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Interstitial Cystitis or Bladder Pain Syndrome
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Interstitial cystitis is unknown etiology syndrome characterized by urinary frequency, urgency, and bladder pain (Nickel, 2004). In the past, it was reported to be frequently affecting middle-aged women; however, recent studies revealed that it affect men and women in all ages (Kusek and Nyberg, 2001). Recent study showed that as high as 12% of women may be affected with early symptoms of interstitial cystitis/bladder pain syndrome (IC/BPS) (Rosenberg and Hazzard, 2005).
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Common symptoms with IC/BPS are bladder pain worsened with bladder filling, certain food intake, and burning on urination. Urinary frequency, nocturia, and urgency are also common.
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The etiology of IC/BPS is unknown and various causes are proposed. These include increased mast cell in the bladder wall, deficiency of glycosaminoglycan layer over bladder mucosa leading to bladder wall inflammation by urine stimulation, unknown virus infection, toxic substance in the urine, autoimmune disorder, etc (Buffington, 2004; Burkman, 2004; Clemens et al, 2008; Elbadawi, 1997; Wesselmann, 2001).
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Laboratory test: The urine is almost always free of infection. Microscopic hematuria may be noted. Results of renal function tests are normal except in the occasional patient in whom vesical fibrosis has led to vesicoureteral reflux or obstruction. No urine cytology or markers are found to be specific to IC/BPS (Hurst et al, 1993). No serologic tests are shown to be diagnostic for this condition.
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Imaging: No radiographic findings are found to be specific to IC/BPS. Excretory urograms are usually normal unless reflux has occurred, in which case hydronephrosis is found. The accompanying cystogram reveals a bladder of small capacity; reflux into a dilated upper tract may be noted on cystography.
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Urodynamic study: Urodynamic study is not required for diagnosis of IC/BPS; however, it can be used to rule out other condition, such as neurogenic bladder or bladder outlet obstruction.
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Cystoscopy: Diagnostic cystoscopy is commonly performed under anesthesia in order to adequately distend the bladder. Typical cystoscopic findings associated with IC/BPS are reduced capacity, scarring and cracking of the mucosa with distention (Hunner's ulcer), and appearance of glomerulation (diffuse petechial hemorrhages in the mucosa) after distension. However, classic Hunner's ulcer is rare. Glomerulation can be seen with other conditions, and the finding is not specific to IC/BPS (Ottem and Teichman, 2005; Simon et al, 1997).
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Histology: Bladder biopsy has been shown to have increase mast cell in the bladder wall (Sant and Theoharides, 1994). However, this finding does not include or exclude the diagnosis (Johansson and Fall, 1990).
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KCl test: Patients with deficiency of the urothelial defense layer (Nickel et al, 1993) may experience severe pain with instillation of potassium chloride solution in the bladder. However, this test is controversial and not widely used.
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Validated questionnaires: The Wisconsin Interstitial Cystitis Scale and The Interstitial Cystitis symptom and Problem Index (O'Leary et al, 1997) are validated questionnaires and useful in diagnosis and evaluation of treatment effectiveness (Lubeck et al, 2001; Sirinian et al, 2005).
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National Institute of Diabetes and Digestive and Kidney Disease criteria: Since IC/BPS is unknown etiology clinical symptom complex, National Institute of Diabetes and Digestive and Kidney Disease criteria was created to rule in/out this diagnosis (Gillenwater and Wein, 1988; Nordling, 2004; Oberpenning et al, 2002) (Table 38–1).
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Differential Diagnosis
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Tuberculosis of the bladder may cause true ulceration but is most apt to involve the region of the ureteral orifice that drains the tuberculous kidney. Vesical ulcers due to schistosomiasis cause symptoms similar to those of interstitial cystitis. The diagnosis is suggested if the patient lives in an area in which schistosomiasis is endemic. Nonspecific vesical infection seldom causes ulceration. Pus and bacteria are found in the urine. Antimicrobial treatment is effective.
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Oral medication: Pentosan polysulfate provides protective coating in the bladder and suppose to reduce IC/BPS-related pain (Parsons and Mulholland, 1987). However, a randomized study has shown no significant benefit of the medicine over placebo (Nordling, 2004; Sairanen et al, 2005; Sant et al, 2003). Cyclosporine A has been shown to be more effective than pentosan polysulfate; however, its toxicity limits the usage (Sairanen et al, 2005). Anticholinergics are frequently used to control frequency and urgency. Amitriptyline has shown to improve IC/BPS symptoms including pain and frequency.
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Instillation therapy: Hydrodistention under anesthesia can improve symptoms. Intravesical instillations of dimethyl sulfoxide (DMSO), heparin, bacille Calmett-Guerrin (Mayer et al, 2005), and sodium hyaluronate (Riedl et al, 2008) are also used with some benefits (Chancellor and Yoshimura, 2004).
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Other therapy: Other nonspecific medications, such as analgesics, anti-inflammatory agents, gabapentin, and serotonin reuptake inhibitors, can be used. Transcutaneous electrical nerve stimulation (Comiter, 2003) and biofeedback therapy may have some benefit for controlling the symptoms (Peters et al, 2007). Diet modification to avoid certain foods or drinks may have a role in the treatment (Chaiken et al, 1993).
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Surgical therapy: Surgical therapy is rarely indicated. Even after cystectomy, some patients continue to experience pain (Baskin and Tanagho, 1992). For those who have small bladder capacity, augmentation procedure can be indicated. Recent trials of botulinum toxin A injection in the bladder wall have shown to improve symptoms and bladder capacity.
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Most patients respond to one of the conservative measures mentioned previously. IC/BPS is a chronic condition and requires patient understanding and support.
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Foreign Body Inserted into the Bladder
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Numerous objects have been found in the urethra and bladder of both men and women. Some of them find their way into the urethra in the course of inquisitive self-exploration (Cardozo, 1997; Mastromichalis et al, 2011). Other objects can migrate in the bladder through erosion. Commonly reported objects are intrauterine contraceptive devices (Bjornerem and Tollan, 1997; Chuang et al, 2010; Hick et al, 2004). Other foreign bodies placed during surgery include hernia repair mesh (Bjurlin and Berger, 2011), drain, vaginal sling material, and bone fragments after trauma (Stone et al, 1995).
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The presence of a foreign body causes cystitis. Hematuria is not uncommon. Embarrassment may cause the victim to delay medical consultation. A plain x-ray of the bladder area discloses metal objects. Nonopaque objects sometimes become coated with calcium. Cystoscopy visualizes them all.
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Cystoscopic or suprapubic removal of the foreign body is indicated. If not removed, the foreign body will lead to infection of the bladder. If the infecting organisms are urea splitting, the alkaline urine (which causes increased insolubility of calcium salts) contributes to rapid formation of stone on the foreign object.
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Vesical Manifestations of Allergy
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So many mucous membranes are affected by allergens that the possibility of allergic manifestations involving the bladder must be considered. Hypersensitivity is occasionally suggested in cases of recurrent symptoms of acute “cystitis” in the absence of urinary infection or other demonstrable abnormality. During the attack, general erythema of the vesical mucosa may be seen and some edema of the ureteral orifices noted. Sometimes, lesions mimic malignancy (Salman et al, 2006; Thompson et al, 2005). Biopsy of the bladder wall reveals diffuse eosinophilic cell infiltrations (eosinophilic cystitis) (Popescu et al, 2009; Rubin and Pincus, 1974).
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A careful history may reveal that these attacks follow the ingestion of a food not ordinarily eaten (eg, fresh lobster). Sensitivity to spermicidal creams is occasionally observed. If vesical allergy is suspected, it may be aborted by the subcutaneous injection of 0.5–1 mL of 1:1000 epinephrine. Control may also be afforded by the use of one of the antihistamines. Steroid therapy is effective for severe cases (Watanabe et al, 2009). Skin testing has shown positive in some cases.
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Most vesical diverticula are acquired and are secondary to either obstruction distal to the vesical neck or the upper motor neuron type of neurogenic bladder. Increased intravesical pressure causes vesical mucosa to insinuate itself between hypertrophied muscle bundles, so that a mucosal extravesical sac develops (Figure 38–4). Often this sac lies just superior to the ureter and causes vesicoureteral reflux. The diverticulum is devoid of muscle and therefore has no expulsive power; residual urine is the rule, and infection is perpetuated. If the diverticulum has a narrow opening that interferes with its emptying, transurethral resection of its neck will improve drainage. Carcinoma occasionally develops on its wall (Prakash et al, 2010). Micic (1983) discovered 13 diverticula harboring malignant tumors: nine transitional cell tumors, two squamous cell tumors, and two adenocarcinomas. Gerridzen and Futter (1982) saw 48 cases of vesical diverticula. Transitional cell tumors were found in five of these patients, but almost all the rest had abnormal histopathology: chronic inflammation and metaplasia. These authors stress the need for visualizing the interior of diverticula during endoscopy. Lack of wall thickness in diverticula makes potential early invasion of tumor and can results in poor prognosis (Yu et al, 1993). Diverticulectomy can be successfully performed laparoscopically (Khonsari et al, 2004; Kural et al, 2009; Macejko et al, 2008). Endoscopic management of bladder outlet obstruction must be performed, if a diverticulectomy is performed.
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Vesical fistulas are common. The bladder may communicate with the skin, intestinal tract, or female reproductive organs (Figure 38–5). The primary disease is usually not urologic. The causes are as follows: (1) primary intestinal disease—diverticulitis, 50–60%; cancer of the colon, 20–25%; and Crohn's disease, 10% (Badlani et al, 1980; Simoneaux and Patrick, 1997); (2) primary gynecologic disease—pressure necrosis during difficult labor; advanced cancer of the cervix (Chapple and Turner-Warwick, 2005; Gilmour et al, 1999); (3) treatment for gynecologic disease following hysterectomy, low cesarean section, or radiotherapy for tumor (Ayhan et al, 1995); and (4) trauma. Ablative therapy of prostate cancer such as, cryosurgery or high intensity focused ultrasound therapy, is a frequent cause of rectourethral fistula, but development of rectovesical fistula is rare.
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Malignant tumors of the small or large bowel, uterus, or cervix may invade and perforate the bladder. Inflammations of adjacent organs may also erode through the vesical wall. Severe injuries involving the bladder may lead to perivesical abscess formation, and these abscesses may rupture through the skin of the perineum or abdomen. The bladder may be inadvertently injured during gynecologic or intestinal surgery; cystotomy for stone or prostatectomy may lead to a persistent cutaneous fistula.
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Symptoms arising from a vesicointestinal fistula include vesical irritability, the passage of debris (fecauria) and gas through the urethra (pneumaturia), and usually a change in bowel habits (eg, constipation, abdominal distention, diarrhea) caused by the primary intestinal disease (Kirsh et al, 1991). Signs of bowel obstruction may be elicited; abdominal tenderness may be found if the cause is inflammatory.
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Urinalysis shows increased WBC and RBC with bacteria. Urine culture commonly grow mixed bacterial flora.
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Imaging studies: CT scan and MRI are sensitive test for enterovesical fistula. It may show thickening of the bladder wall, mass adjacent to the bladder, and air in the bladder (Figure 38–6) (Moon et al, 2001). However, air in the bladder can be seen with an infection caused by gas forming bacteria or instrumentation and is not solely diagnostic (Joseph et al, 1996). Barium enema is not sensitive to describe fistula. However, it may show diverticulosis or malignancy. Cystography may show contrast in the bowel, although the sensitivity of cystography for enterovesical fistula is low. Radionuclide voiding cystography is reported to be sensitive test for enterovesical fistula diagnosis (Tamam et al, 2009).
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Cystoscopy: Cystoscopic examination shows a severe localized inflammatory reaction from which bowel contents may exude. Catheterization of the fistulous tract may be feasible; the instillation of radiopaque fluid often establishes the diagnosis.
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Other test: Charcoal (Huettner et al, 1992) or poppy seed test (Kwon et al, 2008) is to detect orally ingested charcoal or poppy seeds in patient urine. Bourne test detects barium particle in urine after barium enema (Amendola et al, 1984). Those tests may show the evidence of fistula; however, anatomical characterization cannot be achieved.
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Differential Diagnosis
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It is necessary to differentiate ureterovaginal from vesicovaginal fistula. Phenazopyridine (Pyridium) is given by mouth to color the urine orange. One hour later, three cotton pledgets are inserted into the vagina, and methylene blue solution is instilled into the bladder. The patient should then walk around, after which the pledgets are examined. If the proximal cotton ball is wet or stained orange, the fistula is ureterovaginal. If the deep cotton pledget contains blue fluid, the diagnosis is vesicovaginal fistula. If only the distal pledget is blue, the patient probably has urinary incontinence (Raghavaiah, 1974).
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Conservative management: Fistula caused by Crohn's disease is commonly managed with medical therapy with steroid, sulfasalazine, and antibiotics. Patients with poor surgical candidate with fistula from diverticulosis can be managed with antibiotics therapy.
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Surgical therapy: Enterovesical fistula is commonly treated with affected portion of bowel resection with or without bladder repair (Melchior et al, 2009). If inflammation by diverticulosis is severe, staged approach with fecal diversion can be performed (Moss and Ryan, 1990). If malignancy is the cause of the fistula, partial or total cystectomy with affected bowel is necessary.
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For vesicovaginal fistula, tiny openings may become sealed following the introduction of an electrode into the fistula to ablate mature tract epithelium. An indwelling catheter should be left in place for 2 weeks or more. Larger fistulas secondary to obstetric or surgical injuries respond readily to surgical repair, which may be done either through the vagina or transvesically (Huang et al, 2002; McKay, 2004). Persky et al (1979) advised repairing such fistulas immediately rather than waiting for 3–6 months as counseled by most surgeons (Blaivas et al, 1995). Fistulas that develop following radiation therapy for cancer of the cervix are much more difficult to close because of the avascularity of the tissues. Surgical closure of fistulas that arise from direct invasion of the bladder by cervical carcinoma is impossible; diversion of the urinary stream above the level of the bladder (example ureterosigmoidostomy) is therefore necessary.
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The surgical repair of fistulas caused by benign disease or operative trauma is highly successful. Postirradiation necrosis offers a more guarded prognosis. Fistulas secondary to invading cancers present difficult problems.
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The cause of pelvic lipomatosis is not known. The disorder seems to affect principally black men in the 20–40-year age group with hypertension (Heyns, 1991). There are no pathognomonic symptoms. There may be some dysuria or mild urinary obstructive symptoms. Examination may demonstrate microscopic hematuria, a distended or enlarged pear-shaped bladder. Excretory urograms and cystography may show dilatation of both upper tracts and an upward displacement and lateral compression of the bladder (Miglani et al, 2010; Mordkin et al, 1997). In the perivesical area, x-ray reveals areas of radiolucency compatible with fatty tissue. A barium x-ray may show extrinsic pressure on the rectosigmoid. CT scan in association with the preceding findings establishes the diagnosis by clearly demonstrating the fatty nature of the perivesical tissue. Ultrasonography may be equally helpful. Cystitis glandularis is frequently associated with pelvic lipomatosis (Heyns et al, 1991; Masumori and Tsukamoto, 1999). Adenocarcinoma of the bladder can develop in the bladder in this condition (Sozen et al, 2004).
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Noninfectious Hemorrhagic Cystitis
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Some patients, following radiotherapy for carcinoma of the cervix, bladder, or prostate, are prone to intermittent, often serious vesical hemorrhage. The same is true of those given cyclophosphamide or ifosphamide. Cyclophosphamide is metabolized in liver to acrolein. This is excreted in urine to cause bladder damage (Cox, 1979). About 5–10% of patients with a history of pelvic irradiation (Levenback et al, 1994) and up to 70% of patients exposed to high dose of cyclophosphamide or iphosphamide are at risk of hemorrhagic cystitis (Efros et al, 1990).16 Penicillins (Bracis et al, 1977), and danazol (Andriole et al, 1986) are reported to be associated with hemorrhagic cystitis (deVries and Freiha, 1990).
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Gross hematuria with clots without evidence of typical urinary infection symptoms.
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Differential Diagnosis
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Malignancy, urinary tract infection, calculi, and benign prostate hyperplasia can cause gross hematuria.
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Cystoscopy shows abnormal neovascularity that is easy to bleed with distention. Diffuse mucosal bleeding is common (Figure 38–7).
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For prevention of cyclophosphamide or iphosphamide induced hemorrhage, hydration and continuous bladder drainage during chemotherapy are recommended (Ballen et al, 1999). 2-Mercaptoethanesulfonate binds to acrolein to reduce toxic effect, and it can be administered during the chemotherapy (Goren et al, 1997).
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Bladder irrigation with three-way catheter is essential. Oral epsilon aminocaproic acid can be tried. Conservative therapy includes bladder irrigation with alum or silver nitrate. For severe hemorrhage with clots retention, cystoscopic clots evacuation, electro fulguration (Kaplan and Wolf, 2009), and formalin instillation in the bladder can be done under anesthesia (Donahue and Frank, 1989).19 A cystogram to confirm no association of vesicoureteral reflux prior to instillation is important since formalin can damage renal function if it is induced in the kidneys.17
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Giulani et al have reported success by selective transcatheter embolization of the internal iliac arteries (Giuliani et al, 1979). Ostroff and Chenault (1982) believe that the best and least harmful method of treatment is continuous irrigation with 1% alum solution (the ammonium or potassium salt) through a three-way Foley catheter (Giuliani et al, 1979). Alum can induce encephalopathy in renal failure patients, and careful monitoring of serum aluminum level in such patients is recommended (Andriole et al, 1986).15
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Hyperbaric oxygen therapy has been used for both radiation-induced and chemotherapy-induced hemorrhagic cystitis with encouraging results (Chong et al, 2005).18,20 Conjugated estrogen therapy has also demonstrated some effect (Liu et al, 1990).14
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Bilateral nephrostomy to reduce urinary contact to the bladder lumen is moderately effective. For severe refractory hematuria, cystectomy with urinary diversion or neobladder creation is considered as a last resort.