Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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 esthesioneuroblastoma is a rare neuroendocrine tumor that derives from the olfactory cells. In the last 20 years, around 1,000 cases have been described, with an overall survival rate of 60-70% at 5 years. The most common symptoms are nasal bleeding, nasal clogging and, in locally advanced cases, signs/symptoms of intracranic hypertension such as papilla edema, cefalea, and vomiting. The standard treatments are surgery and radiotherapy. Chemotherapy can be used in an adjuvant/neoadjuvant setting and in the metastatic phase, even if its role is still not established with certainty. Here, the case is reported of a young man (38 years old) with a locally advanced esthesioneuroblastoma. Two months before coming to our clinic, he had been treated elsewhere with debulking surgery through bilateral frontal craniotomy. After surgery, MRI showed residual disease in the nasal cavities and in the medial wall of the orbits responsible for blindness and bilateral exophthalmos within a month: a very short time. Octreoscan and whole body CT scan confirmed a locally advanced disease, in the absence of metastases. Chemotherapy was begun with cisplatin and etoposide alternated with doxorubicin, ifosfamide and vincristine with granulocyte colony-stimulating factor (G-CSF) support after every cycle. Soon after the first cycle, an important reduction of pain and decrease of the exophthalmos and vertigos was observed. No improvement in blindness was seen. The patient is still stable after 24 months of follow up.
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PMID:Advanced adult esthesioneuroblastoma successfully treated with cisplatin and etoposide alternated with doxorubicin, ifosfamide and vincristine. 1992 14

Neuroendocrine tumors of the lung represent a broad spectrum of morphologic types that share specific morphologic, immunohistochemical, ultrastructural, and molecular characteristics. The classification of neuroendocrine lung tumors has changed over the last decades and currently four categories are distinguished: typical carcinoid tumor, atypical carcinoid tumor, large cell neuroendocrine carcinoma and small cell carcinoma. Neuroendocrine tumors of the lung comprise approximately 20% of all primary lung cancers. Among them, the most frequent is small cell carcinoma (13-17%). Because of differences in clinical behavior, therapy, and prognosis, a reliable histological diagnosis, as well as clinical and pathological staging system are essential for an appropriate medical proceedings. The most effective treatment of bronchial carcinoids and large cell neuroendocrine carcinoma in an early stage is complete surgical resection, whereas chemotherapy remains the primary treatment for small cell carcinoma. All carcinoids are malignant tumors with the potential to metastasize. The majority of patients with pulmonary carcinoid have an excellent survival, even if they present with lymph node metastases. Large cell neuroendocrine and small cell carcinoma progress rapidly and are generally widespread at the moment of diagnosis. Their overall prognosis is poor. Increased knowledge about pulmonary neuroendocrine tumors biology and the genetic characteristics, imply that carcinoid tumors appear to have a different etiology and pathogenesis than large cell neuroendocrine and small cell carcinoma. In practice, it could be easiest to conceptualize this group of pulmonary tumors as a spectrum of malignancy ranging from the low grade typical carcinoid to the highly malignant large cell neuroendocrine and small cell carcinoma. Typical carcinoid tumors associated with a fairly benign behavior should be classified as low-grade neuroendocrine tumor/carcinoma (G1) and atypical carcinoid tumors as intermediate-grade tumor/carcinoma (G2). Whereas, large cell neuroendocrine and small cell carcinoma should be grouped together under the designation of high-grade neuroendocrine tumor/carcinoma (G3).
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PMID:[Pulmonary neuroendocrine tumors. The spectrum of histologic subtypes and current concept on diagnosis and treatment]. 2016 17

Metastatic Neuroendocrine Tumor (NET) to the pineal gland is a unique manifestation previously unreported in the literature. We describe an unusual case of metastatic bronchial NET to the pineal gland in a 71-year-old male patient. His primary NET had been resected six years previously and there was no indication of the presence of disseminated metastatic disease at that time. Due to increased uptake by the pituitary gland on the post-operative 111Indium-pentetreotide scintigraphy (Octreoscan), an intra-sellar mass was diagnosed and excised using a transsphenoidal approach; histology revealed an unrelated non-functional pituitary macroadenoma. Four years later, a new mass appeared on MRI, involving the pineal gland, and was diagnosed on biopsy as a metastatic lesion from the original bronchial NET. Since this lesion was not accessible to surgery, it was treated successfully with radiosurgery. The case suggests that NETs should be considered in the differential diagnosis of pineal gland metastases and that radiosurgery may be an effective alternative in the treatment of these patients.
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PMID:Metastatic bronchial neuroendocrine tumor to the pineal gland: a unique manifestation of a rare disease. 2036 27

A 53-year-old female patient presented with cough and hoarseness for 3 years. Based on a biopsy of a bronchial tumor, a small cell neuroendocrine tumor of the lung was diagnosed and chemotherapy with etoposide and cisplatin was initiated. As the tumor progressed under chemotherapy, the bronchial biopsy was reevaluated and further biopsies of liver and adrenal metastases were obtained. The diagnosis was corrected, and an atypical neuroendocrine bronchial carcinoma was diagnosed. Under octreotide therapy, the patient remained stable for 1 year, when a discrete progress of the primary tumor in the lung was observed. Treatment with the mTOR (mammalian target of rapamycin) inhibitor everolimus was then initiated. Based on this case, the diagnostic criteria, prognostic factors and therapeutic options of neuroendocrine bronchial carcinomas are discussed.
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PMID:[Neuroendocrine carcinoma of the lung: a diagnostic and therapeutic challenge]. 2045 40

Neuroendocrine tumor (NET) metastases represent at this moment the only accepted indication of liver transplantation (LT) for liver secondaries. Between 1984-2007, nine (1.1%) of 824 adult LTs were performed because of NET. There were five well differentiated functioning NETs (four carcinoids and one gastrinoma), three well differentiated non functioning NETs and one poorly differentiated NET. Indications for LT were an invalidating unresectable tumor (4x), and/or a diffuse tumor localization (3x) and/or a refractory hormonal syndrome (5x). Median post-LT patient survival is 60.9 months (range 4.8-119). One-, 3- and 5-year actuarial survival rates are 88%, 77% and 33%; 1, 3 and 5 years disease free survival rates are 67%, 33% and 11%. Due to a more rigorous selection procedure, results improved since 2000; three out of five patients are alive disease-free at 78, 84 and 96 months. Review of these series together with a review of the literature reveals that results of LT for this oncological condition can be improved using better selection criteria, adapted immunosuppression and neo- and adjuvant surgical as well as medical treatment. LT should be considered earlier in the therapeutic algorithm of selected NET patients as it is the only therapy that can offer a cure.
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PMID:Liver transplantation and neuroendocrine tumors: lessons from a single centre experience and from the literature review. 2047

Neuroendocrine tumors (NETs) comprise a diverse group of slowly growing tumors with an indolent course, characterized by the capacity to synthesize and secrete polypeptide products that are hormonally active. Presence of liver metastases results in significant debilitating hormonal symptoms, and is associated with poor prognosis. Systemic chemotherapy has limited success in the management of patients with NET hepatic metastases. Although somatostatin analogs are effective in controlling symptoms in many of these patients, the disease can become refractory to treatment. For these reasons, interventional radiologic techniques for liver-directed therapy have become an important treatment option in patients with metastatic NETs. Transcatheter arterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) have been shown to reduce hormone levels, palliate symptoms, and reduce the tumor burden in many patients with unresectable and symptomatic NET hepatic metastases. This article summarizes the most recent information on arterial-based liver-directed therapies in the treatment of metastatic NETs.
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PMID:Transarterial liver-directed therapies of neuroendocrine hepatic metastases. 2049 4

Well-differentiated neuroendocrine tumors (carcinoids) arising in the presacral space are rare neoplasms that can arise in association with either sacrococcygeal teratomas or tailgut cysts. Although tumors arising in tailgut cysts are more frequent than those associated with teratomas, they are still very rare, and only 13 cases have been reported in the literature. We describe the first case of a carcinoid composed of ghrelin-producing cells arising in a tailgut cyst. Ghrelin production was demonstrated using immunohistochemistry, electron microscopy, and reverse transcription-polymerase chain reaction methods. A 73-year-old woman with back and pelvic pain was found to have a presacral mass histologically diagnosed, on needle biopsy, as a well-differentiated neuroendocrine tumor. Workup did not show another primary tumor or metastatic disease. The patient underwent laparoscopic resection of the mass, and the pathological diagnosis of the surgical specimen was of a tailgut cyst-associated carcinoid composed of ghrelin-producing cells. In addition, we have accurately reviewed the literature on presacral carcinoids, associated or unassociated with tailgut cysts, to give the reader a comprehensive overview of these very rare tumor types.
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PMID:Ghrelin-producing well-differentiated neuroendocrine tumor (carcinoid) of tailgut cyst. Morphological, immunohistochemical, ultrastructural, and RT-PCR study of a case and review of the literature. 2053 74

Neuroendocrine tumors (NETs) of the thorax, including bronchial and thymic neuroendocrine NETs, are often referred to as NETs of the foregut. The incidence and prevalence of NETs are increasing in the United States as demonstrated in the Surveillance, Epidemiology, and End Results from 1973 to 2004 (J Clin Oncol. 2008;26[18]:3063-3072). Although the majority of bronchial and thymic NETs are sporadic, approximately 5% to 10% can be associated with hereditary syndrome, multiple endocrine neoplasms type 1 (Nat Rev Cancer. 2005;5[5]:367-375). Diagnosis is made by tissue pathology, allowing for characterization and classification of the NET. Radiologic evaluation is performed to determine the extent of disease involvement. Clinical symptoms from hormonal overproduction or from paraneoplastic processes are medically managed to improve patients' quality of life. Locoregional disease can be curative with surgery; however, distant or metastatic disease is rarely curable. Therapeutic options for metastatic/advanced NETs of the thorax are mainly to palliate symptoms. Final treatment recommendations for patients with either bronchial or thymic NETs should be individualized, weighing the risks and benefits of therapy.
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PMID:NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors: well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus). 2066 76

As incidence data on gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have so far only been retrospectively obtained and based on inhomogeneous material, we conducted a prospective study in Austria collecting all newly diagnosed GEP-NETs during 1 year. Using the current WHO classification, the tumor, nodes, metastases (TNM) staging and Ki67 grading and the standard diagnostic procedure proposed by the European Neuroendocrine Tumor Society (ENETS), GEP-NETs from 285 patients (male: 148; female: 137) were recorded. The annual incidence rates were 2.51 per 100,000 inhabitants for men, 2.36 per 100,000 for women. The stomach (23%) was the main site, followed by appendix (21%), small intestine (15%) and rectum (14%). Patients with appendiceal tumours were significantly younger than patients with tumours in any other site. About 46.0% were classified as benign, 15.4% as uncertain, 31.9% as well differentiated malignant and 6.7% as poorly differentiated malignant. Patients with benign or uncertain tumours were significantly younger than patients with malignant tumours. Among the malignant tumours of the digestive tract, 1.49% arose from neuroendocrine cells. For malignant gastrointestinal NETs, the incidence was 0.80 per 100,000: 40.9% were ENETS stage I, 23.8% stage II, 11.6% stage III and 23.8% stage IV. The majority (59.7%) were grade 1, 31.2% grade 2 and 9.1% grade 3. NETs of the digestive tract are more common than previously reported; the majority show benign behaviour, are located in the stomach and are well differentiated. G3 tumours are very rare.
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PMID:Gastroenteropancreatic neuroendocrine tumours: the current incidence and staging based on the WHO and European Neuroendocrine Tumour Society classification: an analysis based on prospectively collected parameters. 2070 25

Among alternative therapeutic strategies in clinically aggressive neuroendocrine tumors (NETs) of the lung, promising results have been obtained in experimental clinical trials with mammalian target of rapamycin (mTOR) inhibitors, though in the absence of a proven mTOR signaling activation status. This study analyzed the expression of phosphorylated mTOR (p-mTOR) and its major targets, the ribosomal p70S6-kinase (S6K) and the eukaryotic initiation factor 4E-binding protein 1 (4EBP1) in a large series of 218 surgically resected, malignant lung NETs, including 24 metastasizing typical carcinoids, 73 atypical carcinoids, 60 large cell neuroendocrine carcinomas (LCNECs), and 61 small cell carcinomas (SCLCs). By immunohistochemistry, low-to-intermediate-grade tumors as compared with high-grade tumors showed higher levels of p-mTOR and phosphorylated S6K (p-S6K) (P<0.001), at variance with phosphorylated 4EBP1 (p-4EBP1), which was mainly expressed in LCNECs and SCLCs (P<0.001). The activated status of mTOR pathway was proved by the strong correlation of p-mTOR with p-S6K and somatostatin receptor(s). Western blot analysis of NET tumor samples confirmed such findings, and differential sensitivity to mTOR inhibition according to mTOR pathway activation characteristics was determined in two lung carcinoid cell lines in vitro. None of the investigated molecules had an impact on survival. However, in low-grade tumors, low p-mTOR expression correlated with lymph node metastases (P=0.016), recurrent disease, and survival (P=0.005). In conclusion, these data demonstrate a differential mTOR activation status in the spectrum of pulmonary NETs, possibly suggesting that mTOR pathway profiling might play a predictive role in candidate patients for mTOR-targeted therapies.
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PMID:Mammalian target of rapamycin signaling activation patterns in neuroendocrine tumors of the lung. 2081 88


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