The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue.

INTRODUCTION: The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. MATERIALS AND METHODS: 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. RESULTS: 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. CONCLUSIONS: Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients.

Antisense DNA inhibition of tumor growth induced by c-Ha-ras oncogene in nude mice.

Antisense DNA has shown an ability to target specific oncogene transcripts and inhibit their expression in cells, but the degree to which sustained treatment can suppress total levels of an oncogenic product and alter tumorigenesis in vivo remains to be determined. In this study, NIH-3T3 cells transformed by the activated c-Ha-ras oncogene from T24 human bladder cancer cells were treated for 3 consecutive days in vitro with an antisense DNA pentadecamer complementary to a target in the 5'-flanking region of the c-Ha-ras RNA transcript. Following antisense DNA treatment, a portion of the cells was lysed for measurement of RAS p21 while the remaining cells were evaluated for tumorigeneity by injection s.c. into athymic nude mice at a dose of 5 x 10(5) cells/mouse. The 3 days of treatment with the anti-c-Ha-ras DNA reduced RAS p21 cellular levels by more than 90% while a nonspecific control DNA reduced p21 levels by approximately 20%. Tumor growth of cells treated with anti-c-Ha-ras DNA was significantly reduced for up to 14 days following the end of treatment and implantation into the mice whereas the nonspecific control DNA had no significant effect. These effects on tumor growth were evident in two different strains of nude mice and in both males and females. It is suggested that the pronounced decrease in RAS p21 levels produced by anti-c-Ha-ras DNA resulted in a reversal of the transformed phenotype, and it is this reversal which accounts for the prolonged inhibition of tumorigenesis following antisense DNA treatment.

Intravesical bacillus Calmette-Guerin for patients with high-risk superficial bladder cancer.

Intravesical bacillus Calmette-Guérin (BCG) was employed in the treatment of 55 patients with aggressive superficial transitional cell carcinoma of the bladder (cTa, cT1, cTis). All of the patients had a previous history of recurrent superficial disease, and 41 (75%) were treatment failures following other intravesical therapy. Thirty-six (66%) patients responded to treatment, and 19 (34%) were treatment failures. Twenty-seven (66%) of 41 patients with cTa-cT1 tumors and 9 (64%) of 14 patients with cTis responded, with a mean follow-up period of 30.5 months. Disease progression was noted in 8 (15%) of the patients and muscle invasive disease in 6. Patients with a history of three or more previous events of tumor recurrence, positive urinary cytology, and multicentric disease, all fared worse than patients without these characteristics (p less than 0.05). BCG is an effective agent in controlling superficial transitional cell carcinoma of the bladder, even in a high-risk group of patients who failed previous intravesical therapy. BCG should be employed in this group of patients prior to radical surgery.

Evaluation of flap valve as an alternative continence mechanism in the Florida pouch.

OBJECTIVES: To evaluate urodynamic findings in a successful flap valve (FV) continence mechanism in association with a continent colonic urinary reservoir (Florida pouch) and to compare the urodynamic findings of the FV mechanism with the doubly plicated (PI) standard anti-incontinence segment in the same reservoir. METHODS: Thirteen patients who successfully received the Florida pouch between 1988 and 1996 agreed to undergo urodynamic evaluation as part of a pilot study. Eight patients had a PI continence mechanism and a mean time from surgery of 51 months; 5 had a FV continence mechanism and a mean time from surgery of 14 months. Enterocystometry was performed with a trans-stomal Bard triple channel 7F catheter. Volume and pressure at first desire to empty (VFDE, PFDE), as well as maximal enterocystometric capacity and pressure (VMEC, PMEC), were recorded. Maximal outlet pressure (MOP) was recorded using the catheter withdrawal technique. RESULTS: PI and FV groups demonstrated the following mean values respectively: VFDE, 692.7 and 403 mL; PFDE, 19.5 and 19.2 cm H2O; VMEC, 876.5 and 515 mL; PMEC, 25.9 and 24.6 cm H2O; MOP, 57.5 and 51.2 cm H2O (reservoir empty) and 50.5 and 52.6 cm H2O (reservoir full); and functional length of outlet, 24.3 and 24.6 cm. MOP measurement demonstrated greater variability in the PI than in the FV group. CONCLUSIONS: Urodynamic comparison of these mechanisms reveals that MOP measurement was closer to the mean among FV than PI patients. In addition, the mean VFDE (692.7 mL for PI versus 403 mL for FV, P < 0.05) and the mean VMEC (876.5 mL for PI versus 515 mL for FV, P < 0.05) were significantly less in the FV group. Lower VMEC and less variability in MOP indicate that continence may be more dependent on MOP in the FV mechanism. A longer follow-up time and a larger number of patients will be of assistance in clarifying these findings.

Predictability of PSA failure in prostate cancer by computerized cytometric assessment of tumoral cell proliferation.

OBJECTIVES: To evaluate the relationship of DNA ploidy and cell proliferation (CP) with Gleason score (GS) and clinical outcome in prostate cancer. METHODS: Sixteen patients with benign prostatic hyperplasia (BPH) and 65 patients with prostate cancer classified by GS (four groups: 2 to 4, 5 to 6, 7, and 8 to 10) were studied. All patients with carcinoma underwent prostatectomy and were separated into prostate-specific antigen (PSA) failure and nonfailure groups (failure if PSA 0.1 ng/mL or more three times after surgery). Tumoral CP (Ki-67 inmunostaining and SG2M phase) and DNA ploidy were evaluated by computerized cytometry. RESULTS: BPH were diploid with low CP (8% SG2M cells or less). Carcinomas were either diploid with high CP (greater than 8% SG2M cells) or aneuploid. CP was significantly higher (P <0.001) in tumors with GS 7 or greater than in tumors with GS less than 7 (mean percent Ki-67 cells 18.3% versus 7.8%, respectively). PSA failure increased with GS (7.1% in GS 2 to 4, 21% in GS 5 to 6, 28.6% in GS 7, and 50% in GS 8 to 10), as well as with aneuploidy (18.5% in diploid tumors versus 72.7% in aneuploid tumors). Those experiencing PSA failure had significantly higher (P <0.001) CP than those not failing (mean percent Ki-67 cells 24% and mean percent SG2M 30.4% versus 8.7% and 13.5%, respectively). Cox regression analysis showed GS, DNA ploidy, Ki-67, and SG2M to each be univariately prognostic for time to PSA failure; however, Ki-67 and SG2M were more highly significant (P <0.0001 for both) than GS (P = 0.007) or DNA ploidy (P = 0.002). After adjusting for either SG2M or Ki-67 measures of CP, neither ploidy nor GS contained additional prognostic value. CONCLUSIONS: Tumor CP and DNA ploidy can be reliably determined in prostate cancer by computerized cytometry. On the basis of our preliminary results, CP correlates well with GS and predicts PSA failure better than DNA ploidy or GS.

NCCN Practice Guidelines for Prostate Cancer.

Systemic therapies for prostate cancer are likely to improve, and as they do, they will have enormous impact on the treatment of high-risk and locally advanced cancers. Further technical improvements in radiotherapy and alternative local modalities, such as cryoablation, are also likely, and will bring even more options for local control. It is certain these guidelines will continue to evolve.

Improvement in dosimetry of ultrasound-guided prostate implants with the use of multiple stabilization needles.

The use of three stabilization needles for ultrasound-guided permanent prostate implants results in better dosimetric coverage of the prostate, all other variables being equal. This technique prevents rocking motion of the prostate when anterior needles are inserted and thus improves accuracy of seed placement and shortens the length of the procedure. On post-implant CT-based dosimetric evaluation, the three stabilization needles technique provides better coverage, with the prescription isodose line encompassing 95% of the target volume compared to 90% for the implant utilizing two stabilization needles. Further improvements in the technique are currently under investigation, with the goal of consistently achieving truly "conformal anatomical prostate brachyradiotherapy."

[Continent urinary diversion with the Florida pouch]. / Dérivation urinaire continente à l'aide de la poche de Floride.

Continent urinary diversion (Florida Pouch) has been performed on 151 patients. The surgical technique utilizes a detubularized extended right colon segment, a doubly-plicated segment of ileum and a non-tunneled uretero-intestinal anastomosis. Mortality rate was 1.3%. Early and late complication rates have been minimal. 2.8% were incontinent. No radiographic renal damage has been noted and electrolyte abnormalities have not been a problem. The procedure is highly recommended to those surgeons performing continent urinary diversions.

Primary cryosurgery for clinically localized prostate cancer--do perioperative tumor characteristics correlate with post-treatment biopsy results?

OBJECTIVE: To investigate the rate and predictive factors of positive post-treatment biopsy in men treated with primary cryosurgery for localized prostate cancer. METHODS: A retrospective review was performed of all patients treated with primary cryosurgery at a single institution between 1999 and 2012. Perioperative prostate-specific antigen (PSA) levels, Gleason score, and number of positive preoperative biopsy cores were obtained and correlated with postoperative biopsy results. Patients were stratified according to the risk classification system of D'Amico to low-, intermediate-, or high-risk groups. RESULTS: Sixty-five men were treated with primary cryosurgery, and 57 of 65 (88%) of them underwent postoperative biopsy on average 9 months after the treatment. Eleven of 57 patients (19%) were found to have persistent tumor on post-treatment biopsy. Men who had positive biopsy had significantly higher perioperative PSA levels than men who had negative biopsy (preoperative PSA 12.5 vs 6.2, P = .002; post-operative PSA nadir 4.3 vs 0.71, P = .005); however, no independent predictor was found on a multivariate analysis. Gleason score and number of positive preoperative biopsy cores did not predict tumor persistence. Positive biopsy results were found more often in the intermediate- and high-risk patients, although this was not statistically significant (low risk 9%, intermediate risk 20%, and high risk 27%). CONCLUSION: Perioperative PSA levels, Gleason score, or number of positive pretreatment biopsy cores do not predict failure after primary cryosurgery for clinically localized prostate cancer. Our findings suggest that physicians, who offer primary cryosurgery to patients with localized prostate cancer, should consider offering post-treatment biopsy to patients to assure adequate cancer control.

The merits of cytology in the workup for upper tract urothelial carcinoma - a contemporary review of a perplexing issue

Introduction The importance of upper tract cytology for evaluating tumors is unclear. We correlated upper tract cytology with histologic findings in patients who underwent nephroureterectomy for upper tract urothelial carcinoma (UTUC) at a single tertiary care referral center. Materials and Methods 137 patients underwent nephroureterectomy between 2004 and 2012. 18 patients were excluded (benign tumors, atrophic kidneys with the remaining 119 patients serving as our study population). Upper tract cytology from the renal pelvis and/or ureter were retrospectively reviewed and analyzed with final pathology data in the remaining patients with UTUC. Results 57% (68/119) had preoperative upper tract cytology collected. 73% (50/68) patients had abnormal cytology (positive, suspicious) with a sensitivity of 74% (which increased to 90% if atypical included), specificity of 50% and a positive predictive value of 98%. High grade tumors were more common than expected (77% high grade vs. 20% low grade). Abnormal cytology did not predict T stage or tumor grade. Interestingly, positive upper tract cytology was found in all of the UTUC CIS specimen. Conclusions Upper tract cytology has been utilized to support the diagnosis of upper tract urothelial carcinoma. Our data demonstrates that abnormal cytology correlates well with the presence of disease but does not predict staging or grading in these respective patients. .

Radical prostatectomy in the management of clinically localized prostate cancer.

BACKGROUND: Several management options are available when prostate cancer is diagnosed at an early stage. However, the optimal treatment for localized prostate cancer is unknown, and reports in the literature are controversial regarding the best treatment modality for this early presentation. METHODS: The authors review improvements in surgical technique that have decreased complications, and they address long-term outcomes of surgery related to cancer control. RESULTS: Improvements in surgical techniques allow for decreased intraoperative complications. The incidence of long-term complications such as incontinence and impotency is also reduced. The 5- and 10-year progression-free survival with radical prostatectomy has improved. CONCLUSIONS: Surgery today is safer with improvements in techniques. The long-term outcomes with surgery are excellent and, in several series, better than outcomes achieved with other treatment modalities.

Contemporary management of superficial bladder cancer.

BACKGROUND: Bladder cancer is the second most common urologic malignancy after prostate cancer. Superficial bladder cancer presents as a heterogeneous group of tumors with variable biological potential. A significant percentage of patients diagnosed with superficial cancer will have multiple recurrences, and some will progress to invasive disease. METHODS: Patients are stratified into low- or high-risk for recurrence and progression. We review the most recent literature regarding intravesical therapy for superficial bladder cancer, and we summarize indications for the use of intravesical agents as well as their efficacy, toxicity, and cost. RESULTS: Several intravesical agents are available for the treatment of superficial bladder cancer. Patients may be identified as low- or high-risk for recurrence and progression. High-risk patients benefit from intravesical therapy. CONCLUSIONS: Superficial bladder cancer is a heterogeneous group of diseases. Treatment is effective in preventing recurrences and progression in the high-risk group.

Combined cystourethropexy for the treatment of type 3 and complicated female urinary incontinence.

We treated 37 women with type 3 stress urinary incontinence or with an associated complicating factor, such as morbid obesity, a large or proximal diverticulum or a urethrovaginal fistula, via combined transvaginal cystourethropexy. All women with type 3 stress incontinence had failed a previous anti-incontinence operation. Patients in both groups underwent suprapubic needle suspension and an additional bladder neck support procedure. Among 33 patients who underwent preoperative urodynamic studies 30 had stable bladders (90%), while 3 had low pressure detrusor instability (10%). The success rate in achieving continence, including cured and improved patients, was 94.6% with a followup of 3 to 72 months. Four patients (10%) required temporary intermittent catheterization for 3 to 4 weeks but none presented with long-term voiding dysfunction. The added bladder neck support improved our results in these complicated female incontinence cases compared to the standard suprapubic needle suspension procedures alone. The combined procedure currently is our method of choice for treatment of type 3 and other complicated cases of female urinary incontinence.

Transabdominal radical nephrectomy in ninety-one consecutive patients with Wilms' tumor.

Ninety-one children that were subjected to transabdominal radical nephrectomy are reviewed. The patients' ages ranged from 20 days to 10 years. Forty cases had a right side tumor and 44 a left side tumor; bilateral tumor incidence was 7.70% (7 cases). The tumor weight incidence was 75% for greater than or equal to 500 g and 37.5% for greater than or equal to 1,000 g. Incidence of local extension of the disease was 21.98%. Intraoperative complications were 12 ruptures of the kidney capsule, 1 laceration of the cecum, 1 opening of the pleura, 1 section of the superior mesenteric artery, and 1 section of the right common iliac artery. The mortality rate in unilateral surgery, because of intraoperative massive hemorrhage, was 3/83 (3.61%). One patient with bilateral tumor died because of acute renal insufficiency and sepsis. One patient with caval thrombus which extended up to the right atrium died because of intraoperative massive pulmonary embolism.

Testicular yolk sac carcinoma in infants: natural history in 56 consecutive patients.

Fifty six patients with yolk sac tumor are registered in the "Instituto Nacional de Enfermedades Neoplásicas" (Lima-Peru), from 1952-1980: 48.22% were less than 2 years of age; 51.78% were beyond that age.- Seventeen patients survived 3 years post diagnosis: 44% when patients less than 2 years of age and 17.2% when over two years of age. 25.9% of the patients less than 2 years of age were found to have metastases whereas 48.5% when over 2 years of age. 21/56 already had metastases when first seen. All tumors were greater than or equal to 3 cm. in diameter when first seen. Metastases were found in 38% of cases when tumors were less than or equal to 6 cm., compared to 61.9% of cases in which tumors exceeded 6 cm. 51.8% of clinical stage I survived 3 years without evidence of disease; 14.3% when stage II while none survived at clinical stage IV. It is to be expected that young patients who survive 3 years after diagnosis and treatment will not suffer a recurrence of the disease.

Female urinary incontinence: preoperative selection, surgical complications and results.

A total of 98 women with stress urinary incontinence underwent surgical repair via 3 different techniques: 38 patients underwent a Burch colposuspension (group 1), 25 underwent a Stamey procedure (group 2) and 35 had a modified Pereyra operation (group 3). The main indication for an operation was clinically unacceptable incontinence, and urodynamic studies were done on all patients with associated stress and urge incontinence or who underwent reoperation. Subtracted bladder pressure recording was an important preoperative screening tool, since patients with high pressure instability did worse surgically than those with a stable bladder or low pressure instability. In patients with detrusor stability similar results were achieved for initial surgery and reoperations. Among the patients with a stable bladder with and without a previous anti-incontinence operation the over-all results were better in groups 1 and 3 than in group 2. Complications were of lesser magnitude in groups 2 and 3 than in group 1.

Bilateral ilioinguinal lymph node dissection in the management of cancer of the penis.

Twenty-nine patients with squamous cell carcinoma of the penis underwent bilateral ilioinguinal groin dissection 6 weeks after removal of the primary penile lesion. Eighty percent of the patients were alive and without evidence of disease at 5 years when the dissected lymph nodes were negative. When positive nodes were found, 62.5% of the patients were alive and without evidence of disease at 5 years: two of these patients had one iliac deep node positive each. The mortality rate at 5 years because of progression of disease was 6.6% when the dissected lymph nodes were negative, as compared to 37.5% when the dissected lymph nodes were positive.

Results, complications and surgical indications of the Florida pouch.

One hundred and seven patients underwent continent urinary diversion using an extended, detubularized right colonic segment as the urinary reservoir and the distal part of the ileum as a continent catheterized efferent system. This reservoir allows the accommodation of a large volume of urine; urodynamics in 28 patients demonstrated a maximum reservoir capacity varying between 550 and 1,200 milliliters (an average of 747 milliliters). The reservoir maximal volume and pressure remains unchanged in six patients studied urodynamically three to four years postoperatively. Maximal reservoir pressures ranged between 10 and 58 centimeters of H2O (an average of 35 centimeters). Of 201 ureterocolonic reimplantations, four ureters were initially reimplanted using a modified Le Duc procedure, 26 ureters were subsequently managed using the Goodwin transcolonic approach and 165 reimplantations were done with a direct (nontunneled) mucosa to mucosal anastomosis. The over-all success rates with each of the three techniques (absence of reflux and obstruction) have been 75.0, 84.7 and 87.4 per cent, respectively. However, the incidence of obstruction was 13.3 per cent for the tunneled and 4.2 per cent for the non-tunneled reimplantations. Six megaureters underwent imbrication and direct reimplantation, and three of these became obstructed. One patient died of pulmonary embolism. Medical and surgical complications markedly predominated in the group who underwent simultaneous cystectomies, and in this group, the over-all complication rate was comparable with that for previously reported series with ileal conduits. The double row plication of the distal part of the ileum and ileocecal valve allows easy catheterization every four to six hours and 105 patients (97.2 per cent) remained continent between catheterizations. The stoma is covered using a small gauze, cap or sterile adhesive strip. This protects clothing from mucus production by the stoma and an occasional episode of urinary dribbling. Seven patients required reoperation for correction of incontinence or other complications. Our satisfactory experience with these patients makes this technique an excellent approach to achieving continent urinary diversion.

Management of yolk sac carcinoma of the testis clinical stage I: lymphadenectomy vs. no lymphadenectomy.

Thirty seven patients with Stage I yolk sac tumor of the testis were registered at the Instituto Nacional de Enfermedades Neoplasicas (I.N.E.N.), Lima-Peru from 1962 through 1980. Eighteen patients underwent retroperitoneal Lymph node dissection. The age incidence was 5 to 29 months except for two patients 50 and 84 months of age each. Bilateral retroperitoneal lymph node dissection was performed in seventeen patients; unilateral dissection was performed in one patient. In two patients both had one positive node at lymphadenectomy (2/18: 11%). Eleven patients (61.11%) are alive and with no evidence of disease in between 7 to 26 years post lymphadenectomy. Seven patients (38.89%) died: 4/18 (22.22%) because of progression of the disease and three patients because of no neoplastic cause. Nineteen patients did not have retroperitoneal lymph node dissection: seven patients (36.84%) are alive with no evidence of disease and 12 patients (63.16%) died: 8/19 (42.10%) because of progression of the disease and 4/19 (21%) with no neoplastic disease. In conclusion, patients with localized disease (Clinical Stage I) benefit from retroperitoneal lymph node dissection when compared to a similar group of patients not submitted to lymphadenectomy.

Transrectal ultrasound of the prostate.

One hundred and twenty-one transrectal ultrasound examinations of the prostate were performed between August and October of 1987. Indications included screening in 41 patients, evaluation of bladder outlet obstruction in 63 patients, evaluation of palpable nodules in 6 patients, and evaluation after transurethral resection of the prostate in 11 patients. A total of five patients were discovered to have prostate cancer after biopsy of a hypoechoic lesion in a normal feeling prostate by digital rectal examination. One patient was from the screening group, two patients with bladder outlet obstruction and two patients from the postransurethral resection group. All six patients with palpable nodules were diagnosed as having a cancer: Stage B2 on the rectal examination and two of the six patients were upstaged to Stage C by ultrasound criteria. In our hands transrectal ultrasound of the prostate is a valuable adjunct in the urological armamentarium with clear application in the diagnosis and staging of prostate cancer.