Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although renal cell carcinoma accounts for only 3% of adult malignancies, it has been increasing in incidence by 2-4% per year since the 1970's. Cigarette smoking, obesity and end-stage renal disease are important risk factors. Genetic syndromes such as von Hippel-Lindau disease are also associated with an increased incidence of renal cell carcinoma. Localized disease should be treated with surgical resection. However, approximately 30% of patients present with metastatic disease. Complete resection of metastases can result in long-term survival in some individuals. Removal of the primary renal tumor in patients with unresectable disseminated disease has also been shown to improve survival in selected good performance status patients receiving systemic immunotherapy. While chemotherapy has been relatively ineffective in the treatment of renal cell carcinoma, biologic therapy with interleukin-2 or interferon does lead to responses in a minority of patients, with occasional long-term survivors. Recently, promising results have been reported with allogeneic stem cell transplantation using a non-myeloablative conditioning regimen. However, therapy for metastatic renal cell carcinoma remains inadequate. Ongoing trials with novel approaches such as anti-angiogenesis agents, cyclin-dependent kinase inhibitors, and tumor vaccines will hopefully lead to improved outcomes in this disease.
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PMID:Renal cell carcinoma: current status and future directions. 1260 28

Despite a rapid improvement in dialysis technology during the last 20 years, the mortality rate is still very high in patients with end-stage renal disease (ESRD), and the death rate is comparable with that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. The high cardiovascular mortality rate suggests that ESRD patients are subjected to a process of accelerated atherogenesis. Because factors proven to contribute to atherosclerosis in the general population, such as dyslipidemia, smoking, diabetes mellitus, and hypertension are highly prevalent in ESRD patients, it is reasonable to assume that such risk factors also apply to these patients. However, as it has been shown that the high cardiovascular risk in ESRD is incompletely accounted for by traditional risk factors, it may be speculated that nontraditional risk factors, seemingly more difficult to reconcile, also contribute. Among several putative nontraditional risk factors, chronic inflammation has attracted a lot of interest recently because it seems to be associated to both increased vascular oxidative stress and endothelial dysfunction, both of which are important predictors of cardiovascular events in nonrenal patient groups.
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PMID:Interactions between inflammation, oxidative stress, and endothelial dysfunction in end-stage renal disease. 1267 39

Despite rapid improvement in dialysis technology during the last 20 years the mortality rate is still very high in patients with end-stage renal disease (ESRD), and is in fact comparable to that of many cancer patients with metastases. The main cause of mortality in ESRD is cardiovascular disease (CVD), and cardiac mortality for dialysis patients aged 45 years or younger is more than 100-fold greater than in the general population. Recent evidence suggests that the high cardiovascular mortality rate in this patient population is associated with extensive vascular and valvular calcification. Although hyperphosphatemia may be the major cause of vascular calcification in this patient group it has been suggested that chronic inflammation also contributes to this process. Indeed, recent evidence suggests that inflammatory mediators, such as pro-inflammatory cytokines and adipocytokines, may promote vascular calcification in vitro. Moreover, a2-Heremans Schmid glycoprotein (fetuin), an intrinsic inhibitor of the calcification process, is down-regulated during chronic inflammation. Lower levels of fetuin have recently been found to predict mortality in ESRD. Thus, further studies are needed to elucidate the roles of calcium-free phosphate binders as well as focused anti-inflammatory treatment strategies in the prevention of vascular and valvular calcification in ESRD.
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PMID:[Why do patients with kidney diseases end up with a heart of stone? Disturbances in calcium-phosphate balance and chronic inflammation important causes]. 1471 5

The incidence of renal tubule carcinogenesis in male and female rats or mice with 69 chemicals from the 513 bioassays conducted to date by the NCI/NTP has been collated, the chemicals categorized, and the relationship between carcinogenesis and renal tubule hyperplasia and exacerbation of the spontaneous, age-related rodent disease chronic progressive nephropathy (CPN) examined. Where information on mechanism or mode of action exists, the chemicals have been categorized based on their ability to directly or indirectly interact with renal DNA, or on their activity via epigenetic pathways involving either direct or indirect cytotoxicity with regenerative hyperplasia, or exacerbation of CPN. Nine chemicals were identified as directly interacting with DNA, with six of these producing renal tubule tumors at high incidence in rats of both sexes, and in some cases also in mice. Ochratoxin A was the most potent compound in this group, producing a high tumor incidence at very low doses, often with metastasis. Three chemicals were discussed in the context of indirect DNA damage mediated by an oxidative free radical mechanism, one of these being from the NTP database. A third category included four chemicals that had the potential to cause DNA damage following conjugation with glutathione and subsequent enzymatic activation to a reactive species, usually a thiol-containing entity. Two chemicals were allocated into the category involving a direct cytotoxic action on the renal tubule followed by sustained compensatory cell proliferation, while nine were included in a group where the cell loss and sustained increase in renal tubule cell turnover were dependent on lysosomal accumulation of the male rat-specific protein, alpha2mu-globulin. In a sixth category, morphologic evidence on two chemicals indicated that the renal tumors were a consequence of exacerbated CPN. For the remaining chemicals, there were no pertinent data enabling assignment to a mechanistic category. Accordingly, these chemicals, acting through an as yet unknown mechanism, were grouped as either being associated with an enhancement of CPN (category 7, 16 chemicals), or not associated with enhanced CPN (category 8, 4 chemicals). A ninth category dealt with 11 chemicals that were regarded as producing increases in renal tubule tumors that did not reach statistical significance. A 10th category discussed 6 chemicals that induced renal tumors in mice but not in rats, plus 8 chemicals that produced a low incidence of renal tubule tumors in mice that did not reach statistical significance. As more mechanistic data are generated, some chemicals will inevitably be placed in different groups, particularly those from categories 7 and 8. A large number of chemicals in the series exacerbated CPN, but those in category 7 especially may be candidates for inclusion in category 6 when further information is gleaned from the relevant NTP studies. Also, new data on specific chemicals will probably expand category 5 as cytotoxicity and cell regeneration are identified as obligatory steps in renal carcinogenesis in more cases. Additional confirmatory outcomes arising from this review are that metastases from renal tubule tumors, while encountered with chemicals causing DNA damage, are rare with those acting through an epigenetic pathway, with the exception being fumonisin B1; that male rats and mice are generally more susceptible than female rats and mice to chemical induction of renal tubule tumors; and that a background of atypical tubule hyperplasia is a useful indicator reflecting a chemically associated renal tubule tumor response. With respect to renal tubule tumors and human risk assessment, chemicals in categories 1 and 2, and possibly 3, would currently be judged by linear default methods; chemicals in category 4 (and probably some in category 3) as exhibiting a threshold of activity warranting the benchmark approach; and those in categories 5 and 6 as representing mechanisms that have no relevance for extrapolation to humans.
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PMID:Chemically induced renal tubule tumors in the laboratory rat and mouse: review of the NCI/NTP database and categorization of renal carcinogens based on mechanistic information. 1523 88

Despite rapid improvements in dialysis technology during the last 20 years, the mortality rate in end-stage renal disease (ESRD) patients treated with dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with earlier stages of chronic kidney disease as compared to the general population. Although traditional risk factors are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause malnutrition and progressive atherosclerotic CVD by several pathogenetic mechanisms. Available data suggest that pro-inflammatory cytokines play a central role in the genesis of both malnutrition and CVD in ESRD. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also be a direct cause of acute vascular injury by several pathogenetic mechanisms. The cause(s) of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. Thus, it could be speculated that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) would improve survival in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status as well as outcome in this patient group are warranted.
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PMID:Systemic inflammation in dialysis patients with end-stage renal disease: causes and consequences. 1546 2

The finding of a polyuropolydispsic syndrome should prompt a complete biological investigation of its etiology. If polyuria can be a minor sign as in psychiatric disorder, it can also be the first manifestation of diabetes mellitus but also central diabetes insipidus, the latter linked to cerebral tumors, metastases in the hypothalamus, granulomatous disease, but also nephrogenic diabetes insipidus such as chronic renal disease or autoimmune disease. Intracellular dehydration is the major risk in case of a polyuropolydipsic syndrome. Prognosis depends on the capacity to maintain water balance through an intact thirst mechanism. After a brief review of the majority of causes of diabetes insipidus, we propose a diagnosis algorithm to easily make the diagnosis.
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PMID:[How to explore... insipidus polyuropolydipsia syndrome]. 1564 41

Despite marked improvements in dialysis technology during the last 20 years, the age-adjusted mortality rate in end-stage renal disease (ESRD) patients treated by dialysis is still unacceptably high and comparable to that of many cancer patients with metastases. The main cause of the increased mortality in ESRD patients is cardiovascular disease (CVD), which is twice as common and advances at twice the rate already in patients with early stages of chronic kidney disease as compared to the general population. Although traditional risk factors for CVD are common in dialysis patients, they can only in part explain the very high prevalence of CVD in this patient group. Recent evidence demonstrates that chronic inflammation, a non-traditional risk factor which is a commonly observed in dialysis patients, may cause progressive atherosclerotic CVD and malnutrition, itself an important risk factor for the development of CVD, by several pathogenetic mechanisms. The causes of inflammation in dialysis are multifactorial and include both dialysis-related and unrelated factors. While the long-term effects of chronic inflammation may be most important in the pathogenesis of CVD, the acute-phase reaction may also cause vascular damage by several pathogenic mechanisms. Indeed, it seems logical to speculate that suppression of the vicious cycle of malnutrition, inflammation, and atherosclerosis (MIA syndrome) in ESRD would improve survival and decrease co-morbidity in dialysis patients. As there are currently no established guidelines for the treatment of chronic inflammation in ESRD patients, more studies on the long-term effects of various anti-inflammatory treatment strategies on the nutritional and cardiovascular status, as well as outcome in this patient group, are clearly warranted and will be helpful in identifying precisely which pathways are most involved in the pathogenic process.
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PMID:Chronic systemic inflammation in dialysis patients: an update on causes and consequences. 1567 81

Parathyroid carcinoma is a rare tumor that is responsible for <1% of cases of hyperparathyroidism in most parts of the world. An increased incidence of this tumor has been reported in patients with the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, but the etiology of most other cases is unknown. Parathyroid carcinomas tend to occur a decade earlier than adenomas, and the sex ratio approaches unity in contrast to the female preponderance of adenomas. Most patients with carcinomas present with marked hypercalcemia and are more likely to have associated bone and renal disease than those with adenomas. Although fibrosis and mitotic activity are common in carcinomas, these features are not specific for malignancy. The diagnosis of carcinoma should be restricted to those tumors that show invasion of blood vessels, perineural spaces, soft tissues, thyroid gland, or other adjacent structures or to tumors with documented metastases. Mutations of the HRPT2 gene (1q21-q32), which are responsible for the HPT-JT syndrome, have been implicated in the development of a high proportion of parathyroid carcinomas. A subset of patients with mutation-positive carcinomas have germline mutations of the HRPT2 gene. This finding suggests that some patients with apparent sporadic parathyroid carcinomas may have the HPT-JT syndrome or a variant of this syndrome. Because of the high frequency of local recurrence following incomplete excision, an en bloc resection is the preferred surgical approach for treatment of parathyroid carcinomas.
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PMID:Parathyroid carcinoma: an overview. 1573 73

Herein, we review the associations between the kidney, renal cancers, and the eye. Renal cancers have been reported to metastasize to the eye and the orbit. As these tumors can be confused with other amelanotic or vascular tumors, a high index of suspicion is required for early detection and management of the primary tumor. We discuss the physiology of metastases, clinical features and management of metastatic disease. A variety of ocular anomalies have been associated with renal disease. Wilms tumor, a renal tumor of childhood, can present with aniridia, which may be the first clue leading to the diagnosis of the primary tumor. Paraneoplastic syndromes are common manifestations of renal cancers and can present as retinopathies and neuro-ophthalmic disorders. Multiple cancer syndromes involve both the eye and the kidney. For example, the diagnosis of von Hippel retinal tumors can lead to a systemic evaluation and discovery of associated visceral tumors. The prognosis, screening, and counseling of such patients is discussed. Newer systemic treatments available for renal tumors, such as interferon alfa, may lead to ocular side effects including retinopathy. These patients require periodic ophthalmic examinations. This review demonstrates the essential role of the ophthalmologist, for early diagnosis and treatment that can help reduce the morbidity and mortality associated with kidney tumors and renal-associated disease.
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PMID:The kidney, cancer, and the eye: current concepts. 1626 67

Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage renal disease (ESRD), particularly with acquired cystic disease of the kidney (ACDK), have been reported to be papillary renal cell carcinoma (RCC). Our initial experience with tumors in such a setting indicated that many tumors were histologically difficult to classify into the known subtypes of RCC or had features that were different from those in sporadically occurring RCCs. In this study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because tumors were detected in them, we found two major groups of RCC. Overall, there were 261 grossly identified tumors in these kidneys, and many additional tumors were observed on microscopic evaluation in some. Of the two major groups of RCCs, one consisted of tumors similar to those seen in sporadic settings (ie, clear-cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12 (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group consisted of two subtypes of RCC that appear quite unique to ESRD. The more common tumor that we have designated as "acquired cystic disease-associated RCC" was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the most common tumor type among the smaller nondominant masses, as well. It was characterized by a typical microcystic architecture, eosinophilic cytoplasm with Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate crystals. Additionally, these tumors frequently, but usually focally, exhibited papillary architecture, and clear cytoplasm. These tumors occurred only in kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%) of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These predominantly cystic tumors showed prominent papillary architecture with purely clear-cell cytology. Immunohistochemical studies in tumors with histology similar to the known subtypes of sporadic RCC showed immunoprofiles similar to that reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD had distinctive immunoprofiles supporting their separate morphologic subcategorization. Only the acquired cystic disease-associated RCC showed lymph node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the latter 2 died with widespread metastatic disease within 34 months of nephrectomy. Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which resemble the sporadic RCCs. Acquired cystic disease-associated RCC is the commonest tumor subtype in ESRD, and biologically it appears to be more aggressive than the other tumor subtypes in ESRD.
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PMID:Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia. 1643 87


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