Unyime O. Nseyo

IMPACT OF PROSTATE-SPECIFIC ANTIGEN LEVEL AND PROSTATE VOLUME AS PREDICTORS OF EFFICACY IN PHOTOSELECTIVE VAPORIZATION PROSTATECTOMY: ANALYSIS AND RESULTS OF AN ONGOING PROSPECTIVE MULTICENTRE STUDY AT 3 YEARS

In a multicentre study from the USA, 3‐year results of the high‐power KTP laser prostatectomy are presented. The authors used preoperative PSA level as a marker of prostate volume and assessed its potential predictive value on the level of clinical efficacy for treating symptomatic BPH. They found that the overall results from the technique were positive and durable, and suggested that there was a significant difference in efficacy between patients presenting with a total PSA of <6 or >6 ng/mL.

CD44 standard form expression as a predictor of progression in high risk superficial bladder tumors

Objective: The purpose of this study was to assess the significance of the standard CD44 adhesion molecule expression in predicting progression of high risk superficial bladder carcinoma in the short term.Methods: Sixty-six patients (51 males and 15 females, aged 27 to 89 years (mean 64.75 years) with primary superficial transitional cell bladder cancer initially treated with transurethral resection (TURBT) were enrolled in the study. Only pTa/pT1 grade 2 multiple tumors as well as all grade 3 tumors were included in this study. All tumor samples obtained after the resection were immunohistochemically evaluated for the expression of the CD44 standard molecule. Fifty eight patients remained during the follow up period which ranged from 3 to 36 months (mean 11.8 months). Tumor progression in the short term was considered as the critical end point of interest in this study. The prognostic significance of tumor stage, grade, presence of carcinoma-in-situ (CIS) and expression of CD44 in determining the risk for progression, was studied with both univariate (log rank test) and multivariate (Cox proportional hazards) methods of analysis.Results: Kaplan-Meier survival curves indicated that a shorter median progression-free survival is expected for those patients with G3 bladder tumors (p = 0.0055), concomitant CIS (p = 0.0051), and loss of expression of CD44 (p = 0.0015), whereas a similar association with stage was not detected (p = 0.5793). The cox regression multivariate analysis did not yield a significant result for any of the studied parameters therefore no one of the factors taken into account can serve as an independent predictor of progression in superficial bladder cancer in the short term.Conclusion: The immunohistochemically detectable loss of the expression of CD44 standard form from superficial bladder tumor samples may be, complementary to the established prognostic factors, a useful predictor of tumor progression in the short term.

High-power (80-w) KTP laser vaporization of the prostate in the management of urinary retention: long-term follow up

Introduction and Objectives: We have previously reported the use of high-powered photoselective vaporization of the prostate (PVP) for patients in urinary retention due to benign prostatic hyperplasia (BPH). PVP is a relatively new treatment for bladder outlet obstruction due to BPH, using laser energy to vaporize obstructing prostatic tissue. This study investigates the long-term follow up of patients treated with PVP for urinary retention. Materials and Methods: All participants signed informed consent, and were treated with high power 80 W quasi-continuous wave potassium-titanyl-phosphate (KTP) laser. Ten patients underwent the procedure from December 2001 until the present. One patient was excluded from the study for failure to return for follow-up. Mean patient follow-up was nine months, maximum of twelve months. Results: The mean pre-operative gland size by trans-rectal ultrasound was 48 grams. Mean urethral length was 3.2 cm. Mean laser time was 48.2 minutes and the mean energy usage was 82.2 kJoules. There were no peri-operative complications such as sepsis or measurable postoperative bleeding. The preoperative AUA Symptom Score (AUASS) decreased from a mean of 22.6 preoperatively to 17 at nine months postoperatively (p = 0.032). The Quality of Life Score (QOL) decreased from 4.6 preoperatively to 3.25 at 12 months postoperatively (p = 0.26). The maximum urine flow rate increased from a mean of 7.7 cc/sec preoperatively to 14.5 cc/sec at six months follow-up (p = 0.03). Conclusions: This follow-up study suggests that HP-KTP has a durable response in patients treated specifically for retention. It significantly improved urine flow rate and symptom score, and had a trend towards improvement in subjective quality of life. HP-KTP prostatectomy should be considered in treating patients in retention, especially those with significant co-morbidities or taking anticoagulation.

Assessment of Urologists' Practice Preferences for the Management of Benign Prostatic Hyperplasia in the Veterans Administration Program

Abstract Objective: The goal of this study was to assess diagnostic and treatment modality preferences of urologists for the management of benign prostatic hyperplasia (BPH) in the Veterans Administration (VA) patient population. Methods: A self-administered mail survey was sent to 294 urologists who provide services to the VA population in 149 VA medical centers across the United States. The survey contained descriptions of simulated BPH cases, for which the urologists were asked to indicate their preferences in diagnostic tests and treatment options. The survey also gathered information on the frequency of failed initial therapy and demographic and practice information. A nonresponse survey was conducted to estimate nonresponse bias. Results: The response rate was 39.0%. There were no significant differences between nonrespondents and respondents on selected important demographic and practice variables. Respondents generally selected practices that were consistent with clinical guidelines for recommended tests, but their preferences for optional tests varied. Alpha-blockers were the most preferred treatment option, regardless of disease severity. The second most preferred option in mild BPH was watchful waiting, whereas in both the moderate and severe cases it was transurethral resection of the prostate. The respondents reported a treatment failure rate of 41.1%. The most common switch in therapy was from alpha-blockers to surgery. Urologists were in moderate agreement in terms of their preference for diagnostic tests and in substantial agreement on treatment preferences. Conclusions: This study provides insight into the preferences of VA urologists regarding the diagnosis and management of BPH. However, the results need to be validated by assessment of the VA clinical records of actual new patients with BPH.

The Potential Role of Chemoprevention in the Management of Non-Muscle Invasive Bladder Urothelial Carcinoma

1.1 Epidemiology and bladder carcinogenesis Cancer represents phenotypic manifestations of abnormal gene expression. Genetic mutations, dysregulation, and gene losses can influence cell proliferation and differentiation, and eventually lead to formation of cancer. Risk factors and etiologic agents involved in the genetic abnormalities influence the distribution of cancer worldwide. This chapter aims at highlighting the epidemiologic significance of urothelial bladder cancer; reviewing its natural history, the roles of industrial and environmental carcinogens and life style factors in urothelial carcinogenesis; and framing possible strategies for chemoprevention in the management of human urothelial cancer of the urinary bladder. Bladder cancer remains a serious public health problem worldwide, and accounts for 5-10% of all malignancies annually in western countries (Cancer Treatment of America). Though the age-adjusted incidence varies in the different parts of the world, the highest rates are found in men from North America (23.3/100,000), North Africa (23.3/100,000) and Southern Europe (22.0/100,000), while the corresponding rates are 5.4, 4.8, and 3.2 per 100000 for women (Cancer Treatment of America). These high rates may be influenced by increased industrialization, cigarette smoking, and infection of schistosomiasis (primarily of concern in North Africa). The lowest rates for both sexes have been reported for the Melanesia region of South Pacific and Middle Africa (Cancer Treatment of America; Prout, Barton et al. 1992; Grasso 2008; American Cancer Society 2010). Bladder cancer, which is immensely impacted by environmental carcinogens and tobacco smokes, remains a common disease in the United States, and it is estimated that 70, 530 persons (52,760 men and 17,770 women) were diagnosed with cancer of the urinary bladder in 2010, (Cancer Treatment of America; American Cancer Society 2010) and an estimated 14, 680 died of the disease accounting for 3% and 2% of all cancer deaths in men and women, respectively (Cancer Treatment of America; American Cancer Society 2010). Estimates of new cancer cases classify urothelial bladder cancer (UBC) as the fourth most common in men and the eighth most common in women. The prevalence of UBC in the US is estimated at about

Localization of hypericin-induced fluorescence after Hypericum perforatum polar fraction instillation in normal rat urinary bladder

The photodynamic action of the Hypericum perforatum L. extract, mainly its polar methanolic fraction (PMF) has recently been substantiated by our group. The herb contains a number of naphthodianthrones - photosensitizers mainly hypericin and pseudohypericin. The concentration of hypericins in PMF was found to be 1.37 %. The distribution of hypericins fluorescence in sections of normal rat bladder tissues after the intravesical instillation of the polar methanolic fraction of hypericum (PMF) was studied by the use of fluorescence microscopy. PMF was dissolved in normal saline containing 0.5 μg/ml concentration of hypericins, and was then instilled in rat bladder for 15, 30, 60 and 120 minutes respectively. PMF solutions were withdrawn, bladders were rinsed through the catheter with normal saline and rats were sacrificed. Bladders were then removed, cut open and immediately mounted in medium, and immersed in liquid nitrogen. Two consecutive 3-μm frozen sections were cut with a cryostat. The first section was examined by fluorescence microscopy and the second section was stained with hematoxylin and eosin. For fluorescence imaging the filter set used included a 535/50 nm bandpass excitation filter and a 610/75 nm emission filter. Fluorescence images were acquired and documented using photography. Fluorescene could be detected in bladder samples after only 15 minutes of instillation with the above described solution. The urothelium / muscle fluorescence ratio ranged from 5/1 to 11/1 in various sites of the samples examined. No fluorescence originating from the muscle could be detected. PMF should be further studied towards the direction of its use in photodynamic therapy.

Herbal tea extract combined with light-induced significant in vitro cytotoxicity of human bladder cancer cells

The anti-inflammatory, anti-microbial, antiviral, and antidepressant activities of the Greek herb, Hypericum Perforatum L, HP L, have been attributed to the total extract or single constituents. We investigated the use of the extract,specifically of the polar methanolic fraction (PMF) of Epirus’HPL in photodynamic therapy (PDT) alone and in combination with recombinant Interferon-a2b (IFN) and gemcitabine (GCB) in the treatment of human bladder cancer cells. The PMF was extracted from the dry herb with methanol, followed by liquid-liquid extraction with petroleum ether. T-24 bladder cancer cells were plated (105 cells/well) and placed in the incubator (370 C, 5%CO) for 24 hours prior to addition of drugs. PMF 60ug/ml was added and incubation continued. After 24 hours, the cells were subjected to laser light (630nm) treatment with 0, 1, 4 and 8 Joules. After reincubation for 24 hours, IFN, (50,000 IU) or GCB, (2ug/ml) was added to the PDT-treated cells. After this incubation cell survival was assessed by the MTT assay. PMF-PDT alone-induced percent cell kill of 0%, 8%, 44% and 80% versus 31%, 64 and 86 % for PMF-PDT and IFN, versus 63%, 80% and 88% for MPF-PDT plus GCB at 1, 2, 4 and 8 Joules respectively. IFN and GCB induced 20% and 53% cell kill respectively. Our data suggest that MPF may be an effective agent for in vitro photodynamic therapy. PMF-PDT combined with Intron A, or gemcitabine achieved improved kill of cultured bladder cancer cells. Confirmation of these results in preclinical studies may lead to clinical trials.

Photoselective vaporization of the prostate (PVP) with green light KTP laser in the management of symptomatic benign prostatic enlargement (BPE): does the anatomy of the TURP-like cavity predict the clinical outcome?

Photoselective vaporization of the prostate (PVP) is evolving as an alternative outpatient surgical treatment to transurethral resection of the prostate (TURP) in the management of patients with symptomatic benign prostatic hypertrophy/enlargement (BPH/BPE). The purported benefits of PVP include rapid vaporization of the prostate with an instant creation of TURP-like anatomic defect, an excellent hemostasis, shorter (<24 hours) duration of catheterization, short (< 24 hours) hospital stay, and quick return to work. We retrospectively reviewed the video clips of our cases to determine whether or not the anatomic appearance of the post-PVP prostatic cavity per se could predict clinical outcome. Forty-three, non-consecutive patients, diagnosed with symptomatic BPH have been treated with PVP using the 80W KTP laser and followed for at least 18 months (range 18-24). A majority (N=32) of the patients was enrolled under an Institutional Review Board approved multi-center protocol at the Hunter McGuire Veterans Administration Medical Center, Richmond, Virginia. We reviewed the urodynamic parameters: AUA-SI, QOL, Qmax and PVR at 3, 6, 12, 18 and 24 months postoperatively. We plan to present video documentations of the various anatomic appearances of the TURP-like prostatic cavity at the conclusion of the PVP treatment along with summaries of the short and long term clinical outcomes.

The role of the prostatic median lobe in urinary symptoms following photoselective vaporization of the prostate (PVP)

Introduction and Objective: Photoselective vaporization of the prostate (PVP) remains a relatively new addition to our armamentarium of minimally invasive surgical treatments for symptomatic benign prostatic hypertrophy/enlargement. Early favorable reports of the safety and efficacy of PVP do not alleviate the need to investigate factors that may further improve the safety margin and efficacy outcomes of PVP in the management of symptomatic benign prostatic enlargement (BPE). Consequently, we investigated the role of enlarged or prominent intravesical median/middle lobe of the prostate in mediating urinary symptoms following PVP. Materials and Methods: Forty-one non-consecutive patients diagnosed with BPE were enrolled under an Institutional Review Board approved multi-center protocol at the Hunter McGuire Veterans Administration Medical Center, Richmond, Virginia, for PVP treatment using the 80W quasi-continuous wave KTP laser. Perioperative and postoperative complications/adverse events were assessed. Urodynamic parameters: AUA-SI, QOL, Qmax and PVR; and PSA were assessed at baseline, 1, 3, 6 and 12 months postoperatively. Results: The forty-one patients were sub-stratified based on cystoscopic evidence of prominent median/middle lobe (n=17)(Study Group), and absence of median lobe (n = 24). Seven of seventeen (41.1%) patients with and 10/24 (41.7%) patients without median lobes experienced adverse urinary symptoms, which resolved within 7-8 months. All 41 patients have demonstrated significant improvements in urodynamic, that is, flow rates, post void residual volumes and clinical (QOL) outcome measures. Conclusion: Niagara Green Light PVP procedure did not result in heightened severity of voiding symptoms in those BPE patients with prominent intravesical median lobes.

Safety of two sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

While 55 - 60% of newly diagnosed bladder cancers are superficial, a significant number recur as higher grade and/or stage tumors. WBPDT has been used to treat some of these recurrent superficial tumors, although its use has been associated with dose-dependent side effects. Preclinical investigation of three sequential WBPDT treatments using lower PDT dose in normal canine bladder resulted in a lack of permanent bladder contracture. Lower dose single PDT treatment has shown less durable tumor response; however, sequential WBPDT treatments with lower dose may result in durable tumor response. Five patients (4 male, 1 female), average age 65.6 (62-72 years), with recurrent or resistant superficial TCC of the bladder received two WBPDT treatments. First treatment occurred at baseline and the second treatment at 6 months. Photofrin (1.5 mg/kg) was given intravenously 48 hours prior to each cystoscopic treatment with laser light (630 nm, Coherent Lambda-Plus laser). Total light treatment doses were 1500 - 2500 Joules at baseline and 1000- 1500 Joules at 6 months. Moderate irritative bladder symptoms occurred in all patients the first week post PDT. No cases of bladder contracture have occurred. 4 of 5 patients showed no evidence of disease during the follow-up period (12 - 18 months post second treatment). One patient had a recurrence at 18 months post second treatment. Mean disease-free interval is 16.2 months. The safety of two sequential WBPDT treatments is suggested by this preliminary data. Assessment of efficacy will be possible wit a large number of patients and a longer follow-up period.