Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With adequate medical management the midgut carcinoid tumor generally is an indolent malignancy associated with substantial life expectancy and appreciable life quality, even in the presence of liver metastases and significant tumor burden. Abdominal complications may occur in this entity of carcinoids owing to entrapment of intestines and encasement of mesenteric vessels by mesenteric metastases and associated marked mesenteric fibrosis. This may be the cause of abdominal pain, disabling diarrhea, weight loss to the extent of malnutrition, and eventually the risk of death with acute or chronic intestinal obstruction or intestinal gangrene. Operative removal of the mesentericointestinal lesion is often indicated to prevent or treat these complications but may be technically difficult when mesenteric metastases extend in the vicinity of major vessels in the mesenteric root. At laparotomy 56 patients with advanced midgut carcinoids underwent removal of the mesenteric tumor with a method for preserving the mesenteric vessels. This was feasible by mobilizing and releasing the right colon and mesenteric root from posterior adhesions, identifying the mesenteric artery below the pancreas, and free-dissecting this artery on the tumor capsule in the mobilized mesentery. Dissection was successful even with tumors initially judged inoperable unless tumor growth completely surrounded the mesenteric vessels or extended retroperitoneally. One patient was subjected to distal intestinal artery bypass. Symptom relief was been substantial and often of long duration after mesenteric tumor removal in patients who prior to surgery often had threatening intestinal ischemia. Patients with advanced midgut carcinoids may benefit markedly from dissectional removal of mesenteric tumors, which (conceivably better than conventional wedge resection) preserves the length of the remaining intestine.
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PMID:Method for dissection of mesenteric metastases in mid-gut carcinoid tumors. 1103 14

Liver metastases are one of the most difficult therapeutic challenges in modern oncologic practice. Few systemic therapies are effective for solid tumors in the liver. Resection is possible in a minority of patients and usually not curative. Image-guided therapies such as chemoembolization offer substantial intensification of treatment by combining tumor ischemia, increased drug concentrations, prolonged dwell time, and reduced systemic toxicity. Although not a curative therapy, durable responses are seen in most adenocarcinomas, which may contribute to prolongation and preservation of quality of life by delaying liver failure in patients with liver-dominant disease.
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PMID:Chemoembolization for hepatic metastases. 1252 44

Hepatic metastases are frequently encountered in patients with digestive endocrine tumors and their presence plays an important role in quality of life and overall prognosis. Surgery is the treatment method of choice for hepatic metastases but this is frequently impossible due to the extent of disease. Systemic chemotherapy is offered to patients with diffuse and/or progressive liver metastases but results are disappointing especially in patients with metastases of midgut origin. In the latter patients with carcinoid syndrome, somatostatin analogs are frequently initially effective but their efficacy wanes due to disease progression and development of tachyphylaxis. Other therapeutic options in the treatment of hepatic metastases are locoregional strategies where vascular occlusion induces ischemia in these highly vascular tumors using either surgical or radiological techniques. Available methods include surgical ligation of the hepatic artery, transient hepatic ischemia or sequential hepatic arterialization. Trans-catheter arterial chemoembolization has proven effective in terms of long palliation and objective tumor responses. Other treatments aimed at regional destruction either alone or in combination with surgery include radiofrequency ablation and cryotherapy. The latter are usually important adjuncts to surgery and are usually reserved for limited disease.
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PMID:Ablative therapies for liver metastases of digestive endocrine tumours. 1471 59

Hepatic metastases are frequent in patients with gastroenteropancreatic (GEP) endocrine tumors. The presence of hepatic metastases affects overall prognosis and quality of life especially in the presence of debilitating functional syndromes. Surgery, although the method of choice for hepatic metastases, is usually impossible due to disease extent. Results of systemic chemotherapy are also disappointing especially in patients with metastases from midgut GEP tumors. These latter patients usually have carcinoid syndrome which can be controlled by somatostatin analogues. Other therapeutic options in the treatment of highly vascular liver metastases from GEP tumors are locoregional strategies by inducing vascular occlusion resulting in ischemia and necrosis of tumoral tissue. Surgical ligation of the hepatic artery or transient hepatic ischemia has been replaced by transcatheter arterial chemoembolization (TACE). TACE has proven effective in controlling symptoms and gives objective tumor response in about half of patients. Other regional destructive methods, used either alone or in combination with surgery, include radiofrequency ablation and cryotherapy. The latter strategies are poorly evaluated to date and are usually adjuncts to surgery and reserved for limited disease.
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PMID:Ablative therapies for liver metastases of gastroenteropancreatic endocrine tumors. 1547 22

Radiofrequency ablation (RFA) of liver tumors was first proposed in 1990. New technologies enable us to produce liver thermal lesions of approximately 3-3.5 cm in diameter; RFA has consequently become an emerging percutaneous therapeutic option both for small hepatocellular carcinoma (HCC) and for non-resectable liver metastases, mainly from colorectal cancer. New devices (for example, triplet of cooled needles, wet needles) and combined therapies (tumor ischemia and RFA) have made it possible to treat large tumors. RFA can be carried out by a percutaneous, laparoscopic or laparotomic approach. Percutaneous RFA can be performed with local anaesthesia and mild sedation; deep sedation or general anaesthesia are also used. The guidance system is generally represented by ultrasound. CT or MR examinations are the more sensitive tests for assessing therapeutic results. The series of patients treated with RFA allow the technique to be considered as effective and safe, achieving a relatively high rate of cure in properly selected cases; it should be classified as curative/effective treatment for HCC, replacing percutaneous ethanol injection. The complication rate of RFA is low but not negligible; key elements in a strategy to minimize them are identified.
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PMID:Radiofrequency thermal ablation of liver tumors. 1575 65

Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five- to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants alpha-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods. In conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon.
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PMID:Ischemia/reperfusion accelerates the outgrowth of hepatic micrometastases in a highly standardized murine model. 1596 18

In 36 consecutive patients with a foregut carcinoid with extensive local tumor growth and liver metastases with a carcinoid syndrome, six patients had complaints of postprandial abdominal pain and attacks of subileus based on segmental intestinal ischemia. A diagnosis of abdominal angina was supported by a positive response to nitroglycerin in two and ischemia of the ileum demonstrated by angiography in two other patients. Complaints were reduced in all patients after surgery. Histopathology of the resected small bowel specimens showed elastic vascular sclerosis in three patients and ischemic changes in three other patients, confirming the clinical diagnosis. Resection of ischemic bowel can provide relief in patients with segmental intestinal ischemia caused by carcinoid-induced vascular sclerosis.
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PMID:Abdominal angina in patients with a midgut carcinoid, a sign of severe pathology. 1608 12

Hepatic metastases are frequent in patients with gastroentero-pancreatic (GEP) endocrine tumours; their presence significantly influences overall prognosis. Surgery, although the treatment of choice for hepatic metastases, is frequently impossible due to disease extent. Systemic chemotherapy in patients with diffuse and/or progressive liver metastases yields disappointing results especially in patients with metastases from midgut origin. In addition, in patients with carcinoid syndrome, the efficacy of somatostatin analogues wanes due to disease progression and development of tachyphylaxis. Locoregional strategies with vascular occlusion inducing ischemia in these highly vascular GEP tumours are indeed other options and may be performed using either surgical or radiological techniques (e.g. surgical ligation of the hepatic artery, transient hepatic ischemia, or sequential hepatic arterialization). Trans-catheter arterial chemoembolization is efficacious in both the control of hormonal symptoms and yields reliable objective tumour responses. Treatments aimed at regional destruction either alone or in combination with surgery include radiofrequency ablation and cryotherapy and may also be considered in certain circumstances.
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PMID:Chemoembolization and other ablative therapies for liver metastases of gastrointestinal endocrine tumours. 1618 29

Ischemia/reperfusion (I/R) is often inevitable during hepatic surgery and may stimulate the outgrowth of colorectal micrometastases. Postischemic microcirculatory disturbances contribute to I/R damage and may induce prolonged tissue hypoxia and consequent stabilization of hypoxia-inducible factor (HIF)-1alpha. The aim of this study was to evaluate the contribution of postischemic microcirculatory disturbances, hypoxia, and HIF-1alpha to I/R-accelerated tumor growth. Partial hepatic I/R attributable to temporary clamping of the left liver lobe induced microcirculatory failure for up to 5 days. This was accompanied by profound and prolonged perinecrotic tissue hypoxia, stabilization of HIF-1alpha, and massive perinecrotic outgrowth of pre-established micrometastases. Restoration of the microcirculation by treatment with Atrasentan and L-arginine minimized hypoxia and HIF-1alpha stabilization and reduced the accelerated outgrowth of micrometastases by 50%. Destabilization of HIF-1alpha by the HSP90 inhibitor 17-DMAG caused an increase in tissue necrosis but reduced I/R-stimulated tumor growth by more than 70%. In conclusion, prevention of postischemic microcirculatory disturbances and perinecrotic hypoxia reduces the accelerated outgrowth of colorectal liver metastases after I/R. This may, at least in part, be attributed to the prevention of HIF-1alpha stabilization. Prevention of tissue hypoxia or inhibition of HIF-1alpha may represent attractive approaches to limiting recurrent tumor growth after hepatic surgery.
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PMID:Perinecrotic hypoxia contributes to ischemia/reperfusion-accelerated outgrowth of colorectal micrometastases. 1739 76

The case review describes a case of a patient, hospitalized with T3N0M1 carcinoma of the splenic flexure, with multiple metastases in the both liver lobes. The patient underwent left-sided hemicolectomy with cholecystectomy. Having considered the inoperable liver findings, a chemoport was implanted. The patient underwent 10 chemotherapy cycles with no major complications recorded. The chemotherapy cycle included Campto, Leucovorin, 5FU and, concomittantly, 5FU as a continual 22-hour infusion into the port. After completion of the Cycle 10, the ultrasound and CT findings showed marked regression of the metastases, by half to two thirds. Following consultation at the onco-surgical seminar, extended left-sided hemihepatectomy was performed. The procedure lasted 6 hours, the blood loss was 3.500 ml, the period of warm ischemia was 8 minutes. Based on the oncologists' recommendation, the chemoport was preserved. The latest abdominal ultrasound detected no focal liver changes, a hypechogenic to unechogenic septed formation, v.s. a postoperative hematoma, was detected near the medial liver margin. Based on the conclusion of the oncological assessment, the patient was indicated for adjuvant chemotherapy, containing the same agents, for a period of 2-3 months. The aim of this report is to present a case of downstaging of the originally inoperable finding of the liver metastases.
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PMID:[An example of the liver metastases downstaging following chemoport implantation]. 1845 43


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