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P Eschwege

Publications and source records attributed to P Eschwege.

At least 19 recordsLinked to original sources

Downregulation of Bcl-2 sensitises interferon-resistant renal cancer cells to Fas.

Interferon alpha (IFNalpha) is used to treat patients with advanced renal cell carcinoma (RCC) despite limited clinical benefit. IFNalpha can induce Fas receptor-mediated apoptosis by direct activation of pro-caspase-8 followed by activation of caspase-3. Alternative, indirect activation of caspase-3 via mitochondrial release of cytochrome c can occur and may explain the rescue from Fas-activated cell death by the antiapoptotic members of the Bcl-2 family. In this study, we examined G3139, a novel antisense compound targeting Bcl-2, in combination with IFNalpha. Human RCC lines (SK-RC-44 and SK-RC-07) were treated with IFNalpha, G3139 or a combination of the two. Fas-mediated cytotoxicity was induced by anti-Fas mAb, CH11. An analysis of Bcl-2, Fas and the cleavage of PARP was performed. IFNalpha induced Fas and Bcl-2 in SK-RC-44 and SK-RC-07. IFNalpha sensitised SK-RC-44 to anti-Fas and induced PARP cleavage confirming that IFNalpha has a cytotoxic effect on RCC lines by induction of the Fas antigen. Cytotoxicity was not evident in SK-RC-07 cells treated with IFNalpha. G3139 induced a specific downregulation of Bcl-2 in SK-RC-07 cells, which were then sensitised to anti-Fas after treatment with IFNalpha. Taken together, these results suggest that Fas-dependent pathways as well as alternative pathways, which can be inhibited by Bcl-2, exist in renal cell carcinoma. G3139 in combination with IFNalpha is a potential therapy in patients with metastatic renal cell carcinoma.

Antineoplastic Agents↗

Prospective evaluation of Ki-67 labeling in predicting the recurrence and progression of superficial bladder transitional cell carcinoma.

PURPOSE: We studied a series of superficial transitional cell carcinoma of the bladder to assess whether the Ki-67 labeling index predicts recurrence and progression in a cohort of patients treated by transurethral resection alone or receiving adjuvant intravesical bacillus Calmette-Guerin therapy (BCG). MATERIALS AND METHODS: From 1989 to 1990, we prospectively studied 70 consecutive cases of superficial transitional cell carcinoma of the bladder using Ki-67 immunostaining. The tumors were 43 pTa and 27 pTl. Thirteen were treated with transurethral resection only and 57 received adjuvant intravesical BCG. The median follow-up times was 64 months. The threshold index values of Ki-67 for recurrence and progression were determined using ROC curves. The relative predictive values of the Ki-67 labeling index and tumor characteristics for recurrence and progression were evaluated using Cox's proportional hazards model. RESULTS: A cutoff value of 13% was determined. The recurrence free survival rate at 5 years was 68% for cases with a Ki-67 labeling index of 13 or higher and 71% for those with an index of less than 13 (NS). The progression-free survival rate at 5 years was 43% in cases with an index of 13 or higher and 89% in those with an index of less than 13 (p<0.0001). Using multivariate analysis the Ki-67 labeling index is an independent risk factor for tumor progression with a relative risk of 4.61 (p<0.05). CONCLUSION: When BCG is used for high and intermediate risk superficial bladder cancers, the Ki-67 labeling index is an independent predictive factor of progression but not of recurrence.

Adult↗

Primary malignant lymphoma of the urinary bladder: report of three cases and review of the literature.

We report three cases of a primary malignant lymphoma of the urinary bladder. The radiological features revealed a sessile mass of the lateral wall for one case, a circumferential thickening in the second, and two separated masses of the bladder wall in the last case. Primary malignant lymphoma of the urinary bladder is extremely rare. From a review of the literature, the clinical and radiological findings are discussed. In this paper we report the first case of urinary bladder lymphoma presented on CTas multiple masses.

Aged↗

Expression of vascular endothelial growth factor in renal cell carcinomas.

Vascular endothelial growth factor (VEGF) is an angiogenic factor that may be involved in tumor growth and metastasis. Only a few data concerning the role of VEGF in renal cell carcinomas (RCCs) are available, and no studies have yet evaluated its prognostic value. The aim of the present study was to assess VEGF expression in a large series of renal tumors with a long follow-up, correlated with the usual histoprognostic factors and survival. VEGF immunostaining was performed on formalin-fixed, paraffin-embedded archival tissue from 74 renal carcinomas (62 conventional renal cell and 12 papillary carcinomas). Positivity of immunostaining was semi-quantitatively scored by two pathologists. Angiogenesis was evaluated by immunostaining with anti-CD34 antibodies on serial sections. Cytoplasmic VEGF expression was detected in tumor cells in 35% (26/74) of RCCs, including 18 out of the 62 (29%) conventional RCCs and 8 out of the 12 (67%) papillary carcinomas (P=0.02). In the group of conventional RCCs, VEGF expression was positively correlated with both nuclear grade (P=0.05) and size of the tumor (P=0.05). Furthermore, a significant correlation was observed between VEGF expression and microvascular count (P=0.04). Finally, cumulative survival rate was significantly lower in the group of patients with conventional RCCs expressing VEGF (log rank test, P=0.01). In the Cox model, VEGF expression was a significant independent predictor of outcome, as well as stage and nuclear grade. This study suggests that VEGF is involved in angiogenesis in conventional RCCs and appears to be a potential prognostic factor in these tumors.

Blood Vessels↗

[Which urologic treatment alternatives are there for the hemophiliac patient?].

OBJECTIVE: Urological procedures are hazardous for hemophilic patients. The aim of this work is to report the treatment of 22 hemophilic patients in order to define prognosis factors and treatment options. MATERIAL AND METHODS: 22 patients have been treated: 8 had severe hemophilia, 5 A (FVIII < 1%), 3 B (F IX < 1%), 2 had moderate hemophilia A (FVIII 2 to 6%) and 10 minor hemophilia A (F VIII 7 to 30%). Two had acquired hemophilia with auto-anti-FVIII antibodies (ab). Four patients were HIV+. Eighteen patients were first referred to our hospital, and 3 were transferred from an other institution for persistent hematuria: one with anuria, one after bladder neck incision, and the other following suprapubic prostatectomy. RESULTS: For patients without FVIII ab, a sufficient level of FVIII or IX (> 60%), could be achieved pre-operatively and maintained post operatively (4 to 20 days, according to the surgical procedure) by injections of FVIII, FIX or by injections of desmopressin. For one haemophilia A patient with anti-F VIII ab, transferred for uncontrollable bleeding after bladder neck incision, selective arterial embolization was successful. But for 2 patients with acquired haemophilia, improvement of the coagulation was insufficient, with human or porcine FVIII, activated prothombic complex concentrates or recombinant activated FVII. In spite of surgical procedures and arterial embolizations the 2 patients died. CONCLUSION: The urological treatment of haemophilic patients needs to be performed in specialised centers. For patients without FVIII ab, classical urological procedures can be performed. But for patients with FVIII ab when alternative treatments (radiotherapy, LHRH agonists) can be used, the surgical procedures must be delayed; in emergency if hemostasis cannot be achieved arterial embolization could be useful.

Adolescent↗

[Emphysematous pyelonephritis: apropos of 4 cases].

PURPOSE: The propose of this study was to describe the imaging findings in four patients with emphysematous pyelonephritis and to perform a review of the literature. MATERIAL AND METHODS: Four cases of emphysematous pyelonephritis are presented. US and CT examinations were available for all patients. RESULTS: Gas within the kidney may be diagnosed by plain film or rarely by ultrasound, but its location and its extent are best evaluated by CT. A review of the literature shows that emphysematous pyelonephritis is a rare and life-threatening infection typically occurring in diabetic patients. CONCLUSION: CT is useful for diagnosing emphysematous pyelonephritis, especially when symptoms fail to resolve promptly with medical therapy.

Adult↗

Clonal analysis of renal sporadic angiomyolipomas.

Renal angiomyolipomas are benign tumors composed of variable amounts of mature fat, smooth muscle, and thick-walled blood vessels. They occur either sporadically or in association with tuberous sclerosis. Such tumors are considered as hamartomas, but few data are available concerning their pathogenesis. Indeed, it is not known whether angiomyolipoma is a congenital malformation or a neoplastic process. To answer this question, we assessed the clonality of sporadic angiomyolipomas using molecular analysis. Seven women (mean age, 59 years) with renal angiomyolipomas were included. DNA of the tumor and the normal adjacent kidney was extracted from archival paraffin-embedded tissue. DNA methylation pattern at a polymorphic site on the HUMARA gene was studied by polymerase chain reaction (PCR) amplification after methylation-sensitive enzyme digestion. This procedure enables the differentiation between polyclonal and monoclonal lesions according to their X-chromosome inactivation pattern. Five of the seven women included were informative for the HUMARA gene. The mean size of the angiomyolipomas was 53 mm (range, 18 to 110). In one case, a tumor thrombus was observed in the inferior vena cava. Clonal analysis showed that all of the angiomyolipomas and the tumor thrombus studied were monoclonal. This study shows that sporadic angiomyolipomas are monoclonal lesions consistent with neoplastic disorders. This result strongly supports the hypothesis that angiomyolipomas arise from the clonal proliferation of an uncommited cell, which will further evolve toward different cell types.

Adult↗

Liver preservation below 0 degrees C with UW solution and 2,3-butanediol.

Long-term preservation of the liver is needed to transform liver transplantation from an emergency operation to an elective procedure and therefore to improve the results of liver transplantation. We explored the possibility of extending the cold ischemia time of the rat liver by using a preservation temperature below 0 degrees C together with the addition of a cryoprotective agent (2,3-butanediol) at a low concentration in the preservation solution. Rat livers were preserved for 72 h either with UW solution at +4 degrees C (group 1) or with a UW solution, to which 2,3-butanediol at 8% (at +4 degrees C (group 2) or at -4 degrees C (group 3, experimental group)) was added. Following the preservation process, the viability of the livers was assessed using the isolated perfused liver model. Enzymatic release, bile production, and portal venous flow were not significantly different between group 1 and group 3. In the two groups in which preservation included 2,3-butanediol, the enzymatic release was significantly greater when the preservation temperature was +4 degrees C. We conclude that, using this method, preservation of the rat liver below 0 degrees C seems feasible. However, despite its low concentration, some toxicity of 2, 3-butanediol was suspected. This would counterbalance the benefit resulting from the temperature-related decrease of the enzymatic activities involved in cold ischemia damage. The potential advantages of this method need to be confirmed by assessing liver viability using a liver transplantation model.

Adenosine↗

[Cadaver donor nephrectomy. Surgical technique in the context of multi-organ donation].

95% of renal transplantations performed in France use cadaver donor kidneys. Two donor nephrectomy techniques are proposed: a beating heart technique and an arrested heart technique. In the very great majority of cases (80%), donor nephrectomy can be performed during multi-organ removal, performed according to bioethical regulations: unrelated, anonymity between donor and recipient, security, traceability and evaluation. The urologist has a role to play at each step of organ donation, in which he is the main protagonist. The first steps are performed in close collaboration with the intensive care unit which established the diagnosis of brain death of the potential donor. The following steps, guided by the French transplant establishment, are the urologist's responsibility: He is responsible for abdominal exploration looking for a tumour or any other abnormality. A strictly aseptic technique is essential to prevent contamination of the organ. He is responsible for removing kidneys in such a way as to ensure the shortest possible warm ischaemia time, the best storage solution, and the best preservation of their anatomical structure. He must be familiar with the outcome of transplants in order to adapt his technique to the results of transplants.

Brain Death↗