S. Pomer

Aetiology, diagnosis and management of spontaneous perirenal haematomas

This study focuses on the diagnostic and therapeutic challenge posed by spontaneous perirenal haematomas (SPHs). The medical records of 18 patients with SPHs seen in the past 8 years were reviewed with respect to aetiology, diagnosis and therapeutic management. SPH was secondary to angiomyolipoma (n = 4), polycystic kidneys (n =4), panarteritis nodosa (n = 3), renal cell carcinomas (RCCs, n = 2), glomerulonephritis, pyelonephritis, Morbus Wegener and cortical adenoma (one each). One case remained unclear. With appropriate imaging techniques (computed tomography and angiography) the underlying disorder was detected in 72%; in 4 cases the diagnosis was revealed by exploration and biopsy. Surgery was necessary in 16 patients. The cause of bleeding can be revealed by appropriate imaging in most cases. When imaging procedures fail to reveal the cause of SPH, exploration and biopsy are mandatory to exclude RCC. If the cause of SPH remains unclear even after exploration, patient monitoring by CT is justified.

Surgical treatment of invasive penile cancer : The Heidelberg experience from 1968 to 1994

OBJECTIVES This study was performed to establish oncological guidelines for the surgical treatment of invasive penile cancer. MATERIALS AND METHODS The medical records of 51 patients with invasive penile cancer seen between 1968 and 1994 were reviewed in respect to treatment and long-term outcome. RESULTS For stage T1 tumors treated with organ-preserving procedures the local recurrence rats was 56%, whereas no patient experienced a local recurrence after partial amputation. For stage T2 tumors, local recurrence rate was 100% (organ preservation) versus 20% (amputative procedures). There was no significant difference related to regional recurrence between surveillance, inguinal radiation and lymphadenectomy for stage N0 tumors. For N+ stages, survival was related to the extent of inguinal metastasis after dissection (5-year survival rate for N1: 71 vs. 33% for N2/3). CONCLUSIONS Organ-preserving procedures include a high risk of local and regional recurrence. Adjuvant regional lymphadenectomy seems beneficial only in patients with solitary metastasis.

Präoperatives Staging von Nierenzellkarzinomen mit Kavazapfen: welches diagnostische Verfahren?

ZusammenfassungZiel dieser Untersuchung war die Evaluation der optimalen und effektiven Diagnostik beim präoperativen Staging von Nierenzellkarzinomen mit Kavazapfen. Ist der Einsatz der MRT gerechtfertigt? Es wurden 7 Nierenzellkarzinome der Tumorstadien T3b und T3c präoperativ in der CT und MRT untersucht und das Staging mit dem histopathologischen Ergebnis korreliert. In der MRT wurden 4 von 7 Kavazapfen in ihrer Ausdehnung korrekt und sicher beurteilt, in der CT keiner korrekt und sicher. Die MRT mit Gadolinium ist der CT im Staging von Nierenzellkarzinomen der hohen Tumorstadien überlegen und kann hier die Kavographie ersetzen. Die MRT ist in den Fällen, in denen sonographisch ein hohes Tumorstadium mit Kavazapfen vermutet wird, als präoperative Diagnostik gerechtfertigt.SummaryTo evaluate whether MRI is usefull in staging renal cell carcinomas with caval thrombus the accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in staging renal tumors with caval thrombus were preoperatively examined. Tumor staging by CT and MR imaging were correlated with histopathological tumor stadium. In MRI 4 out of 7 thrombi were correctly diagnosed with high accuracy, in CT none. In advanced renal carcinoma MRI with Gadolinium was superior to CT imaging, especially in diagnosing tumor thrombus. Consequently the extent of tumor thrombus may be assessed by MRI which therefore may replace conventional cavography.

Prolongation of discordant renal xenograft survival by depletion of complement. Comparative effects of systemically administered cobra venom factor and soluble complement receptor type 1 in a guinea-pig to rat model.

Abstract There is an increasing body of evidence to suggest that inhibition of complement activation may be a valuable approach to avert hyperacute rejection. In our study, the guinea‐pig to rat discordant kidney xenograft model was adapted for the investigation of renal transplant function and an attempt was made to delay the hyperacute rejection using systemically administered cobra venom factor (CVF) and soluble complement receptor type 1 (sCR1). The saline‐treated control recipients experienced a rapid transplant rejection with a xenograft survival averaging 10.5 ± 2.1 min. Administration of a single 60 U/kg i. v. bolus of CVF significantly prolonged renal graft survival to 20.4 ± 2.5 h, and by a single bolus of sCR1 (50 mg/kg) a prolongation of graft survival to 18.8 ± 2.3 h was achieved. The grafts functioned only over periods of 2.5 ± 0.3 and 2.3 ± 0.2 h, respectively. No complications of sCR 1 were noted. We concluded that complement inhibition by sCR 1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.

Investigation of multidrug resistance in cultured human renal cell carcinoma cells by 31P-NMR spectroscopy and treatment survival assays

KTCTL-26 and KTCTL-2 are renal cell carcinoma (RCC) lines with high and lowexpression of P-170 glycoprotein, respectively. Inherent differences between the two cell lines in terms of phosphate metabolites and growth characteristics in culture were examined for possible association with multidrug resistance (MDR). Differences in response to drug treatment were investigated for 40 h incubations with various doses of vinblastine (VBL) alone or as cotreatments with various concentrations of the calcium antagonist diltiazem (DIL) and/or interferon–α (IFN-α). Treatment effects were quantitated using the MTT survival assay and 31P magnetic resonance spectroscopy (MRS) to determine phosphate metabolite profiles in intact cells. KTCTL-2 and KTCTL-26 cells exhibited significant inherent differences in phosphocholine, glycerophosphocholine, glycerophosphoethanolamine, and phosphocreatine levels. KTCTL-26 cells were more sensitive than KTCTL-2 to 0.011μM VBL alone (87% vs. 102% survival) or to 0.011μM BL + 10μM DIL (55% vs. 80% survival). The latter treatment resulted in a significant decrease in the ratio of phosphocholine to glycerophosphocholine in KTCTL-26 cells but no significant changes in phosphate metabolites in KTCTL-2 cells. Metabolomic 31P MRS detects different metabolite profiles for RCC cell lines with different MDR phenotypes and may be useful for noninvasive characterization of tumors in a clinical setting.

Interferon α2b differentially affects proliferation of two human renal cell carcinoma cell lines differing in the P-glycoprotein-associated multidrug-resistant phenotype

Purpose: Interferon α (IFNα) has been used in the immunotherapy of renal cell carcinoma (RCC), but the various mechanisms of its antiproliferative effects are poorly understood. Recent evidence suggests that IFNα is involved in the up-regulation of multidrug resistance (MDR) gene expression, and that the MDR gene product, P-glycoprotein (Pgp), facilitates the transport of several cytokines, some of which have been implicated in mediating tumor antiproliferative effects. We hypothesized that IFNα-induced antiproliferative activity may require Pgp-mediated transport, and that susceptibility to IFNα may thus correlate with Pgp expression. Methods: Pgp expression by the human RCC cell lines KTCTL-2 and KTCTL-26 was characterized by immunofluorescence staining, using the Pgp-specific primary antibodies C219 and JSB1. KTCTL-2 and KTCTL-26 cell lines were subsequently treated with IFNα2b, and growth kinetics of treated and control cell cultures were determined daily by cell counting. Results: KTCTL-2 expresses Pgp at low levels, whereas KTCTL-26 is a highly expressing cell line. IFNα2b treatment abrogated cell proliferation in KTCTL-26, whereas proliferation of KTCTL-2 was only partially inhibited. Conclusions: We have identified two RCC cell lines that differ in the MDR phenotype and exhibit different responses to the antiproliferative activity of IFNα2b. These preliminary findings raise the possibility that susceptibility to the antiproliferative effects of IFNα2b may correlate with Pgp expression, and further studies are warranted.

Laser-Induced Fluorescence Diagnosis and Photodynamic Therapy of Human Renal Cell Carcinoma

Photodynamic therapy (PDT) has recently attracted much attention, especially among urologists, because it appears to be a selective form of cancer treatment which causes minimal damage to normal surrounding tissues. In this study we made use of a new class of photosensitizers for the laser-induced fluorescence diagnosis (LIFD) and photodynamic therapy of human renal cell carcinoma xenotransplanted into nude mice. The purpose of this study was to evaluate the recently developed photosensitizing drug THOPP-MPEG for its efficacy as photosensitizer for LIFD and PDT of renal cell carcinoma. THOPP-MPEG was injected intraperitoneally (0.5 micrograms/g body weight) into the mice 6-8 days after tumor transplantation. On the 18th day after transplantation, the tumors reached a diameter of 3-4 mm. Seven days after administration of the drug the tumor-bearing kidney was irradiated percutaneously with a total light dose of 2 x 60 J/cm2 and a power density in the irradiated area of less than 150 mW/cm2. A continuous-beam argon-pumped dye laser (656 nm) was used. After excitation with laser light (488-514 nm), the vital tumor clusters and the surrounding tissues invaded with tumor cells showed intense red coloration by laser-induced fluorescence. Subsequent to the light exposure (656 nm), a heavy tumor necrosis of up to 3-5 mm resulted. No THOPP-MPEG phototoxicity in normal surrounding tissue at a dose of up to 100 mg/kg body weight was seen. We believe the future role of PDT in the management of tumors of the kidney to be adjuvant within the concept of conservative kidney-preserving surgery.

Biotherapy of cancer: Perspectives of immunotherapy and gene therapy

Prospects for a new biologically based strategy of cancer treatment are being discussed. While physically and chemically based therapies, such as radio- and chemotherapy, are not directed against cancer tissue only and have a suppressive effect on the immune system, immunotherapy and gene therapy, which are discussed here, try to be more selective and to stimulate rather than suppress antitumor immune mechanisms. On the basis of personal experience with these new technologies, good future prospects are predicted for the application of cancer vaccines and immune T lymphocytes for active specific immunization (ASI) and adoptive immunotherapy (ADI) respectively. While ASI strategies aim at micrometastases being affected by activated host immune T cells, and might find a place for postoperative adjuvant treatment in high-risk cancer patients, cellular therapies such as ADI do not require an intact host immune system and could therefore also find application in advanced stages of disease. In spite of the exciting new perspectives of immuno- and gene therapy for the cancer patient, this therapy is not yet a defined discipline and requires years of further research.

Transurethral Incision of the Prostate Following Renal Transplantation

Urinary retention in male patients after renal transplantation may cause serious complications in terms of graft function and even patient survival. Only few data concerning the management and outcome of these patients are reported in the literature. Therefore, we retrospectively analyzed the outcome of patients who underwent transurethral incision of the prostate immediately after renal transplantation. Between 1990 and 1993, we performed 259 renal transplantations and 15 patients had symptoms of urinary retention postoperatively. These patients underwent a midline transurethral incision of the prostate from the bladder neck to the verumontanum. Median peak flow preoperatively was 7 ml. per second (range 0 to 11.4) and median residual urine volume was 100 ml. (range 30 to 500). Median prostate volume was 28 ml. (range 12 to 45). After transurethral incision of the prostate a significant improvement (p < 0.001) in peak flow rates (19.6 ml. per second, range 8 to 49) as well as a significant decrease in residual urine volumes (40 ml., range 20 to 80) could be achieved. After a median followup of 19 months the effect was still present.

Untersuchungen zur Auswirkung der Komplementmodulation mittels des löslichen Komplementrezeptors sCR1 auf das Nierenxenotrans- plantatüberleben und -funktion Eine experimentelle Studie im neuen Meerschweinchen- auf-Ratte-Transplantationsmodell

ZusammenfassungIn der vorliegenden Arbeit wurde ein modifiziertes tierexperimentelles Modell der Nierenxenotransplantation entwickelt, im Rahmen dessen der Verlauf einer hyperakuten Abstoßungsreaktion hochgradig reproduzierbar ist. In diesem Modell wurden Meerschweinchennieren als Spenderorgane auf Wistarratten als Empfängertiere verpflanzt, wobei End-zu-Seit-Gefäßanastomosen mit Spenderaorta, bzw. V. cava und Harnleiterdrainage mittels Schienung zur Diureseüberwachung zum Einsatz kamen. Ziel der vorliegenden Untersuchung war es die protektive Wirkung der Komplementmodulation mit Hilfe des löslichen Komplementrezeptors Typ 1 (sCR1) auf die Nierenxenotransplantate zu analysieren. Insgesamt wurden 24 Xenotransplantationen vorgenommen und randomisiert mit 3 ml 0,9 % NaCl (Kontrollgruppe), bzw. 50 mg/kg sCR1 als 3-ml-Bolus (Behandlungsgruppe) therapiert. Der lösliche Komplementrezeptor Typ 1 (sCR1) war wirksam in bezug auf die Verlängerung der Transplantatüberlebenszeit (von 10,5 ± 2,1 min in der Kontrollgruppe auf mindestens 2 h in der Behandlungsgruppe) und seine Funktion. Serologisch konnte eine deutliche Reduktion der Komplementaktivität in der sCR1-Gruppe festgestellt werden, die auf eine modulatorische Wirkung des sCR1 zurückzuführen ist. Bereits 10 min nach Reperfusionsbeginn zeigten sich histologisch in der Kontrollgruppe massenhaft Thrombozytenaggregate, Fibrinablagerungen in den Kapillaren und interstitielle Infiltrate. Die mit sCR1 behandelten Nierentransplantate wiesen dagegen nach 120 min eine deutlich reduzierte intravasale Thrombenbildung und geringere interstitielle Infiltration auf. Die immunhistologische Studie ließ eine gleichermaßen verminderte Ablagerung von C3 in den Glomeruli und im Interstitium in der Therapiegruppe erkennen.SummaryIn this study a modified experimental kidney xenograft model was developed, which reproduced, in a reliable way, the course of hyperacute rejection. In this model guinea-pig kidneys were transplanted to rats using end-to-side anastomoses with recipient aorta and vena cava, respectively, and ureter drainage for diuresis monitoring. The aim of this study was to investigate the protective effects of complement modulation by soluble complement receptor 1 (sCR1) on the xenografts. Twenty-four xenotransplantations were performed and recipients randomized for treatment either by 3 ml saline or 50 mg/kg sCR1 as a 3-ml bolus. It was found that sCR1 was highly efficient in delaying hyperacute rejection from 10.5 ± 2.1 min in the control group to at least 2 h in the therapy group and in prolongation of graft function. The complement activity was significantly reduced in the sCR1-treated rats, even at the time of rejection, as a result of complement modulation in this group of xenograft recipients. Xenografts from saline-treated animals showed necroses, interstitial haemorrhages and platelet aggregates occluding the vessels as soon as 10 min after the reperfusion started. No such changes could be seen even after 120 min in the xenografted kidneys of sCR1-treated rats. Also C3 deposits in the glomeruli and interstitium were markedly reduced.