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Biomedical subjects

G Staehler

Publications and source records attributed to G Staehler.

At least 37 records · Page 2Linked to original sources

Ureteral complications in renal transplantation with more than one donor ureter.

BACKGROUND: The purpose of this study was to evaluate the ureteral complications of renal transplant recipients with more than one donor ureter METHODS: Between 1967 and 1997, 19 patients (median age 34 years, range 6-62 years) received renal transplants from donors with more than one ureter. There were 18 donor organs with two ureters, and one patient underwent en bloc renal transplantation with four donor ureters. In nine patients, the ureters were implanted separately at the bladder dome according to the extravesical technique of Witzel, Sampson, Lich and Röhl. In 10 patients, we performed a modification of this extravesical technique according to Nghiem with a side-to-side anastomosis of the ureters before completing the ureteroneocystostomy. RESULTS: After a median follow-up of 55 months (range 2-218 months), no graft loss due to ureteral complications was noted. One patient died due to myocardial infarction, seven patients returned to dialysis without ureteral complications. There were two patients (one patient after side-to-side ureteral anastomosis, one patient with separate implantation of the two ureters) with ureteral obstruction of one donor ureter. Both patients underwent open surgical revision with temporarily placement of internal ureteral stents. CONCLUSIONS: The presence of multiple ureters from donor kidneys is associated with a higher complication rate in our patient population compared with donor kidneys with one ureter. There was no difference in the long-term outcome between the two implantation techniques used.

Adolescent↗

Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma.

Human kidney proximal tubule epithelia express the ATP-dependent export pump for anionic conjugates encoded by the MRP2 (cMRP/cMOAT) gene (symbol ABCC2). MRP2, the apical isoform of the multidrug resistance protein, is an integral membrane glycoprotein with a molecular mass of approximately 190 kD that was originally cloned from liver and localized to the canalicular (apical) membrane domain of hepatocytes. In this study, MRP2 was detected in human kidney cortex by reverse transcription-PCR followed by sequencing of a 826-bp cDNA fragment and by immunoblotting using two different antibodies. Human MRP2 was localized to the apical brush-border membrane domain of proximal tubules by double and triple immunofluorescence microscopy including laser scanning microscopy. The expression of MRP2 in renal cell carcinoma was studied by reverse transcription-PCR and immunoblotting in samples from patients undergoing tumor-nephrectomy without prior chemotherapy. Clear-cell carcinomas, originating from the proximal tubule epithelium, expressed MRP2 in 95% (18 of 19) of cases. Immunofluorescence microscopy of MRP2 in clear-cell carcinoma showed a lack of a distinct apical-to-basolateral tumor cell polarity and an additional localization of MRP2 on intracellular membranes. MRP2, the first cloned ATP-dependent export pump for anionic conjugates detected in human kidney, may be involved in renal excretion of various anionic endogenous substances, xenobiotics, and cytotoxic drugs. This conjugate-transporting ATPase encoded by the MRP2 gene has a similar substrate specificity as the multidrug resistance protein MRP1, and may contribute to the multidrug resistance of renal clear-cell carcinomas.

ATP Binding Cassette Transporter, Subfamily B↗

[The intraoperative radiotherapy (IORT) of locally spread and recurrent renal-cell carcinomas].

PURPOSE: Renal cell carcinomas are relatively radioresistant. After macroscopically incomplete tumor resection conventional external beam radiotherapy is dose-limited and additional systemic treatment with chemotherapy ineffective to achieve local control. In a pilot study the role of intraoperative radiotherapy in the treatment of locally advanced or recurrent renal cell carcinomas was analysed. PATIENTS AND METHODS: From January 1992 to July 1994 11 patients with a primary (n = 3) or recurrent renal cell carcinoma had IORT. One patient had complete resection and in 3 respectively 7 patients microscopically or macroscopically residual disease was left. Using 6 to 10 MeV, a single dose of 15 to 20 Gy was delivered to the fossa renalis and the corresponding paraaortic area. Based on three-dimensional treatment planning, additional external beam radiotherapy was given 3 to 4 weeks later (40 Gy, 2 Gy SD, 23 MV). RESULTS: After a mean follow-up of 24.3 months 5 patients had died of distant metastases (lung, liver, bone, mediastinum) with a mean survival time of 11.5 months. Mean disease-free interval was 6.4 months. One patient suffered from a second malignancy. Two patients are alive with distant metastases. Local tumor control in the entire group was 100%. The calculated 4-year overall and disease-free survival was 47% and 34%. The postoperative course was affected in 3 patients (abscess n = 1, short dehiscence of the abdominal wound n = 2). The gastrointestinal toxicity during external beam radiotherapy was low. No IORT-specific late adverse effects were observed. CONCLUSION: After incomplete tumor resection local tumor control with minimal therapy related side effects could be achieved using intraoperative radiotherapy. With IORT the dose limitation in the radiotherapy of renal cell carcinoma could be overcome. The high distant metastases rate relativized overall prognosis. The low morbidity rate justifies further evaluation of this technique.

Carcinoma, Renal Cell↗

[Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new immunosuppressive agent. International Mycophenolate Mofetil Study Group].

1493 patients were enrolled in 55 centers in Europe, Canada, Australia and the USA comparing the efficacy of mycophenolate mofetil (MMF) in daily doses of 2 and 3 g with placebo/azathioprine (PLA/AZA) for the prevention of acute rejection in renal transplant patients. Acute rejections and graft loss and death at 1 year were measured per trial and these data were combined and analyzed in a pooled fashion. The three pooled treatment groups were well balanced regarding demographic characteristics and cause of renal failure leading to transplantation. At one year the graft survival rate was 90.4% and 89.2% in the MMF 2 g and 3 g groups compared with 87.6% in the PLA/AZA-group. MMF 2 and 3 g were significantly better than PLA/AZA in reducing biopsy proven rejection at one year: 40.8% placebo/aza vs. 19.8% in the MMF 2 g group and 16.5% in the MMF 3 g group.

Adult↗

Nonfreezing cryopreservation--a possible means of improving long-term transplant function?

Improving organ preservation techniques for transplantation is one of the most important goals of transplantation research. We have established a new, nonfreezing cryopreservation method to optimize the viability of rat kidneys for transplantation with up to 4 M dimethylsulphoxide (DMSO) in EuroCollins solution (EC) at -5 degrees C to -15 degrees C. We have confirmed the occurrence of a tubular and glomerular defect pattern that mediates acute tubular necrosis (ATN) and that may be a cause of major histocompatibility complex (MHC) independent immunological components of chronic transplant rejection. The extent of this defect [transplant survival and function, 31P-NMR spectroscopy, histological defect index] in the nonfreezing cryopreserved groups (n = 22) is significantly (P = 0.017) lower than in the simple cold storage group (n = 12). Quality and localization of the lesions in kidney transplants can elucidate the context of organ preservation, progressive hyperfiltration defects, and the occurrence of graft failure without elevated frequency of acute rejection episodes. These results indicate that further efforts to provide higher pretransplant organ viability without using it to prolong cold storage intervals may provide better insight into MHC-independent factors of chronic transplant failure and may result in improved long-term transplant outcome.

Animals↗

Superior 3-year kidney graft function in patients with impaired pretransplant Th2 responses.

In a prospective study of 80 patients, we investigated the association of kidney graft rejection with pretransplant CD4 helper/suppressor function, B cell responses, and in vitro cytokine secretion. A pokeweed mitogen-driven allogeneic coculture system was used to assess CD4 helper/suppressor function and T cell-dependent B cell responses. SAC I was used for T cell- and monocyte-independent stimulation of B cell cultures. B cell differentiation was assessed in a reverse hemolytic plaque assay. ELISAs were used to determine in vitro cytokine secretion. None of the 12 patients with pretransplant CD4 helper defects (< 10% helper activity) had acute rejection episodes in contrast to 32 of 68 (47%) patients with normal pretransplant CD4 helper function (P = 0.001). Patients with pretransplant CD4 helper defects exhibited better 3-year graft function than patients without CD4 helper defects (serum creatinine of functioning grafts: 1.2 +/- 0.1 mg/dl compared to 1.7 +/- 0.1 mg/dl, P < 0.05). Low pretransplant IL-10 responses (< 100 pg/ml; 14/80 patients) were significantly associated with a low incidence of acute rejection episodes (P < 0.01) and good 3-year graft function (P < 0.05). These data show that impaired pretransplant Th2 responses-CD4 help and IL-10 responses-predict a low risk of kidney graft rejection and good 3-year graft function, whereas Th1 (IL-2, IFN-gamma) and B cell/monocyte responses are not of predictive value.

B-Lymphocytes↗

[Vena cava invasion in kidney carcinoma--a typical example of multidisciplinary surgery].

Between 1987 and 1998, a total of 79 patients with renal cell carcinoma and venal caval thrombus underwent radical nephrectomy with removal of the tumor thrombus. Of these patients, nine had atrial thrombus extension. Actuarial 5 year survival for patients without metastasis was 39%. For patients with tumor thrombi not invading the right atrium (state I-III) the 5 year survival rate was up to 50% and was not related to the cranial extent of the tumor thrombus. We conclude that an aggressive multispeciality surgical approach is justified as it provides prolonged survival even in patients with large vena caval thrombi.

Aged↗

[Status of organ preserving surgery in renal cell carcinoma].

Nephron-sparing surgery in renal cell carcinoma is an accepted approach in patients with bilateral carcinomas, solitary kidneys and in patients with chronic renal failure in whom radical nephrectomy would necessitate immediate renal replacement therapy (mandatory indications). Because of the improvement of operative techniques-like renal perfusion in hypothermia or work-bench surgery-over 95% of patients can spared dialysis even if multiple tumors or locally advanced renal cancer is present. Based on the excellent outcome of nephron-sparing surgery in mandatory indications (5-year survival rates over 80%), several centers advocate extending the use of partial nephrectomy to selected patients with a normal opposite kidney (elective indications). Several reports on nephron-sparing surgery in elective indications with a median follow-up time of 40 months document similar survival rates compared to radical nephrectomy. Nevertheless, due to the low incidence of bilateral renal carcinomas (under 2%), only 2 of 100 patients would benefit from this approach. Furthermore, local recurrence after nephron-sparing surgery occurs mostly after 4 years (late recurrence); therefore, it seems doubtful whether the short follow-up times really reveal the the true recurrence rate. The prognosis after development of a local recurrence is poor.

Carcinoma, Renal Cell↗

[Renal cell carcinoma with vena cava involvement. Surgical strategies and results].

The elaboration of new operative procedures established in the last decade has led to an improved prognosis in patients with renal cell carcinoma with vena caval extension. We report on our personal operative experience in over 100 patients and present the current analysis of 76 patients with renal carcinoma with vena caval extension seen in our institution between 1985 and 1996. Sixty-six patients underwent nephrectomy and removal of vena caval tumor thrombi. Actuarial 5-year survival for patients without metastasis was 38%. For patients with tumor stages between I and III, 5-year survival was between 40 and 50% and was not significantly related to the rostral extent of the tumor thrombus. The relatively poor outcome for patients with tumor thrombi invading the right atrium was caused by a high perioperative mortality (50%). For patients with distant metastases, medium survival time was 10.5 months, implying that radical surgery is useless in cases of distant metastases.

Adult↗

[Brain metastases in renal cell carcinoma. Results of treatment and prognosis].

Brain metastases develop as a late manifestation of renal cell cancer (RCC) and pose an increasing challenge to urologists as a result of the more frequent prolonged survival of patients with advanced RCC. Therapeutic options, including surgical resection and radiotherapy, were analyzed retrospectively to assess survival and to identify factors influencing prognosis in a group of 90 patients treated either by brain metastasectomy (n = 64) or radiotherapy (n = 26). The analysis confirmed that the overall median survival was a disappointing 461 days and the 1-year survival rate was 31% for patients treated by surgical resection and 310 days and 15% respectively for patients treated by radiotherapy. However, a subgroup of patients who, benefitted significantly from aggressive treatment of metastases could be defined. The following favorable prognostic factors showed a trend toward improved survival: (1) metachronous appearance of brain metastases more than 1 year after nephrectomy (P < 0.0001), (2) good patient performance (Karnofsky > 70) (P < 0.0002), (3) patient's age under 50 years (P < 0.05), (4) solitary lesions (P < 0.05), (5) minimal or no neurological deficit (P < 0.05), and (6) the absence of/or minimal extracranial metastases (P < 0.05). No influence of lesion size and localization (infratentorial vs supratentorial) on survival was detected. Surgical treatment of recurrent brain tumors (n = 17) yielded and additional median survival advantage of 8 months as compared to untreated patients (n = 16). Our results suggest that, especially in patients with good prognostic criteria, a radical metastasectomy plus vigorous surgery of local recurrences and, if required, subsequent systemic immuno- or chemoimmunotherapy should be performed. In patients with poor prognosis, stereotactic radiosurgery is recommended for palliation and survival prolongation.

Adult↗

[The clinical significance of renal cell carcinoma in dialysis dependent patients in comparison with kidney transplant recipients].

The clinical relevance of de novo Renal Cell Cancer was compared in chronic hemodialysis patients and renal allograft recipients. Clinical course of these patients was followed for 15 years. 21 of 788 patients who underwent radical nephrectomy were suffering from renal insufficiency at the time of surgery. Evaluated data included clinical symptoms; tumor histology and clinical course. 19 patients received chronic hemodialysis treatment. 7 patients demonstrated stable function of the allograft. 92% of patients receiving hemodialysis treatment did not show metastasis and none died of renal cell carcinoma. On the contrary, 71% of patients who underwent renal transplantation showed advanced tumor disease or metastasis. 3 patients have died of RCC. Aggressive tumor growth of RCC requires close follow up in patients who received a renal allograft.

Adult↗

[Magnetic resonance urography. First clinical results].

We report our preliminary results using a new magnetic resonance imaging technique for visualization of the urinary tract. Using the paramagnetic contrast medium gadolinium diethylene triamine penta-acetic acid (DTPA), we were able to obtain images of the urinary tract comparable to those obtained by conventional excretory urography. The major advantage of our technique is that besides good morphologic visualization, the excretion of gadolinium-DTPA can be studied simultaneously. We demonstrate our preliminary results in selected cases.

Adult↗

Effects of carbon dioxide pneumoperitoneum in pigs with impaired pulmonary function.

The objective of our study was to investigate the possible adverse hemodynamic effects of a CO2 pneumoperitoneum in an experimental model in pigs with impaired pulmonary function. Thirteen animals were anesthetized with azaperon/ketamine and ventilated with 67% nitrous oxide in oxygen. By intravenous injection of dextran microspheres, a capillary pulmonary embolism was induced. After embolization, three animals served as controls (Group 1), five underwent open nephrectomy (Group 2), and five underwent laparoscopic nephrectomy (Group 3). Intra-abdominal pressure was kept constant at 15 mm Hg. At intervals, hemodynamic parameters were measured, and blood gas measurements were performed. Data were analyzed using a general linear model analysis of variance for differences between groups, and a paired t-test was applied for differences within groups from one condition to the next. The groupwise comparison revealed a significant rise of cardiac output in the laparoscopy group compared with the open nephrectomy group. No differences were noted for heart rate, systemic arterial pressure, central venous pressure, mean pulmonary arterial pressure, or pulmonary arterial wedge pressure. Impairment of pulmonary function caused no negative hemodynamic effect during laparoscopic nephrectomy.

Analysis of Variance↗

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.

Adult↗