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S Pomer

Publications and source records attributed to S Pomer.

At least 37 records · Page 2Linked to original sources

[Traditional and future criteria for progression in renal cell carcinoma. Molecular biology and clinical aspects].

In addition to the commonly used pathologic staging systems such as the TNM classification, the grading and demographic features have been reported to affect survival following surgical extirpation of renal cell carcinoma (RCC). These features, especially the pathologic stage, are well established as prognostic factors. However, several cellular and molecular variables, although potentially important in the ultimate outcome, are not taken into consideration by these criteria. Thus patients with different prognoses may be classified as belonging to the same stages. Attempts are now made to use cytogenetic and molecular findings to predict long-term survival of RCC patients. Chromosome 16 q and 14 q aberrations may play an important role in the future by identifying the high-risk groups of patients with papillary and nonpapillary RCC, resp. In nonpapillary RCC, mutations of the von Hippel-Lindau gene have been implicated as the initial step of carcinogenesis. However, the subsequent steps remain to be elucidated and the search for genetic markers associated with tumor progression is under way. The distinction between patients with high and low risk of progression will become increasingly important as more effective adjuvant therapies are available.

Carcinoma, Renal Cell↗

[Improved organ survival in transplantation of pediatric kidneys by optimizing donor-recipient size relation].

The risk for renal allograft failure in pediatric renal transplantation (donor age below 3 years) is still high, although it has been reduced by the use of potent immunosuppressive therapies. In this study we report on experience with 80 kidneys of donors below 3 years of age (PD) transplanted at the University of California at San Francisco Hospital in accordance with the policy of minimizing donor-recipient size differences. The graft survival rates were comparable with the results for adult donors, 18-50 years of age (AD, n = 891): at 1 year PD 74.1% vs AD 85.5%, at 2 years PD 70.5% vs AD 80.2%, at 3 years PD 63.5% vs AD 76%; there were no significant differences. The policy of minimizing donor-recipient size differences seems to improve graft survival rates, avoiding the tendency for hyperfiltration phenomena and possibly being responsible for this salutary effect. We conclude that the use of pediatric donor kidneys can yield excellent long-term results independent of primary disease if the donor-recipient size difference is minimized and a potent immunosuppressive regimen is employed.

Adolescent↗

[Repetitive immuno-embolization of inoperative liver metastases of renal cell carcinoma. Method characterization and preliminary results].

Interleukin 2 (IL2)-based immunotherapy is effective in a subgroup of patients with metastatic renal cancer, but cure from liver metastases is very rare and even the selection of patients to be treated is very much limited by the toxicity of IL2. To reduce this toxicity and to augment the efficacy of intrahepatic IL2 application, a protocol of combined rIL2 (3 mg/day) and Lipiodol (2-5 ml/day according to tumour size), via a catheter inserted percutaneously into the hepatic artery, was implemented. As an adverse reaction, moderate fever (WHO) grade I and II was noted. A partial remission was seen in one patient and stable disease in four patients over a period of 2-6 years (median 32.2 month). It seems that immuno-embolisation of otherwise intractable liver metastases of renal cancer is well tolerated and its efficacy may be augmented by optimisation of the therapeutic protocol.

Adult↗

The influence of thymectomy on germ-cells of the testis in mice.

We performed thymectomy on the immature and mature male mice and made a quantitative assay of various germ cells of the seminiferous epithelium in the testis with Image Analyser System 35 days following thymectomy. The results indicated that as compared with the control group, all germ cells of the spermatogenesis lineage decreased in the immature group and in the mature group after thymectomy. The present study showed that thymus and its hormone stimulated not only the mitotic division, but also the meiotic division of germ cells during spermatogenesis, suggesting that thymus-sexual axis may play an important role in the process of spermatogenesis in the testis.

Animals↗

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.

Animals↗

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.

Adult↗

[Tumor vaccination in renal cell carcinoma with and without interleukin-2 (IL-2) as adjuvant. A clinical contribution to the development of effective active specific immunization].

Interleukin 2 (IL2) production is known to bypass T-helper-cell function in the generation of an antitumour response. The present analysis was designed to assess the effects of application of renal cancer vaccine with and without IL2 on delayed-type hypersensitivity (DTH) skin responses to the vaccine itself and tumour cell challenge. The renal cancer vaccine consisted of Newcastle disease virus (NDV)-infected autologous irradiated tumour cells and topical application of low-dose rIL2 (75,000 Cetus units). As a result, the coadministration of a supplement of rIL2 proved to be important for augmentation of DTH responsiveness to tumour cell challenge. Patients with aneuploid tumours vaccinated without rIL2 developed an anergy to the vaccine throughout vaccination. This effect could be reversed by the topical coapplication of this cytokine. While the treatment of renal cancer patients with IL2-based immunotherapy regimens appears to be effective in advanced renal cell carcinoma the IL2-supplemented vaccines should be tested to assess their benefit in the situation of "minimal disease" after surgery especially in high-risk patients with aneuploid tumours.

Aneuploidy↗

[The effect of the complement system on the acute reversible rejection of kidney transplants].

Although the involvement of complement in hyperacute renal allograft rejection is well established, its possible implication in acute reversible and chronic graft rejection remains uncertain. In recent clinical studies with a total of 83 patients undergoing renal transplantation, plasma levels of complement activation products were elevated 4-7 days before clinical diagnosis of graft rejection. Immunohistochemical analysis of biopsies revealed local complement activation with glomerular deposition of the terminal C5b-9 complex within 1 h after organ reperfusion. Increasing levels of complement activation products, preceding the clinical manifestation of renal graft rejections may be of diagnostic value in recognizing patients at risk.

Acute Disease↗

[Spontaneous kidney ruptures--a complication of panarteritis nodosa].

Besides renal cell carcinomas and angiomyolipomas panarteritis nodosa (PAN) is a common underlying disorder for spontaneous perirenal hematomas (SPH). Herein we report on 3 cases with PAN associated kidney ruptures where diagnosis of PAN was not known before in 2 instances. The hematoma was identified by computerized tomography (CT) in all patients, nevertheless CT failed to reveal the underlying disorder in any case. In this situation angiography was extremely valuable visualizing multiple renal microaneurysms that are typical for PAN. Operative exploration and drainage of the hematoma was necessary in two patients because of hemodynamic instability. In one patient bleeding could be controlled after an immediate immunosuppressive therapy with prednisone and cyclophosphamide. Due to the high incidence of PAN associated spontaneous perirenal hematomas angiography should be performed in all cases with unclear SPH after CT evaluation. In our opinion an immediate surgical intervention is only indicated in cases with hemodynamic instability. Otherwise a conservative approach including immediate immunosuppression seems justified. Nephrectomy should be avoided whenever possible.

Adolescent↗

Genetic alterations in sporadic renal-cell carcinoma: molecular analyses of tumor suppressor gene harboring chromosomal regions 3p, 5q, and 17p.

On a genetic level, renal-cell carcinoma has been characterized by an abnormality on the short arm of chromosome 3 (3p), which suggests the inactivation of a tumor suppressor gene. One tumor suppressor gene at 3p, the von Hippel-Lindau disease gene, is implicated in tumor development of a whole spectrum of hereditary neoplasms, including renal-cell carcinoma. It is not clear whether the same tumor suppressor gene accounts for all, i.e., hereditary and sporadic, renal-cell carcinomas. Analysis of 28 patients with sporadic renal-cell carcinomas for loss of heterozygosity was performed at chromosomal regions that contain known tumor suppressor genes so as to assess their potential involvement during renal tumorigenesis. We focused on chromosome 3p because it contains the von Hippel-Lindau (VHL) disease gene, on 5q because it harbors tumor suppressor genes involved in colorectal carcinoma, and on 17p because it includes a tumor suppressor gene involved in breast, colon, and lung carcinoma. Loss of alleles at 3p affected 96% of the evaluable patients, with frequencies being highest in the VHL region in 3p25-26 and at loci in 3p21. These data confirm the importance of a 3p defect early during tumorigenesis; however, the question as to the existence of a second renal-cell carcinoma gene remains unresolved. Changes at 5q were 53% and those at 17p were 35%, suggesting that these loci may not contribute to the initiation of the disease but rather may represent accumulating genetic defects associated with progression and malignancy.

Alleles↗

IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function.

We showed previously that the B cell response in renal transplant recipients with long-term stable graft function (ST patients) is significantly affected by T suppressor activity. To further assess the role of the monocyte/B cell compartment in B cell regulation, we tested B cell responses in 30 ST patients (> 1 year after transplant) and 15 patients with chronic rejection (CR patients). PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture system, and SAC I for T cell- and monocyte-independent B cell stimulation. B cell responses were assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimulated cultures of ST patients, we found a diminished immunoglobulin-secreting cell (ISC) formation (P < 0.0001 and P < 0.05, compared with controls and CR patients, respectively) and diminished IgM secretion (P = 0.06 and P < 0.01, respectively), whereas CR patients and controls were not significantly different. Two of 35 (6%) controls and 3 of 15 (20%) CR patients, in contrast to 20 of 30 (67%) ST patients, displayed defective ISC formation (P < 0.0001). This defective B cell response may be the result of reduced CD36+ monocyte counts in ST patients (P < 0.005), as PWM-stimulated B cell responses and CD36+ cell counts were significantly associated (P < 0.05, ISC and IgM response). A role of monocytes in the impairment of B cell function is further supported by decreased plasma neopterin levels in ST compared with CR patients (P = 0.0001), a significant association between plasma neopterin and PWM-stimulated B cell responses (P < 0.05, ISC response; P = 0.0001, IgM response), and by the finding that B cell responses in ST patients after monocyte-independent stimulation with SAC I were unaffected. ST and CR patients showed no significant differences in B cell subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data indicate that an IL-6-independent monocyte or B cell defect plays a role in the maintenance of stable transplant function.

Adult↗

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.

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 sCR1 were noted. We concluded that complement inhibition by sCR1 may be an important component in the therapeutic approach aiming at the prevention of hyperacute rejection in human organ transplantation.

Animals↗

[New immunosuppressive therapies in kidney transplantation].

New approaches to successful prevention and management of transplant rejection include the use of biological immunosuppressants, such as monoclonal antibodies targeting the CD3 and CD4 molecules on native T cells, the interleukin 2 receptor on activated T cells, monocytes and B cells, and adhesion molecules. Several new drugs have been found to be effective immunosuppressive agents: FK 506, a macrolid antibiotic inhibiting lymphokine gene transcription, lymphokine production and secretion, rapamycin, which blocks effects of lymphokine-induced signal transduction, and RS 61443, brequinar and mizoribine, which inhibit DNA/RNA synthesis and lymphocyte proliferation. Initial experience with these drugs clinical protocols currently in use and already devised for use in the near future to test these and other emerging immunosuppressants are reviewed.

Animals↗

[Kidney transplantation in children].

Renal transplantation has become an established form of therapy for children with endstage renal disease. Evaluation and elimination of potential risk factors, standardization of operative technique and better immunosuppressive regimens improved the outcome in paediatric patients. A shortage or organs means that transplantations cannot always be offered to children for whom it would be the treatment of choice. Kidney donation by living relatives opens up the potential for optimal rehabilitation of patients in the paediatric age group.

Adolescent↗

[Tumor involvement of the vena cava in renal cell carcinoma. Surgical technique, results and prognosis].

In 45 patients with a vena cava tumor thrombus secondary to renal cell carcinoma we present the diagnostic and operative management and relevant data on the extent of the thrombus (classified into 4 stages), postoperative complications and patient survival. Extensive thrombi of the vena cava were removed surgically in hypothermia and with extracorporeal circulation. The importance of an interdisciplinary approach involving cardiac and urologic surgeons is therefore emphasized. With due consideration for relevant prognostic parameters such as tumor differentiation or spread, we estimated a 5-year survival of 29% for our Heidelberg patients. Neither the extent of the tumor thrombus nor tumor infiltration of the perirenal adipose tissue had any influence on patient survival.

Adult↗