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Renal cell carcinoma (RCC), the most common form of kidney cancer, initially has an asymptomatic clinical course; 25-30% of patients present with metastatic disease at time of diagnosis. Worldwide incidence and mortality rates are rising at a rate of approximately 2-3% per decade. Metastatic RCC (mRCC) is one of the most treatment-resistant malignancies; outcomes are generally poor and median survival after diagnosis is less than one year. Surgery and chemotherapy have limited or no effect, leaving mRCC patients underserved in the realm of cancer treatment. As the world's population ages and the prevalence of risk factors (obesity, hypertension) increases, the burden of mRCC is predicted to increase significantly. With a shift in treatment of mRCC to novel therapies, such as molecularly targeted therapies (MTTs) (e.g., sorafenib and sunitinib), clinicians, payers, and other healthcare decision-makers must re-evaluate the optimal role for new treatments. Timely understanding of the burden of mRCC on individuals and society clearly is needed at this juncture. Using a comprehensive literature review, we assessed the epidemiologic, economic, and health-related quality of life (HRQOL) burdens of mRCC. The annual incidence of mRCC in major European countries, the US, and Japan ranges from 1500 to 8600 cases. However, prevalence data were lacking. The estimated economic burden of mRCC is large; $107-$556 million (2006 USD) in the US and $446 million-$1.6 billion (2006 USD) collectively in select countries worldwide. MTTs have potential to reduce the burden of mRCC and provide substantial value beyond their clinical effectiveness.
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PMID:Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. 1831 24

Retinitis pigmentosa represents a class of disorders that exhibit dystrophy of the photoreceptors, pigment epithelium, and often systemic abnormalities, Bardet-Biedl syndrome is a form of retinitis pigmentosa that has characteristic non-ocular findings including polydactyly, obesity, learning difficulties, male hypogonadism, and renal anomalies. Though none of these renal anomalies are neoplastic, there is a 17 fold increased risk for renal cell carcinoma in obligate carriers of Bardet-Biedl syndrome. Herein, we describe a case of metastatic renal cell carcinoma discovered in a patient with Bardet-Biedl syndrome.
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PMID:Asymptomatic renal cell carcinoma as a finding of Bardet Biedl syndrome. 1836 71

Overweight and obesity are connected with increased risk of obesity related co-morbidities, such as T2DM, hypertension, cardiovascular diseases, dyslipidaemia and others, as well as in higher risk of some malignant diseases. In obese population there is 2.5-3.3 fold increased risk of renal cell carcinoma in comparison with non-obese population of similar age. It has been proven in many studies that for severely obese patients there is no other more effective treatment of their obesity and co-morbidities than bariatric. Bariatric surgery decreases mortality risks, treat existing, obesity related co-morbidities, and can act as prevention of onset of new obesity related co-morbidities. Moreover at the end bariatric surgery lowers economic burden of health care systems. Nowadays, bariatric surgery is considered to be standard treatment option and pathway in complex management of morbidly obese patients.
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PMID:[Bariatric surgery and the kidneys]. 1863 Jun 28

In this population-based case-control study with 325 Caucasian renal cell carcinoma (RCC) patients and 335 controls matched to cases by age, gender and county of residence, we evaluated the associations between 13 potential functional polymorphisms in nine major nucleotide excision repair (NER) genes and RCC risk. In individual single nucleotide polymorphism analysis, after adjustment for multiple comparisons, a significantly decreased RCC risk was observed for the heterozygous genotype of XPD Asp312Asn [odds ratio (OR) = 0.62; 95% confidence interval (CI): 0.43-0.90] and for the heterozygous and homozygous variant genotypes combined in a dominant model (OR = 0.64; 95% CI: 0.46-0.89). The heterozygous AG genotype of XPA 5'untranslated region was at 1.78-fold increased risk (95% CI: 1.18-2.69) and the risk reached 2.43-fold (95% CI: 1.57-3.75) for the homozygous variant GG genotype; the risk was significant both in the dominant model and in the recessive model. In joint analysis, compared with individuals with fewer than five adverse alleles, individuals with five (OR = 1.17; 95% CI: 0.71-1.93), six (OR = 1.66; 95% CI: 1.03-2.67), seven or more (OR = 1.85; 95% CI: 1.16-2.95) exhibited a progressively increased risk of RCC (P for trend = 0.004). Further, there were significant interactions between NER pathway genes and sex, hypertension and obesity (all P for interaction <0.05). Our results strongly support that common sequence variants of the NER pathway genes predispose susceptible individuals to increased risk of RCC and that the association may be modified by gender, history of hypertension and obesity. These results need to be replicated in larger studies.
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PMID:Case-control analysis of nucleotide excision repair pathway and the risk of renal cell carcinoma. 1871 Nov 49

An increased risk of renal cell carcinoma (RCC) has been linked with obesity. However, there is limited information about the contribution of dietary fat and fat-related food groups to RCC risk. A population-based case-control study of 406 cases and 2434 controls aged 40-85 years was conducted in Iowa (1986-89). For 323 cases and 1820 controls from the present study, information on dietary intake from foods high in fat nutrients and other lifestyle factors was obtained using a mailed questionnaire. Cancer risks were estimated by OR and 95 % CI, adjusting for age, sex, smoking, obesity, hypertension, physical activity, alcohol and vegetable intake and tea and coffee consumption. In all nutrient analyses, energy density estimates were used. Dietary nutrient intake of animal fat, saturated fat, oleic acid and cholesterol was associated with an elevated risk of RCC (OR = 1.9, 95 % CI 1.3, 2.9, P trend < 0.001; OR = 2.6, 95 % CI 1.6, 4.0, P trend < 0.001; OR = 1.9, 95 % CI 1.2, 2.9, P trend = 0.01; OR = 1.9, 95 % CI 1.3, 2.8, P trend = 0.006, respectively, for the top quartile compared with the bottom quartile of intake). Increased risks were also associated with high-fat spreads, red and cured meats and dairy products (OR = 2.0, 95 % CI 1.4, 3.0, P trend = 0.001; OR = 1.7, 95 % CI 1.0, 2.2, P trend = 0.01; OR = 1.8, 95 % CI 1.2, 2.7, P trend = 0.02; OR = 1.6, 95 % CI 1.1, 2.3, P trend = 0.02, respectively). In both the food groups and nutrients, there was a significant dose-response with increased intake. Our data also indicated that the association of RCC with high-fat spreads may be stronger among individuals with hypertension. These findings deserve further investigation in prospective studies.
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PMID:Dietary fat and risk of renal cell carcinoma in the USA: a case-control study. 1878 76

Obesity is considered one of the risk factors for many cancers. Serum leptin levels are often elevated in obese people. Leptin has been reported to act as a mitogenic agent and promote renal cancer cell proliferation, whereas the detailed mechanisms still remain to be elucidated. The purpose of this study is to investigate the proliferation and mobility effects in leptin-treated Caki-2 renal cell carcinoma and analyze the alterations of leptin-inducible STAT3 pathways and mitogenic signaling ERK pathways. Our results indicate the constitutive expression of leptin receptor could not be upregulated upon the stimulation of leptin in Caki-2 cells. Leptin increases the proliferation and mobility capabilities of Caki-2 cells via upregulating the expression of both phosphor-ERK and phosphor-STAT3 and these two pathways could be partially abolished by inhibition of the activation of JAK-STAT3 and completely abrogated by inhibition of ERK1/2 pathways. Our results also suggest that mitogenic actions of leptin are not the consequence of altered its receptor expression; whereas the cellular proliferation appears to be working through the cross-talking of JAK-STAT3 and ERK1/2 pathways in renal cell carcinoma caki-2 cells.
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PMID:Concomitant activation of the JAK/STAT3 and ERK1/2 signaling is involved in leptin-mediated proliferation of renal cell carcinoma Caki-2 cells. 1878

The increasing incidence of renal cell carcinoma over the past 2 decades can be partly explained by the expanding use of abdominal imaging. As a result, the most incident renal cancers today are small, localized, and asymptomatic. However, the well-documented rise in all stages of RCC calls into question the nature of these asymptomatic lesions. The expected "screening effect" of detecting RCC when it is small and localized, with subsequent decreases in disease-specific mortality, has not been observed. Disease-specific mortality is actually rising, especially in African American patients. Effective interventions aimed at reducing obesity, hypertension, and smoking may help in reducing the incidence of RCC in the future.
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PMID:Epidemiology, clinical staging, and presentation of renal cell carcinoma. 1899 12

Some tumors are known to have a definite cause-effect etiology, but renal cell carcinoma (RCC) is not one of them precisely. With regard to RCC we can only try to identify some clinical and occupational factors as well as substances related to tumorigenesis. Smoking, chemical carcinogens like asbestos or organic solvents are some of these factors that increase the risk of the RCC. Viral infections and radiation therapy have also been described as risk factors. Some drugs can increase the incidence of RCC as well as other neoplasms. Of course, genetics plays an outstanding role in the development of some cases of kidney cancer. Chronic renal failure, hypertension, and dialysis need to be considered as special situations. Diet, obesity, lifestyle, and habits can also increase the risk of RCC. The aim of this review is to summarize the well-defined causes of renal cell carcinoma.
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PMID:Epidemiology of kidney cancer. 1900 36

Obesity is considered a strong risk factor for renal cell carcinoma, the most common primary renal malignant neoplasm. An association between renal cell carcinoma and obesity has been reported in numerous trials. Several potential mechanisms may be responsible for the risk of renal cell carcinoma in obese subjects. We report the cases of two patients, submitted to bariatric malabsorbtive surgery, who presented a renal clear cell carcinoma several months after the operation. The diagnosis was made by routine postoperative ultrasound examination and confirmed by computed tomography in both cases. Both were treated surgically. Our approach after diagnosis of cancer consisted in evaluation of the patient's immunological, metabolic and nutritional status to establish whether it was a case of real malnutrition or an oncological risk condition. We judged that restoration of original gastrointestinal continuity was not necessary. In the literature, we found no evidence of an association between a cancer histotype and bariatric surgery. Confirming the association between renal cell carcinoma and morbid obesity, these case reports indicate the importance of imaging control, especially with non-invasive diagnostic studies, in high-risk cancer patients, such as obese patients, to detect lesions incidentally at an early stage. After a thorough review of the literature data, we consider bariatric patients a suitable group to be assessed for an early diagnosis of various types of cancer, detectable at preoperative or postoperative screening. Weight loss and continuous instrumental exams are conditions favourable to an early diagnosis. Guidelines regarding the management of oncological patients with a history of bariatric surgery are indispensable.
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PMID:Role of bariatric surgery in early detection of renal cell carcinoma: report of two cases and review of the literature. 1906 93

A 14 year old Bangladeshi boy presented with obesity, reduced vision, mental retardation, hypogonadism, delayed development and learning difficulty. On examination, he had polydactyly, moon face, bilateral gynaecomastia, small penis and undescended testes. Retinitis pigmentosa was found on fundoscopy. With typical features, he was diagnosed as a case of Laurence-Moon-Bardet-Biedl syndrome. It is a rare autosomal recessive disorder with mutation in 6 loci identified so far. It is commonly found in communities with high inter-family marriage. Clinical features appear early in childhood and diagnosis is usually done by puberty. Prominent features include rod-cone dystrophy leading to blindness, postaxial polydactyly, central obesity, learning disability, hypogonadism in males and renal dysfunction. Relatives with a single affected gene may have obesity, hypertension, diabetes and renal disease. There is increased risk of renal cell carcinoma. There is no definite treatment. Early diagnosis and symptomatic, supportive and rehabilitative measures can reduce the disability. These include dietary modification, oral hypoglycaemic drugs, testosterone supplement etc. Relatives of the patient should be screened for renal abnormality.
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PMID:Laurence Moon Bardet Biedl Syndrome. 1937 20


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