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Urinary tissue polypeptide-specific antigen for the diagnosis of bladder cancer.

OBJECTIVES: To evaluate the diagnostic characteristics of the urinary measurement of cytokeratin tissue polypeptide-specific antigen (TPS) for the detection of bladder cancer. METHODS: Three hundred thirty-five individuals in five groups were studied: group 1, subjects with microhematuria under suspicion for primary bladder cancer; group 2, patients being followed up with scheduled cystoscopic examinations; group 3, patients in follow-up receiving chemotherapy instillations; group 4, patients with other urologic diseases; and group 5, healthy subjects. Urine samples belonging to subjects from groups 1, 2, and 3 were collected immediately before cystoscopy. Additionally, patients from groups 2 and 3 were monitored with urinary TPS for a minimum period between two cystoscopies. TPS was measured by an enzyme immunosorbent assay. RESULTS: Receiver operating characteristic analysis gave a sensitivity of 64% and a specificity of 84% at a threshold value of 279 U/L. The positive and negative predictive value was 66% and 82%, respectively; accuracy was 77%. TPS could discriminate the presence of bladder tumor sooner than the scheduled cystoscopies in 9 of 19 follow-up patients with recurrence. False-positive results during follow-up were found in 112 urine samples, one third of which were associated with urinary tract infections. TPS did not appear to be specific for bladder cancer, with elevated results in 45% of patients from group 4, which might lead to clinical misinterpretation of urinary TPS results. CONCLUSIONS: Urinary TPS might provide additional information for the detection of bladder cancer as an adjunct to cystoscopy. Considering the false-positive rates, different urologic diseases should be ruled out before making clinical decisions on the basis of elevated urinary TPS results.

Administration, Intravesical↗

Mitochondrial DNA deletion of the human detrusor after partial bladder outlet obstruction-correlation with urodynamic analysis.

OBJECTIVES: To investigate mitochondrial DNA (mtDNA) mutations in human detrusor after partial bladder outlet obstruction (BOO) and correlate the findings with the results of urodynamic studies. METHODS: Sixty-two male patients with and without BOO were recruited and assessed by the International Prostate Symptom Score, a quality-of-life assessment index, and sonography. The severity of partial BOO was determined by pressure-flow study with an International Continence Society (ICS) nomogram. Random detrusor biopsies obtained cystoscopically were analyzed by polymerase chain reaction (PCR) techniques to detect possible mtDNA deletions. Primer-shift PCR and DNA sequencing were then performed to characterize specific mtDNA deletions. A semiquantitative PCR method was used to determine the proportion of the deleted mtDNA in detrusor. Finally, the mtDNA deletion and the urodynamic results were compared statistically. RESULTS: A 4977-bp mtDNA deletion was identified in the human detrusor. Its incidence and proportion were found to increase after partial BOO (P = 0.005 and 0.012, respectively). The incidence of the mtDNA deletion was 4.2% (1 of 24) in the unobstructed group, 27.8% (5 of 18) in the equivocal group, and 40% (8 of 20) in the obstructed group. The mean proportion of the 4977-bp deleted mtDNA was 23.7 and 12.7 times higher in the obstructed and equivocal groups, respectively, compared with that of the unobstructed group. CONCLUSIONS: We found mtDNA with the 4977-bp deletion in human detrusor and an increase of this deletion after partial BOO. This molecular change might account for the previous observations of mitochondrial functional impairment and voiding dysfunction after partial BOO.

Aged↗

Laparoscopic pyeloplasty for secondary ureteropelvic junction obstruction: preliminary experience.

OBJECTIVES: To identify whether laparoscopic pyeloplasty is a reasonable treatment option for secondary ureteropelvic junction (UPJ) obstruction. METHODS: Since March 1994, we have performed laparoscopic pyeloplasties for secondary UPJ obstruction on 4 symptomatic patients ranging in age from 26 to 39 years. Prior failed procedures included antegrade endopyelotomies (3) and acucise endopyelotomies (3). Two patients underwent two prior endopyelotomies. Techniques of laparoscopic reconstruction included Anderson-Hines dismembered (3) and Culp-Deweerd flap (1) procedures. Repairs were performed with interrupted and running 3.0 and 4.0 Vicryl sutures using intra-corporeal knots and Lapra-Ty absorbable suture clips. RESULTS: Average operating time was 530 minutes (range, 465 to 645), which included preoperative cystoscopic placement of an external 7 F occlusion balloon catheter into the renal pelvis and placement of an internal double pigtail ureteral stent at the conclusion of the procedure. Average blood loss was 111 cc (range, 75 to 150). All 4 patients were found to have anterior crossing vessels intraoperatively. Average postoperative hospital stay was 4 days (range, 3 to 7). All 4 patients have a patent, nonobstructed UPJ by either Whitaker test or diuretic renography at an average of 3.3 months postoperatively (range, 1 to 5). Average return to normal activity was 4.5 weeks (range, 3 to 8). Utilizing an analogue pain scale, 2 of the patients are pain-free, and the other 2 are improved (45% and 85%) at an average of 8 months (range, 2 to 12) postoperatively. One patient developed stones in the renal pelvis and required percutaneous nephrolithotomy 10 weeks postoperatively. CONCLUSIONS: Laparoscopic pyeloplasty appears to be feasible and effective, although a technically challenging operative procedure for treating secondary (postendopyelotomy) UPJ obstruction. Further clinical experience and long-term follow-up are needed.

Adult↗

Diagnostic tunica vaginoscopy in a rodent model of testicular torsion.

OBJECTIVES: To evaluate the effectiveness of percutaneous endoscopy of the tunica vaginalis for identifying testicular torsion in a rodent model. METHODS: One testis was randomly selected in 10 Wistar rats weighing 500 to 600 g. Following 2 hours of 720 degree torsion, bilateral percutaneous endoscopy of the tunica vaginalis was performed by a blinded investigator utilizing a 70 degree cystoscope lens through a single midline 3 to 4 mm scrotal cutdown incision. RESULTS: Using this technique, the blinded investigator was able to identify the torsed testis rapidly in every case, which was distinguished by its cyanotic color and by the size and color of the testicular surface vessels. CONCLUSIONS: Tunica vaginoscopy is a simple, accurate, rapidly performed, minimally invasive, diagnostic technique in this experimental model of testicular torsion.

Animals↗

Percutaneous electrovaporization of upper tract transitional cell carcinoma in patients with functionally solitary kidneys.

OBJECTIVES: We present the first reported experience using percutaneous electrovaporization with both a rollerball and the VaporTrode electrode of large upper tract transitional cell carcinoma (TCC) in 2 individuals with functionally solitary kidneys. METHODS: Under general anesthesia and in the prone position, 2 patients underwent electrovaporization of upper tract TCC through upper pole percutaneous access. Using either a rollerball (Case 1) or the VaporTrode (Case 2) electrode at 200 W pure cutting current, the tumors were completely vaporized. RESULTS: Average operating room time was 145 minutes. Hemostasis was excellent. No significant perioperative complications were noted. A nephrostogram at the end of the procedure revealed no extravasation in either case. There was no appreciable change in serum creatinine. Both patients received postoperative mitomycin (40 mg in 1000 cc normal saline over 20 hours) through the nephrostomy tube. One patient (Case 2) is completely free of disease via antegrade nephroscopy and biopsy at 2 weeks' follow-up. The other patient (Case 1) had two remaining focal areas of tumor via antegrade nephroscopy 3 weeks postoperatively; both lesions were treated with electrovaporization via a flexible electrode through the flexible cystoscope and the VaporTrode, respectively. CONCLUSIONS: Percutaneous electrovaporization of upper tract TCC appears to provide a simple, rapid, and effective endosurgical treatment in properly selected patients. Long-term follow-up will be needed to assess this new treatment modality definitively.

Aged↗

Interstitial cystitis: a critique of current concepts with a new proposal for pathologic diagnosis and pathogenesis.

Interstitial cystitis (IC) has continued to be an unresolved problem in clinical urology despite intense investigation over the past 16 or more years. Its etiology and pathogenesis are still undetermined, and its pathologic diagnosis is essentially one of exclusion, with no specific or clear criteria. In this review, current concepts of the etiology/pathogenesis and pathology are critically analyzed, new pathologic observations summarized, and a proposal of neurogenic inflammation as the primary pathogenetic factor is presented in the context of all currently available information. The popular postulate attributing IC to a deficient or defective glycosaminoglycan urothelial surface layer is not substantiated by morphologic, experimental, clinical, or therapeutic observations. Although the consensus seems to discount an infectious etiology, there is sufficient evidence that a microbial factor-short of a bona fide clinical infection-may have a role. Both autoimmunity and mast cell infiltration also appear to have a role, despite the lack of evidence that either is involved as the primary etiologic factor. Claims that the so-called feline urologic syndrome may represent a natural animal model of IC are shaky. As it now stands, there is no natural or induced animal model that duplicates IC as it occurs in humans. No specific or diagnostic light microscopic pathologic features are provided by either routine histopathology or immunohistochemistry. Increasingly, it has been recognized that detrusor mast cell count has little or no diagnostic value. On the other hand, electron microscopy has provided important new observations: (a) presence of mast cells, activated by piecemeal degranulation, in close proximity to intrinsic nerves-particularly in suburothelium: (b) distinctive pathologic changes in urothelium, suburothelium, and muscularis in biopsy samples obtained after diagnostic bladder hydrodistension; (c) constant associated changes in venules, capillaries, and neural elements in the same biopsy samples; and (d) diffuse involvement of bladder wall, with the most evident and profound pathologic changes in posthydrodistension biopsy samples obtained from cystoscopically obvious lesions (glomerulations). These features are sufficiently distinctive to allow definitive pathologic diagnosis of IC, and provide a firm basis for primary involvement of neurogenic inflammation in its pathogenesis. A proposal is presented regarding the mechanisms invoked by neurogenic inflammation. This proposal revolves around sensory nerve excitation, the release of neuropeptides, and activated differential secretion of potent mast cell mediators. This proposal can account for the heterogeneity and variability of observed pathologic features, and upholds the tacit acceptance of IC as a disease of pluricausal etiology and multifactorial pathogenesis.

Animals↗

Intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation.

OBJECTIVES: To determine the minimal active dose and extent of activity of intravesicular carboprost for the treatment of hemorrhagic cystitis after marrow transplantation. METHODS: Twenty-four adults with grade 3 or 4 hemorrhagic cystitis were treated. All but 2 had failed other local therapy. Treatment was initiated at a median of 32 days post-transplant. Eleven patients received carboprost intravesicularly at 0.2 mg/dL for 60 minutes every 6 hours, and the dose was escalated every 24 hours until a dose of 1.0 mg/dL was reached unless a response was achieved. Thirteen additional patients were treated at an initial dose of 0.8 mg/dL, with escalation to 1.0 mg/dL after four doses in the absence of a response. RESULTS: Overall, 15 of the 24 patients responded. In the dose-escalation setting, 0.8 mg/dL was the minimal active dose. The total response rate was 62% with doses at or above 0.8 mg/dL and 18% at lower doses. All but one response occurred with 7 or fewer days of therapy, and 9 patients relapsed later. Four additional patients were salvaged following cystoscopy with clot evacuation with or without alum or formalin instillation. In all but 1 patient, bladder spasms developed during treatment with carboprost, but were not sufficiently severe to discontinue therapy. CONCLUSIONS: Intravesicular carboprost at 1.0 mg/dL every 6 hours for no more than 7 days should be considered for a randomized study for treatment of refractory hemorrhagic cystitis. Cystoscopic examination and evacuation of clots prior to therapy may be required to achieve the full benefit of this treatment.

Administration, Intravesical↗

Hematuria in a newborn infant caused by bladder hemangioma.

A newborn boy had gross hematuria caused by hemangiomas of the bladder. The sonographic examination and the voiding cystourethrogram showed an irregular and thick bladder wall with a lesion extending into the vesical lumen. Cystoscopic examination and biopsy of the lesions were diagnostic of hemangioma. Immediately after lesion fulguration, the hematuria disappeared, and 3 weeks later the follow-up ultrasound examination showed resolution of the lesion. At 1 year, the patient's urinalysis and ultrasound scan were normal. To our knowledge, this is the first reported case of hematuria in a newborn caused by a bleeding hemangioma of the bladder.

Hemangioma↗

"Schauta sine utero": technique and results of laparoscopic-vaginal radical parametrectomy.

OBJECTIVES: Radical parametrectomy or radical cervical stump exstirpation is indicated in selected oncologic situations. We evaluated whether radical parametrectomy without or with cervical stump exstirpation can be performed by a combined laparoscopic-vaginal approach. METHODS: Between November 2001 and Dezember 2002 six patients with unexpected cervical cancer (n = 3) after simple hysterectomy, histologically confirmed vaginal recurrence of endometrial cancer (n = 1), or cervical stump recurrence of endometrial cancer after supracervical hysterectomy (n = 2) underwent radical parametrectomy. After cystoscopic placement of bilateral ureteral stents laparoscopic paraaortic and pelvic lymphadenectomy was performed. The vascular part of the cardinal ligament and the bladder pillar were transsected laparoscopically. According to a LARVH type III procedure vaginal vault or cervical stump with parametrial and paravaginal structures was removed transvaginally. RESULTS: In all patients R0 resection could be achieved (n = 4) or no residual tumor was detected (n = 2). There were no intraoperative complications. One patient developed acute kidney failure on postoperative day 1, with spontaneous recovery after 12 days. The median drop of hemoglobin on postoperative day 5 was 2.15 mmol/L (1.3-3.2) and no patient needed transfusion. Restitution of bladder function took 4.3 days on average. The mean operation time was 424 min (385-452). CONCLUSIONS: Radical parametrectomy can be performed by a combined laparoscopic-vaginal technique without complications. Together with laparoscopic paraaortic and pelvic lymphadenectomy, it is a valid alternative to open surgery in selected oncologic patients.

Adnexa Uteri↗

Understanding the epidemiology of fertility treatments.

The science of statistics forms the basis of much of what urologists do and why. Understanding basic statistics is crucial to the appropriate interpretation of urologic studies. As valid as they are, the statistics taught in medical school represent only a small part of what computation can do for the urologist. Contemporary tools such as neural computation coupled with electronic technology that provides increasingly greater computational power in smaller space hold promise to integrate into the field of clinical urology as seamlessly as a ballpoint pen or cystoscope.

Andrology↗

Ureteroscopic surgery: changing times and perspectives.

Ureteroscopy developed as an extension of cystoscopic techniques into the upper urinary tract with smaller, rigid, and flexible endoscopes. Smaller working instruments have made therapeutic procedures possible. Ureteroscopy has become the technique of choice to diagnose and treat benign essential hematuria and has a major role in treating ureteropelvic junction obstruction, upper tract neoplasms, and calculi. Finally, there is a need for smaller and more effective endoscopes and working devices.

Female↗

Office evaluation and management of bladder neoplasms.

Transitional cell carcinoma is the predominant bladder neoplasm. These tumors are heterogeneous, and the risk of recurrence and progression should guide further management. When this approach is used, patients at lower risk avoid the morbidity and expense of unnecessary interventions and tests, whereas higher-risk patients are treated more aggressively. Cystoscopy and IVP remain the standard initial evaluation for patients suspected of having a bladder neoplasm. Intravesical chemotherapy and immunotherapy can be administered safely in the office to reduce disease recurrence when appropriate. The advent of lasers has permitted fulgaration of low-grade neoplasms in the office with local anesthesia. Surveillance of patients with superficial disease is still largely dependent on office-based cystoscopy. Tumor markers for the identification of recurrent disease are being investigated and may prove useful to reduce the number of negative cystoscopic evaluations performed for surveillance. Patients postcystectomy are followed up with attention to detection of recurrent disease in remnant urothelium, metastatic disease, and metabolic and nutritional disturbances, which may result from urinary diversion.

Disease Progression↗

Primary percutaneous approach to upper urinary tract transitional cell carcinoma.

The optimal approach to upper tract TCC remains to be redefined. A routine nephroureterectomy for every filling defect in the upper urinary system, even in the case of a normal contralateral kidney, constitutes an unnecessary mutilation in more than two thirds of the cases. Nephroureterectomy does not reduce the need for a long-term cystoscopic follow-up because of the high rate of bladder tumor recurrence that may happen years later after nephroureterectomy. Relying solely on radiography and cytology, lacking sensitivity and specificity, to recommend a nephroureterectomy is against the principles of oncologic surgery, especially now that preoperative histologic proof is easy to obtain endoscopically without compromising cancer control. Ureteroscopy, rigid and flexible, provides a complete assessment of the upper urinary system. Biopsy specimens taken with ureteroscopy may be sufficient for grading but less adequate for staging of the tumor. The authors reserve ureteroscopy for ureteral tumors and small (< 1.5 cm) single tumors of the renal pelvis. They approach large or multiple tumors of the renal pelvis percutaneously, in which a full histologic assessment is possible along with a complete resection of the tumor. The decision on the therapeutic approach is made only after the final pathologic report is reviewed. Grade I and grade II superficial disease (Ta, T1) can be treated endoscopically with minimal morbidity and with an efficiency comparable with the standard more invasive nephroureterectomy (Table 5). The indications for endourologic treatment in these cases can be extended safely beyond a solitary kidney or a high surgical risk to include any healthy individual with a normal contralateral kidney who is willing to commit to a rigorous lifelong follow-up. Patients with grade II T1 lesions require a more vigilant follow-up. For grade III Ta disease, more caution should be exercised in selecting these patients for elective endourologic management. When criteria of good prognosis are found, such as absence of carcinoma in situ, presence of diploidy, low p53 expression and a single-tumor, endoscopic management can be offered [table: see text] with a closer follow-up and resorting always to immediate nephroureterectomy at the first evidence of upstaging. Because of the high incidence of recurrence and progression, elective endourologic management for grade III T1 tumors is not recommended. Endoscopic conservative surgery still can be offered in the cases of a solitary kidney or chronic renal insufficiency or for poor surgical candidates. Patients with localized stages (T2, T3) TCC should be offered immediate nephroureterectomy. The authors do not expect adequate endoscopic extirpation with muscle invasive tumors. Although the tissue removed may include deep layers, deep resection is precluded by the thin renal pelvic wall and the associated risk for perforation. Patients with more extensive disease (T3, T4) have a bad prognosis regardless of the form of therapy. Achieving local control percutaneously while preserving as many nephrons as possible for the future chemotherapy can be a reasonable option.

Carcinoma, Transitional Cell↗

Urine cytology. It is still the gold standard for screening?

Urine cytology remains the gold standard for bladder cancer screening. It is the test against which all others are compared when evaluating potential bladder tumor markers. The answer to whether urine cytology possess the optimal combination of sensitivity and specificity to retain consideration as the best screening device depends on the goals of the clinical practice. Urine cytology has excellent specificity with few false-positive cases. Its overall sensitivity is poor, but this drawback is explained for the most part by poor criteria for identifying well-differentiated, low-grade TCC. The natural history of such lesions is the occurrence of multiple superficial recurrences in 70% to 80% of patients, with only a minority (10% to 15%) progressing to muscle invasive or metastatic disease. Because patients with low-grade TCC are at low risk for progression, they are monitored primarily for the development of a subsequent tumor. One might argue that the detection of new low-grade lesions is of secondary importance to the early detection of disease progression. The performance characteristics of urine cytology in this regard are much improved. Urine cytology often results in the identification of high-grade malignant cells even before a cystoscopically distinguishable gross lesion is present. Routinely diagnosing grade I TCC may be clinically irrelevant. Ancillary techniques to improve the sensitivity of urine cytology have been insufficiently additive to have much clinical value. Several promising bladder tumor markers have been investigated as potential screening tools and are summarized in Table 3. BTA, nuclear matrix proteins, and fibrin/fibrinogen degradation products share lower specificities than urine cytology and may have high rates of false positivity. Telomerase is highly sensitive and highly specific but is not readily available as a point-of-service test. Hyaluronidase and hyaluronic acid are promising prognostic markers, but hyaluronidase does not detect grade I TCC. Early results from studies of this marker await verification. Combining some of these new markers may optimize their performance status, allowing the advantages of one test to correct the shortcomings of another. Likewise, their combination with urine cytology may prove beneficial. Although adding urine cytology has not increased the sensitivity of some point-of-service tests, few studies have addressed the effect on specificity. Until an obvious winner is declared in the race to find a bladder tumor marker, urine cytology will remain the gold standard screening method because of its comfortable familiarity.

Antigens, Neoplasm↗

Distal urinary obstruction.

Despite the sound experimental basis and initial promise of early animal models, the results of antenatal intervention have been disappointing, with high rates of misdiagnosis of urethral valves, complications from vesicoamniotic shunting, perinatal mortality, and long-term renal impairment and bladder dysfunction in survivors. The recent development of a cystoscopic approach might obviate some of these problems, but to date the procedure been limited by technical difficulty in negotiating the urethrovesical angle. Overcoming these difficulties through equipment modifications might allow definitive testing of whether or not alleviating distal urinary obstruction in utero is beneficial.

Animals↗

Modified Makari skin test in follow-up of bladder-cancer patients.

123 patients who had been treated for carcinoma of the bladder and who were clinically recurrence-free at the time of their initial Makari skin test are being followed-up; 77 were negative and 46 positive. 48 of these patients have been followed-up so far, for 3-9 months, with cystoscopic review and repeat Makari testing; 75 have still to be followed-up. The high initial positive rate of 37% has been largely explained by the discovery of a recurrent tumour at the first cystoscopy after the test. The concordance between tumour status and repeat Makari testing indicates its ability to detect early recurrence.

Cystoscopy↗

Bioresorbable microspheres by spinning disk atomization as injectable cell carrier: from preparation to in vitro evaluation.

Vesico-ureteral reflux, a common pathology in children, can be treated cystoscopically by injection of a bulking material underneath the most distal, intramural ureter, which forces the latter to do a detour, increasing its submucosal path. This increase of the length of the submucosal path of the ureter within the bladder is directly responsible for the anti-reflux effect. So far Teflon and collagen paste have been commonly used as bulking materials. We suggest replacing these materials by living tissue consisting of bladder smooth muscle, normally present at this location. The aim of this work is to provide a long-term effective treatment by producing bioresorbable microspheres which can act as a support matrix and an entrapment substance for bladder smooth muscle cells, with the goal of an in vivo transfer of the in vitro cultured cells with a minimal surgical procedure. By the use of Spinning Disk Atomization, which has specifically been developed for this purpose, we have shown two methods for the preparation of porous poly(lactic acid) microspheres with tunable sizes from 160 to 320 microm. The controlled solvent burst method has shown the advantage over the crystal leaching method in the direct creation of microspheres with large closed pores, by atomizing the polymer solution in controlled temperature conditions. Microspheres with various closed pore structures have thus been prepared. The innovation of this work is in the direct and rapid formation of porous microspheres with a pore morphology which is designed to create cavities suitable for adherence and growth of cells by adapting the temperature conditions of atomization. Injection tests have shown promising results in using these cell-loaded microspheres for future non-invasive tissue engineering.

Absorbable Implants↗