[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.

[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.

Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study.

We assessed the therapeutic potential of riociguat, a novel soluble guanylate cyclase stimulator, in adults with chronic thromboembolic pulmonary hypertension (CTEPH; n = 42) or pulmonary arterial hypertension (PAH; n = 33) in World Health Organization (WHO) functional class II/III. In this 12-week, multicentre, open-label, uncontrolled phase II study, patients received oral riociguat 1.0-2.5 mg t.i.d. titrated according to systemic systolic blood pressure (SBP). Primary end-points were safety and tolerability; pharmacodynamic changes were secondary end-points. Riociguat was generally well tolerated. Asymptomatic hypotension (SBP <90 mmHg) occurred in 11 patients, but blood pressure normalised without dose alteration in nine and after dose reduction in two. Median 6-min walking distance increased in patients with CTEPH (55.0 m from baseline (390 m); p<0.0001) and PAH (57.0 m from baseline (337 m); p<0.0001); patients in functional class II or III and bosentan pre-treated patients showed similar improvements. Pulmonary vascular resistance was significantly reduced by 215 dyn·s·cm(-5) from baseline (709 dyn·s·cm(-5); p<0.0001). 42 (56%) patients were considered to have experienced drug-related adverse events (AEs; 96% mild or moderate). Dyspepsia, headache and hypotension were the most frequent AEs. Study discontinuation because of AEs was 4%. These preliminary data show that riociguat has a favourable safety profile and improves exercise capacity, symptoms and pulmonary haemodynamics in CTEPH and PAH. Randomised controlled trials are underway.

[Urodynamic findings in patients with infantile cerebral palsy]. / Videourodynamische Erstbefunde bei infantiler Zerebralparese.

OBJECTIVE: Aim of study was to evaluate the urodynamic findings in patients with infantile cerebral palsy. MATERIAL AND METHODS: In 29 patients (aged 3-53), a videourodynamic investigation was performed after evaluation of urological anamnesis, clinical assessment and sonographic determination of residual urine. The patients were divided into group 1 (23 symptomatic patients aged 5 years and older with recurrent urinary tract infection, pollakiuria or urinary incontinence) and group 2 (6 asymptomatic patients). RESULTS: In group 1, 21/23 patients (91%) had reduced compliance (0.6 - 16.4 ml/cmH(2)O) and 16/23 patients (70%) increased leak point pressure (> 40 cmH(2)O). In all 23 patients, detrusor instability and detrusor sphincter dyssynergia (during voiding) was found. Fluoroscopy showed bladder trabeculation or diverticula in 14 patients (61%) and 2nd-3rd degree vesicoureterorenal reflux in 2 patients (9%). In group 2, 2/6 patients (33%) had reduced compliance (0.7 and 5.8 ml/cmH(2)O) and 4/6 (67%) increased leak point pressure (> 40 cmH(2)O). In 5/6 patients (83%), detrusor instability and detrusor sphincter dyssynergia was seen. Fluoroscopy showed bladder trabeculation in 3 patients (50%), whereas no reflux was observed. Only one of the 29 patients (3 %) showed no pathological videourodynamic or anamnestic findings. CONCLUSIONS: We conclude that videourodynamic assessment should be performed in all patients with infantile cerebral palsy. The decision should not be based on clinical symptoms such as pollakiuria, recurrent urinary tract infection or urinary incontinence.

[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.

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.

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.

Dosage escalation of intravesical oxybutynin in the treatment of neurogenic bladder patients.

OBJECTIVE: We prospectively analyzed the dose dependent outcome and side effects of neurogenic bladder patients with intravesical application of oxybutynin at our centre. MATERIALS AND METHODS: We examined the data of 32 patients with neurogenic bladders and detrusor hyperreflexia. We registered clinical outcome, continence situation, side effects and urodynamic data of patients with (A) standard dosages of intravesical oxybutynin (0.3 mg/kg bodyweight per day) and (B) with increasing dosages in steps of 0.2 mg/kg bodyweight per day up to 0.9 mg/kg bodyweight per day. RESULTS: We examined 32 patients aged 1 to 34 years, mean age 12 years. 21/32 patients became totally continent with the dosage (A). They showed a significant (P<0.01) decrease in the median max detrusor pressure (MDP) and a significant (P<0.01) increase in the median compliance and the median age adjusted bladder capacity (AABC). Eleven out of 32 patients remained incontinent under this dosage (A). Their median MDP, their median compliance and their median AABC remained nearly unchanged. Seven out of 11 incontinent patients under dosage (A) were treated efficiently with the higher dosages (B). Their median necessary dosage escalation to achieve treatment success was 0.7 mg/kg bodyweight per day (range 0.5 to 0.9 mg/kg bodyweight per day). Their median MDP was significantly (P<0.05) decreased and their median compliance and median AABC were significantly (P<0.05) increased. Four out of 11 patients remained incontinent and showed only little improvement in urodynamic data. Two out of 11 patients with the dosage escalation (B) showed side effects at a dosage of 0. 9 mg/kg bodyweight per day. CONCLUSIONS: The intravesical application of oxybutynin was a well tolerated and efficacious therapy. The topical oxybutynin therapy dosage (A) was efficient in 66% of our selected patients, the escalating dosage titration (B) could increase the efficiency to 87%.

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.

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.

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.