Accepted: 10 June 2017 DOI: 10.1111/and.12870 ORIGINAL ARTICLE Benign Prostatic Hyperplasia: Long-term follow-up of prostate volume reduction after sclerotherapy of the internal spermatic veins Y. Gat1,2 | M. Goren1 1Andrology-Interventional Radiology Maynei Hayeshua Medical Center, B’nei B’rak, Israel Summary 2Department of Physics, Sub Micron The purpose was to examine the results of bilateral percutaneous sclerotherapy of the Research, Weizmann Institute of Science, internal spermatic veins on prostate volume and prostatic symptoms. We previously Rehovot, Israel showed that destruction of one- way valves in the internal spermatic veins (varicocele) Correspondence elevates hydrostatic pressure in the vertical testicular venous drainage system in the Yigal Gat, M.D. PhD. Department of Physics, Sub Micron Research, Weizmann Institute of erect human. This diverts free testosterone (FT) flow at high concentrations directly Science, Rehovot, Israel. from the testes into the prostate. High intraprostatic FT prolongs prostate cell life and Email: [email protected] increases cell proliferation rate—synergistic effects resulting in increased cell popula- tion (BPH). Treatment by interventional radiology (or microsurgery) techniques elimi- nates 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 improve- ment 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 im- provement (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 varico- cele restores normal supply of testosterone to the prostate solely via its arterial sup- ply, resulting in significant decrease of prostate volume and prostatic symptoms. The procedure is safe with only minor transient side effects. KEYWORDS benign prostatic hyperplasia, gat-goren technique, internal spermatic vein, interventional radiology, varicocele 1 | INTRODUCTION The extant medical literature on the prostate reveals a biological paradox: while serum FT levels decrease with age, the incidence of Benign prostate hyperplasia (BPH) is the most common benign neo- BPH increases with age. plasm in ageing men, affecting almost 75% of men in the seventh Our previously published work has resolved this enigma, showing decade. The cause of BPH has not been fully elucidated. Free testos- that venous valve destruction and insufficiency in the internal sper- terone is the controller of the prostate cell. High intraprostatic concen- matic veins, a phenomenon that increases rapidly with age, is critical tration of free testosterone accelerates cell proliferation and prolongs in the development of BPH (Gat, Gornish, Heiblum, & Joshua, 2008). cell life (Chatterjee, 2003; Feldman & Feldman, 2001). Low intrapros- It has been shown that the destruction of the one- way valves in tatic concentration of FT decreases the rate of production of new cells the internal spermatic veins (varicocele) increases remarkably with age and shortens their survival (Isaacs, 1984; Huggins & Stevens, 1940). (Canales et al., 2005; Levinger, Gornish, Gat, & Bachar, 2007). This Andrologia. 2017;e12870. wileyonlinelibrary.com/journal/and © 2017 Blackwell Verlag GmbH | 1 of 8 https://doi.org/10.1111/and.12870 2 of 8 | GAT AND GOREN FIGURE 1 ISV anatomy with physiologic venous pressures. Prostatic venous blood flows through prostate venous plexus of Santorini (PVP), vesicular vein (VV), internal iliac vein (Int.I), common iliac vein (CI) and inferior vena cava (IVC). Testicular venous blood mainly via ISV, with distribution to: deferential vein (DV), scrotal vein (SV) and cremasteric vein (CV). Testicular venous blood via DV flows to VV (common drainage to prostate and DV), meeting blood from VP. Both flow jointly to Int.I, CI then into IVC pathology creates a cascade of pathophysiological effects leading to is a physical connection between the testicular and the prostatic ve- BPH (Figures 1 and 2). nous drainage systems. This connection exists at the meeting point The destruction of the one- way valves occurs on both the left and between the deferential vein arriving from the testes, and periprostatic the right sides. (Comhaire, Kunnen, & Nahoum, 1981; Gat, Bachar, venous plexus (and Santorini plexus) arriving from the prostate gland Zuckerman & Gornish, 2004). Disappearance of the one- way valves (Pierrepoint, Davies, Millington, & John, 1975; Wishahi, 1992). These leads to a vertical column of blood which produces, according to two vessels join and flow into the vesicular vein. The elevated venous Pascal’s principle, hydrostatic pressure in the internal spermatic veins pressure in the deferential vein exceeds the lower pressure in the vesic- that is 7–8 times normal on the left side and six times normal on the ular plexus and in the peri-prostatic venous plexus producing a pressure right (Gat, et al., 2006; Streeter, 1971). That leads to a pathologic gradient between the testicular and the prostatic drainage systems. The change of flow direction of FT- rich blood that is not yet fully diluted to venous pressure difference between the testicular (high pressure) and the prostate gland as described in our previous study (Gat et al., 2008). the prostatic (low pressure) drainage systems causes diversion in the This high pressure is propagated through all connecting vessels flow direction from the deferential vein to the prostate venous drainage according to the principle of communicating vessels, a derivative of system. The free testosterone- rich testicular venous blood in the defer- Bernoulli’s Law of Conservation of Fluid Energy (Streeter, 1971). There ential vein flows directly to the prostate gland. This influx, under elevated GAT AND GOREN | 3 of 8 FIGURE 2 Anatomy of testicular and prostatic venous drainage in Varicocele Figure 2. Loss of one- way valves causes: (i) loss of mechanism to elevate venous blood upwards against gravity; (ii) increased hydrostatic pressures in testicular drainage system (six to eight times physiologic). Elevated pressure propagated to all interconnected vessels, including deferential vein (DV). Testicular venous blood flows along pressure gradient from testes, directly to prostate (obeying Bernoulli’s principle of “communicating vessels”), via testicular- prostate venous drainage systems, carrying undiluted and unbound high concentrations of FT hydrostatic pressures, widens the diameter of the deferential vein and route as we have directly demonstrated in venographic images ob- the periprostatic plexus (Figure 2). This phenomenon has been demon- tained during the interventional radiology procedure (Figure 3). It is to strated by ultrasound in varicocele (Sakamoto & Ogawa, 2008). The be noted that under these circumstances, the prostate gland receives widened deferential vein allows an increase in the rate of flow accord- testosterone from two sources: the physiologic supply via the prostatic ing to Hagen- Poiseuille (Streeter, 1971) enabling these three horizontal arteries, and the pathologic supply of free testosterone via the venous vessels—deferential, cremasteric and scrotal veins—to contain the blood system. This pathologic condition is a unique phenomenon only in the volume that is unable to flow via ISVs without its competent valves. erect human body. Elevated intraprostatic free testosterone has two This free testosterone- rich blood arrives directly to the prostate synergistic effects; on the one hand, it increases the rate of cell prolif- before it has undergone full volumetric dilution (Gat, Joshua & Gornish, eration (Feldman & Feldman, 2001), and, on the other hand, prolongs 2009; Gat et al., 2008; Jarow, Chen, Trentacoste, & Zirkin, 2001; cell life (Chatterjee, 2003). These two factors lead to the development Strunk, Meier, Schild, & Rauch, 2015). Extremely high concentration of BPH by the progressive increase in the prostate cell population. of free testosterone, more than 100 times the systemic serum concen- The treatment we devised is therapeutic occlusion of the ISVs, in- tration, flows directly into the prostate, via this previously unknown cluding all vertically oriented collaterals, each of which contributes to 4 of 8 | GAT AND GOREN their ISVs for the treatment of BPH at our institution. These patients were originally diagnosed with BPH and had been followed in urology Tip catheter in right ISV clinics. Inclusion criteria included patients with BPH and age above 40 years. Exclusion criteria were patients with urinary tract infection, acute urinary retention, sensitivity to iodine, renal insufficiency and patients with coagulopathy. Bilateral varicocele was demonstrated in all patients. Varicocele was assessed by physical examination, ultrasound colour-flow Doppler Bladder and contact thermography, using a flexible liquid crystal thermostrip: Varicoscreen® (FertiPro, Beernem, Belgium).This is a clinical diagnostic ISV tool considered the most accurate and sensitive for detection of bi- lateral and subclinical varicocele, especially on the right side, where it is difficult to detect clinically (Comhaire, Monteyne, & Kunnen, 1976; Gat, Chakraborty, Zukerman, & Gornish, 2005; Kunnen & Comhaire, 1992). Catheter All patients