2 Winge K, Skau AM, Stimpel H, Nielsen KK, Werdelin L (2006) Prevalence of bladder dysfunc- tion in Parkinsons disease. Neurourol Urodyn 25:116 \200\22322. 3 Staskin DS, Vardi Y, Siroky MB (1988) Post-prostatectomy continence in the parkinsonian p a- tient: the signi \201 cance of poor voluntary sphincter control. J Urol 140:117 \200 \2238. 4 Roth B, Studer UE, Fowler CJ, Kessler TM (2009) Benign prostatic obstruction and parkinso n \200\231s disease should transurethral resection of the prostate be avoided? J Urol 181: 2209 \200\22313. 5 McGuire EJ, Woodside JR, Borden TA, Weiss RM (1981) Prognostic value of urodynamic test- ing in myelodysplastic patients. J Urol 126:205 \200\2239. 6 Webster GD, el-Mahrouky A, Stone AR, Zakrzewski C (1986) The urological evaluation and ma nagement of patients with myelodysplasia. Br J Urol 58:261 \200\2235. 7 Edelstein RA, Bauer SB, Kelly MD, et al. (1995) The long-term urological response of neo- nates with myelodysplasia treated proactively with intermittent catheterization and antich olinergic therapy. J Urol 154:1500. 8 Wang SC, McGuire EJ, Bloom DA (1988) A bladder pressure management system for myelo- dysp lasia \200\224clinical outcome. J Urol 140: 1499 \200\223502. 9 MacNeily AE, Jafari S, Scott H, Dalgetty A, Afshar K (2009) Health Related Quality of Lif e in Patients With Spina Bi \201 da: A prospective assessment before and after lower urina ry tract recon- struction. J Urol 182:1984 \200\22392. 10 Sakakibara R, Hattori T, Yasuda K, Yamanishi T (1996) Micturitional disturbance after ac ute hemispheric stroke: analysis of the lesion site by CT and MRI. J Neurol Sci 137:47 \200 \22356. 11 Wade D, Hewer RL (1985) Outlook after an acute stroke: urinary incontinence and loss of consciousness compared in 532 patients. Q J Med 56:601 \200\2238. CHAPTER 14 Neuropathic bladder 636 Neuromodulation in neuropathic and non-neuropathic lower urinary tract dysfunction This is the electrical activation of afferent nerve \201 bres to modulate their function. Electrical stimulation applied anywhere in the body preferentially depo- larizes nerves (hi gher current amplitudes are required to directly depolar- ize muscle). In patients with LUT dysfunction, the relevant spinal segments are S2 \200\2234. Indications: urgency, frequenc y, urge incontinence, chronic uri- nary retention where behavioral and drug therapy has fai led. Several sites of stimulation are available, the electrical stimulus being applied directly to nerves or as close as possible: - - SNS Pudendal nerve: vagina, anus, pelvic \202 oor muscles) or via stimulation of dorsal p enile or clitoral nerve (DPN, DCN). Posterior tibial nerve stimulation ( . direct pelvic \202 oor electrical stimulation (of bladder, PTNS).1 PTNS PTN (L4,5; S1 \200\2233) shares common nerve roots with those innervating the bladder. PTNS can be applied transcutaneously (stick-on surface elec- trodes) or percutaneously (ne edle electrodes). Percutaneous needle sys- tems include the SANS (Stoller) and the UrgentPC system. Stimulation is applied via an acupuncture needle inserted just above the medial ma lleolus with a reference (or returns) electrode \200\22430min of stimulation per week, over 12 weeks. Thereafter, 30min of treatment every 2 \200\2233 weeks can be used to maintain t he treatment effect in those who respond. PTNS has not been compared with placebo ( \200 \230sham \200\231 stimulation) and, therefore, reported ef \201 cacy may represent a place bo response. In a single-blinded, placebo- controlled study (gastrocnemius muscle stimulati on without PTNS), 71% of patients receiving PTNS (12 treatments; 3 per week over 4 weeks) r eported >50% reduction in urge incontinence episodes.2 SNS (sacral nerve modulation \200\224SNM) A sacral nerve stimulator (Medtronic Interstim) d elivers continuous electrical pulses to S3 via an electrode inserted through the sacral for amina and connected to an electrical pulse generator which is implanted subcu- taneously. S upported by NICE3 for patients with urge incontinence who have failed lifestyle modi \201 cation and behavior and drug therapy. A test stimulation (the peripheral nerve evaluation, PNE) is performed, under local anesthe tic, by a percutaneous test electrode placed in S3 foramina to con \201 rm an appropriate clinical response (a reduction in urgency, frequency, or incontinence episodes). A permanen t implant is offered if there is a 50% reduction in frequency and urgency. This is placed i n a subcutaneous pocket and is connected to the sacral elec- trode. It can be switched on a nd off and the amplitude varied within set limits. About 50 \200\22360% of patients have a successful PNE. A multicentre study, randomizing non-neuropathic patients with a successful PNE test NEUROMODULATION IN LOWER URINARY TRACT DYSFUNCTION 637 to immediate vs delayed (for 6 months) implantation (the control group), showed signi \201 cantly better symptomatic outcomes in the implant group, 50 \200\22370% reporting resoluti on of their urge incontinence and 80% report- ing >50% reduction in incontinence episodes, persisting for at least 3 \200\2235y.4 Longer term follow-up studies report a durable respo nse.5,6 Numbers of neuropathic patients treated with SNS are too small to draw meaningful c onclusions.5 For non-obstructive urinary retention of those responding to PNE (68 of 177, 38%) and who w ere subsequently implanted, 58% no longer required ISC at 18 months of follow-up,7 results mirrored by others (50 \200\22355% stopping ISC) at a mean of 41 \200\22343 months (70% wit h Fowler \200\231s syndrome stopped ISC).8,9 The exact mechanism of action of SNM in patients with bladder dys- function is not known. 1 Andrews B, Reynard J (2003) Transcutaneous posterior tibial nerve stimulation for the tre at- ment of detrusor hyper-re \202 exia in spinal cord injury. J Urol 170:926. 2 Finazzi-Agro E, Petta F, Sciobica F, Pasqualetti P, Musco S, Bove P (2010) Percutaneous t ibial nerve stimulation effects on detrusor overactivity incontinence are not due to a plac ebo effect: a randomized, double-blind, placebo controlled trial. J Urol 184:2001 \200\2236 . 3 National Institute for Health and Clinical Excellence (2004) Sacral nerve stimulation for urge incontinence and urgency-frequency [online]. Available from: M http://publications.ni ce.org.uk/ sacral-nerve-stimulation-for-urge-incontinence-and-urgency-frequency-ipg64. 4 Schmidt RA, Jonas U, Oleson KA, et al. (1999) Sacral nerve stimulation for treatment of r efractory urinary incontinence. Sacral Nerve Stimulation Study Group. J Urol 162:325 \200 \2237. 5 Bosch JLHR (2010) An update on sacral neuromodulation: where do we stand with this in the management of lower urinary tract dysfunction in 2010. BJU Int 106:1432 \200\22342. 6 Groen J, et al. (2009) Five-year follow-up of sacral nerve neuromodulation in 60 woen wit h idiopathic refractory urge incontinence. Neurourol Urodyn 28:795 \200\2236. 7 retention: results 18 months after implantation. J Urol 165:15 \200\2239. Jonas U, Fowler CJ, Chancellor MB, et al. (2001) Ef \201 cacy of sacral nerve stimulation for urinary 8 Datta SN, Chaliha C, Singh A, et al. (2008) Sacral neuromodulation for urinary retention: 10 year experience from one UK center. BJU Int 101:192 \200\2236. 9 De Ridder D, Ost D, Bruyninckx F (2007) The presence of Fowler \200\231s syndrome predict s suc- cessful long-term outcome of sacral nerve stimulation in women with urinary retentio n. Eur Urol 51:229 \200\22333. This page intentionally left blank 639 Chapter 15 Urological problems in pregnancy Physiological and anatomical changes in the urinary tract 640 Urinary tract infection (UTI) 642 Hydronephrosis of pregnancy 644 CHAPTER 15 Urological problems in pregnancy 640 Physiological and anatomical changes in the urinary tract Upper urinary tract - Renal size enlarges volume and distended renal vasculature, with renal volume increasing up to 30%. Di latation of the collecting systems hydronephrosis and hydroureters (right > left side), whi ch starts in the second month of pregnancy and is maximal by the middle of the second trime ster. It is caused by mechanical obstruction by the growing uterus and ovarian venous plexu s and smooth muscle relaxation due to progesterone. Renal plasma \202 ow ( reaching an in crease of 775% by 16 weeks \200\231 gestation. This is maintained until 34 weeks \200\231 g estation, followed by a decline of 725% towards term. GFR : increases by 50% by the end of the \201 rst trimester, which is maintained until term. GFR has returned to normal levels by 3 months after delivery. Renal function and biochemical parameters changes in RPF and G FR. Creatinine clearance increases and serum levels of creatinine, urea, and urate fall in normal pregnancy due to glomerular hyper \201 ltration (Table 15.1). Raised GFR causes an increased glucose load at the renal tubules and results in glucose excretion (physiological glycosuria of pregnancy which tends to be intermittent). Of note, patients with persistent glycosuria should be screened for diabetes mellitus. Proteinuria is only increased in wome n with pre-existing proteinuria before pregnancy. Urine output is increased. Salt and water handling plasma osmolality. The kidney compensates by increasing renal tubular reabsorptio n of sodium. Plasma renin activity is increased 10-fold and levels of angiotensinogen and a ngiotensin are increased 5-fold. Osmotic thresholds for ADH and thirst decrease. Acid \200 \223base metabolism progesterone stimulates the respiratory center, resulting in reduced PC O2. : by 1cm, secondary to increased interstitial : producing physiological RPF) rate: goes up early in the \201 rst trimester, : are affected by : a reduction in serum sodium causes reduced : serum bicarbonate is reduced. Increased Lower urinary tract - Bladder the enlarging uterus. The bladder becomes hyperaemic and raised estrogen levels cau se hyperplasia of muscle and connective tissues. Bladder pressures can increase over pregna ncy (from 9 to 20cmH2O), with associated rises in absolute and functional urethral length a nd pressures. Haematuria : there is an increased risk of non-visible haematuria due to elev ation of the trigone and increased bladder vascularity. Persistent non-visible haematuria, patients with associated risk factors (i.e. smoking), or visible haematuria will need furth er investigation : displacement occurs (superiorly and anteriorly) due to PHYSIOLOGICAL AND ANATOMICAL CHANGES 641 similar to non-gravid patients. Placenta precreta (placenta invades the bladder) can cause haematuria and should be excluded as a cause. LUTS : urinary frequency (>7 voids during the day) and nocturia ((cid:116)1 void at night) increase over the duration of gestation (inci dence of 80 \200\22390% in third trimester). Urgency is reported in up to 60% and urge inco ntinence may develop in 10 \200\22320%, predominantly in the third trimester. These effects are contributed to by pressure on the bladder from the enlarging uterus, causing reduced f unctional capacity. Nocturia is also exacerbated due to the increased excretion of water (w hilst lying down) that tends to be retained during the day. Normal bladder function returns in the majority soon after delivery. Acute urinary retention occur at 12 \200\22314 weeks \200\231 gestation in association with a retroverted uterus, which resolves by 16 weeks. Fi broids and other uterine anomalies may predispose to retention. Post-partum urinary retenti on occurs in up to 18%, associated with epidural use, assisted or \201 rst delivery, and long duration of labor. Stress urinary incontinence with parity. It is partly caused by the placental production of peptide hormones (relaxin), which induces collagen remodeling and consequent softening of tissues of the birth canal. Infant weight, duration of \201 rst a nd second stages of labor (vaginal delivery), and instrumental delivery (ventouse extractio n or forceps delivery) increase risks of post-partum stress incontinence. : is uncommon during pregnancy, but may : occurs in around 22% and increases Table 15.1 Biochemistry reference intervals Substance Non-pregnant Pregnant Sodium (mmol/L) 135 \200\223145 132 \200\223141 Urea (mmol/L) 2.5 \200\2236.7 2 \200\2234.2 Urate ( mol/L) 150 \200\223390 100 \200\223270 Creatinine ( mol/L) 70 \200\223150 24 \200\22368 Creatinine clearance (mL/min) 90 \200\223110 150 \200\223200 Bicarbonate (mmol/L) 24 \200\22330 20 \200\22325 Parity = pregnancies that resulted in delivery beyond 28 weeks \200\231 gestation; post-par tum = after delivery of the baby; gravid = pregnant. CHAPTER 15 Urological problems in pregnancy 642 Urinary tract infection (UTI) Pregnancy does not alter the incidence of lower UTI. However, physi- ological and anatomical changes associated with pregnancy can alter the course of i nfection, causing an increased risk of recurrent UTI and pro- gression to acute pyelonephri tis. Asymptomatic bacteriuria An asymptomatic lower UTI which affects 5 \200\22310% of pregnant women, with a 20 \200\22340% risk of developing pyelonephritis during pregnancy. This risk is reduced if the bacteriuria is treated and, therefore, urine screening in pregnancy is ad vocated. Symptomatic UTI - Cystitis suprapubic pain, and dysuria. Acute pyelonephritis women, affecting around 1 \200 \2232%. It is most common in the third trimester and is most likely to affect the right sid e. Most are due to undiagnosed or inadequately treated lower UTI. It presents with fever, \202 ank pain, nausea, and vomiting, often with an elevated WCC. : affects 1 \200\2233% and presents with urinary frequency, urgency, : is more frequently seen than in non-pregnant Risk factors for UTI Previous history of recurrent UTIs, pre-existing anatomical or functio nal urinary tract abnormality (i.e. VUR), diabetes. Physiological changes in pregnancy incl ude hydronephrosis with decreased ureteric peristalsis, causing urinary stasis. Up to 75% o f pyelonephritis occurs in the third trimester when these changes are most prominent. Pathogenesis The most common causative organism is E. coli. An increased risk of gesta- tio nal pyelonephritis is associated with E. coli containing the virulence fac- tor \200\230Dr adhesin \200\231. Other common organisms include Klebsiella and Proteus. Complications UTI generally increases the risk of preterm delivery, low fetal birth weight, intrauterine growth retardation, and maternal anemia. Acute pyelone- phritis can be compli cated by progression to septic shock, signs of preterm labor, and adult respiratory distres s syndrome. Screening tests MSU: should be obtained at the \201 rst antenatal visit (week 10) and sen t for urinalysis and culture to look for bacteria, protein, and blood. Repeated MSU investi gation (urine dipstick 9 culture) is recommended at later ante- natal visits to examine for signs of bacteriuria (usually leukocyte esterase and nitrite-positive), protein, and gluco se, particularly in high-risk patients with a history of urinary tract anomalies or recurre nt UTI. (see b p. 177; Table 6.2 for the recommended criteria for diagnosing UTI.) URINARY TRACT INFECTION (UTI) 643 Treatment All proven episodes of UTI should be treated (asymptomatic or sympto- matic), gui ded by urine culture sensitivities for 3 \200\2237 days, with follow-up cultures 1 week lat er and at one other point before delivery. Antibiotics that are safe to use during pregnanc y include penicillins (i.e. ampicil- lin, amoxicillin, penicillin V) and cephalosporins (i. e. cefaclor, cefalexin, cefotaxime, ceftriaxone, cefuroxime) (Table 15.2). Moderate to seve re pyelonephritis or women with pyelonephritis who develop signs of pre- term labor require hospital admission for IV antibiotics (cephalosporin or aminopenicillin) until apyrexial. This is followed by oral antibiotics to complete a total of 10 \200\22314 days of therapy a nd repeated cultures for the duration of pregnancy. Table 15.2 Antibiotics to avoid in pregnancy* Trimester Antibiotic Potential risk to the fetus 1,2,3 Tetracyclines Effects on skeletal development and dental discol-oration (maternal hepatotoxicity) 1,2,3 Quinolones Arthropathy 1,2,3 Chloramphenicol Neonatal \200\230gray \200\231 syndrome in third trimester 1 Trimethoprim Teratogenic risk (folate antagonist) 2,3 Aminoglycosides Auditory or vestibular nerve damage 3 Sulphonamides Neonatal haemolysis; methaemoglobinaemia Avoid at term Nitrofurantoin Neonatal haemolysis See BNF for full details. Of note, antibiotics which undergo excretion by glomerular \201 ltration may need dose adjustment in pregnancy due to increased renal clearance of these d rugs. CHAPTER 15 Urological problems in pregnancy 644 Hydronephrosis of pregnancy Hydronephrosis is dilatation of the renal collecting system (pe lvis and calyces). It can be associated with hydroureters (dilatation of the ureters) and r epresents a normal physiological event in pregnancy which is usu- ally asymptomatic. Hydron ephrosis develops from 6 \200\22310 weeks \200\231 gestation. By 28 weeks \200\231 gestatio n, 90% of pregnant women have hydronephrosis. The inci- dence appears to be higher in \201 rst pregnancies. It usually resolves within 2 months of delivery. Anatomical causes As the uterus enlarges, it rises out of the pelvis and rests upon the ure ters, compressing them at the level of the pelvic brim. In addition, the ureters become elo ngation and mildly tortuous, with lateral displacement due to the gravid uterus. The right ureter is generally more dilated than the left due to extrinsic compression from the overly ing congested right uterine vein and dextrorotation of the gravid uterus. The left ureter t ends to be cushioned from compression by the colon. Ureteric dilatation tends to be from ab ove the pelvic brim. Physiological causes Early onset of upper urinary tract dilatation is attributed to increas ed lev- els of progesterone, which causes smooth muscle relaxation. This mecha- nism, coupl ed with mechanical obstruction, contributes to the reduced peristalsis observed in the coll ecting system during pregnancy. Diagnostic dilemmas The hydronephrosis of pregnancy poses diagnostic dif \201 culties in w omen presenting with \202 ank pain thought to be due to a renal or ureteric calculi (see b p. 488). To avoid using ionizing radiation in pregnant women, renal USS is often used as the initial imaging technique in those presenting with \202 ank pain. In the non-pregnant patient, the presence of hydronephrosis is taken as surrogate evidence of ureteric obstruc tion. Because hydronephrosis is a normal \201 nding in the majority of pregnancies, its p resence cannot be taken as a sign of a possible ureteric stone. USS is an unreliable way of diagnos- ing the presence of stones in pregnant (and in non-pregnant) women. In a series o f pregnant women, USS had a sensitivity of 34% (i.e. it \200\230misses \200\231 66% of sto nes) and a speci \201 city of 86% for detecting an abnormality in the presence of a stone (i.e. false positive rate of 14%).1 Measurement of resistive index (RI)* (derived from meas uring the velocity of intrarenal blood \202 ow using Doppler) improves the sensitivity an d speci \201 city of the diagnosis of ure- teric obstruction, along with attempts to visua lize ureteric jets. Pregnant women with obstruction secondary to stones have a higher diffe rence in RI between affected and unaffected kidneys than women with non- obstructive hydron ephrosis. Color Doppler and transvaginal USS enhance the diagnostic accuracy further. MRU i s a second-line investigation for evaluating painful hydronephrosis in the second and third trimesters. Resistive index (RI) = peak systolic velocity (PSV) minus end-diastolic velocity (EDV) divi ded by peak systolic velocity (PSV) or RI = (PSV \200\223 EDV)/PSV. 1 Stothers L, Lee LM (1992) Renal colic in pregnancy. J Urol 148:1383 \200\2237. 645 Chapter 16 Pediatric urology Embryology: urinary tract 646 Embryology: genital tract 648 Undescended testes (UDT) 650 Ur inary tract infection (UTI) 654 Antenatal hydronephrosis 658 Vesicoureteric re \202 ux (VU R) 662 Megaureter 666 Ectopic ureter 668 Ureterocele 670 Pelviureteric junction (PUJ) obstr uction 672 Posterior urethral valves (PUV) 674 Cystic kidney disease 676 Hypospadias 678 Di sorders of sex development 682 Exstrophy \200\223epispadias complex 688 Primary epispadias 690 Urinary incontinence in children 692 Nocturnal enuresis 694 CHAPTER 16 Pediatric urology 646 Embryology: urinary tract Following fertilization, a blastocyte (sphere of cells) is create d, which implants into the uterine endometrium on day 6. The early embryonic disc of tis- s ue develops a yolk sac and amniotic cavity, from which are derived the ectoderm, endoderm, and mesoderm. Organ formation occurs between 3 and 10 weeks \200\231 gestation. Most of the genitourinary tract is derived from the mesoderm. Upper urinary tract The pronephros (precursor of the kidney; pro = (Gk) before) is derived from an intermediate plate of mesoderm, which functions between weeks 1 \200\2234. It then regresses. The mesonephros (meso = (Gk) middle) functions from weeks 4 \200\2238 and is als o associated with two duct systems \200\224the mes- onephric duct and adjacent to this, the paramesonephric duct (para = (Gk) beside) (Fig. 16.1a). The mesonephric (Wolf \201 an) du cts develop lat- erally and advance downwards to fuse with the cloaca (Latin = sewer), a pa rt of the primitive hindgut. By week 5, ureteric buds grow from the distal part of the meso nephric ducts and by a process of reciprocal induction, they stimulate the formation of the metanephros (permanent kidney; meta = (Gk) after) when they reach the renal tissue. Branch ing of the ureteric bud forms the ureter, renal pelvis, calyces, and collecting ducts. Glom eruli and nephrons (distal convoluted tubules, proximal convoluted tubules, and loop of Hen le) are derived from metanephric mesenchyme (metane- phros). During weeks 6 \200\22310, the caudal end of the fetus grows rapidly and the fetal kidney effectively moves up the poster ior abdominal wall to the lumbar region. Urine production starts at week 10. Thus, in both males and females, the mesonephric duct forms the ure- ters and renal collect ing system. The paramesonephric duct essentially forms the female genital system (Fallopian tubes, uterus, upper vagina); in males, it regresses. The mesonephric ducts also form the male genital duct sys- tem (epididymis, vas deferens, seminal vesicles) and central zone of the prostate; in females, it regresses (see b p. 648). Lower urinary tract Bladder The mesonephric ducts and ureters drain into the cloaca. During weeks 4 \200\2236, the cloaca is subdivided into the urogenital canal or sinus (anteriorly ) and the anorectal canal (posteriorly) by a process of growth, differentia- tion, and remo deling (Fig. 16.1b).1 The bladder is formed by the upper part of the urogenital canal. Blad der smooth muscle (detrusor) is devel- oped from adjacent pelvic mesenchyme. The trigone de velops separately, arising from a segment of the mesonephric duct. The bladder dome is init ially connected to the allantois, but this connection later regresses to become a \201 br ous cord (urachus). EMBRYOLOGY: URINARY TRACT 647 Urethra The inferior portion of the urogenital canal forms the entire urethra in females an d the posterior urethra in males. Closure of the urogenital groove creates the male anterio r urethra. The mesonephric ducts sepa- rate from the ureters (Fig. 16.1c) and travel caudal ly to join the posterior urethra in males (where they differentiate into the male genital d uct sys- tem at 8 \200\22312 weeks). 5 keeW 8 \200\2236 keeW (Pronephros) Mesonephros Gonad (Mesonephros) Paramesonephric duct Metanephros Mesonephric duct Metanephros Mesonephric duct Ureteric bud Ureter (a) Cloaca Weeks 4 \200\2236 Allantois Urorectal canal Bladder Urogenital canal Anorectal canal Cloacal membrane Urogenital membrane (b) Anal membrane Urogenital canal Trigone Mesonephric duct Ureteric bud Ureter Ejaculatory duct Ureter (c) Fig. 16.1 (a) Development of the upper urinary tract; (b) Development of the lower urinary tract (bladder); (c) Development of the distal ureters and mesonephric ducts. 1 Penington EC, Hutson JM (2003) The absence of lateral fusion in cloacal partition. J Paed iatr Surg 38:1287 \200\22395. CHAPTER 16 Pediatric urology 648 Embryology: genital tract Sexual differentiation and gonadal development is determined by t he sex chromosomes (XY, male; XX, female). The gonads produce hormones which in \202 uence the subsequent differentiation of internal and external genitalia. Both sexes Gonads develop from the genital ridges (formed by cells of the mesoneph- ros and coelomic epithelium). At 5 \200\2236 weeks, primordial germ cells migrate from the yolk sa c to populate the genital ridges. Primitive sex cords are formed, which support germ cell ( sperm and ova) development. From 4 weeks, the mesonephric (Wolf \201 an) ducts are incorporated into the genital syste m when renal function is taken over by the de \201 nitive kidney. At 6 weeks, coelomic epi thelium creates the paramesonephric (M llerian) ducts which develop laterally and are fuse d to the urogenital sinus at their bases. Males Embryos are genetically programmed to be female unless the testis- determining gene ( SRY) is present, in which case the embryo will dif- ferentiate into a male. The SRY gene is located on the Y chromosome. It stimulates medullary sex cords in the primitive testis to differentiate into Sertoli cells which produce M llerian inhibiting substance (MIS) at 7 \200\2238 weeks. The sex cords differentiate into seminiferous cords, which later form the seminiferous tubules of the testis within which the primordial germ cells differentiate int o spermatogonia. MIS triggers regression of the paramesonephric ducts, testosterone secreti on from Leydig cells of the testis, and the initial phase of testicular (abdominal) descent . The androgens testosterone and dihydrotestosterone (DHT) are responsible for masculinizat ion of the fetus. During weeks 8 \200\22312, the mesonephric ducts differentiate into the epidi- dymis, vas d eferens, seminal vesicles, and ejaculatory ducts. Under the in \202 uence of DHT, prolifer ation and budding of the urethral endoderm gives rise to prostatic acini and glands and by a process of reciprocal induc- tion, forms the prostatic capsule and smooth muscle from the surrounding mesenchyme (completed by week 15). After week 23, the second androgen-dependent phase of testicular descent occurs. The testes rapidly descend from the abdomen (via the inguinal canal during weeks 24 \200\22328) and i nto the scrotal sac, aided by cal- citonin gene-related polypeptide acting on the gubernacu lum. The testis is enclosed in a diverticulum of peritoneum called the processus vaginalis. The distal part persists as the tunica vaginalis around the testis, the remain- der usuall y regresses. External genitalia develop from week 7. Urogenital folds form around the opening of the uro genital sinus and labioscrotal swellings develop on either side. The penile shaft and glans are formed by elongation of the genital tubercle and fusion of urogenital folds. The scrot um is created by fusion of labioscrotal folds. EMBRYOLOGY: GENITAL TRACT 649 Females (Figs. 16.2 and 16.3) The genital ridge forms secondary sex cords (primitive sex co rds degener- ate) which surround the germ cells to create ovarian follicles (week 15). Thes e undergo meiotic division to become primary oocytes which are later activated to complete gametogenesis at puberty. Estrogen is pro- duced from week 8 under the in \202 uence of th e aromatase enzyme. In the absence of MIS, the mesonephric ducts regress and the paramesone - phric ducts become the Fallopian tubes, uterus, and upper two-thirds of the vagina. The s inovaginal sinus is developed at the junction of the para- mesonephric ducts and the urogen ital sinus. This forms the lower third of the vagina. The genital tubercle forms the clitoris; the urogenital folds become the labia minora and the labioscrotal swellings form the labia majora. Genital tubercle Urogenital fold Urogenital membrane Labioscrotal swelling Anal membrane Clitoris Glans Genital tubercle Penile shaft Labia minora Urogenital sinus Urethra Labia majora Scrotum Labioscrotal swelling Fig. 16.2 Differentiation of external genitalia (weeks 7 \200\22316). Mesonephros Testis Ovary Fallopian tube Mesonephric duct Paramesonephric ducts Mesonephric duct Paramesonephric duct Fig. 16.3 Differentiation of the genital tract. CHAPTER 16 Pediatric urology 650 Undescended testes (UDT) The \201 rst phase of testicular descent from the genital ridge to internal inguinal ring occurs under the in \202 uence of MIS acting on the gubernaculum (around 7 \200\2238 weeks \200\231 gestation). The second phase of testicular descent thro ugh the inguinal canal into the scrotum occurs at 24 \200\22328 weeks \200\231 ges- tation under the in \202 uence of testosterone. Failure of descent results in cryptorchidism or c ongenital UDT. Incidence Four percent at birth for a full-term neonate, however, many will spontane- ously descend after birth and the incidence at 1y is 1.3 \200\2231.8%. The incidence of unilater al UDT is greater than bilateral UDT. Classi \201 cation - Retractile to retract up and out of the scrotum. Ectopic (<5%) the in guinal canal (to perineum, base of penis, or femoral areas) (Fig. 16.4). Incomplete descent ( inguinal, or pre-scrotal (Fig. 16.4). Atrophic/absent . Acquired UDT (or testicular asce nt): testes that were down in the scrotum have ascended. Risk higher with retractile testes and a patent processus vaginalis. It occurs around 7 \200\2239y old and the incidence is 1 \200\2232%.1 Approximately 20% will fail to return to the scrotum by puberty. Orchidopexy is recommended as the \200\230ascended \200\231 testis is at the same risk of degenerative changes as congenital UDT. : an intermittent active cremasteric re \202 ex causes the testis : abnormal testis migration below the external ring of 795%): testis may be intra-abdominal, intra- Risk factors - - - - Preterm infants (incidence at <30 weeks \200\231 gestation is 40%). Low birthweight or smal l for gestational age. Twins. Family history of UDT. Etiology - Abnormal testis or gubernaculum (tissue that guides the testis into the scrotum during deve lopment). Endocrine abnormalities: low level of androgens, gene-related peptide, or MIS. De creased intra-abdominal pressure (prune belly syndrome, gastroschisis). HCG, LH, calcitonin Pathology UDT demonstrate the degeneration of Sertoli cells, loss of Leydig cells, atrophy, and abnormal spermatogenesis. Male fertility depends on the transformation of gonocytes to dark adult spermatocytes within the \201 rst 3 months of post-natal life. This appears t o be defective in UDT. UNDESCENDED TESTES (UDT) 651 Long-term complications - UDT. There is a 4% lifelong Relative risk of cancer is 8-fold higher in risk of cancer with an intra-abdominal testis. Majority are seminomas. There is a slightly increased risk of c ancer in the contralateral, normally descended testis. Reduced fertility (paternity rate in unilateral UDT is 80 \200\22390% and in bilateral UDT is 45 \200\22365%). Paternity rates improve if orchidopexy is performed before 2y of age. Increased risk of testicular torsion or trauma. Increased risk of indirect inguinal hernias vaginalis). (due to a patent processus Evaluation Examine the scrotum and inguinal region to elucidate if a testis is palpable and to identify its location. Retractile testes may be brought back down into the bottom of th e scrotum without tension. Assess for associated congenital defects. If neither testis is p alpable, consider chromosome analysis (to exclude an androgenized female) and endocrine ana lysis (high LH and FSH with a low testosterone indicates anorchia, con \201 rmed with seru m inhibin B). For the impalpable testis, USS is of limited use. Most proceed directly to ex amination under anesthetic diagnostic laparos- copy and treatment. Treatment - Inguinal old. Surgery consists of inguinal exploration, mobilization of spermat ic cord, ligation of processus vaginalis, and securing the testis into a dartos pouch in th e scrotal wall. Risks include testicular atrophy (5%), damage to vas (1 \200\2232%), and re -ascent of the testis. Intra-abdominal testes the testis for orchidopexy as a single or 2-s tage (Fowler \200\223Stephens) procedure. The Fowler \200\223Stephens approach involves ini tial clipping or division of spermatic vessels to provide extra length (the testis then rel ies on collateral blood \202 ow from the vas). Six months later, the testis is then mobil ized on its vas with its new collateral vessels and brought down into the scrotum. Success rates are 785%. Intra-abdominal testes with a short vas may need microvascular autotranspla ntation. This involves high intra-abdominal ligation of the spermatic vessels, the testis i s brought down into the scrotum, and the vessels are re-anastomosed to the inferior epigast ric vessels. Small, atrophic intra-abdominal testes (nubbin) require orchidectomy 9 orchido pexy of the contralateral normally descended testis. UDT: is treated with orchidopexy between 6 \200\22318 months : require a laparoscopic approach to mobilize Overall success rates of orchidopexy vary according to position of the UDT: 92% for inguina l testes, 87% for canalicular testes, and 74% for abdominal testes.3 CHAPTER 16 Pediatric urology 652 Deep inguinal ring Superficial inguinal ring Superficial inguinal pouch Pubic Pubic symphysis Femoral Perineal Normal (a) Abdominal Canalicular Emergent Normal (b) Fig. 16.4 (a) Ectopic sites for the undescended testis; (b) Incomplete descent of the testi s (Reproduced with permission from Taylor & Francis Books, UK). 1 Hack WW, Sijstermans K, van Dijk J, et al. (2007) Prevalence of acquired undescended test is in 6-year, 9-year and 13-year-old Dutch schoolboys. Arch Dis Child;92:17 \200\22320. 2 Brewster S, Cranston D, Noble J, Reynard J (2001) Urology a Handbook for Students. BIOS S cienti \201 c Publishers Limited. 3 Docimo SG (1995) The results of surgery for cryptorchidism: a literature review and analy sis. J Urol 154:1148 \200\22352. This page intentionally left blank CHAPTER 16 Pediatric urology 654 Urinary tract infection (UTI) De \201 nitions: UTI is a bacterial infection of the urine, which may involve the lower ur inary tract/bladder (cystitis) or upper urinary tract/kidney (pyelonephritis) (see b p. 176 ). Classi \201 cation: children may be asymptomatic or symptomatic. Simple UTI: presents with mild dehydration and pyrexia. Severe UTI: presents as fever \211 38 C, unwell, vomiting, with moderate to severe dehydration. Atypical UTI: includes features of serious illness/septicaemia, poor urinary \202 ow, abn ormal renal function, failure to respond to treatment in <48h, and non-E. coli infection. Recurrent UTI: in children, describes either one episode of cystitis with one episode of py elonephritis, \211 2 episodes of pyelonephritis, or \211 3 epi- sodes of cystitis. It may be due to bacterial persistence, unresolved infec- tion, or re-infection. Incidence: up to age 1, the incidence in boys is higher than girls (male: female ratio is 3 :1), but thereafter, the incidence in girls becomes greater (school age males 1%; females 3 %). Pathology: common bacterial pathogens are E. coli, Enterococcus, Pseudomonas, Klebsiella, P roteus, and S. epidermidis. Bacteria enter via the urethra to cause cystitis and ascending infection causes pyelonephritis. Alternatively, there can be haematogenous spread from othe r systemic infections. Risk factors - Age periurethral area and an immature immune system. VUR Previous Genitourinary abnormaliti es ureterocele, posterior urethral valves, labial adhesions. Voiding dysfunction emptying. Gender Foreskin \201 rst year due to bacterial colonization of the glans and foreskin. Fe cal colonization . Chronic constipation : neonates and infants have increased bacterial colonization of the - (see b p. 662). UTI. : pelvi- or vesicoureteric obstruction, : abnormal bladder activity, compliance or : female > male after 1y old. : uncircumcised boys have a 10-fold higher risk of UTI in the : contributes to perineal bacterial colonization. Presentation - Neonates and infants: poor feeding, failure to thrive, abdominal pain, offensive urine, hae maturia. Children: dif \201 culties, changes to continence, abdominal or \202 ank pain, haematuria. fever, irritability, vomiting, lethargy, diarrhea, fever, nausea, suprapubic pain, dysuria, frequency, voiding URINARY TRACT INFECTION (UTI) 655 Investigation Urine analysis and culture: advised with unexplained fever \211 38 C or if symptomatic of UTI. Clean catch specimen where possible. In toilet- trained children, an MS U specimen is considered diagnostic with \211 105 colony-forming units (CFU)/mL in asympto matic children and \211 104CFU/ mL if symptomatic. In young children, a catheterized urine specimen with \211 10CFU/mL) of one pathogen or a suprapubic aspirate with \211 102CFU/m L are diagnostic of UTI. Collection bag specimens are less reliable due to skin \202 ora contamination. Imaging: refer to NICE recommendations (Tables 16.1 \200\22316.3).1 - USS abnormalities (hydronephrosis, stones). DMSA MCUG functional), VUR, and ureteroceles. is the \201 rst-line investigation. It identi \201 es bladder and kidney renogram can demonstrate and monitor renal scarring. detects urethral and bladder anomalies (anatomical and Management Infants <3 months (and children at risk of serious illness): are managed accordi ng to the \200\230feverish illness in children \200\231 guidelines.2 For children aged 3 m onths to 3y, antibiotics are recommended (before urine culture results are available) for s peci \201 c symptoms of UTI and for non-speci \201 c symptoms where the risk of intermedi ate to serious infection is high (i.e. associated anatomical or functional abnormality).2 I n children older than 3y, antibiot- ics are indicated if urine dipstick analysis is positiv e for nitrites 9 leukocyte esterase or if there is good clinical evidence of UTI. Infants < 3 months: pediatric referral and treat with IV antibiotic such as third-generation cephalos porin (cefotaxime or ceftriaxone).2 Infants and children >3 months with pyelonephritis: ped iatric referral; 7 \200\22310 days of oral cephalosporin or co-amoxiclav or IV cefotaxime o r cefri- axone for 2 \200\2234 days followed by oral antibiotics for a total of 10 days. In fants and children >3 months with cystitis: oral antibiotics for 3 days (trimethoprim, nitr ofurantoin, cephalosporin, or amoxicillin), and reas- sess. The choice of antibiotics shoul d be directed by local hospital guidelines. Asymptomatic bacteriuria does not require antibiotics or routine follow-up. Antibiotic prop hylaxis is not recommended following a \201 rst- time simple UTI, but can be considered a fter recurrent symptomatic UTI.3 Advice on preventing UTI should be given, including good i ntake of \202 uids, regular voiding, and treatment of constipation.