Patient tolerability during office cystoscopy and bladder tumor cauterization: a multivariate analysis of risk factors.

OBJECTIVE: Cystoscopy and cauterization performed in the operating room is expensive and exposes patients to anesthesia risks. Patient tolerability during office cystoscopy and cauterization is critical to the office management of bladder cancer (BC) and other urologic diseases. We evaluated the risk factors for pain of flexible cystoscopy in the office-setting with emphasis on a sub-group of BC patients who underwent cauterization. MATERIALS AND METHODS: Retrospective analyses of 110 anonymous patient surveys completed after cystoscopy and/or cauterization. Survey information included age, gender, indication for cystoscopy, number of prior cystoscopies, number of prior office-based cauterizations, anxiety prior/during cystoscopy, and pain during cystoscopy and/or cauterization. Univariate/multivariate and linear-regression analyses were performed to evaluate the association of pain with clinical parameters. RESULTS: Average pain during cystoscopy (1.75 ±â€¯1.331) was not significantly different when cauterization was also performed (2.37 ±â€¯2.214) (p < 0.001) (p = 0.2840). Patients in the lower age group (<66 years) indicated higher anxiety levels (p = 0.0005), more pain at cystoscopy (P = 0.004) and cauterization (p < 0.001). Although the patients' overall anxiety level was low (1-3/10), it was associated with some pain during cystoscopy (p = 0.0005) and cauterization (p < 0.000). In multivariate analysis, anxiety was the only independent predictor of pain during cystoscopy (p = 0.03, OR: 6.52,95% CI: 1.2-35.6) and cauterization (p = 0.0012, OR: 3.4, 95%CI: 1.6-7.0). In BC patients, pain scores during cystoscopy and cauterization were not significantly different (p = 0.4772) but associated with anxiety. CONCLUSION: Office-based cystoscopy and cauterization are tolerable with minimal pain. Higher pain levels during cystoscopy were associated with procedure anxiety, and pain during cauterization was associated with procedure anxiety and younger age. Younger and more anxious patients may need more counseling before cystoscopy.

Surveillance and office management of low-grade Ta bladder tumors.

OBJECTIVE: Patients with low-grade (LG), grade 1-2, Ta bladder cancer (BC) will frequently have a "recurrence". However, they rarely progress in stage. Although current guidelines mention surveillance and office management for these new or recurrent tumors, transurethral resection (TURBT) is the most common treatment. The purpose of this study is to determine if surveillance and/or office cautery is safe. MATERIALS AND METHODS: This study was conducted as a retrospective case series analysis of 45 patients who had recurrent LG Ta appearing bladder cancer (BC) and were managed primarily with surveillance and/or office cautery. Patients with carcinoma in-situ were excluded. The primary outcome was stage progression. RESULTS: Median follow up was 62 months. 41 (91%) patients did not progress in stage. Three patients recurred with HG T1 BC; one is receiving systemic immunotherapy. One patient developed HG T2 BC and was treated with a bladder preservation protocol. 40 (89%) patients underwent office cauterization. Eleven received BCG and 26 received post-cautery intravesical chemotherapy. Five (11%) patients developed HG BC during follow up. No patients died. None of the 17 (38%) Hispanic patients had progression. CONCLUSIONS: Active surveillance and/or office cautery for patients with small recurrent LG Ta bladder tumors is safe, reduces cost and improves quality of life by avoiding TURBTs.

Presentation and outcome following radical cystectomy in Hispanics with bladder cancer.

OBJECTIVE: Significant racial and ethnic differences in the epidemiology of bladder cancer (BC) exist. Studies have shown African Americans to have lower incidence of bladder cancer than Caucasians, but higher incidence of invasive BC. Hispanics are the largest minority group in the United States. However, no reported studies on bladder cancer among Hispanics are available to date. As our center is in a unique position to study BC in Hispanic patients we were prompted to assess presentation and outcome of patients undergoing radical cystectomy (RC) for BC. MATERIALS AND METHODS: Between January 1992 and May 2006, 448 RC were performed. All relevant data were collected and entered into a database. Patients were categorized by ethnicity as Hispanic and non-Hispanic White. African-American and other minority groups were excluded because of the small number. Comparative analysis of Hispanic and non-Hispanic White patients was performed. RESULTS: 67 (17%) patients were Hispanic. Mean follow-up period was 41 (SD +/- 40) months. Clinical and pathological data between these two groups were compared. Pre-cystectomy T stage was not significantly different between both groups. However, after RC incidence of < or = T1 disease in Hispanics was lower (22%) than Caucasians (37%). This difference, statistically significant (P = 0.024) indicates that Hispanics who undergo RC present with higher stage disease. Kaplan-Meier log rank test indicated a difference in disease free survival and disease specific survival between the two groups but however it did not reach statistical significance (Log Rank P = 0.082, P = 0.063). No significant difference in overall survival was observed (P = 0.465). CONCLUSIONS: Hispanic patients managed with RC for bladder carcinoma present with higher stage disease.

Hemospermia following transrectal ultrasound-guided prostate biopsy: a prospective study.

Hemospermia is known to be associated with transrectal ultrasound-guided prostate biopsy (TRUS-PB). The true incidence of hemospermia, its duration and implications are not well established. We performed a prospective observational study involving patients undergoing TRUS-PB for suspected prostate cancer at our institution. Sixty-three eligible men were included in the study. Most men (84%) undergoing TRUS-PB, who were able to ejaculate, experienced hemospermia, which was associated with some degree of anxiety. The mean duration of hemospermia was 3.5 (+/-1.7) weeks. The number of ejaculations before the complete resolution of hemospermia was 8 (+/-6.7). None of the clinical and pathological factors was a significant predictor of the duration of hemospermia. Patients should be adequately counseled before TRUS-PB to avoid undue anxiety and alterations in sexual activity.

Morphological effects of mitomycin C administered intravesically to normal mice and mice with N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide-induce bladder neoplasms.

The intravesical administration of mitomycin C to normal and N-[4-(5-nitro-2-furyl)-2-thiozolyl]formamide-induced bladder tumor-carrying mice at initial concentrations of 2 and 5 mg/ml for 2 hr resulted in marked morphological effects including cytoplasmic and nuclear abnormalities and disruption of surface architecture. Tumors cells and normal urothelial cells were sensitive to the effects of mitomycin C. These effects were limited to epithelial cells.

Tumor-associated hyaluronic acid: a new sensitive and specific urine marker for bladder cancer.

Hyaluronic acid (HA), a glycosaminoglycan, is known to promote tumor cell adhesion and migration, and its small fragments stimulate angiogenesis. We compared levels of HA in the urine of normal individuals and patients with bladder cancer or other genitourinary conditions, using a sensitive ELISA-like assay. Among the 144 specimens analyzed, the urinary HA levels of bladder cancer patients with G1 (255 +/- 41.7 ng/mg), G2 (291.8 +/- 68.3 ng/mg) and G3 (428.4 +/- 67 ng/mg) tumors are 4-9-fold elevated as compared to those of normal individuals (44.7 +/- 6.2 ng/mg) and patients with other genitourinary conditions (69.5 +/- 6.8 ng/mg; P < 0.001). Urinary HA measurement by the ELISA-like assay shows a sensitivity of 91.9% and specificity of 92.8% to detect bladder cancer. Thus, urinary HA measurement is a simple, noninvasive yet highly sensitive and specific method for bladder cancer detection. The increase in urinary HA concentration is a direct correlate of the elevated tumor-associated HA levels, because the HA levels are also elevated (3-5-fold) in bladder tumor tissues (P < 0.001). The profiles of urinary HA species of normal individuals and bladder cancer patients are different. Although only the intermediate-size HA species are found in the urine of normal and low-grade bladder tumor patients, the urine of high-grade bladder cancer patients contains both the high molecular mass and the small angiogenic HA fragments. These urinary HA fragments stimulate a mitogenic response (2.4-fold) in primary human microvessel endothelial cells, suggesting that the small HA fragments may regulate tumor angiogenesis by modulating endothelial cell functions.

Time- and concentration-dependent inhibition of the clonogenic growth of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced murine bladder tumor cell lines by cis-diamminedichloroplatinum(II).

The influence of the concentration and time of exposure to cis-diamminedichloroplatinum on the inhibition of the clonogenic growth of three N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide mouse bladder tumor cell lines was evaluated in a tumor colony assay. Drug testing was performed in the murine model, and tumor cells were removed from the animals for in vitro testing. Murine drug testing revealed marked cis-diamminedichloroplatinum sensitivity of all three mouse bladder tumor lines. One-hr incubation in cis-diamminedichloroplatinum was an adequate time of drug exposure to produce in vitro colony survival curves predictive of in vivo sensitivity to the drug. Furthermore, it was found that 6- to greater than 24-hr exposure to the drug was required to produce colony survival curves in the tumor colony assay predictive of tumor sensitivity. High drug concentrations using 1-hr drug incubation or continuous incubation in drug both produced colony survival curves predictive of tumor sensitivity. Both methods, however, would require higher products of the drug concentration multiplied by time curves than could theoretically be clinically achievable in the murine model. Until pharmacokinetic data on cis-diamminedichloroplatinum are available in this murine model, higher drug sensitivity boundaries than are presently being used for other chemotherapeutic agents will have to be utilized when testing these mouse bladder tumor cell lines for their sensitivity to cis-diamminedichloroplatinum in a tumor colony assay.

Total, dialyzable, and nondialyzable postabsorptive hydroxyproline. Values in patients with cancer.

The postabsorptive urinary total (T), dialyzable (D), and nondialyzable (ND) hydroxyproline (HYPRO) tests were evaluated to determine whether the patterns of excretion varied according to the predominance of osteoblastic v osteolytic bone involvement in 58 patients with neoplastic disease. In patients with osteolytic lesions from multiple myeloma, elevated T and D levels with normal ND HYPRO values were observed, along with elevated D/ND ratios. In prostate cancer, the T, D, and ND values were all elevated and the D/ND ratio was normal. Patients with Hodgkin's disease had elevated T, D, and ND HYPRO levels, and the D/ND ratio was in the range of patients with prostate cancer. The data suggest that these collagen markers may be useful in the long-term evaluation of these neoplasms in patients.

Secretion of bladder tumor-derived hyaluronidase activity by invasive bladder tumor cells.

Hyaluronic acid (HA), a glycosaminoglycan, promotes tumor metastasis and its small fragments are angiogenic. These small fragments are generated by degradation of HA by hyaluronidase (HAase). We measured urinary HAase levels of 196 individuals using an ELISA-like assay. The urinary HAase levels (31.1 +/- 3.7 mU/mg) of intermediate (G2) to high-grade (G3) bladder cancer patients are five- to seven-fold elevated as compared to those of normal individuals and patients with other genitourinary conditions or low-grade (G1) bladder cancer. The increase in urinary HAase levels is due to the secretion of a tumor-derived HAase which is elevated eight-fold in G2/G3 tumor tissues. The HAase in bladder tumor tissues is secreted by tumor epithelial cells and is associated with the invasive/metastatic potential of the tumor cells.

Sampling of radical prostatectomy specimens. How much is adequate?

Prostate glands from 52 patients with clinical stage B carcinoma were examined using two sampling techniques. After fixation and conization of the apical portions, each gland was serially sectioned with sections mounted whole on oversized glass slides and examined for pathologic features of prognostic importance. A second examination was subsequently conducted on the same tissue using only alternate sections. No differences in tumor type, grade, Gleason score, multiplicity, or capsular penetration were detected in 75% of cases. The discrepancies that did occur were most often minor variations in multiplicity and Gleason score. Of the 20 glands with capsular penetration observed with the serial sectioning method, 17 (85%) were detected using alternate sectioning. The surgical margin was involved in two of the three invasive foci that would have been missed. Although the topography is better displayed, the authors' examinations indicated no significant advantage to whole mount sections compared with sections mounted on standard-sized glass slides. Considering the most effective use of resources, as well as the current modalities available for patient monitoring, the results support the use of an alternate sectioning method for pathologic examination of specimens removed for clinically localized prostate cancer.

Osteogenic differentiation associated with x-ray therapy for adenocarcinoma of the prostate gland.

A case of osteogenic differentiation in a prostate gland associated with high-dose x-irradiation for adenocarcinoma is reported. Heterologous cancerous elements in adults are extremely unusual in the prostate and their occurrence after treatment has rarely been documented. The relationship of this lesion to the primary glandular neoplasm is discussed.

Managing superficial bladder cancer: an overview.

More than 90 percent of bladder cancers are transitional cell carcinoma (TCC). Superficial TCC is defined as a transitional cell tumor that is confined to the mucosa (Stages Ta or carcinoma in situ) or that has invaded the lamina propria (Stage T1). When treating patients with superficial bladder cancer, urologists are faced with a number of important tasks. First, the initial tumor or tumors must be removed. Second, the other parts of the urothelium must be assessed for the presence of premalignant or malignant abnormalities. Third, the depth and extent of invasion (i.e., tumor stage) must be determined. Fourth, the clinician must decide whether additional treatment (e.g., intravesical chemotherapy or immunotherapy, cystectomy, or radiotherapy) is indicated. Finally, the patient must be monitored for the development of subsequent tumors. This article provides an overview of the management of superficial bladder cancer.

Flexible cystourethroscopy: alternative to rigid instruments for evaluation of lower urinary tract.

The flexible nephroscope offers several advantages when used to evaluate the lower urinary tract. Fifty-six men have been endoscoped in an effort to document the ease of urethral passage and visibility with two of these instruments.

Overview of treatment of superficial bladder cancer.

Seventy per cent to 80 per cent of patients with bladder cancer will have their initial tumor confined to the mucosa (Stage Ta or Tcis, carcinoma in situ) or lamina propria (Stage T1), and at least 50 per cent of them will have a true recurrence or new recurrence despite resection of their initial tumor. If the tumor is of low grade and confined to the mucosa, intravesical chemotherapy might be considered either as treatment if the neoplasm is too extensive to resect completely or if multiple prior endoscopic resections have failed, or, alternatively, as prophylaxis against a subsequent tumor after complete endoscopic removal of the existing neoplasm. Thiotepa, until recently the most commonly used agent, completely eradicates all obvious tumor in approximately 30 per cent of patients, and it is effective in preventing subsequent tumor. Myelosuppression occurs in up to 20 per cent of patients receiving this agent, so careful monitoring of the white blood cell and platelet counts is mandatory. Mitomycin has low risk of myelosuppression and is effective in both the treatment and prophylaxis of superficial bladder cancer; the complete response rate is the same whether patients had an initial low-grade papillary or high-grade tumor (carcinoma in situ). Doxorubicin hydrochloride and bacillus Calmette-Guérin (BCG) are other agents that have been used for intravesical therapy. Chemical cystitis, the primary side effect of doxorubicin, has caused discontinuation of treatment in 15 per cent to 20 per cent of patients. The efficacy of doxorubicin varies among those reporting its use. BCG has been shown to be effective in both treatment and prophylaxis, with response rates similar to those reported for mitomycin; however, a comparative trial has not been performed. There is a need to standardize the potency of each BCG vial and to determine fully the necessity of concomitant intradermal administration.

Introduction and overview of intravesical therapy for superficial bladder cancer.

The initial and subsequent management of patients with transitional cell carcinoma of the urinary bladder requires the cooperative effort of the urologist, pathologist, and cytologist. The initial endoscopic session should provide sufficient material to assess accurately the extent of tumor. The tumor is termed superficial if it is confined to the mucosa (Stage Ta and CIS) or lamina propria (T1). Based on the prognostic factors, the clinician decides whether or not intravesical therapy should be incorporated into the treatment plan that is designed to eradicate any remaining postresection tumor(s) as well as retard the development of subsequent tumors. The clinician who chooses to utilize intravesical therapy should be knowledgeable regarding the frequently used drugs: thiotepa, mitomycin C, doxorubicin, and bacillus Calmette-Guérin (BCG). Each has established efficacy in the treatment and prophylaxis of transitional cell carcinoma. Each also has a different spectrum and incidence of local and systemic toxicity.

Newer methods of hormonal therapy for prostate cancer.

At least 80 per cent of prostatic tumors exhibit some degree of hormone responsiveness. The preferred method of hormonal alteration has yet to be determined because new agents are currently undergoing clinical trials. The compounds tested have included cyproterone acetate, a progestational agent; flutamide, an antiandrogen that blocks the DHT-receptor complex in the tumor cell; and aminoglutethimide, which inhibits adrenal steroid production and, therefore, might further lower the level of circulating androgen following bilateral orchiectomy. The introduction of potent, synthetic analogues of gonadotropin-releasing hormone (GnRH) has provided another method of reducing the level of circulating androgen. A recent report on the efficacy of one of these analogues--leuprolide--in men with newly diagnosed metastatic prostatic cancer has revealed an initial response rate of 76 per cent (4% complete remissions, 32% partial remissions, and 40% stable) using National Prostatic Cancer Project criteria.

Morbidity of modified pelvic lymphadenectomy and radiotherapy for prostatic cancer.

The records of 63 patients treated by pelvic lymphadenectomy and radiotherapy at the University of Tennessee, Memphis, Baptist Memorial Hospital of Memphis, and the Memphis Veterans Affairs Hospital were reviewed. Of those patients, 45 received external beam radiation therapy to the prostate while 16 were treated by Iodine-125 implantation. Two patients had only staging lymphadenectomy. The incidence of postoperative and late complications were analyzed.

Retroperitoneal fibrosis and aortic aneurysm.

A case of bilateral ureteral obstruction associated with an abdominal aortic aneurysm is presented. The increasing frequency of this association suggests investigation of the upper urinary tract in patients with an abdominal aortic aneurysm and abdominal ultrasound in patients with bilateral ureteral obstruction.

Response to second-line hormonal manipulation monitored by serum PSA in stage D2 prostate carcinoma.

Changes in prostate-specific antigen (PSA) have been demonstrated to accurately assess response to initial hormone deprivation in metastatic prostate cancer patients. The role of PSA in monitoring response to second-line hormonal treatment has not been documented. In a group of 20 patients with an initial response to androgen deprivation and subsequent relapse, we monitored PSA levels before and after second-line therapy. Ten patients had a clinical response. Four had a more than 90 percent decrease in serum PSA compared with the level at initial progression. This clinical response was maintained for a mean of eighteen months. Six patients had a PSA decrease less than 90 percent; their clinical response was of a mean 5.5 months. Ten patients had no change or increase in PSA. Seven had no clinical response, and 3 responded for an average of four months. Although production of PSA might be under endocrine control, changes in PSA are useful for monitoring response to second-line hormonal therapy.

Susceptibility of urothelium to neoplastic cellular implantation.

This study sought to determine whether or not transitional carcinoma cells can adhere and progressively grow on normal or inflamed bladder urothelium. Inflammation was produced by intravesical N-methyl-N-nitrosourea. Tumor cell implantation occurred in only 13 per cent of mice with normal bladder, whereas in the presence of an altered urothelial surface ther was a 60 per cent incidence of tumors. This study not only has clinical implications but also offers a model to investigate modalities to prevent tumor cell implantation.