titolo breve: CONSENSUS ON THE USE OF CYCLOSPORINE IN DERMATOLOGICAL PRACTICE primo autore: ALTOMARE Rivista: GIORNALE ITALIANO DI DERMATOLOGIA E VENEREOLOGIACod Rivista: G ITAL DERMATOL VENEREOL e additional copies G ITAL DERMATOL VENEREOL 2014;149:607-25 or personal or commercial use is , electronic mailing or an It is not per. aming techniques to enclose an Consensus on the use of cyclosporine
Uro multi doc masterEjaculatory dysfunctionand the treatment ofLUTS Paul Sturch,Urology Department, King'sCollege Hospital, London.
For years ejaculatory dysfunction in group receiving 10mg of alfuzosin experienced no men following medical or surgical reduction in ejaculatory volume and there was no treatment of lower urinary tract significant difference in post-ejaculatory urine symptoms (LUTS) was thought to be sperm concentrations between the two groups a result of disruption of the bladder taking alpha-blockers and a placebo group .
neck mechanism and the subsequent Lower doses of tamsulosin cause a lower incidence retrograde flow of semen. Men commenced on of ejaculatory problems and the inhibitory effect alpha-blockers or consenting to disobstructing on ejaculation varies between different alpha surgery were warned of this risk of retrograde blockers. Silodosin, a new ?1A-adrenoceptor- ejaculation and were expected to live with it. Until selective antagonist has been shown to cause recently there has been little effort put into higher rates of anejaculation than tamsulosin challenging this perceived wisdom, even in the (22.3% vs. 1.6%) in a study of 457 Japanese men .
face of the paradoxical situation of a lower These effects are explained further in animal Sydney Adventist HospitalClinical School, University of incidence of ejaculatory dysfunction following studies. Both serotonin and dopaminergic Sydney, Australia.
bladder neck incision, which also disrupts the receptors play an integral role in the central control bladder neck, compared to transurethral resection of ejaculation. Tamsulosin has a binding affinity for of the prostate (TURP). This review seeks to address 5-HT1a and D2-like receptors almost 10,000 times the reasons for ejaculatory dysfunction with greater than other ? -blockers. Systemic different LUTS / benign prostatic hyperplasia (BPH) administration of tamsulosin has been shown to treatments, and to comment on some new significantly reduce bulbospongiosus contractions developments in the field.
mediated by 8-OH-DPAT, a 5HT1a and D2-likereceptor agonist, in male rats . Alpha-blockers
Alpha-blockers such as tamsulosin are the first-line
medical treatment for moderate to severe LUTS .
5-alpha-reductase inhibitors (5AR-I) have been When tamsulosin was found to cause ejaculatory shown in a number of trials to reduce prostate size, dysfunction in up to a quarter of men, patients improve symptom scores and flow rates and Urology Department, King's were initially told this was also due to retrograde reduce the risk of urinary retention and the need College Hospital, London.
ejaculation. This has now been shown to be a for surgery . They can be used as a monotherapy central inhibitory effect causing anejaculation and or in combination with alpha-blockers and are well has little or nothing to do with the bladder neck or tolerated. Finasteride was the first 5AR-I marketed, Correspondence to:Gordon Muir, backwards flow of semen. The inhibitory effect of followed more recently by dustasteride. The tamsulosin has been shown to be dose dependent mechanism of action of both drugs is to inhibit the and at 0.8mg up to 90% of subjects in one study synthesis of dihydrotestosterone (DHT) medicated experienced a reduction in ejaculate volume with by the 5-alpha-reductase enzyme. Dutasetride Declaration of competing anejaculation in over a third. In comparison, a inhibits the type 1 and 2 isoenzymes, reducing It now seems clear that most ejaculatorydysfunction fol owing medical and surgicaltreatment of LUTS is not retrograde passageof semen and our surgical techniquesshould continue to develop in light of this UROLOGY NEWS
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serum concentrations of DHT by around 90%,whereas finasteride inhibits the type 2isoenyme only, reducing serum DHT by around70% . DHT is important in the embryologicaldevelopment of the male urogenital tractduring pregnancy and exposure of pregnantwomen to 5AR-Is could potentially result ingenital under development. Ingestion andabsorption though the skin should be avoidedin women of child bearing age . It is advisedthat men taking a 5AR-I use condoms toprevent exposure to women via semen,although primate studies have determinedthat the potential concentrations of 5AR-I insemen are minimal . Adverse effects arereported at similar rates with no statisticaldifference for both 5AR-Is. In general, 5AR-Is arewell tolerated with the most common side-effects relating to sexual dysfunction:impotence (8%), reduced libido (6%), andejaculatory dysfunction (1%) . Figure 1: Endoscopic view of the prostatic fossa with preservation of the veru and surrounding tissue with pre-operative view In 2004, Gil Vernet's group publishedenlightening evidence that bladder neckcontraction may not be necessary forantegrade ejaculation . Transrectal ultrasonicimaging of 30 subjects during ejaculationthrough masturbation clearly demonstrates theantegrade propulsion of semen emitted fromthe ejaculatory ducts through the co-ordinatedcontraction of the external sphincter andbulbar urethral smooth muscle. The bladderneck is redundant in this process as there is nodiscernable retrograde flow once the ejaculate Figure 2: the UroLift system.
Figure 3: PET monofilament suture.
is emitted from the ducts . From this study, it and surrounding ejaculatory tissue in a very lateral lobes were carried out transurethrally could be inferred that, as long as the tissue similar way to the GreenLight laser technique under general anaesthetic using the UroLift around the verumontanum is not disrupted, developed by the IGLU group, suggesting that system (NeoTract Inc., Pleasanton, CA, USA) antegrade ejaculation should still occur even anatomy rather than energy type is of prime (Figure 2). Outcomes were encouraging with with an open bladder neck. importance. The bladder neck is resected in the the expected symptoms of haematuria and Rather than focusing on bladder neck same way as with standard TURP technique. By dysuria resolved within a month of the preservation, an increased appreciation of the preserving apical tissue using these anatomical operation and no patients reporting importance of preserving the tissue landmarks, 90% of men experienced preserved ejaculatory dysfunction. A mean International surrounding the verumontanum has led to ejaculation with flowmetric parameters and Prostate Symptom Score (IPSS) improvement developments of ejaculation preserving quality of life scores comparable to non- was seen in almost all patients with a peak surgical techniques. The International ejaculatory preserving transurethral resection improvement at three months of 57%. This GreenLight Users (IGLU) group's work with techniques . In both the laser and improvement in symptoms score receded to anatomical and clinical data suggests that electrosurgical approaches, the anatomical 39% improvement at one-year follow-up. One ejaculatory duct angulation and duct landmark of the verumontanum is used to patient had no significant improvement and obstruction are critical factors in maintaining guide resection of the middle lobe to a point went on to have a conventional TURP .
ejaculation following surgery with more than 1cm proximal to this level. The lateral lobes of Similar experiences were reported in initial 85% of men in an international multicentre the prostate are resected or vaporised to the case series across Europe with rapid and study retaining antegrade ejaculation after level of the veru, without disruption of the noticeable improvements in IPSS and peak GreenLight laser prostatectomy. They have paracollicular tissue (Figure 1).
urinary flow rate and without significant suggested that even men being treated for morbidity from operative complications or retention of urine can have excellent functional sexual dysfunction [11,12]. Since this early outcomes while preserving antegrade A new and exciting minimally invasive experience a greater emphasis has been ejaculation. This work has been published in technique has recently been developed using placed on the anterior position of the channel video format . The Neunkirchen group has tensioning implants to hold open the within the lumen, which has led to reduced re- published similar data on ejaculatory obstructing lateral lobes of the prostate into a operation rates as the technique evolved. The preserving TURP, which can preserve position opening up the urethral lumen. This technique involves the transurethral ejaculatory function in the majority of men. The technique was first termed the "prostatic application of tissue-retracting polyethylene anatomical, monopolar resection they describe urethral lift procedure". The initial case series of teraphthalate (PET) monofilament sutures is focused on preserving the verumontanum 19 patients with LUTS secondary to obstructing (Figure 3) anchored on the fibromuscluar UROLOGY NEWS
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for Men (SHIM), Male Sexual Health Questionnaire for EjaculatoryDysfunction (MSHQ-EjD)), quality of life scores and maximum flow ratedemonstrated a rapid and sustained improvement at 1, 3 and 12 months.
No man has so far reported new ejaculatory dysfunction followingUroLift, and indeed patients treated with the urethral lift procedurereported a trend towards improvements in the ability to ejaculate, as wellas ejaculatory intensity and volume. Also, men entering the study with pre-existing erectile dysfunction (ED) (SHIM<19) showed a small butsignificant improvement in erectile function (mean SHIM increase of 2.4points) after treatment. There was no change in erectile function in menwith normal baseline erectile function. Conclusion
Historically, men seeking treatment for bothersome LUTS have been told
by their urologists that any methods, medical or surgical, will consign
them to dry orgasms. Many men, of all ages enjoy ejaculating and would
surely accept a reduction in treatment efficacy to preserve this importantaspect of quality of life. It now seems clear that most ejaculatorydysfunction following medical and surgical treatment of LUTS is notretrograde passage of semen, unless proven on post orgasm urinesamples, and our surgical techniques should continue to develop in lightof this. The UroLift system provides an exciting development in theminimally invasive treatment for LUTS secondary to BPH. With a relativelyshort operating time and minimal anaesthetic it has a low incidence ofadverse effects and rapid, sustained improvement in symptom scores.
This, and ejaculation preserving surgery, introduce a new qualitative Figure 4: The implant is delivered into a prostate with encroaching lateral lobes (a), byintroducing the device under cystoscopic guidance (b), compressing the lobe with the delivery dimension to the way we will need to counsel patients in the years device and deploying the needle (c), retracting the needle, tensioning the monofilament to seat ahead. Although almost no research has been carried out in the area, we the capsular tab on the prostatic capsule and securing the connecting suture with an urethralend piece (d). Additional implants are delivered as required (e), to maintain the expanded find that nearly all men will express strong preferences if made aware urethral lumen (f). Images copyright NeoTract, Inc.
that LUTS / BPH treatments can impact on their ejaculatory function todifferent levels. We would encourage urologists to discuss ejaculatory prostate capsule with a nitinol metallic tab. The implant is tensioned dysfunction with all sexually active patients in order to allow the best against the urethral aspect of the prostate secured with a stainless-steel selection of treatment for an individual.
urethral end piece, compressing the glandular tissue and expanding thelumen. The implants are delivered under direct vision and placed at the 2 References
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multicentre studies have clearly shown the benefit of the urethral lift Andriole GL, Kirby R. Safety and tolerability of the dual 5alpha-reductase inhibitor
dutasteride in the treatment of benign prostatic hyperplasia. Eur Urol 2003;44:82-8.
procedure. Shore et al. , in their North American study of 51 patients, Roehrborn CG, Boyle P, Nickel JC, et al. Efficacy and safety of dual inhibitor of 5-alpha showed a significant improvement in symptoms in 90% and high reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia (BPH).
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McVary et al.  randomised 206 men to receive the urethral lift or a 11. Delongchamps NB, Conquy S, Defontaines J, et al. [Intra-prostatic UroLift (®) implants for sham procedure at a ratio of 2:1. All subjects were unblinded at three benign prostatic hyperplasia: preliminary results of the four first cases performed in France].
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12. Garrido AP, Coloma Del Peso A, Sinues OB, et al. [Urolift®, a new minimally invasive including the urethral lift procedure. The prostates treated were of similar treatment for patients with low urinary tract symptoms secondary to BPH. Preliminary size to Shore's group but, in contrast, an average of 4.9 implants were results.] Arch Esp Urol 2013;66(6):584-91.
deployed in this group. The most common adverse effects were transient 13. McNicholas TA, Woo HH, Chin PT, et al. Minimally invasive prostatic urethral lift: surgical technique and multinational experience. Eur Urol 2013;64(2):292-9.
dysuria, haematuria and pelvic pain, experienced by both treatment and 14. Shore N, Freedman S, Gange S, et al. Prospective multi-center study elucidating patient sham groups. At three months' follow-up a significant improvement in experience after prostatic urethral lift. Can J Urol 2014;21(1):7094-101.
LUTS was experienced in the treatment group compared to the controls.
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