Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Coexistence of renal cell carcinoma and renal artery disease is an unusual and challenging problem. From 1969 to 1991, 34 patients presented with localized renal cell carcinoma and renal artery disease affecting all of the functioning renal parenchyma. These patients represented 4 categories: 1) a solitary kidney with renal cell carcinoma and renal artery disease (5), 2) bilateral renal cell carcinoma and coexistent renal artery disease (5), 3) unilateral renal cell carcinoma and contralateral renal artery disease (13), and 4) unilateral renal cell carcinoma and bilateral renal artery disease (11). Atherosclerosis was the most common cause of renal artery disease (30), followed by medial fibroplasia (2), renal artery aneurysm (1) and arteriovenous malformation (1). A total of 23 patients (68%) presented with azotemia (serum creatinine 1.5 mg./dl. or more) and 11 (32%) presented with hypertension. All patients underwent complete surgical excision of renal cell carcinoma. A nephron sparing operation was performed preferentially (30 patients) and bilateral renal cancer operations were staged. Eight patients underwent simultaneous partial (6) or radical (2) nephrectomy and surgical renal revascularization. There were no operative deaths. Postoperatively, preservation of renal function was achieved in 33 patients and 1 required chronic dialysis. At mean followup of 47 months 23 patients (68%) were alive with no evidence of malignancy and 2 were alive with recurrent renal cell carcinoma. Three patients died of metastatic renal cell carcinoma, while 6 died of unrelated causes. All of the latter 6 patients were free of renal cell carcinoma at death. Nephron sparing surgery combined occasionally with renal arterial reconstruction can yield gratifying results in this complex patient population.
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PMID:Management of renal cell carcinoma with coexistent renal artery disease. 834 89

Sorafenib is a small molecule inhibitor of several kinases involved in tumour proliferation and tumour angiogenesis including Raf, VEGFR and platelet derived growth factor receptor. In vivo Raf kinase inhibition has been observed in pharmacodynamic studies. Sorafenib is one of several VEGF-targeting compounds with recently demonstrated substantial anti-tumour effects in metastatic renal cell carcinoma. Delay in time to disease progression has been demonstrated in cytokine-refractory metastatic renal cell carcinoma, and further investigation is ongoing in a wide variety of tumour types. Sorafenib is well tolerated, with common toxicities including rash, diarrhoea, hand-foot skin reaction, fatigue and hypertension, when administered as the standard dose of 400 mg b.i.d.
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PMID:Sorafenib. 1650 17

An 80-year-old man presented with a localized tumor of the right occipital scalp. The tumor was a 1-cm, bright red-purple, ulcerated, and crusted exophytic nodule on a smooth base (Figure 1). The lesion had grown asymptomatically over 18 months except for profuse bleeding induced by minimal trauma. It was extirpated with the clinical diagnosis of pyogenic granuloma vs. renal metastasis to the scalp. The patient's medical history included a transurethral prostatic resection 3 years earlier and, 1 year later, a right nephrectomy for a 2-kg kidney tumor verbally reported as "benign." The patient also had a 2-year history of untreated high blood pressure. Histopathologically, the excised tissue was an exo-endophytic nodule of a solid form composed of pleomorphic neoplastic cells with abundant clear cytoplasm, surrounded by fibrous collagen septae, blood vessel proliferation, and areas of hemorrhage (Figures 2 and 3). The histopathologic diagnosis of metastatic renal cell carcinoma was supported by immunohistochemistry with positive epithelial membrane antigen staining (Figure 4). Cytokeratins 7 and 20 were nonreactive. Laboratory studies revealed hematuria and elevated creatinine and urea nitrogen levels, but no malignant cells were observed in five urinary cytologies. Renal ultrasound showed the presence of two simple cysts in the left kidney and data compatible with chronic inflammatory disease.
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PMID:Scalp metastases of a renal cell carcinoma. 1668 87

In the era before cytokine therapy, controversy existed about the need for cytoreductive nephrectomy in treating patients with metastatic renal cell carcinoma. In 1978, Dekernion showed that nephrectomy alone had no effect on survival. During this period, removal of the malignant kidney was confined to palliative therapy in some settings of metastatic RCC, such as pain related to the kidney mass, intractable hematuria, erythrocytosis, uncontrolled hypertension, or poorly controlled hypercalcemia. When interleukin-2 was approved by the Food and Drug Administration in 1992, the role of nephrectomy was reexamined. After a decade of controversy, two randomized controlled studies established that cytoreductive surgery has a role in properly selected patients and offers a survival advantage when done before cytokine therapy. Unfortunately, the mechanisms underlying this benefit remain poorly understood. Immunotherapy may work best when there is a small volume of cancer present, and removing a large primary tumor may prevent the seeding of additional metastases. Data have also suggested that primary tumors were capable of producing immunosuppressive compounds that might decrease the efficacy of immunotherapy. Another hypothesis suggested that removing the kidney altered the acid/base status of the patient to such an extent that the growth of the tumor was hindered. With the emergence in 2006 of two targeted agents for advanced renal cell carcinoma, the role of cytoreductive nephrectomy has re-emerged as a source of controversy. Although evidence-based medical practice suggests a role for nephrectomy before the use of targeted agents, the arguments for and against this practice will be weighed.
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PMID:Cytoreductive nephrectomy for metastatic renal cell carcinoma: is it still imperative in the era of targeted therapy? 1725 95

Until 2006, immunotherapy (interferon-alpha or interleukin 2) was the standard medical treatment for metastatic renal cell carcinoma (RCC), and its results were disappointing: despite a few cases of complete response with prolonged survival, median survival was one year. Better understanding of the molecular mechanisms of tumor angiogenesis, especially in clear cell carcinoma, has led to the development of multiple targeted therapies to inhibit key effectors: vascular endothelial growth factor (VEGF), VEGF receptor, and mTOR (target of rapamycin). Two inhibitors targeting several protein kinases, including the VEGF receptor, have increased progression-free survival in patients with metastatic RCC and are now commercially available: sunitinib (Sutent) as first-line treatment and sorafenib (Nexavar) as second-line treatment. These targeted therapies will certainly affect overall survival, but it is too early for any firm conclusions. Their side-effects, usually low or moderate, include asthenia, anorexia, diarrhea, hand-and-foot syndrome and hypertension. Optimal management is required to ensure prolonged exposure. Other drugs have been effective: bevacizumab (Avastin), a monoclonal antibody inhibiting VEGF, increases progression-free survival as second-line treatment, and temsirolimus (Torisel), an mTOR protein kinase inhibitor, increases overall survival in the population of patients with poor prognosis. These targeted drugs will serve as the basis for development of future therapeutic strategies.
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PMID:[Renal cell carcinoma and antiangiogenic therapies]. 1803 17

Sunitinib-associated hematologic adverse events are well known and include leukopenia, neutropenia, thrombocytopenia, anemia, and lymphopenia. Herein, we report the case of a patient with metastatic renal cell carcinoma who was treated with sunitinib and developed severe hemolysis without hypertension or reversible posterior leukoencephalopathy. Prompt discontinuation of the agent resulted in resolution of this complication.
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PMID:Sunitinib-induced acute hemolysis without hypertension: a case report. 1882 36

We present a case series of seven patients with metastatic renal cell carcinoma treated with bevacizumab (10 mg/kg) in combination with sunitinib 25-50 mg as salvage therapy after disease progression under sunitinib monotherapy. Two patients had a partial response, four had stable disease, and one patient had disease progression. After a median follow-up of 17.2 mo, median progression-free survival and overall survival were 8.5 and 15.1 mo, respectively. Two patients experienced exacerbation of their preexisting hypertension; there were no grade 4 toxicities. The bevacizumab-sunitinib combination in sunitinib-refractory patients seems active and has a tolerable toxicity profile.
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PMID:Salvage therapy with bevacizumab-sunitinib combination after failure of sunitinib alone for metastatic renal cell carcinoma: a case series. 1915 88

Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor that has demonstrated substantial antitumour activity in patients with metastatic renal cell carcinoma. The more common grade 3 or 4 adverse effects of sunitinib include hypertension, fatigue, hand-foot syndrome, elevated lipase and lymphopenia. We report the case of a 69-year-old patient with metastatic renal clear-cell carcinoma, treated with nephrectomy and three lines of therapy (interleukin-2 plus interferon-alpha2a, vinorelbine plus gemcitabine, and capecitabine), who started a fourth-line therapy with oral sunitinib because of disease progression. At the end of his fifth cycle of sunitinib therapy, the patient complained of the development of abnormally large mammary glands associated with pain and peri-areolar erythema. After 2 weeks' off therapy, a partial reduction in mammary gland enlargement, local pain and erythema was observed. However, re-initiation of sunitinib treatment was followed by bilateral breast enlargement again. The mechanism by which sunitinib induces gynaecomastia is thought to be associated with an unknown direct action on breast hormonal receptors. To the best of our knowledge, this is the first report of an association between sunitinib and gynaecomastia.
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PMID:Onset of male gynaecomastia in a patient treated with sunitinib for metastatic renal cell carcinoma. 1949 66

Sorafenib(Nexavar)is a multikinase inhibitor, with disruptive activity at intracellular C-RAF, B-RAF and mutant BRAF receptors, and extracellular C-KIT, FLT-3, VEGFR-2, VEGFR-3 and PDGFRb receptors. In the phase III study, as compared with placebo, treatment with sorafenib significantly prolonged progression free survival(PFS)in patients with advanced renal cell carcinoma in whom previous therapy has failed. Diarrhea, rash, fatigue, hand-foot skin reactions, and hypertension were the most common adverse events associated with sorafenib. As sorafenib was associated with similar rates of clinically manageable side effects in elderly patients as compared to younger patients, response rates to sorafenib in elderly patients were comparable to those of younger patients. Sorafenib was approved multinationally for the treatment of advanced and/or metastatic renal cell carcinoma. Sorafenib and sunitinib are reference standards of care for the treatment of advanced renal cell carcinoma and are recommended by current clinical guidelines. For the future, research of biomarker, adverse drug reaction, and combined regimens are needed to maximize the effects of molecular-targeted drugs.
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PMID:[Sorafenib(Nexavar)]. 1954 31

Metastatic renal cell carcinoma is notoriously resistant to chemotherapy and radiotherapy. Immunotherapy with interferon alpha is widely used for the disease, but its treatment effects are poor. A 69-year-old Japanese women presented with gross hematuria. Imaging studies revealed a left renal tumor, 12 cm in diameter, and multiple pulmonary and hepatic lesions. No abnormal laboratory data were observed other than anemia with Hb 9.2 g/dl. Performance status was 0. She underwent radial left nepherectomy. Pathological examination showed clear cell renal cell carcinoma with moderate histological differentiation (grade 2) and microscopic vessel invasion; pT3aN0M1 (Pul, Hep). Memorial Sloon-Kettering Cancer Center classification was an intermediate risk due to anemia. She received interferon alpha, 5 million IU three times per week, postoperatively. In three months, hepatic lesions rapidly progressed although there was no interval change of pulmonary lesions. Then, the patient received interferon alpha at the same dose as described above and half-dose sorafenib, 400 mg per day. Grade 2 hypertension was under control by calcium channel blocker and the hand-foot syndrome was not obvious. No other grade 3/4 drug-related adverse events were observed. In one month after combination therapy, not only pulmonary lesions but also hepatic lesions were smaller. She has received this combination therapy with stable disease for six months. Performance status was 1 with grade 1 fatigue. The doses of this regimen may be tolerable, and might be an available treatment option for interferon alpha-resistant advanced renal cancer.
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PMID:[Interferon alpha and half-dose sorafenib is an effective treatment modality for interferon alpha-resistant metastatic renal cell carcinoma: a case report]. 1958 63


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