR 1.4, P <.001). Factors associated with increased performance of RALP were aged above 11 years (OR 50.3, P <.001) and living in the northeast (OR 3.0, P = .001), midwest (OR 2.9, P = .001), or west (OR 4.31, P <.001) compared with the south.An estimated 750 robotic pyeloplasties were performed in the United States between the end of 2008 and 2010. There was an increase in the total number of pyeloplasties performed using minimally invasive techniques since 2005. Older children are more likely and patients living in the south are less likely to be treated with robotic assistance.

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.

The prostate, an androgen-regulated exocrine gland, is an integral part of the male reproductive system which has an essential function in sperm survival and motility in its long hostile route to meet and fertilise the egg in the Fallopian tube. Testosterone is known to be the key, obligatory regulator of the prostate that promotes the development and progression of prostate cancer (PCa). Yet, the pathophysiological mechanism of PCa remains unclear and its causal relation to serum testosterone has not been established. Here, we report on the discovery of a previously unrecognized route of flow of free testosterone (FT), at a concentration of 130 times the physiological levels, reaching the prostate via the testicular and prostate venous drainage systems, bypassing the systemic circulation. This condition results from the malfunction of the vertically oriented testicular venous drainage system in humans, a phenomenon with a prevalence that increases rapidly with age, which causes deviation of the testicular venous flow from its normal route. Early results of an interventional radiological procedure, super-selective intraprostatic androgen deprivation therapy are discussed. This treatment has resulted in decrease in prostate volume, and serum PSA, with disappearance of cancerous cells on repeat biopsies in five of six patients. Some of the unresolved biological enigmatic questions associated with PCa are discussed. We conclude that pathological flow of FT from the testes directly to the prostate in an extremely high concentration via the testicular-prostate venous drainage systems was identified may explain the mechanism for the development of PCa. We suggest a time-window for eradication of localised, androgen-sensitive, PCa cells. We anticipate that this treatment may retard, stop or even reverse the development of the disease. A mechanism for the evolution of PCa is discussed.

We commend Dr. Iaccarino on his extensive experience with treating varicocele. We agree that sclerotherapy is the most effective way of treating the main internal spermatic vein (ISV) and assuring that the ever-present collaterals are also sclerosed, reducing recurrences. Retrograde (transcatheter) transfemoral sclerotherapy in experienced hands is both safe and efficacious, with none of the theoretical complications suggested by Dr. Iaccarino. We do not heparinize our patients, who are mobilized within 30 min of the completion of their treatment and told not to lie in bed after the first 4 h. We have seen no cases of clinical symptoms of thromboembolism, either systemic or portal. (We are somewhat surprised at such a case: Does Dr. Iaccarino have one?) It might be expected in esophageal varices sclerotherapy, but the amounts of sclerosant that we use and the sclerosing characteristics of 3% sodium tetradecyl sulfate are such that this is not a consideration. We disagree with Dr. Iaccarino about the treatment of so-called subclinical varicocele. We have shown in several of our articles that the physical (hydrodynamic) principles which explain the pathophysiology of varicocele require only that there be incompetent ISV valves for the abnormally high venous pressures to be directly transmitted to the testicular microcirculation and interfere with normal perfusion of the testicular parenchyma. The result is hypoxia of the testicular tissue and this has been shown on histopathology of varicocele (also cited in our articles in the References section of our original paper: CVIR, Vol. 29, No. 2, 192– 197, 2006). The presence of varicocele on the right cannot be reliably demonstrated clinically by Valsalva maneuver because of the hydrodynamics of the right ISV: specifically, its direct emptying into the inferior vena cava (IVC). It is not possible to adequately distend the IVC during Valsalva and elevate pressures for a prolonged time without nearly arresting venous return to the heart and causing very rapid syncope. At the same time, the angle between the ISV and the IVC is acute, and the changes in the relationship between these two venous structures during Valsalva maneuver act to close that angle and decrease flow. Only in those patients with direct emptying of the right ISV into the right renal vein (about 8% in our study), in which the configuration nearly mirrors the left anatomy, can this maneuver be relied on to result in reflux. And again, reflux does not have to be massive (as Dr. Iaccarino proposes) for it to cause infertility. We have (as have others using microsurgical techniques) shown a small but significant group of responders to bilateral sclerotherapy in patients with Sertoli cell only. Dr. Iaccarino cites Dr. Nagler’s comments in the Journal of Urology (2004), in which he questions whether treatment is at all effective. This is in keeping with the multicenter study which showed poor results for ISV occlusions—surgical and interventional techniques. Our response to Dr. Nagler was that we agree that the treatment of varicocele as described by the various authorities was not effective (more than medical treatment), but not because varicocele does not affect fertility: rather, because the treatments were essentially inadequate, ignoring the physical basis for the pathophysiology and the presence of significant venous reflux on the right, not just by interscrotal collaterals. M. Gornish (&) Y. Gat Y. Siegel Department of Radiology, Maayanei Hayeshua Medical Center, Bnei Brak, Israel e-mail: menachemg@skynet.co.il

The prostate is an androgen-regulated exocrine gland producing over 30% of the noncellular components of the semen and promoting optimal conditions for survival and motility of sperm in the vagina. Benign prostate hyperplasia (BPH) is the most common benign neoplasm in men. Its aetiology is not clear, and therefore, current medical treatments are directed towards the symptoms. Though testosterone is known to be the promoter of prostate cell proliferation, no causal relation between serum testosterone levels and BPH has been found. In this study, we propose a novel and tested pathophysiological mechanism for the evolution of BPH and suggest a tested and effective treatment. We found that in all BPH patients, the one-way valves in the vertically oriented internal spermatic veins are destroyed (clinically manifested as varicocele), causing elevated hydrostatic pressure, some 6-fold greater than normal, in the venous drainage of the male reproductive system. The elevated pressure propagates to all interconnected vessels leading to a unique biological phenomenon: venous blood flows retrograde from the higher pressure in the testicular venous drainage system to the low pressure in the prostatic drainage system directly to the prostate (law of communicating vessels). We have found that free testosterone levels in this blood are markedly elevated, with a concentration of some 130-fold above serum level. Consequently, the prostate is exposed to: (i) increased venous pressure that causes hypertrophy; (ii) elevated concentration of free testosterone causing hyperplasia. We have treated 28 BPH patients using a technique that restores normal pressure in the venous drainage in the male reproductive system. The back-pressure and the back-flow of blood from the testicular to the prostate drainage system were eliminated and, consequently, a rapid reduction in prostate volume and a regression of prostate symptoms took place.

Varicocele is a bilateral vascular disease which occurs when the one-way valves in the internal spermatic veins, the testicular venous drainage system, malfunction. Based on new findings and fluid-mechanics analysis we showed that this process results in vertical blood columns, which cause pathological hydrostatic pressure in the testicular venous microcirculatory system. Ultimately, these pressures exceed the pressure in the arteriolar system. This unique phenomenon of reversal of pressures gradient between the arteriolar and venular systems leads to persistent hypoxia in the testosterone production site, namely, the Leydig cells. The result of bilateral varicocele is decreased testosterone production. Adequate treatment of bilateral varicocele significantly elevates the testosterone production. We found that the prevalence of varicocele increases with age with a rise of about 10% for each decade of life with the incidence reaching 75% in the eight decade of life. Based on our findings the following statements can be made: (1) varicocele prevalence is increased over time. (2) The rise of the incidence is about 10% for each decade of life. (3) 75% of men in the eight decade of their life have varicocele. As varicocele decreases testosterone production and it is reversible by appropriate treatment, it raises two interesting and important issues to be studied: (i) it is possible that varicocele accelerates the process of the ageing male. (ii) It is possible to retard, at least partially, the process of ageing in men by adequate treatment of bilateral 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.

No AccessJournal of UrologyAdult urology1 Apr 2006Varicocele, Hypoxia and Male Infertility. Fluid Mechanics Analysis of the Impaired Testicular Venous Drainage System Y. Gat, Z. Zukerman, J. Chakraborty, and M. Gornish Y. GatY. Gat More articles by this author , Z. ZukermanZ. Zukerman More articles by this author , J. ChakrabortyJ. Chakraborty More articles by this author , and M. GornishM. Gornish More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)01040-2AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Varicocele, Hypoxia and Male Infertility. Fluid Mechanics Analysis of the Impaired Testicular Venous Drainage System." The Journal of Urology, 175(4), p. 1454 Andrology Unit, Department of Obstetrics and Gynecology, Tel Aviv University, Tel Aviv, Israel© 2006 by American Urological AssociationFiguresReferencesRelatedDetails Volume 175Issue 4April 2006Page: 1454 Advertisement Copyright & Permissions© 2006 by American Urological AssociationMetricsAuthor Information Y. Gat More articles by this author Z. Zukerman More articles by this author J. Chakraborty More articles by this author M. Gornish More articles by this author Expand All Advertisement Loading ...

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.

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.

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. (C) 2005 by American Society for Reproductive Medicine.

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. (C)2004 by American Society for Reproductive Medicine.

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.