PROGNOSTIC STAGING SYSTEM FOR METASTATIC GCT 389 Table 7.30 IGCCCG prognostic factor-based staging system for metastatic germ cell cancer* Prognostic Group Seminoma NSGCT Good 90% of patients 56% of patients 5y progression-free survival (%) 86 92 All factors listed present Any primary site; Testis or retroperitoneal primary site; no non-pulmonary visceral metastases; no non-pulmonary visceral metastases; normal AFP; AFP <1000ng/mL; any hCG or LDH HCG <5000mIU/L; and LDH <1.5 times normal upper limit (S1) Intermediate 10% of patients 28% of patients 5y progression-free survival (%) 73 80 All factors listed present Any primary site; Testis or retroperitoneal primary site; non-pulmonary visceral metastases present; no non-pulmonary visceral metastases; normal AFP; AFP 1000 \200\2239999ng/Ml; or any hCG or LDH HCG 5000 \200\22349 999mIU/L; LDH 1.5 \200\22310 times normal upper limit (S2) Poor 16% of patients 5y progression-free survival (%) No patients classi \201 ed as poor prognosis 48 All factors listed present Mediastinal primary; non-pulmonary visceral metastases present; AFP >10 000ng/mL or HCG >50 000mIU/L; LDH >10 times normal upper limit (S3) International Germ Cell Cancer Collaborative Group (IGCCCG) (1997) International Germ Cell Consensus Classi \201 cation: a prognostic factor-based staging system for metastatic germ cell cancers. J Clin Oncol 15 (2): 594 \200\223603. CHAPTER 7 Urological neoplasia 390 Testicular cancer: management of non-seminomatous germ cell tumors (NSGCT) Following radica l orchidectomy and formal staging, the patient is normally managed by the oncologist, thoug h the urological surgeon may perform retroperitoneal lymph node dissection (RPLND) in selec ted cases based on multidisciplinary team discussion. In the presence of elevated AFP, a se minoma would be managed as for teratoma. Combination chemother- apy introduced in the 1970 \200\231s revolutionized the treatment of metastatic testicular teratoma which was hitherto virtually untreatable. Treatment and follow-up varies between the UK and USA. In the UK, it depends largely on the IGCCCG prognostic staging (see b p. 388), as follows. Localized disease pT1-4N0M0S0 (often referred to as stage I) Surveillance results in 30% re lapse rate, mostly <1y post-orchidectomy. Salvage chemotherapy produces excellent responses , with disease-specif- ic survival >99%. Hence, a risk-adapted management is recommended to minimize the risk of toxicity: - Surveillance for pT1 disease without vascular invasion (only 15% relapse). x 2 cycles for t hose unwilling or unsuitable Adjuvant chemotherapy for surveillance, for pT1 disease with v ascular invasion, or for pT2 \200\2234 disease. Metastatic disease - x 3 Good prognosis: chemotherapy (bleomycin, etoposide, cisplatin cycles); RPLND for residual o r recurrent mass; salvage chemotherapy for relapse. Intermediate and poor prognosis: chemot herapy (bleomycin, etoposide, cisplatin x 4 cycles); RPLND for residual or recurrent mass; occasionally, salvage chemotherapy or radiotherapy if histology con \201 rms tumor; salvag e high-dose chemotherapy with autologous stem cells for relapse. Surveillance and follow-up after treatment Surveillance requires the following: - Year 1: CT \200\224months 3 and 12. Year 2: abdominal CT \200\224month 24. Years 3, 4, and 5: X-ray. Annual clinic visit, serum markers, and chest X-ray thereafter to 10y. monthly clinic visit, serum markers and chest X-ray, abdominal 2-monthly clinic visit with serum markers and chest X-ray, 3-monthly clinic visit, serum markers, and chest MANAGEMENT OF NSGCT 391 Follow-up after treatment is slightly less intensive, also to 10y. The risk of relapse is h ighest in the \201 rst 2y. RPLND - Retroperitoneal lymphadenopathy is usually the \201 rst and only evidence of extragonadal metastasis of NSGCT. In the post-chemotherapy. RPLND aortic nodes up to the origin of the superior mesenteric artery and down to the iliac bifurcation. Complications: pancreatitis, ileus, and ejaculatory failure. Modi \201 ed techniques reduce the risk of ejaculatory dis turbance by taking nodes on the unaffected side only down to the inferior mesenteric artery . In the following radical orchidectomy. UK, RPLND is used only to remove or debulk residual mass may remove viable tumor in 10 \200\22330% of patients, taking para- 1% mortality and 25% morbidity includes lymphocele, USA, RPLND remains the gold standard staging investigation CHAPTER 7 Urological neoplasia 392 Testicular cancer: management of seminoma, IGCN, and lymphoma Of all seminomas, 75% are con \201 ned to the testis at presentation and are cured by radical orchidectomy; 10 \200\223 15% of patients harbor regional node metastasis while 5 \200\22310% have more advanced dise ase. Following radical orchidectomy and formal staging, the patient is man- aged by the oncologi st. Treatment and follow-up depends largely on dis- ease stage according to presence of met astases and size of nodal disease as in Table 7.31. Table 7.31 Treatment and follow-up Non-metastatic disease T1N0M0S0 \200\2231 Risk of subsequent para-aortic node relapse is 20%. Adjuvant treatment reduces the risk of recurrence to <1%. Standard treatment for stage 1 disease is either surveillance or single agent carboplatin (some centers use this for those patients with tumors >4cm and/or rete te stis involvement. A randomized MRC study compared one cycle of carboplatin with radiotherap y (RT; results suggested equivalence. If RT is used, 20Gy is delivered in 10 fractions, inc luding para-aortic nodes. Spermatocytic subtype usually warrants surveillance. Metastatic disease T1 \200\2233 N1 M0S0 \200\2231 RT T1 \200\2233 N2 M0 S0 \200\2231 RT; chemotherapy if nodes near kidneys T1 \200\2234 N3 M0 S0 \200\2231 Chemotherapy (either bleomycin, etoposide and cisplatin or etoposide and cisplatin); if res idual node mass >3cm (rare), retroperitoneal lymph node dissection (RPLND) considered altho ugh not usually necessary or performed with pure seminomas T1 \200\2234N0 \200\2233M1 \200\2232S0 \200\2233 Chemotherapy with etoposide and cisplatin 9 bleomycin; if residual node mass (rare), RPLND considered although not usually necessary or performed with pure seminomas Patients should also be classi \201 ed into prognostic grouping classi \201 ca- tion (IGC CCG; see b p. 388) as this provides an overall prognosis for patients. These patients requi re careful long-term follow-up, according to national guidance. MANAGEMENT OF SEMINOMA, IGCN, AND LYMPHOMA 393 Management of intratubular germ cell neoplasia - Observation or orchidectomy for unilateral disease. - Radiotherapy for unilateral disease in the presence of a contralateral tumor. R adiotherapy for bilateral disease to preserve Sertoli cells. Systemic chemotherapy (e.g. ci splatin) controversial, not currently adopted in UK. Sperm storage must be offered. Management of testicular lymphoma This may be a primary disease or a manifestation of disse minated nodal lymphoma. The median age of incidence is 60y, but has been reported in childr en. Twenty- \201 ve percent of patients present with systemic symptoms, 10% have bilateral testicular tumors. These patients have a poorer prog- nosis following radical orchidectomy and chemotherapy, while those with localized disease may enjoy long-term survival. This page intentionally left blank 395 Chapter 8 Miscellaneous urological diseases of the kidney Simple and complex renal cysts 396 Calyceal diverticulum 399 Medullary sponge kidney (MSK) 400 Acquired renal cystic disease (ARCD) 402 Autosomal dominant polycystic kidney disease ( ADPKD) 404 Vesicoureteric re \202 ux in adults 408 Pelviureteric junction obstruction in a dults 412 Anomalies of renal fusion and ascent: horseshoe kidney, ectopic kidney 416 Anomalies of renal number and rotation: renal agenesis and malrotation 420 Upper urinary tract duplication 422 CHAPTER 8 Miscellaneous urological diseases 396 Simple and complex renal cysts Simple renal cysts: do not communicate with any part of the nephron or the renal pelvis. They are mainly con \201 ned to the renal cortex, are \201 lled with clear \202 uid, and contain a membrane composed of a single layer of \202 att ened or cuboidal epithelium. They can be single or multiple, ranging from a few millimeters to several centimeters in diameter. They can be unilateral or bilateral and often affect t he lower pole of the kidney. Parapelvic cysts: describe simple parenchymal cysts located adjacent to the renal pelvis or hilum. Prevalence Increases with age, the precise prevalence depending on the method of diagnosis. On CT, 20% of adults have renal cysts by age 40y and 33% by the age of 60.1 At post-mortem , 50% of subjects aged >50y have simple cysts. Cysts do not usually increase in size with a ge, but may increase in number. Males and females are affected equally. Etiology Both congenital and acquired causes have been suggested. Chronic dialysis is assoc iated with the formation of new simple cysts. Presentation Simple cysts are most commonly diagnosed as an incidental \201 nding followi ng a renal ultrasound scan (USS) or CT performed for other pur- poses. The majority are asy mptomatic; however, very large cysts may present as an abdominal mass or cause dull \202 ank or back pain. Acute severe loin pain may follow bleeding into a cyst (causing sudden di sten- sion of the wall). Rupture (spontaneous or following renal trauma) is rare. Rupture i nto the pelvicalyceal system can produce haematuria. Infected cysts (rare) present with \202 ank pain and fever. Very occasionally, large cysts can cause obstruction and hydroneph rosis. Differential diagnosis - - Renal cell carcinoma (4 \200\2237% of Early autosomal dominant polycystic kidney disease ( multiple or bilateral cysts, associated with hepatic cysts. Complex renal cysts (i.e. those which contain blood, pus or calci \201 cation). RCC are cystic). ADPKD \200\224diffuse, Investigation Renal USS Simple cysts are round or spherical, have a smooth and distinct out line, and are \200\230anechoic \200\231 (no echoes within the cyst, i.e. sound waves are t rans- mitted through the cyst). USS using microbubble contrast agents can im- prove diagnos tic accuracy. Evidence of calci \201 cation, septation, irregular margins or clusters of c ysts requires further investigation (renal triphasic CT). In the absence of these features, no further investigation is required. SIMPLE AND COMPLEX RENAL CYSTS 397 CT Simple cysts are seen as round, smooth-walled lesions with homogenous \202 uid in the cavity (with a typical density of \200\22310 to +20 Houns \201 eld units) and with no enh ancement after contrast (enhancement implies that it contains vascular tissue or communicat es with the collecting system, i.e. that it is not a simple cyst). Hyperdense cysts have a density of +20 \200\22390 Houns \201 eld units, do not enhance with contrast media, and ar e <3cm in diameter. Biopsy Image-guided cyst aspiration or biopsy can be used to help diagnose inde- terminate cysts and prevent unnecessary surgery. Treatment A simple cyst (type I: round or spherical, smooth wall, distinct outline, and no internal echoes) requires no further investigation, no treatment, and no follow-up. In the rare situation where the cyst is thought to be the cause of symptoms (e.g. back or \202 a nk pain), treatment options include percuta- neous aspiration 9 injection of sclerosing age nt or open or laparoscopic surgical excision of the cyst wall. In the rare event of cyst in fection, percu- taneous drainage and antibiotics are indicated. Cysts with features on USS suggesting possible malignancy (calci \201 cation, septation, i rregular margins) should be investigated by CT with contrast. 1 Laucks SP Jr, McLachlan MS (1981) Aging and simple cysts of the kidney. Br J Radiol 54:12 \200\2234. 2 Warren KS, McFarlane J (2005) The Bosniak classi \201 cation of renal cystic masses. BJU Int 95: 939 \200\22342. CHAPTER 8 Miscellaneous urological diseases 398 Table 8.1 Bosniak \200\231s classi \201 cation of CT appearance of simple and complex cyst s Type Description Approx. % of such cysts which are malignant2 Treatment <2% None; no follow-up required I Simple benign cyst with smooth margins, no contrast enhancement, no septation, no calci \201 cation II Benign cyst with smooth margins; few thin septae; minimal calci \201 cation; no contrast e nhancement; <3cm Observation \200\224 repeat USS looking for increase in size or development of malignant fe atures* IIF Increased number of thin septae; thickening and/ or minimal enhancement of septae; may cont ain calcium, but no enhancement. Includes non-enhancing, high- attenuation >3cm cysts 19% Follow-up with USS (or CT). Type IIF cysts have greater malignant potential than type II cy sts (II and IIF combined) III Irregular margins; moderate calci \201 cation; thick septation (septae >1mm thick); enhanc ement 33% Surgical exploration partial nephrectomy IV Cystic malignant lesion; irregular margins and/or solid enhancing elements 93% Radical nephrectomy Bosniak suggested follow-up scans at 6 months and 1y. If the lesion remained stable after t his time, it is considered benign. CALYCEAL DIVERTICULUM 399 Calyceal diverticulum A calyceal diverticulum is a spherical outpouching of the renal colle cting system (speci \201 cally from a calyx) which protrudes into the corticome- dullary r egion of the kidney. It communicates with the renal calyx via a narrow neck or channel. It is lined by a transitional cell epithelium and is covered by a thin layer of renal cortex. They range in size from only a few millimeters to many centimeters in size. Etiology The exact etiology of calyceal diverticula is unknown. Some may be con- genital. A cquired calyceal diverticula can develop after obstruction of a calyceal infundibulum or fo llowing blunt renal trauma. Presentation They are usually asymptomatic and are discovered incidentally on an IVU, most commonly seen in upper pole calyces. Symptoms may result from the development of a stone or infection within the diverticulum, presum- ably caused by urinary stasis. Investigation On IVU, a calyceal diverticulum appears as a rounded collection of con- trast medium next to a papilla, although often, the connecting channel is too narrow to be clear ly seen. They can be identi \201 ed on CT, MRI, and USS; however, the distinction between a renal cyst and an obstructed ca- lyx may be dif \201 cult on unenhanced images. Treatment Stones that form within the calyceal diverticulum may be treated by \202 exi- b le ureteroscopy and laser lithotripsy or, if large, by percutaneous nephro- lithotomy (PCNL ) if percutaneous access is possible. Endoscopic dilatation or incision of the neck of the diverticulum may be attempted at the time of stone surgery to prevent recurrence and this t echnique can also be employed if the diverticulum is thought to be the cause of recurrent u ri- nary infection. Open surgery has also been used to remove stones and to de-roof calycea l diverticula. Extracorporeal shock wave lithotripty (ESWL) therapy is not helpful. ESWL ma y result in stone fragmentation, but it may be dif \201 cult for the stone fragments to ge t out of the diverticulum and they may simply reform into a larger stone. CHAPTER 8 Miscellaneous urological diseases 400 Medullary sponge kidney (MSK) De \201 nition A congenital cystic disorder of the kidneys c haracterized by dilatation of the distal collecting ducts associated with the formation of multiple cysts and diverticula within the medulla of the kidney. Prevalence Dif \201 cult to know as it may be asymptomatic (diagnosed on an IVU per- forme d for other reason or at post-mortem). Estimated to affect between 1 in 5000 to 1 in 20 000 people in the general population; 1 in 200 in those undergoing IVU (a select population). In 75% of cases, both kidneys are affected. Pathology The renal medulla resembles a sponge in cross section due to dilated collecting d ucts in the renal papillae and the development of numerous small cysts. This is associated with urinary stasis and the formation of small calculi within the cysts. Some report a fami lial inheritance. It can be associ- ated with other congenital or inherited disorders, incl uding hemihypertro- phy and Beckwith \200\223Wiedemann syndrome*. Presentation The majority of patients are asymptomatic. When symptoms do occur, they includ e ureteric colic, renal stone disease (calcium oxalate 9 calcium phosphate), UTI, and haema turia (microscopic or macroscopic). Up to 50% have hypercalciuria due to renal calcium leak or increased gastroin- testinal calcium absorption. Renal function is normal unless obstru ction occurs (secondary to renal pelvis or ureteric stones). Differential diagnosis Other causes of nephrocalcinosis (deposition of calcium in the renal me- dulla, e.g. TB, hyperparathyroidism, healed papillary necrosis, multiple my- eloma). Investigation - dipstick 9 culture. Check for UTI and treat Midstream urine: according to sensitivities. Biochemistry: 24h urinary calcium may be eleva ted (hypercalciuria). Detection of hypercalciuria requires further investigation to exclude other causes (i.e. raised serum parathyroid hormone (PTH) levels indicate hyperparathyroid ism). Imaging: and USS may also be used. The characteristic radiological features of MSK, a s seen on IVU, are enlarged kidneys associated with dilatation of the distal portion of the collecting ducts, along with numerous associated cysts and diverticula (the dilated ducts are said to give the appearance of \200\230bristles on a brush \200\231). The collecting d ucts may become \201 lled with calci \201 cations, giving an appearance described as a \200\230bouquet of \202 owers \200\231 or \200\230bunches of grapes \200\231 (Fig. 8.1). IVU is the principle method for diagnosing MSK, although CT MEDULLARY SPONGE KIDNEY (MSK) 401 Treatment Asymptomatic MSK disease requires no treatment. General measures to reduce urine calcium levels help reduce the chance of calcium stone for- mation (high \202 uid intake, vegetarian diet, low salt intake, consumption of fruit and citrus fruit juices). Thiazide diuretics may be required for hyper- calciuria resistant to dietary measures and are design ed to lower urine calcium concentration. Intrarenal calculi are often small and as such, ma y not require treatment, but if indicated, this can take the form of ESWL or \202 exible ureteroscopy and laser treatment. Ureteric stones are again usually small and will, therefo re, pass spontaneously in many cases with a period of observation. Recurrent UTI may need p rophylactic antibiotics. Renal function tends to remain stable in the long term. Rarely, re current infection and nephrocalcinosis may lead to the complication of renal im- pairment. Fig. 8.1 IVU demonstrating bilateral medullary sponge kidneys. Beckwith \200\223Wiedemann syndrome: a growth disorder characterized by macroglossia, macro so- mia, visceromegaly, Wilm \200\231s tumor, neuroblastoma, omphalocele, and renal anomali es. CHAPTER 8 Miscellaneous urological diseases 402 Acquired renal cystic disease (ARCD) A cystic degenerative disease of the kidney with (cid: 116)5 cysts visualized on CT scan. By de \201 nition, this is an acquired condition, as op posed to ADPKD which is inherited (in an autosomal dominant fashion). It is predominantly a ssociated with chronic and end-stage renal failure and as such, is com- monly found in pati ents undergoing haemodialysis or peritoneal dialysis. Over one third of patients develop AR CD after 3y of dialysis. Clinically important because it may cause pain and haematuria and is associated with the development of benign and malignant renal tumors. The male to female ratio is 3:1. Pathology Usually multiple, bilateral cysts found mainly within the cortex of small, contra cted kidneys. Cysts vary in size (average 0.5 \200\2231cm) and are \201 lled with a clear \202 uid which may contain oxalate crystals. They usually have cuboidal or columnar epit helial linings and are in continuity with renal tubules (and, therefore, cannot be de \201 ned as simple cysts). Atypical cysts have a hyperplastic lining of epithelial cells, which may represent a precur- sor for tumor formation. Renal transplantation can cause regressio n of cysts in the native kidneys. Etiology The exact pathogenesis is unknown, but several theories have been pro- posed. Obst ruction or ischaemia of renal tubules may induce cyst forma- tion. Renal failure may predis pose to the accumulation of toxic endoge- nous substances or metabolites, alter the release of growth factors, and result in changes in sex steroid production or cause cell prolifera tion (sec- ondary to immunosuppressive effects) which result in cyst formation. Associated disorders There is an increased risk of benign and malignant renal tumors. The c hance of developing RCC is 720%, 3 \200\2236 times greater than the general population (mal es > females). When on dialysis, RCC usually develops within the \201 rst 10y of treatmen t. Presentation Flank pain; UTI; visible haematuria; renal colic (stone disease); hyperten- si on. Investigation This depends on the presenting symptoms. - - For suspected UTI: For haematuria: On USS, the kidneys are small and hyperechoic, with mult iple cysts of varying size, many of which show calci \201 cation. If the nature of the cys ts cannot be determined with certainty on USS, arrange a renal CT. culture urine. urine cytology, \202 exible cystoscopy, and renal USS. ACQUIRED RENAL CYSTIC DISEASE (ARCD) 403 Treatment Persistent macroscopic haematuria can become problematic, exacerbated by heparini zation (required for haemodialysis). Options include transfer- ring to peritoneal dialysis, renal embolization or nephrectomy (acceptable as these patients already on dialysis by de \201 nition have non-functioning kidneys). Infected cysts, which develop into abscesses, r equire percutane- ous or surgical drainage. Radical nephrectomy is indicated for renal mass es with features suspicious of malignancy. Smaller asymptomatic masses re- quire surveillan ce. Patients with ARCD on long-term dialysis should also be considered for renal surveillan ce with ultrasonography or CT. CHAPTER 8 Miscellaneous urological diseases 404 Autosomal dominant polycystic kidney disease (ADPKD) De \201 nition An autosomal dominant inherited disorder involving multiple expanding renal parenchymal cysts (Fig. 8.2). Epidemiology Incidence is 0.1 \200\2230.5%; 95% are bilateral. ADPKD can affect children an d adults, although symptoms usually occur between ages 30 \200\22350y. ADPKD accounts for 1 0% of all renal failure (which usually manifests at >40y old). Pathology The kidneys reach an enormous size due to multiple \202 uid- \201 lled cysts a nd can easily be palpated on abdominal examination. Expansion of the cysts results in ischa emic atrophy of the surrounding renal parenchyma and ob- struction of normal renal tubules. End-stage renal failure occurs at around age 50y. Associated disorders Ten to thirty percent incidence of Circle of Willis berry aneurysms (a sso- ciated with subarachnoid hemorrhage), cysts of the liver (33%), pancreas (10%), spleen (<5%) and seminal vesicles, mitral valve prolapse; aortic root dilatation, aortic aneurysm s, and diverticular disease. Of note, the inci- dence of renal adenoma is 720%; however, th e risk of RCC is the same as the general population. Etiology Two genes have been identi \201 ed in ADPKD. The PKD1 gene is localized on the sh ort arm of chromosome 16 (16p13.3) and accounts for 85% of cases. The PKD2 gene is on the l ong arm of chromosome 4 (4q21) and causes 15% of cases. A third gene, PKD3, is also implica ted. Pathogenesis theories include intrinsic basement membrane abnormalities, tubular ep- i thelial hyperplasia (causing tubular obstruction and basement membrane weakness), and alter ations in the supportive extracellular matrix due to defective proteins, all of which may c ause cyst formation. Presentation - - - - Positive family history. Hypertension (75%). Palpable abdominal masses. Flank pain (due to mass effect, infection, stones or following acute cystic distension due to hemorrhage or ob struction). Haematuria (visible or non-visible). UTI Renal failure which may present with l ethargy, nausea, vomiting, anemia, confusion, and seizures. - . AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD) 405 Left kidney Right kidney Fig. 8.2 Axial section from a non-contrast CT scan demonstrating bilateral ADPKD. Differential diagnosis Other forms of renal cystic disease (multiple simple cysts, autosoma l recessive polycystic kidney disease (ARPKD), familial juvenile nephro- nophthisis, medull ary cystic disease; see b p. 676). Multiple renal cysts are also found in other autosomal dominant conditions: - Tuberous sclerosis: chromosomes 9 and 16. It presents with adenoma sebaceum, epilepsy, lear ning dif \201 culties, polycystic kidneys, and renal tumors (angiomyolipomas and, more rar ely, RCC). von Hippel \200\223Lindau ( gene mutation on the short arm of chromosome 3 (3p25 ) which causes hypoxia-inducible factor (HIF) to increase levels of growth factors (PDGF, T GF-A, VEGF), which can stimulate the formation of haemangioblastomas (cerebellar and retina l) and RCC. VHL syndrome also includes renal, pancreatic and epididymal cysts, and phaeochr omocytoma. has TSC1 and 2 gene mutations on VHL) syndrome: has a VHL tumor suppressor Investigation This depends on the presenting symptoms: - Adult patients with a family history of patient on the implications of a positive diagnosis . USS*, CT, and MRI of the renal tract are useful for initial diagnosis and investigation o f complications. On USS, the kidneys are small and hyperechoic, with multiple cysts of vary ing size, many of which show calci \201 cation. If the nature of the cysts cannot be deter mined with certainty on USS, arrange a renal CT. Genetic testing can be done if imaging is equivocal or when a de \201 nite diagnosis is required in a young patient. culture urine. For suspected UTI: ADPKD: \201 rst counsel the CHAPTER 8 Miscellaneous urological diseases 406 For haematuria: Renal failure: may be associated with anemia, although conversely, ADPKD ca n cause increased erythropoietin production and polycythaemia. urine cytology, \202 exible cystoscopy, and renal USS. refer for management by a nephrolo gist. Renal failure Treatment The aim is to preserve renal function for as long as possible (monitor and contro l hypertension and UTI). Infected cysts should be drained. Persistent, heavy haematuria can be controlled by embolization or ne- phrectomy. Progressive renal failure requires dialysi s and ultimately, renal transplantation. Due to the high risk of inheritance of ADPKD, offsprings should be fully counseled and offe red genetic testing or USS screening at an appropriate time. USS diagnostic criteria. Patients at 50% risk for developing ADPKD are: (cid:116)2 unilateral or bilateral cysts if aged <30y old. 2 cysts in each kidney in patients aged 30 \200\22359y old. 4 cysts in each kidney in patients aged >60y. This page intentionally left blank CHAPTER 8 Miscellaneous urological diseases 408 Vesicoureteric re \202 ux in adults Vesicoureteric re \202 ux (VUR) is the retrograde \202 ow of urine from the blad- der into the upper urinary tract with or without dilatation of the ureter, renal pelvis, and calyces (see b p. 662). Pathophysiology Re \202 ux is normally prevented by low bladder pressures, ef \201 cient ureteric peristalsis, and the ability of the vesicoureteric junction (VUJ) to occlude the d istal ureter during bladder contraction. This is assisted by the ureters passing obliquely through the bladder wall (the \200\230intramural \200\231 ureter) which is 1 \200\2232cm l ong. Normal intramural ureteric length to ureteric diameter ratio is 5:1. VUR of childhood tends to resolve spontaneously with increas- ing age because as the bladder grows, the intr amural ureter lengthens. Classi \201 cation Primary: a primary anatomical (and therefore, functional) defect, where the intramural length of the ureter is too short (ratio <5:1). Secondary: to some other anatomical or functional problem. - BPO, DSD, urethral stricture, missed Bladder outlet obstruction ( posterior urethral valves ), leading to elevated bladder pressures. Poor bladder compliance or the intermittently ele vated pressures of neuropathic detrusor overactivity (due to neuropathic disorders,1 e.g. S CI, spina bi \201 da). Iatrogenic re \202 ux. A relatively common cause would be direct u reteric reimplantation into the bladder without using an antire \202 uxing technique. Othe r causes include: ureteric meatotomy, i.e. incision of the ureteric ori \201 ce for remova l of ureteric stones stuck at the VUJ; following incision of a ureterocele; following TURP or TURP; and post- pelvic radiotherapy. In \202 ammatory conditions affecting function of the schistosomiasis, UTI. VUJ \200\224TB, Associated disorders VUR is commonly seen in duplex ureters (the Weigert \200\223Meyer law) 2 and associated with PUJ obstruction. Cystitis can cause VUR through bladder in \202 amma tion, reduced bladder compliance, increased pressures, and dis- tortion of the VUJ. Coexist ence of UTI with VUR can cause pyelonephri- tis. Re \202 ux of infected urine under high p ressure may lead to re \202 ux neph- ropathy, resulting in renal scarring, hypertension, a nd renal impairment \200\224 although this is much less common in adults compared to childr en. More commonly, this would manifest as loin pain in adults. Presentation - VUR may be asymptomatic. It may only be detected incidentally during investigations perform ed for other reasons, such as videourodynamics, IVU, or renal USS. Loin pain (sometimes ass ociated with a full bladder or immediately after micturition). symptoms. UTI VESICOURETERIC REFLUX IN ADULTS 409 Investigation The de \201 nitive test for the diagnosis of VUR is cystography, which may b e apparent during bladder \201 lling or during voiding (micturating cystoure- thrography) . Where clinically indicated, urodynamics establishes the pres- ence of voiding dysfunction . If there is radiographic evidence of re \202 ux nephropathy, check BP and the urine for proteinuria, measure serum cre- atinine, and arrange a 99mTc-DMSA renogram study to assess renal cortical scarring and determine split renal function. Management VUR is harmful to the kidney in the presence of infected urine and/or where blad der pressures are markedly elevated (due to severe BOO, poor compliance, or high-pressure o veractive bladder contractions). In the absence of these factors, VUR is not harmful, at le ast in the short term (months). Subsequent management depends on: - - - The presence and severity of symptoms. The presence of recurrent, proven urinary infection. The presence of already established renal damage, as indicated by radiological evidence of re \202 ux nephropathy, hypertension, impaired renal function, or proteinuria. Primary VUR - For the patient with primary VUR, recurrent UTIs with no symptoms between infections, no hy pertension, and good renal function: treat the UTIs when they occur; consider low-dose anti biotic prophylaxis if UTIs occur frequently (>3 per year). If UTIs are regularly associated with systemic symptoms (acute pyelonephritis rather than uncomplicated cystitis), then ure teric reimplantation is indicated. For the patient with primary VUR and objective evidence of deterioration in the affected kidney: ureteric reimplantation. Re \202 ux into a non-fu nctioning kidney scan) with recurrent UTIs and/or hypertension: nephroureterectomy. Primary re \202 ux with severe recurrent loin pain: reimplantation. (<10% function on DMSA ureteric Secondary VUR - - VUR VUR cause \200\224relieve BOO, improve bladder compliance (options: intravesical botuli num toxin injections, augmentation cystoplasty, sacral deafferentation). VUR with no sympto ms, no UTI, no high bladder pressures, and no BOO: for grades I \200\223II re \202 ux, mon itor for infection, hypertension, and evidence of deterioration in the appearance and funct ion of the kidneys. For grades III \200\223V, some urologists would recommend ureteric reim plantation or an endoscopic injection of bulking agent at the ureteric ori \201 ce (see Fi g. 8.3 for VUR grading). into a transplanted kidney: no treatment is necessary. in association with the neuropathic bladder: treat the underlying CHAPTER 8 Miscellaneous urological diseases 410 Grade I II III IV V Grade I Contrast into non-dilated ureter Grade II Contrast into renal pelvis and calyces; n o dilatation Grade III Mild dilatation of ureter; pelvis, and calyces Grade IV Dilated uret er becomes slightly tortuous; moderate dilatation of pelvis and blunting of calyces Grade V Severe ureteric dilatation and tortuosity; gross dilatation of pelvis and calyces Fig. 8.3 International re \202 ux classi \201 cation. 1 Neuropathic disorders cause VUR because they lead to intermittently or chronically raised blad- der pressure (due to bladder outlet obstruction, poor compliance and/or detrusor ove ractivity). 2 The lower renal moiety ureter inserts into the bladder in a higher and more lateral locat ion as compared to the upper moiety ureter, which inserts distally and medially, i.e. neare r the bladder neck. The lower moiety ureter has a shorter intramural length and therefore c an be prone to re \202 ux. The upper moiety ureter has a longer intramural length and tend s to be at risk of obstruction. This page intentionally left blank CHAPTER 8 Miscellaneous urological diseases 412 Pelviureteric junction obstruction in adults De \201 nition PUJO is an obstruction of the proximal ureter at the junction with the re- nal pelvis, resulting in a restriction of urin e \202 ow (see b p. 672); known as \200\230uretero-pelvic junction obstruction \200\231 (UPJO) in North America. Etiology Congenital - Intrinsic: ureter at the PUJ. The ureter can insert high on the renal pelvis (which may be a primary abnormality or secondary to the pelvic dilatation). Extrins ic: over which the PUJ runs. It is unlikely that these vessels are the primary cause of the obstruction. It is more probable that PUJO leads to a dilated PUJ and ballooning of the re nal pelvis over the lower pole vessels, which may thus contribute to, but is not the primar y cause of, the obstruction. smooth muscle defect results in an aperistaltic segment of compression from the lower renal pole ( \200\230aberrant \200\231) vessel Acquired PUJ stricture secondary to ureteric manipulation (e.g. ureteroscopy); trau- ma fro m passage of calculi; \201 broepithelial polyps; TCC of urothelium at PUJ; external compr ession of ureter by retroperitoneal \201 brosis or malig- nancy. Presentation Flank pain precipitated by diuresis (high \202 uid intake, especially after con- sumption of alcohol); \202 ank mass; UTI; haematuria (after minor trauma). It may al so be associated with VUR. Investigation - Blood test: - MSU: - Renal ureter. for renal function (U&E, eGFR). to exclude infection. USS: shows renal pelvis dilatation in the absence of a dilated IVU- : demonstrates a delay of excretion of contrast and a dilated pelvicalyceal system. CT- : shows a dilated renal pelvis and non-dilated ureter. Also helpful in excluding a small, r adiolucent stone, urothelial TCC, or retroperitoneal pathology, which may be the cause of t he obstruction at the PUJ. MAG3 maximum diuresis): is the de \201 nitive diagnostic test f or PUJO. Radioisotope accumulates in the renal pelvis and following intravenous furosemide, it continues to accumulate (a \200\230rising \200\231 curve). Also useful as it provides split renal function. renogram (with administration of furosemide to establish PELVIURETERIC JUNCTION OBSTRUCTION IN ADULTS 413 Retrograde pyelography: obstruction \200\224often performed at the time of PUJ repair to av oid introducing infection into an obstructed renal pelvis. to establish the exact site of the Management Surgery is indicated for recurrent episodes of bothersome pain, renal impairment , where a stone has developed in the obstructed kidney and where infection has supervened ( an acutely infected obstructed kidney in a septic patient will require nephrostomy insertio n). In the absence of symptoms, consider watchful waiting with serial MAG3 renograms. If re nal function remains stable and the patient remains free of symptoms, there is no need to o perate. A non-functioning \200\230burnt-out \200\231 kidney with PUJO may require nephrect omy to avoid the complication of pyonephrosis. Pyeloplasty (see b p. 782) - Laparoscopic pyeloplasty: the dismembered pyeloplasty is the most commonly performed techni que using transperitoneal, retroperitoneal, or robotic-assisted approaches. Success rates a re 795%. Open pyeloplasty: success rates of 95%. Common techniques include dismembered or A nderson \200\223Hynes pyeloplasty. The narrowed area of PUJ is excised, the proximal ureter is spatulated and anastomosed to the renal pelvis. Alternative techniques include \202 a p pyeloplasty (Culp) and Y \200\223V-plasty (Foley). A double J ureteric stent is left for 6 weeks post-operatively, which can be removed with \202 exible cystoscopy as an outpatient procedure. Endopyelotomy (or pyelolysis) A minimally invasive technique to treat PUJO, but tends not t o be offered as \201 rst-line therapy other than in older or frail patients. It can be ut ilized after pyeloplasty has failed. A full thickness incision is made through the obstruct ing proximal ureter from within the lumen of the ureter down into the peripelvic and periur eteral fat, using a sharp knife or Holmium:YAG laser. The incision is stented for 4 weeks t o allow re-epithelialization of the PUJ. Generally not used for PUJO >2cm in length. The in cision may be made percutaneously or by a retrograde approach via a rigid or \202 exible ureteroscope or by using a specially designed endopyelotomy balloon, the Acucise techniqu e. Here, an angioplasty-type balloon (over which runs a cautery wire) is in \202 ated acro ss the PUJ. An electrical current heats the wire and this cuts through the obstructing ring of tissue at the PUJ. The presence of a combination of PUJO and a renal stone that is suitable for PCNL is an ind ication for combined PCNL and percutaneous endopyelotomy. Success rates in terms of relieving obstruction: percutaneous endopyelotomy, 60 \200\223100 % (mean 70%); cautery wire balloon endopyelotomy, 70%; ureteroscopic endopyelotomy, 80%. CHAPTER 8 Miscellaneous urological diseases 414 Follow-up Repeat MAG3 renogram is usually performed 3 months post-operatively. If there has been no improvement, this can be repeated 6 \200\22312 months post-operatively. Failure ma y need re-do surgery or endopyelotomy. Fig. 8.4 IVU demonstrating a right PUJO (dilated pelvicalyceal system and non-dilated urete r). Image kindly provided with permissions from Mr P. Malone. PELVIURETERIC JUNCTION OBSTRUCTION IN ADULTS 415 Fig. 8.5 Retrograde pyelogram demonstrating a right PUJO (circled). Image kindly provided w ith permissions from Mr P. Malone. Fig. 8.6 Contrast-enhanced CT (coronal section) image of a right PUJO (dilated pelvicalycea l system and non-dilated ureter). Image kindly provided with permission from Mr A. Wedderbu rn. CHAPTER 8 Miscellaneous urological diseases 416