Daniel B. Rukstalis

Use of a New Tumor Marker, Urinary NMP22, in the Detection of Occult or Rapidly Recurring Transitional Cell Carcinoma of the Urinary Tract Following Surgical Treatment

PURPOSE We evaluated the ability of an immunoassay for nuclear matrix protein 22 (NMP22 test kit) to predict the subsequent disease status of patients with transitional cell carcinoma of the urinary tract at approximately 10 days after transurethral resection of bladder tumor. MATERIALS AND METHODS A total of 90 patients with transitional cell carcinoma provided voided urine samples at least 5 days postoperatively. NMP22 was determined using a commercial test kit. At initial cystoscopic examination 3 to 6 months later the disease status was recorded, and the NMP22 values before and after transurethral resection of bladder tumor were compared. RESULTS Of 125 followup cystoscopic examinations (60 patients had 1, 26 had 2, 3 had 3 and 1 had 4 recurrences) transitional cell carcinoma was pathologically confirmed in 33. No malignancy was present at 79 examinations (if tumor was seen endoscopically, pathological evaluation indicated atypia, dysplasia or no abnormality). NMP22 values in these 2 populations were significantly different (malignancy median 20.81 units per ml. and no malignancy median 5.72 units per ml., Mann-Whitney U test for differences between 2 medians p = 0.00005). Of the 33 recurrences 23 (70%) had NMP22 values greater than the reference range (10 units per ml.). Additionally, NMP22 identified all 6 subjects (100%) who had invasive disease 3 to 6 months later. Of 72 patients with NMP22 less than 10 units per ml. 62 (86%) had no malignancy at subsequent cystoscopy. CONCLUSIONS NMP22 was highly predictive of tumor status at followup cystoscopy. This quantitative, noninvasive assay, with high negative predictive value (86%) and sensitivity to detect malignancy (100% for invasive disease and 70% overall), may be a helpful adjunct to cytology and endoscopy for monitoring disease status after endoscopic tumor resection.

Complications of Laparoscopic Pelvic Lymph Node Dissection

Intraoperative and postoperative complications were assessed in the first 372 patients undergoing laparoscopic pelvic lymph node dissection at 8 medical centers. In 16 patients laparoscopic node dissection could not be completed due to patient body habitus or technical difficulties. Of these aborted procedures 14 occurred during the initial 8 dissections at each institution. A total of 55 complications (15%) occurred: 14 were noted in the intraoperative and 41 in the postoperative period. Of these patients 13 required open surgical intervention for the treatment of a complication. Complications included vascular injury (11 patients), viscus injury (8), genitourinary problems (10), functional/mechanical bowel obstruction (7), lower extremity deep venous thrombosis (5), infection/wound problem (5), lymphedema (5), anesthetic complications (2) and obturator nerve palsy (2). Based on our experience, there is a significant learning curve associated with performing laparoscopic pelvic node dissection. However, with experience and adherence to laparoscopic surgical principles, the risk of complications may be minimized.

Best Practice Statement on Cryosurgery for the Treatment of Localized Prostate Cancer

Introduction The protracted natural history of clinically localized prostate cancer has confounded the development of a national consensus regarding the optimal treatment for this disease. In the AUA 2007 Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update, multiple treatment modalities are considered as options. This conundrum is further complicated by stage migration and lead time bias, both associated with PSA-based early detection strategies and the resultant increase in the detection of small volume clinically localized cancers. Since the majority of men currently diagnosed with prostate cancer are likely to have the disease eradicated by one of several treatment modalities, the clinical focus on HRQL associated with treatment has intensified. There are no published long-term data on the efficacy of cryosurgery on metastasis-free, prostate cancerspecific, or overall survival as there are with other more established forms of therapy; however, several large, single institution experiences, a pooled analysis, and several prospective evaluation studies report the efficacy and morbidity of cryosurgery of the prostate. Additionally, prostate cryosurgery has been found to result in acceptable HRQLbased outcomes with a reduced cost when compared to other local therapeutic options. Short-term PSA relapse-free survival outcomes following cryoablation of the entire prostate comparable to radiation therapy in men with intermediateand high-risk disease have been reported. Bio-

Urinary Nuclear Matrix Protein as a Marker for Transitional Cell Carcinoma of the Urinary Tract

PURPOSE The purpose of this trial was to evaluate an immunoassay for urinary nuclear matrix protein, NMP22, as an indicator for transitional cell carcinoma of the urinary tract. MATERIALS AND METHODS Three groups of subjects participated in this trial of NMP22: 1-175 with transitional cell carcinoma, 2-117 with benign urinary tract conditions and 3-375 healthy volunteers. Each subject provided a single (3 voids) urine sample for analysis at the time of study entry. Each sample was assayed for the level of NMP22. RESULTS In normal healthy volunteers and in subjects with benign conditions median NMP22 levels were 2.9 and 3.3 units per ml., respectively. Median urinary NMP22 levels in patients with transitional cell carcinoma were significantly greater than in comparison subjects. Patients with active transitional cell carcinoma had significantly greater median urinary NMP22 levels than those with no evidence of disease (6.04 versus 4.11 units per ml., p = 0.027, 1-tailed Mann-Whitney U test). We noted no effect of tumor grade, extent of disease or exposure to intravesical therapy on urinary NMP22 levels. CONCLUSIONS NMP22 is a promising urinary tumor marker for monitoring transitional cell carcinoma. Nuclear matrix proteins are a new class of tumor markers that represent the basis for the development of assays with increased efficacy for the detection and treatment of cancer.

Laparoscopic Retroperitoneal Lymph Node Dissection in a Patient with Stage 1 Testicular Carcinoma

Minimally invasive laparoscopic surgical techniques are being increasingly applied to the treatment of urological diseases. We report a case of a laparoscopically performed modified bilateral retroperitoneal lymph node dissection for clinical stage 1 testicular cancer. The laparoscopic surgical approach to the retroperitoneal nodes is a technically feasible procedure that can remove lymph node tissue from all primary landing sites for testicular cancer metastases with potentially decreased morbidity.

Transdermal estrogen in the treatment of hot flushes in men with prostate cancer

OBJECTIVES To assess the effectiveness and tolerability of transdermal estrogen in men with hot flushes after hormonal therapy for prostate cancer. METHODS Twelve men with moderate to severe hot flushes were randomized to receive either low-dose (0.05 mg) or high-dose (0.10 mg) estrogen patches applied twice weekly for 4 weeks. After a 4-week washout period in which no treatment was given, each patient received the alternative dose for 4 weeks. Treatment response was assessed by daily logs and questionnaires completed every 4 weeks that included a visual analog assessment. Serum luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels were also measured every 4 weeks during the study. RESULTS There was a significant reduction in the overall severity of the hot flushes seen in patients with both the low and high-dose estrogen patch. A significant reduction in the daily frequency of the hot flushes was seen with the high-dose patch only. Overall, 10 (83%) of 12 men reported either mild, moderate, or major improvement in symptoms with either the low or high-dose patch. Mild, painless breast swelling or nipple tenderness was noted in 2 (17%) and 5 (42%) of 12 men treated with the low and high-dose estrogen patch, respectively. FSH levels decreased significantly with both the low and high-dose patch. Estradiol levels increased from 12.1 to 16.4 pg/mL and 26.9 pg/mL with the low and high-dose patch, respectively. There was no significant change in serum testosterone or luteinizing hormone levels. CONCLUSIONS Transdermal estrogen appears to be a promising, well-tolerated therapy for men with hot flushes after endocrine treatment for prostate cancer. Further study in larger groups of patients is necessary to assess the relative effectiveness and morbidity of this treatment.

Group Consensus Reports from the Consensus Conference on Focal Treatment of Prostatic Carcinoma, Celebration, Florida, February 24, 2006

( EPORT OF CONSENSUS GROUP 1: ATHOBIOLOGY OF PROSTATE CANCER: MPLICATIONS FOR FOCAL THERAPY ocal ablative therapy may be reasonable for some atients with prostate cancer; selection factors include variety of clinical and pathologic factors in combiation with informed patient choice. Our group evalated 4 specific pathologic features that may influence his treatment decision. We reviewed the published iterature for applicable studies regarding the natural istory of prostate cancer, multifocality, cancer volme, and accuracy of cancer detection by current ethods. Results were as follows:

Statin-induced autophagy by inhibition of geranylgeranyl biosynthesis in prostate cancer PC3 cells.

Autophagy is a cellular process of degradation of macromolecules and organelles and activated under nutritional stress. Statins are a class of inhibitors of 3‐hydroxyl‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase, a key enzyme in synthesis of cholesterol. Epidemiological studies have shown that statin use decreases the incidence of advanced prostate cancer. We explored the idea that treatment of atorvastatin, a commonly prescribed statin for treatment of hypercholesterolemia, induces autophagy in prostate cancer cells.

Laparoscopic Retroperitoneal Lymphadenectomy: Multi-Institutional Analysis

Modified unilateral laparoscopic retroperitoneal lymph node dissection was attempted in 20 patients with nonseminomatous testicular cancer. The procedure was completed in 18 men at a median operative length of 6 hours. Median estimated blood loss was 250 cc and median number of lymph nodes removed was 14.5. Nodal disease spread was noted in 3 of 18 patients (17%). Most patients were hospitalized for 3 days or less and had returned to normal activity levels within 2 to 3 weeks. Antegrade ejaculation was preserved in all 20 patients. Significant complications occurred in 6 of 20 patients (30%), with bleeding being the most common adverse event encountered. In 2 patients an abdominal incision and completion of the procedure by open retroperitoneal lymph node dissection were required due to significant bleeding following injury to the gonadal vessels. With a median followup of 10 months (range 2 to 25), 2 men had pulmonary disease recurrence and none had abdominal recurrence. Laparoscopic retroperitoneal lymph node dissection can be completed successfully in patients with stage I testicular cancer and may be most appropriate in those with limited risk of metastatic disease spread. The morbidity may be largely attributed to a steep learning curve. The efficacy of laparoscopic retroperitoneal lymph node dissection compared with standard techniques and determination of its role in patients with testicular cancer will require longer followup in larger groups of patients.

Laparoscopic Pelvic Lymph Node Dissection: A Review of 103 Consecutive Cases

Laparoscopic pelvic lymph node dissection is a recently introduced technique for the surgical evaluation of the regional pelvic lymph nodes in genitourinary malignancies. We report the results of a laparoscopic pelvic lymph node dissection performed on 103 consecutive patients for staging of clinically localized prostatic, bladder and penile carcinomas. In 20 patients (group 1) the adequacy of the laparoscopic pelvic lymph node dissection was evaluated with a subsequent open dissection. In this group 87 to 95% of the lymph nodes within a modified template could be reliably removed laparoscopically. In 73 patients (group 2) laparoscopic pelvic lymph node dissection was performed as a solitary operation. Mean hospitalization was 1.6 +/- 2.4 days, while postoperative narcotic requirements were minimal. Mean operative time for bilateral laparoscopic pelvic lymph node dissection was 156 +/- 41.2 minutes. The overall complication rate in these 2 groups was 13.5%. Group 3 includes 10 patients (9.7% of the total) in whom laparoscopic pelvic lymph node dissection was unsuccessful. The minimally invasive surgical techniques of laparoscopic pelvic lymph node dissection seem to provide adequate staging accuracy in patients with genitourinary neoplasms. The complication rate and recovery period appear to be decreased relative to those for open surgical lymphadenectomy.