A control \201 lm is obtained before contrast is given. Intravascular contrast is adminis tered followed by a series of X-rays of the kidneys, ureters, and bladder over the followin g 30min or so to image their anatomy and pathology and to give some indication of renal fun ction. - Radio-opacity of contrast agents depends on the presence of a tri- iodinated benzene ring in the molecule. Ionic monomers (sodium and meglumine salts) ionize, thereby producing high osmolality solutions (e.g. iothalamate \200\224Conray , diatrizoate \200 \224Hypaque , Urogra \201 n ). Non-ionic monomers \200\224low osmolality (e.g. iopamidol \200\224Niopam , iohexol \200\224Omnipaque ). At a concentration of 300mg of iodine per mL, ionic monomers have an osmolality \201 ve t imes higher than plasma, compared with non-ionic monomers which have an osmolality twice th at of plasma. Excreted from plasma by glomerular \201 ltration. Films and \200\230phases \200\231 of the IVU Plain \201 lm: looking for calci \201 cati on overlying the region of the kidneys, ureters, and bladder. Nephrogram phase: \201 rst phase of IVU; \201 lm taken immediately follow- ing intraven ous administration of contrast (peak nephrogram density). The nephrogram is produced by \201 ltered contrast within the lumen of the proximal convoluted tubule (it is a proximal t ubular, rather than distal tubular phenomenon). Pyelogram phase: as the contrast passes along the renal tubule (into the distal tubule), it is concentrated (as water is absorbed, but the contrast agent is not). As a consequence, t he contrast medium is concentrated in the pelvicalyceal system and thus this \200\230pyelo gram \200\231 phase (Fig. 3.5) is much denser than the nephrogram phase. The pyelogram phas e can be made more dense by dehydrating the patient prior to contrast administration. Pelvi c compression can be used to distend the pelvicalyceal system and demonstrate their anatomy more precisely. Compression is released and a \201 lm taken (20 \200\22330min; Fig. 3.6) . INTRAVENOUS UROGRAPHY (IVU) 49 Fig. 3.5 Normal IVU at 15min. Fig. 3.6 Normal IVU at 20min. Lower abdominal compression has been released. CHAPTER 3 Urological investigations 50 Side effects of administration of intravenous contrast media - Occur in 1% of patients give n non-ionic and 5% given ionic contrast media. The most serious reactions represent an anaphylactic reaction \200\224 hypotension with \202 ushing of the skin (marked peripheral vasodilatation), oedema (face , neck, body, and limbs), bronchospasm, urticaria. Rarely, cardiac arrest can occur. The de ath rate, as a consequence of these reactions, is 1 in 40 000 to 1 in 70 000 with the ionic media and 1 in 200 000 with non-ionic contrast agents. A contrast reaction is more likely to occur in patients with an iodine allergy, previous co ntrast reaction, asthma, multiple other allergies, and heart disease and is less likely wit h non-ionic contrast media. Steroid premedication (at least 12h before) can reduce the risk of a contrast reaction. Contrast media are also nephrotoxic. Ten percent of patients with a raised creatinine will develop an increase in creatinine after an IVU (more likely in diabetics, with dehydration, and with large contrast doses). The increase in creatinine usually resolves spontaneously. Uses of the IVU - Investigation of haematuria \200\224detection of renal masses, \201 lli ng defects within the collecting system of the kidney and within the ureters (stones, TCCs) . Localization of calci \201 cation overlying the urinary tract (i.e. is it a stone or not?). Investigation of patients with loin pain (e.g. suspected ureteric colic). Increasingly bein g replaced with CTU which has superior sensitivity and speci \201 city. Very good for identi \201 cation of congenital urinary tract abnormalities (e.g. ureteric anatomy in duplex systems; Fig. 3.7), malrotation, horseshoe kidneys. Used for follow-up of post-ureteric surgery to identify strictures. - There is a trend towa rds IVU being replaced by MDCTU (a rapid acquisition CT done following intravenous contrast administration with high spatial resolution) at least in the investigation of haematuria a nd of loin pain. To a large extent, whether one uses an IVU or MDCTU depends on the availab ility of the latter in your radiology department. INTRAVENOUS UROGRAPHY (IVU) 51 Fig. 3.7 Bilateral duplex as seen on a tomogram from an IVU. CHAPTER 3 Urological investigations 52 Other urological contrast studies Videocystourethrography (VCUG) (Fig. 3.8) To identify the presence of vesicoureteric re \202 ux during \201 lling and emptying of the bladder and the presence and site of obstruction in the outlet of the bladder and within the urethra, particularly in patients with neuropathic bladder problems (e.g. spinal cord injury). Cystography Retrograde \201 lling of the bladder via a catheter with contrast. Identi \201 es vesicocolic and vesicovaginal \201 stulae and bladder rupture (extraperitoneal an d intraperitoneal). Urethrography (Fig. 3.9) Retrograde \201 lling of the urethra with contrast, to identify the site and length of urethral strictures (Fig. 3.10) or presence, extent, and site of ure thral injury (in pelvic fracture, for example). Ileal loopogram Retrograde \201 lling of an ileal conduit with contrast, to establish the pres- ence of free re \202 ux into the ureters (a normal \201 nding; absence of free re \202 ux suggests obstruction at the uretero-ileal junction due to ischaemic stenosis or r ecurrent TCC in the ureters at the uretero-ileal junction) and the presence of TCCs in the ureters or renal pelvis (an occasional \201 nding in patients who have had a cystectomy f or bladder TCC with ileal conduit urinary diversion). Retrograde ureterography Retrograde instillation of contrast into the ureters by a ureteric catheter inserted into the ureter via a cystoscope (rigid or \202 exible). Provides exce l- lent de \201 nition of the ureter and renal pelvis for detection of ureteric and renal pelvic TCCs or radiolucent stones in patients with persistent haema- turia where other test s have shown no abnormality. Also used to diagnose presence and site of ureteric injury (ob struction, ureteric leak) in cases of ureteric injury (e.g. post-hysterectomy or Cesarean s ection). OTHER UROLOGICAL CONTRAST STUDIES 53 Fig. 3.8 VCUG showing bilateral ureteric re \202 ux. Fig. 3.9 Normal urethrogram. Fig. 3.10 A urethrogram showing a bulbar urethral stricture. CHAPTER 3 Urological investigations 54 Computed tomography (CT) and magnetic resonance imaging (MRI) CT Widely used for investigat ion of urological symptoms and disease. It can detect very small differences in X-ray absor ption values of tissues, provid- ing a very wide range of densities (and, therefore, differ entiation between tissues) when compared with plain radiography. The computer calculates th e absorption value (attenuation) of each pixel and reconstructs this into an image. The att enuation values are expressed on a scale from \200\2231000 to +1000 Houns \201 eld units (water = 0, air = \200\2231000, bone = +1000). More recently, advances in computing power have enabled the data to be refor- matted so that images can be produced in sagittal and co ronal planes as well as in the more familiar horizontal plane (Figs. 3.11 and 3.12). \200\230Plain \200\231 CT scans (without contrast) can detect calci \201 cation and calcu li within the urinary tract. Administration of intravenous contrast is used to investigate haema- turia, to evaluate the nature of solid renal lesions, and to determine the nature of soft tissue masses (e.g. to differentiate bowel from lymph nodes in cancer staging CTs). \200\230Spiral \200\231 or \200\230helical \200\231 CT (also known as multidetec- tor CT urography \200\224MDCTU \200 \224when done following intravenous con- trast administration) is very rapid scanning while the table on which the patient is lying is moved though the scanner. Multiple images ( \200\230slices \200\231) of the patient are taken. A large volume of the body can be imaged in a sin- gle breath hold, thus eliminating movement artifact and increasing spatial resol ution \200\224particularly useful for identifying suspected ureteric stones in patients wit h acute loin pain and (with contrast) for determining the nature of renal masses. Overlapping thin sections can be \200\230reconstructed \200\231 into images in multi- ple planes (multiplanar reformatting \200\224MPR) so lesions can be imaged in multiple planes ( sagittal, coronal) as opposed to the traditional transverse sections. Uses of CT Haematuria Investigation of site and cause of urinary tract bleeding. Has the ad vantage of a single investigation which potentially could obviate the need for the traditio nal \200\2304-test \200\231 approach to haematuria (IVU, renal ultrasound, \202 ex- ible cystoscopy, urine cytology), although at the cost of a higher radiation dose. There is evi dence suggesting that MDCTU has reasonable sensitiv- ity and high speci \201 city for diag nosing bladder tumors1 (in patients with macroscopic haematuria \200\22493% sensitivity, 99 % speci \201 city) and that it has equivalent diagnostic accuracy to retrograde uretero-py elography (the retrograde administration of contrast via a catheter inserted in the lower u reter to outline the ureter and renal collecting system).2 Overall, for patients with haema turia and no prior history of urological malignancy, for the detection of all urological tu mors, it has approximately 65% sensitiv- ity and 98% speci \201 city3 \200\224so it only r arely calls a lesion a tumor when, in fact, CT AND MRI 55 Fig. 3.11 Coronal CT image of abdomen showing the left kidney, aorta, and IVC. Fig. 3.12 Coronal CT image of abdomen showing the left kidney and paravertebral muscles. CHAPTER 3 Urological investigations 56 the lesion is benign, but it still fails to diagnose a signi \201 cant proportion of uri- nary neoplasms (sensitivity for upper tract neoplasms 80%, for bladder tumors 60%). The rol e of MDCTU (described by some as the \200\230ultimate \200\231 imaging modality) in the in vestigation of haematuria remains controversial. MDCTU in all patients with haematuria (mic roscopic, macroscopic), when most will have no identi \201 able cause for the haematuria, has a cost (high radiation dose, \201 nan- cial). A targeted approach, aimed at those wit h risk factors for urothelial malig- nancy (age >40y, macroscopic as opposed to microscopic haematuria, smoking history, occupational exposure to benzenes and aromatic amines) might be a better use of this resource, rather than using MDCTU as the \201 rst imaging test fo r both high- and low-risk patients. Thus, the \200\230best \200\231 imaging probably depen ds on the context of the patient. Renal - Investigation of renal masses \200\224characterizes solid from cystic lesions; diff erentiates benign (e.g. angiomyolipoma) from malignant solid masses (e.g. renal cell carcin oma). Staging of renal cancer (establishes local, nodal, and distant spread). - Assessment of sto ne size and location (within the collecting system or within the parenchyma of the kidney). Detection and localization of site of intrarenal and perirenal collections of pus (pyonephrosis, perinephric abscess). \200\230Staging \200\231 (grading) of renal trauma. - Determination of cause of hydronephr osis. Loin pain: imaging the ureters The IVU, previously the mainstay of imaging in patient s with \202 ank pain, has been superseded by CT-KUB, a non-contrast CT of the kidneys, ur eters, and bladder. Compared with IVU, CT-KUB: - Has greater speci \201 city (97%) and sen sitivity (94 \200\223100%) for diagnosing ureteric stones.4 Can identify non-stone causes of \202 ank pain. - Requires no contrast administration so avoiding the chance of a contrast reaction (risk of fatal anaphylaxis following the administration of low osmolality contrast media for IVU is in the order of 1 in 100 000). Is faster, taking just a few minutes to image the kidneys and ureters. An IVU, particularly where delayed \201 lms are required to identify a stone causing high-grade obstruction, may take hours to identify the precise location of the obstructing stone. Is equivalent in cost to IVU in high CT volume hospitals. CTU is able to locate and measure the size and number of ureteric stones. A non-contrast CT-KUB radiation dose: approximatel y 4.7mSv compared to 1.5mSv for IVU (fatal cancer risk is estimated at 1 in 2000 for a 10mS v radiation exposure). Ultra-low dose CT (ULDCT) lowers radiation exposure (0.6 \200\2232mS v), but at the expense of lower sensitivity (68 \200\22386%) for small (<3mm) ureteric ston es.4 Contrast-enhanced ultra- low dose CT (CEULDCT) uses contrast which increases sensitivi ty (97%) and speci \201 city (100%) for detecting small ureteric stone disease while limit ing radiation dose to levels comparable with IVU (1.7mSv vs 1.4mSv). CT AND MRI 57 Bladder Bladder cancer staging (establishes local, nodal, and distant spread). Uses of MRI in the urological patient - Staging of pelvic cancer \200\224bladder and prosta te cancer staging (establishes local, nodal, and distant spread). Good for identifying seminal vesicle invasi on. As with CT, oedema and \201 brosis cannot be reliably distinguished from tumor within the bladder wall, leading to \200\230overstaging \200\231 of cancer. Again, as with CT, m icroscopic disease cannot be identi \201 ed, leading to \200\230understaging \200\231 of cancer. Especially useful for diagnosing phaeochromocytomas (very bright image on T2-weighted images). Investigation of LUTS where the history suggests a possible neurological basis (LUTS in the presence of lumbar or thoracic back pain or associated with loss of perineal sensation or disturbances of bladder sensation or where there is sensory disturbance in the legs or feet). Localization of undescended testes. - Identi \201 cation of ureteric stones, where ionizin g radiation is best avoided (e.g. pregnant women with loin pain). In the authors \200\231 e xperience, few radiologists seem to be able to con \201 dently diagnose or exclude the pre sence of stones on MR urography, at least in part because this test is still so seldom used . PET (positron emission tomography) imaging and PET/ CT in urological patient A nuclear medi cine imaging technique. Produces three-dimensional images of functional processes in the bo dy. Detects gamma rays emitted by positron-emitting radionuclide tracers which are introduc ed into the body on biologically active molecules. The molecules to which the radionuclides are bound allow \200\230visualization \200\231 of metabolic processes. Three-dimensional images of tracer concentration within various organs and tissues are then constructed by CT scanning (or MRI) performed within the same machine. It thus involves exposure to ionizing radiation (typically 5 \200\2237mSv, but if combined with CT, substantially more). Radionuclides with short half-lives are attached to biologically active molecules such as g lucose ( \200\230metabolic \200\231 tracers) or molecules that bind to receptors or sites o f drug action ( \200\230receptor-speci \201 c \200\231 tracers). As a conse- quence of the short half-lives, the radionuclides must be made in a cyclo- tron in a radiochemistry lab in close proximity to the PET imaging unit. In urological practice, one example is \202 uoro-2-Deoxy-d-Glucose labeled with an isotop e of \202 uorine, 18F (18F-FDG). This is taken up by cellular glucose transporters and ph sophorylated to FDG-6-phosphate by glucose-6-phosphokinase. FDG is trapped in cells and so cells are intensely radiolabelled with 18F-FDG. The radioisotopes undergo positron emission decay, emitting positrons (the so-called antipa rticles of the electron). The emitted positrons travel in tissue for a short distance (<1mm depending on the isotope) and in so doing, lose kinetic energy. They decelerate to a point where they can interact with electron, this interaction leading to the destruction of both CHAPTER 3 Urological investigations 58 the electrons and positrons and in the process, producing a pair of gamma photons moving in opposite directions. These photons are detected when they reach a scintillator within the scanning device. Uses 18F-FDG is excreted in urine and this limits the role of 18F-FDG PET scanning in the d etection of primary urological cancers, but it has shown promise in the detection of metast atic disease. Prostate cancer 18F-FDG PET has limited sensitivity for primary staging since prostate canc er cells often do not have increased glucose metabolism (Rioja 2010). It cannot identify ly mph node involvement with suf \201 cient sensitivity. Similarly, it lacks suf \201 cient sensitivity to detect recurrence after primary treatment with radical prostatectomy. 11C-me thionine PET has shown promise in the restaging of patients with advanced prostate cancer. Kidney cancer 18F-FDG PET is showing promise as a technique to detect metastases in renal c ancer. Bladder cancer Again 18F-FDG PET is able to detect metastases in bladder cancer, but is not useful in primary staging. Germ cell tumors 18F-FDG PET cannot distinguish between in \202 ammatory and neoplastic ma sses nor can it distinguish mature teratoma from normal or necrotic tissue. Further reading Rioja J, Rodr guez-Fraile M, Lima-Favaretto R, et al. (2010) Role of positron emission t omography in urological oncology. Br J Urol Int 106:1578 \200\22394. 1 Fowler JC et al. (2011) Clinical evaluation of ultra-low dose contrast-enhanced CT in pat ients presenting with acute ureteric colic. Br J Med Surg Urol 4:56 \200\22363. 2 Turney BW, Willatt JM, Nixon D, et al. (2006) Computed tomography urography for diagnosin g bladder cancer. Br J Urol Int 98:345 \200\2238. 3 Cowan NC, Turney BW, Taylor NJ, et al. (2007) Multidetector computed tomography urography for diagnosing upper urinary tract urothelial tumors. Br J Urol Int 2007; 99:1363 \200\223 70. 4 Sudakoff GS, Dunn DP, Guralnick ML, et al. (2008) Multidetector computed tomography urogr aphy as the primary imaging modality for detecting urinary tract neoplasms in patients with asymptomatic hematuria. J Urol 179:862 \200\2237. This page intentionally left blank CHAPTER 3 Urological investigations 60 Radioisotope imaging A variety of organic compounds can be \200\230labeled \200\231 with a radioactive iso- tope that emits gamma rays, allowing the radiation to penetrate through t issues and reach a \200\230gamma \200\231 camera placed adjacent to the patient. The most commonly used radioisotope is technetium \200\22499mTc (half-life 6h, gamma ray emission en ergy 0.14MeV). The excretion characteristics of the organic compound to which the 99mTc is bound determine the clinical use. MAG3 renogram 99mTc is bound to mercapto acetyl triglycine. Over 90% of mercaptoacetyl- tri glycyl (MAG3) becomes bound to plasma proteins following intravenous injection. It is excre ted from the kidneys, principally by tubular secretion (glomerular \201 ltration is minim al). Following intravenous injection, MAG3 is very rapidly excreted (appearing in the kidne y within 15s of injection and starting to appear in the bladder within about 3min). Approxi mately two- thirds of the injected dose of MAG3 is taken up by the kidneys with each passag e of blood through the kidney. The radioactivity over each kidney thus increases rapidly. T he peak of radioactivity represents the point at which delivery of MAG3 to the kidney from the renal artery is equivalent to excretion of MAG3. The radioactivity starts to decline as excretion out- strips supply. Thus, a time \200\223activity curve can be recorded for each kidney. This time \200\223activity curve is known as a renogram. Images are collected onto a \201 lm at 30s intervals for the \201 rst 3min and then at 5min intervals for the remainder of the study (usually a total of 30min). A normal renogram has three phases - First phase: a steeply rising curve lasting 20 \200 \22330s. - Second phase: a more slowly rising curve, rising to a peak. If the curve does no t reach a peak, the second phase is said to rise continually. A normal second phase ends wi th a sharp peak. Third phase: a curve that descends after the peak. There can be no third phase if there is no peak. Description of the renogram No comment is made about the \201 rst phase. The second phase is described as being absent, impaired, or normal. The third phase is described as being a bsent, impaired, or normal. The time to the peak depends on urine \202 ow and level of hydration and is a crude measu re of the time it takes the tracer to travel through the parenchyma of the kidney and throu gh the renal pelvis. The time to the peak of the renogram normally varies between 2 and 4.5 min. If the renogram continues beyond the time at which the peak should normally occur, then the re may be a distal obstruction (e.g. at the PUJ or lower down the ureter). In this situatio n, an injection of 40mg of fruse- mide is given (at about 18min) and if the curves start to fall rapidly, this is taken as proof that there is no obstruction. If it continues to rise , there is obstruction. If it remains \202 at (neither rising or falling), this is descri bed as an \200\230equivocal \200\231 result. RADIOISOTOPE IMAGING 61 Parenchymal transit time can also be measured (PTTI \200\224parenchymal transit time index) . The normal range for PTTI is 40 \200\223140s and averages 70s. PTTI is prolonged (to >156 s) in obstruction and in renal ischaemia. A normal PTTI excludes obstruction. Uses - \200\230Split \200\231 renal function (i.e. the % function contributed by each kidn ey). - Determination of presence of renal obstruction \200\224based on shape of renogram curve and PTTI. DMSA scanning Dimercaptosuccinic acid (DMSA) is labeled with 99mTc. It is taken up by the p roximal tubules and retained there, with very little being excreted in the urine. A \200 \230static \200\231 image of the kidneys is thus obtained (at about 3 \200\2234h post-intra venous injection of radioisotope). It demonstrates whether a \200\230lesion \200\231 conta ins function- ing nephrons or not. Uses - \200\230Split \200\231 renal function (i.e. the % function contributed by each kidn ey). - Detection of scars in the kidney (these appear as defects in the cortical outline, r epresenting areas in which the radioisotope is not taken up). Radioisotope bone imaging 99mTc-labeled methylene disphosphonate (MDP) is taken up by areas of bone where there is increased blood supply and increased osteoblastic activity. There a re many causes of a focal increase in isotope uptake \200\224 bone metastases, site of frac tures, osteomyelitis, TB, benign bone lesions (e.g. osteoma). Metastases from urological ca ncers are characterized by their predilection for the spine and the fact that they are mult iple (single foci of metastasis are rare). Prostate cancer classically metastasizes in this way. CHAPTER 3 Urological investigations 62 Uro \202 owmetry Measurement of \202 ow rate (Fig. 3.13). Provides a visual image of the \200\230strength \200\231 of a patient \200\231s urinary stream. Urine \202 ow rate is measured in mL/s and is determined using commercially available electronic \202 owmeters (Fig. 3.14). These \202 owmeters are able to provide a printout, recording the voided vol ume, maximum \202 ow rate, and time taken to complete the void, together with a record of the \202 ow pattern. Maximum \202 ow rate, Qmax, is in \202 uenced by the volume of u rine voided, by the contractility of the patient \200\231s bladder, and by the conductivity (resistance) of their urethra. A number of nomograms are available which relate voided volume to \202 ow rate. Interpretation and misinterpretation of urine \202 ow rate The \200\230wag \200\231 arti fact (Fig. 3.13b) is seen as a sudden, rapid increase in \202 ow rate on the uro \202 ow tracing and is due to the urine \202 ow suddenly being directed at the center of the \202 owmeter, producing a sudden artefactual surge in \202 ow rate. In men with \200\230prostatic \200\231 symptoms, for the same voided volume, \202 ow rat e varies substantially on a given day (by as much as 5mL/s if four \202 ows are done).1 M ost guidelines recommend measuring at least two \202 ow rates and using the highest as re presenting the patient \200\231s best effort. What does a low \202 ow mean? Uro \202 owmetry alone cannot tell you why the \202 ow i s abnormal. It can- not distinguish between low \202 ow due to BOO and that due to a poor ly contractile bladder. The principal use of urine \202 ow rate measurement is in the assessment of elderly men w ith suspected prostatic obstruction ( \200\230LUTS/BPH \200\231), but there is debate about its usefulness as a test for predicting outcome of various treatments. Some studies sugges t that men with poor outcomes are more likely to have had higher \202 ows preoperatively compared with those with good outcomes, whereas other studies report equivalent improvement s in symptoms whether or not preoperative \202 ow rate is high or low. A recent Veterans Administration trial comparing transurethral resection of the prostate (TURP) with watchful waiting in men with LUTS/BPH found that \202 ow rate could not predict the likelihood of a good symptomatic outcome after TURP.2 As a consequence, different guidelines give different guidance with regard to performing ur o \202 owmetry in men with LUTS/BPH. It is regarded as an optional test by the AUA (Americ an Urological Association),3 rec- ommended by the 4th International Consultation on BPH,4 a nd the EAU (European Association of Urology) BPH Guidelines state that it \200\230is oblig a- tory prior to undertaking surgical treatment \200\231.5 UROFLOWMETRY 63 (a) 25ml/s flow rate Results of uroflowmetry 13s Voiding time Flow time 13s Time to max flow TQmax 8s Max flow rate Qmax Average flow ra te Qave Voided volume T100 TQ 18.1ml/s 11.7ml/s 151ml Vcomp 30 0 10 20 seconds (b) 25ml/s flow rate Results of uroflowmetry 34s Voiding time Flow time 34s Time to max flow TQmax 9s Max flow rate Qmax Average flow ra te Qave Voided volume T100 TQ 23.5ml/s 10.2ml/s Vcomp 354ml 0 10 20 30 40 50 seconds Fig. 3.13 (a) A uro \202 ow trace; (b) A uro \202 ow trace with a \200\230wag \200\231 a rtifact occurring between 5 \200\22310s. The true Qmax is not 23.5mL/s as the readout sugge sts, but is nearer 18mL/s. Fig. 3.14 Dantec \202 owmeter. CHAPTER 3 Urological investigations 64 Generally speaking, urine \202 ow rate measurement is regarded as having insuf \201 cien t diagnostic accuracy for it to be useful in the assessment of female lower urinary tract d ysfunction. Although urine \202 ow measurement can be used to assess voiding function in men with urethral strictures, it has limited value in younger men because in this age group , the bladder can compensate for a marked degree of obstruction by contracting more forcefu lly. Thus, a young man may have a normal \202 ow rate despite have a marked urethral stri cture. 1 Reynard JM, Peters TJ, Lim C, Abrams P (1996) The value of multiple free- \202 ow studie s in men with lower urinary tract symptoms. Br J Urol 77:813 \200\2238. 2 Bruskewitz RC, Reda DJ, Wasson JH, et al. (1997) Testing to predict outcome after transur e- thral resection of the prostate. J Urol 157:1304 \200\2238. 3 McConnell JD, Barry MJ, Bruskewitz RC, et al. (1994) Benign prostatic hyperplasia: diagno sis and treat- ment. Clinical practice guideline. Rockville: Agency for Health Care Policy and Research. 4 Denis L, Grif \201 ths K, Khoury S, et al. (eds) (1998) Fourth International Consultatio n on Benign Prostatic Hyperplasia (BPH), Paris, July 1997. Plymouth: Health Publications. 5 de la Rosette JJ, Alivizatos G, Madersbacher S, et al. (2001) EAU guidelines on benign pr ostatic hyperplasia (BPH) (2001) Eur Urol 40:256 \200\22363. This page intentionally left blank CHAPTER 3 Urological investigations 66 Post-void residual urine volume measurement Post-void residual (PVR) urine volume is the vo lume of urine remaining in the bladder at the end of micturition. In normal individuals, th ere should be no urine remaining in the bladder at the end of micturition. A PVR may be cau sed by detrusor underactivity (due to ageing \200\224as the older bladder is less able to s ustain a contraction than the younger bladder or neuro- logical disease affecting bladder i nnervation), BOO, or a combination of both. In clinical practice, PVR volume is measured by ultrasound after the patient has attempted to empty their bladder. A commonly used formula for calculating bladder volume is:1 \200\2235 Bladder volume (mL) = bladder height (cm) \227 width (cm) \227 depth (cm) \227 0.7 Interpretation and misinterpretation of PVR volume PVR volume shows considerable day-to-day variability, with volumes recorded on different days over a 3-month period varying between 150 and 670mL.1 Clinical usefulness of PVR volume measurement Analysis of the placebo-treated men (n=737) i n the MTOPS trial suggests that PVR volume did not seem to be a strong predictor of the lik elihood of developing acute urinary retention. There was no difference in reten- tion rates in men with a residual urine volume of <39mL compared with those with a residual urine vol ume 39mL or more (although the higher PVR was associated with a greater chance of symptomat ic progression and of need for invasive therapy).6 Similarly, there was no difference in re tention rates in 389 men treated with alpha blockers or 553 treated with placebo with a res idual urine volume of <300mL compared with those with a residual urine volume of >300mL.7 I n 170 men with urodynamically con \201 rmed BOO who initially opted for conservative (non- surgical) treat- ment, 141 (83%) remained untreated at 10y and 29 (17%) had undergone surge ry (22 for LUTS, 7 for retention). PVR at baseline did not predict the chance of developing urinary retention or of the need for TURP for worsening LUTS.8 PVR volume measurement cannot predict symptomatic outcome from TURP. For these reasons, res idual urine volume measurement is regarded as an optional test in the AUA guidelines, but i s recommended by the 4th International Consultation on BPH.2 Residual urine volume measurement is useful (along with measurement of serum creatinine) as a safety measure. It indicates the likelihood of back pressure on the kidneys and thus it tells the urologist whether it is safe to offer watchful waiting rather than TURP. In men w ith moderate LUTS, it is safe not to operate where the PVR volume is less than 350mL and th is probably holds true for those with higher PVR volumes (<700mL).3 POST-VOID RESIDUAL URINE VOLUME MEASUREMENT 67 Does an elevated residual urine volume predispose to urinary infection? Though intuition wo uld suggest yes, what evidence there is relating residual volume to urine infection suggest s that an elevated residual urine may not, at least in the neurologically normal adult, pre dispose to urine infection.4,5 There has been no longitudinal study to determine of an ele- vated PVR increases the risk of developing urinary tract infection. 1 Dunsmuir WD, Feneley M, Corry DA, et al. (1996) The day-to-day variation (test \200\223re test reli- ability) of residual urine measurement. Br J Urol 77:192 \200\2233. 2 Denis L, Grif \201 ths K, Khoury S, et al. (eds) (1998) Fourth International Consultatio n on Benign Prostatic Hyperplasia (BPH), Paris, July 1997. Plymouth: Health Publications. 3 Bates TS, Sugiono M, James ED, et al. (2003) Is the conservative management of chronic re ten- tion in men ever justi \201 ed? Br J Urol Int 92:581 \200\2233. 4 Riehmann M, Goetzmann B, Langer E, et al. (1994) Risk factor for bacteriuria in men. Urol ogy 43:617 \200\22320. 5 Hampson SJ, Noble JG, Rickards D, Milroy EG (1992) Does residual urine predispose to urin ary tract infection. Br J Urol 70:506 \200\2238. 6 Crawford ED, Wilson SS, McConnell JD, et al. (2006) Baseline factors as predictors of cli nical progres- sion of benign prostatic hyperplasia in men treated with placebo. J Urol 175 :1422. 7 Mochtar CA, Kiemeney LA, van Riemsdijk MM, et al. (2006) Post-void residual urine volume is not a good predictor of the need for invasive therapy among patients with benign prostat ic hyperplasia. J Urol 175:213 \200\2236. 8 Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P (2005) The natural history of lo wer urinary tract dysfunction in men: minimum 10-year urodynamic follow-up of untreated bla dder outlet obstruction. BJU Int 96:1301 \200\2236. CHAPTER 3 Urological investigations 68 Cystometry, pressure \202 ow studies, and videocystometry - Cystometry: the recording of bladder pressure during bladder \201 lling. - Pressure \200\223 \202 ow studies (PFS): t he simultanous recording of bladder pressure during voiding. Videocystometry: \202 uoroscopy (X-ray screening) combined with PFS during voiding (see b p. 57; Fig. 3.8). These techniques provide the most precise measurements of bladder and urethral sphincter be havior during bladder \201 lling and during void- ing. Cystometry precedes the pressure \200\223 \202 ow study. Bladder pressure (Pves, measured by a urethral or suprapubic cathe ter) and abdominal pressure (Pabd, measured by a pressure line inserted into the rectum) ar e recorded as the bladder \201 lls (cystometric phase) and empties (void- ing phase) and \202 ow rate is simultaneously measured during the voiding phase. The pressure developed by the detrusor (the bladder muscle), Pdet, cannot be directly measured, but it can be deri ved by subtracting abdominal pressure from the pressure measured within the bladder (the in travesical pressure). This allows the effect of rises in intra- abdominal pressure caused b y coughing or straining to be subtracted from the total (intravesical) pressure so that a \200\230pure \200\231 detrusor pressure is obtained. All pressures are recorded in cmH2O and \202 ow rate is measured in mL/s. The pressure li nes are small-bore, \202 uid- \201 lled catheters attached to an external pressure trans ducer or catheter-tip pressure transducers can be used. A computerized printout of Pves, Pabd and Pdet, and \202 ow rate (Qmax) is obtained (Fig. 3.15). During bladder \201 lling, the presence of overactive bladder contractions can be detected. During voiding, the key parame- ters are Qmax and the detrusor pressure at the p oint at which Qmax is reached, Pdet Qmax. This pressure, relative to Qmax, can be used to d e \201 ne the presence of BOO by using a variety of nomograms, of which the ICS nomogram i s most widely used. CYSTOMETRY, PRESSURE FLOW STUDIES, VIDEOCYSTOMETRY 69 Fill & void cys to + video (spinal)#1 120 100 80 60 40 20 0 40 20 0 40 20 0 2 1 0 1000 500 0 Pabd cm H2O Pves cm H2O Pdet cm H2O Qura ml/s EMG V 30s 00:00 01:00 02:00 03:00 04:00 Fig. 3.15 A computerized printout of intravesical pressure (Pves), intra-abdominal pressure (Pabd), subtracted detrusor pressure (Pdet), and \202 ow rate (Qmax). This page intentionally left blank 71 Chapter 4 Bladder outlet obstruction Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) 72 Pathophysiology and causes of bladder outlet obstruction (BOO) and BPH 73 Benign prostatic obstruction (BPO): symptoms and signs 74 Diagnostic tests in men with LUTS thought to be due to BPH 76 The management of LUTS in men: NICE 2010 Guidelines 78 Watchful waiting for uncomplicated B PH 84 Medical management of BPH: alpha blockers 86 Medical management of BPH: 5 -reductase inhibitors 88 Medical management of BPH: combination therapy 90 Medical management of BPH: alternative drug therapy 92 Minimally invasive management of BPH: surgical alternatives to TURP 94 Invasive surgical alternatives to TURP 96 TURP and open prostatectomy 100 Acute urinary ret ention: de \201 nition, pathophysiology, and causes 102 Acute urinary retention: initial and de \201 nitive management 106 Indications for and tec hnique of urethral catheterization 108 Technique of suprapubic catheterization 110 Manageme nt of nocturia and nocturnal polyuria 116 Chronic retention 118 High-pressure chronic reten tion (HPCR) 120 Bladder outlet obstruction and retention in women 122 Urethral strictures a nd stenoses 124 CHAPTER 4 Bladder outlet obstruction 72 Regulation of prostate growth and development of benign prostatic hyperplasia (BPH) BPH is characterized by an increase in epithelial and stromal cell numbers (hyperplasia) in the pe ri-urethral area of the prostate. New epithelial gland formation is normally only seen duri ng fetal development. The develop- ment of new glands in the adult prostate has given rise to the concept of \200\230reawakening \200\231 of the inductive effect of the prostatic st roma on the prostatic epithelium. The increase in prostate cell number could re \202 ect proliferation of epithelial and str omal cells, impairment of programmed cell death, or a combination of both. During the early phases of development of BPH, cell proliferation occurs rapidly. In established BPH, cell proliferation slows down and there is impairment of programmed cell death (androgens and oe strogens actively inhibit cell death). The role of androgens in BPH Testosterone can bind directly to the androgen receptor or may be con- verted to a more potent form, dihydrotestosterone (DHT), by the enzyme 5 -reducta se (5AR). There are two isoforms of 5AR, type I or \200\230extraprostatic \200\231 5AR (wh ich is absent in prostatic tissue and present in, for example, skin and liver) and type II or \200\230prostatic \200\231 5AR (which is found exclusively on the nuclear membrane of s tromal cells, but not within prostatic epithelial cells). Type I 5AR is not inhibited by \201 nasteride whereas type II 5AR is. Dutasteride inhibits both types I and II 5AR. Finast eride reduces serum DHT by about 70% and dutasteride by about 95%. Finasteride reduces pros tatic DHT (type II) by about 80% and dutasteride by about 94%. We do not know whether these differences translate into differences in clinical ef \201 cacy since neither drugs has b een compared against the other. Testosterone diffuses into prostate and stromal epithelial cells. Within epithelial cells, it binds directly to the androgen receptor. In prostate stromal cells, a small proportion b inds directly to the androgen receptor, but the majority binds to 5AR (type II) on the nucl ear membrane, is con- verted to DHT, and then binds (with greater af \201 nity and, theref ore, greater potency than testosterone) to the androgen receptor in the stromal cell. Some of the DHT formed in the stromal cells diffuses out of these cells and into nearby epitheli al cells (a paracrine action). The androgen receptor/ testosterone or androgen receptor/DHT complex then binds to speci \201 c binding sites in the nucleus, thereby inducing transcr iption of androgen- dependent genes and subsequent protein synthesis.