A BURST-BAUS consensus document for best practice in the conduct of scrotal exploration for suspected testicular torsion: the Finding consensus for orchIdopeXy In Torsion (FIX-IT) study.

OBJECTIVES: To produce a best practice consensus guideline for the conduct of scrotal exploration for suspected testicular torsion using formal consensus methodology. MATERIALS AND METHODS: A panel of 16 expert urologists, representing adult, paediatric, general, and andrological urology used the RAND/UCLA Appropriateness Consensus Methodology to score a 184 statement pre-meeting questionnaire on the conduct of scrotal exploration for suspected testicular torsion. The collated responses were presented at a face-to-face online meeting and each item was rescored anonymously after a group discussion, facilitated by an independent chair with expertise in consensus methodology. Items were scored for agreement and consensus and the items scored with consensus were used to derive a set of best practice guidelines. RESULTS: Statements scored as with consensus increased from Round 1 (122/184, 66.3%) to Round 2 (149/200, 74.5%). Recommendations were generated in ten categories: consent, assessment under anaesthetic, initial incision, intraoperative decision making, fixation, medical photography, closure, operation note, logistics and follow-up after scrotal exploration. Our statements assume that the decision to operate has already been made. Key recommendations in the consent process included the discussion of the possibility of orchidectomy and the possibility of subsequent infection of the affected testis or wound requiring antibiotic therapy. If after the examination under anaesthesia, the index of suspicion of testicular torsion is lower than previously thought, then the surgeon should still proceed to scrotal exploration as planned. A flow chart guiding decision making dependent on intraoperative findings has been designed. If no torsion is present on exploration and the bell clapper deformity is absent, the testis should not be fixed. When fixing a testis using sutures, 3 or 4-point is acceptable and non-absorbable sutures are preferred. CONCLUSIONS: We have produced consensus recommendations to inform best practice in the conduct of scrotal exploration for suspected testicular torsion.

Reproductive outcomes in women with classic bladder exstrophy: an observational cross-sectional study.

OBJECTIVE: We sought to examine the reproductive outcomes of 52 women with classical bladder exstrophy. STUDY DESIGN: This was an observational study with cross-sectional and retrospective arms. RESULTS: The average age of the sample was 33 years (range, 17-63). Of those who had tried, 19/38 (66%) had conceived. A total of 57 pregnancies (3 sets of twins) were reported for the 19 patients and resulted in 34/57 live births (56%), 21/57 miscarriages (35%), 1/57 (2%) termination, and 4/57 (7%) stillbirths or neonatal deaths. Four deliveries resulted in major complications including 1 transection of the ureter (4%), 1 fistula formation (4%), and 2 postpartum hemorrhages (8%). There were 2 admissions to intensive care, one for urinary sepsis and another for massive obstetric hemorrhage. CONCLUSION: Fertility is impaired in women with bladder exstrophy. Pregnancy is high risk both for the mother and baby. Delivery should be at a tertiary referral obstetric unit with urology cover. In the majority of cases planned cesarean section is the most appropriate mode of delivery.

Changing P2X receptor localization on maturing sperm in the epididymides of mice, hamsters, rats, and humans: a preliminary study.

OBJECTIVE: To study using immunohistochemistry the localization of P2X receptor subtypes on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. DESIGN: Basic research. SETTING: University-based hospital. PATIENT(S): Three human epididymides were obtained from patients undergoing orchidectomy for metastatic prostate cancer. MAIN OUTCOME MEASURE(S): P2X(1), P2X(2), P2X(3), and P2X(4) receptor immunolocalization on sperm. RESULT(S): In the present study, P2X(1,2, and 3) receptor localization was immunohistochemically demonstrated on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. P2X(4) receptor immunostaining was also observed on the head of sperm in the caput epididymidis of mice, hamsters, and humans, but not rats. There was a subsequent loss of receptor staining on sperm in the cauda epididymidis, except in humans where staining of P2X(4) receptors persisted. Comparision with peanut agglutinin (PNA) binding studies suggested the P2X receptors were located on the acrosome membrane. P2X(5-7) receptors were examined but found to be absent. CONCLUSION(S): The change in localization of receptor subtypes is coincidental with the functionally essential morphologic and maturational changes seen in sperm as they travel through the epididymis, and is suggestive of a role for purinergic signaling in sperm maturation and possibly fertility.

The purinergic component of human vas deferens contraction.

OBJECTIVE: To examine purinergic signaling in human vas deferens. DESIGN: To study contractile responses of the scrotal vas deferens. SETTING: Research department of a university teaching hospital. PATIENT(S): Undergoing vasectomy or orchidectomy (aged 27-88 years, n = 14). INTERVENTION(S): Vasectomy or orchidectomy. MAIN OUTCOME MEASURE(S): Strips of vas deferens were suspended in an organ bath and subjected to electrical stimulation to establish frequency-response curves. These stimulations were repeated in the presence of pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2 receptor antagonist), prazosin (adrenergic alpha1 antagonist), and tetrodotoxin. Concentration-response curves were constructed to noradrenaline and the P2X agonists ATP and alpha,beta-methylene ATP (alpha,beta-meATP). The P2X receptor subtype distribution was assessed by immunohistochemistry using specific antibodies. RESULT(S): The response at 32 Hz in the presence of PPADS was reduced by 40% and in the presence of prazosin by 80%. Noradrenaline caused concentration-dependent contractions (EC50 = 11.8 microM). Contractions to ATP and alpha,beta-meATP (EC50 = 6.27 microM) suggested that the functional receptor was P2X1 and/or P2X3. However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor immunoreactivity on the smooth muscle cells. CONCLUSION(S): This study demonstrated that ATP is a co-transmitter with noradrenaline in the contraction of the human vas deferens predominantly acting through the P2X1 receptor.

Alterations in purinergic and cholinergic components of contractile responses of isolated detrusor contraction in a rat model of partial bladder outlet obstruction.

OBJECTIVE: To study the effect of 3 weeks of partial bladder outlet obstruction (BOO), compared to a sham operation, on the cholinergic and purinergic components of detrusor contractile responses to agonists and to electrical field stimulation (EFS); the expression of P2X receptor subtypes was also examined. MATERIALS AND METHODS: Partial BOO was induced in female Sprague-Dawley rats by surgically applying a jeweller's silver 'jump' ring around the urethra, such that the urethra was constricted but not closed. Sham-operated female rats underwent an identical procedure without placement of a ring. RESULTS: After 3 weeks of partial BOO the rat bladders became significantly hypertrophied, doubling in weight. Spontaneous activity was markedly increased, but the contractile response to a single bolus of KCl (120 mM) was unaltered. The neurogenic-induced contractile responses of strips of detrusor from obstructed bladders were significantly greater than those from sham-operated bladders, and the responses of strips of detrusor from obstructed bladders to EFS showed a significantly greater atropine-sensitive component than sham-operated detrusor. However, the response of detrusor strips to EFS that was susceptible to desensitization by alpha,beta-methylene ATP was not significantly changed in obstructed bladders. The sensitivity of the strips from obstructed bladders to carbachol, ATP and beta,gamma-methylene ATP was less than in sham-operated detrusor. Immunohistochemical studies showed no difference in the P2X receptor subtypes expressed on detrusor smooth muscle from obstructed and sham-operated rats. CONCLUSION: In the rat, after moderate bladder hypertrophy, the atropine-sensitive component was significantly up-regulated, but the ATP-sensitive component was marginally reduced, although not significantly. These results suggest that up-regulation of the P2X component of bladder contraction seen in humans with bladder instability, and in other species models of BOO, is not mirrored in the rat, or occurs later in the pathological process of bladder hypertrophy.

Smooth muscle and purinergic contraction of the human, rabbit, rat, and mouse testicular capsule.

The smooth-muscle cells of the testicular capsule (tunica albuginea) of man, rat, and mouse were examined by electron microscopy. They were characteristically flattened, elongated, branching cells and diffusely incorporated into the collagenous matrix and did not form a compact muscle layer. Contractile and synthetic smooth-muscle cell phenotypes were identified. Nerve varicosities in close apposition to smooth muscle were seen in human tissue. Contractions induced by adenosine 5'-triphosphate (ATP), alpha, beta-methylene ATP, noradrenaline (NA), acetylcholine (ACh), and electrical field stimulation (EFS) of autonomic nerves were investigated. Nerve-mediated responses of the rabbit and human tunica albuginea were recorded. The EFS-induced human responses were completely abolished by prazosin. In the rabbit, EFS-induced contractile responses were reduced by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid by 36% and by prazosin by 77%. Both antagonists together almost completely abolished all EFS-induced contractions. The human tunica albuginea was contracted by NA, ATP, and alpha, beta-methylene ATP, but not by ACh. The rabbit and rat tunica albuginea were contracted by NA, ATP, alpha, beta-methylene ATP, and ACh. The mouse tunica albuginea was contracted by ACh, ATP, and alpha, beta-methylene ATP, but relaxed to NA. Immunohistochemical studies showed that P2X1 (also known as P2RX1) and P2X2 (also known as P2RX2) receptors were expressed on the smooth muscle of the rodent testicular capsule, expression being less pronounced in man. The testicular capsule of the rat, mouse, rabbit, and man all contain contractile smooth muscle. ATP, released as a cotransmitter from sympathetic nerves, can stimulate the contraction of rabbit smooth muscle. Human, rat, and mouse testicular smooth muscle demonstrated purinergic responsiveness, probably mediated through the P2X1 and/or P2X2 receptors.