Occupational arsenic exposure and genitourinary cancer: systematic review and meta-analysis.

BACKGROUND: Existing evidence suggests that ingestion of high doses of arsenic through drinking water is associated with an increased risk of genitourinary cancers, while systematic evidence on workers exposed to arsenic is lacking. AIMS: The aim of this study is to systematically review the evidence on the association between occupational exposure to arsenic and genitourinary cancer risk and mortality. METHODS: A systematic literature search was carried out on Pubmed, Web of Science and Embase by including cohort and case-control studies. Study-specific relative risks (RRs) and the corresponding 95% confidence intervals (CIs) were pooled using Mandel-Paule random-effects model. Contour-enhanced funnel plot and Egger's test were used to assess the occurrence of publication bias. RESULTS: A total of 17 studies were included in the meta-analysis, 7 on cancer incidence (n = 161,244 individuals) and 10 on cancer mortality (n = 91,868). Most of them were cohort (71%) and industry-based studies (59%). The meta-analysis failed to detect an increased risk of genitourinary cancers among workers exposed to arsenic, except for a suggestive but not significant positive association for bladder cancer incidence (RR: 1.26, 95% CI: 0.89, 1.80), although this estimate was based on only three studies. No compelling evidence of publication bias was found (P = 0.885). CONCLUSIONS: Our findings did not show an association between occupational exposure to arsenic and genitourinary cancers, although further high-quality studies with detailed exposure assessment at the individual level are needed to clarify this relationship.

Genitourinary Cancers Following Kidney Transplant: Our 20 Years of Experience With Mechanistic Target of Rapamycin Inhibitors.

OBJECTIVES: We investigated patients with genitourinary cancer after kidney transplant and the effects of immunosuppression reduction and switching to mechanistic target of rapamycin inhibitors. MATERIALS AND METHODS: We retrospectively evaluated kidney transplant recipients seen at our center between January 2000 and January 2020. Patients with <1 year of follow-up were excluded. RESULTS: Of 827 patients, genitourinary cancer was detected in 11 (1.3%): prostate cancer in 5 patients (45%), renal cell carcinoma in native kidney in 3 (27%), renal cell carcinoma in allograft kidney in 2 (18%), and transitional cell carcinoma of the bladder in 1 (9%). All patients had surgery. Two patients had bone metastasis due to prostate cancer at diagnosis. Two patients had allograft nephrectomy due to de novo renal cell carcinoma. Mean follow-up and age were 97 ± 45 months (range, 26-189) and 50 ± 10.2 years (19% female). After cancer diagnosis, excluding the 2 patients with allograft nephrectomy, immunosuppression was changed in 8 patients (88.8%) (1 patient received the same treatment before and after cancer diagnosis). Six patients received double-drug and 3 received triple-drug protocols. Of 9 patients, 2 were already using mechanistic target of rapamycin inhibitors before cancer diagnosis and 7 were switched: 4 to double-based and 3 to triple-based regimens. Six were switched from tacrolimus. With new treatments, patients showed no progressive kidney failure or rejection (38 ± 40 mo average follow-up). At last follow-up, mean glomerular filtration rate was 62.8 ± 34 mL/min/1.72 m2, which was similar to rate at cancer diagnosis (58.9 ± 24 mL/ min/1.72 m2; P = .78). During follow-up, no patients developed local recurrence of primary tumor or new metastasis, and none showed adverse effects after switch to mechanistic target of rapamycin inhibitors. Three patients died of malignancy-unrelated reasons (ileus, urinary sepsis, heart failure). CONCLUSIONS: Mechanistic target of rapamycin inhibitor-based drugs can be an important maintenance immunosuppressive treatment option for kidney transplant recipients with genitourinary cancers.

The Cardiologist's Role in the Management of Patients with a Genitourinary Cancer.

BACKGROUND: Increased life expectancy due to improved cancer prognosis, shared determinants (e.g., tobacco use), and cardiovascular toxicities related to cancer therapies, including the adverse cardiometabolic effects of androgen deprivation therapy for prostate cancer, make cardiovascular disease an frequent and important co-morbidity in patients with a genitourinary malignancy. Complex cardiovascular disease can pose significant challenges in the management of these patients given the uncertainties related to the best approach to reconcile ischemic and bleeding risks, and the role of invasive cardiovascular interventions in individuals with advanced cancer. In this review, we discuss the current evidence that informs decision-making in this clinical context.

The role of autophagy in metal-induced urogenital carcinogenesis.

Environmental and/or occupational exposure to metals such as Arsenic (As), Cadmium (Cd), and Chromium (Cr) have been shown to induce carcinogenesis in various organs, including the urogenital system. However, the mechanisms responsible for metal-induced carcinogenesis remain elusive. We and others have shown that metals are potent inducers of autophagy, which has been suggested to be an adaptive stress response to allow metal-exposed cells to survive in hostile environments. Albeit few, recent experimental studies have shown that As and Cd promote tumorigenesis via autophagy and that inhibition of autophagic signaling suppressed metal-induced carcinogenesis. In light of the newly emerging role of autophagic involvement in metal-induced carcinogenesis, the present review focuses explicitly on the mechanistic role of autophagy and potential signaling pathways involved in As-, Cd-, and Cr-induced urogenital carcinogenesis.

Exposición al radón y cáncer genitourinario en mineros / Radon exposure and genitourinary cancer in miners

OBJETIVO: Evaluar la asociación entre la exposición al radón y el cáncer genitourinario en población minera a través de una revisión sistemática de la literatura científica. MÉTODO: Se realizó una revisión sistemática de la literatura científica en MEDLINE (PubMed) combinando términos MeSH (Medical Subject Heading) y términos libres. Se realizó una escala específica de valoración de la calidad de los estudios incluidos. RESULTADOS: Se incluyeron 17 estudios. Todos fueron estudios de cohortes, excepto uno que fue un pool de datos. Todos los estudios incluían análisis de la relación entre la exposición al radón y el cáncer genitourinario. Los resultados son ambiguos: unos estudios apuntan hacia una asociación entre la exposición y el cáncer genitourinario, especialmente de riñón, y otros no encuentran asociación. CONCLUSIÓN: Los estudios incluidos presentan una gran heterogeneidad metodológica. No puede concluirse que exista una asociación entre la exposición al radón y el cáncer genitourinario. Es necesaria más investigación sobre el tema, con estudios que tengan más potencia estadística y mejor control de las variables confusoras, y preferentemente que sean prospectivos

OBJECTIVE: To assess the association between exposure to radon and genitourinary cancer in a mining population through a systematic review of the scientific literature. METHOD: A systematic review of the scientific literature was carried out in MEDLINE (PubMed), combining MeSH (Medical Subject Heading) terms and free terms. We applied a specific scale to assess the quality of the included studies. RESULTS: We included 17 studies; all were cohort studies with the exception of one which was a pooling of data. All studies included analysed the relationship between exposure to radon and genitourinary cancer. While some studies point towards an association between radon exposure and genitourinary cancer, especially kidney cancer, others do not find such association. CONCLUSIONS: The included studies showed great heterogeneity. It cannot be concluded that there is an association between exposure to radon and genitourinary cancer. More research is needed on this topic, designing studies with higher statistical power, better control of confounders, and preferably prospective

De Novo Human Herpesvirus 8 Tumors Induced by Rituximab in Autoimmune or Inflammatory Systemic Diseases.

OBJECTIVE: Human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma (KS)-associated herpesvirus, is involved in KS and other tumors, including multicentric Castleman's disease and primary effusion lymphoma. Rituximab (RTX) is currently used for the treatment of several autoimmune or inflammatory diseases and humoral organ transplant rejection. De novo HHV-8 tumors induced by RTX used for these indications have not been reported previously. This study was undertaken to evaluate de novo HHV-8 tumors induced by RTX. METHODS: In this retrospective study, we investigated the clinical, virologic, and pathologic features of 5 HIV-negative male patients with HHV-8 tumors induced by RTX therapy. RESULTS: Patients were all immunocompromised by previous treatments, which consisted of steroids and/or immunosuppressive agents, and received RTX for insufficient response, disease progression, or transplant rejection. They developed HHV-8 tumors a median of 4 months after beginning treatment with RTX (range 3-13 months). Four patients had at least 1 risk factor for HHV-8, including a high Fitzpatrick skin phototype (of >3) (n = 3) and homosexuality (n = 1). Four patients developed KS (all 4 had skin lesions and 2 had visceral involvement), and 1 patient developed a solid primary effusion lymphoma. RTX was discontinued in all patients, and immunosuppressants were reduced when feasible. After a median follow-up of 20 months, 2 patients died. Remission of KS was complete in 1 patient and partial in 1 patient, and 1 patient had progression. CONCLUSION: Our findings indicate that patients who have a high skin phototype and are at risk of HHV-8 should be carefully screened for HHV-8 before RTX therapy. The safety of RTX, especially in nonlymphomatous disorders, should be carefully evaluated in patients at risk of HHV-8 tumors.

Clinical Significance of Hematuria in Atrial Fibrillation With Oral Anticoagulation Therapy.

BACKGROUND: Hematuria is a common and important complication in atrial fibrillation (AF) patients on oral anticoagulation therapy (OAT). This study evaluated the clinical significance of hematuria and its relationship with genitourinary disease in AF patients receiving OAT.Methods and Results:Among 20,456 consecutive AF patients who visited a tertiary hospital from January 2005 to April 2015, 5,833 had hematuria. Of these 5,833 patients, 3,798 were on OAT (OAT(+) group) and 2,035 were not (OAT(-) group). A total of 1,785 patients from each group were then matched on propensity score analysis. The prevalence of cancer and other diseases in the genitourinary tract was evaluated. While there was no difference in the prevalence of genitourinary stones or urinary tract infection, genitourinary cancer was significantly more common in the OAT(+) group than in the OAT(-) group (1.6% vs. 0.7%, P=0.011). Bladder cancer was the most common genitourinary malignancy, and it was significantly more common in the OAT(+) group (1.2% vs. 0.5%, P=0.019). Subjects on warfarin were more likely to have bladder cancers of lower pathologic grade (63.6% vs. 33.3%, P=0.124). CONCLUSIONS: OAT was associated with a higher prevalence and early detection of genitourinary cancer in AF patients with hematuria. Meticulous evaluation of the cause of hematuria is necessary in AF patients with hematuria receiving OAT.

[Genitourinary malignancies and rheumatoid arthritis]. / Urologische Malignome und rheumatoide Arthritis.

Genitourinary neoplasms are relatively common and the frequency increases with age. Due to demographic changes more patients with inflammatory rheumatic diseases will have concomitant genitourinary tumors or they will develop them under antirheumatic therapy. In such cases, disease-modifying antirheumatic drugs (DMARD) and immunosuppressive therapy have to be carefully balanced on an individual basis. Based on the limited evidence available large increases in the risks from conventional and/or biological DMARDs for patients with genitourinary malignancies appear to be unlikely for most situations. In addition to these more common situations paraneoplastic symptoms in the musculoskeletal system can occur due to genitourinary malignancies. Moreover, novel drugs with immunostimulating activity for some genitourinary tumors may provoke autoimmune symptoms and thus present new challenges for interdisciplinary cooperation between rheumatologists and uro-oncologists. In this review, the diagnostic procedures, therapies and follow-up of cancers in the field of urology are delineated according to the current German and European guidelines. We describe the core issues that both urologists and rheumatologists should bear in mind. Direct communication, routine exchange and involvement of rheumatologists in interdisciplinary tumor boards should improve future treatment quality of our joint patients.

Nonpulmonary outcomes of asbestos exposure.

The adverse pulmonary effects of asbestos are well accepted in scientific circles. However, the extrapulmonary consequences of asbestos exposure are not as clearly defined. In this review the potential for asbestos to produce diseases of the peritoneum, immune, gastrointestinal (GIT), and reproductive systems are explored as evidenced in published, peer-reviewed literature. Several hundred epidemiological, in vivo, and in vitro publications analyzing the extrapulmonary effects of asbestos were used as sources to arrive at the conclusions and to establish areas needing further study. In order to be considered, each study had to monitor extrapulmonary outcomes following exposure to asbestos. The literature supports a strong association between asbestos exposure and peritoneal neoplasms. Correlations between asbestos exposure and immune-related disease are less conclusive; nevertheless, it was concluded from the combined autoimmune studies that there is a possibility for a higher-than-expected risk of systemic autoimmune disease among asbestos-exposed populations. In general, the GIT effects of asbestos exposure appear to be minimal, with the most likely outcome being development of stomach cancer. However, IARC recently concluded the evidence to support asbestos-induced stomach cancer to be "limited." The strongest evidence for reproductive disease due to asbestos is in regard to ovarian cancer. Unfortunately, effects on fertility and the developing fetus are under-studied. The possibility of other asbestos-induced health effects does exist. These include brain-related tumors, blood disorders due to the mutagenic and hemolytic properties of asbestos, and peritoneal fibrosis. It is clear from the literature that the adverse properties of asbestos are not confined to the pulmonary system.

Genitourinary long-term outcomes for childhood cancer survivors.

The treatment of pediatric malignancies represents one of the success stories of modern medicine. As survival has increased, the focus is now on minimizing harmful effects of treatment. There continue to be late toxicities and secondary malignancies of the genitourinary (GU) system for childhood cancer survivors related to the specific therapeutic exposures. A systematic approach is important for prevention and treatment of these adverse late GU effects.

Clinical and epidemiological features of patients with genitourinary tract tumour in a blackfoot disease endemic area of Taiwan.

OBJECTIVES: To evaluate the clinical and epidemiological characteristics of patients with genitourinary (GU) tract transitional cell carcinoma (TCC) in an endemic area of blackfoot disease (BFD), the arsenic-exposed group, to compare them with characteristics among other non-BFD endemic areas (unexposed group). PATIENTS AND METHODS: In all, 474 patients with pathologically diagnosed GU-TCC were enrolled in the study. All follow-up data were prospectively collected and entered into a database throughout the study period. Statistical analysis was used to determine the association between clinical variables and prognosis, and multivariate regression models were used to assess the association between arseniasis and mortality from GU-TCC. RESULTS: There were no significant differences between the groups in age, sex, tumour stage and grade. However, the exposed group had a significantly higher proportion of females. The overall 5-year survival rate of patients with upper urinary tract (UUT) TCC was 49%, and the two groups had similar 5-year survival rates. The overall 5-year survival rate of patients with urinary bladder (UB) TCC was 68.3%, and there was a statistically significant difference in survival between the groups, with a 5-year survival rate of 58.7% for the exposed and 72.4% for the unexposed group. For patients with early-stage (pTa and pT1) UB cancers, the death rate was five times higher in exposed patients with tumour progression and recurrence after transurethral resection of bladder tumour than in the unexposed group. CONCLUSIONS: There was a significantly higher mortality rate for UB-TCC among exposed patients in the area endemic for arseniasis than in those from other non-endemic areas. The arsenic content of artesian-well water might contribute to the increased ratio of female patients with GU-TCC and the unusually high incidence of UUT-TCC in the BFD endemic area in Taiwan.

Offspring of women exposed in utero to diethylstilbestrol (DES): a preliminary report of benign and malignant pathology in the third generation.

BACKGROUND: Animal studies suggest that prenatal exposure to the synthetic estrogen diethylstilbestrol (DES) causes epigenetic changes that may be transmitted to the next generation. Specifically, these studies show an elevated incidence of reproductive tumors in the female offspring of prenatally-exposed mice. METHODS: We assessed cancer and benign pathology diagnoses occurring in the offspring of women whose prenatal exposure to DES (or lack of exposure) was verified by medical record. Our data arose from 2 sources: the mothers' reports of cancers occurring in 8216 sons and daughters, and pathology-confirmed cancers and benign diagnoses self-reported by a subset of 793 daughters. RESULTS: Although statistical power is limited, our data are consistent with no overall increase of cancer in the sons or daughters of women exposed in utero to DES. Based on pathology-confirmed diagnoses reported by the daughters, we saw no association between DES and risk of benign breast disease or reproductive tract conditions. Based on 3 cases, the incidence of ovarian cancer was higher than expected in the daughters of women exposed prenatally to DES. CONCLUSIONS: Our data do not support an overall increase of cancer risk in the sons or daughters of women exposed prenatally to DES, but the number of ovarian cancer cases was greater than expected. While preliminary, this finding supports continued monitoring of these daughters.

Workgroup report: National Toxicology Program workshop on Hormonally Induced Reproductive Tumors - Relevance of Rodent Bioassays.

The National Toxicology Program (NTP) is currently reviewing its research portfolio as part of its efforts to implement the NTP Roadmap to achieve the NTP Vision for the 21st century. This review includes a recent workshop, "Hormonally Induced Reproductive Tumors-Relevance of Rodent Bioassays," held 22-24 May 2006, that was organized to determine the adequacy and relevance to human disease outcome of rodent models currently used in the 2-year bioassay for four types of hormonally induced reproductive tumors (ovary, mammary gland, prostate, and testis). In brief, none of the workshop's breakout groups felt the currently used models are sufficient. For some types of tumors such as prostate, no adequate animal models exist, and for others such as ovary, the predominant tumors in humans are of different cellular origins than those induced by chemicals in rodents. This inadequacy of current models also applies to the testis, although our more complete understanding of the responses of Leydig cells to hormonal changes in rats may prove predictive for effects in humans other than cancer. All breakout groups recommended that the NTP consider modifying its testing protocols (i.e., age at exposure, additional end points, etc.) and/or using alternative models (i.e., genetically engineered models, in vitro systems, etc.) to improve sensitivity. In this article we briefly review the workshop's outcome and outline some next steps forward in pursuing the workshop's recommendations. Breakout group reports and additional information on the workshop, including participants, presentations, public comments and background materials, are posted on the NTP website.

Clinical implications of DES.

Once prescribed to pregnant women to prevent risk of spontaneous abortion, diethylstilbestrol (DES) is now associated with an increased risk of breast cancer, clear cell adenocarcinoma (CCA) of the vagina and cervix, and reproductive anomalies. This article will summarize the potential long-term health implications of DES, the role of nurse practitioners in identifying exposed individuals, and proper clinical management.

Chemoprevention of lung carcinogenesis by cacao liquor proanthocyanidins in a male rat multi-organ carcinogenesis model.

The effects of cacao liquor proanthocyanidins (CLPr) on tumorigenesis were investigated using a multi-organ carcinogenesis model in male F344 rats receiving combined treatment with a single i.p. injection of diethylnitrosamine (100 mg/kg body wt), four i.p. injections of N-methylnitrosourea (20 mg/kg body wt), four s.c. injections of dimethylhydrazine (40 mg/kg body wt), along with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine and then 0.1% 2,2'-dihydroxy-di-n-propylnitrosamine, both in the drinking water, for 2 weeks each, during the initial 4-week period (DMBDD treatment). Starting 1 week thereafter, rats were administered CLPr at a dose of 0.025% or 0.25% and the experiment was terminated at week 36. The final survival rate for the DMBDD+0.25% CLPr group was significantly greater than for the DMBDD alone group. In the lung, significant reduction in the incidence and multiplicity of carcinomas was also observed, and in the thyroid, quantitative values for adenomas also tended to decrease in a CLPr dose-dependent manner. No significant modification in the small intestine, colon or kidney was evident. These results indicate that CLPr exerts chemopreventive effects in the lung without any promoting influence in other major organs.

The Koebner phenomenon in immunosuppression-related Kaposi's sarcoma.

The Koebner phenomenon has been reported to develop in classic or acquired immune deficiency syndrome-related Kaposi's sarcoma (KS). A 12-year-old kidney transplant recipient who developed immunosuppression-related KS showed reoccurrence of lesions in some previously intact incision sites following removal of tumor, suggesting Koebner phenomenon. It is recommended that surgeons be careful when planning surgical interventions in patients with certain skin disorders in which Koebner phenomenon is known to develop.

Multiorgan transplacental and neonatal carcinogenicity of 3'-azido-3'-deoxythymidine in mice.

The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is used successfully for reduction of perinatal viral transmission. However toxic side effects including carcinogenesis are possible. To test this, pregnant CD-1 Swiss mice were given 25.0 or 12.5 mg AZT on gestation days 12-18. Previously we reported an increase in lung, liver, and female reproductive system tumors in offspring euthanized at 1 year (Olivero et al., J. Natl. Cancer Inst. 89, 1602-1608, 1997). Findings for all remaining offspring up to 2 years old are reported here. AZT effects were most prominent in female offspring, with a significant threefold increase in lung tumors, a reduction in lymphoblastic and follicle center cell lymphomas, and a significant increase in histiocytic sarcomas (0 in controls, 3% after low-dose AZT, and 8% after high-dose AZT, p = 0.022). Dose-dependent incidences of mammary gland, ovarian, and seminal vesicle tumors were low but significant: 0/106 controls, 3/105 low-dose, and 8/105 high-dose mice presented one of these neoplasms (p = 0.0025). Incidences of females showing any clearly AZT-related neoplasm, in lung, liver, ovary, or mammary gland or histiocytic sarcoma, in the second year, were 12/32 after the low dose and 14/27 after the high dose vs 3/23 controls (p = 0.0045). Also, the sensitivity of neonatal mice was assessed by administration of 25, 50, 100, or 200 mg/kg AZT on postnatal days 1 through 8. The effects at 2 years were similar to those seen after transplacental exposure, with significant increases in lung, liver, and mammary tumors in females. The results confirm that AZT is a moderately effective perinatal carcinogen in mice, targeting several tissue types.

Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats.

The usefulness of transabdominal ultrasonography in the diagnosis of 3,2'-dimethyl-4-aminobiphenyl- and testosterone propionate-induced tumors of the urogenital organs was evaluated in F344 rats. Seven mass lesions (1 ventral prostate, 1 dorsolateral prostate, 3 seminal vesicles, and 1 kidney) in the urogenital organs could easily be diagnosed concerning size and localization by ultrasound. Histological examination revealed a lesion in the ventral prostate to be an abscess and the other tumors to be malignant. Three hydronephroses by tumor invasion to the ureter, and six tumors in organs other than the urogenital organs could be detected by ultrasound. The threshold of malignant tumor detection by ultrasound was 7 mm in actual length. The size of the mass lesion estimated by ultrasound correlated well with the direct measurement (r = 0.96). Transabdominal ultrasonography is useful for diagnosing the localization of experimental tumors and accurately measuring their size in the urogenital organs of rats.