Re: Use of TP4303 to identify prostate cancer cells in voided urine samples.

Prostate cancer is the second most common cancer in men across the world. Prior to PSA testing, men usually presented with locally advanced disease detected on digital rectal exam or with metastatic disease. PSA ushered in the era of serum biomarkers for prostate cancer. It has taken over three decades to refine the role of PSA in prostate cancer detection. The lack of specificity has spurred research into finding better, readily obtainable biomarkers with high sensitivity and specificity. The trick is to find the prostate cancers that are a threat, not the ones that aren't. Over the last decade and more, many biomarkers have been proposed and tested (HK-2, Pro-PSA, PCA3, TMPRSS2:ERG fusion transcripts, miRNA, just to name a few) but we still await that magical combination of a readily available, reproducible, and hopefully inexpensive biomarker with high sensitivity and specificity. The authors describe the use of a peptide labeled fluorophore for the VPAC1 receptors that are expressed on malignant prostate cancer cells shed in the urine. After initial feasibility work, the authors collected urine from 318 men with lower urinary tract symptoms and a PSA > 4. The patients underwent prostate biopsy yielding Grade Group 2 or higher prostate cancer in 158 patients. One hundred fifty-four or those patients with cancer had a positive result for the biomarker. The sensitivity of the test was 100%, the specificity was 97.56%, positive predictive value was 97.47%, and negative predictive value was 100%.1 These are impressive numbers for a urine biomarker (or any biomarker). This work is certainly promising, BUT, we have seen promising early data on many biomarkers. In this study, the mean PSA in the cancer group was 34.53 ng/mL versus 9.41 in the control (negative) group. Since patients with infection were excluded, the significantly different PSA levels seemed to be selecting the cancers as well. Time and follow up will determine if the "negative biopsy" controls were truly negative. Can the technique and these results be reproduced? The true test will be how this biomarker consistently performs across a broader population of men with a lower, more homogenous PSA elevation. I will eagerly await results of continued study of this promising biomarker for prostate cancer.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Prostate cancer polar localization on core biopsy predicts pathologic stage.

INTRODUCTION: This study investigated the polar sub-localization of prostate cancer on needle core biopsy ('polar' defined as tumor = 1 mm from the tissue polar edge) as a predictor of extraprostatic extension. MATERIALS AND METHODS: Histologic sections from 58 patients who underwent preoperative prostate biopsy and radical prostatectomy at the University of Kentucky from 2006 to 2013 were evaluated. Patients were retrospectively case matched based on pathologic stage (pT2 versus pT3/4) using biopsy Gleason grade and prostate-specific antigen. Histologic sections of needle core biopsies were analyzed for polar involvement. The location of polar involvement was correlated to the presence of extraprostatic extension on final prostatectomy pathology. RESULTS: Average percentage of total polar cores was predictive of extraprostatic extension on final prostatectomy, particularly in the prostatic apex and base (p = 0.029 and 0.006, respectively). Higher grade tumors were identified at the pole in the high stage cohort (p = 0.032). Total percent polar involvement had the greatest sensitivity and specificity for predicting extraprostatic extension when directly compared to previously described histologic parameters (percent greatest involvement of a single core, length of greatest involvement of a single core, presence of perineural invasion, presence of bilateral gland involvement, and percent total positive core involvement). The location of polar involvement on needle core biopsy was also predictive of the precise location of extraprostatic extension on final prostatectomy pathology (Chi-square p < .001, negative predictive value > 70% in all prostate sextants). CONCLUSIONS: These data suggest the use of biopsy polar core involvement as a valuable histologic predictor of increased pathologic stage.

Adherence to AUA guidelines for the work-up, medical management, surgical evaluation and treatment of BPH: Work from a quality improvement collaborative.

INTRODUCTION: Previous studies noted varied adherence to clinical practice guidelines (CPGs), but studies are yet to quantify adherence to American Urological Association BPH guidelines. We studied guideline adherence in the context of a new quality improvement collaborative (QIC). METHODS: Data were collected as part of a statewide QIC. Medical records for patients undergoing select CPT codes from January 2020 to May 2022 were retrospectively reviewed for adherence to selected BPH guidelines. RESULTS: Most men were treated with transurethral resection of the prostate. Notably, 53.3% of men completed an IPSS and 52.3% had a urinalysis. 4.7% were counseled on behavioral modifications, 15.0% on medical therapy, and 100% on procedural options. For management, 79.4% were taking alpha-blockers and 59.8% were taking a 5-ARI. For evaluation, 57% had a PVR, 63.6% had prostate size measurement, 37.4% had uroflowmetry, and 12.3% were counseled about treatment failure. Postoperatively, 51.6% completed an IPSS, 57% had a PVR, 6.50% had uroflowmetry, 50.6% stopped their alpha-blocker, and 75.0% stopped their 5-ARI. CONCLUSIONS: There was adherence to preoperative testing recommendations, but patient counseling was lacking in the initial work-up and preoperative evaluation. We will convey the data to key stakeholders, expand data collection to other institutions, and devise an improvement implementation plan.

Association of CD47 Expression with Clinicopathologic Characteristics and Survival Outcomes in Muscle Invasive Bladder Cancer.

OBJECTIVE: CD47 is an antiphagocytic molecule that plays a critical role in immune surveillance. A variety of malignancies have been shown to evade the immune system by increasing the expression of CD47 on the cell surface. As a result, anti-CD47 therapy is under clinical investigation for a subset of these tumors. Interestingly, CD47 overexpression is associated with negative clinical outcomes in lung and gastric cancers; however, the expression and functional significance of CD47 in bladder cancer is not fully understood. MATERIALS AND METHODS: We retrospectively studied patients with muscle invasion bladder cancer (MIBC) who underwent a transurethral resection of bladder tumor (TURBT) and subsequently underwent radical cystectomy (RC) with or without neoadjuvant chemotherapy (NAC). CD47 expression was examined by IHC in both TURBT and matched RC specimens. The difference in CD47 expression levels between TURBT and RC was also compared. The association of CD47 levels (TURBT) with clinicopathological parameters and survival outcomes was evaluated by Pearson's chi-squared tests and the Kaplan-Meier method, respectively. RESULTS: A total of 87 MIBC patients were included. The median age was 66 (39-84) years. Most patients were Caucasian (95%), male (79%), and aged >60 (63%) and most often (75%) underwent NAC prior to RC. Of those who received NAC, 35.6% were responders and 64.4% were non-responders. The final reported stages as per AJCC for all patients were as follows: stage 0 (32%), stage 1 (1%), stage 2 (20%), stage 3 (43%), and stage 4a (5%). A total of 60% of patients were alive; of those, 30% had disease recurrence and 40% died from bladder cancer at a median follow-up of 3.1 (0.2-14.2) years. CD47 levels were detectable in 38 (44%) TURBT samples. There was no association between CD47 levels and clinicopathological parameters such as age, gender, race, NAC, final stage, disease recurrence, and overall survival (OS). Patients aged >60 (p = 0.006), non-responders (p = 0.002), and at stage ≥ 3 (p < 0.001) were associated with worse OS by a univariate analysis and stage ≥ 3 remained significant even after a multivariate analysis. In patients managed with NAC, there were decreased CD47 levels in RC specimens compared to the TURBT specimens, but this did not reach statistical significance. CONCLUSION: CD47 expression was not a predictive nor prognostic marker for MIBC patients. However, expression of CD47 was detected in nearly half of MIBCs, and future studies are needed to explore the potential role of anti-CD47 therapy in these patients. Furthermore, there was a slight positive trend in decreased CD47 levels (from TURBT to RC) in patients receiving NAC. As a result, more research is needed to understand how NAC may modify immune surveillance mechanisms in MIBC.

Locally advanced solitary fibrous tumour of the prostate.

Solitary fibrous tumours (SFTs) are rare mesenchymal neoplasms composed of spindle cells, most often occurring in the pleura. SFTs arising from the prostate are exceptionally rare, with only around 40 cases reported in literature to date. We report a man in his 60s who was referred to our clinic for elevated prostate-specific antigen and presented with mild obstructive lower urinary tract and defecatory symptoms. Prostate needle-core biopsy revealed neoplastic spindle cells that strongly expressed CD34. Cross-sectional imaging demonstrated a 12 cm locally advanced heterogeneous prostate mass with intravesical extension and mass effect on the anterior rectum. Radical cystoprostatectomy with orthotopic neobladder reconstruction was performed, and the diagnosis of primary prostatic SFT was made based on histological characteristics and immunophenotyping. We present diagnostic, clinical management and prognostic considerations in patients with primary prostatic SFT.

A Phase I Dose Escalation and Expansion Study of Epidiolex (Cannabidiol) in Patients with Biochemically Recurrent Prostate Cancer.

PURPOSE: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. EXPERIMENTAL DESIGN: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/- salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. RESULTS: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1-2), 25% nausea (grade 1-2), and 20% fatigue (grade 1-2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). CONCLUSION: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies.

Association of tumor size, location, R.E.N.A.L., PADUA and centrality index score with perioperative outcomes and postoperative renal function.

PURPOSE: Multiple scoring systems have been proposed to standardize the description of anatomical features of renal tumors. However, it remains unclear which of these systems, if any, is most useful, or whether any performs better than simply reporting tumor size or location in patients undergoing partial nephrectomy. To clarify these issues we evaluated the association of tumor size, location, R.E.N.A.L. (Radius/Exophytic/Nearness to collecting system/Anterior/Location), PADUA (Preoperative Aspects and Dimensions Used for an Anatomical classification) and centrality index scores with perioperative outcomes. MATERIALS AND METHODS: Patients undergoing partial nephrectomy with available preoperative imaging were identified from 2005 to 2011. R.E.N.A.L., PADUA and centrality index scores were assigned according to the described protocols for those systems. Associations between each variable and ischemia time, estimated blood loss, total operative time and change in estimated glomerular filtration rate were examined. RESULTS: A total of 162 patients were identified with a median tumor size of 3.1 cm (IQR 2.2 to 4.6). Median estimated blood loss, ischemia time and total operative time were 200 ml (IQR 100 to 300), 24 minutes (IQR 20 to 30) and 211 minutes (IQR 179 to 249), respectively. Each scoring system was found to have a statistically significant (p <0.001) correlation with ischemia time, with the centrality index system showing the strongest correlation. Furthermore, each of the scoring systems showed a stronger correlation with ischemia time than tumor size or tumor location. CONCLUSIONS: Each scoring system outperformed tumor size and location, and may be useful when describing the surgical complexity of renal tumors treated with partial nephrectomy.

Aggressive angiomyxoma presenting as urinary retention in a male: a case report and literature review.

We present a case of pelvic aggressive angiomyxoma presenting as urinary retention in a male. A 46-year-old male presented with urinary retention and was found on computed tomography (CT) scan of the pelvis to have a large pelvic tumor. A transrectal ultrasound guided needle biopsy of the tumor and prostate revealed a myxoid tumor; low volume, low grade prostate cancer was also detected. The patient underwent radical prostatectomy and excision of the pelvic tumor which was diagnosed as aggressive angiomyxoma (AAM). The patient was free of recurrence after 1 year of follow up. AAM is a benign myxoid tumor seen very rarely in males. Treatment consists of surgical excision with negative margins. Tumors variably express estrogen and progesterone receptors. Immunohistochemistry should be used to exclude other benign and malignant tumors. Patients should be followed with axial imaging as recurrence is common.

Evaluation of Glutaminase Expression in Prostate Adenocarcinoma and Correlation with Clinicopathologic Parameters.

High Glutaminase (GLS1) expression may have prognostic implications in colorectal and breast cancers; however, high quality data for expression in prostate cancer (PCa) are lacking. The purpose of this study is to investigate the status of GLS1 expression in PCa and correlated expression levels with clinicopathologic parameters. This study was conducted in two phases: an exploratory cohort analyzing RNA-Seq data for GLS1 from The Cancer Genome Atlas (TCGA) data portal (246 PCa samples) and a GLS1 immunohistochemical protein expression cohort utilizing a tissue microarray (TMA) (154 PCa samples; 41 benign samples) for correlation with clinicopathologic parameters. In the TCGA cohort, GLS1 mRNA expression did not show a statistically significant difference in disease-free survival (DFS) but did show a small significant difference in overall survival (OS). In the TMA cohort, there was no correlation between GLS1 expression and stage, Gleason score, DFS and OS. GLS1 expression did not significantly correlate with the clinical outcomes measured; however, GLS1 expression was higher in PCa cells compared to benign epithelium. Future studies are warranted to evaluate expression levels in greater numbers of high-grade and advanced PCa samples to investigate whether there is a rational basis for GLS1 targeted therapy in a subset of patients with prostate cancer.

Evaluation of three laparoscopic modalities: robotics versus three-dimensional vision laparoscopy versus standard laparoscopy.

PURPOSE: Standard laparoscopy has undergone many recent advances with the advent of three-dimensional visual systems and robotic surgical systems. In evaluating the usefulness of these new systems, it is difficult to objectively measure their advantages in the operating room. Therefore, we designed a trial using three different laparoscopic modalities to evaluate the strengths and weaknesses of each modality. MATERIALS AND METHODS: Twenty-seven subjects were entered into the study. Three different laparoscopic modalities were tested. These included standard laparoscopy with two-dimensional cameras, the 3Di Endosite visual system, and the daVinci Robotic Surgical System. A standard laparoscopic trainer was utilized and testing consisted of three different tasks: peg transfer, ring manipulation, and cannulation. RESULTS: Of the 27 subjects, 16 (60%) reported some degree of laparoscopic experience. The number of pegs transferred with standard laparoscopy and the Endosite 3Di system was significantly greater than with the robot. The number of errors committed during the peg transfer test and the amount of time required was significantly lower with the Endosite 3Di system compared to the robot. Subjects completed the ring manipulation task significantly faster with the robot, but the number of errors committed was no different among the three modalities. Subjects were able to complete the cannulation task with their dominant hand significantly faster with the robot compared to the Endosite 3Di system or standard laparoscopy, and committed fewer errors using the robot compared to standard laparoscopy. CONCLUSIONS: This study showed improved performance using three-dimensional optics on some tasks, but not a significant improvement in overall results. Three-dimensional vision does appear beneficial during performance of some complex tasks. The wrist-like action of the robot improved performance on some tasks, while the lack of tactile feedback likely was a source of errors on other tasks.

The addition of robotic surgery to an established laparoscopic radical prostatectomy program: effect on positive surgical margins.

PURPOSE: The addition of robotic assistance with the da Vinci surgical system for performing laparoscopic radical prostatectomy has been reported to improve surgical outcomes. In order to evaluate the benefit of robotic assistance to improve cancer control in a center with an established laparoscopic radical prostatectomy program, we evaluated the incidence of positive surgical margins in both transperitoneal laparoscopic (LRP) and robotically assisted laparoscopic radical prostatectomy (RALP). MATERIALS AND METHODS: We performed an Institutional Review Board (IRB) approved, retrospective review of 247 men with clinically localized prostate cancer treated with either a LRP or a RALP from March 2000 to August 2006. Pathology reports were reviewed for both preoperative and postoperative Gleason score as well as clinical and pathological stage. Surgical pathology specimens were evaluated using a whole mount, step section technique. Extracapsular extension, seminal vesicle invasion and positive margins were noted when present in the final surgical pathologic specimens. RESULTS: One hundred ninety seven patients underwent LRP, and 50 patients underwent RALP. Seven of the 197 LRP required open conversion to retropubic radical prostatectomy, and were excluded. None of the RALP were converted. The overall positive surgical margin rate for LRP and RALP was 18% (35/190) and 6% (3/50), respectively (p = 0.032). When examining pathologically organ confined specimens (pT2), the positive surgical margin rate was 12% (20/161) and 4.7% (2/43) for the LRP and RALP cohorts, respectively (p = 0.181). For pathologic disease that has spread outside the capsule (pT3/T4), the positive surgical margin rate was 54% (15/28) and 14% (1/7) for LRP and RALP, respectively (p = 0.062). Patient age, race and prostate volume were not significant factors in the incidence of positive surgical margins. CONCLUSION: The addition of robotic assistance to an established laparoscopic radical prostatectomy program appears to reduce the incidence of positive surgical margins. Data is maturing to determine whether this will lead to improved functional and oncologic outcomes.

Hand-assisted laparoscopic nephroureterectomy (HALNU): an assessment of the impact of obesity in 50 procedures.

OBJECTIVE: The aims of this study was to review our experience with hand-assisted laparoscopic nephroureterectomy (HALNU) and to evaluate the impact of body-mass index (BMI) on outcomes. METHODS: We retrospectively analyzed 50 HALNU patients. Twenty had body mass indices (BMIs) <25 (normal cohort), 18 had BMIs between 25 and 29.9 (overweight cohort), and 12 had BMIs >/=30 (obese cohort). RESULTS: The cohorts had similar operative times: 349, 326, and 320 minutes, respectively. Most patients (38) underwent a total HAL distal ureterectomy, but 9 underwent an initial transurethral ureteral dissection (5 [25%], 2 [11%], and 2 [17%]). Five patients were converted to open and 1 had a planned open ureterectomy. The cystotomy was sutured closed in most but left open in 6 (3 [15%], 2 [11%], and 1 [8%]), and a stapled ureteral division was performed in 7 (3 [15%], 2 [11%], and 2 [17%]). Increased BMI was associated with delayed oral intake (P = 0.034). No significant cohort differences were observed for estimated blood loss (EBL), transfusion rate, complication rate, surgical margin status, distant metastases, or death rate. The obese cohort demonstrated trends toward increased hospitalization and bladder cancer recurrence (P = 0.083, P = 0.097). Patients with prior open surgery had longer hospitalizations (P = 0.024). Patients without prior surgery were more commonly alive with persistent disease (P = 0.027). EBL was greater for patients who had transurethral ureteral dissection (P = 0.030). Patients undergoing a stapled ureteral division had delayed oral intake, bowel function, and discharge (P = <0.001, P = 0.034, and P = 0.034). CONCLUSIONS: HALNU is an effective surgical treatment for patients with BMIs as great as 45.

Optimization of Patient Selection for Neoadjuvant Chemotherapy in Muscle-invasive Urothelial Carcinoma of the Bladder.

BACKGROUND: Radical cystectomy (RC) is delayed in a subset of patients who respond poorly to neoadjuvant chemotherapy (NAC). The present study investigated the clinicopathologic characteristics predicting extravesical disease at RC and the factors associated with NAC tolerability to improve patient selection and the sequence of definitive therapy. MATERIALS AND METHODS: Patients with cT2 urothelial carcinoma of the bladder who underwent NAC were stratified by the final pathologic stage: complete (ypT0N0), partial (≤ pT2), and nonresponse (> pT2 and/or N+). Patients treated with upfront cystectomy were divided into those with organ-confined (≤ pT2) and those with extravesical disease (> pT2 and/or N+). RESULTS: Of 145 patients, 89 received NAC and 56 underwent upfront RC. The univariate predictors of extravesical disease in the patients treated with upfront RC included increased age (P = .021), higher Eastern Cooperative Oncology Group performance status (P < .001), hydronephrosis (P = .021), and cardiovascular risk factors. The complete, partial, and nonresponse rates to NAC were 25.8%, 39.3%, and 34.8%, respectively. The multivariate predictors of pathologic progression on NAC included low serum albumin (P = .005), hydronephrosis (P = .040), incomplete NAC (P = .014), and alternative NAC (non-gemcitabine/cisplatin or MVAC, P = .022). Significant multivariate predictors of incomplete NAC included increased age, coronary artery disease (P = .027), and Eastern Cooperative Oncology Group performance status. CONCLUSION: Redundant clinicopathologic features predicted adverse cystectomy pathology in patients treated with both NAC and upfront RC. The results of the present study demonstrated an inferior pathologic response to alternative NAC regimens in clinically organ-confined disease and implicated cardiovascular comorbidities and nutritional status in the tolerability and response to NAC. Our findings predicate the importance of using patient-specific factors to guide the sequence of definitive treatment toward timely, centralized care to improve clinical outcomes.

Interstitial laser ablation of the kidney: acute and chronic porcine study using new-generation diffuser tip fiber.

BACKGROUND AND PURPOSE: Many ablative techniques have been described for treatment of small renal tumors. We investigated interstitial laser ablation (ILA) of porcine kidneys with a new-generation diffuser tip fiber. MATERIALS AND METHODS: Six female farm pigs underwent bilateral lower-pole ILA of normal kidneys via a midline approach. The acute group consisted of three pigs that underwent immediate post-treatment bilateral nephrectomy, while the chronic group survived for 45 days prior to bilateral nephrectomy. The lower pole of each kidney was treated with a diode laser in temperature-adaptive mode (100 degrees C) with the diffuser tip fiber. The treatment time was increased for each pig in each group, from 4 minutes to 8 minutes to 12 minutes. RESULTS: The acute lesions were elliptical, with the depth being longer than the width. The dimensions of the acute lesions on gross inspection were 18 x 9 and 17 x 9 mm in the 4-minute treatment pig, 25 x 6 and 18 x 15 mm in the 8-minute treatment pig, and 22 x 18 and 19 x 12-mm in the 12-minute treatment pig. Reduced nicotinamide adenine dinucleotide staining of the acute lesions revealed a nonviable zone of 14 x 18 and 15 x 10 mm in the 4-minute treatment pig, 16 x 8 and 12 x 7 mm in the 8-minute treatment pig, and 11 x 7 and 14 x 9 mm in the 12-minute treatment pig. Histologic architecture was preserved. Gross examination of the chronic kidney revealed a divot with a scar in the treatment area. Histologic examination showed an irregularly shaped area of fibrosis and loss of normal architecture, with the lesions being smaller than those seen on the acute sections. CONCLUSIONS: Interstitial laser ablation of the kidney with a diffuser tip fiber produces adequate cell death but small lesions. Further studies with multiple fibers or active monitoring and repositioning of the fiber to produce larger lesions are necessary.

Reversion of epithelial-mesenchymal transition by a novel agent DZ-50 via IGF binding protein-3 in prostate cancer cells.

Dysregulation of transforming growth factor-ß1 (TGF-ß1) and insulin-like growth factor (IGF) axis has been linked to reactive stroma dynamics in prostate cancer progression. IGF binding protein-3 (IGFBP3) induction is initiated by stroma remodeling and could represent a potential therapeutic target for prostate cancer. In previous studies a lead quinazoline-based Doxazosin® derivative, DZ-50, impaired prostate tumor growth by targeting proteins involved in focal adhesion, anoikis resistance and epithelial-mesenchymal-transition (EMT). This study demonstrates that DZ-50 increased expression of the epithelial marker E-cadherin, and decreased the mesenchymal marker N-cadherin in human prostate cancer cells. In DU-145 cells, the effect of DZ-50 on EMT towards mesenchymal epithelial transition (MET) was inhibited by talin1 overexpression, a focal adhesion regulator promoting anoikis resistance and tumor invasion. DZ-50 treatment of human prostate cancer cells and cancer-associated fibroblasts (CAFs) downregulated IGFBP3 expression at mRNA and protein level. In TGF-ß1 responsive LNCaPTßRII, TGF-ß1 reversed DZ-50-induced MET by antagonizing the drug-induced decrease of nuclear IGFBP3. Furthermore, co-culture with CAFs promoted prostate cancer epithelial cell invasion, an effect that was significantly inhibited by DZ-50. Our findings demonstrate that the lead compound, DZ-50, inhibited the invasive properties of prostate cancer epithelial cells by targeting IGFBP3 and mediating EMT conversion to MET. This study integrated the mechanisms underlying the effect of DZ-50 and further supported the therapeutic value of this compound in the treatment of advanced metastatic prostate cancer.

Use of Lowsley tractor during laparoscopic prostatectomy to reduce urethrovesical anastomotic tension.

We describe a technique to reduce the tension on the urethra while performing the urethrovesical anastomosis during a laparoscopic radical prostatectomy. A Lowsley tractor is passed through the urethral stump, and a single traction stitch is placed in the posterior bladder neck. The first anastomotic stitch is placed through the urethra and bladder neck at the 6 o'clock position but not tied. The traction stitch is then grasped with the wings of the Lowsley and retracted into the urethra, bringing the bladder neck and urethral stump into close proximity. While maintaining traction on the bladder neck, the previously placed 6 o'clock suture is tied. Before releasing the traction stitch from the Lowsley tractor and bladder neck, two additional stitches are placed at the 4 and 8 o'clock positions, completing the posterior anastomosis. Grasping the traction stitch with the Lowsley tractor relieves tension on the posterior urethra and places it on the bladder neck. This prevents urethral tears and gaps in the posterior wall. The anterior portion of the urethra and bladder neck remains open, maintaining vision. Creating a secure posterior anastomosis allows the remaining sutures to be placed under minimal tension. This technique uses an instrument readily available in the urology operating room and facilitates completion of the difficult anastomosis under minimal tension, resulting in a high-quality anastomosis with fewer gaps.

University of Kentucky experience with laparoscopic live donor nephrectomy using two different techniques.

Laparoscopic live donor nephrectomy (LDN) is becoming increasingly popular for its minimum donor morbidity and accelerated return to work. Hand-assisted laparoscopic donor nephrectomy (HALDN) may be more acceptable if the modified technique would offer easier performance. We compared our experience with HALDN and conventional LDN. From November 1998 to June 2004, two groups of patients underwent conventional LDN (n = 71) or HALDN (n = 12). Operative and extraction times, complications, and immediate graft function were compared. Mean operative and extraction times are significantly shorter in the HALDN group (206.7 versus 143.4 minutes and 225 versus 141 seconds). Two in the LDN group required open conversion (3%). Three in the LDN group showed delayed graft function (4%). Three in the LDN group developed graft renal artery thrombosis (4%). There was no ureteral complication in both groups. HALDN provides shorter operative and extraction times and better recipient surgeon satisfaction without increasing donor morbidity.

Association of epithelial-mesenchymal transition and nuclear cofilin with advanced urothelial cancer.

Tumor epithelial cells undergo a morphologic shift through the process of EMT with characteristic loss of cell polarity, conferring invasive and metastatic properties during cancer progression. Signaling by transforming growth factor-ß mediates EMT programming and its phenotypic reversal to mesenchymal-epithelial transition. The role of EMT in bladder cancer progression to advanced disease is poorly understood. In this study, we conducted a retrospective analysis of the EMT landscape and actin cytoskeleton remodeling in a series of human bladder cancer specimens. Immunoreactivity for E-cadherin, N-cadherin, and vimentin protein expression was performed toward establishing an EMT signature in human bladder cancer. Serial sections were assessed for the primary regulator of the actin cytoskeleton remodeling and transforming growth factor-ß signaling effector, cofilin. Our results demonstrate that EMT induction in clinical bladder cancer specimens is significantly associated with bladder cancer progression to high-grade, invasive disease. Evaluation of expression and cellular localization of the cytoskeleton regulator cofilin revealed a significant association between overexpression of nuclear cofilin with bladder cancer progression. This study is of translational significance in defining the value of EMT signature and cytoskeletal cofilin as potential tumor markers and targetable platforms for the treatment of invasive bladder cancer.