Intraprostatic ethanol diffusion: comparison of two injection methods using ex vivo human prostates.

BACKGROUND: Intraprostatic injection of ethanol has been previously tested in clinical trials as a potential treatment of BPH, with variable outcomes. As evident from animal studies, the inconsistency was owing to various degrees of ethanol backflow along the needle tract. In acute canine experiments, we previously documented that using convection enhanced delivery (CED) eliminates backflow and improves ethanol distribution. The goal of this study was to compare the diffusion pattern between a microporous hollow fiber catheter (MiHFC) and a standard needle in human prostates from organ donors. METHODS: Prostates were harvested from cadaveric organ donors immediately after removal of organs for transplant. After trimming off excess fat and weighing, prostates were injected with absolute ethanol. The total injected volume was 25% of the calculated prostate volume. One lateral lobe was injected using a single lumen 21-gauge control needle. The contralateral lobe was injected with the same volume but using a MiHFC. Immediately after injection, prostates were fixed en bloc in 10% neutral-buffered formalin, and then sectioned. Three-dimensional reconstruction was performed to determine lesion volume based on hematoxylin- and eosin-stained cross-sections. RESULTS: Three fresh human prostates were harvested and injected. The time from harvest to intraprostatic injection was 15-35 min. The lesion created by the MiHFC was 1.14±0.52 cm(3), whereas that from the control needle was 0.28±0.10 cm(3) (P=0.038). No backflow was observed along the needle tract of the MiHFC. CONCLUSIONS: This study shows that freshly harvested human prostates can be used to evaluate new treatments using intraprostatic injection. Similar to in vivo canine experiments, the ethanol lesion sizes were significantly bigger with the use of a MiHFC when compared with a standard single lumen needle.

Ethanol promotes cytotoxic effects of tumor necrosis factor-related apoptosis-inducing ligand through induction of reactive oxygen species in prostate cancer cells.

BACKGROUND: Effective treatment of prostate cancer (PCa) remains a major challenge due to chemoresistance to drugs including tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Ethanol and ethanol extracts are known apoptosis inducers. However, cytotoxic effects of ethanol on PCa cells are unclear. METHODS: In this study we utilized PC3 and LNCaP cell culture models. We used immunohistochemical analysis, western blot analysis, reactive oxygen species (ROS) measurement, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) Cell Proliferation Assay, Annexin-V staining and flow cytometry for quantification of apoptosis. In vitro soft agar colony formation and Boyden chamber invasion assays were used. Tumorigenicity was measured in a xenotransplantation mouse model. RESULTS: Here, we demonstrate that ethanol enhances the apoptosis-inducing potential of TRAIL in androgen-resistant PC3 cells and sensitizes TRAIL-resistant, androgen sensitive LNCaP cells to apoptosis through caspase activation, and a complete cleavage of poly (ADP)-ribose polymerase, which was in association with increased production of ROS. The cytotoxicity of ethanol was suppressed by an antioxidant N-acetyl cystein pretreatment. Furthermore, ethanol in combination with TRAIL increased the expression of cyclin-dependent kinase inhibitor p21 and decreased the levels of Bcl-2 and phosphorylated-AKT. These molecular changes were accompanied by decreased proliferation, anchorage-independent growth and invasive potential of PC3 and LNCaP cells. In vivo studies using a xenotransplantation mouse model with PC3 cells demonstrated significantly increased apoptosis in tumors treated with ethanol and TRAIL in combination. CONCLUSIONS: Taken together, use of ethanol in combination with TRAIL may be an effective strategy to augment sensitivity to TRAIL-induced apoptosis in PCa cells.

Retroperitoneoscopic living donor nephrectomy: initial experience with a unique hand-assisted approach.

The retroperitoneoscopic (RP) approach to live donor nephrectomy (LDN) may be advantageous for the donor because it avoids mobilization of peritoneal organs and provides direct access to the renal vessels. Notwithstanding, this approach is not popular, likely because of the steeper learning curve. We feel that hand-assistance (HA) can reduce the learning curve and in this study, we present our experience with a novel hand-assist approach to retroperitoneoscopic live donor nephrectomy (HARP-LDN). Over a one-yr period, 10 consecutive patients underwent left HARP-LDN with a mean body mass index of 29 and three with prior left abdomen surgery. The surgical technique utilizes a 7 cm, muscle-sparing incision for the hand-port with two endoscopic ports. Operative time was an average of 155 min., with no open conversions. Mean blood loss was 68 mL, and warm ischemia time was 2.5 min. Hospital stay averaged 2.7 d with postoperative complications limited to one urinary retention. Our modified HARP approach to left LDN is safe, effective and can be performed expeditiously. Our promising initial results require a larger patient cohort to confirm the advantages of the hand-assisted retroperitoneal technique.

Phase I/II examination of transurethral ethanol ablation of the prostate for the treatment of symptomatic benign prostatic hyperplasia.

PURPOSE: We assessed the safety of transurethral ethanol ablation of the prostate as a treatment for men with symptomatic benign prostatic hyperplasia and determined the efficacy of this procedure. MATERIALS AND METHODS: We performed a multicenter randomized trial on 79 men, 50 to 79 years old, who had drug refractory voiding symptoms (International Prostate Symptom Score greater than 12) and prostate volumes of 30 to 80 cc. Ethanol was injected transurethrally into the prostate with a curved cystoscopic needle in men randomly assigned to 1 of 3 doses: 15%, 25% or 40% of prostate volume by transrectal ultrasound. Followup evaluations were performed 1, 3 and 6 months later. Postoperative cystoscopy was performed on all patients to evaluate ablation extent and extraprostatic effects. Transrectal ultrasound volume determinations were obtained before and 6 months after transurethral ethanol ablation of the prostate. RESULTS: Adverse events were generally mild or moderate, and included hematuria (42.9%), irritative voiding symptoms (40.3%), pain/discomfort (25.6%) and urinary retention (22.1%). No serious adverse events were reported. Statistically significant improvements were seen in International Prostate Symptom Score, quality of life, maximum flow rate and prostate volume reduction (p<0.05). Improvements were consistently observed across the 3 groups without an apparent dose effect. CONCLUSIONS: In this randomized clinical trial transurethral ethanol ablation of the prostate was safe and effective at 6-month followup. No serious adverse events were encountered. Although ethanol can safely ablate prostatic tissue, further studies will be necessary before widespread clinical application.

Intraprostatic ethanol chemoablation via transurethral and transperineal injection.

OBJECTIVES: To further assess the safety and feasibility of prostatic chemoablation with ethanol and to address previous concerns associated with transperineal injection using a canine model. MATERIALS AND METHODS: The study included 25 dogs; normal saline or 98% dehydrated ethanol were injected into the prostate using both routes, at volumes of 25-50% of the total prostate volume. The prostate and adjacent structures were examined grossly and histopathologically after the dogs were killed humanely at 4 h, 7 days and 12 weeks after injection. RESULTS: Transperineal injection resulted in tissue necrosis in all prostates and significant extraprostatic necrosis in two of three animals treated. With transurethral injection, the control groups showed minimal change, whereas the group injected with ethanol resulted in lesions with variable necrosis and location. CONCLUSIONS: Intraprostatic chemoablation is possible with ethanol injection both transperineally and transurethrally. Transperineal ethanol injections were associated with more extraprostatic necrosis. Transurethral injections resulted in larger amounts of necrosis in the prostatic parenchyma with minimal extraprostatic effects. However, the extent of prostatic necrosis/ablation was inconsistent and further research is warranted.

Transurethral prostatic tissue ablation via a single needle delivery system: initial experience with radio-frequency energy and ethanol.

We report an initial clinical experience to evaluate the safety and efficacy of outpatient prostatic ablation for the treatment of symptomatic benign prostatic hyperplasia (BPH) using local anesthesia (OPAL) with radio-frequency energy and intraprostatic absolute ethanol injection (EI). Twenty-three patients were treated with OPAL and five patients were treated with EI. Pre-operative data for all patients included international prostate symptom score (IPSS), quality of life score (QL), maximum flow rate (Q(max)), and post void residual determination. Prostate specific antigen (PSA) and transrectal ultrasound prostate volume determination were also done for EI patients. Needle deployment into the prostate was carried out at the 2, 4, 8 and 10 o'clock positions for lateral lobe hyperplasia and the 6 o'clock position for middle lobe hyperplasia. IPSS, QL, Q(max) and post void residual data were collected at 1, 3, 6 and 12 months post procedure. Both procedures resulted in statistically significant reductions of IPSS and QL. Trends towards improvement were seen both for Q(max) and post void residual, with Q(max) significantly improved after OPAL. Among EI patients, the prostate volume was reduced at 6 months post treatment to 37.2+/-17.9 g from 53.0+/-19.0 g (P=0.03) preoperatively. OPAL was safe but suffered from a high re-treatment rate. EI demonstrated encouraging results with regards to safety, symptom improvement and prostate volume reduction.

Pheochromocytoma of the urinary bladder: update on new diagnostic modalities plus case report.

Extra-adrenal pheochromocytoma (PCC) is a rare entity. Its occurrence in the urinary bladder has only been reported less than 200 times. Here we present two case reports of a bladder PCC with an update on the diagnostic techniques, treatment modalities and follow-up of patients with this disease.

Ablation of canine prostate using transurethral intraprostatic absolute ethanol injection.

OBJECTIVES: Despite extensive research involving numerous treatments for benign prostatic hyperplasia (BPH), the ideal modality has yet to be discovered. This study evaluated chemoablation of the prostate using transurethral intraprostatic absolute ethanol injection (AEI) in an in vivo canine model. METHODS: Eight mongrel dogs, 7 to 10 years old, underwent transurethral intraprostatic AEI with various ethanol volumes (10 to 26 mL/animal, mean 19.9). Injection was performed using a 20-gauge, passive deflection, hollow-core needle, introduced cystoscopically by way of a perineal urethrotomy. Oral antibiotics were administered perioperatively. Blood alcohol levels were determined. The canines were kept alive for 1 hour (n = 1), 7 days (n = 2), and 21 days (n = 5) after the treatment. The dogs were observed twice daily for a minimum of 30 minutes to determine continence. At least one spontaneous voiding was recorded at each observation. Before the dogs were sacrificed, the prostate and surrounding tissues were harvested, with gross and microscopic examination performed by a single pathologist. RESULTS: Seven and 21 days after AEI, the prostates demonstrated necrosis and cavity formation. Deep injection resulted in cavity formation in a subcapsular location. Superficial injection resulted in cavity formation that was confluent with the urethra and resulted in a widened urethral lumen. No complications directly related to AEI were seen, and systemic absorption of ethanol was minimal. CONCLUSIONS: AEI can effectively ablate prostatic tissue in canines with minimal systemic absorption. No disruption of the prostatic capsule or injury to the bladder urothelium and urethral sphincter was identified. Human studies of intraprostatic AEI for BPH adenomatous tissue chemoablation are ongoing at our institution.

The Internet and patient education--resources and their reliability: focus on a select urologic topic.

OBJECTIVES: The information revolution triggered by the rapid growth of the Internet has allowed healthcare providers and patients to access a rapidly expanding volume of information. To address the quality of this information, a survey of the data on a single urology-related topic available on the Internet was performed. METHODS: The search on the World Wide Web (Web) was performed using the search engine HotBot and search directory Yahoo. The Web pages were assessed according to their relevancy to the topic chosen. Relevance rates were derived from the number of relevant sites divided by the total number of sites found. Relevant sites were subsequently ranked for quality on the basis of their accuracy, comprehensiveness, and objectivity. HotBot was then subsequently divided by domain, with each assessed separately. Yahoo was analyzed in its entirety. The resources were then compared for relevance and quality of information. RESULTS: When using the keyword "Viagra," HotBot responded with 15,109 hits. Yahoo presented 51 hits under the category, "Health: Pharmacy: Drugs and Medications: Specific Drugs and Medications: Viagra (Sildenafil)." The relevance rate for the first 50 hits in the search engine HotBot was 0.08. The relevance rates for the edu and org domains found by HotBot were 0.22 and 0.24, respectively; those for com and net were both 0.10. The relevance rate for the search directory Yahoo was 0.20. For relevant sites, the quality of the information presented was significantly higher in the Yahoo and in the HotBot domains hosted by nonprofit organizations when compared with HotBot in general and with its commercially oriented domains. HotBot overall was found to contain seven excellent sites, of which only three were found within Yahoo. CONCLUSIONS: Although the medical information available on the Web has proliferated at a remarkable rate, the number of Web sites providing complete, nonbiased information continues to represent only a small portion of the total. We have shown that the search directory Yahoo reduced the number of irrelevant sites significantly, but at the same time, some very valuable information available in HotBot was missing. At present, it may be useful to conduct searches within Yahoo followed by a review of both the edu and org HotBot domains.

Cystic hamartoma of the renal pelvis: a rare pathologic entity.

We report a case of a rare cystic renal tumor previously termed cystic hamartoma of the renal pelvis. A 53-year-old woman presented to her gynecologist with menometorrhagia. She subsequently had a computed tomographic scan that demonstrated an incidental cystic mass in the lower pole of the left kidney. Histologically, the tumor was composed of a mixture of benign mesenchymal and epithelial components. The stroma consisted of spindle cells with monomorphic nuclei and abundant eosinophilic cytoplasm that resembled smooth muscle and that reacted positively with antibodies to alpha-smooth muscle actin, desmin, and vimentin. The epithelial component was composed mostly of cysts lined by cuboidal-to-columnar epithelium. Focal dilated cysts were lined by epithelium with oncocytic features. We think that this entity is distinct from other renal tumors, including mesoblastic nephroma, cystic nephroma, or a cystic, partially differentiated nephroblastoma, and that it is best classified as a cystic hamartoma of the renal pelvis.