Ayhan Verit ^* Fatma Ferda Verit

• Health Sciences University, Istanbul, Türkiye

Introduction Chronic prostatitis (CP) and also defined among Chronic pelvic pain syndromes (CPPS) with largely unknown etiology is a pathology makes the patients’ life miserable with a quite decrease in quality of life in addition with significant economic burden (1,2). Its Worldwide prevalence was reported in a range of 2-25% but overall one was supposed to be near to the upper limit (3,4). CP/CPPS are a group condition that supposed to be related with the prostate gland in men that continues or gets worse over a long period of time at least more than 3 months. Main symptoms are body aches, lower back pain and genital area, dissuria, and problems with emptying the bladder (1-4). Unfortunately, there is neither widely confirmed classical treatment option nor a remedy for curing the disease other than just relieving the symptoms for CP. The combination of improper immunity system and increased oxidative stress that induced by local ischemia are among the reported patho-physiology events that connect in the etiology of CP besides the ranking endocrine/neurologic/infectious ones (5-8). Vinclozolin is an antiandrogenic to block the activity of gonadal hormones upon male reproductive organs including perineum (9). Vinclozolin exposure in embryologic life showed to reduce anogenital distance (AGD), that simply calculated of the length of the skin between the center of anus and the junction between the smooth perineal skin and skin of the scrotum or penis represented as AGDAS or AGDAP respectively (9-11). There are some clinical studies, which support AGD that may have association with well-known androgen-sensitive pathologies such as prostate cancer (PC), male infertility, hypospadias, cryptorchidism and even to benign prostatic hyperplasia (BPH) and premature ejaculation (11-20). Thus, this physical variance was suggested in clinical evaluations of the patients’ medical records as a diagnostic helper. However, unlikely to the current literature, in this text, our aim is to indicate the prospect of this physical marker as a real physical squeeze, other than the endocrine related disorder, defining the etiology of CP through the physical compression inside the narrowed perineum. Additionally, in this study, we would like to improve our pioneer hypothesis at this topic with additional contribution and discussion about possible surgical treatments (21). The Main Text Perineal structures represent the bottom flooring of pelvis that can be considered as geometrically the apex of the reversed cone. Whereas the superficial anatomical tip of this cone was noted in an anterior-posterior line appeared as AGD, the internal side of this line extends between lower urinary tract, mainly urethra and rectum, that exactly the location of prostate, the unique parenchymal organ without a true capsule of this zone (Fig.1). So that, we may hypothese that narrowing of this internal side of cone may compress directly and constantly on prostatic tissue with its accessories as neurovascular pedicle that result in chronic hypoxia (21). We think that Denonvilliers’ fascia at anterior side of rectum as a real tight structure has a special role that reflecting the pressure on the prostate more than the rectum itself in this physiopathology process. The main factor that restrict prostate at anterior side is os pubis. Moreover, the ability of stabilizing effect of urethra that extends inside the prostate, and also the prostatic ligament and endopelvic fascia, should be mentioned among the apparatus to make prostate immobile and expose chronic pressure on prostatic tissue (Fig. 1). As a result, prostate is trapped between internal perineal structures mainly between os pubis and rectal fascia in antero-postero direction and this quantity of strength can be quite variable in individual basis due to the length of the defined area appeared as AGD. Besides all, all uro-oncologic surgeons have experienced difficulty during the dissection of prostate from the surrounding tissues in radical prostatectomy that we think that it is a clear example of trapped prostate at the bottom of the pelvis. Furthermore, the eliminating the constipation problem in patients with CP is the initial goal among the management strategies to discharged of internal pressure of the rectal involvement on the neighborhoods. Actually, it is surely difficult to confirm all these physical dynamic pressure disseminations in vivo. Overall, while the internal side of the landmark AGD begins anteriorly by internal face of os pubis, urethra, endopelvic facia and prostatic ligament that fix prostate in its longitudinal axis that restricts also lateral movements, it lasts posteriorly at rectum and mainly its Denonvilliers’ fascia. Nevertheless, narrowed perineum for prostate is supposed to occur two parallel blocks for compression on prostate and its accessories as seminilovesicalis and vascular structures that lays posteriolateral of prostate. The severity of pressure mechanism may deem to increase by shrinking of the above-mentioned area that can be estimated by measurement of AGD in regard of the aim this study (Fig. 1). On the other hand, although AGD is only a one dimensional marker, we think that this simple measurement can give also fine estimation about the tip of the size of the cone in two and three dimensions. It is noteworthy that this zone is surely also the main point of the abdominal cavity that incur the highest pressure due to the gravity especially at standing position. While this significant pressure gives rise to the “pelvic organ prolapsus” in women, there is not a similiar pathology in men that support our fiction about trapped strain at the region. In parallel, this up position specific to human species among the land mammals, may superpose the severity of lower abdomen venous pathologies that all thought to have common origin (22). The most common one is rectal hemorrhoids and the others; pelvic venous diseases named as “pelvic congestion syndrome” associated with CPPS in women and varicocele in man (23,24). In addition, flavonoids with their healing efficacy on vessels are current systemic medication for revealing rectal hemorrhoids also reported to be effective in CP treatment that confirms varicose impairment extends to prostate in theory (25,26). To a sub-conclusion, the increased of hydraulic venous pressure also seems to upgrade the intra-prostatic strain, or vice versa. The condensed mentioned physical pressure on prostate facilitate to occur intra and/or periprostatic varicose disorder appears clinically as CP. All in all, as a sub hypothesis, we insist on that prostate also the target of varicose disturbance as its anatomically neighborhoods depending deductive literature knowledge about treatment option of CP. Moreover, it can be claimed that this external pelvic pressure on prostate can be transmit to the urethra inside the prostate that may be another physical factor to decrease urinary flow rate. Currently, this can be even calculated by low-cost digital home uroflowmetry systems appropriate for telemedicine (27). The present below suggested prostate relaxing surgical procedures may also have potential to reduce the bladder outlet obstruction (BOO). However, BOO due to the CP was excluded from this discussion. Furthemore, some improvements in bacterial prostatitis (5-10%) were also reported such as the prescription of nutraceutical antioxidant products besides appropriate spectrum antibiotics (28). This limited group also excluded from the discussion due to their well-known standard medical approach. We think that the histological appearance of aforementioned mechanism that resulted from local inflammatory reaction related with improper immune response and oxidative stress due to the chronic hypoxia are noted as CP in random prostate biopsy reports in the searching of PC. It is noteworthy that the definition of histological CP takes part in a high rate with 60-80 in biopsy materials that were indicated for suspicion PC with or without symptomatic prostatitis and no bacterial induction confirmed in most of them (29, 30). Although the hypotheses of endocrine disturbance in the etiology of CP was excluded in the present discussion in regard to aim of this study, we should mention that in-utero antiandrogens/estrogens such as Vincozolin/Dinesterol respectively, were showed to induce dose dependent histologic post-pubertal prostatitis in animal models (9, 31). Actually it may be claimed that initial androgen deficiency which result in shortening AGD, also prepare the histological and/or clinical basement for CP, enhance the impact of ischemia induce CP later in adulthood life described in the present text. Nevertheless, in another explanation, do we speculate that there is not an endocrinologic etiology in CP without the mechanism of shortening AGD and the present mechanism begin to work in perinatal period and progress life-long via accumulation of the ischemic inflammation? In related with neurologic etiology that was also excluded for the discussion, we just would like to remind that perineal “pain” and “tenderness” are some of the common symptoms of CP that may cause prostate itself or the perineum which surely be the direct target of synchronous mentioned physical forces and chronic ischemia at the external side of prostate location (32). It should also be considered that afferents pathways of prostate related with pain transmission are complicated and not fully understood (33). Overall, it should be strongly emphasized that CP, and in general CPPS, are a group of not fully understood clinical disorders without confirmed pathophysiology, and in addition, they are difficult for the investigation with the well-designed study protocols. However, in this study, we tried to introduce special perspective for this miserable clinical status via discussion of pure physical forces supported by the literature that can be predict by simple measurements at routine physical investigation besides the classical possible reported etiologies. For the clinical practice, we think that AGD is a simple measurement that can be applied even the inspection phase during digital rectal investigation for the CP that can help the physician to confirm the diagnoses of CP. Moreover, if our hypotheses confirmed by further well designed experimental and clinical studies, some novel surgical techniques -empirically like ureterolysis in retroperitoneal fibrosis or for some gynecologic operations- to loosen the prostate from the fascia like connective surrounding structures to mobilize against the detrimental effects of chronic tension may be improved for the surgical treatment for CP especially for the selected cases who have reduced AGD. In regard to aim of the study, we suggest the releasing of the pubo-prostatic ligaments, endopelvic, levator and prostatic facias to possible help to decompression on prostate in patients with CP but care to the destruction of neurovascular bundle to preserve erection strongly advised. All these structures and their dissection were defined in detail by Walsh (34) Current surgical interventions involve transurethral removal of prostatic tissue as TURP, radical TURP and transurethral vaporization of the prostate (TUVP), even extends to radical prostatectomy for the refractory cases, however, efficacy and safety of these surgical treatment options were extremely suspicious for the evidence based practice and generally conducted mostly for the chronic bacterial prostatitis (4). Nevertheless, the defined prostate releasing present surgeries especially with minimal invasive laparoscopic surgery, with/without robot assist, cannot be considered as unsafe in comparison with current ones that targeting the removing of prostatic tissue. However, as an interesting noteworthy critic, novel surgical methods on prostate were supposed to have upward trend in cost as a significant load on health system (35). To conclude, apart from the current knowledge, AGD, a personal variation, can not only provide information about the male urogenital system pathologies via embryologic hormonal pathways, but also, we think that AGD may be a physical sign of the histological/clinical prostatitis due to the diminished perineum.