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Biomedical subjects

D Theodorescu

Publications and source records attributed to D Theodorescu.

At least 37 records · Page 2Linked to original sources

Molecular determination of perivesical and lymph node metastasis after radical cystectomy for urothelial carcinoma of the bladder.

PURPOSE: Current methods used to determine the pathological stage of the primary tumor and associated lymphatics after radical cystectomy are tedious, costly, and may lack the sensitivity afforded by molecular approaches such as reverse transcription-PCR (RT-PCR) for markers specific for urothelial tissue such as the uroplakin II (UPII) gene. Thus, we sought to evaluate an objective and sensitive molecular approach for the assessment of perivesical extension and lymph node status after radical cystectomy, based on the detection of UPII expression using RT-PCR and compare this assay to standard clinical and pathological examination. EXPERIMENTAL DESIGN: From November 1999 to September 2000, 27 patients with clinical T(a)-T(3)N(0)M(0) urothelial bladder cancer underwent radical cystectomy, 19 (70%) of which also had pelvic lymphadenectomy. At the completion of cystectomy, systematic biopsies of the external surface of the bladder specimen as well as from the largest palpable lymph node found at lymphadenectomy were obtained for molecular analysis. RT-PCR analysis for UPII mRNA was carried out on these biopsy specimens, and results were compared with data obtained from conventional pathological examination. RESULTS: Pathologically organ-confined tumors had a 42% (5 of 12) incidence of positive signals in the perivesical tissues and 17% (1 of 7) in the lymph nodes. Corresponding percentages for pT(3a)N(0) and pT(3b)-T(4)N(0) lesions were 67% (4 of 6)/25% (1 of 4) and 67% (4 of 6)/33% (2 of 6), respectively. Overall, pathologically node-negative cancers had a perivesical positivity rate of 54% (13 of 24) and a lymph node positivity rate of 25% (4 of 16). All patients with pathologically positive nodes had positive UPII signals in the lymph node sample. CONCLUSIONS: This molecular assay aimed at assessing perivesical extension and lymph node status after radical cystectomy appears to identify patients that may harbor residual disease not appreciated by conventional histology. Larger studies with 5-7-year follow-up will be required to determine the prognostic significance of such molecular information.

Aged↗

Prostate specific antigen kinetics at tumor recurrence after radical prostatectomy do not suggest a worse disease prognosis in black men.

PURPOSE: It has been shown that black men with clinically localized prostate adenocarcinoma treated with radical prostatectomy have poorer disease-free and disease specific survival than white men with similar tumors. These findings suggest that a potentially more aggressive variant of prostate cancer exists in black men. Because prostate specific antigen (PSA) velocity at tumor recurrence is a good indicator of disease aggressiveness, we determine whether there was evidence that PSA velocity at biochemical recurrence after radical prostatectomy is faster in black men. MATERIALS AND METHODS: Our retrospective data search at 2 university centers resulted in 127 white and 37 black men with clinical stage cT1 to 2 prostate adenocarcinoma who underwent radical prostatectomy between 1990 and 1994 and had evidence of biochemical recurrence (PSA greater than 0.2 ng./ml.) on followup available for analysis. No neoadjuvant or adjuvant treatments were given before or after radical prostatectomy, and all PSA relapses and subsequent treatments were recorded. PSA velocity modeling was performed in patients before any form of treatment for PSA failure. Preoperative PSA, Gleason score and pathological stage were also included in the model to assess the impact on PSA velocity after recurrence. RESULTS: Our data suggested that PSA velocity at tumor recurrence was related to preoperative PSA on a continuous scale (p = 0.063). However, in our analysis there was little evidence that race had any effect on PSA velocity at tumor recurrence in our patient cohort (p = 0.58). Likewise, little difference in PSA velocity was seen in regard to Gleason score (p = 0.89) or pathological stage (p = 0.23) in these patients. With data on 37 black men available for analysis it was likely that only large or extreme trends could be detected. Results could be used to estimate required sample sizes for assessment of less extreme trends. CONCLUSIONS: Our data on tumor growth rate at recurrence, as reflected by PSA velocity kinetics, do not support the hypothesis that prostate tumors in black men are necessarily more aggressive due to enhanced growth. Further studies comparing the molecular and biological differences between prostate cancers in black and white males are needed to clarify reasons for the apparent differences in initial presentation, as compared to that at tumor recurrence in these 2 groups.

Adenocarcinoma↗

Prostatourethral-rectal fistula after prostate brachytherapy.

BACKGROUND: Brachytherapy (BT) has seen increased utilization as a potentially curative treatment for patients with localized initial or recurrent prostate carcinoma. This modality can be delivered by palladium 103 (Pd(103)) or iodine 125 (I(125)) implant with or without external beam radiotherapy (EBRT). Prostatourethral-rectal fistula (PRF) is a serious complication of this approach, and its incidence, clinical presentation, and risk factors for occurrence have not been documented thoroughly. Thus, the authors sought to determine these factors in a large series of patients who were treated at two institutions. METHODS: Seven hundred sixty-five patients received outpatient BT using a computed tomography (CT)-guided or transrectal ultrasound (TRUS)-guided technique between July 1994 and June 1999 using either Pd(103) or I(125) implants. Of the 754 patients with follow-up, 640 patients received BT monotherapy, 69 patients received BT monotherapy as a boost after EBRT, and 45 patients received BT as salvage therapy after locally recurrent prostate carcinoma that was treated initially with BT (20 patients), EBRT (20 patients), surgery plus EBRT (3 patients), surgery and high dose rate radiotherapy (HDR) (1 patient), or EBRT plus HDR (1 patient). CT dosimetry of the TRUS-guided implants was carried out in all patients 1-7 days postprocedure. Patient follow-up and clinical status were compiled in a data base. RESULTS: Seven PRFs developed in 754 patients (1%) between 9 months and 12 months after treatment. One PRF (0.2%) occurred in patients who were treated with BT monotherapy. PRFs occurred in patients who were treated with combination therapy (2 of 69 patients; 2.9%) and in patients who underwent salvage BT (4 of 45 patients; 8.8%) patients. All six patients who developed fistulas in the context of combination BT/EBRT or salvage BT had biopsy of an anterior rectal lesion overlying the prostate noted on physical examination during routine follow-up. Gastrointestinal endoscopic evaluation alone was not associated with any PRF. Five of the seven PRFs resolved with either surgical repair (3 patients) or conservative management (2 patients). CONCLUSIONS: There is a low incidence of PRF formation after BT monotherapy. Because all patients who developed PRF did so subsequent to prior rectal biopsies, the authors currently are discouraging such practices strongly if the rectal lesion is consistent with radiation-induced effects.

Adult↗

Prostate tumor progression and prognosis. interplay of tumor and host factors.

The prognosis for prostate cancer is largely dependent on the probability of metastatic dissemination. Prognostic markers currently in use are very poor predictors of metastatic potential, and as of yet none of the battery of new molecular markers has proven greatly superior. This may be due in part to their inability to assess the degree of interaction of subpopulations of prostate cancer cells with each other and with their microenvironment. A growing body of evidence indicates that these types of interactions are a major factor in the eventual genesis of cancer cells capable of metastasis. Recent research has demonstrated that specialized components of prostate tumors may play a critical supporting role for the overall growth of the larger tumor. The multifocal nature and apparent polyclonal origins of prostate tumors suggest that carcinogenesis and tumor progression are promoted by global influences or "field effects." It appears that these effects extend beyond the proliferating epithelial component to the tissue stroma. Prostate cancer cells and stromal cells seem to act in concert to modify the microenvironment, leading to metastasis. An understanding of this synergy may provide a new class of prognostic markers which more accurately measure the complex set of interactions that determine tumor behavior.

Journal Article↗

Surgical and postoperative factors affecting length of hospital stay after radical prostatectomy.

BACKGROUND: Radical prostatectomy continues to comprise the mainstay of therapy for localized prostate carcinoma. However, caring for radical prostatectomy patients accounts for approximately half of the $1.7 billion annual cost of prostate carcinoma treatment. Length of stay (LOS) after surgery appears to be one of the main components of this cost. The first step in reducing cost is to identify those variables associated with LOS. Radical prostatectomy can be performed using two very different surgical techniques and with each technique different costs are incurred. The objective of the current study was to identify factors associated with LOS as a function of surgical approach. To reduce potential biases due to patient requests for longer hospitalization or physician preferences in that regard, secondary objectives were to identify factors associated with time to fluid intake (TTF) and time to consume solid foods (TTS). METHODS: An institutional-based, retrospective chart review of 313 men with clinically localized prostate carcinoma who underwent either a perineal (RPP) or retropubic (RRP) prostatectomy at a single university center from March 1988 to October 1996 was undertaken. Information regarding LOS was available for 311 patients. Linear regression models were used to assess the association between covariables and LOS. Poisson regression models for count data were used to assess associations between covariables and the secondary endpoints of TTF and TTS. Covariables included: preoperative (age, race, prostate specific antigen, Gleason score, clinical stage, lymph node resection, comorbidity, and admission time), intraoperative (surgical approach, surgeon, operative time, estimated blood loss, transfusion requirement, anesthetic approach, and American Society of Anesthesiologists score), and postoperative (pain management complications and transfusions) parameters. RESULTS: The median LOS was 4 days (range, 1-19 days) for RPP and 5 days (range, 3-16 days) for RRP approaches. The final model included six main effects and three interaction terms. Overall, LOS decreased over time with LOS decreasing at a faster rate in patients who underwent RPP. In general, patients who underwent RRP had an increased LOS compared with patients who underwent RPP. Complications from surgery and age increased the LOS for all patients; however, the increase was greater in patients who underwent RPP. In addition, the use of intraoperative epidural anesthesia and the increased use of postoperative narcotics were associated with increased LOS for patients undergoing both surgical approaches. TTF and TTS were significantly longer for patients who underwent the retropubic approach compared with those patients who underwent the perineal approach. After adjustment for surgical approach no other covariables were found to be associated with TTF. After adjustment for surgical approach, the occurrence of complications was found to be associated with TTS, indicating that patients who experienced complications took longer before they could tolerate solid foods. CONCLUSIONS: In view of the importance of clinical care pathways in reducing medical expenditures from radical prostatectomy, the results of the current study may contribute to the further refining of these pathways by highlighting the differences and similarities among the variables affecting LOS as a function of surgical approach.

Adult↗

Focal adhesion kinase, Rap1, and transcriptional induction of vascular endothelial growth factor.

BACKGROUND: Signals from a cell's environment are sensed by receptors, which activate pathways that, in turn, transmit the signals to the nucleus, informing decisions on growth, angiogenesis, and other cell functions. Transcription of vascular endothelial growth factor (VEGF), a potent angiogenic factor, can be induced by cell-cell contact. In the current work, we sought to determine if this induction is dependent on transformation of cells to a malignant phenotype and subsequently to determine which signaling molecules mediate activation of VEGF transcription. METHODS: Normal and transformed prostate epithelial cell lines were examined at various cell densities to simulate the effect of increased cell contact on expression of VEGF messenger RNA. Transformed cells were also cotransfected with a VEGF promoter-reporter construct and with constructs that express dominant negative or activated versions of signal transduction proteins hypothesized to be involved in the cell-cell contact process, and reporter activity was assessed at various cell densities. All P values are two-sided. RESULTS: Direct cell-cell contact, but not extracellular matrix components, resulted in transcriptional activation of a VEGF promoter-reporter construct in malignant (P<.0001) but not in nonmalignant (P =.37) prostate cells. This process was mediated via a mitogen-activated protein kinase (MAPK); it required the activity of focal adhesion kinase (FAK), Rap1, and Raf and was Ras independent. In addition, transcriptional activation of a Ras-sensitive Elk-1 chimeric reporter by cell-cell contact suggests that Rap1 is a key factor in regulating the specificity of convergent MAPK-signaling pathways arising from different upstream extracellular stimuli. CONCLUSIONS: Cell contact induction of VEGF transcription via FAK and Rap1 provides a novel Ras-independent, but transformation-dependent, mechanism for stimulus-specific regulation of tumor VEGF expression via MAPK.

Blotting, Northern↗

Genetic and phenotypic changes associated with the acquisition of tumorigenicity in human bladder cancer.

There has been a general lack of human paired cell lines that both reproduce the in vivo spectrum of tumor progression of bladder cancer and have some of the genetic changes associated with progression in human tumor tissue. T24, a cell line established from an invasive human transitional cell carcinoma (TCC) of the bladder, has been used extensively in bladder cancer research. However, a significant limitation of this cell line is its lack of tumorigenicity when injected into immunocompromised mice. This characteristic was used to our advantage as we sought to characterize T24T, a highly tumorigenic variant that could then be used to elucidate the genes responsible for human bladder tumor progression. In culture, T24T has a faster doubling time, reaches a higher cell density in monolayer culture, and is more motile than T24 at higher cell densities. T24T is able to form colonies in soft agar, whereas T24 is not, and expresses HRAS, a gene associated with increased aggressiveness in human TCC, at higher levels than T24. Most importantly, T24T forms solid tumors when injected subcutaneously in SCID mice both with and without Matrigel (Sigma, St. Louis, MO), whereas T24 does not. Cytogenetically, the 2 cell lines contain at least 5 shared structural anomalies, as determined by detailed karyotyping. Interestingly, T24T has acquired 4 new structural changes, 3 of which [add(10)(p12), i(10)(q10), -15] have been observed in loss of heterozygosity (LOH) studies of tumor progression in human TCC. It appears that the T24/T24T model may be an excellent tool for the study of human TCC progression because of its relationship with known karyotypic changes associated with human bladder cancer progression. We are currently taking advantage of these paired cell lines to identify genes involved in human TCC progression. Genes Chromosomes Cancer 27:252-263, 2000.

Animals↗

Quality-of-life comparison of radical prostatectomy and interstitial brachytherapy in the treatment of clinically localized prostate cancer.

OBJECTIVES: Interstitial brachytherapy (BT) is increasingly utilized as a curative treatment for localized prostate cancer because it is perceived as less morbid than surgical alternatives. However, to date no studies have directly compared the quality of life and symptoms of patients with localized prostate cancer treated with curative intent by radical prostatectomy with those treated by either BT alone or BT combined with external beam radiation. METHODS: On June 1, 1998, 242 men with clinically localized Stage T1c to T3 adenocarcinoma of the prostate, treated at our institution with curative intent from January 1, 1997 to June 1, 1998, were mailed a questionnaire. Cross-sectional analysis of returned questionnaires was carried out. Patients were treated with either radical prostatectomy (RP), palladium-103 (Pd(103)) brachytherapy (115 Gy) monotherapy (BTM), or Pd(103) combined brachytherapy (90 Gy) and external beam radiation (40 to 45 Gy) (BTC). The primary outcome measures were the Functional Assessment of Cancer Therapy scale (FACT-G), American Urological Association (AUA)/international prostate symptom score (IPSS), "Urinary Function Questionnaire for Men after Radical Prostatectomy," and Brief Sexual Function Inventory. RESULTS: Data from 138 patients were included in the analysis; 27 had RP, 70 had BTM, and 41 had BTC. Total FACT-G and personal well-being scores were significantly lower in the BTC group. Brachytherapy monotherapy and RP had similar scores on the FACT-G, with surgical patients having the lowest IPSS scores. Correlations were noted between total FACT-G and urinary symptom score, degree of sexual function, frequency of diarrhea, and frequency of hot flashes. Bothersomeness of urinary function correlated with the degree of urinary control. The radical prostatectomy and BTM groups had improvement in quality of life, voiding, diarrhea, and sexual function with time, whereas the BTC group experienced a decline. CONCLUSIONS: Patients treated with BTC had an overall lower quality of life compared with those treated by RP and BTM, and RP patients reported fewer irritative or obstructive voiding complaints. Although the consistency and magnitude of these trends require further study, our data suggest that RP remains a well-tolerated and accepted option.

Adenocarcinoma↗

The relationship of BRMS1 and RhoGDI2 gene expression to metastatic potential in lineage related human bladder cancer cell lines.

We have recently characterized a human bladder cancer cell line T24 and a more aggressive lineage related variant of it, T24T. To gain further insights, we have studied their metastatic ability in an in vivo model system. Results show that T24 forms significantly fewer [4/12 (1/11) mice had metastases with 1-2 lesions/mouse] metastasis in SCID/bg mice than T24T [14/14 (6/6) mice had metastases with a mean of 24-28 lesions/mouse]. To begin exploring the mechanisms underlying this difference, we evaluated the mRNA and protein expression levels of metastasis-suppressor genes, known to be important in the progression of other cancers, in our model of bladder cancer progression. A higher mRNA expression of BRMS1, a metastasis suppressor in breast cancer, was observed in T24 cells. In addition, RhoGDI2 mRNA expression was only observed in T24 when compared to T24T, suggesting that Rho activation might play a significant role in the metastatic cascade. However, a basal level mRNA expression of KISS1, described as metastasis suppressor in melanoma and breast, was observed in both the lines and had slightly higher expression in T24T. No difference of Nm23-H1, KAI1, MKK4/SEK1 and E-Cadherin protein levels were noted between these two lines. In summary, it appears that the T24/T24T paired cell lines constitute a useful model for the study of human bladder cancer metastasis that will allow both the discovery and mechanistic evaluation of genes potentially involved in this process.

Animals↗

A prospective pilot evaluation of urinary and immunohistochemical markers as predictors of clinical stage of urothelial carcinoma of the bladder.

OBJECTIVE: To determine, in patients newly diagnosed with bladder cancer, whether p53, epidermal growth factor receptor (EGFR), microvessel density (MVD), urinary bladder tumour antigen (BTA TRAKtrade mark, Bion Diagnostic Sciences, Redmond, WA) and cytology were predictive of clinical stage, evaluated as a function of the clinical stage obtained at transurethral resection of the bladder tumour with and without the addition of clinical grade, a known strong predictor of clinical stage. PATIENTS AND METHODS: Between December 1997 and September 1998, 22 men and seven women with a cystoscopic diagnosis of urothelial bladder carcinoma were prospectively enrolled in the study. Urine was collected for cytological and BTA TRAK evaluation before transurethral resection. Tumour grade and clinical stage were obtained from the transurethral resection specimen. MVD was evaluated by computerized calculations of 'optimal MVD' (OMVD) and 'area-weighted MVD' (AWMVD) while p53 and EGFR information was obtained by manual immunohistochemical techniques; 21 patients had sufficient tissue for all immunohistochemical assessments and comprised the study group. Univariate and multivariate comparisons were carried out to determine the contribution of each variable to the prediction of clinical stage. RESULTS: Although there was a trend, cytological analysis and p53 and MVD immunoreactivity did not significantly correlate with clinical stage, while tumour grade, BTA TRAK and EGFR immunoreactivity did. In a univariate analysis, tumour grade and BTA TRAK were related to clinical stage. In a multivariate analysis, grade was the single best predictor of clinical stage. This analysis also showed that the addition of BTA TRAK and MVD information to grade incrementally improved the predictive ability of grade. CONCLUSIONS: This pilot study suggests that BTA TRAK and MVD contribute incremental information to tumour grade in predicting the clinical stage of urothelial carcinomas of the bladder; grade remains the most important predictor. These results suggest that further work with BTA TRAK and MVD in more patients and on biopsy material obtained during clinic cystoscopy is warranted for the future development of less invasive methods of identifying patients with invasive bladder cancer.

Aged↗

Transmembrane motility assay of transiently transfected cells by fluorescent cell counting and luciferase measurement.

Current in vitro assays used in assessing tumor motility could be improved by the development of a simple technique that would facilitate studies of the impact of specific genes on pharmacologically altered chemotaxis. We developed a technique that improves on the classic transwell assay by using fluorescence and luminescence to assess chemotaxis. In this transient transfection system, co-transfection of a reporter construct and a gene with an unknown impact on motility are coupled with biochemical assays to quantitate the number of cells that have received a transferred gene, which subsequently crosses the membrane. This assay was found to be less variable than the conventional transwell chamber and is easily adaptable to studies of cell motility or cell invasion. We also demonstrate that this assay can detect the effect of both genetic and pharmacological inhibition of motility alone and in combination. It therefore has the potential to reveal additive or synergistic effects.

Cell Count↗

Molecular cloning and characterization of a lysophosphatidic acid receptor, Edg-7, expressed in prostate.

Two G protein-coupled receptors (Edg-2) and (Edg-4) for the lysolipid phosphoric acid mediator lysophosphatidic acid have been described by molecular cloning. However, the calcium-mobilizing receptor Edg-4 is not expressed in some cell lines that exhibit robust calcium responses to this ligand, thus predicting the existence of additional receptor subtypes. We report here on the characterization of a third human lysophosphatidic acid receptor subtype, Edg-7, which mediates lysophosphatidic acid-evoked calcium mobilization. In a rat hepatoma Rh7777 cell line that lacks endogenous responses to lysophosphatidic acid, this lipid mediator, but not others, evokes calcium transients when the cells have been transfected with Edg-7 or Edg-4 DNAs. Furthermore, frog oocytes exhibit a calcium-mediated chloride conductance in response to mammalian-selective lysophosphatidic acid mimetics after injection of Edg-7 mRNA. Edg-7-expressing Rh7777 cells do not show inhibition of forskolin-driven rises in cAMP in response to lysophosphatidic acid. However, membranes from HEK293T cells cotransfected with Edg-7 and G(i2)alpha protein DNAs show lysophosphatidic acid dose-dependent increases in [gamma-(35)S]GTP binding with an EC(50) value of 195 nM. When we used this assay to compare various synthetic LPA analogs at Edg-2, Edg-4, and Edg-7 receptors, we found that ethanolamine-based compounds, which are full LPA mimetics at Edg-2 and Edg-4, exhibit little activity at the Edg-7 receptor. Edg-7 RNA was detected in extracts of several rat and human tissues including prostate. Together, our data indicate that Edg-7 is a third lysophosphatidic acid receptor that couples predominantly to G(q/11)alpha proteins.

Amino Acid Sequence↗

Alternative medicine use in patients with localized prostate carcinoma treated with curative intent.

BACKGROUND: Alternative medicine therapies are estimated to be used by 7-64% of cancer patients but up to 72% do not inform their physician. To the authors' knowledge little useful information is available regarding the prevalence of alternative medicine use by patients with prostate carcinoma. Thus, the authors attempted to evaluate the prevalence of alternative medicine use by prostate carcinoma patients treated with curative intent by either radical prostatectomy, brachytherapy alone, or a combination of brachytherapy and external radiation therapy. METHODS: Between January 1997 and May 1998, 234 men with clinically localized prostate carcinoma underwent radical prostatectomy (54 patients) or brachytherapy (180 patients) with (74 patients) or without (106 patients) external beam radiation therapy. In July 1998 a questionnaire was mailed to all patients comprised of multiple questions regarding alternative medicine use to which 190 patients (81%) responded. The overall prevalence and types of alternative medicine therapies used were assessed and the relation between age at procedure, pretreatment prostate specific antigen level, clinical stage, pretreatment Gleason score, and type of treatment with the use of alternative medicine therapies was evaluated using univariate and multivariate analysis. RESULTS: The prevalence of alternative medicine use by prostate carcinoma patients responding to the survey was 43% (81 of 190 patients). No significant differences in alternative medicine use were observed between the patients who received brachytherapy alone (38%), those who underwent radical prostatectomy (40%), and those treated with combined brachytherapy and external beam radiation therapy (51%). Vitamins, prayer or other religious practices, and herbal medicines were the most commonly used therapies in these patients. Higher pretreatment Gleason scores were associated with a greater use of alternative medicine therapies on both multivariate and univariate analyses. Finally, using multivariate analysis, younger prostate carcinoma patients were more likely to use alternative medicine therapies than older patients. CONCLUSIONS: Alternative medicine use is very prevalent among patients treated for localized prostate carcinoma. Because some of these treatments may have a potential biologic impact on tumor behavior and, consequently, on definitive or surrogate therapeutic endpoints, patients should be questioned carefully regarding alternative medicine use during routine tumor follow-up.

Aged↗

Prospective evaluation of the effect of ionizing radiation on the bladder tumor-associated (BTA) urine test.

PURPOSE: To prospectively evaluate the effect of ionizing radiation on the results of the bladder tumor-associated antigen (BTA) test. By examining this question, we sought to determine its potential use as a monitoring test for the detection of recurrent transitional carcinoma of the bladder in patients who have received prior radiotherapy for bladder preservation. MATERIALS AND METHODS: Between February 1996 and April 1997, 18 patients with nonbladder pelvic malignancies and no history of bladder cancer, received irradiation to the bladder. These patients were prospectively evaluated using the BTA test at the end of the external-beam radiation (EBRT) and at 3-month follow-up intervals. Urine cytology was analyzed in 16 of the 18 patients at the end of EBRT. A median of 3 separate measurements were made (range 1-6) on each patient. The median dose of EBRT was 50.4 Gy (range 30-68 Gy). Seven patients underwent brachytherapy as part of their treatment course. BTA results and time intervals were recorded and analyzed using univariate and Kaplan-Meyer methodologies. RESULTS: A total of 10 (56%) of the 18 patients had a positive BTA test at some time following completion of EBRT. Of the 10 positive tests, 9 returned to negative in a median of 42 weeks from completion of EBRT. Treatment with chemotherapy, brachytherapy, calculated bladder dose, and total external beam dose did not significantly influence either the number of positive tests or the time to resolution of the positive test in this small group of patients. All screened urine samples were negative for malignant cells and 11 (69%) of 16 showed changes consistent with ionizing radiation. CONCLUSION: Our findings support the hypothesis that ionizing radiation can cause transient positive results in the BTA test, but that these normalize with time. Although it requires further testing, it seems that the BTA test may be useful in the detection of recurrence in patients with bladder cancer who have been treated with definitive irradiation for bladder preservation.

Antigens, Neoplasm↗

Urinary function after radical prostatectomy: a comparison of the retropubic and perineal approaches.

OBJECTIVES: Urinary continence is one of the most significant outcomes after radical surgery for prostate cancer. Although both retropubic and perineal approaches to radical prostatectomy are commonly used, they have not yet been compared with respect to urinary continence and voiding function in a single-institution study using a validated patient-administered instrument. This study had two primary objectives: first, to assess whether differences exist between these two procedures with respect to the overall prevalence and resolution of postoperative urinary incontinence, and second, to determine the impact of the urinary incontinence on patient lifestyle in this patient population. METHODS: A written instrument composed of the Urinary Function Questionnaire for Men after Radical Prostatectomy, the American Urological Association (AUA) Symptom Score, and seven items querying urinary retention and urinary function bother were mailed in February 1996 to 209 men who underwent radical prostatectomy by either the perineal (43%) or retropubic (57%) approach between January 1990 and December 1995. Descriptive statistics were used to summarize the prevalence of urinary incontinence and urinary function bother as reported from this cross-sectional questionnaire. Logistic regression models were used to assess the association between reported urinary incontinence and surgical approach, AUA symptom scores, and treatment of incontinence after adjusting for possible confounders (eg, the time between surgery and questionnaire, and patient age). RESULTS: One hundred sixty-seven men (80%) responded to the questionnaire. The median age of the participants at questionnaire administration was 68 years (range 43 to 80). Overall, 57% (95% confidence interval [CI] 50% to 63%) of the responders reported complete urinary continence at the time of the questionnaire, with a median time between surgery and the questionnaire of 2.7 years (range 0.3 to 5.4). When continence was defined as either complete dryness or minimal urinary leakage, 75% (95% CI 69% to 81%) of the responders reported being continent. In men who responded to the questionnaire within 2 years of surgery, the probability of experiencing complete urinary continence was similar between the two surgical approaches. In men who responded to the questionnaire more than 2 years after surgery, patients who had undergone perineal prostatectomy were more likely to report complete continence than those who underwent retropubic surgery. However, this observed difference disappears when continence was defined as either complete dryness or minimal urinary leakage. The major impact of urinary incontinence on patient lifestyle was observed in patients with more than just minimal leakage. CONCLUSIONS: Radical perineal and radical retropubic prostatectomy have similar outcomes when patients with minor degrees of incontinence are grouped together with continent patients. Since the impact of a minimal degree of urinary incontinence on the patient's lifestyle after radical prostatectomy seems to be minor, currently we do not believe that postoperative continence status is a major factor in choosing one procedure over the other.

Adult↗