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Purpose: T stage stratification of organ confined renal tumors is based only on tumor size. Currently T1a and T1b are defined as tumors less or greater than 4 cm. However, to our knowledge the validity of this stratification has not been determined. We determined whether symptoms could add additional prognostic information when integrated with tumor size into the TNM classification., Materials and Methods: Patients with T1-T2N0M0 renal tumors at 6 academic centers in Europe and the United States were included in this study. T stage was defined according to the 2002 TNM classification. Age, gender, T stage, tumor size, symptoms at presentation, Fuhrman grade and cancer specific survival were determined in all cases. Survival estimates were compared using the Kaplan-Meier method and multivariate analysis of the data were performed with the Cox model., Results: A total of 1,771 patients with pT1-T2N0M0 renal tumors were included in this study. There were 1,148 males and 623 females. Mean age was 59.6 years. Median tumor size was 5 cm. Of the tumors 781 (44.1%), 616 (34.8%) and 374 (21.1%) were stages T1a, T1b and T2, respectively. In 825 patients (46.6%) symptoms were related to renal cancer. T stage and symptoms strongly correlated, in that 67%, 51% and 29% of patients with T1a, T1b and T2 tumors, respectively, were asymptomatic. Symptoms increased the risk of cause specific death for each T stage level. On multivariate analysis Fuhrman grade (HR 1.46), T stage (HR 1.81) and symptoms (HR 2.98) were independent predictors of survival. Based on these results 4 groups resulting from combinations of 2002 TNM stage and symptoms with significantly different risks of death were defined, namely 1) T1a-4 cm or less without symptoms, 2) T1b-4 cm or less with symptoms and greater than 4 cm without symptoms, 3) T2a-greater than 4 cm and 7 cm or less with symptoms, and 4) T2b-greater than 7 cm with symptoms, Conclusions: In this study we noted that a system combining tumor size and symptoms can accurately stratify patients for predicting survival in those with organ confined renal tumors. Our data support the idea that symptoms should be integrated in further modifications of the TNM system.

Purpose: We validate the prognostic value of a symptom based classification (S classification) in a multi-institutional study., Materials and Methods: A total of 2,242 patients from 5 European centers were included in this study. Based on symptoms at diagnosis, patients were stratified into 3 groups of S1-asymptomatic tumors, S2-tumors with local symptoms and S3-tumors with systemic symptoms. Variables such as age, gender, tumor size, TNM stage, Fuhrman grade, Eastern Cooperative Oncology Group (ECOG) performance status, perinephric fat, renal vein and adrenal invasion were also considered for prognostic value. The end point of the study was cancer specific survival. Survival assessment was made with univariate and multivariate analyses using the Kaplan-Meier method and Cox regression analysis., Results: Of the patients 1,018 (45.4%) were classified as S1, 865 (38.6%) S2 and 339 (16.0%) S3. The S classification correlated to tumor stage, grade and ECOG (p <0.001). On univariate analysis ECOG performance status, S classification, tumor size, TNM stage, Fuhrman grade, and adrenal, perinephric fat or vein invasion were significant prognostic factors (p <0.001). The S classification provided a significant prognostic stratification in the aggregate as well at each of the 5 centers. On multivariate analysis the S classification, TNM stage, Fuhrman grade, and perinephric fat and renal vein invasion remained independent prognostic factors (p <0.001)., Conclusions: This study confirms that it is possible to graduate symptoms for a prognostic purpose. The proposed symptom score should be evaluated for its integration in prognostic algorithms.

Purpose: We compared cancer specific survival of patients undergoing partial and radical nephrectomies for T1N0M0 renal tumors according to tumor size in a large multicenter series., Materials and Methods: A retrospective analysis of 1454 patients undergoing partial or radical nephrectomy for T1N0M0 renal tumors from 7 international academic centers was performed. Data were obtained for each patient including TNM stage (determined according to the 2002 TNM criteria), tumor size, type of surgery (partial versus radical nephrectomy) and cancer specific survival. Recurrence events were recorded when available., Results: Partial and radical nephrectomies were performed in 379 (26.1%) and 1075 (73.9%) cases, respectively. Mean followup +/- SD was 62.5 +/- 51.8 months. Recurrence data were available on 544 patients. There were no significant differences in local or distant recurrence rates between patients undergoing partial or radical nephrectomy for either T1a (p = 0.6) or T1b tumors (p = 0.5). For patients with T1a tumors, there was no significant difference in the rate of cancer specific deaths between the partial (314) and radical (499) nephrectomy groups (2.2% versus 2.6%, respectively, p = 0.8). For patients with T1b tumors there was also no significant difference in the rate of cancer specific deaths between patients undergoing partial (65) and patients undergoing radical (576) nephrectomy (6.2% versus 9%, respectively, p = 0.6)., Conclusions: Partial nephrectomy is becoming the gold standard for renal tumors less than 4 cm but this treatment is much more controversial for larger T1 tumors. This large multicenter study suggests that it is safe to expand the indications of partial nephrectomy to include patients with T1N0M0 tumors up to 7 cm. However, careful patient selection remains necessary.

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses, while IL-10 is released during T helper 2 responses. We evaluated the prognostic value of urinary IL-2, interferon-gamma and IL-10 levels in patients with superficial bladder cancer treated with bacillus Calmette-Guerin (BCG) instillation., Methods: Urinary IL-2, interferon-gamma and IL-10 were measured by enzyme-linked immunosorbent assay in 37 patients receiving BCG for stages Ta/T1 superficial bladder cancer, and carcinoma in situ. Measurements were made after instillations 5 and 6 during a course of 6 weekly instillations of 150 mg. BCG, Pasteur strain. Correlations of cytokine levels with the clinical outcome were evaluated using the log rank test., Results: Median followup was 29 months. Patients with urinary IL-2 less than 27 pg./micromol. creatinine were significantly more likely to have recurrences than those with higher values (log rank test p = 0.0009). Urinary IL-10 and interferon-gamma levels had no apparent impact on the risk of recurrence or progression., Conclusion: Urinary IL-2 levels may serve to identify patients at risk for bladder cancer recurrence after a single course of BCG and, thus, to tailor individual treatment.

Purpose: Interleukin (IL)-2 and interferon-gamma are released during T helper 1 lymphocyte responses and IL-10 is released during T helper 2 lymphocyte responses. We have previously reported that a T helper 1 lymphocyte urinary cytokine profile is associated with a favorable prognosis after bacillus Calmette-Guerin (BCG) treatment. We evaluated the T helper 1/2 lymphocyte cytokine profiles during courses 1 and 2 of 6 weekly BCG instillations., Materials and Methods: Urinary interferon-gamma, IL-2 and IL-10 were measured by enzyme-linked immunosorbent assay after each of 6 weekly instillations of 150 mg. BCG, Pasteur strain, in 19 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. The 11 patients who did not respond to course 1 were re-treated according to the same schedule and reevaluated., Results: During course 1 interferon-gamma was higher than during course 2 (p <0.001), which was associated with nonrecurrence (p <0.001). In contrast, IL-2 cytokine was higher after course 2 (p <0.01), which was associated with a BCG response (p = 0.01). Interferon-gamma and IL-10 correlated during courses 1 and 2 (p = 0.04 and 0.0004, respectively). We distinguished groups 1-immediate T helper 1 lymphocyte profile consisting of responders to course 1 with high interferon-gamma, IL-2 and IL-10, 2-delayed T helper 1 lymphocyte profile consisting of responders to course 2 with early high IL-2 and 3-consisting of nonresponders to the 2 courses with low interferon-gamma, IL-2 and IL-10., Conclusions: A T helper 1 lymphocyte urinary cytokine profile was associated with a clinical response to BCG. A repeat BCG course induces a favorable immune response in a subset of patients, suggesting that maintenance therapy may be beneficial.

Purpose: To determine the occurrence of penile small nerve fiber damage following transurethral resection of the prostate (TURP) for benign prostatic hypertrophy (BPH)., Materials and Methods: Penile nerve function was evaluated in 18 consecutive patients prior to and one month after TURP for BPH. To test nerve fibers of small diameter, the penile warm and cold sensory thresholds were measured by means of a Peltier-based device, as well as the penile sympathetic skin potentials obtained following electrical stimulation at the wrist. To test nerve fibers of large diameter, the pudendal nerve somatosensory evoked potentials (pSEPs) and the penile vibratory thresholds were recorded. Clinical erectile function was quantified using a standardized questionnaire (erectile dysfunction symptom score, EDSS). Urinary handicap was assessed by the measurement of maximum flow rate (MFR) at uroflowmetry and by a standardized questionnaire (AUA symptom score, AUASS)., Results: Penile warm threshold (+7.8 vs +6.3C, p = 0.005), cold threshold (-8.5 vs -5.7C, p = 0.003) and vibratory threshold (9.3 vs 7.9 microm., p = 0.03) were significantly higher after than prior to TURP. The amplitude of pSEPs tended to decrease (1.7 versus 2.3 microV, p = 0.06), whereas the remaining neurophysiological parameters were unchanged. Clinical assessment by EDSS demonstrated a significant postoperative erectile function impairment (20.2 vs 17.5, p = 0.04), whereas mictional function improved (MFR: 19 vs 8.8 ml./s and AUASS: 4.9 versus 15.1, p < 0.0001)., Conclusions: This study highlights the occurrence of penile small nerve fiber damage following TURP and supports the hypothesis of neurogenic damage as the primary cause of post-operative erectile dysfunction.

Purpose: We investigate the potential use of the phytotherapeutic PC-SPES to treat human prostate cancer, and evaluate its in vivo and in vitro activity, and clinical efficacy., Materials and Methods: PC-SPES was evaluated for its ability to induce apoptosis on prostate cancer cell lines LNCaP, PC3 and DU145. The effect of oral PC-SPES on growth of PC3 tumors present in male immunodeficient mice was studied. A total of 30 male nude mice were divided in 5 groups. In groups 1 control and 2 full dose therapy was started the same day of the tumor injection. In groups 3 control, 4 half dose and 5 full dose PC-SPES therapy was initiated 1 week after tumor injection. A total of 69 patients with prostate cancer were treated with 3 capsules of 320 mg. PC-SPES daily. Serum prostate specific antigen (PSA) responses and side effects were evaluated., Results: All of the cultured prostate cancer cell lines had a significant dose dependent induction of apoptosis following exposure to an alcoholic PC-SPES extract. Immunodeficient mice xenografted with the PC3 cell line had reduced tumor volume compared with sham treated controls when they were treated with a PC-SPES extract from the time of tumor cell implantation (931 +/- 89 versus 1,424 +/- 685 mm.3, p not significant) but not when the treatment was begun 1 week after tumor cell implantation. The testis, prostate, bladder and seminal vesicles of the treated mice were significantly reduced in weight compared with the sham treated animals. Of the patients with prostate cancer 82% had decreased serum PSA 2 months, 78% 6 months and 88% 12 months after treatment with PC-SPES. Side effects in the treated patient population included nipple tenderness in 42% and phlebitis requiring heparinization in 2%., Conclusions: An extract of the phytotherapeutic agent PC-SPES proved to be active in inducing apoptosis of hormone sensitive and insensitive prostate cancer cells in vitro, and in suppressing the growth rate of a hormone insensitive prostate cancer cell line in vivo. The overwhelming majority of patients with prostate cancer treated with the agent experienced a decrease in serum PSA but also demonstrated a side effect profile comparable to estrogen treatment.

Purpose: Laparoscopy has gradually gained acceptance for a variety of ablative procedures of the retroperitoneal organs, and the indications are being extended to more complex reconstructive and organ preserving procedures. We report our experience with retroperitoneal laparoscopic partial nephrectomy., Materials and Methods: Retroperitoneal laparoscopic partial nephrectomy was performed for benign conditions in 6, equivocal solid masses in 4 and indeterminate cysts in 3 patients. If malignancy was suspected, laparoscopic sonography was used to assess the intrarenal anatomy and the mass. To facilitate parenchymal closure during nephron sparing surgery we used a hemostatic biological glue that consisted of gelatin, resorcinol and formaldehyde., Results: Average operating time was 113 minutes and average blood loss was 72 ml. Histological examination revealed malignancy in 1 of the 3 cystic lesions and 2 of the 4 equivocal solid masses. There were 2 postoperative urinomas., Conclusions: Partial nephrectomy with retroperitoneal laparoscopy is feasible, and has a reasonable operating time and blood loss. Laparoscopic ultrasound was an important decision making aid during surgery. The use of biological glue simplified hemostasis and closure of the collecting system but good quality drainage of the collecting system is still required to decrease the risk of urinoma. The development of surgical tools that allow bloodless and nontraumatic section of the renal parenchyma is required to facilitate laparoscopic nephron sparing surgery. The ultrasonic scalpel needs further evaluation in this setting.

Purpose: We analyze the retroperitoneal approach to laparoscopic radical nephrectomy in regard to feasibility, safety, morbidity and cancer control, and compare results and outcomes in patients who underwent retroperitoneal laparoscopic or open radical nephrectomy from 1995 to 1998., Materials and Methods: The records of 58 consecutive patients with renal cancer who underwent radical nephrectomy from 1995 through 1998 were reviewed. Of the patients 29 underwent open radical nephrectomy (group 1) and 29 underwent retroperitoneal laparoscopic radical nephrectomy (group 2). Various parameters were compared and statistical analyses were performed., Results: The 2 groups were similar in regard to age, gender and side of the tumor. Operative time was slightly shorter in group 1 (mean 121.4 versus 145 minutes in group 2, p = 0.047). Mean tumor size plus or minus standard deviation was larger in group 1 (5.71 +/- 2.01 versus 4.02 +/- 1.87 cm. in group 2). Group 2 patients had significantly less operative blood loss (mean 100.0 versus 284.5 ml. in group 1, p < 0.005) and used significantly less parenteral pain medication (p < 0.05). Postoperative hospital stay was significantly longer in group 1 (9.7 +/- 3.6 versus 4.8 +/- 2.0 days in group 2, p < 0.001), and the complication rate was higher (24 versus 8%, respectively). One group 1 patient died of renal cancer (pT2G2) after 14 months and local recurrence with hepatic metastasis occurred after 9 months in a group 2 patient with a pT3G2 tumor., Conclusions: Retroperitoneal laparoscopic nephrectomy for kidney cancer requires further assessment. It seems to have several advantages over open radical nephrectomy, and to be effective and safe for less than 50 cm. renal tumors but a risk of spillage cannot be ruled out for larger tumors.

Purpose: Retroperitoneal laparoscopy, by providing direct access to the retroperitoneal cavity, is a useful approach to urological surgery. We applied this technique to nephroureterectomy in patients with tumors of the renal pelvis., Materials and Methods: Between January 1995 and March 1997 we performed 4 retroperitoneal laparoscopic nephroureterectomies in patients with tumors of the renal pelvis. The patients were placed in the lateral decubitus position. Five trocars were used. Balloon dilation was not contributory. Radical nephrectomy was performed and the kidney was left in the retroperitoneal space. Via an iliac incision ureterectomy with a bladder cuff was performed and the specimen was removed (kidney and ureter) en bloc via this incision without opening the urinary tract., Results: One right and 3 left nephroureterectomies were performed with an average operating time of 220 minutes (range 160 to 300). Average kidney size was 110 mm. (range 100 to 120). Average hospital stay was 5.7 days (range 5 to 7). Blood loss was minimal and postoperative analgesic requirements were moderate. Conversion to open surgery was never necessary. The morbidity rate was zero. The pathological stages were pT2 G2, pT3 G2, pT3G3 and pT3 G2-G3 N+. A local recurrence was observed in a patient with a pT3 G3 tumor., Conclusions: Nephroureterectomy can be performed by retroperitoneal laparoscopy. The perioperative morbidity and hospital stay are reduced. Further followup is required to evaluate long-term results in terms of cancer outcome.

Purpose: The treatment of symptomatic stone filled caliceal diverticula has evolved from open surgery to less invasive procedures, such as extracorporeal shock wave lithotripsy, percutaneous techniques, retrograde ureteroscopy and laparoscopy, but it remains controversial. We describe a laparoscopic technique for the management of symptomatic caliceal diverticula., Materials and Methods: An extraperitoneal laparoscopic procedure was done in 3 women with symptomatic caliceal diverticula. Watertight obliteration of the diverticular cavity was achieved without suturing, using gelatin resorcinol formaldehyde glue., Results: Average operating time was 80 minutes, including ureteral catheterization. All patients became stone-free, there were no complications and average hospital stay was 6.6 days. At 6-month followup the patients remained asymptomatic with no diverticula or stone recurrence., Conclusions: Retroperitoneoscopy allows safe access to caliceal diverticula regardless of location, and permits complete removal of stone and fulguration of the diverticular neck. Gelatin resorcinol formaldehyde glue minimizes the risk of urinoma formation, and provides a simple, quick and safe alternative for nephrotomy closure.

Purpose: Retroperitoneal laparoscopy, by providing direct access to the retroperitoneal cavity, is an interesting approach to urological surgery. We report our initial experience with retroperitoneal laparoscopic adrenalectomy., Materials and Methods: Between January 1995 and April 1997, 23 adrenalectomies were performed by retroperitoneal laparoscopy in 10 men and 12 women. The patients were placed in the lateral decubitus position and 5 trocars were used. The retroperitoneal working space was created by digital dissection and was completed by insufflation without balloon dissection. The surgical indications were Conn's adenoma in 12 cases, Cushing's adenoma in 4, bilateral adrenal hyperplasia (Cushing's disease) in 1 (treated in a single procedure), a nonfunctioning adenoma in 2, pheochromocytoma in 2 and adrenal metastasis in 1., Results: We removed 7 right and 16 left adrenal glands in an average operating time of 97 minutes (range 45 to 160). Average tumor size was 26 mm. (range 10 to 40). Average hospital stay was 3.3 days (range 1 to 10). Blood loss was minimal. Postoperative analgesic requirements were moderate. Conversion to open surgery was not necessary. The morbidity rate was low, with 1 postoperative hematoma and 1 case of persistent fever (greater than 38.5C)., Conclusions: Retroperitoneal adrenalectomy is a reliable and effective technique. At our institution retroperitoneal laparoscopy is now the standard adrenal surgery procedure for tumors less than 5 cm.

We report on a patient with atypical clinical findings in whom magnetic resonance imaging confirmed the suspicion of penile rupture. The tear appeared as an obvious discontinuity of the low signal intensity of the tunica albuginea and was associated with a hematoma. We conclude that magnetic resonance imaging is useful for confirming the diagnosis of penile rupture when clinical findings are atypical, indicating surgical repair.

Acidic fibroblast growth factor is a regulatory peptide involved in cell proliferation, differentiation and motility. We used a polyclonal antiserum raised against purified native bovine acidic fibroblast growth factor, with no cross-reactivity for basic fibroblast growth factor to detect acidic fibroblast growth factor in tissue extracts and urine samples by means of a competitive enzyme immunoassay. Histochemical analysis was also performed on 10 specimens of normal urothelium and 50 of bladder cancer. Acidic fibroblast growth factor immunoreactive material was found in normal urothelium (1.77 +/- 2 ng./gm. tissue) and was increased more than 10-fold in patients with transitional cell carcinoma of the bladder (20.36 +/- 12 ng./gm. tissue). Immunohistochemical analysis localized immunoreactivity in the epithelial compartment of bladder tumors. Acidic fibroblast growth factor was assayed in urine from 579 individuals comprising a control group (114) and patients with benign prostatic hypertrophy (133), carcinoma of the prostate (96) or transitional cell carcinoma of the bladder (236). There was a significant difference in the frequency of urinary acidic fibroblast growth factor detection among the patients with invasive transitional cell carcinoma, the control group (p < 0.001) and the patients with prostatic disease (p < 0.01). The sensitivity was 72% and the specificity was 91%. Furthermore, the frequency of acidic fibroblast growth factor detection by enzyme immunoassay in the urine and the intensity of immunostaining was correlated with the stage of the disease. These data strongly suggest that acidic fibroblast growth factor is a potential marker for bladder tumors that may be of use in the noninvasive followup of patients with bladder cancer. We present a simple and reliable enzyme immunoassay for the detection of acidic fibroblast growth factor in voided urine that might be useful to quantitate this marker.

A prospective study was conducted on 9 patients with suspected obstruction of the inferior vena cava on ultrasonography, dynamic computerized tomography and/or inferior venacavography during the course of a retroperitonal tumor to assess the value of magnetic resonance imaging with gradient echo sequences. The findings on gradient echo magnetic resonance imaging were compared with the other imaging modalities and surgical or necropsy results. Our results suggest that gradient echo magnetic resonance imaging is the most appropriate imaging modality to diagnose and delineate the extent of inferior vena caval obstruction.

The diagnosis of transitional cell carcinoma by cytological examination of exfoliated urinary cells is important in the early detection and followup of patients with this disease. Proper interpretation requires a skilled pathologist. Accuracy also is influenced by collection methods and nonmalignant pathological conditions of the bladder. An immunocytochemical technique using monoclonal antibodies G4 and E7 successfully identified tumor-associated antigens on the surface of transitional carcinoma cells obtained by bladder washings. The method, which uses immunoperoxidase staining, was compared to conventional Papanicolaou staining of bladder washings from 75 patients with and without transitional cell carcinoma. Patients were divided into 4 groups: group 1 (nontumor control)--15 patients with no pathological condition of the bladder or nonmalignant urological diseases, group 2 (nontransitional cell carcinoma)--19 patients with other urological malignancies, group 3-18 patients with active transitional cell carcinoma and group 4-23 patients with a history of transitional cell carcinoma but no evidence of tumor at the time of the washing. The incidence of positive staining in these groups was 0, 5, 78 and 0 per cent, respectively. The diagnostic value of immunoperoxidase staining was similar to that of Papanicolaou staining in the control group and in patients with high grade transitional cell carcinoma, and provided specific morphological criteria not possible by conventional cytology studies. Interpretation of immunoperoxidase staining was difficult in washings with a large number of inflammatory cells if endogenous peroxidase activity was not blocked properly. The application of the immunoperoxidase staining method for diagnosis of low grade tumor is under further investigation.

During cadaveric organ harvesting removal of the right renal vein and a segment of the vena cava may facilitate venous anastomosis of the right kidney. The technique to obtain adequate length of the right renal vein using the vena cava is simple, physiological and effective. A segment of the inferior vena cava should be harvested with the right but not necessarily with the left kidney. The use of a long segment of vena cava makes the renal transplantation much easier and does not interfere with multiorgan procurement. The method is most useful when the right renal vein is extremely short or when the recipient has a large abdomen and a deep pelvis.

Renal-sparing treatment of spontaneous renal allograft rupture remains a surgical challenge, since profuse hemorrhage may result from these friable kidneys during surgical repair. A technique is proposed to achieve control of local bleeding with a synthetic glue (gelatin, resorcin and formaldehyde) and external compression with a polyglactin 910 absorbable mesh. We report 4 cases of spontaneous allograft rupture associated with rejection and bleeding was controlled in all 4. Three grafts were preserved with more than 1 year of followup. The other graft had to be removed for uncontrolled vascular rejection despite satisfactory control of renal fractures. Renal wrapping with external compression is proposed to improve results of conservative management of renal allograft rupture.