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)

In summary, neuroendocrine tumors of the pancreas comprise a unique and relatively rare group of tumors, of which gastrinoma and insulinoma are the most common types. Insulinomas tend to be small, solitary and benign, with surgical resection curable in most cases. The remainder of the neuroendocrine tumors are usually large, and unlikely to be cured with surgery; their slow-growing nature, however, mandates aggressive surgical therapy; even in cases where metastatic disease is present. Somatostatin analogs such as octreotide, are used to control the symptoms of hormone secretion; they are generally less effective in patients with insulinoma than in those with the other neuroendocrine tumors. Streptozocin, 5-fluorouracil, and doxorubicin are the most widely used chemotherapeutic agents in metastatic neuroendocrine tumors; their efficacy is limited, and significant side effects limit their use. Finally, liver transplantation in very select patients may prolong survival and alleviate debilitating symptoms.
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PMID:Neuroendocrine tumors of the pancreas, excluding gastrinoma. 1688 94

Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumours. Previous molecular studies have shown that gain of chromosome 9q rather than MEN1 gene mutation is an important early event in tumour development and that chromosomal instability is associated with metastatic disease. In order to identify new gene loci and to define further the critical genetic events in insulinoma tumourigenesis, 27 insulinomas were investigated by array-based comparative genomic hybridization (array CGH) on 3.7 k genomic BAC arrays (resolution < or =1 Mb). Fluorescence in situ hybridization was used to validate alterations in a subset of tumours. Array CGH most frequently detected loss of chromosomes 11q and 22q and gains of chromosome 9q. The chromosomal regions of interest (CRI) included 11q24.1 (56%), 22q13.1 (67%), 22q13.31 (56%), and 9q32 (63%). Evaluation of the simultaneous occurrence of these aberrations in the individual tumours revealed that gain of 9q32 and loss of 22q13.1 are early genetic events in insulinomas, occurring independently of the other alterations. In tumours with increased genomic complexity, these alterations were often detected simultaneously, occurring in the same tumour cells. Losses of 11q24.1 and 22q13.31 were also associated with these more advanced tumour cases. The CRIs identified most likely harbour crucial candidate genes important in insulinoma tumourigenesis.
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PMID:Novel candidate tumour suppressor gene loci on chromosomes 11q23-24 and 22q13 involved in human insulinoma tumourigenesis. 1706 44

Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumors (EPTs). Their metastatic potential cannot be predicted reliably using histopathological criteria. In the past few years, several attempts have been made to identify prognostic markers, among them TP53 mutations and immunostaining of p53 and recently cytokeratin 19 (CK19). In a previous study using conventional comparative genomic hybridization (CGH) we have shown that chromosomal instability (CIN) is associated with metastatic disease in insulinomas. It was our aim to evaluate these potential parameters in a single study. For the determination of CIN, we applied CGH to microarrays because it allows a high-resolution detection of DNA copy number changes in comparison with conventional CGH as well as the analysis of chromosomal regions close to the centromeres and telomeres, and at 1pter-->p32, 16p, 19 and 22. These regions are usually excluded from conventional CGH analysis, because they may show DNA gains in negative control hybridizations. Array CGH analysis of 30 insulinomas (15 tumors of benign, eight tumors of uncertain and seven tumors of malignant behavior) revealed that >or=20 chromosomal alterations and >or=6 telomeric losses were the best predictors of malignant progression. A subset of 22 insulinomas was further investigated for TP53 exon 5-8 gene mutations, and p53 and CK19 expression. Only one malignant tumor was shown to harbor an arginine 273 serine mutation and immunopositivity for p53. CK19 immunopositivity was detected in three malignant tumors and one tumor with uncertain behavior. In conclusion, our results indicate that CIN as well as telomeric loss are very powerful indicators for malignant progression in sporadic insulinomas. Our data do not support a critical role for p53 and CK19 as molecular parameters for this purpose.
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PMID:Molecular parameters associated with insulinoma progression: chromosomal instability versus p53 and CK19 status. 1712 12

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET. GRS was directly compared with SRS. If lesions were visible on GRS but not detectable by SRS, other imaging modalities (MRI, CT) and follow-up were used for verification. Of the 60 evaluable patients, 51 had carcinoid tumours, 3 gastrinomas, 2 glucagonomas, 1 insulinoma and 3 paragangliomas. The overall tumour-detection rate was 73.7% for GRS and 82.1% for SRS. In the 11 patients with negative SRS, GRS was positive in 6 (54.5%). Based on the number of tumour sites detected and the degree of uptake, GRS performed better than SRS in 13 patients (21.7%), equivalent images were obtained in 18 cases (30.0%) and SRS performed better in 24 (40.0%) cases. In six of the SRS positive patients, 18 additional sites of tumour involvement could be detected. Overall, GRS detected additional tumour sites in 20% of the patients. Localisation of the primary tumours or their functional status had no influence on the outcome of imaging. GRS should be performed in selected patients as it may provide additional information in patients with NET with equivocal or absent somatostatin uptake.
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PMID:Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours. 1715 65

Numerous peptide receptors have recently been reported to be expressed or overexpressed in various human cancers. For instance, somatostatin receptors are particularly frequently expressed in gastroenteropancreatic neuroendocrine tumors (GEP-NET), including both primaries and metastases. The density is often high, and the distribution is usually homogenous. While various somatostatin receptor subtypes can be expressed in these tumors, the sst(2) is clearly predominant. These receptors represent the molecular basis for a number of clinical applications, including symptomatic therapy with octreotide in hormone-secreting GEP-NET, in vivo diagnostic with radiolabeled diethylene triamine pentaacetic acid octreotide (Octreoscan) to evaluate the extend of the disease, and (90)Y- or (177)Lu-[(90)Y-DOTA]-D: -Phe(1)-Tyr(3) octreotide radiotherapy. GEP-NET can, however, express peptide receptors other than somatostatin receptor: Insulinomas have more glucagon-like peptide 1 receptors than somatostatin receptors; gastrinomas express very high levels of secretin receptors. GEP-NET may also express cholecystokinin 2, bombesin, neuropeptide Y, or vasoactive intestinal peptide receptors. Often, several of these peptide receptors are expressed simultaneously in GEP-NET, providing a molecular basis for in vivo multireceptor targeting of those tumors.
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PMID:Peptide receptor expression in GEP-NET. 1768 67

A 14-year-old domestic shorthair cat was presented with hypoglycaemia and seizures of several weeks duration. Bloodwork revealed hypoglycaemia (1.83 mmol/l; reference range 4.22-8.05 mmol/l) with concurrent normal insulin levels (171 pmol/l; reference range 72-583 pmol/l). An insulinoma was suspected and medical and dietary management were attempted with minimal success. An exploratory laparotomy was performed and a single, well-defined mass was found within the left lobe of the pancreas. The mass was removed and histologically classified as an islet cell carcinoma, consistent with an insulinoma. The cat had an episode of presumed postoperative pancreatitits, but recovered with appropriate treatment. The cat has had no clinical signs of recurrence of greater than 32 months postsurgery. There are only four cases of insulinoma in cats reported in the literature. All prior insulionomas reported were in older cats and were malignant in character, which is similar to the reports in the dog. This case is unique because of the apparent lack of local recurrence and development of metastatic disease, leading to the prolonged survival.
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PMID:Insulinoma in a cat. 1778 34

The clinical behavior of endocrine pancreatic tumors (EPTs) is difficult to predict in the absence of metastases or invasion to adjacent organs. Several markers have been indicated as potential predictors of metastatic disease, such as tumor size > or =2 cm, Ki67 proliferative index > or =2%, cytokeratin (CK) 19 status, and recently in insulinomas, chromosomal instability (CIN). The goal of this study was to evaluate the value of these markers, and in particular of the CIN, to predict tumor recurrence or progression and tumor-specific death, using a series of 47 insulinomas and 24 non-insulinoma EPTs. From these EPT cases, a genomic profile has been generated and follow-up data have been obtained. The proliferative index has been determined in 68 tumors and a CK19 expression pattern in 50 tumors. Results are statistically analyzed using Kaplan-Meier plots and the log-rank statistic. General CIN, as well as specific chromosomal alterations such as 3p and 6q loss and 12q gain, turned out to be the most powerful indicators for poor tumor-free survival (P< or =0.0004) and tumor-specific death (P< or =0.0113) in insulinomas. The CIN, chromosome 7q gain, and a proliferative index > or =2% were reliable in predicting a poor tumor-free survival in non-insulinoma EPTs (P< or =0.0181, whereas CK19 expression was the most optimal predictor of tumor-specific death in these tumors. In conclusion, DNA copy number status is the most sensitive and efficient marker of adverse clinical outcome in insulinomas and of potential interest in non-insulinoma EPTs. As a consequence, this marker should be considered as a prognosticator to improve clinical diagnosis, most practically as a simple multi-target test.
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PMID:DNA copy number status is a powerful predictor of poor survival in endocrine pancreatic tumor patients. 1791 6

A 67 year old female patient was admitted to our clinic with recurrent hypoglycemia in December 2006. Laboratory findings revealed an elevated insulin, and C-peptide. Imaging techniques revealed a tumor of the pancreas involving the spleen with metastases of the liver, expressing somatostatin receptors. Ultrasound-guided biopsy was performed and confirmed the suspected insulinoma. Since the hypoglycemias could not sufficiently be controlled by subcutaneous administration of octreotide and by oral glucose intake, surgical debulking was performed in a palliative intention. After resection the patient was free of hypoglycemia. In case of diagnosed insulinoma, underlying MEN (multiple endocrine neoplasia) should be considered. Excision of the tumor is recommended in patients with benign solitary insulinomas. If complete excision is impossible, there are several therapeutic options that aim at preventing hypoglycemia. Thus, in contrast to other extended tumors, surgery is reasonable in malignant insulinoma even in case of metastatic disease.
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PMID:[A 67-year-old patient with recurrent hypoglycemia]. 1832 81

We conducted a nationwide survey to estimate the incidence of neuroendocrine gastrointestinal tumors (NETs) newly diagnosed in Japan from 2002 through 2004. Five hundred and fourteen pancreatic endocrine tumors (PETs) and 1,027 gastrointestinal carcinoids (GICs) were recorded and analyzed. Nonfunctioning tumors (NF-PET) constituted 47.7% of PETs. Next in frequency were insulinoma (31.7%) and gastrinoma (8.6%). Malignancy was frequent in NF-PETs (46.1%) and gastrinomas (45.5%), but only 7.4% of insulinomas were malignant. The incidence of multiple endocrine neoplasia type-1 associated with PETs was 7.4%. The incidence of GICs was 28.8%, 5.2%, and 66.0% in the foregut, midgut, and hindgut, respectively. Carcinoid syndrome and metastases were observed in only 1.7% and 5.6% of GICs, respectively. The incidence of NETs in Japan was clarified by this preliminary study. Comparatively large differences in GICs between Japan and Western nations were present with regard to the location, symptomatic status, and prevalence of malignancy. At present, the results of an epidemiologic investigation in 2005 in Japan are being analyzed, and the outcome of the survey in 2005 will be clarified in the very near future.
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PMID:[Results of a nationwide survey of gastrointestinal tumors in Japan]. 1853 15

Multiple endocrine neoplasia type 1 (MEN 1) is a syndrome characterized by tumors of the parathyroid glands, pancreatic islet cells, duodenum, and pituitary gland. We report a case of cervical metastases of glucagonoma with MEN 1. The patient was a 34-year-old woman admitted to our hospital with epigastric pain. Her medical history included two resections of prolactinoma and two upper GI hemorrhages secondary to duodenal ulcers. Computed tomography (CT) showed two hypervascular lesions in the tail of the pancreas and cervical ultrasound showed multiple hypoechogenic ovoid images in the neck. A cervical CT scan confirmed two 15-mm lymph nodes in the left cervical region and 111In-DOTATOC imaging showed focal abnormal somatostatin expression in the pancreatic tail and the cervical nodes. The patient had asymptomatic hypoglycemic episodes, with blood sugar levels as low as 30 mg/dl, which raised our suspicion of MEN 1 associated with pancreatic insulinoma. Thus, we performed a distal pancreatectomy with bilateral cervical dissection and parathyroid gland resection. Histopathological examination revealed 12 pancreatic tumors as well as metastases in four cervical lymph nodes. The resected parathyroid glands had normal structure, suggesting parathyroid hyperplasia. A follow-up CT scan, 18 months after surgery, showed new tumors in the head of the pancreas and in the duodenal wall. A pancreatoduodenectomy was performed and histopathological examination revealed nine nonfunctioning endocrine tumors in the pancreas, one tumor in the duodenal wall, and metastases in two peripancreatic lymph nodes. The patient recovered well and remains asymptomatic.
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PMID:Cervical metastases of glucagonoma in a patient with multiple endocrine neoplasia type 1: report of a case. 1903 43


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