CHAPTER II LITERATURE

2.1 ANATOMY AND PHYSIOLOGY OF PROSTATE GLAND 2.1.1 Anatomy Prostate Gland The prostate is a fibromuscular and glandular organ lying just inferior to the bladder. The normal prostate weighs about 25 g and contains the posterior urethra, which is about 2.5 cm in length. It is supported anteriorly by the puboprostatic ligaments and inferiorly by the urogenital diaphragm. The prostate is perforated posteriorly by the ejaculatory ducts, which pass obliquely to empty through the verumontanum on the floor of the prostatic urethra just proximal to the striated external urinary sphincter. According to the classification of Lowsley, the prostate consists of 5 lobes: anterior, posterior, median, right lateral, and left lateral. According to McNeal (1972), the prostate has a peripheral zone, a centralzone, and a transitional zone, an anterior segment, and a preprostatic sphincteric zone.

Fig 1. Anatomy of the prostate gland and surrounding structures. Zonal model of the prostate

Fig 2. Anatomy of the prostate gland and surrounding structures. Fascial planes around the prostate. A, artery; AFS, anterior fibromuscular stroma; CZ, central zone; ED, ejaculatory duct; N, nerve; PZ, peripheral zone; TZ, transition zone; U, urethra; V, vein.

The urethra that traverses the prostate gland is the prostatic urethra. It is lined by an inner longitudinal layer of muscle (continuous with a similar layer of the vesical wall). Incorporated within the prostate gland is an abundant amount of smooth musculature derived primarily from the external longitudinal bladder musculature. This musculature represents the true smooth involuntary sphincter of the posterior urethra in males. The prostate consists of a thin fibrous capsule under which are circularly oriented smooth muscle fibers and collagenous tissue that surrounds the urethra (involuntary sphincter). Deep in this layer lies the prostatic stroma, composed of connective and elastic tissues and smooth muscle fibers in which are embedded the epithelial glands. These glands drain into the major excretory ducts (about 25 in number) which open chiefly on the floor of the urethra between the verumontanum and the vesical neck. Just beneath the transitional epithelium of the prostatic urethra lie the periurethral glands.

10

The prostate gland receives arterial supply from the inferior vesical, internal pudendal, and middle rectal (hemorrhoidal) arteries. The veins from the prostate drain into the periprostatic plexus, which has connections with the deep dorsal vein of the penis and the internal iliac (hypogastric) veins. The prostate gland receives a rich nerve supply from the sympathetic and parasympathetic nerve plexuses. The lymphatics from the prostate drain into the internal iliac (hypogastric), sacral, vesical, and external iliac lymph nodes.

2.1.2 Physiology Prostate Gland Secretions of the prostate gland is a milky fluid that together secretions from the seminal vesicles are a major component of semen. Semen contains citric acid so that a slightly acidic pH (6.5). Moreover, it can be found fibrinolysin enzymes that act as a strong, acid phosphates, other enzymes and lipids. Prostatic secretions released during ejaculation through the contraction of smooth muscle.

2.2 BENIGN PROSTATE HYPERPLASIA 2.2.1 Epidemiology BPH is the most common benign tumor in men, and its incidence is agerelated. The prevalence of histologic BPH in autopsy studies rises from approximately 20% in men aged 41-50, to 50% in men aged 51-60, and to over 90% in men older than 80. Although clinical evidence of disease occurs less commonly, symptoms of prostatic obstruction are also agerelated. At age 55, approximately 25% of men report obstructive voiding symptoms. At age 75, 50% of men complain of a decrease in the force and caliber of their urinary stream.

2.2.2 Etiology The etiology of BPH is not completely understood, but it seems to be multifactorial and endocrine controlled. The prostate is composed of

11

both stromal and epithelial elements, and each, either alone or in combination, can give rise to hyperplastic nodules and the symptoms associated with BPH.. Some theories or hypotheses are suspected as the cause of prostatic hyperplasia are: 1. Dihydrotestosterone Testosterone is produced by the Leydig cells of the testis (90%) and a portion of the adrenal gland (10%) in the blood circulation and 98% will be bound by sex hormone binding globulin to globulin (SHBG). Being only 2% in a state of free testosterone. Free testosterone is what can get into the "target cell" that prostate cells directly through the cell membrane into the cytoplasm, the cell, testosterone is reduced by the enzyme 5-alpha reductase into 5-dihydrotestosterone were then met with cytoplasmic receptors become "hormone receptor complex". Then "hormone receptor complex" is undergoing transformation receptors, a "nuclear receptor" that went into the core which is then attached to the chromatin and lead to m-RNA transcription. RNA will cause protein synthesis result in the growth of the prostate gland. This theory was proven that the castration before puberty do not happen BPH, also the regression of BPH when done castration. 2. Estrogen-testosterone imbalance In addition to androgens (testosterone / DHT), estrogen also contributes to the occurrence of BPH. With age will change the hormonal balance, which is between testosterone and estrogen, as testosterone production decreases and the conversion of testosterone to estrogen in peripheral adipose tissue with the help of the enzyme aromatase, which is the nature of estrogen will stimulate hyperplasia of the stroma, causing notion that testosterone is necessary for the initiation of cell proliferation but then estrogen which contribute to the development of the stroma. Another possibility is that changes in the relative concentrations of

12

testosterone and estrogen will cause the production and potentiation of other growth factors that can lead to an enlarged prostate. From various experimental and clinical findings concluded that under normal circumstances would cause the pituitary gonadotropin production of testicular androgens that will control the growth of the prostate. With increasing age, there will be a decrease of testicular function (spermatogenesis), which will lead to a progressive decline of androgen secretion. This result will greatly stimulate gonadothropin hormone estrogen production by the Sertoli cells. While the views of the functional histological, prostate consists of two parts, namely a central around the urethra that reacts to estrogen and peripheral parts that do not respond to estrogen. 3. Interaction stroma- epitel This theory is based on the interaction between the elements of prostate stromal and epithelial elements that cause prostate hyperplasia. The growth factor was made by stromal cells under the influence of androgens. The existence of over-expression of the epidermal growth factor (EGF) and or fibroblast growth factor (FGF) and or a decrease in the expression of transforming growth factor- (TGF-) will cause an imbalance of prostate growth and produce an enlarged prostate. 4. Decrease in cell death The aging process can lead to blockade the process of maturation in stem cells, prevent them from entering the stage of programmed cell death (apoptosis). As a result of the aging process in animal studies appears to be mediated through the estrogen synergism induces androgen receptor, steroi disrupt metabolism, resulting in increased levels of DHT in the prostate that inhibit cell death when given in conjunction with androgen nd poduksi stimulate collagen stroma. 5. Stem Cell Theory (stem cell hypothesis) As in other organs, prostate gland periuretral in this case in an adult is in a state of equilibrium "steady state", between cell growth and cell death,

13

the balance is due to the presence of certain levels of testosterone in the prostate tissue that can affect the stem cells that can proliferate. In certain circumstances the number of stem cells can be increased resulting in more rapid proliferation. Abnormal stem cell proliferation leading to the production or proliferation of stromal cells and epithelial cells periuretral prostate gland becomes redundant.

2.2.3 Pathophysiology One can relate the symptoms of BPH to either the obstructive component of the prostate or the secondary response of the bladder to the outlet resistance. The obstructive component can be subdivided into the mechanical and the dynamic obstruction. As prostatic enlargement occurs, mechanical obstruction may result from intrusion into the urethral lumen or bladder neck, leading to a higher bladder outlet resistance. Prior to the zonal classification of the prostate, urologists often referred to the "3 lobes" of the prostate, namely, the median and the two lateral lobes. Prostatic size on digital rectal examination (DRE) correlates poorly with symptoms, in part because the median lobe is not readily palpable. The dynamic component of prostatic obstruction explains the variable nature of the symptoms experienced by patients. The prostatic stroma, composed of smooth muscle and collagen, is rich in adrenergic nerve supply. The level of autonomic stimulation thus sets a tone to the prostatic urethra. Use of alpha-blocker therapy decreases this tone, resulting in a decrease in outlet resistance. The irritative voiding complaints of BPH result from the secondary response of the bladder to the increased outlet resistance. Bladder outlet obstruction leads to detrusor muscle hypertrophy and hyperplasia as well as collagen deposition. Although the latter is most likely responsible for a decrease in bladder compliance, detrusor instability is also a factor. On gross inspection, thickened detrusor muscle

14

bundles are seen as trabeculation on cystoscopic examination. If left unchecked, mucosal herniation between detrusor muscle bundles ensues, causing diverticula formation (so-called false diverticula composed of only mucosa and serosa).

2.2.4 Clinical Findings Symptoms The symptoms of BPH can be divided into obstructive and irritative complaints. Obstructive symptoms include hesitancy, decreased force and caliber of stream, sensation of incomplete bladder emptying, double voiding (urinating a second time within 2 hour of the previous void), straining to urinate, and post-void dribbling. Irritative symptoms include urgency, frequency, and nocturia. The self-administered questionnaire developed by the American Urological Association (AUA) is both valid and reliable in identifying the need to treat patients and in monitoring their response to therapy. The AUA Symptom Score questionnaire is perhaps the single most important tool used in the evaluation of patients with BPH and is recommended for all patients before the initiation of therapy.

15

Fig 4. The AUA Symptom Score questionnaire

This assessment focuses on 7 items that ask patients to quantify the severity of their obstructive or irritative complaints on a scale of 0-5. Thus, the score can range from 0 to 35. A symptom score of 0-7 is considered mild, 8-19 is considered moderate, and 20-35 is considered severe. Physical Examination Digital Rectal Examination (DRE) is examination to determine the size and consistency of the prostate is noted, even though prostate size. BPH usually results in a smooth, firm, elastic enlargement of the prostate. Induration, if detected, must alert the physician to the possibility of cancer and the need for further evaluation.

16

On physical examination, when upper urinary tract abnormalities occurs sometimes kidney may be palpable and when pyelonefritis happens it will be accompanied by pain and percussion pain on the waist. Gallbladder may be palpable urinary retention occur when it is total, the inguinal area should begin to be considered to determine the hernia. External genitalia should also be checked to see if there are other possible causes that can lead to micturition disorders such as stones or urethral fossa navicularis anterior, urethral fibrosis area, phimosis, condiloma meatus area.

Laboratory Findings A urinalysis to exclude infection or hematuria and serum creatinine measurement to assess renal function are required. BSS to find possibility of diabetes that can cause neurological gallbladder. Serum PSA is considered optional, if suspicious of carcinoma prostate.

Imaging a. Plain abdominal (BNO) This examination use to look for the opaque stones in the urinary tract, the presence of stones and sometimes may show a shadow of

gallbladder that filled with urine which is the sign of a urinary retention. And also to know presence of bone metastases of prostate carcinoma. b. Pyelography Intravenous (IVP) Enlargement of the prostate can be seen as a filling defect / prostate indentation at the base of the bladder or ureter distal end turned up shaped like the eye of the hook (hooked fish). Can also be aware of any abnormalities in the kidneys or ureters or hydronephrosis hidroureter form and complications (trabeculation or diverticular). Photos after micturition residual urine can be seen there. c. Ultrasonography

17

Ultrasound can be either trans abdominal or trans rectal. Its use to find an enlarged prostate, this examination can also determine abnormalities in the bladder (mass, stone, blood clot), measuring residual urine and kidney damage caused by prostatic obstruction. In TRUS prostate malignancy likely hypoechoic area.

2.2.5 Differential Diagnosis Other obstructive conditions of the lower urinary tract, such as urethral stricture, bladder neck contracture, bladder stone, or prostate cancer must be entertained when evaluating men with presumptive BPH. A history of previous urethral instrumentation, urethritis, or trauma should be elucidated to exclude urethral stricture or bladder neck contracture. Hematuria and pain are commonly associated with bladder stones. Prostate cancer may be detected by abnormalities on the DRE or an elevated PSA. A urinary tract infection, which can mimic the irritative symptoms of BPH, can be readily identified by urinalysis and culture. However, a urinary tract infection can also be a complication of BPH. Although irritative voiding complaints are also associated with carcinoma of the bladder, especially carcinoma in situ, the urinalysis usually shows evidence of hematuria. Likewise, patients with neurogenic bladder disorders may have many of the signs and symptoms of BPH, but a history of neurologic disease, stroke, diabetes mellitus, or back injury may be present as well. In addition, examination may show diminished perineal or lower extremity sensation or alterations in rectal sphincter tone or the bulbocavernosus reflex. Simultaneous alterations in bowel function (constipation) might also alert one to the possibility of a neurologic origin.

2.2.6 Treatment After patients have been evaluated, they should be informed of the various therapeutic options for BPH. Specific treatment recommendations can be offered for certain groups of patients. For those with mild symptoms

18

(symptom score 0-7), watchful waiting only is advised. On the other end of the therapeutic spectrum, absolute surgical indications include refractory urinary retention (failing at least one attempt at catheter removal), recurrent urinary tract infection from BPH, recurrent gross hematuria from BPH, bladder stones from BPH, renal insufficiency from BPH, or large bladder diverticula (McConnell et al, 1994).

A. Watchful Waiting As mentioned above, watchful waiting is the appropriate management of men with mild symptom scores (0-7). Men with moderate or severe symptoms can also be managed in this fashion if they so choose. Neither the optimal interval for follow-up nor specific endpoints for intervention have been defined.

B. Medical Therapy 1. Alpha blockers The human prostate and bladder base contains alpha-1-

adrenoreceptors, and the prostate shows a contractile response to corresponding agonists. The contractile properties of the prostate and bladder neck seem to be mediated primarily by the subtype a1a receptors. Alpha blockade has been shown to result in both objective and subjective degrees of improvement in the symptoms and signs of BPH in some patients. Examples of alpha inhibition include prazosin, terazosin, doxazosin and newer tamslosin (selective blockade of receptors 1a). Side effects include hypotension APHA inhibitors ortostatik, dizziness, fatigue, retrograde ejaculation, rhinitis and headache. This side effect is less on the use of a more selective inhibition 1a.

2. 5a-Reductase inhibitors This drug is a 5a-reductase inhibitor that blocks the conversion of testosterone to dihydrotestosterone. This drug affects the epithelial

19

component of the prostate, resulting in a reduction in the size of the gland and improvement in symptoms. Six months of therapy are required to see the maximum effects on prostate size (28% reduction) and symptomatic improvement. Side effects include decreased libido, decreased ejaculate volume and impotence.

3. Phytotherapy Phytotherapy refers to the use of plants or plant extracts for medicinal purposes. The use of phytotherapy in BPH has been popular in Europe for years, and its use in the United States is growing as a result of patient-driven enthusiasm. Several plant extracts have been popularized, including the saw palmetto berry, the bark of Pygeum africanum, the roots of Echinacea purpurea and Hypoxis rooperi, pollen extract, and the leaves of the trembling poplar. The mechanisms of action of these phytotherapies are unknown, and the efficacy and safety of these agents have not been tested in multicenter, randomized, double-blind, placebocontrolled studies.

C. Conventional Surgical Therapy 1. Transurethral Resection of The Prostate (TURP) Ninety-five percent of simple prostatectomies can be done endoscopically. Most of these procedures involve the use of a spinal anesthetic and require 1 to 2 day hospital stay. Risks of TURP include retrograde ejaculation (75%), impotence (5-10%), and incontinence (< 1%). Complications include bleeding, urethral stricture or bladder neck contracture, perforation of the prostate capsule with extravasation, and if severe, TUR syndrome resulting from a hypervolemic, hyponatremic state due to absorption of the hypotonic irrigating solution. Clinical manifestations of the TUR syndrome include nausea, vomiting, confusion, hypertension, bradycardia, and visual disturbances. The risk of the TUR syndrome increases with resection times over 90 min.

20

Treatment includes diuresis and, in severe cases, hypertonic saline administration.

2. Transurethral Incision of The Prostate Men with moderate to severe symptoms and a small prostate often have posterior commissure hyperplasia (elevated bladder neck). These patients will often benefit from an incision of the prostate. This procedure is more rapid and less morbid than TURP. Outcomes in wellselected patients are comparable, although a lower rate of retrograde ejaculation with transurethral incision has been reported (25%).

3. Open Simple Prostatectomy When the prostate is too large to be removed endoscopically, an open enucleation is necessary. What constitutes "too large" is subjective and will vary depending upon the surgeon's experience with TURP. Glands over 100 g are usually considered for open enucleation. Open prostatectomy may also be initiated when concomitant bladder diverticulum or a bladder stone is present or if dorsal lithotomy positioning is not possible. Open prostatectomies can be done with either a suprapubic or retropubic approach.

D. Minimally Invasive Therapy 1. Laser Therapy Two main energy sources of lasers have been utilized is neodymium/yttrium-aluminum garnet (Nd:YAG) and holmium :YAG. Several different coagulation necrosis techniques have been described. Transurethral laser-induced prostatectomy (TULIP) is done with transrectal ultrasound guidance. Advantages of laser surgery include (1) minimal blood loss, (2) rare instances of TUR syndrome, (3) ability to treat patients receiving anticoagulation therapy, and (4) ability to be done as an outpatient

21

procedure. Disadvantages include (1) lack of availability of tissue for pathologic examination, (2) longer postoperative catheterization time, (3) more irritative voiding complaints, and (4) high cost of laser fibers and generators.

2. Transurethral Electrovaporization of The Prostate Transurethral electrovaporization uses the standard resectoscope but replaces a conventional loop with a variation of a grooved rollerball. High current densities cause heat vaporization of tissue, resulting in a cavity in the prostatic urethra. The procedure usually takes longer than a standard TURP.

3. Hyperthermia Microwave hyperthermia is most commonly delivered with a transurethral catheter. Some devices cool the urethral mucosa to decrease the risk of injury. However, if temperatures do not exceed 45 C, cooling is unnecessary.

4. Transurethral Needle Ablation of The Prostate Transurethral needle ablation uses a specially designed urethral catheter that is passed into the urethra. Interstitial radiofrequency needles are then deployed from the tip of the catheter, piercing the mucosa of the prostatic urethra. The use of radio frequencies to heat the tissue results in a coagulative necrosis. This technique is not adequate treatment for bladder neck and median lobe enlargement.

5. High-Intensity Focused Ultrasound High-intensity focused ultrasound is another means of performing thermal tissue ablation. A specially designed, dual-function ultrasound probe is placed in the rectum. This probe allows transrectal imaging of the prostate and also delivers short bursts of high-intensity focused

22

ultrasound energy, which heats the prostate tissue and results in coagulative necrosis. Bladder neck and median lobe enlargement are not adequately treated with this technique..

6. Intraurethral Stents Intraurethral stents are devices that are endoscopically placed in the prostatic fossa and are designed to keep the prostatic urethra patent. These devices are typically used for patients with limited life expectancy who are not deemed to be appropriate candidates for surgery or anesthesia.

7. Transurethral balloon dilation of the prostate Balloon dilation of the prostate is performed with specially designed catheters that enable dilation of the prostatic fossa alone or the prostatic fossa and bladder neck. The technique is most effective in small prostates (< 40 cm3).

2.3

BLADDER CALCULI In the lower urinary tract, most calculi occur in the bladder. Vesical calculi

can be classified as migrant, primary idiopathic, or secondary calculi, which include calculi related to urinary stasis, infection, and foreign bodies.4,5

2.3.1

Migrant Calculi Migrant bladder calculi are formed in the upper tracts, pass into the

bladder, and are retained there. Most calculi that migrate out of the ureter into the bladder are smaller than 1 cm and, in adults, are easily passed per urethra. Calculi that are retained are associated with a small bladder outlet (children) or bladder outlet obstruction. Retained upper tract stones may grow to a large size in the bladder. The primary etiology of the calculus is related to the metabolic factors associated with renal calculi formation.5,6

23

2.3.2

Primary Idiopathic (Endemic) Calculi Endemic bladder stones form in children in the absence of obstruction,

local disease, neurologic lesion, or known primary infection. The incidence has decreased with industrialization and affluence, such that it is rare in developed countries. However, endemic bladder calculi remain common in infants and children of lower socioeconomic background in North Africa and the Middle and Far East. They are uncommon in Central and South Africa, Central and South America, and the Pacific Islands. Similarities are seen in the afflicted children of these areas. Stone formation results from dietary and nutritional deficiencies. Children in these areas are dependent on a cereal-based diet that is lacking in animal proteins, especially cow's milk. Cereals commonly used are whole wheat flour, millet, and rice.4,5,6 Less than 25% of the total protein intake is of animal origin. Compared with cow's milk, human breast milk and foods such as polished rice and cereals are low in phosphorus. This dietary phosphate deficiency leads to low urine phosphate excretion and high peaks of ammonia excretion. Chronic dehydration, excessive protein or oxalate consumption, high endogenous oxalate production, and deficiencies in vitamins A, B1, and B6 and magnesium have been associated with stone formation. These conditions act to decrease urine production, acidify the urine, and increase the concentration of uric acid and calcium oxalate excretion, leading to precipitation of insoluble salts in the urine. Endemic bladder calculi are most commonly composed of ammonium acid urate alone or in combination with calcium oxalate, but many also contain calcium phosphate. 6 Children younger than 10 years are typically affected, with the peak incidence around 3 years. The cloudy, sandy urine produced by children in endemic areas indicates the early stages of stone formation. Girls are able to pass most of the debris through their short, nontortuous urethra, but boys may retain these potential nidi. This accounts for the male-to-female ratio of 10:1 for endemic bladder calculi. Common symptoms are vague abdominal pain, hypogastric discomfort, interruption of the urinary stream, and pulling and rubbing of the penis. Some children complain of dysuria, frequency, suprapubic

24

pain, and dribbling. The sudden onset of symptoms of urinary tract obstruction is rare. Rectal prolapse or conjunctival hemorrhages may be seen in association with straining to void. The duration of symptoms ranges from a few days to several years. Symptoms caused by mechanical obstruction or irritation and cystitis may be mistaken for an infectious or inflammatory process. Small calculi may be passed with hydration, antispasmodics, and analgesics, but most cases will require surgical intervention. Endemic bladder calculi are usually solitary and rarely recur once removed. A mixed cereal diet with milk supplements reduces the incidence of endemic bladder calculi.4,5

2.3.3

Secondary Bladder Calculi Progress in nutrition and diet has decreased the incidence of bladder

calculi; it is now predominantly a disease of adults and accounts for approximately 5% of urinary calculi in developed countries. These secondary bladder calculi are most often related to urinary stasis or recurrent urinary tract infection due to bladder outlet obstruction or neurogenic bladder dysfunction. Patients with intestinal mucosa or foreign bodies in the urinary tract are also at risk for development of calculi. 5,6

2.3.4

Calculi Related to Bladder Outlet Obstruction Bladder outlet obstruction may be an etiologic factor in more than 75% of

bladder calculi cases. Bladder calculi associated with outlet obstruction primarily affect men older than 50 years and are most often related to benign prostatic hyperplasia. However, only 1% to 2% of men undergoing surgery for benign prostatic hyperplasia will have bladder calculi. Calculi resulting from obstruction may be composed of uric acid, calcium oxalate, or magnesium ammonium phosphateif infected. In a review of 652 cases of vesical calculi, Smith and O'Flynn (1975) reported that 92% occurred in men, and 80% of the cases were found in patients older than 50 years. Incomplete bladder emptying was identified as the greatest single factor in vesical stone formation, and prostatic hypertrophy was the most frequent condition causing incomplete emptying. The major

25

components of vesical calculi were phosphate (59.4%), oxalate (25.6%), and uric acid (5.4%). In a more recent review of 100 patients with vesical calculi, Douenias and associates (1991) found that 80% occurred in patients older than 60 years, and all but two patients were male. Eighty-eight cases were attributed to some form of outlet obstruction. Fifty percent of the patients had uric acid calculi; this was attributed to the diet of the mostly Jewish population they served. Other causes of outlet obstruction are urethral stricture, bladder neck contracture, neurogenic bladder dysfunction, and, in women, urogenital prolapse. No definite correlation between stone composition and etiology of obstruction has been identified. 6

26

Single stones are usually encountered in the bladder, but multiple stones are seen in 25% to 30% of cases. Bladder diverticula may predispose to the formation of multiple stones; these may become faceted and vary in size.4,6 Bladder calculi may also be observed in post-prostatectomy patients. These calculi are usually associated with obstruction, bladder neck contracture, residual nidus from liberated prostatic calculi, and urinary stasis from neurogenic bladders. Bladder calculi form in 40% of patients with bilharziasis as a result of outlet obstruction from bladder neck fibrosis. There is often superimposed infection. 6

2.3.5

Calculi Related to Infection or Catheterization Although urinary stasis may be the only cause of bladder calculi in some

cases, infection is frequently a coexistent lithogenic factor. Residual urine from outlet obstruction predisposes to infection, and combined, these factors may result in stone formation. Between 22% and 34% of bladder calculi are associated with urinary tract infection, most commonly with Proteus. Organisms such as Pseudomonas, Ureaplasma urealyticum, Providencia, Klebsiella, Staphylococcus, and Mycoplasma are also capable of producing bacterial urease. The urease hydrolyzes urea, forming ammonium and carbon dioxide, which increases urine pH. Alkaline urine promotes supersaturation and precipitation of crystals of magnesium ammonium phosphate and carbonate apatite. Although magnesium ammonium phosphate and carbonate apatite are pathognomonic of infection, calcium oxalate and phosphate calculi may be associated. 4,5,6 Long-term bladder catheterization often places patients at risk for urinary infection and calculus formation. A study identified a prevalence of 0.07% of long-term catheterization (0.5% for patients older than 75 years) in a population of more than 825,000, of which 2.2% were found to have bladder calculi. Approximately 50% to 98% of catheter-associated calculi are composed of magnesium ammonium phosphate; the remainder are a combination of calcium oxalate and phosphate or pure calcium phosphate. Patients who are particularly prone to infectious bladder calculi include those with neurogenic bladder from

27

trauma, stroke, or similar conditions or with foreign bodies in the urinary system. Patients with spinal cord injury frequently require catheterization, either continuous or intermittent, for bladder management. Of 898 patients with spinal cord injury, 261 (29%) were found to have bladder calculi; 62.5% were managed with indwelling catheters, whereas the remainder wore external appliances for urine collection. 4,5,6 Thirty-six percent of patients with spinal cord injury at one institution developed bladder calculi during an 8-year period; patients with spinal cord injury and bladder calculi were more likely to have a neurologically complete lesion, to have urinary tract infection caused by a Klebsiella species, and to use chronic indwelling catheterization. In a follow-up study, the initial incidence of bladder stone formation decreased to 15% for patients with spinal cord injury who had contemporary urologic management. Patients managed with an indwelling urethral or suprapubic catheter had a ninefold increased risk and those using intermittent catheterization or a condom catheter had a fourfold increased risk for development of a bladder stone compared with patients who were catheter free and had continent bladder control within the first year after injury. 4,5 The relative risk for initial development of a bladder stone for those with indwelling and intermittent catheterization was stronger in later years after injury. Another study also found a substantial difference in the risk of bladder stone formation according to the method of bladder management. The risk of stone formation was 0% to 0.5% per year for condom drainage combined with sphincterotomy, 0.2% per year for intermittent catheterization, and 4% per year for indwelling urethral or suprapubic drainage. This increased to a 16% annual risk for patients managed with indwelling catheters who had already developed one bladder stone. This may represent persistent or recurrent infection. 6

2.6.6

Foreign Body Nidus Calculi The urinary tract is the occasional repository for a wide array of foreign

objects, and calculi may form around those that find their way into the bladder. These foreign bodies can be classified as self-induced, iatrogenic, or migrant.Self-

28

induced insertion may be the result of autoerotic behavior, psychological abnormalities, senility, or inebriation. Dalton and colleagues (1975) reviewed foreign bodyinduced stone formation in an animal model and noted that (1) calculi may develop on foreign objects in the absence of infection; (2) stone formation is inhibited by dilution, diuresis, and acidification of urine; (3) stone formation is enhanced with infection, especially with urea-splitting organisms; and (4) calculi may form around nearly any type of suture. They also catalogued an extensive list of items involved in bladder stone formation, including a steel washer, chewing gum, fountain pen, knife blade, hairpins, and thermometers. Multiple cases of self-induced bladder calculi have been reported in the literature with infrequent significant morbidity or mortality.4,5,6 Iatrogenic nidi from urinary tract manipulation and stenting have been widely reported. As mentioned previously, Foley catheters act as foreign bodies; encrustations may form around the tip or the balloon of the catheter. These encrustations may act as nidi for further stone growth. Furthermore, patients on intermittent self-catheterization may introduce pubic hairs into the bladder, which may act as nidi for stone formation. Retained ureteral stents may often have encrustations or calculus on the bladder portion. Calculi may form around sutures and staples used in urinary diversions that are exposed to urine.6 Bladder calculi from migrant foreign bodies have been reported as complications of urologic and nonurologic surgical procedures. Calculi have been reported around a migrated titanium prostatic stent, a penile prosthesis reservoir, and a silk suture initially used to ligate the dorsal vein complex during a radical prostatectomy. Although there are numerous reports in the literature concerning migration of intrauterine and intravaginal gynecologic devices into the bladder with subsequent calculus,cholelithiasis, surgical clips used in a laparoscopic hernia repair, vascular graft, and methyl methacrylate cement have also been reported as nonurologic nidi. Thus, any foreign body placed in proximity to the bladder has calculus potential, and the best treatment of these calculi is prevention.4,6

29

2.3.7

Calculi in Augmentations and Urinary Diversions The popularity of lower urinary tract reconstruction with intestinal

segments has contributed to an increased frequency of bladder calculi. The incidence of bladder calculi in the pediatric and adult population with bladder augmentation varies between 0% and 53%. The incidence of stones in urinary diversions is primarily dependent on the type constructed. Calculi have been reported in 4% to 20% of ileal conduit series, 5% of ileocecal conduits, and 3% to 11% of colon conduits. In general, conduits have lower calculi rates than continent diversions do. The Indiana pouch has a stone incidence of 3% to 13% the Kock pouch, 4% to 43%; the orthotopic hemi-Kock pouch, 3% to 16%; the Mainz pouch, 8%; and the cecal reservoir, 20%.6 Risk factors associated with calculi formation include urinary stasis, mucus production, urinary infection with a urea-splitting organism, foreign bodies, and metabolic disturbances. The efficiency of bladder drainage has been implicated as a risk factor for stone formation. This is reflected in the finding that continent diversions had a stone rate three times that of orthotopic cystoplasties; those with orthotopic diversions who voided by catheterization urethrally and abdominally had a rate five and ten times, respectively, that of those who voided spontaneously. 4 Furthermore, bladder calculi were found in 6% of patients with augmentation only; 14% with augmentation with either a bladder neck procedure or an abdominal stoma; and 21% with augmentation, bladder neck surgery, and stoma creation. Mucus may be a factor in stone formation because it could act as a nidus, hinder adequate bladder drainage with voiding or catheterization, and harbor urea-splitting organisms.6 In some augmentation series, lower stone rates were seen with the regular use of an irrigation protocol to minimize mucus; in others, it made no difference. Bowel that normally lives symbiotically with bacteria, when interposed in the urinary tract, may serve as a source for asymptomatic bacteriuria or infection with subsequent calculus formation. The majority of calculi in augmentations and diversions are composed of magnesium ammonium phosphate or carbonate

30

apatite, signifying that infection with urea-spitting bacteria plays a role in calculi formation. 4 The use of stomach for augmentation significantly lowers the incidence of calculi compared with other intestinal segments. Gastric segments produce minimal mucus and secrete acid, thereby lowering urine pH and inhibiting bacterial growth. Bladder calculi that do develop are usually uric acid or are seen in conjunction with the use of histamine blockade medications. Contemporary series reporting the results of interposing intestinal mucosa into the urinary tract report lower rates of bladder calculi.6 This is believed to be due to the recognition of the lithogenic potential of nonabsorbable material and its avoidance in lower tract reconstruction. The predominant location of calculi in the Kock pouch is along staple lines of the afferent nipple valve. Substituting polyglycolic mesh for Marlex mesh in collar construction and limiting the number of staples reduced the incidence of pouch calculi from 28% to 10% in one study. Arif and colleagues (1999) reported a sixfold reduction in stone formation with absorbable compared with nonabsorbable staples in the construction of hemi-Kock pouches.6

2.3.8

Symptoms and Diagnosis Most bladder or urinary diversion calculi are asymptomatic and are found

incidentally. Patients with significant bladder outlet obstruction may initially present with lower urinary tract symptoms or recurrent (persistent) urinary tract infections, especially with a urea-splitting organism. The typical presentation in patients with symptomatic bladder calculi includes intermittent, painful voiding and hematuria. The pain may be of varying quality and may be exacerbated by exercise and sudden movement. The pain is usually located in the lower abdomen but may be referred to the tip of the penis, the scrotum, or the perineum and on occasion to the back or the hip. The urinary stream may be interrupted intermittently, with the accompanying increase in terminal dysuria caused by lodging of the calculus at the bladder neck. Assuming a recumbent position may

31

alleviate the symptoms. Whereas smaller bladder calculi may spontaneously pass, larger calculi may cause acute urinary retention.6 Patients with urinary diversions and calculi may present with gross hematuria, pressure sensations in the diversion, difficultly with catheterization or emptying, mild incontinence, lower abdominal discomfort, or recurrent urinary tract infections .Calculi in diversions may also impair drainage and lead to renal insufficiency.6 Although bladder calculi can be visualized on plain radiographs, a significant number may be missed because of overlying bowel gas, soft tissue shadowing, and the radiolucent quality of some calculi. Ultrasonography can be used to detect radiolucent calculi but may be limited by bowel gas in the setting of urinary diversion. Computed tomography is superior to ultrasonography in detection of calculi in cases of lower tract reconstruction. Radiolucent calculi may be identified as filling defects in the partially filled bladder or diversion on excretory urogram, pouchogram, or loopogram. 6 Cystoscopy is the single most accurate examination to document the presence of a bladder calculus. Cystoscopy assists in surgical planning by identifying prostatic enlargement, bladder diverticulum, or urethral stricture that may need correction before or in conjunction with the treatment of the stone.4,5

2.3.9

Management of Bladder Calculi The majority of bladder calculi are treated endoscopically, but treatment

strategies may range from chemolysis to open surgery. Bladder calculi may be surgically treated by shockwave lithotripsy; cystolitholapaxy; cystolithotripsy with mechanical, electrohydraulic, ultrasonic, or laser energy sources; percutaneous cystolithotomy; and open cystolithotomy. The approach is influenced by the patient's anatomy and comorbidities; stone size, location, and composition; previous stone treatment; and risks and complications. In addition to removal of the calculi, treatment should address predisposing factors such as bladder outlet obstruction, urinary stasis, infection, and foreign bodies to minimize recurrence.6

32

1. Chemolysis Suby solution G or hemiacidrin has been used in the past to dissolve magnesium ammonium phosphate calculi. The calculi are dissolved because of the acidity (pH 4), and the magnesium salts formed are more soluble than calcium salts. Uric acid calculi may be amenable to dissolution with oral sodium or potassium citrate. In refractory cases, direct irrigation of the calculus with sodium bicarbonate may be successful. Dissolution for primary treatment of bladder calculi can be protracted and is now rarely employed. Hemiacidrin may be used as an adjunct to surgical treatment or prophylactically to prevent encrustation of indwelling catheters. Similarly, irrigations with 0.25% or 0.5% acetic acid solution or use of medications that inhibit urease may prevent recurrent magnesium ammonium phosphate calculi on chronic indwelling catheters.4,5

2. Shockwave Lithotripsy Shockwave lithotripsy (SWL) has been used successfully in the treatment of bladder calculi. A three-way Foley catheter is placed, and the patient is placed in the prone position on the cushion. The prone position avoids the dampening effects of air interfaces from the rectum and gluteal crease and the interference from the projection of the coccyx over a portion of the focusing ellipsoid. The bladder is filled with 100 to 150 mL of normal saline through the catheter to improve visualization. After the calculus has been localized, the bladder is drained, which minimizes stone migration. Intermittent saline irrigation through the catheter is used to create an expansion chamber for better. Catheterization may also introduce air and obscure stone localization. 4 Obstructed patients with high postvoid residuals and patients with larger calculi have lower success rates of SWL and higher rates of ancillary procedures. Multiple treatments of bladder calculi with SWL may be required to achieve stone-free status. Poor results with SWL have been reported with use of a piezoelectric lithotriptor. SWL may be considered for those who are unfit for surgery because of comorbid medical conditions or who refuse surgery. Stone

33

recurrence may be high because SWL fails to address the etiology of bladder calculi.6

3.

Cystolitholapaxy Cystolitholapaxy is the crushing of the calculus with irrigation of the

fragments from the bladder in a single operation. Introduced by Bigelow, this procedure has been accomplished with either a tactile or optical lithotrite since the late 1800s. Contraindications include small-capacity bladders, multiple stones or calculi larger than 2 cm that cannot be engaged, hard stones, bladder calculi in children, and small-caliber urethras. During the procedure, the bladder should be filled with about 200 mL of irrigant. 4,5,6 When the stone is grasped, bladder mucosa should be excluded from the instrument. The stone is then crushed manually, and the procedure is repeated several times until fragments can no longer be caught. Cystolitholapaxy has a high success rate in experienced hands. However, it can be technically difficult and is associated with a complication rate of between 9% and 25%. Amplatz sheath use after initial urethral dilation may help reduce urethral trauma and operative time during cystolitholapaxy. 6 Complication rates when cystolitholapaxy and transurethral prostatectomy are combined have varied widely. Transurethral prostatectomy may be performed after cystolitholapaxy if the bladder is in adequate condition. Cystolitholapaxy with mechanical crushing of the calculus has been eschewed for endourologic techniques with energy sources that are safer and more effective.4 Pneumatic lithotripsy uses mechanical energy for fragmentation. It is almost always successful at fragmentation and produces multiple small fragments. Pneumatic lithotripsy was found to be more efficient than ultrasonic lithotripsy or electrohydraulic lithotripsy for large or particularly hard calculi. The device is compact, the cost is relatively inexpensive, and the probes are reusable and may be used through a standard cystoscope. A combination of pneumatic lithotripsy and transurethral prostatectomy has been found to be safe and effective with minimal increases in overall operative. 4,5

34

Electrohydraulic lithotripsy can efficiently fragment most bladder calculi. A success rate of 92% in 302 patients treated with electrohydraulic lithotripsy with a mean operative time of 26 minutes has been reported. Bladder rupture occurred in 1.9% of all cases; only one patient required laparotomy for an intraperitoneal perforation. 4,5 The electrohydraulic lithotripsy probes are flexible and are able to be passed through standard cystoscopic equipment, but the probe must be kept away from the mucosa and the lens to prevent injury or damage. Stone and fragment propulsion may be problematic during use; the ideal setting is the lowest that will fragment the stone without excessive movement. Hard or large calculi may require prolonged procedure times, consume multiple probes, and result in incomplete fragmentation. Ultrasonic lithotripsy is effective in the treatment of bladder calculi. An 88% stone-free rate was reported in patients with stones of 12 to 50 mm (average, 29 mm) with a mean anesthesia time of 56 minutes. Two cases were converted to open cystolithotomy because of stone hardness. Ultrasonic energy has no significant adverse effects on bladder mucosa other than a local edematous reaction; it is able to clear large stone burdens with simultaneous stone evacuation and relatively low cost. The rigid lithotrite must be passed through a cystoscope with an offset lens and can perforate the bladder. Operative times may be prolonged with calcium oxalate monohydrate and calcium phosphate calculi larger than 3 cm; uric acid calculi are resistant to ultrasonic fragmentation.4 Use of the holmium:YAG laser for lithotripsy of large bladder calculi is safe, effective, and facile. A side- or end-firing laser fiber can be used to contact and ablate the stone. To prevent mucosal injury, the fiber is kept a minimum of 0.5 mm from the urothelium. A stone-free rate of 100% was reported in 14 patients with bladder calculi larger than 4 cm treated with the holmium:YAG laser and either a 365-m end-firing fiber or a 550-m side-firing fiber in a mean anesthetic time of 57 minutes. Migration of fragments was minimal, and the 550m side-firing fiber was found to be almost twice as fast at stone vaporization as

35

the 365-m end-firing fiber .The authors have had satisfying results with the 1000-m end-firing fiber for lithotripsy of bladder calculi.6

4. Percutaneous Cystolithotomy Percutaneous cystolithotomy is indicated in pediatric patients with narrow urethras and in patients with large stone burdens or multiple calculi with anticipated prolonged operative times. Contraindications include a history of bladder malignant disease, prior abdominal or pelvic surgeries, prior pelvic radiotherapy, active urinary or abdominal wall infection, and pelvic prosthetic devices. The percutaneous puncture is positioned above the symphysis or at a prior suprapubic tube site to avoid inadvertent bowel or vascular injury. Cystoscopic guidance through either the urethra or the cutaneous stoma can facilitate access and track dilation when Amplatz fascial dilators are used. Amplatz sheaths (26 to 36 French) allow the use of large instruments for rapid lithotripsy or removal of large intact fragments. Success rates for percutaneous cystolithotomy range from 85% to 100% with various energy sources. One report suggested that this approach be used for all children with vesical calculi and for adults with stones larger than 4 cm or more than three calculi.6 5. Cystolithotomy 4,6 Although rarely used today, open cystolithotomy for the treatment of bladder calculi is associated with a high success rate. For very large stone burdens or hard stones, cystolithotomy is certainly the most expeditious. Other indications are abnormal anatomy precluding safe access, failure of an endoscopic approach, and concomitant open prostatectomy or diverticulectomy.4 Management of Calculi in Augmentations and Urinary Diversions Most treatment options available for bladder calculi are applicable to calculi in augmentations and diversions. Surgical management of calculi in augmentations and urinary diversions is dependent on the anatomy and the stone burden.Stones in conduit diversions often pass spontaneously, and intervention may not be required.4

36

Endoscopic lithotripsy or stone extraction is best suited for the adult with a simple augmentation and normal urethra and bladder neck. Prudent use of any of the energy sources will provide effective stone clearance. In adult patients with reconstructed bladder necks or urethras, gentle dilation to 21 French, use of safety guide wires, and peel-away sheaths allow safe access for multiple passes of the cystoscope without any apparent detriment to urinary continence. Patients with an orthotopic diversion and a low stone burden may also be rendered stone free with transurethral lithotripsy and any of the energy sources. Endoscopic removal of multiple small fragments lodged within the mucosal folds of capacious diversions may be difficult. Prolonged operative times may increase the risk of bladder neck contracture or sphincter damage in orthotopic diversions. Patients with continent cutaneous diversions and low stone burdens may also be treated trans-stomally through intussuscepted nipple valves of adequate caliber. 4 There are multiple reports of successful treatment with a rigid nephroscope passed under direct vision into the efferent nipple without dilation of the valve and without apparent detrimental effect on the continence mechanism in Kock and Indiana pouches. Flexible pouchoscopy may be used in cases of minimal stone burden. Despite the reported high success rate of trans-stomal and transurethral therapy, lithotripsy through the efferent limb or urethra can be difficult because of location, size, and composition of the stone or the efficiency of the small-diameter instruments that are used.4 The percutaneous approach is ideally suited for patients with impassable or obliterated bladder necks or urethras, small-caliber stomas such as the Mitrofanoff valve, Monte procedure or tapered imbricated terminal ileum, or large stone burdens. Passage of large instruments through an abdominal stoma may cause disruption of the continence mechanism or postoperative stenosis. In this setting, percutaneous treatment of augmented bladder and pouch calculi with dilation of tracks for working ports and trocars has been rewarding. Access to the augmented bladder is carried out two to four fingerbreadths above the pubic symphysis or at a previous suprapubic tube site. If the augmented bladder is not

37

well fixed to the anterior abdominal wall, extravasation of the irrigating fluid could lead to peritonitis.4 Open surgical removal is considered in augmentations and diversions when endoscopic techniques cannot be accomplished safely or expeditiously because of stone location, excessive burden or number, or abnormal anatomy or when open surgery is planned on the diversion.4 SWL is best suited for small solitary calculi of augmented bladders in male children and adults. Although it has been used with success in the Kock and Indiana pouches, SWL in diversions can result in multiple small fragments that may lead to stone recurrence in the face of impaired clearance from the diversion, and endoscopic removal is often required to achieve a stone-free state.4 The recurrence rate in this population of patients is estimated to be 65% during 5 years.Thus, prophylactic measures, such as adequate oral fluid intake, ensuring complete regular evacuation of the reservoir, daily irrigation of the pouch with saline or tap water to remove mucus and crystals, and eradication of urea-splitting organisms, should be instituted. Routine endoscopic surveillance, particularly in an active stone former, may be warranted.4