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PubMed2004

Identification of bladder cancer antigens recognized by IgG antibodies of a patient with metastatic bladder cancer.

To identify tumor antigens useful for the diagnosis and treatment of patients with bladder cancer, a lambda phage cDNA library constructed from a high-grade bladder cancer cell line was screened with autologous serum from a patient with metastatic bladder cancer. Forty-eight distinct antigens were isolated. By evaluating the immunogenicity and the tissue-specific expression, KU-BL-1 and KU-BL-2 were identified as immunogenic antigens with restricted tissue expression. KU-BL-1 was found to be a putative human lipoic acid synthetase with a metal-binding site, CXXXCXXC, that was expressed in bladder cancer cell lines and most bladder cancer tissues, as well as normal bladder mucosa and testis tissues. Immunoglobulin (Ig)G antibody to KU-BL-1 was detected in 2 of 28 patients with bladder cancer, but not in 30 healthy individuals. KU-BL-2 was found to be a putative human kelch-like protein that was homologous to Drosophila kelch, with a BTB/POZ domain and kelch repeats. KU-BL-2 was expressed in bladder cancer cell lines, most bladder cancer tissues, testis and heart, but not in normal bladder mucosa. IgG antibody to KU-BL-2 was detected in 8 of 28 patients with bladder cancer, but not in 16 healthy individuals. Tumor reactive T cells were induced from peripheral blood mononuclear cells (PBMC) by stimulation with one of the HLA-A24 binding KU-BL-2 peptides. Therefore, KU-BL-1 and KU-BL-2, which showed preferential expression in bladder cancer with restricted expression in normal tissues, as well as immunogenicity in multiple patients with bladder cancer, may be useful for the development of diagnostic and therapeutic methods for patients with bladder cancer.

Aged↗
PubMed2000

A bladder preservation regimen using intra-arterial chemotherapy and radiotherapy for invasive bladder cancer: a prospective study.

BACKGROUND: A prospective study was performed to investigate combined treatment with intra-arterial chemotherapy and radiation therapy for bladder preservation in locally invasive bladder cancer. METHODS: Patients with invasive bladder cancer, stage T2-3N0M0, were included in the study. Intra-arterial chemotherapy was performed with three injections of methotrexate and cisplatin at 3-week intervals. Simultaneously, the patients underwent X-ray irradiation (40 Gy) of the small pelvic space. Where a post-treatment transurethral resection (TUR) biopsy showed no residual tumor, the tumor site was irradiated by a 30 Gy proton beam and the bladder was preserved. Where tumors remained, radical cystectomy was performed. RESULTS: Between 1990 and 1996, 42 patients were treated according to this protocol. Post-treatment TUR biopsy and urine cytology showed no residual tumors in 39 of 42 cases (93%). The bladder was preserved in accordance with the study protocol in 36 cases. A median follow-up of 38 months showed 3-year non-recurrence in 72% of bladder-preserved patients and the rate of bladder preservation was 84%. The nine recurrences included eight cases of superficial bladder recurrence. One cancer death occurred among the bladder-preservation patients, giving 3-year survival and cause-specific survival rates of 84% and 100%, respectively. Although bladder function decreased slightly in compliance, bladder capacity was retained in almost all cases. CONCLUSIONS: This regimen is useful for bladder preservation in T2-3 locally invasive bladder cancer. Information from more cases and the results of more long-term observations are needed, as is an evaluation of appropriate subject selection and factors associated with quality of life issues, particularly regarding bladder function.

Aged↗
PubMed2004

Fetal bladder sagittal length: a simple monitor to assess normal and enlarged fetal bladder size, and forecast clinical outcome.

PURPOSE: We examined if the parameter of fetal bladder sagittal length (FBSL) could serve as a monitor of normative and enlarged fetal bladder size. MATERIALS AND METHODS: There were 76 consecutive cases examined between 1984 and 2000 that included measurement of fetal bladder size as FBSL and postnatal urological followup. Fetal images used to assess normal bladder size were derived from cases in which the bladder was normal on prenatal imaging and postnatal testing. An enlarged bladder was categorized as being greater than the 95% CI for a given gestational age (GA). The presence and extent of renal pelvic dilatation were also noted and correlated with FBSL. RESULTS: Measuring normal FBSL in 39 fetuses showed an exponential growth pattern (r = 0.76), which could be represented by the approximate linear formula FBSL = GA in weeks -5 (+/- 95% upper/lower CI = 7). An enlarged bladder was diagnosed in 37 fetuses. A dilated bladder in 9 fetuses, defined as FBSL greater than the 95% upper CI of normal (ie between GA + 2 and GA + 12), showed outcomes of posterior urethral valves, vesicoureteral reflux or a normal outcome. Megacystis in 28 fetuses, defined as FBSL greater than 10 mm larger than that of a dilated bladder (ie greater than GA + 12), showed additional outcomes of megacystis megaureter/vesicoureteral reflux or prune-belly syndrome. A normal outcome was significantly more likely in fetuses with a dilated bladder than in those with megacystis (p < or = 0.05). The incidence of azotemia in those with a dilated bladder or megacystis and pyelectasis was significantly lower than that in those with megacystis with hydronephrosis (p < or = 0.03). CONCLUSIONS: Postnatal diagnosis of fetuses that show an enlarged bladder is predicted based on whether the bladder is enlarged as a dilated bladder or megacystis and if the renal pelvis is enlarged as pyelectasis or hydronephrosis.

Female↗
PubMed2005

Reproducibility of the bladder shape and bladder shape changes during filling.

The feasibility of high precision radiotherapy to the bladder region is limited by bladder motion and volume changes. In the near future, we plan to begin treatment delivery of bladder cancer patients with the acquisition of a cone beam CT image on which the complete bladder will be semi-automatically localized. Subsequently, a bladder shape model that was developed in a previous study will be used for bladder localization and for the prediction of shape changes in the time interval between acquisition and beam delivery. For such predictions, knowledge about urinary inflow rate is required. Therefore, a series of MR images was acquired over 1 h with time intervals of 10 min for 18 healthy volunteers. To gain insight in the reproducibility of the bladder shape over longer periods of time, two additional MRI series were recorded for 10 of the volunteers. To a good approximation, the bladder volume increased linearly in time for all individuals. Despite receiving drinking instructions, we found a large variation in the inflow rate between individuals, ranging from 2.1 to 15 cc/min (mean value: 9 +/- 3 cc/min). In contrast, the intravolunteer variation was much smaller, with a mean standard deviation (SD) of 0.4 cc/min. The inflow rate was linearly correlated with age (negative slope). To study the reproducibility of the bladder shape, we compared bladder shapes of equal volume. For all individuals, the caudal part of the bladder was the most reproducible (variations<0.3 cm in all cases). The cranial and posterior parts of the bladder was much less reproducible, with local SD values up to approximately 1.2 cm for bladders with a volume of 200 cc. These large long-term variations were primarily caused by changes in position and filling of the small bowel and rectum. However, for short time intervals, the rectal filling was (nearly) constant. Therefore, the reproducibility of urinary inflow, combined with the previously developed shape model gives us an excellent tool to predict short-term shape changes. We intend to use this tool for further improvement of image-guided radiotherapy for bladder cancer patients.

Adult↗
PubMed2001

Metallothionein isoform 1 and 2 gene expression in the human bladder: evidence for upregulation of MT-1X mRNA in bladder cancer.

The goals of this study were to determine the expression of metallothionein isoform 1 and 2 proteins (MT-1 and MT-2) in bladder cancer and then to determine which MT isoform-specific genes promoted the expression of these proteins. Immunohistochemical analysis disclosed no immunoreactivity for MT-1 and MT-2 (designated as MT-1/2 to reflect the nonspecificity of the antibody for the two isoforms) in cells comprising the normal bladder or in nonmalignant bladder disorders, such as cystitis and interstitial cystitis. Immunohistochemical analysis demonstrated that MT-1/2 was overexpressed in all samples of carcinoma in situ and in high-grade bladder cancer, with variable overexpression in low-grade bladder cancer and dysplastic lesions. The intensity and frequency of MT-1/2 staining correlated with the grade of the tumor. The MT-1 and MT-2 proteins are encoded by a family of eight genes (MT-1A, MT-1B, MT-1E, MT-1F, MT-1G, MT-IH, MT-1X, and MT-2A), and reverse transcriptase-polymerase chain reaction was used to determine which genes were expressed in the normal bladder and in bladder cancer. This analysis demonstrated that both normal and cancerous bladder tissue expressed mRNA for the MT-2A and MT-1X genes. The expression of MT-1E mRNA was variable in both normal bladder and bladder cancer specimens. Comparison of expression relative to that of beta-actin demonstrated that the level of MT-1X mRNA was overexpressed greatly in bladder cancer as compared to the level in normal bladder tissue. In contrast, the level of MT-2A mRNA was similar in both the normal and the bladder cancer specimens. The level of MT-1X expression did not vary with tumor grade. These studies suggest that the overexpression of MT-1/2 protein in bladder cancer is a result of the overexpression of the MT-1X gene.

Adult↗
PubMedDate not supplied

Analysis of bladder histology and urodynamics in female rats submitted to bladder reconstruction with rectus abdominis muscle.

INTRODUCTION: Bladder histology and measures of maximal bladder pressure and maximal bladder volume during urinary loss in female rats submitted to bladder reconstruction with a myoperitoneal flap of rectus abdominis muscle were studied. MATERIALS AND METHODS: Fifty female adult Wistar rats were studied, separated in 5 groups: Group 1 (immediate): submitted to laparotomy, cystostomy, and cystometry; Group 2 (sham): submitted to laparotomy, anterior bladder wall incision, immediate suture and cystostomy; Group 3 (cystectomy): laparotomy, partial cystectomy, cystostomy; Group 4 (cystoplasty): midline laparotomy, partial cystectomy, augmentation with rectus abdominis muscle flap peritonized, cystostomy, total cystectomy, the rats were sacrificed and an histological study of the augmented bladder performed; Group 5 (cystostomy): midline laparotomy and cystostomy. Cystometry was always performed in post-operative day 7, excepting for Group 1. Assessment was comparative maximal bladder pressure and maximal bladder volume during urinary loss among the different groups. RESULTS: In cystoplasty group, mean maximal bladder pressure during urinary loss was lower than in immediate, sham, and cystostomy groups. It was also observed that maximal bladder volume during urinary loss presented mean and median values very close in each group, and cystectomy group showed much lower values. The group submitted to cystoplasty presented mean maximal bladder volume during urinary loss higher than all groups analyzed. Histological analysis of myoperitoneal flap augmented bladders showed partial and/or total epithelization in the muscular flap interspersed region with transitional cells, squamous metaplasia region and chronic inflammatory process. CONCLUSION: The use of peritonized rectus abdominis muscle flap to perform bladder augmentation was technically viable in the animals, showing urothelial epithelization in the muscular region of the flap, and a satisfactory gain of capacity and maintenance of low bladder pressures.

Journal Article↗
PubMed2001

Clinical sensitivity of p53 mutation detection in matched bladder tumor, bladder wash, and voided urine specimens.

BACKGROUND: Mutations in the p53 tumor suppressor gene may correlate with an increased risk of recurrence and disease progression in patients with bladder carcinoma. The ability to accurately and sensitively detect p53 mutations in cytology specimens may be of benefit in the treatment of bladder carcinoma patients with superficial, minimally invasive disease. METHODS: Genomic DNA was isolated from 49 cases, each of which was comprised of matched bladder tumor tissue, bladder wash, and voided urine specimens obtained concurrently at a single institution. The genomic DNA was analyzed for mutations in the p53 tumor suppressor gene using a p53 mutation detection assay. Automated dideoxy sequencing of mutant specimens also was performed. RESULTS: Of the 49 cases, 29 (59%) showed no evidence of p53 mutations in the tumor, bladder wash, or voided urine specimens. Of the remaining 20 cases, 19 showed evidence of mutations in the tumor. Of these 19 p53 mutant bladder tumors, 16 (84%) were detected in the matched bladder wash and 16 (84%) were detected in the matched voided urine specimens. One case resulted in the detection of mutant p53 in the voided urine and the bladder wash, but not in the tumor. Analysis of the results between tumor tissue and bladder wash or tumor and voided urine showed 84.2% sensitivity, 96.8% specificity, and 91.8% accuracy. Sequence analysis of the mutant cases showed that the mutations detected in the tumor tissue were the same mutations detected in the bladder wash and the voided urine specimens. CONCLUSIONS: Both voided urine and bladder wash specimens from patients with bladder carcinoma were found to provide a high rate of clinical accuracy for the determination of the p53 gene status in patients with bladder tumors.

Aged↗
PubMed2006

Neonatal urinary bladder inflammation produces adult bladder hypersensitivity.

UNLABELLED: Inflammatory events experienced during early development may permanently alter sensory processing. Because urinary tract infections frequently occur during early development in females and painful bladder disorders have a high female prevalence, the present studies were undertaken to determine whether inflammation of the bladder in female rats could lead to altered sensory processing later in life. Female rat pups were anesthetized and treated as neonates (14th-16th days of life) or as adolescents (28th-30th days of life) with either intravesical zymosan (yeast cell wall component that produces robust inflammation), intravesical normal saline, or only with anesthesia. As adults, rats that had their bladders inflamed as neonates exhibited increased spontaneous micturition frequency and, after reinflammation of the bladder, increased cardiovascular and abdominal muscle contractile responses to urinary bladder distension when compared with controls. Similar effects were not observed in rats which did not experience inflammation of the bladder until adolescence. Evan's blue extravasation, a measure of the magnitude of inflammatory changes, was also greater in rats treated as neonates with intravesical zymosan. Thermal and mechanical hindpaw sensitivity was not altered by bladder inflammation. Altogether, this suggests that neonatal bladder inflammation increases bladder sensitivity and may be a cause of the hypersensitivity of painful bladder syndromes. PERSPECTIVE: The present study observed that bladder inflammation experienced in a neonatal rat led to accentuated responses to urinary bladder distension when tested as adults. This suggests that events experienced during development may permanently sensitize visceral sensory systems and so represent one of the causes of painful bladder disorders.

Abdominal Muscles↗
PubMed2001

Should we treat vesicoureteral reflux in patients who simultaneously undergo bladder augmentation for neuropathic bladder?

PURPOSE: If high pressure is responsible for vesicoureteral reflux in neurogenic bladders, eliminating the high pressure should resolve reflux in noncompliant bladders. Nevertheless, the need for simultaneous ureteral reimplantation and bladder augmentation remains controversial in patients with a noncompliant bladder and vesicoureteral reflux. MATERIALS AND METHODS: Bladder augmentation was performed in 8 boys and 8 girls with a noncompliant bladder and vesicoureteral reflux at a mean age of 10 years (range 2 to 17) because they had not responded satisfactorily to clean intermittent catheterization and anticholinergic therapy alone. No effort had been made to correct reflux surgically in these patients. Before bladder augmentation reflux was grade II to III in 4 ureters (3 patients) and IV to V in 18 (13). The bladder was augmented with intestine in 14 patients and with ureter in 2. Mean followup was 5.2 years (range 2.8 to 7.5). RESULTS: After bladder augmentation bladder compliance improved in all patients. Of the 18 ureters with high grade reflux 2 were used for bladder augmentation, and reflux resolved in 13, was downgraded in 1 and persisted in 2. Of the 4 ureters with low grade reflux, reflux disappeared in 2 and was down graded in 2. The rate of high and low grade vesicoureteral reflux resolution or improvement was 87.5% and 100%, respectively. At the end of the study only 3 patients had persistent reflux, which was downgraded in 2. No urinary tract infections developed in any patient and none was receiving chemoprophylaxis 6 months postoperatively. CONCLUSIONS: Our experience indicates that antireflux procedures are not routinely needed in patients with a noncompliant bladder and associated vesicoureteral reflux who undergo bladder augmentation.

Child↗
PubMed2003

Comparison of telomerase activity and matrix metalloproteinase-9 in voided urine and bladder wash samples as a useful diagnostic tool for bladder cancer.

OBJECTIVES: This study was undertaken to evaluate the diagnostic efficacy of telomerase in urine, and bladder wash and also the matrix metalloproteinase-9 (MMP-9) in urine, compared with voided urine cytology (VUC) and bladder wash cytology (BWC) for the detection of bladder cancer cells. MATERIAL AND METHODS: A total of 110 subjects provided a single preoperative voided morning urine sample for telomerase, matrix metalloproteinase-9 (MMP-9) and cytology. Bladder wash samples were obtained for telomerase and cytology. Cystoscopy was done for all patients as the reference standard for the identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of 110 cases 73 were histologically diagnosed as bladder cancer, whereas the remaining 16 had benign urological disorders. A group of 21 healthy volunteers were also enrolled in this study. RESULTS: The optimal threshold values for telomerase activity in urine, bladder wash and MMP-9 were calculated by receiver-operator characteristics (ROC) curves as 0.05, 0.088 and 0.51 (ng/ml), respectively. The levels and the positivity rates of the 2 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group, telomerase activity in urine, bladder wash, and MMP-9 were positive in 92%, 87% and 61%, respectively in bladder cancer patients with positive cytology. Moreover, these positive rates for them were significantly higher in bilharzial bladder cancer cases (88%, 89%, 69%, respectively) compared to non-bilharzial cases (50%, 62.5%, 50%). The overall sensitivity and specificity were 83% and 88.6%, 86.3% and 78.3% for telomerase activity in urine, and in bladder wash, respectively; 66.6% and 80% for MMP-9 and 58.5% and 100% for voided urine cytology and 64.4% and 100% for bladder wash cytology. Combined sensitivity of VUC with the 2 biomarkers together was higher than either combined sensitivity of VUC with one of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that urinary telomerase and MMP-9 had superior sensitivities over VUC. The combined use of markers increased the sensitivity of cytology from 58.46% to 95%. The higher sensitivities of markers in bilharzial bladder cancer than non-bilharzial type highlight their clinical utility in screening patients with urinary bilharziasis.

Adult↗
PubMed1998

Functional rat bladder regeneration through xenotransplantation of the bladder acellular matrix graft.

OBJECTIVE: To determine the decreased antigenicity of the bladder acellular matrix graft (BAMG) through xenotransplantation and to assess the in vivo and in vitro functional properties of the rat urinary bladder thus regenerated. MATERIALS AND METHODS: After partial cystectomy (> 50%), BAMGs prepared from hamster, rabbit and dog urinary bladders were grafted to male and female Sprague-Dawley rats; 10 control rats underwent partial cystectomy only. Urinary storage and voiding function were monitored in 15 animals using a specially designed 'micturition cage' and cystometry. After 4 months, organ-bath studies and histological techniques were used to evaluate bladder regeneration in vitro in the grafted animals. RESULTS: Clinically relevant antigenicity was not evident; no animal died from rejection and all bladder wall components regenerated in all BAMG xenografts. However, the degree and quality of regeneration varied. Muscularization, peak pressure, and bladder capacity were higher in the hamster BAMG-grafted animals, whereas in vitro contractility and compliance were best in the dog BAMG-regenerated bladders. All grafted bladders had significantly better capacity and compliance than the autoregenerated bladders after partial cystectomy alone. CONCLUSIONS: The present in vivo and in vitro studies show that BAMG-augmentation cystoplasty can lead to morphological and functional regeneration of the rat bladder, preserving its low-pressure reservoir function. Because BAMG-regenerated bladders show functional innervation that is similar to normal bladders, they can work in coordination with the host bladder components, thus generating adequate intravesical pressure to produce sustained voiding. The decreased antigenicity makes heterologous BAMG transplants feasible without immunosuppression.

Animals↗
PubMed2000

The current status of bladder preservation in the treatment of muscle invasive bladder cancer.

PURPOSE: Bladder preserving strategies for muscle invasive bladder cancer have evolved from single modality to multimodality treatment approaches with improved results. MATERIALS AND METHODS: We review the rationale for a multimodality approach to treat invasive bladder cancer and the results of some recent multimodality bladder sparing treatments. In addition, we compare this approach to radical cystectomy. RESULTS: Multimodality bladder sparing treatment involves combined transurethral bladder resection, external beam radiation with concurrent radiosensitizers and cisplatin based chemotherapy. With this approach overall 5-year survival is 48% to 63% and overall 5-year survival with the bladder intact is 36% to 43%. Survival with this approach is comparable to that in series of patients treated with primary radical cystectomy. The primary impetus for a multimodality bladder sparing approach is the improved quality of life associated with retaining the native bladder. However, the multimodality bladder sparing approach involves a complex treatment schedule associated with significant morbidity and mortality. Cystectomy is eventually required after attempted bladder preservation in 34% to 45% of cases and the rate of superficial recurrence is approximately 28%. CONCLUSIONS: Multimodality bladder sparing treatment is a viable option at centers with a dedicated multidisciplinary team. However, primary radical surgery remains the standard of care for invasive bladder cancer.

Antineoplastic Agents↗
PubMed1994

Simultaneous measurement of cystometry and diuresis renography during full and empty bladder in neurogenic bladder patients: a preliminary report.

In 9 patients (4 male and 5 female; mean 24.7 years old) with neurogenic bladder dysfunction, diuresis renography and water filling cystometry were simultaneously monitored with a full and empty bladder, and findings of diuresis renography with a full bladder were compared with those of diuresis renography with an empty bladder. According to O'Reilly's classification, findings of diuresis renography with a full bladder were significantly worse than those of diuresis renography with an empty bladder, regardless of cystometry patterns and bladder compliances. Although every kidney without hydronephrosis on intravenous pyelogram showed normal diuresis renography with an empty bladder, some kidneys with hydronephrosis showed an obstructive pattern even with an empty bladder. These results suggest that in some patients with neurogenic bladder dysfunction, deterioration of the upper urinary tract occurs more easily with a full than with an empty bladder, regardless of bladder pressure and bladder compliance.

Adult↗
PubMed1991

[Mechanical properties and functions of the urinary bladder. I. Stretch behavior of the bladder in vivo].

A stretch test in vivo for living material was newly developed and applied to the dog bladder. The stress-strain curve of the bladder was speed-dependent and with hysteresis. The mechanical properties of the bladder in vivo was essentially viscoelastic. The stress-strain curve of a normal living bladder was downward convex and rose very slowly. On the other hand, that of an extirpated bladder or neurogenic bladder after denervation of the pelvic nerves demonstrated a rapid elevation. A computer analysis based on a visco-elastic simulation model proposed by Glantz was carried out to evaluate changes of the curve under various conditions, which successfully demonstrated the mechanical properties of the bladder. The model proposed by Glantz explained the mechanical properties of the bladder wall. The following formula represented the stress-strain curve by the model: psi = -beta(psi + alpha)2/gamma + beta(psi + alpha) C + alpha 2 beta e beta ct/gamma psi: force, alpha & beta: elastic constant, gamma: viscous constant. According to their properties, alpha was designated as proportional stiffness and beta as exponential stiffness. The three constants, alpha, beta and gamma for the stress-strain curve obtained experimentally from the bladder under different conditions were calculated by computer analysis. Both proportional and exponential stiffness elevated in the extirpated bladder. In the denervated bladder, changes of the constants were not significant immediately after cutting the pelvic nerves. However, the proportional stiffness (alpha) elevated remarkably two weeks after the cutting. Compared with these abnormal bladders, the elastic constants in the normal living bladder were very low. The viscous constant did not change under any conditions that were examined in this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Herpes simplex virus mediated nerve growth factor expression in bladder and afferent neurons: potential treatment for diabetic bladder dysfunction.

PURPOSE: Diabetic cystopathy resulting from sensory neuropathy may potentially be treated by direct gene therapy. It has been suggested that nerve growth factor (NGF) has an ameliorative effect in preventing the death in diabetes of afferent dorsal root ganglion neurons, which control bladder function. We investigated NGF gene transfer to the bladder and bladder afferent pathways for treating diabetic cystopathy. We used replication competent and replication defective herpes simplex virus type 1 (HSV-1) vectors that express a functionally active form of the beta-subunit of mouse NGF (beta-NGF) to examine the level and duration of therapeutic gene expression after administration of the vectors. MATERIALS AND METHODS: NGF expression during acute (3 days) and latent (21 days) infections was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical testing after the injection of 1 x 106 to 1 x 108 pfu HSV-NGF expression vectors into the bladder wall of adult rats. RESULTS: HSV vectors with the strong human cytomegalovirus immediate early promoter used to drive beta-NGF gene expression exhibited increased NGF 3 days after infection in the bladder and L6 to S1 dorsal root ganglia, where bladder afferent neurons are located. ELISA analysis revealed that NGF in the bladder tissue and dorsal root ganglia was increased 7 to 9 and 2 to 4-fold, respectively, over the control vector. Increased NGF expression in L6 to S1 dorsal root ganglia neurons was also detected by immunohistochemical staining with antiNGF antibodies. Extended NGF expression was detected by ELISA 21 days after injection. Replication defective vectors containing HSV-1 latency promoter (LAP-2) driving NGF expressed NGF in the bladder and dorsal root ganglia 21 days after bladder injection. ELISA analysis confirmed an approximate 2 to 3-fold increase of NGF expression in the bladder and L6 to S1 dorsal root ganglia. CONCLUSIONS: The NGF gene may be transferred and expressed in the bladder and bladder afferent pathways using HSV vectors. To our knowledge our study represents the first demonstration of the effectiveness of gene therapy for altering neurotrophic expression in visceral sensory neurons. This technique of gene transfer may be useful for treating certain types of neurogenic bladder dysfunction, such as diabetic cystopathy, in which decreased NGF transport may be a causative factor.

Animals↗
PubMed1996

Laplace's law and the risks and prevention of bladder rupture after enterocystoplasty and bladder autoaugmentation.

The purpose of this study was to utilize a rat model of bladder augmentation to determine the effect on bladder rupture pressure and volume of bladders augmented using myomyotomy autoaugmentation, intestinal patch ileocystoplasty alone, and a combination of ileocystoplasty and detrusor-myoplasty techniques. Four groups of female rats were studied: 1) sham animals served as controls, 2) ileocystoplasty, 3) autoaugmentation using a myomyotomy technique, and 4) ileocystoplasty reinforced with a rectus muscle flap to envelop the augmented bladder (detrusormyoplasty). One month after surgery bladder rupture pressure and volume were determined by cystometry. Sham control rats manifested bladder rupture at a mean pressure of 154 +/- 43 mmHg and mean volume of 2.5 +/- 2.0 ml. Myomyotomy animals demonstrated a diminished mean rupture pressure and rupture volume (101 +/- 13 mmHg and 1.2 +/- 0.4 ml, respectively) compared to control (both P < 0.05). Ileocystoplasty animals demonstrated bladder rupture at a significantly higher volume of 4.0 +/- 1.9 ml than either myomyotomy or control animals (P < 0.05), although rupture pressure of 111 +/- 49 mmHg did not differ significantly from control values (P = 0.55). The combination of ileocystoplasty and detrusor-myoplasty yielded a statistically significant increase in rupture pressure (262 +/- 108 mmHg) than the other three groups (P < 0.05). Rupture volume in this group of animals did not differ significantly from animals with ileocystoplasty but without detrusormyoplasty (P = 0.46). Bladder autoaugmentation results in a significantly reduced rupture pressure and volume than noted in the native bladder. Although ileocystoplasty significantly increases bladder capacity, the risk of urinary extravasation is also increased with this technique. The combination of ileocystoplasty and detrusor-myoplasty affords not only an increase in bladder capacity, but also significantly increases rupture pressure and thereby decreases the risk of bladder rupture after bladder augmentation.

Animals↗
PubMed1996

Functional restoration of rat bladder after subtotal cystectomy: in vivo cystometry and in vitro study of whole bladder.

Functional restoration of the rat urinary bladder following subtotal cystectomy was studied via in vivo infusion cystometry and an in vitro whole bladder model. After the bladder had been separated from the prostate, subtotal cystectomy was achieved by ligating the bladder completely at a level just above the insertion of the ureters into the bladder. Bladder function was investigated immediately and 7, 14, and 28 days after surgery. Bladder weight was reduced to 17% that in sham-operated controls immediately after surgery, but recovered to 76% of that in controls 28 days after the operation. In vivo capacity also increased after surgery from 13% that of controls to 59% 28 days later. However, voiding pressure remained low (34% of control) 28 days later. An in vitro whole bladder study showed that the response to field stimulation decreased significantly on day 7, but had recovered considerably by day 28. The maximal response to bethanechol decreased significantly 7 days after surgery, but recovered thereafter. The response to phenylephrine increased significantly immediately after surgery, but gradually returned to the control level. An in vitro volume-pressure study showed that passive compliance of the cystectomized bladder decreased after surgery, but improved with time. The peak of the active pressure increase to field stimulation occurred at a low infusion volume immediately after surgery, but bladder capacity increased gradually until 28 days later, when the maximal active pressure was obtained. Our results suggest that restoration of the bladder following subtotal cystectomy may not derive simply from an expansion of the bladder wall. Functional alteration involving the bladder base was also observed.

Animals↗
PubMed2000

Penile reconstruction combined with bladder closure in the management of classic bladder exstrophy: illustration of technique.

OBJECTIVES: Interest has increased in combining procedures during reconstruction of bladder exstrophy in an effort to reduce the number of procedures required for reconstruction and to improve results. This study illustrates our technique of reconstruction and summarizes our current experience with the combination of epispadias repair and bladder closure during initial reconstruction or following prior failed bladder closure. METHODS: Twenty-four boys with classic bladder exstrophy underwent combined bladder closure and epispadias repair. The mean patient age was 20 months, and 18 boys had a prior failed closure. Osteotomies were performed in all patients. RESULTS: No instances of bladder prolapse or dehiscence were noted on follow-up. Urethrocutaneous fistula developed in 7 patients. Eventual bladder neck reconstruction has been performed in 11 boys (6 boys are dry day and night, 3 are dry during the day with occasional wet episodes at night, 2 have required follow-up bladder augmentation and continent diversion for persistent incontinence), and 1 boy had augmentation at the same time as bladder neck reconstruction. Twelve boys are awaiting adequate capacity for bladder neck reconstruction, and 1 is awaiting bladder augmentation and continent stoma construction. CONCLUSIONS: Epispadias closure can be safely combined with bladder closure in select patients with classic bladder exstrophy. Complication rates and cosmesis approximate that achieved with staging the two procedures. This achievement represents strict patient selection and attentive follow-up.

Abnormalities, Multiple↗