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)

This 17-year-old male patient with tuberous sclerosis developed increased headaches and lethargy. Magnetic resonance imaging of the brain revealed increased ventricle size and increased size of a subependymal giant cell astrocytoma at the foramen of Monro, as well as spinal cord metastases of giant cell tumors. Decompressive surgery of the foramen of Monro lesion resulted in temporary resolution of the hydrocephalus. Increased Ki-67 labeling of tumor as well as rare spinal enhancement both possibly indicated malignant features for this entity.
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PMID:Subependymal giant cell astrocytoma with cranial and spinal metastases in a patient with tuberous sclerosis. Case report. 1528 62

This review is focused on pathways and mechanisms that might provide molecular links between the pathogenesis of renal and pulmonary disease in tuberous sclerosis complex and the pathogenesis of the neurologic manifestations of tuberous sclerosis complex. Tuberous sclerosis complex is an autosomal dominant disorder in which the manifestations can include seizures; mental retardation; autism; benign tumors of the brain, retina, skin, and kidneys; and pulmonary lymphangiomyomatosis. Lymphangiomyomatosis is a life-threatening lung disease affecting almost exclusively young women. Genetic data have demonstrated that the cells giving rise to renal angiomyolipomas, the most frequent tumor type in patients with tuberous sclerosis complex, exhibit differentiation plasticity. Genetic studies have also shown that the benign smooth muscle cells of angiomyolipomas and pulmonary lymphangiomyomatosis have the ability to migrate or metastasize to other organs. These findings indicate that hamartin and tuberin play functional roles in the regulation of cell migration and differentiation. The biochemical pathways responsible for these effects are not yet fully understood but might involve dysregulation of the small guanosine triphosphatase Rho. Similar pathways might contribute to aberrant neuronal differentiation and migration in tuberous sclerosis complex.
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PMID:Aberrant cellular differentiation and migration in renal and pulmonary tuberous sclerosis complex. 1556 18

In the belief that the advantages stemming from a minimally invasive approach are significant, particularly in cirrhosis patients, we decided to apply this technique in the treatment of a group of patients suffering from HCC associated with cirrhosis. Sixteen patients (10 men, 6 women; mean age 60.1 years) underwent laparoscopic surgery for HCC associated with well compensated HCV-related liver cirrhosis (Child-Pugh class A; mean tumour size 2.9 cm). Seven of these lesions were located in the left liver and 9 in the right lobe. Laparoscopy was performed with a CO2 pneumoperitoneum (12-14 mmHg). The Pringle manoeuvre was not used. There was one conversion to laparotomy due to inadequate exposure. We performed 13 non-anatomical resections, 1 VI segmentectomy and 1 anatomical left lobectomy. None of the patients required blood transfusions. One patient died of severe respiratory distress syndrome on postoperative day 3. Major morbidity included 2 moderate postoperative ascites successfully resolved with conservative treatment. To date (mean follow-up: 18 months) no recurrences at the resection site or port-site metastases have been observed. Limited laparoscopic liver resections for HCC in cirrhotic patients are technically feasible and safe when careful selection criteria are adopted (hepatic involvement limited and located in the left or anterior right segments, tumour size smaller than 5 cm, Child-Pugh class A).
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PMID:[Laparoscopic liver resection without a Pringle maneuver for HCC in cirrhotic patients]. 1583 34

Lymphangioleiomyomatosis (LAM) affects exclusively women of reproductive age, involves the lungs and axial lymphatic system, and is frequently complicated with renal angiomyolipomas. LAM lesions are generated by the proliferation of LAM cells with mutations of one of the tuberous sclerosis complex (TSC) genes. Recent studies indicate that LAM cells can migrate or metastasize to form new lesions in multiple organs, although they show a morphologically benign appearance. In the previous study, we reported LAM-associated lymphangiogenesis and implicated its role in the progression of LAM. In this study, we further focused on the lymphatic abnormalities in LAM: LAM-associated chylous fluid (5 pleural effusion and 2 ascites), surgically resected diaphragm (1 patient), and axial lymphatic system including the thoracic duct, lymph nodes at various regions, and diaphragmatic lymphatic system (5 autopsy cases). We demonstrated that LAM cell clusters enveloped by lymphatic endothelial cells (LCC) in all chylous fluid examined. We identified LAM lesion in the diaphragm (2 of 5 autopy cases and one surgical specimen), thoracic duct (5 of 5), and lymph nodes (retroperitoneal (5 of 5), mediastinal (4 of 5), left venous angle (5 of 5) with total positive rate of 68% to 88% at each region of the lymph node, but less frequent or none at remote lymph nodes located away from the axial lymph trunk (cervical [1 of 5] and axillary [0 of 5]). LCCs were identified in intra-LAM lesional lymphatic channels where LAM cells proliferate along lymphatic system. In in vitro culture system, LCC can fragment into each proliferating LAM cell. These findings suggest that LAM-associated lymphangiogenesis demarcates LAM lesion into bundle- or fascicle-like structure and eventually shed LCC into the lymphatic circulation and that LCCs play a central role in the dissemination of LAM lesion.
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PMID:Lymphangiogenesis-mediated shedding of LAM cell clusters as a mechanism for dissemination in lymphangioleiomyomatosis. 1616 Apr 79

Uterine perivascular epithelioid cell tumor (PEComa) is very rare, and there have been only 27 reported cases. The differentiation of the tumor has been enigmatic, and the biologic behavior remains unclear. This study describes the clinical, histologic, and immunohistochemical features of four cases of uterine PEComa. The patients were 30, 32, 36, and 40 years old, and none of them had tuberous sclerosis complex. The size of the tumors ranged from 1 to 30 cm in diameter, and 3 of the 4 tumors were confined in the uterus. One tumor involved the left ovary and omentum. Microscopically, the tumors were characterized by an epithelioid arrangement of tumor cells, which had abundant clear to eosinophilic pale granular cytoplasm, and one tumor had moderately atypical nuclei. Coagulative necrosis was found in two cases. The mitotic figures ranged from 0 to 11 per 10 high power fields. Immunohistochemically, the tumors were positive for vimentin (4/4), HMB45 (4/4), h-caldesmon (4/4), alpha-smooth muscle actin (3/4), muscle actin (2/4), and desmin (3/4). They were uniformly negative for Melan A, CD10, and S-100 protein. Ultrastructural examinations were performed on one case and revealed no melanosomes, premelanosomes, or evidence of smooth muscle differentiation. One patient died of intestinal metastases 17 months after surgery. The other patients have been well with no evidence of disease 8, 12, and 36 months after surgery. Uterine PEComa should be regarded as tumors with an uncertain malignant potential until long-term outcome data for a larger number of patients become available.
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PMID:Perivascular epithelioid cell tumor of the uterus: report of four cases. 1617 79

PEComas, occasionally associated with the tuberous sclerosis complex, are defined by the presence of perivascular epithelioid cells that coexpress muscle and melanocytic markers. This family of tumors includes angiomyolipoma (AML), clear cell sugar tumor of the lung (CCST), lymphangioleiomyomatosis (LAM), and very rare tumors in other locations. Because non-AML/non-LAM PEComas are extremely rare and their natural history and prognostic features undefined, we present our experience with 26 PEComas of soft tissue and the gynecologic tract, the largest series to date. We also performed a detailed review of the literature, with special attention to features predictive of clinical behavior. All PEComas exclusive of AML and LAM were retrieved from our consultation files. Immunohistochemistry for pan-cytokeratin (CK), S-100 protein, smooth muscle actins (SMA), desmin, vimentin, HMB45, Melan-A, microphthalmia transcription factor (MiTF), TFE3, CD117, and CD34 was performed. Clinical follow-up information was obtained. Fisher's exact test was performed. The median patient age was 46 years (range, 15-97 years); there was a marked female predominance (22 females, 4 males). Sites of involvement included the omentum or mesentery (6 cases), uterus (4 cases), pelvic soft tissues (3 cases), abdominal wall (2 cases), uterine cervix (2 cases), and vagina, retroperitoneum, thigh, falciform ligament, scalp, broad ligament, forearm, shoulder, and neck (1 case each). The tumors ranged from 1.6 to 29 cm in size (median, 7.8 cm). Tumors were epithelioid (N = 9), spindled (N = 7), or mixed (N = 10). Multinucleated giant cells were present in 18 cases. High nuclear grade was noted in 10 cases, high cellularity in 7 cases, necrosis in 8 cases, and vascular invasion in 3 cases. Mitotic activity was 0 to 50 mitotic figures (MF)/50 high power fields (HPF) (median, 0 MF/50 HPF) with atypical MF in 6 cases. IHC results were: SMA (20/25), desmin (8/22), HMB45 (22/24), Melan-A (13/18), MITF (9/18), S-100 protein (8/24), CK (3/23), vimentin (12/14), TFE3 (5/17), c-kit (1/20), and CD34 (0/7). Clinical follow-up (24 of 26 patients, 92%; median, 30 months; range, 10-84 months) showed 3 local recurrences and 5 distant metastases. At last available clinical follow-up, 2 patients (8%) were dead of disease, 4 patients (17%) were alive with metastatic or unresectable local disease, and 18 patients (75%) were alive with no evidence of disease. No patient in our series had a history of tuberous sclerosis complex. Recurrence and/or metastasis was strongly associated tumor size > median size (8 cm), mitotic activity greater than 1/50 HPF, and necrosis. We conclude that PEComas of soft tissue and gynecologic origin may be classified as "benign," "of uncertain malignant potential," or "malignant." Small PEComas without any worrisome histologic features are most likely benign. PEComas with nuclear pleomorphism alone ("symplastic") and large PEComas without other worrisome features have uncertain malignant potential. PEComas with two or more worrisome histologic features should be considered malignant. Occasional PEComas express unusual markers, such as S-100 protein, desmin, and rarely CK. The role of TFE3 in PEComas should be further studied.
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PMID:Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. 1632 28

Lymphangioleiomyomatosis (LAM) is a rare disease of women that is characterized by a proliferation of abnormal smooth muscle-like cells (LAM cells), which leads to cystic lung lesions, lymphatic abnormalities, and abdominal tumors (e.g., angiomyolipomas). LAM occurs sporadically or in association with tuberous sclerosis complex, an autosomal dominant syndrome characterized by hamartoma-like tumor growths. The tumor suppressor genes TSC1 and TSC2 have been implicated in the etiology of LAM, as mutations and loss of heterozygosity (LOH) in TSC2 have been detected in LAM cells. TSC1 encodes hamartin, with a postulated role in actin cytoskeleton reorganization. TSC2 encodes tuberin, a protein with roles in cell growth and proliferation, transcriptional activation, and endocytosis. LAM cells, as defined by TSC2 LOH, have been detected in blood and body fluids, and can metastasize. LAM presents insidiously with progressive breathlessness, or dramatically with recurrent pneumothorax, chylothorax, or sudden abdominal hemorrhage. CT scans show numerous thin-walled cysts throughout the lungs, abdominal angiomyolipomas, and lymphangioleiomyomas. Pulmonary function tests show reduced flow rates (FEV1) and diffusion capacity (DL(CO)). Twenty per cent of patients have positive bronchodilator responses. Exercise testing shows gas-exchange abnormalities, ventilatory limitation, and hypoxemia that may occur with near-normal lung function. Progression of disease is best assessed by measurements of DL(CO) and FEV1. In the proper clinical setting, LAM may be diagnosed by a thoraco-abdominal CT scan. Tissue biopsy with special stains (HMB-45) should be reserved for cases with atypical presentations. There is no effective treatment for LAM, but on-going therapeutic trials with rapamycin appear promising.
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PMID:Clinical and molecular insights into lymphangioleiomyomatosis. 1645 17

Analyses of genome orthologs in cancer on the background of tumor heterogeneity, coupled with the recent identification that the tumor propagating capacity resides within a very small fraction of cells (the tumor stem cells-TSCs), has not been achieved. Here, we describe a strategy to explore genetic drift in the mitochondrial genome accompanying varying stem cell dynamics in epithelial ovarian cancer. A major and novel outcome is the identification of a specific mutant mitochondrial DNA profile associated with the TSC lineage that is drastically different from the germ line profile. This profile, however, is often camouflaged in the primary tumor, and sometimes may not be detected even after metastases, questioning the validity of whole tumor profiling towards determining individual prognosis. Continuing mutagenesis in subsets with a mutant mitochondrial genome could result in transformation through a cooperative effect with nuclear genes - a representative example in our study is a tumor suppressor gene viz. cAMP responsive element binding binding protein. This specific profile could be a critical predisposing step undertaken by a normal stem cell to overcome a tightly regulated mutation rate and DNA repair in its evolution towards tumorigenesis. Our findings suggest that varying stem cell dynamics and mutagenesis define TSC progression that may clinically translate into increasing tumor aggression with serious implications for prognosis.
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PMID:Nuclear-mitochondrial genomic profiling reveals a pattern of evolution in epithelial ovarian tumor stem cells. 1673 29

The intraoperative hemorrhage is the most life threatening complication during a liver resection, reason why the intraoperative vascular control represents one of the key points in the liver resection. This work presents the liver vascular exclusion without caval occlusion technique and also studies the first cases operated in University Surgery Clinic Nr. 1, Targu Mures, Romania. LVE consists of an association between hilum occlusion by Pringle manoeuvre and selective clampage of the three hepatic veins. Once achieved, the technique allows resection without blood lose and no special cautions, a continue clampage of 60-90 minutes being useful for the reconstruction of the possibly harmed or resected structures during the hepatectomy. The indications of the technique are voluminous center located liver tumors, multiple liver tumors, tumors in contact with hepatic veins or with hilum bifurcation. University Surgery Clinic Nr. 1 Targu Mures's experience in this technique began in 2005 consists in 8 cases. Preoperative diagnosis were: 2 right liver voluminous benign tumors (hemangiomas), 5 cases of colo-rectal metastasis and one resection for metastases of gastro-intestinal stromal tumor. Postsurgery evolution was very good with an average hospitalisation of 6 days. Mortality rate and morbidity were zero. We strongly recommend the use of LVE technique for selected cases of difficult liver resection, LVE being one of the most advanced techniques of liver resection.
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PMID:[Vascular exclusion of the liver: surgical technique and initial clinical experience]. 1761 19

The growing clinical impact of radiofrequency ablation of liver lesions is reflected by a rapidly increasing number of published papers. Experimental work focuses on factors that reduce the variability of the ablation zone. The Pringle-maneuver plays a key role in this question from a surgeon's perspective. Large single center studies and a meta-analysis show a sharp rise in the rate of local recurrences for tumors larger 3 cm. An open surgical approach is significantly correlated to a low local recurrence rate. Bile duct lesions and intrahepatic abscesses are the most frequent complications. Intraductal bile duct cooling can prevent these complications. Three prospective randomized trials support the use of RFA for small hepatocellular carcinoma. The use of RFA in patients with multiple colorectal metastases is supported by single center studies showing a 3 year survival of > 35%. The favourable cost / benefit ratio will make RFA a part of future multimodal cancer therapy concepts.
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PMID:[Percutaneous, laparoscopic and open surgical radiofrequency ablation of malignant liver lesions]. 1772 30


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