Psychological distress and adjustment to disease in patients before and after radical prostatectomy. Results of a prospective multi-centre study.

The aim of this prospective multi-centre study was to evaluate the level of psychological distress (PD) and adjustment to disease in patients who underwent radical prostatectomy. Furthermore, the impact of urinary incontinence and erectile dysfunction on PD was assessed. Anxiety, depression and PD were evaluated using the Hospital Anxiety and Depression Scale in 329 prostate cancer patients before surgery as well as 3, 6 and 12 months after surgery. These results were compared with those of a male German general population reference group. Adjustment to disease was assessed using the Perceived Adjustment to Chronic Illness Scale. Patients reported low levels of PD at all points of assessment similar to population norms of age-matched German men. Persistent PD was seen in about 8% of the patients and 20% had PD at least two of the measurement points. Relevant predictors for PD after surgery were urinary symptoms and baseline PD. Adjustment to disease was highest before surgery and had significantly reduced at 3 and 6 months after surgery. In general, men are resilient to the experience of localised prostate cancer and adjust well psychologically after surgery. However, between 8% and 20% of patients could possibly benefit from mental health support.

Monitoring brain activation changes in the early postoperative period after radical prostatectomy using fMRI.

Urinary incontinence is a major concern following radical prostatectomy. The etiology is multifactorial involving intrinsic sphincter deficiency and/or detrusor hyperactivity and/or decreased bladder compliance. Recent studies employing functional imaging methodology nicely demonstrated the reference regions of the micturition circuit. Based on these landmarks this work complements this field of research by studying patients with bladder dysfunction. Our aim was to evaluate, whether iatrogenic impairment of the pelvic floor muscles after retropubic radical prostatectomy (RRP) causes detectable changes in fMRI in the early postoperative period. fMRI was performed at 3T in 22 patients before and after RRP with urge to void due to a filled bladder. In a non-voiding model they were instructed to contract or to relax the pelvic floor muscles repetitively. As previously reported in healthy men, contraction and relaxation of pelvic floor muscles induced strong activations in the brainstem and more rostral areas in our group of patients before and after RRP. In general, all of them had stronger activations during contraction than during relaxation in all regions before and after the operation. Even though there was no difference in the activation level when relaxing the pelvic floor before and after the operation, we found stronger activation during contraction when comparing the preoperative with the postoperative level in some of the regions. The results suggest that the same cortical and subcortical networks can be demonstrated for micturition control in patients with prostate cancer as in healthy subjects. However, impaired pelvic floor muscle function after RRP seems to induce different activation intensities.

[Spontaneous perirenal hematomas in patients taking anticoagulation medication or having a bleeding diathesis]. / Spontane perirenale Hämatome bei Patienten mit Koagulopathien oder unter Antikoagulanzientherapie.

Spontaneous perirenal hematoma is a rare condition. The clinical features are acute flank or abdominal pain, haematuria, hypotension and shock. Bleeding is most commonly caused by renal tumours, especially angiomyolipomas. Other known causes are long-term haemodialysis, arteriosclerosis or arteritis. A total of 6 patients with spontaneous perirenal haemorrhage have been treated in our hospital since 2003. Nearly all patients had been taking anticoagulation medication. One had a bleeding diathesis. One of the patients died immediately after admission at the hospital. All other patients had an exploratory laparotomy. In three cases total nephrectomy had to be performed, two other patients could be treated with partial nephrectomy. In patients with non-traumatic acute flank or abdominal pain it is important to determine whether the patient has been taking anticoagulation medication or suffers from bleeding diathesis because there is a high incidence of bleeding complications in these cases. If an emergent laparotomy is not necessary we recommend that these cases should be treated surgically after clinical stabilisation because tumours are the main reason for the haematomas and the patients have an urgent need for further anticoagulation therapy.

Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma.

PURPOSE: In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2). PATIENTS AND METHODS: One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6. RESULTS: There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency. CONCLUSION: In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.

Interleukin-2- and interferon alfa-2a-based immunochemotherapy in advanced renal cell carcinoma: a Prospectively Randomized Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.

Concentrations of lysosomal cysteine proteases are decreased in renal cell carcinoma compared with normal kidney.

Renal cell carcinoma contains significantly lower concentrations of the lysosomal cysteine proteases, cathepsins B, C, H, L and S, than does normal kidney, as shown by several methods, such as activity determination, enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry. The same low levels of enzyme activity and concentration have been determined in renal cell carcinoma metastases in the lung. Our results on the decreased concentration of cysteine peptidases at the protein level would seem to conflict with earlier results on an increased concentration of the cathepsin L mRNA in renal cell carcinoma.

Endopeptidase 24.11/CD10 is down-regulated in renal cell cancer.

The regulatory mechanisms responsible for malignant transformation, tumor progression and metastasis in renal cell cancer (RCC) are still unclear, but there is some evidence that biologically active peptides might have regulatory effects on the behavior of this malignancy. Tumor cells can change local concentrations of active peptides by modulating their cell-surface enzymes. Using immunohistochemistry and enzyme-histochemistry, the expression of various membrane peptidases was examined in RCC and adjacent noninvaded renal parenchyma (n = 44). We describe the down-regulation of neutral endopeptidase 24.11 (NEP) protein expression in RCC of the clear cell/chromophilic type when compared with renal parenchyma, and show for the first time the lack of enzyme activity of NEP in RCC. The strongest expression could be found for dipeptidyl peptidase IV (DPIV) which is only decreased in RCC of the chromophobe cell type and is even present in oncocytoma. Aminopeptidase N (APN) and aminopeptidase A (APA) show attenuated expression in up to one third of clear cell/ chromophilic RCC. Chromophobe RCC and oncocytomas do not express APN, APA, NEP and gamma-glutamyltranspeptidase.

Efficacy and safety of inhaled recombinant interleukin-2 in high-risk renal cell cancer patients compared with systemic interleukin-2: an outcome study.

Systemic IL-2 is an effective treatment for low to intermediate risk mRCC patients, its efficacy is marginal in high-risk cases. Therefore, other treatment approaches are required for this population. Ninety-four high-risk patients with RCC and pulmonary metastases were treated with inhaled plus concomitant low-dose subcutaneous rhIL-2. Clinical response, survival and safety were compared with those from IL-2 given systemically at the registered dose and schedule in 103 comparable historical controls. In the rhIL-2 INH group, treatment consisted of 6.5 MIU rhIL-2 nebulized 5x/day and 3.3 MIU rhIL-2 SC once daily. The rhIL-2 SYS group received treatment which consisted of intravenous infusion of 18.0 MIU/m2/day rhIL-2 or SC injection of 3.6-18.0 MIU rhIL-2. Some patients in both groups also received IFNalpha. Mean treatment durations were 43 weeks rhIL-2 INH and 15 weeks rhIL-2 SYS. Significantly longer overall survival and progression-free survival durations were observed in the rhIL-2 INH group. The probability of survival at 5 years was 21% for the rhIL-2 INH group. No patients survived 5 years in the rhIL-2 SYS group. A multivariate analysis of overall survival adjusting for differences in baseline characteristics between the two treatment groups resulted in a risk ratio of 0.43 (95% CI 0.30-0.63; P < 0.0001). The data suggested an association between the response (SD or better) and survival, especially in the rhIL-2 INH group. The inhalation regimen was well tolerated. This outcome study suggests that administration of rhIL-2 by inhalation is efficacious and safe in high-risk mRCC patients with pulmonary metastases, who have no other treatment option available.

[Tetanic equivalents, cephalgia, absences]. / Tetanische Aquivalente, Cephalaea, Absenzen.

Real hypoparathyroidism may develop after surgery of the thyroid, more rarely of the parathyroid. The idiopathic form is thought to be connected with autoimmune processes. We present the case of a female patient with acquired hypoparathyroidism after strumectomy 40 years ago. A clinical picture, not only with neurologic and dermatologic manifestations but also late organic sequelae of chronic hypocalcemia, i.e. calcification of basal ganglia, had developed impressively. Without the proof of laboratory tests diagnosis is difficult to establish at the first go in medical practice, since clinical symptoms may be few or widely scattered. Since the rate of strumectomies has dropped as a consequence of restricted indications, acquired hypoparathyroidism has become rarer. A simple long-term treatment with vitamin D and calcium relieves the patient from tetanic problems and prevents severe and irreversible late organic lesions.

Erectile dysfunction after radical prostatectomy: the impact of nerve-sparing status and surgical approach.

The core question of the study was whether the nerve-sparing status and surgical approach affected the patients' sexual life in the first year after surgery. In addition, determinants of erectile function (EF) and the extent of sexual activity were investigated. We conducted a multicentric, longitudinal study in seven German hospitals before, 3, 6 and 12 months after radical prostatectomy (RP). A total of 329 patients were asked to self-assess the symptoms associated with erectile dysfunction (ED). These symptoms were assessed using the International Index of Erectile Function and EORTC QLQ-PR25 questionnaires. A multiple regression model was used to test the influence of clinical, socio-demographic and quality-of-life-associated variables on the patients' EF 1 year after RP. Before surgery, 39% of patients had a severe ED (complete impotence). At 3, 6 and 12 months after surgery, it was 80, 79 and 71%, respectively. Although the surgical approach had no significant effect on EF, patients who had undergone nerve-sparing surgery had significantly lower ED rates. Nevertheless, 1 year after RP, 66% of these patients had severe ED. Age, nerve-sparing status and the burden of urinary symptoms had the greatest impact on the patients' EF. Regardless of nerve-sparing status and surgical approach, postsurgical improvement of EF does not mean a full convalescence of presurgical EF. Instead, it may rather reduce the degree of postsurgical ED in time. Consequently, urologists should disclose to the patient that ED is a likely side effect of RP.

[Asymptomatic Renal Stones: Do they really Exist?]. / Gibt es den symptomlosen Nierenstein?

BACKGROUND: Asymptomatic renal calculi without any history of colic, hematuria or infection can be found as an incidental finding during preven-tive check-ups. The aim of our study was to eval-uate whether these stones provoke symptoms with the need for further treatment during the follow-up and whether they cause cortical defects which may consecutively affect the renal func-tion. PATIENTS AND METHODS: In a prospective study we evaluated 104  patients with renal calculi. The -medical history, radiological findings and functional imaging as well as urine and blood analyses were recorded and evaluated. The influence of stone size and localisation on the development of acute stone-related symptoms, renal function and renal scarring were evaluated. Furthermore, we analysed whether localised pathological findings in radiographic or functional imaging may influence the creatinine level. The follow-up was be-tween 12 and 48  months (median: 25  months). RESULTS: During the study period 27 / 104 of our patients (26 %) developed symptomatic events (renal colic, hematuria, infection) in which patients with middle pole calculi with a mean -cumulative stone diameter of 9.8  mm had the -highest risk. A localised renal scarring could be found in 36.6 %. These patients had a significantly higher risk in presenting an increased creatinine level. Increasing stone size was diagnosed in 39  cases (37.5 %). CONCLUSIONS: Asymptomatic renal stones have to be controlled regularly in order to prevent the -patient from loss of renal function and hypertension caused by increasing stones or urinary tract infection.

Interleukin-2/interferon-alpha2a/13-retinoic acid-based chemoimmunotherapy in advanced renal cell carcinoma: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN).

We performed a prospectively randomised clinical trial to compare the efficacy of four subcutaneous interleukin-2-(sc-IL-2) and sc interferon-alpha2a (sc-IFN-alpha2a)-based outpatient regimens in 379 patients with progressive metastatic renal cell carcinoma. Patients with lung metastases, an erythrocyte sedimentation rate < or =70 mm h(-1) and neutrophil counts < or =6000 microl(-1) (group I) were randomised to arm A: sc-IL-2, sc-IFN-alpha2a, peroral 13-cis-retinoic acid (po-13cRA) (n=78), or arm B: arm A plus inhaled-IL-2 (n=65). All others (group II) were randomised to arm C: arm A plus intravenous 5-fluorouracil (iv-5-FU) (n=116), or arm D: arm A plus po-Capecitabine (n=120). Median overall survival (OS) was 22 months (arm A; 3-year OS: 29.7%) and 18 months (arm B; 3-year OS: 29.2%) in group I, and 18 months (arm C; 3-year OS: 25.7%) and 16 months (arm D; 3-year OS: 32.6%) in group II. There were no statistically significant differences in OS, progression-free survival, and objective response between arms A and B, and between arms C and D, respectively. Given the known therapeutic efficacy of sc-IL-2/sc-INF-alpha2a/po-13cRA-based outpatient chemoimmunotherapies, our results did not establish survival advantages in favour of po-Capecitabine vs iv-5-FU, and in favour of short-term inhaled-IL-2 in patients with advanced renal cell carcinoma receiving systemic cytokines.

[Cisplatin-induced nephrotoxic side effects of cytostatic chemotherapy of testicular tumors]. / Cisplatin induzierte nephrotoxische Nebenwirkungen der zytostatischen Chemotherapie von Hodentumoren.

The nephrotoxic side effect of Cis-platin was investigated in 38 patients with testicular tumors. The serum creatinine and the creatinine clearance served as function parameters. A temporary or permanent restriction of the creatinine clearance developed 31 of 38 patients during the therapy period. Increased creatinine levels were found in 6 patients. Two of them got into a chronic renal insufficiency. A pretherapeutic risk group of patients or a precarious dose of Cis-platin could not be found out.

[1st experiences with a urethral endothesis in bladder neck adenoma]. / Erste Erfahrungen mit einer Harnröhrenendothese beim Blasenhalsadenom.

Our examinations hitherto performed allow the following conclusions: 1. The placed before endothesis for the pars prostatica urethrae allows a spontaneous miction which is nearly free of residual urine. Here the endothesis cannot render possible the physiologic funnel-shaping of the vesical neck. This is theoretically not possible and was confirmed by means of fluoroscopic control of the act of miction in lying endothesis. By the endothesis the pars prostatics urethrae is passively kept open. The continence takes place by the so-called sphincter externus and the diaphragma urogenitale (5). The voluntary relaxation of the diaphragma urogenitale and the contraction of the detrusor render possible the depletion of the urinary bladder. By reason of the lacking funnelling the residual urine proved in several patients can be explained as well as the relatively low maximum value of the urinary flow of about 15 ml/s despite a miction which was subjectively regarded as good. 2. The disadvantages of the permanent catheter mentioned at the beginning as well as the usual care of the catheter and bladder irrigations are unnecessary. 3. Incrustations were not observed up to the 78th day.

[Effect of the stable prostacyclin analog (iloprost) on survival of ischemically-stressed swine kidney transplants]. / Einfluss eines stabilen Prostazyklin-Analogons (Iloprost) auf die Konservierung ischämisch-belasteter Schweinenierentransplantate.

Kidneys of 5 pigs were pretreated in situ with Iloprost (Fa. Schering) (0.5 micrograms X kg-1 X min-1) and exposed to a warm ischaemia time of 45 minutes. The perfusion behaviour of these kidneys during the initial fall current perfusion and hypothermic machine perfusion for 24 hours was to be compared with that of kidneys with a warm ischaemia time of less than 5 minutes. After retransplantation in all kidneys a good blood supply and an immediate urine production was to be seen for the duration of the experiment of 3 hours.

[Extended storage preservation of swine kidneys to 72 hours using iloprost]. / Die Verlängerung der Lagerungskonservierung von Schweinenieren auf 72 Stunden durch Einsatz von Iloprost.

The intraaortal infusion of Iloprost (1 micrograms/kg X min) for the duration of 15 minutes leads to an increase of the renal hematorrhea by 85.2%, to a decrease of the renal resistance by 51.6% and to a slight decrease of the average arterial blood pressure by 13.3%. After a 72-hour hypothermic storage preservation under addition of Iloprost the renal blood supply after retransplantation corresponded to the initial values of the blood flow before nephrectomy. The production of urine began after 1-2 minutes. Enzyme investigations of the transplant urine resulted in an increased excretion of the cytosolic enzymes, the structure-bound enzymes, however, remained in the area of the norm. The investigation of the electrolytes of the urine showed a hypersodiuria as well as a hypopotassiuria and calciuria. As to urea and creatinine the values were below the parameters used for comparison. In the contralateral kidneys used as control kidneys no blood supply developed after retransplantation. The application of Iloprost for the conditioning of donor kidneys is very well suited and shows some advantages compared with the preparation used up to now. The prolongation of the hypothermic storage preservation to 72 hours seems to be possible by the application of Iloprost.