Gary H. Weiss

Cytoreductive surgery prior to interleukin-2-based therapy in patients with metastatic renal cell carcinoma

PURPOSE We defined the outcome of a strategy using cytoreductive surgery before high dose interleukin-2 (IL-2) therapy in patients with metastatic renal cell carcinoma. MATERIALS AND METHODS During an 11-year period, 195 patients underwent cytoreductive surgery as preparation for high dose IL-2 based therapy. The renal primary and locoregional metastatic disease that could be safely resected was removed. RESULTS Because of the large size 176 of 195 renal tumors (90%) were resected through transabdominal incision and in 45 patients (23%) a second additional significant procedure was performed. Five cases (2.6%) were unresectable and 2 (1%) perioperative deaths occurred. After surgery 121 of 195 patients (62%) were eligible for treatment with high dose IL-2 based protocols. Overall response rate to IL-2 based protocols was 18%. CONCLUSIONS Cytoreductive surgery can be performed safely in patients with metastatic renal cell carcinoma. Although the impact of cytoreductive surgery on response to immunotherapy remains undefined, this combination of primary debulking and systemic IL-2 can result in durable complete tumor regression in some patients with metastatic renal cell carcinoma.

Percutaneous Management of Transitional Cell Carcinoma of the Renal Collecting System: 9-Year Experience

PURPOSE We establish the effectiveness of percutaneous resection of transitional cell carcinomas of the renal collecting system. MATERIALS AND METHODS A retrospective analysis was done of 36 kidneys treated during a 9-year period. Adjunctive therapy with bacillus Calmette-Guerin was given in 19 cases. RESULTS Of 36 kidneys 6 were treated by immediate nephroureterectomy for aggressive disease, leaving 30 units treated by a complete course. The recurrence rate was 33%, which varied with histology as specific recurrence rates for grades 1 to 3 tumors (18%, 33% and 50%, respectively). The only cancer related mortalities occurred with grade 3 tumors. These tumors also had a higher incidence of understanding and vascular complications. Bacillus Calmette-Guerin therapy showed no significant improvement in survival. CONCLUSIONS With vigilant followup, percutaneous management of transitional cell carcinoma of the renal collecting system is an acceptable alternative to nephroureterectomy in patients with grade 1 disease, grade 2 disease who are at risk for renal insufficiency and medical contraindications to a major open operation.

URINARY AND TISSUE LEVELS OF SCATTER FACTOR IN TRANSITIONAL CELL CARCINOMA OF BLADDER

PURPOSE We previously reported increased titers of scatter factor in urine of 20 patients with transitional cell carcinoma of the bladder compared to noncancer and cancer control groups. Scatter factor was also found in bladder tumor extracts but the number of samples examined was too small for detailed analysis. We report a followup study of larger numbers of patients with transitional cell carcinoma and controls. MATERIALS AND METHODS The scatter factor content of urine samples and bladder tissue extracts was measured by enzyme-linked immunosorbent assay. Values were normalized per milligram creatinine or tissue protein. Statistical analysis was performed using the Mann-Whitney U test or, for multiple comparisons, the Kruskal-Wallis H test. RESULTS Patients with transitional cell carcinoma of the bladder (52) had higher urinary scatter factor titers than did 24 normal subjects (p < 0.001) or 14 with benign prostatic hypertrophy (p < 0.001), 49 with prostate cancer (p < 0.001) and 13 with other genitourinary tract cancers (p < 0.01). Transitional cell carcinoma cases with clinicopathological evidence of disease had greater urinary scatter factor levels than those with no evidence of disease at urine sampling (p < 0.01). However, patients with transitional cell carcinomas in remission still had much greater urinary scatter factors than did normal subjects (p < 0.001). In contrast, patients with active prostate cancer had urinary scatter factor levels similar to those in remission. Patients with muscle invasive or high grade transitional cell carcinomas tended to have higher urinary scatter factor levels than patients with nonmuscle invasive or low grade tumors, respectively, but the differences were not significant. Greater levels of scatter factor were present in tissue extracts of muscle invasive transitional cell carcinomas than in nonmuscle invasive tumors (p < 0.001) or nontumor tissue (p < 0.02). Invasion was more closely related to tissue scatter factor content than tumor grade, since high grade noninvasive transitional cell carcinomas had a scatter factor content similar to that of low grade noninvasive transitional cell carcinomas. CONCLUSIONS These studies suggest that scatter factor may be a marker of bladder cancer, urinary scatter factor titers tend to reflect disease activity and particularly high tissue titers of scatter factor are found in muscle invasive cancers. A larger prospective study will be necessary to determine the clinical significance of elevated scatter factor titers in transitional cell carcinoma of the bladder.

Lymphoceles after laparoscopic pelvic node dissection

OBJECTIVE Lymphocele formation has been infrequently reported as a complication of laparoscopic pelvic lymph node dissection (LPLND). We determined the incidence of clinical and subclinical lymphocele formation in patients undergoing transperitoneal LPLND. METHODS Charts and radiological records of 111 patients undergoing transperitoneal LPLND at this institution between January 1991 and December 1995 were reviewed to determine the incidence of lymphocele formation. RESULTS Of 111 patients undergoing LPLND, 12.6% had positive lymph nodes and received hormonal therapy. Radical retropubic (12) or perineal (28) prostatectomy was performed either simultaneously or within 2 weeks in 41% of the node-negative patients. Radiation therapy was the treatment modality in the remaining node negative patients (N = 57). Twenty-three patients undergoing radiation therapy had preplanning pelvic computed tomography (CT) scans 2 to 16 weeks (mean 8.2 weeks) after LPLND. These were reviewed by a single radiologist to determine the presence of subclinical lymphoceles. Seven patients (30.4%) had lymphoceles of varying sizes (3 large and 4 small). Although most were identified on CT scans 4 weeks after the procedure, two were identified on scans 12 and 16 weeks after the procedure (mean 6.5 weeks). None of these patients developed symptoms referable to or had treatment for the lymphocele during a 2 to 37 month follow-up (mean 20 months). Only two patients (3.5%) undergoing LPLND as an isolated procedure had clinical evidence of lymphocele formation, both of which were subsequently confirmed with CT scans (1 large, 1 small). One was treated with CT-guided drainage and sclerosis and the other resolved spontaneously. CONCLUSION The clinical incidence of lymphocele formation following LPLND remains relatively low. Only a portion of these patients requires intervention. Subclinical lymphoceles, as detected on follow-up CT scans, occur with a much greater frequency. These seldom become symptomatic requiring treatment. Rather, they appear to resolve spontaneously. Nevertheless, clinical suspicion should remain high in order to detect and properly treat symptomatic lymphoceles when they occur.

Fever Following Intracavitary Bacillus Calmette-Guerin Therapy for Upper Tract Transitional Cell Carcinoma

PURPOSE We attempted to identify the source of fever during intracavitary upper tract instillation of bacillus Calmette-Guerin (BCG). MATERIALS AND METHODS Of 34 patients who had previously undergone percutaneous resection of upper tract transitional cell carcinoma 18 received weekly intracavitary BCG through the nephrostomy tubes for 6 consecutive weeks. After treatment 6 all patients underwent nephroscopy and biopsy, and all cases were retrospectively reviewed. Parameters analyzed were BCG related symptoms, maximum temperature during treatment, maximum renal pelvic pressure during treatment, culture results, chest x-ray findings, pretreatment serum creatinine concentration, serum liver enzyme values, untoward events and treatments performed for BCG related complications. RESULTS No obvious pattern in appearance of fever occurred. During 88 treatment episodes evaluated there were 14 temperature elevations to more than 100F in 7 patients (39%). Positive urine cultures were associated with fever in only 4 cases and none was positive for Mycobacterium. There was no correlation between greater renal pelvic pressures and fever. All chest radiographs and serum creatinine levels were unchanged, and liver enzymes were normal in all but 1 patient. Two patients had prolonged fever with elevations to greater than 104F following treatment: 1 died in a motor vehicle accident and 1 died after the third BCG infusion led to overwhelming sepsis. No source of fever was identified in either patient. CONCLUSIONS Patients with low grade fever coincident with upper tract BCG may be treated conservatively simply by withholding the infusion. Fever greater than 103F should be considered an emergency condition with high potential for mortality. Immediate and aggressive attempts at identifying a source along with institution of antituberculous therapy are priorities.

Primary synovial sarcoma of the kidney: a case report with literature review.

We describe a case of primary renal synovial sarcoma (SS) in a 48-year-old man. The patient presented with hematuria and was found to have a large tumor in his left kidney on computed tomography scan. Histology revealed a highly cellular spindle cell neoplasm with minimal pleomorphism. The major differential diagnoses included leiomyosarcoma, hemangiopericytoma, and SS. The presence of focal areas with a biphasic pattern, uniformly positive immunostain for bcl-2, focally positive immunostains for epithelial membrane antigen and cytokeratin, and negative immunostains for CD-34, smooth muscle actin and S-100 established the diagnosis. This was subsequently confirmed by molecular testing for t(X;18) translocation. Since the existence of primary SS in the kidney was first suggested in 1999, to the best of our knowledge a total of 19 cases including the present case have been reported to date. Although primary renal SS is rare, these findings indicate that it should be included in the differential diagnosis of spindle cell tumors of the kidney.

A Model of Bladder Tumor Xenografts in the Nude Rat

PURPOSE An in vivo tumor model for the study of human urothelial carcinoma is desirable. Orthotopic xenografts are useful in order to better approximate human tumor cell behavior in situ. A prior model has been described in the nude mouse. However, its small bladder size limits both histologic characterization and the application of intravesical therapeutics. In the absence of preirradiation, orthotopic xenografts of human transitional cell carcinoma in the nude rat has not been previously reported. MATERIALS AND METHODS Nude rats 2 to 4 weeks of age were inoculated with 1-5 x 10(6) cells of RT4 (well differentiated papillary human bladder tumor cell line). Inoculation was performed via open cystotomy. Techniques of mucosal injury including acid treatment and cautery were explored in an effort to optimize tumor implantation and growth. Animals were sacrificed at varying intervals and histologic assessment was performed. RESULTS The overall rate of tumor implantation and growth was 93.4% (57 of 61). Tumors reliably grew within the muscularis and mucosal growth was seen as well. Intramuscular tumor growth was less differentiated and had a higher fraction of mitotic cells than mucosal tumor. Tumor growth was consistently seen as early as 2 weeks after inoculation which facilitates experimental trials. Distant metastasis was not observed. Mucosal injury did not increase the rate of tumor implantation. CONCLUSION This model is highly reproducible and will prove useful in the further study of bladder cancer progression as well as in the development of therapeutic modalities for both superficial and muscle invasive bladder carcinoma.

Tandem ureteral stents for the decompression of malignant and benign obstructive uropathy.

PURPOSE To evaluate the utility of two ipsilateral ureteral stents placed for benign and malignant ureteral obstruction. METHODS We performed a retrospective analysis of all cases of tandem ureteral stent (TUS) insertion at our institution from July 2007 through January 2013. Student t, Fisher exact, and log-rank test were used. RESULTS TUS insertion or exchange was performed in 187 cases. There were 66 patients (75 renal units) who underwent successful TUS insertion. Malignant ureteral obstruction (MUO) was the cause for obstruction in 39 renal units (34 patients) vs benign ureteral obstruction (BUO) in 36 renal units (32 patients). Four patients with BUO and 15 patients with MUO underwent stent exchanges at a mean 145 and 128 days, respectively. Serum creatinine levels were stable poststent placement (P=0.4). Degree of hydronephrosis improved (paired t test P<0.03) after stent placement for both benign and malignant cohorts. TUS placement was noted to fail (flank pain with worsening hydronephrosis or increasing creatinine level) in five renal units with MUO (12.8%) and none with BUO. Stent failure (either conventional or TUS) suggested worsening survival in those with MUO. Median survival for those with MUO and a history of stent failure (10 of 14 died, 71%) was 66 days compared with 432 days for those without a history of stent failure (8 of 20 died, 40%) (log-rank test P=0.007). CONCLUSION Our experience with the TUS, the largest to date, demonstrated that they are highly successful in both benign and malignant causes of obstruction, comparing favorably with metallic ureteral stents. Stent failure may be predictive for shorter survival.

PROSTATE CANCER SCREENING AND MANAGEMENT

Several other newer therapeutic modalities are being investigated to determine their potential role in the treatment of prostate cancer. Cryotherapy, microwave hyperthermia, laser therapy, and high-intensity focused ultrasound have all been introduced in recent years. Each of these techniques is based on a different principle, yet they all attempt to kill prostate cancer cells in a minimally invasive manner. Insufficient follow-up data are available to allow strong recommendations regarding these treatments.

Patients with bladder and lung cancer: a long-term outcome analysis.

To report on patient characteristics, stage of disease and long‐term outcome and prognosis of patients with dual bladder and lung cancers, as there is an established increased risk of smoking‐related second primary cancers, especially lung cancer, developing in patients with bladder cancer.