Correlation between urodynamic function and 3D cat scan anatomy in neobladders: does it exist?

INTRODUCTION: We compared the functional and anatomical differences among three different orthotopic neobladders, utilizing video urodynamics and 3D CT to determine what parameters, if any, correlate to function. MATERIALS AND METHODS: Thirty-four patients were able to participate in the evaluation of their neobladder by 3D CT and video urodynamics. Three different orthotopic neobladders were identified (12 ileal, 7 ileocecal, 15 sigmoid). Multiple measurements, observations and functional data have been obtained. Statistical analysis for this study employed a linear regression test and an odds ratio calculation (using StatSoft V. 5.1). RESULTS: In comparing three different neobladders, no significant differences were noted. Looking at the entire population, the following association was statistically significant in linear correlation: the maximal capacity and the neobladder volume; the pressure at the maximal capacity and the distance from the symphysis, the pressure at maximal flow and both the distance from the symphysis and the thickness of the neobladder. The distance from the left femoral head was directly correlated with the post void residual and inversely correlated with the maximal flow. The Odds ratio calculation revealed (with significant P < 0.05) that the further the center of the neobladder is from the right femoral head, the higher risk of incontinence. CONCLUSIONS: The study seems to show no significant anatomical or functional difference among the three different types of neobladders. A possible correlation between the position of the neobladder and urinary incontinence is suggested, recognizing further study in a larger population is required.

Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential.

The reduction or loss of plakoglobin expression in late-stage bladder cancer has been correlated with poor survival where upregulation of this catenin member by histone deacetylase inhibitors has been shown to accompany tumour suppression in an in vivo model. In this study, we directly addressed the question of the role of plakoglobin in bladder tumorigenesis following restoration, or knockdown of expression in bladder carcinoma cell lines. Restoration of plakoglobin expression resulted in a reduction in migration and suppression of tumorigenic potential in vivo. Immunocytochemistry revealed cytoplasmic and membranous localisation of plakoglobin in transfectants with < 1% of cells displaying detectable nuclear localisation of plakoglobin. siRNA knockdown experiments targeting plakoglobin, revealed enhanced migration in all cell lines in the presence and absence of E-cadherin expression. In bladder cell lines expressing low levels of plakoglobin and desmoglein-2, elevated levels of desmoglein-2 were detected following restoration of plakoglobin expression in transfected cell lines. Analysis of wnt signalling revealed no activation event associated with plakoglobin expression in the bladder model. These results show that plakoglobin acts as a tumour suppressor gene in bladder carcinoma cells and the silencing of plakoglobin gene expression in late-stage bladder cancer is a primary event in tumour progression.

Urinary incontinence after radical retropubic prostatectomy: the outcome of a surgical technique.

OBJECTIVE: To analyse the incidence of incontinence after radical retropubic prostatectomy (RRP) and the time to return of continence, using an RRP technique including a novel posterior bladder plication PATIENTS AND METHODS: We retrospectively reviewed the medical records of 200 consecutive patients who underwent RRP between September 1995 and February 1997, by one surgeon, at our institution. Patient characteristics including age, preoperative prostate-specific antigen (PSA) level and Gleason grade, were assessed. Continence was assessed before and after RRP by either a third-party patient interview or a prospective validated questionnaire. Continence was defined as not requiring the use of any sanitary pads or diapers. The continence rate was determined immediately after catheter removal, and at 3, 6, 12 and 15 months after RRP. RESULTS: The mean age of the patients was 59.4 years, the preoperative PSA level 8.5 ng/mL and the Gleason grade 6.1. The time to continence and percentage of continent patients was 63.5% immediately, 82% at 3 months, 91% at 6 months, and 98.5% at 12 months after RRP. At 15 months, 199 of 200 consecutive patients were continent (99.5%). CONCLUSION: With our technique there was an early return to continence and only a minor incontinence rate at 15 months. The cumulative effect of sequential technical manoeuvres in our RRP technique, including posterior bladder plication, is critical for continence after RRP.

Loss of heterozygosity and microsatellite instability at chromosomal sites 1Q and 10Q in morphologically distinct regions of late stage prostate lesions.

PURPOSE: We investigated the incidence of loss of heterozygosity (LOH) and microsatellite instability in sporadic prostate cancer and surrounding tissue at loci encompassing the HPC1 and PTEN genes. MATERIALS AND METHODS: Surgical specimens from 63 patients with sporadic stage T3 or T4 prostatic adenocarcinoma were analyzed for LOH and microsatellite instability. Microdissected tissue included morphologically normal foci, benign prostatic hyperplasia (BPH) and prostatic adenocarcinoma. LOH analysis was performed using 4 microsatellite markers that map in the region of the 1q24 to 25 locus of the putative prostate cancer susceptibility gene HPC1 and 4 that map in the region of the 10q23 locus of the PTEN gene. RESULTS: The incidence of LOH on 10q was consistent with that previously reported in prostatic tumors. LOH associated with the PTEN locus was recorded in morphologically normal foci, BPH and adenocarcinoma. Sequence analysis of PTEN in a limited number of lesions revealed mutations in nontumor and tumor tissue. Analysis of the DS10215 locus showed significant LOH in tumor but not in benign tissue, suggestive of a tumor suppressor gene in this region associated with prostatic neoplastic progression. In contrast, no significant LOH was observed in the same tissues at 4 loci on chromosome 1q. In this study we recorded elevated levels of microsatellite instability in benign prostatic tissue with an additional increase associated with prostatic adenocarcinoma. CONCLUSIONS: The low incidence of LOH in the region of the HPC1 locus in all prostate lesions studied suggests that this putative hereditary prostate cancer susceptibility locus does not appear to have a role in sporadic prostate cancer, at least not in the context of LOH. In contrast, analysis of the same tissues for LOH at chromosome 10q confirmed frequent alterations in this region linked to late stage prostate cancer. PTEN mutations in microdissected morphologically normal and BPH tissue showed alterations in nontumor tissue surrounding adenocarcinoma. Microsatellite instability was increased in adenocarcinomas over an elevated background recorded in surrounding tissues.

Ca 125 as a marker of tumor activity in advanced urothelial malignancy.

PURPOSE: The discovery of increased CA 125 in a patient with metastatic bladder carcinoma prompted a prospective study to screen those referred for consideration of adjuvant or palliative chemotherapy of advanced urothelial malignancy for high serum CA 125. Although CA 125 is a useful marker of ovarian cancer and, reportedly, is expressed by a few other tumors, to our knowledge no association with transitional cell malignancy of the urothelium has been previously described. MATERIALS AND METHODS: A group of 68 patients with nodal or metastatic disease was examined. A total of 60 patients had lower urinary tract tumors, 6 had renal or ureteral transitional cell carcinoma and 2 had both lesions. Of these patients 21 underwent surgery alone, 40 underwent both surgery and chemotherapy, and 5 were treated by chemotherapy only. There were 2 patients who received no treatment. Periodic serum CA 125 was obtained in cases found to be initially marker positive and with a change in clinical status. RESULTS: Of the 68 patients 48 (71%) had increased CA 125. Variation in the serum level with change in disease status was often dramatic (mean 516.3 units per dl.). Of 30 radiologically measurable disease progressions 16 were accompanied by increasing CA 125. Increases were seen in 80% of patients who had increased baseline levels. In 5 cases marker increases were seen in the absence of measurable progression but the clinical course indicated therapeutic failure. Decreasing CA 125 reflected 3 of 5 imaged regressions. Overall, a 42% decrease in median levels was seen after chemotherapy. Significantly more cases of metastatic or residual disease were marker positive. CONCLUSIONS: CA 125 appears to be a marker of disease activity in a patient subset with advanced urothelial malignancy. The clinical use of CA 125 in this population is worthy of further study.

Expression of classic cadherins type I in urothelial neoplastic progression.

Loss or reduced expression of E-cadherin has been shown to be associated with poor survival in patients with bladder cancer. In numerous cases, loss of E-cadherin expression in bladder tumors has been accompanied by continued association of catenins with the membrane, suggestive of the expression of an alternative cadherin member. In this study we examined 75 bladder tumors using immunohistochemistry for the expression of E-, P-cadherin, and alpha-, beta-, and gamma-catenins. As reported previously, loss or reduced E-cadherin expression is a frequent event in late stage bladder cancer, accompanied by less frequent alterations associated with different catenin family members. Analysis of 51 tumors for expression of E-, P-, and N-cadherin showed P-cadherin localized to the basal cell layers of normal urothelium, with retention of expression in the majority of tumors. In low-grade tumors P-cadherin was found localized to an expanded basal cell compartment, contrasting with the more extensive staining observed in late stage tumors. Membranous P-cadherin staining was often found in the absence of E-cadherin staining. N-cadherin is not expressed in normal bladder mucosa, but detection of this cadherin member was recorded in 39% (20/51) of bladder tumors. Unlike P-cadherin, membranous N-cadherin was detected in focal regions within tumors, representing novel expression in urothelial neoplastic progression. Although focal N-cadherin staining was observed in 3 noninvasive lesions, the majority of tumors expressing N-cadherin were invasive (17/20). Coexpression of E-, P-, and N-cadherin was recorded in 5 grade 2 bladder tumors. Expression of P-cadherin is maintained throughout bladder tumorigenesis, accompanied by aberrant expression of N-cadherin. Clearly, neither P- nor N-cadherin act in an invasive-suppressor mode in bladder cancer, but whether they have a primary role to play in urothelial neoplastic progression has yet to be established.

Molecular analysis of PTEN and MXI1 in primary bladder carcinoma.

Loss of heterozygosity (LOH) on 10q is associated with late-stage events in urothelial neoplastic progression. The tumor suppressor gene PTEN, which is mutated or homozygously deleted in numerous cancers, maps to a region of 10q within the reported region of minimal loss in bladder tumors. In two recent studies alterations in the PTEN gene occur at a low frequency in bladder tumors displaying 10q LOH. We have screened 35 late-stage bladder tumors for mutations in PTEN and MXI1, both genes mapping to chromosome 10q. Using single-strand conformation polymorphism analysis, we identified 6 tumors harboring mutations in PTEN and 2 additional tumors displaying homozygous deletion at this locus. No MXI1 mutations were identified within the same tumor panel. Of 16 bladder tumor cell lines analyzed, 2 showed homozygous deletion of PTEN and 3 harbored point mutations resulting in an amino acid change. Two cell lines harbored missense mutations in MXI1. We report a significantly higher frequency of PTEN alterations in bladder carcinoma (23%) than was previously recorded, with no accompanying mutations in the MXI1 gene.

Clinical features and prognostic factors associated with adrenocortical carcinoma: Lahey Clinic Medical Center experience.

Adrenocortical carcinoma is a rare tumor associated with a commonly poor prognosis. However, data on the natural history and response to therapy of patients with this malignancy have often been conflicting. Our objective of this retrospective study was to evaluate the clinical course and survival of patients with adrenocortical carcinoma and to identify relevant prognostic factors. Between 1966 and 1996, 31 patients with histologically documented adrenocortical carcinoma were observed at the Lahey Clinic Medical Center. Patient information was obtained from chart review. At the time of diagnosis, 48 per cent of patients had endocrine symptoms with compatible hormonal studies, 19 per cent had involvement of the inferior vena cava by tumor thrombus, and 32 per cent had metastatic disease. The median survival time was 17 months (range, 1-205 months) for the entire group, and the 5-year survival rate was 26 per cent. Age <54 years, absence of metastatic disease at the time of diagnosis, and completeness of surgical resection were associated with better prognosis. Evaluation of survival with the Cox proportional hazards model suggested that age <54 years, absence of metastatic disease, and nonfunctioning tumor status were independently associated with improved survival. The prognosis of patients with adrenocortical carcinoma is poor but appears more favorable in patients <54 years, with localized disease, or nonfunctioning tumor status. Complete tumor resection may be associated with improved survival.

Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.

OBJECTIVES: No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS: The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS: Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS: Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.

Vascular reconstruction in urology.

Vascular reconstructive surgery in urology includes techniques of revascularization of the renal artery for renovascular hypertension or ischemic nephropathy in situ or extracorporeal renal artery reconstruction. The indications for aortorenal bypass, extra-anatomic bypass, or simultaneous aortic substitution and renal revascularization are based on the cause, location, and extent of the vascular lesion. Techniques of bench surgery mainly depend on location of the renal artery disease and availability of autologous graft material.

Renovascular hypertension.

Approximately 5% of all hypertensive patients have renovascular hypertension, although its true incidence is unknown. The pathophysiology of renovascular hypertension has been linked to other intrarenal systems, the lipoxygenase pathway, and renin angiotensin. Many advances have been made in this field, but emphasis is now being placed on using less invasive or non-invasive tests to identify functionally significant lesions with a high degree of accuracy. The treatment modalities have shifted from aggressive surgical revascularization to less invasive management. The use of arterial stents has simplified the management of patients with renovascular hypertension, but long-term results are not yet available.

Radiolabeled monoclonal antibody indium 111-labeled CYT-356 localizes extraprostatic recurrent carcinoma after prostatectomy.

OBJECTIVES: The sites of recurrent carcinoma of the prostate were localized with radiolabeled monoclonal antibody, and these sites were correlated with the response of patients treated with pelvic radiation after prostatectomy. METHODS: Radionuclide scans were performed with indium 111-labeled CYT-356, a monoclonal antibody that binds to prostate epithelial cells, in 48 men diagnosed with recurrent carcinoma detected by prostate-specific antigen (PSA) screening after radical retropubic prostatectomy. RESULTS: In 48 patients with recurrent carcinoma detected by PSA screening following radical retropubic prostatectomy, 73% had monoclonal antibody activity beyond the prostatic fossa, and only 3 patients (6%) had activity in the prostatic fossa alone; 65% had monoclonal antibody activity in pelvic lymph nodes despite the fact that lymph node dissections were pathologically negative at the time of prostatectomy in 90% of the patients; and 23% of patients had monoclonal antibody activity in abdominal and extrapelvic retroperitoneal nodes. Of 48 patients, 13 underwent external beam radiation therapy after monoclonal antibody scans. Six patients had scans showing activity beyond the field of radiation, and radiation therapy failed in 4 of these patients. Seven patients had scans with no activity beyond the field of radiation therapy, and radiation therapy failed in only 2 of these patients. CONCLUSIONS: The scans frequently show monoclonal antibody uptake in pelvic, abdominal, and extrapelvic retroperitoneal sites beyond the region of limited obturator node dissections and may account for the understaging and subsequent failure of radical prostatectomy in some patients. The monoclonal antibody scan seems to be a good predictor of which patients will respond to radiation therapy after radical prostatectomy, but because these patients often have nodal activity beyond the radiated field, this initial response may not be curative.

111Indium-capromab pendetide in the evaluation of patients with residual or recurrent prostate cancer after radical prostatectomy. The ProstaScint Study Group.

PURPOSE: Standard diagnostic methods are limited for detecting distant metastases in patients with prostate cancer in whom the only evidence of disease after radical prostatectomy is a detectable prostate specific antigen (PSA) level. We evaluated the role of immunoscintigraphy with the radiolabeled monoclonal antibody, 111indium ((111)In)-capromab pendetide, to differentiate between local and distant recurrence in this patient population. MATERIALS AND METHODS: We enrolled 183 men who had undergone radical prostatectomy in whom PSA later increased. Gamma camera images were acquired twice after infusion of a single dose of (111)In-capromab pendetide. RESULTS: Immunoscintigraphy revealed disease in 108 of 181 patients (60%) with interpretable scans. The antibody was localized most frequently to the prostatic fossa (34% of the cases), abdominal lymph nodes (23%) and pelvic lymph nodes (22%). Of the 181 men the scan localized the antibody outside the prostatic fossa in 42%. Half of the positive localizations in the fossa were confirmed by biopsy. CONCLUSIONS: These findings suggest that immunoscintigraphy with (111)In-capromab pendetide can assist in determining the extent of disease in patients who have increasing PSA after prostatectomy.

Endoscopic injection of glutaraldehyde cross-linked collagen for efferent limb incompetence in the Indiana reservoir.

PURPOSE: We determined the clinical applicability, safety and efficacy of endoscopically injected glutaraldehyde cross-linked collagen for the treatment of efferent limb incompetence in the incontinent Indiana urinary reservoir. MATERIALS AND METHODS: Six patients were diagnosed with incompetence of the efferent limb of the Indiana reservoir by video urodynamics. Glutaraldehyde cross-linked collagen was injected through the efferent limb at the level of the ileocecal valve. Outcome was assessed by evaluation of dryness and pouchograms. RESULTS: With a mean followup time of 26 months (range 6 to 36) after the last injection 5 of the 6 patients were cured. The remaining patient, although improved, had a small capacity and subsequently underwent ileal patch augmentation. No patient failed to improve. The mean volume of collagen was 16 ml. (range, 5 to 26). Reservoir volume increased from 150 to 400 ml. CONCLUSIONS: The use of glutaraldehyde cross-linked collagen in the treatment of the incontinent Indiana reservoir is safe and effective.

Ischemic nephropathy.

Ischemic nephropathy is an independent pathway towards end-stage renal disease. Its prevalence is estimated to be significant and increasing among populations with vascular disease, hypertension, and chronic renal failure. Angiography remains the gold standard for evaluation of ischemic nephropathy; however, selection by clinical criteria and noninvasive screening with ultrasound are recommended for most patients. Surgical revascularization of ischemic kidneys can halt or reverse deterioration of renal function and is preferable to medical treatment. Direct comparison of angioplasty and stent placement with surgery is needed.