[Pulmonary hypertension due to chronic lung disease. Recommendations of the Cologne Consensus Conference 2010]. / Pulmonale Hypertonie bei chronischen Lungenerkrankungen. Empfehlungen der Kölner Konsensus-Konferenz 2010.

The 2009 European Guidelines on Pulmonary Hypertension did not cover only pulmonary arterial hypertension (PAH) but also some aspects of pulmonary hypertension (PH) in chronic lung disease. The European Guidelines point out that the drugs currently used to treat patients with PAH (prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors) have not been sufficiently investigated in other forms of PH. Therefore, the European Guidelines do not recommend the use of these drugs in patients with chronic lung disease and PH. This recommendation, however, is not always in agreement with medical ethics as physicians feel sometimes inclined to treat other form of pulmonary hypertension which may affect quality of life and survival of these patients in a similar manner. In June 2010, a group of German experts met in Cologne, Germany, to discuss open and controversial issues surrounding the practical implementation of the European Guidelines. The conference was sponsored by the German Society of Cardiology, the German Society of Respiratory Medicine and the German Society of Pediatric Cardiology. One of the working groups was dedicated to the diagnosis and treatment of PH in patients with chronic lung disease. The recommendations of this working group are summarized in the present paper.

[Vacuum sealing of extensive wound healing disorders after kidney transplantation]. / Vakuumversieglung bei ausgeprägten Wundheilungsstörungen nach Nierentransplantation.

With the introduction of mycophenolate mofetil (MMF) in renal transplantation, acute rejection episodes diminished and short-term graft survival improved. Better graft outcome, however, is followed by several surgical complications attributed to MMF. Patients with risk factors (adiposity, diabetes mellitus, advanced age) show an increased rate of healing by second intention. We treated two patients with the vacuum sealing technique so that after 15 days a secondary suture became possible in each case. To date the vacuum sealing technique has been used mainly in traumatology, abdominal surgery, surgery for acute infections of soft tissue and bone, and problem wounds with reduced wound-healing capacity (chronic leg ulcer). This article presents two cases of successful application of the vacuum sealing technique in renal transplantation after prolonged wound healing.

[Laparoscopic liver donor nephrectomy. Personal experiences and review of the literature]. / Laparoskopische Lebendspendernephrektomie. Eigene Erfahrungen und Literaturübersicht.

Despite improved success rates, the number of kidney transplantations in Germany in the last few years has stagnated, resulting in increasing waiting lists of patients on dialysis. In Germany, only 16.7% of kidney transplantations are living-donor nephrectomies, representing a relatively low rate compared to other countries (The Netherlands 28%, Sweden 35%). Since April 1998, we have performed ten retroperitoneoscopic living-donor nephrectomies (six left, four right side). The mean operating time was 216 min (155-290) with minimal blood loss. No intraoperative complications were observed. Warm ischemia time amounted to a mean of 4 min (2-7). The mean cold ischemia time was 165 min (76-290). Postoperative hospital stay of the donors was 6 days (4-10). All transplants functioned immediately; mean serum creatinine dropped from initially 8.0 mg/dl (5.3-11.5) on day 1 to 1.4 mg/dl (0.9-1.6) 3 months after surgery. This did not differ from previously operated open donor nephrectomies. An analysis of the literature included data of 4240 patients from 25 publications between 1980 and 2000 reporting on either open or laparoscopic living donor nephrectomies.

Impaired bone metabolism following augmentation cystoplasties in growing rats.

OBJECTIVE: The aim of this study was to evaluate the possible risk of impaired bone metabolism following augmentation cystoplasties with different gastrointestinal segments. METHOD: 60 young rats underwent augmentation cystoplasties using gastric, ileal or sigma segments, or sham operations. An additional group undergoing sigma-cystoplasty received the bisphosphonate ibandronate to inhibit osteoclast-mediated bone resorption. Bone mass in the lumbar spine and tibia was analyzed monthly by in vivo densitometry. Bone turnover was assessed monthly using current bone metabolism markers for a period of 16 weeks. Bone ashing and serum analyses of the osteotropic hormones parathyroid hormone (PTH), and 25-OH vitamin D3 were performed at study conclusion. RESULTS: Following ileocystoplasty, reduced bone mineral density (BMD) was seen throughout the observation period; this was pronounced in the trabecular bone. The decline in BMD was associated with decreased serum 25-OH vitamin D3 levels. Following sigmacystoplasty, bone calcium content was significantly decreased; this could be prevented by ibandronate. No skeletal changes occurred in the gastrocystoplasty group. Serum pH was not altered in any group, and markers of bone resorption indicated normal bone resorption rates. CONCLUSION: There is a significant correlation between impaired bone metabolism and the type of segment used for bladder augmentation. While the use of the ileum (and probably the colon too) causes osteopenia, gastrocystoplasties seem to have little influence on bone turnover.

Detection of hematogenous micrometastasis in patients with transitional cell carcinoma.

PURPOSE: Cytokeratin 20 (CK 20) is selectively expressed in urothelium, gastric intestinal epithelium, in Merkel cells and in a variety of malignant neoplasms. CK 20 RT-PCR assay has been extensively used to detect isolated cancer cells in peripheral blood, lymph nodes and bone marrow samples of patients with colorectal carcinoma. Since CK-20 is also actively expressed in transitional cell carcinoma (TCC), we analyzed, whether CK 20 Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) is suitable to detect residual tumor cells in patients with transitional cell carcinoma of the bladder and the upper urinary tract. MATERIALS AND METHODS: Nested Reverse Transcriptase Polymerase Chain Reaction assay was used to analyze CK 20 transcripts in peripheral venous blood samples and tumor biopsies of 49 patients with transitional cell carcinoma. Blood samples of 22 healthy volunteers served as negative controls. RESULTS: CK 20 mRNA was detectable in blood samples of 12 of 49 patients with TCC. All blood samples of the control group tested negative. The detection rate for CK 20 mRNA significantly correlated (p = 0.0019, Cochran-Armitage Trend Test) to the stage of disease and increased from 0% in stage pTa to 63% in stage pT4. CONCLUSIONS: These results suggest that CK 20 is a suitable marker for the detection of disseminated TCC cells in peripheral venous blood samples and may be helpful in the molecular staging of TCC patients. The prognostic relevance has to be evaluated in further followup.

Pitfalls of repeat subureteral bovine collagen injections for the endoscopic treatment of vesicoureteral reflux.

PURPOSE: Collagen has been used for the endoscopic subureteral treatment of vesicoureteral reflux since the late 1980s. We evaluated the long-term efficacy of repeat subureteral glutaraldehyde bovine cross-linked collagen injections for the endoscopic management of vesicoureteral reflux. MATERIALS AND METHODS: We prospectively evaluated 14 girls and 2 boys (21 ureteral units) 6 months to 16 years old (median age 6 years). In all patients initial treatment failed or reflux recurred after a single subureteral collagen injection and injection was repeated. Patients were followed with voiding cystography. Reflux-free periods after each injection and reflux grade were documented. RESULTS: All patients were treated twice with subureteral bovine collagen injection. Mean injected collagen volume of injections 1 and 2 was 1. 5 ml. (range 0.7 to 3.0) and 1.6 ml. (range 1.0 to 2.3), respectively, at a concentration of 35 mg./ml. In all but 4 cases reflux disappeared after injection 2. Mean followup was 11 months (range 1 to 41) after treatment 2. However in 10 patients (13 ureteral units) treatment failed or reflux recurred a mean of 10 months after injection 2. The reflux-free period after injection 2 was prolonged compared to that after injection 1 (p <0.05). CONCLUSIONS: Our results suggest that repeat endoscopic subureteral bovine collagen injections prolong the reflux-free period but remain ineffective at long-term followup for correcting vesicoureteral reflux.

Failure of subureteral bovine collagen injection for the endoscopic treatment of primary vesicoureteral reflux in long-term follow-up.

OBJECTIVES: To evaluate the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of primary vesicoureteral reflux (VUR). METHODS: We prospectively studied 36 patients (58 ureteral renal units), 30 girls and 6 boys with a median age of 6 years (range 2 months to 18 years). All patients had primary VUR and were treated with a single subureteral collagen injection (GAX 35). The patients were followed up by voiding cystography. RESULTS: According to the International Reflux Study Classification, we found the following reflux grades preoperatively: grade I, 2 ureteral units; grade II, 21 units; grade III, 28 units; grade IV, 4 units, and grade V, 3 units. All patients were treated with subureteral bovine collagen injection (GAX 35, mean volume 1.7 mL, range 0.7 to 3.5). All but 3 cases of reflux resolved initially. The mean follow-up was 13 months (range 1 to 108). After 37 months of follow-up, only 5 (9%) of 57 treated units remained reflux free. One unit was followed up for 17 months and also remained reflux free. CONCLUSIONS: These data suggest that a single endoscopic subureteral collagen injection is not effective in the long-term follow-up of patients with primary VUR. In the future, it will be important to determine whether the new, currently used, and soon be approved bulking agents show better long-term clinical results to prevent VUR recurrence than bovine collagen does.

The role of radical surgery for renal cell carcinoma with extension into the vena cava.

PURPOSE: New operative technologies, such as the bypass procedures that have become established in the last decade, have led to improved prognosis in patients with renal cell carcinoma and vena caval thrombi. We report the outcome of stage dependent surgical strategies in patients with renal cell carcinoma extending into the vena cava. MATERIALS AND METHODS: From January 1987 to August 1998, 93 patients with renal cell carcinoma invading the inferior vena cava were seen at our institution. Of the patients 79 underwent radical nephrectomy, phlebotomy and thrombus extraction, including 74 who underwent surgical treatment with cardiopulmonary bypass and deep hypothermic circulatory arrest. In 2 patients with retrohepatic thrombi we placed a pump driven femoro-axillary shunt during surgical resection of the retrohepatic tumor portion. RESULTS: Distant metastases and lymph node involvement proved to be highly significant prognostic factors for survival, while the cranial extent of the tumor thrombi had no prognostic impact. Patients without distant metastases had a 5-year survival rate of 34%, which improved to 39% if regional lymph nodes were not involved. There were 5 perioperative deaths (6.3%) and the highest perioperative mortality rate (40%) was seen in patients with supradiaphragmatic thrombi. CONCLUSIONS: Radical surgery for renal cell carcinoma extending to the vena cava is justified when the tumor thrombus does not extend beyond the level of the diaphragm in the cranial direction. In view of the high perioperative mortality decisions about radical surgery must be made individually in patients with level IV thrombi, even if long-term survival is possible.

[Preoperative staging of renal cell carcinoma with caval thrombus: is staging in MRI justified? Prospective histopathological correlated study]. / Präoperatives Staging von Nierenzellkarzinomen mit Kavazapfen: welches diagnostische Verfahren?.MRT oder CT - Prospektive histologisch kontrollierte Studie.

To 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.

Long-term efficacy of subureteral collagen injection for endoscopic treatment of vesicoureteral reflux in neurogenic bladder cases.

PURPOSE: We evaluated the long-term efficacy of subureteral glutaraldehyde cross-linked collagen injection (GAX 35) for endoscopic treatment of vesicoureteral reflux in patients with neurogenic bladder dysfunction due to meningomyelocele. MATERIALS AND METHODS: We prospectively studied 12 women and 8 men (26 ureteral renal units) with a median age of 8 years (range 1 to 51) who had neurogenic bladder due to meningomyelocele. Reflux into single collecting systems was treated with subureteral collagen injection (GAX 35). Followup with video urodynamics included voiding cystography. RESULTS: All patients performed intermittent catheterization to control the bladder. During the study all bladders were areflexic with normal compliance. Preoperative reflux according to the International Reflux Study Classification was grade I in 1, II in 9, III in 10, IV in 4 and V in 2 ureteral renal units. All patients were treated with subureteral collagen injection (mean volume 1.9 ml., range 0.7 to 3.5). Reflux resolved initially in all but 2 cases. Mean followup was 16 months (range 1 to 71). Reflux was still absent in only 15% of treated units after 24 months. CONCLUSIONS: Our data suggest that endoscopic subureteral collagen injection in neurogenic bladder cases is not effective with long-term followup. New biocompatible and biodegradable materials should be tested to control vesicoureteral reflux.

[Spontaneous kidney rupture after delivery due to an urothelial carcinoma]. / Spontanruptur einer Niere post partum aufgrund eines urothelialen Karzinoms. Bedeutung für die bildgebende Diagnostik.

The case of a spontaneous kidney rupture due to an urothelial carcinoma one week after delivery is presented. Diagnosis was made during operation. In comparison to the carcinoma, which is diagnosed and treated in time, the prognosis is poor. The patient deserved continuous gynecological follow-up and showed the classic symptoms of an urothelial carcinoma for six months. In spite of regular sonographic controls during pregnancy the tumor was not diagnosed. Diagnosis and management of renal carcinomas during pregnancy are discussed.

[The role of surgery in renal cell carcinoma]. / Die chirurgische Therapie des Nierenzellkarzinoms.

Renal cell carcinoma accounts about three percent of all adult neoplasms. This review provides a current status about the surgical management of renal cell carcinoma. In localised carcinomas radical nephrectomy is still the standard treatment and provides 5 Year survival rates up to 98 %. As nephron-sparing surgery in mandatory indications can achieve similar survival doubt can be expressed whether lymphadenectomy or adrenalectomy are necessary in every case. Nephron-sparing surgery is associated with a higher rate of operative complications up to 40 % and probably with a higher risk of local recurrence. However, parenchymal-sparing surgery in elective indications is possible for small tumors, if long term follow up is guaranteed. But there is no convincing advantage of nephron-sparing surgery to recommend this procedure as a general approach in patients with a normal contralateral kidney. Radical surgery in renal carcinomas invading to the vena cava still remains a challenging surgical intervention. Nevertheless, in selected patients surgery can realise long term survival in over a third of cases. Palliative nephrectomy in metastatic renal carcinomas is only justified in real palliative indications (bleeding, pain) or in clinical trials investigating cytoreductive surgery before immunotherapy. In highly selected patients with metastatic renal carcinoma a radical surgical approach including nephrectomy and complete metastasectomy can achieve long term survival.

Role of color-coded Doppler sonography in the assessment of internal ureteral stent patency.

OBJECTIVE: To evaluate the role of color-coded Doppler sonography (CCDS) in the assessment of internal ureteral stent patency. PATIENTS AND METHODS: We compared micturating cystography (MC) and CCDS in 48 patients with internal ureteral stents. Forty-five of these patients had pyelocaliectasis on renal sonography. RESULTS: In all of the 48 patients, the distal end of the internal ureteral stent could be seen sonographically in the bladder. The color images of 30 patients showed typical flow from the distal holes of the stent. Micturating cystography demonstrated patency of the stents in 36 patients. The two procedures showed the same results in 42 of 48 patients. Six patients had no detectable flow by CCDS, but the MCs showed patency of the stents. CONCLUSION: The CCDS is a valid noninvasive method for the assessment of internal ureteral stent patency with a sensitivity of 100%, a specificity of 83%, a positive predictive value of 67%, and a negative predictive value of 100%.

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.

[Mycophenolate mofetil (MMF) for prevention of kidney transplant rejection. A new immunosuppressive agent. International Mycophenolate Mofetil Study Group]. / Mycophenolate Mofetil (MMF) zur Prophylaxe von Nierentransplantatabstossungen. Ein neues Immunsuppressivum. 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.

[The intraoperative radiotherapy (IORT) of locally spread and recurrent renal-cell carcinomas]. / Intraoperative Radiotherapie (IORT) lokal ausgedehnter und rezidivierter Nierenzellkarzinome.

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.

[Vena cava invasion in kidney carcinoma--a typical example of multidisciplinary surgery]. / Der Cavazapfen beim Nierenkarzinom--ein typisches Beispiel zum multidisziplinären chirurgischen Vorgehen.

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.

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.