[Pyeloplasty - pro robotic-assisted]. / Nierenbeckenplastik - pro robotisch.

Open pyeloplasty is still the gold standard in the treatment of ureteropelvic junction (UPJ) obstructions in many clinics. Similar functional results could be shown in diverse publications using conventional laparoscopic pyeloplasty (CLPP). The reconstruction of the UPJ is the main step during this type of surgery and constitutes a major challenge to surgeons working with minimally invasive techniques. The more complex the surgery the more obvious the benefits of robotic assistance (seven grades of freedom, 3D view etc.) in comparison to conventional laparoscopy. Thus robotic assistance is optimally suitable for pyeloplasty. The robotic-assisted laparoscopic pyeloplasty (RLPP) facilitates intracorporeal suturing and shortens the learning curve. Residents benefit from this shortened learning curve. Disorders caused by the non-physiological position during conventional laparoscopy are avoided during RLPP, which is an additionally benefit. Robotics also seem to be the optimum platform for the future of reconstructive LESS. The RLPP rather than the CLPP technique has therefore the potential to replace open pyeloplasty as the gold standard in treatment of UPJ.

Does the distance to normal renal parenchyma (DTNRP) in nephron-sparing surgery for renal cell carcinoma have an effect on survival?

BACKGROUND: The effect of the distance to normal renal parenchyma (DTNRP) on survival after nephron-sparing surgery (NSS) for renal cell cancer (RCC) was analyzed. Additionally, the role of T-classification, tumor diameter and tumor grading was considered. PATIENTS AND METHODS: NSS was performed on 126 patients with RCC between 1988 and 2000. Eighty-six patients were submitted to annual follow-up. These 86 patients were sub-classified into statistical groups according to the distance to normal renal parenchyma (< or = 2mm; > 2mm - < or = 5mm; >5 mm), T-classification, tumor diameter (< or = 20mm; > 20mm - < or = 30 mm; >30 mm - < or = 50mm; > 50mm) and tumor grading. The effect of belonging to one of these groups on survival was analyzed using the Log-Rank-Test (SPSS; version 11.0) and the Kaplan and Meier survival data. The level of significance was set at p < 0.05. RESULTS: During the follow-up period, 4 patients died related to RCC and 15 patients died from other causes. The tumor-specific survival was 95.4%. At the end of 2002, the mean follow-up time was 5.5 years (range 0.1 - 14.7). None of the variables which had been analyzed in our statistical groups had an effect on the overall survival. CONCLUSION: The distance to normal renal parenchyma does not influence survival, suggesting an additional resection to be unnecessary even in cases where the DTNRP is reported by frozen section to be less than 2 mm. RCC up to 5 cn in tumor diameter can be safely removed by NSS, even in the presence of a functional intact contralateral kidney.

Radiochemotherapy after transurethral resection is an effective treatment method in T1G3 bladder cancer.

AIM: Conservative therapy using deep transurethral resection (TUR) followed by radiochemotherapy is a novel treatment strategy in stage TI grade 3 (TIG3) transitional cell carcinoma (TCC) of the bladder. The aim of this study was to present our long-term results of radiochemotherapy in T1G3 TCC patients. MATERIALS AND METHODS: A total of 64 patients with TIG3 TCC of the bladder underwent a TUR and a subsequent radiochemotherapy protocol at our institution. Following TUR, a median dose of 55.8 (range; 45-69.4) Gy radiation therapy was applied to the bladder, and simultaneous chemotherapy was initiated using cisplatin, carboplatin and/or 5-fluorouracil. After completion of the protocol, response was evaluated by repeat TUR, and check cystoscopies were performed at regular intervals. Median patient age was 66 (range; 30-82) years and median follow-up was 43.2 (range; 6-127) months. RESULTS: Complete response was achieved in 55 (90.2%) patients. Of the complete responders, 7 patients experienced a superficial (Ta, T1) recurrence and 8 patients had progression. In 8 patients with refractory superficial and invasive relapses, a salvage cystectomy was mandated. The overall progression rate was 14%. The overall and disease-free survival rates were 76% and 93%, respectively at 5 years. During followup, 4 patients suffered from reduced bladder capacity, and 2 patients underwent cystectomy due to shrinking bladder. CONCLUSION: Combined multimodality therapy is a safe and curative treatment option for patients with T1G3 TCC of the bladder in the hands of dedicated multimodality teams. Therefore, it is reasonable to justify radiochemotherapy combined with TUR in the first-line treatment of T1G3 tumors.

[Postischemic reperfusion injury. Biochemical and methodological principles]. / Der postischämische Reperfusionsschaden. Biochemische und methodische Grundlagen.

The term "ischemic reperfusion injury" encompasses all toxic events in a cell that occur during ischemia and subsequent reoxygenation. These reactions have a significant effect, for example, on the rate of organ survival in kidney transplantation. Reactive oxygen intermediates (ROI) play an important role in the process of postischemic reperfusion. The basic mechanisms of generation and detoxification of ROI as well as the possibilities for their registration and quantification under conditions of ischemic reperfusion injury in the rat kidney are demonstrated in this report. A prerequisite to developing cytoprotective strategies is understanding the precise course of these mechanisms to minimize damage caused by ischemia and the subsequent reperfusion, thus retaining the organ's function to the greatest extent.

Lipid peroxidation and the expressional regulation of the heat-shock response during ischemia-reperfusion of rat kidney.

Because of the continuing shortage of donor organs, 'marginal kidneys' are increasingly being used. The purpose of our experiments was to characterize the extent of lipid peroxidation after ischemia-reperfusion (IR) injury in rat kidney, to analyze the expressional regulation of the heat-shock response and now to discuss the clinical application of these results. After ischemia, xanthine oxidase (XO) is thought to be the main oxygen radical-generating system and malondialdehyde (MDA) is considered to be a marker of LPO. In young rats (10 weeks) a unilateral warm ischemia of 40 and 60 min duration with subsequent reperfusion up to 1 h was conducted. Beside the 'footprints' of oxidative stress, the cytosolic antioxidative capacity, expressed as superoxide anion (SOA) scavenging capacity, was investigated. There was only a moderate and transient increase of renal MDA 5 and 10 min after the onset of reoxygenation (133.57/70.67 and 97.84/91.57 vs. 49.47 nmol/g wet weight (ww) in preischemic controls). ATP breakdown (to 83/65 from 2,947 nmol/g ww) with consecutive accumulation of hypoxanthine (up to 1,105 nmol/g ww) at the end of the ischemic period and the subsequent rapid decline of hypoxanthine by XO during reperfusion were used for an assessment of the SOA-generating capacity of these kidneys. Only 1/25-1/50 of the kidney cytosol was able to scavenge the whole amount of SOA generated by the total XO activity of rat kidney. Thus, it could be analytically and stoichiometrically shown that after IR there is only a moderate oxidative stress in kidneys of young rats; this is due to their high SOA-scavenging capacity compared to their SOA-generating ability. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in renal cortex after different periods of unilateral warm renal ischemia (10-60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats, since IR is known to cause induction of both genes. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA - generally being expressed on a far lower level than HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped down to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period thus showing a good relation to the heat-shock (protein) gene expression. We conclude that the HSP70-2 is the more sensitive gene with a lower threshold activation by mild injury, while the HSP70-1 gene mediates the big response of HSP induction after severe injury. Thus, the measurement of the cytosolic antioxidative capacity and the differential expression of HSP70-1 and -2 mRNA could be promising clinical tools to assess the donor viability.

During ischemia-reperfusion in rat kidneys, heat shock response is not regulated by expressional changes of heat shock factor 1.

Ischemia-reperfusion injury is known to induce the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72) mainly via rapid activation of heat shock transcription factor 1 (HSF1). However, little is known about the regulation of the HSF1 gene. We therefore studied the time course of HSF1 mRNA transcription and its relation to the expression pattern of the HSP70i mRNA in the renal cortex, this being the most vulnerable and functionally most important part of the kidney, after different periods of unilateral renal ischemia (10-180 min) and reperfusion (up to 60 min) in male Wistar rats (10 weeks old). Immediately after ischemia there was a significant induction of HSP70i genes. While HSP70i expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSF1 mRNA remained constitutively expressed under all conditions. Thus, we conclude that during ischemia-reperfusion in rat kidneys, the heat shock response is regulated by other means than expressional changes of HSF1.

Experimental study showing a diminished cytosolic antioxidative capacity in kidneys of aged rats.

In response to the rising demand for renal transplantations, more and more marginal (e.g. older) organs are being transplanted with the result of decreasing graft survival rates. Ischemia-reperfusion injury via oxidative stress is thought to be the main pathogenetic factor for this phenomenon. The cytosolic antioxidative capacity (CAC; expressed as superoxide anion radical scavenging capacity and quantified as the amount of cytosol (=ID(50)), which scavenges 50% of superoxide anions generated by a defined xanthine oxidase activity in vitro) and the catalase activity were therefore quantified in renal tissues of young (10 weeks) and older (40 and 60 weeks) Wistar rats and compared to each other. CAC with an ID(50) of 0.064 microl in 10-week-old rats was significantly higher than in older rats (0.152 microl in 40- and 0.100 microl in 60-week-old rats; p < 0.01). The catalase activity in 10-week-old rats was 18, 200 +/- 3,500 U/g w/w and 18,900 +/- 850 U/g w/w in 40-week-old rats. In 60-week-old rats, however, catalase activity was found to be significantly less (7,500 +/- 175 U/g w/w; p < 0.01). In conclusion, the aforementioned significant decrease of the cytosolic antioxidative capacity of kidneys in older rats should be the rationale for extensive cytoprotective, antioxidative treatment trials especially after renal transplantation from aged donors.

Differential expression of heat shock proteins 70-1 and 70-2 mRNA after ischemia-reperfusion injury of rat kidney.

Ischemia-reperfusion injury in the kidney is known to cause induction of the inducible form of the 70 kDa heat shock protein HSP70i (or HSP72). However, knowledge of the expressional regulation of the two coding genes for HSP70i - HSP70-1 gene and HSP70-2 gene - is very limited. We investigated the time course of HSP70-1 and -2 mRNA expression and its relation to cellular ATP levels in the renal cortex after different periods of unilateral warm renal ischemia (10-60 min) and reperfusion (up to 60 min) in 10-week-old male Wistar rats. Immediately after ischemia there was a significant induction of both HSP70i genes. While HSP70-1 expression constantly increased (up to 4-fold) during reperfusion, even to a higher extent with prolongation of ischemia, HSP70-2 mRNA - which was generally expressed at a far lower level than HSP70-1 mRNA - was strongly induced (3-fold) during reperfusion only after brief periods (10 min) of ischemia. Cellular ATP levels rapidly dropped to 5% with ischemia and the pattern of recovery during reperfusion significantly depended on the duration of the ischemic period, thus showing a good relation with the heat shock (protein) gene expression. We conclude that HSP70-2 is the more sensitive gene with a lower activation threshold by mild injury, while the HSP70-1 gene mediates the major response of heat shock protein induction after severe injury.

Evidence for only a moderate lipid peroxidation during ischemia-reperfusion of rat kidney due to its high antioxidative capacity.

The extent of lipid peroxidation after ischemia-reperfusion (I-R) injury in rat kidney has been controversial. After I, xanthine oxidase (XO) is thought to be the main oxygen radical-generating system and malondialdehyde (MDA) is considered to be a marker of lipid peroxidation (LPO). In young rats (10 weeks old) a unilateral warm I of 40 and 60 min duration with subsequent R up to 1 h was conducted. Beside the "footprints" of oxidative stress, the cytosolic antioxidative capacity, expressed as superoxide anion (SOA) scavenging capacity, and the renal catalase were also investigated. There was only a moderate and transient increase of renal MDA 5 and 10 min after the onset of reoxygenation (133.57/70. 67 and 97.84/91.57 vs. 49.47 nmol/g ww in preischemic controls). ATP breakdown (to 83/65 from 2947 nmol/g ww) with consecutive accumulation of hypoxanthine (up to 1105 nmol/g ww) at the end of ischemic period and the subsequent rapid decline of hypoxanthine by XO during reperfusion were used for an assessment of the SOA-generating capacity of these kidneys. Superoxide dismutase (SOD) activity, glutathione (GSH) and the high activity of catalase (18000 U/g ww) remained nearly unchanged during R. Only 1/25-1/50 of the kidney cytosol was able to scavenge the whole amount of SOA generated by the total XO activity of rat kidney. Thus, it could be analytically and stoichiometrically shown that after IR there is only a moderate oxidative stress in kidneys of young rats; this is due to their high SOA-scavenging capacity compared with their SOA-generating ability.

[Interdisciplinary surgical therapy of renal tumors with intracardiac tumor thrombi]. / Interdisziplinäre operative Therapie der renalen Tumoren mit intrakardialen Tumorthromben.

A combination of increased perioperative morbidity, together with the technical difficulty of an R 0 (curative) resection, is responsible for the poor prognostic factors of supradiaphragmatically extending renal tumors. Six patients aged 53-70 years with vena cava thrombosis extending into the right atrium or ventricle underwent en bloc resection of the primary tumor and tumor thrombus removal. If the atrial tumor mass was large or extended into the ventricle, resection was performed during cardiopulmonary arrest using a cardiopulmonary bypass method with the patient in deep hypothermia (< 18 degrees C). Alternatively if the cardiac tumor infiltration was minimal, resection was performed during an optionally short cardiopulmonary arrest period using a cardiopulmonary bypass method with the patient in hypothermia (23 degrees C). The operative procedure was determined by intracardiac tumor extension, tumor wall adhesions and tumor wall infiltrations, all of which were assessed intraoperatively by vena cava sonography. Six patients were strongly symptomatic preoperatively. Three developed sudden life-threatening cardiopulmonary insufficiency, possibly due to longer-lasting tricuspital valve prolapse with a consecutive right-to-left shunt through a newly reopened foramen ovale. One patient died 14 months postoperatively because of multiple metastases (hepatic, pulmonary and bone). One patient is still alive and has had a local recurrence for 2 months, which was diagnosed 65 months postoperatively. The remaining four patients are alive and well. They have been tumor-free for extended periods of time (29, 34, 62 and 84 months, respectively).

Epididymo-orchitis as a complication of brucellosis.

A study of 84 patients who were diagnosed with epididymo-orchitis between July 1987 and September 1993 is presented. Brucellosis was a complication in 14 cases (17%). All 14 cases had elevated agglutination titers. Brucella blood culture was found to be positive in 4 of 14 cases (28.5%). Standard therapy regime (streptomycin plus tetracycline) was effective in 13 of 14 (93%) cases.

Urinary factors of kidney stone formation in patients with Crohn's disease.

An increased frequency of kidney stone formation is reported in patients with inflammatory bowel disease. In order to investigate its pathogenesis, the concentrations of factors known to enhance calcium oxalate stone formation (oxalate, calcium, uric acid) as well as of inhibitory factors for nephrolithiasis (magnesium, citrate) were determined in the urine of 86 patients with Crohn's disease and compared with those of 53 metabolically healthy controls. Six patients with Crohn's disease already had experienced calcium oxalate nephrolithiasis. Patients with Crohn's disease had significantly higher urinary oxalate and lower magnesium and citrate concentrations. Among all patients magnesium and citrate were significantly lower in those with a positive history of kidney stones. Our results demonstrate that the increased propensity for renal stone formation in patients with Crohn's disease is a result not only of increased urinary oxalate, but also of decreased urinary magnesium and citrate concentrations.

Ketogenic effects of low and high levels of carnitine during total parenteral nutrition in the rat.

Male Wistar rats received total parenteral alimentation for 3 d. The animals were divided into three groups: group 1, without L-carnitine; group 2, 10 mg (62.1 mumol) L-carnitine X kg-1 X d-1; and group 3, 100 mg (621.1 mumol) L-carnitine X kg-1 X d-1. Fat oxidation was followed by indirect calorimetry. Maximal oxidative metabolism of fatty acids was achieved with supplementation of L-carnitine in small amounts (10 mg X kg-1 X d-1). This was demonstrated by a decrease of the RQ and of the serum concentrations of fatty acids and by an increase of beta-OH-butyric acid. Decreased liver free and long-chain acylcarnitine and increased short-chain acylcarnitine concentrations in this group also demonstrate an increased ketogenicity. This ketogenic effect of carnitine decreases when higher concentrations of carnitine are used. This study demonstrates that the ketogenic effect of carnitine is dose dependent.

The effect of preoperative L-carnitine supplementation on myocardial metabolism during aorto-coronary bypass surgery.

68 patients with defined myocardial ischemia, undergoing aorto-coronary bypass operation were assigned either to a group supplemented with L-carnitine (n = 41) or to a control group (n = 27). When extracorporeal circulation was established, a small piece of the right atrial appendage was biopsied and prepared for analysis for ATP, lactate and carnitine fractions. The ATP concentrations were higher in the patients supplemented with carnitine. A negative correlation existed between ATP and lactate levels. The amount of total carnitine was similar in both groups. However, free carnitine was higher, and long-chain acylcarnitine was lower when L-carnitine was supplemented. Postoperatively, the patients needed less inotropic medicaments, when supplemented with L-carnitine. L-carnitine supplementation in patients needed less inotropic medicaments, when supplemented with L-carnitine. L-carnitine supplementation in patients undergoing aorto-coronary bypass operation proved to be effective and beneficial for the normalization of myocardial energy metabolism parameters.

The influence of intravenous medium- and long-chain triglycerides and carnitine on the excretion of dicarboxylic acids.

Four groups of male Wistar rats were alimented parenterally for 3 days. Groups 1 and 2 received medium-chain triglycerides (MCT) and groups 3 and 4 long-chain triglycerides (LCT). Groups 2 and 4 were supplemented with 100 mg L-carnitine/kg/day. The MCT-alimented rats presented with a distinct excretion of the dicarboxylic acids: adipic acid (C6), suberic acid (C8), and sebacic acid (C10). The acids excreted corresponded to the infused pattern of monocarboxylic acids: caproic acid (C6), caprylic acid (C8), and capric acid (C10). Dicarboxylic acid excretion after MCT administration may reflect an insufficient capacity of beta-oxidation on one hand or a preferential omega-oxidation of medium-chain fatty acids on the other. Carnitine supplementation lead to a further increase of the dicarboxylic acids in the MCT-group. beta-OH-butyric acid excretion decreased after carnitine in the MCT as well as in the LCT group. An increased transport of fatty acid-carnitine compounds out of the mitochondria is discussed as an important effect of carnitine supplementation. Hereby medium-chain fatty acids may be more accessible for omega-oxidation.