[Urinary bladder cancer as a late sequela of spinal cord injury : Decision-making aids for assessment of this causal association]. / Harnblasenkarzinom als Spätfolge einer Querschnittlähmung : Entscheidungshilfe für eine Zusammenhangsbegutachtung.

BACKGROUND: There is to date no convincing literature that has assessed the association between traumatic spinal cord injury (SCI) and the later development of urinary bladder cancer. The aim of this work is to present medical experts as well as the national accident insurance and the social courts decision-making aids based on the latest medical scientific knowledge, for assessment of this causal association. MATERIALS AND METHODS: A study conducted between April 1998 and March 2017 in the BG Trauma Hospital Hamburg forms the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 32 out of 6432 treated outpatient and inpatient SCI patients. Furthermore, relevant published literature was taken into consideration for the decision-making aids. RESULTS: It was found that urinary bladder cancer in SCI patients occurs at a considerably younger age as compared to the general population, more frequently shows muscle invasive carcinoma with a higher grade at first diagnosis and a higher proportion of the more aggressive squamous cell carcinoma than that of the general population. Correspondingly, the survival time is extremely unfavorable. For medical experts a matrix was compiled where the various influencing factors, either for or against the recognition of an association between SCI and urinary bladder cancer, were weighted according to their relevance. CONCLUSION: The results showed that urinary bladder cancer in SCI patients differs considerably from that of able-bodied patients. These differences drastically shorten the survival time. A study on patients with spina bifida, i.e., a congenital spinal cord disorder, corroborates these observations. They indicate histopathological differences that have so far been intangible.

Impact of preoperative antiandrogen medication and nerve-sparing surgery on the outcome of radical prostatectomy.

OBJECTIVES: Radical prostatectomy in antiandrogen-medicated patients, as well as nerve-sparing surgery, has increased within recent years. We investigated the impact of antiandrogen medication on loss of blood and of nerve-sparing surgery on continence and potency. METHODS: A total of 401 men who underwent radical prostatectomy between January 1995 and September 1999 at our clinic were asked about antiandrogenic medication prior to radical prostatectomy and about daily life activities, overall satisfaction, voiding ability, and sexual activities. Consumption of erythrocyte concentrates and cryoprecipitated plasma was taken from the records. RESULTS: The average follow-up was 36 months. Seventy-two percent (n = 289) of our patients replied. Sixty-seven men (23%) who replied to our questionnaire had received antiandrogen medication prior to radical prostatectomy. In 53 (18%) of the men, the nerve-sparing technique was used. In antiandrogen-medicated patients, we observed a significantly elevated consumption of erythrocyte concentrates (antiandrogen-medicated 0.93, not antiandrogen-medicated 0.44; P = 0.013) and of cryoprecipitated plasma (antiandrogen-medicated 0.39, not antiandrogen-medicated 0.08; P = 0.010). Patients who underwent the nerve-sparing technique reported better results in daily life activities, general health status, International Prostate Symptom Score (IPSS), and continence. CONCLUSION: Our results point to a higher quality of life in patients who had undergone nerve-sparing surgery.

[Procedures for determining occupational diseases in cases of urological disorders]. / Das Berufskrankheitenverfahren bei urologischen Erkrankungen.

According to section sign 202 of the German Social Security Code VII, individuals diagnosed with bladder cancer or renal cell cancer who had been occupationally exposed to carcinogens known to induce cancer in these human tissues must be reported to the statutory accident insurance. In this paper, the course of the administrative procedure, particularly considering the reporting procedure and screening for occupational risk factors by a CD-based tool, developed by the authors, is described.

[Prerequisites for a convincing (neuro-)urology opinion : Importance of objectivity in the legal sense of full proof, occurring under duty of compliance of the surveyed person]. / Voraussetzungen für ein überzeugendes (neuro)urologisches Gutachten : Stellenwert der Objektivierung im Sinne des Vollbeweises unter Mitwirkung(spflicht) des Probanden.

Convincing urological expert opinions require the objectification of medical history complaints of health and functional disorders in the legal sense of obtaining full proof. This means that there is such a high degree of likelihood, beyond any doubt of a reasonable person observing the condition (Bundessozialgericht Entscheidung [BSGE] 32, 203/207). This requires a comprehensive general and special medical history survey, as well as a series of urological examination procedures in the hands of experienced urologists. In addition, it is necessary to observe the fundamentals of the various legal areas, from which the opinion order comes from, without exception. However, it would not be possible in all cases to achieve an unequivocal clarification of the problem in question. Nevertheless, it should be ensured that the best possible approximation to the actual truth of the case is reached. In this way, the democratic fundamental right of all the appraised persons to equal treatment could be met in the best possible way and optimal support to the commissioning institutions would be made available.

[Analgesia with acupuncture in extracorporeal shock wave lithotripsy of kidney stones--first results]. / Akupunktur während der ESWL von Nierensteinen--erste Ergebnisse.

INTRODUCTION: To date, extracorporeal shock wave lithotripsy (ESWL) has been successfully used with awake anaesthesia. The aim of this study was to investigate whether acupuncture at certain acupuncture points can lower or even substitute the demand for analgesics. SUBJECTS AND METHODS: ESWL treatments were selected for the two groups using the registration number for randomisation. Both groups rated pain sensation prior to the ESWL treatment using a numeric pain scale. The subjects in the analgesic group received 50 mg pethidine and 10 mg diazepam whereas the subjects in the acupuncture group received acupuncture at the points colon 4 bilateral, liver 3 bilateral, urinary bladder 23 bilateral, gall bladder 25 contralateral to the stone, circulation 6 bilateral, and Ren Mai. Every minute till 21 min after starting the therapy and 10 min after termination, the pain sensation was rated. Analgesics were intravenously applied in all subjects reporting a pain sensation higher than 5. Additionally, the pain management was rated with a non-evaluated questionnaire. RESULTS: In the present study on 102 patients, analgesia by acupuncture was successfully applied to patients who underwent ESWL. The analgesic effect of acupuncture was significantly superior to the analgesic effect of analgesics. In the group treated by acupuncture, 20 subjects received additionally analgesics. In general, these subjects presented bigger kidney stones and were younger. Subjects with left-sided kidney stones required more frequently analgesics. The results were not significant.

[The causes of urinary bladder cancer and possibilities of prevention]. / Harnblasenkarzinom. Ursachen und Möglichkeiten der Vermeidung.

Bladder cancer is a malignant disease with exogenous and thus avoidable causative factors. Cigarette smoking is by far the most relevant risk factor and a clear dose-response relationship has been documented. That the bladder cancer risk decreases only a few years after the cessation of smoking is noteworthy. Occupational exposure, particularly to aromatic amines such as benzidine and beta-naphthylamine and to certain azo dyes, represents another important risk factor. At high risk are workers involved in the production of these chemicals and, to a lesser extent, those processing them. The currently known environmental factors seem to play a minor role. Treatment-induced risks causing secondary bladder cancer also have to be considered. Currently, the prevention of bladder cancer mainly involves avoiding exposure to known causative factors and early detection of the disease in high risk populations.

[Retroperitoneal leiomyosarcoma. A rare differential diagnosis of an adrenal tumor]. / Retroperitoneales Leiomyosarkom. Eine seltene Differentialdiagnose des Nebennierentumors.

A pararenal mass is a clinical finding that cannot be explored preoperatively regarding its parent organ even nowadays. We report in the following about a patient who was admitted with dull pain located in the flank and upper abdomen. Ultrasound investigation at admission showed a solid homogeneous mass close to the upper pole of the left kidney. Urinalysis and catecholamine levels were normal. Intraoperatively, a sarcoma infiltrating the renal capsule and renal vein was observed. In the case of a mass located in the area of the adrenal gland, an extra-adrenal tumor must be considered especially if there are normal findings for urinalysis and catecholamine levels even if modern imaging techniques had been applied.

[Occupational and non-occupational risk factors in bladder cancer patients in an industrialized area located in former East-Germany]. / Berufliche und ausserberufliche Risikofaktoren für das Harnblasenkarzinom in einem ehemaligen Industriegebiet der neuen Bundesländer.

PURPOSE: Several occupational carcinogens are metabolized by polymorphic enzymes. The distribution of the polymorphic enzymes N-acetyltransferase 2 (NAT2; substrates: aromatic amines), glutathione S-transferase M1 (GSTM1; substrates: e. g., reactive metabolites of polycyclic aromatic hydrocarbons), and glutathione S-transferase T1 (GSTT1; substrates: small molecules with 1 - 2 carbon atoms) were investigated. MATERIAL AND METHODS: At the urological department in Lutherstadt Wittenberg, 136 patients with a histologically proven transitional cell cancer of the urinary bladder were investigated for all occupations performed for more than 6 months. Several occupational and non-occupational risk factors were asked. The genotypes of NAT2, GSTM1, and GSTT1 were determined from leucocyte DNA by PCR. RESULTS: Compared to the general population in Middle Europe, the percentage of GSTT1 negative persons (22.1 %) was ordinary; the percentage of slow acetylators (59.6 %) was in the upper normal range, while the percentage of GSTM1 negative persons (58.8 %) was elevated in the entire group. Shifts in the distribution of the genotypes were observed in subgroups who had been exposed to asbestos (6/6 GSTM1 negative, 5/6 slow acetylators), rubber manufacturing (8/10 GSTM1 negative), and chlorinated solvents (9/15 GSTM1 negative). CONCLUSIONS: The overrepresentation of GSTM1 negative bladder cancer patients also in this industrialized area and more pronounced in several occupationally exposed subgroups points to an impact of the GSTM1 negative genotype in bladder carcinogenesis.

Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: a pooled analysis of genotype-based studies.

The aim of this study was to investigate the association of NAT2 gene polymorphism with bladder cancer using the data derived from the International Project on Genetic Susceptibility to Environmental Carcinogens. Four case control studies conducted in four European countries, plus two case series, one from England and one from Germany, for a total of 1530 cases and 731 controls (all Caucasian) were included. The interaction between NAT2 and bladder cancer considering smoking habits and occupational exposure was studied. There was a significant association between NAT2 and bladder cancer (odds ratio: 1.42, 95% confidence interval: 1.14-1.77), with a slightly significant heterogeneity among studies. However, heterogeneity disappeared when smokers were divided into current and ex-smokers. The risk of cancer was elevated in smokers and occupationally exposed subjects, with the highest risk among slow acetylators. The increase in risk was limited, in fact, to current smokers (odds ratio = 1.74, 95% confidence interval: 0.96-3.15). This analysis confirms that the NAT2 genotype is a risk factor for bladder cancer by interacting with smoking or occupational exposures. Our observation suggests that NAT2 is not a risk factors per se but modulates the effect of carcinogens contained in tobacco smoke (probably arylamines) or associated with occupational exposures.

Induction of unscheduled DNA synthesis in primary human urothelial cells by the mycotoxin ochratoxin A.

Ochratoxin A (OTA) is a widespread contaminant in human staple food. Exposure of humans to this mycotoxin is a matter of concern because OTA is a known rodent carcinogen. As the urothelium is one target tissue of this mycotoxin, primary cultured human urothelial cells (HUC) from adults and children were used to analyze the induction of unscheduled DNA synthesis (UDS) by OTA. HUC were isolated from the ureters or renal pelves of two nephrectomized adults and of two children with ureteropelvic junction stenosis and cultured under serum-free conditions. After a confluency of 70-80% was reached, cell proliferation was suppressed by arginine-deficient medium (ADM), and UDS was assessed autoradiographically by 3H-thymidine incorporation upon exposure to OTA (10-2000 nM), ethyl methanesulfonate (EMS, 5 mM, positive control), or dimethyl sulfoxide (DMSO, 0.2%, solvent control). In control cultures the level of UDS was low. Exposure to EMS resulted in an induction of UDS (2-to 5-fold compared to control), thus allowing the sensitive detection of repair resulting from induction of DNA lesions in all four specimens, and demonstrating that repair of EMS-induced DNA lesions can take place under the chosen culture conditions. In two HUC cultures derived from adults, a significant induction of UDS was observed in the concentration range of 50-500 nM OTA. The highest fraction of cells in repair (CIR) was found at 50 nM OTA for the HUC from the older male (50% CIR). The maximum response in the other specimens from the adult female and the 7-year-old boy were seen at OTA concentrations of 500 and 250 nM, respectively. In contrast to all other specimens, no significant induction of UDS by OTA was found in the HUC cultures derived from an infant's urothelium. Signs of cytotoxicity were observed above 500 nM OTA in all cultures. The varying susceptibility toward OTA observed in vitro may hint at varying predispositions of individuals in vivo.

Subjective symptoms due to solvent mixtures, dioxin, and toluene: impact of exposure versus personality factors.

In this study, we analyse the impact of personality factors on the frequency of self-reported symptoms for workers under different exposure conditions. Reported symptoms may depend on the level and type of exposure, as well as on personality factors such as trait anxiety of the worker or his general sensitivity with regard to the environment. The employed data stems from three studies: The first study contains information of 60 workers who suspected to be exposed to polychlorined dibenzodioxins and dibenzofuranes (Lifetime Weighted Average Exposure, LWAE, as an index for contact with the substances). The second study concerns 40 workers who are exposed to different concentrations of solvent mixtures in paint manufacturing (LWAE of total hydrocarbons about 10 ppm). The third study includes repeated measurements of two subgroups of workers from rotogravure printing plants who are exposed to different concentrations of toluene: a "high" exposure group (n = 129, LWAE about 46 ppm, current exposure 25 ppm) and a "low" exposure group (n = 96, LWAE for toluene about 9 ppm, current exposure 3 ppm). Trait anxiety, environmental sensitivity, and self-reported symptoms are measured by validated questionnaires and age as well as verbal intelligence are controlled. To determine the effect of the individual characteristics and the different exposures on self-reported symptoms, frequency analyses and variance analyses are conducted and linear models are fitted. For all analyses, trait anxiety explains the highest share of the variance. If there is no effect of the exposure on the reported symptoms (dioxin and low-level toluene study), trait anxiety seems to have a larger explanatory power in comparison with those studies where the exposure has an effect on the reported symptoms (solvent-mixture and high-level toluene study). Neurotoxicological risk analysis has to account for the detected dependence of self-reported symptoms on personality traits: assessments for elevated symptoms should not only be linked to the intensity of exposure but also related to benchmarks derived from the normal variability of personality factors.

Physiological and psychological approaches to chemosensory effects of solvents.

Workplace related standard settings for solvents are based in a remarkable extent on information about sensory irritations. However, data from controlled human exposure studies are seldom available. Therefore, the aim of this study was to present the association of self-reported symptoms and physiological processes leading to sensory irritations. Three series of laboratory experiments each with 24 young male subjects were performed. Ethyl benzene (EB), 2-butanone (methyl ethyl ketone or MEK), isopropyl alcohol (IPA), 1-octanol (OCT), and 2-ethylhexanol (EHEX) were investigated in low and high concentrations. Ratings for sensory irritations (eyes and nose), olfactory symptoms, and annoyance were assessed repeatedly before, during and after the 4-h-exposures. The anterior active rhinomanometry (AAR) was employed measuring the nasal flow. The nasal lavage was used for the analysis of the neuropeptide substance P as indicator of nasal chemosensory irritations. Goodness-of-fit was calculated for non-linear regression analyses by fitting the sine function on the data of the ratings given during the 4-h-exposure. In general, ratings for annoyance and odor symptoms were fitted on a higher level than those for sensory irritations. However, a high fit could be shown for nasal irritations due to EHEX. In these experiments, a significant reduction of the nasal flow and a significant increase of substance P could be proved.

Polymorphic methyl group metabolism genes in patients with transitional cell carcinoma of the urinary bladder.

Because polymorphisms in the methyl group metabolism genes methylene-tetrahydrofolate reductase (MTHFR), methionine synthase (MS), and cystathione beta-synthetase (CBS) affect plasma homocysteine levels and intracellular concentrations of S-adenosylmethionine (SAM), they modify the susceptibility to cardiovascular diseases and cancer. Specifically, genome-wide decreased DNA methylation ('hypomethylation') in human cancers might be a consequence of decreased SAM levels. Because hypomethylation is particularly prevalent in transitional cell carcinoma of the urinary bladder (TCC), the genotype distributions for the two each most prevalent MTHFR, MS, and CBS alleles were compared between 165 TCC patients and 150 population controls. The distributions of the MTHFR 677A/V and the MS 919G/D alleles were not significantly different between cancer patients and controls, even after stratification according to age, gender, tumor stage or grade. The CBS 844INS68 allele was slightly less frequent in TCC patients than in controls (q=0.07 versus 0.10), but was rarer among males in both groups. Among the TCC patients, this gender difference was highly significant (Mantel-Haenszel and chi(2)-test P=0.007). No significant difference between TCC patients and controls was found for any combined genotype. Likewise, the extent of DNA hypomethylation determined in 62 carcinoma specimens was not related to the respective genotypes. Thus, on their own, the MTHFR, MS and CBS genotypes do not appear to act upon susceptibility to TCC or influence the extent of DNA hypomethylation in this cancer.

Occupational history and genetic N-acetyltransferase polymorphism in urothelial cancer patients of Leverkusen, Germany.

OBJECTIVES: The study was designed to realize possible shifts in the ratio of slow to fast acetylators within a group of 196 urothelial cancer patients in an area with earlier benzidine production. METHODS: The subjects were interviewed for occupational and nonoccupational risk factors. The patients were phenotyped for N-acetyltransferase 2 (NAT2) by Grant's caffeine test. A subgroup of 54 patients was additionally genotyped for NAT2. RESULTS: The antimode in the NAT2 phenotyping with the caffeine test (AFMU: IX ratio) was 1.0, as evidenced by additional genotyping of the subgroup of 54 patients. The prevalence of slow acetylators in the entire group of bladder cancer patients was 55%, in accordance with published figures for European populations. In a subgroup of 40 patients with occupational histories as workers in chemical or rubber industries 65% were slow acetylators. In a further subgroup of 28 cases having specifically worked at chemical production sites of the local chemical industry, 68% were slow acetylators. CONCLUSIONS: In contrast to earlier studies, this study shows no increased prevalence of slow acetylators among urothelial cancer patients in comparison with the normal population. However, in subgroups of cases with a likelihood of past occupational contacts with aromatic amines, there was a trend towards a higher representation of slow acetylators. This finding is in accordance with observations of others that the percentage of slow acetylators in urothelial cancer patients is generally decreasing, possibly because the production of benzidine and benzidine-based dyes ceased in the early 1970s.

Psychological effects upon exposure to polyhalogenated dibenzodioxins and dibenzofurans.

Thirty workers who had been exposed to combustion products for several years due to testing of flame retarding qualities of building materials and 30 controls from the same facility were investigated. Concentrations found in samples taken from different places of the facility were up to 14,660 microg/kg for polybrominated dibenzofurans and up to 67.1 microg/kg for polychlorinated dibenzodioxins (PCDDs) and dibenzofurans (PCDFs). Physical examination, routine laboratory parameters, and blood fat concentrations of PCDDs and PCDFs revealed normal findings. Neurotoxic symptoms showed a weak tendency of overrepresentation among the exposed workers. The frequency of neurobehavioural symptoms increased significantly with trait anxiety independent of exposure to combustion products.

Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus.

The etiology of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is still unknown. In several cases, however, xenobiotics (i.e. drugs and occupational agents) were identified as etiologic agents and associations with certain polymorphic alleles of xenobiotic-metabolizing enzymes have been reported. Cytochrome P4501A1 (CYP1A1) and N-acetyltransferase 2 (NAT-2) are xenobiotic-metabolizing enzymes of phase 1- and phase 2-metabolism, respectively. CYP1A1 may activate drugs and other chemicals to reactive metabolites. NAT-2 is the most important enzyme in acetylation of aromatic amines, and thus may be responsible for detoxification of many of these compounds. Two polymorphisms of the human CYP1A1 gene, a point mutation in the 3' flanking region of the gene (Msp1) and a mutation in exon 7 leading to an isoleucine-valine-exchange in the heme-binding region of the enzyme, have been described and may lead to a higher basal and inducible enzyme activity. With respect to NAT-2, several alleles which combine for the two phenotypes "fast" and "slow" acetylators have been described. We analyzed the gene frequencies of the CYP1A1 polymorphisms and the phenotypes of NAT-2 in patients suffering from idiopathic SLE or SSc. CYP1A1 polymorphisms were analyzed in genomic DNA by PCR, whereas NAT-2 phenotypes were measured by the caffeine method. For CYP1A1 polymorphisms, 106 patients have been typed until now. The SLE group (n = 68) exhibited a significant increase (p < 0.05) in the mutant Val-allele (OR = 2.59) when compared to controls (n = 184). However, no significant differences in allele frequencies for MspI in the SLE group and for both CYP1A1 polymorphisms in the SSc group could be observed. Regarding the NAT-2 phenotype, patients suffering from SLE (n = 88) 75% and SSc (n = 26) 80.2%, respectively, were slow acetylators compared to 55% slow acetylators in the healthy German population (p < 0.05). The observed increased frequencies of the CYP1A1 mutant Val-allele and the slow actylator phenotype in idiopathic autoimmune disease support our concept that in slow acetylators non-acetylated xenobiotics may accumulate and are subsequently metabolized by other enzymes into reactive intermediates. Thus, enhanced formation of reactive metabolites could alter self-proteins presented to the immune system thus stimulating autoreactive T cells which induce autoimmunity.

Urothelial cancer of the bladder in an area of former coal, iron, and steel industries in Germany: a case-control study.

In a case-control study performed in an area of former coal, iron, and steel industries, the professional and lifestyle histories of 412 male urothelial bladder cancer inpatients (cases) and 414 inpatients with benign prostatic hyperplasia (controls) were investigated. Smoking habits were identified as the main confounder for occupational bladder cancer risk. Two hundred and forty (58.3%) of the bladder cancer inpatients and 146 (35.3%) of the inpatients with benign prostatic hyperplasia were smokers. The percentage of ex-smokers in the bladder cancer cases was 10.2%; the percentage of ex-smokers in the controls was 9.7%. Smoking-adjusted Mantel-Haenszel estimates of the odds ratios (OR&infMH;) for bladder cancer were elevated in underground hard-coal miners (OR&infMH; =2. 54, 95% CI =[1.64; 3.93]), chemical workers (OR&infMH; =2.16, 95% CI =[0.87; 5.38]), painters/varnishers (OR&infMH; = 2.42, 95% CI =[1. 05; 5.57]), technicians (OR&infMH; = 1.99, 95% CI =[0.95; 4.16]), and foundry workers (OR&infMH; = 2.22, 95% CI = [0.53; 9.08]). Administrative officers had significantly lower smoking-adjusted odds ratios (OR&infMH; = 0.61, 95% CI = [0.42; 0.88]). Although statistically not significant, the results of the Breslow-Day test of homogeneity of the odds ratios over the strata are compatible with interactions between tobacco smoking and the occupations of underground hard-coal miners (chi(2)&infBD; = 4.91, p=0.07) and chemical workers (chi(2)&infBR; = 3.32, p=0.06).