Chapter 38: Urology

A basic understanding of genitourinary embryology facilitates learning many aspects of urology. Embryologically, the genital and urinary systems are intimately related. Associated anomalies of the two systems are commonly encountered.

The Kidneys

The kidneys pass through three embryonic phases (Figure 38–1): (1) The pronephros is a vestigial structure without function in human embryos that, except for its primary duct, disappears completely by the fourth week. (2) The pronephric duct gains connection to the mesonephric tubules and becomes the mesonephric duct. While most of the mesonephric tubules degenerate, the mesonephric duct persists bilaterally; from where it bends to open into the cloaca, the ureteral bud grows cranially to interact with the metanephric blastema. (3) This forms the metanephros, which is the final phase. The metanephros develops into the kidney. During cephalad migration and rotation, the metanephric tissue progressively enlarges, with rapid internal differentiation into the nephron and the uriniferous tubules. Simultaneously, the cephalad end of the ureteral bud expands and divides within the metanephros to form the renal pelvis, calices, and collecting tubules.

The Bladder & Urethra

Subdivision of the cloaca (the blind end of the hindgut) into a ventral (urogenital sinus) and a dorsal (rectum) segment is completed during the seventh week and initiates early differentiation of the urinary bladder and urethra. The urogenital sinus receives the mesonephric duct and absorbs its caudal end, so that by the end of the seventh week, the ureteral bud and mesonephric duct have independent openings. The ureteral orifice migrates upward and laterally. The mesonephric duct orifice moves downward and medially, and the structure in between (the trigone) is formed by the absorbed mesodermal tissue, which maintains direct continuity between the two tubes (Figure 38–2).

The fused müllerian ducts also meet the urogenital sinus at Müller’s tubercle. The urogenital sinus above Müller’s tubercle differentiates to form the bladder and the part of the prostatic urethra proximal to the seminal colliculus in the male or the bladder and the entire urethra in the female (Figure 38–3). Below Müller’s tubercle, the urogenital sinus differentiates into the distal part of the prostatic urethra and the membranous urethra in the male or the distal vagina and vaginal vestibule in the female. The rest of the male urethra is formed by fusion of the urethral folds on the ventral surface of the genital tubercle. In the female, the genital folds remain separate and form the labia minora.

The prostate develops at the end of the 11th week as several groups of outgrowths of urethral epithelium both above and below the entrance of the ejaculatory duct (distal vas deferens). The developing glandular element (seminal colliculus) incorporates the differentiating mesenchymal cells surrounding it to form the muscular stroma and capsule of the prostate. The seminal vesicles form as duplicate buds from the distal end of the mesonephric duct (vas deferens).

The Gonads

The potential to differentiate along male or female lines is present in every embryo initially. The development of one set of sex primordia and the gradual involution of the other are determined by the genetic sex of the embryo and differential secretion of numerous hormones. The SRY gene—or testis-determining factor—on the Y chromosome drives the gonad to differentiate into a testicle. Gonadal differentiation begins during the seventh week (Figure 38–3). If the gonad develops into a testis, the germinal epithelium progressively grows into radially arranged, cord-like seminiferous tubules. The production of müllerian-inhibiting factor by the testicle causes regression of the müllerian duct and acts in a local (paracrine) fashion so that only the ipsilateral müllerian duct is affected. The subsequent production of testosterone by the testicle leads to masculinization of the mesonephric (wolffian) duct structures (ie, epididymides, vas deferens, seminal vesicles, and ejaculatory duct). If the gonad develops into an ovary, it becomes differentiated into a cortex and a medulla; the cortex later differentiates into ovarian follicles containing ova. The lack of testosterone leads to the disappearance of the mesonephric duct.

The testes remain in the abdomen until the seventh month and then pass through the inguinal canal to the scrotum, following the path of the gubernaculum. The mechanism of descent remains uncertain. Lack of complete testicular descent is known as cryptorchidism; descent to an abnormal site beyond the external inguinal ring is known as testicular ectopia.

The ovary, which is attached to ligaments, undergoes internal descent to enter the pelvis.

In the female, the genital duct system develops from the müllerian ducts, which fuse at their caudal ends and differentiate into the uterine tubes, the uterus, and the proximal two-thirds of the vagina.

The external genitalia start to differentiate by the eighth week. The genital tubercle and genital swellings develop into the penis and scrotum in the male and the clitoris and labia majora in the female. The external genitalia are masculinized by dihydrotestosterone (DHT), which is created from testosterone under the influence of 5α-reductase.

With the breakdown of the urogenital membrane in the seventh week, the urogenital sinus achieves a separate opening on the undersurface of the genital tubercle. The expansion of the infratubercular part of the urogenital sinus forms the vaginal vestibule and the distal third of the vagina. The two folds on the undersurface of the genital tubercle unite in the male to form the penile urethra; in the female, they remain separate to form the labia minora.

The Kidneys

The kidneys lie retroperitoneally in the posterior abdomen and are separated from the surrounding renal fascia (Gerota’s fascia) by perinephric fat. The renal vascular pedicle enters the renal sinus; the vein is anterior to the artery, and both are anterior to the renal pelvis. The renal artery divides just outside the renal sinus into anterior and posterior branches that undergo further subdivisions with variable extents of distribution. They are end arteries and thus result in segmental infarction when occluded. The venous tributaries anastomose freely and usually drain into one renal vein.

The Renal Parenchyma

The renal parenchyma consists of more than 1 million functioning units (nephrons) and is divided into a peripheral cortex containing secretory elements and a central medulla containing excretory elements. The nephron starts as Bowman’s capsule, which surrounds the glomerulus and leads to elongated proximal and distal convoluted tubules with the loop of Henle in between, ending in a collecting duct that opens into a minor calix at the tip of a papilla.

The Renal Pelvis & Calices

The renal pelvis and calices are within the renal sinus and function as the main collecting reservoir. The pelvis, which is partly extrarenal and partly intrarenal (but occasionally is totally extrarenal or intrarenal), branches into three major calices that in turn branch into several minor calices. These calices are directly related to the tips of the medullary pyramids (the papillae) and act as a receiving cup to the collecting tubules. The pelvicaliceal system is a highly muscular structure; the fibers run in many directions and are directly continuous from the calices to the pelvis, allowing synchronization of contractile activity.

The Ureter

The ureter connects the renal pelvis to the urinary bladder. It is a muscularized tube; its muscle fibers lie in an irregular helical arrangement and function primarily in peristaltic activity. Ureteral muscle fibers are directly continuous from the renal pelvis cranially to the vesical trigone distally.

The blood supply to the renal pelvis and ureters is segmental, arising from multiple sources, including the renal, gonadal, and vesical arteries, with rich subadventitial anastomoses.

The Bladder

The bladder is primarily a reservoir with a meshwork of muscle bundles that not only change from one plane to another but also branch and join each other to constitute a synchronized organ. Its musculature is directly continuous with the urethral musculature and thus functions as an internal urethral sphincteric mechanism in spite of the lack of a true circular sphincter.

The ureters enter the bladder posteroinferiorly through the ureteral hiatus; after a short intravesical submucosal course, they open into the bladder and become continuous with the trigone, which is superimposed on the bladder base though deeply connected to it.

The Urethra

The adult female urethra is about 4 cm long and is muscular in its proximal four-fifths. This musculature is arranged in an inner longitudinal coat that is continuous with the inner longitudinal fibers of the bladder and an outer circular coat that is continuous with the outer longitudinal coat of the bladder. These outer circular fibers comprise the sphincteric mechanism. The striated external sphincter surrounds the middle third of the urethra.

In the male, the prostatic urethra is heavily muscular and sphincteric. The membranous urethra is within the urogenital diaphragm and is surrounded by the striated external sphincter. The penile urethra is poorly muscularized and traverses the corpus spongiosum to open at the tip of the glans.

The Prostate

The prostate surrounds the proximal portion of the male urethra; it is a fibromuscular, cone-shaped gland about 2.5 cm long and normally weighing about 20 g in the adult. It is traversed from base to apex by the urethra and is pierced posterolaterally by the ejaculatory ducts from the seminal vesicles and vas deferens that converge to open at the verumontanum (seminal colliculus) on the floor of the urethra.

The prostatic glandular elements drain through about 12 paired excretory ducts that open into the floor of the urethra above the verumontanum. The prostate is surrounded by a thin capsule, derived from its stroma, which is rich in musculature, and part of the urethral musculature and the sphincteric mechanism. A rich venous plexus surrounds the prostate, especially anteriorly and laterally. Its lymphatic drainage is into the hypogastric, sacral, obturator, and external iliac lymph nodes.

The Testis, Epididymis, & Vas

The testis is a paired organ surrounded by the tunica albuginea and subdivided into numerous lobules by fibrous septa. The extremely convoluted seminiferous tubules gather to open into the rete testis, where they join the efferent duct and drain into the epididymis. The epididymis drains into the vas deferens, which courses through the inguinal canal into the pelvis and is joined by the duct from the seminal vesicle to form the ejaculatory duct, which opens before opening into the prostatic urethra on either side of the verumontanum.

Arterial supply is via the spermatic, vas deferential, and external cremasteric arteries. Venous drainage is through the pampiniform plexus, which drains into the internal spermatic veins; the right spermatic vein joins the vena cava, and the left joins the renal vein.

Testicular lymphatics drain into the retroperitoneal lymph nodes; the right primarily into the interaortocaval area, the left into the para-aortic area, both just below the renal vessels.

The Kidneys

The kidneys maintain and regulate homeostasis of body fluids by glomerular filtration, tubular reabsorption, and tubular secretion.

A. Glomerular Filtration

This mechanism is dependent on glomerular capillary arterial pressure minus plasma colloid osmotic pressure plus Bowman’s capsular resistance. The resultant glomerular filtration pressure (about 8-12 mm Hg) forces protein-free plasma through the capillary filtering surface into Bowman’s capsule. Normally, about 130 mL of plasma is filtered every minute through the renal circulation; the entire volume of plasma recirculates through the kidney and is subjected to the filtration process once every 27 minutes.

B. Tubular Reabsorption

About 99% of the filtered volume is reabsorbed through the tubules, together with all the valuable constituents of the filtrate (chlorides, glucose, sodium, potassium, calcium, and amino acids). Urea, uric acid, phosphates, and sulfates are also reabsorbed to varying degrees. The process of reabsorption is a combination of active and passive transport mechanisms. Reabsorption of water and electrolytes is under the control of adrenal, pituitary, and parathyroid hormones.

C. Tubular Secretion

Tubular secretion helps (1) to eliminate certain substances and thus maintain their plasma levels and (2) to exchange valuable ions from the filtrate for less desirable ions in the plasma (eg, a sodium ion from the urine for a hydrogen ion in the plasma). Failure of adequate secretory function leads to the acidosis commonly encountered in chronic renal disease.

The Ureteropelvicaliceal System

This system is one continuous tubular structure with a syncytial type of smooth musculature that is imperceptibly in motion from one segment to the other. Waves of peristaltic contractions start from the calices and are propagated along the smooth muscle cells to the renal pelvis. At normal urine flow rates, many of these contraction waves are terminated at the ureteropelvic junction; however, some are transmitted to the ureter and down toward the urinary bladder. These peristaltic waves occur at a rate of about 5-8/min, involve a 2-cm to 3-cm segment at a time, and usually proceed at the velocity of 3 cm/s. Frequency, amplitude, and velocity are influenced by urine output and flow rate. In a state of diuresis, there may be a 1:1 relationship between caliceal contractions and ureteral contractions. Ureteral filling is primarily passive and occurs by reception of a bolus of urine from a renal pelvis contraction. The ureteropelvic junction closes after passing a bolus of urine, preventing back-pressure and back-flow of urine into the renal pelvis secondary to the elevated ureteral contraction pressure. A contraction ring forms in the proximal ureter, and as it migrates down the ureter, it pushes the bolus of urine antegrade. In states of diuresis, the size of the bolus increases and the pressure in the bolus may be greater than the pressure in the contraction ring ahead of it. In this case, the ureteral walls cannot coapt, and urine is transported as an uninterrupted column of fluid.

The Ureterovesical Junction

The ureterovesical junction allows flow of urine from the ureter to the bladder and at the same time prevents retrograde flow. The continuity and the specific muscular arrangement of the intravesical ureter and the trigone provide a muscularly active valvular mechanism that can efficiently adapt itself to the variable phases of bladder activity during filling and voiding.

The normal resting pressure of the ureterovesical junction (10-15 cm H₂O) is greater than the more cephalad ureteral resting pressure (0-5 cm H₂O). Progressive bladder filling leads to firm occlusion of the intravesical ureter against retrograde urine flow and to increased resistance to antegrade flow resulting from trigonal stretching. During voiding, trigonal contraction completely seals the intravesical ureter against any antegrade or retrograde flow of urine.

The Urinary Bladder

The urinary bladder functions primarily as a reservoir that can accommodate variable volumes without increasing its intraluminal pressure. When the bladder reaches full capacity, the detrusor muscle voluntarily contracts following relaxation of the external sphincter and maintains its contraction until the bladder is completely empty. Funneling of the bladder outlet with progressive downward movement of the dome ensures complete emptying.

The vesical sphincteric mechanism is primarily a smooth muscle sphincter in the bladder neck and male prostatic urethra and in the proximal four-fifths of the female urethra. There is no purely circular sphincteric entity, but there are abundant circularly oriented smooth muscle fibers that are directly continuous with the outer coat of the detrusor muscles. The sphincter has an abundance of alpha receptors that respond to sympathetic neural input from the pelvic nerve to maintain urethral closure. Parasympathetic input from the pelvic nerve facilitates bladder contracture and voiding.

There is a voluntary striated muscle sphincter that is part of the urogenital diaphragm and surrounds the mid urethra in the female and the membranous urethra in the male. It responds to somatic neural input from the pudendal nerve. It is essential for continence when the internal sphincter is nonfunctional. Its pathologic irritability or spasticity can lead to obstructive manifestations.

Genitourinary tract anomalies constitute about one-third of all congenital abnormalities and occur in over 10% of the population. The severity varies from lesions incompatible with life to insignificant findings detected during diagnostic studies for unrelated reasons. The anatomic abnormalities are often not intrinsically harmful, yet they may predispose to infection, stone formation, or chronic renal failure.

RENAL ANOMALIES

Bilateral absence of the kidneys is rare and is associated with oligohydramnios, Potter facies, and pulmonary hypoplasia. It occurs more often in males and results in death shortly after birth. Unilateral renal agenesis is seen more often but is not usually associated with illness. Renal agenesis is thought to be due to both lack of a ureteral bud and lack of subsequent development of the metanephric blastema. The trigone is absent on the affected side. Because adrenal gland development is unrelated to kidney development, both adrenals are usually present in the normal position. Rarely, more than two kidneys are seen, a condition clearly dissimilar to ureteral duplication, as described later.

Abnormal ascent of the metanephros leads to an ectopic kidney, which may be unilateral or bilateral. Lumbar, pelvic, and the less common thoracic and crossed ectopic varieties are seen. Ectopic kidneys are associated with genital anomalies in 10%-20% of cases. Fusion abnormalities are also associated with failure of normal ascent and include fused pelvic kidneys and horseshoe kidneys (the most common), which are typically fused at the lower poles. Intravenous urography typically establishes the diagnosis. The relationship of the kidneys to the psoas muscles is abnormal: Instead of an oblique orientation with the medial border of the kidney parallel to the psoas muscle, the kidneys are vertical and the medial border intersects and crosses the psoas muscle. Horseshoe kidneys have an elevated incidence of vesicoureteral reflux and are at increased risk of ureteropelvic junction obstruction (UPJO). The latter may be related to a high ureteral insertion in the renal pelvis, crossing of the ureter over the isthmus, or compression by one of many anomalous arteries. Failure of rotation during ascent results in “malrotated” kidneys and is rarely significant.

Polycystic Kidneys

Parenchymal anomalies include a variety of cystic and dysplastic lesions. Polycystic kidney disease is hereditary and bilateral. The autosomal recessive polycystic kidney disease (ARPKD), previously called infantile PKD, has numerous small cysts that arise only from the collecting ducts and result in bilateral symmetrical enlargement of the kidneys. The autosomal dominant ADPKD, previously called adult PKD, has cysts arising from all areas of the nephron, which are usually larger and more variable in size than the ARPKD cysts. ARPKD occurs in 1 in 40,000 births and may be detected in utero by the presence of enlarged hyperechogenic kidneys and oligohydramnios. Infants usually die of respiratory failure rather than renal problems; however, the 1-year survival probability after the first month is over 85%. These children have declining renal function as well as severe hypertension and hepatic periportal fibrosis with portal hypertension leading to hypersplenism and esophageal varices.

The genes mutated in ADPKD may include the PKD1 gene (located on chromosome 16p13.3) in 85% of patients or the PKD2 gene (on chromosome 4q21-23) in 12%-15% of patients. These genes code for the polycystin-1 and polycystin-2 proteins, respectively. ADPKD occurs in 1 in 1000 individuals and is a major cause of end-stage renal disease in adults. Cysts may also be present in the liver, pancreas, and spleen, and cerebral arterial aneurysms may occur. Renal cystic enlargement exerts pressure on normal parenchyma, leading to its gradual destruction and glomerulosclerosis.

The diagnosis is often made during a workup for hypertension or uremia discovered in the third to sixth decades. Hematuria with or without flank pain is a common finding. An intravenous urogram reveals the enlarged kidneys, with marked elongation of the calices, which are compressed by large cysts. Ultrasonography or CT scan readily makes the diagnosis.

Surgery is rarely warranted. Therapy is medical and ultimately includes dialysis. The median age for reaching end-stage renal disease is 54 years in PKD1 and 74 years in PKD2. Renal transplantation is often indicated, though potential family donors must be carefully screened to determine whether they have the same disorder. The leading cause of death in ADPKD is cardiovascular disease, which may relate to early untreated hypertension.

Medullary Sponge Kidney

Medullary sponge kidney results from collecting tubular ectasia (see section on Polycystic Kidneys) and is associated with recurrent urolithiasis and an increased incidence of infection in 50% of patients. The lesion is often bilateral and may involve all of the calices. Intravenous urograms reveal dilated collecting tubules as a “blush” in the renal papilla. Microscopic hematuria is common. Specific antibiotics should be given for documented infections, and prophylactic therapy for renal stones should be recommended on the basis of metabolic stone evaluation.

Simple Renal Cysts

Simple renal cysts are common (approximately 50% after age 50) and are thought to arise from tubular dilation. They may be solitary or bilateral and multiple. They rarely have pathologic significance except in the differentiation from solid renal masses. (See the section on Renal Adenocarcinoma.)

Multicystic Dysplastic Kidney

Multicystic dysplastic kidney is a congenital abnormality consisting of macroscopic cysts of variable sizes compressing dysplastic renal parenchyma. It is usually associated with an atretic proximal ureter. The disorder occurs in about 1 in 3000 live births and is frequently noted on prenatal ultrasound. Rarely, it may occur bilaterally and is associated with oligohydramnios and renal failure. It may be distinguished from other causes of hydronephrosis by the absence of any renal function on renal scan. There is an increased incidence of contralateral UPJO (5%-10%) and reflux (18%-43%), either of which increases the patient’s risk of subsequent chronic renal insufficiency.

The chance of developing a malignancy in multicystic dysplastic kidney appears to be no greater than 1 in 2000. There may also be an increased incidence of hypertension. These two factors constitute a rationale for treatment by nephrectomy. However, conservative management with routine ultrasound examinations at intervals of 6-12 months is reasonable practice, since about half involute within 5 years.

Renal Vascular Abnormalities

Multiple renal arteries occur in 15%-20% of patients and are significant only when they cause UPJO. Congenital renal artery aneurysms are infrequent; they are differentiated from acquired lesions by their location at the bifurcation of the main renal artery or at a distal branch point. The lesions are usually asymptomatic, but they can cause hypertension. They require surgical treatment only if hypertension is uncontrolled, if they are incompletely calcified, or if they have a diameter of more than 2.5 cm. Congenital arteriovenous fistulas are rare but may result in hematuria, hypertension, or cardiac failure necessitating operative treatment.

Renal Pelvis Anomalies

UPJO is the most common cause of antenatal hydronephrosis. The condition may be associated with compression by anomalous renal arteries or intrinsic stenosis of the junction. The diagnosis is not uncommonly made when gross hematuria follows minor trauma. Symptoms include intermittent flank pain, particularly with orally induced diuresis. There is a bimodal age at presentation, with an initial peak in infancy and a secondary presentation in early adulthood. Renal ultrasound provides a safe screening technique in patients suspected of having UPJO. Diuretic renal scan may confirm the diagnosis and suggest functional significance. Intravenous pyelogram or retrograde pyelography may further define the anatomy. Bilaterality is not uncommon, and the condition requires surgical repair if symptomatic or severe. With the advent of laparoscopic and robotic surgery, minimally invasive repair of UPJO with dismemebered pyeloplasty has become standard of care. Success rates with pyeloplasty are superior to endoscopic approaches in the primary setting. Percutaneous or ureteroscopic incision of the obstruction with short-term stenting has been successful in adults, but endoscopic incision is most useful in the setting of recurrent UPJO, when redo pyeloplasty becomes much more difficult, or when patients are poor surgical candidates due to comorbidities.

URETERAL ANOMALIES

Congenital Obstruction of the Ureter

Congenital obstruction of the ureter may be due to ureterovesical and UPJO or to neurologic deficits such as sacral agenesis or myelomeningocele. Functional ureteral obstruction—also known as primary obstructive megaureter—is not uncommon. Symptoms are renal pain during diuresis or resulting from pyelonephritis. Excretory urograms depict dilation above the obstruction. Vesicoureteral reflux is uncommonly associated with megaureter. Milder forms without symptoms or significant hydronephrosis are the rule and do not require treatment if renal function is normal. When treatment is necessary, it consists of division of the ureter proximal to the obstruction and reimplantation of the ureter into the bladder, often involving ureteral tapering or plication.

Duplication of Ureters

Bifurcation of the ureteral bud before it interacts with the metanephric blastema results in incomplete ureteral duplication, commonly in the mid or upper ureter. A second ureteral bud from the metanephric duct leads to complete ureteral duplication (Figure 38–4; right kidney) draining one kidney. This represents the most common ureteral anomaly, occurring in 1 in 125 people. It occurs twice as often in females. The presence of more than two ureters on each side is not common, but bilaterality of ureteral duplication occurs in 40%. Usually, all of the duplicated ureters enter the bladder; the ureter draining the upper pole of the kidney enters closest to the bladder neck (due to its later reabsorption into the bladder). Because of this relationship, the ureter draining the lower pole often has a short intramural tunnel and an inadequate surrounding musculature and is thus prone to vesicoureteral reflux. The ureter draining the upper pole may be ectopic (because of its late absorption) and thus empty into the bladder neck, urethra, or genital structures (vagina or vestibule in the female and seminal vesicle or vas deferens in the male [Figure 38–4; left kidney]). The ureter draining the upper pole is prone to obstruction and may be associated with a ureterocele, which is a common cause of obstruction. Duplication becomes significant when hydronephrosis or pyelonephritis occurs. The diagnosis is made by intravenous urography. Ureteral reimplantation to prevent recurrent infection is necessary in some cases. An anastomosis between the upper pole renal pelvis and the lower pole ureter or a low ureteroureterostomy are alternatives in selected cases. The upper pole of the kidney and its ureter may require removal if obstruction is severe and renal function of that segment is poor.

Ectopic Ureteral Orifice

Ureteral ectopia can occur in the absence of duplication and drain into any of the abnormal positions mentioned previously. If the orifice lies proximal to the external urinary sphincter, no incontinence ensues, but vesicoureteral reflux is common. In contradistinction to the female, the ectopic orifice in the male never lies distal to the external sphincter, making incontinence an extremely rare presentation. Should the ectopic orifice in the female drain into the vagina or at the vestibule, there may be continuous leakage of urine apart from voiding. Most ectopic orifices involve the ureter draining the upper pole of a duplicated system, and most are observed in females. Hydroureteronephrosis of the involved segment frequently occurs due to ureteral obstruction as it traverses the muscle of the bladder neck.

An ectopic orifice may be seen beside the urethral orifice or in the roof of the vagina on endoscopy. Renal ultrasound or intravenous urograms often demonstrates hydroureteronephrosis of the upper renal segment. Cystography may show reflux into the ectopic orifice but may require cyclic voiding first to decompress the obstructed segment with bladder neck relaxation and subsequently to permit reflux. In the rare case when there is significant upper pole renal function, the ureter can be divided and reimplanted into the bladder or lower pole ureter. Usually, however, heminephroureterectomy is necessary.

Ureterocele

A ureterocele is a ballooning of the distal submucosal ureter into the bladder. This structure commonly has a pinpoint orifice and therefore leads to hydroureteronephrosis. If large enough, it may obstruct the vesical neck or the contralateral ureter. It is most common in females with ureteral duplication and always involves the ureter draining the upper renal pole.

Most ureteroceles are now detected by prenatal ultrasound. Symptoms are usually those of pyelonephritis or obstruction. Intravenous urograms may show a negative shadow in the bladder cast by the ureterocele. The ureter and renal calices may be normal or may reveal marked dilation or no excretory function at all. A cystogram may show reflux into the ipsilateral lower pole ureter.

Treatment of ureteroceles depends on multiple factors, including the presence or absence of reflux in any or all of the ureters as well as whether or not the ureterocele is completely contained within the bladder (intravesical/orthotopic) or if a portion is at the bladder neck or urethra (extravesical/ectopic). A simple method of establishing drainage involves cystoscopy and puncture of the ureterocele. Associated reflux, if present, can be managed with prophylactic antibiotics until the child has grown larger, at which time a technically easier ureteral reimplant may be performed with a decompressed ureter. In the relatively uncommon situation when there is no associated reflux, an upper pole heminephrectomy is considered. Minimally obstructive ureteroceles within the bladder in adults do not require treatment.

VESICOURETERAL REFLUX

The main function of the ureterovesical junction is to permit free drainage of the ureter and simultaneously prevent urine from refluxing back from the bladder. Anatomically, the ureterovesical junction is well equipped for this function, because the ureteral musculature continues uninterrupted into the base of the bladder to form the superficial trigone. Additionally, the terminal 4-5 cm of ureter are surrounded by a musculofascial sheath (Waldeyer’s sheath) that follows the ureter through the ureteral hiatus and continues in the base of the bladder as the deep trigone (Figure 38–5).

Direct continuity between the ureter and the trigone offers an efficient, muscularly active, valvular function. Any stretch of the trigone (with bladder filling) or any trigonal contraction (with voiding) leads to firm occlusion of the intravesical ureter, thus increasing resistance to flow from above downward and sealing the intravesical ureter against retrograde flow (Figure 38–6).

Etiology & Classification

Vesicoureteral reflux may be classified as primary reflux due to developmental ureterotrigonal weakness or associated with ureteral anomalies such as ectopic orifice or ureterocele, and secondary reflux due to bladder outlet or urethral obstruction, neuropathic dysfunction, iatrogenic causes, and inflammation, especially specific infection (eg, tuberculosis). Primary reflux is associated with some degree of congenital muscular deficiency in the trigone and terminal ureter.

Reflux is associated with an increased incidence of pyelonephritis and renal damage. It also allows bacteria free access from the bladder to the kidney.

Reflux is the most common cause of pyelonephritis and is found in 30% to 50% of children presenting with urinary tract infection. It is present in over 75% of patients with radiologic evidence of chronic pyelonephritis and is responsible for end-stage renal disease in a large percentage of patients requiring chronic dialysis or renal transplantation.

In primary reflux, the child (on average, between 2 and 3 years of age) usually presents with symptoms of pyelonephritis or cystitis. Vague abdominal pain is not uncommon. Renal pain and pain with voiding are relatively uncommon. On rare occasions, the patient may present with advanced renal failure with bilateral renal parenchymal damage. Significant reflux and its sequelae are more common in females and are usually detected after a urinary tract infection. About one-third of the siblings of a child with reflux will also have reflux, and one-half of the children of a mother with reflux will also have reflux.

In secondary reflux, manifestations of the primary disease (neuropathic, obstructive, etc) are usually the presenting symptoms.

Clinical Findings

A. Symptoms and Signs

With acute pyelonephritis, fever, chills, and costovertebral angle tenderness may be present. Children usually do not have renal pain but may complain of vague abdominal pain. Occasionally, daytime frequency, incontinence, or enuresis may be caused by infection associated with reflux. In cases of obstruction or neuropathic deficit, a palpable hydronephrotic kidney or a distended bladder may be found. The diagnosis may be elusive in infants who present with ill-defined symptoms.

B. Laboratory Findings

Urinalysis usually reveals evidence of infection (pyuria and bacteriuria). Urine cultures are mandatory when infection is suspected. Renal function tests may be abnormal if reflux and infection have caused renal scarring.

C. Imaging Studies

The most useful study for conclusive diagnosis of reflux continues to be voiding cystourethrography (Figure 38–7). This study demonstrates the grade of reflux as well as the urethral anatomy. Radionuclide voiding studies are extremely sensitive at detecting reflux but do not demonstrate the anatomic detail seen with a voiding cystourethrogram. Radionuclide voiding studies are often performed as follow-up after an initial voiding cystourethrogram because they offer the advantage of decreased radiation exposure.

Radioisotopic renal scanning provides accurate differential renal function data and detection of renal scars. Ultrasound can provide accurate measurement of renal size and may demonstrate the presence of renal scarring and ureteral or caliceal dilation. In many cases, there may be no abnormality visible in the upper urinary tract, or only mild distal ureteral dilation may be seen.

D. Urodynamic Considerations

A significant number of children with dysfunctional voiding present with urinary tract infections and are subsequently found to have reflux. These children contract the bladder against a closed external sphincter. Elevated voiding pressures associated with dysfunctional voiding may increase renal damage with an associated urinary tract infection and may also lessen the chance for either spontaneous or surgical resolution of reflux. When the history suggests the possibility of voiding dysfunction (incontinence, frequency, urgency), urodynamic studies are conducted to evaluate the voiding dynamics. Treatment of voiding dysfunction may result in resolution of the reflux.

Treatment

Although some children with lower grades of reflux may not require antibiotics, traditionally any child with reflux was maintained on prophylactic antibiotics to attempt to decrease the incidence of urinary tract infections. Several recent studies suggest that the practice of daily antibiotic prophylaxis in all children with reflux may be of limited benefit in preventing urinary tract infection. Prompt treatment of pyelonephritis prevents renal scar formation. Factors causing secondary reflux—such as dysfunctional voiding or obstruction—should be corrected.

In many children, reflux resolves with time. Reflux is graded as seen on voiding cystourethrography as follows:

Grade I: Contrast enters ureter

Grade II: Contrast enters the renal collecting system

Grade III: Slight dilation of the calices or ureter

Grades IV and V: Progressively increased amounts of caliceal dilation and ureteral dilation or tortuosity

Reflux most likely to resolve is of lower grade or detected at a younger age. Over 70% of children with grades I, II, or unilateral grade III reflux will have resolution within 5 years. Resolution in children with grade V or bilateral grade IV reflux can be anticipated in less than 10% of cases. Other factors that appear to negatively affect the chance for reflux resolution include early reflux during bladder filling, presentation with a febrile urinary tract infection, renal scars, and voiding dysfunction.

In obstructive secondary reflux (eg, posterior urethral valves), release of obstruction may cure reflux. Occasionally, surgical reimplantation is still required. In neuropathic reflux, intermittent catheterization for control of infection may allow return of valvular competence. However, many cases require bladder augmentation for a noncompliant bladder and ureteral reimplantation. In reflux associated with ectopic orifices, duplication with ureterocele, and other congenital malformations, reimplantation is generally required.

The aim of surgery is to correct the reflux. This is accomplished by the creation of a longer submucosal tunnel for the ureter. With bladder filling and increased pressure, the ureter is compressed between the mucosa and underlying detrusor muscle. This flap valve prevents reflux of urine. The necessary length of the tunnel to stop reflux depends on the diameter of the ureter, with a 5:1 length-to-diameter ratio being ideal. One of three methods is used in most cases: (1) in suprahiatal repair (Politano-Leadbetter procedure), a new ureteral hiatus is developed about 2.5 cm above the original one, and the ureter—after passing through a submucosal tunnel—is sutured to the cut edge of the trigone at the level of the original orifice. (2) In the cross-trigonal repair (Cohen procedure), the original hiatus is maintained, and the ureter is advanced through a submucosal tunnel, extending across the trigone to the contralateral bladder wall. (3) A totally extravesical ureteral advancement procedure (extravesical ureteroplasty) achieves results similar to those achieved with the intravesical methods, with a shorter hospital stay and shorter convalescence.

Injections of subureteric bulking agents have also been used to increase submucosal support of the ureter. With proper placement beneath the ureteral orifice under endoscopic vision, these injections act to bolster the deficient antireflux mechanism. Concern regarding late sequelae of Teflon injections (eg, particle migration) has prevented use of this approach in the United States. Currently, hyaluronic acid/dextranomer (NASHA/Dx) gel (Deflux) is the only FDA-approved material for endoscopic injection to manage vesicoureteral reflux in children. Short-term success in stopping reflux with the injection techniques appears to be around 75% overall, with most success with grades I-III reflux. The long-term success rates still need to be evaluated, as many studies only have short term (ie, 3 month) follow up.

Prognosis

The long-term prognosis is excellent for patients with mild to moderate reflux successfully treated with antibiotic prophylaxis. There are few instances of recurrent infection or renal insufficiency. Patients with more significant reflux or persistent urinary tract infections may benefit from subureteric injection or surgical reimplantation; the success rate is approximately 95% with the open surgical technique (cessation of reflux, clearance of renal infection, and absence of obstruction). Unfortunately, for patients with advanced disease (irreversible ureteral decompensation and severe bilateral scars), the prognosis is less favorable. These patients account for a significant proportion of patients with end-stage renal disease who ultimately require chronic dialysis, renal transplantation, or both.

BLADDER ANOMALIES

Anomalies of the bladder are infrequent and include the following: (1) agenesis, or complete absence, which results in a persistent cloaca; (2) bladder duplication, which may be complete, with separate ureteral openings drained by duplicated urethras, or incomplete, with a septum or hourglass deformity; and (3) urachal anomalies, which in the most severe forms appear as a patent opening at the umbilicus and are usually associated with some form of bladder outlet obstruction. In less severe forms, a urachal diverticulum may be present at the dome of the bladder or a urachal cyst along the course of the partially obliterated urachus. These latter conditions may cause abdominal pain and umbilical or bladder infection requiring surgical treatment. Occasionally, adenocarcinoma develops in a urachal remnant (see section on Tumors of the Bladder).

Failure of cloacal division results in a persistent cloaca. Incomplete division is more frequent (though still rare) and results in a rectovesical, rectourethral, or rectovestibular fistula (usually with imperforate anus or anal atresia).

Exstrophy of the Bladder

Exstrophy of the bladder is the most severe bladder anomaly—the result of a complete ventral defect of the urogenital sinus and the overlying inferior abdominal wall musculature and integument. The lower central portion is devoid of skin and muscle. The anterior bladder wall is absent, and the posterior wall is contiguous with surrounding skin. Urine drains onto the abdominal wall, the rami of the pubic bones are widely separated, and the open pelvic ring may affect gait. In males, the penis is shortened and the urethra is epispadiac. The exposed bladder mucosa tends to be chronically inflamed.

Currently, the favored treatment is bladder salvage, which includes closure of the bladder in the newborn period. Urethral closure and penile reconstruction have also been advocated at the time of the initial bladder closure. Ureteral obstruction or vesicoureteral reflux may develop and require ureteral reimplantation. The closed bladder may have a small capacity, and incontinence is often a complication. Patients frequently require multiple operations, including bladder augmentation and bladder neck reconstruction. Good results have been observed in more than half of all patients treated, with preservation of renal function and continence.

Prune Belly Syndrome

Prune belly syndrome consists of a triad of abnormalities: deficient abdominal wall musculature, bilateral cryptorchidism, and variable amounts of dilation of the urogenital tract. The cause is not known. Almost all children with prune belly syndrome have reflux. The incidence of eventual renal failure is 25%-30%. Risk factors for renal failure include bilateral abnormal kidneys on ultrasound or renal scan, a serum creatinine that never falls below 0.7 mg/dL, and clinical pyelonephritis. These children are managed with prophylactic antibiotics and frequent urine cultures, followed by prompt treatment of any urinary tract infections. Abdominoplasty may be performed to help correct the abdominal wall defect.

Congenital Neurovesical Dysfunction

Congenital neurovesical dysfunction frequently accompanies a posterior myelomeningocele or sacral agenesis, with associated spinal abnormalities. Both conditions may result in incontinence and recurrent urinary infection with late sequelae (ureteral reflux, pyelonephritis, and renal failure). These children require frequent evaluation of their kidneys and kidney function because high bladder storage pressures may harm the kidneys.

PENILE & URETHRAL ANOMALIES

Hypospadias

Hypospadias results from failure of fusion of the urethral folds on the undersurface of the genital tubercle. The urethral meatus is ventrally displaced on the glans on the shaft of the penis or more proximal at the level of the scrotum or perineum. With more proximal displacement, chordee (ventral curvature of the penile shaft) frequently occurs and requires treatment, or it precludes straight erections and normal intercourse (Figure 38–8). The midscrotal hypospadiac penis may resemble female external genitalia with an enlarged clitoris and labia. Sexual assignment in these latter infants requires hormonal and chromosomal analysis.

In hypospadias with the meatus positioned proximal to the corona, the prepuce is abnormal—not forming a complete cylinder due to a ventral defect. Circumcision should not be done in these patients, as the prepuce can be used later in surgical repair.

The degree of hypospadias dictates the need for repair. If the opening is glandular or coronal (85% of patients), the penis is usually functional both for micturition and procreation, and repair is done primarily for cosmetic reasons. Openings that are more proximal on the shaft require correction to allow voiding while standing, normal erection, and proper sperm deposition during intercourse. Surgical plastic repair of hypospadias is currently accomplished by a variety of highly successful one-stage operations and is routinely performed between 6 and 18 months of age. The most common complications of hypospadias surgery include meatal stenosis and fistula formation; however, improved techniques have decreased the incidence of these complications.

Epispadias

Epispadias is a rare congenital anomaly that is commonly associated with bladder exstrophy. When it occurs alone, it is considered a milder degree of the exstrophy complex.

The urethra opens on the dorsum of the penis, with deficient corpus spongiosum and loosely attached corpora cavernosa. If the defect is extensive, it may extend to the bladder neck, causing incontinence because of deficient sphincter muscles. The pubic bones are separated, as in exstrophy. Marked dorsiflexion of the penis is usually present.

Treatment consists of correction of penile curvature, reconstruction of the urethra, and reconstruction of the bladder neck in incontinent patients.

Urethral Strictures

Congenital urethral strictures are rare but when present are most common in the fossa navicularis (just proximal to the meatus) and in the bulbomembranous urethra. Commonly, these strictures are thin diaphragms that may respond to simple dilation or to direct vision internal urethrotomy. Rarely is open surgical repair necessary. Congenital urethral strictures in girls and meatal stenosis in boys are uncommon. When the latter does occur, it appears to be acquired, as it is seen only in circumcised boys.

Urethral Diverticulum

In males, urethral diverticula are nearly always in the pendulous or bulbous urethra. They are often associated with an obstructive flap of the urethral mucosa (anterior urethral valve), thought to represent incomplete closure of the urethral folds. Treatment by endoscopic unroofing is usually successful, though most diverticula are small and require no therapy. In females, they occur in adult life and are usually manifested by irritative symptoms and recurrent infection. The cause is unknown, but the disorder is most likely congenital. Treatment is usually by transvaginal excision. Diverticula may occasionally harbor stones or tumors.

Posterior Urethral Valves

Posterior urethral valves are the most common obstructive urethral lesion in newborn and infant males and the most common cause of end-stage renal disease in boys. They consist of obstructive folds of mucosa, which originate at or are attached at some point to the verumontanum in the prostatic urethra. The embryologic derivation is indefinite. They are partially obstructive and thus lead to variable degrees of back-pressure damage to the urinary bladder and upper urinary tract. Dilation and obstruction of the prostatic urethra are always present. Spontaneous urinary ascites from the kidneys is often seen in neonates. This clears when the obstruction is relieved.

About one-third of children with posterior urethral valves are now diagnosed by prenatal ultrasound. Another one-third are diagnosed in the first year of life, with the remaining third presenting later. Clinical manifestations consist of difficult voiding, a weak urinary stream, and a midline lower abdominal mass that represents a distended bladder. In some cases, the kidneys are palpable and the child may have signs and symptoms of uremia and acidosis. Urinary incontinence and urinary tract infection may occur. Laboratory findings include elevated serum urea nitrogen and creatinine and evidence of urinary infection. Ultrasound shows evidence of bladder thickening and trabeculation, hydroureter, and hydronephrosis. Demonstration of urethral valves on a voiding cystourethrogram establishes the diagnosis, as does endoscopic identification of valves. Up to 70% of children with valves may have vesicoureteral reflux.

Treatment consists of destruction of the valves by endoscopic incision. In a premature infant with a small urethra prohibiting transurethral resection, a temporary cutaneous vesicostomy may be required to provide drainage and improve impaired kidney function.

The prognosis depends on the original degree of kidney damage and the success of efforts to prevent or treat infection. Rates of chronic renal failure or end-stage renal disease range from 25% to 67% of boys with valves. Poor prognostic factors include the presence of bilateral reflux or an elevated nadir serum creatinine in the first year of life. Many of these children have delayed development of urinary continence due to bladder changes and impaired urinary concentration.

SCROTAL & TESTICULAR ANOMALIES

Testicular Torsion

Neonatal testicular torsion (extravaginal torsion) is an extremely rare condition. The entire testicle and the tunica vaginalis are twisted. No trigger mechanism associated with the torsion has been identified. Although the vast majority are necrotic and nonsalvageable, several studies have reported salvage of testicular tissue when torsion is detected immediately following birth. Any scrotal swelling in the neonate requires close follow-up. Intravaginal testicular torsion in adolescents is described later in this chapter.

Scrotal Lesions

Congenital scrotal lesions include hypoplasia of the scrotum (unilateral or bilateral) in association with cryptorchidism and bifid scrotum with extensive hypospadias. Midline inclusion cysts may also occur.

CRYPTORCHIDISM

Etiology & Classification

True undescended testicles stop along the normal path of descent into the scrotum. They may remain in the abdominal cavity (least common), in the inguinal canal (canalicular), or just outside the external ring (suprascrotal, most common). Testes may also pass through the external ring and then be located ectopically, most commonly in a superficial inguinal pouch. The incidence of undescended testicles increases from 3% to 5% in full-term infants to 30% in premature infants. Most undescended testicles descend within the first 6 months of life, and by 1 year of age the prevalence is 1%. The left testicle is affected more often, and 1%-2% of children with cryptorchidism will have both testicles affected. Twenty percent of boys who present with cryptorchidism have one nonpalpable testis. Of nonpalpable testes, 20% are intra-abdominal; 40% are canalicular, scrotal, or ectopic testes; and 40% are atrophic or absent.

Clinical Findings

The diagnosis of cryptorchidism relies on physical examination. Absence of an identifiable testicle with ultrasound, computed tomography, or magnetic resonance imaging (MRI) does not prove testicular agenesis and therefore does not alter the need for surgical exploration. Testicular examination in the infant and young child requires two hands, with the first hand being swept from the anterior iliac spine along the inguinal canal to gently express any retained testicular tissue into the scrotum, which is palpated with the other hand. A true undescended or ectopic inguinal testis may slip or “pop” under the examiner’s fingers. To distinguish a retractile testicle, the testicle is brought into the scrotal position, holding it in place for a minute to fatigue the cremaster muscle. After this, a retractile testicle remains in the scrotum, whereas an ectopic or undescended testis immediately snaps back out of the scrotum. If a testis cannot be palpated in the inguinal canal or the scrotum, or in the typical ectopic sites, evaluation for a nonpalpable testis must be performed.

A child with bilateral nonpalpable testes should undergo hormonal evaluation for testicular absence. Elevations in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and absence of detectable müllerian-inhibiting substance suggest testicular absence. Testicular absence is confirmed by a negative human chorionic gonadotropin (hCG) stimulation test. The hCG stimulation test is performed by the administration of intramuscular hCG (2000 IU/day for 3-4 days). Raised gonadotropin levels (FSH and LH) and a lack of a testosterone rise from hCG indicate bilateral absent testes, and a formal surgical exploration is unnecessary. When one or both components are lacking or there is detectable müllerian-inhibiting substance, surgical exploration is warranted.

Surgical Therapy

Treatment of the undescended testicle offers the possibility of improved fertility, correction of patent processus vaginalis, prevention of testis torsion, and improvement in body image. There is controversy whether orchidopexy decreases the risk of malignancy, but placement of an undescended testicle in the scrotum assists physical examination of the testis. Histologic changes related to infertility occur in the undescended testicle as young as 1 year of age, and spontaneous descent rarely occurs after 6 months of age, making this the optimal time for surgical correction.

Almost 90% of undescended testes have an associated patent processus vaginalis, which predisposes to formation of a hydrocele or hernia. Occult inguinal hernia in patients with untreated undescended testis can present at any time with the typical symptoms or complications, including incarceration.

Prior to any surgical intervention, the patient is reexamined while under anesthesia because on occasion a retractile testicle descends under anesthesia or a previously nonpalpable testicle becomes palpable. For a palpable testicle, an open inguinal approach is performed. For the nonpalpable testicle in a child, a laparoscopic approach is preferred, but an open inguinal approach may be performed.

Outcomes

Success rates following orchidopexy are 74% for the abdominal testis, 87% for canalicular, and 92% for those distal to the external ring. The most significant complication is testicular atrophy, which occurs in 1%-2% of cases of orchidopexy, while complete devascularization of the testis is rare. Paternity rates have been reported at 65%, 90%, and 93% in men with bilateral cryptorchidism, unilateral cryptorchidism, and normally descended testicles, respectively. If only one testis is undescended, the sperm count is subnormal in 25%-33% patients, and serum FSH concentration is slightly elevated. These abnormalities suggest that both testes are abnormal, perhaps congenitally, although only one fails to descend. If both testes are undescended, sperm count usually is severely subnormal, and serum testosterone may be reduced.

Alternative Therapy

Hormonal therapy is an option in the treatment of cryptorchidism because the condition may be related to hypogonadotropic hypogonadism. hCG is the only hormone approved for use in the treatment of cryptorchidism in the United States. Side effects of hCG treatment include enlargement of the penis, growth of pubic hair, increased testicular size, and aggressive behavior during administration. The likelihood of success with hormonal therapy is greatest for the most distal undescended testes or for testes that have been previously descended. Some suggest that hormonal therapy is effective only for retractile and not truly undescended testes. Although hormonal therapy may not be effective in achieving testicular descent, it may improve fertility in cryptorchid boys.

OBSTRUCTIVE UROPATHY

Obstruction is one of the most important abnormalities of the urinary tract, since it eventually leads to decompensation of the muscular conduits and reservoirs, back-pressure, and atrophy of renal parenchyma. It also invites infection and stone formation, which cause additional damage and can ultimately end in complete unilateral or bilateral destruction of the kidneys.

Both the level and the degree of obstruction are important to an understanding of the pathologic consequences. Any obstruction at or distal to the bladder neck may lead to back-pressure affecting both kidneys. Obstruction at or proximal to the ureteral orifice leads to unilateral damage unless the lesion involves both ureters simultaneously. Complete obstruction leads to rapid decompensation of the system proximal to the site of obstruction. Partial obstruction leads to gradual progressive muscular hypertrophy followed by dilation, decompensation, and hydronephrotic changes.

Etiology

Acquired urinary tract obstruction may be due to inflammatory or traumatic urethral strictures, bladder outlet obstruction (benign prostatic hyperplasia or cancer of the prostate), vesical tumors, neuropathic bladder, extrinsic ureteral compression (tumor, retroperitoneal fibrosis, or enlarged lymph nodes), ureteral or pelvic stones, ureteral strictures, or ureteral or pelvic tumors.

Pathogenesis

Regardless of its cause, acquired obstruction leads to similar changes in the urinary tract, which vary depending on the severity and duration of obstruction.

A. Urethral Changes

Proximal to the obstruction, the urethra dilates and balloons. A urethral diverticulum may develop, and dilation and gaping of the prostatic urethra and ejaculatory ducts may occur.

B. Vesical Changes

Early detrusor and trigonal thickening and hypertrophy compensate for the outlet obstruction, allowing complete bladder emptying. This change leads to progressive development of bladder trabeculation, cellules, saccules, and, finally, diverticula. Subsequently, bladder decompensation occurs and is characterized by the above changes plus incomplete bladder emptying (ie, postvoid residual urine). Trigonal hypertrophy leads to secondary ureteral obstruction owing to increased resistance to flow through the intravesical ureter. With detrusor decompensation and residual urine accumulation, there is stretching of the hypertrophied trigone, which appreciably increases ureteral obstruction. This is the mechanism of back-pressure on the kidney in the presence of vesical outlet obstruction (while the ureterovesical junction maintains its competence). Catheter drainage of the bladder relieves trigonal stretch and improves drainage from the upper tract.

A very late change with persistent obstruction (more frequently encountered with neuropathic dysfunction) is decompensation of the ureterovesical junction, leading to reflux. Reflux aggravates the back-pressure effect on the upper tract by transmitting abnormally high intravesical pressures and favors the onset or persistence of urinary tract infection.

C. Ureteral Changes

The first change noted is a gradual increase in ureteral distention. This increases ureteral caliber and stimulates hyperactive ureteral contraction and ureteral muscular hypertrophy. Because the ureteral musculature runs in an irregular helical pattern, stretching of its muscular elements leads to lengthening as well as widening, causing the dilated ureter to assume a tortuous, serpiginous course, weaving back and forth across the relatively straight course of the ureteral vessels, which are unaffected by the ureteral obstruction. This is the start of ureteral decompensation, where tortuosity and dilation become apparent. These changes progress until the ureter becomes atonic, with infrequent, ineffective, or completely absent peristalsis.

D. Pelvicaliceal Changes

The renal pelvis and calices, subjected to increased volumes of retained urine, distend. The pelvis shows evidence first of hyperactivity and hypertrophy and then of progressive dilation and atony. The calices show similar changes to a variable degree, depending on whether the renal pelvis is intrarenal or extrarenal. In the latter, caliceal dilation may be minimal in spite of marked pelvic dilation. In the intrarenal pelvis, caliceal dilation and renal parenchymal damage are maximal. The successive phases seen with obstruction are rounding of the fornices, followed by flattening of the papillae and finally clubbing of the minor calices.

E. Renal Parenchymal Changes

With continued pelvicaliceal distention, there is parenchymal compression against the renal capsule and, more importantly, compression of the arcuate vessels results in a marked drop in renal blood flow leading to parenchymal ischemic atrophy. With increased intrapelvic pressure, there is progressive dilation of the collecting and distal tubules, with compression and atrophy of tubular cells.

Clinical Findings

A. Symptoms and Signs

The findings vary according to the site of obstruction.

1. Infravesical obstruction—Infravesical obstruction (eg, due to urethral stricture, benign prostatic hypertrophy, bladder neck contracture) leads to difficulty in initiation of voiding, a weak stream, and a diminished flow rate with terminal dribbling. Burning and frequency are common associated symptoms. A distended or thickened bladder wall may be palpable. Urethral induration due to stricture, benign prostatic hypertrophy, or cancer of the prostate may be noted on rectal examination. Meatal stenosis and impacted urethral stones are readily diagnosed by physical examination.

2. Supravesical obstruction—Renal pain or renal colic and gastrointestinal symptoms are commonly associated. Supravesical obstruction (eg, due to ureteral stone, UPJO) may be completely asymptomatic when it develops gradually over a period of months. An enlarged kidney may be palpable. Costovertebral angle tenderness may be present.

B. Laboratory Findings

Evidence of urinary tract infection, hematuria, or crystalluria may be seen. Impaired renal function may be noted in cases of bilateral obstruction. Postrenal azotemia (serum changes reflecting impaired renal function due primarily to obstruction) is suggested by elevation of serum urea nitrogen and serum creatinine with a ratio greater than 10:1.

C. Imaging Studies

Radiologic examination is usually diagnostic in cases of stasis, tumors, and strictures. Dilation and anatomic changes occur above the level of obstruction, whereas distal to the obstruction, the configuration is usually normal. This helps in localizing the site of obstruction. Combined antegrade imaging by intravenous urograms and retrograde imaging by ureterograms or urethrograms is sometimes needed to demonstrate the obstructed segment. In supravesical obstruction, demonstration of stasis and delayed drainage is essential to establish and quantitate the severity of obstruction.

1. Ultrasonography—Ultrasonography reveals the degree of dilation of the renal pelvis and calices and allows for diagnosis of hydronephrosis even in the prenatal period. Color Doppler ultrasound can reveal blood flow and restrictive indices to help determine functional impairment.

2. Isotope studies—A technetium-99m DTPA scan or MAG-3 scan portray the degree of hydronephrosis as well as renal function. Use of diuretics during the scan can provide specific data on the significance of the obstruction and the need for treatment. Multiple studies can reveal ongoing functional changes.

3. CT scan—CT scan is of particular value in revealing the degree and site of obstruction as well as the cause in many cases. The use of contrast (CT urogram) agents allows estimation of residual renal function.

4. MR urogram—MRI provides anatomic images and identification of the site of obstruction. With dynamic contrast-enhanced MR urography, functional information is also obtained without the use of ionizing radiation.

5. Antegrade urography—Antegrade urography via percutaneous needle or tube nephrostomy is valuable when the obstructed kidney fails to excrete the radiopaque material on excretory urography. The Whitaker test requires percutaneous catheter access to the collecting system above the site of suspected obstruction. This permits fluid introduction into the renal pelvis and simultaneous measurement of urine flow rate and pressures in the bladder and renal pelvis, thus providing a quantitative assessment of the degree and severity of obstruction. The fluid transport can be measured and the degree of obstruction estimated by the use of a pressure monitor.

Complications

The most important complication of urinary tract obstruction is renal parenchymal atrophy as a result of back-pressure. Obstruction also predisposes to infection and stone formation, and infection occurring with obstruction leads to rapid kidney destruction.

Treatment

The first goal of therapy is relief of the obstruction (eg, catheterization for relief of acute urinary retention). Definitive therapy often requires surgery, but minimally invasive techniques are becoming utilized more often. Simple urethral stricture may be managed by dilation or internal urethrotomy (incision of the stricture under direct vision through the resectoscope). However, urethroplasty (open surgical graft or flap of skin or buccal mucosa to replace urethral diameter) may be required and have better long-term success. Benign prostatic hyperplasia classically requires excision, but laser techniques are providing satisfactory outcomes with less morbidity. Impacted ureteral stones may either be removed or bypassed by a catheter unless it is thought that they may pass spontaneously.

Ureteral or UPJO requires surgical repair; however, endoscopic approaches within the ureter or by laparoscopy may be equal to open repair. Renal stones may be removed instrumentally via retrograde or antegrade percutaneous approach by direct extraction with baskets or by ultrasonic or laser lithotripsy or by irrigation through a tube placed directly into the kidney.

Preliminary drainage above the obstruction is sometimes needed to improve kidney function. Occasionally, intestinal urinary diversion or permanent nephrostomy is required. If damage is advanced, nephrectomy may be indicated.

Prognosis

The prognosis depends on the cause, site, duration, and degree of kidney damage and renal decompensation. In general, relief of obstruction leads to improvement in kidney function except in seriously damaged kidneys, especially those destroyed by inflammatory scarring.

URETEROPELVIC JUNCTION OBSTRUCTION

Stenosis of the renal pelvis outlet is commonly due to congenital narrowing of the junction or compression by anomalous vessels. However, the lesion may be acquired. Presentation in adults often includes the abrupt onset of flank pain usually following ingestion of large amounts of fluids. Presentation in childhood is now most often made following the diagnosis of hydronephrosis by prenatal ultrasonography.

The diagnosis may be confirmed with a diuretic nuclear renal scan or intravenous urography, which reveals hydronephrosis with a dilated renal pelvis and slow drainage of either radiotracer or contrast medium. Occasionally, patients present with intermittent hydronephrosis and normal urograms, except during attacks of pain, when x-rays show typical obstruction. These patients generally have normal renal parenchyma. Retrograde ureteropyelography is usually needed in patients with chronic moderate to severe obstruction to determine the extent of the lesion and to provide assurance that the distal ureter is normal. Marked obstruction may make it difficult to determine whether kidney function is surgically salvageable. In these cases, it may be necessary to perform either (1) differential radioisotope renography with use of a diuretic during the study or (2) percutaneous nephrostomy and creatinine clearance by 24-hour urine collection.

Severe obstruction with minimal remaining renal function is best treated by unilateral nephrectomy. If renal function is adequate (> 10%-15% of total renal function or > 10 mL/min creatinine clearance), surgical repair of the stenosis, either by creation of a renal pelvis flap or by resection of the stenotic area and reanastomosis (dismembered repair), is warranted. Laparoscopic and/or robotic pyeloplasty has emerged as the standard of care in adults for the repair of UPJO. The use of ureteroscopy or percutaneous nephroscopy with endopyelotomy, incising the strictured ureteropelvic junction, offers an alternative method of therapy and is most useful in secondary UPJO, after primary repair has failed. Endoscopic approaches are less successful in the presence of a crossing vessel, poor renal function, and significant hydronephrosis. The surgical results of all the above methods are excellent in terms of functional preservation, improvement of urine flow, and relief of symptoms, but dilation of the calices may persist.

URETERAL STENOSIS

Ureteral stenosis can be secondary to congenital or acquired lesions. Congenital causes can include compression by an anomalous vessel such as a lower pole renal artery in UPJO or a retroperitoneal vein or primary megaureter where the distal ureter is partially obstructed. More commonly, the ureter is secondarily obstructed due to acquired conditions such as inflammation from chronic ureteral stones, trauma secondary to gynecologic or vascular surgery, or external penetrating trauma from a knife or gunshot wound. Enlarged pelvic lymph nodes or an iliac artery aneurysm or retroperitoneal fibrosis may obstruct the ureter, as can intrinsic ureteral cancer or bladder cancer infiltrating the ureter at its insertion into the bladder. Finally, infection such as urinary tuberculosis can cause distal ureteral strictures, and bilateral ureteral obstruction can occur from bladder neck obstruction with urinary retention secondary to benign prostatic hyperplasia.

Chronic conditions with slow development may not cause symptoms, whereas acute obstruction such as that from a stone will cause severe flank pain that may radiate to the groin or testes/labia. Diagnosis is most often made by a CT urogram with contrast that will show delayed function and a dilated renal pelvis and ureter down to the site of the obstruction. This is often an unsuspected finding on a CT done for other reasons in an asymptomatic patient.

Treatment depends entirely on the cause. Severe stenosis may require resection of the lesion and spatulated end-to-end anastomosis of the ureter. Less-severe obstruction may be managed by cystoscopy and ureteral or balloon dilation of the narrowed area under direct vision via a ureteroscope. Placement of an indwelling ureteral stent may dilate the stenosis over time and be a useful treatment as well in selected patients.

RETROPERITONEAL FIBROSIS

See also Chapter 22.

One or both ureters may be compressed by a chronic inflammatory process, usually of unknown cause, which involves the retroperitoneal tissues of the lumbosacral area. When the source of fibrosis is unknown, the entity is known as idiopathic retroperitoneal fibrosis. Patients treated for migraine with methysergide may develop this fibrosis. Sclerosing Hodgkin disease and fibrosis from metastatic cancer have also been implicated. Symptoms include flank pain, lower back and abdominal pain (from ureteral obstruction), and those associated with uremia. Some patients present with complete anuria. Urinary infection is unusual. If both ureters are obstructed, the serum creatinine is elevated, but unilateral renal obstruction from fibrosis may present with normal or slightly elevated creatinine levels.

Excretory urograms show hydronephrosis and a dilated ureter down to the point of obstruction. The ureters are displaced medially in the lumbar area. Retrograde ureterograms show a long segment of ureteral stenosis, though a catheter usually passes easily through the ureter. Ultrasound lacks the anatomic specificity to make the diagnosis, but obstruction proximal to the fibrotic mass yields hydronephrosis and hydroureter. Large areas of fibrosis can be identified with ultrasound. CT scans and MRI offer the most diagnostic information about the fibotic mass and both the degree and level of obstruction. If the patient has significant worsening of renal function, indwelling ureteral stent(s) or percutaneous nephrostomy tube(s) should be placed. When the patient’s condition has improved, definitive therapy can be accomplished. If methysergide is suspected to be the causative agent, fibrosis may subside when the drug is discontinued. When malignancy is in the differential diagnosis, a percutaneous or laparoscopic biopsy should be considered prior to treatment. These patients may benefit from administration of corticosteroids and/or other immunosuppressive agents. Chronic indwelling ureteral stents have also been used successfully. If these methods fail, ureterolysis must be performed to free the ureter from the fibrous plaque. The involved ureter should be dissected from the plaque, moved to a lateral position, and wrapped with omentum to prevent recurrent entrapment. This has been accomplished quite successfully with laparoscopic and robotic approaches.

BENIGN PROSTATIC HYPERPLASIA

General Considerations

The cause of benign prostatic enlargement is not known but is probably related to hormonal factors. The mechanism for opening and funneling the vesical neck at the time of voiding is altered by hyperplasia of the prostate, which causes increased outflow resistance. Consequently, a higher intravesical pressure is required to accomplish voiding, causing hypertrophy of the vesical and trigonal muscles. This may lead to the development of bladder diverticula—outpocketings of vesical mucosa between the detrusor muscle bundles. Hypertrophy of the trigone causes excessive stress on the intravesical ureter, producing functional obstruction and resulting in hydroureteronephrosis in late cases. Stagnation of urine can lead to infection; the onset of cystitis exacerbates the obstructive symptoms. The periurethral and subtrigonal prostate enlargement produces the most significant obstruction.

The prostate in young men has an anatomic capsule like an apple peel. In men with prostatic enlargement, there is a thick “surgical” capsule similar to an orange peel, composed of peripherally compressed true prostatic tissue (“peripheral zone”). The hyperplastic benign periurethral glands correspond to the “transition zone” and are the cause of the obstruction (Figure 38–9).

Clinical Findings

A. Symptoms and Signs

Typically, the patient has lower urinary tract symptoms and notices hesitancy and loss of force and caliber of the stream. The urgent need to void when the bladder is nearly full may be an early sign. He may also be awakened by the urge to void several times at night (nocturia). Postvoid dribbling (“terminal dribbling”) is particularly disturbing. The complication of infection increases the degree of obstructive symptoms and is often associated with burning on urination. Acute urinary retention may supervene. This is associated with severe urgency, suprapubic pain, and a distended, palpable bladder.

The size of the prostate rectally is not of primary diagnostic importance, since there is a poor correlation between the size of the gland and the degree of symptoms and amount of residual urine. The American Urological Association (AUA) developed a 7-item, self-administered questionnaire (AUA symptom score) that can assist the patient and physician in evaluating the patient’s lower urinary tract symptoms.

B. Laboratory Findings

Urinalysis may reveal evidence of infection. Residual urine is commonly increased (> 50 cc), and a timed urinary flow rate is decreased (< 10-15 cc/s). The serum creatinine may be elevated in cases with prolonged severe obstruction.

C. Imaging Studies

Pelvic ultrasound can easily identify post-void urine residual as well as estimate prostate size and anatomy, in particular, the presence or absence of median lobe tissue. Bladder wall thickness, trabeculation, and diverticula can also be identified with ultrasound. Renal ultrasound can identify hydronephrosis in advanced cases of BPH. Transrectal ultrasound of the prostate provides better imaging of the prostate than the transabdominal approach but is more invasive and typically not required. Computerized tomography (CT), MRI, and excretory urography also provide anatomical information for an enlarged prostate, but are more time consuming and costly and should only be utilized in unusual circumstances (eg, ruling out malignancy).

D. Cystoscopic Examination

Cystourethroscopy reveals secondary vesical changes (eg, trabeculation and diverticula) and enlargement of the prostatic urethra. Lateral lobe hypertrophy (so-called “kissing lobes”) as well as median lobe tissue can be easily visualized. Although cystoscopy is not required to make the diagnosis of BPH, it may identify other conditions in the differential diagnosis (eg, urethral stricture, bladder neck contracture, malignancy) as well as complications secondary to BPH (eg, bladder stones).

E. Urodynamic Studies

Simultaneous physiologic monitoring of bladder filling and emptying, urethral sphincter activity, abdominal pressure, and pelvic floor muscle activity (electromyography) can be extremely useful in documenting whether bladder outlet obstruction, poor bladder function, or other causes are responsible for lower urinary tract symptoms. While urodynamic studies are not required for diagnosis in all cases, they are helpful in cases with large postvoid residual volumes or underlying neurologic disease to help determine appropriate management.

Differential Diagnosis

Neurogenic bladder may produce a similar syndrome. A history suggesting a neuropathic etiology, such as diabetes mellitus, stroke, Parkinson’s disease, or spinal cord injury or compression, may be obtained. Neurologic deficit involving the spinal nerves S2-4 is particularly significant.

Cancer of the prostate also causes symptoms of vesical neck obstruction. Serum prostate-specific antigen (PSA) may be elevated in patients with benign prostatic hypertrophy, and the level increases as the volume of the prostate increases. Thus, an absolute value is not diagnostic, but in general, if it is over 10 ng/mL, the possibility of cancer should be evaluated.

Acute prostatitis may cause symptoms of obstruction, but the patient is septic and has infected urine. The prostate is exquisitely tender.

Urethral stricture diminishes the caliber of the urinary stream. There is usually a history of gonorrhea or local trauma. A retrograde urethrogram or cystoscopy shows the stenotic area. A stricture blocks the passage of an instrument or catheter.

Complications

Obstruction and residual urine lead to vesical and prostatic infection and occasionally pyelonephritis; these may be difficult to eradicate. Long-term obstruction can lead to renal failure.

The obstruction may lead to the development of bladder diverticula. Infected residual urine may contribute to the formation of calculi.

Functional obstruction of the intravesical ureter, caused by the hypertrophic trigone, may lead to hydroureteronephrosis.

Treatment

The indications for operative management are impairment of or threat to renal function and bothersome symptoms. Because the degree of obstruction progresses slowly in most patients, conservative treatment may be adequate. Drugs that relax the prostatic capsule and internal sphincter (α-adrenergic blocking agents) or decrease the volume of the prostate (5α-reductase inhibitors or antiandrogens) have been tried with considerable success.

A. Conservative Measures

Treatment of chronic prostatitis may reduce symptoms. The resolution of a complicating cystitis usually affords some relief. In order to protect vesical tone, the patient should be cautioned to void as soon as the urge develops. Forcing fluids over a short time causes rapid vesical filling and decreasing vesical tone; this is a common cause of sudden acute urinary retention and thus should be avoided. Patients with urinary obstructive symptoms should avoid the use of cold remedies, including antihistamines and alpha agonists, because they are also a common cause of urinary retention. These conservative measures are of only temporary help—if any—in patients with BPH. There has been recent great interest, particularly by patients, in the use of phytotherapy for treatment of lower urinary tract symptoms, including saw palmetto, pumpkin seeds, and other plant extracts. Despite previous claims of efficacy based on small retrospective studies, a recent large, multicenter randomized trial of 369 men comparing placebo versus saw palmetto showed no improvement in AUA symptom score or secondary outcomes (eg, peak flow and PVR) in the saw palmetto group. Thus, the use of saw palmetto extracts for the treatment of BPH is not recommended.

Controversy surrounds choices in the treatment of benign prostatic hyperplasia. No treatment (watchful waiting) may be appropriate in patients who complain of mild to moderate symptoms and thus have low AUA symptom scores and residual urine less than 70-100 cc. Interest has also focused on nonoperative medical therapy for those with more significant symptoms. α-Adrenergic blocking agents relax the internal (bladder neck) sphincter and prostatic capsule. Selective agents that are long-acting and preferentially work for this purpose include tamsulosin and silodosin. 5α-Reductase inhibitors block conversion of testosterone to DHT (the androgen active in promoting prostate growth) and are useful for large glands, particularly in combination with an alpha-blocker, which has been shown to best prevent urinary retention and other common progressive symptoms of prostatic obstruction. More recently, daily tadalafil, a PDE-5 inhibitor commonly used in the treatment of erectile dysfunction, has been shown to have efficacy in treating symptoms related to BPH.

Catheterization is mandatory for acute urinary retention. Spontaneous voiding may return, but a catheter should be left indwelling for at least a few days and preferably one week while detrusor tone returns. Several studies have documented improved success of voiding trials after retention if α-blockers are initiated for at least 48 hours prior to catheter removal. If several voiding trials fail, additional treatment is indicated.

B. Surgery

Surgery for BPH is offered to men in whom medical therapy fails to provide adequate symptom relief and/or objective parameters such as post-void residual fail to improve. Additionally, men may request surgery because of poor compliance with medical therapy or desire to stop medications. Absolute indications for BPH surgery include recurrent infections, development of bladder stones, renal failure due to BPH, and persistent urinary retention due to obstruction. Men with large amounts of median lobe tissue (intravesical protrusion) tend to have a poor response to medical therapy and benefit most from early surgery.

There are two common approaches used in surgery for BPH: transurethral and transabdominal (open vs. minimally invasive). The transurethral route is by far the most common and preferred in patients with glands weighing less than 100 g because morbidity rates are lower and the hospital stay is shorter. With new technology, even larger glands can be managed with the transurethral approach. Larger glands, however, may require open surgery (suprapubic or retropubic enucleation), depending on the preference and experience of the urologist. Open surgery for BPH is the exception rather than the rule because of increased morbidity.

Transurethral approaches are the least invasive and require the shortest hospital stay (typically ambulatory or one night). The gold standard is the monopolar transurethral resection of the prostate (TURP), by which a resectoscope with a monopolar loop electrode is utilized to remove the obstructing BPH tissue. Hypotonic irrigation solution is required and hyponatremia due to excess systemic absorption (“TURP Syndrome”) is a unique complication of this approach. Additional complications of TURP include hematuria, UTI, stress incontinence, impotence, retrograde ejaculation, urethral stricture, and bladder neck contracture. Incontinence and impotence are rare complications in the hands of experienced surgeons (< 5%). TURP has reliably demonstrated improvement in AUA symptom score, flow rate, and PVR in randomized controlled trials. The more recent use of bipolar energy has allowed for the use of saline irrigation during TURP, eliminating the risk of hyponatremia.

Transurethral laser vaporization of the prostate with holmium or KTP (potassium titanyl phosphate) laser technology has demonstrated similar efficacy to TURP in well-selected patients with smaller glands. The major advantage of the laser approaches is less risk of bleeding, and even the ability to perform the procedure while patients remain on anticoagulation. Holmium-laser enucleation of the prostate (HOLEP) utilizes laser energy to enucleate the prostate adenoma (rather than vaporize the tissue). The tissue must then be morecellated to be removed via the resectoscope. HOLEP has similar efficacy to TURP and laser vaporization but may be more technically challenging.

An alternative transurethral approach for the treatment of BPH is transurethral incision of the prostate (TUIP). This procedure consists of a linear incision starting at the bladder neck and ending distally at the verumontanum, allowing expansion of the entire prostatic urethra. Typically two incisions are made with a cutting current at the 5 and 7 O’clock positions. TUIP is typically reserved for men with a steep/high bladder neck or small, obstructive prostates of 30 g or less in size.

Open and robotic enucleation of the prostate for BPH is reserved for larger glands where transurethral approaches would be unable to remove sufficient tissue to provide long-term relief of the obstruction.

Prognosis

Most patients with marked symptoms receive considerable relief and substantial improvement in urine flow following surgical treatment; however, those with milder forms may benefit from drug therapy. Unless absolute indications for surgery exist (see above), most men begin with medical therapy and progress to surgical interventions if substantial symptoms persist.

URETHRAL STRICTURE

Acquired urethral strictures in men may be due to external trauma or to prior instrumentation (most common). Strictures may be inflammatory, due to gonorrhea, tuberculous urethritis, or schistosomiasis, or may rarely be a complication of cancer. The common presenting symptoms are dysuria, weak stream, splaying of the urinary stream, urinary retention, and urinary tract infection. Evidence of scarring due to trauma or induration and perineal fistula may be seen. Urethroscopy reveals the degree of narrowing. A retrograde urethrogram delineates the site and degree of stricture.

Urethral stricture must be differentiated from bladder outlet obstruction due to BPH, impacted urethral stones, urethral foreign bodies, and tumors.

Initial treatment consists of transurethral direct-vision internal urethrotomy (incision of the stricture). Successful results are obtained in 75% of patients. For long, dense strictures or those failing to respond to an initial internal urethrotomy, open surgical repair is indicated. This is probably best achieved by the transpubic or perineal route if the lesion involves the membranous urethra. If the bulbar urethra is involved, the perineal approach is indicated; if the distal/penile urethra is involved, the ventral penile approach is appropriate. End-to-end anastomosis is satisfactory for short segment strictures, usually 2 cm or less, with a more than 90% success rate. Longer strictures often require pedicle flaps for distal urethral strictures or onlay grafts (eg, buccal mucosa) for proximal strictures.

HEMATURIA

Hematuria, gross or microscopic, is a common urologic consult because it can be a presenting sign for underlying urologic malignancies. Red-colored urine may not necessarily include blood, and microscopic examination looking for red blood cells is prudent. Microscopic hematuria is defined as three or more red blood cells per high-powered field on urine microscopy in two of three properly collected specimens. The degree of hematuria bears no relation to the seriousness of the underlying cause. Urine dipstick test is the simplest method to check for blood and has a sensitivity of 91%-100% and a specificity of 65%-99%. Caution should be taken because false positives (menstrual blood, myoglobin, and hemolysis, among others) and false negatives (dipstick exposed to moisture and presence of reducing agents like ascorbic acid) can lead to confusing results. For this reason, further evaluation of microscopic hematuria performed only when microscopic analysis confirms the diagnosis. Knowledge of the medical history and medications can help rule out other causes of colored urine. Beets, rifampin, and phenazopyridine, among other substances, can cause urine discoloration. Anticoagulation at normal therapeutic levels does not predispose to hematuria, and patients should be evaluated for the hematuria, because 13%-45% of these patients may have significant urologic disease.

Ideally, a clean-catch midstream sample should be collected. If that is not possible, a catheterized specimen is indicated. It is important to note that hematuria can be due to urologic or renal parenchymal disease. The differential diagnosis thus includes benign causes like renal or bladder stones, papillary necrosis, urinary tract infections, prostatitis, or instrumentation, and malignant causes like renal, renal pelvis, bladder, prostate, or urethral cancer. Renal parenchymal causes of hematuria include glomerular and interstitial renal disease. These patients may have proteinuria and casts on the urinalysis, and the red blood cells are typically dysmorphic. Nephrology evaluation is required for hematuria associated with glomerular or interstitial renal disease.

Patients with hematuria referred to urology are classified into low-risk and high-risk groups. High-risk groups include smokers, age older than 40 years, history of exposure to pelvic radiation or cyclophosphamide, occupational exposure to chemicals or dyes, and history of urinary tract infections or other urological disorders. It is recommended that a complete workup be performed for all patients with symptomatic hematuria, all patients with gross hematuria, and high-risk patients with microscopic hematuria. The workup includes history and physical examination, serum creatinine, upper tract imaging (typically CT urogram), cystoscopy, and urine cytology. Asymptomatic patients younger than 40 years who have microscopic hematuria and have no risk factors can be evaluated with upper tract imaging and either cystoscopy or voided cytology, as the risk of significant pathology in this population is very low. If the workup is negative, it is recommended that the patient be evaluated with urinalysis, voided cytology, and blood pressure check at 6, 12, 24, and 36 months.

Urinary tract infection is the second-most common type of infection in humans and is frequently encountered by primary care physicians as well as urologists.

These infections are caused by a variety of pyogenic bacteria that typically produce a nonspecific tissue response. The most common organisms are gram-negative bacteria, particularly Escherichia coli. Less common are Enterobacter aerogenes, Proteus vulgaris, Proteus mirabilis, Pseudomonas aeruginosa, and Enterococcus faecalis.

Owing to the short length of the female urethra and bacterial colonization of the introitus, ascending infection is a common occurrence in young girls and in sexually active women. In men, ascending infection is often a consequence of urethral instrumentation.

Although relatively uncommon, descending or hematogenous urinary tract infection is usually associated with local urinary tract disorders—most commonly, obstruction and stasis; less commonly, trauma, foreign bodies, or tumors.

Lymphatic spread occasionally occurs from the large bowel or from the cervix and adnexa in the female through the perivesical and periureteral lymphatics.

Direct extension to the urinary bladder of nearby inflammatory processes (eg, appendiceal abscess, enterovesical fistula, or pelvic abscess) may occur.

Predisposing Factors

Infection is usually initiated or sustained by predisposing factors. Predisposing systemic factors include diabetes mellitus, immunosuppression, and malnutrition; these disorders likely interfere with normal bladder and body defense mechanisms. Predisposing local factors include incontinence, constipation, organic or functional obstruction, stasis (residual urine), foreign bodies (especially catheters and stones), tumors, or necrotic tissue. Vesicoureteral reflux facilitates transport of bacteria from the bladder to the kidney, which subsequently predisposes to pyelonephritis.

Classification of Urinary Tract Infection

Urinary tract infection is classified as (1) upper urinary tract infection (most commonly acute or chronic pyelonephritis or infection due to renal abscess), (2) lower urinary tract infection (cystitis or urethritis), or (3) genital infection (prostatitis, epididymitis, seminal vesiculitis, or orchitis).

Urologic Instrumentation or Surgery & Urinary Tract Infection

In the absence of urinary tract infection, surgery of the upper urinary tract should require only short-term prophylactic antibacterial therapy. In the presence of infection, one attempts to sterilize the system before operation. If stenting or tube drainage is required and there are no symptoms of infection, colonization does not call for antibacterial therapy until the stent or tube is to be changed or removed. Broad-spectrum antibacterial prophylaxis is started at that time.

With lower urinary tract surgery, antibacterial therapy is advised before operations involving the urethra and the bladder, especially for women in whom contamination from vaginal organisms is likely. Men undergoing prostatectomy for obstructive prostatism often have urinary tract infection, particularly when catheter drainage is used preoperatively. In these cases, antimicrobial therapy is necessary before and after surgery to prevent bacteremia.

In the presence of urinary tract infection, any urethral instrumentation poses a threat of bacteremia, and possibly sepsis—more apt to occur in men than in women. Appropriate antibacterial coverage should be instituted before manipulation.

A. Principles of Catheterization

After a short-term single catheterization, the rate of infection is 1%-5%. However, in certain patients—pregnant women, elderly, or debilitated patients—and in the presence of urologic disease, the risk is much higher. An indwelling catheter often leads to bacterial colonization, especially in women. The incidence is proportionate to the duration of catheterization and reaches approximately 95% after 5 days.

Strict aseptic technique is of critical importance in catheterization. Proper cleansing of the genitalia is essential. Iodophor preparations may be used for cleaning the vaginal introitus or the glans penis. Many common urinary tract pathogens are present in normal colonic flora, and these organisms often gain access to the urinary tract of catheterized patients. Cross-contamination of urinary catheters (passive transmission of bacteria from patient to patient on the hands of hospital personnel) is a frequent mode of transfer of resistant organisms. Measures directed to the prevention of catheter cross-contamination are essential. Closed catheter drainage is probably the best way to reduce cross-contamination.

With sterile technique during catheterization and a closed drainage system, most catheters can be kept sterile for 48-72 hours. In a closed drainage system, an added airlock or one-way valve preventing reflux of urine from the collecting bag to the draining tubes also helps prevent infection. The general principles are as follows: (1) Indwelling catheters should be used only when absolutely necessary. (2) Catheters should be inserted with strict aseptic technique. (3) A closed drainage system, preferably with a one-way valve, is advisable. (4) Nonobstructed dependent drainage is essential. (5) Unnecessary irrigation of the system should be avoided. (6) If the catheter is needed for a prolonged period, it should be changed every 2-4 weeks to minimize encrustation and stone formation. (7) Catheterized patients with asymptomatic catheter colonization should be given antibiotics just before the catheter is changed or removed—not during the period of catheterization unless symptomatic infection occurs.

B. Evaluation

Imaging of the urinary tract is recommended in every febrile infant or young child following the first urinary tract infection. Imaging includes a renal and bladder ultrasound and a voiding cystourethrogram. The renal ultrasound may detect hydronephrosis, duplication anomalies, stones, or abnormalities of the bladder wall and should be obtained at the earliest convenient time. A cystogram may be obtained by instillation of contrast medium with fluoroscopy or by instillation of a radionuclide. Radionuclide cystography has the advantage of decreased radiation, while the contrast-voiding cystourethrogram has the advantage of providing better anatomic detail, which may help detect bladder or urethral abnormalities. Either method should include a voiding phase because reflux is the most likely abnormality to be detected and may only occur with voiding. The cystogram should be obtained once the child is free of infection.

Imaging recommendations in adults with a urinary tract infection vary depending on the patient’s past history and present symptoms. Renal/bladder ultrasound is a good initial study to identify upper- (eg, hydronephrosis, stones, or abscess) and lower- (eg, urinary retention or bladder calculi) tract sources of infection. CT scan with intravenous contrast can identify stigmata of pyelonephritis (see below).

C. Antibacterial Therapy

The choice of antibiotics depends on the type of organism and its sensitivity, as determined by urine cultures. For uncomplicated infection, adequate urine concentrations of the antibiotic determine efficacy, but in cases of bacteremia and septic shock, serum concentrations are crucial. Commonly used oral medications are sulfonamides, nitrofurantoin, ampicillin, trimethoprim-sulfamethoxazole, fluoroquinolones, and oxytetracycline. For parenteral therapy, aminoglycosides and cephalosporins are effective against the most common organisms (ie, P. mirabilis, E. aerogenes, and P. aeruginosa).

ACUTE PYELONEPHRITIS

General Considerations

Except in the presence of stasis, foreign bodies, trauma, or instrumentation, pyelonephritis is an ascending type of infection. Pathogenic organisms usually reach the kidney from the bladder, often via an incompetent ureterovesical junction.

Clinical Findings

A. Symptoms and Signs

In acute attacks, pain is present in one or both flanks. Diagnosis in infants requires a high index of suspicion, since they may present with nonspecific symptoms such as fever and failure to thrive. Young children commonly present with poorly localized abdominal pain; irritative lower urinary tract symptoms may be present. Chills and fever are common. Severe infection may produce hypotension, peripheral vasoconstriction, and acute renal failure. Gross hematuria is not common but can be observed more frequently in women and the elderly.

B. Laboratory Findings

Pyuria and bacteriuria are consistent findings. Leukocytosis with a shift to the left is common. Urine culture identifies the organism.

C. Imaging Studies

In acute attacks, only minimal changes such as delayed visualization and poor concentrating ability are noted on intravenous urography. CT scans may demonstrate zones of decreased enhancement in the renal parenchyma as well as perinephric fat stranding. Renal or ureteral calculi may be seen on plain abdominal x-rays or nonenhanced CT scans. Chest x-ray may show a small ipsilateral pleural effusion.

Differential Diagnosis

Pneumonia, acute cholecystitis, or splenic infarction can be confused with pyelonephritis. Acute appendicitis sometimes causes pyuria and microhematuria. Any acute abdominal illness such as pancreatitis, diverticulitis, or intestinal ischemia can simulate pyelonephritis. Appropriate history, examination, urinalysis and imaging usually make the distinction.

Complications

If the diagnosis is missed in the acute stage, the infection may become chronic. Both acute and chronic pyelonephritis may lead to progressive renal damage and abscess formation.

Treatment

Specific antibiotic therapy should be given for at least 7 days to eradicate the infecting organism after proper identification and sensitivity determination. Symptomatic treatment is indicated for pain and irritative voiding symptoms. Adequate fluid intake to assure optimum urinary output is required. Failure to simultaneously identify and treat predisposing factors (eg, obstruction) is the principal cause of failure to respond to therapy, leading to progressive infection, chronic pyelonephritis, and possibly sepsis. Patients not responding to culture-sensitive antibiotics should be imaged, looking for intrinsic (eg, calculi) or extrinsic obstruction or renal abscess.

Prognosis

The prognosis is good with adequate treatment of both the infection and its predisposing cause, depending on the degree of preexisting renal parenchymal damage.

EMPHYSEMATOUS PYELONEPHRITIS

Emphysematous pyelonephritis is a form of acute necrotizing pyelonephritis secondary to a gas-producing bacteria (E. coli in 66% of cases and Klebsiella in 26%). It is commonly seen in patients with poorly controlled diabetes (over 90% of cases) or in patients with upper urinary tract obstruction. The diagnosis is made by the usual signs of acute pyelonephritis and by the presence of gas in the renal collecting system and parenchyma seen on plain films, ultrasound, or CT. The condition is life threatening, with a mortality rate of 40%-80% with intravenous antibiotics alone. Obstruction requires drainage either percutaneously or by stent placement. Operative treatment, including nephrectomy and drainage along with antibiotics, decreases the mortality rate to less than 20%.

CHRONIC PYELONEPHRITIS

Chronic pyelonephritis is the result of inadequately treated or recurrent acute pyelonephritis. The diagnosis is primarily made by x-ray, since patients rarely have signs or symptoms until late in the course, when they develop chronic flank pain, hypertension, anemia, or renal failure. Pyuria is not a consistent finding. Because chronic pyelonephritis may be a progressive, localized immune response initiated by bacteria long since eradicated, urine cultures are usually sterile. Early cases may have no findings on intravenous urography, whereas in late cases it may reveal small kidneys with typical caliceal deformities (clubbing), with evidence of peripheral scarring and a thin cortex. Voiding cystourethrography may document vesicoureteral reflux as the cause. Complications include hypertension, stone formation, and chronic renal failure.

Antibiotic treatment is not helpful in these patients unless ongoing infection can be documented. The prognosis depends on the status of renal function but is generally not good, particularly when the disease is contracted in childhood. Progressive deterioration of renal function usually occurs.

Xanthogranulomatous pyelonephritis is a form of chronic pyelonephritis seen most frequently in middle-aged diabetic women and rarely in children. The disease is usually unilateral and is associated with prolonged obstructing nephrolithiasis. Patients often have nonspecific symptoms similar to those of acute pyelonephritis but have an enlarged kidney with calculi and a mass often indistinguishable from tumor. Proteus species are common causative agents. Nephrectomy is usually the treatment of choice, though a partial nephrectomy may be performed for focal disease. Histologic examination confirms the diagnosis following nephrectomy by the demonstration of foamy lipid-laden macrophages.

PAPILLARY NECROSIS

This disorder consists of ischemic necrosis of the renal papillae or of the entire pyramid. Excessive ingestion of analgesics, sickle cell trait, diabetes, obstruction with infection, and systemic conditions decreasing renal blood flow are common predisposing factors.

The symptoms are usually those of chronic cystitis with recurring exacerbations of pyelonephritis. Renal pain or renal colic may be present. Azotemic manifestations may be the presenting symptoms. In acute attacks, localized flank tenderness and generalized toxemia may occur. Laboratory findings consist of pyuria, hematuria, occasionally glycosuria, and acidosis. Impaired kidney function is shown by elevated serum creatinine and urea nitrogen. Intravenous urography usually shows impaired function and poor visualization in advanced cases. Evidence of ulceration, cavitation, or linear breaks in the base of the papillae and radiolucent defects due to sloughed papillae may be seen; the latter may become calcified. Retrograde urograms may be needed for proper imaging if kidney function is markedly impaired.

Preventive measures consist of proper management of diabetic patients with recurrent infections and avoidance of chronic use of analgesic compounds containing phenacetin and aspirin.

Intensive antibacterial therapy may be needed, though it is commonly unsuccessful in eradicating infection. Little can be done surgically except to remove obstructing papillae and correct predisposing factors (eg, reflux, obstruction) if identified.

In severe cases, the prognosis is poor. Renal transplantation may be required.

RENAL ABSCESS

While renal abscess is occasionally due to hematogenous spread of a distant staphylococcal infection, most abscesses are secondary to chronic nonspecific infection of the kidney, often complicated by stone formation. The onset may be acute, with high fever, but occasionally low-grade fever and general malaise are the presenting symptoms. Localized costovertebral angle tenderness and a palpable flank mass may be present. A mass may be evident on intravenous urograms, DTPA scans, sonograms, CT scans, or renal angiograms. If the abscess is due to hematogenous spread, the urine does not contain bacteria unless the abscess has broken into the pelvicaliceal system. More frequently, gram-negative organisms are found, as would be expected in light of the preponderance of ascending infection.

If organism sensitivity can be established by appropriate tests (blood and urine cultures and sensitivity tests), treatment with the proper antibiotic is indicated. Many infections have responded to percutaneous drainage and irrigation with antibiotic solutions, especially in cases of unilocular abscess cavity seen on either ultrasound or CT examination. In multilocular abscess or persistent bacteremia despite percutaneous drainage, surgical drainage or even heminephrectomy may be necessary.

When the abscess is found to be secondary to chronic renal infection, nephrectomy is usually indicated because of advanced destruction of the kidney.

PERINEPHRIC ABSCESS

Abscess between the renal capsule and the perirenal fascia most often results from rupture of an intrarenal abscess into the perinephric space. E. coli is the most common causative organism. The pathogenesis usually begins with severe pyonephrosis secondary to obstruction, as with renal or ureteral calculi. Clinical findings are similar to those of renal abscess. A pleural effusion on the affected side and signs of psoas muscle irritation are common. Abdominal plain films may show obliteration of the psoas muscle shadow, and an intravenous urogram may show poor concentration of contrast medium and hydronephrosis. CT scan is the current study of choice for diagnosis.

Treatment involves prompt drainage of the abscess and use of appropriate systemic antibiotics, including coverage of anaerobes. Percutaneous drainage is often successful; however, open surgical drainage is necessary if percutaneous drainage is incomplete.

CYSTITIS

Cystitis is more common in females and is usually an ascending infection. In males, it usually occurs in association with urethral or prostatic obstruction, prostatitis, foreign bodies, or tumors. The urinary bladder is normally capable of clearing bacterial inoculation unless an underlying pathologic process interferes with its defensive mechanisms.

In the acute phase, the principal symptoms of cystitis are dysuria, frequency, urgency, and hematuria; low-grade fever and suprapubic, perineal, and low back pain may be present. In chronic cystitis, irritative symptoms are usually milder.

Evidence of prostatitis, urethritis, or vaginitis may be present. Laboratory findings, in addition to hematuria, consist of bacteriuria and pyuria. Leukocytosis is not common. Urine culture identifies the organism. Cystoscopy is not advisable in the acute phase. In chronic cystitis, evidence of mucosal irritation may be present.

In any documented recurrent lower urinary tract infection (particularly in males), a complete urologic workup is indicated. Instrumentation is contraindicated in the acute phase, but cystoscopy is essential to identify the predisposing factor in chronic or recurrent bacterial cystitis. Upper tracts should be investigated with renal ultrasound when a lower tract source of infection is not identified.

Specific antibacterial therapy is given according to sensitivity testing of recovered organisms (E. coli in > 80% of cases). Sterilization of urine should usually be followed by a variable period of continuous antibiotic therapy (depending on the predisposing factor or the chronicity and recurrence of the disease). Prolonged suppressive medication is usually indicated in cases associated with voiding dysfunction.

In females with recurrent postcoital cystitis, premedication (eg, sulfonamides, nitrofurantoin) on the night of intercourse and the following day in addition to immediate postcoital voiding decreases recurrences.

PROSTATITIS

Acute Bacterial Prostatitis

Acute bacterial prostatitis is a severe acute febrile illness caused by ascending coliform bacteria, which frequently colonize the male urethra. Symptoms include high fever, chills, low back and perineal pain, and urinary frequency and urgency with diminished stream or retention. On examination, the prostate is extremely tender, swollen, and warm to the touch. A fluctuant abscess may be palpable. The prostate must be examined cautiously, because vigorous palpation may cause acute septicemia. Laboratory findings include pyuria, bacteriuria, and leukocytosis.

Transurethral manipulation by catheter or cystoscopy should be avoided if possible; urinary retention should be treated by gently introducing a urethral catheter or introducing a percutaneous suprapubic tube. Treatment with systemic antibiotics (fluoroquinolones or aminoglycosides and ampicillin-cephalosporin) should be started immediately and should be adjusted later when results of urine culture or blood culture (or both) and sensitivity tests are known. E. coli is found in 80% of cases. Treatment with oral anti­biotics for several weeks after the initial phase has subsided is necessary to eradicate the bacteria completely.

Prostate abscess can develop from a smoldering acute prostatitis (typically gram negative bacteria) or from hematogenous seeding, often from gram-positive staphylococcus species. Pelvic imaging (CT, MRI, or ultrasound) identifies a hypodense fluid collection within the prostate parenchyma. Treatment includes a long course of culture-sensitive antibiotics and drainage of the abscess. Transrectal needle drainage and transurethral unroofing of the abscess are both successful modalities. Ultrasound-guided transrectal needle drainage can be done under local anesthesia, with or without intravenous sedation, whereas transurethral unroofing is performed with a resectoscope in the operating room, typically under general anesthesia. Thus, if feasible, it seems reasonable to attempt transrectal drainage first, and if the abscess recurs or persists then proceed to transurethral unroofing.

Chronic Prostatitis

Chronic prostatitis is a common and complex problem. With differential diagnosis including urethritis, bacterial and nonbacterial prostatitis, prostatodynia (chronic pelvic pain syndrome [CPPS]), and seminal vesiculitis, assigning the correct diagnosis may challenge even the expert. The symptoms are varied and include suprapubic pain, low back pain, orchialgia, dysuria at the tip of the penis, and urinary frequency and urgency. The urinalysis may be normal. There may be a clear white urethral discharge. Prostate examination may be normal or reveal a soft, boggy prostate.

Expressed prostatic secretions may contain numerous leukocytes (> 10 per high-power field) in clumps as well as macrophages. Cultures of urine are usually sterile, but cultures of expressed prostatic secretions and urine obtained after prostatic massage are usually positive in bacterial prostatitis. Chlamydia or Ureaplasma may be an offending organism, particularly in men under age 35. Determination of the site of infection may require differential cultures. The first part of the voided urine stream is collected as VB₁ and the midstream specimen as VB₂. The prostate is then massaged to obtain expressed prostatic secretions, and the postmassage urine is collected as VB₃. The differential leukocyte and bacterial counts from each of these specimens can help localize the site of infection. If VB₁ has high levels of leukocytes and bacteria relative to the other specimens, urethritis is likely; if VB₂ has high levels, a site above the bladder neck is likely; and if the expressed prostatic secretions, VB₃, or both have high counts, prostatitis is likely.

For chronic bacterial prostatitis, at least a 4- to 6-week course of a fluoroquinolone or trimethoprim-sulfamethoxazole is often given. Surgical treatment for prostatitis is rarely indicated or helpful. Some patients improve following discontinuation of caffeine and alcohol, and a few respond to repeated prostatic massage. Patients with no evidence of bacterial infection or obstructive findings, and those who have recurrent pelvic pain in association with voiding dysfunction (eg, intermittent or weak urinary stream) may be treated with α-adrenergic blocking agents or biofeedback to decrease the internal and external sphincter tone. 5α-Reductase inhibitors may be helpful.

ACUTE EPIDIDYMITIS

Acute epididymitis is most commonly a disease of young males, caused by bacterial infection ascending from the urethra or prostate. The disease is less common in older males, but when it does occur, it is most often due to infection secondary to urinary tract obstruction or instrumentation.

The symptoms are sudden pain in the scrotum, rapid unilateral scrotal enlargement, and marked tenderness that extends to the spermatic cord in the groin and may be relieved by scrotal elevation (Prehn’s sign). Fever is present. An acute hydrocele may result, and secondary orchitis with a swollen, painful testicle may occur. Laboratory studies reveal pyuria, bacteriuria, and marked leukocytosis.

Epididymitis must be differentiated from torsion of the testis, testicular tumor, and tuberculous epididymitis. A technetium-99m pertechnetate scan reveals increased uptake with epididymitis but decreased uptake with torsion. Scrotal ultrasound distinguishes between the solid mass of a testicular tumor and an enlarged, inflamed epididymis and can also identify epididymal or testicular abscess, which requires operative treatment. Increased blood flow on Doppler ultrasound also helps distinguish epididymitis from torsion, though it is not completely reliable.

Cultured aspirates from inflamed epididymides of males under age 35 tend to show gonococci and chlamydiae; in men older than 35, E. coli is most common. Epididymal aspiration for culture is not required routinely, however. Pyuria with a negative urine culture suggests the presence of chlamydial infection in both prostate and epididymis. (See also section on Tuberculosis.)

Treatment consists of antibiotics, usually ceftriaxone and doxycycline in males under age 35 and fluoroquinolones in those over age 35. In some patients, pain is relieved by scrotal hypothermia, and consideration should be given to infiltration of the spermatic cord by 1% bupivacaine. Nonsteroidal anti-inflammatory drugs are recommended to aid in pain relief. In most instances, prompt treatment results in rapid resolution of pain, fever, and swelling. Patients must refrain from exertion for 1-3 weeks.

Exacerbations can be controlled by treating the predisposing factor. Chronic epididymitis rarely resolves completely; it has no consequences except, occasionally in bilateral cases, sterility due to scarring and obstruction of the delicate epididymal tubules. Rarely, epididymectomy is necessary for severe and refractory pain.

TUBERCULOSIS

Tuberculosis is a commonly missed genitourinary infection that should be considered in any case of pyuria without bacteriuria or in any case of urinary tract infection that does not respond to treatment.

Genitourinary tuberculosis is always secondary to pulmonary infection, though in many cases, the primary focus has healed or is quiescent. Infection occurs via the hematogenous route. The kidneys and (less commonly) the prostate are the principal sites of urinary tract involvement, though any part of the genitourinary system can be affected.

Pathology

Renal tuberculosis usually starts as a tuberculoma that gradually enlarges, caseates, and finally ulcerates, breaking into the pelvicaliceal system. Caseation and scarring are the principal pathologic features of renal tuberculosis. In the ureter, tuberculosis usually leads to distal strictures, periureteritis, and mural fibrosis.

In the bladder, the infection is characterized by areas of hyperemia and a coalescent group of tubercles, followed by ulcerations. Bladder wall fibrosis and contraction are the end results.

Urethral involvement in the male is uncommon but when present leads to urethral stricture, usually in the bulbous portion. Periurethral abscess and fistula are possible complications.

Genital tuberculosis may involve the prostate, seminal vesicles, and epididymides, either separately or in association with renal involvement. Tubercle formation with later caseation and fibrosis is the basic pathologic feature. The prostate becomes enlarged, with palpable nodules and an irregular consistency. The affected seminal vesicle is fibrotic and distended. Induration and thickening of the epididymis and beading of the vas deferens are characteristic findings. The testicles are rarely involved.

Clinical Findings

A. Symptoms and Signs

The patient commonly presents with lower urinary tract irritation, usually with pyuria. Less common manifestations are hematuria, renal pain, and renal colic.

B. Laboratory Findings

“Sterile” pyuria is the rule, but 15% of cases have secondary bacterial infection (eg, E. coli). Mycobacteria can be identified on an acid-fast stain of the centrifuged sediment of the first morning urine collected on three successive days (positive in 90% of cases). Culture of the sediment should yield the mycobacteria, which may then be speciated by niacin and nitrate tests, both of which must be positive for a diagnosis of Mycobacterium tuberculosis.

C. Imaging Studies

Radiologic findings that suggest genitourinary tuberculosis include moth-eaten, caseous renal cavities, or bizarre, irregular calices. Strictures in straight, rigid, moderately dilated ureters and a contracted bladder with vesicoureteral reflux are all suggestive evidence.

Treatment

A. Medical Treatment

Tuberculosis must be treated as a systemic disease. Once the diagnosis is established, medical treatment is indicated regardless of the need for surgery. Whenever possible, medical treatment should be continued for at least 3 months before surgery is considered.

Active medications against tuberculosis include rifampin, isoniazid, pyrazinamide, ethambutol, and streptomycin. Standard initial treatment is with rifampin, isoniazid, and pyrazinamide for 8 weeks. Pyridoxine, 100 mg/d, is given in divided doses to counteract the vitamin B₆ depletion effect of isoniazid. In patients with more severe infections, ethambutol or streptomycin may be added to the initial treatment. Following the initial 8 weeks of therapy, rifampin and isoniazid are continued in combination three times per week for another 8 weeks. Liver function tests must be followed in view of the hepatotoxicity of rifampin, isoniazid, and pyrazinamide.

B. Surgical Measures

If medical therapy fails to cure a unilateral lesion, nephrectomy may be necessary. However, this is rare. In bilateral disease that has seriously damaged one kidney and is in an early stage in the other, unilateral nephrectomy may be considered; in localized polar lesions, partial nephrectomy may be done.

In unilateral epididymal involvement, epididymectomy plus contralateral vasectomy is indicated to prevent descent of the infection to the prostate; bilateral epididymectomy should be done if both sides are involved.

For a severely contracted bladder, augmentation enterocystoplasty increases vesical capacity following eradication of the infection.

Prognosis

In a high percentage of cases, cure is obtained by medical means. Unilateral renal lesions have the best prognosis.

RENAL STONE

General Considerations

Stone disease is common, with the lifetime risk of stone formation in the United States exceeding 12% in males and 6% in females. Prevalence of stone disease varies by racial background and geographic location within the United States, with older white males and southeastern states having the highest prevalence. Seventy-five percent of most stones are composed of calcium salts (oxalate and phosphate), while uric acid and struvite stones (magnesium-ammonium phosphate stones that form secondary to urea-splitting organisms) constitute 10% each. Formation of calcium stones can be due to one or multiple factors that include hypercalciuria, hypocitraturia, hyperoxaluria, and hyperuricosuria. In patients with hyperparathyroidism or those who ingest large amounts of calcium or vitamin D or in patients who are dehydrated or immobilized, hypercalciuria promotes stone formation.

Uric acid stones form in acidic urine. Cystine stones, which make up 1% of all stones, usually form secondary to impaired renal reabsorption of cystine. Owing to the radiodensity of sulfur, cystine stones are radiopaque (albeit less so than calcium stones), whereas uric acid stones are radiolucent. Stones that obstruct the ureteropelvic junction or ureter lead to hydronephrosis and possibly infection.

Clinical Findings

A. Symptoms and Signs

If the stone acutely obstructs the ureteropelvic junction or a calix, moderate to severe renal pain is noted, often accompanied by nausea, vomiting, and ileus. The pain starts in the upper lateral back and may radiate anteriorly and inferiorly toward the groin. Gross or microscopic hematuria is common. Symptoms of infection, if present, are exacerbated. Nonobstructing calculi are usually painless. This includes staghorn calculi, which may form a cast of all calices and the pelvis. In the symptomatic patient, there may be costovertebral angle tenderness and a quiet abdomen. Infection secondary to obstruction may lead to high fever and a rigid abdomen.

B. Laboratory Findings

With acute infection, leukocytosis is to be expected. Urinalysis may reveal red and white blood cells and bacteria. A pH of 7.6 or higher implies the presence of urea-splitting organisms. A pH consistently below 5.5 is compatible with the formation of uric acid or cystine stones. If the pH is fixed between 6.0 and 7.0, renal tubular acidosis should be considered as a cause of nephrocalcinosis. Crystals of uric acid (rhomboid) or cystine (hexagonal) in the urine are suggestive. A 24-hour urine collection can help identify the metabolic effect that predisposes to stone formation (hypercalciuria, hypocitraturia, hyperoxaluria). Hypercalciuria can be resorptive (due to hyperparathyroidism), absorptive (increased gastrointestinal absorption), or renal (increased urine loss of calcium). Citrate is a stone inhibitor and hypocitraturia predisposes to stone formation.

Increases in urine calcium and phosphate plus hypercalcemia (and hypophosphatemia) suggest the presence of hyperparathyroidism, and measurement of serum parathyroid hormone is helpful. Excessive urinary uric acid is compatible with uric acid stone formation.

A qualitative test for urinary cystine should be part of the routine evaluation. If levels are elevated, a 24-hour quantitative measurement should be made. Hyperchloremic acidosis suggests distal renal tubular acidosis with secondary renal calcifications. Total renal function is impaired only if the stones are bilateral, and particularly if chronic infection complicates the clinical presentation.

C. Imaging Studies

About 90% of calculi are radiopaque; the majority are calcium stones and can be seen on plain x-ray. However, stones smaller than 5 mm can be difficult to see on plain x-ray, and bowel gas may obscure stone visualization as well.

Renal ultrasound can be an excellent initial and follow-up imaging modality to identify renal calculi, although results depend on the quality of the sonographer. Stones are hyperechoic and cast an acoustic shadow. Small stones can be missed on ultrasound and sizing estimates can be poor. Hydronephrosis implies a downstream obstruction in the ureter, possibly from obstructing calculus, but ureteral stones are poorly visualized with ultrasound.

Spiral (helical) CT has become the study of choice, because the entire urinary tract can be scanned rapidly and without contrast injection (Figure 38–10). Calculi can be readily identified and distinguished from clot or tumor. Stones are accurately sized and localized with CT, and the anatomic detail is very helpful prior to operative intervention. CT scans deliver significant doses of ionizing radiation, making ultrasound an attractive initial modality to look for stones or obstruction, followed by CT for confirmation and more anatomic detail.

D. Stone Analysis

If a stone has previously been passed or if one is recovered, its chemical composition should be analyzed. Such information may be useful when planning a preventive program.

Differential Diagnosis

Acute pyelonephritis may begin with acute renal pain mimicking that of renal stone. Urinalysis reveals pyuria, and urograms or CT fails to reveal a calculus.

Renal adenocarcinoma may bleed into the tumor, causing acute pain mimicking that of an obstructing stone. Imaging can make the differentiation.

Transitional cell tumors of the renal pelvis or calices mimic uric acid stone; both are radiolucent. CT scan without contrast or ultrasound reveal the stone by virtue of increased density compared with adjacent soft tissues.

Renal tuberculosis is complicated by stone formation in 10% of cases. Pyuria without bacteriuria is suggestive. Urography reveals the moth-eaten calices typical of tuberculosis.

Papillary necrosis may cause renal colic if a sloughed papilla obstructs the ureteropelvic junction. Imaging (particularly CT) settles the issue.

Renal infarction may cause renal pain and hematuria. Evidence of a cardiac lesion, nonfunction of the kidney on urography, and exclusion of a calculus help in differentiation. Infarction is confirmed by angiography, radioisotopic renography, or color Doppler ultrasound.

Other conditions to be considered in the differential diagnosis include UPJO, obstruction due to blood clots, ureteral strictures or fungal bezoars, and renal abscess.

Complications

Acting as a foreign body, a stone increases the probability of infection. However, primary infection may incite stone formation. A stone lodged in the ureteropelvic junction leads to progressive hydronephrosis. A staghorn calculus, as it grows, may destroy renal tissue by pressure, and the infection that is usually present also contributes to renal damage. The presence of an obstructed renal unit with associated infection should be considered a urologic emergency. Drainage of the kidney should be performed promptly with insertion of a ureteral stent or percutaneous nephrostomy tube. Obstruction without infection can be managed without immediate drainage if renal function is preserved and pain is controlled (see ureteral calculi section below). Persistent obstruction for longer than 2-4 weeks requires intervention because permanent renal damage can ensue.

Prevention

An effective preventive regimen depends on stone analysis and chemical studies of the serum and urine.

A. General Measures

Ensure a high fluid intake (3-4 L/d) to keep solutes well diluted. This measure alone may decrease stone-forming potential by 50%. Treat infection, relieve stasis or obstruction, and advise the patient to avoid prolonged immobilization.

B. Specific Measures

1. Calcium stones

Remove the parathyroid tumor, if present. High dietary sodium promotes renal calcium absorption, and restriction to 100 mEq/d may be helpful. Limitation of proteins and carbohydrates may also reduce hypercalciuria. Recent randomized trials have shown that in men with recurrent calcium oxalate stones and hypercalciuria, restricted intake of animal protein and salt, combined with a normal calcium intake, provides greater protection than the traditional low-calcium diet. Potassium citrate can decrease stone formation by increasing urine levels of citrate, which is a stone inhibitor.

Oral orthophosphates are effective in reducing the stone-forming potential of urine by decreasing urine calcium and increasing inhibitor activity. Thiazide diuretics such as hydrochlorothiazide, 50 mg twice daily, decrease the calcium content in urine by 50%. If hyperuricosuria is coincident with calcium urolithiasis, then allopurinol and urinary alkalinization can reduce the formation of urate crystals, which may act as a nidus for calcium crystallization.

For a patient with primary absorptive hypercalciuria, cellulose sodium phosphate can be given. This substance combines with calcium in the gut to prevent absorption.

2. Oxalate stones (calcium oxalate)

Consider a phosphate or a thiazide diuretic (see above). Elimination of excessive oxalate in coffee, tea, colas, leafy green vegetables, and chocolate may also be helpful. Excess vitamin C can be metabolized to oxalate and thus should be avoided.

3. Magnesium-ammonium-phosphate stones

These stones are usually secondary to urinary tract infection due to bacteria that produce urease (primarily proteus species). Eradication of the infection prevents further stone formation but is impossible when stones are present. Acetohydroxamic acid, a urease inhibitor, can be used for oral chemolysis and can potentiate antibiotic action. After all calculi have been removed, prevention of stone growth is best accomplished by urinary acidification and suppression antibiotic therapy.

4. Metabolic stones (uric acid, cystine)

These substances are most soluble at a pH of 7.0 or higher. Give potassium citrate, 10-20 mEq by mouth three times a day, and monitor the urine pH with a litmus paper indicator or urine dipstick test. For uric acid stone formers, limit purines in the diet and give allopurinol if they have hyperuricemia. Patients with mild cystinuria may need only urinary alkalinization, as described previously. For severe cystinuria, penicillamine, 30 mg/kg/d orally, reduces urinary cystine to safe levels. Penicillamine should be supplemented with pyridoxine, 50 mg/d orally. Tiopronin, which has fewer side effects than D-penicillamine and captopril, can be used as well.

Treatment

A. Conservative Measures

Intervention is not required for small, nonobstructive, asymptomatic caliceal stones. Hydration and dietary management may be sufficient to prevent growth of existing or new calcium stones in patients without metabolic abnormalities. Those with identifiable metabolic disorders may benefit from the specific measures described previously. Patients with known uric acid stones can be treated with hydration and urinary alkalinization, which can help dissolve the stone. Patients with active infection, obstruction, or intractable nausea or pain may need definitive treatment. In the acute setting, a ureteral stent or percutaneous nephrostomy tube can be inserted.

B. Ureteroscopic Intervention

Patients with small stones can be managed with ureteronephroscopy and laser lithotripsy or basketing of the stones. The presence of a ureteral stent several days prior helps passively dilate the ureter and facilitates the procedure, but new, smaller caliber ureteroscopes preclude the need for elective preoperative stenting. As described above, stents should be placed emergently in the setting of infection/sepsis with obstructing calculus. After stenting and an appropriate course of antibiotics (typically 10-14 days), the definitive stone surgery is undertaken. Post-operatively, a ureteral stent is often left in place for several days to prevent acute obstruction secondary to edema or small stone fragments.

C. Percutaneous Intervention (Endourology)

In selected patients with symptomatic or large upper tract stones, percutaneous stone removal may be indicated. A percutaneous tract enters the renal collecting system through an appropriate calix (percutaneous nephrostomy). The tract is subsequently dilated, and endoscopic extraction of the stones (percutaneous nephroscopy and percutaneous nephrolithotomy [PCNL]) is done. Pulverization of the fragments is accomplished by means of ultrasonic, electrohydraulic, or laser probes passed through the nephrostomy tract. For cystine and uric acid stones, alkaline or other irrigants that increase the specific crystal solubility may be used (eg, N-acetyl-L-lysine or propionyl glycine for cystine stones). Specific antibiotic treatment for infection must be given before irrigation to prevent sepsis.

Success with these endourologic methods approaches 100%. The advantages over surgical procedures include no incision and rapid recovery and return to full activity. Disadvantages include the occasional need for multiple treatments to completely remove the calculi and the uncommon occurrence of significant hemorrhage, collecting system perforation, or stricture.

D. Extracorporeal Shock Wave Lithotripsy

With this technique, patients are positioned in the path of shock waves focused on the renal calculi with the aid of fluoroscopy or ultrasound. General or regional anesthesia is required in selected patients, but sedation may be sufficient. The shock waves (more than 1500 are usually given) pulverize the stones, and the small particles pass spontaneously in the postoperative period. With appropriate patient selection, results are excellent. Lower pole renal stones have lower success rates because pulverized fragments are less likely to completely pass. In addition, stones greater than 1.5 cm may produce to many fragments to successfully pass. PCNL is the treatment of choice for larger stones greater than 1.5-2.0 cm. Calcium stones and magnesium-ammonium-phosphate stones have been treated successfully. Because of the physical properties of the crystal lattice, extracorporeal shock wave lithotripsy (ESWL) is not as effective in fragmenting cystine stones. Radiolucent uric acid stones, which can be visualized using contrast medium are amenable to ESWL treatment. A variety of ESWL devices now effectively pulverize stones using less energy and thus can be used with only intravenous sedation; an increased number of pulses are required to obtain the same results as with previous higher energy devices. Some instruments use ultrasound instead of x-ray for stone localization. Complications include incomplete fragmentation and need for secondary procedures, ureteral obstruction from stone fragments, and perinephric hematoma.

E. Open and Laparoscopic Surgical Removal of Stones

Endourologic intervention and ESWL have markedly decreased the indications for open surgery. Rarely, both percutaneous nephrolithotomy and ESWL are contraindicated, and open nephrolithotomy is necessary. The goal of any approach is to remove all stone fragments, and the approach chosen must allow for intraoperative localization by radiography or ultrasonography. Incisions into the renal pelvis (pyelolithotomy) or the renal parenchyma (radial nephrotomy or anatrophic nephrolithotomy) may be required for complete stone removal. Instillation of a mixture of thrombin and calcium into the kidney causes the fragments to become trapped in a dense clot, which is removed through a pyelotomy incision (coagulum pyelolithotomy). Operative nephroscopy allows a full view of all the calices and removal of all fragments. “Bench” surgery with autotransplantation of the kidney may be required in very few instances. Rarely, poorly functioning kidneys containing symptomatic stones require nephrectomy, especially in cases of XGP. Laparoscopic and robotic pyelolithotomy have been used with excellent success and decreased morbidity compared with open surgery. This is especially the case in patients undergoing concomitant robotic pyeloplasty for UPJ obstruction.

Prognosis

The recurrence rate of renal stone can be as high as 40% and can be decreased with sufficient attention to measures for prevention of stone formation. The danger of recurrent stones is progressive renal damage due to obstruction and infection.

URETERAL STONE

General Considerations

Ureteral stones originate in the kidney. When symptoms occur, ureteral obstruction is implicit and renal function endangered. Complicating infection may occur. Most ureteral stones pass spontaneously, or with the assistance of medical expulsive therapy, especially if they are less than 0.5 cm in greatest dimension.

Clinical Findings

A. Symptoms and Signs

The onset of pain is usually abrupt. Pain is felt in the costovertebral angle and radiates to the ipsilateral lower abdominal quadrant. Nausea, vomiting, abdominal distention, and gross hematuria are common. When the stone approaches the bladder, symptoms mimic cystitis, with frequency and urgency. If the kidney is infected, acute ureteral obstruction exacerbates the infection.

The patient is usually in such agony that only parenteral opioids and NSAIDS will give relief. Costovertebral angle tenderness and guarding may be evident. Absence of bowel sounds and abdominal distention signify ileus. Fever may occur as a result of complicating renal infection.

B. Laboratory Findings

Laboratory findings are similar to those for renal stone. Unilateral obstruction secondary to ureteral stone may cause acute exacerbation of renal function, but not in all cases.

C. Imaging Studies

CT stone protocol is the gold standard to confirm stone size, location and degree of obstruction (Figure 38–11). Plain films may reveal an opacity in the region of the ureter and ultrasound will demonstrate ipsilateral hydronephrosis. Excretory urograms and retrograde urography reveal a filling defect (lack of dye) at the location of the stone. Almost all stones are radiopaque on CT scan. The density (hardness) of the stone can be estimated using the Hounsfield Units (HU). Calcium based stones are, on average, more than 1000 HU. Uric acid and struvite (infection) stones have lower HU.

Differential Diagnosis

A tumor of the kidney or renal pelvis may bleed, and passage of a blood clot may cause ureteral colic. Urograms may reveal a radiolucent area in the ureter surrounded by the radiopaque urine. A CT scan with and without contrast agents reveals no radiopacity in the ureter and helps define the renal parenchymal or renal pelvis tumor.

A primary tumor of the ureter may cause obstructing pain and hematuria. The urogram reveals the ureteral filling defect, often with secondary obstruction. A CT scan can differentiate a stone from tumor. Urinary cytologic study may reveal malignant urothelial cells.

Acute pyelonephritis may cause pain as severe as that seen with stone. Pyuria and bacteriuria are found but do not rule out stone. Stone is absent on noncontrast CT or urography.

A sloughed papilla (consequent to conditions such as diabetes mellitus) traversing the ureter may cause colic and produces a urogram compatible with uric acid stone. Papillary sloughs should be evident, however.

Complications

If obstruction from the ureteral stone is prolonged, progressive renal damage may ensue. Bilateral stones may cause oliguria or anuria, requiring immediate drainage of the proximal collecting system with indwelling ureteral stents or percutaneous nephrostomy. Unilateral obstructing stone in patients with a solitary kidney requires immediate drainage.

Infection may supervene, but many renal infections are iatrogenic (ie, introduced at the time of stone manipulation).

Prevention

See Renal Stone.

Treatment

A. General Measures

Most ureteral stones pass spontaneously—particularly those less than 0.5 cm in diameter. Once the diagnosis has been established, analgesics should be given and the patient hydrated. Recent reports have found alpha-antagonist therapy useful in expulsion of distal ureteral stones by relaxing smooth muscle. Randomized controlled trials have confirmed shorter time to stone passage with the use of alpha antagonists when compared with placebo. Periodic plain films should be taken to follow the progress of the stone and interval renal ultrasound studies obtained to assess the degree of hydronephrosis. The urine should be strained until the stone passes in order to recover the calculus for analysis. With larger stones, acute obstruction can be temporarily relieved by inserting an indwelling ureteral stent.

B. Specific Measures

If the stone causes intractable pain, progressive hydronephrosis, or acute infection, it should be removed. Obstructing stones in the upper two-thirds of the ureter can often be successfully treated by ureteroscopy or ESWL, with or without ureteral stent insertion to help facilitate stone passage. Ureteroscopy permits laser fragmentation or stone basket retrieval under direct vision. Open and laparoscopic/robotic surgical removal (ureterolithotomy) is only very rarely required for very large ureteral stones. ESWL has been applied to ureteral stones in the proximal ureter but is more problematic in the distal ureter owing to bone interference by surrounding pelvis, which interferes with imaging and attenuates shock wave force. Ureteral stones which have not spontaneously passed with medical expulsive therapy after 4 weeks should be considered for surgical removal with the above techniques.

Prognosis

About 80% of ureteral stones pass spontaneously. Stones larger than 1 cm rarely pass spontaneously. Periodic clinical evaluation, plain films, and renal ultrasound should be performed to document ureteral stone passage and prevent long-term renal damage from obstruction. Patients often do not witness small stones pass if a strainer is not utilized. If still uncertain about definitive stone passage, repeat CT scan can be obtained with the caveat of additional radiation exposure.

VESICAL STONE

Primary vesical calculi are rare in the United States but are common in Southeast Asia and the Middle East. The cause is probably dietary. Secondary stones usually complicate vesical outlet obstruction with residual urine and infection; 90% of those affected are men. Other causes of bladder stasis such as neurogenic bladder, and bladder diverticula also promote vesical stone formation. They are common in vesical schistosomiasis or in association with radiation cystitis. Foreign bodies in the bladder may act as a nidus for the precipitation of urinary salts. Most stones contain uric acid or struvite (in infected urine).

Clinical Findings

A. Symptoms and Signs

Symptoms of bladder neck obstruction are elicited. There may be sudden interruption of the stream and urethral pain if a stone occludes the bladder neck during voiding. Hematuria is common. Vesical distention may be noted; evidence of urethral stricture or an enlarged prostate is usually found.

B. Laboratory Findings

Pyuria and hematuria are almost always present.

C. Imaging Studies

Vesical calculi may be missed on plain x-rays due to the high component of radiolucent uric acid. Excretory urograms reveal a filling defect in the bladder and ultrasound reveals a large echogenic shadowing focus. CT scan easily identifies the number and size of the stones. Cystoscopy directly visualizes the stone(s) and also evaluates the entire urethra for stricture and/or prostate hypertrophy.

Differential Diagnosis

A pedunculated vesical tumor may suddenly occlude the vesical neck during voiding. Excretory urograms, pelvic ultrasound, CT scan, or cystoscopy leads to definitive diagnosis.

Extravesical opacifications may simulate stones on a plain film.

Complications

Acting as foreign bodies, bladder stones exacerbate urine infection and can cause obstruction at the level of the bladder neck. Antibiotic therapy for concomitant UTI is often unsuccessful given that the stones harbor persistent bacteria.

Prevention

Prevention requires relief of the primary obstruction, removal of the stones, and sterilization of the urine.

Treatment

A. General Measures

Analgesics should be given for pain and antimicrobials for control of infection until the stones can be removed.

B. Specific Measure

Small stones can be removed or crushed transurethrally (cystolitholopaxy). Larger stones are often disintegrated by transurethral electrohydraulic lithotripsy (shock wave–generating probe) or laser destruction, or they may require suprapubic transvesical removal (vesicolithotomy). If the nidus for stone formation is urinary stasis due to BPH, concomitant TURP or suprapubic transvesical prostatectomy should be performed at the time of stone removal.

Prognosis

Recurrent vesical stone is uncommon if the obstruction and infection are treated.

NEPHROCALCINOSIS

Nephrocalcinosis is a precipitation of calcium in the tubules, parenchyma, and, occasionally, the glomeruli. It always causes renal functional impairment, often severe. Stones may be found in the calices and pelvis. The common causes are primary or secondary hyperparathyroidism, excessive milk-alkali or vitamin D intake, or they may be found with severe renal damage associated with renal tubular acidosis, or sarcoidosis. Calcifications may also be seen in the skin, lungs, stomach, spleen, and corneas, or around the joints.

Clinical Findings

A. Symptoms and Signs

There are no specific symptoms. In childhood, the patient may merely fail to thrive. Stones or sand may be passed. The complaints are usually those of the primary disease. Physical examination may reveal an enlarged parathyroid gland, corneal calcifications, and pseudorickets.

B. Laboratory Findings

The urine may be infected. In renal tubular acidosis, the pH is fixed between 6.0 and 7.0. Urinary calcium is high in hyperparathyroidism, both primary and secondary. Tests of renal function are depressed; uremia is common. Hypercalcemia and hypophosphatemia are seen with primary hyperparathyroidism; secondary hyperparathyroidism may be associated with a low serum calcium and an elevated serum phosphate. Hyperchloremic acidosis and hypokalemia accompany renal tubular acidosis.

C. Imaging Studies

A plain x-ray reveals punctate calcifications in the papillae of the kidneys. Caliceal or pelvic stones may also be noted. The pattern of calcification may have to be differentiated from renal tuberculosis and medullary sponge kidney.

Complications

Complications include renal damage caused by the calcifications and renal and ureteral calculi. Chronic renal infection may complicate the primary disease.

Treatment & Prognosis

The primary cause should be treated if possible (eg, parathyroidectomy). Hydration with isotonic saline along with furosemide can help enhance calcium excretion. Discontinue vitamin D and milk-alkali producers if the primary cause was due to excessive intake. With hyperchloremic acidosis, alkalinize the urine with potassium citrate. Osteomalacia requires administration of vitamin D and calcium even though nephrocalcinosis is present.

If nephrocalcinosis is secondary to primary renal disease, the outlook is poor. If the cause is correctable and renal function is fairly good, the prognosis is more favorable.

INJURIES TO THE KIDNEY

General Considerations

Renal injury is uncommon but potentially serious and often accompanied by multisystem trauma. The most common causes are athletic, industrial, or automobile accidents. The degree of injury may range from contusion to laceration of the parenchyma or disruption of the renal pedicle.

Clinical Findings

A. Symptoms and Signs

Gross hematuria following trauma means injury to the urinary tract. Pain and tenderness over the renal area may be significant but could be due to musculoskeletal injury. Hemorrhagic shock may result from renal laceration and lead to oliguria. Nausea, vomiting, and abdominal distention (ileus) are the rule. Physical examination may reveal ecchymosis or penetrating injury in the costovertebral angle or flank. Extravasation of blood or urine may produce a palpable flank mass. Other injuries should be sought.

B. Laboratory Findings

Serial hematocrit determinations will give clues to persistent bleeding. Hematuria is to be expected, but the absence of hematuria does not exclude renal injury (as in renal vascular injury).

C. Imaging Studies

A plain film may reveal obliteration of the psoas shadow; this suggests the presence of a retroperitoneal hematoma or urinary extravasation. Bowel gas may be displaced from the area. Evidence of transverse vertebral process or rib fractures may be noted. In the past, the excretory urogram was used for evaluating renal trauma. Excretory urograms may show a normal kidney if it is mildly contused or may show extravasation of contrast medium if the kidney is lacerated. Nonfunction suggests injury to the vascular pedicle. The excretory urogram should demonstrate that the contralateral kidney is normal. CT scan with intravenous contrast medium is now the method of choice for staging a patient with hemodynamically stable renal trauma. CT scans may miss urinary extravasation if performed too rapidly following intravenous contrast administration—before the contrast is excreted into the collecting system and ureter. Therefore, trauma protocol CT scans should include a delayed phase of imaging, allowing time for contrast to be excreted in to the collecting system. If renal vascular damage is suspected and the patient’s condition is stable, preoperative renal angiography may facilitate planning of renovascular reconstruction or permit arterial stenting. In special circumstances, selective renal artery embolization may control segmental arterial bleeding. Renal imaging is indicated in any adult with gross hematuria or microscopic hematuria with shock. Imaging is also required with deceleration injuries and is indicated in children with gross or microscopic hematuria in the setting of trauma.

Differential Diagnosis

Bony fractures or contusion of soft tissues in the region of the kidney may cause confusion. Hematuria might be secondary to ureteral or vesical injury. The absence of a perirenal mass (ie, hematoma or urinoma) or contrast extravasation on urograms or CT scan would rule out significant trauma.

Complications

A. Early

The most serious complication is continued perirenal hemorrhage, which may be fatal. Serial hematocrit, blood pressure, and pulse determinations are essential. Serial CT scans may also be useful. Evidence of an enlarging flank mass implies persistent bleeding. In most cases, bleeding stops spontaneously, probably as a result of tamponade by the perirenal fascia. Delayed bleeding 1 or 2 weeks later is rare. Infection of the perirenal hematoma may occur.

B. Late

History, examination, and imaging are recommended 1-3 months after management of renal trauma to look for persistent renal damage from prolonged perinephric hematoma, obstruction, and/or urinary extravasation. Ultrasound is a good imaging modality to evaluate the integrity of the kidney and to assess for residual perinephric fluid collections and/or hydronephrosis. The blood pressure should be checked at regular intervals, because hypertension may be a late sequela.

Treatment

Treat shock and hemorrhage with fluids and transfusion. Most patients with blunt renal trauma stop bleeding and heal spontaneously. Bed rest is indicated until hematuria resolves and blood counts stabilize. If bleeding persists, angiography with possible segmental arterial embolization is an option if the patient is hemodynamically stable. Persistent hemodynamic instability requires laparotomy with renorrhaphy or nephrectomy.

Penetrating renal trauma usually requires exploration. Lacerations may be sutured, the collecting system closed, and urinary extravasation drained. Nephrectomy or partial nephrectomy may be necessary to remove devitalized tissue and secure the collecting system.

Late complications may occur. Perinephric abscess/infected hematoma should be drained. Hypertension may be due to renal ischemia and requires medical or surgical correction.

Prognosis

Most injured kidneys heal spontaneously, though the patient must be examined at intervals for the onset of hypertension due to renal ischemia or progressive hydronephrosis due to secondary ureteral stricture. Many patients with genitourinary trauma have associated injuries. In most cases, death is due to associated injury rather than renal injury.

INJURIES TO THE URETER

General Considerations

Most ureteral injuries are iatrogenic in the course of pelvic surgery. Ureteral injury may occur during transurethral bladder or prostate resection or ureteral manipulation for stone or tumor. Ureteral injury is rarely a consequence of penetrating trauma. Unintentional ureteral ligation during operation on adjacent organs may be asymptomatic, though hydronephrosis and loss of renal function results. Ureteral division leads to extravasation and urinoma.

Clinical Findings

A. Symptoms

If the ureteral injury is not recognized at surgery, the patient may complain of flank and lower abdominal pain on the injured side. Ileus and pyelonephritis may develop. Later, urine may drain through the wound (or through the vagina following transvaginal surgery) or there may be increased output through a surgical drain. Wound drainage may be evaluated by comparing creatinine levels found in the drainage fluid with serum levels; urine exhibits very high creatinine levels when compared with serum. Intravenous administration of 5 mL of indigo carmine causes the urine to appear blue-green; therefore, drainage from a ureterocutaneous fistula becomes blue, compared to serous drainage. Anuria following pelvic surgery not responding to intravenous fluids may rarely signify bilateral ureteral ligation or injury. Peritoneal signs may occur if urine leaks into the peritoneal cavity.

B. Laboratory Findings

Microscopic hematuria is usually found but may be absent. Tests of renal function may be normal unless both ureters are occluded. Drainage fluid will have increased levels of creatinine when compared with serum creatinine.

C. Imaging Studies

Excretory urograms may show evidence of ureteral occlusion. Extravasation of radiopaque fluid may be seen in the region of the ureter. Retrograde ureterography depicts the site and nature (occlusion or division) of the injury.

Ultrasonography may reveal hydroureter and hydronephrosis or a fluid mass representing urinary extravasation. CT urography (including delayed phase imaging) identifies the location of the ureteral injury, surrounding urinary extravasation, and potential urinoma or fistula.

Differential Diagnosis

Ureteral injury may mimic peritonitis if urine leaks into the peritoneal cavity. Excretory urography reveals the ureteral involvement.

Oliguria may be due to dehydration, transfusion reaction, or bilateral incomplete ureteral injury. A survey of fluid and electrolyte intake and output, including serial body weights, should prove helpful in delineating a medical versus surgical etiology for oliguria. Nephrology consultation should be considered. Total anuria may signify bilateral ureteral injury and indicates the need for immediate urologic evaluation.

Vesicovaginal and ureterovaginal fistulas may be confused. Methylene blue solution instilled into the bladder stains the vaginal drainage in the case of vesicovaginal fistula. Cystoscopy may show the vesical defect. Retrograde ureterography should reveal a ureteral fistula. The presence of both injuries occurring simultaneously should also be considered and evaluated.

Complications

These include urinary fistula, ureteral obstruction or stenosis with hydronephrosis, renal infection, peritonitis, and uremia (with bilateral injury).

Prevention

Before operation for large pelvic masses, which may cause displacement of the ureters, catheters should be placed in the ureters to facilitate their identification at surgery. Although the catheters may not prevent injury, they facilitate recognition of a ureteral injury intraoperatively and allow for immediate repair.

Treatment

A. Injury Recognized at Surgery

1. Ureteral division

Repair of a ureter inadvertently cut during surgery consists of anastomosis of the ends over an indwelling stent (ureteroureterostomy), reimplanting the ureter into the bladder if the injury is juxtavesical (neoureterocystostomy), or anastomosing the proximal segment of divided ureter to the side of the contralateral ureter (transureteroureterostomy). The anastomosis must be tension free, and the area of repair must be drained. Injuries resulting from cautery must be adequately debrided prior to reanastomosis.

2. Ureteral resection

Repair of a ureter from which a substantial segment has been removed requires interposition of a ureteral substitute or mobilization of the proximal and distal ureter to provide a tension-free anastomosis. With loss of the distal ureter, the bladder may be hitched cephalad to the psoas muscle, or a bladder flap may be created to facilitate a ureteral implant. In extreme cases, autotransplant of the kidney to the pelvis or bowel interposition may be necessary.

B. Injury Discovered After Surgery

Early intervention is recommended as soon as the ureteral injury is recognized. Depending on the findings, any of the procedures noted above may be utilized. If a long segment of ureter is not viable, an intestinal ureter may be constructed. If hydronephrosis is advanced or if sepsis develops, percutaneous nephrostomy should precede repair. When the patient’s condition is stable, definitive repair can be accomplished. If the injury is partial or incomplete, attempted ureteral stent placement for 4-6 weeks followed by repeat evaluation may obviate the need for laparotomy and open repair. Delayed nephrectomy may be indicated if the repair is unsuccessful and the contralateral kidney is normal.

Prognosis

In cases of iatrogenic injury, the results are best if the injury is recognized at the time of surgery. Late repair, if severe periureteral fibrosis has developed, is less likely to afford a good outcome.

INJURIES TO THE BLADDER

General Considerations

The most common cause of vesical injury is an external blow over a full bladder. Rupture of the organ is seen in 15% of patients with pelvic fracture. The bladder may be inadvertently opened during pelvic surgery or injured by cystoscopic maneuvers (eg, transurethral resection of bladder tumor). If the injury is intraperitoneal (40% of all bladder ruptures), blood and urine will extravasate into the peritoneal cavity, producing signs of peritonitis. If it is extraperitoneal (54% of all bladder ruptures), a mass develops in the pelvis. About 6% of all bladder ruptures have a combination of both intraperitoneal and extraperitoneal extravasation.

Clinical Findings

A. Symptoms and Signs

There is usually a history of hypogastric or pelvic trauma. Hematuria and suprapubic pain and possible inability to void are expected. Associated injury may cause hemorrhagic shock. There is suprapubic tenderness and guarding. Intraperitoneal extravasation causes peritoneal signs, while extraperitoneal extravasation results in formation of a pelvic urinoma.

B. Laboratory Findings

A falling hematocrit reflects continued bleeding. Hematuria is expected in patients who are able to void. A patient who cannot void should be catheterized unless pelvic fracture (and urethral injury) is suspected or blood is noted at the urethral meatus.

C. Imaging Studies

A plain film may reveal fracture of the pelvis. An extraperitoneal collection of blood and urine may displace the bowel gas laterally or out of the pelvis. If bladder trauma is suspected, cystography should precede excretory urography. Extravasation is most reliably demonstrated by a postdrainage cystogram film showing persistent contrast outside the area of the suspected bladder. If one suspects urethral trauma, a retrograde urethrogram should precede catheter insertion. The excretory urogram may suggest the diagnosis of bladder perforation but by itself is insufficient to exclude bladder injury. A CT cystogram is diagnostic for bladder injury and urinary extravasation. It also reliably distinguishes between intra- and extraperitoneal injury. A catheter is placed, the bladder filled by gravity with diluted contrast (350-400 mL), and subsequently the CT scan is performed.

Differential Diagnosis

Renal injury is also associated with bladder trauma and usually presents with hematuria. Imaging shows changes compatible with renal trauma; the cystogram is negative.

Injury to the membranous urethra can mimic extraperitoneal rupture of the bladder. A urethrogram reveals the site of injury. Urethral disruption is a contraindication to urethral catheterization.

Complications

Extraperitoneal extravasation may lead to pelvic abscess. Intraperitoneal extravasation causes delayed peritonitis, oliguria, and azotemia.

Treatment

Treat shock, hemorrhage, and other life-threatening injuries. Marked extraperitoneal extravasation should be drained, the bladder decompressed by either a suprapubic or urethral catheter, and appropriate antibiotics administered. Small extraperitoneal extravasations are treated nonoperatively by urethral catheter.

Intraperitoneal extravasation of bladder urine requires exploratory laparotomy, midline cystotomy, bladder closure, and bladder catheter drainage. Penetrating injuries (ie, gunshot, stabbing) require exploration, +/− debridement, and closure of the bladder. The ureters should also be evaluated in all cases of bladder injury by preoperative imaging or intraoperative assessment, which may be done by injecting indigo carmine and looking for ureteral extravasation or by retrograde passage of 5F feeding tubes through the ureteral orifice. A closed surgical drain is left in place.

Prognosis

Early diagnosis minimizes morbidity and mortality rates. The prognosis depends chiefly on the severity of associated injuries.

INJURIES TO THE URETHRA

Membranous Urethra

Injury to the membranous urethra is usually a consequence of pelvic fracture and thus is associated with hemorrhage and multiorgan injury. The mechanism of injury is blunt trauma and deceleration resulting in shearing forces applied to the prostate and urogenital diaphragm. Penetrating injuries result from external missiles or laceration by bone fragments acting as secondary projectiles.

If the urethral disruption is incomplete, the patient may be able to void, and hematuria would be inevitable. Urethral injury is suspected if blood is expressed from the urethral meatus. In cases of complete avulsion, extravasation causes a suprapubic mass. Rectal examination may reveal a nonpalpable or upwardly displaced prostate.

X-ray reveals a fractured pelvis; urethrography delineates any extravasation, and cystography identifies an associated bladder injury. An immediate excretory urogram or CT scan should be obtained in all cases to assess kidney and ureteral function.

Treatment must be coordinated with care of associated injury. Once a membranous urethral injury with urinary extravasation has been identified, suprapubic cystostomy should be performed either at the time of laparotomy or percutaneously before placement of external pelvic fixation. Definitive urethral repair may be delayed until the patient has recovered from the acute injury and pelvic fractures have healed. Occasionally, when urethral disruption is incomplete, late repair is unnecessary. Primary repair may be indicated in cases of severe prostatomembranous dislocation, major bladder neck laceration, or concomitant pelvic vascular or rectal injury.

Late sequelae are urethral stricture, impotence, and incontinence. Urethral stricture must be identified by retrograde urethrography and may be treated by transurethral incision of the stricture or urethroplasty. Impotence due to injury of nerves to the corpora cavernosa that course adjacent to the membranous urethra may resolve without treatment during the year following injury. Vascular injury of the hypogastric or pudendal arteries may cause impotence following trauma. Cavernosometry and arteriography confirms the diagnosis; appropriate treatment may include vascular reconstruction. Incontinence depends on the neurologic status of the patient. Medical or surgical therapy is utilized to increase bladder capacity and bladder outlet resistance.

Bulbous Urethra

The bulbous urethra may be injured as a result of instrumentation or, more commonly, falling astride an object (straddle injury). Urethral contusion may cause a perineal hematoma without injury to the urethral wall. Laceration leads to urinary extravasation.

Perineal pain and some urethral bleeding are to be expected. Sudden swelling in the perineum may develop following attempted urination. Examination reveals a perineal mass; swelling due to extravasation of blood and urine involves the penis and scrotum and may spread onto the abdominal wall.

If the patient can void well and the perineal hematoma is small, no treatment is necessary. If urethrography reveals significant extravasation, suprapubic cystostomy should be performed. Minor injury without extravasation (contusion, compression by hematoma) may be managed by careful insertion of a urethral catheter.

The only serious complication is stricture, which requires subsequent internal urethrotomy or surgical repair.

Pendulous Urethra

External injury to this portion of the urethra is not common, since the penis is so mobile. The erect organ, however, is vulnerable, and pendulous urethral injury often occurs in conjunction with penile fracture (see below). Injury during urethral instrumentation (eg, urethral catheter and urethroscopy) is another common etiology.

Urethral bleeding and penile swelling are to be expected. A urethrogram reveals the site and severity of injury.

If voiding is normal, no treatment is required. A large hematoma may require drainage. If significant injury is present, a suprapubic tube should be inserted and delayed surgical repair performed after swelling and inflammation have resolved.

INJURIES TO THE PENIS

Mechanisms of penile injury include penetration, blunt trauma to the erect penis during sexual activity (eg, fracture of corpora cavernosa), avulsion of skin, and amputation.

Tourniquet injury is also uncommon; the circumferential compression may be due to a rubber band, a steel ring, string, or a hair and may be exacerbated by subsequent erection. The tourniquet may have been applied unintentionally, but child abuse cases have been reported in which the penis has been ligated as punishment for enuresis.

Treatment includes assessment and care of urethral injuries if present. Removal of tourniquet, split-thickness skin grafting of avulsion injuries, and primary closure of corporal lacerations are principles of therapy. Penile fracture is considered a urologic emergency and immediate repair minimizes the inherent risk of future impotence and penile curvature. The penis may be acutely reimplanted up to 16 hours following amputation using microsurgical techniques.

INJURIES TO THE SCROTUM & TESTIS

Avulsion of the scrotal skin may require a meshed split-thickness skin graft. If the avulsion is severe, involving the skin and dartos muscle, then the testes may be implanted in the subcutaneous tissue of the thigh and dressed outside the wound with 0.25% acetic acid-soaked gauze. Scrotal reconstruction is performed at a later time, frequently by using skin grafts.

Penetrating trauma rarely injures the mobile testes. Lacerations should be explored, debrided, and closed primarily. If hemorrhage into the tunica vaginalis is noted, drainage is indicated.

Blunt trauma to the testes may cause contusion or rupture. Rupture of the tunica albuginea may be demonstrated by ultrasonography as abnormal echotexture of the parenchyma. In cases of rupture, scrotal exploration is imperative allows debridement and closure of the tunica albuginea. The testes may ultimately undergo atrophy despite these efforts.

Tumors of the genitourinary tract are among the most common neoplastic diseases found in adults. Prostate cancer, for example, is the most common cancer in men (33%), and renal and bladder cancer account for nearly 10% of all malignant tumors in men, but only about 3% in women. Even though excellent diagnostic methods are available, one-third of all genitourinary tumors are not found until regional or distant spread has occurred. Advances in diagnosis and treatment of genitourinary tract tumors have occurred in recent years, and the prognosis has improved in conditions such as Wilms tumor, testicular cancer, and bladder cancer. The mainstay of diagnosis continues to be physical examination, complete urinalysis, CT urography and cystoscopy whenever indicated. Curative treatment of these tumors continues to be surgical in most instances.

RENAL ADENOCARCINOMA (RENAL CELL CARCINOMA)

General Considerations

Malignant tumors of the kidney account for approximately 3% of all tumors in adults. Often, the diagnosis is found incidentally on ultrasound, CT scan, or MRI. Microscopic or gross hematuria evaluation can also identify renal cell carcinoma (RCC). Advanced or metastatic disease can present with flank mass, weight loss, or pathologic fracture. rRisk factors for RCC include cigarette smoking, obesity, and hypertension. The disease occurs in men three times more commonly than in women. A suppressor gene on chromosome 3p has been shown to be present in von Hippel–Lindau renal cancers as well as in most sporadic RCC. The most common cell type is clear cell (also called conventional) carcinoma, accounting for 70%-80% of renal carcinomas. The cell of origin is in the proximal convoluted tubule. Other cell types include papillary (10%-15%), chromophobe (3%-5%), and collecting duct renal carcinoma (1%). The tumor metastasizes commonly to the lungs (50%-60%), adjacent renal hilar lymph nodes (25%), ipsilateral adrenal (12%), opposite kidney (2%), and lytic lesions in mainly long bones (30%-40%).

Numerous conditions predispose to renal cell cancer, including von Hippel–Lindau syndrome (cerebellar hemangioblastomas, retinal angiomatosis, and bilateral RCC), tuberous sclerosis, and acquired renal cystic disease developing in patients with end-stage renal disease. Paraneoplastic syndromes are common in RCC and are often what suggests the diagnosis, yet they rarely have prognostic significance. These syndromes include hypercalcemia, erythrocytosis, hypertension, fever of unknown origin, anemia, and elevated liver enzymes (Stauffer’s syndrome). RCC has a predilection for producing occlusive tumor thrombi in the renal vein and the inferior vena cava (particularly from the right kidney), manifested by signs of lower extremity edema and acute scrotal varicocele when occluding the left renal vein. This phenomenon of inferior vena cava thrombus occurs in approximately 5%-10% of patients. Occasionally, the tumor thrombus reaches up to the right atrium.

Clinical Findings

A. Symptoms and Signs

Painless gross or microscopic hematuria throughout the urinary stream (“total hematuria”) occurs in some patients. The degree of hematuria is not necessarily related to the size or stage of the tumor. Although a triad of hematuria, flank pain, and a palpable flank mass suggests RCC, fewer than 10% of patients will so present. Both pain and a palpable mass are late events occurring only with tumors that are very large or invade surrounding structures or when hemorrhage into the tumor has occurred. Symptoms due to metastases may be the initial complaint (eg, bone pain, respiratory distress). Localized disease is often identified incidentally on imaging.

B. Laboratory Findings

Microscopic urinalysis reveals hematuria in most patients. The erythrocyte sedimentation rate may be elevated but is nonspecific. Elevation of the hematocrit and levels of serum calcium, alkaline phosphatase, and aminotransferases occur in fewer than 10% of patients. These findings nearly always resolve with curative nephrectomy and thus are not usually signs of metastases. Anemia unrelated to blood loss occurs in 20%-40% of patients, particularly those with advanced disease.

C. Imaging Studies

The diagnosis of RCC is often made by CT (and, less frequently, by intravenous urography) performed as an initial step in the workup of hematuria, an enigmatic metastatic lesion, or suspicious laboratory findings (Figure 38–12). Ultrasonography and CT scan often reveal incidental renal masses, which now account for 50% of the initial diagnoses of RCC in patients without manifestations of renal disease. Plain abdominal x-rays may reveal a calcified renal mass, but only 20% of renal masses contain demonstrable calcification. (Twenty percent of masses with peripheral calcification are malignant; more than 80% with central calcification are malignant.) The initial technique for workup of hematuria is currently CT urography which can accurately identify an enhancing renal mass which is diagnostic for RCC. CT scan is also helpful in local staging and can reveal tumor penetration of perinephric fat; enlargement of local hilar lymph nodes, indicating metastases; or tumor thrombi in the renal vein or inferior vena cava. CT angiography can delineate the renal vasculature, which is helpful in surgical planning for partial nephrectomies.

1. Ultrasonography

Occasionally, some masses detected on CT require further characterization by ultrasound. Abdominal ultrasonography can define the mass as a benign simple cyst or a solid mass in 90%-95% of cases. Abdominal ultrasound can also identify a vena caval tumor thrombus and its cephalad extent in the cava.

2. MRI

MRI is not more accurate than CT and is much more expensive. It is, however, the most accurate noninvasive means of detecting renal vein or vena caval thrombi. With the further refinement of pulse sequencing and the use of paramagnetic contrast agents, MRI has become one of the primary techniques for staging solid renal masses. Magnetic resonance angiography (MRA) has become particularly useful for mapping the blood supply and the relationship to adjacent structures in candidates for partial nephrectomy.

D. Other Diagnostic or Staging Techniques

Isotopic bone scanning is useful in patients with bone pain, elevated alkaline phosphatase, or known metastases. Chest x-ray is sufficient if negative, but if equivocal, then CT scan of the chest can be used to detect metastases. Identification of metastatic disease in the thorax warrants consideration of brain imaging to rule out occult disease. There are currently no tumor markers specific for RCC. Occasionally, biopsy of the mass can be useful in when imaging is not definitive, or when metastases from another primary malignancy are a possibility. Previously, such procedures were discouraged because of fear of disseminating the tumor along the needle tract, but this has proved to be rare, and the technique is safe. False negative results and insufficient tissue for diagnosis are limitations of renal mass biopsy. Fortunately, imaging is diagnostic in most cases.

Differential Diagnosis

A variety of lesions in the retroperitoneum and kidney other than renal cysts may simulate renal cancer. These include lesions due to hydronephrosis, adult polycystic kidney disease, tuberculosis, xanthogranulomatous pyelonephritis, metastatic cancer from another primary cancer, angiomyolipoma or other benign renal tumors, or adrenal cancer and retroperitoneal lipomas, sarcomas, or abscesses. In general, one or more imaging techniques described above should make the differentiation. Percutaneous biopsy is necessary in rare instances when imaging cannot make the diagnosis.

Hematuria may be caused by renal, ureteral, or bladder calculi; renal pelvis, ureteral, or bladder tumors; or many other benign conditions usually delineated by the studies described. Cystoscopy is obligatory in hematuric patients with a normal CT scan or intravenous urogram to rule out disease of the bladder and to determine the source of the hematuria.

Complications

Occasionally, patients may present with acute flank pain secondary to hemorrhage within a tumor or colic secondary to obstructing ureteral clots. Tumor in the renal vein or vena cava may cause an acute left varicocele or lower extremity edema associated with proteinuria. Pathologic fractures are due to osteolytic metastases in long bones. Brain metastases can present with seizure or other neurologic symptoms.

Treatment

Staging is the key to designing the treatment plan (Table 38–1). Patients with disease confined within the renal fascia (Gerota’s fascia) or limited to nonadherent renal vein or vena caval tumor thrombi (stages T1, T2, and T3a) are best treated by surgical extirpation with either radical nephrectomy or partial nephrectomy. Radical nephrectomy traditionally includes en bloc removal of the kidney and surrounding Gerota fascia (including the ipsilateral adrenal), the renal hilar lymph nodes, and the proximal half of the ureter. However, adrenal-sparing radical nephrectomy is routinely performed for mid- and lower-pole renal tumors with equivalent outcomes.

In patients with very large or central tumors and a normal contralateral kidney, radical nephrectomy is recommended. In all other cases, attempts should be made for nephron-sparing surgery. Successful partial nephrectomy with negative surgical margins offers the same survival benefit as radical nephrectomy. Typically hilar-vessel occlusion with bulldog or satinsky clamp(s) is performed to allow for resection in a relatively bloodless field.

Laparoscopic radical or partial nephrectomy has been advocated as a method equal to the open approach with the advantages of less blood loss, shorter hospitalization, and earlier return to normal function. It is the gold standard in institutions with appropriate expertise. Laparoscopic or percutaneous cryoablation of RCC has also shown considerable promise. Alternatively, radiofrequency ablation has been utilized for small renal tumors. These ablative technologies do not provide pathologic diagnosis; so percutaneous biopsy can be performed before the procedure or intraoperatively.

Nephrectomy has not been associated with improved survival rates in patients with multiple distant metastases (stage IV), and the procedure is not recommended unless patients are symptomatic or a promising therapeutic protocol is being studied. Flanigan and others have shown, however, that up to a 6-month improvement in survival can be achieved with nephrectomy—even with soft tissue metastasis—in selected patients who also receive interferon alpha systemic therapy. Patients with solitary pulmonary metastases have benefited from joint surgical removal of both the primary lesion and the metastatic lesion (30% survival at 5 years). Preoperative arterial embolization in patients with or without metastases does not improve survival rates, though it may be helpful as a single treatment measure in patients with symptomatic but nonresectable primary lesions. Radiation therapy is of little benefit except as treatment for symptomatic bone metastases. Medroxyprogesterone for metastatic RCC has given an equivocal 5%-10% response rate of short duration. Vinblastine has also had a response rate of approximately 20%, again of minimal duration. There are no other cytotoxic chemotherapeutic agents of benefit.

Immunotherapy with interferon alpha has had a 15%-20% response rate. Other interferons, alone (interferon beta, interferon gamma) or in combination with chemotherapeutic agents, have been less effective than interferon alpha. Adoptive immunotherapy—using lymphocytes (lymphokine-activated killer cells) from exposure of the patient’s own peripheral blood lymphocytes to interleukin-2 (IL-2) in vitro followed by reinfusion into the patient along with systemic IL-2 infusion—has shown up to 33% objective response rates. High-dose intravenous IL-2 causes a profound capillary leak syndrome and substantial toxicity. Subsequent studies have shown only a 16% response rate.

Recent advances in research on the von Hippel–Lindau tumor suppressor gene has led to identification of growth factors including vascular endothelial growth factor (VEGF) and platelet-derived growth factor as molecular targets in treating advanced renal cancer. Initial studies using bevacizumab, an anti-VEGF antibody, have shown promising results. Sorafenib, a tyrosine kinase inhibitor that blocks the pathway leading to the production of several growth factors, has been studied in patients with metastatic renal cancer and shown longer median progression-free survival than placebo (24 weeks vs. 6 weeks). Sunitinib, another tyrosine kinase inhibitor, has shown longer progression-free survival and higher response rates than interferon alpha in patients with metastatic renal cancer. These oral agents are currently used as first-line therapy in this group of patients.

Temsirolimus is another targeted agent that is a specific inhibitor of the mammalian target of rapamycin kinase (mTOR inhibitor) and has shown promising results. It is now used as first-line therapy in poor prognosis patients. Many other agents are currently being studied.

Prognosis

Patients with localized RCC (stages T1, T2, and T3a) treated surgically have 5-year survival rates of approximately 70%-80%, whereas rates for those with local nodal extension or distant metastases are 15%-25% and less than 10%, respectively. Most patients who present with multiple distant metastases succumb to disease within 15 months (Table 38–1). The advent of new agents for RCC may improve the outcome in these patients.

RENAL SARCOMA

Renal sarcomas include rhabdomyosarcoma, liposarcoma, fibrosarcoma, and leiomyosarcoma; the latter is the most common, though all are very uncommon. Sarcomas are highly malignant and are usually detected at a late stage and thus have a poor prognosis. The diagnostic approach is similar to that of RCC. The histology of the lesion is rarely suspected preoperatively, although local invasion into surrounding retroperitoneal structures is more common than with RCC. These tumors have a tendency to surround the renal vasculature and do not exhibit neovascularity on MRA.

Treatment is surgical, with wide local excision; however, local recurrence and subsequent distant metastases are the rule. There is no therapy of proved benefit for metastatic disease.

SECONDARY MALIGNANT RENAL TUMORS

Metastatic tumors to the kidney are more common than primary renal tumors and often develop from primary tumors of distant sites, most commonly the lung, stomach, and breast. It is rare for the diagnosis to be made before autopsy; this suggests that renal metastasis is a late event. There are usually no symptoms, though microscopic hematuria occurs in 10%-20% of cases. Imaging reveals a renal mass, often difficult to distinguish from RCC. Contiguous spread of a tumor adjacent to the kidney is not infrequent (eg, tumors of the adrenal, colon, and pancreas and retroperitoneal sarcomas). Tumors such as lymphoma, leukemia, and multiple myeloma may also infiltrate the kidney. Routine radiologic, hematologic, and chemical examinations should demonstrate the primary tumor in most cases. Percutaneous biopsy may be appropriate in certain circumstances.

BENIGN RENAL TUMORS

Renal Oncocytoma

Renal oncocytomas are benign renal neoplasms. The tumors are generally asymptomatic and not associated with the paraneoplastic syndromes. The finding of a central stellate scar on CT or a spoke-wheel pattern of feeding arteries on angiography may suggest the diagnosis, although these findings have been found to be unreliable. Oncocytomas can coexist with renal carcinoma in the same lesion or in other lesions in the same kidney (7%-30%). This finding, along with difficulty differentiating oncocytoma from clear cell or chromophobe renal cancers on fine-needle aspirates, make it difficult to make a definitive diagnosis preoperatively. Consequently, definitive treatment of these lesions with radical or partial nephrectomy, or with ablation (cryoablation or RFA) has been recommended.

Mesoblastic Nephroma

Mesoblastic nephroma is a benign congenital renal tumor seen in early childhood, which must be distinguished from the highly malignant nephroblastoma, or Wilms tumor. Unlike Wilms tumor, mesoblastic nephroma is commonly diagnosed within the first few months of life. Histologically, it is distinguished from Wilms tumor by cells resembling fibroblasts or smooth muscle cells and by the lack of epithelial elements. The prognosis is excellent; complete surgical resection is curative, and neither chemotherapy nor radiotherapy is required.

Angiomyolipoma

Angiomyolipoma is a benign hamartoma seen most often bilaterally in adults with tuberous sclerosis (which also includes adenoma sebaceum, epilepsy, and mental retardation). The tumor is also common in middle-aged women, but only unilaterally. These tumors can be detected following spontaneous retroperitoneal hemorrhage, though 50% of these lesions are currently diagnosed incidentally. CT scan can be diagnostic, with negative Hounsfield units detected in the fat-containing area of the tumor. Occasionally, an angiomyolipoma eludes diagnosis preoperatively and requires resection (especially the lipid-poor angiomyolipoma). Asymptomatic patients with small (< 4 cm) tumors and typical findings on CT scan of fat within the tumor do not require surgery, as the prognosis is excellent without treatment. These patients can be followed with serial imaging. Those presenting with a retroperitoneal hemorrhage or a size greater than 4 cm should have the tumor removed surgically with partial nephrectomy or embolized via angioinfarction, which has been shown to be effective.

Other Benign Renal Tumors

Other benign renal tumors include (1) fibroma, a renal parenchymal capsular or perinephric fibrous mass; (2) lipoma, an adipose deposit within or around the kidney, often perihilar or within the renal sinus; (3) leiomyoma, a common retroperitoneal tumor that may arise from the renal capsule or renal vascular walls; and (4) hemangioma, which is occasionally found to be the elusive cause of hematuria. Hemangiomas are generally quite small, and the diagnosis can be confirmed by direct vision of the lesion in the renal collecting system on ureteroscopy.

TUMORS OF THE RENAL PELVIS & CALICES

General Considerations

In over 90% of cases, tumors involving the collecting system of the kidney are urothelial (or transitional cell) carcinomas. Fewer than 5% of tumors in this location are squamous carcinomas (often in association with chronic inflammation and stone formation) or adenocarcinomas. The cause of urothelial carcinoma of the upper urinary tract is similar to that of epithelial tumors in the ureter or bladder; there is a strong association with cigarette smoking and exposure to industrial chemicals. Excessive use of phenacetin-containing analgesics and the presence of Balkan nephritis are also predisposing factors.

Clinical Findings

A. Symptoms and Signs

Gross or microscopic painless hematuria occurs in over 70% of patients. The lesions are usually asymptomatic unless bleeding causes acute flank pain secondary to obstructing clots. Presenting symptoms can often be due to metastases to bone, the liver, or the lungs. Physical examination is usually negative for any positive findings.

B. Laboratory Findings

Microscopic hematuria on urinalysis is the rule. Pyuria is not seen. Cytologic examination of voided urine specimens may be diagnostic in high-grade tumors. Urine obtained from the ureter by retrograde catheterization or by brushing with specialized ureteral instruments can improve the diagnostic accuracy of cytologic examinations. Direct biopsy during ureteroscopy is the most accurate. There are no commonly associated paraneoplastic syndromes or diagnostic serum tumor markers in urothelial carcinoma. A large number of urine markers are currently being studied, but only in situ hybridization studies identifying abnormalities in chromosomes 3, 7, 17, and 9p21 can be recommended at present.

C. Imaging Studies

The diagnosis is commonly made on CT urography or intravenous urography and confirmed by retrograde pyelography and ureteroscopy with biopsy. Renal ultrasound or CT scan can be used to rule out calculus. CT scan is also useful in local staging of the tumor. The tumors metastasize to the lungs, liver, and bone, so chest x-ray, CT scan of the lungs and liver, and a bone scan are useful to determine the presence of metastases. Urothelial carcinoma tends to be multifocal in the urinary tract, involving the opposite kidney (1%-2%), ipsilateral ureter, or bladder (38%-50%). Surveillance of these potential sites is important.

D. Endoscopic Findings

Cystoscopy is necessary when gross hematuria is present to determine the location of the bleeding. Lateralizing hematuria can be identified with cystoscopy (bloody efflux from one ureteral orifice). Retrograde pyelography and ureteral cytologic studies or brushing, as described previously, can be useful, though mildly abnormal cytologic findings may occur in patients with upper tract inflammation or calculi. Rigid or flexible ureteroscopes can be used to view the upper ureter and renal pelvis directly. Biopsy of upper tract lesions is possible through these instruments. Although percutaneous approaches to the renal collecting system have been perfected, their use for diagnosis or treatment of suspected urothelial carcinoma in routine cases is not recommended, because of the possibility of spreading tumor cells outside the kidney.

Differential Diagnosis

A variety of conditions may mimic transitional cell carcinoma of the renal pelvis, including calculi, sloughed renal papillae, tuberculosis, and RCC with pelvic extension of the tumor. These can usually be ruled out by the diagnostic studies described previously.

Complications

Occasionally, bleeding may be severe enough to require immediate nephrectomy. Infection may develop, particularly when there is obstruction and hydronephrosis, requiring prompt use of systemic antibiotics.

Treatment

Renal urothelial carcinoma is treated by nephroureterectomy (perifascial nephrectomy and removal of the entire ureter, down to and including the ureteral orifice within the bladder). Transureteral or percutaneous endoscopic techniques for resection of selected low-grade lesions have been successful, particularly in patient with significant chronic kidney disease and/or solitary renal units. Upper tract instillation of bacille Calmette-Guérin (BCG) or mitomycin C has been reported with modest results. High recurrence rates and the potential for local tumor spread would argue against this approach in high-grade or extensive lesions. Laparoscopic nephroureterectomy has become common practice, but management of the distal ureter and bladder cuff by this technique has been the subject of controversy. Regional lymph node dissections have not been traditionally performed, although recent reports have shown some benefit for patients with aggressive disease. Because 50% of these patients will develop urothelial carcinoma of the bladder, cystourethroscopy must be performed postoperatively; it is usually done quarterly during the first year, twice the second year, and then annually.

Prognosis

Because most of these tumors are low grade and noninvasive, the 5-year tumor-free survival rate is higher than 90% for lesions treated with complete removal of the ipsilateral upper urinary tract. Survival rates are much lower for lesions that invade the renal parenchyma or are of high histologic grade. A poor prognosis is associated with tumors having histologic features of squamous carcinoma or adenocarcinoma. These tumors are mildly radiosensitive, but preoperative or postoperative radiotherapy has not been particularly helpful. Metastatic lesions are particularly problematic, and survivors are rare. Chemotherapy combinations, which have shown benefit in urothelial carcinoma of the bladder (methotrexate, vinblastine, Adriamycin, and cisplatin [MVAC] or gemcitabine and cisplatin), are also efficacious in urothelial carcinoma of the upper urinary tract.

TUMORS OF THE URETER

General Considerations

Ureteral tumors are rarely benign, but benign fibroepithelial polyps do occasionally occur within the ureter. More than 90% of ureteral tumors are urothelial carcinomas. The cause is unknown, but tobacco smoking and exposure to industrial chemicals are known to be associated. Ureteral urothelial carcinoma is often found in association with renal pelvis urothelial carcinoma and slightly less often with bladder urothelial carcinoma. The lesions develop in persons aged 60-70 years and are twice as common in men as in women. More than 60% of these tumors occur in the lower ureter.

Clinical Findings

A. Symptoms and Signs

Gross or microscopic hematuria is the rule (80% of cases). Because ureteral tumors grow slowly, they may not cause symptoms even though they completely obstruct the kidney. Occasionally, gross hematuria may cause acute obstruction because of clots. The initial presentation may be due to symptomatic metastases to bone, lungs, or liver.

B. Laboratory Findings

Urinalysis commonly reveals hematuria. There are no biochemical markers specific to the diagnosis, though patients with metastases may have abnormal liver function tests or anemia. Serum creatinine levels may be elevated with complete unilateral obstruction in elderly patients. Cytologic studies of voided urine or ureteral urine or brush biopsy studies may be diagnostic.

C. Imaging Studies

The diagnosis may be made on CT or intravenous urography, though the tumor often obstructs the ureter completely, so that cystoscopy and retrograde pyelography are required for definition of the lesion. These studies often reveal a filling defect in the ureter (classically described as a goblet sign). The ureter is dilated proximal to the lesion. CT scan is useful in ruling out nonopaque calculi and in abdominal tumor staging. Chest x-ray, CT scans, and bone scans are helpful in determining the presence of metastases.

D. Endoscopic Findings

Cystoscopy is necessary when gross hematuria is present to determine the site of bleeding. Retrograde pyelography may then be necessary. Ureteroscopy may provide a direct view of the tumor and access for biopsy.

Differential Diagnosis

Nonopaque calculi, sloughed renal papillae, blood clots, or extrinsic compression by retroperitoneal masses or nodes may all produce signs, symptoms, and x-ray findings similar to those with ureteral tumors. The radiographic, cytologic, and endourologic studies listed above should make the distinction, but surgical exploration is required occasionally.

Treatment

Most ureteral transitional cell carcinomas are not associated with metastases and can be definitively treated with nephroureterectomy. Selected patients with noninvasive low-grade lesions may be treated by segmental ureteral resection with end-to-end anastomosis (ureteroureterostomy), or ureteral reimplanation for lesions in the distal one-third of the ureter. In some patients carefully selected with low-grade noninvasive tumors, resection or laser ablation can be considered. Regional lymph node dissections have not been traditionally performed, although recent reports have shown some benefit. Preoperative or postoperative radiation therapy appears to be of no benefit. As with renal pelvis and bladder urothelial carcinoma, cystoscopy should be performed periodically postoperatively. Patients with metastases are rarely helped by removal of the primary tumor. These tumors are responsive to chemotherapy. Traditional agents that have been used include cisplatin with gemcitabine or MVAC. These have shown reasonable response rates but poor long-term outcomes.

Prognosis

The 5-year survival rate for patients with low-grade noninvasive lesions treated surgically approaches 100%. Those with high-grade or invasive lesions have a poorer prognosis, and those with metastases have a 5-year survival rate of less than 10%.

TUMORS OF THE BLADDER

General Considerations

Vesical neoplasms account for nearly 6% of all cancers in men and are the second-most common cancer of the genitourinary tract in men. In women, these tumors account for 2% of all cancers and are the most common cancer of the genitourinary tract. Men are affected twice as often as women. More than 90% of tumors are urothelial carcinomas, while a few are squamous cell carcinomas (associated with chronic inflammation, as in bilharziasis) or adenocarcinomas (often seen at the dome of the bladder in patients with a urachal remnant).

Most urothelial carcinomas (70%-80%) are nonmuscle invasive (not invasive into the bladder detrusor musculature) when recognized. Only 10%-15% of recurrent tumors become invasive.

The cause of urothelial carcinoma is unknown; there is a strong association with chronic cigarette smoking and exposure to chemicals prevalent in dye, rubber, leather, paint, and other chemical industries.

The treatment and prognosis depend entirely on the degree of anaplasia (grade) and the depth of penetration of the bladder wall or beyond (Table 38–2). Most of these tumors develop on the trigone and the adjacent posterolateral wall; thus, ureteral involvement with obstruction is a possibility. Tumors tend to be multifocal within the bladder. Approximately 5% of patients develop upper urinary tract urothelial carcinoma as well.

Clinical Findings

A. Symptoms and Signs

Gross or microscopic hematuria is a common finding that leads to the diagnosis. Patients with diffuse noninvasive tumors, particularly carcinoma in situ, may have urinary frequency and urgency. Occasionally, large necrotic tumors become secondarily infected, and patients exhibit symptoms of cystitis. Pain secondary to clot retention, tumor extension into the bony pelvis, or ureteral obstruction may occur but are not frequent presenting complaints. When both ureters are obstructed, azotemia with attendant secondary symptoms may be the finding that requires diagnostic studies.

External physical examination is not generally revealing, though occasionally a suprapubic mass may be palpable. Rectal examination may reveal large tumors, particularly when they have invaded the pelvic sidewalls. Thus, bimanual examination is a necessary part of staging evaluation.

B. Laboratory Findings

Microscopic hematuria is the only consistent diagnostic finding. Patients with bilateral ureteral obstruction may have azotemia and anemia. Liver metastases may cause elevation of serum transaminases and alkaline phosphatase. There are no paraneoplastic syndromes or tumor markers consistently present in patients with urothelial carcinoma. Urinary markers currently being studied are various tumor-associated antigens, growth factors, and nuclear matrix proteins, but none are proved to be accurate enough to obviate cystoscopy for diagnosis.

C. Imaging Studies

Small bladder tumors are not seen on intravenous urography but may be seen on CT. Larger tumors usually produce filling defects in the bladder on both urography or CT (Figure 38–13). Ureteral obstruction with hydroureteronephrosis may occur as well. Invasion of the bladder wall may be predicted in patients with asymmetry or marked irregularity of the bladder wall. Noninvasive lesions seen on CT or intravenous urography tend to be exophytic within the bladder, without evidence of bladder wall distortion.

Ultrasonography by external, transrectal, or transurethral routes can accurately define moderate-sized bladder tumors and can often depict deep invasion.

CT scan can be useful for staging, but the depth of bladder wall penetration and delineation of tumor deposits in adjacent nonenlarged lymph nodes are not accurately defined. In patients with nodal metastases suspected on CT scans, fine-needle aspiration and cytologic studies may confirm the diagnosis and eliminate the need for surgical exploration. MRI is helpful in the pelvis, where motion artifacts are minor and the scant pelvic fat is just enough to provide organ differentiation. However, the information is not superior to that obtained with CT.

D. Urinary Cytologic Studies

Urothelial tumors shed neoplastic cells into the urine in large numbers. Low-grade tumor cells may not appear abnormal on cytologic examination, but higher-grade tumor cells can be detected by cytologic study with high specificity. These studies are most useful in checking for recurrence of urothelial carcinoma. Flow cytometry (differential staining of DNA and RNA within urine cells to measure the amount of nuclear protein and thus the relative number of aneuploid [abnormal] cells) has been used to screen patients with some success. This technique may be useful for early diagnosis of recurrence. The urinary fluorescence in situ hybridization assay is more sensitive and comparably specific for bladder cancer cells as compared to cytology.

E. Endoscopic Findings

Cystoscopy is mandatory in any adult patient with unexplained hematuria and a normal upper-tract imaging study. Many urothelial carcinomas are not identified on CT or intravenous urography. Cystoscopic examination should detect nearly all tumors in the bladder (Figure 38–14). Only a few patients will have carcinoma in situ (high-grade noninvasive tumor) that is not visible. Any tumor seen should be biopsied and preferably resected to completion if the patient is under anesthesia. The entire bladder, including the bladder neck, should be routinely scrutinized in all patients with microscopic hematuria. In patients without visible tumor and no other causes of hematuria, random biopsies may be diagnostic of carcinoma in situ. A bimanual examination should be done during cystoscopy in all patients with urothelial carcinoma to be certain that the bladder is not fixed, signifying extensive extravesical extension.

F. Staging

Therapy depends on the stage of the tumor as seen on histologic sections and examinations for metastases. Table 38–2 sets forth the stage, treatment, and prognosis of patients with urothelial carcinoma of the bladder. The histologic grade of the tumor is also important in determining treatment and prognosis, but in general, low- and high-grade histologic characteristics tend to occur in low- and high-stage tumors, respectively.

As previously discussed, CT scan, MRI, or both may be helpful in predicting the stage of the tumor. Isotope bone scanning, chest x-ray, and chest CT scan evaluate the possibility of bone or pulmonary metastases and should be done before determining therapy in patients with invasive lesions.

Treatment

A. Transurethral Resection, Fulguration, and Laser Therapy

Endoscopic transurethral resection of superficial and submucosally invasive low-grade tumors can be curative. Nevertheless, because the tumor recurs in more than 50% of patients, cystoscopy should be performed periodically. Quarterly examinations are recommended during the first year following tumor resection, every 6 months during the second year, and annually thereafter. Periodic urinary cytologic examinations can be helpful as well. Upper tract surveillance with CT urography is recommended for high-grade tumors, typically every 2 years. Low-grade tumors do not require upper tract surveillance unless hematuria recurs without evidence for tumor recurrence in the bladder. Recurrent small tumors without obvious invasion may be treated by fulguration only, though biopsy is recommended to document the stage and grade.

Neodymium:YAG lasers have been used for desiccation of low-grade, low-stage tumors. There is as yet no proven advantage to this approach except that patients can be treated under local anesthesia as outpatients and perhaps that tumor cells are rendered nonviable and thus incapable of reimplantation elsewhere in the bladder or urethra. Biopsies for diagnosis and staging are still required.

B. Intravesical Therapy

A variety of chemotherapeutic agents have been used in patients with recurrent low-grade, low-stage tumors. Mitomycin C is instilled into the bladder by catheter (40 mg in 40 mL of water) and left indwelling for 1-2 hours. Patients are treated once a week for 6 weeks and may undergo a less frequent maintenance regimen. Treatment results in decreased frequency of recurrence or no recurrence in nearly 50% of patients. Other agents include thiotepa and doxorubicin.

Immunotherapeutic drugs, which include BCG, are effective in prophylaxis (60%) of recurrent papillary tumors and curative (70%) in carcinoma in situ, a highly malignant lesion less responsive to the cytotoxic agents described earlier. Intravesical BCG is the gold-standard first line therapy for carcinoma in situ of the bladder. Side effects of BCG include vesical irritability (90%), low-grade fever, and systemic BCG-osis (1%). Although the mechanism of action of BCG is not entirely known, it is suspected to induce T-cell recruitment and subsequent cytokine release locally at the tumor site. It is the most effective agent currently used. Interferon alpha has also been studied and is effective (nearly 50% of cases) for carcinoma in situ, with less toxicity than BCG; however, its durability as a single agent is poor. The combination of BCG and interferon alpha has shown nearly 50% response rates and is occasionally used in patients who have failed BCG. BCG is contraindicated in immunocompromised patients due to risk of systemic BCG infection and the likely decreased efficacy.

Immediate instillation of Mitomycin C after transurethral resection has shown a substantial decrease in recurrence rates and is now standard of care.

C. Radiation Therapy

Definitive radiation therapy should be reserved for patients who have inoperable muscle-invasive bladder cancer localized to the pelvis or who refuse surgical treatment, as the 5-year survival rate is only 30%. In some patients with recurrence after radiation therapy, salvage cystectomy can be curative (in at least 30% of cases), though surgical morbidity rates are high. Radiation, when used, is combined with systemic chemotherapy.

D. Surgical Therapy

Occasional patients are seen with muscle-invasive lesions (T2) localized to an area in the bladder well away from the bladder base or orifices and without tumor in other sites of the bladder (proved by multiple biopsies) or beyond. Partial cystectomy (removal of the tumor with a cuff of normal bladder) may be appropriate in these patients. Such tumors are rare, and patients must be selected carefully for partial cystectomy. All other patients with high-grade or invasive (T2 and T3) lesions without distant spread or a fixed pelvis on bimanual examination are best treated by radical cystectomy and pelvic lymph node dissection. This includes removal of the bladder and the prostate in men. Removal of the entire urethra may be necessary in selected patients with tumors at the bladder neck or in the prostate or in those with diffuse carcinoma in situ in the bladder. In women, the uterus, ovaries, fallopian tubes, urethra, and the anterior vaginal wall are usually removed en bloc with the bladder. Vaginal-sparing cystectomy can be performed as well.

Urinary diversion is required and is accomplished with the use of intestinal conduits, pouches or neobladders. Ileal conduit urinary diversion creates a urostomy on the skin and requires continuous bag drainage. This is the most common urinary diversion with the lowest complication rates. Continent cutaneous urinary diversions requiring intermittent cutaneous catheterization rather than cutaneous bag drainage became popular in the late 1980s. The basic principles are large-volume reservoirs with detubularization of bowel to maintain low intrapouch pressures and construction of an intussuscepted or plicated ileal segment to provide cutaneous continence. Orthotopic neobladder reservoirs also have been devised using bowel configurations similar to those described above to connect directly to the membranous urethra in men and in the distal two thirds of the female urethra, permitting the patient to void normally. These procedures are appropriate in both men and women and have been shown to be safe, with minimal increase in morbidity over cutaneous diversions.

Robotic cystectomy has been done in large numbers at select centers in the United States and Europe. With short-term follow up, oncologic outcomes appear equivalent to open surgery with potentially less blood loss and faster convalescence postoperatively. In most cases, the urinary diversion is done via open surgery, but more recently, ileal conduit and neobladder urinary diversions have been performed intracorporeally with robotic assistance.

E. Systemic Chemotherapy

Chemotherapy in the form of CMV (cisplatin, methotrexate, and vinblastine) or MVAC (CMV plus doxorubicin [Adriamycin]) has been used precystectomy (neoadjuvant) or postcystectomy (adjuvant) for muscle-invasive tumors or as treatment of metastatic urothelial cancer. More recently, gemcitabine and cisplatin have become standard of care after a randomized trial showed similar efficacy to MVAC with fewer side effects. A recent randomized trial showed improved survival in patients with locally advanced bladder cancer who received neoadjuvant chemotherapy and cystectomy compared to those who underwent cystectomy alone. Adjuvant chemotherapy has been shown in randomized trials to help patients with locoregional disease but not patients with localized disease (stage T1-T2). Several reports of efficacy with either CMV or MVAC for treatment of metastatic disease have shown a 60% overall objective response rate with a 30% complete response rate. A few long-term survivors with apparent cure have been reported (10%-15%), and either of these regimens thus appears to be a definite advance in the treatment of urothelial cancer. Other chemotherapeutic agents used in urothelial cancer include paclitaxel and carboplatin in various regimens that appear to have similar efficacy with less toxicity.

Prognosis

Approximately half of the low-grade superficial tumors are controlled by transurethral surgery or intracavitary use of chemotherapeutic agents (Table 38–2). Following radical cystectomy, the 5-year survival rate varies with the extent, stage, and grade of the tumor, but with T2N0M0 tumors averages about 50%-70%. The complications of urinary diversion (ureteral obstruction with hydronephrosis, pyelonephritis, and nephrolithiasis) also influence the outcome.

CARCINOMA OF THE PROSTATE

General Considerations

In adult men, prostate cancer is the most common neoplasm (after skin cancer) and the second-most common (after lung cancer) cause of death due to cancer. The tumor is more prevalent in black men than in any other group in the United States. The tumor rarely occurs before age 40, and the incidence increases with age such that more than 75% of men older than age 85 have prostate cancer on autopsy. In most of these older men, however, the disease is not clinically apparent; only 10% of men over age 65 develop clinical evidence of the disease. Ninety-five percent of tumors are adenocarcinomas. The tumor arises primarily in the peripheral zone (85%), an area that differs in embryologic derivation from the periurethral (transition) zone, which is the site of formation of benign prostatic hyperplasia. The cause of prostate cancer is unknown, but many factors appear to be involved, including genetic, hormonal, dietary (particular high-fat diets), and perhaps environmental carcinogenic influences.

Screening

Screening with PSA monitoring and digital rectal examination (DRE) has been controversial due to conflicting evidence regarding a decrease in mortality. Two very large randomized controlled trials examining the effects of PSA screening on mortality have recently been completed, one in the United States and one in Europe. The US trial did not show a survival benefit in the screening group, although the control group was significant contaminated with men who had some previous PSA testing. The European study showed a relative survival benefit of 20% in the screening group after 10 years of follow-up, and the data will be reanalyzed with longer follow-up.

Based on all available evidence, the US Preventive Services Task Force released a recommendation against routine screening for prostate cancer in 2011. The American Urological Association recommends a shared decision making discussion about prostate cancer screening with men between the ages 55-69, and at a younger age for those men with a positive family history in a first degree relative or for African Americans. If screening is agreed upon, serum PSA level and DRE are performed annually or every two years based on the clinician’s discretion.

Clinical Findings

A. Symptoms and Signs

Nonpalpable (T1) carcinoma of the prostate presents without physical signs and is only diagnosed by the pathologist when prostate tissue is removed as treatment for symptomatic bladder outlet obstruction presumed to be caused by benign prostatic hyperplasia or is found by an elevated PSA (T1c). Patients T2 or higher disease have a hard nodule on the prostate that can be felt during rectal examination (Table 38–3). T3 disease is palpable (or visible by imaging) beyond the capsule of the prostate or demonstrates seminal vesicle involvement. T4 disease invades adjacent organs including the rectum and pelvic sidewall. Previously, 50% of patients presented with evidence of metastases, including weight loss, anemia, bone pain (commonly in the lumbosacral area), or acute neurologic deficit in the lower limbs. Today, however, fewer than 20% of patients present in this way because of earlier diagnosis due to wide use of PSA screening (stage migration).

B. Laboratory Findings

Patients with extensive metastases may have anemia due to bone marrow replacement by tumor. Those with bilateral ureteral obstruction secondary to trigonal compression by tumor may exhibit azotemia and uremia. Serum alkaline phosphatase is often elevated in patients with bone metastases but not in those with localized disease.

PSA is elevated in the serum of most men with prostate cancer, but high-grade (Gleason 8-10) cancers and ductal variant adenocarcinomas can present with normal PSA levels. Values above 4 ng/mL are considered abnormal but rise normally with age and significant benign prostatic hypertrophy. PSA can also be falsely elevated due to cystoscopy, prostate biopsy, urethral catheterization, and urinary tract infection. Routine DRE does not usually affect PSA levels.

Methods for enhancing PSA specificity include the following: (1) age-specific PSA (younger men [< age 50 years], normal < 2.5 ng/mL; older men [> age 70 years], normal > 6.5 ng/mL); (2) PSA density (PSA divided by prostate volume), where less than 0.15 ng/mL suggests cancer; (3) percent-free PSA (total PSA minus complexed PSA), where lower values signify an increased risk of cancer (useful for total PSA levels between 4 and 10). While total PSA is useful for staging, it is not absolute. PSA appears to be most helpful in following up on patients after treatment, as levels fall to undetectable after surgery and decrease dramatically after radiation therapy when there is a complete response. There are several new prostate cancer markers currently being investigated, but none have become widely used to date. PCA3 urinary assay shows promise in men with persistently elevated PSA levels and previous negative biopsies.

C. Imaging Studies

Transrectal ultrasound has become very useful for evaluating prostate volume and guiding biopsy needles into the peripheral zone and other specific areas, such as the base, the apex, and the transition zone of the prostate. The study can also reveal typical hypoechoic peripheral zone lesions in 70% of patients with palpable lesions. Because many prostate cancers are not hypoechoic and not all hypoechoic lesions are cancer, transrectal ultrasound alone for screening for prostate cancer is not recommended. CT scan may reveal urinary retention, distal ureteral obstruction with resultant hydronephrosis, and pelvic lymphadenopathy. Locally advanced disease and bony metastases can also be visualized on CT scan. A chest x-ray or CT may help in identifying the uncommon lung metastases but more often shows typical osteoblastic metastases in the thoracic spine or ribs. An abdominal x-ray may reveal metastases in the lumbosacral spine or ilium. Abdominopelvic CT is not usually recommended unless the disease is palpable, Gleason score is 7 or more, or PSA level is more than 20 ng/mL.

Endorectal MRI (eMRI) appears to be more helpful than CT scan in the staging of prostate cancer. This study allows for localization of malignant lesions within the prostate as well as assessment for extracapsular extension, seminal vesical invasion, involvement of adjacent organs, and lymph node involvement. eMRI is useful for clinical staging and preoperative planning but is reliant upon having a radiologist with expertise in this field.

Positron emission tomography is not typically utilized for prostate cancer staging.

D. Biopsy

The diagnosis is established by transrectal ultrasound–guided biopsies in most instances. Because the great majority of patients have biopsies due to an elevated serum PSA (stage T1c) and no abnormal findings on exam or imaging, biopsies of the base, middle, and apex of the prostate—concentrating on the peripheral zone, with 6 biopsies per side of the prostate—are required for accurate diagnosis.

Differentiation of the tumor is graded by the pathologist using the Gleason score, which assigns a grade of 1-5 (low to high grade) for both the primary and secondary forms of the tumor. The two numbers are added, and the cancer can thus be Gleason sum 2-10, with 10 being the most poorly differentiated cancer. Gleason score is an independent predictor of disease recurrence. Typically, pathologists give Gleason scores between 6 and 10.

E. Staging

Rectal examination can provide initial staging in patients with palpable tumors (Table 38–3). Needle biopsy is confirmatory, and histologic grading (Gleason score) can fairly accurately predict the metastatic potential of the tumor. Imaging as described above can be useful for staging of the primary tumor (eMRI) and to rule out metastatic disease (eMRI, bone scan).

Differential Diagnosis

Nodules caused by benign prostatic hyperplasia may be difficult to distinguish from cancer; benign nodules are usually rubbery, whereas cancerous nodules have a much harder consistency. Fibrosis following a prior prostatectomy for benign disease or secondary to chronic prostatitis or prior biopsies may be associated with lesions indistinguishable from cancerous nodules and require biopsy for definition. Occasionally, phleboliths or prostatic calculi on the surface of the prostate may be confusing; however, transrectal ultrasound can be helpful in the differentiation and for biopsy guidance.

Treatment

A. Curative Therapy

Curative treatment for localized prostate cancer includes radical prostatectomy and various forms of radiation therapy (external beam radiation therapy, transperineal radioactive seed placement [brachytherapy with ¹²⁵I, ¹⁰³Pd, or ¹⁹²Ir], and cyberknife). Complete staging is important so that appropriate candidates will be selected. Patients with localized prostate cancer are stratified into three risk groups (Table 38–4). Low-risk patients have similar 5-year recurrence survival rates irrespective of the curative treatment modality. Intermediate-risk and high-risk patients have better recurrence-free rates with prostatectomy or external beam radiation compared to brachytherapy. None of these modalities have been compared in randomized trials. The only reported randomized trial compared watchful waiting to radical prostatectomy and showed improved disease-free as well as overall survival in the prostatectomy group. Studies have shown that compared to external beam radiotherapy alone, combined androgen deprivation (for 6 months to 3 years) and external beam radiation improve survival in patients with localized prostate cancer, especially patients in the intermediate and high-risk groups. Patients with grossly positive pelvic lymph nodes are not candidates for curative therapy. Recent advances in surgical technique have led to a low incidence of incontinence (1%-4%) and preservation of potency in up to 70% of patients. Alternative procedures include external beam pelvic irradiation plus brachytherapy and transperineal cryoablation of the prostate for primary and recurrent disease after radiation.

For the past decade, robotic-assisted radical prostatectomy has increased in popularity and has been shown to have decreased blood loss and length of hospital stay and more rapid return to normal activity than open surgery. Oncological and functional (continence and potency) outcomes are equivalent to open surgery. More than 80% of prostatectomies in the United States are now performed with the da Vinci™ Robot.

B. Palliative Therapy

Patients with metastatic disease cannot be cured, but significant palliation can be offered. Androgen deprivation therapy in the form of luteinizing hormone–releasing hormone (LHRH agonist or bilateral orchiectomy) is effective in 70%-80% of symptomatic patients. Estrogen-based treatments are less commonly used due to the numerous side effects (in about 25% of patients), including congestive heart failure, thrombophlebitis, and myocardial infarction, and thus should not be used except in selected patients. These hormonal treatments are not additive, and use of both treatments simultaneously has no advantages over use of either alone. LHRH agonists have shown efficacy comparable to that of estrogen or orchiectomy, with reduced side effects, and are preferred by patients who find bilateral orchiectomy unacceptable. The drug must be given by injection every 1-6 months (depending on dosage) or via subcutaneous pellet annually. Studies have also shown that if an LHRH agonist is used, concomitant administration of an antiandrogen (flutamide or bicalutamide) may slightly improve survival. Studies to determine if orchiectomy plus an antiandrogen is more effective than orchiectomy alone have not shown an advantage to the combination. Antiandrogens should be administered for at least one week prior to inception of LHRH agonists to prevent the short-term flare that occurs with initiation of LHRH monotherapy. LHRH antagonists have more recently become available and have a faster onset to castration, and do not require pre-treatment with antiandrogens.

Hot flashes, osteoporosis, cardiac disease, and cognitive impairment are all potential long-term side effect of androgen deprivation.

Controversy continues concerning whether to treat asymptomatic patients at the time of diagnosis or to wait until symptoms develop. Because either approach is palliative only and there are no definitive studies showing survival advantages with early treatment, it is recommended that treatment be withheld until PSA is relatively high (> 20 ng/mL) or symptoms occur except in patients who cannot accept a no-treatment philosophy. Recent studies do show that patients who have had a radical prostatectomy and have node-positive disease do have a slight survival advantage with early hormonal treatment.

Patients whose prostate cancer becomes hormone refractory (median of 18 months after starting treatment) can be treated by ketoconazole (which inhibits adrenal androgen production) with oral corticosteroids for short-term response. Radiation therapy for symptomatic bone lesions can be helpful, as can local irradiation for an obstructing or bleeding prostate tumor. On occasion, transurethral prostatectomy is required to relieve bladder outlet obstruction. Chemotherapy with docetaxel and prednisone has shown a slight survival advantage in phase III trials.

Prostate Cancer Prevention

Because the etiology of prostate cancer is not known, prevention is difficult to determine. However, there is evidence that a low-fat diet and lycopene (found in processed tomatoes) decrease the growth of prostate cancer cells in vitro and in vivo in animals. Further large-scale epidemiologic studies suggest a decrease in prostate cancer in humans who consumed vitamin E and selenium. However, these studies were not planned specifically for this purpose, and thus the results were questionable. A current randomized trial comparing selenium and vitamin E (SELECT) was recently halted due to the lack of evidence of prostate cancer prevention. The largest chemoprevention trial (Prostate Cancer Prevention Trial [PCPT]), with over 18,000 men, compared finasteride (5α-reductase) to placebo and found a 25% reduction in prostate cancer with finasteride but also showed an increased risk of high-grade cancer in the finasteride-treated patients. While this is thought to be an artifact of the study, these results have limited enthusiasm for recommending prevention therapy with finasteride routinely.

Prognosis

Radical prostatectomy cures 70%-80% of the patients suitable for that operation, but its use should be limited to those with a reasonable life expectancy (Table 38–3). Currently, about 60%-70% of patients with prostatic cancer are amenable to curative therapy when their disease is discovered.

TUMORS OF THE URETHRA

Malignant tumors of the urethra are rare. The disease is more common in women than in men (4:1). Squamous cell types are seen most often in both sexes.

In women, urethral bleeding is the most common symptom. Distal urethral lesions of low grade and without extension can be treated by radiotherapy or wide local excision. Advanced disease is best treated by combination radiotherapy, chemotherapy, and surgery to achieve good local and distant disease control. Surgery includes anterior exenteration (removal of the bladder, uterus, adnexa, and urethra with the anterior vaginal wall), including pelvic lymphadenectomy and urinary diversion. The prognosis is excellent for distal lesions without extension, but 5-year survival rates are less than 50% for those with proximal lesions.

In men, the lesion is most commonly in the bulbomembranous urethra and is associated with a history of chronic urethral strictures, often secondary to gonorrheal infection. Patients present with urethral bleeding, a weak urinary stream, and a perineal mass. The diagnosis is made by urethroscopy and biopsy. Distal penile urethral lesions can be treated by partial or total penectomy. Lesions in the bulbous urethra or more proximal lesions require extensive surgical resection, including en bloc removal of the penis, urethra, prostate, bladder, pelvic lymph nodes, and urinary diversion. In both men and women with distal lesions, inguinal lymphatics may be involved, but node dissection is required only when gross disease is palpable. Prophylactic node dissection is controversial. Five-year survival rates are 60% for distal urethral tumors but less than 40% for the more common proximal lesions.

Primary irradiation—other than to distal lesions in the female—is rarely helpful. Patients with metastatic disease may respond to methotrexate or cisplatin alone or in combination, but objective remissions are usually of short duration.

TUMORS OF THE TESTIS

General Considerations

Most testicular tumors are malignant germ-cell tumors. Non–germ-cell tumors such as Sertoli cell tumors and Leydig cell tumors are rare and usually benign. Germ-cell tumors are categorized as either seminomatous (35%) or nonseminomatous (embryonal, 20%; teratocarcinoma, 38%; teratoma, 5%; and choriocarcinoma, 2%). Cryptorchidism predisposes to testicular cancer, with the incidence increasing inversely with the level of testicular descent (ie, testicles remaining in the abdomen have a much higher incidence of cancer). Metastases first develop in the retroperitoneal nodes; right-sided tumors metastasize primarily to the interaortocaval region just below the renal vessels and left-sided tumors primarily to the left para-aortic area at the same level. Distant spread is to supraclavicular areas (left, primarily) and the lungs. Almost 50% of patients have metastases when first evaluated, and this is more common for nonseminomatous tumors.

Clinical Findings

A. Symptoms and Signs

Testicular tumors present as a painless firm mass within the testicular substance. They often have been present for several months before the patient seeks consultation. Occasionally (10%), a hydrocele is present, obscuring palpation of the mass. A few patients have spontaneous bleeding into the mass, causing pain. Patients with high serum levels of hCG may have gynecomastia. Patients with extensive abdominal metastases may present with abdominal pain, anorexia, and weight loss. Examination may reveal palpable retroperitoneal nodes when spread is extensive or palpable supraclavicular nodes, particularly on the left side.

B. Laboratory Findings

In general, testicular tumors do not alter the usual laboratory parameters, but serum tumor markers are diagnostically helpful. Patients with extensive retroperitoneal metastases may have bilateral ureteral obstruction that causes azotemia and anemia.

Serum lactic dehydrogenase, particularly isoenzyme I, is elevated in approximately 60% of patients. β-HCG, a particularly sensitive marker, is a glycoprotein produced by 65% of nonseminomatous testicular tumors but only 10% of seminomas. The alpha-subunit of the molecule is identical to LH, but the beta-subunit is unique to testicular tumors in adult men. There is cross-reactivity in some assays between the alpha- and beta-subunits; treated patients who develop modest elevations should have simultaneous assay of LH to be certain the marker detected is β-hCG.

α-Fetoprotein is elevated in 70% of patients with nonseminomatous testicular cancer but is not elevated in patients with seminoma. Patients in whom histologic study has shown seminoma but in whom serum AFP is elevated should be suspected of having nonseminomatous elements in the primary specimen or metastatic lesions.

Approximately 85% of patients demonstrate elevation of one of these markers at presentation. Serum levels decrease when the tumor is completely removed or regresses. Markers are used mainly to follow tumor regression or predict recrudescence, as even minute amounts of tumor may cause serum elevations; however, tumor may be present without elevation of serum markers.

C. Imaging Studies

Abdominal CT scan defines enlarged lymph nodes in approximately 90% of cases when they are present. Chest x-ray and CT scan will detect most pulmonary metastases.

Scrotal ultrasound is useful for identifying the typical hypoechoic lesion in the testicle. Regardless of the findings on ultrasound, however, a young man with an intratesticular mass on palpation requires surgical definition of the mass.

Differential Diagnosis

Testicular masses in men aged 18-40 are frequently malignant and should be treated accordingly. Confusion can occur with scrotal hydroceles, cord hydroceles, epididymal masses or cysts, or epididymitis. Most of these can be differentiated from masses within the testicle by palpation, but if not, scrotal ultrasound is usually helpful.

Treatment

See also Table 38–5.

Inguinal orchiectomy with high ligation of the cord at the internal ring is proper initial treatment for all subtypes of testicular cancer. Rarely is incisional biopsy of the testicle advisable. Recommendations for further therapy (retroperitoneal node dissection, chemotherapy, radiation therapy) are then based on the pathologic findings. A staging workup, including postoperative measurement of serum markers, chest x-ray, and chest and abdominal CT scan, is conducted to determine the extent of disease.

A. Nonseminomatous Tumors

Following orchiectomy, three management options are available: (i) active surveillance, (ii) retroperitoneal lymph node dissection (RPLND), and (iii) systemic chemotherapy. Treatment is based on clinical staging and pathology from the orchiectomy specimen. Patients with no evidence of metastatic disease on imaging and normal serum tumor markers postorchiectomy are candidates for close surveillance with the knowledge that about 20% will relapse and require salvage therapy. This strategy avoids the adverse effects of RPLND and/or systemic chemotherapy. Surveillance, however, is rigorous and should only be offered to motivated and reliable patients.

RPLND is recommended for clinical stage I patients (no evidence of metastatic disease on imaging) or for those with retroperitoneal lymphadenopathy that is not bulky (stage IIA-IIB). The extent of lymphadenectomy depends on the testicle involved but in general includes para-aortic and paracaval nodes from the renal vessels down to the aortic bifurcation and along the external iliac artery to the internal inguinal ring on the involved side. Adverse effects of RPLND include severe hemorrhage from vascular injury to the vena cava, aorta or major branches, chylous ascites, loss of seminal emission, and damage to surrounding structures. If necessary, adjacent organs involved are removed en bloc with the lymph node tissue (eg, nephrectomy). Seminal emission can be preserved with modified templates or nerve sparing techniques that prospectively identify and preserve the sympathetic fibers that coalesce near the bifurcation of the aorta.

Patients with any nonseminomatous cell type who have extensive retroperitoneal or chest metastases are best treated after orchiectomy by multiagent chemotherapy—typically bleomycin, etoposide, and cisplatin. Residual masses postchemotherapy are surgically excised. Combination chemotherapy with bleomycin, etoposide, and cisplatin achieves over a 90% cure rate in stage II patients and a 70% cure rate in stage III patients. Patients who do not respond may be treated with ifosfamide, doxorubicin, or both, with some expectation of success.

B. Seminoma

In the absence of extensive distant spread, patients with pure seminoma should be treated with external beam radiation therapy (2500 cGy) to the retroperitoneum following orchiectomy. A recent study showed that one cycle of carboplatin is equivalent to radiation therapy for stage I seminoma. In the presence of bulky abdominal disease or more distant metastases, survival rates are better with multiagent chemotherapy (described earlier) given initially in lieu of radiation therapy. Patients with substantial residual retroperitoneal tumor (> 3 cm) after chemotherapy may benefit from surgical removal of the remaining tumor.

Prognosis

Even in the presence of metastases, many of these patients can be cured, with overall survival rates more than 90%. The only exception is patients with pure choriocarcinoma, who still have a poor survival rate (35% at 5 years) despite extensive chemotherapy.

TUMORS OF THE PENIS

Cancer of the penis is a rare disease occurring in the fifth to sixth decades. The cause is uncertain. The disease is rarely seen in circumcised men. The lesion commonly is on the glans penis or foreskin. Early cases may exhibit a painless red, velvety lesion, but most often the lesion is an exophytic nodular or wart-like growth with secondary infection. The initial diagnosis is made by a generous incisional biopsy of the lesion, which reveals squamous cell carcinoma in over 95% of cases. The tumors tend to metastasize to superficial or deep inguinal nodes, though the attendant infection may cause enlarged, tender nodes, which may be difficult to differentiate from metastatic cancer.

The differential diagnosis includes syphilitic chancre, soft chancre due to Haemophilus ducreyi infection, and simple or giant condyloma. Biopsy usually differentiates among these conditions.

Small, noninfiltrating lesions (carcinoma in situ) can be treated with fluorouracil cream, external beam radiation, or laser therapy. However, close follow-up is mandatory in patients so treated. Larger lesions not involving deep structures that are limited to the distal penis are treated by partial penile amputation at least 2 cm proximal to the lesion, leaving enough of the penis for adequate direction of the urinary stream. Deeply infiltrating and proximal lesions require total penectomy, with formation of a perineal urethrostomy.

Patients with high-risk features (high T stage, high grade, or presence of lymphovascular invasion) are at risk of inguinal nodal metastases. Prophylactic node dissection has been associated with improved survival.

Palpable inguinal nodes should be treated with antibiotics for 6 weeks following treatment of the primary lesion to eliminate infection. Persistently palpable nodes require bilateral ilioinguinal lymphadenectomy. An alternative would be fine-needle aspiration of the palpable nodes and node dissection if positive for metastases. Even those who undergo delayed node dissection when the nodes become palpable can be cured, though this is a lower percentage. Radiation therapy for palpable nodes or as prophylaxis for nonpalpable nodes has been occasionally effective, but mostly in the palliative setting.

Patients with distant metastases (to the pelvic nodes, lungs, or bone) have a poor prognosis, though cisplatin and methotrexate have shown objective but not durable responses. Five-year survival rates for patients with noninvasive lesions localized to the penis are 80%; for those with inguinal node involvement, 50%; and for those with distant metastases, nil.

A neuropathic bladder has abnormal activity secondary to a neurologic condition. To understand the variety of neuropathic bladder conditions, a basic understanding of the normal innervation and myoneurophysiology is required.

Myoneural Anatomy

The urinary bladder and its involuntary sphincter develop and differentiate from the tubular urogenital sinus. The differentiation of the encasing mesenchymal cells forms the musculature of the detrusor and urethral sphincter.

Innervation

The innervation of the bladder and its involuntary sphincter is via the autonomic nervous system. The parasympathetic supply to the bladder and the sphincter is via the pelvic nerves, which arise from S2-4. These fibers also carry the stretch sensory receptors to the same spinal cord center (S2-4).

The sensory supply for pain, touch, and temperature is carried via the sympathetic fibers arising from the thoracolumbar segments (T11-L2).

Motor and sensory supply of the trigone is via the thoracolumbar sympathetic fibers.

The striated external sphincter, as well as the entire urogenital diaphragm, receives its motor and sensory innervation from the somatic fibers arising from S2-4 (via the pudendal nerve).

It is clear that the S2-4 segment is the origin of the motor supply to the bladder musculature, to the involuntary sphincter, and to the striated external sphincter. The trigone is the only structure that is partly independent in its innervation. This is why segment S2-4 is called the spinal cord center for micturition. It is located at the level of the T12 and L1 vertebral bodies. There are connections between the spinal reflex center and the midbrain and cerebral cortex. Through these connections, inhibition, and control of the spinal cord reflexes can be maintained. The micturition reflex is coordinated in the pontine micturition center.

Myoneurophysiology

The primary functions of the urinary bladder are to store and empty urine at a safe pressure and in a continent fashion. Intact myoneural elements are essential for these functions. The primary reservoir function is possible because of the specialized detrusor muscle arrangement and because of the bladder compliance phenomenon. The normal adult bladder can accommodate volumes up to 400 mL without increasing intravesical pressure. Bladder fullness is perceived through increases in stretching of bladder mechanoreceptors.

Distention and stretch initiate detrusor activity that can be controlled and inhibited by the high cortical centers or can be allowed to progress to active detrusor contraction and voiding. Normally during voiding, detrusor contraction continues until the bladder is completely empty unless voiding is voluntarily interrupted or inhibited.

Before voiding begins, the pelvic floor and the striated external sphincter relax, the bladder base descends, and the bladder outlet assumes a funnel shape. As a result, urethral resistance decreases. This is followed by detrusor muscle contraction and a rise in intravesical pressure to 20-40 cm of water, which results in a urine flow of about 15-30 mL/s. When the bladder is completely empty, the pelvic floor and striated external sphincter contract, elevating the bladder base, increasing urethral pressure, and ending voiding. Intact nerve pathways are essential for these synchronized activities to occur.

Cystometry

Cystometry is a simple method for testing the bladder’s storage function and gives the following information: bladder capacity, extent of accommodation or compliance, the ability to sense bladder filling and temperature, and the presence of an appropriate detrusor muscle contraction. In addition, postvoid residual urine can be measured at the same time. A normal cystometrogram is shown in Figure 38–15A.

Uroflowmetry

Uroflowmetry is the measurement of urine flow rate. If detrusor contraction is properly coordinated with sphincter relaxation, then the outlet resistance falls as the bladder pressure increases, and the flow rate is adequate. Normally, the flow rate changes with age but is more than 20 mL/s in men under 60 and more than 25 mL/s in women under 50 years of age. Any flow rate below 12 mL/s suggests obstruction or detrusor dysfunction. A flow rate under 10 mL/s strongly suggests underlying pathology.

Urodynamics

Urodynamic studies require measurement of bladder pressure during micturition. The pressure measured within the bladder (intravesical pressure) is a combination of the intra-abdominal pressure and the pressure generated by the detrusor. To determine the detrusor pressure, the intra-abdominal pressure is measured with a rectal catheter, and this pressure is subtracted from the total intravesical pressure (measured by the bladder catheter). The urine flow rates may then be assessed in light of the detrusor pressure. No consensus exists on a critical value for pressure and flow that is diagnostic of obstruction. Nomograms have been developed for evaluating the pressure-flow relationship and thus to categorize these values as obstructed, equivocal, or unobstructed.

Electromyographic Recording

Needle or patch electrodes may be employed to record the activity of the external sphincter. This information is useful when obtained during micturition. Increased activity in the sphincter after voiding begins suggests detrusor-sphincter dyssynergia.

Classification & Clinical Findings

Several classification systems exist that describe the variety of pathologic bladder conditions that develop secondary to neuropathies. Many bladder conditions are predictable on the basis of the neurologic lesion. A lesion above the brain stem (ie, stroke) affecting micturition frequently results in involuntary bladder contractions (detrusor hyperreflexia) with coordinated (synergistic) sphincter relaxation. These patients have urge incontinence.

A complete lesion of the spinal cord (ie, trauma) above the T12 vertebral body may leave the spinal reflex center intact. This often leads to what has been categorized as an upper motor neuron lesion. These patients have detrusor hyperreflexia and uncoordinated sphincter activity (detrusor-sphincter dyssynergia). Although detrusor contractions can generate abnormally high intravesical pressure, they are not effective in producing adequate urine flow because of the spastic external sphincter. Thus, there is residual urine. Bladder capacity is reduced. Detrusor contraction and mass reflexes can be initiated from certain trigger areas.

Figure 38–15B is a typical cystometrogram of a hyperreflexic bladder.

An injury to the spinal reflex center or below often leads to what has been categorized as a lower motor neuron lesion. These patients often develop detrusor areflexia. Trauma is the most common cause, but tumors, ruptured intervertebral disks, and meningomyelocele may also cause this type of neuropathic bladder. Both motor and sensory fibers are usually affected, and there is loss of sense of fullness (Figure 38–15C). These contractions are usually weak and unsustained, and bladder emptying is incomplete, resulting in large amounts of residual urine.

The bladder dynamics in a person with a neuropathic bladder often change over time. This may occur secondary to changes in innervation (ie, tethering of spinal cord, multiple sclerosis, recovery from spinal shock) or changes in the bladder. For example, a patient with a hyperreflexic bladder and dyssynergic sphincter often develops a trabeculated, noncompliant bladder over time. These changes require periodic reevaluation of all patients with neuropathic bladders regardless of the initial classification.

Differential Diagnosis

Cystitis, interstitial cystitis, and organic obstruction (eg, due to BPH or urethral stricture) are occasionally confused with neuropathic bladder, but associated neurologic lesions usually help make the diagnosis of neuropathic bladder. Psychosomatic disturbances can cause spasm of the external sphincter, incomplete voiding, retention, or incontinence.

Complications

Common complications include urinary tract infection, stone formation, and incontinence. The most serious consequences of these lesions are the hydrodynamic back-pressure on the kidneys, hydronephrosis, infection, decompensation of the ureterovesical junction, and loss of renal function.

Treatment

Immediately following spinal cord injury, there is a shock phase that may last a few weeks up to 2-3 years. The average time is 2-3 months. The bladder is completely dissociated from nervous control and thus has no sensation and is areflexic.

Treatment is aimed at avoiding the aforementioned complications in the hope of partial or complete recovery. During the shock phase, continuous closed drainage or, preferably, clean intermittent (every 4-6 hours) catheterization should be instituted until bladder activity is restored.

A. Hyperreflexic Bladder

In the hyperreflexic bladder, attaining a functional bladder depends on mobilizing residual urine and increasing the bladder capacity. Residual urine volume can be decreased by reducing urethral resistance by several methods: alpha antagonists, surgery (eg, TURP), or clean intermittent catheterization.

Functional capacity can be increased by decreasing detrusor instability with anticholinergic drugs (eg, oxybutynin), Botox injection into the bladder with cystoscopic guidance, or by operative bladder augmentation. This is often performed with small or large intestine (enterocystoplasty).

Conversion to a flaccid areflexic bladder can be achieved by cord rhizotomy. The storage function of the bladder is preserved, and the patient can be managed by clean intermittent catheterization.

Supravesical urinary diversion may be called for in patients with upper tract deterioration due to elevated storage pressures or female incontinence. Male incontinence may be controlled by a condom catheter.

B. Areflexic Bladder

Function of the flaccid bladder can be improved by measures that facilitate complete emptying; these include voiding by the Credé maneuver (suprapubic pressure), transurethral resection of the bladder neck to reduce outlet resistance, and timed voiding or timed clean intermittent catheterization. An indwelling urethral catheter or suprapubic cystostomy is required in a few cases, but chronic indwelling tubes should be avoided if possible.

Suprapubic urinary diversion (ileal or colon conduit, etc) can circumvent deterioration of upper tracts. Implantable prosthetic sphincters, periurethral bulking agent injections, or urethral slings may also improve urinary control.

A new technique of microanastomosis of a lumbar ventral nerve root to the S3 ventral root has generated promising results in children with spina bifida. This technique is reported to result in improved bladder function in children with an areflexic bladder as well as those with a hyperreflexic bladder.

Prognosis

Renal injury from elevated bladder pressure and infection are the most serious consequences of neuropathic bladder. When diversion or bladder augmentation is required, proper timing of the operation is essential for preservation of kidney function. Patients with a neuropathic bladder require close follow-up of their kidneys with renal ultrasound and serum creatinine determinations.

SIMPLE RENAL CYST

A simple renal cyst is usually unilateral and solitary but may be multiple and bilateral. The cause of this disorder is unclear. The cyst can compress and destroy adjacent parenchyma. Cysts contain fluid that resembles (but is not) urine. Most are diagnosed in patients after the fourth decade. Occasionally, what appears to be a simple cyst may in fact be a papillary cystadenocarcinoma—an uncommon form of renal cancer with both solid and cystic components. In those cases, however, ultrasound usually demonstrates a complex mass with both cystic and solid components.

Flank pain may be a presenting symptom, though most renal cysts are found incidentally on imaging for other purposes. CT scan and ultrasound are the most common imaging modalities. A mass may be felt in the flank or upper quadrant and must be distinguished from tumor. Urinalysis and tests of renal function are normal. If the CT scan or ultrasound reveals an equivocal cystic mass, cyst aspiration may be performed, the fluid submitted for cytologic examination, and the cyst filled with contrast material to delineate its wall. A simple cyst must be distinguished from adenocarcinoma of the kidney; ultrasonography or CT scan usually makes that distinction.

Complications are rare, but bleeding into or infection of a cyst may occur.

If the diagnosis of cyst is established, surgery is not necessary unless the lesion causes pain due to mass effect or endangers renal function. Simple percutaneous aspiration with instillation of 95% ethanol may suffice. If sclerosis fails, laparoscopic or open cyst decortication may be performed.

RENAL ARTERY ANEURYSM

Aneurysm of the renal artery is relatively rare. It results from weakening of the artery wall by arteriosclerosis, poststenotic dilation, intimal or perimedial fibroplasia, or trauma. If the aneurysm causes stenosis of the artery, hypertension may ensue secondary to ischemia and activation of the renin-angiotensin system. A plain abdominal x-ray may reveal a ring-like calcification in the wall. Angiography or CT scan is diagnostic.

Surgery is indicated in the following situations: (1) secondary renal ischemia and hypertension, (2) dissecting aneurysm, (3) aneurysm associated with pain or hematuria, (4) anticipation of pregnancy, (5) aneurysm coincident with significant stenosis, (6) radiographic evidence of incomplete calcification or increase in size on serial films, and (7) aneurysm containing thrombus with evidence of distal embolization. If the aneurysm ruptures, emergency nephrectomy may be necessary.

RENAL INFARCTION

The common causes of renal artery occlusion include emboli due to subacute infective endocarditis, atrial or ventricular thrombi, arteriosclerosis, polyarteritis nodosa, trauma, and, in the neonate, umbilical artery catheterization. Multiple emboli are common and lead to patchy renal ischemia. Occlusion of a main renal artery causes renal total infarction.

The patient may suffer from severe flank pain, or the lesion may be silent. Hematuria is common. Excretory urograms may reveal no excretion of radiopaque material or may only opacify a portion of the kidney. With complete acute occlusion of the main renal artery, a ureteral catheter drains no urine, yet the retrograde urogram reveals normal anatomy. Renal angiography, color Doppler ultrasound, or MRA makes the diagnosis by revealing occlusion of the artery or arterioles; a renal scan shows similar findings. CT scan after the intravenous injection of radiopaque medium shows no concentration in the ischemic area. Ureteral stone may mimic renal infarction, but urograms, CT scan, or angiograms distinguish one from the other. Following renal infarction, hypertension may develop secondary to renal ischemia; it may later resolve spontaneously.

If the diagnosis is made promptly (within 5-8 hours), thrombectomy or endarterectomy should be considered. Otherwise, anticoagulation therapy should be instituted (eg, heparin). Thrombolytic therapy (eg, streptokinase) may be used to lyse the clot. If permanent hypertension develops, definitive treatment of the arterial occlusion or nephrectomy (preferably laparoscopic) should be performed.

RENAL VEIN THROMBOSIS

Thrombosis of the renal vein affects both infants and adults and can be either acute or chronic. In children, thrombosis may be caused by severe dehydration (eg, due to ileocolitis and diarrhea or the nephrotic syndrome). In adults, it may be secondary to renal infection, ascending thrombosis of the vena cava, or caval occlusion due to tumor thrombus. There is usually flank pain and a palpable distended kidney. If renal vein thrombosis is secondary to infection, the patient is septic and urinalysis reveals pus cells and bacteria. In noninfectious cases, the urine may reveal microhematuria and mild proteinuria. The patient with bilateral involvement is azotemic. Nephrotic syndrome may develop. Excretory urograms show delayed opacification in an enlarged kidney. The calices are elongated. Later, the kidney may become atrophic. Renal angiography reveals stretching and bowing of arterioles. Selective renal venography demonstrates the thrombus, as does renal ultrasound.

Treatment should attempt to eliminate the underlying cause whenever possible. If the diagnosis of unilateral infected renal vein thrombosis can be established, nephrectomy should be performed. In bilateral disease, anticoagulant or thrombolytic therapy (or both) is required.

VESICAL FISTULAS

Vesical fistulas may be congenital or acquired. Congenital fistulas usually involve the urachus. Acquired fistulas may be iatrogenic or due to trauma, tumor, or inflammation.

The most common types of vesical fistulas are vesicovaginal, vesicointestinal, and vesicocutaneous. Vesicovaginal fistulas are commonly secondary to gynecologic or birth trauma; rarely, they occur as a complication of infiltrating cervical carcinoma. Vesicointestinal fistulas are most often due to inflammatory bowel disease: Crohn disease, diverticulitis, and appendicitis. Cystostomy in the presence of bladder outlet obstruction, bladder cancer, or foreign body may result in vesicocutaneous fistula.

Diagnostic maneuvers include cystoscopy, conventional cystography, barium enema or barium swallow, and CT scan with contrast infusion. Oral charcoal may be useful for detecting a urinary intestinal fistula, as the granules can be seen in spun urine under the microscope.

Therapy for vesicovaginal fistula requires surgical closure, with placement of an omental flap between the bladder and the vagina. For vesicointestinal fistula, the primary intestinal lesion must be resected and the bladder closed. An indwelling urethral catheter is necessary during the healing period.

INTERSTITIAL CYSTITIS

This lesion is most commonly found in middle-aged women. Urinary frequency both day and night is most often accompanied by suprapubic pain with bladder distention. The cause is uncertain, though some suggest an autoimmune collagen disease, while others have documented the presence of mast cells and mast cell mediators (histamine and prostaglandin) in bladder biopsy specimens of affected patients.

The diagnosis is based on the history and the results of cystoscopy under general anesthesia. Cystoscopy reveals a small-capacity bladder and punctate hemorrhage following hydrodistention. (Studies suggest this is a nonspecific finding.) Biopsy may reveal lymphocytic infiltration, mast cell infiltration, and submucosal fibrosis. In patients suspected of having interstitial cystitis, one must rule out carcinoma in situ with cystoscopy, urine cytologic study, and possible bladder biopsies of suspicious areas.

Treatment of established cases of interstitial cystitis often fails. First line treatment is with dietary modification of foods that can irritate the bladder mucosa (eg, caffeine, spicy foods). If poorly controlled by diet alone, pharmacotherapy with several different agents has shown utility. Pentosan polysulfate sodium is FDA approved for the treatment of interstitial cystitis. Antidepressants, antihistamines, and anticholinergics have also been utilized with some benefit. Temporary response has been obtained with bladder hydrodistention and intravesical instillations with agents such as dimethylsulfoxide. Systemic corticosteroids have their proponents as well, and BCG has been tried with limited success. Some patients who are refractory to the above therapies undergo operative intervention. Neuromodulation with Interstim has demonstrated limited success. Finally, the last resorts of therapy include augmentation of bladder capacity by enterocystoplasty or, rarely, cystectomy and permanent urinary diversion.

URINARY STRESS INCONTINENCE

Involuntary loss of urine during stress (coughing, sneezing, or physical strain) is a common complaint of postmenopausal women. The cause is related to pelvic relaxation with age, resulting in descent of the trigone and proximal urethra. There is obliteration of the urethrovesical angle, which normally provides resistance at the bladder outlet. The diagnosis is made by the history and physical examination and urodynamic evaluation. When the bladder is full, the patient should be asked to cough while in both the supine and upright positions, producing incontinence. Digital pressure applied to the paraurethral tissues in an anterior direction through the vagina reestablishes the urethrovesical angle and prevents stress incontinence (Marshall test).

Treatment in patients with normal bladder function and low residual urine is initiated with behavioral therapy and Kegel exercises; if unsuccessful, pharmacologic methods include anticholinergics to minimize any concomitant urge incontinence. Definitive management is surgical. Currently, the most effective surgical approach is a transvaginal sling procedure with a piece of autologous fascia or synthetic mesh placed at the level of the bladder neck or mid-urethra. Other approaches include the use of bulking agents (eg, calcium hydroxylapatite) injected into the periurethral tissues, resulting in increased urethral outflow resistance.

FEMALE URETHRITIS & PERIURETHRITIS

Urethritis in the female may be acute or chronic. Acute urethritis can be gonorrheal in origin. Chemical urethritis is occasionally acquired from exposure to soap or bath oils. Chronic urethritis is a common problem in women, since the female urethra is exposed to pathogenic bacteria because of its anatomic location. Urethral trauma, instrumentation, and increase in the number of pathogenic organisms lead to infection and overt urethritis. Urethritis usually precedes cystitis.

Hormonal changes associated with menopause cause vaginal and urethral mucosal changes, leading to irritative symptoms and increased susceptibility to inflammation.

Urethritis usually causes irritative voiding symptoms similar to those of cystitis and, occasionally, functional obstructive symptoms. Examination may reveal urethral discharge, marked tenderness, or congested everted mucosa at the external meatus. Induration of the urethra may be associated with vaginitis and cervicitis. Endoscopy may reveal obstruction, mucosal congestion, and inflammatory polyps. Urethral calibration rarely reveals obstruction. Spasm of the external sphincter may be noted.

Treatment is directed to the underlying cause. Estrogen cream is indicated for senile vaginitis. Surgical treatment consists of urethral dilation and opening and draining infected periurethral ducts. Alpha-blockers given orally may also help decrease urethral resistance. Correction of vaginitis, cervicitis, and cervical erosions helps in ameliorating symptoms.

FEMALE URETHRAL CARUNCLE

Urethral caruncle, commonly seen after menopause, represents granulomatous overgrowth of the posterior lip of the external meatus. The caruncle is tender and causes pain with intercourse and urination. The primary concern is exclusion of urethral cancer. Treatment is complete excision.

FEMALE URETHRAL DIVERTICULUM

Urethral diverticulum in the female commonly presents as recurrent lower urinary tract infection. It should be suspected whenever urinary infection fails to resolve with treatment. Symptoms are urinary dribbling and cystic swelling in the anterior vaginal wall during voiding. If diverticulum is suspected, it can usually be identified during panendoscopy and opacified by contrast medium on a voiding cystourethrogram while occluding the external meatus. Pelvic MRI provides excellent diagnostic detail. These lesions occasionally contain stones or tumors. Treatment consists of transvaginal diverticulectomy.

SPERMATOCELE

Spermatocele is a retention cyst of a tubule of the rete testis or the head of the epididymis. The cyst is distended with a milky fluid that contains sperm. Located at the superior pole of the testis and caput epididymidis, the spermatocele is soft and fluctuant and can be transilluminated. No treatment is needed unless the spermatocele is painful, in which case surgical excision may be performed.

VARICOCELE

Varicocele is due to incompetent valves in the testicular vein, permitting transmission of hydrostatic venous pressure; distention and tortuosity of the pampiniform plexus results. Varicocele is found in 15% of male adolescents with left-sided predominance (90%), presumably because of venous drainage of the left testes to the left renal vein, causing increased retrograde venous pressure. Bilateral varicoceles are palpable in fewer than 2% of male adults.

Mild varicoceles are commonly asymptomatic, but a dragging scrotal sensation may be noted. Varicocele may lead to infertility in some men.

Asymptomatic varicocele is best untreated unless it is a suspected factor in male infertility. Treatment then consists of operative ligation of the spermatic vein at or above the internal inguinal ring. In recurrent varicocele, transfemoral catheterization and occlusion or ablation of the spermatic vein may be performed with a detachable balloon or sclerosing agents. The technical success rate is high.

TORSION OF THE SPERMATIC CORD

Torsion of the spermatic cord (intravaginal torsion or torsion within the space of the tunica vaginalis) is most common in adolescent boys. A twist in the spermatic cord interferes with testicular blood supply. If torsion is complete, testicular infarction may occur within 4-6 hours. The cause is unknown, but an underlying anatomic abnormality (spacious tunica vaginalis, loose epididymotesticular connection, undescended testis) is usually present.

Clinical findings consist of precipitous onset of lower abdominal and scrotal pain and scrotal swelling. There may be a history of previous trauma in young adolescents. The testis is swollen, tender, and retracted. The pain is not relieved by testicular support. The cord above the swelling is normal. The cremasteric reflex is usually absent on the affected side.

Torsion must be differentiated from orchitis, epididymitis, and pain due to testicular trauma. Technetium 99m pertechnetate scan may differentiate orchitis-epididymitis from testicular torsion if performed early in the course of symptoms: The former demonstrates increased blood flow, in contrast to the ischemic pattern of torsion. Color Doppler ultrasound is more definitive and less time consuming and can delineate the lack of testicular blood flow. No radiologic study is completely accurate, and imaging should be used to confirm the clinical decision that the cause of the acute scrotum is not torsion. If the diagnosis cannot be established by examination, history, and imaging, exploration is required.

Torsion of the spermatic cord is a surgical emergency! Contralateral orchiopexy is always necessary because of frequent bilateral involvement (ie, the “bell clapper” deformity: lack of fixation of the cord structures by the testicular mediastinum) and the high incidence of recurrent torsion and infertility in bilateral cases.

TORSION OF TESTICULAR APPENDAGES

The epididymis and the testicle often have a vestigial remnant of embryologic ducts known as an appendix testis or appendix epididymis. These structures can undergo spontaneous infarction usually in young boys, causing acute testicular pain and swelling that may be difficult to differentiate from testicular torsion. With torsion of the appendix testis or epididymis, physical examination often demonstrates point tenderness at the site of the torsed appendage. Occasionally, the infarcted appendage can be seen through the scrotal wall as a “blue dot” sign on the scrotum. This sign is only visible early in the course, prior to hydrocele formation and onset of scrotal edema. Scrotal ultrasound occasionally delineates the enlarged appendage and a normal testicle, establishing the diagnosis. In most cases—and certainly in equivocal ones—immediate scrotal exploration and removal of the infarcted appendage is required to rule out testicular torsion. Although the appendages often occur bilaterally, appendiceal torsion does not; thus, removal of the opposite appendage is not indicated.

MALE INFERTILITY

Male infertility accounts for 30%-50% of infertile couples (10%-15% of marriages). Both partners should be evaluated for causes of infertility.

The causes of male infertility include the following: congenital anomalies (genetic, such as Klinefelter’s syndrome, or developmental, such as absent vas deferens); trauma (both testicular, resulting in atrophy, and neurologic, resulting in erectile or ejaculatory dysfunction); infections (either systemic or reproductive organ specific); endocrine disorders (pituitary insufficiency, androgen deficiency); acquired anatomic abnormalities (varicocele, vasectomy); or drug side effects (nitrofurantoin, estrogens, antineoplastic agents).

Diagnosis

The most important aspect of infertility evaluation is the history, which uncovers the cause in many patients. The physical examination is no less important and may reveal small testicles, a varicocele, or absence of the vas deferens.

A. Semen Analysis

Semen analysis is essential in evaluation of male factor infertility. At least two samples should be analyzed, since values may vary over time and with the method of collection. The specimen is produced by masturbation after 3 days of ejaculatory abstinence and collected in a clean wide-mouth container and examined within 2 hours. Determination of the volume, pH, liquefaction, sperm count, viability, abnormal forms, and motility constitutes a complete analysis. Normal values include volume of more than 2.0 mL, concentration greater than 20 million sperm per mL, more than 50% motile sperm, and 75% or more viable sperm (World Health Organization criteria).

B. Hormone Studies

Patients with no sperm in the ejaculate (azoospermia) or very low counts (oligospermia, < 10 million sperm/mL) should have serum FSH, LH, and testosterone levels measured. Patients with low testosterone should have prolactin levels checked and, if elevated, should be investigated for pituitary tumor. A significant elevation of FSH represents a problem with spermatogenesis.

C. Testicular Biopsy

Testicular biopsies are indicated in azoospermic patients to distinguish obstructive versus parenchymal disease. Testicular biopsy should be performed in patients with unexplained oligospermia to establish a histologic diagnosis, to assess prognosis, and to direct treatment. If the serum FSH is more than two times normal, one may presume the presence of severe and irreversible testicular damage without confirmatory testis biopsy.

Vasography requires injection of contrast material into the vas. The purpose of this study is to delineate obstruction of the vas, epididymis, seminal vesicle, or ejaculatory duct. Vasography is used in patients who are azoospermic and have no evidence of retrograde ejaculation while demonstrating normal spermatogenesis on testicular biopsy. Seminal fructose levels should be obtained before operative exposure of the vas. Absence of fructose would indicate obstruction of the ejaculatory duct, and if this diagnosis is confirmed by vasography, the obstructing tissue may be resected by transurethral methods.

D. Other Diagnostic Studies

The sperm penetration assay, performed by incubation of sperm with hamster eggs whose zona pellucida has been enzymatically removed, offers an objective method of determining the ability of sperm to penetrate the ovum. The cervical mucus penetration test compares sperm motility in cervical mucus with a known standard. Although these two important parameters of sperm function can be evaluated, neither test alone can establish the cause of male factor infertility.

Antisperm antibodies can be measured in the serum of either the male or female partner or in the seminal fluid. This assessment is indicated when spontaneous sperm agglutination or decreased sperm motility is noted on semen analysis. If antisperm antibodies are found, immunosuppressive therapy in the form of steroids may be effective in reducing agglutination (clumping) and increasing motility. Another method of treating antisperm antibodies is in vitro sperm washing with immunobeads coated by antihuman antibody. The sperm not bound by antibody remain in the supernatant and can be used for intrauterine insemination.

Studies to detect a nonpalpable varicocele are not recommended except in cases in which the physical examination is inadequate. Physical examination is the most effective method of detecting clinically significant varices. Venography is reserved for patients with recurrent varices, since identification of collateral venous channels would direct choice of therapy.

Transrectal ultrasound is used to support the diagnosis of ejaculatory duct obstruction in the azoospermic patient. Absence of the seminal vesicles or distention due to distal obstruction can be identified. This study should be preceded by measurement of fructose in the ejaculate (lack of fructose suggests obstruction of the ejaculatory duct) and examination of postejaculate urine (to determine the presence of sperm, suggesting retrograde ejaculation).

Treatment

A. Nonoperative Treatment

Primary male infertility may be caused by hypogonadotropic hypogonadism, diagnosed by demonstrating low serum levels of FSH, LH, and testosterone. Spermatogenesis may be stimulated by administration of hCG followed by FSH. Isolated absence of either FSH or LH is rare; the LH deficiency is overcome by administration of testosterone, and lack of FSH is treated by administration of menotropins. Hyperprolactinemia may contribute to male infertility and would be treated with bromocriptine.

Infection of the reproductive organs should be treated when found during evaluation of male infertility. Infection may cause infertility immediately by several mechanisms: decreased spermatogenesis due to hyperthermia, immune interaction with sperm causing agglutination and decreased motility, as well as later sequelae such as obstruction of the ejaculatory tract. Pyospermia suggests the diagnosis, and treatment should be designed to eliminate the common pathogens: Neisseria gonorrhoeae, Chlamydia trachomatis, and Ureaplasma urealyticum (all are sensitive to tetracycline).

If antisperm antibodies are found in either partner, steroids may be used to suppress the immune system. One must use steroids with caution and after thorough discussion of possible side effects with the patient; acne, hypertension, gastrointestinal bleeding, and avascular necrosis of the hip have been reported with steroid administration. Response to treatment is assessed by repeat semen analysis and measurement of antisperm antibodies in the patient’s serum. Sperm washing in an attempt to remove cytotoxic antibodies may improve motility and decrease clumping; washed semen may then be instilled into the uterus (artificial insemination of the husband’s semen) or used in conjunction with in vitro fertilization (IVF) techniques.

Retrograde ejaculation or lack of seminal emission—usually due to spinal cord injury or sympathetic nerve injury during retroperitoneal surgery leading to bladder neck (ie, internal sphincter) incompetence—can be treated with α-adrenergic drugs or antihistamines to reestablish internal sphincter function and antegrade ejaculation. Alternatively, alkalinized postejaculate urine can be collected and centrifuged and the concentrated sperm instilled into the female partner’s uterus.

Clomiphene and tamoxifen are antiestrogens that are currently used in patients with idiopathic oligospermia, though the efficacy of these medications has been doubted.

B. Operative Therapy

Ligation of varicocele yields pregnancy in 30%-50% of patients. Several approaches are available, including inguinal and retroperitoneal. Transvenous occlusion of the spermatic vein by balloon is useful especially in cases of recurrent varicocele.

Obstruction of the epididymis-vas system may be amenable to vasovasostomy or vasoepididymostomy. Currently, these procedures are performed with the aid of the operating microscope, and patency is established in 50%-90% of cases.

Obstruction of the ejaculatory ducts is rare. When this diagnosis is made, transurethral resection of the ducts may establish patency.

C. Assisted Reproductive Techniques

These include the following: artificial insemination with husband’s sperm (AIH), gamete intrafallopian transfer, and IVF using intracytoplasmic sperm injection after retrieving eggs by transvaginal ultrasound guidance and sperm by testicular aspiration in selected partners. In cases of male factor infertility not amenable to treatment, artificial insemination by donor sperm is also available.

PRIAPISM

Priapism is a rare disorder in which prolonged, painful erection occurs, usually not associated with sexual stimulation. The blood in the corpora cavernosa becomes hyperviscous but not clotted. About 25% of cases are associated with leukemia, metastatic carcinoma, sickle cell anemia, or trauma. In most cases, the cause is uncertain.

If the erection does not subside, needle aspiration of the sludged blood of the corpora followed by lavage with alpha-adrenergic agents such as phenylephrine should be performed. Delayed or unsuccessful treatment may result in impotence. Unsuccessful treatment calls for the Winter procedure, in which a biopsy needle is passed through the glans into one of the corpora, creating a fistula between corpora cavernosa and corpus spongiosum. If this procedure is successful, then potency is usually maintained. Other procedures include excising the tunica albuginea at the tip of the corpora cavernosum, proximal cavernosal-spongiosum shunt, and saphenous vein-cavernous shunt. If priapism persists, impotence results.

In sickle cell anemia, hydration and hypertransfusion often give relief and should constitute initial therapy.

PEYRONIE’S DISEASE