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)

Positron emission tomography (PET) makes it possible to study effects of medical treatment in vivo. Carcinoid tumors with liver metastases, especially those of midgut origin, produce serotonin via the precursors tryptophan and 5-hydroxytryptophan (5-HTP) and this overproduction contributes to the clinical symptoms of the carcinoid syndrome. Seven patients with histopathologically verified neuroendocrine tumors and liver metastases, five of whom with ileal carcinoids, one a lung carcinoid and one an endocrine pancreatic tumor, were included in the study. All patients had elevation of urinary 5-HIAA with the exception of one patient with a solitary liver metastasis of midgut origin. After an intravenous injection of 11C-5-HTP, PET was performed and the uptake of radioactivity in tumor tissue, normal liver and plasma were compared. All patients with elevated urinary 5-HIAA and also the patient with a solitary liver metastasis and normal urinary 5-HIAA had high accumulation and signs of a high rate of binding of 5-HTP in the liver metastases. The uptake was relatively homogeneous in midgut carcinoid liver metastases but in large necrotic metastases the radioactivity was localized to the periphery. In three patients PET examination was repeated after 3 months of interferon treatment and in agreement with circulating tumor markers and ultrasonography the uptake of 5-HTP was unchanged. Another patient who received the somatostatin analog somatuline progressed on treatment and accordingly the uptake of 5-HTP also increased. The experience with PET in neuroendocrine gastrointestinal tumors is very limited. Our results so far indicate that 5-HTP can be used to visualize serotonin-producing neuroendocrine tumors and furthermore it might prove to be of value to monitor the effects of treatment, possibly also as an early predictive test of the outcome of treatment.
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PMID:Positron emission tomography (PET) in neuroendocrine gastrointestinal tumors. 768 63

Clinical manifestation of carcinoide syndrome are often difficult to control with medical treatment and so present a large problem for doctors. In the majority of cases, such manifestations are seen in patients with hepatic metastases. In such cases the control of the problem can be achieved by local hepatic treatment. A 57 year old patient with carcinoide syndrome for a year, with extensive hepatic tumor from a carcinoide tumor, whose origins were not lokted, had a urinary excretion 5-hidroxi-indolacetic = 73 mg in 24 hours, he used cyproheptadin, loperamida and metisergida without showing improvement. In light of the failure of medical treatment and the impossibility of surgery he was given into hepatic chemoembolization (QEH) with lipiodol, doxorrubicin (1.0 mg/Kg) and mitomicin (10.0 mg) twice. Clinical control with absolute recovery of "flushing" and diarrhea were achieved, a dose of 5-HIAA U (5.5 mg) after the first application. Transitory alterations of the aminotransferasis alkaline phosphates and leucocytosis. Besides the post embolization syndrome that regressed in 20 days, there were no complications recurring after treatment. The period of recovery was more than 9 months. We can then conclude that hepatic chemoembolization is an efficient treatment to control carcinoid syndrome.
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PMID:[Hepatic chemoembolization for the treatment of carcinoid syndrome]. 856 Jan 56

An observed case of carcinoid tumor of the large-bowel in a 68-year-old woman leads to an analysis of the clinical-diagnostic and therapeutic aspects of this rare gastrointestinal tumour. Carcinoid tumour represents 0.8-1.5% of malignant digestive tumours, in 6% of cases it is localized in large-bowel and in 2-3% in cecal-bowel. In our experience there is no specific symptoms and diagnosis was based on postoperative histopathologic analysis. Right hemicolectomy with lymphadenectomy performed and the operative specimen included a 7 cm diameter tumour, which had narrowed the lumen by 80% and infiltrated ileocecal valve. Carcinoid tumour presents considerable problems of diagnosis because symptoms are aspecific. Diagnosis is possible only in patients with high urinary levels of 5-HIAA, in presence of carcinoid syndrome and by endoscopic biopsy when tumour infiltrated gastrointestinal mucosa. False negative cases are frequent in small carcinoids ( < 2 cm) because the tumour tissues are covered by integral mucosa. C.T., ultrasonography and angiography play a primary role in the diagnosis of this tumour but octreotide scintigraphy is very important for tumour and metastases localization in consequence of its ability to demonstrate somatostatin receptor positive tumours. Radical surgery is the only treatment in very little carcinoids to prevent metastases risk. Determinant risk factors are: primary size, localization, serosal penetration. In patients with any of these risk factors, resection with regional lymphadenectomy is recommended. Other prognostic factors include histologic differentiation, the presence of macroscopic residual disease after initial surgery and level of 5-HIAA in urine. We think that neither adjuvant chemotherapy, or radiotherapy may play a significant role in this neoplasm. Many authors report considerable unsuccessful with this treatment and it is used mainly for palliation. At present, the medical treatment of inoperable gastrointestinal carcinoid consist in association with interferon alpha and octreotide. During this treatment the size of the tumour is stable: reduction of symptoms and 5-HIAA urinary levels are noted.
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PMID:[A carcinoid with cecal localization. Apropos a case]. 867 47

The classical carcinoid tumour (WHO) of the pancreas is extremely rare and its diagnosis may puzzle physicians and pathologists. Here, 29 previously published cases of pancreatic carcinoid tumours, including one new case, are reviewed. Literature research was done using MedLine from 1966 to 1995. Pancreatic carcinoids produce an atypical carcinoid syndrome. Skin flushing was reported in only 34%. The main symptom was pain, followed by diarrhoea and weight loss. Elevated urinary 5-HIAA levels were found in 85% (17/20). The immunocytochemical sensitivity for serotonin was 100% (11/11). The diagnosis of pancreatic carcinoid tumour is based on the typical endocrine histological features together with increased serotonin metabolism. Generally, the slow growth rate and late invasion of adjacent organs render local resection possible, but the high incidence of distant metastases (69%) prevents long-term survival in the majority of patients. The possible role of the Octreoscan, a new radionuclide imaging technique, is discussed with regard to this tumour entity.
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PMID:Carcinoid of the pancreas: clinical characteristics and morphological features. 875 39

A 55-yr-old woman with a midgut carcinoid syndrome due to metastatic spread of an ileal tumor to the liver, paraortic and mediastinal lymph nodes and to the skeleton was given systemic radionuclide therapy with 111In-DTPA-D-Phe1-octreotide. Before therapy, dosimetric calculations were performed on whole-body scintigraphs and 111In retention was shown to be long-lasting. Excretion was mainly seen during the first 24 hr after injection; thereafter whole-body retention remained stationary at 30%. Indium-111 activity in tumor biopsies and blood was measured using a gamma counter. Very high tumor-to-blood ratios were obtained: 150 for the primary tumor and 400-650 for liver metastases, which further justified radiation therapy. Indium-111-DTPA-D-Phe1-octreotide treatment was given on three separate occasions (3.0, 3.5 and 3.1 GBq) 8 and 4 wk apart. After each therapy, the patient experienced facial flush and pain over the skeletal lesions followed by symptomatic relief, even though no objective tumor regression was found radiologically after 5 mo. After initiation of octreotide treatment, there was a 14% reduction of the main tumor marker, urinary 5-HIAA. After three subsequent radionuclide therapies, there was a further 31% reduction of 5-HIAA levels. No adverse reactions, other than a slight decrease in leukocyte counts, were seen. The mean absorbed radiation dose after the three treatments was estimated to be about 10-12 Gy in liver metastases and 3-6 Gy in other tumors, depending on the size and location of the metastases. Assuming internalization of 111In into tumor cells and a radiobiological effect from short range Auger and conversion electrons, there might be a therapeutic effect on the tumor.
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PMID:Systemic radionuclide therapy using indium-111-DTPA-D-Phe1-octreotide in midgut carcinoid syndrome. 879 Feb 6

A case of sporadic, histamine-producing gastric carcinoid with liver metastases is reported. The patient was treated with somatostatin analogue (octreotide) combined with cortisone and blockade of histamine receptors prior to surgery, which included subtotal gastrectomy, excision of lymph node metastases and superficial liver metastases. Residual liver metastases were injected with ethanol. These interventions markedly reduced the urinary excretion of the main histamine metabolite (MelmAA). Eighteen months later combined immuno- and chemotherapy was initiated due to tumour progression and recurrent hormonal symptoms with good clinical results over 12 months. Scintigraphy, using 111In-DTPA-D-Phe1-octreotide, visualized somatostatin receptors (sstr) in primary tumour, lymph node metastases and liver metastases. The tissue/blood 111In concentration ratios of tumour biopsies were very high. Northern analyses confirmed expression of all subtypes of sstr1-5. Immunocytochemically, tumour cells were strongly positive for chromogranin A, histamine and vesicular monoamine transporter (VMAT) 2 (histamine transporter), but negative for VMAT 1, suggesting an origin from gastric enterochromaffin-like cells. In primary tumour cell cultures, histamine, 5-HTP and 5-HIAA, but not 5-HT, could be detected in conditioned culture medium, indicating a defective decarboxylation of the tryptamine precursor. This rare case of histamine-producing gastric carcinoid demonstrates that excellent symptom relief can be achieved despite disseminated disease, if active, multimodal treatment strategy is instituted. The presence of high numbers of sstr in tumour tissue also raises the possibility of receptor-guided radiotherapy.
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PMID:Gastric carcinoid with histamine production, histamine transporter and expression of somatostatin receptors. 958 30

Positron emission tomography (PET) performed with various radiolabelled compounds facilitates the study of tumor biochemistry. If the tumor uptake of an administered tracer is greater than that of surrounding normal tissue, it is also possible to localize the tumor. In initial studies, 18F-labeled deoxyglucose (FDG) was attempted to visualize the tumors, since this tracer had been successfully used in oncology, reflecting increased glucose metabolism in cancerous tissue. However, this tracer was not to any significant degree taken up by the neuroendocrine tumors. Instead, the serotonin precursor 5-hydroxytryptophan (5-HTP) labeled with 11C was used and showed an increased uptake and irreversible trapping of this tracer in carcinoid tumors. The uptake was selective and the resolution so high that we could detect more liver and lymph node metastases with PET than with CT or octreotide scintigraphy. One problem was, however, the high renal excretion of the tracer producing streaky artifacts in the area of interest. Using the decarboxylase inhibitor carbidopa, given as peroral premedication, the renal excretion decreased 6-fold and at the same time the tumor uptake increased 3-fold, hence improving the visualization of the tumors. When patients were followed during treatment with PET using 5-HTP as a tracer, a > 95% correlation between changes in urinary 5-hydroxyindoleacetic acid (U-5-HIAA) and changes in the transport rate constant for 5-HTP was observed. Thus, PET can be used to monitor treatment effects. Elevation of U-5-HIAA is considered to be uncommon in endocrine pancreatic tumors (EPTs). Initially, 11C-labeled L-DOPA was attempted as another amine important in the APUD system. With L-DOPA about half of the EPTs, mainly functioning tumors, could be detected. Recently, 5-HTP was explored as a universal tracer also for EPT and foregut carcinoids, extending the PET-examination to both thorax and abdomen (whole-body PET-examination). With this method we were able to visualize small lesions in the pancreas and thorax (e.g. ACTH-producing bronchial carcinoids) not detectable by any other method including octreotide scintigraphy, MRI and CT. Several other tracers have been investigated, e.g. the monoamineoxidase (MAO-A) inhibitor harmine with promising results in non-functioning EPTs. We are currently exploring a wide range of biochemical systems, including enzymes and receptors, both for neurotransmitters and for peptides and proteins in in vitro assays with the potential to use some of the developed tracers for in vivo visualization and tumor biological studies. In conclusion, PET is a valuable tool in the diagnosis of neuroendocrine tumors. It can detect small lesions in the thorax and abdomen not detected by other methods, which has been of great value preoperatively in several cases. It detects more lesions in the liver and lymph nodes than other methods and furthermore, it can be used to monitor treatment effects.
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PMID:Use of PET in neuroendocrine tumors. In vivo applications and in vitro studies. 1093 3

The management of advanced digestive endocrine tumors is often challenging. Liver metastases are usually diffuse at the time of diagnosis, and surgical resection is rarely feasible. Objective response rates with systemic chemotherapy are disappointing. Arterial hypervascularization of most liver metastases from digestive endocrine tumors argues in favor of hepatic arterial chemoembolization (HACE). It is assumed that embolization-induced ischemia sensitizes tumor cells to cytotoxic drugs, whose tumor concentrations are increased by blood flow slowing down. The aims of HACE are: (1) to control otherwise untractable hormone-related symptoms, particularly the carcinoid syndrome (>50% urinary 5-HIAA decrease: 57-91%) and insulinoma-related life-threatening hypoglycemias; (2) to inhibit tumor growth (objective response rates: 33-80%; mean duration: 6-42.5 months), and (3) to improve patients' survival. The postembolization syndrome, usually mild and transient, is the commonest side effect. Major extrahepatic complications are rare. In conclusion, HACE seems to be an attractive alternative treatment for diffuse (unresectable) and progressive metastases confined to the liver in patients with digestive endocrine tumors, mainly following unsuccessful systemic chemotherapy. Further studies assessing the long-term results of HACE and comparing it to other treatments, particularly systemic chemotherapy, are needed.
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PMID:Hepatic arterial chemoembolization in the management of advanced digestive endocrine tumors. 1094 Jun 92

A 57-year-old female patient with known cardiac disease developed a 4 to 6 week history of diarrhea, followed by onset of orthopnea and subsequent right-sided cardiac failure. On hospital admission she was found to have pure tricuspid regurgitation, without evidence of cardiac ischemia, pulmonary embolism, bacterial endocarditis or pericardial disease. A 24-hour urine collection for 5-HIAA was elevated, and a subsequent octreotide scan documented abnormal uptake in the pelvic cul-de-sac. Bilateral ovarian masses were found at laparotomy, which on pathological examination were found to be a benign left ovarian cystic teratoma, and a right carcinoid tumor of the ovary. This patient presented with systemic complaints of diarrhea, and orthopnea and right sided heart failure that on evaluation were ultimately found to be due to a unilateral primary carcinoid tumor of the ovary, which accounts for less than 0.1% of all ovarian carcinomas, and only 5% of all carcinoids. Treatment of this malignant carcinoid syndrome presentation consisted of debulking of the tumor and continuation of her diuretics and digoxin. Diarrhea and orthopnea ceased within 2 weeks after her oophorectomy. On evaluation 6 weeks and 6 months postoperatively, her cardiac function was stable, though unchanged. 5-HIAA levels were within normal limits, demonstrating the curative function of surgery in patients with unilateral ovarian carcinoid without evidence of metastases, as well as preserved cardiac function in otherwise stable patients.
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PMID:A case of diarrhea and orthopnea in a 57-year-old female. 1106 Oct 23

Midgut carcinoids developing in the small intestine represent the most common cause of the carcinoid syndrome, with severe symptoms of flush, diarrhoea, and fibrotic valvular heart disease. The tumours may be histologically identified with specific chromogranin A or synaptophysine immunostainings, and by serotonin reactivity, which supports a midgut origin. Urinary 5-HIAA excretion and serum chromogranin A measurements are used as biochemical tumour markers for clinical diagnosis, and as important monitors of treatment effects and prognostic predictors. The midgut carcinoids have typically slow proliferation and extended disease course, and surgical treatment has become increasingly important for their management. Surgery should aim to remove primary tumours and mesenteric metastases, which may cause long-term abdominal complications, by typical fibrotic intestinal entrapment and small bowel ischaemia due to encasement of mesenteric vessels. Attempts should also be made to surgically remove or ablate liver metastases, since this may significantly contribute to palliation of the carcinoid syndrome. In patients with this syndrome surgery is combined with continuous biotherapy with long-acting somatostatin analogues and interferon, which may alleviate symptoms and cause stable disease with slow progression. Favourable survival and life-quality can be expected with this treatment also in patients with advanced midgut carcinoids.
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PMID:Management of midgut carcinoids. 1571 73


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