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Apart from a few exceptions, there is currently little scientific evidence on the oncological relevance of neuro-urological diseases. Most research has been conducted into the association between long-term spinal cord injury with its consequences for the lower urinary tract and the occurrence of bladder cancer. These cancers differ in many ways from bladder cancers in patients without spinal cord injury: patients are 20 years younger on average, tumours are very often already muscle-invasive and poorly differentiated with a high proportion of squamous cell carcinomas, and the prognosis is poor. These characteristics also occur in spinal cord injury patients without permanent catheter drainage of the urinary bladder. Although the pathophysiological association has not been clarified in detail, the presence of a neurogenic bladder appears to be the decisive link between spinal cord injury and the occurrence of bladder cancer. Pathological pressure conditions in the urinary bladder and frequent urinary tract infections or asymptomatic bacteriuria resulting from neurogenic lower urinary tract dysfunction could be the decisive pathophysiological factors. In this respect, urinary bladder cancer in persons with a chronic spinal cord injury represents a model tumour after denervation. The clinically important question of screening requires future interdisciplinary research approaches., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Occupation-related cancers are of considerable importance, which is not yet adequately recognized in the field of urology. The three numerically most significant entities are tumors of the urinary tract caused by carcinogenic aromatic amines or polycyclic aromatic hydrocarbons, renal cell cancer after high exposure to the solvent trichloroethylene, and mesotheliomas of the tunica vaginalis of the testis after exposure to asbestos; however, these can only be recognized as occupation-related if an occupational history regarding the hazard relevant to the organ bearing the tumor is documented from the beginning of employment, e.g. by a questionnaire. This is because the relevant exposures generally date back several decades. With the exception of high exposure to trichloroethylene, the substances mentioned can also environmentally trigger the same tumors. In the context of environmental risk factors, it is of considerable importance that smoking is now considered to be a trigger for some 50% of all bladder cancers in men and women; however, smoking cessation results in a reduction in smoking-related cancer risk of over 30% after only 3-4 years. Work and commuting accidents, which are considered occupational risks, can lead to urological sequelae. For example, increased tumors of the bladder can occur after spinal cord injury lasting longer than 10 years., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Physicians are obliged to report the suspected presence of an occupational disease to the German Social Accident Insurance Institutions or to the state authority responsible for occupational health and safety. In the field of urology, tumors of the urinary tract are the most common, followed by the less common renal cell cancer and mesothelioma of the tunica vaginalis testis; however, for such a suspicion to arise at all, sufficient knowledge of urological occupational diseases must be present and the occupational or work history over the entire training and working life since the beginning of employment must be collected. In daily life the notification often fails at this point. In addition to the legal foundation and the principal course of the procedure, this article explains how a relevant comprehensive medical history by means of questionnaires can contribute to the fact that neither too many or all tumor diseases are unreflectedly reported, nor that occupational diseases are overlooked due to the lack of a medical history or detailed knowledge (or fear of this). Urological sequelae of accidents are often not adequately appreciated in the primary process or may take a long time to develop. In this case reporting the aggravation of the consequences of the accident is essential., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Tumors of the urinary tract are among the most common types of occupational cancer. A significant proportion of about 5-15% may be of occupational etiology. Suspicion of an occupational genesis is subject to mandatory reporting. However, epidemiological analyses show that the number of reports received by accident insurance companies and employers' liability insurance associations is significantly lower than expected. Finally, the economic and administrative effort in surveying a patient's occupational history hinders adequate reporting. By routinely and systematically using a structured questionnaire as part of clinical routine in our hospital, a significantly improved detection of justified suspected cases (from about 4.8% to about 67% of the theoretically expected value) has been achieved since about 2006. In addition to improved medical care and adequate compensation for recognition as an occupational disease, disease-related care is subject to extra-budgetary remuneration in Germany (UV-GOÄ)., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: Radical cystectomy in people with spinal cord injury (SCI) provides numerous additional difficulties, compared to able-bodied people. Therefore, it is important to obtain information from an experienced team about optimally managing these patients., Methods: Surgical procedures, based on the experience of 12 radical cystectomies in SCI patients with bladder cancer between January 1st, 2001, and December 31st, 2020, were recorded and the operative and perioperative clinical data were evaluated. Surgery was performed in a high-volume center by the surgeon most experienced in radical cystectomies, assisted by the neuro-urologist, involved in the care of the patient from the spinal cord center. Furthermore, a checklist based on the experience of the surgeon and the assisting neuro-urologist was developed., Results: SCI patients mostly suffered from an advanced disease and were always operated by the same team. The hospital stays ranged from 23 to 134 days (median 42 days). Four of the patients suffered from a postoperative paralytic ileus. Otherwise, both the operation time and the intraoperative blood loss as well as intraoperative and postoperative complications were basically comparable with those in able-bodied patients. The special features of radical cystectomy in SCI bladder cancer patients are described. Furthermore, a checklist addressing preoperative red flags, intra-operative challenges and post-operative challenges is presented., Conclusion: Radical cystectomy in SCI patients should be performed in a high-volume department by the most experienced surgical team. The inclusion of the urologist caring for the patient from the spinal cord injury center is highly recommended., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Urinary bladder cancer is the second most common tumour disease after lung cancer leading to death in people with a spinal cord injury. This paper provides a comprehensive overview of the differences relevant to urologists between urinary bladder tumours in this population compared with urinary bladder tumours in the general population.People with a spinal cord injury are 1 to 2 decades younger on average at the time of tumour diagnosis than patients without a spinal cord injury. Histopathologic findings at the initial diagnosis of urinary bladder cancer in people with a spinal cord injury are much less favourable than for urinary bladder cancers in the general population. Muscle-invasive tumours and tumours with poor differentiation are much more common, and the proportion of squamous cell carcinomas is significantly higher. The incidence rises after more than 10 years of paralysis. Urinary bladder cancer mortality is significantly elevated and increases with the duration of paralysis. In diagnostic procedures and, in particular, in radical cystectomy, clinically important features have to be considered. For example, urodynamic examinations or cystoscopy may trigger autonomic dysreflexia with hypertensive crises and the risk of life-threatening bradycardia.In the case of radical cystectomy, frequent adhesions and callosities of the urinary bladder, among other things, must be taken into account intraoperatively. Severe paralysis, prolonged intestinal atony and other conditions are frequently observed after the surgical procedure due to neurogenic bowel dysfunction. Correct positioning of the patient immediately after surgery to avoid decubitus and to support breathing, as well as bowel management specific to spinal cord injury, must be strictly observed.Other special features of paraplegic patients with urinary bladder cancer that should also be considered in clinical practice, as well as considerations for screening for urinary bladder tumors, are presented in the article., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Mesotheliomas are very aggressive tumors, almost exclusively caused by asbestos. Four of the 5 mesotheliomas assessed in the years 2014-2020 were recognized as occupational diseases, the 5th case was discontinued due to lack of the patient's cooperation. Surgical exposure of the testis was performed under the suspected diagnoses of hydrocele (n = 3), spermatocele (n = 1) as well as "unknown" (n = 1). This proves that a histopathological examination of removed tissue is the gold standard in scrotal interventions. Every mesothelioma must always be reported as an occupational disease., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: For individuals with spinal cord injury/disease (SCI/D) the risk of developing a stone in the upper urinary tract is up to six times higher than in the able-bodied population. Upper urinary tract carcinomas, in general, are rare and account for only 5-10% of all urinary tract carcinomas. It is believed that chronic upper urinary tract irritation caused by e.g., kidney stones or recurrent upper urinary tract infections may be associated with an increased risk of renal squamous cell carcinoma (RSCC)., Case Presentation: We report on a 64-year-old male who suffered a spinal cord injury in 1981 resulting in a complete sensory and motor impairment below T6, AIS A. Recurrent left-sided kidney stone disease had to be treated repeatedly from 1984 onwards. Despite repeated surgical attempts, it was ultimately not possible to achieve stone clearance in the long term. Within the concept of life-long surveillance of SCI/D, the patient was examined regularly, including ultrasound examinations of the kidneys. Six months after the last control examination, the patient was admitted to our hospital with a locally advanced tumor of the left kidney, so that only the option of palliative treatment remained. Histologically an RSCC was found., Discussion: As people with SCI/D have a higher risk of developing kidney stones, it is of utmost importance to check regularly for stone disease and, if necessary, treat with the aim of long-term stone clearance in order to protect renal function and to avert potentially malignant changes at an early stage., (© 2021. The Author(s), under exclusive licence to International Spinal Cord Society.)

Cancers can be triggered by occupational causes. In the field of urology, bladder cancer is by far the most frequent occupationally induced tumor disease. Causes are particularly carcinogenic aromatic amines and carcinogenic polycyclic aromatic hydrocarbons. The frequency of this disease has shifted over the last decades from the classical hazard in the chemical industry to the users. Among a variety of hazardous occupations, hairdressers and painters are the best known. Rarely, renal cell carcinoma can be triggered by high trichloroethylene exposure and mesothelioma of the tunica vaginalis testis by asbestos. If a disease that can be caused by occupational activities has been confirmed (e.g. urinary bladder cancer), the risk factors must be recorded by a complete occupational history from the first employment on in order to be able to report a suspected occupational disease. In addition, spinal cord injury due to occupational and commuting accidents can lead to urinary bladder cancer over the long term., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Traumatic spinal cord injury (SCI) is also a combat-related injury that is increasing in modern warfare. The aim of this work is to inform medical experts regarding the different course of bladder cancer in able-bodied patients compared with SCI patients based on the latest medical scientific knowledge, and to present decision-making aids for the assessment of bladder cancer as a late sequela of traumatic SCI., Methods: A study conducted between January 1998 and December 2019 in the BG Trauma Hospital Hamburg formed the basis for the decision-making aids. Urinary bladder cancer was diagnosed in 40 out of 7396 treated outpatient and inpatient SCI patients. General patient information, latency period, age at initial diagnosis, type of bladder management and survival of SCI patients with bladder cancer were collected and analysed. T category, grading and tumour entity in these patients were compared with those in the general population. Relevant bladder cancer risk factors in SCI patients were analysed. Furthermore, relevant published literature was taken into consideration., Results: Initial diagnosis of urinary bladder cancer in SCI patients occurs at a mean age of 56.4 years (SD ± 10.7 years), i.e., approximately 20 years earlier as compared with the general population. These bladder cancers are significantly more frequently muscle invasive (i.e., T category ≥ T2) and present a higher grade at initial diagnosis. Furthermore, SCI patients show a significantly higher proportion of the more aggressive squamous cell carcinoma than that of the general population in areas not endemic for the tropical disease schistosomiasis. Consequently, the survival time is extremely unfavourable. A very important finding, for practical reasons is that, in the Hamburg study as well as in the literature, urinary bladder cancer is more frequently observed after 10 years or more of SCI. Based on these findings, 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., Conclusions: The results showed that urinary bladder cancer in SCI patients differs considerably from that in able-bodied patients. The presented algorithm is an important aid in everyday clinical practice for assessing the correlation between SCI and bladder cancer.

Purpose: Life expectancy for people with traumatic spinal cord injury (SCI) is increasing due to advances in treatment methods and in neuro-urology. Thus, developing urinary bladder cancer (UBC) is gaining importance., Methods: Single-centre retrospective evaluation of consecutive in- and out-patient data with spinal cord injury between January 1st, 1998 and December 31st, 2018 was carried out and data were compared with UBC data of the German population from the German Centre for Cancer Registry Data at Robert Koch Institute., Results: A total of 37 (4 female, 33 male) out of 7004 patients with SCI were diagnosed with histologically proven UBC (median follow-up 85 months). Median age at UBC diagnosis was 54.0 years (general population: 74 years). The SCI patients had significantly (p < 0.0001, each) more frequent muscle-invasive tumors (81% ≥ T2) and unfavorable grading (76% G3), compared to the general population. Median survival was 13 months for transitional cell carcinoma (n = 31) and 4 months for squamous cell carcinoma (n = 5) (p = 0.0039), resp. The median survival of the 24 cystectomized patients was 15.0 months. Long-term suprapubic or indwelling catheterization was found in only eight patients for a total of only 5.09% (median 15.5 months) of the latency of all patients. No significant differences for T category and grading were observed between the bladder emptying methods intermittent catheterisation and catheter-free voiding., Conclusion: The results indicate that in patients with SCI bladder management even without permanent catheterization represents a considerable risk for the development of UBC.

Study Design: Retrospective descriptive study., Objectives: To compare histopathological findings and the long-term course of SCI patients with bladder cancer found incidentally at the initial urological workup to those diagnosed with bladder cancer many years after the onset of SCI., Setting: Spinal cord injury center in Germany., Methods: Data and follow-up of consecutive in- and out-patients with SCI admitted at a tertiary spinal cord injury center between January 1, 1998 and December 31, 2018 were screened retrospectively. All patients with acquired SCI were evaluated for pathological findings in the urinary bladder present at the time of SCI on the initial urological workup. Data of 37 long-term SCI patients from the same center with diagnosed bladder cancer and data of the general German population served as reference groups. Descriptive statistics were applied., Results: In total, four patients with bladder cancer at initial urological workup were assessed. They all had non-muscle invasive bladder cancer. Two of the patients were cystectomized 34 and 106 months after first bladder cancer diagnosis, due to relapsing tumor and progressive renal failure, respectively. In both cases no tumor was found in the resected bladder. All four patients are currently alive with no tumor and a mean follow-up of 105 months., Conclusions: In incidental bladder cancer observed at the initial urological workup after acquired SCI, the duration of SCI, at least in the first 5 years, does not noticeably contribute to a poor prognosis, i.e., progression to muscle invasive bladder cancer (≥T2) or a higher grading (G3).

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.

Introduction and Objectives:  Life expectancy for people with spinal cord injury/disease (SCI/D) is increasing, due to modern advances in treatment methods and in neuro-urology. However, with the increased life expectancy the risk of developing urinary bladder cancer is gaining importance. How is this patient group different from the general population?, Methods:  Single-centre retrospective evaluation of consecutive patient data with spinal cord injury and proven urinary bladder cancer., Results:  Between January 1st 1998 and March 31st 2017, 32 (3 female, 29 male) out of a total of 6432 patients with SCI/D were diagnosed with bladder cancer.The average age at bladder cancer diagnosis was 54.5 years, which is well below the average for bladder cancer cases in the general population (male: 74, female: 75).Twenty-seven patients suffered from urodynamically confirmed neurogenic detrusor overactivity, while five patients (all male) had detrusor acontractility.The median latency period between the onset of SCI/D and tumor diagnosis was 29.5 years. Temporary indwelling catheterisation was found in four patients for only 1.61 % of the overall latency period of all patients.The majority of the patients (n = 27) had transitional cell carcinoma, while five had squamous cell carcinoma. Of the 32 patients, 25 (78 %) had muscle invasive bladder cancer at ≥ T2 at the time of diagnosis. Regarding tumour grading, 23 out of 32 patients showed a histologically poorly differentiated G3 carcinoma; two patients each had G2 and G1 tumours repectively (no information on tumour grading was available in five patients).The median survival for all patients was 11.5 months. The prognosis of patients with squamous cell carcinoma was even worse; 4 out of 5 died within 7 months (median 4 months)., Conclusions:  The significantly younger age at onset and the frequency of invasive, poorly differentiated tumour at diagnosis indicate that SCI/D influences both bladder cancer risk and prognosis significantly. The latency period between paralysis and tumour disease seems to be a decisive risk parameter.The type of neurogenic bladder dysfunction and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients.Early detection of bladder cancer in patients with spinal cord injury remains a challenge., Competing Interests: Die Autoren geben an, dass keine Interessenkonflikte vorliegen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Introduction: Life expectancy for people with spinal cord injury has shown a marked increase due to modern advances in treatment methods and in neuro-urology. However, since life expectancy of people with paralysis increases, the risk of developing of urinary bladder cancer is gaining importance., Materials and Methods: Single-centre retrospective evaluation of patient data with spinal cord injuries and proven urinary bladder cancer and summary of the literature., Results: Between 1998 and 2014, 24 (3 female, 21 male) out of a total of 6599 patients with spinal cord injury were diagnosed with bladder cancer. The average age at bladder cancer diagnosis was 57.67 years, which is well below the average for bladder cancer cases in the general population (male: 73, female: 77). All but one patient had a latency period between the onset of the spinal paralysis and tumour diagnosis of more than 10 years. The median latency was 29.83 years. The median survival for these patients was 11.5 months. Of the 24 patients, 19 (79%) had muscle invasive bladder cancer at ≥T2 at the time of diagnosis. The type of neurogenic bladder (neurogenic detrusor overactivity or acontractility) and the form of bladder drainage do not appear to influence the risk. Long-term indwelling catheter drainage played only a minor role in the investigated patients., Conclusions: The significantly younger age at onset and the frequency of invasive tumours at diagnosis indicate that spinal cord injury influences bladder cancer risk and prognosis as well. Early detection of bladder cancer in patients with spinal cord injury remains a challenge.

Recently, rs11892031[A] has been identified in a genome-wide association study (GWAS) to confer increased risk of urinary bladder cancer (UBC). To confirm this association and additionally study a possible relevance of exposure to urinary bladder carcinogens, we investigated the IfADo UBC study group, consisting of eight case-control series from different regions including 1,805 cases and 2,141 controls. This analysis was supplemented by a meta-analysis of all published data, including 13,395 cases and 54,876 controls. Rs11892031 A/A was significantly associated with UBC risk in the IfADo case-control series adjusted to cigarette smoking, gender, age and ethnicity (OR = 1.18; 95% CI = 1.02-1.37; P = 0.026). In the meta-analysis, a convincing association with UBC risk was obtained (OR = 1.19; 95% Cl = 1.12-1.26; P < 0.0001). Interestingly, the highest odds ratios were obtained for individual case-control series with a high degree of occupational exposure to polycyclic aromatic hydrocarbons and aromatic amines: cases with suspected occupational UBC (OR = 1.41) and cases from the highly industrialized Ruhr area (OR = 1.98) compared with Ruhr area controls (all combined OR = 1.46). Odds ratios were lower for study groups with no or a lower degree of occupational exposure to bladder carcinogens, such as the Hungary (OR = 1.02) or the ongoing West German case-control series (OR = 1.06). However, the possible association of rs11892031[A] with exposure to bladder carcinogens still should be interpreted with caution, because in contrast to the differences between the individual study groups, interview-based data on occupational exposure were not significantly associated with rs11892031. In conclusion, the association of rs11892031[A] with UBC risk could be confirmed in independent study groups.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

Genotyping N-acetyltransferase 2 (NAT2) is of high relevance for individualized dosing of antituberculosis drugs and bladder cancer epidemiology. In this study we compared a recently published tagging single nucleotide polymorphism (SNP) (rs1495741) to the conventional 7-SNP genotype (G191A, C282T, T341C, C481T, G590A, A803G and G857A haplotype pairs) and systematically analysed if novel SNP combinations outperform the latter. For this purpose, we studied 3177 individuals by PCR and phenotyped 344 individuals by the caffeine test. Although the tagSNP and the 7-SNP genotype showed a high degree of correlation (R=0.933, P<0.0001) the 7-SNP genotype nevertheless outperformed the tagging SNP with respect to specificity (1.0 vs. 0.9444, P=0.0065). Considering all possible SNP combinations in a receiver operating characteristic analysis we identified a 2-SNP genotype (C282T, T341C) that outperformed the tagging SNP and was equivalent to the 7-SNP genotype. The 2-SNP genotype predicted the correct phenotype with a sensitivity of 0.8643 and a specificity of 1.0. In addition, it predicted the 7-SNP genotype with sensitivity and specificity of 0.9993 and 0.9880, respectively. The prediction of the NAT2 genotype by the 2-SNP genotype performed similar in populations of Caucasian, Venezuelan and Pakistani background. A 2-SNP genotype predicts NAT2 phenotypes with similar sensitivity and specificity as the conventional 7-SNP genotype. This procedure represents a facilitation in individualized dosing of NAT2 substrates without losing sensitivity or specificity.