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1.
Am J Case Rep ; 22: e933168, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34620815

RESUMO

BACKGROUND Kidney transplantation is a treatment option for patients with end-stage renal disease. However, life-long immunosuppressive therapy, which is obligatory for renal transplant recipients, increases the risk of cancer recurrence and de novo tumor formation. Cancer is one of the leading causes of death in kidney transplant recipients. Renal cell carcinoma (RCC) of an allograft kidney is an extremely rare type of neoplasm and occurs in only about 0.22-0.25% of all kidney recipients. RCC is often asymptomatic and can be an incidental finding on routine examination. CASE REPORT In this case study, we describe a patient who developed chromophobe renal cell carcinoma 3 years after kidney transplantation from a living related donor. At the time of detection of the tumor, the graft function was impaired. A renal allograft biopsy was performed, and the pathological examination showed signs of chronic inflammation and chronic graft rejection. The graft biopsy failed to differentiate between oncocytoma and chromophobe carcinoma. Due to impaired graft function, presence of neoplasm in the graft, and morphologic chronic rejection, it was decided to perform a transplantectomy. The final histological examination showed the eosinophilic type of chromophobe carcinoma. CONCLUSIONS Chromophobe carcinoma in a kidney allograft is extremely rare in kidney transplant recipients. This clinical observation confirms the necessity and effectiveness of regular ultrasound and magnetic resonance imaging of the graft, not only for monitoring the functioning of the graft, but also for early detection of neoplasms in the transplanted kidney.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Aloenxertos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/cirurgia , Humanos , Rim , Neoplasias Renais/diagnóstico , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Transplante de Rim/efeitos adversos , Recidiva Local de Neoplasia
2.
Transplant Proc ; 53(8): 2552-2555, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34474910

RESUMO

BACKGROUND: We present a rare case of de novo renal cell carcinoma that developed in an allograft kidney 14 years after transplantation. CASE REPORT: A 39-year-old man underwent living donor kidney transplantation from his mother. After 14 years, routine screening ultrasonography revealed a solid mass of 30-mm diameter in the kidney allograft. Partial nephrectomy was performed by clamping the renal artery under in situ cooling. Tissue histology revealed clear cell carcinoma with negative surgical margins. We explored the tumor's genetic origin using fluorescence in situ hybridization to analyze the X and Y chromosomes of the tumor cells. Postoperative hemodialysis was avoided, and the patient's serum creatinine level remained stable. CONCLUSIONS: Fluorescence in situ hybridization clearly indicated that the tumor originated from the donor and that the tumor vasculature originated from the recipient. The patient recovered well and remains without any tumor recurrence.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Adulto , Aloenxertos , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/genética , Humanos , Hibridização in Situ Fluorescente , Rim , Neoplasias Renais/etiologia , Neoplasias Renais/genética , Transplante de Rim/efeitos adversos , Masculino , Recidiva Local de Neoplasia
3.
Beijing Da Xue Xue Bao Yi Xue Ban ; 53(4): 811-813, 2021 Aug 18.
Artigo em Chinês | MEDLINE | ID: mdl-34393251

RESUMO

With the continuous development of kidney transplantation technique, the survival time after kidney transplantation is gradually prolonged. Thus, the malignant tumor has been the important influencing factor on the long-term survival for kidney transplantation patients. Renal cell carcinoma is a relatively common tumor after kidney transplantation. Besides, clear cell renal cell carcinoma and papillary renal cell carcinoma are the relatively common pathological types for renal cell carcinoma following kidney transplantation. However, bilateral renal cell carcinoma following kidney transplantation is comparatively rare. In this article, we presented a case of bilateral papillary renal cell carcinoma, which occurred after kidney transplantation. And the diagnosis and treatment were introduced in detail. The patient was 37 years old, and he underwent kidney transplantation 13 years ago in our hospital, because of kidney failure. After kidney transplantation, he had regular medical check-up every year. In this year, his urological ultrasound results indicated bilateral renal tumors. And then, he received abdominal and pelvic computed tomography, and the result also showed bilateral renal tumors, which were likely to be malignant tumors. After adequate consultation, the patient chose surgical treatment. The patient received long-term immunosuppressive therapy, because of kidney transplantation. Considering this, the surgeon decided to choose a staging surgical treatment, in order to reduce the bad influence of one-stage surgery. Then, the patient first underwent retroperitoneal laparoscopic radical nephrectomy for right renal tumor in our hospital, and he had no complications after operation. The pathological results showed papillary renal cell carcinoma. He was discharged successfully. He underwent retroperitoneal laparoscopic radical nephrectomy for left renal tumor in our hospital one month later, and he had no complications after operation. The pathological results also showed papillary renal cell carcinoma. He was discharged successfully two days after surgery. In the 3-month follow-up, the patient was recovering well. To sum up, the incidence of bilateral renal cell carcinoma following kidney transplantation is relatively rare, and bilateral radical nephrectomy is effective and safe treatment. Above all, it is the patient's condition that determines the choice of staging surgery or simultaneous surgery.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Transplante de Rim , Adulto , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/cirurgia , Humanos , Rim , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Nefrectomia
4.
Cancer Sci ; 112(10): 4100-4111, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339558

RESUMO

SHANK-associated RH domain interacting protein (SHARPIN) plays an important role in carcinogenesis, as well as inflammation and immunity. Our study explored the effects and underlying mechanisms of SHARPIN in clear cell renal cell carcinoma (ccRCC). By analyzing The Cancer Genome Atlas database, we found that upregulated SHARPIN in patients with ccRCC led to a poor prognosis. Semiquantitative immunohistochemical analysis of clinical samples was carried out and the results suggested the positive association between SHARPIN and hypoxia-induced factor-2α (HIF-2α). Von Hippel-Lindau protein (pVHL) is a tumor suppressor that contributes to degrading HIF-2α. Mechanically, SHARPIN promoted the ubiquitination and proteasomal degradation of pVHL, resulting in the sustained activation of HIF-2α. The α and ß domains of pVHL and ubiquitin-like domain of SHARPIN are required for the interaction. The knockdown of SHARPIN effectively inhibited acquired sorafenib resistance in ccRCC cell lines and tumor growth in xenograft models. In conclusion, our work reveals a novel posttranslational regulation of SHARPIN on pVHL, indicating that SHARPIN could be a potential target for ccRCC treatment.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Carcinoma de Células Renais/etiologia , Neoplasias Renais/etiologia , Ubiquitinas/fisiologia , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Animais , Antineoplásicos/farmacologia , Apoptose , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Inativação Gênica , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Processamento de Proteína Pós-Traducional , Proteólise , RNA Interferente Pequeno , Distribuição Aleatória , Sorafenibe/farmacologia , Ubiquitinação , Ubiquitinas/genética , Ubiquitinas/metabolismo , Regulação para Cima
5.
Transplant Proc ; 53(8): 2539-2542, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34315637

RESUMO

De novo tumors in renal allograft recipients are a severe complication during long-term follow-up after transplantation and may require transplantectomy. Herein we present a case of de novo renal tumor arising in the renal allograft, treated with the less invasive image-guided radiofrequency ablation (RFA) with long-term follow-up. A tumor was detected during the routine annual follow-up in a patient with good renal function who underwent renal transplantation in 1989. Computed tomography (CT) showed a mass in the allograft whose shape, vascularization, and density suggested the presence of a solid, malignant mass, located in the upper renal pole, that measured 17 mm. CT-guided RFA was performed successfully, and the outcome was verified by an immediate control CT after the intervention. No residual pathologic tissue, major bleeding, or damage to the adjacent parenchyma was evidenced. The patient was discharged with stable renal function. CT scan and ultrasound were performed 3, 6, 12, 18, 24, and 36 months after RFA. No signs of change in renal function, recurrence, neovascularization, or damage to the adjacent microcirculation were observed during the 3-year follow-up. In conclusion, percutaneous RFA of small renal tumors occurring in renal allografts can be considered a function-sparing, safe, and effective therapeutic option when difficult surgical removal may be anticipated. Our experience also supports the need for yearly renal allograft ultrasound follow-up for early identification of small neoplasm than can be treated less invasively.


Assuntos
Carcinoma de Células Renais , Ablação por Cateter , Neoplasias Renais , Transplante de Rim , Aloenxertos , Carcinoma de Células Renais/cirurgia , Seguimentos , Humanos , Rim/fisiologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Transplante de Rim/efeitos adversos , Resultado do Tratamento
6.
Eur J Epidemiol ; 36(9): 927-936, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34195879

RESUMO

Limited information is available on carcinogenicity of asbestos on non-respiratory organs. We aimed at conducted an updated systematic review and meta-analysis of cohort studies on occupational exposure to asbestos and risk of kidney cancer. We searched through three databases, PubMed, Embase and Scopus for article published after 2000, and after eliminating duplicates and non-relevant studies, we identified 13 studies. We combined their results with those of 31 non-overlapping studies included in a previous review up to 2000. We conducted a meta-analysis based on random-effects models. The pooled relative risk of kidney cancer for asbestos exposure was 0.94 (95% confidence interval, 0.84-1.04), with no differences according to type of asbestos fiber, geographic region, period of exposure, or estimated quality of the study. Our results showed a lack of association between occupational asbestos exposure and risk of kidney cancer.


Assuntos
Asbestos/efeitos adversos , Neoplasias Renais/etiologia , Exposição Ocupacional/efeitos adversos , Carcinógenos , Humanos , Neoplasias Renais/epidemiologia , Medição de Risco , Fatores de Risco
7.
Cancer Causes Control ; 32(9): 1029-1038, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34089471

RESUMO

PURPOSE: Weight cycling is common in populations. However, it is unclear whether frequency and magnitude of weight cycling is associated with kidney cancer risk, independent of body mass index (BMI). METHODS: A prospective cohort study followed 85,562 participants from Health Professionals Follow-up Study and Nurses' Health Study (1992-2014). At baseline, participants reported frequency and magnitude of intentional weight loss in the past 4 years. Cox proportional hazard model was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). We also conducted a meta-analysis of all available observational studies including our two cohorts. RESULTS: During 22 years of follow-up, we identified 441 kidney cancer cases. Compared with non-weight cyclers (no attempt of intentional weight loss), severe cyclers (≥ 3 times of intentional weight loss of ≥ 4.5 kg) were at increased kidney cancer risk after adjusting for BMI before weight cycling (pooled multivariable-adjusted HR, 1.78; 95% CI, 1.19, 2.66). Additional adjustment for attained BMI after weight cycling had minimal influence. There was a positive trend between weight cycling by frequency and magnitude and kidney cancer risk (P-trend = 0.01). Moreover, the observed positive association did not differ by subtypes of cyclers (e.g., adiposity status, weight-loss methods). In the meta-analysis, we found a strong positive association between weight cycling and kidney cancer risk (summary relative risk for weight cyclers vs. non-cyclers, 1.51; 95% CI, 1.16, 1.96; I2: 52.2%; 6 studies). CONCLUSION: Frequent substantial weight cycling was associated with increased risk of kidney cancer, independent of BMI. Our study suggests that weight cycling may be an important risk factor for kidney cancer.


Assuntos
Neoplasias Renais , Ganho de Peso , Índice de Massa Corporal , Seguimentos , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/etiologia , Estudos Observacionais como Assunto , Estudos Prospectivos , Fatores de Risco , Perda de Peso
8.
Front Immunol ; 12: 681615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149719

RESUMO

Although natural killer (NK) cells infiltrate clear cell renal cell carcinomas (ccRCC), the most frequent malignancy of the kidney, tumor progression suggests that they become dysfunctional. As ccRCC-driven subversion of NK cell effector functions is usually accompanied by phenotypic changes, analysis of such alterations might lead to the identification of novel biomarkers and/or targets in immuno-oncology. Consequently, we performed a phenotypic analysis of peripheral blood NK cells (PBNK) and tumor-infiltrating NK cells (TINK) from ccRCC patients. Compared to HD, PBNK from ccRCC patients exhibited features of activated cells as shown by CD25, CD69 and CD62L expression. They also displayed increased expression of DNAM-1, CD48, CD45, MHC-I, reduced expression of NKG2D, and higher frequencies of CD85j+ and PD-1+ cells. In addition, compared to PBNK from ccRCC patients, TINK exhibited higher expression of activation markers, tissue residency features and decreased expression of the activating receptors DNAM-1, NKp30, NKp46, NKp80 and CD16, suggesting a more inhibitory phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that CD48, CD45, CD85j and PD-1 are significantly overexpressed in ccRCC and that their expression is associated with an NK cell infiltration signature. Calculation of z-scores revealed that their expression on PBNK, alone or combined, distinguished ccRCC patients from HD. Therefore, these molecules emerge as novel potential biomarkers and our results suggest that they might constitute possible targets for immunotherapy in ccRCC patients.


Assuntos
Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/etiologia , Neoplasias Renais/metabolismo , Células Matadoras Naturais/imunologia , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Idoso , Biomarcadores , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Células Matadoras Naturais/metabolismo , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia
9.
Expert Opin Investig Drugs ; 30(5): 495-504, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33945366

RESUMO

INTRODUCTION: Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant syndrome caused by a germline mutation and/or deletion of the VHL gene. Inappropriate hypoxia-inducible factor (HIF)-mediated transcription of proangiogenic and metabolic genes leads to the development of tumors and cysts in multiple organs. Surgery is a standard treatment for localized tumors with a risk of metastasis or organ dysfunction. Repeated surgeries cause substantial morbidity and have a major impact on quality of life. There is an urgent need to develop effective and safe systemic treatments for VHL disease manifestations. The small-molecule HIF 2 alpha inhibitor MK-6482 (belzutifan) has demonstrated significant efficacy in VHL disease related renal cell carcinomas, hemangioblastomas, and pancreatic neuroendocrine tumors while demonstrating an acceptable safety profile. AREAS COVERED: This paper reviews the development of the HIF-2 alpha inhibitor, MK-6482, and discusses preliminary results of ongoing phase I/II studies in renal cell carcinoma (RCC) and VHL disease. An examination of ongoing clinical development of MK-6482 and perspectives on potential future developments and challenges are offered. EXPERT OPINION: Because of its favorable safety profile, its clear efficacy in VHL disease, promising findings in sporadic, advanced RCC, and convenient oral formulation, MK-6482 is expected to become a leading treatment for VHL disease. Among other currently available oral agents, we believe that MK-6482 will be a preferred treatment for VHL-associated RCC.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Administração Oral , Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Carcinoma de Células Renais/etiologia , Humanos , Neoplasias Renais/etiologia , Qualidade de Vida , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/tratamento farmacológico
10.
Ann R Coll Surg Engl ; 103(6): e184-e188, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955281

RESUMO

Angiomyolipoma is a benign solid renal neoplasm. A giant angiomyolipoma is more than 10cm by size, but it can grow to huge proportions. Our case appears to be the third largest angiomyolipoma and the largest among bilateral giant renal angiomyolipoma in the indexed literature. A 26-year-old man presented with large right abdominal swelling for the past three years, which was occupying his right flank and iliac region, extending beyond the midline. Computed tomography of the abdomen revealed a large well-defined mass in the right side of the abdomen, crossing the midline and measuring 35 × 20 × 12cm. The left kidney showed a similar fatty lesion of 14 × 6cm. The findings were consistent with angiomyolipoma. Further evaluation for tuberous sclerosis by magnetic resonance imaging the brain demonstrated multiple subependymal nodules. Giant renal angiomyolipoma is an uncommon tumour with bilateral giant angiomyolipoma being a rare entity. Preoperative embolisation helps in reducing size of the tumour. In case of giant and bilateral angiomyolipoma, evaluation for tuberous sclerosis should always be done.


Assuntos
Angiomiolipoma/patologia , Neoplasias Renais/patologia , Neoplasias Primárias Múltiplas/patologia , Adulto , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/etiologia , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/etiologia , Imageamento por Ressonância Magnética , Masculino , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/etiologia , Tomografia Computadorizada por Raios X , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagem , Carga Tumoral
11.
Am J Epidemiol ; 190(10): 2042-2052, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33984862

RESUMO

Chronic kidney disease in its later stages is associated with increased risk of kidney cancer. We investigated whether chronic kidney disease at milder stages is associated with increased kidney cancer risk, using a retrospectively selected cohort of 9,809,317 adults in the Republic of Korea who participated in a nationwide health screening (2009-2016). We examined the impact of estimated glomerular filtration rate (eGFR), dipstick proteinuria, and interactive associations between the 2 factors on the risk of incident kidney cancer. During a median follow-up period of 7.3 years, 10,634 kidney cancers were identified. After adjustment for multiple confounders, participants with a reduced eGFR had an increased risk of kidney cancer (for eGFR <30 mL/minute/1.73 m2, adjusted hazard ratio = 1.18 (95% confidence interval: 1.01, 1.39); for eGFR 30-59 mL/minute/1.73 m2, adjusted hazard ratio = 1.22 (95% confidence interval: 1.14, 1.31)) compared with those with an eGFR of 60-89 mL/minute/1.73 m2. A dose-response relationship between the severity of proteinuria and incident kidney cancer was observed. Analyses of joint effects of eGFR and dipstick proteinuria showed that with the presence of proteinuria, kidney cancer incidence was markedly increased along with decreasing eGFR. Reduced eGFR and proteinuria are significantly associated with subsequent risk of kidney cancer, possibly in a synergistic manner.


Assuntos
Neoplasias Renais/epidemiologia , Proteinúria/complicações , Insuficiência Renal Crônica/complicações , Adulto , Idoso , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular , Humanos , Incidência , Rim/fisiopatologia , Neoplasias Renais/etiologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
12.
Int J Cancer ; 149(7): 1448-1454, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34058014

RESUMO

The ccA and ccB molecular subtypes of clear cell renal cell carcinoma (ccRCC) have well-characterized prognostic relevance. However, it is not known whether they possess distinct etiologies. We investigated the relationships between these subtypes and RCC risk factors within a case-control study conducted in Eastern Europe. We analyzed risk factor data for ccA (n = 144) and ccB (n = 106) cases and 1476 controls through case-only and case-control comparisons to assess risk factor differences across subtypes using logistic and polytomous regression models. We also performed a meta-analysis summarizing case-only results from our study and three patient cohorts. Patients with ccB tumors had poorer survival than those with ccA tumors and were more likely to be male (case-only odds ratio [OR] 2.68, 95% confidence interval [CI] 1.43-5.03). In case-control analyses, body mass index was significantly associated with ccA tumors (OR 2.45, 95% CI 1.18-5.10 for ≥35 vs <25 kg/m2 ) but not with ccB tumors (1.52, 0.56-4.12), while trichloroethylene was associated with ccB but not ccA (OR 3.09, 95% CI 1.11-8.65 and 1.25, 0.36-4.39 respectively for ≥1.58 ppm-years vs unexposed). A polygenic risk score of genetic variants identified from genome-wide association studies was associated with both ccA and, in particular, ccB (OR 1.82, 1.11-2.99 and 2.87, 95% CI 1.64-5.01 respectively for 90th vs 10th percentile). In a meta-analysis of case-only results including three patient cohorts, we still observed the ccB excess for male sex and the ccA excess for obesity. In conclusion, our findings suggest the existence of etiologic heterogeneity across ccRCC molecular subtypes for several risk factors.


Assuntos
Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Idoso , Carcinoma de Células Renais/classificação , Carcinoma de Células Renais/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Neoplasias Renais/classificação , Neoplasias Renais/etiologia , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de Sobrevida
13.
Genes (Basel) ; 12(4)2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805346

RESUMO

Urea is largely derived from the urea cycle reactions through hepatic detoxification of free ammonia and cleared by urination, and the serum urea level is a crucial medical indicator for measuring the kidney function in patients with nephropathy; however, investigative revelations pointing to the serum urea level as a risk factor for cancer are very scarce, and relevant studies are restricted by potential biases. We aimed to explore the causal relationships of the serum urea level with cancer development by focusing on renal cell carcinoma (RCC) using the Mendelian randomization (MR) analyses. Summary estimates were collected from the inverse-variance weighted (IVW) method based on six single nucleotide polymorphisms (SNPs). The selected SNPs related to the serum urea were obtained from a large genome-wide association study (GWAS) of 13,312 European participants. The summary statistics of RCC were also available from public databases (IARC, n = 5219 cases, n = 8011 controls). Sensitivity analyses included the weighted median and MR-Egger methods. Serum urea was inversely associated with RCC in females (effect = 1.93; 95% CI: 1.24 to 3.01; p = 0.004) but exhibited null association with RCC in males, breast cancer (BRCA) in both genders and prostate cancer (PCa) in males. Similar conclusions were also drawn from the weighted median and MR-Egger. These findings reveal an intriguing link between serum urea and cancer risks for the very first time. Without ambiguity, the serum urea is causatively related to RCC specifically in females, although the mechanism(s) by which urea is involved in RCC development remains to be experimentally/clinically investigated. Our studies may well provide novel insights for RCC diagnosis, intervention and/or therapy.


Assuntos
Neoplasias da Mama/patologia , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologia , Análise da Randomização Mendeliana/métodos , Neoplasias da Próstata/patologia , Ureia/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/etiologia , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/etiologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/etiologia , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/sangue , Neoplasias da Próstata/etiologia , Fatores de Risco
14.
Mayo Clin Proc ; 96(6): 1470-1489, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33526281

RESUMO

OBJECTIVE: To study the clinical features and identify unique renal neoplasia subtypes and their prognostic implications in individuals with tuberous sclerosis complex (TSC). PATIENTS AND METHODS: The Mayo Clinic nephrectomy registry included 37 patients with TSC diagnosed between 1970 and 2018. Four additional patients were identified from the pathology consultation and autopsy files. All available renal tumors were further characterized using immunohistochemistry and fluorescence in situ hybridization. Clinicopathologic features and follow-up were obtained from the medical record. The American Association for Cancer Research Project GENIE registry was accessed using cBioPortal for molecular profiling of angiomyolipoma (AML). RESULTS: A total of 276 renal tumors from 41 patients were analyzed. Renal tumors were classified into 9 distinct morphological subtypes, with AML predominating (238 [86%]). Interestingly, all these tumors acted in a benign fashion except one renal cell carcinoma with clear cells and fibromyomatous stroma and one epithelioid AML that metastasized. Molecular profiling studies revealed that epithelioid AMLs were enriched for alterations of TP53, RB1, and ATRX. Eight patients died of direct complications of TSC, including 3 of end-stage renal disease. To date, none have died of a renal epithelial neoplasm. CONCLUSION: The identification of unique renal neoplasia subtypes may provide important clues to establish a diagnosis of TSC, and in the somatic setting, this finding has important implications for accurate prognostication. These tumors tend to be indolent, and only 2 of 276 tumors in our study exhibited metastatic behavior. Our results support multidisciplinary management with a focus on preservation of renal function.


Assuntos
Neoplasias Renais/etiologia , Esclerose Tuberosa/complicações , Adolescente , Adulto , Angiomiolipoma/etiologia , Angiomiolipoma/patologia , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/patologia , Criança , Pré-Escolar , Feminino , Humanos , Hibridização in Situ Fluorescente , Lactente , Rim/patologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Esclerose Tuberosa/diagnóstico , Esclerose Tuberosa/genética , Esclerose Tuberosa/patologia , Adulto Jovem
15.
J Immunol Res ; 2021: 6617841, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628845

RESUMO

As the most prevalent internal eukaryotic modification, N6-methyladenosine (m6A) is installed by methyltransferases, removed by demethylases, and recognized by readers. However, there are few studies on the role of m6A in clear cell renal cell carcinoma (ccRCC). In this study, we researched the RNA-seq transcriptome data of ccRCC in the TCGA dataset and used bioinformatics analyses to detect the relationship between m6A RNA methylation regulators and ccRCC. First, we compared the expression of 18 m6A RNA methylation regulators in ccRCC patients and normal tissues. Then, data from ccRCC patients were divided into two clusters by consensus clustering. LASSO Cox regression analysis was used to build a risk signature to predict the prognosis of patients with ccRCC. An ROC curve, univariate Cox regression analysis, and multivariate Cox regression analysis were used to verify this risk signature's predictive ability. Then, we internally validated this signature by random sampling. Finally, we explored the role of the genes in the signature in some common pathways. Gene distribution between the two subgroups was different; cluster 2 was gender-related and had a worse prognosis. IGF2BP3, IGF2BP2, HNRNPA2B1, and METTL14 were chosen to build the risk signature. The overall survival of the high- and low-risk groups was significantly different (p = 7.47e - 12). The ROC curve also indicated that the risk signature had a decent predictive significance (AUC = 0.72). These results imply that the risk signature has a potential value for ccRCC treatment.


Assuntos
Adenosina/análogos & derivados , Carcinoma de Células Renais/etiologia , Neoplasias Renais/etiologia , RNA/genética , Adenosina/metabolismo , Biomarcadores Tumorais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Biologia Computacional/métodos , Epigênese Genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Metilação , Prognóstico , Modelos de Riscos Proporcionais , RNA/metabolismo , Transdução de Sinais
16.
Clin Exp Nephrol ; 25(6): 674-682, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33641007

RESUMO

BACKGROUND: The data regarding oncological outcome in advanced renal cell carcinoma (RCC) arising in end-stage renal disease (ESRD) are limited. METHODS: Patients diagnosed with advanced RCC on maintenance dialysis therapy (ESRD-RCC) and treated with tyrosine kinase inhibitors (TKIs) were retrospectively evaluated. Progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) after initiation of first-line TKI therapy in ESRD-RCC patients were compared to those in RCC arising in the general population (sporadic RCC). RESULTS: A total of 36 and 240 patients were diagnosed with advanced ESRD-RCC and sporadic RCC, respectively. PFS and OS were significantly shorter in patients with ESRD-RCC than in those with sporadic RCC (p = 0.0004 and p = 0.0045). After adjusting for histopathological type, MSKCC risk and liver metastasis status, ESRD status (ESRD-RCC vs. sporadic RCC) was not an independent risk factor for PFS or OS (both, p > 0.05). The ORR tended to be lower in patients with ESRD-RCC than in those with sporadic RCC (11% vs. 28%, p = 0.0833). In 34 patients with ESRD-RCC treated with sorafenib, longer duration of dialysis was an independent prognostic factor for shorter OS (hazard ratio 3.21, p = 0.0370). CONCLUSIONS: Outcome of advanced ESRD-RCC was poorer than that of sporadic RCC, but this finding was affected by other prognostic factors. Nevertheless, the study suggested that advanced ESRD-RCC was not an indolent disease. Additionally, patients with a longer duration of dialysis therapy might require careful monitoring.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Falência Renal Crônica/complicações , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Bases de Dados Factuais , Duração da Terapia , Feminino , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Neoplasias Renais/etiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Diálise Renal , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo
17.
Sci Signal ; 14(664)2021 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402335

RESUMO

Understanding the mechanisms of the Warburg shift to aerobic glycolysis is critical to defining the metabolic basis of cancer. Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an aggressive cancer characterized by biallelic inactivation of the gene encoding the Krebs cycle enzyme fumarate hydratase, an early shift to aerobic glycolysis, and rapid metastasis. We observed impairment of the mitochondrial respiratory chain in tumors from patients with HLRCC. Biochemical and transcriptomic analyses revealed that respiratory chain dysfunction in the tumors was due to loss of expression of mitochondrial DNA (mtDNA)-encoded subunits of respiratory chain complexes, caused by a marked decrease in mtDNA content and increased mtDNA mutations. We demonstrated that accumulation of fumarate in HLRCC tumors inactivated the core factors responsible for replication and proofreading of mtDNA, leading to loss of respiratory chain components, thereby promoting the shift to aerobic glycolysis and disease progression in this prototypic model of glucose-dependent human cancer.


Assuntos
Carcinoma de Células Renais/genética , Ciclo do Ácido Cítrico , Dano ao DNA , DNA Mitocondrial/metabolismo , Fumarato Hidratase/genética , Neoplasias Renais/genética , Leiomiomatose/enzimologia , Síndromes Neoplásicas Hereditárias/enzimologia , Neoplasias Cutâneas/enzimologia , Neoplasias Uterinas/enzimologia , Adulto , Idoso , Carcinoma de Células Renais/etiologia , Carcinoma de Células Renais/metabolismo , Reparo do DNA , Replicação do DNA , Feminino , Fumarato Hidratase/deficiência , Perfilação da Expressão Gênica , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/metabolismo , Leiomiomatose/complicações , Masculino , Pessoa de Meia-Idade , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mutação , Síndromes Neoplásicas Hereditárias/complicações , Neoplasias Cutâneas/complicações , Neoplasias Uterinas/complicações , Adulto Jovem
18.
Eur Urol ; 79(1): 133-140, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950296

RESUMO

BACKGROUND: Despite being the most frequent renal fusion anomaly, tumors arising from horseshoe kidneys (HSKs) are extremely rare and management guidance is lacking. OBJECTIVE: To evaluate the perioperative, oncological, and functional outcomes of surgically treated HSK tumors. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, multicenter cohort study of 43 HSK tumors in 40 patients was conducted, and technical description of the surgical approach has been provided. SURGICAL PROCEDURE: Surgical resection of renal tumors arising from HSKs was performed either via open surgery or via minimally invasive surgery (MIS). MEASUREMENTS: We analyzed patient and tumor characteristics as well as surgical technique, and functional and oncological outcomes. RESULTS AND LIMITATIONS: Eight patients were treated by MIS and 32 by open surgery. One patient (2.5%) experienced an intraoperative complication and 13 patients (32.5%) experienced postoperative complications, of which three (7.5%) were Clavien-Dindo ≥3 complications. Surgical margins were positive in two tumors (4.7%). The most frequent histology was clear-cell renal cell carcinoma (46.5%). The median follow-up was 51 (interquartile range [IQR] 17-73) mo. The 5-yr overall, cancer-specific, and recurrence-free survival rates were 81.2%, 86.8%, and 83.1%, respectively. The percent decreases in estimated glomerular filtration rate at discharge and the last follow-up were 15% (IQR 4-26%) and 17% (IQR 1-31%), respectively. Limitations include the cohort's retrospective nature, heterogeneity, and small sample size. CONCLUSIONS: Surgical management of tumors in HSKs can be approached via both open surgery and MIS, with maximal preservation of functional renal parenchyma. In this cohort, rates of complications, positive surgical margins, and renal functional decrease were acceptable, considering the anatomical complexity of these kidneys and tumors. These tumors display great variation in histological subtypes. Meticulous presurgical planning, taking advantage of advanced imaging techniques, can aid in achieving good outcomes. PATIENT SUMMARY: We evaluated the surgical management of renal tumors in horseshoe kidneys, which are very rare. Although these procedures are highly complex, outcomes are acceptable. Modern imaging techniques are often required in presurgical planning.


Assuntos
Rim Fundido/complicações , Neoplasias Renais/etiologia , Neoplasias Renais/cirurgia , Idoso , Estudos de Coortes , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
19.
J Pediatr Hematol Oncol ; 43(2): e198-e202, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31815888

RESUMO

Constitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer predisposition syndrome results from biallelic germline mutations affecting the key DNA mismatch repair gene: MLH1, MSH2, MSH6, or PMS2. CMMRD is associated with a high risk of developing early onset of central nervous system tumors, hematologic, and intestinal tract tumors. Clinical manifestations, genetic screening, and cancer prevention strategies are limited. In this report we present a patient with metachronous Wilms tumor, glioblastoma, and acute T-cell lymphoblastic leukemia. He had cutaneous features of neurofibromatosis type 1 (NF1). Molecular testing revealed a novel homozygous mutation in MSH6 (c.2590G>T; p.G864*) that has not been reported previously. CMMRD should be considered in patients with cutaneous features similar to NF1 if tumor is found other than expected tumors in NF, early onset cancer, and strong family history of cancer.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Colorretais/complicações , Proteínas de Ligação a DNA/genética , Glioblastoma/patologia , Leucemia de Células T/patologia , Mutação , Segunda Neoplasia Primária/patologia , Síndromes Neoplásicas Hereditárias/complicações , Tumor de Wilms/patologia , Neoplasias Encefálicas/genética , Pré-Escolar , Neoplasias Colorretais/genética , Evolução Fatal , Glioblastoma/etiologia , Homozigoto , Humanos , Neoplasias Renais/etiologia , Neoplasias Renais/patologia , Leucemia de Células T/etiologia , Masculino , Segunda Neoplasia Primária/etiologia , Síndromes Neoplásicas Hereditárias/genética , Tumor de Wilms/etiologia
20.
Nutr Cancer ; 73(2): 239-245, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32238007

RESUMO

Background: Epidemiological studies have demonstrated separately that patients with kidney stone may have higher dietary intake of zinc and higher risk of developing kidney cancer. We prospectively assessed the associations of dietary zinc and other trace elements with kidney cancer risk for the first time.Methods: We used data from the prospective Singapore Chinese Health Study that recruited 63,257 adult Chinese residing in Singapore between 1993 and 1998. A validated food frequency questionnaire and the Singapore Food Composition Database was used to compute the values of intake for zinc, copper and manganese. We identified incident cancer cases via linkage with nationwide cancer registry, and used Cox proportional hazard models to compute hazard ratio (HR) and 95% confidence interval (CI) for the association with kidney cancer risk.Results: There were 229 incident kidney cancer cases after median follow-up of 20.1 years. Dietary zinc intake was positively associated with higher kidney cancer risk; the HR comparing the extreme quartiles of zinc intake was 1.74 (95% CI: 1.02-2.97; P-trend = 0.033). Conversely, intakes of copper and manganese were not associated with kidney cancer risk.Conclusions: The positive association between dietary zinc and risk of kidney cancer suggests that zinc may be implicated in renal carcinogenesis.


Assuntos
Neoplasias Renais , Oligoelementos , Adulto , China/epidemiologia , Ingestão de Alimentos , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/etiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Singapura/epidemiologia
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