Pharmacoangiographic evidence of the presence and anatomical dominance of accessory pudendal artery(s).

PURPOSE: Potency preservation is one of the principal concerns surrounding newer developments in the management of organ confined carcinoma prostate. Nerve sparing techniques may not solely preserve erectile function and it is known that vascular factors may be an etiology of the dysfunction. The role of accessory pudendal arteries in the etiology and prevention of erectile dysfunction after radical prostatectomy is at present unclear. We reviewed pudendal angiograms in patients with erectile dysfunction to evaluate the prevalence and importance of these vessels. MATERIALS AND METHODS: Selective pudendal pharmacoangiograms were obtained in 79 consecutive patients with a history of erectile dysfunction. The aim was to identify accessory pudendal arteries, their origin and their significance relative to all identifiable pudendal arteries and the dorsal penile artery with respect to penile arterial inflow. RESULTS: An accessory pudendal artery was identified in 28 (35%) of the patients. The most common origin was the obturator artery. In 15 of the 28 men (54%) in whom an accessory artery was identified it appeared angiographically to be the dominant penile artery. In 3 patients it was apparently the only major arterial inflow to the penis. CONCLUSIONS: Accessory pudendal arteries may be identifiable with pharmacoangiograms in approximately a third of all men. Because they may be the dominant source of blood supply to the penis in some cases, their preservation during radical prostatectomy could be critical to erectile function following radical prostatectomy.

Delivery of intercellular adhesion molecule-1 antisense oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy/ischemia model.

OBJECTIVES: Ischemia/reperfusion injury is a leading cause of renal damage which can be improved with antisense oligonucleotide gene therapy. We have shown that polyethylene glycol (PEG) hydrogel, which also functions as a tissue sealant, is an effective topical delivery vehicle for oligonucleotides in a murine partial nephrectomy model. The objective of this study was to use and evaluate this method against intercellular adhesion molecule-1 (ICAM-1) to prevent tissue damage. METHODS: Sixty mice underwent left upper pole partial nephrectomy with 45 minutes of warm ischemia, randomized to treatment with 50 microg ICAM-1 antisense oligonucleotides embedded in PEG hydrogel, no therapy, or sham surgery. Kidneys were harvested at 24 hours and 3, 4, and 5 days. The specimens were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) for ICAM-1 messenger ribonucleic acid (mRNA), immunohistochemical staining for ICAM-1 protein, and standard histology. RESULTS: At 24 hours, qRT-PCR and immunohistochemistry data showed a significant reduction in ICAM-1 mRNA and protein expression in the antisense group versus the ischemia group, but no difference at 3 to 5 days. Histologically there was reduced inflammation and necrosis in the cortex at 24 hours. The outer and inner medulla also showed improvement at 3 to 5 days in the antisense group as opposed to the ischemia group. CONCLUSIONS: Topical PEG hydrogel delivery of antisense ICAM-1 oligonucleotides demonstrated decreased ICAM-1 mRNA expression, reduced ICAM-1 protein staining, and decreased cellular damage. The application of gene therapy through this novel topical delivery system holds potential for a highly specific, localized method of preventing tissue damage after ischemia/reperfusion injury.

Application of fibrin glue to damaged bladder mucosa in a case of BK viral hemorrhagic cystitis.

BK virus is a common cause of severe hemorrhagic cystitis refractory to standard treatment. We describe a technique to achieve hemostasis after failed conservative therapy using fibrin glue applied suprapubically while visualizing and insufflating the bladder through a cystoscope. Long-term hemostasis was achieved using this novel procedure.

Novel delivery of oligonucleotides using a topical hydrogel tissue sealant in a murine partial nephrectomy model.

PURPOSE: Ischemia/reperfusion injury is a leading cause of renal damage and antisense gene therapy has been shown to ameliorate its effects. However, this approach has been limited by current delivery methods that require high concentrations of intravenous nucleic acids lacking specificity for targeting tissues. To overcome these limitations we developed a novel murine partial nephrectomy model to evaluate polyethylene-glycol (PEG) hydrogel tissue sealant as a topical oligonucleotide delivery system. MATERIALS AND METHODS: A total of 18 male C57BL/6 mice underwent left partial nephrectomy with vascular occlusion. Hydrogel primer and then sealant were applied to the cut surface and photopolymerized. Using this method 16 additional mice received hydrogel primer mixed with Cy5 labeled fluorescent oligonucleotide (10 to 100 microg). Kidneys were harvested at various time points and assessed for oligonucleotide penetration using fluorescence microscopy. RESULTS: A survival rate of 100% (34 subjects) was obtained using this mouse model of partial nephrectomy. PEG hydrogel provided adequate protection against renal hematoma and intraperitoneal blood. Fluorescent images revealed that 50 microg was the minimum dose resulting in complete progressive cellular penetration with time. In addition to direct diffusion from the application site, movement of oligonucleotide through the subcapsular space into the cortex was an observed mechanism of distribution. CONCLUSIONS: A murine partial nephrectomy model was successfully created using PEG hydrogel. In addition to achieving hemostasis, hydrogel served as a successful depot for delivering oligonucleotides throughout the kidney.

Effect of retinoic acid and interferon alpha-2a on transitional cell carcinoma of bladder.

PURPOSE: Retinoids modulate the growth and differentiation of normal and malignant epithelial cells in vitro and in vivo. Retinoids and their analogues have been used in animal models and clinical trials of chemoprevention and superficial bladder cancer treatment. Interferons are cytokines that have antiviral, antiproliferative and immunomodulatory function. They are used in many clinical trials for the treatment of different cancers. To identify new effective agents and develop novel approaches for the chemoprevention and treatment of superficial bladder cancer we investigated the effects of a combination of retinoids and interferon alpha-2a (IFN) on growth and apoptosis in bladder cancer cell lines. MATERIALS AND METHODS: The 4 bladder cancer cell lines UM-UC-6, UM-UC-9, UM-UC-10 and UM-UC-13 were treated with 2 retinoids, namely all-trans-retinoic acid (ATRA) and 9-cis retinoic acid (9cRA), as well as with IFN or with combinations of retinoids and IFN. The ability of these agents used alone and in combination to inhibit growth, induce apoptosis and modulate gene expression was investigated. The effects of retinoids on an INF related gene were also examined. RESULTS: Most bladder cancer cell lines were resistant to growth inhibition and apoptosis induction by ATRA and 9cRA, even at a high concentration. The effects of these retinoids on cell growth and apoptosis were enhanced by IFN. The combination of ATRA and IFN induced retinoic acid receptor beta, and signal transducer and activator of transcription 1 expression in 3 bladder cancer cell lines, as detected by reverse transcriptase-polymerase chain reaction and Western blot analysis. Retinoids increased IFN-related gene expression detected by microarray analysis and real-time reverse transcriptase-polymerase chain reaction. CONCLUSIONS: The results demonstrate that IFN acts synergistically with ATRA and 9cRA in the growth and apoptosis of bladder cancer cells in vitro and suggest that this combination has a potential for the treatment of transitional cell carcinoma of the bladder.

Evaluation of polyethylene glycol based hydrogel for tissue sealing after laparoscopic partial nephrectomy in a porcine model.

PURPOSE: Polyethylene glycol (PEG) based hydrogel is available as a tissue sealant and hemostatic aid. We determined the long-term safety and efficacy of its use as a tissue sealant for laparoscopic partial nephrectomy in a porcine model. MATERIALS AND METHODS: A total of 16 swine were cycled to 1 control group and 3 treatment groups, which underwent laparoscopic partial nephrectomy with hemostasis achieved only with application of a biodegradable PEG based hydrogel. The 3 treatment groups were sacrificed at 2, 6 and 12 weeks, respectively. Humoral immune response to the hydrogel used in the porcine abdomen was examined using enzyme-linked immunosorbent assay to detect antibodies in the serum at 0, 2, 6 and 12 weeks. Cell mediated immune response was examined using a lymphocyte proliferation assay to measure the response of leukocytes to various mitogens and antigens, including the polymerized hydrogel, at the same intervals. RESULTS: Hemostasis was satisfactory after hydrogel application. No adverse effects in the immediate and delayed periods were noted. At 2, 6 and 12 weeks there were no significant differences in hemoglobin or creatinine levels, or in the humoral immune response by enzyme-linked immunosorbent assay. There was no significant difference between test and control pig reactivity to hydrogel as an antigen in the lymphocyte proliferation assay at any time point. Histologically by 6 weeks the animals had almost absorbed the hydrogel with acute inflammation and foreign body reaction resolving by 6 to 12 weeks. No deleterious effect to renal tubules was seen. CONCLUSIONS: Biodegradable PEG based hydrogel is effective for long-term use as an agent for hemostasis. There was no detectable humoral immune response and no cell mediated immune response to sealant after 2 weeks. This represents promising sealant technology and it should be further investigated for human use.

Multicentric papillary renal carcinoma in renal allograft.

A renal transplant recipient with 13 years of excellent allograft function was found incidentally to have a malignant mass in his transplanted kidney. After resection, pathological analysis showed 29 separate lesions of renal cell carcinoma. All tumors were confined within the renal capsule. The majority of tumors (21 of 29 tumors) were chromophil basophilic carcinoma with papillary architecture, 5 tumors were clear cell, 2 tumors were mixed cell type, and 1 tumor was chromophil eosinophilic papillary carcinoma. These histological findings are similar to those reported in hereditary papillary renal carcinoma. To our knowledge, this is the first case of multicentric papillary renal carcinoma occurring in the renal allograft. We speculate that the allograft in this case is predisposed to malignant changes because of preexisting genetic mutations, as well as prolonged immunosuppression.

Laparoscopic radical nephroureterectomy: results of an international multicenter study.

OBJECTIVE: To report a multicenter analysis after laparoscopic radical nephroureterectomy for pathologically confirmed upper tract transitional cell carcinoma. MATERIALS AND METHODS: A total of 116 patients (72 males; mean age 68 years) underwent laparoscopic radical nephroureterectomy at five international institutions: 51 transperitoneally, 65 retroperitoneally. Location of the primary tumor was pelvicalyceal in 70 patients (60%), ureteral in 27 (23%), and multifocal in 19 (17%). In 18 patients (15%), transurethral resection was performed for concomitant bladder tumor. The median follow-up time was 25 months (range 3-93). A minimum follow-up of 1 and 2 years was available in 77 and 41 patients, respectively. RESULTS: Five patients (4%) were converted to open surgery. The specimen was extracted intact in all 116 patients: using an Endocatch bag in 78 patients, a Lapsac in 5, and manually in 33. Pathologic staging was pTis in 5 (4%), pTa in 41 patients (35%), pT1 in 31 (26%), pT2 in 18 (15%), pT3 in 16 (13%), and pT4 in 5 (4%). Pathological grade was grade I in 26 patients (23%), grade II in 41 (35%), grade III in 34 (29%) and grade IV in 15 (12%). Histopathology revealed a positive surgical margin in five patients (4.5%): renal hilum (one), periureteral soft tissue (two), distal edge of the ureter/ bladder cuff (two). Local recurrence was noted in two patients (1.7%). Bladder recurrence was noted in 28 patients (24%) with a mean time to recurrence of 13.9+/-11.5 months. Distant metastases occurred in 11 patients (9%): lung (5), liver (3), bones (2), adrenal (1); mean time to metastasis was 13 months. Overall, 23 patients (20%) died. One-year and 2-year cancer-specific survival was 92% and 87%, respectively. Two-year cancer-specific survival according to pathologic stage was 89% for patients with pT1 disease, 86% for pT2, 77% for pT3, and 0% for pT4 (p=0.0001). Two-year survival according to pathologic grade was 88% for grade I, 90% for grade II, 80% for grade III, and 90% for grade IV (p>0.05). CONCLUSION: Laparoscopic radical nephroureterectomy appears to be an effective minimally invasive treatment for select patients with upper tract transitional cell carcinoma. Although the 2-year survival data reported herein are encouraging, longer follow-up is needed before laparoscopy can be considered as a standard treatment.

Robotic percutaneous access to the kidney: comparison with standard manual access.

PURPOSE: To evaluate the efficiency, accuracy, and safety of robotic percutaneous access to the kidney (PAKY) for percutaneous nephrolithotomy in comparison with conventional manual techniques. MATERIALS AND METHODS: We compared the intraoperative access variables (number of access attempts, time to successful access, estimated blood loss, complications) of 23 patients who underwent robotic PAKY with the remote center of motion device (PAKY-RCM) with the same data from a contemporaneous series of 23 patients who underwent conventional manual percutaneous access to the kidney. The PAKY-RCM incorporates a robotic arm and a friction transmission with axial loading system to accurately position and insert a standard 18-gauge needle percutaneously into the kidney. The blood loss during percutaneous access was estimated on a four-point scale (1 = minimal to 4 = large). The color of effluent urine was graded on a four-point scale (1 = clear to 4 = red). RESULTS: The mean target calix width was 13.5 +/- 9.2 mm in the robotic group and 12.2 +/- 4.5 mm in the manual group (P = 0.57). When comparing PAKY-RCM with standard manual techniques, the mean number of attempts was 2.2 +/- 1.6 v 3.2 +/- 2.5 (P = 0.14), time to access was 10.4 +/- 6.5 minutes v 15.1 +/- 8.8 minutes (P = 0.06), estimated blood loss score was 1.3 +/- 0.49 v 1.7 +/- 0.66 (P = 0.14), and color of effluent urine following access was 2.0 +/- 0.90 v 2.1 +/- 0.7 (P = 0.82). The PAKY-RCM was successful in obtaining access in 87% (20 of 23) of cases. The other three patients (13%) required conversion to manual techniques. There were no major intraoperative complications in either group. CONCLUSIONS: Robotic PAKY is a feasible, safe, and efficacious method of obtaining renal access for nephrolithotomy. The number of attempts and time to access were comparable to those of standard manual percutaneous access techniques. These findings provide the groundwork for the development of a completely automated robot-assisted percutaneous renal access device.

Local hemostasis during laparoscopic partial nephrectomy using biodegradable hydrogels: initial porcine results.

BACKGROUND AND PURPOSE: Despite the advance of laparoscopic partial nephrectomy, significant technical limitations remain with regard to control of bleeding and closure of the collecting system. An attractive approach on the horizon for local hemostatic and wound control is the use of local tissue sealants. To date, sealants remain largely derived from natural biologic products and are difficult to apply laparoscopically with precise local control. In this study, we examined the novel strategy of forming occlusive tissue-adherent hydrogels utilizing a synthetic biodegradable polyethylene glycol-lactide copolymer (PEG-lactide) as an in situ occlusive barrier for hemostasis and wound control. Specifically, the objects of this study were to determine if PEG-lactide hydrogels could be formed intraperitoneally on renal tissue, to test the adhesiveness of the hydrogels to injured renal parenchyma, and to evaluate the ability of adherent hydrogel barriers to limit renal parenchymal bleeding and collecting system leakage following renal pole amputation or wedge excision. MATERIALS AND METHODS: Five kidneys from three female pigs were used in a nonsurvival study. A standardized model for laparoscopic partial nephrectomy was created by performing wedge excision or polar amputation under vascular control using a laparoscopic Satinsky clamp. Bleeding briskness following injury was assessed utilizing a scoring system and free blood quantitated comparing a conventional "clamp and wait" strategy with an adherent hydrogel strategy. For the hydrogel group, PEG-lactide hydrogel primer and macromer were applied through laparoscopic ports. The hydrogel was polymerized using a xenon light source, and the pedicle clamp was released to observe for bleeding. A subsequent opposite polar injury was created to confirm renal perfusion and the sites were compared. The kidneys were removed, and the adhesion of the hydrogel to the renal parenchyma was examined. RESULTS: The PEG-lactide macromer was effectively applied to five kidneys following partial nephrectomy. In all cases, successful intraperitoneal in situ polymerization was achieved, with resultant hydrogel formation. Polymeric hydrogel adhesion to the cut renal parenchyma was assessed semiquantitatively following vigorous cyclic washing. In all cases, polymer gels remained adherent without any evidence of peeling, delamination, or separation from the underlying tissue surface. In the control group, the mean bleeding score was 2.63 +/- 0.48 v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). Blood loss in the control group was 56 +/- 5 ml v 0.00 +/- 0.00 in the gel-treated group (P < 0.001). In an ex vivo retrograde ureteral perfusion, no leakage was observed at pressure as high as 100 mm Hg. CONCLUSIONS: In this feasibility study, a biodegradable PEG-lactide polymer system photopolymerized rapidly in situ on exposed renal parenchymal surfaces, forming adherent hydrogel barriers. When applied during vascular clamping, an adequate physical bond and patch-like cap was created to prevent bleeding at physiologic renal perfusion pressures. Use of locally applied occlusive hydrogels holds promise for hemostasis and local wound control during laparoscopic urologic procedures.

A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine.

PURPOSE: We determine the sensitivity and specificity of various assays for the detection of urothelial carcinoma. MATERIALS AND METHODS: A total of 280 voided urine specimens from 265 patients were obtained immediately before cystoscopy for BTA stat, (Bard Diagnostic, Redmond, Washington) hemoglobin dipstick, (Bayer, Elkhart, Indiana) telomerase and UroVysion (Vysis, a wholly owned subsidiary of Abbott Laboratories, Abbott Park, Illinois) analysis. RESULTS: Of the 265 patients 75 had biopsy proven urothelial carcinoma, and the sensitivity of the assays was determined from these patients. From most sensitive to least sensitive, the overall sensitivity of UroVysion (73 cases), BTA stat (72), hemoglobin dipstick (73) and telomerase (70) was 81%, 78%, 74%, and 46%, respectively. Each of the first 3 tests was statistically significantly more sensitive than the telomerase assay (p <0.05). However, the differences in overall sensitivity of UroVysion, BTA stat and hemoglobin dipstick were not statistically significant. The specificity of the tests was calculated for 80 of the 265 patients in this study who had no history of urothelial carcinoma and negative cystoscopy findings despite common urological complaints. From most specific to least specific, the specificity of UroVysion, telomerase, BTA stat and hemoglobin dipstick was 96%, 91%, 74% and 51%, respectively. UroVysion and telomerase were statistically significantly (p <0.01) more specific than the BTA stat and hemoglobin dipstick assays, and all of the assays were more specific than hemoglobin dipstick testing (p <0.001). CONCLUSIONS: Our study reveals that UroVysion is the most sensitive and specific assay among those tested for the detection of urothelial carcinoma. Telomerase testing had good specificity but poor sensitivity. The BTA stat and hemoglobin dipstick tests had good sensitivity but relatively poor specificity. UroVysion is a promising new assay for the detection of urothelial carcinoma in urine specimens. However, further studies are needed to explore the role of the various assays in the treatment of patients with superficial urothelial carcinoma.

Early repeated exploration after laparoscopic urologic surgery: comparison of clinical, radiologic, and surgical findings.

OBJECTIVES: To correlate the clinical scenarios and radiographic findings with the operative findings in patients who underwent repeated exploration to define a management strategy. Postoperative complications after laparoscopy may cause diagnostic challenges because of atypical presentation. METHODS: We retrospectively reviewed the records from 1226 urologic laparoscopic procedures between July 1993 and July 2000. We compared the clinical, radiologic, and surgical findings of patients who underwent repeated exploration within the first month after laparoscopy. RESULTS: During the study period, 9 patients (0.7%) were taken back to the operating room for repeated exploration. The median time for the appearance of symptoms was the second postoperative day. Eight patients were evaluated by computed tomography (CT) and one by both renal Doppler ultrasonography and MAG-3 renal perfusion scan. Repeated operations were laparoscopic in 4 and open in 5 patients. In all the patients evaluated by CT scan, the radiologic findings were consistent with the surgical findings. In the patients who underwent diagnostic laparoscopy because of the severity of clinical findings, despite negative CT findings, no abnormality was discovered at exploration. In 1 patient who was not evaluated by CT, duodenal perforation was detected at exploration. CONCLUSIONS: Clinical findings may not be sufficient for the decision of repeated operation for patients acutely ill after laparoscopy. CT findings correlated well with the findings at exploration. In cases in which no abnormality is detected by CT, it appears reasonable to withhold surgical exploration unless the clinical situation deteriorates.

Laparoscopic pyeloplasty with concomitant pyelolithotomy.

PURPOSE: We present our experience with laparoscopic pyeloplasty plus pyelolithotomy in patients in whom stones were not the cause of ureteropelvic junction obstruction. MATERIALS AND METHODS: A transperitoneal approach was used for laparoscopic pyeloplasty and pyelolithotomy in 19 patients (20 renal units). Before ureteropelvic junction repair stones were extracted through a small pyelotomy that was eventually incorporated into the final pyeloplasty incision. Stones in the renal pelvis were removed with rigid graspers under direct laparoscopic vision. A flexible cystoscope introduced through a port was used to extract stones in the calices. The renal pelvis was reconstructed based on the anatomy of the ureteropelvic junction. RESULTS: A median of 1 stone (range 1 to 28) was recovered. In 11, 8 and 1 patients the Anderson-Hynes dismembered pyeloplasty, Y-V plasty and the Heinecke Mickulicz procedure were performed, respectively. At 3 months 2 patients had residual calculi for a procedural stone-free rate of 90%. There was no evidence of obstruction in 18 of the 20 cases (90%), as confirmed by negative diuretic scan or radiological improvement of hydronephrosis. At a mean followup of 12 months (range 3 to 57) 2 additional patients had recurrent stones for an overall long-term stone-free rate of 80% (16 of 20). CONCLUSIONS: Laparoscopic pyelolithotomy is feasible when combined with pyeloplasty. Our results are comparable to those of stone removal during open pyeloplasty or percutaneous endopyelotomy. The advantages of open surgery appear to be maintained in this minimally invasive approach.