E. P. Allhoff

Prognostic significance of Ki-67 immunostaining in nonmetastatic renal cell carcinoma.

PURPOSE Fresh tissue samples from nonmetastatic renal cell carcinoma (RCC) patients were analyzed by Ki-67 immunostaining to determine the prognostic significance of this tumor-biologic parameter. MATERIALS AND METHODS In a prospective study, Ki-67 immunostaining was performed on frozen sections of histologically proven node-negative RCC from 58 patients operated on between 1986 and 1988 to examine the methods prognostic value and its association with other clinicopathologic parameters such as tumor stage (pT) and grade (G). RESULTS The percentage of Ki-67-positive cells (ie, the proliferation rate [PR]) of all 58 RCC tumors ranged between 1% and 23%, while normal renal tissue exhibited PRs up to 2% only. In almost all cases, the highest PRs were observed in the peripheral zone of malignant tissue close to the normal renal tissue. PR did not correlate with pT, whereas a strongly significant correlation was observed between PR and G, as well as recurrence rate. Twenty-three of 58 patients (39.6%) developed tumor recurrence. Disease-free survival was strongly associated with PR. In a multivariate analysis, G and PR were independent prognostic markers. CONCLUSION The tumor-specific PR obtained by Ki-67 labeling seems to be an independent marker to describe the proliferative activity and aggressiveness of individual tumors. This new tumor-biologic marker detects RCC patients at high risk for recurrent disease, especially in those cases with identical pT and G.

The pelvic plexus and antireflux surgery: topographical findings and clinical consequences.

PURPOSE Voiding dysfunction and urinary retention are rare complications of antireflux surgery. As mainly reported after bilateral antireflux surgery with extravesical technique, bladder insufficiency has been suspected to be caused by intraoperative damage to neural structures. We studied the topography of the pelvic plexus and assessed the injury to the plexus resulting from antireflux surgery. MATERIALS AND METHODS Human cadavers fixed with Thiel solution were used for dissection. The superior hypogastric plexus and hypogastric nerves were identified as the pathway to the pelvic plexus. After dissecting the surrounding fatty tissue the S2 to S4 nerves and efferent nerve bundles from the pelvic plexus were identified. RESULTS The main portion of the pelvic plexus was located about 1.5 cm. dorsal and medial to the ureterovesical junction. The bundles of the pelvic plexus ended at the distal ureter, trigone and rectum. When simulating an antireflux procedure, there was a high risk of injury to the pelvic plexus and its efferent nerves if dissection was performed distal to the ureter and dorsal trigone. CONCLUSIONS Careful dissection close to the ureter avoids inadvertent injury to the pelvic plexus. To minimize the risk of voiding dysfunction bilateral antireflux surgery should be performed at 2 sessions unless the operative technique allows preservation of the neural structures.

Refluxing Ureterointestinal Anastomosis for Continent Cutaneous Urinary Diversion

PURPOSE We question the statement that anti-refluxing ureteral implantation is mandatory in low pressure, high capacity reservoirs. In a series of patients with ureteral obstruction after implantation with an anti-refluxing submucosal tunnel reimplantation was performed as a direct ureter-pouch anastomosis. The same technique was used for primary anastomosis in a later group of patients as the method of choice for ileocolic and colonic continent urinary diversion. MATERIALS AND METHODS Direct ureteral reimplantation was performed in 10 patients in whom a total of 19 obstructed renal units were associated with an ileocolic reservoir. The retroperitoneal supracostal approach was used to avoid complications caused by repeat laparotomy. The ileocecal reservoir was opened superior and the obstructed ureter was identified and reimplanted via a buttonhole. The same technique was used for primary anastomosis in 20 patients (40 renal units), in whom the ureter was implanted in an ileocecal (10) or colonic (10) pouch. RESULTS Postoperatively complications did not develop in any patient. Radiography of the pouch postoperatively showed renal reflux in only 1 renal unit. In the group with reimplanted ureters median followup was 81 months (range 10 to 120). Of the 19 obstructed ureters 14 returned to normal, while 5 showed persistent grade I dilatation. Median followup in patients with primary direct ureteral anastomosis was 20 months (range 2 to 36). Of the 22 preoperatively dilated systems 20 returned to normal and none of the 18 nondilated systems was obstructed. CONCLUSIONS Direct ureter-pouch reimplantation proved to be simple and safe. When performed primarily for continent urinary diversion, the anastomosis was anti-refluxing in pouches with high capacity and low pressure. The advantage of this technique is the low risk of ureteral obstruction and subsequent deterioration in kidney function.

A randomized study of docetaxel and dexamethasone with low‐ or high‐dose estramustine for patients with advanced hormone‐refractory prostate cancer

To test the combination of docetaxel with two different doses of estramustine in patients with hormone‐refractory prostate cancer (HRPC), to improve response rates and to lower side‐effects, as docetaxel‐based chemotherapy is an increasing option for men with advanced HRPC, and alone or combined with estramustine, docetaxel improves median survival.

Evaluation of peri-operative peripheral and renal venous levels of pro- and anti-angiogenic factors and their relevance in patients with renal cell carcinoma

To evaluate peri‐operative peripheral and renal venous plasma levels of vascular endothelial growth factor (VEGF), platelet‐derived growth factor type BB (PDGF‐BB), transforming growth factor (TGF)‐β1, endostatin, and thrombospondin‐1 (TSP‐1) in relation to pathological variables and prognosis, as pro‐ and anti‐angiogenic factors are important for tumour growth and treatment of patients with renal cell carcinoma (RCC).

Pretreatment with interleukin-2 modulates peri-operative immuno-dysfunction in patients with renal cell carcinoma.

OBJECTIVE Complex peri-operative immuno-dysfunction occurs in patients with renal cell carcinoma undergoing nephrectomy. Here, the effect of pretreatment with interleukin-2 (IL-2) is addressed. METHODS Of 63 patients who underwent tumor nephrectomy, 26 patients received 4 doses of 10 Mio IE/m(2) IL-2 b.d. s.c. (i.e. a total of 40 Mio IE/m(2)) a week before operation, 37 did not. Parameters of cellular and humoral immunity (differential blood count, T-cell markers CD2, CD3, CD4, and CD8, B-cell markers CD19 and CD20, monocyte markers CD13 and CD14, NK (natural killer)-cell marker CD16, activation markers CD25, CD26, CD69, and HLA-DR, and cytokines IL-1-receptor antagonist (IL-1RA), IL-2, soluble IL-2-receptor (sIL-2R), IL-6, IL-10, and TGFbeta) were measured in venous blood. Blood was drawn before IL-2, 1 day before and immediately after the operation, and on the 1st, 3rd, 5th, and 10th postoperative day. RESULTS All patients showed postoperatively elevated leukocyte and granulocyte counts, and elevated serum levels of cytokines IL-6 and IL-10. T-cell and activation markers were decreased. However, all these alterations were less accentuated in patients who had been pretreated with IL-2. Monocyte counts and IL-2 and TGFbeta levels were decreased, but IL-1RA and sIL-2R levels were elevated in pretreated patients. IL-2 related toxicity was WHO grades I-II in all patients, grade III in one patient. The anesthetic regimen had no measurable effect. IL-6 concentrations were higher in renal venous than in venous pool blood, indicating IL-6 production in the tumor in vivo. CONCLUSIONS Pretreatment with IL-2 modulates peri-operative immuno-dysfunction in patients undergoing tumor nephrectomy. This affects in particular T-cell-mediated immunity and levels of cytokines IL-10 and IL-6. The IL-2 administration scheme used here was followed by distinct counter-regulation including monocytes, IL-2, sIL-2R, IL-1RA and TGFbeta.

Pretreatment with Interferon-α2a Modulates Perioperative Immunodysfunction in Patients with Renal Cell Carcinoma

Introduction: Complex perioperative immunodysfunction occurs in patients with renal cell carcinoma undergoing surgery. Here, we report on the effect of preoperative treatment with interferon-α2a (IFN-α2a). Materials and Methods: 30 patients with a renal tumour received preoperative IFN-α2a for 6 days beginning 1 week before nephrectomy, 30 did not. Parameters of cellular and humoral immunity were measured in venous blood at various intervals using flow cytometry and ELISA. Endpoints included effects on immune parameters, toxicity, and survival. Results: Toxicity was grade 1 in 52%, 2 in 30%, and 3 in 4%. During IFN-α2a administration, leukocytes, monocytes, granulocytes, B-cell marker CD19, activation markers, CD4+CD25+ regulatory T-cells, and vascular endothelial growth factor (VEGF) dropped significantly, but no difference was observed in T-cell and natural killer (NK)-cell markers, and IL-10. Postoperatively, T-cell and activation markers decreased in both groups, but CD4, CD28, IL-6, IL-10, and HLA-DR alterations were significantly less accentuated in patients who had been treated with IFN-α2a. After a median follow-up of 23 months, survival did not differ between the groups (p = 0.54). Conclusions: Perioperative immunodysfunction can be modulated by preoperative administration of IFN- α2a. IFN-α2a decreased the level of VEGF and CD4+CD25+ regulatory T-cells implicating a potential combination with tyrosine kinase inhibitors and vaccines.

Characterization of Prognostic Factors and Efficacy in a Phase-II Study with Docetaxel and Estramustine for Advanced Hormone Refractory Prostate Cancer

Background: Docetaxel based chemotherapy not only reduces pain and improves quality of life in advanced hormone refractory prostate cancer (HRPC), but it also improves survival. We investigated the combination of docetaxel and estramustine in patients with HRPC regarding efficacy and prognostic parameters. Patients and Methods: We conducted a phase-II trial, administering docetaxel (70 mg/m2 i.v., day 2, every 3 weeks) and estramustine (280 mg 3 times daily p.o., 1 day prior to docetaxel, on 5 consecutive days) to patients with HRPC. Patients were monitored for PSA (prostate-specific antigen) response and toxicity. Results: 62 patients were treated. The median age was 67.5 years, the median PSA was 177.9 ng/ml. The median number of cycles was 6. The median time to progression (TTP) and median survival time were 14 (±2) and 24 (±5) months, respectively. A = 50% decrease in PSA levels from baseline occurred in 38 (61.3%) patients of whom 25 (40.3%) had a = 75% PSA decrease. The main grade 3-4 hematologic toxicities were neutropenia 34% and anemia 18%. Conclusions: The combination of docetaxel and estramustine exerts substantial activity in HRPC suggesting an overall survival benefit with manageable toxicity. This trial also demonstrated a survival advantage for patients with early chemotherapeutic intervention. We identified PSA relapse, baseline PSA and hemoglobin as valuable prognostic factors in this setting.

COMPLEX PERIOPERATIVE IMMUNO-DYSFUNCTION IN PATIENTS WITH RENAL CELL CARCINOMA

PURPOSE Patients with renal cell carcinoma have an impaired function of the immune system, which is the basis for different approaches of immunotherapy. We address perioperative changes of several parameters of the immune system in these patients. MATERIALS AND METHODS Parameters of cellular and humoral immunity, including differential blood count, T cell markers CD2, 3, 4 and 8, B cell markers CD19 and 20, monocyte markers CD13 and 14, natural killer cell marker CD16, activation markers CD25, CD26 and HLA-DR, and cytokines interleukin-1 (IL-1) receptor antagonist, IL-2, soluble IL-2 receptor, IL-6, IL-10 and transforming growth factor-beta, were measured in the venous blood of patients who underwent renal surgery extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia). Patients were grouped and age matched, and 37 underwent tumor nephrectomy, 20 open renal surgery for nonmalignant reasons and 24 ESWL. A group consisting of 39 controls received no treatment. RESULTS Little change was detected in controls and those patients who received ESWL. Patients who underwent open renal surgery had increased leukocyte and granulocyte counts until postoperative day 3 but had low T cell counts. The postoperative decrease in CD25 expressing cells corresponded to an increase in the soluble IL-2-receptor. Cytokines IL-6 and 10, which also have immunosuppressive properties, were markedly increased postoperatively. These changes were more noted (p <0.01) in those patients who underwent tumor nephrectomy than open renal surgery for nonmalignant reasons and remained detectable when paired patients with similar surgical trauma were compared. In tumor nephrectomy cases renal venous IL-6 was higher than peripheral venous levels. CONCLUSIONS Patients with renal cell carcinoma suffer from selective immuno-dysfunction, indicating a rationale for perioperative immunomodulation.

TREATMENT OF LARGE PROSTATIC CYST WITH RETROPUBIC INSERTION OF A FAT TISSUE FLAP

Little attention has been given to the significance of prostatic cysts in urology although they are frequently seen in systematic studies. Since the initial report on prostatic cysts in 1869, about 100 cases have been reported. They are difficult to treat in the case of symptomatic enlargement because fertility is always jeopardized. Therapy is performed either transurethrally or by open surgery. We report on a patient with a mullerian duct cyst.