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)

The liver is a common site for metastases from various forms of primary tumors. Colorectal cancer most commonly, but also neuroendocrine tumors, gastrointestinal sarcoma, ocular melanoma and others metastasize to the liver. A complete staging is important before considering treatment options. Surgical resection is the only form of curative treatment for colorectal cancer metastases. Systemic or intraarterial hepatic chemotherapy may be an alternative for patients with unresectable disease. Other promising treatment options such as cryotherapy and radiofrequency ablation are curRently under evaluation. The treatment of metastases from neuroendocrine tumors and other noncolorectal primary malignancies has to be individualized based on the patient's clinical status and the extent of the disease.
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PMID:[Surgical treatment of hepatic metastases]. 1128 91

Progressive growth of unresectable metastatic or primary malignancies confined to the liver is a significant clinical problem. Approximately 25% of patients with colorectal cancer will develop metastatic disease exclusively or largely confined to liver, the vast majority of which are not amenable to surgical resection. Despite aggressive systemic or regional chemotherapy, survival is only 12 to 18 months. More than 80% of patients with ocular melanoma develop liver metastases as the first site of recurrent disease, and death from hepatic disease progression typically occurs 2 to 7 months after diagnosis. In addition, the liver is also the preferred site of metastatic disease for gastrointestinal or pancreatic neuroendocrine tumors. A number of physiological and anatomic features of the liver make it an ideal organ for regionally directed therapy to allow dose intensification to the cancer-burdened area while reducing or eliminating unnecessary systemic toxicity. To that end, complete vascular isolation and perfusion of the liver using a recirculating extracorporeal circuit, also called isolated hepatic perfusion (IHP), has been under clinical evaluation at our institution and others. In this article, we review the current results with IHP and its potential utility in the treatment of patients with unresectable hepatic malignancies.
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PMID:Transarterial perfusion of liver metastases. 1195 Dec 11

Thousands of patients die annually from unresectable metastatic or primary hepatic cancers confined to liver. Isolated hepatic perfusion (IHP) is a regional treatment strategy in which the vascular supply to the liver is isolated and perfused with a therapeutic regimen using an extracorporeal circuit consisting of a reservoir, heat exchanger, and oxygenator. Drug doses that would cause severe toxicities if delivered systemically can be confined to the liver by isolated hepatic perfusion, resulting in the ability to intensify treatment to the cancer-burdened region of the body. Agents and mechanisms commonly used in IHP include melphaIan, hyperthermia, and tumor necrosis factor. IHP appears to be efficacious for patients with advanced disease, as reflected by large tumor size, high number of lesions, or significant overall tumor burden in the liver. In addition, responses are observed for patients whose cancer is refractory to systemic and hepatic arterial infusion chemotherapy. Recent clinical trials have demonstrated that IHP has anti-tumor efficacy against primary hepatic neoplasms and metastases from various primary tumors, such as colorectal carcinoma, ocular melanoma, and neuroendocrine tumors. Current studies demonstrate that combining hepatic arterial infusion with floxuridine after IHP for patients with colorectal cancer metastases is associated with significant and durable response rates. Continued clinical evaluation is warranted for the use of IHP in the treatment of unresectable liver metastases.
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PMID:Isolation perfusion of the liver. 1200 3

Malignant melanoma of the uvea is remarkable for purely haematogenous dissemination and its tendency to metastasise to the liver. Although the liver is involved in up to 95% of patients, 50% of these also develop extrahepatic metastases, most often in the lungs, bone, skin, and brain. The only effective treatments reported to date relied on hepatic arterial chemoembolisation or -perfusion. The objective of this study was to establish a therapy protocol addressing patients with both sole liver involvement and systemic disease. Forty-eight patients with metastatic ocular melanoma received fotemustine 100 mg m(-2) either as 60-min infusion into the hepatic artery or as 15-min infusion via a peripheral vein, depending on the metastatic sites involved, i.e., restriction to the liver or hepatic together with extrahepatic disease. For the first treatment cycle this infusion was repeated after one week. For all cycles, subsequent to a three week resting period, patients received an immunotherapy consisting of subcutaneous interleukin 2 and interferon alpha(2). Although objective responses were more frequent within the cohort receiving intraarterial fotemustine (21.7 vs 8%), this difference did not translate into a significant benefit in overall survival, i.e., 369 and 349 days, respectively. Of note, this overall survival is much longer than that repeatedly reported for stage IV uveal melanoma not treated with fotemustine, suggesting a therapeutic activity of this cytostatic drug even after systemic administration.
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PMID:Treatment of disseminated ocular melanoma with sequential fotemustine, interferon alpha, and interleukin 2. 1237 96

Systemic therapy alone for metastatic melanoma is relatively ineffective, and surgical resection of metastases to a solitary site remains the best single treatment to improve survival. While cytoreductive surgery plus chemotherapy play a significant role in the management of advanced ovarian cancer, the precise role of surgery as an adjunct to systemic therapy for melanoma metastatic to multiple sites is not well defined. We report a patient with ocular melanoma metastatic to liver and pancreas treated by cytoreductive surgery consisting of mesohepatic resection, distal pancreatectomy, and portal node dissection, followed by biochemotherapy with dacarbazine and interferon alpha. The concept of cytoreductive surgery is reviewed, with particular attention to its use in the management of metastatic melanoma. The patient's postoperative course was unremarkable and she remains alive and asymptomatic with no detectable disease at 20 months' follow-up. Cytoreductive surgery as a part of an aggressive multidisciplinary approach may play a role in the treatment of cutaneous and ocular melanoma metastatic to multiple visceral sites. Data from well-designed, innovative clinical trials of cytoreductive surgery and biochemotherapy are required to determine the effectiveness of this multidisciplinary approach.
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PMID:Combined liver and pancreas resection with biochemotherapy for metastatic ocular melanoma. 1248 77

We report on a case of a 70-year-old woman with an ocular melanoma, which was diagnosed and treated 14 years ago. The patient was referred to the hospital with a suspected lymphoma. Cytological examination of bone marrow proved a marked infiltration with melanoma cells. Because detection of isolated tumor cells in the bone marrow of patients with various types of tumors was shown to be of prognostic significance and since current tumor-staging techniques are unable to detect single disseminated tumor cells or small aggregates of tumor cells, which might be the seed for subsequent metastatic relapse, we therefore evaluated the feasibility of immunocytochemical screening of bone marrow aspirates of 36 melanoma patients in different clinical stages using three monoclonal antibodies against melanoma-associated antigens in comparison with 43 non-melanoma control patients. Two of these antibodies (HMB45 and NKI-beteb) are directed against the melanoma antigen gp100/pmel17, whereas the third one (TA99) recognizes gp75/Tyrosinase-related protein 1 (TRP-1). None of the patients demonstrated a macroscopic bone marrow infiltration as was present in our patient with metastatic ocular melanoma. Seven (20.6%) of the 34 eligible melanoma patients presented with cells in the bone marrow positive for one or more of the above-mentioned melanosomal markers. Four of the positive patients were clinically free of tumors by the time of puncture, whereas the remaining 3 patients showed overt metastases in the subcutaneous fat (2 patients) and the brain (1 patient). On the other hand, 20 (66%) of the 29 patients with negative bone marrow findings also presented with clinical advanced disease with overt metastasis in the skin, lymph node, spleen, liver, lung, bone and brain. In conclusion, immunocytochemical screening of bone marrow samples is a feasible procedure that allows the detection of micrometastatic tumor cells in a subset of melanoma patients. Massive invasion of bone marrow with melanoma cells is a rare event even in far-advanced metastatic stages and no clear correlation between tumor load and bone marrow infiltration could be established.
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PMID:Limitations of the immunocytochemical detection of isolated tumor cells in frozen samples of bone marrow obtained from melanoma patients. 1270 45

Melanoma of the choroid is a fatal disease because of its metastases. The quest is ongoing for more reliable serum markers for detecting and staging ocular melanoma. Total serum sialic acid and acute phase proteins are valuable adjuncts in the management of malignancies, including melanoma. The aim of the paper was to asses the level of total sialic acid (TSA), total sialic acid to total protein (TP) ratio (TSA/TP) and the level of alfa-antitrypsin (AAT) and ceruloplasmin (CER) in patients with choroidal melanoma. The concentrations of TSA, TP, AAT and CER were evaluated in 61 patients with choroidal melanoma and 84 healthy controls. 36 patients had larger tumors and 25 patients had smaller melanomas. 36 patients were treated with brachytherapy. The mean concentration of TSA in all intraocular melanoma patients was 84.86 +/- 19.37 mg/dl and was significantly higher than in control group 53.63 +/- 8.47 mg/dl (p < 0.001). TSA level was significantly higher in patients with large tumors than in those with smaller choroidal melanomas. There were not differences between groups of patients treated with brachy-therapy and those not treated. TSA/TP in melanoma patients was 11.88 +/- 2.97 and it was higher than in control group 7.32 +/- 1.21 (p < 0.001). AAT level was 236.56 +/- 141.53 mg/dl in the group of melanoma patients and in the control group was 226.42 +/- 46.74 mg/dl but the differences were not statistically significant. The concentration of CER in the study group was 28.25 +/- 11.01 mg/dl and in the control group it was 29.56 + 6.33 mg/dl but the differences were not statistically significant. The assessment of TSA in blood serum may be useful in evaluation of patients with choroidal melanoma.
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PMID:The level of total sialic acid, alfa-antitrypsin, ceruloplasmin in the serum of patients with choroidal melanoma. 1289 29

Ocular melanoma is the most common primary ocular malignancy and has a significant predilection for metastasis to the liver. More than 40% of patients have hepatic metastases present at initial diagnosis, and the liver becomes involved in up to 95% of individuals who develop metastatic disease. The median survival of patients after diagnosis of liver metastasis ranges from 2 to 7 months. Metastatic disease localized to the liver has proven to be resistant to most available chemotherapy and immunotherapy regimens. Recognition of the grave prognosis associated with liver metastasis from ocular melanoma has led to the evaluation of new regional treatment modalities primarily designed to control tumor progression in the liver, including hepatic arterial chemotherapy, hepatic artery chemoembolization, regional immunotherapy, isolated hepatic perfusion, and percutaneous hepatic perfusion. This article reviews the efficacy, outcomes, and morbidities of the multiple locoregional therapies available today.
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PMID:Regional treatment options for patients with ocular melanoma metastatic to the liver. 1499 17

In this article the author discusses advances in the treatment of ocular melanoma over the past 25 years. However, owing to metastatic disease, patient survival has not improved. Research into molecular and cellular biology and genetic factors is needed to better understand metastasis in order to improve survival.
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PMID:Uveal melanoma: update and future directions. 1532 97

The eye provides unique opportunities to study complex biochemical pathways and to describe how components of these pathways contribute to the molecular basis of disease. In this article, the role of calcium-binding proteins in cancer-related diseases of the eye is reviewed. First, paraneoplastic syndromes, or so-called remote effects of cancer, arise from damage to tissues distant from any tumor or its metastases. Many of these syndromes are believed to be immune-mediated. Cancer-associated retinopathy (CAR), a blinding disease due to the degeneration of retinal photoreceptor cells, is one of the best characterized of the paraneoplastic syndromes. The CAR autoantigen has been identified as recoverin, a calcium-binding protein of the EF-hand superfamily. Its features as a calcium-binding protein, along with its function in photoreceptor cells and its role as the CAR autoantigen, are discussed. Next, unlike visual symptoms instigated by a distant tumor, ocular melanoma is the primary malignancy originating in the eye. ALG-2 encodes a pro-apoptotic calcium-binding protein that is down-regulated in ocular melanoma, thus providing these tumor cells with a selective advantage. In addition to background discussion of ALG-2, data describing the expression, cellular localization, and dimerization characteristics of ALG-2 in melanoma cells are presented. Biochemical studies of ALG-2 and its interactions with its target Alix/AIP1 also are presented. Finally, the function of ALG-2 in calcium-induced cell death is discussed. Additional calcium-binding proteins in retina and in ocular tumors are described in relation to different disease entities. Such proteins and their expression in the eye provide valuable examples bridging studies of protein chemistry, cellular function, and human disease.
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PMID:Cancer-related diseases of the eye: the role of calcium and calcium-binding proteins. 1533 63


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