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Sample records for advanced well-differentiated neuroendocrine

  1. Continuous 5-fluorouracil infusion plus long acting octreotide in advanced well-differentiated neuroendocrine carcinomas. A phase II trial of the Piemonte Oncology Network

    International Nuclear Information System (INIS)

    Well-differentiated neuroendocrine carcinomas are highly vascularized and may be sensitive to drugs administered on a metronomic schedule that has shown antiangiogenic properties. A phase II study was designed to test the activity of protracted 5-fluorouracil (5FU) infusion plus long-acting release (LAR) octreotide in patients with neuroendocrine carcinoma. Twenty-nine patients with metastatic or locally advanced well-differentiated neuroendocrine carcinoma were treated with protracted 5FU intravenous infusion (200 mg/m2 daily) plus LAR octreotide (20 mg monthly). Patients were followed for toxicity, objective response, symptomatic and biochemical response, time to progression and survival. Assessment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria showed partial response in 7 (24.1%), stable disease in 20 (69.0%), and disease progression in 2 patients. Response did not significantly differ when patients were stratified by primary tumor site and proliferative activity. A biochemical (chromogranin A) response was observed in 12/25 assessable patients (48.0%); symptom relief was obtained in 9/15 symptomatic patients (60.0%). There was non significant decrease in circulating vascular epithelial growth factor (VEGF) over time. Median time to progression was 22.6 months (range, 2.7-68.5); median overall survival was not reached yet. Toxicity was mild and manageable. Continuous/metronomic 5FU infusion plus LAR octreotide is well tolerated and shows activity in patients with well-differentiated neuroendocrine carcinoma. The potential synergism between metronomic chemotherapy and antiangiogenic drugs provides a rationale for exploring this association in the future. NCT00953394

  2. NANETS treatment guidelines: Well-differentiated neuroendocrine tumors of the stomach and pancreas

    NARCIS (Netherlands)

    M. Kulke (Matthew); L.B. Anthony (Lowell); D.L. Bushnell (David); W.W. de Herder (Wouter); S.J. Goldsmith (Stanley); D.S. Klimstra (David); S.J. Marx (Stephen); J.L. Pasieka (Janice); R.F. Pommier (Rodney); J.C. Yao (James); R.T. Jensen (Robert)

    2010-01-01

    textabstractWell-differentiated neuroendocrine tumors (NETs) of the stomach and pancreas represent 2 major subtypes of gastrointestinal NETs. Historically, there has been little consensus on the classification and management of patients with these tumor subtypes. We provide an overview of well-diffe

  3. Profile of capecitabine/temozolomide combination in the treatment of well-differentiated neuroendocrine tumors

    Science.gov (United States)

    Kotteas, Elias A; Syrigos, Konstantinos N; Saif, Muhammad Wasif

    2016-01-01

    Neuroendocrine tumors are a rare and heterogeneous group of tumors with a variety of primary origins and variable aggressiveness. Platinum-based chemotherapy has been the cornerstone of treatment for the poorly differentiated tumors. However, well-differentiated neuroendocrine tumors are quite chemoresistant and therapy options are limited. Octreotide analogs and tyrosine kinase inhibitors are widely acceptable treatments due to substantial efficacy and tolerable toxicity. On the contrary, monotherapy or combinations of the only approved cytotoxic agent streptozocin with other drugs have been almost abandoned because of excessive toxic events. In recent years, the combination of capecitabine and temozolomide has emerged as the most promising and efficacious treatment. The oral route of administration and the substantial improvement in the outcomes with manageable toxicity are the major advantages. We reviewed the current literature and presented the profile of the capecitabine/temozolomide combination in the management of well-differentiated neuroendocrine tumors. PMID:26929640

  4. Sporadic Gastric Well-Differentiated Neuroendocrine Tumors Have a Higher Ki-67 Proliferative Index.

    Science.gov (United States)

    Lee, Hee Eun; Mounajjed, Taofic; Erickson, Lori A; Wu, Tsung-Teh

    2016-09-01

    Well-differentiated neuroendocrine tumor (WDNET) of the stomach can arise in three distinct clinical settings: (1) in association with autoimmune atrophic gastritis, (2) in association with multiple neuroendocrine neoplasia type I (MEN I) or Zollinger-Ellison syndrome (ZES), or (3) sporadic. The Ki-67 proliferative index (PI) in gastric WDNETs in these three distinct clinical settings has not been evaluated in detail. Forty-five gastric WNETs underwent polypectomy (n = 4), endoscopic mucosal resection (n = 12), and surgical resection (n = 29) between 1994 and 2015 were included. H&E slides from each case were reviewed, and Ki-67 immunostain was performed on one representative tumor block. Ki-67 PI was determined by quantitative Aperio image analysis software in areas of strongest nuclear labeling ("hot spots"), and correlated with underlying clinical and pathological features. Twenty-one patients were male and 24 female with a median age of 57 years (range, 30-80 years). Tumors were classified as type I (n = 17), type II (n = 6), and type III (n = 22) WDNETs. Types II and III showed more advanced TNM stage compared to type I (p = 0.02, overall). WHO grade based on Ki-67 PI was higher in type III WDNETs [grade 1 (G1), n = 3; grade 2 (G2), n = 15; and grade 3 (G3), n = 4] than in type I WDNETs [G1, n = 5; G2, n = 12] and in type II WDNETs [G1, n = 2; G2, n = 4] (p = 0.050, overall). Ki-67 PI was significantly higher in type III WDNETs (mean ± SD = 13.0 ± 13.3 %) than in non-sporadic (type I and II) WDNETs (mean ± SD = 5.3 ± 3.3 %; p = 0.015). There was no difference in Ki-67 PI between type I WDNETs (mean ± SD = 5.2 ± 3.5 %) and type II WDNETs (mean ± SD = 5.6 ± 3.1%; p = 0.817). Higher Ki-67 PI was associated with higher tumor T stage (p = 0.003) and also tended to be associated with lymph node metastasis (p = 0.071). In the Kaplan-Meier survival analysis, type I was associated with a

  5. Well Differentiated Neuroendocrine Tumors with a Morphologically Apparent High Grade Component: A Pathway Distinct from Poorly Differentiated Neuroendocrine Carcinomas

    Science.gov (United States)

    Tang, Laura H.; Untch, Brian R.; Reidy, Diane L.; O'Reilly, Eileen; Dhall, Deepti; Jih, Lily; Basturk, Olca; Allen, Peter J.; Klimstra, David S.

    2016-01-01

    Purpose Most well-differentiated neuroendocrine tumors (WD-NETs) of the enteropancreatic system are low-intermediate grade (G1,G2). Elevated proliferation demonstrated by either a brisk mitotic rate (>20/10 high power fields) or high Ki67 index (>20%) defines a group of aggressive neoplasms designated as high grade (G3) neuroendocrine carcinoma (NEC). High grade NEC is equated with poorly-differentiated NEC (PD-NEC) and is associated with a dismal outcome. Progression of WD-NETs to a high grade neuroendocrine neoplasm very rarely occurs and their clinicopathologic and molecular features need to be characterized. Methods We investigated the 31 cases of WD-NETs with evidence of component of a high grade neoplasm. The primary sites included pancreas, small bowel, bile duct, and rectum. Histopathology of the cases was retrospectively reviewed and selected immunohistochemistry and gene mutation analyses performed. Results The high grade component occurred either within the primary tumor (48%) or at metastatic sites (52%). The clinical presentation, radiographic features, biomarkers, and the genotype of these WD-NETs with high grade component remained akin to those of G1-G2 WD-NETs. The median disease specific survival (DSS) was 55 months (16-119 months), and 2-year and 5-year DSS was 88% and 49%, respectively – significantly better than that of a comparison group of true PD-NEC (DSS 11 months). Conclusion Mixed grades can occur in WD-NETs, which are distinguished from PDNECs by their unique phenotype, proliferative indices, and the genotype. This phenomenon of mixed grade in WD-NET provides additional evidence to the growing recognition that the current WHO G3 category contains both WD-NETs as well as PDNECs. PMID:26482044

  6. Succinate Dehydrogenase B Subunit Immunohistochemical Expression Predicts Aggressiveness in Well Differentiated Neuroendocrine Tumors of the Ileum

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    Milione, Massimo [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pusceddu, Sara [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Gasparini, Patrizia [Molecular Cytogenetics Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Melotti, Flavia [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Maisonneuve, Patrick [Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan 20141 (Italy); Mazzaferro, Vincenzo [Division of Gastrointestinal Surgery and Liver Transplantation, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Braud, Filippo G. de [Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Pelosi, Giuseppe, E-mail: giuseppe.pelosi@unimi.it [Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan I-20133 (Italy); Department of Medicine, Surgery and Dentistry, Università degli Studi, Facoltà di Medicina, Milan 20122 (Italy)

    2012-08-16

    Immunohistochemical loss of the succinate dehydrogenase subunit B (SDHB) has recently been reported as a surrogate biomarker of malignancy in sporadic and familial pheocromocytomas and paragangliomas through the activation of hypoxia pathways. However, data on the prevalence and the clinical implications of SDHB immunoreactivity in ileal neuroendocrine tumors are still lacking. Thirty-one consecutive, advanced primary midgut neuroendocrine tumors and related lymph node or liver metastases from 24 males and seven females were immunohistochemically assessed for SDHB. All patients were G1 tumors (Ki-67 labeling index ≤2%). SDHB immunohistochemistry results were expressed as immunostaining intensity and scored as low or strong according to the internal control represented by normal intestinal cells. Strong positivity for SDHB, with granular cytoplasmatic reactivity, was found in 77% of primary tumors (T), whilst low SDHB expression was detected in 90% of metastases (M). The combined analysis (T+M) confirmed the loss of SDHB expression in 82% of metastases compared to 18% of primary tumors. SDHB expression was inversely correlated with Ki-67 labeling index, which accounted for 1.54% in metastastic sites and 0.7% in primary tumors. A correlation between SDHB expression loss, increased Ki-67 labeling index and biological aggressiveness was shown in advanced midgut neuroendocrine tumors, suggesting a role of tumor suppressor gene.

  7. Comparison of methods for proliferative index analysis for grading pancreatic well-differentiated neuroendocrine tumors.

    Science.gov (United States)

    Goodell, Pamela P; Krasinskas, Alyssa M; Davison, Jon M; Hartman, Douglas J

    2012-04-01

    Assessment of proliferative activity is required for grading well-differentiated pancreatic neuroendocrine tumors. However, a standardized method for obtaining the Ki-67 proliferative index is lacking. This study compared proliferative activity obtained by 3 methods: single-field hot spot (Ki-67 HS) and 10 consecutive field average (Ki-67 CFA) using the Ventana image analysis system (Ventana Medical Systems, Tucson, AZ) and mitotic index (MI). These methods resulted in discrepant grades in 30 (67%) of our 45 cases. With the current Ki-67 cutoff of more than 2% for intermediate-grade tumors, MI, CFA, and HS resulted in specificities of 91%, 94%, and 31%, respectively, for detecting metastasis, with positive predictive values (PPVs) of 25%, 67%, and 31%, respectively. At a higher Ki-67 cutoff of 7.5%, HS analysis resulted in a specificity of 94% and PPV of 71% for predicting metastasis. While single-field HS analysis may be practical and reliable at a higher cutoff, this study emphasizes the variability that can exist when different methods of assessment are used.

  8. CT differentiation of poorly-differentiated gastric neuroendocrine tumours from well-differentiated neuroendocrine tumours and gastric adenocarcinomas

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    Kim, Seong Ho; Kim, Se Hyung; Shin, Cheong-il; Han, Joon Koo; Choi, Byung Ihn [Seoul National University Hospital, Department of Radiology, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Hospital, Institute of Radiation Medicine, Jongno-gu, Seoul (Korea, Republic of); Kim, Min-A [Seoul National University Hospital, Department of Pathology, Jongno-gu, Seoul (Korea, Republic of)

    2015-07-15

    To evaluate the differential CT features of gastric poorly-differentiated neuroendocrine tumours (PD-NETs) from well-differentiated NETs (WD-NETs) and gastric adenocarcinomas (ADCs) and to suggest differential features of hepatic metastases from gastric NETs and ADCs. Our study population was comprised of 36 patients with gastric NETs (18 WD-NETs, 18 PD-NETs) and 38 patients with gastric ADCs who served as our control group. Multiple CT features were assessed to identify significant differential CT findings of PD-NETs from WD-NETs and ADCs. In addition, CT features of hepatic metastases including the metastasis-to-liver ratio were analyzed to differentiate metastatic NETs from ADCs. The presence of metastatic lymph nodes was the sole differentiator of PD-NETs from WD-NETs (P =.001, odds ratio = 56.67), while the presence of intact overlying mucosa with mucosal tenting was the sole significant CT feature differentiating PD-NETs from ADCs (P =.047, odds ratio = 15.3) For hepatic metastases, metastases from NETs were more hyper-attenuated than those from ADCs. The presence of metastatic LNs and intact overlying mucosa with mucosal tenting are useful CT discriminators of PD-NETs from WD-NETs and ADCs, respectively. In addition, a higher metastasis-to-liver ratio may help differentiate hepatic metastases of gastric NETs from those of gastric ADCs with high accuracy. (orig.)

  9. [Primary metastatic well-differentiated neuroendocrine tumor arising in a tailgut cyst].

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    Wöhlke, M; Sauer, J; Dommisch, K; Görling, S; Valdix, A; Hinze, R

    2011-03-01

    Tailgut cysts are unusual benign cystic retrorectal malformations arising from persistent remnants of the postanal gut. Malignant transformation within this dysontogenetic lesion is very uncommon. We report the rare occurrence of a neuroendocrine tumor arising in a tailgut cyst with primary liver and lymph node metastases in a 55-year-old woman. The neuroendocrine differentiation of the tumor determines the therapeutic approach and prognosis. PMID:21046106

  10. Giant type III well-differentiated neuroendocrine tumor of the stomach: A case report

    Directory of Open Access Journals (Sweden)

    Omar Bellorin

    2016-01-01

    Conclusion: The incidence of gastric neuroendocrine tumors has been increasing during the last decade, underscoring the need to improve our understanding of their biology and behavior. When identified histologically, patient outcomes depend on appropriate determination of tumor biology and subsequent choice of treatment.

  11. Well-differentiated neuroendocrine tumor of tailgut cyst. A rare entity with controversial medical opportunities.

    Science.gov (United States)

    Damato, Angela; Pusceddu, Sara; Milione, Massimo; Mazzaferro, Vincenzo; Magli, Michelle; Seregni, Ettore; De Braud, Filippo; Buzzoni, Roberto

    2013-01-01

    The incidence of neuroendocrine tumors is rising, and this rise is explained by more than just better diagnostic procedures. About 85% of these neoplasms arise in gastrointestinal or pulmonary sites, but cases where the location is more unusual also occur in clinical practice. The tailgut cyst is a rare entity well described in the medical literature, but a neuroendocrine tumor within such a cyst is a very rare event, with about 30 cases described in the literature to date. In this report we present the case of a young woman with this unusual diagnosis. The characteristics of the case differ from most previous case reports in a few respects: the patient was a young rather than middle-aged female; she had a presacral mass with a significant solid component; at diagnosis, there was evidence of a lytic lesion in the coccyx. Despite this particular medical presentation, radical surgery was accomplished. In this disease the greatest risk is local relapse, but adjuvant radiotherapy may compromise the patient's fertility. We therefore opted for strict control only, but this decision might be debatable. PMID:24326850

  12. Non-functioning well-differentiated neuroendocrine tumor of the extrahepatic bile duct:an unusual suspect?

    Institute of Scientific and Technical Information of China (English)

    Harsheet Sethi; Mansoor Madanur; Parthi Srinivasan; Bernard Portmann; Nigel Heaton; Mohamed Rela

    2007-01-01

    BACKGROUND: Neuroendocrine tumors (NETs) arising in the biliary tree are extremely rare, and 37 cases were identiifed in the English literature. METHODS: A well-differentiated NET was found arising from the junction of the cystic and common hepatic ducts, in a 51-year-old male presenting with pedal edema and weight loss with abnormal liver enzymes and a normal serum bilirubin level. No mass was seen on radiological imaging and biopsy of the liver was suggestive of an early cholangiopathy. A bile leak complicating the liver biopsy led to an ERCP that demonstrated a iflling defect suggestive of a mass in the common bile duct (CBD). RESULTS: He underwent a successful excision of the tumor with a Roux-en-Y hepaticojejunostomy. The diagnosis of NET was made on histological and immunohistochemical analysis of the resected specimen. He remains well and disease free 22 months after surgery. CONCLUSIONS: Recognition of biliary NET continues to be a challenge and an increased awareness of these tumors in rare sites will result in optimal management of these tumors.

  13. Well-differentiated pancreatic neuroendocrine tumor with solitary hepatic metastasis presenting as a benign cystic mass: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Su Joa; Choi, Seung Joon; Kim, Hyung Sik; Kim, Jeong Ho; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2014-05-15

    Pancreatic neuroendocrine tumors and their hepatic metastases have an inconsistent appearance with only a small percentage of lesions appearing as cystic masses in computed tomography (CT) and magnetic resonance imaging (MRI). Therefore, they can be mistaken as benign or infectious lesions, which can lead to a false diagnosis with delayed or inadequate treatment. We reported a patient with upper abdominal pain that lasted for several months, caused by a huge cystic neuroendocrine carcinoma of the liver. This was mistakenly interpreted as a complicated or hydatid cyst, and the findings in the CT and MRI was presented.

  14. 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.

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    La Rosa, Stefano; Boni, Luigi; Finzi, Giovanna; Vigetti, Davide; Papanikolaou, Nikolaos; Tenconi, Silvia Maria; Dionigi, Gianlorenzo; Clerici, Moira; Garancini, Silvana; Capella, Carlo

    2010-09-01

    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. PMID:20532674

  15. Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

    International Nuclear Information System (INIS)

    Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier http://clinicaltrials.gov/show/NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18

  16. Treatment with octreotide in patients with well-differentiated neuroendocrine tumors of the ileum: prognostic stratification with Ga-68-DOTA-TATE positron emission tomography.

    Science.gov (United States)

    Koch, Walter; Auernhammer, Christoph J; Geisler, Julia; Spitzweg, Christine; Cyran, Clemens C; Ilhan, Harun; Bartenstein, Peter; Haug, Alexander R

    2014-01-01

    We investigated the use of Ga-68-DOTA-Tyr3-octreotate (Ga-68-DOTA-TATE) positron emission tomography (PET) and standardized uptake values (SUVs) to predict the effectiveness of treatment with the somatostatin analogue octreotide acetate (Sandostatin LAR) in patients with neuroendocrine tumors (NETs). Thirty patients with well-differentiated NETs of the ileum (grades G1 and G2) were studied with Ga-68-DOTA-TATE. The average SUV of a 50% isocontour volume of interest covering the lesion with maximum uptake (SUV mean) and the maximum SUV (SUV max) were determined. Patients were followed up, and the time to progression was recorded. Twenty-one patients showed progressive disease at the end of the study; nine patients had stable disease. The median progression-free survival (PFS) was 51.0 weeks (95% confidence interval [CI] 26.4-75.6). A cutoff for the SUV max of 29.4 and for the SUV mean of 20.3 could separate between patients with a long PFS (69.0 weeks; 95% CI 9.8-128.2) and a short PFS (26.0 weeks; 95% CI 8.7-43.3) response to octreotide acetate therapy. Patients with high radiotracer uptake had significantly higher PFS with a 2.9-fold higher chance for stable disease after 45 weeks; however, the prognostic performance of SUV max on an individual basis was poor, with a sensitivity of 75% and a specificity of 64%. SUV max and SUV mean of NET tumor lesions in Ga-68-DOTA-TATE PET are important prognostic indices for predicting the response to therapy with octreotide acetate.

  17. Intraindividual comparison of 68Ga-DOTA-TATE and 18F-DOPA PET in patients with well-differentiated metastatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    To compare the diagnostic impact of 68Ga-DOTA-TATE and 18F-DOPA PET in the diagnosis of well-differentiated metastatic neuroendocrine tumours (NET). PET/CT using both 68Ga-DOTA-TATE and 18F-DOPA was performed in 25 patients with histologically proven metastatic NET (nine gut, five pancreas, six lung, one paranasal sinus, four with unknown primary). Analyses of PET examinations were patient-based (pathological uptake: yes/no), and based on tumour regions (primary tumour if present and metastases of liver, lung, bones and lymph nodes). The results were compared with the results of contrast enhanced CT, and with plasma serotonin levels, which were available in 24 of the 25 patients. Patient-based sensitivities were 96% for 68Ga-DOTA-TATE PET and 56% for 18F-DOPA PET. 68Ga-DOTA-TATE PET delineated metastases in 54 of 55 positive metastatic tumour regions in contrast to 29 of 55 delineated by 18F-DOPA PET. Overall, 68Ga-DOTA-TATE was superior to 18F-DOPA in 13 patients (two patients showed fewer positive tumour regions with 18F-DOPA PET). The results were comparable in 12 patients. In 13 of 24 patients, plasma serotonin levels were elevated, and 11 of these 13 patients showed pathological uptake of 18F-DOPA. Of the 11 patients with normal levels of serotonin, 3 also showed positive 18F-DOPA uptake. In patients positive for 18F-DOPA uptake the maximum tumour SUVs were correlated with the levels of serotonin (r=0.66, p=0.01). In this study 68Ga-DOTA-TATE PET proved clearly superior to 18F-DOPA PET for detection and staging of NET. 18F-DOPA uptake tended to be increased in those patients with elevated plasma serotonin. We conclude that 18F-DOPA PET should be employed in patients with NET with negative 68Ga-DOTA-TATE PET and elevated plasma serotonin. (orig.)

  18. A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas.

    Science.gov (United States)

    Tang, Laura H; Basturk, Olca; Sue, Jillian J; Klimstra, David S

    2016-09-01

    High-grade neuroendocrine neoplasms (World Health Organization [WHO] G3) of the pancreas include both well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC). According to the WHO classification scheme, the diagnosis of this group of tumors is based on both the histopathology of the tumor and the assessment of proliferation fraction. However, the former can be challenging due to the lack of well-defined histologic criteria, and the latter alone (ie, >20 mitoses/10 high-power fields or Ki67>20%) may not sufficiently distinguish WD-NETs from PD-NECs. Given the considerable differences in treatment strategies and clinical outcome, additional practical modalities are required to facilitate the accurate diagnosis of high-grade pancreatic neuroendocrine neoplasms. We examined 33 cases of WHO G3 neuroendocrine neoplasms of the pancreas and attempted to classify them into WD-NET, small cell PD-NEC (PD-NEC-SCC), and large cell PD-NEC (PD-NEC-LCC) or to designate them as "ambiguous" when an uncertain diagnosis was rendered by any of the observers or there was any disagreement in classification among the 3 observers. To simplify the interpretation, both PD-NEC-SCC and PD-NEC-LCC were considered together as PD-NECs in the final analysis. The initial approach was to assess microscopically a single morphologically challenging hematoxylin and eosin section from each case without the knowledge of Ki67 values, performed independently by 3 pathologists to assess the degree of diagnostic concordance, and then evaluate immunohistochemical staining for surrogate biomarkers of known genotypes of WD-NET and PD-NEC, respectively, and, lastly, complete a clinicopathologic review to establish a final definitive classification. Loss of DAXX or ATRX protein expression defined WD-NET, and abnormal p53, Rb, SMAD4 expression signified PD-NEC. When the chosen section displayed an element of WD histopathology, or other tumor sections contained

  19. A Practical Approach to the Classification of WHO Grade 3 (G3) Well-differentiated Neuroendocrine Tumor (WD-NET) and Poorly Differentiated Neuroendocrine Carcinoma (PD-NEC) of the Pancreas.

    Science.gov (United States)

    Tang, Laura H; Basturk, Olca; Sue, Jillian J; Klimstra, David S

    2016-09-01

    High-grade neuroendocrine neoplasms (World Health Organization [WHO] G3) of the pancreas include both well-differentiated neuroendocrine tumor (WD-NET) and poorly differentiated neuroendocrine carcinoma (PD-NEC). According to the WHO classification scheme, the diagnosis of this group of tumors is based on both the histopathology of the tumor and the assessment of proliferation fraction. However, the former can be challenging due to the lack of well-defined histologic criteria, and the latter alone (ie, >20 mitoses/10 high-power fields or Ki67>20%) may not sufficiently distinguish WD-NETs from PD-NECs. Given the considerable differences in treatment strategies and clinical outcome, additional practical modalities are required to facilitate the accurate diagnosis of high-grade pancreatic neuroendocrine neoplasms. We examined 33 cases of WHO G3 neuroendocrine neoplasms of the pancreas and attempted to classify them into WD-NET, small cell PD-NEC (PD-NEC-SCC), and large cell PD-NEC (PD-NEC-LCC) or to designate them as "ambiguous" when an uncertain diagnosis was rendered by any of the observers or there was any disagreement in classification among the 3 observers. To simplify the interpretation, both PD-NEC-SCC and PD-NEC-LCC were considered together as PD-NECs in the final analysis. The initial approach was to assess microscopically a single morphologically challenging hematoxylin and eosin section from each case without the knowledge of Ki67 values, performed independently by 3 pathologists to assess the degree of diagnostic concordance, and then evaluate immunohistochemical staining for surrogate biomarkers of known genotypes of WD-NET and PD-NEC, respectively, and, lastly, complete a clinicopathologic review to establish a final definitive classification. Loss of DAXX or ATRX protein expression defined WD-NET, and abnormal p53, Rb, SMAD4 expression signified PD-NEC. When the chosen section displayed an element of WD histopathology, or other tumor sections contained

  20. Advances in the Diagnosis of Neuroendocrine Neoplasms.

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    Kulkarni, Harshad R; Singh, Aviral; Baum, Richard P

    2016-09-01

    Somatostatin receptor PET/CT using (68)Ga-labeled somatostatin analogs, is a mainstay for the evaluation of the somatostatin receptor status in neuroendocrine neoplasms. In addition, the assessment of glucose metabolism by (18)F-FDG PET/CT at diagnosis can overcome probable shortcomings of histopathologic grading. This offers a systematic theranostic approach for the management of neuroendocrine neoplasms, that is, patient selection for the appropriate treatment-surgery, somatostatin analogs, peptide receptor radionuclide therapy, targeted therapies like everolimus and sunitinib, or chemotherapy-and also for therapy response monitoring. Novel targets, for example, the chemokine receptor CXCR4 in higher-grade tumors and glucagon like peptide-1 receptor in insulinomas, appear promising for imaging. Scandium-44 and Copper-64, especially on account of their longer half-life (for pretherapeutic dosimetry) and cyclotron production (which favors mass production), might be the potential alternatives to (68)Ga for PET/CT imaging. The future of molecular imaging lies in Radiomics, that is, qualitative and quantitative characterization of tumor phenotypes in correlation with tumor genomics and proteomics, for a personalized cancer management. PMID:27553465

  1. Pazopanib Hydrochloride in Treating Patients With Advanced Neuroendocrine Cancer

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    2015-10-15

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Multiple Endocrine Neoplasia Type 1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor

  2. Comparison of the prognostic values of {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT in patients with well-differentiated neuroendocrine tumor

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Punit; Naswa, Niraj; Kc, Sudhir Suman; Yadav, Yashwant; Kumar, Rakesh; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Alvarado, Luis Andres; Dwivedi, Alok Kumar [Texas Tech University Health Sciences Center, Division of Biostatistics and Epidemiology, El Paso, TX (United States); Ammini, Ariachery C. [All India Institute of Medical Sciences, Department of Endocrinology and Metabolism, New Delhi (India)

    2014-12-15

    To determine the prognostic value of {sup 68}Ga-DOTANOC PET/CT in patients with well-differentiated neuroendocrine tumor (NET), and to compare the prognostic value with that of {sup 18}F-FDG PET/CT and other conventional clinicopathological prognostic factors. Data from 37 consecutive patients (age 46.6 ± 13.5 years, 51 % men) with well-differentiated NET who underwent {sup 68}Ga-DOTANOC PET/CT and {sup 18}F-FDG PET/CT were analyzed. All patients underwent a baseline visit with laboratory and radiological examinations. Clinical and imaging follow-up was performed in all patients. Progression-free survival (PFS) was measured from the date of the first PET/CT scan to the first documentation of progression of disease. {sup 68}Ga-DOTANOC PET/CT was positive in 37 of the 37 patients and {sup 18}F-FDG PET/CT was positive in 21. During follow-up 10 patients (27 %) showed progression of disease and 27 (73 %) showed no progression (24 stable disease, 3 partial response). The median follow-up was 25 months (range 2 - 52 months). Among the variables evaluated none was significantly different between the progressive disease and nonprogressive disease groups, with only SUVmax on {sup 68}Ga-DOTANOC PET/CT being borderline significant (P = 0.073). In the univariate analysis for PFS outcome, SUVmax on {sup 68}Ga-DOTANOC PET/CT (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026) and histopathological tumor grade (HR 4.238, 95 % CI 1.058 - 16.976; P = 0.041) were found to be associated with PFS. Other factors including age, sex, primary site, Ki-67 index, TNM stage, {sup 18}F-FDG PET/CT status (positive/negative), SUVmax on {sup 18}F-FDG PET/CT and type of treatment were not significant. In multivariable analysis, only SUVmax on {sup 68}Ga-DOTANOC PET/CT was found to be an independent positive predictor of PFS (HR 0.122, 95 % CI 0.019 - 0.779; P = 0.026). SUVmax measured on {sup 68}Ga-DOTANOC PET/CT is an independent, positive prognostic factor in patients with well-differentiated NET and

  3. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  4. Treatment of advanced pancreatic neuroendocrine tumors: potential role of everolimus

    OpenAIRE

    Cen P; Amato RJ

    2012-01-01

    Putao Cen, Robert J AmatoDivision of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston (Medical School), Houston, TXAbstract: Pancreatic neuroendocrine tumors (PanNETs) are frequently diagnosed at unresectable stage and remain a medical challenge. Everolimus (RAD001, Afinitor®, Novartis, Basel, Switzerland), an orally administered inhibitor of mammalian target of rapamycin (mTOR), was recently approved by the Food and Drug Administration t...

  5. Topotecan Monotherapy in Heavily Pretreated Patients with Progressive Advanced Stage Neuroendocrine Carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Knigge, Ulrich; Federspiel, Birgitte;

    2014-01-01

    BACKGROUND: Neuroendocrine carcinomas (WHO grade 3) are highly aggressive tumors with an immense tendency to metastasize and with a poor prognosis. In advanced disease, there is no standard treatment beyond first-line platin/etoposide-based chemotherapy. Topotecan is widely used as second......-line treatment in small cell lung cancer, which also responds markedly on first-line platin/etoposide. Hence, we investigated the feasibility of topotecan in previously treated patients with neuroendocrine carcinomas. MATERIAL AND METHODS: Retrospective analysis of 22 patients with disseminated and progressive...... neuroendocrine carcinomas (Ki67>20%, G3) successively treated with oral topotecan 2.3 mg/m(2) d1-5 every 3 weeks. All patients had previously received treatment with carboplatin/etoposide. Demographic, clinical and pathological features were recorded. CT-evaluations according to RECIST 1.1 were performed after...

  6. Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

    Science.gov (United States)

    2016-03-18

    Poorly Differentiated Neuroendocrine Carcinoma,; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

  7. Cixutumumab, Everolimus, and Octreotide Acetate in Treating Patients With Advanced Low to Intermediate Grade Neuroendocrine Carcinoma

    Science.gov (United States)

    2016-07-14

    Gastrin-Producing Neuroendocrine Tumor; Lung Carcinoid Tumor; Metastatic Digestive System Neuroendocrine Tumor G1; Pancreatic Glucagonoma; Pancreatic Insulinoma; Pancreatic Polypeptide Tumor; Paraganglioma; Recurrent Digestive System Neuroendocrine Tumor G1; Recurrent Merkel Cell Carcinoma; Recurrent Pancreatic Neuroendocrine Carcinoma; Regional Digestive System Neuroendocrine Tumor G1; Somatostatin-Producing Neuroendocrine Tumor; Stage III Merkel Cell Carcinoma; Stage IV Merkel Cell Carcinoma; Thyroid Gland Medullary Carcinoma

  8. Advanced Gastric Neuroendocrine Carcinoma with an Adenocarcinoma Component

    Directory of Open Access Journals (Sweden)

    Masashi Miguchi

    2012-01-01

    Full Text Available In the present study, we observed that the adenocarcinoma component in the mucosa was continuous with neuroendocrine carcinoma (NEC in the deeper layers; this suggests the normal course of NEC carcinogenesis at the histological level. A 72-year-old man was admitted to our hospital with a chief complaint of tarry stools. Endoscopic examination of the upper gastrointestinal tract revealed a 2-cm tumor, with a deep central depression, surrounded by a smooth elevated area, in the middle of the stomach body. A biopsy showed that the tumor was a moderately differentiated gastric adenocarcinoma. The patient underwent total gastrectomy and standard lymph node dissection. The resected tumor was a 3.5 × 2.5 cm type 2 lesion. It comprised two elements at the histological level: (i a moderately differentiated adenocarcinoma in the superficial portion of the mucous membrane layer, and (ii NEC-like cells with dark, round nuclei and scant cytoplasm, presenting a solid and trabecular pattern, in the submucosal and muscularis propria layers. Immunohistochemical findings showed that the NEC-like cells were diffusely positive for chromogranin A, synaptophysin, neural cell adhesion molecule, and neuron-specific enolase, but were negative for carcinoembryonic antigen. The Ki-67 labeling index was 95%. The final pathological diagnosis was gastric NEC with an adenocarcinoma component and a high cellular proliferative potential.

  9. Aggressive Multi-Visceral Pancreatic Resections for Locally Advanced Neuroendocrine Tumours. Is It Worth It?

    Directory of Open Access Journals (Sweden)

    Mohammed Abu Hilal

    2009-05-01

    Full Text Available Context Traditional surgical principles state that pancreatic resection should not be contemplated when malignancies arise in the pancreas and involve other organs. While this is logic for ductal adenocarcinoma and other tumours with aggressive biological behavior; for even large neuroendocrine tumours, aggressive multivisceral resection may achieve useful palliation and excellent survival. Design Case records were retrospectively analyzed. Patients and interventions Twelve consecutive patients (7 males, 5 females; median age 57 years, range: 37-79 years underwent multi-visceral en bloc resections for neuroendocrine tumour arising in the pancreas between 1994 and 2008. Results Three patients underwent pancreaticoduodenectomy; 9 patients had left sided pancreatic resections for neuroendocrine tumour of median diameter 9.5 cm ( 5-25 cm. They had a median of 3 (range: 1-4 additional organs resected. There were no post-operative deaths or late mortality with median follow up of 24 months. Five patients experienced a complication (major in 3 patients. Median disease free survival was not attained and 3 patients experienced recurrent disease mostly in the liver and may be candidates for further resection. Conclusion Aggressive multi-visceral resection for locally advanced neuroendocrine tumour involving the pancreas is technically feasible and in selected patients can be achieved with low mortality and acceptable morbidity, offering good disease free and overall survival. However this complex surgery should be only performed in specialist centers.

  10. Advances in the Treatment of Pancreatic Neuroendocrine Tumors (pNETs)

    OpenAIRE

    Strosberg, Jonathan

    2013-01-01

    Recent clinical trials have led to significant advancements in treatment options for metastatic neuroendocrine tumors of the pancreas. Sunitinib and everolimus have been approved by the Food and Drug Administration for treatment of progressive pancreatic NETs based on phase III trial data demonstrating improvements in progression-free survival. Cytotoxic drugs such as temozolomide and capecitabine have been associated with high radiographic response rates; however data derives primarily from ...

  11. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  12. Neuroendocrine differentiation as a survival prognostic factor in advanced non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Petrović Marina

    2007-01-01

    Full Text Available Beckground/Aim. Neuroendrocine lung tumors are histologically heterogenous group of cancers with different clinical progression. In non-small cell lung cancer (NSCLC neuroendocrine differentiation exists in 10-30% of patients. The aim of this study was to determine the frequency and influence of neuroendocrine differentiation on survival of treated patients with advanced non-small cell lung cancer (NSCLC. Methods. A clinical trial included 158 patients (74% males and 26% females, with the diagnosis of NSCLC, determined by histological verification. The patients were treated by combined chemo - and X-ray therapy in stage III (without pleural effusion or chemotherapy only in stage III (with pleural effusion and stage IV. Chemotherapy was conducted until progression of the disease, but no more than six cycles. When the progression had been noted in stage III (without pleural effusion, the treatment was continued with X-ray therapy. Neuron specific enolase, chromogranin A, as well as synapthophysin expression in tissue examples were determined by immunohistochemical analysis with monoclonal mouse anti-human-bodies. Survival was assessed within a year and two years follow-up examination. Results. A total of 53 patients (34% had NSCLC with neuroendocrine differentiation, confirmed rather in large cell lung cancer and lung adenocarcinoma (66.7% and 40%, respectively. Neuron specific enolase, chromogranin A and synapthophysin expression was noted in 45 (28.5%, 34 (21.5% and 33 (20.1% patients, respectively. The one year and two years follow-up survival periods were confirmed in 39% and 17% of patients respectively. The median survival time in the patients with the neuroendocrine expression as compared to those without the expression was 15.6 vs 10.8 months; one year survival time with the expression compared to those without the expression achieved in 62% vs 27% of the patients, (p < 0.001; a two - year survival time noted in 30% of the patients (p = 0

  13. Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3)

    DEFF Research Database (Denmark)

    Sorbye, H; Welin, S; Langer, S W;

    2013-01-01

    Background As studies on gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) are limited, we reviewed clinical data to identify predictive and prognostic markers for advanced GI-NEC patients. Patients and methods Data from advanced GI-NEC patients diagnosed 2000-2009 were retrospectively...

  14. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning;

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However...

  15. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning;

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However...

  16. Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms – Predictive and Prognostic Markers for Treatment Stratification

    Science.gov (United States)

    Krug, Sebastian; Boch, Michael; Daniel, Hanna; Nimphius, Wilhelm; Müller, Daniela; Michl, Patrick; Rinke, Anja; Gress, Thomas Matthias

    2015-01-01

    Background and Aim Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers. Patients and Methods We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed. Results The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities. Conclusions STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response. PMID:26630134

  17. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    Science.gov (United States)

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well-differentiated

  18. Treatment of gastrointestinal neuroendocrine tumors with inhibitors of growth factor receptors and their signaling pathways: Recent advances and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Michael H(o)pfner; Detlef Schuppan; Hans Scherübl

    2008-01-01

    The limited efficacy of conventional cytotoxic treatment regimes for advanced gastrointestinal neuroendocrine cancers emphasizes the need for novel and more effective medical treatment options.Recent findings on the specific biological features of this family of neoplasms has led to the development of new targeted therapies,which take into account the high vascularization and abundant expression of specific growth factors and cognate tyrosine kinase receptors.This review will briefly summarize the status and future perspectives of antiangiogenic, mTOR- or growth factor receptor-based pharmacological approaches for the innovative treatment of gastrointestinal neuroendocrine tumors.In view of the multitude of novel targeted approaches, the rationale for innovative combination therapies, i.e.combining growth factor (receptor)-targeting agents with chemoor biotherapeutics or with other novel anticancer drugs such as HDAC or proteasome inhibitors will be taken into account.

  19. Neuroendocrine Tumors of the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Fisseler-Eckhoff, Annette, E-mail: Annette.Fisseler-Eckhoff@hsk-wiesbaden.de; Demes, Melanie [Department of Pathology und Cytology, Dr. Horst-Schmidt-Kliniken (HSK), Wiesbaden 65199 (Germany)

    2012-07-31

    Neuroendocrine tumors may develop throughout the human body with the majority being found in the gastrointestinal tract and bronchopulmonary system. Neuroendocrine tumors are classified according to the grade of biological aggressiveness (G1–G3) and the extent of differentiation (well-differentiated/poorly-differentiated). The well-differentiated neoplasms comprise typical (G1) and atypical (G2) carcinoids. Large cell neuroendocrine carcinomas as well as small cell carcinomas (G3) are poorly-differentiated. The identification and differentiation of atypical from typical carcinoids or large cell neuroendocrine carcinomas and small cell carcinomas is essential for treatment options and prognosis. Pulmonary neuroendocrine tumors are characterized according to the proportion of necrosis, the mitotic activity, palisading, rosette-like structure, trabecular pattern and organoid nesting. The given information about the histopathological assessment, classification, prognosis, genetic aberration as well as treatment options of pulmonary neuroendocrine tumors are based on own experiences and reviewing the current literature available. Most disagreements among the classification of neuroendocrine tumor entities exist in the identification of typical versus atypical carcinoids, atypical versus large cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas versus small cell carcinomas. Additionally, the classification is restricted in terms of limited specificity of immunohistochemical markers and possible artifacts in small biopsies which can be compressed in cytological specimens. Until now, pulmonary neuroendocrine tumors have been increasing in incidence. As compared to NSCLCs, only little research has been done with respect to new molecular targets as well as improving the classification and differential diagnosis of neuroendocrine tumors of the lung.

  20. Well-differentiated liposarcoma of esophagus

    Institute of Scientific and Technical Information of China (English)

    YANG Bin; SHI Pei-zhi; LI Xiao; XU Ru-jun

    2006-01-01

    @@ Gastrointestinal liposarcoma is rare, and the esophagus is the. least common location at which this kind of liposarcoma may occur. We reported a patient with a well-differentiated liposarcoma of esophagus, and discussed the diagnostic utility of these imaging techniques in patient management.

  1. Pulmonary neuroendocrine (carcinoid) tumors

    DEFF Research Database (Denmark)

    Caplin, M E; Baudin, E; Ferolla, P;

    2015-01-01

    carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review...... of the relevant literature was carried out, followed by expert review. RESULTS: PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs......, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing...

  2. Well differentiated endocrine carcinomas of the pancreas

    Directory of Open Access Journals (Sweden)

    Čolović Radoje

    2011-01-01

    Full Text Available Introduction. For the difference from poorly differentiated, well differentiated endocrine carcinomas of the pancreas are the tumours in whom with aggressive surgery and chemotherapy fair results can be achieved. Objective. The aim of the study was to point out the importance of such treatment. Methods. Over a 6-year period eight patients (seven female and one male of average age 51 years (ranging from 23 to 71 years were operated on for well differentiated endocrine carcinoma: six of the head and two of the tail of the pancreas. There were two functional and six nonfunctional tumours. Pain in the upper part of the abdomen in seven, mild loss in weight in two, strong heartburn in two, obstructive jaundice in three, diarrhoea in one, sudden massive bleeding from gastric varicosities due to prehepatic portal hypertension caused by pancreatic head tumour in one, and bruise in one patient were registered preoperatively. US and CT in all, angiography in one, octreoscan in two and PET scan in one patient were performed. Whipple’s procedure was performed in six and distal pancreatectomy in two patients, as well as systemic lymphadenectomy in all and excision of liver secondary tumours in two patients. In the patient with massive gastric bleeding a total gastrectomy was performed first, followed by Whipple’s procedure a month later. Results. R0 resection was achieved in all patients. Lymph nodes metastases were found in six patients. Six patients were given chemotherapy. One patient died 3 years after surgery, seven are still alive, on average 2.5 years. A local recurrence after distal pancreatectomy that occurred 5 years after surgery was successfully reresected and the patient is on peptide-receptor radiotherapy. In other six patients there were no local recurence or distant metastases. Conclusion. With aggressive surgery and chemotherapy fair results can be achieved in well differentiated endocrine carcinomas of the pancreas.

  3. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  4. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2) : a randomised, placebo-controlled, phase 3 study

    NARCIS (Netherlands)

    Pavel, Marianne E.; Hainsworth, John D.; Baudin, Eric; Peeters, Marc; Hoersch, Dieter; Klimovsky, Judith; Lebwohl, David; Jehl, Valentine; Wolin, Edward M.; Oberg, Kjell; Van Cutsem, Eric; Yao, James C.

    2011-01-01

    Background Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), has shown antitumour activity in patients with advanced pancreatic neuroendocrine tumours. We aimed to assess the combination of everolimus plus octreotide long-acting repeatable (LAR) in patients with low-grade or

  5. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    functionality [hazard ratio (HR) 2.1, 95 % CI 1.0-4.5, p = 0.05] and high plasma chromogranin A (CgA) levels > 600 ng/ml (HR 2.9, 95 % CI 1.5-5.5, p < 0.001) at baseline. PRRT is well tolerated and very effective in advanced well-differentiated small intestinal (midgut) NET. A high disease control rate and long PFS can be achieved with this modality after failure of standard biotherapy with somatostatin analogues. Tumour functionality and high plasma CgA appear to be independent predictors of unfavourable patient outcome. (orig.)

  6. Outcome of peptide receptor radionuclide therapy with 177Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    International Nuclear Information System (INIS)

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with 177Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with 177Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial 99mTc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis. Variables linked

  7. [Grading of neuroendocrine tumors].

    Science.gov (United States)

    Saeger, W; Schnabel, P A; Komminoth, P

    2016-07-01

    The current WHO classification of neuroendocrine tumors (NET) differentiates between typical carcinoids (low grade NET), atypical carcinoids (intermediate grade NET) and small cell and large cell carcinomas (high grade NET) according to the prognosis. Neuroendocrine neoplasms (NEN) of the gastrointestinal tract and the pancreas are graded in an identical way. Together with the TNM system this enables a preoperative estimation of the prognosis in biopsies and fine needle aspirates. Well-differentiated tumors are graded into G1 tumors by the number of mitoses, tumors (2-20 mitoses/10 HPF, Ki-67 3-20 %). Discrepancies between the number of mitoses and the Ki-67 index are not uncommon and in these cases the higher value of the two should be applied. The more differentiated tumors of the G3 type have to be differentiated from undifferentiated carcinomas of the small cell type and large cell type with a much poorer prognosis. Prognosis relevant grading of thyroid cancers is achieved by special subtyping so that the G1-G3 system is not applicable. The rare cancers of the parathyroid gland and of the pituitary gland are not graded. Adrenal tumors also have no grading system. The prognosis is dependent on the Ki-67 index and with some reservations on the established scoring systems. PMID:27379621

  8. A systematic review of management of neuroendocrine tumors: An experience from a tertiary care centre from India

    Directory of Open Access Journals (Sweden)

    Rakesh Kapoor

    2014-01-01

    Full Text Available Neuroendocrine tumors (NETs encompass a heterogeneous group of tumors demonstrating varied clinical behavior. The field has recently witnessed several important developments stemming from improvements in the histopathological classification schemes, advanced imaging techniques, and a deeper understanding of the molecular mechanisms underlying tumor progression. These tumors have indolent clinical courses, with long survival rates even for the patients with metastatic disease. The mainstay of treatment is surgery. Somatostatin analogs play a key role in controlling the symptoms; however, they are seldom associated with tumor regression. Traditional cytotoxic chemotherapies have a very limited role in well differentiated NETs, but platinum based chemotherapy is highly effective in neuroendocrine carcinomas. Recently, the biological targeted agents have shown promise in patients with metastatic disease. Evolving modalities like peptide receptor targeted therapies and radioembolization have opened up new avenues in refractory and advanced disease.

  9. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

    Birkenkamp-Demtröder, Karin; Wagner, Ludwig; Brandt Sørensen, Flemming;

    2005-01-01

    Our previous microarray-based studies identified secretagogin to be highly expressed in normal colon mucosa compared to basal expression in colon adenocarcinomas. The aim of this study was to analyze the differential expression of secretagogin in normal mucosa, adenocarcinomas, and neuroendocrine......, synaptophysin) in neuroendocrine cells in crypts of normal mucosa, and in tumor cells of carcinoids. Secretagogin was strongly expressed in the cytosol and the nucleus of 19 well-differentiated neuroendocrine carcinoids and carcinoid metastases, as well as in neuroendocrine tumors from the lung, pancreas...... and adrenal gland. Secretagogin was detected in plasma from carcinoid patients with distant metastasis. Combined immunohistochemical analysis of secretagogin and FK506-binding protein 65, a protein de novo synthesized in adenocarcinomas, distinguished well-differentiated carcinoids, adenocarcinoids...

  10. Mucinous Carcinoma of the Breast with Neuroendocrine Differentiation

    OpenAIRE

    Varadharajan, Eswari; Priya, Shanmuga; Prakash, Geetha; Mugundan, Archana; Easwaramurthi, Praveen

    2015-01-01

    Mucinous carcinoma of the breast is a well-differentiated type of adenocarcinoma accounting for 2-5% of all breast cancers. Pure mucinous carcinoma of the breast has a favorable prognosis, usually seen in post-menopausal women. Neuroendocrine differentiation has been described in both in-situ and infiltrating breast cancers .Mucinous carcinomas of the breast appear to have the greatest association with neuroendocrine differentiation. Chromogranin A and synaptophysin are specific immunohistoch...

  11. Nuclear Image Analysis Study of Neuroendocrine Tumors

    OpenAIRE

    Park, Meeja; Baek, Taehwa; Baek, Jongho; Son, Hyunjin; Kang, Dongwook; Kim, Jooheon; Lee, Hyekyung

    2012-01-01

    Background There is a subjective disagreement about nuclear chromatin in the field of pathology. Objective values of red, green, and blue (RGB) light intensities for nuclear chromatin can be obtained through a quantitative analysis using digital images. Methods We examined 10 cases of well differentiated neuroendocrine tumors of the rectum, small cell lung carcinomas, and moderately differentiated squamous cell lung carcinomas respectively. For each case, we selected 30 representative cells a...

  12. Staging of gastroenteropancreatic neuroendocrine tumors: how we do it based on an evidence-based approach.

    LENUS (Irish Health Repository)

    McDermott, Shaunagh

    2013-01-01

    In contrast to other common types of malignant tumors, the vast majority of gastroenteropancreatic neuroendocrine tumors are well differentiated and slowly growing with only a minority showing aggressive behavior. It is important to accurately stage patients radiologically so the correct treatment can be implemented and to improve prognosis. In this article, we critically appraise the current literature in an effort to establish the current role of radiologic imaging in the staging of neuroendocrine tumors. We also discuss our protocol for staging neuroendocrine tumors.

  13. Retroperitoneal well-differentiated inflammatory liposarcoma: a diagnostic dilemma.

    Science.gov (United States)

    Kawano, Rinsaku; Nishie, Akihiro; Yoshimitsu, Kengo; Irie, Hiroyuki; Tajima, Tsuyoshi; Hirakawa, Masakazu; Ishigami, Kousei; Ushijima, Yasuhiro; Okamoto, Daisuke; Yabuuchi, Hidetake; Taketomi, Akinobu; Nishihara, Yunosuke; Fujita, Nobuhiro; Honda, Hiroshi

    2008-08-01

    We present a case of retroperitoneal well-differentiated inflammatory liposarcoma that was extremely difficult to diagnose preoperatively. Computed tomography and magnetic resonance images showed a 5-cm homogeneous soft-tissue mass with a decreased apparent diffusion coefficient and without fat component in the retroperitoneum. Minimal fat stranding was detected around the mass. The preoperative working diagnosis was malignant lymphoma or inflammatory pseudotumor, whereas the final diagnosis after surgery was well-differentiated inflammatory liposarcoma. As a result, only a large component of lymphoid infiltration was recognized as a tumor preoperatively, and minimal fat stranding represented a component of lipoma-like liposarcoma. In this entity, a lipomatous component could easily be missed on radiologic imaging because of the conspicuity of lymphoid infiltration. We should consider the possibility of this variant when we evaluate a retroperitoneal tumor. PMID:18770006

  14. [Surgical treatment for pancreatic neuroendocrine neoplasmas].

    Science.gov (United States)

    Wu, Junli; Guo, Feng; Wei, Jishu; Lu, Zipeng; Chen, Jianmin; Gao, Wentao; Li, Qiang; Jiang, Kuirong; Dai, Cuncai; Miao, Yi

    2016-01-01

    Pancreatic neuroendocrine neoplasmas (PNENs) are classified into functioning & non-functioning tumors. The radical surgery is the only effective way for the cure & long-term survival. For the locoregional resectable tumors, the surgical resection is the first choice of treatment; the surgical procedures include local resection (enucleation) and standard resection. For the insulinomas and non-functioning tumors less than 2 cm, local resection (enucleation),distal pancreatectomy with spleen-preservation or segmental pancreatectomy are the commonly selected procedures. The radical resections with regional lymph nodes dissection, including pancreaticoduodenectomy, distal pancreatectomy and middle segmental pancreatectomy, should be applied for tumors more than 2 cm or malignant ones. For the locoregional advanced or unresectable functioning tumors, debulking surgery should be performed and more than 90% of the lesions including primary and metastatic tumors should be removed; for the non-functioning tumors, if complicated with biliary & digestive tract obstruction or hemorrhage, the primary tumors should be resected. The liver is the most frequent site of metastases for PNENs and three types of metastases are defined. For typeⅠmetastasis, patients are recommended for surgery if there are no contraindications; For type II metastasis, debulking surgery should be applied and at least 90% of metastatic lesions should be resected, and for patients with primary tumors removed and no extrahepatic metastases, or for patients with well-differentiated (G1/G2) tumors, liver transplantation may be indicated. For the unresectable type Ⅲ metastasis, multiple adjuvant therapies should be chosen. PMID:27045238

  15. Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Ying Wu; Zhong-wu Li; Ji-you Li

    2009-01-01

    Objective: To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance.Methods: Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte(Hep) and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin.Results: Of 64 cases, 33(51.6%) were intestinal type, 3(4.7%) were gastric type, 25(39.1%) were gastrointestinal type and 3(4.7%) were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors (invasion or metastasis). The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes

  16. Neuroendocrine Tumor: Statistics

    Science.gov (United States)

    ... Tumor > Neuroendocrine Tumor - Statistics Request Permissions Neuroendocrine Tumor - Statistics Approved by the Cancer.Net Editorial Board , 04/ ... the body. It is important to remember that statistics on how many people survive this type of ...

  17. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    OpenAIRE

    Patil, Vijay M.; Amit Joshi; Vanita Noronha; Vibhor Sharma; Saurabh Zanwar; Sachin Dhumal; Shubhada Kane; Prathamesh Pai; Anil D’Cruz; Pankaj Chaturvedi; Atanu Bhattacharjee; Kumar Prabhash

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were...

  18. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Thomas Gress

    2012-02-01

    Full Text Available Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-a, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  19. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Rinke, Anja, E-mail: sprengea@staff.uni-marburg.de; Michl, Patrick; Gress, Thomas [Department of Gastroenterology, University Hospital Marburg, Baldinger Strasse, Marburg D-35043 (Germany)

    2012-02-08

    Treatment of the clinically and prognostically heterogeneous neuroendocrine neoplasms (NEN) should be based on a multidisciplinary approach, including surgical, interventional, medical and nuclear medicine-based therapeutic options. Medical therapies include somatostatin analogues, interferon-α, mTOR inhibitors, multikinase inhibitors and systemic chemotherapy. For the selection of the appropriate medical treatment the hormonal activity, primary tumor localization, tumor grading and growth behaviour as well as the extent of the disease must be considered. Somatostatin analogues are mainly indicated in hormonally active tumors for symptomatic relief, but antiproliferative effects have also been demonstrated, especially in well-differentiated intestinal NET. The efficacy of everolimus and sunitinib in patients with pancreatic neuroendocrine tumors (pNET) has been demonstrated in large placebo-controlled clinical trials. pNETs are also chemosensitive. Streptozocin-based chemotherapeutic regimens are regarded as current standard of care. Temozolomide in combination with capecitabine is an alternative that has shown promising results that need to be confirmed in larger trials. Currently, no comparative studies and no molecular markers are established that predict the response to medical treatment. Therefore the choice of treatment for each pNET patient is based on individual parameters taking into account the patient’s preference, expected side effects and established response criteria such as proliferation rate and tumor load. Platin-based chemotherapy is still the standard treatment for poorly differentiated neuroendocrine carcinomas. Clearly, there is an unmet need for new systemic treatment options in patients with extrapancreatic neuroendocrine tumors.

  20. Diagnosis and management of gastrointestinal neuroendocrine tumors: An evidence-based Canadian consensus.

    Science.gov (United States)

    Singh, Simron; Asa, Sylvia L; Dey, Chris; Kennecke, Hagen; Laidley, David; Law, Calvin; Asmis, Timothy; Chan, David; Ezzat, Shereen; Goodwin, Rachel; Mete, Ozgur; Pasieka, Janice; Rivera, Juan; Wong, Ralph; Segelov, Eva; Rayson, Daniel

    2016-06-01

    The majority of neuroendocrine tumors originate in the digestive system and incidence is increasing within Canada and globally. Due to rapidly evolving evidence related to diagnosis and clinical management, updated guidance on the diagnosis and treatment of gastrointestinal neuroendocrine tumors (GI-NETs) are of clinical importance. Well-differentiated GI-NETs may exhibit indolent clinical behavior and are often metastatic at diagnosis. Some NET patients will develop secretory disease requiring symptom control to optimize quality of life and clinical outcomes. Optimal management of GI-NETs is in a multidisciplinary environment and is multimodal, requiring collaboration between medical, surgical, imaging and pathology specialties. Clinical application of advances in pathological classification and diagnostic technologies, along with evolving surgical, radiotherapeutic and medical therapies are critical to the advancement of patient care. We performed a systematic literature search to update our last set of published guidelines (2010) and identified new level 1 evidence for novel therapies, including telotristat etiprate (TELESTAR), lanreotide (CLARINET), everolimus (RADIANT-2; RADIANT-4) and peptide receptor radionuclide therapy (PRRT; NETTER-1). Integrating these data with the clinical knowledge of 16 multi-disciplinary experts, we devised consensus recommendations to guide state of the art clinical management of GI-NETs.

  1. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation

    Directory of Open Access Journals (Sweden)

    Vijay M. Patil

    2016-01-01

    Full Text Available Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years. Grades 3-4 toxicity with NACT were seen in 19 patients (76%. The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48% patients and radical chemoradiation in 9 (36% patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort.

  2. [A CASE OF ADVANCED BLADDER NEUROENDOCRINE CARCINOMA (SMALL CELL CARCINOMA) SIGNIFICANTLY IMPROVED BY LOW DOSE OF ORAL TEGAFUR-URACIL].

    Science.gov (United States)

    Nomi, Hayahito; Takahara, Kiyoshi; Minami, Koichiro; Maenosono, Ryoichi; Matsunaga, Tomohisa; Yoshikawa, Yuki; Tsujino, Takuya; Hirano, Hajime; Inamoto, Teruo; Yamamoto, Ikuhisa; Tsuji, Motomu; Kiyama, Satoshi; Azuma, Haruhito

    2015-10-01

    A 81-old-woman underwent a transurethral resection of bladder tumor (TURBT) at a nearby hospital in April 2011. The diagnosis was invasive urothelial carcinoma, G3 with a component of bladder small cell carcinoma, T1 or more. She was recommended to visit our hospital for combined modality therapy of bladder cancer, but she refused the treatment for over one year. In May 2012, she came to our hospital with the chief complaint of pain at urination. Cystoscopy revealed non-papillary sessile tumor in the top of the bladder, and CT scan demonstrated the presence of the right obturator lymph nodes swollen up to 1.2 cm in size. The second TURBT was performed and the diagnosis was bladder small cell carcinoma (pT3N2M0) according to urothelial cancer guidelines of the Japanese Urological Association (JUA). Because she strongly refused hospitalization anymore, we started daily oral intake of low dose Tegafur-Uracil (100 mg) for the treatment. After one month, the serum Neuron-Specific Enolase (NSE; tumor maker of small cell cancer) level was elevated to 27.6 ng/ml and the right obturator lymph node was enlarged up to 1.9 cm. Therefore, the Trgafur-Uracil dose was increased to 200 mg daily. After then, the serum NSE level was decreased to 15.5 ng/ml following reduction in size of the obturator lymph nodes with partial response in December 2013. After two years of follow-up period, her regular urine test showed normal findings, and no apparent recurrence was detected on urinary bladder with MRI and Cystoscopy. This is a case of advanced bladder small cell carcinoma significantly improved by oral administration of Tegafur-Uracil 200 mg/day for over 2 years. PMID:26717786

  3. Targeting the mTOR Signaling Pathway in Neuroendocrine Tumors

    OpenAIRE

    Chan, Jennifer; Kulke, Matthew

    2014-01-01

    Opinion statement Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies characterized by variable but most often indolent biologic behavior. Well-differentiated NETs can be broadly classified as either carcinoid or pancreatic NET. Although they have similar characteristics on routine histologic evaluation, the 2 tumor subtypes have different biology and respond differently to treatment, with most therapeutic agents demonstrating higher response rates in pancreatic NETs compar...

  4. Profile of lanreotide autogel and its potential in the treatment of gastroenteropancreatic neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Rinke A

    2015-09-01

    Full Text Available Anja Rinke, Daniela Müller Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Philipps University, Marburg, Germany Abstract: Gastroenteropancreatic neuroendocrine tumors (GEPNETs comprise a heterogenous group of neoplasm, and their incidence is increasing in the population. Approximately one-third of these tumors are associated with characteristic hormonal syndromes like flushing and diarrhea in carcinoid syndrome. Most GEPNETs express receptors for somatostatin. The somatostatin analogs octreotide and lanreotide constituted a major therapeutic advance in palliating hypersecretion syndromes. Lanreotide autogel is a viscous aqueous solution of lanreotide that is usually administered deep subcutaneously every 4 weeks, but extended dosing intervals have also been proposed. In recent years, increasing evidence has supported the use of somatostatin analogs (SSA as antitumor agents. In the double-blind, placebo-controlled, Phase III CLARINET trial, lanreotide autogel 120 mg every 4 weeks was associated with a significant prolongation of progression-free survival in patients with nonfunctioning GEPNETs, with a Ki-67 of <10%. This antiproliferative effect and the favorable toxicity profile make lanreotide autogel attractive for long-term treatment in patients with well-differentiated GEPNETs. Further studies are needed to evaluate the role of lanreotide autogel as a combination partner and the efficacy of high-dose lanreotide. Keywords: neuroendocrine tumor, somatostatin analogs, lanreotide, symptomatic treatment, antiproliferative treatment

  5. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  6. Differentiation of soft tissue lipoma from well-differentiated liposarcom on MRI

    International Nuclear Information System (INIS)

    Objective: To evaluate the value of magnetic resonance imaging features in differentiating soft tissue lipoma from well-differentiated liposarcoma. Methods: MR images of 30 patients with histologically verified fat-containing tumors (22 lipomas and 8 well-differentiated liposarcomas) were retrospectively reviewed. Well-differentiated liposarcomas and benign lipomas were compared in terms of the size of the lesion, percentage of adipose component, number of thick septa, nodular and (or) patchy nonadipose component, contrast enhancement patterns and the margin characters of the lesion. Results: The mean size of lipomas [(64±35) mm] was significantly smaller (t=4.263, P<0.01) than that of well- differentiated liposarcomas [(138±44) mm], and the mean percentage of adipose component of lipomas [(94±6)%] was significantly larger (t=5.903, P<0.01) than that of well-differentiated liposarcomas [(74±9)%]. Thelipomas with more than two thick septa(3/22) were significantly less (P<0.01) than well-differentiated liposarcomas with (8/8), and lopomas with nodular and/ or patchy nonadipose components (4/22) were significantly less (P<0.01) than well-differentiated liposarcomas with (8/8). The degree of contrast enhancement in 15 lipomas (4/15 mild to moderate enhancement ) was significantly lower (P<0.01) than that in well-differentiated liposarcomas (1/8 moderate and 7/8 strong enhancement). Conclusion: MRI is helpful in distinguishing soft tissue lipoma and well-differentiated liposarcoma. Compared with lipoma, features that suggest well-differentiated liposarcoma include large lesion size, decreased percentage of fat composition, presence of more than two thick septa, presence of nodular and/or patchy nonadipose areas and strong enhancement. (authors)

  7. Neuroendocrine-immune interaction

    NARCIS (Netherlands)

    Kemenade, van Lidy; Cohen, Nicholas; Chadzinska, Magdalena

    2016-01-01

    It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only

  8. Advanced Composite of Large Cell Neuroendocrine Carcinoma and Squamous Cell Carcinoma: A Case Report of Uterine Cervical Cancer in a Virgin Woman

    Directory of Open Access Journals (Sweden)

    Ryusuke Murakami

    2013-01-01

    Full Text Available Large cell neuroendocrine carcinoma (LCNEC of the uterine cervix is very rare and aggressive. The prognosis is very poor despite multimodal treatment. We report a virgin woman with FIGO stage 4b LCNEC of uterine cervix coexisting with squamous cell carcinoma. An early thirties virgin woman presented with 2-month history of abdominal pain. A chest X-ray showed multiple lung metastatic tumors. A vaginal smear showed malignant cells, and a biopsy specimen had features of LCNEC. The tumor showed trabecular patterns. Tumor cells possessed a moderate amount of cytoplasm, prominent nucleoli, and large nuclei. The tumor cells are stained positive for synaptophysin, chromogranin A, and neuron specific enolase (NSE. The invasive tumor cells in connection with cervical squamous epithelium were focally positive for 34bE12. We made a diagnosis of composite LCNEC and nonkeratinizing squamous cell carcinoma. High-risk HPV test was negative with hybridized captured method 2.

  9. Advances and pathological diagnostic standard of gastroenteropancreatic neuroendocrine neoplasms%胃肠胰神经内分泌肿瘤病理诊断的规范和进展

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Neuroendocrine neoplasm (NEN)is a group of heterogeneous tumors originated from the peptidergic neurons and neuroendocrine cells. A revised system of classification, nomenclature and grading of NEN was proposed by the fourth edition of“World Health Organization classification of tumours of the digestive system”in 2010. It apparently contributes to unify the method of classification, put an end of the confusion in nomenclature, standardize the grading system and predict the outcomes more accurately. With the combination of the results by immunohistochemical studies, pathologists should be in accordance with the requirements to make a diagnosis of NEN with accurate classification, grading and the pathological parameters essential to staging. Recently, new advances in NEN study put forward a new view in the classification and grading system that will lead to the updates of the diagnostic system after further studies on a large scale of samples.%  神经内分泌肿瘤(neuroendocrine neoplasm,NEN)是一组起源于肽能神经元和神经内分泌细胞的异质性肿瘤。2010年第4版《世界卫生组织(World Health Organization,WHO)消化系统肿瘤分类》对NEN的命名、分类和分级进行修订和统一,纠正以往NEN诊断名称使用的混乱、规范NEN的病理分类和分级,增加NEN诊断的互认性,为NEN的临床治疗、预后判断提供必要的病理学信息。病理医师在常规病理诊断报告时应当按照一定的步骤要求,结合免疫组织化学染色结果进行准确的诊断、分类和分级,并提供临床分期必需的病理参数。近年来,有关NEN的临床和基础研究结果,使学者们对2010年第四版《WHO消化系统肿瘤分类》的部分内容和分级标准有了新的认识,提出了新观点,一些数据有待于进一步的大样本探讨证实。

  10. Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Jeanny; Wu, Hong Gyun; Youn, Yeo Kyu; Lee, Kyu Eun; Kim, Kwang Hyun; Park, Do Joon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

  11. Neuroendocrine Responses to Hypoglycemia

    OpenAIRE

    Tesfaye, Nolawit; Seaquist, Elizabeth R.

    2010-01-01

    The counterregulatory response to hypoglycemia is a complex and well-coordinated process. As blood glucose concentration declines, peripheral and central glucose sensors relay this information to central integrative centers to coordinate neuroendocrine, autonomic, and behavioral responses and avert the progression of hypoglycemia. Diabetes, both type 1 and type 2, can perturb these counterregulatory responses. Moreover, defective counterregulation in the setting of diabetes can progress to hy...

  12. Neuroendocrine tumors (carcinoids of the stomach and intestines - early diagnosis and minimally invasive endoscopic procedures

    Directory of Open Access Journals (Sweden)

    Kuryk O.G.

    2014-03-01

    Full Text Available Background. Neuroendocrine tumors of the stomach and intestines are rare diseases. Increasing incidence and complexity of diagnosis of these diseases cause acuteness of the problem. Objective. To evaluate the effectiveness of morphological examination of endoscopic biopsy material for diagnostics of neuroendocrine tumors and for evaluation of completeness of minimally invasive endoscopic surgical interventions (endoscopic mucosal resection and endoscopic submucosal dissection at neuroendocrine tumors. Methods. On the basis of Medical center "Oberig" in 2009 - 2013 in eight cases neuroendocrine tumors were diagnosed: 2 (25 % in the stomach, 2 (25% – in the duodenum, 2 (25% - in the small intestine, 1 (12.5 % - in the ascending colon, 1 (12.5% - in the rectum. Neuroendocrine tumors of stomach and ileum were removed by endoscopic mucosal resection, duodenal bulb and rectum neuroendocrine tumors – by endoscopic submucosal dissection, papillary duodenum, colon and jejunum neuroendocrine tumors – by surgical resection. Results. It was shown, that morphological evaluation of endoscopic mucosal biopsies is effective way to diagnose the neuroendocrine tumors. Conclusion. Endoscopic mucosal resection and endoscopic submucosal dissection allows to get advanced material for morphological diagnosis of neuroendocrine tumors and an adequate method of their removing Citation: Kuryk OG, Yakovenko VO, Bazdyrev VV, Bodnar LV. [Neuroendocrine tumors (carcinoids of the stomach and intestines - early diagnosis and minimally invasive endoscopic procedures]. Morphologia. 2014;8(1:58-64. Ukrainian.

  13. Neuroendocrine mechanisms in athletes.

    Science.gov (United States)

    Misra, Madhusmita

    2014-01-01

    Athletic activity may be associated with alterations in various neuroendocrine axes depending on the state of energy availability. In addition, genetic factors and an underlying predilection for polycystic ovarian syndrome (PCOS) may predispose some athletes to develop functional hypothalamic amenorrhea earlier than other athletes. In conditions of low energy availability associated with athletic activity, changes that occur in various neuroendocrine axes are primarily adaptive, and aim to either conserve energy for the most essential functions, or allow the body to draw on its reserves to meet energy needs. These hormonal changes, however, then lead to changes in body composition and bone metabolism. Impaired bone accrual in younger athletes and low bone density in older athletes constitutes the major pathologic consequence of neuroendocrine changes associated with low energy availability. The female athlete triad of low energy availability, menstrual dysfunction, and low bone density is prevalent in certain kinds of sports and activities, particularly endurance sports, gymnastics, and ballet. It is essential to screen for this condition in athletes at every preparticipation physical and during office visits, and to put in place an effective treatment team to manage the triad early, in order to optimize outcomes. PMID:25248600

  14. Neuroendocrine aspects of prostate oncogenesis

    Directory of Open Access Journals (Sweden)

    P.V. Glybochko

    2010-03-01

    Full Text Available The prostate cancer is a widespread disease in Russia with high growth rate and high death rate. Active work in discovery of methods of early diagnostics of prostate cancer is carrying out. it will allow to increase considerably the efficiency of treatment. the data on topography, structural and functional organization, physiology and regulatory effect of neuroendocrine cells and neuroendocrine hormones and peptides of prostate produced by neuroendocrine cells are presented in the review. Neuroendocrine mechanisms of development, prospects of early diagnostics and prognosis of prostate cancer are analyzed

  15. Nordic guidelines 2014 for diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms

    DEFF Research Database (Denmark)

    Janson, Eva Tiensuu; Sorbye, Halfdan; Welin, Staffan;

    2014-01-01

    BACKGROUND: The diagnostic work-up and treatment of patients with neuroendocrine neoplasms (NENs) has undergone major recent advances and new methods are currently introduced into the clinic. An update of the WHO classification has resulted in a new nomenclature dividing NENs into neuroendocrine...

  16. Gastric hyperplastic polyps coexisting with early gastric cancers, adenoma and neuroendocrine cell hyperplasia.

    Science.gov (United States)

    Karpińska-Kaczmarczyk, K; Lewandowska, M; Białek, A; Ławniczak, M; Urasińska, E

    2016-03-01

    Gastric hyperplastic polyps (GHP) constitute up to 93% of all benign epithelial polyps of the stomach. The average probability of malignant transformation in GHP is 0.6-22% in large series. The aim of the study was to present the coexistence of GHP with early gastric cancer (EGC), gastric adenoma (GA), neuroendocrine cell hyperplasia (NH) and well-differentiated neuroendocrine tumour (NET G1). Three cases were studied to reveal clinical data and morphological changes and to assess the relationship between GHP and accompanying gastric neoplastic lesions. PMID:27179272

  17. Epidemiology of Neuroendocrine Tumors.

    Science.gov (United States)

    Fraenkel, Merav; Faggiano, Antongiulio; Valk, Gerlof D

    2015-01-01

    Formerly named carcinoids, neuroendocrine tumors originate from diffuse endocrine cells, can involve any part of the gastrointestinal tract, endocrine pancreas and bronchopulmonary (BP) tree, and have a wide range of malignant potential. This chapter summarizes the data available on the epidemiology of neuroendocrine neoplasia (NEN) from around the world, including the relative frequency according to organ of origin, annual incidence rates (IR) and trends in IR at the various anatomic sites, age and stage at presentation, racial and gender differences in IR and 5-year survival rates. Over time, changes have been made in the classification and registration of NEN, both in the same registry and across the globe, thus confounding the possibility to draw conclusions as to the true rise in IR of NEN that is observed all over the world. BP NEN has become the most common site in many western countries, while NEN of the rectum is more common in the Far East. In some countries, appendiceal NEN is the most common site in females. When compared to adenocarcinoma of the same location, the prognosis of NEN patients is better. Five-year survival rates are highest for NEN originating in the rectum and appendix, but lower in small intestinal and pancreatic NEN. Future research is needed to understand the contribution of genetic and environmental factors to NEN epidemiology. PMID:26303701

  18. Management of gastric and duodenal neuroendocrine tumors

    Science.gov (United States)

    Sato, Yuichi; Hashimoto, Satoru; Mizuno, Ken-ichi; Takeuchi, Manabu; Terai, Shuji

    2016-01-01

    Gastrointestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, like all NETs. However, the incidence of GI-NETS has been increasing in recent years. Gastric NETs (G-NETs) and duodenal NETs (D-NETs) are the common types of upper GI-NETs based on tumor location. G-NETs are classified into three distinct subgroups: type I, II, and III. Type I G-NETs, which are the most common subtype (70%-80% of all G-NETs), are associated with chronic atrophic gastritis, including autoimmune gastritis and Helicobacter pylori associated atrophic gastritis. Type II G-NETs (5%-6%) are associated with multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome (MEN1-ZES). Both type I and II G-NETs are related to hypergastrinemia, are small in size, occur in multiple numbers, and are generally benign. In contrast, type III G-NETs (10%-15%) are not associated with hypergastrinemia, are large-sized single tumors, and are usually malignant. Therefore, surgical resection and chemotherapy are generally necessary for type III G-NETs, while endoscopic resection and follow-up, which are acceptable for the treatment of most type I and II G-NETs, are only acceptable for small and well differentiated type III G-NETs. D-NETs include gastrinomas (50%-60%), somatostatin-producing tumors (15%), nonfunctional serotonin-containing tumors (20%), poorly differentiated neuroendocrine carcinomas (< 3%), and gangliocytic paragangliomas (< 2%). Most D-NETs are located in the first or second part of the duodenum, with 20% occurring in the periampullary region. Therapy for D-NETs is based on tumor size, location, histological grade, stage, and tumor type. While endoscopic resection may be considered for small nonfunctional D-NETs (G1) located in the higher papilla region, surgical resection is necessary for most other D-NETs. However, there is no consensus regarding the ideal treatment of D-NETs. PMID:27570419

  19. Endocannabinoid Regulation of Neuroendocrine Systems.

    Science.gov (United States)

    Tasker, Jeffrey G; Chen, Chun; Fisher, Marc O; Fu, Xin; Rainville, Jennifer R; Weiss, Grant L

    2015-01-01

    The hypothalamus is a part of the brain that is critical for sustaining life through its homeostatic control and integrative regulation of the autonomic nervous system and neuroendocrine systems. Neuroendocrine function in mammals is mediated mainly through the control of pituitary hormone secretion by diverse neuroendocrine cell groups in the hypothalamus. Cannabinoid receptors are expressed throughout the hypothalamus, and endocannabinoids have been found to exert pronounced regulatory effects on neuroendocrine function via modulation of the outputs of several neuroendocrine systems. Here, we review the physiological regulation of neuroendocrine function by endocannabinoids, focusing on the role of endocannabinoids in the neuroendocrine regulation of the stress response, food intake, fluid homeostasis, and reproductive function. Cannabis sativa (marijuana) has a long history of recreational and/or medicinal use dating back to ancient times. It was used as an analgesic, anesthetic, and antianxiety herb as early as 2600 B.C. The hedonic, anxiolytic, and mood-elevating properties of cannabis have also been cited in ancient records from different cultures. However, it was not until 1964 that the psychoactive constituent of cannabis, Δ(9)-tetrahydrocannabinol, was isolated and its chemical structure determined (Gaoni & Mechoulam, 1964). PMID:26638767

  20. Pre-therapeutic dosimetry and biodistribution of 86Y-DOTA-Phe1-Tyr3-octreotide versus 111In-pentetreotide in patients with advanced neuroendocrine tumours

    International Nuclear Information System (INIS)

    For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy. (orig.)

  1. Current concepts in neuroendocrine disruption.

    Science.gov (United States)

    León-Olea, Martha; Martyniuk, Christopher J; Orlando, Edward F; Ottinger, Mary Ann; Rosenfeld, Cheryl S; Wolstenholme, Jennifer T; Trudeau, Vance L

    2014-07-01

    In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and

  2. REFRACTORY OF WELL-DIFFERENTIATED THYROID CANCER TO THE TREATMENT WITH RADIOACTIVE IODINE

    OpenAIRE

    P O Rumyantsev

    2013-01-01

    Resistance of well-differentiated distant metastases to radioactive iodine treatment severely deteriorate survival prognosis of patients. Chemotherapy (doxorubicin and combinations) and retinoid acid analoques (isotretinоin, roaccutan) implimentation did not allow to recommend them as a therapy of choice. Effectiveness of several multikinase inhibitors (vandetanib, sorafenib, sunitinib) was confirmed in phase II clinical trials. In result of phase III clinical trial of sorafenib (reported on ...

  3. Recent trends in the treatment of well-differentiated endocrine carcinoma of the small bowel

    Institute of Scientific and Technical Information of China (English)

    Gilles; Poncet; Jean-Luc; Faucheron; Thomas; Walter

    2010-01-01

    Well-differentiated endocrine carcinomas of the small bowel are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that may cause carcinoid syndrome. However, many are clinically silent until late presentation with major effects. Initial treatment aims to control carcinoid syndrome with somatostatin analogs. Even if there is metastatic spread, surgical resection of the primitive tumor should be discussed in cases of retractile mesenteritis, small bowel ischemi...

  4. Gastric-Type Extremely Well-Differentiated Adenocarcinoma of the Stomach: A Challenge for Preoperative Diagnosis

    OpenAIRE

    Joo, Mee; Han, Song Hee

    2015-01-01

    Gastric-type extremely well-differentiated adenocarcinoma (EWDA) is a rare type of gastric adenocarcinoma characterized by infiltration of well-formed mucinous glands with little or no nuclear atypia, which resemble foveolar epithelium or pyloric glands. Because of its high degree of differentiation, preoperative biopsy diagnosis of gastric-type EWDA is very difficult. We encountered a case of gastric-type EWDA, manifesting as a Borrmann type 4 lesion, in a 47-year-old man. Despite four repea...

  5. Neuroendocrine targets of endocrine disruptors

    OpenAIRE

    Gore, Andrea C.

    2010-01-01

    The central neuroendocrine systems are responsible for the control of homeostatic processes in the body, including reproduction, growth, metabolism and energy balance, and stress responsiveness. These processes are initiated by signals in the central nervous system, specifically the hypothalamus, and are conveyed first by neural and then by endocrine effectors. The neuroendocrine systems, as the links between the brain and peripheral endocrine systems, play critical roles in the ability of an...

  6. Neuroendocrine Immunoregulation in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Nathalie Deckx

    2013-01-01

    Full Text Available Currently, it is generally accepted that multiple sclerosis (MS is a complex multifactorial disease involving genetic and environmental factors affecting the autoreactive immune responses that lead to damage of myelin. In this respect, intrinsic or extrinsic factors such as emotional, psychological, traumatic, or inflammatory stress as well as a variety of other lifestyle interventions can influence the neuroendocrine system. On its turn, it has been demonstrated that the neuroendocrine system has immunomodulatory potential. Moreover, the neuroendocrine and immune systems communicate bidirectionally via shared receptors and shared messenger molecules, variously called hormones, neurotransmitters, or cytokines. Discrepancies at any level can therefore lead to changes in susceptibility and to severity of several autoimmune and inflammatory diseases. Here we provide an overview of the complex system of crosstalk between the neuroendocrine and immune system as well as reported dysfunctions involved in the pathogenesis of autoimmunity, including MS. Finally, possible strategies to intervene with the neuroendocrine-immune system for MS patient management will be discussed. Ultimately, a better understanding of the interactions between the neuroendocrine system and the immune system can open up new therapeutic approaches for the treatment of MS as well as other autoimmune diseases.

  7. Additive value of pinhole imaging in well differentiated thyroid cancer after surgery

    Energy Technology Data Exchange (ETDEWEB)

    Park, Soon A.; Lim, Seok Tae; Sohn, Myung Hee [Chonbuk National Univ., Chonju (Korea, Republic of)

    2000-07-01

    It is well known that the image by pinhole collimator (PH) has more good resolution than that by high resolution parallel-hole collimator (HRPH). We performed this study to compare PH and HRPH for the detection of metastatic cervical lymphadenopathy (MCL) from remnant thyroid tissue (RT). One hundred forty three studies in 71 patients (M :F=12: 59, age 43.3{+-}13.9 yrs) were included in our investigation. In 111 of 143 studies which were received 1110 MBq of I-131, HRPH and PH were performed 3 days after intake. PH were obtained with 6 mm aperture in size and for 10 minutes. Markers were placed to the submental and sternal notch region. We compared two image modality for the detection of MCL and RT in cervcal region. All of the patients were revealed well differentiated thyroid cancer (papillary: follicular=68: 3). Sixty five of 111 studies (58.6%) showed concordant results and 46 of 111 (41.4%) showed discordant results. In the group of discordant result, PH study was more useful for the detection of lesions with RT and MCL 25/46 (54.3%) and 29/46 (63%), respectively. In well differentiated thyroid cancer after surgery, we conclude that PH has more useful value in monitoring of therapeutic response in RT, and provides additive information for the necessity of high dose radioactive iodine therapy in patient with MCL.

  8. Pericytic mimicry in well-differentiated liposarcoma/atypical lipomatous tumor.

    Science.gov (United States)

    Shen, Jia; Shrestha, Swati; Rao, P Nagesh; Asatrian, Greg; Scott, Michelle A; Nguyen, Vi; Giacomelli, Paulina; Soo, Chia; Ting, Kang; Eilber, Fritz C; Peault, Bruno; Dry, Sarah M; James, Aaron W

    2016-08-01

    Pericytes are modified smooth muscle cells that closely enwrap small blood vessels, regulating and supporting the microvasculature through direct endothelial contact. Pericytes demonstrate a distinct immunohistochemical profile, including expression of smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Previously, pericyte-related antigens have been observed to be present among a group of soft tissue tumors with a perivascular growth pattern, including glomus tumor, myopericytoma, and angioleiomyoma. Similarly, malignant tumor cells have been shown to have a pericyte-like immunoprofile when present in a perivascular location, seen in malignant melanoma, glioblastoma, and adenocarcinoma. Here, we examine well-differentiated liposarcoma specimens, which showed some element of perivascular areas with the appearance of smooth muscle (n = 7 tumors). Immunohistochemical staining was performed for pericyte antigens, including smooth muscle actin, CD146, platelet-derived growth factor receptor β, and regulator of G-protein signaling 5. Results showed consistent pericytic marker expression among liposarcoma tumor cells within a perivascular distribution. MDM2 immunohistochemistry and fluorescence in situ hybridization for MDM2 revealed that these perivascular cells were of tumor origin (7/7 tumors), whereas double immunohistochemical detection for CD31/CD146 ruled out an endothelial cell contribution. These findings further support the concept of pericytic mimicry, already established in diverse malignancies, and its presence in well-differentiated liposarcoma. The extent to which pericytic mimicry has prognostic significance in liposarcoma is as yet unknown. PMID:27063472

  9. Rare Cause of Dysphagy: Giant Polypoid Esophageal Well-Differentiated Liposarcoma

    Directory of Open Access Journals (Sweden)

    Ladislav Mica

    2007-06-01

    Full Text Available Liposarcoma represents one of the most frequent (10–20% malignant mesenchymal tumors in the adult, affecting mostly the soft tissue of extremities, the trunk or the retroperitoneum. This tumor type occurs exceptionally rarely in the gastrointestinal tract with only few cases described in the literature. In this case we present a 73-year-old male patient who was admitted due to loss of weight, anorexia and postprandial emesis with dysphagy. Gastrographin esophagography failed to make precise diagnostics. CT scan of the upper gastrointestinal tract revealed a large esophageal tumor filling out the whole length of the esophagus. The tumor was removed by parasternocleidomastoidal approach with a stapler. Histopathological examination revealed a well-differentiated liposarcoma (grade I. Well-differentiated liposarcomas are characterised by amplified material of the 12q13–15 chromosomal region, present in the form of giant or ring chromosomes and leading to the overexpression of MDM2 and CDK4 genes. MDM2 and CDK4 proteins can be detected immunhistochemically, which was the case in the reported tumor. Overexpression of these proteins leads to suppression of tumor suppressor genes, leading to increased cell survival.

  10. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Langer, Seppo W; Ringholm, Lene; Dali, Christine I;

    2015-01-01

    occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  11. Liver cell adenoma showing sequential alteration of radiological findings suggestive of well-differentiated hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Takayuki Kogure; Yoshiyuki Ueno; Satoshi Sekiguchi; Kazuyuki Ishida; Takehiko Igarashi; Yuta Wakui; Takao Iwasaki; Tooru Shimosegawa

    2009-01-01

    A liver tumor 35 mm in diameter was found incidentally in a 40-year-old woman who had no history of liver diseases or the use of oral contraceptives. Radiological diagnostics showed the typical findings of liver cell adenoma (LCA). Dynamic computed tomography revealed that the tumor showed a homogenous enhancement in the arterial phase and almost the same enhancement as the surrounding liver parenchyma in the delayed phase. The tumor was found to contain fat on magnetic resonance imaging. A benign fat containing liver tumor was suggested. However, radiological findings altered, which caused us to suspect that a welldifferentiated hepatocellular carcinoma (HCC) containing fat was becoming dedifferentiated. Partial hepatectomy was performed and the pathological findings showed the typical findings of LCA. This case was an extremely rare LCA, which had no background of risk for LCA and developed the sequential alteration of the radiological findings to suspect well-differentiated HCC.

  12. Neuroendocrine control of ionic balance in zebrafish.

    Science.gov (United States)

    Kwong, Raymond W M; Kumai, Yusuke; Perry, Steve F

    2016-08-01

    Zebrafish (Danio rerio) is an emerging model for integrative physiological research. In this mini-review, we discuss recent advances in the neuroendocrine control of ionic balance in this species, and identify current knowledge gaps and issues that would benefit from further investigation. Zebrafish inhabit a hypo-ionic environment and therefore are challenged by a continual loss of ions to the water. To maintain ionic homeostasis, they must actively take up ions from the water and reduce passive ion loss. The adult gill or the skin of larvae are the primary sites of ionic regulation. Current models for the uptake of major ions in zebrafish incorporate at least three types of ion transporting cells (also called ionocytes); H(+)-ATPase-rich cells for Na(+) uptake, Na(+)/K(+)-ATPase-rich cells for Ca(2+) uptake, and Na(+)/Cl(-)-cotransporter expressing cells for both Na(+) and Cl(-) uptake. The precise molecular mechanisms regulating the paracellular loss of ions remain largely unknown. However, epithelial tight junction proteins, including claudins, are thought to play a critical role in reducing ion losses to the surrounding water. Using the zebrafish model, several key neuroendocrine factors were identified as regulators of epithelial ion movement, including the catecholamines (adrenaline and noradrenaline), cortisol, the renin-angiotensin system, parathyroid hormone and prolactin. Increasing evidence also suggests that gasotransmitters, such as H2S, are involved in regulating ion uptake. PMID:27179885

  13. Primary neuroendocrine tumor of the sacrum: case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Dujardin, Fanny; Muret, Anne de [Hopital Trousseau, CHRU de Tours, Department of Pathology, Tours (France); Beaussart, Pauline; Waynberger, Eric [Hopital Trousseau, CHRU de Tours, Department of Radiology, Tours (France); Rosset, Philippe [Hopital Trousseau, CHRU de Tours, Department of Orthopaedic Surgery, Tours (France); Mulleman, Denis [Hopital Trousseau, CHRU de Tours, Department of Rheumatology, Tours (France); Pinieux, Gonzague de [Hopital Trousseau, CHRU de Tours, Department of Pathology, Tours (France); Hopital Trousseau, CHRU de Tours, Service d' Anatomie et Cytologie Pathologiques, Tours Cedex 09 (France)

    2009-08-15

    Primary carcinoid tumor (well-differentiated neuroendocrine tumor) of the bone involving the sacrum is extremely rare. We report the case of a 72-year-old man who presented with a 20-year history of intermittent low back pain and was found to have an intraosseous sacral mass on imaging. A needle biopsy revealed that this lesion was a well-differentiated neuroendocrine tumor. Workup did not show any primary tumor or other metastatic disease. There was no associated tailgut cyst or sacrococcygeal teratoma. The lesion was treated with radiation therapy because a surgical approach was rejected. The patient is free of metastatic disease after 28 years evolution of the lesion, retrospectively seen to be present on a conventional radiography performed in 1980. A review of the literature revealed 20 case reports of neuroendocrine tumors arising from the presacral region (with or without associated tailgut cyst or sacrococcygeal teratoma) and sometimes extending to the sacrum. One additional case was located within the neural canal and involved the sacrum, the presacral region, and the rectal wall. Our case is the only tumor arising primarily from the sacrum. The long evolution of this lesion without any other location makes metastatic disease very improbable and this case appears to be a unique example of primary intraosseous sacral carcinoid tumor. (orig.)

  14. Primary neuroendocrine tumor of the sacrum: case report and review of the literature.

    Science.gov (United States)

    Dujardin, Fanny; Beaussart, Pauline; de Muret, Anne; Rosset, Philippe; Waynberger, Eric; Mulleman, Denis; de Pinieux, Gonzague

    2009-08-01

    Primary carcinoid tumor (well-differentiated neuroendocrine tumor) of the bone involving the sacrum is extremely rare. We report the case of a 72-year-old man who presented with a 20-year history of intermittent low back pain and was found to have an intraosseous sacral mass on imaging. A needle biopsy revealed that this lesion was a well-differentiated neuroendocrine tumor. Workup did not show any primary tumor or other metastatic disease. There was no associated tailgut cyst or sacrococcygeal teratoma. The lesion was treated with radiation therapy because a surgical approach was rejected. The patient is free of metastatic disease after 28 years evolution of the lesion, retrospectively seen to be present on a conventional radiography performed in 1980. A review of the literature revealed 20 case reports of neuroendocrine tumors arising from the presacral region (with or without associated tailgut cyst or sacrococcygeal teratoma) and sometimes extending to the sacrum. One additional case was located within the neural canal and involved the sacrum, the presacral region, and the rectal wall. Our case is the only tumor arising primarily from the sacrum. The long evolution of this lesion without any other location makes metastatic disease very improbable and this case appears to be a unique example of primary intraosseous sacral carcinoid tumor. PMID:19360403

  15. Sorafenib in radioactive iodine-refractory well-differentiated metastatic thyroid cancer

    Directory of Open Access Journals (Sweden)

    McFarl

    2014-07-01

    Full Text Available Daniel C McFarland,1 Krzysztof J Misiukiewicz2,31Division of Hematology and Medical Oncology, Mount Sinai Medical Center, New York, NY, USA; 2Division of Hematology and Medical Oncology, 3Department of Otolaryngology, Mount Sinai Medical Center, Ruttenberg Treatment Center, New York, NY, USAAbstract: Recent Phase III data presented at the American Society of Clinical Oncology (ASCO 2013 annual conference by Brose et al led to the US Food and Drug Administration (FDA approval of sorafenib for the treatment of well-differentiated radioactive iodine-resistant metastatic thyroid cancer. This is the second drug in 40 years to be FDA approved for this indication. Recent reviews and a meta-analysis reveal a modest ability to induce a partial remission but substantial ability to halt disease progression. Given the significant activating mutations present in thyroid cancer, many of which are inhibited by sorafenib, the next logical approach may be to combine targeted rational therapies if permitted by collective toxicity profiles. This systematic review aims to summarize the recent Phase II/III data leading to the FDA approval of sorafenib for radioactive iodine therapy differentiated thyroid cancer and highlights recent novel combination therapy trials.Keywords: tyrosine kinase inhibitors, targeted therapy, RAI DTC, novel thyroid cancer treatment

  16. Changing trends in the management of well-differentiated thyroid carcinoma in Korea.

    Science.gov (United States)

    Lee, Yong Sang; Chang, Hang-Seok; Park, Cheong Soo

    2016-06-30

    A questionnaire administered in 2009 found that members of the Korean Association of Thyroid-Endocrine Surgeons (KATES) favored more aggressive treatment of well-differentiated thyroid carcinoma (WDTC) than physicians from other countries. This study assessed the changes in practical management of WDTC in Korea from the previous survey. Questionnaires were sent by e-mail to KATES members. A total of 101 members completed the questionnaire. Their responses were compared with response for the 2009 survey. Of the respondents, 53.5% and 80.2% indicated that they would perform fine-needle aspiration cytology on nodules that were radioactive iodine therapy slightly increased, whereas the percentage favoring external irradiation decreased, in 2014 compared with 2009. The management of Korean patients with WDTC changed from 2009 to 2014. In 2009, Korean respondents favored more aggressive treatment of WDTC compared with respondents from other countries. In 2014, however, Korean respondents favored a more conservative approach, especially in patients with microcarcinomas. PMID:26961223

  17. Effect of radioiodine therapy on pulmonary metastases from well-differentiated thyroid cancer

    International Nuclear Information System (INIS)

    Objective: To investigate effect of radioiodine therapy on pulmonary metastases from well-differentiated thyroid cancer. Methods: Fifty-eight cases of pulmonary metastases were studied utilizing chest X-ray, pulmonary function test and 99Tcm-DTPA aerosol clearance examination. Results: The data of pulmonary function test were of no difference between groups of various radiation doses cumulation (P > 0.05). The differences of vital capacity (VC), fast vital capacity (FVC) and forced expiratory volume in one second (FEV1) were not remarkable between the two groups of male or female patients (P > 0.05), but the difference of maximal volume ventilation (MVV) was P 99Tcm-DTPA aerosol clearance rates between various groups were of no difference (P > 0.05). Only for one female, 43 years old who had received an accumulative dose of 51.8 GBq radioiodine over an 8-yr period, her pulmonary function test showed evidence of restrictive lung disease, chest X-ray showed haziness and DTPA half-time clearance was 26.4 min, which is suggestive of interstitial fibrosis. Conclusion: The cumulative dose of radioiodine and gender of the patients had not statistically significant effects on the pulmonary function. Interstitial fibrosis must be carefully watched when the cumulative radioiodine dose is over 37 GBq

  18. Diagnostic criteria of well differentiated thyroid tumor of uncertain malignant potential; a histomorphological and immunohistochemical appraisal

    International Nuclear Information System (INIS)

    Background: Well differentiated thyroid tumor of uncertain malignant potential (WDTUMP) represents a true ‘‘gray zone’’ of ‘‘follicular patterned’’ thyroid lesions, that needs to be characterized in order to outright the diagnosis of carcinoma and avoid unnecessary aggressive treatment. Aim: To emphasize on the histomorphological criteria for more accurate diagnosis of WDT-UMP. Also to compare the immunohistochemical expression of CK19 of WDT-UMP versus adenoma and papillary thyroid carcinoma (PTC). Materials and methods: The study included 60 thyroid specimens; 18 WDT-UMPs, 24 PTC (18 classic variant and 6 follicular variants) and 18 benign thyroid lesions (8 adenoma, 6 Hashimoto’s thyroiditis and 4 hyperplastic nodules). H and E stained sections were assessed according to the published major and minor criteria of malignancy in the thyroid. CK 19 immunostaining was examined and evaluated according to the proportion and intensity scores. Results: We could detect the absence of nuclear inclusions, presence of characteristic nuclear groove, nuclear clearing, ovoid nuclei, nuclear crowdness, nuclear enlargement and pleomorphism as important reliable features for diagnosis of WDT-UMP with Ρ value (<0.0001 for each). WDT-UMP showed moderate to strong CK 19 immunostaining with proportion scores 3 and 4; an intermediate expression profile; higher than adenoma and less than papillary carcinoma ( Ρ < 0.0001). Conclusion: The constellations of both major and minor criteria of malignancy are important clues for WDT-UMP diagnosis which could be ascertained by CK 19 immunostaining.

  19. CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.

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    Sanghoon Lee

    Full Text Available The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD and dedifferentiated (DD liposarcomas.From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR.There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05. Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7% and MDM2 amplification in 46 cases (95.8%. WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041. High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54 was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012 and multivariate analyses (P = 0.020.Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

  20. Contrast enhanced multi-detector CT and MR findings of a well-differentiated pancreatic vipoma

    Institute of Scientific and Technical Information of China (English)

    Luigi; Camera; Rosa; Severino; Antongiulio; Faggiano; Stefania; Masone; Gelsomina; Mansueto; Simone; Maurea; Rosa; Fonti; Marco; Salvatore

    2014-01-01

    Pancreatic vipoma is an extremely rare tumor accounting for less than 2% of endocrine pancreatic neoplasms with a reported incidence of 0.1-0.6 per million. While cross-sectional imaging findings are usually not specific, exact localization of the tumor by means of either computed tomography(CT) or magnetic resonance(MR) is pivotal for surgical planning. However, cross-sectional imaging findings are usually not specific and further characterization of the tumor may only be achieved bysomatostatin-receptor scintigraphy(SRS). We report the case of a 70 years old female with a two years history of watery diarrhoea who was found to have a solid, inhomogeneously enhancing lesion at the level of the pancreatic tail at Gadolinium-enhanced MR(Somatom Trio 3T, Siemens, Germany). The tumor had been prospectively overlooked at a contrast-enhanced multi-detector CT(Aquilion 64, Toshiba, Japan) performed after i.v. bolus injection of only 100 cc of iodinated non ionic contrast media because of a chronic renal failure(3.4 mg/mL) but it was subsequently confirmed by SRS. The patient first underwent a successful symptomatic treatment with somatostatin analogues and was then submitted to a distal pancreasectomy with splenectomy to remove a capsulated whitish tumor which turned out to be a well-differentiated vipoma at histological and immuno-histochemical analysis.

  1. A New Strategy for the Surgical Management of RLN Infiltrated by Well-Differentiated Thyroid Carcinoma

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    Jan Boucek

    2014-01-01

    Full Text Available Well-differentiated thyroid carcinoma (WDTC represents the most common endocrine malignancy. Despite excellent prognoses exceeding 90% in 10-year follow-up, there are clinically controversial issues. One of these is extrathyroidal tumour extension invading recurrent laryngeal nerve (RLN. The spread outside of the thyroid parenchyma and invasion to the surrounding structures, classified as always T4a, are the most important negative prognostic factor for the WDTC. Conversely, resection of the RLN leads to vocal cord paralysis with hoarseness, possible swallowing problems, and finally decreased quality of life. We propose a new algorithm for intraoperative management based on the MACIS classification, which would allow swift status evaluation pre/intraoperatively and consider a possibility to preserve the infiltrated RLN without compromising an oncological radicality. In the case of a preoperative vocal cord paralysis (VCP and confirmation of the invasive carcinoma, a resection of the RLN and the nerve graft reconstruction are indicated. Preoperatively, unaffected vocal cord movement and intraoperatively detected RLN infiltration by the invasive WDTC require an individual assessment of the oncological risk by the proposed algorithm. Preservation of the infiltrated RLN is oncologically acceptable only in specific groups of patients of a younger age with a minor size of primary tumour.

  2. Lipoma-like hibernoma: an atypical lipoma/well-differentiated liposarcoma mimicker

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    Reis-Filho Jorge S.

    2002-01-01

    Full Text Available Hibernomas are benign lipomatous tumors which show differentiation toward brown fat. Recently, unusual variants have been described, including myxoid, spindle cell, and lipoma-like variants. Lipoma-like hibernoma (LLH is characterized by mature univacuolated adipocytic cells with rare admixed multivacuolated brown fat-like cells, which may resemble lipoblasts, leading to a misdiagnosis of atypical lipoma/well-differentiated liposarcoma (AL/WDLS. We herein report a case of LLH arising on the anterior aspect of the left thigh of a 17-year-old female. A marginal excision was performed. The patient was discharged and remains well four months after surgery. Histological examination showed a lobulated neoplasm composed of univacuolated mature adipose cells admixed with small vessels and occasional mast cells. Scattered islands of brown fat-like cells accounting for less than 10% of the neoplasm were found. Sometimes these cells presented indented and scalloped nuclei, resembling lipoblasts. A final diagnosis of LLH was made based on the presence of focal areas with typical hibernoma morphology, and the lack of atypical hyperchromatic stromal cells. Pathologists must be aware of the typical histological findings of LLH, not to confuse it with AL/WDLS.

  3. Illuminating somatostatin analog action at neuroendocrine tumor receptors

    OpenAIRE

    Reubi, Jean Claude; Schonbrunn, Agnes

    2013-01-01

    Somatostatin analogs for the diagnosis and therapy of neuroendocrine tumors (NETs) have been used in clinical applications for more than two decades. Five somatostatin receptor subtypes have been identified and molecular mechanisms of somatostatin receptor signaling and regulation have been elucidated. These advances increased understanding of the biological role of each somatostatin receptor subtype, their distribution in NETs as well as agonist-specific regulation of receptor signaling, int...

  4. Radioiodine therapy in skeletal metastases from well-differentiated thyroid cancer: a Johannesburg experience

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    Nalini Sindy Perumal

    2010-03-01

    Full Text Available Aim.The purpose of this study was to examine the outcome of patients with skeletal metastases from well-differentiated thyroid carcinoma and analyse the effect of variables that influence the prognosis of this disease. Method. We retrospectively reviewed 352 patients treated and followed-up at the Charlotte Maxeke Johannesburg Academic Hospital’s thyroid cancer clinic from 1982 - 1999. Findings. Skeletal metastases were diagnosed in 24 (6.8%, 17 at presentation to the thyroid clinic, and 7 at follow-up. Patients’ ages ranged from 30 - 77 years (mean 53.9 years and the female:male ratio was 3.8:1. Based on the original pathology reports from resected tumours, 9 were papillary and 15 were follicular cancers. Twenty-three of the 24 patients underwent thyroid surgery as the initial management – total thyroidectomy in 18, subtotal thyroidectomy in 3, and lobectomy plus neck dissection in one. The diagnosis of thyroid cancer was based on lobectomy in a single subject. Radioactive iodine (RAI was used as part of the original treatment; external radiation therapy (XRT was mainly used to alleviate severe symptoms. Twenty-one patients (87.5% were treated with RAI; 11 (45.8% received radiotherapy. Seven patients died – 4 from neurological disease directly associated with bone metastases. Of the 17 surviving patients, 2 appeared to be disease-free, 8 were asymptomatic despite overt bony disease, and 7 had persistent symptoms which much improved in 5. Bone metastases were uncommon, and follicular cancer predominated in this survey. Conclusion. RAI therapy improves quality of life in most patients. There is a place for XRT.

  5. Defining a Valid Age Cutoff in Staging of Well-Differentiated Thyroid Cancer

    Science.gov (United States)

    Nixon, Iain J.; Kuk, Deborah; Wreesmann, Volkert; Morris, Luc; Palmer, Frank L.; Ganly, Ian; Patel, Snehal G.; Singh, Bhuvanesh; Tuttle, R. Michael; Shaha, Ashok R.; Gönen, Mithat; Shah, Jatin P.

    2016-01-01

    Background Age 45 years is used as a cutoff in the staging of well-differentiated thyroid cancer (WDTC) as it represents the median age of most datasets. The aim of this study was to determine a statistically optimized age threshold using a large dataset of patients treated at a comprehensive cancer center. Methods Overall, 1807 patients with a median follow-up of 109 months were included in the study. Recursive partitioning was used to determine which American Joint Committee on Cancer (AJCC) variables were most predictive of disease-specific death, and whether a different cutoff for age would be found. From the resulting tree, a new age cutoff was picked and patients were restaged using this new cutoff. Results The 10-year disease-specific survival (DSS) by Union for International Cancer Control (AJCC/UICC) stage was 99.6, 100, 96, and 81 % for stages I–IV, respectively. Using recursive partitioning, the presence of distant metastasis was the most powerful predictor of DSS. For M0 patients, age was the next most powerful predictor, with a cutoff of 56 years. For M1 patients, a cutoff at 54 years was most predictive. Having reviewed the analysis, age 55 years was selected as a more robust age cutoff than 45 years. The 10-year DSS by new stage (using age 55 years as the cutoff) was 99.2, 98, 100, and 74 % for stages I–IV, respectively. Conclusion A change in age cutoff in the AJCC/UICC staging for WDTC to 55 years would improve the accuracy of the system and appropriately prevent low-risk patients being overstaged and overtreated. PMID:26215199

  6. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

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    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  7. Immune-Neuroendocrine Interactions and Autoimmune Diseases

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    Luis J. Jara

    2006-01-01

    Full Text Available The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.

  8. Gastroenteropancreatic Neuroendocrine Tumors: Hormonal Treatment Updates

    Directory of Open Access Journals (Sweden)

    Simon Khagi

    2014-03-01

    Full Text Available Gastroenteropancreatic neuroendocrine tumors are a heterogeneous group of carcinomas that remain difficult to treat withconventional cytotoxic regimens. The 2014 American Society of Clinical Oncology (ASCO Gastrointestinal CancersSymposium brought us new insights into the management of gastroenteropancreatic neuroendocrine tumors. The focus ofthis review will serve to highlight specific Abstracts (#268 and #273 that help shed light on a novel, targeted means oftreating gastroenteropancreatic neuroendocrine tumors.

  9. Morphologic Analysis of Pulmonary Neuroendocrine Tumors

    OpenAIRE

    Lee, Seung Seok; Kang, Myunghee; Ha, Seung Yeon; An, Jungsuk; Roh, Mee Sook; Ha, Chang Won; Han, Jungho

    2013-01-01

    Background Few studies on how to diagnose pulmonary neuroendocrine tumors through morphometric analysis have been reported. In this study, we measured and analyzed the characteristic parameters of pulmonary neuroendocrine tumors using an image analyzer to aid in diagnosis. Methods Sixteen cases of typical carcinoid tumor, 5 cases of atypical carcinoid tumor, 15 cases of small cell carcinoma, and 51 cases of large cell neuroendocrine carcinoma were analyzed. Using an image analyzer, we measure...

  10. [Neuroendocrine neoplasms of the mediastinum].

    Science.gov (United States)

    Brcic, L; Heidinger, M; Popper, H

    2016-09-01

    Primary neuroendocrine tumors (NET) in the mediastinum are very rare and among them thymic NETs are the most common. They represent 5 % of all thymic and mediastinal tumors. The WHO classification from 2015 subdivides thymic NETs into three groups; low grade (typical carcinoid), intermediate grade (atypical carcinoid) and high grade (large cell neuroendocrine carcinoma and small cell carcinoma). Through this change of mediastinal/thymic NET classification into three groups of malignancy, the nomenclature was adapted to that of the lungs, while the histological criteria for each entity remained the same. Thymic NETs typically occur in middle-aged adults and predominantly in males. Approximately 30 % are asymptomatic and the rest present with symptoms caused by local tumor growth, distant metastases and/or endocrine manifestations. Carcinoids can also occur as a part of multiple endocrine neoplasia type 1 (MEN1) and at the time of diagnosis commonly present with regional lymph node or distant metastases, which most often affect the lungs and bones. For the correct diagnosis tumor cell morphology, mitotic count and/or necrosis are crucial. Patients with typical carcinoids have the best prognosis, whereas the prognosis is slightly worse for atypical carcinoids but very poor for large cell neuroendocrine carcinomas. Small cell carcinomas have the worst prognosis and the shortest median survival time of approximately 14 months.

  11. Extremely well-differentiated adenocarcinoma of the stomach: Clinicopathological and immunohistochemical features

    Institute of Scientific and Technical Information of China (English)

    Takashi Yao; Takashi Utsunomiya; Masafumi Oya; Kenichi Nishiyama; Masazumi Tsuneyoshi

    2006-01-01

    AIM: Minimal deviation carcinoma of the uterine cervix,otherwise known as extremely well-differentiated adenocarcinoma (EWDA), is characterized by its benign microscopic appearance in contrast to its aggressive behavior.In order to elucidate the clinicopathological features and biological behavior of the gastric counterpart of EWDA,we, using immunohistochemistry, analyzed nine lesions for the phenotypic expression, proliferative activity, and the expression of oncogene-associated products.METHODS: Clinicopathological features, including preoperative biopsy diagnosis, were reviewed. Using immunohitstochemistry, Ki-67 labeling index and expression of p53 and c-erbB-2 protein in the gastric lesions were detected.RESULT: Locations in the middle or upper third of the stomach and polypoid macroscopic features are characteristic of EWDA of the stomach. Although 4 of the 9 lesions showed only focal lymphatic or venous invasion,lymph node metastasis was not present and none of the patients died of the lesions (mean follow-up period, 56mo). All 9 cases of EWDA could be classified into gastric phenotype (5 lesions) and intestinal phenotype (4 lesions). The former resembled gastric foveolar epithelium,mucous neck cells or pyloric glands, but their papillary structures were frequently elongated and the tumor cells and their nuclei were slightly larger and more hyperchromatic compared to normal epithelium. The latter resembled intestinal metaplasia with minimal nulcear atypia and irregular glands; two of these lesions demonstrated complete intestinal phenotype, while two demonstrated incomplete intestinal phenotype. Ki-67 labeling index was low and none of the cases revealed over-expression of p53 and c-erbB-2 protein.CONCLUSION: Unlike minimal deviation carcinoma of the cervix, these findings suggest that EWDA of the stomach is a lesion of low-grade malignancy. This favorable biological behavior is supported by the data of a low Ki-67 labeling index and a lack of p53 or c

  12. Method of Detection of Well-Differentiated Thyroid Cancers in Obese and Non-Obese Patients.

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    Jonathan Zagzag

    Full Text Available The incidence of well-differentiated thyroid cancer (WDTC is increasing rapidly. Many authors feel that this increase is due to over-diagnosis and that one of the contributing factors is the increasing use of various imaging studies. The rate of obesity has also been increasing in the United States. It has been suggested that patients with an increased body mass index (BMI kg/m2 have a higher incidence of WDTC than patients with normal BMI. One might hypothesize that thyroid nodules are more difficult to palpate in obese patients and that as more cancers are detected by imaging the apparent rate of increase in WDTC in obese patients would appear to be greater than in non-obese patients. This study was undertaken to evaluate this hypothesis by determining if there is any difference in the way thyroid cancers are initially detected in obese and non-obese patients.The medical records of all 519 patients with a postoperative diagnosis of WDTC who underwent thyroidectomy at NYU Langone Medical Center from January 1, 2007 through August 31, 2010 by the three members of NYU Endocrine Surgery Associates were reviewed. Patients were divided into Non-obese (BMI<30 kg/m2 and Obese (BMI≥30 kg/m2 groups. Patients were also divided by the initial method of detection of their tumor into Palpation, Imaging, and Incidental groups.The final study group contained 270 patients, 181(67% of whom were in the Non-obese Group and 89(33% were in the Obese Group. In the Non-obese group, 81(45% of tumors were found by palpation, 72(40% were found by imaging, and 28(16% were found incidentally. In the Obese group, 40(45% were found by palpation, 38(43% were found by imaging, and 11(12% were found incidentally. These differences were not statistically significant (p-value 0.769.We show that BMI does not play a role in the method of initial detection in patients with WDTC. This suggests that the prevalence of WDTC detected by imaging is not an artifact caused by an

  13. Neuroendocrine disorders: pituitary imaging.

    Science.gov (United States)

    Faje, Alexander; Tritos, Nicholas A; Swearingen, Brooke; Klibanski, Anne

    2016-01-01

    Significant advances in pituitary imaging have taken place in the past several decades, including the introduction of magnetic resonance imaging (MRI). This imaging modality has vastly improved our ability to detect and characterize sellar masses and more accurately characterize the extent and spread of lesions in and around the sella. Intraoperative MRI may help improve the completeness of resection of sellar masses. Other imaging modalities, including magnetic resonance angiography, computed tomography (CT), and CT angiography, have an important role in specific cases. Interventional methods, including bilateral inferior petrosal sinus sampling, may establish the pituitary origin of corticotropin (ACTH) excess in patients with ACTH-dependent Cushing's syndrome. Pituitary imaging should be obtained in patients with pituitary hormone excess, hypopituitarism, or mass effect in the sella. Despite rapid advances in pituitary imaging, there are several diagnostic challenges remaining. Future research may help improve the radiographic detection of small sellar lesions, such as ACTH-secreting adenomas causing Cushing's disease, accurately characterize the type and extent of sellar pathologies, and provide prognostic information regarding their growth potential. PMID:27430447

  14. Refractory hypercalcemia and ectopic calcitonin secretion in a malignant pancreatic neuroendocrine tumor: hypocalcemic effects on cinacalcet

    OpenAIRE

    Valdes Socin, Hernan Gonzalo; Rubio Almanza, Matilde; LOLY, Jean-Philippe; Polus, Marc; Beckers, Albert

    2013-01-01

    Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments. Observation: In 2009, a well differentiated pancreatic neuroendocrine tumor (Ki-67= 2%) is diagnosed in a 52-year-old diabetic man. The tumor is revealed with a splenic and hepatic carcinomatosis. Plasmatic calcium was: 3.54 mmol/L (2.15 - 2.6). Biology showed hypophosphatemia, PTH < 4 ng/ml, high 1-25 OH VitD, calcitonin: 1016 ng/ml (< 12 ng/ml). H...

  15. Neuroendocrine Carcinomas of the Gastroenteropancreatic System

    DEFF Research Database (Denmark)

    Ilett, Emma Elizabeth; Langer, Seppo W; Olsen, Ingrid Holst;

    2015-01-01

    To date, empirical literature has generally been considered lacking in relation to neuroendocrine carcinomas (NECs), the highly malignant subgroup of neuroendocrine neoplasms. NECs are often found in the lungs or the gastroenteropancreatic (GEP) system and can be of small or large cell type...

  16. Management of low-risk well-differentiated thyroid cancer based only on thyroglobulin measurement after recombinant human thyrotropin.

    Science.gov (United States)

    Wartofsky, Leonard

    2002-07-01

    A multicenter study was undertaken to ascertain prevalence and significance of recombinant human thyrotropin (rhTSH)-stimulated increases in thyroglobulin (Tg) levels in thyroid cancer patients classified to be at low risk for recurrence. Patients were eligible for enrollment if they had undergone near-total or total thyroidectomy and remnant ablation between 1-10 years prior to enrollment and had received thyroxine suppression therapy (THST) with a TSH level of < 0.5 mU/L and Tg level less than or equal to 5 ng/mL within the prior year. Patients with anti-Tg antibodies, distant metastases, or other evidence of residual disease were excluded. Four hundred eighty-six patients were entered into the study, and 300 were considered eligible and comprise the study population. TSH, Tg, and anti-Tg antibody levels were obtained at baseline, followed by intramuscular injection of 0.9 mg of rhTSH on days 1 and 2 and measurement of Tg on day 5. After rhTSH, 53 patients (18%) had elevations in Tg of at least 2 ng/mL, including 33 patients (11%) with increases from baseline of equal to or greater than 5 ng/mL. Patients with an initial advanced stage of disease were more likely to display elevations in Tg after rhTSH. One third of those with stage III disease displayed elevations in Tg of 2 ng/mL or more. Patients within 5 years of thyroidectomy were as likely to display elevations in rhTSH-stimulated Tg as those 5-10 years from surgery. In conclusion, these data suggest rhTSH-stimulated Tg testing without scan may be a useful tool in the follow-up of patients with low-risk thyroid cancer, and may serve to identify patients previously thought free of disease on the basis of undetectable Tg levels while undergoing THST. A strategy is presented for incorporation of this approach into the management of patients with low-risk well-differentiated thyroid cancer.

  17. DMBT1 is frequently downregulated in well-differentiated gastric carcinoma but more frequently upregulated across various gastric cancer types

    DEFF Research Database (Denmark)

    Conde, Ana R; Martins, Ana P; Brito, Miguel;

    2007-01-01

    Well-differentiated gastric carcinomas are considered to represent a distinct entity emerging via specific molecular changes different from those found in other gastric carcinoma types. The gene deleted in malignant brain tumours 1 (DMBT1) at 10q25.3-q26.1 codes for a protein presumably involved ...

  18. The value of fat-suppressed T2 or STIR sequences in distinguishing lipoma from well-differentiated liposarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Galant, J. [Servicio de Radiodiagnostico, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain); Resonancia Magnetica del Sureste, Murcia (Spain); Marti-Bonmati, L. [Department of Radiology, Hospital Universitario Dr. Peset, Valencia (Spain); Saez, F. [Department of Radiology, Hospital Cruces de Baracaldo, Vizcaya (Spain); Soler, R. [Department of Radiology, Hospital Juan Canalejo, A Coruna (Spain); Alcala-Santaella, R. [Department of Traumatology, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain); Navarro, M. [Servicio de Radiodiagnostico, Hospital Universitario San Juan de Alicante, Ctra. Nacional 332 Alicante-Valencia s/n, 03550 San Juan de Alicante (Spain)

    2003-02-01

    The objective of this study was to evaluate the diagnostic value of fat-suppressed T2-weighted (FS-T2) images or short tau inversion recovery (STIR) imaging in distinguishing lipoma from lipoma-like subtype of well-differentiated liposarcoma. Spin-echo T1-weighted and STIR or fat-suppression T2-weighted sequences were performed in 60 lipomas and 32 lipoma-like well-differentiated liposarcomas, histologically proven, looking for thick septa or nodules in T1-weighted images and linear, nodular, or amorphous hyperintensities on FS-T2/STIR sequences. Fourteen lipomas (23.3%) showed thick septa and/or nodules on T1, whereas on FS-T2 or STIR sequences only seven (11.7%) displayed hyperintense nodules and/or septa. All well-differentiated liposarcomas contained these signs on FS-T2 or STIR sequences. The presence of hyperintense septa or nodules in a predominantly lipomatous tumor on FS-T2/STIR sequences helps to differentiate malignant tumors from lipomas. Employing the presence of hyperintense nodules and/or septa as criteria of malignancy specificity was 76.6% and sensitivity 100%. Overdiagnoses of well-differentiated liposarcoma can occur due to the presence of non-lipomatous areas within lipomas. (orig.)

  19. Role of radiotherapy for pancreatobiliary neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Shim; Choi, Jin Hyun; Choi, Chihwan; Seong, Jinsil [Dept. of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2013-09-15

    We investigated the role of radiotherapy (RT) for pancreatobiliary neuroendocrine tumors (PB-NETs). We identified 9 patients with PB-NETs who received RT between January 2005 and March 2012. Of these 9 patients, 4 were diagnosed with NETs in the pancreas and 5 were diagnosed with NETs in the gallbladder. All patients received RT to the primary tumor or resection bed with a median total irradiation dose of 50.4 Gy, with or without chemotherapy. The tumor response rate and tumor control rate in the RT field were 60% and 100 %, respectively. All 4 patients who underwent surgery had no evidence of disease in the RT field. Of the 5 patients who received RT to the primary gross tumor, 1 had complete response, 2 had partial response, and 2 had stable disease in the RT field. The median time to progression was 11 months. Of the 9 patients, four patients had no progression, and 5 patients had progression of disease (locoregional, 2; distant, 2; locoregional/distant, 1). Of the 4 patients without progression, 3 were treated with RT in adjuvant or neoadjuvant setting, and one received RT to primary tumor. One patient experienced radiation-induced duodenitis at 3 months after concurrent chemoradiation without treatment-related mortality. RT can yield local control for advanced PB-NETs. RT should be considered an essential part of multimodality treatment in management of advanced PB-NETs.

  20. Pancreatic Neuroendocrine Tumors: Role of Novel Agents

    Directory of Open Access Journals (Sweden)

    Alexios S Strimpakos

    2011-03-01

    Full Text Available Neuroendocrine tumors of pancreas (PNET are very rare, consisting of heterogeneous histological subtypes with a variable natural history and different clinical manifestations. Although the vast majority of these neoplasms are sporadic, it is possible to be part of a genetic syndrome such as multiple endocrine neoplasia 1 (MEN-1 or tuberous sclerosis (TSC. When systemic treatment is required the options are limited and management strategy is generally based on experts’ consensus or clinical experience. The prognosis is usually better than in pancreatic adenocarcinoma, though poorly differentiated PNET behave aggressively and survival is shortened. Since last year, there has been a significant advance in the management of PNET, after reported data confirmed the efficacy of everolimus, an mTOR inhibitor, in patients with advanced disease. At the 2011 American Society of Clinical Oncology (ASCO Gastrointestinal Symposium, updated results of the phase III trial (RADIANT-3 regarding the efficacy of everolimus in PNET (Abstract #158 were reported, along with the results of a subgroup analysis of the Japanese patients enrolled in this study (Abstract #289. Another agent with promising activity in PNET which will be discussed in this review is sunitinib, a biological agent with multikinase inhibitor properties (Abstract #244.

  1. Role of radiotherapy for pancreatobiliary neuroendocrine tumors

    International Nuclear Information System (INIS)

    We investigated the role of radiotherapy (RT) for pancreatobiliary neuroendocrine tumors (PB-NETs). We identified 9 patients with PB-NETs who received RT between January 2005 and March 2012. Of these 9 patients, 4 were diagnosed with NETs in the pancreas and 5 were diagnosed with NETs in the gallbladder. All patients received RT to the primary tumor or resection bed with a median total irradiation dose of 50.4 Gy, with or without chemotherapy. The tumor response rate and tumor control rate in the RT field were 60% and 100 %, respectively. All 4 patients who underwent surgery had no evidence of disease in the RT field. Of the 5 patients who received RT to the primary gross tumor, 1 had complete response, 2 had partial response, and 2 had stable disease in the RT field. The median time to progression was 11 months. Of the 9 patients, four patients had no progression, and 5 patients had progression of disease (locoregional, 2; distant, 2; locoregional/distant, 1). Of the 4 patients without progression, 3 were treated with RT in adjuvant or neoadjuvant setting, and one received RT to primary tumor. One patient experienced radiation-induced duodenitis at 3 months after concurrent chemoradiation without treatment-related mortality. RT can yield local control for advanced PB-NETs. RT should be considered an essential part of multimodality treatment in management of advanced PB-NETs.

  2. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...... be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later....

  3. Pulmonary Neuroendocrine Tumor with Thyroid Gland Metastasis: Case Report

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    Cristina Corina Pop Radu

    2015-04-01

    Full Text Available Neuroendocrine tumors (NET represent approximately 20% of all primary neoplasms of the lung. Histologic confirmation is important for treatment and prognosis determination. NET are classified according to four subtypes in the lung: typical carcinoid tumor (TC, atypical carcinoid tumor (AC, small cell carcinoma (SCC, and large cell neuroendocrine carcinoma (LCNEC. TC is low-grade, AC is intermediate-grade, and SCC and LCNEC are high-grade malignancies. Case report: A 57 years old woman, affected by a cervical anterior tumor and a proliferative tissue below the glottis was referred to our Endocrinology Department from ENT service for a second opinion. An ultrasound scan of the neck showed a polynodular goiter with bilaterally lymph nodes enlargement with suspicious malignancy characters. She had undergone surgery for the cervical anterior mass and for the laryngeal biopsy. Histopathological examination results were consistent with a SCC; neoplastic cells showed immunoreactivity to synaptophysin, neuron specific enolase and chromogranin. The serum levels of serotonin, cromogranin A, calcitonin, carcinoembryonic antigen, ACTH, PTH, TSH, FT4 were normal. Fine needle aspiration biopsy of her left thyroid lobe nodule was performed and the cytopathological exam was compatible with a neuroendocrine tumor metastasis. Thoracic and abdominal computed tomography was normal at that moment. Chest CT revealed the primary pulmonary tumor at 6 months after presentation. The therapeutic option for advanced or metastatic NETs is mainly palliation of symptoms; options need to be individualized and, therefore, rely on the knowledge of multidisciplinary teams.

  4. Neuroendocrine differentiation in prostate cancer%前列腺癌的神经内分泌分化

    Institute of Scientific and Technical Information of China (English)

    Jingwen Wang; Yang Yao

    2008-01-01

    Hormonal therapy is an important treatment for advanced/metastatic prostate cancer. But it can induce neuroen-docrine (NE) differentiation in prostate cancer cells. These NE cells will secrete manifold neural peptide or hormones which can lead to androgen-independent growth of non-NE tumor cells. When this happens, hormonal therapy becomes useless and indicates bad prognosis. In this paper, the mechanism of neuroendocrine differentiation and its relationship with androgen-independent were reviewed.

  5. 热疗联合化疗治疗晚期非小细胞肺癌伴神经内分泌化的临床研究%Clinical study of thermotherapy with chemotherapy in advanced non-small cell lung cancer with neuroendocrine differentiation

    Institute of Scientific and Technical Information of China (English)

    王勇; 张延顺

    2014-01-01

    Objective To study the clinical efficacy of thermotherapy combined chemotherapy in the treatment of the advanced non-small cell lung carcinoma with neuroendocrine differentiation (NSCLC-NED).Methods The clinical data of 16 patients with NSCLC-NED were retrospectively reviewed.To analyzed the efficacy and survival of these patients.All patients were treated by thermotherapy with the combined chemotherapy regiment of platinum agents.Results There were 7 partial responses and 4 stable disease,The overall response rate (RR) was 43.8%.The one year survival rate was 37.5% (6/16).The improvement rate of quality of life was 62.5% (10/16).Conclusion Neuroendocrine differentiation is an important indicator of biological behavior of NSCLC.Thermochemotherapy is an active regimen in the advanced NSCLC-NED with an acceptabe toxicity.%目的 探讨热疗联合化疗治疗晚期非小细胞肺癌伴神经内分泌化(NSCLC-NED)的临床疗效.方法 回顾性分析16例NSCLC-NED患者的临床资料,所有患者接受含铂类联合方案化疗,同时给予局部热疗,随访其疗效及生存情况.结果 16例患者中部分缓解(PR)7例,稳定(SD)4例,近期有效率(RR)43.8%,1年生存率为37.5% (6/16),生活质量改善率62.5% (10/16).结论 神经内分泌分化是NSCLC生物学行为的重要指标,化疗联合热疗安全、有效.

  6. Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

    Science.gov (United States)

    Hatton, M Q; Reed, N S

    1997-01-01

    The role of chemotherapy in malignant neuroendocrine tumours is difficult to assess because of their rarity and variation in biological behaviour. We present a retrospective review of chemotherapy given to 18 patients with metastatic and one with locally advanced neuroendocrine tumours. There were eight poorly differentiated neuroendocrine tumours, six thyroid medullary carcinomas, two phaeochromocytomas, two pancreatic islet cell tumours and one undifferentiated neuroblastoma. Four patients were given 3-weekly dacarbazine, vincristine and cyclophosphamide (DOC) chemotherapy. In eight patients, this regimen was modified by substituting the dacarbazine and cisplatin and etoposide (OPEC). A further six patients were treated with dacarbazine reintroduced into the 3-weekly regimen (DOPEC). The remaining patient received cisplatin and etoposide. There were two complete responses (both with OPEC) and eight partial responses (two with DOC, three with OPEC and three with DOPEC). Five patients had stable disease and four progressed. Four received further chemotherapy on relapse, producing one complete and one partial response. The median response duration to initial chemotherapy was 10 months (range 3-34). The median survival was 12 months (range 1-42). The main toxicity was haematological, with grade 3-4 neutropenia in 12 patients; eight suffered episodes of sepsis. One death was treatment related. Other toxicity was mild although three patients discontinued vincristine with grade 2 neurotoxicity. The response rate and side effects of these three regimens appear comparable. We conclude that, although these patient numbers are small, combination chemotherapy produces an encouraging response rate (53%; 95% CI 30-75) in malignant neuroendocrine tumours, with acceptable toxicity. PMID:9448967

  7. Biomarkers in Pancreatic Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Maria Serafeim Theochari

    2014-03-01

    Full Text Available The aim of biomarkers is to identify patients most likely to benefit from a therapeutic strategy. Pancreatic neuroendocrinetumors are rare neoplasms that arise in the endocrine tissues of the pancreas. Pancreatic neuroendocrine tumors represent3% of primary pancreatic neoplasms and their incidence has risen. The SMAD4 gene is located on chromosome 18q andsomeday the SMAD4 gene status may be useful for prognostic stratification and therapeutic decision. The cells respond toenvironmental signals by modulating the expressions of genes contained within the nucleus, when genes are activated aretranscribed to generate messenger RNA (mRNA. The examination of multiple expressed genes and proteins provides moreuseful information for prognostication of individual tumors. Here we summarize and discuss findings presented at the 2014ASCO Gastrointestinal Cancers Symposium. Anna Karpathakis et al. (Abstract #212 reported data about the role of DNAmethylation in gastrointestinal neuroendocrine tumors. Christina Lynn Roland et al. (Abstract #250 looked the impact OfSMAD4 on oncologic outcomes. Bong Kynn Kang et al. (Abstract #251 investigated prognostic biomarker using microRNAarray technology.

  8. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas

    DEFF Research Database (Denmark)

    Christensen, Lene; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-01-01

    , a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers...... are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas....

  9. Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

    OpenAIRE

    Ash Gargya; Elizabeth Chua

    2012-01-01

    Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an und...

  10. Gastric Large Cell Neuroendocrine Carcinoma

    Science.gov (United States)

    Rustagi, Tarun; Alekshun, Todd J.

    2010-01-01

    Case: A 63-year-old male presented with unintentional weight loss of 20 pounds over a 4-month duration. He reported loss of appetite, intermittent post-prandial nausea, bloating and early satiety. He also complained of dyspepsia and had been treated for reflux during the previous 2 years. He denied vomiting, dysphagia, odynophagia, abdominal pain, melena, hematochezia, or alterations in bowel habits. Additionally, he denied fevers, night sweats, cough, or dyspnea. He quit smoking 25 years ago, and denied alcohol use. His past medical history was significant for basal cell carcinoma treated with local curative therapy and he was without recurrence on surveillance. Pertinent family history included a paternal uncle with lung cancer at the age of 74. Physical examination was unremarkable except for occult heme-positive stools. Laboratory evaluation revealed elevated liver enzymes (ALT-112, AST-81, AlkPhos-364). CT scan of the chest, abdomen and pelvis showed diffuse heterogeneous liver with extensive nodularity, raising the concern for metastases. Serum tumor-markers: PSA, CEA, CA 19-9, and AFP were all within normal limits. Screening colonoscopy was normal, but esophagogastroduodenoscopy revealed a malignant-appearing ulcerative lesion involving the gastro-esophageal junction and gastric cardia. Pathology confirmed an invasive gastric large cell neuroendocrine carcinoma. Ultrasound-guided fine needle aspiration of a hepatic lesion revealed malignant cells with cytologic features consistent with large-cell type carcinoma and positive immunostaining for synaptophysin favoring neuroendocrine differentiation. A PET-CT demonstrated intense diffuse FDG uptake of the liver, suggesting diffuse hepatic parenchymal infiltration by tumor. There were multiple foci of intense osseous FDG uptake with corresponding osteolytic lesions seen on CT scan. The remaining intra-abdominal and intra-thoracic structures were unremarkable. The patient will receive palliative systemic therapy

  11. Development of the Neuroendocrine Hypothalamus.

    Science.gov (United States)

    Burbridge, Sarah; Stewart, Iain; Placzek, Marysia

    2016-01-01

    The neuroendocrine hypothalamus is composed of the tuberal and anterodorsal hypothalamus, together with the median eminence/neurohypophysis. It centrally governs wide-ranging physiological processes, including homeostasis of energy balance, circadian rhythms and stress responses, as well as growth and reproductive behaviours. Homeostasis is maintained by integrating sensory inputs and effecting responses via autonomic, endocrine and behavioural outputs, over diverse time-scales and throughout the lifecourse of an individual. Here, we summarize studies that begin to reveal how different territories and cell types within the neuroendocrine hypothalamus are assembled in an integrated manner to enable function, thus supporting the organism's ability to survive and thrive. We discuss how signaling pathways and transcription factors dictate the appearance and regionalization of the hypothalamic primordium, the maintenance of progenitor cells, and their specification and differentiation into neurons. We comment on recent studies that harness such programmes for the directed differentiation of human ES/iPS cells. We summarize how developmental plasticity is maintained even into adulthood and how integration between the hypothalamus and peripheral body is established in the median eminence and neurohypophysis. Analysis of model organisms, including mouse, chick and zebrafish, provides a picture of how complex, yet elegantly coordinated, developmental programmes build glial and neuronal cells around the third ventricle of the brain. Such conserved processes enable the hypothalamus to mediate its function as a central integrating and response-control mediator for the homeostatic processes that are critical to life. Early indications suggest that deregulation of these events may underlie multifaceted pathological conditions and dysfunctional physiology in humans, such as obesity. © 2016 American Physiological Society. Compr Physiol 6:623-643, 2016. PMID:27065164

  12. Neuroendocrine Cancer of Rectum Metastasizing to Ovary

    Science.gov (United States)

    Amin, Sapna Vinit; Kumaran, Aswathy; Bharatnur, Sunanda; Vasudeva, Akhila; Udupa, Kartik; Venkateshiah, Dinesh Bangalore; Bhat, Shaila T.

    2016-01-01

    Neuroendocrine carcinomas (NECs) are rare malignancies that originate from the hormone-producing cells of the body's neuroendocrine system. Rectal high grade NEC (HG-NEC) constituting less than 1% of colorectal cancers can cause large ovarian metastasis that may be the initial presenting complaint. Ovarian Krukenberg tumor from a primary rectal HG-NEC is a very unusual and exceedingly uncommon differential diagnosis for secondary ovarian malignancy. This case report describes one such extremely rare case of a woman who had presented to the gynecology department with features suggestive of ovarian malignancy and was ultimately diagnosed to have Krukenberg tumor originating from neuroendocrine cancer of rectum. We felt this is a good opportunity to spread more light on neuroendocrine neoplasms that are very rare in gynecological practice. PMID:27293931

  13. Diagnosis and treatment of bronchopulmonary neuroendocrine tumours

    DEFF Research Database (Denmark)

    Tabaksblat, Elizaveta Mitkina; Langer, Seppo W; Knigge, Ulrich;

    2016-01-01

    Bronchopulmonary neuroendocrine tumours (BP-NET) are a heterogeneous population of neoplasms with different pathology, clinical behaviour and prognosis compared to the more common lung cancers. The management of BP-NET patients is largely based on studies with a low level of evidence and extrapol...... and extrapolation of data obtained from more common types of neuroendocrine tumours. This review reflects our view of the current state of the art of diagnosis and treatment of patients with BP-NET....

  14. Pathologic research update of colorectal neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Colorectal neuroendocrine tumors (NETs) originate from neuroendocrine cells in the intestinal tract, and represent a small area within oncology, but one which has provided increasing new data during the past years. Although the World Health Organization has determined clinical and histological features to predict prognosis for such tumors, they may not be valid on an individual basis. We aim to give an overview of the recent findings with regard to pathology, molecular genetics and diagnosis of NETs.

  15. Mucin phenotypic expression and p53 gene abnormality of gastric super-minute well-differentiated adenocarcinoma: Re-evaluation with relationship between histogenesis of well-differentiated adenocarcinoma and intestinal metaplasia in distal stomach

    Directory of Open Access Journals (Sweden)

    Yamaguchi Toshikazu

    2005-01-01

    Full Text Available Abstract Background Although the gastric well-differentiated adenocarcinoma in the distal stomach has been thought to develop via a intestinal metaplasia-carcinoma sequence, there are some disproofs from new mucin examinations for minute-size lesions in same type carcinoma. The current study was performed and pointed out the new findings for the solution to the problem according to the point described above. Methods 12 super-minute lesions (less than 1 mm in maximum diameter of well-differentiated adenocarcinoma in distal stomach (SMCa, which were detected from the pathological examinations of 210 surgically resected stomach specimens, and the mucosa adjacent to these carcinoma lesions, were examined by immunohistochemical mucin stainings (MUC2 and CD-10: intestinal phenotype, 45M1 and MUC6: gastric phenotype and p53-overexpression. And the analyses of the replication error of the microsatellites in chromosome 17 related p53 gene (TP53 and D17S786 (RER-p53MS were performed in SMCa lesions, adjacent mucosa to each lesion and other gastric mucosa with intestinal metaplasia, because all SMCa lesions showed p53-overexpression immunohistochemically, decribed below. Results 1. The carcinoma cells in all SMCa lesions were positive for 45M1 and p53. On the other hand, no positive carcinoma cells for MUC6 were seen although the pyloric glands and the remnant pyloric gland in the SMCa lesions in the same slides were positive for MUC6. Ten lesions (83% had intestinal phenotypic mucin (10 lesions: MUC2 (+, 4 lesions: CD10 (+. Two lesions (17% were positive for only 45M1 (gastric phenotypic mucin. 2. All of the mucosa adjacent to SMCa showed intestinal metaplasia (complete type: 7 regions, incomplete type: 5 regions. 3. RER-p53MS was confirmed in 42% (5/12 regions of SMCa, in 42% (5/12 regions of the mucosa adjacent to SMCa and 14% (6/42 regions of the other intestinal metaplasia mucosa. Conclusion Most of the super-minute well-differentiated adenocarcinoma

  16. NEUROENDOCRINE DISTURBANCES FOLLOWING HEAD INJURIES

    Directory of Open Access Journals (Sweden)

    Vinayak

    2015-05-01

    Full Text Available INTRODUCTION: Traumatic brain injury (TBI is one of the main causes of death and disability in young adults, with consequences ranging from physical disabilities to long - term cognitive, behavioural, psychological and social defects. Recently, c linical evidence has demonstrated that TBI may frequently cause hypothalamic – pituitary dysfunction, probably contributing to a delayed or hampered recovery from TBI. CASE REPORT: 32 year s old female presented with a history of fall from two wheeler on back hitting the head on occipital region with no history of vomiting, loss of consciousness, ENT bleed. Her GCS was 15/15. Patient was asymptomatic and was discharged from hospital on fifth day. Seven days after discharge patient again presented with heavine ss in her both breasts associated with pain and whitish discharge from both the nipples and mild fever since last two days. CONCLUSION: TBI is a public health problem that requires more effective strategies to improve the outcome and minimize disability of the affected patients. Changes in pituitary hormone secretion may be observed during the acute phase post - TBI, representing part of the acute adaptive response to the injury. Neuroendocrine disturbances, caused by damage to the pituitary and/or hypothalam us, is a frequent complication of TBI and may occur at any time after the acute event. Pituitary dysfunction presents more frequently as an isolated, and more rarely as a complete, deficiency.

  17. Drug therapy in metastatic neuroendocrine tumors of the gastroenteropancreatic system.

    Science.gov (United States)

    Faiss, S; Scherübl, H; Riecken, E O; Wiedenmann, B

    1996-01-01

    Successful treatment of neuroendocrine tumor disease of the gastroenteropancreatic system requires a multimodal approach. Radical tumor surgery is required before other therapies are initiated. So far, only surgery has proven to be curative. If surgical intervention is not possible or a tumor-free state cannot be achieved, biotherapy with the somatostatin analogues octreotide or lanreotide should then be preferably carried out in patients with functional tumors. Interferon-alpha can alternatively be given. In patients with gastrinoma, therapy with proton pump inhibitors (e.g., omeprazol) is the initial treatment of choice. In patients with nonfunctional tumors, indication for treatment is only given in cases of documented tumor progress. In case of progressive tumor disease or functionality under the above-mentioned therapies, treatment with somatostatin analogues can be intensified by dose escalation or alternatively by a combination therapy with interferon-alpha and a somatostatin analogue. On the basis of the less favorable response of neuroendocrine foregut tumors to biotherapy, chemotherapy should be initiated after failure of biotherapy in documented tumor progression. A combination of streptozotocin and 5-fluorouracil, possibly combined with D,L-folinic acid, is the treatment of choice, considering the response and side effect rates. In case of predominantly anaplastic neuroendocrine tumors in advanced stages, good tumor response rates with a chemotherapeutic scheme consisting of cisplatin and etoposide can be achieved. Since the chemotherapy scheme is less effective in patients with midgut or hindgut tumors, chemoembolization of liver metastases should follow biotherapy. The response to chemoembolization may be increased by simultaneous systemic chemotherapy. Attention should always be paid to an adequate analgesic drug administration. PMID:8893342

  18. Focal Bronchiectasis Causing Abnormal Pulmonary Radioiodine Uptake in a Patient with Well-Differentiated Papillary Thyroid Carcinoma

    Directory of Open Access Journals (Sweden)

    Ash Gargya

    2012-01-01

    Full Text Available Background. False-positive pulmonary radioactive iodine uptake in the followup of differentiated thyroid carcinoma has been reported in patients with certain respiratory conditions. Patient Findings. We describe a case of well-differentiated papillary thyroid carcinoma treated by total thyroidectomy and radioiodine ablation therapy. Postablation radioiodine whole body scan and subsequent diagnostic radioiodine whole body scans have shown persistent uptake in the left hemithorax despite an undetectable stimulated serum thyroglobulin in the absence of interfering thyroglobulin antibodies. Contrast-enhanced chest computed tomography has confirmed that the abnormal pulmonary radioiodine uptake correlates with focal bronchiectasis. Summary. Bronchiectasis can cause abnormal chest radioactive iodine uptake in the followup of differentiated thyroid carcinoma. Conclusions. Recognition of potential false-positive chest radioactive iodine uptake, simulating pulmonary metastases, is needed to avoid unnecessary exposure to further radiation from repeated therapeutic doses of radioactive iodine.

  19. Large Cell Neuroendocrine Carcinoma of the Lung

    Directory of Open Access Journals (Sweden)

    Yusuf Aydemir

    2015-11-01

    Full Text Available Large-cell neuroendocrine carcinomas of the lung are extremely rare. There are difficulties related to the diagnosis and treatment and there are no consensus because of the small number of studies. 65-year-old male patient presented with hemoptysis. Chest X-ray and thoracic computorized tomography scan showed a mass lesion and it could not be diagnosed by bronchoscopic biopsy and lavage. Lobectomy was performed due to the high value of standardized uptake value in positron emission tomography. Large cell neuroendocrine carcinoma was diagnosed with pathological evaluation and immunohistochemical study and after 20-month follow-up there was no recurrence. The diagnosis, treatment, and prognosis of large cell neuroendocrine carcinoma in the light of the literature is presented.

  20. Neuroendocrine and Molecular Interactions in Eating Disorders

    Directory of Open Access Journals (Sweden)

    Selma Bozkurt Zincir

    2014-08-01

    Full Text Available There are three basic pillars for the development of eating disorders: genetic predisposition, neuro-endocrine-molecular changes in the brain and metabolic response to it. As a result of neuroendocrine research, a close relationship has been found between neuroendocrine functions and symptom domains of psychiatric disorders such as eating disorders and mood disorders. Certain hormones, neurotransmitters and other molecules which might have effect on the basis of eating disorders can be listed as estrogen, serotonin, leptin, ghreline, alpha-melanocyte stimulating hormone, cholecystokinin, dopamine, noradrenaline, brain-derived neurotropic factor, agouti-related protein, neuropeptide-Y, opioids and their receptors, thiamine, zinc, omega-3 acids. In this review, main neuroendocrine-molecular changes and interactions that occur in the eating disorders have been discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(4.000: 389-400

  1. Neuroendocrine aspects of Tourette syndrome.

    Science.gov (United States)

    Martino, Davide; Macerollo, Antonella; Leckman, James F

    2013-01-01

    There is sparse evidence suggesting the participation of neuroendocrine mechanisms, mainly involving sex and stress steroid hormones, to the pathophysiology of neurodevelopmental disorders such as Tourette syndrome (TS) and obsessive-compulsive disorder (OCD). Patients with TS exhibit a sex-specific variability in gender distribution (male/female ratio=3-4/1) and in its natural history, with a severity peak in the period around puberty. The administration of exogenous androgens may worsen tics in males with TS, whereas drugs counteracting the action of testosterone might show some antitic efficacy. This suggests a higher susceptibility of patients with TS to androgen steroids. There are insufficient data on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis in TS. However, preliminary evidence suggests that a subgroup of women with TS might be more sensitive to the premenstrual trough of estrogen levels. Patients with TS exhibit differences in a number of behavioral, cognitive, and anatomical traits that appear to be sex related. There is a body of evidence supporting, albeit indirectly, the hypothesis of an increased exposure to androgenic steroids during the very early phases of neural development. Animal models in rodents suggest a complex role of gonadal hormones upon the modulation of anxiety-related and stereotyped behaviors during adult life. Patients with TS exhibit an enhanced reactivity of the hypothalamic-pituitary-adrenal axis to external stressors, despite a preserved diurnal cortisol rhythm and a normal restoration of the baseline activity of the axis following the acute stress response. Preliminary evidence suggests the possible implication of oxytocin (OT) in disorders related to the TS spectrum, especially non-tic-related OCD. The injection of OT in the amygdala of rodents was shown to be able to induce hypergrooming, suggesting the possible involvement of this neuropeptide in the pathophysiology of complex, stereotyped behaviors. In

  2. Primary Neuroendocrine Tumor of the Breast: Imaging Features

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Eun Deok [Department of Clinical Pathology, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 480-717 (Korea, Republic of); Kim, Min Kyun [Department of Radiology, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 480-717 (Korea, Republic of); Kim, Jeong Soo [Department of Surgery, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 480-717 (Korea, Republic of); Whang, In Yong [Department of Radiology, Uijeongbu St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu 480-717 (Korea, Republic of)

    2013-07-01

    Focal neuroendocrine differentiation can be found in diverse histological types of breast tumors. However, the term, neuroendocrine breast tumor, indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population. The imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type. We present a case of a pathologically confirmed, primary neuroendocrine breast tumor in a 42-year-old woman, with imaging findings difficult to be differentiated from that of invasive ductal carcinoma.

  3. Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma.

    Science.gov (United States)

    Shah, Ketan; Perez-Ordóñez, Bayardo

    2016-03-01

    Neuroendocrine neoplasms (NENs) can occur in organs or tissues that do not contain neuroendocrine cells normally and do not necessarily imply embryologic derivation from the neuroectoderm; but rather reflect a shared phenotype characterized by the expression of multiple genes encoding both endocrine and neuronal features. NENs are rare in the sinonasal tract and are subdivided into epithelial and neural subtypes based on the presence of keratins or neurofilaments, respectively. Although relatively rare, neuroendocrine carcinomas (NECs) and olfactory neuroblastoma (ONB) are the most common neuroendocrine neoplasms of the sinonasal tract. The focus of this review is to highlight recent developments in the pathology of sinonasal NECs and ONB in light of the upcoming update of the World Health Organization (WHO) 2005 classification of tumors of the head and neck. PMID:26830400

  4. Surgical management of pancreatic neuroendocrine tumors

    NARCIS (Netherlands)

    A.P.J. Jilesen

    2015-01-01

    This thesis gives an overview of the surgical management and prognosis of patients with pancreatic neuroendocrine tumors (pNET). A systematic review including 2600 studies, was performed on complications and survival after different surgical procedures for pNETs. The overall pancreatic fistula rate

  5. Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

    Directory of Open Access Journals (Sweden)

    Anna M. M. Daubenbüchel

    2015-03-01

    Full Text Available Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement, a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92% but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007. Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients.

  6. Skin manifestations of endocrine and neuroendocrine tumors.

    Science.gov (United States)

    Leventhal, Jonathan S; Braverman, Irwin M

    2016-06-01

    The skin signs of benign and malignant endocrine and neuroendocrine tumors are manifold and early identification of these dermatologic features is crucial in initiating timely diagnosis and management. This article reviews the salient cutaneous features of these tumors that arise in the classic endocrine glands, lung and gastrointestinal tract either as individual neoplasms or as part of a syndrome.

  7. Neuroendocrine differentiation in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jiaoti Huang

    2008-01-01

    @@ The treatment of choice for advanced/metastatic prostate cancer(PC) is hormonal therapy. Although patients respond initially to this therapy, the tumor will recur and enter the androgen-independent state, which is the major obstacle in therapy.

  8. Immunohistochemical consistency between primary tumors and lymph node metastases of gastric neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Uchiyama Chieko

    2012-06-01

    Full Text Available Abstract Background Gastric neuroendocrine carcinoma (G-NEC is a rare, highly malignant tumor that exhibits aggressive growth leading to vascular invasion, distant metastasis and extremely poor prognosis. We studied the clinicopathological findings of seven patients at our institute to better under this disease. Methods Seven cases of G-NEC were identified among 1,027 cases of gastric carcinoma that underwent gastrectomy at Kansai Rousai Hospital between 2002 and 2010. We studied the pathological and immunohistochemical features of gastric neuroendocrine carcinomas at both the primary site and metastatic lymph nodes. Results The mean patient age was 73 years (range 63 to 86 years. There were no females in this series. The final staging was Stage I in one case, Stage II in two, Stage III in two and Stage IV in two. A total of 31 metastatic lymph nodes were found in these patients. This study revealed that the ratio of neuroendocrine cells was similar between the primary and metastatic sites, which tended to show the same expression patterns of neuroendocrine markers. Conclusions Metastatic lymph nodes showed heterogeneous immunohistochemical expression patterns similar to the primary sites. G-NEC is far advanced at diagnosis and rapidly reaches the lymph nodes retaining its heterogeneity, carrying a worse prognosis than common gastric cancer. Mini abstract G-NEC grows rapidly and metastasizes to the lymph nodes, retaining its pathological and immunohistochemical heterogeneity even at the metastatic sites.

  9. Well-Differentiated Liposarcoma, an Atypical Lipomatous Tumor, of the Mesentery: A Case Report and Review of the Literature

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    Takashi Yuri

    2011-03-01

    Full Text Available Mesenteric liposarcoma is a rare neoplasm. Here, we report the case of a 73-year-old Japanese man with a well-differentiated (WD liposarcoma of the mesentery. Due to rapid growth of the abdominal mass and abdominal insufficiency, a tumorectomy was performed. The excised tumor was 12.4 × 9.6 cm in size and weighed 548 g. Cut sections showed a lobulated yellow and/or grayish-colored appearance. The histological features were predominantly those of the sclerotic and lipoma-like variants of WD liposarcoma. The cytoplasm of most spindle cells was diffusely immunoreactive for CD34, while fat cells were positive for S-100 protein. Some spindle cell nuclei were positive for CDK4, and a few were positive for MDM2. The average Ki-67 proliferation index in tumor cells was 10%, and androgen receptor expression was detected in tumor cell nuclei. The present case and 11 cases identified from a literature search were reviewed. The WD mesenteric liposarcomas developed in patients in the fourth to seventh decades of life (mean age 57.9 years. The patients consisted of 7 men and 5 women. All tumors were larger than 10 cm in diameter at the time of surgery. Complete resection might be the only curative therapy for WD liposarcomas of the mesentery, but long-term follow-up is needed because of the possibility of a local recurrence of the tumor.

  10. Loss of ATRX or DAXX expression and concomitant acquisition of the alternative lengthening of telomeres phenotype are late events in a small subset of MEN-1 syndrome pancreatic neuroendocrine tumors

    OpenAIRE

    de Wilde, Roeland F.; Heaphy, Christopher M.; Maitra, Anirban; Meeker, Alan K.; Barish H Edil; Wolfgang, Christopher L; Ellison, Trevor A.; Schulick, Richard D; Molenaar, I. Quintus; Valk, Gerlof D.; Vriens, Menno R.; Rinkes, Inne HM Borel; Offerhaus, G. Johan A.; Ralph H. Hruban; Matsukuma, Karen E.

    2012-01-01

    Approximately 45% of sporadic well-differentiated pancreatic neuroendocrine tumors harbor mutations in either ATRX (alpha thalassemia/mental retardation X-linked) or DAXX (death domain-associated protein). These novel tumor suppressor genes encode nuclear proteins that interact with one another and function in chromatin remodeling at telomeric and peri-centromeric regions. Mutations in these genes are associated with loss of their protein expression and correlate with the alternative lengthen...

  11. A Rare Case of Mixed Neuroendocrine Tumor and Adenocarcinoma of the Pancreas.

    Science.gov (United States)

    Xenaki, Sofia; Lasithiotakis, Konstantinos; Andreou, Alexandros; Aggelaki, Sofia; Tzardi, Maria; Daskalaki, Anna; Chalkiadakis, George; Chrysos, Emmanuel

    2016-01-01

    Introduction. Neuroendocrine carcinoma (NEC) of pancreas is a rare tumor with aggressive progression and poor prognosis. Its coexistence with adenocarcinoma poses significant clinical problems and has not been addressed in the literature. Methods. We describe a case of a 51-year-old male who underwent pancreatoduodenectomy due to pancreatic head tumor 1.5 × 1 × 1.4 cm. Histological examination of the specimen revealed a mixed neoplasm: (1) a well differentiated adenocarcinoma, neoplastic blasts of which are extended focally to the submucosa without invading the muscular layer, and (2) a low differentiated NEC consisting of solid clusters and pagetoid formations. All 18 lymph nodes of the specimen were free of neoplastic disease and the surgical margins of the specimen were tumor-free. No adjuvant treatment was administered and two months after the operation the patient developed liver metastasis. FNA cytology of the hepatic lesions revealed low grade carcinoma with neuroendocrine characteristics. Five lines of chemotherapy were administered: VP + CDDP, paclitaxel + ifosfamide + Mesna + CDDP, Folfox + Avastin, Folfiri + Avastin, and CAV. During his treatment he revealed PD and succumbed to his disease 13 months after the operation. Conclusion. Coexistence of NEC with adenocarcinoma of the pancreas is a very rare entity presenting significant challenges regarding its adjuvant treatment and the treatment of distant relapse. PMID:27610261

  12. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report.

    Science.gov (United States)

    Orsi, Nicolas M; Menon, Mini

    2016-08-01

    Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10-12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade), arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area. PMID:27508272

  13. Primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma: A case report

    Directory of Open Access Journals (Sweden)

    Nicolas M. Orsi

    2016-08-01

    Full Text Available Primary ovarian carcinoid tumors are exceptionally rare entities accounting for approximately 0.1% of all ovarian neoplasms. This report describes a primary ovarian neuroendocrine tumor arising in association with a mature cystic teratoma in a 65 year-old woman. Macroscopically, the unilateral adnexal tumor was composed of cystic, solid and mucinous elements which resolved into a dual component lesion histologically. The majority of the tumor displayed an organoid architecture with mild to moderate pleomorphism and no discernible mitotic activity, while approximately 10% consisted of sheets and groups of cells with highly pleomorphic nuclei, necrosis and occasional mitoses. Features of a mature cystic teratoma were seen very focally. Immunohistochemistry revealed strong, diffuse positivity for CD56 and synaptophysin. Chromogranin immunonegativity was noted and there was an absence of nuclear β-catenin accumulation. Ki-67 index was 10–12%. Although there is no established diagnostic framework for primary ovarian carcinoid tumors, this case was diagnosed as a well-differentiated neuroendocrine tumor, Grade 2 (intermediate grade, arising in association with a mature cystic teratoma/dermoid cyst. This case highlights the need to develop ovarian diagnostic criteria in this area.

  14. MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Cros, J; Hentic, O; Rebours, V; Zappa, M; Gille, N; Theou-Anton, N; Vernerey, D; Maire, F; Lévy, P; Bedossa, P; Paradis, V; Hammel, P; Ruszniewski, P; Couvelard, A

    2016-08-01

    Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.

  15. Programming of neuroendocrine self in the thymus and its defect in the development of neuroendocrine autoimmunity

    Directory of Open Access Journals (Sweden)

    Vincent eGeenen

    2013-10-01

    Full Text Available For centuries after its first description by Galen, the thymus was considered as only a vestigial endocrine organ until the discovery in 1961 by Jacques FAP Miller of its essential role in the development of T (thymo-dependent lymphocytes. A unique thymus first appeared in cartilaginous fishes some 500 million years ago, at the same time or shortly after the emergence of the adaptive (acquired immune system. The thymus may be compared to a small brain or a computer highly specialized in the orchestration of central immunological self-tolerance. This was a necessity for the survival of species, given the potent evolutionary pressure imposed by the high risk of autotoxicity inherent in the stochastic generation of the diversity of immune cell receptors that characterize the adaptive immune response. A new paradigm of ‘neuroendocrine self-peptides’ has been proposed, together with the definition of ‘neuroendocrine self’. Neuroendocrine self-peptides are secreted by thymic epithelial cells (TECs not according to the classic model of neuroendocrine signaling, but are processed for presentation by, or in association with, the thymic major histocompatibility complex (MHC proteins. The autoimmune regulator (AIRE gene/protein controls the transcription of neuroendocrine genes in TECs. The presentation of self-peptides in the thymus is responsible for the clonal deletion of self-reactive T cells, which emerge during the random recombination of gene segments that encode variable parts of the T cell receptor for the antigen (TCR. At the same time, self-antigen presentation in the thymus generates regulatory T (Treg cells that can inhibit, in the periphery, those self-reactive T cells that escaped negative selection in the thymus. Several arguments indicate that the origin of autoimmunity directed against neuroendocrine glands results primarily from a defect in the intrathymic programming of self-tolerance to neuroendocrine functions. This defect may

  16. Azithromycin treatment alters gene expression in inflammatory, lipid metabolism, and cell cycle pathways in well-differentiated human airway epithelia.

    Directory of Open Access Journals (Sweden)

    Carla Maria P Ribeiro

    Full Text Available Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent

  17. Gastric extremely well differentiated adenocarcinoma of gastric phenotype: as a gastric counterpart of adenoma malignum of the uterine cervix

    Directory of Open Access Journals (Sweden)

    Ae Lee Won

    2005-05-01

    Full Text Available Abstract Background Most of gastric adenocarcinoma can be simply diagnosed by microscopic examination of biopsy specimen. Rarely the structural and cellular atypia of tumor cells is too insignificant to discriminate from benign foveolar epithelium. Case presentation A 67-year-old male presented with a gastric mass incidentally found on the abdominal computed tomography (CT for routine medical examination. Gastric endoscopic examination revealed a huge fungating mass at the cardia and mucosal biopsy was performed. Microscopically the biopsy specimen showed proliferation of bland looking foveolar epithelia in the inflammatory background and diagnosed as foveolar epithelial hyperplasia. Because the clinical and endoscopic features of this patient were strongly suggestive of malignancy, the patient underwent radical total gastrectomy. The resected stomach revealed a huge fungating tumor at the cardia. The cut surface of the tumor was whitish gelatinous. Microscopically the tumor was sharply demarcated from surrounding mucosa and composed of very well formed glandular structures without significant cellular atypia, which invaded into the whole layer of the gastric wall. Tumor glands were occasionally complicated or dilated, and glandular lumina were filled with abundant mucin. Immunohistochemically the tumor cells revealed no overexpression of p53 protein but high Ki-67 labeling index. The tumor cells and intraluminal mucin were diffusely expressed MUC1 and MUC5AC and only focally expressed MUC2. On abdominal CT taken after 12 months demonstrated peritoneal carcinomatosis and multiple metastatic foci in the lung. Conclusion The clinicopathologic profiles of gastric extremely well differentiated adenocarcinoma of gastric phenotype include cardiac location, fungating gross type, very similar histology to foveolar epithelial hyperplasia, foveolar mucin phenotype, lack of p53 overexpressoin and high proliferative index.

  18. A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values

    International Nuclear Information System (INIS)

    Differential diagnosis of high-grade dysplastic nodules (HGDN) and well-differentiated hepatocellular carcinoma (WDHCC) represents a challenge to experienced hepatic clinicians, radiologists and hepatopathologists. The expression profiles of aminoacylase-1 (ACY1), sequestosome-1 (SQSTM1) and glypican-3 (GPC3) in low-grade dysplastic nodules (LGDN), HGDN and WDHCC were assessed by immunohistochemistry. The differential diagnostic performances of these three markers alone and in combination for HGDN and WDHCC were investigated by logistic regression models (HGDN = 21; WDHCC = 32) and validated in an independent test set (HGDN, n = 21; WDHCC n = 24). Postoperative overall survival and time to recurrence were evaluated by univariate and multivariate analyses in an independent set of 500 patients. ACY1, SQSTM1 and GPC3 were differentially expressed in each group. For the differential diagnosis of WDHCC from HGDN, the sensitivity and specificity of the combination of ACY1 + SQSTM1 + GPC3 for detecting WDHCC were 93.8% and 95.2% respectively in the training set, which were higher than any of the three two-marker combinations. The validities of the four diagnostic models were further confirmed in an independent test set, and corresponding good sensitivity and specificity were observed. Interestingly, GPC3 expression in HCC tissues combined with serum α-fetoprotein (AFP) was found to be an independent predictor for overall survival and time to recurrence. ACY1 + SQSTM1 + GPC3 combination represents a potentially valuable biomarker for distinguishing between WDHCC and HGDN using immunohistochemistry. Meanwhile, low GPC3 staining combined with positive serum AFP may play a practical role in predicting poor postoperative outcome and high tumor recurrence risk

  19. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    International Nuclear Information System (INIS)

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7±12.3 years) who had HD-RIT (dose 159.1±25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive (≥50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62±66.1 dpm in increased one of follow-up UBT, and 153.3±157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection

  20. Clinical Usefulness between High Dose Radioiodine Therapy and Helicobacter Pylori Infection after Total Thyroidectomy due to Well Differentiated Thyroid Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yun, Kuk No; Lim, Seok Tae; Moon, Eun Ha; Kim, Jin Suk; Jeong, Young Jin; Kim, Dong Wook; Jeong, Hwan Jeong; Sohn, Myung Hee [Chonbuk National University Medical School and Hospital, Jeonju (Korea, Republic of)

    2009-12-15

    Helicobacter (H) pylori infection has been considered the most important cause of gastritis, dyspepsia, and gastroduodenal ulcer. Radioiodine can be accumulated in the remaining thyroid tissue, salivary gland, and stomach. We investigated if the high radiation induced by radioiodine in the stomach after high dose radioiodine therapy (HD-RIT) is effective in the eradication of H. pylori infection. One hundred ninety nine patients (M:F=33:166, age 46.7{+-}12.3 years) who had HD-RIT (dose 159.1{+-}25.9 mCi, range 120-250 mCi) after thyroidectomy due to well differentiated thyroid cancer were enrolled. To detect H. pylori infection, the urea breath tests (UBT) were performed at 1 hour before HD-RIT and at 4 weeks after HD-RIT. The results of UBT were classified as positive ({>=}50 dpm) or negative (<50 dpm), and analyzed its values. Of 199 patients, 103 (51.8%) patients had positive UBT before HD-RIT. Of these, 80 patients had follow-up UBT after HD-RIT. Among them, 76 (95.0%) patients had persistent positive UBT and only 4 (5.0%) patients were changed negative UBT. Among 76 patients with persistent positive UBT, 26 (34.2%) patients had increased the values of follow-up UBT, 49 (64.5%) had decreased them, and 1 (1.3%) had shown the same value. The different values of UBT between before and after HD-RIT were 62{+-}66.1 dpm in increased one of follow-up UBT, and 153.3{+-}157.1 dpm in decreased one of follow-up UBT. We conclude that the radiation induced by HD-RIT is ineffective in the eradication of H. pylori infection. However, it could be influential the degree or distribution of H. pylori infection.

  1. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Todorović-Tirnanić Mila

    2015-01-01

    Full Text Available The new positron emission tomography (PET/CT methods for neuroendocrine tumors detection are presented and compared with classic, conventional methods. Conventional methods use a gamma scintillation camera for patients with neuroendocrine tumor imaging, after intravenous injection of one of the following radiopharmaceuticals: 1 somatostatin analogues labeled with indium-111 (111In-pentetreotide or technetium-99m (99mTc-EDDA/HYNIC-TOC; 2 noradrenaline analogue labeled with iodine-131 or -123 (131I/123I-MIBG; or 3 99mTc(V-DMSA. Contemporary methods use PET/CT equipment for patients with neuroendocrine tumor imaging, after intravenous injection of pharmaceuticals labeled with positron emitters [fluorine-18 (18F, galium-68 (68Ga, or carbon-11 (11C]: 1 glucose analogue (18FDG; 2 somatostatin analogue (68Ga-DOTATOC/68Ga-DOTATATE/68Ga-DOTANOC; 3 aminoacid precursors of bioamines: [a dopamine precursor 18F-DOPA (6-18F-dihydroxyphenylalanine, b serotonin precursor 11C-5HTP (11C-5-hydroxytryptophan]; or 4 dopamine analogue 18F-DA (6-18F-fluorodopamine. Conventional and contemporary (PET/ CT somatostatin receptor detection showed identical high specificity (92%, but conventional had very low sensitivity (52% compared to PET/CT (97%. It means that almost every second neuroendocrine tumor detected by contemporary method cannot be discovered using conventional (classic method. In metastatic pheochromocytoma detection contemporary (PET/ CT methods (18F-DOPA and 18F-DA have higher sensitivity than conventional (131I/123I-MIBG. In medullary thyroid carcinoma diagnostics contemporary method (18F-DOPA is more sensitive than conventional 99mTc(V-DMSA method, and is similar to 18FDG, computed tomography and magnetic resonance. In carcinoid detection contemporary method (18F-DOPA shows similar results with contemporary somatostatin receptor detection, while for gastroenteropancreatic neuroendocrine tumors it is worse. To conclude, contemporary (PET/CT methods for

  2. Simultaneous Non-Functioning Neuroendocrine Carcinoma of the Pancreas and Extra-Hepatic Cholangiocarcinoma. A Case of Early Diagnosis and Favorable Post-Surgical Outcome

    Directory of Open Access Journals (Sweden)

    Simone Maurea

    2011-05-01

    Full Text Available Context Thanks to the wide use of diagnostic imaging modalities, multiple primary malignancies are being diagnosed more frequently and different associations of malignancies have been reported in this setting. Case report In this paper, we describe the case of a patient with non-functioning well-differentiated neuroendocrine carcinoma of the head of the pancreas associated with extra-hepatic cholangiocarcinoma, in which an early diagnosis using magnetic resonance imaging allowed a good outcome. Conclusion The simultaneous association of neuroendocrine pancreatic tumors and cholangiocarcinoma has not yet been described; however, this association should be considered and, due to the high contrast of magnetic resonance imaging, this technique is recommended in such patient in order to reach an accurate diagnosis.

  3. Vascular thrombosis as a cause of abdominal pain in a patient with neuroendocrine carcinoma of pancreas: Findings on 68Ga-DOTANOC PET/CT

    International Nuclear Information System (INIS)

    Neuroendocrine tumors of pancreas are relatively rare neoplasms and are classified as either functioning or non-functioning tumors. A 55-year-old female diagnosed with a large, well-differentiated, non-functional neuroendocrine carcinoma of pancreas, presented with abdominal pain of increasing severity. A contrast-enhanced examination of the abdomen was performed to reveal a large, diffuse, enhancing pancreatic mass with multiple filling defects within the mesenteric vasculature. We present findings on 68Ga-labeled [1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-NaI3-Octreotide, positron emission tomography-computed tomography (68Ga-DOTANOC PET/CT) and the importance of somatostatin receptor-based PET imaging in such patients

  4. Neuroendocrine gastric carcinoma expressing somatostatin: A highly malignant, rare tumor

    Institute of Scientific and Technical Information of China (English)

    Jaques Waisberg; Leandro Luongo de Matos; Ana Maria do Amaral Antonio Mader; Sérgio Pezzolo; Esmeralda Miristene Eher; Vera Luiza Capelozzi; Manlio Basilio Speranzini

    2006-01-01

    Poorly differentiated gastric neuroendocrine carcinomas,although rare, deserve particular attention, as they are aggressive and have an extremely poor prognosis. In this report we describe a gastric neuroendocrine carcinoma with rapidly fatal outcome. Immunohistological staining of the resected specimens revealed that the tumor was an endocrine carcinoma. The tumor disclosed intense immunoreactivity to pan-neuroendocrine markers and diffuse somatostatin immunoreactivity. There were no psammoma bodies and no demonstrable association with von Recklinghausen's neurofibromatosis. In the gastrointestinal tract, neuroendocrine tumors producing predominantly somatostatin have been described only in the duodenum. To the best of our knowledge, the present report is the second case report of a neuroendocrine gastric carcinoma expressing diffusely somatostatin as the only neuroendocrine regulatory peptide.

  5. Interventional treatment of neuroendocrine liver metastases

    DEFF Research Database (Denmark)

    Knigge, U.; Hansen, C.P.; Stadil, F.

    2008-01-01

    Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases s...... symptomatic response rate is 90% with a mean duration of two years. Liver transplantation should be restricted to very few and highly selected patients without extrahepatic disease. Recurrence is inevitable in nearly all patients Udgivelsesdato: 2008/8......Neuroendocrine gastroenteropancreatic tumours are rare with an incidence of 2-4/100.000 per year. More than 75% of the patients develop hepatic metastases, which reduce the five year survival from 70-80% to 30-40%. In addition to chemo- and biotherapy, interventional therapy of liver metastases...

  6. Early host responses of seasonal and pandemic influenza A viruses in primary well-differentiated human lung epithelial cells.

    Directory of Open Access Journals (Sweden)

    Rachael L Gerlach

    Full Text Available Replication, cell tropism and the magnitude of the host's antiviral immune response each contribute to the resulting pathogenicity of influenza A viruses (IAV in humans. In contrast to seasonal IAV in human cases, the 2009 H1N1 pandemic IAV (H1N1pdm shows a greater tropism for infection of the lung similar to H5N1. We hypothesized that host responses during infection of well-differentiated, primary human bronchial epithelial cells (wd-NHBE may differ between seasonal (H1N1 A/BN/59/07 and H1N1pdm isolates from a fatal (A/KY/180/10 and nonfatal (A/KY/136/09 case. For each virus, the level of infectious virus and host response to infection (gene expression and apical/basal cytokine/chemokine profiles were measured in wd-NHBE at 8, 24, 36, 48 and 72 hours post-infection (hpi. At 24 and 36 hpi, KY/180 showed a significant, ten-fold higher titer as compared to the other two isolates. Apical cytokine/chemokine levels of IL-6, IL-8 and GRO were similar in wd-NHBE cells infected by each of these viruses. At 24 and 36 hpi, NHBE cells had greater levels of pro-inflammatory cytokines including IFN-α, CCL2, TNF-α, and CCL5, when infected by pandemic viruses as compared with seasonal. Polarization of IL-6 in wd-NHBE cells was greatest at 36 hpi for all isolates. Differential polarized secretion was suggested for CCL5 across isolates. Despite differences in viral titer across isolates, no significant differences were observed in KY/180 and KY/136 gene expression intensity profiles. Microarray profiles of wd-NHBE cells diverged at 36 hpi with 1647 genes commonly shared by wd-NHBE cells infected by pandemic, but not seasonal isolates. Significant differences were observed in cytokine signaling, apoptosis, and cytoskeletal arrangement pathways. Our studies revealed differences in temporal dynamics and basal levels of cytokine/chemokine responses of wd-NHBE cells infected with each isolate; however, wd-NHBE cell gene intensity profiles were not significantly

  7. Autophagy sensitivity of neuroendocrine lung tumor cells

    OpenAIRE

    HONG, SEUNG-KEUN; Kim, Jin-Hwan; Starenki, Dmytro; Park, Jong-In

    2013-01-01

    Neuroendocrine (NE) phenotypes characterize a spectrum of lung tumors, including low-grade typical and intermediate-grade atypical carcinoid, high-grade large-cell NE carcinoma and small cell lung carcinoma. Currently, no effective treatments are available to cure NE lung tumors, demanding identification of biological features specific to these tumors. Here, we report that autophagy has an important role for NE lung tumor cell proliferation and survival. We found that the expression levels of...

  8. Neuroendocrine effects of perfluorooctane sulfonate in rats.

    OpenAIRE

    Austin, Maureen E; Kasturi, Badrinarayanan S.; Barber, Matthew; Kannan, Kurunthachalam; MohanKumar, Puliyur S.; MohanKumar, Sheba M.J.

    2003-01-01

    Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were inj...

  9. Neuroendocrine Stress Response after Burn Trauma

    OpenAIRE

    Lindahl, Andreas

    2013-01-01

    Some aspects of the stress response during acute intensive care for severe burns are described and quantified by measuring hormonal and neuroendocrine patterns and relating these to organ function in the short term. This includes an assessment of whether there are markers for the severity of stress that are better than conventional descriptors of the severity of a burn in predicting failing organ function. P-CgA after a major burn injury is an independent and better predictor of organ dysfunc...

  10. Neuroendocrine changes in patients with anorexia nevosa

    OpenAIRE

    Weiss, Deike

    2013-01-01

    Patients with anorexia nervosa show neuroendocrine changes compared to healthy controls. It remains unclear, whether those are preexisting alterations or caused by the disease and if they contribute to maintain the disease. The hormone leptin not only influences energy homeostasis but neuronal networks. We could show that patients with lower leptin lewels show higher drive for thinness and reported more sexual problems and hyperactivity, even when adjusted for the BMI. That confirms prior...

  11. Somatostatin analogue treatment of neuroendocrine tumours.

    OpenAIRE

    de Herder, W. W.; van der Lely, A.J.; Lamberts, S. W.

    1996-01-01

    The long-acting analogues of somatostatin have an established place in the medical treatment of patients with neuroendocrine tumours. They act through binding with specific, high-affinity membrane receptors. Somatostatin analogue therapy is an effective and safe treatment for most growth hormone and thyrothropin-secreting pituitary adenomas. The potential therapeutic consequences of the presence of somatostatin receptors on clinically 'nonfunctioning' pituitary tumours are still uncertain. So...

  12. Large cell neuroendocrine carcinoma of the ampulla of Vater.

    LENUS (Irish Health Repository)

    Beggs, Rachel E

    2012-09-01

    Large cell neuroendocrine carcinomas of the ampulla of Vater are rare and confer a very poor prognosis despite aggressive therapy. There are few case reports of large cell neuroendocrine carcinomas of the ampulla of Vater in the literature and to date no studies have been done to establish optimal management. We describe a pooled case series from published reports of neuroendocrine carcinomas of the ampulla of Vater including a case which presented to our institution.

  13. [Neuroendocrine tumors: Peptide receptors radionuclide therapy (PRRT)].

    Science.gov (United States)

    Papamichail, Dimitris G; Exadaktylou, Paraskevi E; Chatzipavlidou, Vasiliki D

    2016-01-01

    Neuroendocrine tumors (neuroendocrine tumors-NET) are a heterogeneous group of neoplasms with a common embryological origin and diverse biological behavior, derived from cells of the neuroendocrine system, the system APUD (amine precursor uptake and decarboxylation). They are characterized by overexpression of all five somatostatin receptors (SSTR1-SSTR5), particularly type 2 (SST2). Surgical resection of the tumor is the treatment option, with a possibility of complete remission in patients with limited disease. Somatostatin analogs (octreotide and lanreotide) are the treatment of choice in patients with residual disease, particularly when it comes to NET non-pancreatic origin. Systemic chemotherapy is administered primarily to patients with poorly differentiated carcinomas. PRRT treatment is recommended in case of non-responsiveness of the disease. The ideal candidates for PRRT are patients with unresectable disease of high and intermediate differentiation. Somatostatine analogs radiolabelled with Indium-111 ((111)In), Yttrium-90 ((90)Y), Lutetium-177 ((177)Lu) and Bismuth-213 ((213)Bi), are selectively concentrated in the tumor cells, causing maximum tissue damage to tumors and with fewer effects on healthy tissue and the immune system. In the current review, it was demonstrated that patients with unresectable grade 1 or 2 disease showed increased PFS (progression free survival) and OS (overall survival), while quality of life was improved after PRRT treatment as compared to somatostatin analogs, chemotherapy and other targeted therapies. PMID:27035909

  14. GEP- NETS UPDATE: Genetics of neuroendocrine tumors.

    Science.gov (United States)

    Crona, Joakim; Skogseid, Britt

    2016-06-01

    Neuroendocrine tumors (NETs) are a heterogeneous group of neoplasms, arising from neuroendocrine cells that are dispersed throughout the body. Around 20% of NETs occur in the context of a genetic syndrome. Today there are at least ten recognized NET syndromes. This includes the classical syndromes: multiple endocrine neoplasias types 1 and 2, and von Hippel-Lindau and neurofibromatosis type 1. Additional susceptibility genes associated with a smaller fraction of NETs have also been identified. Recognizing genetic susceptibility has proved essential both to provide genetic counseling and to give the best preventive care. In this review we will also discuss the knowledge of somatic genetic alterations in NETs. At least 24 genes have been implicated as drivers of neuroendocrine tumorigenesis, and the overall rates of genomic instability are relatively low. Genetic intra-tumoral, as well as inter-tumoral heterogeneity in the same patient, have also been identified. Together these data point towards the common pathways in NET evolution, separating early from late disease drivers. Although knowledge of specific mutations in NETs has limited impact on actual patient management, we predict that in the near future genomic profiling of tumors will be included in the clinical arsenal for diagnostics, prognostics and therapeutic decisions. PMID:27165966

  15. Assessment of recombinant human thyrotropin application in following-up patients with well-differentiated thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Rajkovača Zvezdana

    2012-01-01

    Full Text Available Background/Aim. The most sensitive indicators for detecting recurrence of well-differentiated thyroid cancer (DTC are 131I whole body scintigraphy (WBS and measurement of serum thyroglobulin (Tg. In order to perform it, it is necessary to raise the level of endogenous tiroidstimulating hormon (TSH, which can be achieved by Lthyroxine withdrawal for 3-5 weeks or administration of recombinant human thyrotropin (rhTSH without requiring the discontinuation of thyroid hormone therapy. The aim of this study was to assess the effect of rhTSH using in comparison to the traditional thyroid hormone withdrawal in the follow-up of patients with DTC. Methods. This retrospective study included 44 patients, mean age 48.8 years, with DTC divided into 2 groups. The group I consisted of patients (n = 31 in which the analysis in the follow-up (WBS with 131I, TSH, Tg and antiTgAt made in the hypothyroid state, and group II patients (n = 13 in which they made after the administration of rhTSH. The presence of 13 symptoms and signs of hypothyroidism was investigated on the day of giving 131I. Quality of life was evaluated using a modified form: the quality of life scale (SF-36 completed on the day of giving 131I. Results. In both groups, serum TSH reached a very good stimulation level, but significantly higher in the group II (group I 30.3-101.5 µlU/mL, group II 68.6-192.0 µlU/mL, p < 0.05. In both groups, TSHstimulated Tg was higher (group I 0.1-546.0 ng/mL, group II 0.1-7517 ng/mL comapred to value during the Lthyroxine therapy (group I 0.1-495.0 ng/mL, group II 0.1- 2785 ng/mL. There was no difference in technical quality of WBS obtained from both groups. The patients in the group I had attended 8-13 symptoms of hypothyroidism, while patients in group II did not have symptoms of hypothyroidism. The patients after application of rhTSH, showed statistically significantly better quality of life as compared with those who showed to have L-thyroxine withdrawal, (74

  16. Multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated hepatocellular carcinoma in a patient with alcohol-related liver cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Yoshitake Hayashi; Hirotsugu Ikawa; Kenji Ando; Keiji Mita; Shuichi Fuki; Michiie Sakamoto; Yoshihiro Kanbara; Toshiyuki Matsuoka; Masatoshi Kudo

    2007-01-01

    We describe a rare case of the transformation of a dysplastic nodule into well-differentiated hepatocellular carcinoma (HCC) in a 56-year-old man with alcoholrelated liver cirrhosis. Ultrasound (US) disclosed a 10 mm hypoechoic nodule and contrast enhanced US revealed a hypovascular nodule, both in segment seven.US-guided biopsy revealed a high-grade dysplastic nodule characterized by enhanced cellularity with a high N/C ratio, increased cytoplasmic eosinophilia,and slight cell atypia. One year later, the US pattern of the nodule changed from hypoechoic to hyperechoic without any change in size or hypovascularity. US-guided biopsy revealed well-differentiated HCC of the same features as shown in the first biopsy, but with additional pseudoglandular formation and moderate cell atypia.Moreover, immunohistochemical staining of cyclaseassociated protein 2, a new molecular marker of well-differentiated HCC, turned positive. This is the first case of multistep hepatocarcinogenesis from a dysplastic nodule to well-differentiated HCC within one year in alcohol-related liver cirrhosis.

  17. Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Cardoso, Rodolfo C; Herkimer, Carol; Veiga-Lopez, Almudena; Padmanabhan, Vasantha

    2016-08-01

    Gestational testosterone (TS) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E2) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. This study investigated (1) the organizational contribution of prenatal estrogen excess and (2) the impact of postnatal exposure to E2 in modulating the effects of prenatal androgen excess (TS and dihydrotestosterone (DHT)) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with TS, DHT, E2, or E2 plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), TS, and DHT female offspring received a constant-release E2 implant postnatally. Findings revealed that (1) prenatal E2-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and (2) prenatal E2D-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal TS excess. More importantly, continuous postnatal E2-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E2 on tonic luteinizing hormone (LH) release, failed to amplify the E2-positive feedback and periovulatory defects induced by prenatal TS-treatment. Our results indicate that disruptions in E2-positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal TS-treatment are programmed predominantly during the prenatal life with postnatal exposure to E2 excess not contributing further to these disruptions. PMID:27222598

  18. Developmental programming: postnatal estradiol modulation of prenatally organized reproductive neuroendocrine function in sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Cardoso, Rodolfo C; Herkimer, Carol; Veiga-Lopez, Almudena; Padmanabhan, Vasantha

    2016-08-01

    Gestational testosterone (TS) excess, acting via both the androgenic and estrogenic pathways, advances puberty and disrupts the neuroendocrine estradiol (E2) feedback and periovulatory hormonal dynamics in female sheep. These prenatally programmed defects may be subject to postnatal modifications by continued organizational and/or activational effects of steroids. This study investigated (1) the organizational contribution of prenatal estrogen excess and (2) the impact of postnatal exposure to E2 in modulating the effects of prenatal androgen excess (TS and dihydrotestosterone (DHT)) on puberty, neuroendocrine feedback mechanisms, and periovulatory hormonal dynamics in sheep. Pregnant Suffolk sheep were treated with TS, DHT, E2, or E2 plus DHT (ED) from days 30 to 90 of gestation. A subset of the control (C), TS, and DHT female offspring received a constant-release E2 implant postnatally. Findings revealed that (1) prenatal E2-treatment failed to reproduce the neuroendocrine disruptions predicted to be programmed by the estrogenic pathway and (2) prenatal E2D-treatment did not adequately replicate the reproductive neuroendocrine defects induced by prenatal TS excess. More importantly, continuous postnatal E2-treatment, while delaying the onset of puberty and reducing the inhibitory effects of E2 on tonic luteinizing hormone (LH) release, failed to amplify the E2-positive feedback and periovulatory defects induced by prenatal TS-treatment. Our results indicate that disruptions in E2-positive feedback mechanisms and periovulatory gonadotropin secretion induced by prenatal TS-treatment are programmed predominantly during the prenatal life with postnatal exposure to E2 excess not contributing further to these disruptions.

  19. Neuroendocrine carcinomas arising in ulcerative colitis:Coincidences or possible correlations?

    Institute of Scientific and Technical Information of China (English)

    Roberto Grassia; Paolo Bodini; Paolo Dizioli; Teresa Staiano; Elena Iiritano; Guglielmo Bianchi; Federico Buffoli

    2009-01-01

    Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal malignancies. Adenocarcinoma is the commonest type of colorectal neoplasm associated with ulcerative colitis (UC) and Crohn's disease,but other types of epithelial and non-epithelial tumors have also been described in inflamed bowel.With regards to non-epithelial malignancies, lymphomas and sarcomas represent the largest group oftumors reported in association with IBD, especially in immunosuppressed patients. Carcinoids and in particular neuroendocrine neoplasms other than carcinoids (NENs) are rare tumors and are infrequently described in the setting of IBD. Thus, this association requires further investigation. We report two cases of neoplasms arising in mild left-sided UC with immunohistochemical staining for neuroendocrine markers: a large cell and a small cell neuroendocrine carcinoma of the rectum. The two patients were different in age (35 years vs 77 years) and disease duration (11 years vs 27 years), and both had never received immunosuppressant drugs. Although the patients underwent regular endoscopic and histological follow-up, the two neoplasms were locally advanced at diagnosis. One of the two patients developed multiple liver metastases and died 15 mo after diagnosis. These findings confirm the aggressiveness and the poor prognosis of NENs compared to colorectal adenocarcinoma. While carcinoids seem to be coincidentally associated with IBD,NENs may also arise in this setting. In fact, long-standing inflammation could be directly responsible for the development of pancellular dysplasia involving epithelial,goblet, Paneth and neuroendocrine cells. It has yetto be established which IBD patients have a higher risk of developing NENs.

  20. Neuroendocrine effects of perfluorooctane sulfonate in rats.

    Science.gov (United States)

    Austin, Maureen E; Kasturi, Badrinarayanan S; Barber, Matthew; Kannan, Kurunthachalam; MohanKumar, Puliyur S; MohanKumar, Sheba M J

    2003-09-01

    Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats. PMID:12948888

  1. Pulmonary neuroendocrine tumors with nuclear inclusion.

    Science.gov (United States)

    Kobayashi, Saori; Tsuta, Koji; Sekine, Shigeki; Yoshida, Akihiko; Sasaki, Naoshi; Shibuki, Yasuo; Sakurai, Hiroyuki; Watanabe, Shun-Ichi; Asamura, Hisao; Tsuda, Hitoshi

    2013-09-01

    Nuclear inclusion or pseudoinclusion is a peculiar cytological feature, and its recognition in appropriate clinicopathological settings can aid in the diagnosis of several disease entities. To the best of our knowledge, only 1 case of pulmonary neuroendocrine tumor (NET) with nuclear pseudoinclusion has been reported. A review of 227 patients who had undergone surgical resection for pulmonary NETs revealed 2 tumors with different mechanisms of nuclear inclusion. To explore the cause of nuclear inclusion, NET with nuclear inclusion was characterized immunohistochemically and ultrastructurally. Nuclear inclusions were observed in 2 of the 227 (0.9%) patients with pulmonary NETs. The first patient was a 46-year-old woman with small cell carcinoma. Tumor cells with nuclear inclusions were distributed focally. Ultrastructural analysis showed that these inclusions were pseudoinclusions. The second patient was a 62-year-old man with large-cell neuroendocrine carcinoma. Nuclear inclusions were observed in the focal area of the tumor. Immunohistochemical analysis revealed that the intra-nuclear materials consisted of biotin and aberrant cytoplasmic and nuclear accumulation of β-catenin. Mutational analysis revealed a CTNNB1 gene mutation. Although very rare, diagnostic errors may be observed in cases of pulmonary NETs with nuclear inclusions. The mechanisms of nuclear inclusion differed, with one due to herniation of the cytoplasm into the nucleus (pseudoinclusion) and the other due to accumulation of biotin resulting from a CTNNB1 gene mutation. PMID:23896262

  2. Gestational dexamethasone alters fetal neuroendocrine axis.

    Science.gov (United States)

    Ahmed, R G

    2016-09-01

    This study tested whether the maternal transport of dexamethasone (DEXA) may affect the development of the neuroendocrine system. DEXA (0.2mg/kg b.w., subcutaneous injection) was administered to pregnant rats from gestation day (GD) 1-20. In the DEXA-treated group, a decrease in maternal serum thyroxine (T4), triiodothyronine (T3), and increase in thyrotropin (TSH) levels (hypothyroid status) were observed at GDs 15 & 20 with respect to control group. The reverse pattern (hyperthyroid status) was observed in their fetuses at embryonic days (EDs) 15 & 20. Although the maternal body weight was diminished, the weight of the thyroid gland was increased at studied GDs as compared to the control group. The fetal growth retardation, hyperleptinemia, hyperinsulinism, and cytokines distortions (transforming growth factor-beta; TGF-β, tumor necrosis factor-alpha; TNF-α, and interferon-γ; IFN-γ) were noticed at examined EDs if compared to the control group. Alternatively, the maternofetal thyroid dysfunctions due to the maternal DEXA administration attenuated the levels of fetal cerebral norepinephrine (NE) and epinephrine (E), and elevated the levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) at considered days. These alterations were age-dependent and might damage the nerve transmission. Finally, maternal DEXA might act as neuroendocrine disruptor causing dyshormonogenesis and fetal cerebral dysfunction. PMID:27220267

  3. Neuroendocrine differentiation in prostate cancer – a review

    Directory of Open Access Journals (Sweden)

    R. Popescu

    2015-12-01

    Full Text Available Objectives: This review aims to provide practicing clinicians with the most recent knowledge of the biological nature of prostate cancer especially the information regarding neuroendocrine differentiation. Methods: Review of the literature using PubMed search and scientific journal publications. Results: Much progress has been made towards an understanding of the development and progression of prostate cancer. The prostate is a male accessory sex gland which produces a fraction of seminal fluid. The normal human prostate is composed of a stromal compartment (which contains: nerves, fibroblast, smooth muscle cells, macrophages surrounding glandular acins – epithelial cells. Neuroendocrine cells are one of the epithelial populations in the normal prostate and are believed to provide trophic signals trough the secretion of neuropeptides that diffuse and influence surrounding epithelial cells. Prostate cancer is the most frequently diagnosed malignancy in men. In prostate cancer, neuroendocrine cells can stimulate growth of surrounding prostate adenocarcinoma cells (proliferation of neighboring cancer cells in a paracrine manner by secretion of neuroendocrine products. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that commonly arises in later stages of castration resistant prostate cancer. The detection of neuroendocrine prostate cancer has clinical implications. These patients are often treated with platinum chemotherapy rather than with androgen receptor targeted therapies. Conclusion: This review shows the need to improve our knowledge regarding diagnostic and treatment methods of the Prostate Cancer, especially cancer cells with neuroendocrine phenotype.

  4. Radiofrequency ablation of high-grade dysplastic nodules in chronic liver disease: comparison with well-differentiated hepatocellular carcinoma based on long-term results

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Hyun; Lim, Hyo K.; Kim, Min Ju; Choi, Dongil; Rhim, Hyunchul [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea); Park, Cheol Keun [Sungkyunkwan University School of Medicine, Department of Pathology, Samsung Medical Center, Seoul (Korea)

    2008-04-15

    This retrospective study compared the long-term results of percutaneous radiofrequency (RF) ablation for high-grade dysplastic nodules (DNs) and well-differentiated hepatocellular carcinomas (HCCs). Between April 1999 and December 2006, 20 patients with 21 high-grade DNs (range, 1.2-3.0 cm; mean, 1.9 cm) (group 1) and 49 with a well-differentiated HCC (range, 1.0-5.0 cm; mean, 2.3 cm) (group 2) underwent RF ablation. The technique effectiveness, local tumor progression, cancer-free and cumulative survivals using the Kaplan-Meier method were compared. The technique effectiveness rates at 1 year after RF ablation were 100% (19/19) and 94.1% (32/34) in groups 1 and 2, respectively (P > 0.05). The local tumor progression rates in groups 1 and 2 were 0% and 20.6% (7/34), respectively (P = 0.041). The local tumor progression in group 2 was seen on follow-up computed tomography 4-58 months (mean, 17 months) after RF ablation. The 1-, 3-, and 5-year cancer-free survival rates in groups 1 and 2 were 95.0% and 76.9%, 56.2% and 44.6%, and 38.5% and 24.8%, respectively (P > 0.05). The 1-, 3-, and 5-year cumulative survival rates in groups 1 and 2 were 100% and 97.9%, 73.0% and 68.0%, and 63.8% and 51.1%, respectively (P > 0.05). Percutaneous RF ablation is effective for treating high-grade DNs and well-differentiated HCCs. The long-term results after RF ablation of high-grade DNs may be improved compared with those of well-differentiated HCCs. (orig.)

  5. Aberrant LRP16 protein expression in primary neuroendocrine lung tumors

    OpenAIRE

    Shao, Yun; Li, Xiaoying; Lu, Yali; Liu, Lin; Zhao, Po

    2015-01-01

    Background: The Leukemia related protein 16 gene (LRP16) localized on chromosome 11q12.1, is an important estrogen-responsive gene and a crucial regulator for NF-kB activation. LRP16 is frequently expressed in human cancers; however, the LRP16 gene remains unexplored in lung neuroendocrine tumors. The aim of this study was to investigate the role of LRP16 expression in primary lung neuroendocrine tumors. Methods: lung neuroendocrine tumors were analyzed for LRP16 gene expression by two-step n...

  6. PET tracers for somatostatin receptor imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Knigge, Ulrich; Kjær, Andreas

    2014-01-01

    Neuroendocrine tumors have shown rising incidence mainly due to higher clinical awareness and better diagnostic tools over the last 30 years. Functional imaging of neuroendocrine tumors with PET tracers is an evolving field that is continuously refining the affinity of new tracers in the search...... for the perfect neuroendocrine tumor imaging tracer. (68)Ga-labeled tracers coupled to synthetic somatostatin analogs with differences in affinity for the five somatostatin receptor subtypes are now widely applied in Europe. Comparison of sensitivity between the most used tracers - (68)Ga-DOTA-Tyr3-octreotide...

  7. Neuroendocrine tumour arising inside a retro-rectal tailgut cyst: report of two cases and a review of the literature.

    Science.gov (United States)

    Spada, F; Pelosi, G; Squadroni, M; Lorizzo, K; Farris, A; de Braud, F; Fazio, N

    2011-01-01

    Tailgut cysts (or retro-rectal cyst-hamartomas (RCHs)) are developmental abnormalities consisting of multiloculated cysts lined by squamous, transitional or glandular epithelium which, albeit rarely, may give rise to malignant transformations. Carcinoid tumours arising in the presacral region are extremely rare and usually benign, and only a few are described in the literature. Case 1: A 63-year-old female diagnosed as having bilateral ovarian cysts underwent surgery to remove a right adnexial mass that was histopathologically diagnosed as a well-differentiated carcinoid tumour. She is currently disease free after 18 months of follow-up. Case 2: A 41-year-old-female diagnosed with hepatic metastases and a solid pelvic mass arising from a moderately differentiated neuroendocrine carcinoma is currently alive with disease after having undergone surgical removal of the mass and several medical treatments. We here describe two different clinical histories of well- and moderately differentiated neuroendocrine tumours (NETs) arising from tailgut cysts in the prerectal space together with a review of the relevant literature. PMID:22276050

  8. Observational study of patients with gastroenteropancreatic and bronchial neuroendocrine tumors in Argentina: Results from the large database of a multidisciplinary group clinical multicenter study

    Science.gov (United States)

    O’CONNOR, JUAN MANUEL; MARMISSOLLE, FABIANA; BESTANI, CLAUDIA; PESCE, VERONICA; BELLI, SUSANA; DOMINICHINI, ENZO; MENDEZ, GUILLERMO; PRICE, PAOLA; GIACOMI, NORA; PAIROLA, ALEJANDRO; LORIA, FERNANDO SÁNCHEZ; HUERTAS, EDUARDO; MARTIN, CLAUDIO; PATANE, KARINA; POLERI, CLAUDIA; ROSENBERG, MOISES; CABANNE, ANA; KUJARUK, MIRTA; CAINO, ANALIA; ZAMORA, VICTOR; MARIANI, JAVIER; DIOCA, MARIANO; PARMA, PATRICIA; PODESTA, GUSTAVO; ANDRIANI, OSCAR; GONDOLESI, GABRIEL; ROCA, ENRIQUE

    2014-01-01

    Neuroendocrine tumors (NET) include a spectrum of malignancies arising from neuroendocrine cells throughout the body. The objective of this clinical investigation of retrospectively and prospectively collected data was to describe the prevalence, demographic data, clinical symptoms and methods of diagnosis of NET and the treatment and long-term follow-up of patients with NET. Data were provided by the participating centers and assessed for consistency by internal reviewers. All the cases were centrally evaluated (when necessary) by the pathologists in our group. The tissue samples were reviewed by hematoxylin and eosin and immunohistochemical staining techniques to confirm the diagnosis of NET. In total, 532 cases were documented: 461 gastroenteropancreatic-NET (GEP-NET) and 71 bronchial NET (BNET). All the tumors were immunohistochemically defined according to the World Health Organization (WHO) and European Neuroendocrine Tumor Society criteria. The most common initial symptoms in GEP-NET were abdominal pain, diarrhea, bowel obstruction, flushing, gastrointestinal bleeding and weight loss. The most common tumor types were carcinoid (58.0%), non-functional pancreatic tumor (23.0%), metastatic NET of unknown primary (16.0%) and functional pancreatic tumor (3.0%). Of the BNET, 89.0% were typical and 11.0% atypical carcinoids. Of the patients with GEP-NET, 59.2% had distant metastasis at diagnosis. The locations of the primary tumors in GEP-NET were the small bowel (26.9%), pancreas (25.2%), colon-rectum (12.4%), appendix (7.6%), stomach (6.9%), esophagus (2.8%), duodenum (2.0%) and unknown primary (16.3%). The histological subtypes based on the WHO classification were well-differentiated NET (20.1%), well-differentiated neuroendocrine carcinomas (66.5%) and poorly differentiated neuroendocrine carcinomas (10.3%). Overall, 67.3% of the patients underwent surgery, 41.2% with curative intent and 26.1% for palliative purposes. The 5-year survival rates were 65.1% (95

  9. Neuroendocrine tumors of the gastro-entero-pancreatic system

    Institute of Scientific and Technical Information of China (English)

    Sara Massironi; Valentina Sciola; Maddalena Peracchi; Clorinda Ciafardini; Matilde Pia Spampatti; Dario Conte

    2008-01-01

    Gastro-entero-pancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms,although their prevalence has increased substantially over the past three decades.Moreover,there has been an increased clinical recognition and characterization of these neoplasms.They show extremely variable biological behavior and clinical course.Most NETs have endocrine function and secrete peptides and neuroamines that cause distinct clinical syndromes,including carcinoid syndrome; however,many are clinically silent until late presentation with mass effects.Investigation and management should be individualized for each patient,taking into account the likely natural history of the tumor and general health of the patient.Management strategies include surgery for cure or palliation,and a variety of other cytoreductive techniques,and medical treatment including chemotherapy,and biotherapy to control symptoms due to hormone release and tumor growth,with somatostatin analogues (SSAs) and alphainterferon.New biological agents and somatostatintagged radionuclides are under investigation.Advances in the therapy and development of centers of excellence which coordinate multicenter studies,are needed to improve diagnosis,treatment and therefore survival of patients with GEP NETs.(C)2008 The WIG Press.All rights reserved.

  10. Endoscopic diagnosis and treatment of pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Rustagi, Tarun; Farrell, James J

    2014-01-01

    Pancreatic neuroendocrine tumors (PNETs) are rare pancreatic neoplasms comprising only 1% to 2% of all pancreatic tumors. In recent years, the number of incidentally discovered PNETs has greatly increased given the widespread use of axial imaging. However, a significant proportion of PNETs may not be visualized on conventional imaging such as computed tomography, magnetic resonance imaging, and somatostatin receptor scintigraphy. Endoscopic ultrasound (EUS) has become an integral part of the diagnosis of PNETs because of its high sensitivity for detecting, localizing, and diagnosing PNETs. EUS-guided tissue acquisition provides histologic and immunologic confirmation, and may also allow prognostication about tumor behavior. In addition to preoperative assessment of these tumors, EUS has also been shown to have an important role in nonoperative management of small nonfunctional PNETs. Finally, recent developments suggest that interventional EUS may be used to aid intraoperative localization of PNETs and to deliver therapeutic agents for the treatment of PNETs. This review will discuss the endoscopic diagnosis and treatment of PNETs, with focus on recent advances in the utility of EUS in the clinical management of these tumors.

  11. Update on Novel Therapies for Pancreatic Neuroendocrine Tumors: 2013

    Directory of Open Access Journals (Sweden)

    Anastasios Dimou

    2012-07-01

    Full Text Available Neuroendocrine tumors of the pancreas (pNETs are classified on the basis of their differentiation as well as the functionalstatus. Current treatment options for non resectable disease include everolimus, sunitinib, somatostatin analogs andchemotherapy. A number of trials with novel compounds and drug combinations were reported at the recent ASCO AnnualMeeting. Pasireotide is a novel somatostatin analog with broader affinity for the somatostatin receptors compared to thetraditional octreotide and lantreotide and it appears to be safe in patients with pNETs according to a phase I study (Abstract#e15126. The combination of octreotide with everolimus showed promising response rate and progression free survival ina phase II study (Abstract #4136. In another phase II study, the AKT inhibitor MK-2206 was well tolerated with moderateefficacy (Abstract #e15133. Last but not least, we discuss the updated data from a phase II study that used the combinationof temsirolimus with bevacizumab in patients with advanced pNETs (Abstract #4032.

  12. Peptide receptor radionuclide therapy of neuroendocrine tumours.

    Science.gov (United States)

    Brabander, Tessa; Teunissen, Jaap J M; Van Eijck, Casper H J; Franssen, Gaston J H; Feelders, Richard A; de Herder, Wouter W; Kwekkeboom, Dik J

    2016-01-01

    In the past decades, the number of neuroendocrine tumours that are detected is increasing. A relative new and promising therapy for patients with metastasised or inoperable disease is peptide receptor radionuclide therapy (PRRT). This therapy involves an infusion of somatostatin analogues linked to radionuclides like Yttrium-90 or Lutetium-177. Objective response rates are reported in 15-35%. Response rates may vary between type of tumour and radionuclide. Besides the objective response rate, overall survival and progression free survival increase significantly. Also, the quality of life improves as well. Serious side-affects are rare. PRRT is usually well tolerated, also in patients with extensive metastasised disease. Recent studies combined PRRT with other types of therapies. Unfortunately no randomised trials comparing these strategies are available. In the future, more research is needed to evaluate the best therapy combinations or sequence of therapies. PMID:26971847

  13. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs;

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  14. Somatostatin-Immunoreactive Pancreaticoduodenal Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Engelund Luna, Iben; Monrad, Nina; Binderup, Tina;

    2016-01-01

    in the pancreas, metastatic disease at diagnosis and higher tumour grade were all associated with a significantly poorer survival. CONCLUSION: None of the patients with p-dSOM presented with the full somatostatinoma syndrome. Prognostic factors are localisation of the primary tumour, dissemination and tumour......OBJECTIVE: Neuroendocrine neoplasms in the pancreas and duodenum with predominant or exclusive immunoreactivity for somatostatin (p-dSOMs) are rare, and knowledge on tumour biology, treatment, survival and prognostic factors is limited. This study aimes to describe clinical, pathological...... with duodenal SOM the m/f ratio was 4/5. All males and one female had NF-1. Seven patients had stage 1A-B and 2 had stage 2B disease. The Ki-67 index was 1-5% (median 2%). Plasma somatostatin was elevated in patients with 2B disease. Of the 14 patients with pancreatic SOM or unknown primary tumour the m/f ratio...

  15. Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

    International Nuclear Information System (INIS)

    Pancreatic neuroendocrine tumors (PNETs) are rare primary neoplasms of the pancreas and arise sporadically or in the context of genetically determined syndromes. Depending on hormone production and sensing, PNETs clinically manifest due to a hormone-related syndrome (functional PNET) or by symptoms related to tumor bulk effects (non-functional PNET). So far, radical surgical excision is the only therapy to cure the disease. Development of tailored non-surgical approaches has been impeded by the lack of experimental laboratory models and there is, therefore, a limited understanding of the complex cellular and molecular biology of this heterogeneous group of neoplasm. This review aims to summarize current knowledge of tumorigenesis of familial and sporadic PNETs on a cellular and molecular level. Open questions in the field of PNET research are discussed with specific emphasis on the relevance of disease management

  16. [Renal neuroendocrine tumor (carcinoid) : a case report].

    Science.gov (United States)

    Inagaki, Yusuke; Fujita, Kazutoshi; Nakai, Yasutomo; Takayama, Hitoshi; Tsujimura, Akira; Nonomura, Norio

    2013-11-01

    A 32-year-old man was referred to our hospital for treatment of left renal cystic tumor, which was detected by computed tomographic (CT) scan 3 years ago. CT scan showed a multilocular cyst (5 cm in diameter) with a solid tumor in the left kidney which was enhanced with contrast. There was no evidence of extrarenal invasion or distant metastasis. We performed retroperitoneal laparoscopic radical nephrectomy. Pathological examinations revealed a cellular arrangement specific to carcinoid tumor and positive for CD56 (NCAM) and neuron-specific enolase. The cell proliferation rate was estimated to be under 2% with Ki67 staining. The pathological diagnosis was renal neuroendocrine tumor (carcinoid). At the 9-month follow up, he had no evidence of local recurrence or metastasis.

  17. New pharmacologic therapies for gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Lawrence, Ben; Gustafsson, Bjorn I; Kidd, Mark; Modlin, Irvin

    2010-09-01

    Successful treatment of unresectable and metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) requires the thoughtful choice of systemic therapy as a component of a multidisciplinary therapeutic approach. The role of somatostatin analogues is established in symptom relief, but the efficacy of interferon and radiopeptide targeted therapy is not clear. The utility of a variety of tyrosine kinase and antiangiogenic agents is variable and under investigation, whereas the role of cytotoxic chemotherapy in poorly differentiated GEP-NETs is accepted. Overall, the ideal treatment of more indolent tumors is less certain. Reassessments of the GEP-NET pathology classification has provided improved logic for the role of a variety of agents, whereas the precise positioning of many new agents that target molecular pathways of angiogenesis and proliferation is under examination. This article describes the current options for systemic therapy for GEP-NETs within the framework of the current World Health Organization classification system. PMID:20951920

  18. Prenatal programming of neuroendocrine reproductive function.

    Science.gov (United States)

    Evans, Neil P; Bellingham, Michelle; Robinson, Jane E

    2016-07-01

    It is now well recognized that the gestational environment can have long-lasting effects not only on the life span and health span of an individual but also, through potential epigenetic changes, on future generations. This article reviews the "prenatal programming" of the neuroendocrine systems that regulate reproduction, with a specific focus on the lessons learned using ovine models. The review examines the critical roles played by steroids in normal reproductive development before considering the effects of prenatal exposure to exogenous steroid hormones including androgens and estrogens, the effects of maternal nutrition and stress during gestation, and the effects of exogenous chemicals such as alcohol and environment chemicals. In so doing, it becomes evident that, to maximize fitness, the regulation of reproduction has evolved to be responsive to many different internal and external cues and that the GnRH neurosecretory system expresses a degree of plasticity throughout life. During fetal life, however, the system is particularly sensitive to change and at this time, the GnRH neurosecretory system can be "shaped" both to achieve normal sexually differentiated function but also in ways that may adversely affect or even prevent "normal function". The exact mechanisms through which these programmed changes are brought about remain largely uncharacterized but are likely to differ depending on the factor, the timing of exposure to that factor, and the species. It would appear, however, that some afferent systems to the GnRH neurons such as kisspeptin, may be critical in this regard as it would appear to be sensitive to a wide variety of factors that can program reproductive function. Finally, it has been noted that the prenatal programming of neuroendocrine reproductive function can be associated with epigenetic changes, which would suggest that in addition to direct effects on the exposed offspring, prenatal programming could have transgenerational effects on

  19. Neuroendocrine cells in the urogenital tract of the buffalo

    Directory of Open Access Journals (Sweden)

    A. Vittoria

    2010-02-01

    Full Text Available Neuroendocrine cells or paraneurons are cytotypes producing biogenic amines and/or hormonal peptides, scattered in the glandular and lining epithelia of the body. In this study the presence of chromogranin A-, serotonin- and somatostatin-immunoreactive neuroendocrine cells has been described immunohistochemically in the urethro- prostatic complex and female urethra of subjects of the buffalo Bubalus bubalis. The chromogranin A- containing neuroendocrine cells resulted the most numerous cytotype, the serotonin- containing ones the most irregular in shape for the presence of dendritic-like cytoplasmic extensions and the somatostatin- containing the rarest. The role played by the amine serotonin in the genital tract has been related to the determinism of sexual climax and to the contraction of smooth muscle. The function played by the neuroendocrine genital somatostatin is unknown. Analogically to what described for the same gastrointestinal hormone, it could inhibit both exocrine and endocrine secretions.

  20. Fast-growing large cell neuroendocrine carcinoma of mediastinum.

    Science.gov (United States)

    Lukina, Olga; Gorbunkov, Stanislav; Dvorakovskaja, Ivetta; Varlamov, Vladimir; Akopov, Andrey

    2011-05-01

    Neuroendocrine carcinomas combine a heterogeneous group of tumors occurring in lungs on a rare occasion, and in some cases, they appear to have extraordinary quick growth and extrapulmonary localization. In this case we present a 42-year-old patient who underwent a right upper lobectomy for emphysema, and 6 months later, the tumor developed again into a giant neuroendocrine carcinoma of the mediastinum. PMID:21524479

  1. A case of an intussuscepted neuroendocrine carcinoma of the appendix

    Institute of Scientific and Technical Information of China (English)

    Rachel E Thomas; Karen Maude; Olorunda Rotimi

    2006-01-01

    We have described a previously unreported entity of an intussuscepted neuroendocrine carcinoma of the appendix. Our patient was a 70-year-old man whose only complaint was insipient weight loss. Colonoscopy showed a malignant cecal "polyp", and an extended right hemicolectomy was performed. We have reviewed the literature on the causes of appendiceal intussusception and their appropriate treatment options, and clarified the classification of neuroendocrine tumors of the gastrointestinal tract.

  2. Antiproliferative effect of somatostatin analogs in gastroenteropancreatic neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    Jonathan; Strosberg; Larry; Kvols

    2010-01-01

    Somatostatin analogs were initially developed for the control of hormonal syndromes associated with neuro-endocrine tumors (NETs). In recent years, accumul ating data has supported their role as antiproliferative agents, capable of stabilizing tumor growth in patients with metastatic neuroendocrine malignancies, including carci-noid and pancreatic endocrine tumors. A phase Ⅲ, ran-domized, placebo-controlled trial has now demonstrated that octreotide long-acting repeatable (LAR) 30 mg can significantly prolo...

  3. Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism

    OpenAIRE

    Park, Hyeong-Kyu; Ahima, Rexford S.

    2014-01-01

    Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Leptin administration has been shown to restore metabolic and neuroendocrine abnormalities in individuals with leptin-deficient states, including hypothalamic amenorrhea and lipoatrophy. In contrast, obese individuals are resistant to leptin. Recombinant leptin is beneficial in pa...

  4. [Contemporary management of neuroendocrine neoplasms of the female genital organs].

    Science.gov (United States)

    Kuc-Rajca, Małgorzata; Dańska-Bidzińska, Anna

    2011-09-01

    Neuroendocrine neoplasms are a rare and heterogeneous group of diseases that account for only 2% of all gynecologic malignancies. The most common types are ovarian carcinoid tumor and small cell neuroendocrine carcinoma of the cervix. The tumors are staged according to FIGO clinical staging system. The diagnosis is usually made retrospectively after obtaining the results of histopathological evaluation of the primary tumor They rarely cause syndromes related to hormone overexpression. Neuroendocrine neoplasms are characterized by aggressive behaviour Even at an early stage there is high incidence of nodal and distant metastases. Survival is poor regardless of stage at diagnosis. The most important is to diagnose the neuroendocrine tumor accurately and treat it in multimodal, aggressive approach to control the disease better and reduce the incidence of reccurences. Apart from typical therapeutic approach, treatment may encompass isotope therapy using radiolabeled somatostatin analogs. This method should be reserved for patients with expression of somatostatin receptors detected by the somatostatin receptor scyntygraphy. Data concerning the management of neuroendocrin tumors are based mainly on retrospective studies and clinical case series. Lack of randomized trials makes it impossible to select the best treatment option. Better understanding of the biology of neuroendocrine tumors, especially the molecular genetics, will in the future help to determine the optimal treatment strategies for these tumors.

  5. Case Report of a Well-Differentiated Papillary Mesothelioma of the Tunica Vaginalis in an Undescended Testis With Review of Literature.

    Science.gov (United States)

    Parcesepe, Pietro; Sina, Sokol; Zanella, Caterina; Pancione, Massimo; Giuliani, Jacopo; Detogni, Paolo; Curti, Pierpaolo; Bonetti, Andrea; Manfrin, Erminia; Remo, Andrea

    2016-08-01

    Well-differentiated papillary mesothelioma (WDPM) affecting the tunica vaginalis testis is a rare tumor, and very little is known about the clinicopathological spectrum of this variant as a distinct entity. Most patients with WDPM suffer from scrotal pain or swelling, but hydrocele seems to be the most common presenting symptom. These lesions are usually not aggressive and are accompanied by an indolent clinical behavior. In this article, we report the first case known of WDPM in an undescended testis, and in addition, we review the literature for similar cases. PMID:26873338

  6. Refractory Thrombocytopenia Responds to Octreotide Treatment in a Case of Evans Syndrome with Gastric Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Kocfa Chung-Delgado

    2013-01-01

    Full Text Available A 37-year-old woman with history of Evans Syndrome with poor response to high-dose corticoid treatment presented to the emergency department with gastrointestinal and vaginal bleeding. The patient was later diagnosed with severe thrombocytopenia and a stage G1, well-differentiated gastric neuroendocrine tumor, confirmed by a biopsy. A total gastrectomy was performed to eradicate the tumor. After being treated with a total splenectomy for her Evans Syndrome with no clinical or laboratory improvement, she began regular treatment with octreotide on the basis of a possible hepatic metastasis. Days after the initiation of the octreotide, an increase in the platelet count was evidenced by laboratory findings, from 2,000 platelets/mm3 to 109,000 platelets/mm3. Weeks later, the hepatic metastasis is discarded by a negative octreotide-body scan, and the octreotide treatment was interrupted. Immediately after the drug interruption, a progressive and evident descent in the platelet count was evidenced (4000 platelets/mm3. The present case report highlights the possible association between octreotide treatment and a severe thrombocytopenia resistant to conventional treatment.

  7. Neuroendocrine tumor in gastric adenoma: a diagnostic pitfall mimicking invasive adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lee Sun-Mi

    2012-08-01

    Full Text Available Abstract Neuroendocrine tumor (NET in adenoma of the gastrointestinal tract is a rare mixed glandular-endocrine neoplasm and has uncommonly been described mostly in the colon. Histologically, this tumor is composed of a predominant proportion of benign adenomatous component and a small portion of well-differentiated NE component. Only three cases of NET in gastric adenoma have been reported in the literature. We present 4 cases of NET in gastric adenoma mimicking invasive adenocarcinoma. The NETs were 0.62 mm to 4.1 mm in size and located at the basal lamina propria, muscularis mucosa and submucosa. Histologically, NETs consisted of nests, cords, tubules, and clusters of cells that predominantly interposed between the foveolar base without disturbing the overall polyp architecture. The lesions were completely removed by endoscopic submucosal dissection in three cases and in one case, subtotal gastrectomy was performed because endoscopic biopsy was invasive adenocarcinoma. The patients’ clinical course was uneventful without an evidence of recurrence or metastasis. The recognition of NET in gastric adenoma will help avoid potential diagnostic pitfalls masquerading as invasvie adenocarcinomas posed by their infiltrative pattern into submucosa. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1688552293761001

  8. Neuroendocrine and Immune System Responses with Spaceflights

    Science.gov (United States)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  9. [Summary of the Israeli Endocrine Society's consensus statement on the diagnosis, treatment and follow-up of well-differentiated thyroid cancer].

    Science.gov (United States)

    Arbelle, Jonathan E; Shalom, Sophia Ish; Benbassat, Carlos; Dickstein, Gabriel; Glasser, Benjamin; Liel, Yair

    2008-10-01

    Well differentiated epithelial cell thyroid cancer is not classified amongst the most aggressive diseases. Notwithstanding, it can potentially both impair quality of life and affect life expectancy. Appropriate treatment has been shown to be crucial in obtaining optimal outcomes on the course of the disease. Successful treatment rests upon strict adherence to confirmed principles of diagnosis, treatment and follow-up. The aim of the position paper is to present the Israeli medical community with a set of commonly accepted principles for the diagnosis, treatment and follow-up of patients with well differentiated epithelial thyroid cancer and in addition to highlight areas of legitimate differences in approach where those differences occur. We have attempted to provide a link between the various medical disciplines involved in care of these patients: family physicians, surgeons, nuclear medicine specialists, oncologists, pathologists, radiologists and endocrinologists; and have attempted to decrease to a minimum areas of uncertainty and to offer a common approach for the best possible care of thyroid cancer patients in Israel. In addition, we find it our duty to point out those areas and resources which, in our opinion, need to be upgraded in Israel and even included in the Israeli official "health basket". PMID:19039917

  10. The expression of MDM2/CDK4 gene product in the differential diagnosis of well differentiated liposarcoma and large deep-seated lipoma

    Science.gov (United States)

    Pilotti, S; Torre, G Della; Mezzelani, A; Tamborini, E; Azzarelli, A; Sozzi, G; Pierotti, M A

    2000-01-01

    Ordinary lipomas are cytogenetically characterized by a variety of balanced rearrangements involving chromosome segment 12q13–15, whereas well differentiated liposarcomas (WDL) show supernumerary ring and giant marker chromosomes, known to contain amplified 12q sequences. The tight correlation between the presence of ring chromosomes and both amplification and overexpression of MDM2 and CDK4 genes suggests the exploration of the possibility that immunocytochemistry (ICC) might assist in the differential diagnosis of lipoma-like well differentiated liposarcomas (LL-WDL) and large deep-seated lipomas (LDSL). For this purpose, 21 cases of the former and 19 cases of the latter tumours were analysed by ICC and, according to the availability of material, by molecular and cytogenetic approaches. All lipomas displayed a null MDM2/CDK4 phenotype, whereas all LL-WDL showed MDM2/CDK4 or CDK4 phenotypes. Southern blot analysis performed on 16 suitable cases, complemented by fluorescence in situ hybridization and classical cytogenetic analysis in 11 cases, was consistent with, and further supported the immunophenotyping data. In conclusion, MDM2/CDK4 product-based immunophenotyping appears to represent a valuable method for the categorization of arguable LDSL. © 2000 Cancer Research Campaign PMID:10755400

  11. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

    2016-04-15

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  12. Contemporary nuclear medicine imaging of neuroendocrine tumours

    International Nuclear Information System (INIS)

    Neuroendocrine tumours (NETs) are rare, heterogeneous, and often hormonally active neoplasms. Nuclear medicine (NM) imaging using single photon- and positron-emitting radiopharmaceuticals allows sensitive and highly specific molecular imaging of NETs, complementary to anatomy-based techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Somatostatin-receptor scintigraphy is a whole-body imaging technique widely used for diagnosis, staging and restaging of NETs. The increasing availability of hybrid single-photon emission CT (SPECT)/CT cameras now offers superior accuracy for localization and functional characterization of NETs compared to traditional planar and SPECT imaging. The potential role of positron-emission tomography (PET) tracers in the functional imaging of NETs is also being increasingly recognized. In addition to 2-[18F]-fluoro-2-deoxy-D-glucose (FDG), newer positron-emitting radiopharmaceuticals such as 18F-dihydroxyphenylalanine (DOPA) and 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) peptides, show promise for the future. This article will summarize the role of current and emerging radiopharmaceuticals in NM imaging of this rare but important group of tumours.

  13. Digestive neuroendocrine neoplasms: A 2016 overview.

    Science.gov (United States)

    Merola, Elettra; Rinzivillo, Maria; Cicchese, Noemi; Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco

    2016-08-01

    Digestive neuroendocrine neoplasms (DNENs) have an incidence of 2.39 per 100,000 inhabitants per year, and a prevalence of 35 cases per 100,000; the gap between these rates is to be referred to the relatively long survival that characterizes the majority of these tumors, which can be thus considered as chronic oncological diseases. Up to 80% of patients are stage IV since the first diagnosis, presenting a 5-yr overall survival rate of 35%-55% and a twice higher mortality than limited disease. DNENs express somatostatin receptors in more than 80% of cases, detected through immunohistochemistry or functional imaging tests (FITs). This feature identifies patients who may benefit from "cold" somatostatin analogs (SSAs) or peptide receptors radionuclide therapy, although SSAs are sometimes used also with a negative uptake at FITs. The therapeutic options have been recently increased after the identification of molecular pathways involved in DNENs pathogenesis, and the subsequent use of targeted therapies (i.e., Everolimus and Sunitinib) for these neoplasms. This review offers an overview about pancreatic and small bowel NENs, critically underlining the issues that still need to be clarified and the future perspectives to be investigated. PMID:27212431

  14. Neurogenic and neuroendocrine effects of goldfish pheromones.

    Science.gov (United States)

    Chung-Davidson, Yu-Wen; Rees, Christopher Benjamin; Bryan, Mara Beth; Li, Weiming

    2008-12-31

    Goldfish (Carassius auratus) use reproductive hormones as endocrine signals to synchronize sexual behavior with gamete maturation and as exogenous signals (pheromones) to mediate spawning interactions between conspecifics. We examined the differential effects of two hormonal pheromones, prostaglandin F(2alpha) (PGF(2alpha)) and 17alpha,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P) on neurogenesis, neurotransmission, and neuronal activities, and on plasma androstenedione (AD) levels. Exposure to waterborne PGF(2alpha) induced a multitude of changes in male goldfish brain. Histological examination indicated an increase in the number of dividing cells in male diencephalon (p GnRH) in the male telencephalon and cerebellum (p chicken-II GnRH) in the female cerebellum (p < 0.05, one-way ANOVA). PGF(2alpha) and 17,20beta-P thereby seemed to act through distinct pathways to elicit different responses in the neuroendocrine system. This is the first finding that links a specific pheromone molecule (PGF(2alpha)) to neurogenesis in a vertebrate animal. PMID:19118184

  15. Primary hepatic neuroendocrine tumor: A case report

    Science.gov (United States)

    MORISHITA, ASAHIRO; YONEYAMA, HIROHITO; NOMURA, TAKAKO; SAKAMOTO, TEPPEI; FUJITA, KOJI; TANI, JOJI; MIYOSHI, HISAAKI; HABA, REIJI; MASAKI, TSUTOMU

    2016-01-01

    We herein present a case of an 87-year-old patient with multiple liver tumors identified on abdominal ultrasound. The assessment performed on admission included physical examination, computed tomography (CT) during hepatic angiography and CT during arterial portography. The examination revealed contrast enhancement of a proportion of the liver tumors (20 mm maximum diameter) during the arterial phase and mild contrast washout of those tumors during the delayed phase. On contrast-enhanced magnetic resonance imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid, certain liver tumors exhibited contrast enhancement during the early phase and contrast washout during the hepatocyte phase in both lobes. By contrast, no lesions were identified during positron emission tomography imaging of the liver. A liver biopsy was performed and immunohistochemical staining revealed enhanced expression of cytokeratin AE1/AE3, synaptophysin, chromogranin A and CD56 and no expression of hepatocyte antigen or CΚ7. The mindbomb E3 ubiquitin protein ligase-1 index was ~2% in most of the tumor. The liver tumors were finally diagnosed as multiple intrahepatic metastases from a primary hepatic neuroendocrine tumor (PHNET). The patient underwent transarterial chemoembolisation with a combination of miriplatin (84 mg) mixed with gelatin sponge particles and lipiodol. To the best of our knowledge, this is the first report of PHNET in an patient aged >85 years. PMID:27284429

  16. Breast Carcinoma With Unrecognized Neuroendocrine Differentiation Metastasizing to the Pancreas: A Potential Diagnostic Pitfall.

    Science.gov (United States)

    Christensen, Lene; Mortensen, Michael Bau; Detlefsen, Sönke

    2016-08-01

    The current World Health Organization classification recognizes 3 subtypes of breast carcinomas with neuroendocrine features. Their reported prevalence is highly variable, ranging from breast carcinomas. We report the case of a 73-year-old woman who underwent lumpectomy with a postoperative diagnosis of invasive ductal breast carcinoma. Six weeks after lumpectomy, pancreatic biopsies showed tumor cells with neuroendocrine features. The first immunohistochemical panel showed positivity for synaptophysin and cytokeratins, raising suspicion of a pancreatic neuroendocrine tumor. However, a second panel revealed positivity for estrogen receptors and GATA3. On review of the lumpectomy specimen, a significant neuroendocrine component was found, leading to the final diagnosis of breast carcinoma with neuroendocrine features metastasizing to the pancreas. Neuroendocrine markers are not routinely analyzed in breast tumors. Hence, metastases from breast carcinomas with unrecognized neuroendocrine features may lead to false diagnoses of primary neuroendocrine tumors at different metastatic sites, such as the pancreas. PMID:26912472

  17. Factors Associated with Survival of Veterans with Gastrointestinal Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Bryan L. Balmadrid

    2012-01-01

    Full Text Available Background. Gastrointestinal (GI neuroendocrine tumor (NET incidence has been increasing; however, GI NET within the national Veterans Affairs (VA health system has not been described. Methods. We used the VA Central Cancer Registry to identify the cohort of patients diagnosed with GI NET in 1995–2009. Cox regression models were constructed to explore factors associated with survival. Results. We included 1793 patients with NET of the stomach (9%, duodenum (10%, small intestine (24%, colon (19% or rectum (38%. Twenty percent were diagnosed in 1995–1999, 35% in 2000–2004, and 45% in 2005–2009. Unadjusted 5-year survival rates were: stomach 56%, duodenum 66%, small intestine 52%, colon 67%, and rectum 84%. Factors associated with shorter survival were increasing age, hazard ratio (HR 1.05 (95% CI 1.04–1.06, NET location [compared to rectum: stomach HR 2.26 (95% CI 1.68–3.05, duodenum HR 1.70 (95% CI 1.26–2.28, small intestine HR 1.85 (95% CI 1.42–2.42, and colon 1.83 (95% CI 1.41–2.39], stage [compared to in situ/local: regional HR 1.15 (95% CI 0.90–1.47, distant HR 2.38 (95% CI 1.87–3.05], and earlier period of diagnosis [compared to 1995–1999: 2000–2004 HR 0.70 (95% CI 0.59–0.85, 2005–2009 HR 0.43 (95% CI 0.34–0.54]. Conclusions. The incidence of GI NET has also increased over time in the VA system with similar survival rates to those observed in non-VA settings. Worsened survival was associated with older age, tumor site, advanced stage, and earlier year of diagnosis.

  18. Biological characteristics of breast carcinomas with neuroendocrine cell differentiation

    Institute of Scientific and Technical Information of China (English)

    姚根有; 周吉林; 赵仲生; 阮俊

    2004-01-01

    Background The aim of this study was to investigate DNA content and expression of c-erbB-2, PS2, and prostate-specific antigen (PSA) proteins in breast carcinomas with neuroendocrine (NE) cell differentiation.Methods Chromogranin, c-erbB-2, PS2, and PSA in 131 samples of breast cancer were detected immunohistochemically. Classic Feulgen staining image analysis techniques were used to quantify DNA content in 81 of the breast cancer samples.Results The c-erbB-2 positive rate in breast carcinoma samples containing neuroendocrine cells was 37.5% and the rate of high expression of c-erbB-2 (++ or +++) was 33.3%, both significantly lower than that in breast carcinomas without neuroendocrine cells (62.6% and 68.7%, respectively, P 5c aneuploidy cells, and rate of aneuploidy among cells were all lower than that in NE (-) breast carcinomas (P<0.01). In NE (+) grade I or II breast carcinomas, these indices were also all lower than that in the NE (-) breast carcinoma samples (P<0.01).Conclusion Breast carcinomas with neuroendocrine differentiation have a lower rate of malignancy. Neuroendocrine differentiation could serve as a prognostic marker in clinical practice.

  19. Concomitant Small Cell Neuroendocrine Carcinoma of Gallbladder and Breast Cancer

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    Paolo Aiello

    2014-01-01

    Full Text Available The neuroendocrine carcinoma is defined as a high-grade malignant neuroendocrine neoplasm arising from enterochromaffin cells, usually disposed in the mucosa of gastric and respiratory tracts. The localization in the gallbladder is rare. Knowledge of these gallbladder tumors is limited and based on isolated case reports. We describe a case of an incidental finding of small cell neuroendocrine carcinoma of the gallbladder, observed after cholecystectomy for cholelithiasis, in a 55-year-old female, who already underwent quadrantectomy and sentinel lymph-node biopsy for breast cancer. The patient underwent radiotherapy for breast cancer and six cycles of chemotherapy with cisplatin and etoposide. Eighteen months after surgery, the patient was free from disease. Small cell neuroendocrine carcinoma of the gallbladder has poor prognosis. Because of the rarity of the reported cases, specific prognostic factors have not been identified. The coexistence of small cell neuroendocrine carcinoma of the gallbladder with another malignancy has been reported only once. The contemporary presence of the two neoplasms could reflect that bioactive agents secreted by carcinoid can promote phenotypic changes in susceptible cells and induce neoplastic transformation.

  20. Neoadjuvant Chemotherapy with Capecitabine and Temozolomide for Unresectable Pancreatic Neuroendocrine Tumor

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    Sumana Devata

    2012-11-01

    Full Text Available Pancreatic neuroendocrine tumors (PNETs are relatively rare tumors that arise in the endocrine cells of the pancreas. Historically, somatostatin analogues have been used in this disease primarily for symptom control and, to a limited extent, disease stability. More recently, sunitinib and everolimus have been approved for advanced stage PNETs based on a survival benefit. However, both agents have a <10% actual response rate and cause nontrivial side effect profiles that limit duration of therapy. In locally advanced disease, there is a paucity of data to support an optimal neoadjuvant approach with the expectation of down-staging to allow for curative resection. We describe in this case a young woman who was successfully down-staged using a chemotherapy regimen of capecitabine and temozolomide with minimal toxicity.

  1. [Neuroendocrine carcinoma of the ampullar region with oat-cell histological features and adenocarcinoma].

    Science.gov (United States)

    Fresno, M F; Floriano, P; Díaz Iglesias, J M; Ablanedo, P; Pérez del Río, M J; Barneo, L; Herrero, A

    1997-01-01

    We report a case of primary duodenal carcinoma showing neuroendocrine and glandular differentiation, in a 65-years-old male. Both components were closely related and transition between them was observed. The neuroendocrine component was composed of an undifferentiated "oat-cell" type, with positive immunostaining for neuroendocrine and epithelial markers. Ultrastructural findings confirmed this double differentiation, with dense cytoplasmatic granules of neurosecretory type. The neuroendocrine component showed greater aggressiveness with lymph node metastasis.

  2. 高分化星形细胞瘤的蛋白质组学研究%Proteomic study of well-differentiated astrocytoma

    Institute of Scientific and Technical Information of China (English)

    肖惠生; 熊光仲; 路俊仙; 梁宋平; 袁峰

    2012-01-01

    目的 研究高分化星形细胞瘤差异蛋白质表达,为星形细胞瘤的治疗及预后的判断提供依据.方法 取经病理证实的29例正常脑组织及36例高分化的星形细胞瘤(KernohanⅡ级),经蛋白电泳、染色,采用PDQUEST和2-DE分析系统软件进行分析.以MALDI-TFO质谱或MALDI-TOF/TOF串联质谱技术结合数据库检索对蛋白质进行鉴定.结果 通过双向电泳得到正常脑组织和高分化星形细胞瘤标本的双向凝胶电泳图谱;生物质谱技术鉴定了24个差异蛋白质点,与正常脑组织相比,高分化星形细胞瘤有9个蛋白质下调,15个蛋白质上调.结论 以蛋白质组学技术鉴定了正常脑组织和高分化星形细胞瘤的差异蛋白质,其中部分蛋白质有助于深入研究星形细胞瘤的发生、发展机制并对进一步发现肿瘤标记物及治疗靶点有重要的参考价值.%Objective To study the differential proteins of well-differentiated astrocytoma and identify tumor-associated protein markers for diagnosis and prognosis. Methods The specimen of normal brain tissue (29 cases) and well-differentiated astrocytoma (36 cases, Kemohan Ⅱ) identified by pathological method were electrophoresed and dyed, and then were analyzed by PDQUEST and two-dimentional electrophoresig(2-DE) softwares. The proteins were identified by MALDI-TOF mass spectrometry or MALDI-TOF/ TOF tandem mass spectrometry. Results We obtained 2-DE gel atlas of normal brain and well-differentiated astrocytoma by 2-DE and 24 prominent different proteins spots by mass spectrometry. Compared with normal brain tissue, 9 down-regulated and IS up-regulated proteins were found in astrocytoma. Conclusion We have got different proteins from normal brain and well-differentiated astrocytoma by proteomics. Some proteins are useful for discovering the molecular mechanisms of genesis development and helpful to find the markers of tumor and treatment target.

  3. Fluorescence In Situ Hybridization for MDM2 Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center

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    Khin Thway

    2015-01-01

    Full Text Available Background. The assessment of MDM2 gene amplification by fluorescence in situ hybridization (FISH has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL in specialist sarcoma units. We describe our experience of its utility at our tertiary institute. Methods. All routine histology samples in which MDM2 amplification was assessed with FISH over a 2-year period were included, and FISH results were correlated with clinical and histologic findings. Results. 365 samples from 347 patients had FISH for MDM2 gene amplification. 170 were positive (i.e., showed MDM2 gene amplification, 192 were negative, and 3 were technically unsatisfactory. There were 122 histologically benign cases showing a histology:FISH concordance rate of 92.6%, 142 WDL/DDL (concordance 96.5%, and 34 cases histologically equivocal for WDL (concordance 50%. Of 64 spindle cell/pleomorphic neoplasms (in which DDL was a differential diagnosis, 21.9% showed MDM2 amplification. Of the cases with discrepant histology and FISH, all but 3 had diagnoses amended following FISH results. For discrepancies of benign histology but positive FISH, lesions were on average larger, more frequently in “classical” (intra-abdominal or inguinal sites for WDL/DDL and more frequently core biopsies. Discrepancies of malignant histology but negative FISH were smaller, less frequently in “classical” sites but again more frequently core biopsies. Conclusions. FISH has a high correlation rate with histology for cases with firm histologic diagnoses of lipoma or WDL/DDL. It is a useful ancillary diagnostic tool in histologically equivocal cases, particularly in WDL lacking significant histologic atypia or DDL without corresponding WDL component, especially in larger tumors, those from intra-abdominal or inguinal sites or core biopsies. There is a significant group of well-differentiated adipocytic neoplasms

  4. Neuroendocrine tumors involving the gastroenteropancreatic tract: a clinicopathological evaluation of 773 cases

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    Bruna Estrozi

    2011-01-01

    Full Text Available OBJECTIVE: Description of some of the clinical pathological characteristics of neuroendocrine tumors of the gastroenteropancreatic tract in Brazilian patients. INTRODUCTION: Neuroendocrine tumors arise in many organs and share common pathological features. In 2010, the World Health Organization published a new classification for neuroendocrine tumors using a three-tiered system that applies the terms neuroendocrine tumor Grade 1, neuroendocrine tumor Grade 2, and neuroendocrine carcinoma. The tumor grades are based on their mitotic rate and the Ki-67 index. In Brazil, information on neuroendocrine tumors of gastroenteropancreatic tract is scarce. METHODS: This study investigated clinicopathological features of 773 Brazilian gastroenteropancreatic neuroendocrine tumor cases from all the geographic regions of Brazil. All of the cases emerged from the files of a single institution (a large pathology reference laboratory between 1997 and 2009. In addition, the gastroenteropancreatic neuroendocrine tumors were graded according to the new 2010 World Health Organization classification. RESULTS: Overall there were a higher number of neuroendocrine tumors in female over male. The lower ages were seen in patients with appendiceal tumors. The most common anatomic location involved was stomach followed by small and large intestines. All cases involving the appendix were of grade 1 and 92.1% of the neuroendocrine tumors of the esophagus were neuroendocrine carcinomas (grade 3. CONCLUSIONS: In this series, the proportion of NET cases in the total number of surgical pathology cases at our institution over the past 12 years is increasing.

  5. Impact of Prenatal Stress on Neuroendocrine Programming

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    Odile Viltart

    2007-01-01

    programming strongly, notably when hormonal surges occur during sensitive periods of development, so-called developmental windows of vulnerability. Stressful events occurring during the perinatal period may impinge on various aspects of the neuroendocrine programming, subsequently amending the offspring's growth, metabolism, sexual maturation, stress responses, and immune system. Such prenatal stress-induced modifications of the phenotypic plasticity of the progeny might ultimately result in the development of long-term diseases, from metabolic syndromes to psychiatric disorders. Yet, we would like to consider the outcome of this neuroendocrine programming from an evolutionary perspective. Early stressful events during gestation might indeed shape internal parameters of the developing organisms in order to adapt the progeny to its everyday environment and thus contribute to an increased reproductive success, or fitness, of the species. Moreover, parental care, adoption, or enriched environments after birth have been shown to reverse negative long-term consequences of a disturbed gestational environment. In this view, considering the higher potential for neonatal plasticity within the brain in human beings as compared to other species, long-term consequences of prenatal stress might not be as inexorable as suggested in animal-based studies published to date.

  6. Octreoscan SPET evaluation in the diagnosis of pancreas neuroendocrine tumors.

    Science.gov (United States)

    Briganti, V; Matteini, M; Ferri, P; Vaggelli, L; Castagnoli, A; Pieroni, C

    2001-12-01

    The study describes the results of Octreoscan SPET (OCTSPET) qualitative and semi-quantitative evaluation in 38 patients with suspected pancreatic neuroendocrine tumors. SPET studies were acquired at 4 and 24 hours after the injection of 111-220 MBq of 111-In-pentetreotide (Octreoscan). Qualitative and semi-quantitative evaluations were performed. The semi-quantitative approach was based on the time course of Tumor/Non Tumor ratios (TNTinc) from 4 and 24 hours. The OCTSPET results were true positive in 18 of 19 patients (10 gastrinoma, 5 insulinoma, 1 neuroendocrine tumor, 1 glucagonoma and 1 carcinoid) and false negative in one insulinoma. Besides, 20 of 38 patients (52%) had clinical plans modified after OCTSPET; OCTSPET was the only positive diagnostic test in 14 of 19 patients (73%) and guided the surgery decision in 14 of 25 patients (56%). In conclusion, these data indicate that Octreoscan represents an excellent tool for the diagnosis of pancreatic neuroendocrine tumors. PMID:11789028

  7. Metastatic neuroendocrine carcinoma of aortic body origin in a cat.

    Science.gov (United States)

    Hansen, Sonya C; Smith, Annette N; Kuo, Kendon W; Fish, Eric J; Koehler, Jey W; Martinez-Romero, Gisela; Bacek, Lenore M

    2016-09-01

    An 8-year-old, female spayed Domestic Shorthair cat was presented to the Auburn University Emergency and Critical Care service for evaluation of pleural effusion and a suspected intrathoracic mass. Computed tomography was performed which confirmed the presence of a large intrathoracic mass, likely heart-based. Fine-needle aspirates were obtained and a cytologic diagnosis of a neuroendocrine tumor was made. Treatment with toceranib phosphate was briefly attempted at home by the owners. The cat died at home approximately 6 weeks after diagnosis. Necropsy and subsequent histopathologic examination revealed a metastatic neuroendocrine carcinoma of aortic body origin. Aortic body tumors are extremely rare in cats and to the authors' knowledge, a neuroendocrine carcinoma of aortic body origin with distant metastases has not yet been reported in a cat. PMID:27564688

  8. Possible new antiaging strategies related to neuroendocrine-immune interactions.

    Science.gov (United States)

    Mocchegiani, Eugenio; Malavolta, Marco

    2008-01-01

    The aging process demonstrates gradual and spontaneous changes, resulting in maturation through childhood, puberty and young adulthood, and then decline through middle and late age. However, animals and humans are capable of reaching the extreme limit of life span characteristic for the species with a very efficient network of antiaging mechanisms. Among them, neuroendocrine-immune interactions play a pivotal role. The loss of the capacity of the organism in remodeling the neuroendocrine-immune response leads to the appearance of age-associated pathologies. We herein report some substances which can be proposed as new antiaging strategies because of their capacity to remodel some biological functions in old animals and humans. These substances are: L-deprenyl, leptin, ghrelin, carnosine and NO donors. Their role as possible antiaging strategies in healthy people in relation to neuroendocrine-immune responses and zinc ion bioavailability is reported and discussed. PMID:19047810

  9. Large-cell Neuroendocrine Carcinoma of the Lung: Unusual Presentation

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    Miguel Ángel Serra Valdés

    2014-11-01

    Full Text Available Lung cancer is the leading cause of death among malignant tumors. Pulmonary neuroendocrine tumors encompass a broad spectrum of tumors including the large-cell neuroendocrine carcinoma. The case of a 57-year-old white housewife with a history of smoking, diabetes, hypothyroidism and hypertension who sought medical attention because of headache, vomiting, weight loss, neuropsychiatric symptoms and metastatic inguinal lymphadenopathy is presented. The symptoms resulted from the extrapulmonary metastases found. Imaging studies, histology and immunohistochemistry confirmed the diagnosis of large-cell carcinoma of the lung with neuroendocrine pattern. This type of highly aggressive tumor is usually diagnosed when there are already multiple metastases, which affects the short-term prognosis. The aim of this paper is to inform the medical community of this case due to the scarce reports in the literature.

  10. Second cancers in patients with neuroendocrine tumors.

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    Hui-Jen Tsai

    Full Text Available BACKGROUND: Second cancers have been reported to occur in 10-20% of patients with neuroendocrine tumors (NETs. However, most published studies used data from a single institution or focused only on specific sites of NETs. In addition, most of these studies included second cancers diagnosed concurrently with NETs, making it difficult to assess the temporality and determine the exact incidence of second cancers. In this nationwide population-based study, we used data recorded by the Taiwan Cancer Registry (TCR to analyze the incidence and distribution of second cancers after the diagnosis of NETs. METHODS: NET cases diagnosed from January 1, 1996 to December 31, 2006 were identified from the TCR. The data on the occurrence of second cancers were ascertained up to December 31, 2008. Standardized incidence ratios (SIRs of second cancers were calculated based on the cancer incidence rates of the general population. Cox-proportional hazards regression analysis was performed to estimate the hazard ratio (HR and 95% confidence interval (CI for the risk of second cancers associated with sex, age, and primary NET sites. RESULTS: A total of 1,350 newly diagnosed NET cases were identified according to the selection criteria. Among the 1,350 NET patients, 49 (3.63% developed a second cancer >3 months after the diagnosis of NET. The risk of second cancer following NETs was increased compared to the general population (SIR = 1.48, 95% CI: 1.09-1.96, especially among those diagnosed at age 70 or older (HR = 5.08, 95% CI = 1.69-15.22. There appeared to be no preference of second cancer type according to the primary sites of NETs. CONCLUSIONS: Our study showed that the risk of second cancer following NETs is increased, especially among those diagnosed at age 70 or older. Close monitoring for the occurrence of second cancers after the diagnosis of NETs is warranted.

  11. Neuroendocrine tumors presenting with thyroid gland metastasis: a case series

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    Sivrikoz Emre

    2012-02-01

    Full Text Available Abstract Introduction Autopsy series have shown that metastasis to the thyroid gland has occurred in up to 24% of patients who have died of cancer. Neuroendocrine tumors may metastasize to thyroid gland. Case presentations Case 1 was a 17-year-old Turkish woman who was referred from our Endocrinology Department for a thyroidectomy for treatment of neuroendocrine tumor metastasis. She was treated with a bilateral total thyroidectomy. Histopathological examination results were consistent with a neuroendocrine tumor; neoplastic cells showed strong immunoreactivity to chromogranin A and synaptophysin, but the immunohistochemical profile was inconsistent with medullary thyroid carcinoma in that the tumor was negative for calcitonin, carcinoembryonic antigen, and thyroid transcription factor-1. Case 2 was a 54-year-old Turkish woman who presented with a 3-cm nodule on her right thyroid lobe. She had undergone surgery for a right lung mass four years previously. After a right pneumonectomy, thymectomy and lymph node dissection, a typical carcinoid tumor was diagnosed. Under ultrasonographic guidance, fine needle aspiration biopsy of her right thyroid pole nodule was performed and the biopsy was compatible with a neuroendocrine tumor metastasis. She was treated with a bilateral total thyroidectomy. Histopathological examination indicated three nodular lesions, 5 cm and 0.4 cm in diameter in her right lobe and 0.1 cm in diameter in her left lobe. The tumors were consistent with a neuroendocrine phenotype, showing strong immunoreactivity to chromogranin A and synaptophysin. Conclusion Thyroid nodules detected during follow-up of neuroendocrine tumor patients should be thoroughly investigated. A fine needle aspiration biopsy of the thyroid confirms the diagnosis in most cases and leads to appropriate management of those patients and may prevent unnecessary treatment approaches.

  12. Neuroendocrine Adenoma of the Middle Ear: A Rare Histopathological Diagnosis

    Science.gov (United States)

    McGinness, Sam; Coleman, Hedley; Varikatt, Winny; da Cruz, Melville

    2016-01-01

    Neuroendocrine tumours occur throughout the body but are rare in the head and neck region and particularly rare in the middle ear. Clinical findings are often nonspecific and therefore pose a diagnostic challenge. Furthermore, the nomenclature of neuroendocrine tumours of the middle ear is historically controversial. Herein a case is presented of a middle ear adenoma in a 33-year-old patient who presented with otalgia, hearing loss, and facial nerve palsy. A brief discussion is included regarding the histopathological features of middle ear adenomas and seeks to clarify the correct nomenclature for these tumours. PMID:27429819

  13. Co-expression of TTF-1 and neuroendocrine markers in the human fetal lung and pulmonary neuroendocrine tumors.

    Science.gov (United States)

    Miskovic, Josip; Brekalo, Zdrinko; Vukojevic, Katarina; Miskovic, Helena Radic; Kraljevic, Daniela; Todorovic, Jelena; Soljic, Violeta

    2015-01-01

    The expression pattern of thyroid transcription factor 1 (TTF-1) and neuroendocrine markers, neuron cell adhesion molecule (NCAM; CD56), chromogranin A (CgA) and synaptophysin (Syp), of different lung cell lineages was histologically analyzed in 15 normal human fetal lungs and 12 neuroendocrine tumors (NETs) using immunohistochemical methods. During pseudoglandular phase strong nuclear TTF-1 staining was detected in the columnar nonciliated epithelial cells, while NCAM, CgA and Syp had a moderate expression in the proximal airways and mild expression in the distal airways. Neuroendocrine cells (NECs) in proximal lung airway were co-localizing TTF-1 and other neuroendocrine markers while neuroendocrine bodies (NEBs) exhibit only staining with NCAM and Syp. In the canalicular phase TTF-1 nuclear staining was expressed only in several epithelial cells in proximal airways, while budding airways epithelium showed strong TTF-1 expression. Expression of NCAM, CgA and Syp in this phase equals the one in pseudoglandular phase. NEBs cells were co-localizing TTF-1 and NCAM in proximal airways and few NECs in distal airway were co-localizing TTF-1 and Syp. TTF-1 staining in the saccular phase was limited to subsets of epithelial cells in the proximal airways with stronger positivity in the distal airways. NCAM expression is moderate only in proximal airways, while Syp and CgA show mild expression in proximal and distal airways. NECs were co-localizing TTF-1 and NCAM in proximal lung airway. With regard to NECs, all small cell lung cancer (SCLC) cells had strong TTF-1, NCAM, Syp and CgA positivity and TTF-1 co-localized with other neuroendocrine markers. All pulmonary typical carcinoids were TTF-1 negative, while pulmonary atypical carcinoids were focal positive for TTF-1 and some neoplastic cells co-localized TTF-1 with neuroendocrine markers. Our results indicate that TTF-1 expression in NECs suggests a possible role in their normal development and differentiation. Our

  14. Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

    Energy Technology Data Exchange (ETDEWEB)

    Santhanam, Prasanna; Chandramahanti, Sangeeta [Marshall University, Section of Endocrinology, Department of Internal Medicine, Joan C Edwards School of Medicine, Huntington, WV (United States); Kroiss, Alexander [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Yu, Run [Cedars-Sinai Medical Center, Division of Endocrinology and Carcinoid and Neuroendocrine Tumor Center, Los Angeles, CA (United States); Ruszniewski, Philippe [Beaujon Hospital and Paris-Diderot University, Department of Gastroenterology-Pancreatology, Paris (France); Kumar, Rakesh [All India Institute of Medical Sciences, Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, New Delhi (India); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France)

    2015-03-13

    Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSTa) and {sup 18}F-DOPA have shown promise. In direct comparisons between {sup 68}Ga-DOTA-SSTa PET/CT and {sup 99m}Tc-HYNIC-octreotide/{sup 111}In-pentetreotide SPECT(/CT), {sup 68}Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. {sup 18}F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of {sup 18}F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with {sup 68}Ga-DOTA-SSTa, alternatively {sup 18}F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and {sup 18}F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly

  15. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    NARCIS (Netherlands)

    B.L. Kam (Boen); J.J.M. Teunissen (Jaap); E.P. Krenning (Eric); W.W. de Herder (Wouter); S. Khan (Saima); E.I. van Vliet (Esther); D.J. Kwekkeboom (Dirk Jan)

    2012-01-01

    textabstractTreatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuc

  16. Factors associated with survival of veterans with gastrointestinal neuroendocrine tumors.

    NARCIS (Netherlands)

    Balmadrid, B.L.; Thomas, C.M.G.; Coffman, C.J.; Liddle, R.A.; Fisher, D.A.

    2012-01-01

    Background. Gastrointestinal (GI) neuroendocrine tumor (NET) incidence has been increasing; however, GI NET within the national Veterans Affairs (VA) health system has not been described. Methods. We used the VA Central Cancer Registry to identify the cohort of patients diagnosed with GI NET in 1995

  17. Composite neuroendocrine and adenomatous carcinoma of the papilla of Vater

    Institute of Scientific and Technical Information of China (English)

    Joanna A Musialik; Maciej J Kohut; Tomasz Marek; Anatol Wodo(I)a(z)ski; Marek Hartleb

    2009-01-01

    Malignant tumors of papilla are usually adenocarcinomas.We present a 67-year-old female who became icteric as result of a malignant tumor infiltrating the papilla of Vater. Histopathological assessment of surgically excised tumor showed both neuroendocrine and adenocarcinomatous features. To our knowledge, this is the seventh report of this rare neoplastic association in the duodenal periampullary region.

  18. A Retroperitoneal Neuroendocrine Tumor in Ectopic Pancreatic Tissue

    OpenAIRE

    Okasha, Hussein Hassan; Al-Bassiouni, Fahim; El-Ela, Monir Abo; Al-Gemeie, Emad Hamza; Ezzat, Reem

    2013-01-01

    Ectopic pancreas is the relatively uncommon presence of pancreatic tissue outside the normal location of the pancreas. We report a case of abdominal pain due to retroperitoneal neuroendocrine tumor arising from heterotopic pancreatic tissue between the duodenal wall and the head of the pancreas. Patient underwent surgical enucleation of the tumor.

  19. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment.

  20. CENTRAL AMYGDALOID INVOLVEMENT IN NEUROENDOCRINE CORRELATES OF CONDITIONED STRESS RESPONSES

    NARCIS (Netherlands)

    ROOZENDAAL, B; KOOLHAAS, JM; BOHUS, B

    1992-01-01

    The purpose of this study was to examine the effects of bilateral electrolytic lesions of the central nucleus of the amygdala (CEA) in comparison with sham lesions on neuroendocrine responses during conditioned emotional stress in male Wistar rats. Lesions in the CEA, made either before or after the

  1. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Kim, Ji Hoon; Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2015-05-01

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  2. Neuroendocrine neoplasms of the pancreas at dynamic enhanced CT: comparison between grade 3 neuroendocrine carcinoma and grade 1/2 neuroendocrine tumour

    International Nuclear Information System (INIS)

    To identify the CT features in differentiating grade 3 neuroendocrine carcinomas from grade 1/2 neuroendocrine tumours. This study included 161 patients with surgically confirmed pancreatic neuroendocrine neoplasms. Pathology slides were reviewed to determine the tumour grade. CT image analysis included size, pattern, calcification, margin, pancreatic duct dilatation, bile duct dilatation, vascular invasion, arterial enhancement ratio, and portal enhancement ratio. We used 2 cm, 3 cm, and 4 cm as cutoff values of tumour size and 0.9 and 1.1 of enhancement ratio to determine the sensitivity and specificity. Pathology analysis identified 167 lesions in 161 patients. 154 lesions (92 %) were grade 1/2 and 13 (8 %) were grade 3. Portal enhancement ratio (< 1.1) showed high sensitivity and specificity 92.3 % and 80.5 %, respectively in differentiating grade 3 from grade 1/2. It showed the highest odds ratio (49.60), followed by poorly defined margin, size (> 3 cm), bile duct dilatation, and vascular invasion. When at least two of these five criteria were used in combination, the sensitivity and specificity for diagnosing grade 3 were 92.3 % (12/13) and 87.7 % (135/154), respectively. By using specific CT findings, grade 3 can be differentiated from grade 1/2 with a high diagnostic accuracy leading to an appropriate imaging staging. (orig.)

  3. Neuropeptide S receptor 1 (NPSR1) activates cancer-related pathways and is widely expressed in neuroendocrine tumors

    OpenAIRE

    Pulkkinen, V.; Ezer, S.; Sundman, L.; Hagström, J; Remes, S; Söderhäll, C; Dario, G. (ed.); Haglund, C.; Kere, J; Arola, J.

    2014-01-01

    Neuroendocrine tumors (NETs) arise from disseminated neuroendocrine cells and express general and specific neuroendocrine markers. Neuropeptide S receptor 1 (NPSR1) is expressed in neuroendocrine cells and its ligand neuropeptide S (NPS) affects cell proliferation. Our aim was to study whether NPS/NPSR1 could be used as a biomarker for neuroendocrine neoplasms and to identify the gene pathways affected by NPS/NPSR1. We collected a cohort of NETs comprised of 91 samples from endocrine glands, ...

  4. Neuroendocrine system response modulates oxidative cellular damage in burn patients.

    Science.gov (United States)

    Xie, Xiao-Qi; Shinozawa, Yotaro; Sasaki, Junichi; Takuma, Kiyotsugu; Akaishi, Satoshi; Yamanouchi, Satoshi; Endo, Tomoyuki; Nomura, Ryosuke; Kobayashi, Michio; Kudo, Daisuke; Hojo, Nobuko

    2007-02-01

    Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.

  5. Neuroendocrine pancreatic carcinoma after initial diagnosis of acute postpartal coeliac disease in a 37-year old woman - fatal coincidence or result of a neglected disease?

    Science.gov (United States)

    Gundling, Felix; Nerlich, Andreas; Heitland, Wolf; Schepp, Wolfgang

    2014-05-01

    An acute presentation after pregnancy of coeliac disease (CD) in the puerperium is a rare condition which has been described mostly in primigravidae in patients highly suspicious of latent CD. We report the case of a 37-year-old woman who was referred to our Hospital because of refractory watery diarrhea and malnutrition syndrome. Endoscopy of the upper gastrointestinal tract revealed the classic visual features of CD and in addition, some duodenal ulcers negative for Helicobacter pylori, which seems to be another clinical feature in patients with CD. The diagnosis of acute onset of fulminant postpartal CD (Marsh score stage 3c) was confirmed histologically. Remarkably, simultaneous well-differentiated neuroendocrine non-functioning pancreatic neuroendocrine carcinoma (PNET) was diagnosed on radiological abdominal imaging which was performed since serum gastrin was remarkably high, treated by distal pancreatectomy and splenectomy. This report is, to our knowledge, the first description of the two entities, CD and PNET occurring together. Since results of antral histological studies showed diffuse hyperplasia of G-cells, probably in response to hypergastrinaemia, enterochromaffin cell carcinogenesis might have served as a possible link between both diseases.

  6. The imaging of neuroendocrine tumors using single photon emission computed tomography/computed tomography

    International Nuclear Information System (INIS)

    There have been several advances in technology over the past decade with the advent of hybrid imaging having a large impact on nuclear medicine, first with PET/CT and then more recently with SPECT/CT. Initial SPECT/CT systems used low dose but very low quality CT and except for attenuation correction offered no great advantage over reviewing SPECT and CT images side by side. More recently hybrid machines have become available and a series of studies have shown improved accuracy compared to SPECT alone with resulting changes in patient management. This has been true not only with somatostatin analogue imaging but also for demonstrating amine uptake using MIBG. Whilst PET/CT may be seen as the ideal, this may be less accessible due to the high cost and limited availability. In this case hybrid SPECT/CT offers hope for providing high quality and accurate imaging of neuroendocrine tumors.

  7. Concordance between results of somatostatin receptor scintigraphy with {sup 111}In-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide and chromogranin A assay in patients with neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, Margarida [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Hietzing Hospital, Institute of Nuclear Medicine, Vienna (Austria); Gabriel, Michael; Heute, Dirk; Putzer, Daniel; Virgolini, Irene [Medical University of Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Griesmacher, Andrea [Medical University of Innsbruck, Central Institute of Medical and Chemical Laboratory Diagnostics, Innsbruck (Austria)

    2008-10-15

    Somatostatin receptor scintigraphy (SRS) and chromogranin A (CgA) assay have successfully been implemented in the clinical work-up and management of neuroendocrine tumour (NET) patients. However, there is still a lack of studies comparing results in these patients. Our aim was to compare directly in NET patients SRS and CgA assay results with special regard to tumour features such as grade of malignancy, primary origin, disease extent and function. One hundred twenty consecutive patients with histological confirmed NETs were investigated with {sup 111}In-DOTA-DPhe{sup 1}-Tyr{sup 3}-octreotide ({sup 111}In-DOTA-TOC) SRS and CgA immunoradiometric assay. Tumours were classified by cell characteristics [well-differentiated NETs, well-differentiated neuroendocrine carcinomas, poorly differentiated neuroendocrine carcinomas (PDNECs)], primary origin (foregut, midgut, hindgut, undetermined), disease extent (limited disease, metastases, primary tumour and metastases) and functionality (secretory, nonsecretory). SRS was positive in 107 (89%) patients; CgA levels were increased in 95 (79%) patients. Overall, concordance between SRS and CgA results was found in 84 patients. Positive SRS but normal CgA level were found in 24 patients, with higher prevalence (p<0.05) in patients with nonsecretory tumours. Conversely, negative SRS but CgA level increased were seen in 12 patients, with higher proportion (p < 0.05) in patients with PDNECs and tumours of hindgut origin. Overall, {sup 111}In-DOTA-TOC SRS proved to be more sensitive than CgA in NETs patients. Tumour differentiation, disease extent and presence of liver metastases impact both SRS and CgA results, whereas nonsecretory activity is a negative predictor of only CgA increase. PDNECs and hindgut origin of tumours predispose to discrepancies with negative SRS but increased CgA levels. (orig.)

  8. The relative frequency in which empiric dosages of radioiodine would potentially overtreat or undertreat patients who have metastatic well-differentiated thyroid cancer.

    Science.gov (United States)

    Kulkarni, K; Van Nostrand, D; Atkins, F; Aiken, M; Burman, K; Wartofsky, L

    2006-10-01

    The dosage of (131)I for the treatment of metastatic well-differentiated thyroid cancer is typically selected empirically. Benua and Leeper implemented a method to estimate the maximum dosages of (131)I that could be administered to a patient so as not to exceed a maximum tolerated radiation absorbed dose (MTD), which was defined as 200 rads (cGy) to the blood. The objective of this study was to determine the frequency of (131)I treatments in which the patient (1) would have exceeded the MTD (i.e., overtreatment) or (2) would have been able to receive higher dosages of (131)I thereby delivering a potentially higher radiation absorbed dose to their metastases (i.e., undertreatment) had the patient been administered various assumed empiric dosages of (131)I. The dosimetrically-determined maximum tolerated radioactivities (MTA) to deliver 200 rads to the blood (MTD) were tabulated at our facility. Data were then grouped to determine the percentage of patients who would have received less than or more than the MTD for various assumed empiric dosages of (131)I. A total of 127 dosimetries were performed. For assumed empiric dosages of (131)I (100 mCi, 150 mCi, 200 mCi, 250 mCi, and 300 mCi), the percentage of treatments for which patients would have exceeded the MTD were less than 1%, 5%, 11%, 17%, and 22%, respectively, and could have received a higher dosage of (131)I were more than 99%, 95%, 89%, 83%, and 78%, respectively. A significant number of patients receiving various empiric dosages of (131)I may exceed 200 rads (cGy) to the blood (potential overtreating). Likewise, the majority of patients may be able to receive much higher dosages of (131)I relative to empiric dosages thereby delivering potentially higher radiation absorbed doses to the metastases without exceeding 200 rads (cGy) to the blood (potential undertreating).

  9. Neuroendocrine predictors of the evolution of depression

    OpenAIRE

    Duval, Fabrice; Mokrani, Marie-Claude; Monreal Ortiz, Jose Antonio; Schulz, Pierre; Champeval, Christiane; Macher, Jean-Paul

    2005-01-01

    Depression is both clinically and biologically a heterogeneous entity Despite advances in psychopharmacology a significant proportion of depressed patients either continue to have residual symptoms or do not respond to antidepressants, It has therefore become essential to determine parameters (or predictors) that would rationalize the therapeutic choice, taking into account not only the clinical features, but also the “biological state, ” which is a major determinant in the antidepressant res...

  10. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Josef Zihl

    2015-05-01

    Full Text Available Endocrine dysfunction is a common effect of traumatic brain injury (TBI. In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments.

  11. Orbital metastatic primary mediastinal neuroendocrine tumor: a histopathological case report

    Directory of Open Access Journals (Sweden)

    Ayman Ayoubi

    2012-01-01

    Full Text Available Neuroendocrine tumors most frequently involve the gastrointestinal tract and bronchopulmonary system. Few cases of presumed primary neuroendocrine tumors in the orbit have been reported so far and most of the orbital cases are actually metastatic. We describe the unusual occurrence of this tumor in the orbit of a 16-year-old boy. The lesion was initially thought to be primary; however, the diagnosis of a metastatic orbital lesion was later supported by the histopathological appearance of his orbital biopsy, characteristic immunohistochemical profile and the presence of a primary mediastinal tumor. The patient did not have any symptoms suggestive of a carcinoid syndrome during the course of his disease. Unfortunately, tests showed lymph node involvement and distant metastatic lesions and he died from these a few months later while on palliative therapy.

  12. Neuroendocrine carcinoma of the mammary gland in a dog.

    Science.gov (United States)

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. PMID:25670668

  13. Neuroendocrine differentiation in a case of cervical cancer

    Directory of Open Access Journals (Sweden)

    Mona Mohamed Rashed

    2010-07-01

    Full Text Available Neuroendocrine neoplasms may occur in the uterine cervix, although rarely; it accounts for 0.5-1% of all malignant tumors of the uterine cervix. A case report of an Ethiopian female presented at the Gynecology Out-Patient Clinic at Jimma University Hospital, complaining from irregular vaginal bleeding over the previous three months. Clinically there was a cauliflower cervical mass; histopathologically it was formed of sheets of small cell tumor; that further showed neuroendocrine differentiation, as demonstrated by chromogranin-A positivity. It is important to differentiate small cell carcinoma from other malignant tumors of the uterine cervix. Morphological features play an important role in making a diagnosis and the immunohistochemistry study can offer an additional useful assistance

  14. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury.

    Science.gov (United States)

    Zihl, Josef; Almeida, Osborne F X

    2015-01-01

    Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental functions, the consequences of TBI on mental health and neuroendocrine homeostasis, and the effects of hormone substitution on mental dysfunction caused by TBI. The available empirical evidence suggests that comprehensive assessment of mental functions should be standard in TBI subjects presenting with hormone deficiency and that hormone replacement therapy should be accompanied by pre- and post-assessments. PMID:26239465

  15. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    OpenAIRE

    Kam, Boen; Teunissen, Jaap; Krenning, Eric; de Herder, Wouter; Khan, Saima; van Vliet, Esther; Kwekkeboom, Dirk Jan

    2012-01-01

    textabstractTreatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with 177Lu-[DOTA 0,Tyr3]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with 177Lu-DOTATATE as well as the limi...

  16. Evaluating obesity in fibromyalgia: neuroendocrine biomarkers, symptoms, and functions

    OpenAIRE

    Okifuji, Akiko; Bradshaw, David H.; Olson, Chrisana

    2009-01-01

    The aim of this study was to investigate the associations between obesity and fibromyalgia syndrome (FMS). This study was conducted at the University of Utah Pain Management and Research Center, Salt Lake City, Utah. Thirty-eight FMS patients were included in this study. Neuroendocrine indices (catecholamines, cortisol, C-reactive protein [CRP], and interleukin-6), symptom measures (Fibromyalgia Impact Questionnaire), sleep indices (Actigraph), and physical functioning (treadmill testing) wer...

  17. Behavioural and Neuroendocrine Effects of Stress in Salmonid Fish

    OpenAIRE

    Øverli, Øyvind

    2001-01-01

    Stress can affect several behavioural patterns, such as food intake and the general activity level of an animal. The central monoamine neurotransmitters serotonin, dopamine, and norepinephrine are important in the mediation of both behavioural and neuroendocrine stress effects. This thesis describes studies of two salmonid fish model systems: Fish that become socially dominant or subordinate when reared in pairs, and rainbow trout (Oncorhynchus mykiss) genetically selected for high (HR) and l...

  18. Primary neuroendocrine breast carcinoma: a case report and literature review

    Directory of Open Access Journals (Sweden)

    Maria Helena Valentim

    2014-04-01

    Full Text Available The authors present a case of a neuroendocrine carcinoma in an asymptomatic 75-year-old woman, detected in routine breast screening. The lesion was visible at mammography as a well circumscribed, medium density nodule, with no associated microcalcifications, and at ultrasonography as a hypoechoic nodule, with irregular shape and ill-defined margins. Magnetic resonance imaging revealed findings consistent with malignancy.

  19. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells.

    Science.gov (United States)

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  20. [Biotherapy of neuroendocrine tumours of the gastrointestinal tract and pancreas

    DEFF Research Database (Denmark)

    Hansen, C.P.; Knigge, U.

    2008-01-01

    Biotherapy of hormonal symptoms and tumour growth is a mainstay in the therapy of metastatic neuroendocrine tumours of the gastrointestinal tract and pancreas. Symptomatic relief can be achieved by somatostatin analogues and interferon, either alone or in combination. The effect on tumour growth...... is less convincing although a stabilization of disease is recorded in almost 50% of patients. Interferon treatment should mainly be considered for tumours with a low proliferation index Udgivelsesdato: 2008/6/9...

  1. Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

    OpenAIRE

    Gligorijević Jasmina V.; Veličković Ljubinka V.; Jančić Snežana A.; Radovanović Zoran; Krstić Miljan S.; Katić Vuka V.

    2011-01-01

    Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylineosin (HE), Alcian blu-periodic acid schiff (ABPAS) at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC), were pe...

  2. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells

    Science.gov (United States)

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  3. Leptin as a Modulator of Neuroendocrine Function in Humans

    OpenAIRE

    Khan, Sami M; Brinkoetter, Mary; Hamnvik, Ole-Petter Riksfjord; Mantzoros, Christos

    2012-01-01

    Leptin, a peptide hormone secreted by adipocytes in proportion of the amount of energy stored in fat, plays a central role in regulating human energy homeostasis. In addition, leptin plays a significant permissive role in the physiological regulation of several neuroendocrine axes, including the hypothalamic-pituitary-gonadal, -thyroid, -growth hormone, and -adrenal axes. Decreased levels of leptin, also known as hypoleptinemia, signal to the brain a state of energy deprivation. Hypoleptinemi...

  4. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Science.gov (United States)

    Ragab Shalaby, Ahmed M.; Kazuei, Hoshi; Koichi, Honma; Naguib, Saeed; Al-Menawei, Lubna A.

    2016-01-01

    Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20%) in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21%) in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis. PMID:27365963

  5. Neuropsychology of Neuroendocrine Dysregulation after Traumatic Brain Injury

    OpenAIRE

    Josef Zihl; Almeida, Osborne F X

    2015-01-01

    Endocrine dysfunction is a common effect of traumatic brain injury (TBI). In addition to affecting the regulation of important body functions, the disruption of endocrine physiology can significantly impair mental functions, such as attention, memory, executive function, and mood. This mini-review focuses on alterations in mental functioning that are associated with neuroendocrine disturbances in adults who suffered TBI. It summarizes the contribution of hormones to the regulation of mental f...

  6. The Neuroendocrine Functions of the Parathyroid Hormone 2 Receptor

    Directory of Open Access Journals (Sweden)

    Arpad eDobolyi

    2012-10-01

    Full Text Available The G-protein coupled parathyroid hormone 2 receptor (PTH2R is concentrated in endocrine and limbic regions in the forebrain. Its endogenous ligand,tuberoinfundibular peptide of 39 residues (TIP39, is synthesized in only 2 brain regions, within the posterior thalamus and the lateral pons. TIP39-expressing neurons have a widespread projection pattern, which matches the PTH2R distribution in the brain. Neuroendocrine centers including the preoptic area, the periventricular, paraventricular, and arcuate nuclei contain the highest density of PTH2R-positive networks. The administration of TIP39 and an antagonist of the PTH2R as well as the investigation of mice that lack functional TIP39 and PTH2R revealed the involvement of the PTH2R in a variety of neural and neuroendocrine functions. TIP39 acting via the PTH2R modulates several aspects of the stress response. It evokes corticosterone release by activating corticotropin-releasing hormone-containing neurons in the hypothalamic paraventricular nucleus. Block of TIP39 signaling elevates the anxiety state of animals and their fear response, and increases stress-induced analgesia. TIP39 has also been suggested to affect the release of additional pituitary hormones including arginine vasopressin and growth hormone. A role of the TIP39-PTH2R system in thermoregulation was also identified. TIP39 may play a role in maintaining body temperature in a cold environment via descending excitatory pathways from the preoptic area. Anatomical and functional studies also implicated the TIP39-PTH2R system in nociceptive information processing. Finally, TIP39 induced in postpartum dams may play a role in the release of prolactin during lactation. Potential mechanisms leading to the activation of TIP39 neurons and how they influence the neuroendocrine system are also described. The unique TIP39-PTH2R neuromodulator system provides the possibility for developing drugs with a novel mechanism of action to control

  7. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress

    Directory of Open Access Journals (Sweden)

    Sarah J Spencer

    2013-06-01

    Full Text Available Feeding behavior is closely regulated by neuroendocrine mechanisms that can be influenced by stressful life events. However, the feeding response to stress varies among individuals with some increasing and others decreasing food intake after stress. In addition to the impact of acute lifestyle and genetic backgrounds, the early life environment can have a life-long influence on neuroendocrine mechanisms connecting stress to feeding behavior and may partially explain these opposing feeding responses to stress. In this review I will discuss the perinatal programming of adult hypothalamic stress and feeding circuitry. Specifically I will address how early life (prenatal and postnatal nutrition, early life stress, and the early life hormonal profile can program the hypothalamic-pituitary-adrenal (HPA axis, the endocrine arm of the body’s response to stress long-term and how these changes can, in turn, influence the hypothalamic circuitry responsible for regulating feeding behavior. Thus, over- or under-feeding and / or stressful events during critical windows of early development can alter glucocorticoid (GC regulation of the HPA axis, leading to changes in the GC influence on energy storage and changes in GC negative feedback on HPA axis-derived satiety signals such as corticotropin-releasing-hormone. Furthermore, peripheral hormones controlling satiety, such as leptin and insulin are altered by early life events, and can be influenced, in early life and adulthood, by stress. Importantly, these neuroendocrine signals act as trophic factors during development to stimulate connectivity throughout the hypothalamus. The interplay between these neuroendocrine signals, the perinatal environment, and activation of the stress circuitry in adulthood thus strongly influences feeding behavior and may explain why individuals have unique feeding responses to similar stressors.

  8. Synchronous Collision Neuroendocrine Tumor and Rectal Adenocarcinoma: a Case Report

    OpenAIRE

    Zhu, Jie-gao; Zhang, Zhong-Tao; WU, GUO-CONG; Han, Wei; Wang, Kang-Li

    2015-01-01

    Collision tumors are thought to arise from the accidental meeting of two independent tumors. Adenocarcinoma is the most common malignant rectal tumor, while neuroendocrine tumor (NET) is relatively rare. Due to the endoscopy and reporting, the overall incidence of NETs was increasing recently but still less than 1 per 100,000. This means that a combination of an adenocarcinoma and NET is a very rare finding and an actual collision of these tumors even more so. We report here a highly unusual ...

  9. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

    Directory of Open Access Journals (Sweden)

    Ahmed M Ragab Shalaby

    2016-01-01

    Full Text Available Background: The most common sites of origin for neuroendocrine carcinoma are gastrointestinal tract and its accessory glands, and lungs. Materials and Methods: One-hundred fifty cases diagnosed with metastatic brain lesions were retrieved from hospital records within 5 years. For these cases, the primary neoplasm, histopathological classification, metastasis, treatment, and fate all were studied. Results: Intracranial deposits were detected in 10%. The primary lesion was in the lungs in 87% of patients, and 1 patient in the breast and 1 in esophagus. Pathological classification of the primary lesion was Grade 2 (MIB-1: 3–20% in 1 patient and neuroendocrine carcinoma (MIB-1: ≥21% in 14 patients. The median period from onset of the primary lesion up to diagnosis of brain metastasis was 12.8 months. About 33% of patients had a single metastasis whereas 67% patients had multiple metastases. Brain metastasis was extirpated in 33% of patients. Stereotactic radiotherapy alone was administered in 20% of patients, and brain metastasis was favorably controlled in most of the patients with coadministration of cranial irradiation as appropriate. The median survival period from diagnosis of brain metastasis was 8.1 months. Conclusion: Most of patients with brain metastasis from neuroendocrine carcinoma showed the primary lesion in the lungs, and they had multiple metastases to the liver, lymph nodes, bones, and so forth at the time of diagnosis of brain metastasis. The guidelines for accurate diagnosis and treatment of neuroendocrine carcinoma should be immediately established based on further analyses of those patients with brain metastasis.

  10. Bcl-2 protein expression in lung cancer and close correlation with neuroendocrine differentiation.

    OpenAIRE

    Jiang, S. X.; Kameya, T.; Sato, Y.; Yanase, N.; Yoshimura, H.; Kodama, T

    1996-01-01

    For determination of the cellular distribution of bcl-2 expression in lung cancer and clarification of its correlation with cell neuroendocrine differentiation, Bcl-2 immunostaining was carried out on a large series of formalin-fixed, paraffin-embedded lung cancer samples, and four general neuroendocrine marker and seven peptide hormone stainings were carried out on all Bcl-2-positive squamous cell carcinomas and adenocarcinomas of the lung as well as on 8 pulmonary neuroendocrine carcinomas ...

  11. Unusual Paraneoplastic Syndrome Accompanies Neuroendocrine Tumours of the Pancreas

    Directory of Open Access Journals (Sweden)

    Helga Bertani

    2011-01-01

    Full Text Available Neuroendocrine tumours comprise a small percentage of pancreatic neoplasia (10% (1. Diagnosis of neuroendocrine tumours is difficult, especially if the tumours are small and nonfunctional. CT scans, MRI, and nuclear scans are sufficiently sensitive assessment tools for tumours with diameters of at least 2 cm; otherwise, the sensitivity and specificity of these techniques is less than 50% (2. Myasthenia gravis (MG is a heterogeneous neuromuscular junction disorder that is primarily caused when antibodies form against the acetylcholine receptors (Ab-AchR. MG can develop in conjunction with neoplasia, making MG a paraneoplastic disease. In those cases, MG is most commonly associated with thymomas and less frequently associated with extrathymic malignancies. The mechanism underlying this paraneoplastic syndrome has been hypothesized to involve an autoimmune response against the tumour cells (3. No published reports have linked malignant pancreatic diseases with MG. Here, we report the case of a young woman, negative for Ab-AchR, with a neuroendocrine tumour in the pancreatic head, who experienced a complete resolution of her MG-like syndrome after surgical enucleation of the tumour.

  12. Rectal neuroendocrine tumor with uncommon metastaticspread: A case report and review of literature

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Neuroendocrine tumors of the gastrointestinal tract arerare neoplasms. Rectal neuroendocrine tumors consistapproximately the 5%-14% of all neuroendocrine neoplasmsin Europe. These tumors are diagnosed in relativelyyoung patients, with a mean age at diagnosis of 56years. Distant metastases from rectal neuroendocrinetumors are not very common. Herein we describe a caseof a rectal neuroendocrine tumor which metastasized tothe lung, mediastinum and orbit. This case underscoresthe importance of early identification and optimalmanagement to improve patient's prognosis. Therefore,the clinical significance of this case is the necessityof physicians' awareness and education regardingneuroendocrine tumors' diagnosis and management.

  13. Treatment of Liver Metastases in Patients with Neuroendocrine Tumors of Gastroesophageal and Pancreatic Origin

    Directory of Open Access Journals (Sweden)

    Ping Gu

    2012-01-01

    Full Text Available Well-to-moderately differentiated neuroendocrine tumors of gastroesophageal and pancreatic origin (GEP-NETs with liver metastasis are a heterogeneous group of malignancies for which a range of therapeutic options have been employed. Surgical resection of hepatic metastases or hepatic artery embolization may be beneficial in patients with hepatic-predominant metastatic disease. Patients with “carcinoid” syndrome and syndromes associated with functional pancreatic NET (PNET can be effectively treated with somatostatin analogs. On the other hand, the efficacy of systemic chemotherapy for these patients is limited. A placebo-controlled, double-blind, prospective, and randomized study showed that octreotide LAR improves progression-free survival in patients with advanced midgut functional “carcinoids.” In patients with advanced pancreatic NET, randomized, placebo-controlled studies have recently demonstrated that treatment with the tyrosine kinase inhibitor sunitinib or with mTOR inhibitor everolimus is associated with improved progression-free survival. Based on these studies, octreotide LAR, sunitinib, or everolimus are now considered as first-line therapeutic options in patients with advanced NET. Future studies will likely further define the role of these agents in patients with carcinoid liver metastasis and pancreatic NET liver metastasis.

  14. Isoform 1 of TPD52 (PC-1) promotes neuroendocrine transdifferentiation in prostate cancer cells

    KAUST Repository

    Moritz, Tom

    2016-02-05

    The tumour protein D52 isoform 1 (PC-1), a member of the tumour protein D52 (TPD52) protein family, is androgen-regulated and prostate-specific expressed. Previous studies confirmed that PC-1 contributes to malignant progression in prostate cancer with an important role in castration-resistant stage. In the present work, we identified its impact in mechanisms leading to neuroendocrine (NE) transdifferentiation. We established for long-term PC-1 overexpression an inducible expression system derived from the prostate carcinoma cell line LNCaP. We observed that PC-1 overexpression itself initiates characteristics of neuroendocrine cells, but the effect was much more pronounced in the presence of the cytokine interleukin-6 (IL-6). Moreover, to our knowledge, this is the first report that treatment with IL-6 leads to a significant upregulation of PC-1 in LNCaP cells. Other TPD52 isoforms were not affected. Proceeding from this result, we conclude that PC-1 overexpression enhances the IL-6-mediated differentiation of LNCaP cells into a NE-like phenotype, noticeable by morphological changes and increased expression of typical NE markers, like chromogranin A, synaptophysin or beta-3 tubulin. Immunofluorescent staining of IL-6-treated PC-1-overexpressing LNCaP cells indicates a considerable PC-1 accumulation at the end of the long-branched neuron-like cell processes, which are typically formed by NE cells. Additionally, the experimentally initiated NE transdifferentiation correlates with the androgen receptor status, which was upregulated additively. In summary, our data provide evidence for an involvement of PC-1 in NE transdifferentiation, frequently associated with castration resistance, which is a major therapeutic challenge in the treatment of advanced prostate cancer.

  15. Unusual prostate carcinoma characterized by extensive metastasis, significantly increased serum level of prostatic-specific antigen, and neuroendocrine differentiation: a case report

    Institute of Scientific and Technical Information of China (English)

    HU Yuxin; YE Juan; JIANG Ying; ZHANG Qin-fang; WU Yue-long; CHEN Yue-yu

    2005-01-01

    @@ Some rare variants of prostate carcinoma have been described in recent years.1-3 In this article we report a man with uncommon prostate carcinoma with the following three pathological characteristics: (a) extensive metastasis to bone and lymph nodes of the abdomen, pelvis, and supraclavicular area; (b) significantly increased serum level of prostatic-specific antigen (PSA) as high as 1800 ng/ml; and (c) partial neuroendocrine differentiation in cancer tissue. The patient died 7 months after pathological diagnosis or 22 months after appearance of initial signs. This case has drawn our attention to the fact that pathological diversity of prostate neoplasm might easily lead to misdiagnosis or to delayed diagnosis, and moreover, reasonable therapy for such a case should be based on a thorough investigation. On the other hand, early initiation of appropriate treatment of advanced neuroendocrine carcinoma may improve the prognosis.

  16. Temozolomide as second or third line treatment of patients with neuroendocrine carcinomas

    DEFF Research Database (Denmark)

    Olsen, Ingrid Marie Holst; Sørensen, Jens B; Federspiel, Birgitte;

    2012-01-01

    Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results.......Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results....

  17. Reclassification of neuroendocrine tumors improves the separation of carcinoids and the prediction of survival

    DEFF Research Database (Denmark)

    Skov, B.G.; Krasnik, M.; Lantuejoul, S.;

    2008-01-01

    INTRODUCTION: The classification of neuroendocrine lung tumors has changed over the last decades. Reliable diagnoses are crucial for the quality of clinical databases. The purpose of this study is to determine to which extent the use of different diagnostic criteria of neuroendocrine lung tumors ...

  18. Genetic analysis of an orbital metastasis from a primary hepatic neuroendocrine carcinoma

    DEFF Research Database (Denmark)

    Rasmussen, Jacob Ø; von Holstein, Sarah L; Prause, Jan U;

    2014-01-01

    A 71-year-old female with a known history of primary hepatic neuroendocrine carcinoma, presented with a visual defect, proptosis and restricted eye movements of the right eye. Biopsies from the orbit and from the primary hepatic neuroendocrine carcinoma showed similar morphological and...

  19. Molecular imaging in neuroendocrine tumors : Molecular uptake mechanisms and clinical results

    NARCIS (Netherlands)

    Koopmans, Klaas P.; Neels, Oliver N.; Kema, Ido P.; Elsinga, Philip H.; Links, Thera P.; de Vries, Elisabeth G. E.; Jager, Pieter L.

    2009-01-01

    Neuroendocrine tumors can originate almost everywhere in the body and consist of a great variety of subtypes. This paper focuses on molecular imaging methods using nuclear medicine techniques in neuroendocrine tumors, coupling molecular uptake mechanisms of radiotracers with clinical results. A non-

  20. Aberrant Menin expression is an early event in pancreatic neuroendocrine tumorigenesis

    NARCIS (Netherlands)

    Hackeng, Wenzel M.; Brosens, Lodewijk A A; Poruk, Katherine E.; Noë, Michaël; Hosoda, Waki; Poling, Justin S.; Rizzo, Anthony; Campbell-Thompson, Martha; Atkinson, Mark A.; Konukiewitz, Björn; Klöppel, Günter; Heaphy, Christopher M.; Meeker, Alan K.; Wood, Laura D.

    2016-01-01

    Pancreatic neuroendocrine tumors (PanNETs) are the second most common pancreatic malignancy and cause significant morbidity and mortality. Neuroendocrine microadenomas have been proposed as a potential precursor lesion for sporadic PanNETs. In this study, we applied telomere-specific fluorescent in

  1. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor: A Presentation of Two Cases

    OpenAIRE

    Langer, Seppo W.; Lene Ringholm; Dali, Christine I.; Rene Horsleben Petersen; Åse Krogh Rasmussen; Anne-Marie Gerdes; Birgitte Federspiel; Ulrich Peter Knigge

    2015-01-01

    Cowden Syndrome is a rare autosomal dominantly inherited disorder. Patients with Cowden Syndrome are at increased risk of various benign and malignant neoplasms in breast, endometrium, thyroid, gastrointestinal tract, and genitourinary system. Neuroendocrine tumors are ubiquitous neoplasms that may occur anywhere in the human body. Bronchopulmonary neuroendocrine tumors include four different histological subtypes, among these, typical and atypical pulmonary carcinoids. No association between...

  2. 6-L-(18)F-fluorodihydroxyphenylalanine PET in neuroendocrine tumors : Basic aspects and emerging clinical applications

    NARCIS (Netherlands)

    Jager, Pieter L.; Chirakal, Raman; Marriott, Christopher J.; Brouwers, Adrienne H.; Koopmans, Klaas Pieter; Gulenchyn, Karen Y.

    2008-01-01

    In recent years, 6-L-(18)F-fluorodihydroxyphenylalanine ((18)F-DOPA) PET has emerged as a new diagnostic tool for the imaging of neuroendocrine tumors. This application is based on the unique property of neuroendocrine tumors to produce and secrete various substances, a process that requires the upt

  3. Neuroendocrine reactivity and recovery from work with different physical and mental demands

    NARCIS (Netherlands)

    Sluiter, JK; Frings-Dresen, MHW; van der Beek, AJ; Meijman, TF; Heisterkamp, SH

    2000-01-01

    Objectives The purpose of this study was to examine the extent to which the type or nature (physical, mental or mixed mental and physical) of work and work characteristics is related to the course of neuroendocrine reactivity and recovery from work. Methods Neuroendocrine reactivity and recovery wer

  4. Prolonged clinical benefit of everolimus therapy in the management of high-grade pancreatic neuroendocrine carcinoma.

    Science.gov (United States)

    Fonseca, Paula J; Uriol, Esther; Galván, José A; Alvarez, Carlos; Pérez, Quionia; Villanueva, Noemi; Berros, José P; Izquierdo, Marta; Viéitez, José M

    2013-01-01

    Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET) are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS) and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR). Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.

  5. Prolonged Clinical Benefit of Everolimus Therapy in the Management of High-Grade Pancreatic Neuroendocrine Carcinoma

    Directory of Open Access Journals (Sweden)

    Paula J. Fonseca

    2013-08-01

    Full Text Available Treatment options for patients with high-grade pancreatic neuroendocrine tumors (pNET are limited, especially for those with progressive disease and for those who experience treatment failure. Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR, has been approved for the treatment of patients with low- or intermediate-grade advanced pNET. In the randomized phase III RADIANT-3 study in patients with low- or intermediate-grade advanced pNET, everolimus significantly increased progression-free survival (PFS and decreased the relative risk for disease progression by 65% over placebo. This case report describes a heavily pretreated patient with high-grade pNET and liver and peritoneal metastases who achieved prolonged PFS, clinically relevant partial radiologic tumor response, and resolution of constitutional symptoms with improvement in Karnofsky performance status while receiving a combination of everolimus and octreotide long-acting repeatable (LAR. Radiologic and clinical responses were maintained for 19 months, with minimal toxicity over the course of treatment. This case supports the findings that the combination of everolimus plus octreotide LAR may be considered for use in patients with high-grade pNET and progressive disease. Although behavior and aggressiveness are different between low- or intermediate-grade and high-grade pNET, some high-grade pNET may express mTOR; hence, everolimus should be considered in a clinical trial.

  6. Neuroendocrine carcinoma of the ampulla of Vater causing ectopic adrenocorticotropic hormone-dependent Cushing's syndrome

    Science.gov (United States)

    KATO, AKIHISA; HAYASHI, KAZUKI; NAITOH, ITARU; SENO, KYOJI; OKADA, YUKIKO; BAN, TESSHIN; KONDO, HIROMU; NISHI, YUJI; UMEMURA, SHUICHIRO; HORI, YASUKI; NATSUME, MAKOTO; JOH, TAKASHI

    2016-01-01

    Ectopic adrenocorticotropic hormone (ACTH) is rarely secreted by neuroendocrine tumors. Although neuroendocrine tumors may occur at any site in the gastrointestinal system, they very rarely occur in the ampulla of Vater and have a poor prognosis. The present study described the first Cushing's syndrome as a result of ectopic ACTH arising from the ampulla of Vater neuroendocrine carcinoma. A 69-year-old female was admitted with clinical features of Cushing's syndrome, confirmed biochemically by hypokalemia, and elevated levels of ACTH and cortisol. In further investigations, a tumor of the ampulla of Vater and liver metastases were detected. Pathological analysis of the biopsy confirmed a neuroendocrine carcinoma, which was immunohistochemically positive for chromogranin A, synaptophysin, cluster of differentiation 56 and ACTH. Therefore, the present study diagnosed a functional and metastatic neuroendocrine carcinoma of the ampulla of Vater with ectopic ACTH production causing Cushing's syndrome. The patient succumbed to mortality 4 months later, despite administration of combined chemotherapy with irinotecan and cisplatin. PMID:27330779

  7. Circulating neuroendocrine tumors biomarkers. Why? When? How? Suggestions for clinical practice from guidelines and consensus

    Institute of Scientific and Technical Information of China (English)

    Paola Razzore; Giorgio Arnaldi

    2016-01-01

    Neuroendocrine neoplasms (NETs) are rare tumors that are increasing in incidence. NETs are characterized by heterogeneous biological behaviour, clinical presentation and course. A sensitive and speciifc diagnostic and prognostic circulating biomarker useful for all sites, grading and staging of neuroendocrine tumors is still an unmet need. The aim of this article was to review current neuroendocrine and oncologic scientiifc society guidelines and position statements, and propose recommendations for the most frequent clinical practice queries on circulating neuroendocrine tumors biomarkers. The authors searched for NCCN, NANETS, ESMO, ENETS, UKINETS, AME management guidelines or position statements available from PubMed up to 7th January 2016. From these results we chose guidelines or position statements published by scientiifc societies or institutions in USA, Europe and Italy with recognized expertise in neuroendocrine tumor patient management. The authors present suggestions for clinical practice based on this analysis.

  8. Global hypomethylation and promoter methylation in small intestinal neuroendocrine tumors

    OpenAIRE

    Fotouhi, Omid; Adel Fahmideh, Maral; Kjellman, Magnus; Sulaiman, Luqman; Höög, Anders; Zedenius, Jan; Hashemi, Jamileh; Larsson, Catharina

    2014-01-01

    Aberrant DNA methylation is a feature of human cancer affecting gene expression and tumor phenotype. Here, we quantified promoter methylation of candidate genes and global methylation in 44 small intestinal-neuroendocrine tumors (SI-NETs) from 33 patients by pyrosequencing. Findings were compared with gene expression, patient outcome and known tumor copy number alterations. Promoter methylation was observed for WIF1, RASSF1A, CTNNB1, CXCL14, NKX2–3, P16, LAMA1, and CDH1. By contrast APC, CDH3...

  9. Hepatic-directed Therapies in Patients with Neuroendocrine Tumors.

    Science.gov (United States)

    Kennedy, Andrew S

    2016-02-01

    Neuroendocrine tumors (NETs) of the gastrointestinal (GI) tract have a propensity for producing hepatic metastases. Most GI NETs arise from the foregut or midgut, are malignant, and can cause severe debilitating symptoms adversely affecting quality of life. Aggressive treatments to reduce symptoms have an important role in therapy. Patients with GI NETs usually present with inoperable metastatic disease and severe symptoms from a variety of hormones and biogenic amines. This article describes intra-arterial hepatic-directed therapies for metastases from NETs, a group of treatments in which the therapeutic and/or embolic agents are released intra-arterially in specific hepatic vessels to target tumors. PMID:26614377

  10. The Role of Cdk5 in Neuroendocrine Thyroid Cancer

    OpenAIRE

    Pozo, Karine; Castro-Rivera, Emely; Tan, Chunfeng; Plattner, Florian; SCHWACH, GERT; Siegl, Veronika; Meyer, Douglas; Guo, Ailan; Gundara, Justin; Mettlach, Gabriel; RICHER, Edmond; Guevara, Jonathan A.; Ning, Li; Tsai, Li-Huei; Sun, Xiankai

    2013-01-01

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation. A conditional MTC mouse model was generated and corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC, which was arrested by repre...

  11. Spontaneous rupture of thymic neuroendocrine carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chan Yeong; Lee, In Jae; Min, Soo Kee [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2015-11-15

    Thymic neuroendocrine carcinoma (NEC) is a rare neoplasm with tendencies of local invasion and metastasis. Usually, it is detected incidentally or by its symptoms caused by mass effect. Rupture of the tumor is extremely rare. In this study, we report a case of a ruptured thymic NEC that was combined with a potentially fatal hemorrhage. This lesion was manifested as a progressive bulging of the right cardiac border on serial chest radiographs, and on CT as a large anterior mediastinal mass with heterogeneous enhancement, internal necrosis, and hematoma.

  12. Genetic associations with neuroendocrine tumor risk: results from a genome-wide association study.

    Science.gov (United States)

    Du, Yeting; Ter-Minassian, Monica; Brais, Lauren; Brooks, Nichole; Waldron, Amanda; Chan, Jennifer A; Lin, Xihong; Kraft, Peter; Christiani, David C; Kulke, Matthew H

    2016-08-01

    The etiology of neuroendocrine tumors remains poorly defined. Although neuroendocrine tumors are in some cases associated with inherited genetic syndromes, such syndromes are rare. The majority of neuroendocrine tumors are thought to be sporadic. We performed a genome-wide association study (GWAS) to identify potential genetic risk factors for sporadic neuroendocrine tumors. Using germline DNA from blood specimens, we genotyped 909,622 SNPs using the Affymetrix 6.0 GeneChip, in a cohort comprising 832 neuroendocrine tumor cases from Dana-Farber Cancer Institute and Massachusetts General Hospital and 4542 controls from the Harvard School of Public Health. An additional 241 controls from Dana-Farber Cancer Institute were used for quality control. We assessed risk associations in the overall cohort, and in neuroendocrine tumor subgroups. We identified no potential risk associations in the cohort overall. In the small intestine neuroendocrine tumor subgroup, comprising 293 cases, we identified risk associations with three SNPs on chromosome 12, all in strong LD. The three SNPs are located upstream of ELK3, a transcription factor implicated in angiogenesis. We did not identify clear risk associations in the bronchial or pancreatic neuroendocrine subgroups. This large-scale study provides initial evidence that presumed sporadic small intestine neuroendocrine tumors may have a genetic etiology. Our results provide a basis for further exploring the role of genes implicated in this analysis, and for replication studies to confirm the observed associations. Additional studies to evaluate potential genetic risk factors for sporadic pancreatic and bronchial neuroendocrine tumors are warranted. PMID:27492634

  13. {sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

    Energy Technology Data Exchange (ETDEWEB)

    Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

    2013-06-15

    6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

  14. Androgen-targeted therapy induced epithelial mesenchymal plasticity and neuroendocrine transdifferentiation in prostate cancer: an opportunity for intervention

    Directory of Open Access Journals (Sweden)

    Mannan eNouri

    2014-12-01

    Full Text Available Androgens regulate biological pathways to promote proliferation, differentiation and survival of benign and malignant prostate tissue. Androgen receptor targeted therapies exploit this dependence and are used in advanced prostate cancer to control disease progression. Contemporary treatment regimens involve sequential use of inhibitors of androgen synthesis or androgen receptor function. Although targeting the androgen axis has clear therapeutic benefit, its effectiveness is temporary, as prostate tumor cells adapt to survive and grow. The removal of androgens (androgen deprivation has been shown to activate both epithelial-to-mesenchymal transition (EMT and neuroendocrine transdifferentiation programs. EMT has established roles in promoting biological phenotypes associated with tumor progression (migration/invasion, tumor cell survival, cancer stem cell-like properties, resistance to radiation and chemotherapy in multiple human cancer types. Neuroendocrine transdifferentiation in prostate cancer is associated with resistance to therapy, visceral metastasis and aggressive disease. Thus, activation of these programs via inhibition of the androgen axis provides a mechanism by which tumor cells can adapt to promote disease recurrence and progression. Brachyury, Axl, MEK and aurora kinase A are molecular drivers of these programs, and inhibitors are currently in clinical trials to determine therapeutic applications. Understanding tumor cell plasticity will be important in further defining the rational use of androgen targeted therapies clinically and provides an opportunity for intervention to prolong survival of men with metastatic prostate cancer.

  15. Developmental exposure to ethinylestradiol affects reproductive physiology, the GnRH neuroendocrine network and behaviors in female mouse

    Directory of Open Access Journals (Sweden)

    Lyes eDerouiche

    2015-12-01

    Full Text Available During development, environmental estrogens are able to induce an estrogen mimetic action that may interfere with endocrine and neuroendocrine systems. The present study investigated the effects on the reproductive function in female mice following developmental exposure to pharmaceutical ethinylestradiol (EE2, the most widespread and potent synthetic steroid present in aquatic environments. EE2 was administrated in drinking water at environmentally relevant (ENVIR or pharmacological (PHARMACO doses (0.1 and 1 µg/kg (body weight/day respectively, from embryonic day 10 until postnatal day 40. Our results show that both groups of EE2-exposed females had advanced vaginal opening and shorter estrus cycles, but a normal fertility rate compared to CONTROL females. The hypothalamic population of GnRH neurons was affected by EE2 exposure with a significant increase in the number of perikarya in the preoptic area of the PHARMACO group and a modification in their distribution in the ENVIR group, both associated with a marked decrease in GnRH fibers immunoreactivity in the median eminence. In EE2-exposed females, behavioral tests highlighted a disturbed maternal behavior, a higher lordosis response, a lack of discrimination between gonad-intact and castrated males in sexually experienced females, and an increased anxiety-related behavior. Altogether, these results put emphasis on the high sensitivity of sexually dimorphic behaviors and neuroendocrine circuits to disruptive effects of EDCs.

  16. Specific targeting for the treatment of neuroendocrine tumors; Ciblage specifique pour le traitement des tumeurs neuro-endocrines

    Energy Technology Data Exchange (ETDEWEB)

    Hoefnagel, C.A. [Netherlands Cancer Institute 1066 CX Amsterdam, Dept. of Nuclear Medicine (Netherlands)

    2003-09-01

    For the treatment of neuroendocrine tumors three ways of specific targeting of radionuclides prevail: by {sup 131}I-meta-iodo-benzyl-guanidine (MIBG), which is taken up by an active uptake-1 mechanism and stored in neurosecretory granules of neural crest tumor cells, by radiolabeled peptides, in particular the somatostatin analogs octreotide and lanreotide, targeting the peptide receptors, and by radiolabeled antibodies, which target tumor cell surface antigens. The choice depends on the indication, the results of diagnostic imaging using tracer amounts of these agents, the availability and feasibility of radionuclide therapy and of other treatment modalities. The applications, clinical results and developments for the major indications are reviewed. {sup 131}I-MIBG therapy has a cumulative response rate of 50%, associated with little toxicity, in metastatic pheochromocytoma, paraganglioma and neuroblastoma, whereas its role is primarily palliative in patients with medullary thyroid carcinoma and carcinoid tumors. Treatment using {sup 90}Y- or {sup 177}Lu-labeled octreotide/lanreotide is mostly used in neuroendocrine gastro-entero-pancreatic (GEP) tumors and paraganglioma, attaining stabilization of disease anti-palliation in the majority of patients. As this treatment is specific for the receptor rather than for the tumor type, it may also be applicable to other, non-neuroendocrine tumors. Radioimmunotherapy is applied in medullary thyroid carcinoma, in which a phase I/II study using bi-specific anti-DTPA/anti-CEA immuno-conjugates followed by {sup 131}I-hapten has proven some degree of success, and may be used in neuroblastoma more effectively than before, once chimeric and humanized monoclonal antibodies become available for therapy. Integration of these specific and noninvasive therapies at an optimal moment into the treatment protocols of these diseases may enhance their effectiveness and acceptance. (author)

  17. The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates

    Directory of Open Access Journals (Sweden)

    Ather MH

    2012-11-01

    Full Text Available M Hammad Ather,1 Tahmeena Siddiqui21Dept of Surgery, Aga Khan University, 2Karachi Medical and Dental College, Karachi, PakistanAbstract: Prostate cancer (PC displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation; besides this, chromatin remodeling and micro RNA (miRNA are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in

  18. Endoscopic imaging in the management of gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Pellicano, Rinaldo; Fagoonee, Sharmila; Altruda, Fiorella; Bruno, Mauro; Saracco, Giorgio M; De Angelis, Claudio

    2016-12-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors deriving from the gastrointestinal (GI) neuroendocrine system. Since these neoplasms are usually very small, located deeply within the retroperitoneum or into an extramucosal site of the GI tract and, lastly, because they may be multi-sited, radiological imaging modalities, in combination with endoscopy, are the diagnostic workhorses in patients with GEP-NETs. Endoscopic approach is useful for detection, bioptic diagnosis and curative resection of small GEP-NETs of stomach, duodenum, jejuno-ileum, and colon-rectum. Moreover, endoscopic ultrasonography (EUS), associated with high frequency miniprobes, is a valuable procedure in regional staging of lesions of the GI wall and can provide information which has a remarkable impact on therapeutic choices. EUS is still the sole technique, in a substantial number of cases, providing a definitive diagnosis of pancreatic insulinoma and it detects and follows small lesions of the pancreas in patients with Multiple Endocrine Neoplasia type 1 syndrome. EUS should be performed in those cases in which morphological or molecular imaging modalities need to be supported because of negative or dubious results. In this review we describe the applications of endoscopic procedures in the management of GEP-NETs. PMID:27600643

  19. Endoscopic mucosal resection of early stage colon neuroendocrine carcinoma.

    Science.gov (United States)

    Yamasaki, Yasushi; Uedo, Noriya; Ishihara, Ryu; Tomita, Yasuhiko

    2015-01-01

    Early stage colorectal neuroendocrine carcinoma is rare. A small colon tumour was found in a 56-year-old man during diagnostic colonoscopy performed after a positive faecal occult blood test, and he was referred for treatment. A slightly reddish superficial elevated lesion with a shallow depression 10 mm in size was found in the transverse colon. Magnifying narrow-band imaging revealed disrupted irregular microvessels and the absence of a surface pattern in the depressed area. En bloc endoscopic mucosal resection (EMR) of the tumour was undertaken. The tumour was positive for chromogranin A and synaptophysin, and had a mitotic rate of >20/10 high-power fields and a Ki-67 proliferative index of >50%; it was diagnosed as a neuroendocrine carcinoma. The tumour minimally invaded the submucosa (300 μm) without lymphovascular involvement. The patient was followed up carefully, and at 1 year after EMR, no recurrence was found using colonoscopy and CT scans. PMID:25737221

  20. Small bowel neuroendocrine tumors: From pathophysiologyto clinical approach

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Neuroendocrine tumors (NETs), defined as epithelialtumors with predominant neuroendocrine differentiation,are among the most frequent types of smallbowel neoplasm. They represent a rare, slow-growingneoplasm with some characteristics common to allforms and others attributable to the organ of origin. Thediagnosis of this subgroup of neoplasia is not usuallystraight-forward for several reasons. Being a rare formof neoplasm they are frequently not readily consideredin the differential diagnosis. Also, clinical manifestationsare nonspecific lending the clinician no clue that pointsdirectly to this entity. However, the annual incidence ofNETs has risen in the last years to 40 to 50 cases permillion probably not due to a real increase in incidencebut rather due to better diagnostic tools that havebecome progressively available. Being a rare malignancy,investigation regarding its pathophysiology and effortstoward better understanding and classification of thesetumors has been limited until recently. Clinical societiesdedicated to this matter are emerging (NANETS,ENETS and UKINETS) and several guidelines werepublished in an effort to standardize the nomenclature,grading and staging systems as well as diagnosis andmanagement of NETs. Also, some investigation on thegenetic behavior of small bowel NETs has been recentlyreleased, shedding some light on the pathophysiologyof these tumors, and pointing some new directions onthe possible treating options. In this review we focus onthe current status of the overall knowledge about smallbowel NETs, focusing on recent breakthroughs and itspotential application on clinical practice.

  1. Calcium dynamics in the secretory granules of neuroendocrine cells.

    Science.gov (United States)

    Alvarez, Javier

    2012-01-01

    Cellular Ca(2+)signaling results from a complex interplay among a variety of Ca(2+) fluxes going across the plasma membrane and across the membranes of several organelles, together with the buffering effect of large numbers of Ca(2+)-binding sites distributed along the cell architecture. Endoplasmic and sarcoplasmic reticulum, mitochondria and even nucleus have all been involved in cellular Ca(2+) signaling, and the mechanisms for Ca(2+) uptake and release from these organelles are well known. In neuroendocrine cells, the secretory granules also constitute a very important Ca(2+)-storing organelle, and the possible role of the stored Ca(2+) as a trigger for secretion has attracted considerable attention. However, this possibility is frequently overlooked, and the main reason for that is that there is still considerable uncertainty on the main questions related with granular Ca(2+) dynamics, e.g., the free granular [Ca(2+)], the physical state of the stored Ca(2+) or the mechanisms for Ca(2+) accumulation and release from the granules. This review will give a critical overview of the present state of knowledge and the main conflicting points on secretory granule Ca(2+) homeostasis in neuroendocrine cells.

  2. Neuroendocrine Tumours : From Radiomolecular Imaging to Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    GEORGIOS eLIMOURIS

    2012-02-01

    Full Text Available Transhepatic radionuclide infusion (THRI has been introduced as a new treatment approach for unresectable liver neuroendocrine metastatic lesions with the prerequisite of a positive In-111 Pentetreotide (Octreoscan. Patients with multiple liver neuroendocrine metastases can be locally treated after selective hepatic artery catheterization and infusion of radiolabelled somatostatin analogues, and in case of extra-hepatic secondary spread, after simple i.v. application. According to the world wide references, the average dose per session to each patient is 6.3±0.3 GBq (~ 160-180 mCi of In-111-DTPA-Phe1- Pentetreotide, 10-12 fold in total, administered monthly or of 4.1± 0.2 GBq (~105-116 mCi of Y-90 DOTA TOC, 3 fold in total or of 7.0 ± 0.4 GBq (~178-200 mCi of Lu-177 DOTA TATE, 4-6 fold in total (the choice of which being based on the tumor size, assessed by CT or MRI . Follow-up at monthly intervals has to be performed by means of ultrasonography (US. Treat- ment response has to be assessed according to the WHO criteria (RECIST or SWOG.

  3. Focal neuroendocrine differentiation in prostatic gland carcinoma with basaloid pattern

    Directory of Open Access Journals (Sweden)

    Gligorijević Jasmina V.

    2011-01-01

    Full Text Available Introduction. Prostatic gland basal cell proliferations exhibit morphological continuum ranging from basal cell hyperplasia to basal cell carcinoma. In the following report, we described clinical features, morphological spectrum, neuroendocrine differentiation and histogenesis of prostatic gland basal cell carcinoma in our patient. Case report. Hematoxylineosin (HE, Alcian blu-periodic acid schiff (ABPAS at pH 2.5 stained sections and the avidin-biotinperoxidase complex (ABC, were performed on prostate gland paraffin-embedded tissue. Monoclonal antibodies directed against cytokeratin (34βE12 which selectively stains basal cells, prostate specific antigen (PSA, chromogranine A, neuron-specific enolase (NSE, synaptophysin and CD56, were used. Basal cell proliferations exhibited a morphological continuum ranging from basal cell hyperplasia to prostatic gland carcinoma. In these prostatic lesions, positive reactivity was demonstrated for 34βE12 and CD56. These findings indicate that the basaloid cells of basal cell hyperplasia, florid basal cell hyperplasia, atypical basal cell hyperplasia and basal cell carcinoma are derived from basal cells of the normal prostate gland suggesting a continuum in the progression of hyperplasia to benign and then malignant neoplasia. The presence of CD56 protein in the discovered lesions may be related to their neuroendocrine differentiation. Conclusion. The fact, that our patient was well six years after the radical prostatectomy supports the belief of some authors that basal cell carcinoma represents a low grade carcinoma with an excellent prognosis.

  4. Irritable bowel syndrome: the role of gut neuroendocrine peptides.

    Science.gov (United States)

    El-Salhy, Magdy; Seim, Inge; Chopin, Lisa; Gundersen, Doris; Hatlebakk, Jan Gunnar; Hausken, Trygve

    2012-01-01

    Irritable bowel syndrome (IBS) is a common chronic disorder with a prevalence ranging from 5 to 10 percent of the world's population. This condition is characterised by abdominal discomfort or pain, altered bowel habits, and often bloating and abdominal distension. IBS reduces quality of life in the same degree of impairment as major chronic diseases such as congestive heart failure and diabetes and the economic burden on the health care system and society is high. Abnormalities have been reported in the neuroendocrine peptides/amines of the stomach, small- and large intestine in patients with IBS. These abnormalities would cause disturbances in digestion, gastrointestinal motility and visceral hypersensitivity, which have been reported in patients with IBS. These abnormalities seem to contribute to the symptom development and appear to play a central role in the pathogenesis of IBS. Neuroendocrine peptides/amines are potential tools in the treatment and diagnosis of IBS. In particular, the cell density of duodenal chromogranin A expressing cells appears to be a good histopathological marker for the diagnosis of IBS with high sensitivity and specificity. PMID:22652678

  5. Pancreatic neuroendocrine tumors: biology, diagnosis,and treatment

    Institute of Scientific and Technical Information of China (English)

    Cynthia Ro; Wanxing Chai; Victoria E.Yu; Run Yu

    2013-01-01

    Pancreatic neuroendocrine tumors (PNETs),a group of endocrine tumors arising in the pancreas,are among the most common neuroendocrine tumors.The genetic causes of familial and sporadic PNETs are somewhat understood,but their molecular pathogenesis remains unknown.Most PNETs are indolent but have malignant potential.The biological behavior of an individual PNET is unpredictable; higher tumor grade,lymph node and liver metastasis,and larger tumor size generally indicate a less favorable prognosis.Endocrine testing,imaging,and histological evidence are necessary to accurately diagnose PNETs.A 4-pronged aggressive treatment approach consisting of surgery,Iocoregional therapy,systemic therapy,and complication control has become popular in academic centers around the world.The optimal application of the multiple systemic therapeutic modalities is under development; efficacy,safety,availability,and cost should be considered when treating a specific patient.The clinical presentation,diagnosis,and treatment of specific types of PNETs and familial PNET syndromes,including the novel Mahvash disease,are summarized.

  6. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kam, B.L.R.; Teunissen, J.J.M.; Krenning, E.P.; Khan, S.; Vliet, E.I. van; Kwekkeboom, D.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, W.W. de [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2012-02-15

    Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with {sup 177}Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with {sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with {sup 177}Lu-DOTATATE as well as the limited side effects with additional cycles of {sup 177}Lu-DOTATATE suggest that more cycles of {sup 177}Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of {sup 90}Y-[DOTA{sup 0},Tyr{sup 3}]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with {sup 177}Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with {sup 177}Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours. (orig.)

  7. The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations.

    Directory of Open Access Journals (Sweden)

    Nicola Fusco

    Full Text Available Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

  8. Everolimus in the treatment of renal cell carcinoma and neuroendocrine tumors.

    Science.gov (United States)

    Chan, Hiu-yan; Grossman, Ashley B; Bukowski, Ronald M

    2010-08-01

    Renal cell carcinoma (RCC) and neuroendocrine tumors (NET) are uncommon malignancies, highly resistant to chemotherapy, that have emerged as attractive platforms for evaluating novel targeted regimens. Everolimus is an oral rapamycin derivative within the mammalian target of rapamycin class of agents. Preclinical series have shown that everolimus exhibits anticancer effects in RCC and NET cell lines. A phase 3 placebo-controlled study in advanced clear-cell RCC, known as RECORD-1 (for "REnal Cell cancer treatment with Oral RAD001 given Daily"), documented that everolimus stabilizes tumor progression, prolongs progression-free survival and has acceptable tolerability in patients previously treated with the multikinase inhibitors sunitinib and/or sorafenib. Everolimus has been granted regulatory approval for use in sunitinib-pretreated and/or sorafenib-pretreated advanced RCC and incorporated into clinical practice guidelines, and the RECORD-1 safety data are being used to develop recommendations for managing clinically important adverse events in everolimus-treated patients. Ongoing clinical trials are evaluating everolimus as earlier RCC therapy (first-line for advanced disease and as neoadjuvant therapy), in non-clear-cell tumors, and in combination with various other approved or investigational targeted therapies for RCC. Regarding advanced NET, recently published phase 2 data support the ability of everolimus to improve disease control in patients with advanced NET as monotherapy or in combination with somatostatin analogue therapy, octreotide long-acting release (LAR). Forthcoming data from phase 3 placebo-controlled trials of everolimus, one focused on monotherapy for pancreatic NET and the other on combination use with octreotide LAR for patients with advanced NET and a history of carcinoid syndrome, will provide insight into its future place in NET therapy. The results of a number of ongoing phase 3 evaluations of everolimus will determine its broader

  9. Endocrine and neuroendocrine regulation of fathering behavior in birds.

    Science.gov (United States)

    Lynn, Sharon E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Although paternal care is generally rare among vertebrates, care of eggs and young by male birds is extremely common and may take on a variety of forms across species. Thus, birds provide ample opportunities for investigating both the evolution of and the proximate mechanisms underpinning diverse aspects of fathering behavior. However, significant gaps remain in our understanding of the endocrine and neuroendocrine influences on paternal care in this vertebrate group. In this review, I focus on proximate mechanisms of paternal care in birds. I place an emphasis on specific hormones that vary predictably and/or unpredictably during the parental phase in both captive and wild birds: prolactin and progesterone are generally assumed to enhance paternal care, whereas testosterone and corticosterone are commonly-though not always correctly-assumed to inhibit paternal care. In addition, because endocrine secretions are not the sole mechanistic influence on paternal behavior, I also explore potential roles for certain neuropeptide systems (specifically the oxytocin-vasopressin nonapeptides and gonadotropin inhibitory hormone) and social and experiential factors in influencing paternal behavior in birds. Ultimately, mechanistic control of fathering behavior in birds is complex, and I suggest specific avenues for future research with the goal of narrowing gaps in our understanding of this complexity. Such avenues include (1) experimental studies that carefully consider not only endocrine and neuroendocrine mechanisms of paternal behavior, but also the ecology, phylogenetic history, and social context of focal species; (2) investigations that focus on individual variation in both hormonal and behavioral responses during the parental phase; (3) studies that investigate mechanisms of maternal and paternal care independently, rather than assuming that the mechanistic foundations of care are similar between the sexes; (4

  10. Endocrine and neuroendocrine regulation of fathering behavior in birds.

    Science.gov (United States)

    Lynn, Sharon E

    2016-01-01

    This article is part of a Special Issue "Parental Care". Although paternal care is generally rare among vertebrates, care of eggs and young by male birds is extremely common and may take on a variety of forms across species. Thus, birds provide ample opportunities for investigating both the evolution of and the proximate mechanisms underpinning diverse aspects of fathering behavior. However, significant gaps remain in our understanding of the endocrine and neuroendocrine influences on paternal care in this vertebrate group. In this review, I focus on proximate mechanisms of paternal care in birds. I place an emphasis on specific hormones that vary predictably and/or unpredictably during the parental phase in both captive and wild birds: prolactin and progesterone are generally assumed to enhance paternal care, whereas testosterone and corticosterone are commonly-though not always correctly-assumed to inhibit paternal care. In addition, because endocrine secretions are not the sole mechanistic influence on paternal behavior, I also explore potential roles for certain neuropeptide systems (specifically the oxytocin-vasopressin nonapeptides and gonadotropin inhibitory hormone) and social and experiential factors in influencing paternal behavior in birds. Ultimately, mechanistic control of fathering behavior in birds is complex, and I suggest specific avenues for future research with the goal of narrowing gaps in our understanding of this complexity. Such avenues include (1) experimental studies that carefully consider not only endocrine and neuroendocrine mechanisms of paternal behavior, but also the ecology, phylogenetic history, and social context of focal species; (2) investigations that focus on individual variation in both hormonal and behavioral responses during the parental phase; (3) studies that investigate mechanisms of maternal and paternal care independently, rather than assuming that the mechanistic foundations of care are similar between the sexes; (4

  11. Features of the immunohistochemical diagnostics of neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Poslavs’ka O.V.

    2015-12-01

    Full Text Available Background. The possibility of neuroendocrine tumor (NET development from almost any organ causes problems in determination of a true primary site after detection of such metastases in lymph nodes or liver. It impels to consider the expression of immunohistochemical organ-specific markers such as cytokeratin (СК along with the morphological characteristics. Objective. Determine the immunophenotype of neuroendocrine tumors of different localizations. Methods. Material from 52 patients (30 women and 22 men aged 31 to 79 years (median 57 years had been retrospectively analyzed during Jan 2012 – Oct 2014. Material included NET of different localization (9 cases in stomach, 7 in lung, 5 in colon, 3 in small intestine, 3 in larynx, 3 in mammary gland, 2 in pancreas, 1 in cervix and 1 in uterus body or its metastasis from an unknown primary site (12 in lymph nodes, and 6 in the liver. СК Рan (clone AE1/AE3, Chromogranin A (CHR A (clone LK2H10, Synaptophysin (SYN (clone SYP02, CD95 (clone АВ3, CK 7 (clone OV-TL 12/30, Vimentin (VIM (clone V9 were used as a primary monoclonal antibodies. Results. 96% of cases have turned out to be CK Рan+, except 2 (3.8% NET with a localization in lymph nodes. 84.6 % of tumors expressed SYN, except 2 (22.2% in stomach, 1 (14.3% in lung, 1 (100% in uterus body, 3 (25% in lymph node and 1 (16.7% in liver metastasis. 82.7% gave a positive staining for CHR A, except for 3 (60% in colon, 1 (33.3% in small intestine, 1 (11,1% in stomach , 3 (25 % in lymph nodes metastases (both of which are NET with СК Рan- and 1 (16.7% of liver metastases. VIM+ were only 4 cases (both of which are NET, 1 (100% of uterus body and 1 (16.7% of liver metastasis. Positive cases of CK 7 expression were 6 (66.7% in stomach NET (all carcinoids, 3 (42.9% in lung, 1 (20% in colon, 1 (33.3% in larynx, 2 (16.7% in lymph node and 2 (33.3% in liver metastasis. Conclusions. The most common NET phenotype of these localizations is CK Рan+, CHR A

  12. Somatostatin analogues according to Ki67 index in neuroendocrine tumours: an observational retrospective-prospective analysis from real life.

    Science.gov (United States)

    Faggiano, Antongiulio; Carratù, Anna Chiara; Guadagno, Elia; Tafuto, Salvatore; Tatangelo, Fabiana; Riccardi, Ferdinando; Mocerino, Carmela; Palmieri, Giovannella; Damiano, Vincenzo; Siciliano, Roberta; Leo, Silvana; Mauro, Annamaria; Tozzi, Lucia Franca; Battista, Claudia; De Rosa, Gaetano; Colao, Annamaria

    2016-02-01

    Somatostatin analogues (SSAs) have shown limited and variable antiproliferative effects in neuroendocrine tumours (NETs). Whether tumour control by SSAs depends on grading based on the 2010 WHO NET classification is still unclear. The aim of this study is to evaluate the efficacy of long-acting SSAs in NETs according to Ki67 index. An observational Italian multicentre study was designed to collect data in patients with gastro-entero-pancreatic or thoracic NETs under SSA treatment. Both retrospective and prospective data were included and they were analysed in line with Ki67 index, immunohistochemically evaluated in tumour samples and graded according to WHO classification (G1 = Ki67 index 0-2%, G2 = Ki67 index 3-20%, G3 = Ki67 index > 20%). Among 601 patients with NET, 140 with a histologically confirmed gastro-entero-pancreatic or thoracic NET or NET with unknown primary were treated with lanreotide autogel or octreotide LAR. An objective tumour response was observed in 11%, stability in 58% and progression in 31%. Objective response and tumour stability were not significantly different between G1 and G2 NETs. Progression free survival was longer but not significantly different in G1 than G2 NETs (median: 89 vs 43 months, p = 0.15). The median PFS was significantly longer in NETs showing Ki67 < 5% than in those showing Ki67 ≥ 5% (89 vs 35 months, p = 0.005). SSA therapy shows significant antiproliferative effects in well differentiated low/intermediate-proliferating NETs, not only G1 but also in G2 type. A Ki67 index of 5% seems to work better than 3% to select the best candidates for SSA therapy. PMID:26701729

  13. Comparison between 68Ga-DOTA-NOC and 18F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

    International Nuclear Information System (INIS)

    18F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that 18F-DOPA and 68Ga-DOTA-NOC are more accurate for disease assessment and 68Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare 68Ga-DOTA-NOC and 18F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for 18F-DOPA and 68Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. 68Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while 18F-DOPA PET was positive in 9/13. On a lesions basis, 68Ga-DOTA-NOC identified more lesions than 18F-DOPA (71 vs 45), especially at liver, lung and lymph node level. 68Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while 18F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that 68Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over 18F-DOPA. (orig.)

  14. Comparison of {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC PET/CT imaging in the same patient group with neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Cerrahpasa Tip Fakultesi, Nukleer Tip Anabilim Dali, Aksaray, Istanbul (Turkey); Demirci, Emre; Uslu, Ilhami; Kanmaz, Bedii [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem; Araman, Ahmet; Ozsoy, Yildiz [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Decristoforo, Clemens [Medical University of Innsbruck, Clinical Department of Nuclear Medicine, Innsbruck (Austria)

    2012-08-15

    Recent studies have suggested that positron emission tomography (PET) imaging with {sup 68}Ga-labelled DOTA-somatostatin analogues (SST) like octreotide and octreotate is useful in diagnosing neuroendocrine tumours (NETs) and has superior value over both CT and planar and single photon emission computed tomography (SPECT) somatostatin receptor scintigraphy (SRS). The aim of the present study was to evaluate the role of {sup 68}Ga-DOTA-1-NaI{sup 3}-octreotide ({sup 68}Ga-DOTANOC) in patients with SST receptor-expressing tumours and to compare the results of {sup 68}Ga-DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotate ({sup 68}Ga-DOTATATE) in the same patient population. Twenty SRS were included in the study. Patients' age (n = 20) ranged from 25 to 75 years (mean 55.4 {+-} 12.7 years). There were eight patients with well-differentiated neuroendocrine tumour (WDNET) grade1, eight patients with WDNET grade 2, one patient with poorly differentiated neuroendocrine carcinoma (PDNEC) grade 3 and one patient with mixed adenoneuroendocrine tumour (MANEC). All patients had two consecutive PET studies with {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC. All images were evaluated visually and maximum standardized uptake values (SUV{sub max}) were also calculated for quantitative evaluation. On visual evaluation both tracers produced equally excellent image quality and similar body distribution. The physiological uptake sites of pituitary and salivary glands showed higher uptake in {sup 68}Ga-DOTATATE images. Liver and spleen uptake values were evaluated as equal. Both {sup 68}Ga-DOTATATE and {sup 68}Ga-DOTANOC were negative in 6 (30 %) patients and positive in 14 (70 %) patients. In {sup 68}Ga-DOTANOC images only 116 of 130 (89 %) lesions could be defined and 14 lesions were missed because of lack of any uptake. SUV{sub max} values of lesions were significantly higher on {sup 68}Ga-DOTATATE images. Our study demonstrated that the images obtained by {sup 68}Ga-DOTATATE and {sup 68}Ga

  15. Interventions in 131I-MIBG treatment of neuroendocrine tumours

    International Nuclear Information System (INIS)

    Full text: Specific targeting of neuroendocrine tumours for therapy may be achieved either via the metabolic route (MIBG), via receptor binding (peptides) or via the immunological route (antibodies). Any malignant neural crest tumour, showing sufficient uptake and retention of 131I-meta-odobenzylguanidine (MIBG) on a diagnostic tracer study is a candidate for therapy using this agent. The principle indications for 131I-MIBG therapy are malignant pheochromocytoma and paraganglioma, neuroblastoma stage III and IV, medullary thyroid carcinoma and symptomatic, metastatic carcinoid tumors. At an EANM Radionuclide Therapy Committee workshop on 131IMIBG therapy in 1999 the results of treatment in 534 patients with neural crest tumours were gathered, showing cumulative objective response rates of 51% for malignant pheochromocytoma, 48% for paraganglioma, 51% for neuroblastoma, 23% for medullary thyroid carcinoma and 8% for carcinoid tumors. Moreover, symptomatic palliation occurred in more than 60% of the patients. These results compare favorably with the best reported results of combination chemotherapy. An active uptake-1 mechanism at the cell membrane and neurosecretory storage granules in the cytoplasm of neural crest tumours are responsible for the uptake and retention of 131I-MIBG, respectively, resulting in high tumour/nontumour ratio's. Many drugs are known or may be expected to interfere with (i.e. have a negatively effect on) the uptake and/or retention of 131I-MIBG by the tumour cell. In contrast, there are also factors which may influence either the uptake/retention of 131I-MIBG or the results of therapy in a positive way. Possible interventions: 1. Use of other labels, for example 125I-MIBG, 211At-MABG and 76Br-MBBG, which, in view of their ultrashort pathway, may have a role in the treatment of micrometastases and bone marrow infiltration, particularly as the results of 131I-MIBG therapy under these circumstances are poor. 2. By increasing the specific

  16. Role of 18F - DOPA PET/CT in evaluation of patients with neuroendocrine tumors (NETs)

    International Nuclear Information System (INIS)

    Full text: NETs are heterogeneous group of tumors which take up amino acids, transform them into biogenic amines and store the amines in vesicles, this forms the basis of uptake of 18F-DOPA in these tumors. These tumors can be small and situated almost throughout the body and may also present as advanced disease with multiple metastatic sites. Like in management of any other tumor it is imperative to stage the status of disease in NETs for the effective management of these patients and 18F-DOPA PET/CT is one such imaging modality used in the evaluation of neuroendocrine tumors (NETs). Here is our initial experience using 18F-DOPA PET/CT imaging in these patients. Twenty-seven patients with NETs (carcinoids, medullary thyroid carcinomas, phaeochromocytomas Insulinoma) were prospectively enrolled and scheduled for 18F-DOPA PET/CT. Wherever possible, tissue diagnosis was attempted. Results obtained were compared with other conventional diagnostic procedures (mainly 18F-FDG PET/CT, and 68Ga-DOTANOC PET/CT, and with ultrasound, CT, etc) and with follow-up. 18F-DOPA PET/CT identified 17/24 positive cases in either the primary/metastatic/recurrent tumor. In case of Insulinoma 18F-DOPA was found to be most superior than other imaging modalities in localizing the disease and staging of disease

  17. Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-Related Outcomes With or Without Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Zagar, Timothy M. [Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC (United States); White, Rebekah R. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Tyler, Douglas S. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Papavassiliou, Paulie [Department of Pathology, Duke University Medical Center, Durham, NC (United States); Papalezova, Katia T. [Department of Surgery, Duke University Medical Center, Durham, NC (United States); Guy, Cynthia D. [Department of Pathology, Duke University Medical Center, Durham, NC (United States); Broadwater, Gloria [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC (United States); Clough, Robert W. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States); Czito, Brian G., E-mail: czito001@mc.duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

    2012-07-15

    Purpose: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. Methods: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. Results: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). Conclusions: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

  18. Resected Pancreatic Neuroendocrine Tumors: Patterns of Failure and Disease-Related Outcomes With or Without Radiotherapy

    International Nuclear Information System (INIS)

    Purpose: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic disease. Little is known regarding the use of radiotherapy in the prevention of local recurrence after resection. To better define the role of radiotherapy, we performed an analysis of resected patients at our institution. Methods: Between 1994 and 2009, 33 patients with NET of the pancreatic head and neck underwent treatment with curative intent at Duke University Medical Center. Sixteen patients were treated with surgical resection alone while an additional 17 underwent resection with adjuvant or neoadjuvant radiation therapy, usually with concurrent fluoropyrimidine-based chemotherapy (CMT). Median radiation dose was 50.4 Gy and median follow-up 28 months. Results: Thirteen patients (39%) experienced treatment failure. Eleven of the initial failures were distant, one was local only and one was local and distant. Two-year overall survival was 77% for all patients. Two-year local control for all patients was 87%: 85% for the CMT group and 90% for the surgery alone group (p = 0.38). Two-year distant metastasis-free survival was 56% for all patients: 46% and 69% for the CMT and surgery patients, respectively (p = 0.10). Conclusions: The primary mode of failure is distant which often results in mortality, with local failure occurring much less commonly. The role of radiotherapy in the adjuvant management of NET remains unclear.

  19. Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Cives, M; Ghayouri, M; Morse, B; Brelsford, M; Black, M; Rizzo, A; Meeker, A; Strosberg, J

    2016-09-01

    The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O(6)-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n=52), grade (n=128) and ALT activation (n=46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time. PMID:27552969

  20. Identification of tumorigenic cells and therapeutic targets in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Krampitz, Geoffrey Wayne; George, Benson M; Willingham, Stephen B; Volkmer, Jens-Peter; Weiskopf, Kipp; Jahchan, Nadine; Newman, Aaron M; Sahoo, Debashis; Zemek, Allison J; Yanovsky, Rebecca L; Nguyen, Julia K; Schnorr, Peter J; Mazur, Pawel K; Sage, Julien; Longacre, Teri A; Visser, Brendan C; Poultsides, George A; Norton, Jeffrey A; Weissman, Irving L

    2016-04-19

    Pancreatic neuroendocrine tumors (PanNETs) are a type of pancreatic cancer with limited therapeutic options. Consequently, most patients with advanced disease die from tumor progression. Current evidence indicates that a subset of cancer cells is responsible for tumor development, metastasis, and recurrence, and targeting these tumor-initiating cells is necessary to eradicate tumors. However, tumor-initiating cells and the biological processes that promote pathogenesis remain largely uncharacterized in PanNETs. Here we profile primary and metastatic tumors from an index patient and demonstrate that MET proto-oncogene activation is important for tumor growth in PanNET xenograft models. We identify a highly tumorigenic cell population within several independent surgically acquired PanNETs characterized by increased cell-surface protein CD90 expression and aldehyde dehydrogenase A1 (ALDHA1) activity, and provide in vitro and in vivo evidence for their stem-like properties. We performed proteomic profiling of 332 antigens in two cell lines and four primary tumors, and showed that CD47, a cell-surface protein that acts as a "don't eat me" signal co-opted by cancers to evade innate immune surveillance, is ubiquitously expressed. Moreover, CD47 coexpresses with MET and is enriched in CD90(hi)cells. Furthermore, blocking CD47 signaling promotes engulfment of tumor cells by macrophages in vitro and inhibits xenograft tumor growth, prevents metastases, and prolongs survival in vivo. PMID:27035983

  1. The future of nuclear medicine imaging of neuroendocrine tumors: on a clear day one might see forever..

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Yale School of Medicine, Department of Gastroenterological Surgery, New Haven, CT (United States); Kidd, Mark; Modlin, Irvin M. [Yale School of Medicine, Department of Gastroenterological Surgery, New Haven, CT (United States); Prasad, Vikas [Charite University Hospital, Department of Nuclear Medicine, Campus Virchow-Klinikum, Berlin (Germany); Baum, Richard P. [Zentralklinik Bad Berka, THERANOSTICS Center for Molecular Radiotherapy and Molecular Imaging (PET/CT), ENETS Center of Excellence, Bad Berka (Germany); Drozdov, Ignat [Bering Limited, Richmond (United Kingdom)

    2014-12-15

    Early identification of neuroendocrine tumors (NETs) is a critical prerequisite to establishing effective treatment. While substantial advances have occurred in the last two decades, there is little progress regarding the identification of small subcentimeter lesions and the determination of tumor proliferative rates and metabolic characteristics. At this time, delineation of lesions mainly utilizes various combinations of somatostatin receptor (SSR) density, glucose metabolism and Hounsfield units. This editorial addresses unmet needs in nuclear medicine (molecular) imaging with a view to identifying areas that require amplification. The principal goal is to amplify and extend the diagnostic and prognostic role of imaging. Specific focus is required to validate and standardize current techniques while introducing strategies that will resolve currently unmet needs.

  2. Long-term results of PRRT in advanced bronchopulmonary carcinoid

    Energy Technology Data Exchange (ETDEWEB)

    Mariniello, Annapaola; Bodei, Lisa; Baio, Silvia Melania; Gilardi, Laura; Colandrea, Marzia; Papi, Stefano; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Tinelli, Carmine [IRCCS Foundation Policlinico San Matteo, Epidemiology and Biometric Unit, Pavia (Italy); Valmadre, Giuseppe [Presidio Ospedaliero E. Morelli AOVV, Sondalo (Italy); Fazio, Nicola [European Institute of Oncology, Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, Milan (Italy); Galetta, Domenico [European Institute of Oncology, Thoracic Surgery Division, Milan (Italy); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy)

    2016-03-15

    Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ({sup 90}Y-DOTATOC vs. {sup 177}Lu-DOTATATE vs. {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE) were compared with regard to their efficacy and tolerability. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The {sup 177}Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with {sup 90}Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. In a large cohort of patients with advanced BPC treated in a ''real-world'' scenario and followed up for a median of 45.1 months (range 2 - 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite

  3. Radiofrequency ablation for neuroendocrine liver metastases: a systematic review.

    Science.gov (United States)

    Mohan, Helen; Nicholson, Patrick; Winter, Des C; O'Shea, Donal; O'Toole, Dermot; Geoghegan, Justin; Maguire, Donal; Hoti, Emir; Traynor, Oscar; Cantwell, Colin P

    2015-07-01

    To determine the efficacy of radiofrequency (RF) ablation in neuroendocrine tumor (NET) liver metastases. A systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eight studies were included (N = 301). Twenty-six percent of RF ablation procedures were percutaneous (n = 156), with the remainder conducted at surgery. Forty-eight percent of patients had a concomitant liver resection. Fifty-four percent of patients presented with symptoms, with 92% reporting symptom improvement following RF ablation (alone or in combination with surgery). The median duration of symptom improvement was 14-27 months. However, recurrence was common (63%-87%). RF ablation can provide symptomatic relief in NET liver metastases alone or in combination with surgery. PMID:25840836

  4. The role of Cdk5 in neuroendocrine thyroid cancer.

    Science.gov (United States)

    Pozo, Karine; Castro-Rivera, Emely; Tan, Chunfeng; Plattner, Florian; Schwach, Gert; Siegl, Veronika; Meyer, Douglas; Guo, Ailan; Gundara, Justin; Mettlach, Gabriel; Richer, Edmond; Guevara, Jonathan A; Ning, Li; Gupta, Anjali; Hao, Guiyang; Tsai, Li-Huei; Sun, Xiankai; Antich, Pietro; Sidhu, Stanley; Robinson, Bruce G; Chen, Herbert; Nwariaku, Fiemu E; Pfragner, Roswitha; Richardson, James A; Bibb, James A

    2013-10-14

    Medullary thyroid carcinoma (MTC) is a neuroendocrine cancer that originates from calcitonin-secreting parafollicular cells, or C cells. We found that Cdk5 and its cofactors p35 and p25 are highly expressed in human MTC and that Cdk5 activity promotes MTC proliferation. A conditional MTC mouse model was generated and corroborated the role of aberrant Cdk5 activation in MTC. C cell-specific overexpression of p25 caused rapid C cell hyperplasia leading to lethal MTC, which was arrested by repressing p25 overexpression. A comparative phosphoproteomic screen between proliferating and arrested MTC identified the retinoblastoma protein (Rb) as a crucial Cdk5 downstream target. Prevention of Rb phosphorylation at Ser807/Ser811 attenuated MTC proliferation. These findings implicate Cdk5 signaling via Rb as critical to MTC tumorigenesis and progression. PMID:24135281

  5. Pancreatic neuroendocrine tumor accompanied with multiple liver metastases

    Institute of Scientific and Technical Information of China (English)

    Tomohide; Hori; Kyoichi; Takaori; Shinji; Uemoto

    2014-01-01

    Pancreatic neuroendocrine tumor(P-NET) is rare and slow-growing. Current classifications predict its progno-sis and postoperative recurrence. Curative resection is ideal, although often difficult, because over 80% of pa-tients have unresectable multiple liver metastases and extrahepatic metastasis. Aggressive surgery for liver metastases is important to improve survival. Aggressive or cytoreductive surgery for liver metastases is indi-cated to reduce hormone levels and improve symptoms and prognosis. Liver transplantation was originally con-ceived as an ideal therapy for unresectable liver metas-tases. Unfortunately, there is no clear consensus on the role and timing of surgery for primary tumor and liver metastases. Surgeons still face questions in deciding the best surgical scenario in patients with P-NET with unresectable liver metastases.

  6. An unusual presentation of "silent" disseminated pancreatic neuroendocrine tumor

    Institute of Scientific and Technical Information of China (English)

    Dragomir Marisavljevic; Natasa Petrovic; Nikola Milinic; Vesna Cemerikic; Miodrag Krstic; Olivera Markovic; Dragoljub Bilanovic

    2004-01-01

    To present a patient diagnosed with pancreatic carcinoid that was extremely rare and produced an atypical carcinoid syndrome.We reported a 58-year old male patient who presented with long standing,prominent cervical lymphadenopathy and occasional watery diarrhea.Pathohistological and immunohistochemical examination of lymph node biopsy showed a metastatic neuroendocrine tumor,which was histological type A of carcinoid (EMA+,cytokeratin+,CEA-,NSE+,chromogranin A+,synaptophysin+,insulin-).Bone marrow biopsy showed identical findings.Primary site of the tumor was pancreas and diagnosis was made according to cytological and immunocytochemical analysis of the tumor cells obtained with aspiration biopsy of pancreatic mass (12 mm in diameter) under endoscopic ultrasound guidance.However,serotonin levels in blood and urine samples were normal.It is difficulty to establish the precise diagnosis of a "functionally inactive" pancreatic carcinoid and aspiration biopsy of pancreatic tumor under endoscopic ultrasound guidance can be used as a new potent diagnostic tool.

  7. Circadian neuroendocrine physiology and electromagnetic field studies: Precautions and complexities

    Energy Technology Data Exchange (ETDEWEB)

    Warman, G.R.; Tripp, H.M.; Harman, V.L.; Arendt, J

    2003-07-01

    The suppression of melatonin by exposure to low frequency electromagnetic fields (EMFs) 'the melatonin hypothesis' has been invoked as a possible mechanism through which exposure to these fields may result in an increased incidence of cancer. While the effect of light on melatonin is well established, data showing a similar effect due to EMF exposure are sparse and, where present, are often poorly controlled. The current review focuses on the complexities associated with using melatonin as a marker and the dynamic nature of normal melatonin regulation by the circadian neuroendocrine axis. These are issues which the authors believe contribute significantly to the lack of consistency of results in the current literature. Recommendations on protocol design are also made which, if followed, should enable researchers to eliminate or control for many of the confounding factors associated with melatonin being an output from the circadian clock. (author)

  8. [Neuroendocrine dysfunction and brain damage. A consensus statement].

    Science.gov (United States)

    Leal-Cerro, Alfonso; Rincón, María Dolores; Domingo, Manel Puig

    2009-01-01

    This consensus statement aims to enhance awareness of the incidence and risks of hypopituitarism in patients with traumatic brain injury (TBI) and/or brain hemorrhages among physicians treating patients with brain damage. The importance of this problem is related not only to the frequency of TBI but also to its prevalence in younger populations. The consequences of TBI are characterized by a series of symptoms that depend on the type of sequels related to neuroendocrine dysfunction. The signs and symptoms of hypopituitarism are often confused with those of other sequels of TBI. Consequently, patients with posttraumatic hypopituitarism may receive suboptimal rehabilitation unless the underlying hormone deficiency is identified and treated. This consensus is based on the recommendation supported by expert opinion that patients with a TBI and/or brain hemorrhage should undergo endocrine evaluation in order to assess pituitary function and, if deficiency is detected, should receive hormone replacement therapy.

  9. Neonatal testosterone suppresses a neuroendocrine pulse generator required for reproduction

    Science.gov (United States)

    Israel, Jean-Marc; Cabelguen, Jean-Marie; Le Masson, Gwendal; Oliet, Stéphane H.; Ciofi, Philippe

    2014-02-01

    The pituitary gland releases hormones in a pulsatile fashion guaranteeing signalling efficiency. The determinants of pulsatility are poorly circumscribed. Here we show in magnocellular hypothalamo-neurohypophyseal oxytocin (OT) neurons that the bursting activity underlying the neurohormonal pulses necessary for parturition and the milk-ejection reflex is entirely driven by a female-specific central pattern generator (CPG). Surprisingly, this CPG is active in both male and female neonates, but is inactivated in males after the first week of life. CPG activity can be restored in males by orchidectomy or silenced in females by exogenous testosterone. This steroid effect is aromatase and caspase dependent, and is mediated via oestrogen receptor-α. This indicates the apoptosis of the CPG network during hypothalamic sexual differentiation, explaining why OT neurons do not burst in adult males. This supports the view that stereotypic neuroendocrine pulsatility is governed by CPGs, some of which are subjected to gender-specific perinatal programming.

  10. Somatostatin receptor imaging of neuroendocrine tumors with indium-111 pentetreotide (Octreoscan).

    Science.gov (United States)

    Olsen, J O; Pozderac, R V; Hinkle, G; Hill, T; O'Dorisio, T M; Schirmer, W J; Ellison, E C; O'Dorisio, M S

    1995-07-01

    Somatostatin, a naturally occurring 14-amino acid peptide, can be thought of as an anti-growth hormone and functional down-regulator of sensitive tissue. Most neuroendocrine tumors seem to possess somatostatin receptors in sufficient abundance to allow successful scintigraphic imaging with radiolabeled somatostatin congeners. Several of these, including Indium-III-DTPA Pentetreotide (Octreoscan [Mallinckrodt Medical, St. Louis, MO]), which was approved for clinical use by the Food and Drug Administration in June 1994, have been of considerable value in scintigraphically identifying various neuroendocrine tumors. The Octreoscan compares favorably with other imaging modalities. The success of somatostatin receptor imaging in evaluating patients with suspected neuroendocrine tumors, including identifying otherwise radiographically occult lesions, has resulted in ranking somatostatin receptor imaging as the prime imaging procedure in patients with suspected neuroendocrine tumors at The Ohio State University. PMID:7570044

  11. SPECT/CT in neuroendocrine cancers; SPECT/CT bei neuroendokrinen Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Miederer, M. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Mainz Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Castrop, C.; Scheidhauer, K. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik und Poliklinik; Buck, A.K. [Universitaetsklinikum Wuerzburg (Germany). Nuklearmedizinische Klinik und Poliklinik

    2011-03-15

    The accuracy of functional SPECT imaging has been significantly improved by addition of CT. This is especially relevant for functional imaging of neuroendocrine tumors using highly specific radiopharmaceuticals. Parathyroid adenomas can be detected by {sup 99m}Tc-MIBI SPECT/CT with very high sensitivity and specificity, playing an important role especially when minimally invasive techniques are used for surgical resection. With SPECT/CT, extra-adrenal manifestations of pheochromocytomas and tumors of the adrenal cortex can be detected with high accuracy. Because of the availability of PET radiopharmaceuticals such as {sup 68}Ga-DOTATOC, the clinical relevance of {sup 111}In-Octreotide SPECT for detection of neuroendocrine cancers has been recently reduced. Because of the better availability, SPECT and SPECT/CT still represent standard tools for imaging neuroendocrine cancers. SPECT/CT represents the superior imaging modality for monitoring radiopeptide based therapies, which are now increasingly used for treatment of neuroendocrine cancers. (orig.)

  12. Stress and the neuroendocrine system: the role of exercise as a stressor and modifier of stress

    OpenAIRE

    Hackney, Anthony C

    2006-01-01

    In this article, the physiological impact of one form of stress – physical exercise – on the neuroendocrine system will be discussed. The specific intent of the review is to present an overview of stress endocrinology, the conceptual models associated with this area of study, and a discourse on the dual role of exercise as both a stressor and a modifier of stress within the neuroendocrine system. These points are addressed with respect to the current research literature dealing with exercise ...

  13. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    OpenAIRE

    Surlin Valeriu; Ramboiu Sandu; Ghilusi Mirela; Plesea Iancu

    2012-01-01

    Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic) is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performe...

  14. Opponent recognition and social status differentiate rapid neuroendocrine responses to social challenge

    OpenAIRE

    Ling, Travis J.; Summers, Cliff H.; Renner, Kenneth J.; Watt, Michael J.

    2010-01-01

    Individual social status discriminates rapid neuroendocrine responses to non-social stress in male Anolis carolinensis, but whether such status-influenced reactions are retained in response to subsequent social stress is unknown. Dominant and subordinate males modify their behavioral responses to social challenge according to familiarity of the opponent, suggesting that accompanying neuroendocrine responses may differ according to opponent recognition despite social rank. We examined endocrin...

  15. Toppling high-grade pulmonary neuroendocrine tumors with a DLL3-targeted trojan horse.

    Science.gov (United States)

    Dylla, Scott J

    2016-03-01

    Delta-like protein 3 (DLL3) is a novel and tractable tumor-initiating cell-associated target for the antibody-drug conjugate SC16LD6.5 in high-grade pulmonary neuroendocrine tumors. Elevated expression of DLL3, an inhibitor of Notch pathway activation, marks the second recent observation that impairment of Notch receptor signaling may play a critical role in neuroendocrine tumorigenesis. PMID:27308627

  16. Basaloid squamous carcinoma of the supraglottic larynx with neuro-endocrine features

    Directory of Open Access Journals (Sweden)

    Rajjyoti Das

    2015-01-01

    Full Text Available Basaloid squamous carcinoma (BSC is a rare aggressive variant of squamous cell carcinoma and occurs mainly at the larynx, oropharynx and tongue of the head and neck region. Neuro-endocrine differentiation of BSC is further rare occurrence in laryngeal cancers. We report here a case of BSC of supraglottic larynx with neuro-endocrine differentiation, which was treated by radiotherapy and its response to treatment.

  17. Diffuse Neuroendocrine Hyperplasia with Obliterative Bronchiolitis and Usual Interstitial Pneumonia: An Unusual "Headcheese Pattern" with Nodules.

    Science.gov (United States)

    Pietrangeli, V; Piciucchi, S; Tomassetti, S; Ravaglia, C; Gurioli, C; Gurioli, Ch; Cavazza, A; Dubini, A; Poletti, V

    2015-12-01

    A 74-year-old non-smoker female presented to our attention with a history of dyspnea and cough. CT scan revealed multiple areas of patchy ground glass attenuation associated to a diffuse mosaic oligoemia. Scattered bilateral subcentimetric pulmonary nodules were also present. Patient underwent a surgical lung biopsy. Specimens showed features of diffuse neuroendocrine hyperplasia, microhoneycombing, fibroblast foci. A final diagnosis of diffuse neuroendocrine hyperplasia with obliterative bronchiolitis and UIP was rendered. PMID:26446675

  18. Long Term Survival Analysis of Hepatectomy for Neuroendocrine Tumour Liver Metastases

    OpenAIRE

    Tsang, SHY; Dai, WC; Chan, ACY; Lang, HHB; Yau, TCC; Chan, SC; Poon, RTP; Fan, ST; Lo, CM; Chok, KSH; Cheung, TT

    2014-01-01

    Background. Liver is the commonest site for metastasis in patients with neuroendocrine tumour (NET). A vast majority of treatment strategies including liver directed nonsurgical therapy, liver directed surgical therapy, and nonliver directed therapy have been proposed. In this study we aim to investigate the outcome of liver resection in neuroendocrine tumour liver metastases (NELM). Method. 293 patients had hepatectomy for liver metastasis in our hospital between June 1996 and December 2010....

  19. Clinical relevance of F-18 FDG PET for imaging of neuroendocrine tumors; Wertigkeit der F-18-FDG-PET bei neuroendokrinen Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Adams, S. [Klinikum der Ruhr-Univ. Bochum - Marienhospital, Herne (Germany). Klinik fuer Radiologie und Nuklearmedizin; Baum, R.P. [Zentralklinik Bad Berka (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Hoer, G. [Frankfurt Univ., Frankfurt am Main (Germany). Klinik fuer Nuklearmedizin

    2001-04-01

    Neuroendocrine tumors are characterized immunocytochemically by the expression of different peptides and biogenic amines. Hormones induce their biological action by binding to and stimulating specific membrane-associated receptors for e.g. somatostatin. The presence of somatostatin receptors (SR) has been described mainly in endocrine glands and the central nervous system. Interestingly, a large variety of human tumors, including gastroenteropancreatic (GEP) tumors and medullary thyroid carcinomas (MTC) also express a high density of SR and can be imaged with [{sup 111}In-DTPA-D-Phe{sup 1}]-pentetreotide. Cell proliferative activity is an important indicator of the growth of various malignant tumors associated with a poorer prognosis and Ki-67 expression. {sup 18}F-FDG is a marker of tumor viability, based upon the increased glycolysis that is associated with malignancy as compared with normal tissue. SR-containing neuroendocrine tumors are well-differentiated and tend to grow slowly. Furthermore, these tumors demonstrate inverse relationship between in vivo SR expression, cell proliferation (low Ki-67 expression) and FDG uptake (normal biodistribution). In comparison, less differentiated tumors, e.g. atypical carcinoids or MTC with increasing CEA levels show mitotic activity (high levels of Ki-67 immunoreactivity and increased FDG uptake) and often lack of SR. In conclusion, SR scintigraphy has been shown to localize well-differentiated neuroendocrine tumors. In contrast, PET imaging is valuable for predicting malignancy only in less differentiated tumors with incresed glucose metabolism. Therefore, an additional F-18 FDG PET should be performed if SR scintigraphy (GEP tumors) or combined imaging using [{sup 111}In-DTPA-D-Phe{sup 1}]-pentetreotide and {sup 99m}Tc(V)-DMSA (MTC) is negative. (orig.) [German] Neuroendokrine Tumoren werden durch die spezifische Produktion von Polypeptidhormonen und biogenen Aminen klassifiziert. Die Informationsuebertragung der

  20. Neuroendocrine and behavioral implications of endocrine disrupting chemicals in quail

    Science.gov (United States)

    Ottinger, M.A.; Abdelnabi, M.A.; Henry, P.; McGary, S.; Thompson, N.; Wu, J.M.

    2001-01-01

    Studies in our laboratory have focused on endocrine, neuroendocrine, and behavioral components of reproduction in the Japanese quail. These studies considered various stages in the life cycle, including embryonic development, sexual maturation, adult reproductive function, and aging. A major focus of our research has been the role of neuroendocrine systems that appear to synchronize both endocrine and behavioral responses. These studies provide the basis for our more recent research on the impact of endocrine disrupting chemicals (EDCs) on reproductive function in the Japanese quail. These endocrine active chemicals include pesticides, herbicides, industrial products, and plant phytoestrogens. Many of these chemicals appear to mimic vertebrate steroids, often by interacting with steroid receptors. However, most EDCs have relatively weak biological activity compared to native steroid hormones. Therefore, it becomes important to understand the mode and mechanism of action of classes of these chemicals and sensitive stages in the life history of various species. Precocial birds, such as the Japanese quail, are likely to be sensitive to EDC effects during embryonic development, because sexual differentiation occurs during this period. Accordingly, adult quail may be less impacted by EDC exposure. Because there are a great many data available on normal development and reproductive function in this species, the Japanese quail provides an excellent model for examining the effects of EDCs. Thus, we have begun studies using a Japanese quail model system to study the effects of EDCs on reproductive endocrine and behavioral responses. In this review, we have two goals: first, to provide a summary of reproductive development and sexual differentiation in intact Japanese quail embryos, including ontogenetic patterns in steroid hormones in the embryonic and maturing quail. Second, we discuss some recent data from experiments in our laboratory in which EDCs have been tested in

  1. OLD AND NEW NEUROENDOCRINE MOLECULES: SOMATOSTATIN, CYSTEAMINE, PANTETHINE AND KYNURENINE.

    Science.gov (United States)

    Vécsei, László; Horváth, Zoltán; Tuka, Bernadett

    2014-03-30

    The aim of this review is to commemorate Hans Selye, endocrinologist, the most famous researchers of stress and to briefly summarize the major features of somatostatin (SST), cysteamine (CysA) and patethine (PAN) in neuroendocrinological aspect, which are closely related to his scientific work. In addition, some metabolites of kynurenine pathway (KP) were also mentioned in this paper, as new, possible target molecules in neuroendocrinology. R. Guillemin and A. V. Schally were the main pioneers of the discovery of SST in the 1970's. SST primarily is known as an inhibitor of growth hormone secretion and additionally reduces the gastric acid and pepsin release and also the gastroduodenal mucosal blood flow. These effects are very important in the pathophysiology of peptic ulcer bleeding, which is related to the CysA-evoked perforating duodenal ulcer experimental stress model in rats developed by Selye and Szabo. CysA is a naturally occurring duodenal ulcerogen, which depletes SST in the gastric mucosa and certain brain regions. Furthermore, in addition to depleting SST, CysA also causes adrenocortical necrosis, suggesting an interaction between the central/peripheral nervous system and the neuroendocrine system. The antioxidant PAN, formulated besides the CysA, has similar effects: it attenuates the levels of SST and prolactin in the cerebral cortex and hypothalamus through the accumulation of CysA within cells throughout the body. As new perspectives the KP may be involved in the modulation of neuroendrocrine processes: different agonists and antagonists of glutamate receptors regulate the hypothalamic-pituitary-adrenal axis and kynurenic acid augments the anxiolytic stress responses in neonatal chicks. The pro-inflammatory cytokine-induced and the toxic heavy oil contaminations-evoked alterations in the KP indirectly contribute to the development of neuroendocrine disorders. In summary, there have been highly important developments in neuroendocrinology since the

  2. Intracerebroventricular leptin injection affects neuroendocrine reproductive axis in ovariectomized rats

    Institute of Scientific and Technical Information of China (English)

    Yuebing Qiao; Huixian Cui

    2008-01-01

    BACKGROUND: Leptin regulates neuroendocrine function of the hypothalamus-pituitary-ovary axis in humans.OBJECTIVE: To verify effects of intracerebroventricular leptin injection on neuroendocrine function of the hypothalamus-pituitary-ovary axis in nvariectomized rats.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed at the Basic Medical Institute, Chengde Medical College between June and October 2007.MATERIALS: Thirty healthy, female, Wistar rats were included in this study. The following compounds were used: leptin; gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) enzyme-linked immunosorbent assay kits.METHODS: Rats were randomly divided into 3 groups at 1, 2, and 4 hours after injection. Each group was subdivided into control and experimental groups (n = 5 animals per group and time point). All rats were subjected to bilateral ovariectomy and, beginning on day 7 after surgery, animals received daily subcutaneous injections of estradiol benzoate (2 μ g) for 7 consecutive days. The experimental groups were injected with 5 μ L leptin (1 g/L) into the lateral cerebral ventricle, and control groups received an equal volume of physiological saline.MAIN OUTCOME MEASURES: GnRH and LH secretion were examined 1, 2, and 4 hours after injection using GnRH and LH ELISA kits, respectively.RESULTS: In the experimental groups, GnRH secretion significantly increased (P < 0.01), followed by LH secretion (P < 0.01), compared with the control groups. GnRH secretion significantly increased l hour after leptin injection (P < 0.01). The LH increase was less pronounced, but still significant (P < 0.01); however,the most prominent LH increase occurred between 1 and 2 hours. Both GnRH and LH secretion reached peak levels at 2 hours after leptin injection. Thereafter, both GnRH and LH secretion decreased, but still maintained very high levels, compared with the control group (P < 0.01).CONCLUSION: lntracerebroventricular leptin injection

  3. Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues

    International Nuclear Information System (INIS)

    Peptide receptor scintigraphy with the radioactive somatostatin-analogue (111In-DTPA0)octreotide (DTPA=diethylenetriaminepentaacetic acid) is a sensitive and specific technique to show in vivo the presence and abundance of somatostatin receptors on various tumors. With this technique primary tumors and metastases of neuroendocrine cancers as well as of many other cancer types can be localised. A new application is the use of peptide receptor radionuclide therapy, administrating high doses of 111In- or 90Y-labeled octreotide-analogues. In the preclinical situation it was investigated on the radiotherapeutic effect of 90Y-and 111In-labeled (DOTA0, Tyr3)octreotide (DOTA=tetraazacyclododecanetetraacetic acid) or 111In-DTPA0)octreotide in Lewis rats bearing the somatostatin receptor-positive rat pancreatic tumor CA20948 in A) the flank of B) in the liver. Thirty end-stage patients with mostly neuroendocrine progressing tumors were treated with (111In-DTPA0)octreotide, up to a maximal cumulative patient dose of about 74 GBq, in a phase 1 trial. A) Flank model: at least two 111MBq injections of (111In-DOTA0, Tyr3) octreotide were needed to reach tumor response, in 40% of the animals complete tumor remission was found after a follow-up period of 10 months. One or two injections of (90Y-DOTA0, Tyr3) octreotide yielded transient stable disease. B) Liver model: it was found that peptide receptor radionuclide therapy is only effective if somatostatin receptors are present on the tumors, and is therefore receptor-mediated. High radioactive doses of 370 MBq (111In-DTPA0)octreotide or 93 MBq (90Y-DOTA0, Tyr3)octreotide can inhibit the growth of somatostatin receptor-positive metastases. There were no major clinical side effects after up to 2 years treatment, except that a transient decline in platelet counts and lymphocyte subsets can occur. Promising beneficial effects on clinical symptoms, hormone production and tumor proliferation were found. Of the 21 patients with

  4. Actions of Bisphenol A and Bisphenol S on the Reproductive Neuroendocrine System During Early Development in Zebrafish.

    Science.gov (United States)

    Qiu, Wenhui; Zhao, Yali; Yang, Ming; Farajzadeh, Matthew; Pan, Chenyuan; Wayne, Nancy L

    2016-02-01

    Bisphenol A (BPA) is a well-known environmental, endocrine-disrupting chemical, and bisphenol S (BPS) has been considered a safer alternative for BPA-free products. The present study aims to evaluate the impact of BPA and BPS on the reproductive neuroendocrine system during zebrafish embryonic and larval development and to explore potential mechanisms of action associated with estrogen receptor (ER), thyroid hormone receptor (THR), and enzyme aromatase (AROM) pathways. Environmentally relevant, low levels of BPA exposure during development led to advanced hatching time, increased numbers of GnRH3 neurons in both terminal nerve and hypothalamus, increased expression of reproduction-related genes (kiss1, kiss1r, gnrh3, lhβ, fshβ, and erα), and a marker for synaptic transmission (sv2). Low levels of BPS exposure led to similar effects: increased numbers of hypothalamic GnRH3 neurons and increased expression of kiss1, gnrh3, and erα. Antagonists of ER, THRs, and AROM blocked many of the effects of BPA and BPS on reproduction-related gene expression, providing evidence that those three pathways mediate the actions of BPA and BPS on the reproductive neuroendocrine system. This study demonstrates that alternatives to BPA used in the manufacture of BPA-free products are not necessarily safer. Furthermore, this is the first study to describe the impact of low-level BPA and BPS exposure on the Kiss/Kiss receptor system during development. It is also the first report of multiple cellular pathways (ERα, THRs, and AROM) mediating the effects of BPA and BPS during embryonic development in any species.

  5. Future Directions in the Treatment of Neuroendocrine Tumors : Consensus Report of the National Cancer Institute Neuroendocrine Tumor Clinical Trials Planning Meeting

    NARCIS (Netherlands)

    Kulke, Matthew H.; Siu, Lillian L.; Tepper, Joel E.; Fisher, George; Jaffe, Deborah; Haller, Daniel G.; Ellis, Lee M.; Benedetti, Jacqueline K.; Bergsland, Emily K.; Hobday, Timothy J.; Van Cutsem, Eric; Pingpank, James; Oberg, Kjell; Cohen, Steven J.; Posner, Mitchell C.; Yao, James C.

    2011-01-01

    Neuroendocrine tumors (NETs) arise from a variety of anatomic sites and share the capacity for production of hormones and vasoactive peptides. Because of their perceived rarity, NETs have not historically been a focus of rigorous clinical research. However, the diagnosed incidence of NETs has been i

  6. Peptide receptor radionuclide therapy with Y-90-Dotatoc (somatostatin analog) in neuroendocrine tumours: The Chilean experience

    International Nuclear Information System (INIS)

    done in minicolumns Sep-Pak C18 previously to the patient injections. Radiochemical control showed a labeling efficiency of the radiopharmaceutical higher than 99%. In 16 patients with more than one cycle there has been complete remission of the tumor activity in 1, significant partial remission in 10, partial remission in 3 with further relapse and progression in 2. The treatment was well tolerated in all the patients except in one in whom by causes not yet determined the 'in vivo' biodistribution of DOTATOC was altered showing mainly bone marrow uptake (non-tumor) of 90Y presenting a severe but reversible hematological toxicity. This patient was considered non-treated since there was no selective tumor irradiation. The other patients showed mild reversible hematological toxicity. In a 36 y.o. female patient suffering a progressing pancreatic NT with multiple metastasis and severe bone marrow involvement presenting partial response and further relapse, a high rescue dose of 240 mCi was administered following a successful autologous stem cells transplantation. The patient is now asymptomatic with significant partial response. These preliminary data indicate that the treatment with 90Y-DOTATOC, now available in Chile, is a valuable therapeutic option for these type tumors that frequently do not respond to conventional treatments like chemotherapy or external radiotherapy. Peptide receptor therapy should be considered as first line treatment in well-differentiated NT. (author)

  7. Primary infertility associated with neuroendocrine tumor (Carcinoid) of the appendix

    Institute of Scientific and Technical Information of China (English)

    Brad B Swelstad; Paul R Brezina; Clark T Johnson; Nina Resetkova; Irene Woo; Lisa Kolp

    2012-01-01

    Neuroendocrine tumors of the appendix(NET-A), formerly called appendiceal carcinoids, are rare tumors of the gastrointestinal tract.Appendiceal tumors have also been associated with infertility. However, in many of these cases, significant abdominal pathology, specifically pseudomyxoma peritonei, was identified during definitive surgical intervention.A34-year-old nulligravid woman undergoing infertility evaluation presented to an academic tertiary care fertility center. An abnormal mass was identified on hysterosalpingogram andCT confirmed appendiceal mass. Surgical removal of the mass was performed and histopathology was consistent with anNET-A with negative margins extending to the serosa.Two months after surgical intervention, the patient spontaneously conceived pregnancy and subsequently delivered a normal infant.This case exemplifies the importance of careful inspection of radiologic films by the gynecologic physician. Of added interest, this case describes an asymptomaticNET-A associated with primary infertility. To our knowledge, this is the first report of an incidentally indentifiedNET-A that resulted in primary infertility.

  8. Pancreatic neuroendocrine tumours: correlation between MSCT features and pathological classification

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Yanji; Dong, Zhi; Li, Zi-Ping; Feng, Shi-Ting [The First Affiliated Hospital, Sun Yat-Sen University, Department of Radiology, Guangzhou, Guangdong (China); Chen, Jie [The First Affiliated Hospital, Sun Yat-Sen University, Department of Gastroenterology, Guangzhou, Guangdong (China); Chan, Tao; Chen, Minhu [Union Hospital, Hong Kong, Medical Imaging Department, Shatin, N.T. (China); Lin, Yuan [The First Affiliated Hospital, Sun Yat-Sen University, Department of Pathology, Guangzhou, Guangdong (China)

    2014-11-15

    We aimed to evaluate the multi-slice computed tomography (MSCT) features of pancreatic neuroendocrine neoplasms (P-NENs) and analyse the correlation between the MSCT features and pathological classification of P-NENs. Forty-one patients, preoperatively investigated by MSCT and subsequently operated on with a histological diagnosis of P-NENs, were included. Various MSCT features of the primary tumour, lymph node, and distant metastasis were analysed. The relationship between MSCT features and pathologic classification of P-NENs was analysed with univariate and multivariate models. Contrast-enhanced images showed significant differences among the three grades of tumours in the absolute enhancement (P = 0.013) and relative enhancement (P = 0.025) at the arterial phase. Univariate analysis revealed statistically significant differences among the tumours of different grades (based on World Health Organization [WHO] 2010 classification) in tumour size (P = 0.001), tumour contour (P < 0.001), cystic necrosis (P = 0.001), tumour boundary (P = 0.003), dilatation of the main pancreatic duct (P = 0.001), peripancreatic tissue or vascular invasion (P < 0.001), lymphadenopathy (P = 0.011), and distant metastasis (P = 0.012). Multivariate analysis suggested that only peripancreatic tissue or vascular invasion (HR 3.934, 95 % CI, 0.426-7.442, P = 0.028) was significantly associated with WHO 2010 pathological classification. MSCT is helpful in evaluating the pathological classification of P-NENs. (orig.)

  9. Occupational doses in neuroendocrine tumors by using 177Lu DOTATATE

    International Nuclear Information System (INIS)

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of 177Lu DOTATATE radiopharmaceutical which is a type of treatment presently used in the experimental form in Brazil and, therefore, not contemplated in norms or specific use. This research studied the occupational doses of this treatment and suggested guidelines or rules of procedures viewing the radiological protection of workers involved and the public. The treatment were followed up by using two types of radiation detection, one a scintillator and a Geiger-Muller, and the measurements were performed in a public hospital at Rio de Janeiro and the other in a private hospital at Sao Paulo. It was observed that the equivalent occupational doses can variate from 160 μSv to 450 μSv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 μSv/h

  10. Synchronous collision neuroendocrine tumor and rectal adenocarcinoma: a case report.

    Science.gov (United States)

    Zhu, Jie-Gao; Zhang, Zhong-Tao; Wu, Guo-Cong; Han, Wei; Wang, Kang-Li

    2015-04-01

    Collision tumors are thought to arise from the accidental meeting of two independent tumors. Adenocarcinoma is the most common malignant rectal tumor, while neuroendocrine tumor (NET) is relatively rare. Due to the endoscopy and reporting, the overall incidence of NETs was increasing recently but still less than 1 per 100,000. This means that a combination of an adenocarcinoma and NET is a very rare finding and an actual collision of these tumors even more so. We report here a highly unusual case of a 64-year-old woman who had collision tumors composed of a primary rectal adenocarcinoma and NET showing a "side by side" pattern. Resection margins are free of both the tumors. The postoperative course was uneventful. The patient underwent a protocol CT scan at 3 months after surgery, which did not show any recurrence. Both the malignant adenocarcinoma and the NET would make a great influence in the rest lifetime and a follow up will be continued, although the CT did not show any recurrence until now. To the best of our knowledge, this is the first reported case of such an occurrence. PMID:25972691

  11. Hepatic arterial embolization in patients with neuroendocrine tumors

    Science.gov (United States)

    2014-01-01

    Liver metastases occur in 46-93% of patients with neuroendocrine neoplasms (NENs). Presence and extension of liver metastases are considered important prognostic factors, as they may significantly impair the patient’s quality of life, because of either tumor bulk or hormonal hypersecretion. Therapies for NEN liver metastases include surgical resection, liver transplantation, chemotherapy and biotherapy. Surgery is the gold standard for curative therapy, but in most of NEN patients with liver metastases, when surgery can not be applied, minimally invasive therapeutic approaches are adopted. They include trans-arterial embolization (TAE), trans-arterial chemoembolization (TACE), radiofrequency thermal ablation and new emerging techniques. TAE is based on selective infusion of particles in the branch of the hepatic artery supplying the tumor lesions. The goal of TAE is to occlude tumor blood vessels resulting in ischemia and necrosis. Many reports have shown that TAE can reduce tumor size and hormone output, resulting in palliation of symptoms without the use of cytotoxic drugs, resulting in better tolerability. This review will focus on TAE performance and safety in NEN patients with liver metastases. PMID:24887262

  12. Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones

    NARCIS (Netherlands)

    F.R.E. Nobels (Frank); D.J. Kwekkeboom (Dirk Jan); W. Coopmans; C.H.H. Schoenmakers (Christian); J. Lindemans (Jan); E.P. Krenning (Eric); R. Bouillon; S.W.J. Lamberts (Steven); W.W. de Herder (Wouter)

    1997-01-01

    textabstractChromogranin A (CgA) is gaining acceptance as a serum marker of neuroendocrine tumors. Its specificity in differentiating between neuroendocrine and nonneuroendocrine tumors, its sensitivity to detect small tumors, and its clinical value, compared with other neuroendocr

  13. Report on Infiltrating Well-differentiated Squamous Carcinoma in a Siberian Tiger%东北虎上腭发生浸润性高中分化鳞癌的报告

    Institute of Scientific and Technical Information of China (English)

    马再玉; 马君; 罗林丰

    2009-01-01

    东北虎上颚浸润性高中分化鳞癌的临床特点是:病初精神、饮食、粪便等无明显变化,随着肿瘤增大,鼻肿大,鼻孔出血,鼻孔通气不畅,不食,最后衰竭死亡.%The clinical characteristics of infiltrating well-differentiated and severe-differentiated squamous carcinoma in a Siberian tiger's upper jaw are as follows: consciousness, food and drink and dejecta barely changed markedly during the catadrome period. As the tumor grew, nose intumescentiae occurred with apertura narium bleeding, cessation of feeding and finally death.

  14. The neuroendocrine system and stress, emotions, thoughts and feelings.

    Science.gov (United States)

    Vaillant, George E

    2011-01-01

    The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions), and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain") terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct) or agape (noble, non-specific valuing of all other people) miss the motivational forest for the trees. Neither Eros (hypothalamic) nor agape (cortical) has a fraction of the power to relieve stress as attachment (limbic love), yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points. PMID:21694965

  15. Reproductive seasonality in the mare: neuroendocrine basis and pharmacologic control.

    Science.gov (United States)

    Williams, G L; Thorson, J F; Prezotto, L D; Velez, I C; Cardoso, R C; Amstalden, M

    2012-08-01

    Reproductive seasonality in the mare is characterized by a marked decline in adenohypophyseal synthesis and secretion of LH beginning near the autumnal equinox. Thus, ovarian cycles have ceased in most mares by the time of the winter solstice. Endogenous reproductive rhythms in seasonal species are entrained or synchronized as a result of periodic environmental cues. In the horse, this cue is primarily day length. Hence, supplemental lighting schemes have been used managerially for decades to modify the annual timing of reproduction in the mare. Although a full characterization of the cellular and molecular bases of seasonal rhythms has not been realized in any species, many of their synaptic and humoral signaling pathways have been defined. In the mare, neuroendocrine-related studies have focused primarily on the roles of GnRH and interneuronal signaling pathways that subserve the GnRH system in the regulatory cascade. Recent studies have considered the role of a newly discovered neuropeptide, RF-related peptide 3 that could function to inhibit GnRH secretion or gonadotrope responsiveness. Although results that used native peptide sequences have been negative in the mare and mixed in all mammalian females, new studies that used an RFRP3 antagonist (RF9) in sheep are encouraging. Importantly, despite continuing deficits in some fundamental areas, the knowledge required to control seasonal anovulation pharmacologically has been available for >20 yr. Specifically, the continuous infusion of native GnRH is both reliable and efficient for accelerating reproductive transition and is uniquely applicable to the horse. However, its practical exploitation continues to await the development of a commercially acceptable delivery vehicle. PMID:22579068

  16. Multidimensional assessment of neuroendocrine and psychopathological profiles in maltreated youth.

    Science.gov (United States)

    Puetz, Vanessa B; Zweerings, Jana; Dahmen, Brigitte; Ruf, Caroline; Scharke, Wolfgang; Herpertz-Dahlmann, Beate; Konrad, Kerstin

    2016-09-01

    It has been debated whether children who have experienced early life stress (ELS), such as early caregiver separation show elevated risk for stress-related psychiatric disorders and a multi-symptom psychopathological profile that is not fully reflected in categorical assessments. In this study, we investigated dimensional measures of stress-related psychopathology in children in permanent out-of-home care, taking into account potential neuroendocrine interactions. In the current study, 25 children who had been placed in permanent out-of-home care before age 3 (years) and 26 controls (aged 10.6 ± 1.75 years) were investigated with categorical (DSM-IV) and dimensional assessments (CBCL) of psychopathology and diurnal salivary cortisol levels were assessed. Semi-structured interviews (K-DIPS) revealed no significant group differences in full-scale psychiatric diagnoses, whereas dimensional assessment (CBCL) revealed significant group differences in externalizing and total problem behaviours within the clinical range for children with ELS. Only children with ELS showed a combined symptom profile of clinical-range internalizing and externalizing problems. Lower morning cortisol values and subsequent flatter decline was found in subjects with ELS children compared to controls, showing group differences in diurnal cortisol secretion. Lower morning cortisol values were associated with more problem behaviour in the ELS group. Results show that ELS children exhibited increased psychopathological symptom severity and complexity associated with lower morning cortisol levels, which was not fully reflected in categorical assessments. This highlights the importance of incorporating dimensional assessments and neurobiological factors into psychopathological evaluations of children in out-of-home care in order to facilitate early identification of children at high risk for stress-related disorders. PMID:26875183

  17. Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases

    Institute of Scientific and Technical Information of China (English)

    Gen-You Yao; Ji-Lin Zhou; Mao-De Lai; Xiao-Qing Chen; Pei-Hui Chen

    2003-01-01

    AIM: To investigate the incidence of neuroendocrine (NE)cells and their hormone products in adenocarcinomas and evaluate their significance in clinical pathology and prognosis.METHODS: By using tissue sectioning and immunocytochemistry, 356 cases of adenocarcinomas were studied to examine the presence of chromorgranin and polypeptide hormones in adenocarcinoma samples from our hospital.RESULTS: The positive rate of NE cells and hormone products was 41.5 % (54/130) and 59.3 % (32/54), respectively in large intestinal adenocarcinoma cases; 39.6 % (38/96) and 36.8 % (14/38), respectively in gastric cancer cases; 38.1%(8/21) and 50.0 % (4/8), respectively in prostatic cancer cases; 21.0 % (17/81) and 17.6 % (3/17), respectively in breasr cancer cases; 17.9 % (5/28) and 60.0 % (3/5),respectively in pancreatic cancer cases. Among carcinomas of large intestine, pancreas and breast, the highly differentiated NE cell numbers were higher than the poorly differentiated NE cell numbers; while the gastric carcinoma cases had more poorly differentiated NE cells than highly differentiated NE cells. The higher detection rate of NE cells and their hormone products, the higher 5-year survival rate among the large intestine cancer cases.CONCLUSION: Close correlation was observed between NE cells and their hormone products with the cancer differentiations. For colorectal carcinomas, there is a close correlation of the presence of NE cells and their hormone products with the tumor staging and prognosis.

  18. Unraveling tumor grading and genomic landscape in lung neuroendocrine tumors.

    Science.gov (United States)

    Pelosi, Giuseppe; Papotti, Mauro; Rindi, Guido; Scarpa, Aldo

    2014-06-01

    Currently, grading in lung neuroendocrine tumors (NETs) is inherently defined by the histological classification based on cell features, mitosis count, and necrosis, for which typical carcinoids (TC) are low-grade malignant tumors with long life expectation, atypical carcinoids (AC) intermediate-grade malignant tumors with more aggressive clinical behavior, and large cell NE carcinomas (LCNEC) and small cell lung carcinomas (SCLC) high-grade malignant tumors with dismal prognosis. While Ki-67 antigen labeling index, highlighting the proportion of proliferating tumor cells, has largely been used in digestive NETs for assessing prognosis and assisting therapy decisions, the same marker does not play an established role in the diagnosis, grading, and prognosis of lung NETs. Next generation sequencing techniques (NGS), thanks to their astonishing ability to process in a shorter timeframe up to billions of DNA strands, are radically revolutionizing our approach to diagnosis and therapy of tumors, including lung cancer. When applied to single genes, panels of genes, exome, or the whole genome by using either frozen or paraffin tissues, NGS techniques increase our understanding of cancer, thus realizing the bases of precision medicine. Data are emerging that TC and AC are mainly altered in chromatin remodeling genes, whereas LCNEC and SCLC are also mutated in cell cycle checkpoint and cell differentiation regulators. A common denominator to all lung NETs is a deregulation of cell proliferation, which represents a biological rationale for morphologic (mitoses and necrosis) and molecular (Ki-67 antigen) parameters to successfully serve as predictors of tumor behavior (i.e., identification of pathological entities with clinical correlation). It is envisaged that a novel grading system in lung NETs based on the combined assessment of mitoses, necrosis, and Ki-67 LI may offer a better stratification of prognostic classes, realizing a bridge between molecular alterations

  19. The neuroendocrine system and stress, emotions, thoughts and feelings

    Directory of Open Access Journals (Sweden)

    George E. Vaillant

    2011-03-01

    Full Text Available The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions, and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain" terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct or agape (noble, non-specific valuing of all other people miss the motivational forest for the trees. Neither Eros (hypothalamic nor agape (cortical has a fraction of the power to relieve stress as attachment (limbic love, yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  20. The neuroendocrine system and stress, emotions, thoughts and feelings

    Directory of Open Access Journals (Sweden)

    Vaillant George

    2011-01-01

    Full Text Available The philosophy of mind is intimately connected with the philosophy of action. Therefore, concepts like free will, motivation, emotions (especially positive emotions, and also the ethical issues related to these concepts are of abiding interest. However, the concepts of consciousness and free will are usually discussed solely in linguistic, ideational and cognitive (i.e. "left brain" terms. Admittedly, consciousness requires language and the left-brain, but the aphasic right brain is equally conscious; however, what it "hears" are more likely to be music and emotions. Joy can be as conscious as the conscious motivation produced by the left-brain reading a sign that says, "Danger mines!!" However, look in the index of a Western textbook of psychology, psychiatry or philosophy for positive emotions located in the limbic system. Notice how discussion of positive spiritual/emotional issues in consciousness and motivation are scrupulously ignored. For example, the popular notions of "love" being either Eros (raw, amoral instinct or agape (noble, non-specific valuing of all other people miss the motivational forest for the trees. Neither Eros (hypothalamic nor agape (cortical has a fraction of the power to relieve stress as attachment (limbic love, yet until the 1950s attachment was neither appreciated nor discussed by academic minds. This paper will point out that the prosocial, "spiritual" positive emotions like hope, faith, forgiveness, joy, compassion and gratitude are extremely important in the relief of stress and in regulation of the neuroendocrine system, protecting us against stress. The experimental work reviewed by Antonio Damasio and Barbara Fredrickson, and the clinical example of Alcoholics Anonymous, will be used to illustrate these points.

  1. Simultaneous large cell neuroendocrine carcinoma and adenocarcinoma of the stomach

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada; Hirotoshi Maruo

    2011-01-01

    A large cell neuroendocrine carcinoma (LCNEC) of the stomach is very rare. A 76-year-old Japanese man was admitted to our hospital because of epigastralgia and nausea. Endoscopy revealed 2 large tumors in the stomach. He did not have multiple endocrine neoplasia type Ⅰ or Zollinger-Ellison syndrome. Imaging modali-ties, including computed tomography and magnetic resonance imaging, revealed no other tumors. Gas-trectomy, cholecystectomy, and lymph node dissection were performed. The resected stomach had 2 tumors: one was an antral ulcerated type 3 tumor measuring 5 cm x 5 cm, and the other was a polypoid type 1 tumor measuring 6 cm x 6 cm x 3 cm in the fundus. Micro-scopically, the antral ulcerated tumor was a well differ-entiated adenocarcinoma with deep invasion. The fun-dus polypoid tumor was a LCNEC, being composed of malignant large cells arranged in trabecular and nested patterns. The tumor cells were large and the nuclei were vesicular. Nucleoli were frequently present, and there were many mitotic figures, apoptotic bodies, and necrotic areas. Much lymphovascular permeation was seen. Seven out of 29 dissected lymph nodes showed metastatic foci; 6 were from the LCNEC and 1 from the adenocarcinoma. Many intravascular tumor emboli of LCNEC were seen in the peritoneum around the lymph nodes. Mucins were present in the adenocarcinoma but not in the LCNEC. Immunohistochemically, the LCNEC tumor cells were positive for pancytokeratins, synaptophysin (50% positive), chromogranin A (10% positive), Ki-67 (90% labeled), and platelet-derived growth factor-α (80% positive). They were negative for KIT, p53, CD56, and neuron-specific enolase. The non-cancerous stomach showed a normal number of endocrine cells. The patient is now treated with adju-vant chemotherapy.

  2. Calcitonin-negative neuroendocrine tumor of thyroid gland mimicking anaplastic carcinoma: an unusual entity

    Science.gov (United States)

    Arpaci, Rabia Bozdogan; Berkesoglu, Mustafa; Dag, Ahmet; Sezer, Emel; Bal, Kemal Koray; Vayısoğlu, Yusuf

    2015-01-01

    Medullary thyroid cancer is the neuroendocrine tumor (NET) of thyroid with mostly both secreting calcitonin and immunohistochemically showing calcitonin positivity. Occasionally; NETs of thyroid may have little or no calcitonin expression. We present a case of serum calcitonin negative and immunohistochemically calcitonin-negative staining tumor with positive reaction to neuroendocrine markers synaptophysin and chromogranin-A. The patient’s right vocal cord was paralytic and thyroid mass was huge with descending to thorax till hilar region. We discussed diagnostic difficulties and way of treatment about NETs of thyroid with the light of current literature with this case. PMID:26312221

  3. Coexistence of small cell neuroendocrine carcinoma and villous adenoma in the ampulla of Vater

    Institute of Scientific and Technical Information of China (English)

    Ji-Hong Sun; Ming Chao; Shi-Zheng Zhang; Guang-Qiang Zhang; Bin Li; Jian-Jun Wu

    2008-01-01

    Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT)and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

  4. Unique case of caecum plasmablastic lymphoma CD138+ in patient with late diagnosed colon neuroendocrine carcinoma

    International Nuclear Information System (INIS)

    Neuroendocrine tumors are frequently associated with other primary malignancies. Plasmablastic lymphoma is a rare, aggressive neoplasm, derived from large B-cell, associated with human immunodeficiency virus infection. Plasmablastic lymphoma cells share many cytomorphologic and immunophenotypic features with plasmablastic cells, causing some diagnostic problems. We present a unique case of coexisting two very uncommon neoplasms: plasmablastic lymphoma and neuroendocrine carcinoma in 54-years-old men. This is the first report of caecum localization of plasmablastic lymphoma. Presented case images diagnostic problems in rare neoplasms. (author)

  5. Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord.

    Science.gov (United States)

    Zubeldia-Brenner, L; Roselli, C E; Recabarren, S E; Gonzalez Deniselle, M C; Lara, H E

    2016-07-01

    This review highlights the principal effects of steroid hormones at central and peripheral levels in the neuroendocrine axis. The data discussed highlight the principal role of oestrogens and testosterone in hormonal programming in relation to sexual orientation, reproductive and metabolic programming, and the neuroendocrine mechanism involved in the development of polycystic ovary syndrome phenotype. Moreover, consistent with the wide range of processes in which steroid hormones take part, we discuss the protective effects of progesterone on neurodegenerative disease and the signalling mechanism involved in the genesis of oestrogen-induced pituitary prolactinomas. PMID:27262161

  6. Neuroendocrine-immune system interactions in amphibians: implications for understanding global amphibian declines.

    Science.gov (United States)

    Rollins-Smith, L A

    2001-01-01

    Amphibians are ancient creatures valued by biologists and naturalists around the world. They share with all other vertebrates a complex neuroendocrine system that enables them to flourish in a variety of aquatic and semiaquatic environments. Studies from a number of laboratories have demonstrated that the immune system of amphibian species is nearly as complex as that of mammals. Yet for reasons that are not well understood, amphibian species are facing greater survival challenges than in the recent past. This article will review our current understanding of the neuroendocrine immune system interactions in amphibians and address the question of whether environmental stressors may contribute to immunosuppression and amphibian declines.

  7. Expression and Clinicopathologic Significance of Human Achaete-scute Homolog 1 in Pulmonary Neuroendocrine Tumors

    OpenAIRE

    Donghan ZHENG; Wang, Lijun; Huang, Heyu; Li, Rui; Zhong, Zhiyong; Li, Fei; Daorong ZHANG

    2010-01-01

    Background and objective Human achaete-scute homolog 1 (hASH1) gene plays a critical role in development of the central nervous system, automatic nervous system, adrenal medullary chromaffin cells, thyroid C cells and pulmonary neuroendocrine cells. The aim of this study is to determine hASH1 gene expression in the normal lung tissue and various types of lung tumors, to analyze whether its expression correlated with pulmonary neuroendocrine markers, and to explore the possibility of hASH1 as ...

  8. Malignant Glomus Tumour (Glomangiosarcoma) with Additional Neuroendocrine Differentiation in a Horse.

    Science.gov (United States)

    Peters, M; Grafen, J; Kuhnen, C; Wohlsein, P

    2016-05-01

    A 13-year-old Icelandic crossbred horse was presented with headshaking and progressive impairment of chewing. A slowly growing mass was identified in the anterior maxilla. This was associated with lysis of the alveolar bone and the roots of the incisors and there were nodular proliferations affecting the nasal septum and conchae. There was no response to chemotherapy and so the horse was humanely destroyed. Based on morphological, immunohistochemical and ultrastructural findings the mass was classified as a malignant glomus tumour with multifocal vascular spaces and additional neuroendocrine differentiation. An oronasal glomus tumour with neuroendocrine differentiation has not been described previously in an animal. PMID:27102445

  9. {sup 213}Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    Energy Technology Data Exchange (ETDEWEB)

    Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2014-11-15

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

  10. Unusual presentation of high-grade neuroendocrine carcinoma of the Urinary bladder with small-cell and large-cell features

    Directory of Open Access Journals (Sweden)

    Vitor Fiorin de Vasconcellos

    2013-10-01

    Full Text Available High-grade neuroendocrine carcinoma of the urinary bladder comprehends small-cell and large-cell variants. It is a rare and aggressive neoplasm, mostly diagnosed in advanced stages. It is more frequently encountered among Caucasian men in the sixth decade of life. Urinary symptoms are the most common clinical presentation. Diagnosis is generally not troublesome once the lesions are easily detectable by imaging exams and cystoscopy. This neoplasia is associated with tobacco smoking, and is frequently associated with other carcinomatous components such as urothelial carcinoma, adenocarcinoma, and sarcomatoid carcinoma. The authors report a case of an apparently healthy female patient who presented cervical lymph node enlargement not accompanied by systemic symptoms. The supraclavicular lymph node biopsy revealed metastatic small cell carcinoma. The computed tomography scan showed a bladder wall nodular thickening, enlarged lymph nodes along the iliac, periaortic, mediastinal, cervical and supraclavicular chains, as well as an insufflating lytic bone lesion in the right iliac wing. The positron emission tomography-fluorodeoxyglucose (PET-FDG added to these findings, the presence of a paraesophageal lymph node, lymphadenomegaly in the gluteal region and a vertebral lytic lesion in T10. Resected specimen of the bladder tumor revealed a high-grade neuroendocrine carcinoma with small-cell and large-cell features.

  11. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    International Nuclear Information System (INIS)

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90Y/177Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90Y/177Lu-DOTATOC were treated with an intraarterial infusion of 213Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of 213Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

  12. Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

    International Nuclear Information System (INIS)

    Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not significantly associated with

  13. The genetics of neuroendocrine prostate cancers: a review of current and emerging candidates.

    Science.gov (United States)

    Ather, M Hammad; Siddiqui, Tahmeena

    2012-01-01

    Prostate cancer (PC) displays a strong familial link and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions, and, ultimately, carcinogenesis. The most widely studied epigenetic event in PC is aberrant DNA methylation (hypo- and hypermethylation); besides this, chromatin remodeling and micro RNA (miRNA) are other studied alterations in PC. These all lead to genomic instability and inappropriate gene expression. Causative dysfunction of histone modifying enzymes results in generic and locus-specific changes in chromatin remodeling. miRNA deregulation also contributes to prostate carcinogenesis, including interference with androgen-receptor signaling and apoptosis. These epigenetic alterations have the potential to act as biomarkers for PC for screening and diagnosis as well as prognosis and follow-up. The variable biological potential for a newly diagnosed PC is one of the biggest challenges. The other major clinical problem is in the management of castration-resistant PC. Neuroendocrine (NE) differentiation is one of the putative explanations for the development of castration-resistant disease. Most advanced and poorly differentiated cancer does not produce prostate-specific antigen (PSA) in response to disease progression. Circulating and tissue biomarkers like chromogranin A (CgA) thus become important tools. There is the potential to use various genetic and epigenetic alterations and NE differentiation as therapeutic targets in the management of PC. However, we are still some distance from developing clinically effective tools. Valuable insights into the nature of NE differentiation in PC have been gained in the last decades, but additional understanding of its pathogenetic mechanisms is needed. This will help in devising novel therapeutic strategies to develop targeted therapies. CgA has the potential to become an important marker of advanced castration

  14. Miliary pulmonary metastases of well-differentiated thyroid carcinoma (medullary excluded) about 10 cases; Les metastases pulmonaires micronodulaires de type miliaire dans le cancer thyroidien bien diff encie (medullaires exclus) a propos de dix cas

    Energy Technology Data Exchange (ETDEWEB)

    Ennibi, G. [Hopital Hassan-2, Service de Medecine Nucleaire, Agadir (Morocco); Ben Rais, N. [Centre Hospitalier Universitaire IBN Sina, Service de Medecine Nucleaire, Rabat (Morocco)

    2007-03-15

    Thyroid cancer is relatively a rare cancer; about 1% from all cancers: between 10 and 1591 of patients with differentiated thyroid cancer develop micro or macro-nodular pulmonary metastases. In this study we examined the characteristics and evolution after treatment of 10 patients with micro-nodular or miliary metastases of well-differentiated thyroid carcinoma. Total body scintigraphy with 131 iodine, chest X-ray or CT scan, and thyroglobulin assay were performed for all patients. The treatment was iodine 131 (3. 7 GBq). therapeutic 131 iodine scan was done for all patients seven days after the 131 administration. The effect of 131 iodine treatment was evaluated by means of changes in the number and size of lung metastases on the total body scintigraphy with 131 iodine and by serum thyroglobulin levels six months after 131 iodine ablation, they all received L-thyroxine (2,4 {mu}g/kg/j). The minimum duration of follow-up was 12 months. There were six females and four males within a range of 13-70 years old. Eight had papillary and two follicular thyroid cancer. These 10 patients benefited 131 iodine therapy. The effect of 131 iodine treatment and the prognostic values of the following variables mere examined: age at the time of 131 iodine. treatment and histological findings. The miliary was rarely diagnosed on the initial investigation. only in to o cases by 131 iodine scar. alter surgery. two cases by chest X-ray, and two cases by CT scan, the initial thyroglobulin levels was very high in seven cases, between 10 and 40 ng/ml in one case and less than 10 ng/ml in two cases. These results indicate that age, 131 iodine uptake. histological findings and the presence of other metastases are important factors in predicting the effects of 131 treatment for pulmonary metastases of well-differentiated thyroid carcinoma. Among all the variables studied. the best prognosis for survival was demonstrated by increased 131 uptake in pulmonary metastases and by early diagnosis

  15. Social Transitions Cause Rapid Behavioral and Neuroendocrine Changes.

    Science.gov (United States)

    Maruska, Karen P

    2015-08-01

    behavior during the initial rise in rank, suggesting that behavior is dissociated from endocrine status. These changes during social ascent are then compared with our current knowledge about males descending in rank, who rapidly show faded coloration, decreased dominance behaviors, increased subordinate behaviors, and higher circulating levels of cortisol. Collectively, this work highlights how the perception of similar social cues that are opposite in value are rapidly translated into adaptive behavioral and neuroendocrine changes that promote survival and reproductive fitness. Finally, future directions are proposed to better understand the mechanisms that govern these rapid changes in social position. PMID:26037297

  16. Aspectos neuroendocrinos de la obesidad Neuroendocrine aspects of obesity

    Directory of Open Access Journals (Sweden)

    Mario Perello

    2004-06-01

    Full Text Available En la fisiopatología de la obesidad intervienen factores genéticos, sociales, metabólicos, endocrinos y neurológicos. Esta multifactoriedad junto al hecho que estos factores se interrelacionan a través de mecanismos muy complejos, que son sólo parcialmente conocidos, ha llevado a que la comprensión íntima de este trastorno resulte una tarea sumamente ardua. Por estos motivos, el conocimiento integral de esta afección plantea un desafío al que actualmente están abocados numerosos grupos de investigadores. El análisis de la obesidad como un trastorno neuroendocrino, propone el estudio de este fenómeno desde una visión particular que implica disfunciones en casi todos los órganos endocrinos y en el sistema nervioso central, fundamentalmente en la actividad hipotalámica. Estas alteraciones afectan principalmente a los ejes neuroendocrinos hipotálamo-hipofiso-adrenal, adipo-insular y al control hipotalámico, tanto de la ingesta de alimento como del almacenamiento y gasto energético. Este artículo plantea una actualización en este campo; en primer lugar, se realiza una breve descripción, en forma independiente, de los principales sistemas antes mencionados y luego una descripción de su funcionamiento normal integrado. Finalmente, se describen desregulaciones de estos mecanismos y se discute como ellas contribuirían al desarrollo y/o mantenimiento de la obesidad.Genetic, social, metabolic, endocrine and neural events participate in the physiopathological development of obesity. Because of the multifactorial background of obesity, up to now, it has been very difficult to fully understand the whole disease. In fact, the relationship between several signals, through very complex mechanisms, is only partially known. Obesity, from a neuroendocrine point of view, implies taking into account abnormalities in both hypothalamic and endocrine functions. Among altered functions in obesity, namely those involving the hypothalamo

  17. Neuroendocrine abnormalities in patients with traumatic brain injury

    Science.gov (United States)

    Yuan, X. Q.; Wade, C. E.

    1991-01-01

    . Increased intracranial pressure, which releases vasopressin by altering normal hypothalamic anatomy, may represent a unique type of stress to neuroendocrine systems and may contribute to adrenal secretion by a mechanism that requires intact brainstem function. Endocrine function should be monitored in brain-injured patients with basilar skull fractures and protracted posttraumatic amnesia, and patients with SIADH or DI should be closely monitored for other endocrine abnormalities.

  18. Studies on the Relationship between Neuroendocrine Cellular Differentiation in Gastric Cancers and Post-operative Survival Time

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To examine the ultrastructure of gastric cancer cells by the electron microscope, in order to assess the relationship between neuroendocrine differentiation and post-operative survival time.METHODS NSE, Syn and CgA immunohistochemical labeling was conducted in 168 cases with a common-type of gastric cancer. Electron microscopy was performed in 80 cases with positive immunohistochemical labeling.These cases were followed-up for over 5 years and the post-operative survival data analyzed.RESULTS Neuroendocrine granules were found by electron microscopy in 39 cases. The rate of neuroendocrine differentiation found was 23% (39/168), using routine diagnostic criteria and electron microscopy (REM).The post-operative survival time of gastric cancer patients with neuroendocrine differentiation was significantly shorter (P=0.0032) compared to those without neuroendocrine differentiation.CONCLUSION It is of significant clinical importance to determine if the neuroendocrine cells are differentiated in gastric cancers. The gastric cancer patients with neuroendocrine differentiation have a shorter post-operative survival time and a poorer prognosis. Electron microscopy is a reliable method of providing a diagnosis.

  19. The incidence and clinical characteristics of gastroenteropancreatic neuroendocrine neoplasm in Chengdu City in 2010

    Institute of Scientific and Technical Information of China (English)

    郭林杰

    2013-01-01

    Objective To investigate the incidence of gastroenteropancreatic neuroendocrine neoplasm(GEP-NEN) in Chengdu City in 2010 and summarize clinical characteristics of GEP-NEN. Methods The incidence of GEP-NEN was estimated with the data in 2010 from the

  20. Localization of Neuroendocrine Tumors Using Somatostatin Receptor Imaging With Indium-111-Pentetreotide (OctreoScan).

    Science.gov (United States)

    Ellison; Schirmer; Olsen; Pozderac; Hinkle; Hill; O'Dorisio; O'Dorisio

    1997-01-01

    BACKGROUND: Many imaging methods have been used to detect neuroendocrine tumors of the gastrointestinal system. There is no gold standard for identifying the location of primary tumors and their potential metastases, and most conventional imaging techniques cannot detect tumors less than 1.0 cm in size. METHODS: The authors have investigated the use of 111-In-pentetreotide as an imaging agent for abdominal neuroendocrine tumors. RESULTS: The agent is cleared rapidly by the kidneys and is primarily excreted intact with a biologic half-life of six hours. The largest radiation burden is to the spleen and kidneys. A nine-center study conducted in Europe involved 365 patients with gastroenteropancreatic neuroendocrine tumors that were also imaged by other methods. The results of 111-In-pentetreotide were in agreement with those obtained by other methods for 79% of tumor locations. An additional 110 tumor localizations were detected that were not seen with conventional methods. The smallest gastrinoma imaged by 111-In-pentetreotide was a 4-mm duodenal tumor. CONCLUSIONS: Scintigraphy with 111-In-pentetreotide is effective in visualizing various somatostatin receptors characteristic of neuroendocrine tumors of the gastrointestinal tract. Insulinomas, however, are not well imaged. Concurrent computed tomography scanning is advised to minimize the risk of missing liver metastases. PMID:10763002

  1. Options for clinical management of cancers of neuroendocrine system and liver

    International Nuclear Information System (INIS)

    Cancers of neuroendocrine system and liver forms a significant fraction of the total number of cancer cases reported in India. In this context, nuclear medicine has an important role to play in the diagnosis as well as therapy of these diseases. Here, options offered by nuclear medicine for the diagnosis and therapy of these diseases are discussed. (author)

  2. A case of giant prolactinoma, initially misdiagnosed as sinonasal neuroendocrine carcinoma

    Directory of Open Access Journals (Sweden)

    Yasaman Mohtasebi, M.D.

    2015-09-01

    Full Text Available Giant prolactinomas are defined as pituitary tumors greater than 4 cm, often associated with very high prolactin level (>1000 ng/mL. They are relatively rare tumors and can present differently from typical prolactinomas. They can be highly invasive, resulting in acute neurological complication at the time of presentation. We present a case of a young woman with giant prolactinoma initially misdiagnosed as sinonasal neuroendocrine carcinoma. The acute presentation of headache, ptosis and impending brain herniation, requiring emergent ventriculostomy and intubation, led to the clinical suspicion of a more sinister diagnosis. Transnasal biopsy of the mass was consistent with sinonasal neuroendocrine carcinoma, and chemotherapy was planned. Laboratory testing, however, revealed an elevated prolactin (27,400 ng/mL, after 1:100 dilution. Re-review of pathology with additional immunohistochemical staining was requested and confirmed the diagnosis of prolactinoma. After 5 months of cabergoline treatment, prolactin level has decreased to 118 ng/mL. There has been a marked reduction in tumor size and an almost complete resolution of neurological symptoms. Given their atypical presentation and potential for sharing common immunohistochemical stains with other neuroendocrine neoplasms, giant prolactinomas extending into the nasal cavity can be misdiagnosed as other neuroendocrine neoplasms which may develop at this site. Accurate diagnosis is imperative to prevent unnecessary surgery and/or radiation and to ensure implementation of dopamine agonist therapy.

  3. Mechanical stress induces neuroendocrine and immune responses of sea cucumber ( Apostichopus japonicus)

    Science.gov (United States)

    Tan, Jie; Li, Fenghui; Sun, Huiling; Gao, Fei; Yan, Jingping; Gai, Chunlei; Chen, Aihua; Wang, Qingyin

    2015-04-01

    Grading procedure in routine sea cucumber hatchery production is thought to affect juvenile sea cucumber immunological response. The present study investigated the impact of a 3-min mechanical perturbation mimicking the grading procedure on neuroendocrine and immune parameters of the sea cucumber Apostichopus japonicus. During the application of stress, concentrations of noradrenaline and dopamine in coelomic fluid increased significantly, indicating that the mechanical perturbation resulted in a transient state of stress in sea cucumbers. Coelomocytes concentration in coelomic fluid increased transiently after the beginning of stressing, and reached the maximum in 1 h. Whereas, coelomocytes phagocytosis at 3 min, superoxide anion production from 3 min to 0.5 h, acid phosphatase activity at 0.5 h, and phenoloxidase activity from 3 min to 0.5 h were all significantly down-regulated. All of the immune parameters recovered to baseline levels after the experiment was conducted for 8 h, and an immunostimulation occurred after the stress considering the phagocytosis and acid phosphatase activity. The results suggested that, as in other marine invertebrates, neuroendocrine/immune connections exist in sea cucumber A. japonicus. Mechanical stress can elicit a profound influence on sea cucumber neuroendocrine system. Neuroendocrine messengers act in turn to modulate the immunity functions. Therefore, these effects should be considered for developing better husbandry procedures.

  4. Large cell neuroendocrine carcinoma of the parotid gland: case report and literature review.

    Science.gov (United States)

    Casas, Pablo; Bernáldez, Ricardo; Patrón, Mercedes; López-Ferrer, Pilar; García-Cabezas, Miguel A

    2005-03-01

    A 74-year-old male presented with a large polinodular mass in the neck. Fine needle aspiration cytology (FNAC) showed an undifferentiated large cell carcinoma. Computed tomography (CT) showed a large parotid mass with multiple satelite nodules. The remaining radiological studies were normal. Radical parotidectomy was performed. The tumor was a large cell carcinoma with neuroendocrine features and positive immunostain for neuroendocrine markers. The patient received postoperative radiotherapy and was free of tumor eight months later. Only four cases of large cell neuroendocrine carcinoma (LCNEC) of the salivary gland have been communicated. All of them have involved the parotid gland. This tumor presents in elderly patients as a large infiltrating parotid mass. Fine needle aspiration cytology serves to recognize the carcinoma, but it fails in recognizing the neuroendocrine features of the tumor. The histopathological features of this tumor are the same as in other organs. Chromogranin and synaptophysin are useful immunohistochemical markers. A primary location of the tumor in another organ, specially the lung, should be ruled out. Surgery is the main treatment modality and can be complemented with postoperative radiotherapy. The prognosis seems to be poor. More studies are needed to better define the therapeutical alternatives and prognostic factors of these rare tumors.

  5. Large Cell Neuroendocrine Carcinoma of the Rectum Presenting with Extensive Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Vinay Minocha

    2014-01-01

    Full Text Available Introduction. Rectal large cell neuroendocrine carcinoma (LCNEC is a poorly differentiated neoplasm that is very rare and belongs within the poorest prognostic subgroup among primary colorectal neoplasms. Here, we describe a case of LCNEC of the rectum, which highlights the aggressive clinical course and poor prognosis associated with this disease. Case Presentation. We report a case of a 63-year-old male who presented to our hospital with a one-month history of lower abdominal pain, constipation, and weight loss. A computed tomography (CT scan of the chest, abdomen, and pelvis revealed a rectal mass as well as metastatic disease of the liver and lung. Flexible sigmoidoscopy revealed a fungating, ulcerated and partially obstructing rectal mass located 6 cm from the anal verge. This mass was biopsied and pathological examination of the resected specimen revealed features consistent with a large cell neuroendocrine carcinoma. Conclusion. Rectal large cell neuroendocrine carcinomas are rare and have a significantly worse prognosis than adenocarcinomas. At diagnosis, a higher stage and metastatic disease are likely to be found. It is important to differentiate large cell, poorly differentiated neuroendocrine carcinomas from adenocarcinomas of the colon and rectum pathologically because patients may benefit from alternative cytotoxic chemotherapeutic regimens.

  6. Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

    Directory of Open Access Journals (Sweden)

    Caroline I. E. Renner

    2015-09-01

    Full Text Available Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed.

  7. Neuroendocrine and Behavioral Effects of Vasopressin in Resting and Mild Stress Conditions

    NARCIS (Netherlands)

    Buwalda, B.; Nyakas, C.; Koolhaas, J.M.; Bohus, B.

    1993-01-01

    Neuroendocrine and behavioral effects of subcutaneously administered AVP (6 mug/kg b.wt.) were determined in resting conditions and after the mild stress of transportation to and placement in a novel environment. In resting conditions, systemic administration of AVP caused a rapid increase in blood

  8. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  9. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S; Pieterman, Carolina R C; de Laat, Joanne M; Hermus, Ad R; Dekkers, Olaf M; de Herder, Wouter W; van der Horst-Schrivers, Anouk N; Drent, Madeleine L; Bisschop, Peter H; Havekes, Bas; Borel Rinkes, Inne H M; Vriens, Menno R; Valk, Gerlof D; Valk, GD

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  10. Neuroendocrine-immune interaction: regulation of inflammation via G-protein coupled receptors

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Aa, van der L.M.; Chadzinska, M.K.

    2013-01-01

    Neuroendocrine- and immune systems interact in a bi-directional fashion to communicate the status of pathogen recognition to the brain and the immune response is influenced by physiological changes. The network of ligands and their receptors involved includes cytokines and chemokines, corticosteroid

  11. Basal cell carcinoma with progression to metastatic neuroendocrine carcinoma: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Volkan Adsay

    2010-03-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Merkel cell carcinoma (MCC or primary cutaneous neuroendocrine carcinoma is a malignant tumor considered to demonstrate differentiation towards Merkel cells that are present at the base of the epidermis or around the apical end of some hair follicles and are thought to play an yet uncertain role in sensory transduction. Here we present the case of a 54-year-old female with a basal cell carcinoma (BCC of the skin with neuroendocrine features (positivity for chromogranin that has evolved during multiple recurrences and radiotherapy into a high-grade neuroendocrine carcinoma with morphologic and immunohistochemical features of MCC (trabecular and nesting arrangement, positivity for chromogranin, cytokeratin 20, neuron specific enolase, and also neurosecretory granules on electron microscopy. The progression from a chromogranin positive basal cell carcinoma of the skin, to a high grade neuroendocrine carcinoma demonstrates the potential for cross differentiation among skin tumors.

  12. The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity

    NARCIS (Netherlands)

    Meerlo, P; Horvath, KM; Nagy, GM; Bohus, B; Koolhaas, JM

    1999-01-01

    Environmental stimuli during early stages of life can influence the development of an organism and may result in permanent changes in adult behaviour and physiology. In the present study we investigated the influence of early postnatal handling on adult neuroendocrine and behavioural stress reactivi

  13. Rare neuroendocrine tumours : Results of the surveillance of rare cancers in Europe project

    NARCIS (Netherlands)

    van der Zwan, Jan Maarten; Trama, Annalisa; Otter, Renee; Larranaga, Nerea; Tavilla, Andrea; Marcos-Gragera, Rafael; Dei Tos, Angelo Paolo; Baudin, Eric; Poston, Graeme; Links, Thera

    2013-01-01

    Because of the low incidence, and limited opportunities for large patient volume experiences, there are very few relevant studies of neuroendocrine tumours (NETs). A large population-based database (including cancer patients diagnosed from 1978 to 2002 and registered in 76 population-based cancer re

  14. Does Fetal antigen 1 (FA1) identify cells with regenerative, endocrine and neuroendocrine potentials?

    DEFF Research Database (Denmark)

    Jensen, Charlotte Floridon; Jensen, Charlotte Harken; Thorsen, Poul;

    2000-01-01

    in the subcellular localisation indicating differential post-translational/post-transcriptional modifications during fetal development. FA1 may be a new marker of cellular subtypes with a regenerative potential and of specific cells with endocrine or neuroendocrine functions. Udgivelsesdato: 2000-Aug...

  15. Effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella

    DEFF Research Database (Denmark)

    Cymborowski, B.; Sørensen, Ilona Kryspin

    1975-01-01

    1. Studies were made on the effect of reserpine on development and its neuro-endocrine regulation in Galleria mellonella. It was shown that resperine greatly restricts the development of this insect. 2. Reserpine causes inhibition of the activity of the neurosecretory cells of pars intercerebralis...

  16. Long-term follow-up of two patients with metastatic neuroendocrine tumours treated with octreotide

    NARCIS (Netherlands)

    van de Loosdrecht, AA; van Bodegraven, AA; Sepers, JM; Sindram, JW

    1998-01-01

    Two patients are described with metastatic neuroendocrine tumours of the pancreas head and region of Vater. After surgery, administration of the long-acting somatostatin analogue octreotide was started. In the first patient we found an IgG-lambda paraproteinaemia and a parathyroid hormone-related pr

  17. The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning

    Science.gov (United States)

    Conradt, Elisabeth; Hawes, Katheleen; Guerin, Dylan; Armstrong, David A.; Marsit, Carmen J.; Tronick, Edward; Lester, Barry M.

    2016-01-01

    This study tested whether maternal responsiveness may buffer the child to the effects of maternal depressive symptoms on DNA methylation of "NR3C1," "11ß-HSD2," and neuroendocrine functioning. DNA was derived from buccal epithelial cells and prestress cortisol was obtained from the saliva of 128 infants. Mothers with depressive…

  18. Small cell carcinoma of the lung and large cell neuroendocrine carcinoma interobserver variability

    NARCIS (Netherlands)

    den Bakker, Michael A.; Willemsen, Sten; Gruenberg, Katrien; Noorduijn, L. Arnold; van Oosterhout, Matthijs F. M.; van Suylen, Robert J.; Timens, Wim; Vrugt, Bart; Wiersma-van Tilburg, Anne; Thunnissen, Frederik B. J. M.

    2010-01-01

    Aims: To test the hypothesis that the published morphological criteria permit reliable segregation of small cell carcinoma of the lung (SCLC) and large cell neuroendocrine carcinoma (LCNEC) cases by determining the interobserver variation. Methods and results: One hundred and seventy cases of SCLC,

  19. Genetics of Endocrine and Neuroendocrine Neoplasias (PDQ®)—Health Professional Version

    Science.gov (United States)

    Expert-reviewed information summary about the genetics of endocrine and neuroendocrine neoplasias. This summary contains information about the MEN1 gene, the RET gene, genetic testing, and clinical interventions. Psychosocial issues associated with genetic testing and counseling of individuals who may have a hereditary medullary thyroid cancer syndrome are also discussed.

  20. Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Marco Marzioni; Giammarco Fava; Antonio Benedetti

    2006-01-01

    Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases.Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones,neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth,survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.

  1. Attenuated Cardiovascular, Neuroendocrine, and Behavioral Responses After a Single Footshock in Central Amygdaloid Lesioned Male Rats

    NARCIS (Netherlands)

    Roozendaal, B.; Koolhaas, J.M.; Bohus, B.

    1991-01-01

    The effect of bilateral electrolytical CEA lesioning on behavioral, cardiovascular and neuroendocrine changes has been studied in male Wistar rats before, during and shortly after a brief aversive stimulus of an unavoidable footshock. Blood samples were withdrawn via a permanent heart catheter. Lesi

  2. Diagnosis of prostatic neuroendocrine carcinoma: Two cases report and literature review

    Institute of Scientific and Technical Information of China (English)

    Hai-Qing; He; Shu-Feng; Fan; Qiong; Xu; Zhen-Jing; Chen; Zheng; Li

    2015-01-01

    Two cases of prostatic neuroendocrine carcinoma(PNEC) imaged by computed tomography(CT) and magnetic resonance imaging(MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusionweighted image were emphasized, the complementary roles of ultrasound, CT, MRI, clinical and laboratory characteristic’s features in achieving accurate diagnosis were valued in the preoperative diagnosis of PNEC.

  3. Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas

    NARCIS (Netherlands)

    K. Kamp; R.A. Damhuis (Ronald); R.A. Feelders (Richard); W.W. de Herder (Wouter)

    2012-01-01

    textabstractAn increased association between neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NET) and other second primary malignancies has been suggested. We determined whether there is indeed an increased risk for second primary malignancies in GEP-NET patients compared with

  4. Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

    Directory of Open Access Journals (Sweden)

    Menon Santosh

    2010-01-01

    Full Text Available Primary sinonasal tumors with neuroendocrine differentiation (SCND are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC, sinonasal neuroendocrine carcinoma (SNEC, esthesioneuroblastoma (ENB and small cell carcinoma (SmCC. The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute′s pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With

  5. Chromophobe renal cell carcinoma with neuroendocrine differentiation/morphology: A clinicopathological and genetic study of three cases

    Directory of Open Access Journals (Sweden)

    Chisato Ohe, MD

    2014-09-01

    Full Text Available Chromophobe renal cell carcinoma (ChRCC with neuroendocrine differentiation/morphology (NED/NEM is exceedingly rare. We present three cases of ChRCC with NED/NEM, two of which showed positivity for neuroendocrine markers on immunohistochemical analysis. Patients ranged in age from 49 to 79 years (mean: 64.3 years. One of the three patients died of metastatic disease to multiple organs. Of the remaining two patients, one is currently alive without disease and the other is alive with disease. Histologically, all three tumors were composed of conventional ChRCC and NEM showed glandular and rosette formation. Immunohistochemically, tumor cells were positive for CK7, KAI1, E-cadherin, and c-kit in both ChRCC and neuroendocrine areas in three cases. CD56 and synaptophysin immunoreactivity were detected in two cases; in only the neuroendocrine area in one case and in both components in the other. Neuroendocrine granules were ultrastructurally observed at both neuroendocrine and conventional areas of ChRCC. Array comparative genomic hybridization (CGH study indicated losses of chromosomes 1, 2, 6, 10, 17, 21, and Y in both conventional ChRCC and NED in one case. In addition, losses of chromosomes 1, 2, 4, 6, 9, 10, 13, 16p, 17, and 21 were observed in both components of the remaining one tumor. Furthermore, loss of chromosome 5 was identified only in the neuroendocrine area in this case. We concluded that the neuroendocrine area may reflect dedifferentiation within ChRCC. It is possible that losses of chromosomes 4, 5, and 16p may be involved in the neuroendocrine differentiation or progression of ChRCC.

  6. Computed tomography characterization of neuroendocrine tumors of the thymus can aid identification and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Wang, De-ling; Liu, Xue-wen; Geng, Zhi-jun; Xie, Chuan-miao [State Key Lab. of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen Univ., Guangzhou (China)], e-mail: xchuanm@sysucc.org.cn

    2013-03-15

    Background: Neuroendocrine tumors of the thymus are extremely rare anterior mediastinal tumors. The few studies reporting these tumors have focused on the clinical manifestations and do not provide a summary of characteristic computed tomography (CT) findings. Purpose: To investigate the CT appearances of neuroendocrine tumors of the thymus in order to improve the diagnostic and resection efficacy. Material and Methods: Nine cases of pathologically identified thymic neuroendocrine tumors were retrospectively analyzed by CT. All the patients underwent non-enhanced and contrast-enhanced CT. Multiple CT features were examined, including tumor location, shape, margins, CT attenuation, involvement of surrounding structures, and distant metastasis. Results: A total of nine masses were examined in this study. The maximum tumor diameter ranged from 5 to 14 cm (average, 9 cm). The shapes of six masses were lobulated and three were rounded or oval and the margins of seven masses were unclear while two masses were sharp. All the masses showed hypo density or isodensity compared to muscles in the anterior thoracic wall on non-enhanced CT images. Two masses showed homogeneous attenuation by non-enhanced CT imaging and moderate homogeneous enhancement after contrast administration, while seven masses showed heterogeneous attenuation with patchy low-attenuation foci and showed moderate to strong heterogeneous enhancement. Involvement of adjacent structures was observed in six cases. Five cases were observed to have lymph node metastases and four cases had distant metastases. Conclusion: Neuroendocrine tumors of the thymus are rare tumors of the anterior mediastinum with a number of distinct CT characteristics. Most importantly, the density of the tumors was heterogeneous with necrosis or cystic degeneration and moderately or strongly enhancement after bolus injection of contrast medium, which may allow for more efficient tumor identification. Thus, CT can improve of the diagnosis

  7. Chromophobe renal cell carcinoma of the kidney with neuroendocrine differentiation: A case report with review of literature

    Directory of Open Access Journals (Sweden)

    Ghadeer A Mokhtar

    2015-01-01

    Full Text Available Chromophobe renal cell carcinoma (chRCC is a distinctive type of malignant kidney tumor characterized by large cells with defined cell membrane. Primary renal neuroendocrine tumors (NET are rare with morphology similar to NET at other sites. There are few case reports describing the coexistence of these 2 neoplasms within the same tumor mass. We describe a case of chRCC with neuroendocrine features in a 70-year-old male patient who presented with hematuria and right flank pain. The histological and immunohistochemical features of both components were characteristic with no overlapping features. The neuroendocrine element was associated with nodal metastasis.

  8. NeuroD1 regulation of migration accompanies the differential sensitivity of neuroendocrine carcinomas to TrkB inhibition

    OpenAIRE

    Osborne, J K; Larsen, J E; Gonzales, J X; Shames, D S; Sato, M.; Wistuba, I. I.; Girard, L; Minna, J D; Cobb, M H

    2013-01-01

    The developmental transcription factor NeuroD1 is anomalously expressed in a subset of aggressive neuroendocrine tumors. Previously, we demonstrated that TrkB and neural cell adhesion molecule (NCAM) are downstream targets of NeuroD1 that contribute to the actions of neurogenic differentiation 1 (NeuroD1) in neuroendocrine lung. We found that several malignant melanoma and prostate cell lines express NeuroD1 and TrkB. Inhibition of TrkB activity decreased invasion in several neuroendocrine pi...

  9. Comparison between {sup 68}Ga-DOTA-NOC and {sup 18}F-DOPA PET for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano [Azienda Ospedaliero Universitaria di Bologna, Policlinico S.Orsola-Malpighi, Unita Operativa di Medicina Nucleare, Bologna (Italy); Policlinico S.Orsola-Malpighi, Unita Operativa di Medicina Internal, Bologna (Italy)

    2008-08-15

    {sup 18}F-FDG positron emission tomography (PET) value for the assessment of neuro-endocrine tumours (NET) is limited. Preliminary studies indicate that {sup 18}F-DOPA and {sup 68}Ga-DOTA-NOC are more accurate for disease assessment and {sup 68}Ga-DOTA peptides provide additional data on receptor status that are crucial for targeted radionuclide therapy. At present, there are no comparative studies investigating their role in NET. The aim of this study was to compare {sup 68}Ga-DOTA-NOC and {sup 18}F-DOPA for the evaluation of gastro-entero-pancreatic and lung neuro-endocrine tumours. Thirteen patients with biopsy-proven NET (gastro-entero-pancreatic or pulmonary) were prospectively enrolled and scheduled for {sup 18}F-DOPA and {sup 68}Ga-DOTA-NOC PET. PET results obtained with both tracers were compared with each other, with other conventional diagnostic procedures (CT, ultrasound) and with follow-up (clinical, imaging). The most common primary tumour site was the pancreas (8/13) followed by the ileum (2/13), the lung (2/13) and the duodenum (1/13). The carcinoma was well differentiated in 10/13 and poorly differentiated in 3/13 cases. {sup 68}Ga-DOTA-NOC PET was positive, showing at least one lesion, in 13/13 cases while {sup 18}F-DOPA PET was positive in 9/13. On a lesions basis, {sup 68}Ga-DOTA-NOC identified more lesions than {sup 18}F-DOPA (71 vs 45), especially at liver, lung and lymph node level. {sup 68}Ga-DOTA-NOC correctly identified the primary site in six of eight non-operated cases (in five cases, the primary was surgically removed before PET), while {sup 18}F-DOPA identified the primary only in two of eight cases. Although the patients studied are few and heterogeneous, our data show that {sup 68}Ga-DOTA-NOC is accurate for the detection of gastro-entero-pancreatic and lung neuro-endocrine tumours in either the primary or metastatic site and that it offers several advantages over {sup 18}F-DOPA. (orig.)

  10. Adiposity is associated with blunted cardiovascular, neuroendocrine and cognitive responses to acute mental stress.

    Directory of Open Access Journals (Sweden)

    Alexander Jones

    Full Text Available Obesity and mental stress are potent risk factors for cardiovascular disease but their relationship with each other is unclear. Resilience to stress may differ according to adiposity. Early studies that addressed this are difficult to interpret due to conflicting findings and limited methods. Recent advances in assessment of cardiovascular stress responses and of fat distribution allow accurate assessment of associations between adiposity and stress responsiveness. We measured responses to the Montreal Imaging Stress Task in healthy men (N = 43 and women (N = 45 with a wide range of BMIs. Heart rate (HR and blood pressure (BP measures were used with novel magnetic resonance measures of stroke volume (SV, cardiac output (CO, total peripheral resistance (TPR and arterial compliance to assess cardiovascular responses. Salivary cortisol and the number and speed of answers to mathematics problems in the task were used to assess neuroendocrine and cognitive responses, respectively. Visceral and subcutaneous fat was measured using T(2 (*-IDEAL. Greater BMI was associated with generalised blunting of cardiovascular (HR:β = -0.50 bpm x unit(-1, P = 0.009; SV:β = -0.33 mL x unit(-1, P = 0.01; CO:β = -61 mL x min(-1 x unit(-1, P = 0.002; systolic BP:β = -0.41 mmHg x unit(-1, P = 0.01; TPR:β = 0.11 WU x unit(-1, P = 0.02, cognitive (correct answers: r = -0.28, P = 0.01; time to answer: r = 0.26, P = 0.02 and endocrine responses (cortisol: r = -0.25, P = 0.04 to stress. These associations were largely determined by visceral adiposity except for those related to cognitive performance, which were determined by both visceral and subcutaneous adiposity. Our findings suggest that adiposity is associated with centrally reduced stress responsiveness. Although this may mitigate some long-term health risks of stress responsiveness, reduced performance under stress may be a more immediate

  11. Effectiveness of Magnifying Narrow-Band Imaging Endoscopy for Differential Diagnosis between the High-Risk Mixed-Type and Low-Risk Simple-Type of Low-Grade, Well-Differentiated Gastric Tubular Adenocarcinoma.

    Science.gov (United States)

    Saitoh, Takashi; Takamura, Asako; Watanabe, Gen; Sugitani, Suzuko; Ajioka, Yoichi

    2016-01-01

    Backgrounds. Magnifying endoscopy with narrow-band imaging (NBI-ME) is useful for diagnosing differentiated early gastric cancer (D-EGC). D-EGC is classified as high- or low-grade based on its glandular architectural and cytological atypia. Low-grade, well-differentiated tubular adenocarcinoma (LG-tub1) mixed with high-grade tub1 (HG-tub1) and/or other histological types (M-LG-tub1) may indicate a primitive high-risk malignant lesion compared to histologically simple-type LG-tub1 (S-LG-tub1). Because LG-tub1 is occasionally difficult to diagnose due to its unclear demarcation under conventional white light endoscopy, early precise diagnoses are important. Methods. We compared NBI-ME and postendoscopic submucosal dissection histological findings for 30 S-LG-tub1 and 15 M-LG-tub1 lesions. We classified the NBI-ME findings of S-LG-tub1 (and not D-EGC) into four patterns. The differential diagnosis between M-LG-tub1 and S-LG-tub1 depended on the presence of more than one of these patterns without or with other patterns (referred to as "limited-to-four-pattern [LFP] sign-positive" and "sign-negative", resp.). Result. The sensitivity, specificity, accuracy, positive and negative predictive values, and intraobserver and interobserver agreement, using the "LFP sign" for the differential diagnosis between M-LG-tub1 and S-LG-tub1, were 87.9%, 91.7%, 88.9%, 96.7%, 73.3%, and k = 0.842 and k = 0.737, respectively. Conclusion. NBI-ME may be useful in differentiating between high-risk M-LG-tub1 and low-risk S-LG-tub1. PMID:27127502

  12. Expression of a neuroendocrine gene signature in gastric tumor cells from CEA 424-SV40 large T antigen-transgenic mice depends on SV40 large T antigen.

    Directory of Open Access Journals (Sweden)

    Fritz Ihler

    Full Text Available BACKGROUND: A large fraction of murine tumors induced by transgenic expression of SV40 large T antigen (SV40 TAg exhibits a neuroendocrine phenotype. It is unclear whether SV40 TAg induces the neuroendocrine phenotype by preferential transformation of progenitor cells committed to the neuroendocrine lineage or by transcriptional activation of neuroendocrine genes. METHODOLOGY/PRINCIPAL FINDINGS: To address this question we analyzed CEA424-SV40 TAg-transgenic mice that develop spontaneous tumors in the antral stomach region. Immunohistology revealed expression of the neuroendocrine marker chromogranin A in tumor cells. By ELISA an 18-fold higher level of serotonin could be detected in the blood of tumor-bearing mice in comparison to nontransgenic littermates. Transcriptome analyses of antral tumors combined with gene set enrichment analysis showed significant enrichment of genes considered relevant for human neuroendocrine tumor biology. This neuroendocrine gene signature was also expressed in 424GC, a cell line derived from a CEA424-SV40 TAg tumor, indicating that the tumor cells exhibit a similar neuroendocrine phenotype also in vitro. Treatment of 424GC cells with SV40 TAg-specific siRNA downregulated expression of the neuroendocrine gene signature. CONCLUSIONS/SIGNIFICANCE: SV40 TAg thus appears to directly induce a neuroendocrine gene signature in gastric carcinomas of CEA424-SV40 TAg-transgenic mice. This might explain the high incidence of neuroendocrine tumors in other murine SV40 TAg tumor models. Since the oncogenic effect of SV40 TAg is caused by inactivation of the tumor suppressor proteins p53 and RB1 and loss of function of these proteins is commonly observed in human neuroendocrine tumors, a similar mechanism might cause neuroendocrine phenotypes in human tumors.

  13. Guidelines for the management of gastroenteropancreatic neuroendocrine tumours (including bronchopulmonary and thymic neoplasms). Part II-specific NE tumour types

    DEFF Research Database (Denmark)

    Oberg, Kjell; Astrup, Lone Bording; Eriksson, Barbro;

    2004-01-01

    Part II of the guidelines contains a description of epidemiology, histopathology, clinical presentation, diagnostic procedure, treatment, and survival for each type of neuroendocrine tumour. We are not only including gastroenteropancreatic tumours but also bronchopulmonary and thymic neuroendocri...

  14. UTSW Researchers Identify Potential Therapeutic Targets for High-grade Neuroendocrine Lung Cancers | Office of Cancer Genomics

    Science.gov (United States)

    Neuroendocrine specific lung cancers comprise about 10% of non-small cell lung cancer (NSCLC) cases and all small cell lung cancer (SCLC) cases. Studies have previously shown that the transcription factor achaete-scute homolog 1 (ASCL1) is a cancer “lineage” factor required for the development and survival of SCLC, and is highly expressed in neuroendocrine-specific NSCLC (NE-NSCLC).

  15. Small cell neuroendocrine tumor of the breast in a 40 year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Pasquini Enzo

    2010-06-01

    Full Text Available Abstract Introduction Small cell neuroendocrine cancer of the breast is a rare tumor with less than 30 cases reported in the literature. The morphological and immunohistochemical patterns of this tumor are similar to small cell neuroendocrine cancer of the lung. For this reason, it is often difficult to distinguish a primary small cell neuroendocrine cancer of the breast from a metastatic lesion from other sites. Case presentation We report and characterize with immunohistochemical techniques a case of primary small cell neuroendocrine cancer of the breast occurring in a 40-year-old Caucasian woman. A palpable and mobile 3.0 cm tumor was located in the upper-outer quadrant of her right breast. Lumpectomy and subsequent radical mastectomy with axillary lymph node resection were performed. Microscopically, the tumor consisted predominantly of a diffuse proliferation of small oat cells. The tumor cells were positive for neuroendocrine markers chromogranin A and synaptophysin. One of 16 lymph nodes was metastatic. A correct treatment needs to be chosen. Conclusions It has recently been demonstrated that early small cell neuroendocrine cancer of the breast shows a good prognosis with adjuvant treatments with high disease free survival. Our patient is alive and well without disease eight years after treatment. We performed an adjuvant therapy with the classic scheme doxorubicin and cyclophosphamide, followed by carboplatin and etoposide. A more extensive review is required to define a standard treatment protocol for this rare neoplasm.

  16. Acute Pancreatitis Associated with Neuroendocrine Tumor of the Pancreas

    OpenAIRE

    José Jukemura; André Luis Montagnini; José Luiz Jesus de Almeida; Joaquim José Gama Rodrigues; José Eduardo Monteiro da Cunha; Marcos Vinícius Perini

    2006-01-01

    Context :Endocrine tumors are a less commonly known cause of acute pancreatitis. This report presents the case of a patient who have had acute pancreatitis secondary to a pancreatic endocrine neoplasm. The majority of the cases previously reported were nonfunctioning tumors and the pancreatitis tended to be mild. Moreover, the majority of the tumors were diagnosed in advanced stages, hindering curative treatment. Case report: A 31-year-old female patient presented with epigastric pain and a ...

  17. Somatostatin Receptor-Based Molecular Imaging and Therapy for Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2013-01-01

    Full Text Available Neuroendocrine tumors (NETs are tumors originated from neuroendocrine cells in the body. The localization and the detection of the extent of NETs are important for diagnosis and treatment, which should be individualized according to the tumor type, burden, and symptoms. Molecular imaging of NETs with high sensitivity and specificity is achieved by nuclear medicine method using single photon-emitting and positron-emitting radiopharmaceuticals. Somatostatin receptor imaging (SRI using SPECT or PET as a whole-body imaging technique has become a crucial part of the management of NETs. The radiotherapy with somatostatin analogues labeled with therapeutic beta emitters, such as lutetium-177 or yttrium-90, has been proved to be an option of therapy for patients with unresectable and metastasized NETs. Molecular imaging can deliver an important message to improve the outcome for patients with NETs by earlier diagnosis, better choice of the therapeutic method, and evaluation of the therapeutic response.

  18. The value of the immunohistochemistry in a case of gastric neuroendocrine tumor and thyroid metastasis.

    Science.gov (United States)

    Poiană, Cătălina; Carşote, Mara; Ardeleanu, Carmen; Terzea, Dana; Avramescu, Elena Taina; Neamţu, M C; Miulescu, Rucsandra Dănciulescu

    2011-01-01

    Thyroid metastasis is atypical. We present a 70-year-old female case that was first diagnosed as gastric cancer after surgical approach. Two years later a thyroidectomy was performed and the immunohistochemistry (IHC) profile revealed a neuroendocrine tumor (NET): poorly differentiated neuroendocrine carcinoma (with small cells), with positive reaction for SYN, CROMO, negative for calcitonin, TTF1 and thyreoglobulin. The Ki-67 index was 25%. Considering the unusual metastasis, the IHC exam of the stomach tumor was performed pointing the same features as the thyroid findings. This proved that the thyroid tumor was a metastasis from a primary gastric neoplasia. This is an unusual case of NET because of the thyroid involvement. Nevertheless, the IHC exam played the major role in elucidating the diagnosis and the prognosis of the case. PMID:21424054

  19. A gastric neuroendocrine carcinoma expressing somatostatin in a bearded dragon (Pogona vitticeps).

    Science.gov (United States)

    Lyons, Jeremiah A; Newman, Shelley J; Greenacre, Cheryl B; Dunlap, John

    2010-03-01

    A metastatic gastric neuroendocrine carcinoma in a 2.5-year-old inland bearded dragon (Pogona vitticeps) with a chronic history of anorexia, weight loss, depression, and acute melena is described. Histologic examination of the gastric mass revealed a densely cellular tumor arranged in nests and occasional rosettes of hyperchromatic cells with oval to spindle-shaped nuclei and minimal cytoplasm; the tumor was supported by a moderate fibrovascular stroma. Similar cells invaded through the gastric mucosa, and there were multiple hepatic metastases. The neoplastic cells were weakly immunopositive for neuron-specific enolase and moderately positive for somatostatin but were negative for chromogranin AB and gastrin. Ultrastructural studies revealed scattered neurosecretory granules in the neoplastic cells, confirming the diagnosis of a neuroendocrine carcinoma. PMID:20224102

  20. Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

    Institute of Scientific and Technical Information of China (English)

    William; J; Salyers; Kenneth; J; Vega; Juan; Carlos; Munoz; Bruce; W; Trotman; Silvio; S; Tanev

    2014-01-01

    Neuroendocrine tumors(NET)previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome.The annual incidence of patients with NET is 8.4 per 100000;yet many NET remain asymptomatic and clinically undetected.A majority of NET follows a benign course;however,some will display malignant characteristics.NET most commonly occur in the gastrointestinal tract(67%)and bronchopulmonary system(25%).Gastrointestinal NET occur within the stomach,small intestine,liver,and rectum.We report a retrospective study of 11 subjects:Eight with benign carcinoid tumors:duodenal bulb(n=2),terminal ileum(n=1),sigmoid colon(n=2),and rectum(n=3);three with malignant carcinoid:liver(n=1)and intra-abdominal site(n=2).The diagnosis,endoscopic images,outcome,treatment and review of the literature are presented.

  1. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Norsk, Peter; Gustafsson, Finn;

    2006-01-01

    Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme....... In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does......-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure...

  2. Hemodynamic and neuroendocrine responses to changes in sodium intake in compensated heart failure

    DEFF Research Database (Denmark)

    Damgaard, Morten; Norsk, Peter; Gustafsson, Finn;

    2005-01-01

    Patients with untreated heart failure (HF) exhibit a blunted hemodynamic and neuroendocrine response to a high sodium intake, leading to excessive sodium and water retention. However, it is not known whether this is the case for patients with compensated HF receiving angiotensin-converting enzyme....... In conclusion, high sodium intake was tolerated without any excessive sodium and water retention in medically treated patients with compensated HF. The observation that high sodium intake improves cardiac performance, induces peripheral vasodilatation, and suppresses the release of vasoconstrictor hormones does......-state conditions, hemodynamic and neuroendocrine examinations were performed at rest and during bicycle exercise. In seated HF patients, high sodium intake increased body weight (1.6 +/- 0.4%), plasma volume (9 +/- 2%), cardiac index (14 +/- 6%), and stroke volume index (21 +/- 5%), whereas mean arterial pressure...

  3. Neuroendocrine and renal effects of intravascular volume expansion in compensated heart failure

    DEFF Research Database (Denmark)

    Gabrielsen, A; Bie, P; Holstein-Rathlou, N H;

    2001-01-01

    To examine if the neuroendocrine link between volume sensing and renal function is preserved in compensated chronic heart failure [HF, ejection fraction 0.29 +/- 0.03 (mean +/- SE)] we tested the hypothesis that intravascular and central blood volume expansion by 3 h of water immersion (WI) elicits...... sustained angiotensin-converting enzyme inhibitor therapy, n = 9) absolute and fractional sodium excretion increased (P Renal free water clearance increased during WI in control subjects but not in HF......, albeit plasma vasopressin concentrations were similar in the two groups. In conclusion, the neuroendocrine link between volume sensing and renal sodium excretion is preserved in compensated HF. The natriuresis of WI is, however, modulated by the prevailing ANG II and Aldo concentrations. In contrast...

  4. Mathematical modeling of the circadian dynamics of the neuroendocrine-immune network in experimentally induced arthritis.

    Science.gov (United States)

    Rao, R; DuBois, D; Almon, R; Jusko, W J; Androulakis, I P

    2016-08-01

    The circadian dynamics of important neuroendocrine-immune mediators have been implicated in progression of rheumatoid arthritis pathophysiology, both clinically as well as in animal models. We present a mathematical model that describes the circadian interactions between mediators of the hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines. Model predictions demonstrate that chronically elevated cytokine expression results in the development of adrenal insufficiency and circadian variability in paw edema. Notably, our model also predicts that an increase in mean secretion of corticosterone (CST) after the induction of the disease is accompanied by a decrease in the amplitude of the CST oscillation. Furthermore, alterations in the phase of circadian oscillation of both cytokines and HPA axis mediators are observed. Therefore, by incorporating the circadian interactions between the neuroendocrine-immune mediators, our model is able to simulate important features of rheumatoid arthritis pathophysiology. PMID:27221115

  5. Modified liver-free multivisceral transplantation for a metastatic small bowel neuroendocrine tumor: a case report.

    Science.gov (United States)

    Frilling, A; Giele, H; Vrakas, G; Reddy, S; Macedo, R; Al-Nahhas, A; Wasan, H; Clift, A K; Gondolesi, G E; Vianna, R M; Friend, P; Vaidya, A

    2015-04-01

    Neuroendocrine tumors originating from the small bowel frequently metastasize to the lymph nodes and/or liver. Although surgical extirpation of the primary tumor and locoregional metastases epitomizes the management of patients with such tumors, this is not always possible with conventional surgical techniques. Nonresectable, slow-growing tumors involving the mesenteric root represent a generally accepted indication for deceased donor intestinal and multivisceral transplantation. Furthermore, vascularized sentinel forearm flaps offer opportunities for monitoring graft rejection and tailoring immunosuppression regimens. Here, we report the first documented case of modified liver-free multivisceral transplantation preceded by neoadjuvant 177-lutetium peptide receptor radionuclide therapy in a patient with a small bowel neuroendocrine tumor and extensive lymph node metastases in the mesenterium. At a follow-up of 21 months the patient is biochemically and radiologically disease-free. PMID:25689880

  6. PICK1 expression in the Drosophila central nervous system primarily occurs in the neuroendocrine system

    DEFF Research Database (Denmark)

    Jansen, Anna M; Nässel, Dick R; Madsen, Kenneth L;

    2009-01-01

    in the adult and larval Drosophila central nervous system. PICK1 was found in cell bodies in the subesophageal ganglion, the antennal lobe, the protocerebrum, and the neuroendocrine center pars intercerebralis. The cell types that express PICK1 were identified using GAL4 enhancer trap lines. The PICK1...... (AMPA) receptor subunit GluR2 and the dopamine transporter. PICK1 is strongly implicated in GluR2 trafficking and synaptic plasticity. In mammals, PICK1 has been characterized extensively in cell culture studies. To study PICK1 in an intact system, we characterized PICK1 expression immunohistochemically...... neurons in the neuroendocrine system, which express the transcription factor DIMM and the amidating enzyme peptidylglycine-alpha-hydroxylating monooxygenase (PHM). The PICK1-positive cells include neurosecretory cells that produce the insulin-like peptide dILP2. PICK1 expression in insulin-producing cells...

  7. An Eustachian Tube Neuroendocrine Carcinoma: A Previously Undescribed Entity and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Gavin J. le Nobel

    2016-01-01

    Full Text Available Primary sinonasal and middle ear neuroendocrine carcinomas are rare malignancies of the head and neck. Owing to the rarity of these tumors, the clinical behavior and optimal management of these tumors are not well defined. We present a case of an incidentally discovered sinonasal neuroendocrine carcinoma that was found to originate from the Eustachian tube, which has not previously been described in the literature. This patient was treated with primary surgical resection using a combination of transnasal and transaural approaches and achieved an incomplete resection. Follow-up imaging demonstrated continued tumor growth in the Eustachian tube as well as a new growth in the ipsilateral cerebellopontine angle and findings suspicious of perineural invasion. However, the tumor exhibited a benign growth pattern and despite continued growth the patient did not receive additional treatment and he remains asymptomatic 35 months following his original surgery.

  8. Somatostatin Analogs Therapy in Gastroenteropancreatic Neuroendocrine Tumors: Current Aspects and New Perspectives

    OpenAIRE

    Baldelli, Roberto; Barnabei, A.; Rizza, L; Isidori, A. M.; Rota, F.; Di Giacinto, P.; Paoloni, A.; F. Torino; Corsello, S. M.; Lenzi, A; Appetecchia, M

    2014-01-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP-NET while in metastatic disease multiple therapeutic approaches are possible. GEP-NETs are able to express somatostatin receptors...

  9. Somatostatin analogues therapy in gastroenteropancreatic neuroendocrine tumours: current aspects and new perspectives

    OpenAIRE

    Roberto eBaldelli

    2014-01-01

    Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP NET while in metastatic disease multiple therapeutic approaches are possible. GEP NETs are able to express somatostatin recepto...

  10. Expression of O6-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm

    OpenAIRE

    Yang, Qiu-chen; Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Chen, Yuan-Jia; Chen, Min-hu; Chen, Jie

    2014-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O6-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to Novem...

  11. The Thymus–Neuroendocrine Axis: Physiology, Molecular Biology, and Therapeutic Potential of the Thymic Peptide Thymulin

    OpenAIRE

    Reggiani, Paula C.; Morel, Gustavo R.; Cónsole, Gloria M.; Barbeito, Claudio G; Rodriguez, Silvia S.; Brown, Oscar A.; Bellini, Maria Jose; Pléau, Jean-Marie; Dardenne, Mireille; Goya, Rodolfo G.

    2009-01-01

    Thymulin is a thymic hormone exclusively produced by the thymic epithelial cells. It consists of a nonapeptide component coupled to the ion zinc, which confers biological activity to the molecule. After its discovery in the early 1970s, thymulin was characterized as a thymic hormone involved in several aspects of intrathymic and extrathymic T cell differentiation. Subsequently, it was demonstrated that thymulin production and secretion is strongly influenced by the neuroendocrine system. Conv...

  12. Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

    Directory of Open Access Journals (Sweden)

    Petersenn Stephan

    2006-04-01

    Full Text Available Abstract Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide

  13. Therapy evaluation and diagnostic accuracy in neuroendocrine tumours: assessment of radiological methods

    Energy Technology Data Exchange (ETDEWEB)

    Elvin, A.

    1993-01-01

    The diagnostic accuracy of ultrasonically guided biopsy-gun biopsies was assessed in a group of 47 patients with suspected pancreatic carcinoma. A correct diagnosis was obtained in 44 of the 47 patients (94%). Twenty-five patients with known neuroendocrine tumour disease were biopsied with 1.2 mm and 0.9 mm biopsy-gun needles. The influence of treatment-related fibrosis was also evaluated. The overall diagnostic accuracy with the 0.9 mm needle was 69% as compared to 92% with the 1.2 mm needle. In order to assess the diagnostic accuracy rate for radiologists with different experience of biopsy procedures 175 cases of renal biopsy-gun biopsies were evaluated. No statistical significant difference was found between the different operators. The role of duplex Doppler ultrasound in monitoring interferon treatment-related changes in carcinoid metastases was evaluated. It present duplex Doppler ultrasound does not seem to play a role in the evaluation of tumour therapy in carcinoid patients. Therapy response evaluation was performed with MR imaging in a group of 17 patients with neuroendocrine liver metastases. A significant difference was found between patients responding to and patients with failure of treatment in terms of tumour T1, contrast enhancement and signal intensity ratio. This indicates that MR investigation may be used in therapy monitoring of patients with neuroendocrine metastases. The neuroendocrine-differentiated colonic carcinoma cell line (LCC-18) was transplanted to 29 mice to establish a tumour/animal model that would allow the monitoring of changes with MR imaging induced by interferon therapy and to evaluate whether the therapeutic response could be modulated by different interferon dosages. Interferon does not seem to have any prolonged anti-proliferative effect on the LCC-18 tumour cell line when transplanted to nude mice.

  14. Adiponectin Depolarizes Parvocellular Paraventricular Nucleus Neurons Controlling Neuroendocrine and Autonomic Function

    OpenAIRE

    Hoyda, Ted Donald; Samson, Willis Kendrick; Ferguson, Alastair Victor

    2008-01-01

    Adiponectin plays important roles in the control of energy homeostasis and autonomic function through peripheral and central nervous system actions. The paraventricular nucleus (PVN) of the hypothalamus is a primary site of neuroendocrine (NE) and autonomic integration, and, thus, a potential target for adiponectin actions. Here, we investigate actions of adiponectin on parvocellular PVN neurons. Adiponectin influenced the majority (65%) of parvocellular PVN neurons, depolarizing 47%, whereas...

  15. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

    OpenAIRE

    Barbara Seroczyńska; Patrycja Koszałka; Zofia Woźniak; Tomasz Bączek; Anna Lewczuk; Ilona Olędzka; Natalia Miękus; Jarosław Skokowski; Alina Plenis

    2013-01-01

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnos...

  16. Diagnosis, treatment and prognosis of neuroendocrine tumor in stomach and duodenum

    Directory of Open Access Journals (Sweden)

    Xiang-yao WANG

    2016-04-01

    Full Text Available Objective  To investigate the clinicopathological characteristics and prognosis of patients with neuroendocrine tumor in stomach and duodenum for early diagnosis. Methods  The clinical, endoscopic and pathological data of 20 patients admitted to the PLA General Hospital from Jan. 2012 to Jan. 2015 and diagnosed as gastric and duodenal neuroendocrine tumor were collected for retrospective analysis. The histopathological classification of the disease was made according to the WHO 2010 Classification of the Neuroendocrine Neoplasms. Result  Ten male and 10 female patients aged between 35 and 77 (mean 55.5±10.6 years old were recruited in the present study. Tumor located in the stomach in 13 cases, and in duodenum in 7 cases. The maximum diameter of the tumor was 0.2-2.5cm. Endoscopic features included polypoid protrusion, hemispheric submucosal protrusion, and mucosal erosion. All the patients were treated endoscopically, among them, four patients were treated with electrocoagulation and electrosection, 10 by endoscopic resection (EMR, and 6 by endoscopic submucosal dissection (ESD. In one patient, surgical excision was done after ESD. Biopsy under gastroscopy and endoscopic ultrasonography were conducive to the diagnosis and treatment. According to the histopathological classification, 19 cases were classified as NET grade 1, and another one as NET grade 2. The follow-up study showed no metastasis and recurrence. Conclusions  The early diagnosis and treatment for gastric and duodenal neuroendocrine tumor can lead to satisfactory results. DOI: 10.11855/j.issn.0577-7402.2016.03.12

  17. Positive affect and health-related neuroendocrine, cardiovascular, and inflammatory processes

    OpenAIRE

    Steptoe, A; Wardle, J; Marmot, M.

    2005-01-01

    Negative affective states such as depression are associated with premature mortality and increased risk of coronary heart disease, type 2 diabetes, and disability. It has been suggested that positive affective states are protective, but the pathways through which such effects might be mediated are poorly understood. Here we show that positive affect in middle-aged men and women is associated with reduced neuroendocrine, inflammatory, and cardiovascular activity. Positive affect was assessed b...

  18. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells

    OpenAIRE

    Lee, JK; Phillips, JW; Smith, BA; Park, JW; Stoyanova, T; McCaffrey, EF; Baertsch, R.; Sokolov, A.; Meyerowitz, JG; Mathis, C.; Cheng, D; Stuart, JM; Shokat, KM; Gustafson, WC; Huang, J.

    2016-01-01

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarci...

  19. Effect of Compassion Meditation on Neuroendocrine, Innate Immune and Behavioral Responses to Psychosocial Stress

    OpenAIRE

    Pace, Thaddeus W. W.; Negi, Lobsang Tenzin; Adame, Daniel D.; Cole, Steven P.; Sivilli, Teresa I.; Brown, Timothy D.; Issa, Michael J.; Raison, Charles L.

    2008-01-01

    Meditation practices may impact physiological pathways that are modulated by stress and relevant to disease. While much attention has been paid to meditation practices that emphasize calming the mind, improving focused attention, or developing mindfulness, less is known about meditation practices that foster compassion. Accordingly, the current study examined the effect of compassion meditation on innate immune, neuroendocrine and behavioral responses to psychosocial stress and evaluated the ...

  20. Neuroendocrine Profile in a Rat Model of Psychosocial Stress: Relation to Oxidative Stress

    OpenAIRE

    Colaianna, Marilena; Schiavone, Stefania; Zotti, Margherita; Tucci, Paolo; Morgese, Maria Grazia; Bäckdahl, Liselotte; Holmdahl, Rikard; Krause, Karl-Heinz; Cuomo, Vincenzo; Trabace, Luigia

    2013-01-01

    Aims: Psychosocial stress alters the hypothalamic-pituitary-adrenal axis (HPA-axis). Increasing evidence shows a link between these alterations and oxidant elevation. Oxidative stress is implicated in the stress response and in the pathogenesis of neurologic and psychiatric diseases. NADPH oxidases (NOXs) are a major source of reactive oxygen species (ROS) in the central nervous system. Here, we investigated the contributory role of NOX2-derived ROS to the development of neuroendocrine altera...

  1. Neuroendocrine tumours of the head and neck: anatomical, functional and molecular imaging and contemporary management

    OpenAIRE

    Subedi, Navaraj; Prestwich, Robin; Chowdhury, Fahmid; Patel, Chirag; Scarsbrook, Andrew

    2013-01-01

    Abstract Neuroendocrine tumours (NETs) of the head and neck are rare neoplasms and can be of epithelial or non-epithelial differentiation. Although the natural history of NETs is variable, it is crucial to establish an early diagnosis of these tumours as they can be potentially curable. Conventional anatomical imaging and functional imaging using radionuclide scintigraphy and positron emission tomography/computed tomography can be complementary for the diagnosis, staging and monitoring of tre...

  2. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression

    OpenAIRE

    Flavie eDarcet; Indira eMendez-David; Laurent eTritschler; Gardier, Alain M.; Jean-Philippe eGuilloux; Denis Joseph David

    2014-01-01

    Cognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders. Such deficits have been observed in various animal models based on environmental stress.Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression based on a chronic (4 weeks) corticosterone administration (CORT). Cognitive performances were assessed using behavioral tests measuring episodic (novel object r...

  3. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression

    OpenAIRE

    Darcet, Flavie; Mendez-David, Indira; Tritschler, Laurent; Gardier, Alain M.; Guilloux, Jean-Philippe; David, Denis J.

    2014-01-01

    Cognitive disturbances are often reported as serious incapacitating symptoms by patients suffering from major depressive disorders (MDDs). Such deficits have been observed in various animal models based on environmental stress. Here, we performed a complete characterization of cognitive functions in a neuroendocrine mouse model of depression based on a chronic (4 weeks) corticosterone administration (CORT). Cognitive performances were assessed using behavioral tests measuring episodic (novel ...

  4. Is There a Role for Liver Transplantation in Metastatic Pancreatic Neuroendocrine Tumors (PNET)?

    OpenAIRE

    Anthony Paul Gulati; Muhammad Wasif Saif

    2012-01-01

    Dear Sir, recently, we published an important report on the role of radiotherapy in pancreatic neuroendocrine tumors (PNET) consisting of our experience and the data presented at the 2012 ASCO Gastrointestinal Cancers Symposium by the University of Maryland School of Medicine, Baltimore, MD, USA and Johns Hopkins University School of Medicine, Baltimore, MD, USA [1, 2]. We received multiple calls, emails as well as questions by the patients about the role of liver transplant in this popula...

  5. New model for gastroenteropancreatic large-cell neuroendocrine carcinoma: establishment of two clinically relevant cell lines.

    Directory of Open Access Journals (Sweden)

    Andreas Krieg

    Full Text Available Recently, a novel WHO-classification has been introduced that divided gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN according to their proliferation index into G1- or G2-neuroendocrine tumors (NET and poorly differentiated small-cell or large-cell G3-neuroendocrine carcinomas (NEC. Our knowledge on primary NECs of the GEP-system is limited due to the rarity of these tumors and chemotherapeutic concepts of highly aggressive NEC do not provide convincing results. The aim of this study was to establish a reliable cell line model for NEC that could be helpful in identifying novel druggable molecular targets. Cell lines were established from liver (NEC-DUE1 or lymph node metastases (NEC-DUE2 from large cell NECs of the gastroesophageal junction and the large intestine, respectively. Morphological characteristics and expression of neuroendocrine markers were extensively analyzed. Chromosomal aberrations were mapped by array comparative genomic hybridization and DNA profiling was analyzed by DNA fingerprinting. In vitro and in vivo tumorigenicity was evaluated and the sensitivity against chemotherapeutic agents assessed. Both cell lines exhibited typical morphological and molecular features of large cell NEC. In vitro and in vivo experiments demonstrated that both cell lines retained their malignant properties. Whereas NEC-DUE1 and -DUE2 were resistant to chemotherapeutic drugs such as cisplatin, etoposide and oxaliplatin, a high sensitivity to 5-fluorouracil was observed for the NEC-DUE1 cell line. Taken together, we established and characterized the first GEP large-cell NEC cell lines that might serve as a helpful tool not only to understand the biology of these tumors, but also to establish novel targeted therapies in a preclinical setup.

  6. Posttraumatic stress disorder under ongoing threat: a review of neurobiological and neuroendocrine findings

    Directory of Open Access Journals (Sweden)

    Iro Fragkaki

    2016-08-01

    Full Text Available Background: Although numerous studies have investigated the neurobiology and neuroendocrinology of posttraumatic stress disorder (PTSD after single finished trauma, studies on PTSD under ongoing threat are scarce and it is still unclear whether these individuals present similar abnormalities. Objective: The purpose of this review is to present the neurobiological and neuroendocrine findings on PTSD under ongoing threat. Ongoing threat considerably affects PTSD severity and treatment response and thus disentangling its neurobiological and neuroendocrine differences from PTSD after finished trauma could provide useful information for treatment. Method: Eighteen studies that examined brain functioning and cortisol levels in relation to PTSD in individuals exposed to intimate partner violence, police officers, and fire fighters were included. Results: Hippocampal volume was decreased in PTSD under ongoing threat, although not consistently associated with symptom severity. The neuroimaging studies revealed that PTSD under ongoing threat was not characterized by reduced volume of amygdala or parahippocampal gyrus. The neurocircuitry model of PTSD after finished trauma with hyperactivation of amygdala and hypoactivation of prefrontal cortex and hippocampus was also confirmed in PTSD under ongoing threat. The neuroendocrine findings were inconsistent, revealing increased, decreased, or no association between cortisol levels and PTSD under ongoing threat. Conclusions: Although PTSD under ongoing threat is characterized by abnormal neurocircuitry patterns similar to those previously found in PTSD after finished trauma, this is less so for other neurobiological and in particular neuroendocrine findings. Direct comparisons between samples with ongoing versus finished trauma are needed in future research to draw more solid conclusions before administering cortisol to patients with PTSD under ongoing threat who may already exhibit increased endogenous

  7. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles

    OpenAIRE

    Grippo, Angela J.; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C. Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks o...

  8. A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells

    OpenAIRE

    Garabedian, Emily M.; Humphrey, Peter A.; Jeffrey I Gordon

    1998-01-01

    A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides −6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progres...

  9. Functional characterization of pulmonary neuroendocrine cells in lung development, injury, and tumorigenesis

    OpenAIRE

    Song, Hai; Yao, Erica; Lin, Chuwen; Gacayan, Rhodora; Chen, Miao-Hsueh; Chuang, Pao-Tien

    2012-01-01

    Pulmonary neuroendocrine cells (PNECs) are proposed to be the first specialized cell type to appear in the lung, but their ontogeny remains obscure. Although studies of PNECs have suggested their involvement in a number of lung functions, neither their in vivo significance nor the molecular mechanisms underlying them have been elucidated. Importantly, PNECs have long been speculated to constitute the cells of origin of human small-cell lung cancer (SCLC) and recent mouse models support this h...

  10. Liver metastases of neuroendocrine tumours; early reduction of tumour load to improve life expectancy

    Directory of Open Access Journals (Sweden)

    Lips Cornelis JM

    2006-06-01

    Full Text Available Abstract Background Neuroendocrine tumours frequently metastasize to the liver. Although generally slowly progressing, hepatic metastases are the major cause of carcinoid syndrome and ultimately lead to liver dysfunction, cardiac insufficiency and finally death. Methods A literature review was performed to define the optimal treatment strategy and work-up in patients with neuroendocrine hepatic metastases. Based on this, an algorithm for the management of these patients was established. Results Platelet serotonin and chromogranin A are useful biomarkers for detection and follow-up of neuroendocrine tumour. Helical computed tomography and somatostatin receptor scintigraphy are the most sensitive diagnostic modalities. Surgical debulking is an accepted approach for reducing hormonal symptoms and to establish better conditions for medical treatment, but is frequently impossible due to the extent of disease. A novel approach is the local ablation of tumour by thermal coagulation using therapies such as radiofrequency ablation (RFA or laser induced thermotherapy (LITT. These techniques preserve normal liver tissue. There is a tendency to destroy metastases early in the course of disease, thereby postponing or eliminating the surgically untreatable stage. This can be combined with postoperative radioactive octreotide to eliminate small multiple metastases. In patients with extensive metastases who are not suitable for local destruction, systemic therapy by octreotide, 131I-MIBG treatment or targeted chemo- and radiotherapy should be attempted. A final option for selective patients is orthotopic liver transplantation. Conclusion Treatment for patients with neuroendocrine hepatic metastases must be tailored for each individual patient. When local ablative therapies are used early in the course of the disease, the occurrence of carcinoid syndrome with end stage hepatic disease can be postponed or prevented.

  11. Classification of gastro-entero-pancreatic neuroendocrine tumors; Klassifikation gastroenteropankreatischer neuroendokriner Tumoren

    Energy Technology Data Exchange (ETDEWEB)

    Perren, A. [Klinikum Rechts der Isar, Technische UniversitaetMuenchen, Institut fuer Pathologie und pathologische Anatomie, Muenchen (Germany); Schmitt, A. [Universitaetsspital Zuerich, Institut fuer Klinische Pathologie, Departement Pathologie, Zuerich (Switzerland); Komminoth, P. [Stadtspital Triemli, Zuerich (Switzerland). Institut fuer Pathologie; Pavel, M. [Charite, Universitaetsmedizin Berlin (Germany). Medizinische Klinik mit Schwerpunkt Hepatologie and Gastroenterologie

    2009-03-15

    Tumors of the disseminated/diffuse neuroendocrine system (NET) are characterized by a common phenotype. However, the biology varies according to histomorphology, endocrine symptoms and organ of origin. The WHO classification takes these differences into account and uses a common framework, where the parameters size and extent of invasion vary according to the organ of origin. In order to achieve a further standardization of reporting the European Neuroendocrine Tumor Society (ENETS) recently proposed a tumor-node-metastasis (TNM) staging and grading system for gastro-entero-pancreatic NET. (orig.) [German] Tumoren des disseminierten/diffusen neuroendokrinen Systems sind durch einen gemeinsamen Phaenotyp gekennzeichnet. In ihrer Biologie unterscheiden sich neuroendokrine Tumoren (NET) jedoch bzgl. Morphologie, endokrinologischer Symptomatik und Ursprungsorgan. Die WHO-Klassifikation traegt diesen Unterschieden Rechnung und klassifiziert NET nach einem einheitlichen Vorgehen, wobei die Parameter Groesse und Invasionstiefe je nach Ursprungsorgan variieren. Um die Nomenklatur weiter zu vereinheitlichen, wurde vor kurzem von der ''European Neuroendocrine Tumor Society'' (ENETS) der Vorschlag einer TNM-Stadien-Einteilung und Graduierung gastroenteropankreatischer NET vorgelegt. (orig.)

  12. Temozolomide as Second or Third Line Treatment of Patients with Neuroendocrine Carcinomas

    Directory of Open Access Journals (Sweden)

    Ingrid H. Olsen

    2012-01-01

    Full Text Available Background. Knowledge of the clinical efficacy in recurrent neuroendocrine carcinomas is sparse. Treatment with temozolomide alone or in combination with capecitabine and bevacizumab has recently shown promising results. Patients and Methods. Analysis of consecutive patients with neuroendocrine carcinomas (Ki-67 proliferation index >20% and performance status 0–2 treated with temozolomide 200 mg/sqm orally days 1–5 every 28 days after at least one previous platin-containing chemotherapy regimen. Results. Twenty-eight eligible patients received a median of 3 courses. Sixteen patients were evaluable for response: Six achieved stable disease and ten progressed. The median survival for the 28 patients was 3.5 months. Survival in patients with tumors of pancreatic origin (n=7 was 7.0 months versus 2.9 months in non-pancreatic origin (n=21. Patients in PS 0-1 (n=22 had a median survival of 4.5 months versus 1.1 months in patients in PS 2 (n=6. Ki-67 index ≥50% was associated with a significantly shorter median survival than Ki-67 index <50% (2.7 months versus 10.9 months. The treatment was well tolerated. Conclusion. Temozolomide monotherapy has limited effect in treatment of recurrent neuroendocrine carcinomas. Second line treatment with temozolomide in combination with other compounds should be further investigated in patients in good performance with Ki-67 index <50%.

  13. Tumeur neuroendocrine mammaire primitive: à propos d'un cas rare

    Science.gov (United States)

    Laabadi, Kamilia; Jayi, Sofia; El Houari, Aziza; Tawfic, Harmouch; Bouguern, Hakima; Chaara, Hikmat; Melhouf, Abdilah; Amarti, Afaf

    2013-01-01

    Les carcinomes neuroendocrine primitifs du sein sont des tumeurs rares et représentent 2 à 5% des cancers mammaires. Nous rapportons le cas de localisation mammaire chez une patiente de 50 ans. Il s'agit d'une tumeur classée T4d N1 M0. La tumeur est suspecte radiologiquement. Une microbiopsie est réalisée. L’étude anatomopathologique et immunohistochimique est en faveur d'une tumeur neuroendocrine primitive du sein à grande cellules exprimant les récepteurs progestéroniques seulement. Vu le caractère inflammatoire de la tumeur une chimiothérapie est démarrée avec bonne évolution clinique. A la fin de la chimiothérapie on prévoit de réaliser une mastectomie avec curage axillaire et en fonction des résultats définitifs, une radiothérapie. Une hormonothérapie sera envisagée une 2ème étude immunohistochimique sur la pièce de mastectomie. Vu la rareté des carcinomes neuroendocrines mammaires primitifs, il n'existe pas de standard thérapeutique et le pronostic demeure difficile à déterminer. PMID:24772221

  14. Regulation of neuroendocrine cells and neuron factors in the ovary by zinc oxide nanoparticles.

    Science.gov (United States)

    Liu, Xin-Qi; Zhang, Hong-Fu; Zhang, Wei-Dong; Zhang, Peng-Fei; Hao, Ya-Nan; Song, Ran; Li, Lan; Feng, Yan-Ni; Hao, Zhi-Hui; Shen, Wei; Min, Ling-Jiang; Yang, Hong-Di; Zhao, Yong

    2016-08-10

    The pubertal period is an important window during the development of the female reproductive system. Development of the pubertal ovary, which supplies the oocytes intended for fertilization, requires growth factors, hormones, and neuronal factors. It has been reported that zinc oxide nanoparticles (ZnO NPs) cause cytotoxicity of neuron cells. However, there have been no reports of the effects of ZnO NPs on neuronal factors and neuroendocrine cells in the ovary (in vivo). For the first time, this in vivo study investigated the effects of ZnO NPs on gene and protein expression of neuronal factors and the population of neuroendocrine cells in ovaries. Intact NPs were detected in ovarian tissue and although ZnO NPs did not alter body weight, they reduced the ovary organ index. Compared to the control or ZnSO4 treatments, ZnO NPs treatments differentially regulated neuronal factor protein and gene expression, and the population of neuroendocrine cells. ZnO NPs changed the contents of essential elements in the ovary; however, they did not alter levels of the steroid hormones estrogen and progesterone. These data together suggest that intact ZnO NPs might pose a toxic effect on neuron development in the ovary and eventually negatively affect ovarian developmental at puberty. PMID:27215404

  15. Neuroendocrine and squamous colonic composite carcinoma: Case report with molecular analysis

    Institute of Scientific and Technical Information of China (English)

    Sabrina C Wentz; Cindy Vnencak-Jones; William V Chopp

    2011-01-01

    Composite colorectal carcinomas are rare. There are a modest number of cases in the medical literature, with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There are to our knowledge no reports of composite carcinoma molecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau casian male to investigate the presence and prognos tic significance of molecular alterations in rare colonic carcinoma subtypes. Formalin-fixed paraffin-embedded (FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol, and immuno-stained with cytokeratin (CK)7, CK20, CDX2, AE1/AE3, chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performedaccording to lab-developed methods, followed by capil lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squa mous cells. Positive nuclear CDX2 expression confirmed intestinal derivation. CK7 and CK20 were negative. Neuroendocrine cells stained positively for synaptophy sin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar im munohistochemical profile. Molecular analysis revealed a G13D KRAS mutation. BRAF mutational testing was negative and microsatellite instability was not detected. The patient had rapid disease progression on chemo therapy and died 60 d after presentation. Although the G13D KRAS mutation normally predicts an intermediate outcome, the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

  16. CT and magnetic resonance imaging features of middle ear adenoma of neuroendocrine differentiation: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Kwon; Choe, Mi Sun [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    2013-09-15

    Middle ear adenoma is a rare benign epithelial tumor. We report the CT and magnetic resonance imaging findings of a case of middle ear adenoma of neuroendocrine differentiation in a 36-year-old man. On high-resolution CT, the mass was found to fill the middle ear, in which the ossicles were embedded, but not destroyed, with outward bulging of the intact tympanic membrane. On MRI, the mass, which was intensely enhanced on 3-dimensional (3D) gadolinium (Gd)-enhanced spoiled gradient-recalled (SPGR) sequence, involved the middle ear, aditus ad antrum and a portion of mastoid antrum. Histological and immunohistochemical findings of the specimen obtained by surgical excisions were consistent with middle ear adenoma of neuroendocrine differentiation. Middle ear adenoma of neuroendocrine differentiation should be included in the differential diagnosis of an intensely enhancing mass filling the middle ear/mastoid antrum without ossicular destructions. The extent of the mass can be excellently assessed with 3D Gd-enhanced SPGR sequence.

  17. CT and magnetic resonance imaging features of middle ear adenoma of neuroendocrine differentiation: A case report

    International Nuclear Information System (INIS)

    Middle ear adenoma is a rare benign epithelial tumor. We report the CT and magnetic resonance imaging findings of a case of middle ear adenoma of neuroendocrine differentiation in a 36-year-old man. On high-resolution CT, the mass was found to fill the middle ear, in which the ossicles were embedded, but not destroyed, with outward bulging of the intact tympanic membrane. On MRI, the mass, which was intensely enhanced on 3-dimensional (3D) gadolinium (Gd)-enhanced spoiled gradient-recalled (SPGR) sequence, involved the middle ear, aditus ad antrum and a portion of mastoid antrum. Histological and immunohistochemical findings of the specimen obtained by surgical excisions were consistent with middle ear adenoma of neuroendocrine differentiation. Middle ear adenoma of neuroendocrine differentiation should be included in the differential diagnosis of an intensely enhancing mass filling the middle ear/mastoid antrum without ossicular destructions. The extent of the mass can be excellently assessed with 3D Gd-enhanced SPGR sequence.

  18. INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

    2013-03-22

    Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

  19. Relaxin-3/RXFP3 signaling and neuroendocrine function – A perspective on extrinsic hypothalamic control

    Directory of Open Access Journals (Sweden)

    Despina E Ganella

    2013-09-01

    Full Text Available Complex neural circuits within the hypothalamus that govern essential autonomic processes and associated behaviors signal using amino acid and monoamine transmitters and a variety of neuropeptide (hormone modulators, often via G-protein coupled receptors (GPCRs and associated cellular pathways. Relaxin-3 is a recently identified neuropeptide that is highly conserved throughout evolution. Neurons expressing relaxin-3 are located in the brainstem, but broadly innervate the entire limbic system including the hypothalamus. Extensive anatomical data in rodents and non-human primate, and recent regulatory and functional data, suggest relaxin-3 signaling via its cognate GPCR, RXFP3, has a broad range of effects on neuroendocrine function associated with stress responses, feeding and metabolism, motivation and reward, and possibly sexual behavior and reproduction. Therefore, this article aims to highlight the growing appreciation of the relaxin-3/RXFP3 system as an important ‘extrinsic’ regulator of the neuroendocrine axis by reviewing its neuroanatomy and its putative roles in arousal-, stress- and feeding-related behaviors and links to associated neural substrates and signaling networks. Current evidence identifies RXFP3 as a potential therapeutic target for treatment of neuroendocrine disorders and related behavioral dysfunction.

  20. Somatostatin receptor subtypes in neuroendocrine tumor cell lines and tumor tissues.

    Science.gov (United States)

    Jonas, S; John, M; Boese-Landgraf, J; Häring, R; Prevost, G; Thomas, F; Rosewicz, S; Riecken, E O; Wiedenmann, B; Neuhaus, P

    1995-01-01

    Somatostatin receptor scintigraphy (SRS) is positive in approximately 80% of all patients who have been found to have neuroendocrine (NE) gastroenteropancreatic (GEP) tumors. The reasons for negative results are unclear. The aim of the present study was identification of the specific somatostatin receptor (SSTR) subtypes that are responsible for the in vivo binding of the widely used somatostatin (SST) analogues octreotide and lanreotide in human neuroendocrine gastroenteropancreatic tumors. Ten patients were subjected to SRS with radiolabeled octreotide. Following surgical resection, tumor tissues were analyzed for SSTR subtype mRNA expression by the reverse transcription-polymerase chain reaction (RT-PCR). In addition, SSTR subtype transcripts were investigated by Northern blot analysis and RT-PCR in neuroendocrine tumor cell lines. Expression of SSTR at the protein level was studied by chemical cross-linking experiments. Three patients were negative by SRS. However, RT-PCR revealed most prominently SSTR 2 expression in all tumor specimens. In addition, all tumor tissues analyzed by chemical crosslinking exhibited SST-14 binding sites, indicating that at least some NE tumors were false-negative on SRS.

  1. Clinical Analysis of 22 Cases of Pulmonary Large Cell Neuroendocrine Cancer

    Directory of Open Access Journals (Sweden)

    Zhe QIAN

    2016-02-01

    Full Text Available Background and objective Pulmonary large cell neuroendocrine carcinoma (LCNEC is a rare primary malignant tumor. Due to poor understanding of its biologic behaviors, pathological features, image manifestations and clinical effects, clinical study is urgent. Analysis of clinical data of pulmonary LCNEC, in order to improve the clinical diagnosis and treatment. Methods Retrospective analysis of 22 pulmonary LCNEC cases of clinical features, diagnosis, treatments and prognosis. Results Pulmonary large cell neuroendocrine carcinoma occurs in older men with heavy smoking history., clinical symptoms are cough, sputum, hemoptysis, and chest pain. Computed tomography (CT features are peripheral mass mainly, accompanied by heterogeneous density and necrosis. Immunohistochemical neuroendocrine differentiation markers Syn, CgA and CD56 positive expression rates were: 72.7%, 68.2% and 68.2%, respectively. 17 patients underwent surgical treatment, 10 patients received adjuvant therapy, 5 underwent palliative chemotherapy. Univariate analysis indicated that smoking index (P=0.029, lymph node metastasis (P=0.034, tumor-node-metastasis (TNM stage (P=0.005, treatment (P=0.047, postoperative chemotherapy (P=0.014 are prognostic factors. Multivariate analysis showed that lymph node metastasis (P=0.045 and postoperative chemotherapy (P=0.024 are prognostic factors. Conclusion Pulmonary LCNEC is lack of specific clinical symptoms, and its pathological diagnosis depends on postoperative specimens, poor efficacy of various treatments is its current situation. Lymph node metastasis and postoperative chemotherapy are important prognostic factors.

  2. Immune neuroendocrine phenotypes in Coturnix coturnix: do avian species show LEWIS/FISCHER-like profiles?

    Directory of Open Access Journals (Sweden)

    F Nicolas Nazar

    Full Text Available Immunoneuroendocrinology studies have identified conserved communicational paths in birds and mammals, e.g. the Hypothalamus-Pituitary-Adrenal axis with anti-inflammatory activity mediated by glucocorticoids. Immune neuroendocrine phenotypes (INPs have been proposed for mammals implying the categorization of a population in subgroups underlying divergent immune-neuroendocrine interactions. These phenotypes were studied in the context of the LEWIS/FISCHER paradigm (rats expressing high or low pro-inflammatory profiles, respectively. Although avian species have some common immunological mechanisms with mammals, they have also evolved some distinct strategies and, until now, it has not been studied whether birds may also share with mammals similar INPs. Based on corticosterone levels we determined the existence of two divergent groups in Coturnix coturnix that also differed in other immune-neuroendocrine responses. Quail with lowest corticosterone showed higher lymphoproliferative and antibody responses, interferon-γ and interleukin-1β mRNA expression levels and lower frequencies of leukocyte subpopulations distribution and interleukin-13 levels, than their higher corticosterone counterparts. Results suggest the existence of INPs in birds, comparable to mammalian LEWIS/FISCHER profiles, where basal corticosterone also underlies responses of comparable variables associated to the phenotypes. Concluding, INP may not be a mammalian distinct feature, leading to discuss whether these profiles represent a parallel phenomenon evolved in birds and mammals, or a common feature inherited from a reptilian ancestor millions of years ago.

  3. Common Diagnostic Challenges in the Histopathologic Diagnosis of Neuroendocrine Lung Tumors: A Case Report

    Directory of Open Access Journals (Sweden)

    Monica Valente

    2010-07-01

    Full Text Available Bronchopulmonary neuroendocrine tumors are an uncommon group of neoplasms, accounting for about 20% of all lung carcinomas, arising from stem cells of the bronchial epithelium known as Kulchitsky cells. In the past, these tumors were grouped among benign or less aggressive malignant pulmonary tumors. Currently, according to the 2004 World Health Organization categorization, these tumors are separated into 4 subtypes characterized by increasing biologic aggressiveness: low-grade (typical carcinoid; TC, intermediate-grade (atypical carcinoid; AC and high-grade (large-cell neuroendocrine carcinoma, LCNEC, and small-cell lung carcinoma, SCLC. They differ by morphologic, immunohistochemical and structural features. At histopathologic analysis, these tumors share progressive increase in a number of mitotic figures per 10 high-power fields and in the extent of necrosis, with TC having the lowest values and SCLC having the highest. TCs and ACs make up approximately 1–2% of all primary lung tumors. Differentiating ACs from TCs or LCNEC and SCLC is clinically important because the treatment modalities and prognoses for these types of tumors are different. We report a case of misdiagnosis of bronchopulmonary neuroendocrine tumor in a young woman which has heavily influenced her clinical history.

  4. Late neuro endocrinological sequelae of radiation therapy; Effets tardifs de la radiotherapie sur la sphere neuroendocrine

    Energy Technology Data Exchange (ETDEWEB)

    Bieri, S.; Bernier, J. [Ospedale San Giovanni (Switzerland); Sklar, C. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Constine, L. [Rochester Univ., NY (United States)

    1997-12-01

    When the hypothalamic-pituitary axis (HPA) is included in the treatment field in children and adults, a variety of neuroendocrine disturbances are more common than has been appreciated in the past. Clinical damage to the pituitary and thyroid glands usually occurs months to years after treatment, and is preceded by a long subclinical phase. Primary brain tumors represent the largest group of malignant solid tumors in children. The survival rates of 50 reported in the literature are achieved at the expense of late occurring effects. Radiation-induced abnormalities are generally dose-dependent. Growth hormone deficiency and premature sexual development can occur at doses as low as 18 Gy in conventional fractionation, and is the most common neuroendocrine problem in children. In patients treated with > 40 Gy on the HPA, deficiency of gonadotropins, thyroid stimulation hormone, and adrenocorticotropin (> 50 Gy), hyperprolactinemia can be seen, especially among young women. Most neuroendocrine disturbances that develop as a result of HPA can be treated efficiently, provided that an early detection of these endocrine dysfunctions abnormalities is done. (authors)

  5. Recombinant TSH (Thyrogen) administration to a patient with metastatic well differentiated thyroid carcinoma in whom six weeks of T-4 withdrawal led to a sub-optimal TSH response

    International Nuclear Information System (INIS)

    increased uptake in the majority of the lung nodules, unresponsive to the I-131 therapy. Conclusion: A case is presented in which functioning thyroid metastases inhibited TSH stimulation after T-4 withdrawal, precluding the administration of I-131 therapy. Administration of Thyrogen facilitated I-131 therapy. Despite two more I-131 therapies , the patient died less than four years later from progressive metastases to the skull, spine and femur, and displayed a reduction in TG levels with increasing Tl-201 uptake. Delayed I-131 treatment for well-differentiated thyroid carcinoma may seriously compromise patient's survival

  6. Influence of chemiotherapeutic protocol and neuroendocrine differentiation on metastatic non-small cell lung cancer treatment results

    Directory of Open Access Journals (Sweden)

    Tomić Ilija

    2007-01-01

    Full Text Available Background/Aim. In 40-50% of patients with non-small cell lung cancer (NSCLC at the time of making a diagnosis, the disease is yet at IIIb and IV stage. Standard in the treatment of these patient is the application of systemic chemiotherapy based on CIS/Carboplatin preparations. The aim of this study was to determine the influence of two different chemiotherapeutic protocols and neuroendocrine differentiation on treatment response and survival in patients with metastatic NSCLC. Methods. We examined 85 patients with metastatic NSCLC, of which 51 with stage IIIb, and 34 with stage IV of the disease. The histologic diagnosis of NSCLC was determined by tissue assays using hematoxylin eosin method. Neuroendocrine differentiation was determined by immunohistochemical analysis of neuron- specific enolase (NSE, chromogranin A, and synapthophysin expression using monoclonal mouse anti- human bodies (DAKO, Denmark. According to chemiotherapeutic protocol, the patients were randomly assigned into combined Taxol + Cisplatin group (Tax + Cis, n = 35, and Cyclophosphamide + Etoposide + Carboplatin group (CEP, n = 50. The treatment was conducted within 4-6 chemiotherapeutic cycles. The efficacy was assessed after the therapy regimen and median survival time was assessed after the randomization. Results. A total of 31 (36.47% patients had a favourable therapeutic response, both partial and complete response (54.2% in the Tax + Cis group and 24% in CEP group of patients, respectively, p < 0.001. The median survival time in both groups was 13.1 months (15.3 months in the Tax + Cis group and 10.6 months in the CEP group, respectively, p < 0.001. A one-year follow-up survival period was confirmed in 40% of patients (60% only in the Tax + Cis group. A total of 23 (27.05% patients with metastatic NSCLC had neuroendocrine differentiation. The disease progression or stable disease was noted only in patient with NSCLC without neuroendocrine differentiation (n = 42, 67

  7. Interleukin-6- and Cyclic AMP-Mediated Signaling Potentiates Neuroendocrine Differentiation of LNCaP Prostate Tumor Cells

    Science.gov (United States)

    Deeble, Paul D.; Murphy, Daniel J.; Parsons, Sarah J.; Cox, Michael E.

    2001-01-01

    Neuroendocrine (NE) differentiation in prostatic adenocarcinomas has been reported to be an early marker for development of androgen independence. Secretion of mitogenic peptides from nondividing NE cells is thought to contribute to a more aggressive disease by promoting the proliferation of surrounding tumor cells. We undertook studies to determine whether the prostate cancer cell line LNCaP could be induced to acquire NE characteristics by treatment with agents that are found in the complex environment in which progression of prostate cancer towards androgen independence occurs. We found that cotreatment of LNCaP cells with agents that signal through cyclic AMP-dependent protein kinase (PKA), such as epinephrine and forskolin, and with the cytokine interleukin-6 (IL-6) promoted the acquisition of an NE morphological phenotype above that seen with single agents. Convergent IL-6 and PKA signaling also resulted in potentiated mitogen-activated protein kinase (MAPK) activation without affecting the level of signal transducer and activator of transcription or PKA activation observed with these agents alone. Cotreatment with epinephrine and IL-6 synergistically increased c-fos transcription as well as transcription from the β4 nicotinic acetylcholine receptor subunit promoter. Potentiated transcription from these elements was shown to be dependent on the MAPK pathway. Most importantly, cotreatment with PKA activators and IL-6 resulted in increased secretion of mitogenic neuropeptides. These results indicate that PKA and IL-6 signaling participates in gene transcriptional changes that reflect acquisition of an NE phenotype by LNCaP cells and suggest that similar signaling mechanisms, particularly at sites of metastasis, may be responsible for the increased NE content of many advanced prostate carcinomas. PMID:11713282

  8. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

    International Nuclear Information System (INIS)

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [90Y-DOTA]-TOC or [177Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [90Y-DOTA]-TOC and 141 patients underwent 259 cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC. (orig.)

  9. C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

    Science.gov (United States)

    Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery. PMID:24599901

  10. 18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen;

    2014-01-01

    INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

  11. Imaging secondary neuroendocrine tumours of the liver: comparison of I123 metaiodobenzylguanidine (MIBG) and In111-labelled octreotide (Octreoscan).

    Science.gov (United States)

    Ramage, J K; Williams, R; Buxton-Thomas, M

    1996-07-01

    Functional imaging of neuroendocrine tumours with Octreoscan and I123-metaiodobenzylguanidine (MIBG) is important for assessment prior to various therapies and assessing response. The two imaging methods have not been directly compared in hepatic neuroendocrine tumours. Patients (n = 18) were studied with both imaging techniques. The sensitivity of Octreoscan was 94%, and that of MIBG 39%. No previously occult primary sites were detected. Concurrent octreotide therapy did not reduce the sensitivity of Octreoscan. Widespread bone metastases were seen in two post-liver-transplant patients using Octreoscan. Octreoscan is a sensitive means of detecting hepatic neuroendocrine tumours, and the more specific technique. MIBG has poor sensitivity, reducing its clinical utility. Therapy with I131-MIBG is likely to be applicable to relatively few patients. PMID:8759495

  12. Filial caregiving is associated with greater neuroendocrine dysfunction: Evidence from the 2005 National Survey of Midlife in the United States

    Directory of Open Access Journals (Sweden)

    SunWoo Kang

    2014-01-01

    Full Text Available Objectives: This study examined associations between providing caregiving for a biological or adoptive parent and clinically assessed biological risk factors (allostatic load and its three subscales—inflammatory dysfunction, metabolic dysfunction, and neuroendocrine dysfunction, as well as moderation of these associations by gender. Methods: Regression models were estimated using telephone and self-report data from 962 men and women who participated in the National Survey of Midlife in the United States in 2005. Results: Filial caregivers demonstrated higher levels of neuroendocrine dysfunction. No gender difference in biological risks was found. Discussion: Filial caregiving is the most prevalent form of family caregiving, and results indicating the presence of greater neuroendocrine dysfunction among filial caregivers in contrast to noncaregivers suggest an important public health concern. Future research needs to continue to examine different relationship types of caregivers and include a range of biological risk measurement to further the understanding of how family caregiving is linked to biological health risks.

  13. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    International Nuclear Information System (INIS)

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  14. Neuroendocrine tumors of the lung: hystological classification, diagnosis, traditional and new therapeutic approaches.

    Science.gov (United States)

    Cueto, A; Burigana, F; Nicolini, A; Lugnani, F

    2014-01-01

    Lung neuroendocrine tumors are neoplasms originating from bronchopulmonary neuroendocrine cells, usually Kulchitsky cells, loaded with argentaffin granules. They account for 20-25% of all primitive lung tumors, the most common being the small-cell undifferentiated carcinoma. They include different tumors, from tumors of low-grade malignancy, especially the typical carcinoids, with high survival rates after surgical therapy, to the high-grade malignancy tumors, especially small-cell undifferentiated carcinomas. The latter have very few indications for surgical treatment with a low survival rate, even after multimodal therapy. The aim of this review is to describe the present knowledge and discuss possible new developments in the management of pulmonary neuroendocrine tumors. The authors examine and discuss in particular the role that surgical techniques should have in the treatment of small-cell lung cancer in opposition to a nihilism position that has limited therapies to non-surgical approaches. The critical review of this attitude opens the door to a more aggressive approach. In the meantime the review shows that it might be possible to include the new minimally invasive percutaneous ablative techniques as cryosurgery, thermotherapy and irreversible electroporation within a modern and flexible framework. The authors also present the hypothesis that cancer stem cells (CSC) are at the basis of recurrences of small-cell lung cancer (SCLC) and therefore that the issue is of difficult solution with the conventional oncologic approach considering the chemo-resistance of CSC to drugs. For these reasons an epigenetic therapy based on differentiation factors is proposed alongside the usual surgical and chemo-radiation protocols. PMID:24304279

  15. Prenatal caffeine ingestion induces transgenerational neuroendocrine metabolic programming alteration in second generation rats

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Deng, Zixin; Liu, Lian; Shen, Lang; Kou, Hao; He, Zheng [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, Jie; Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology and Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2014-02-01

    Our previous studies have demonstrated that prenatal caffeine ingestion induces an increased susceptibility to metabolic syndrome with alterations of glucose and lipid metabolic phenotypes in adult first generation (F1) of intrauterine growth retardation (IUGR) rats, and the underlying mechanism is originated from a hypothalamic–pituitary–adrenal (HPA) axis-associated neuroendocrine metabolic programming alteration in utero. This study aims to investigate the transgenerational effects of this programming alteration in adult second generation (F2). Pregnant Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. Four groups in F2 were set according to the cross-mating between control and caffeine-induced IUGR rats. F2 were subjected to a fortnight ice water swimming stimulus on postnatal month 4, and blood samples were collected before and after stress. Results showed that the majority of the activities of HPA axis and phenotypes of glucose and lipid metabolism were altered in F2. Particularly, comparing with the control group, caffeine groups had an enhanced corticosterone levels after chronic stress. Compared with before stress, the serum glucose levels were increased in some groups whereas the triglyceride levels were decreased. Furthermore, total cholesterol gain rates were enhanced but the high-density lipoprotein-cholesterol gain rates were decreased in most caffeine groups after stress. These transgenerational effects were characterized partially with gender and parental differences. Taken together, these results indicate that the reproductive and developmental toxicities and the neuroendocrine metabolic programming mechanism by prenatal caffeine ingestion have transgenerational effects in rats, which may help to explain the susceptibility to metabolic syndrome and associated diseases in F2. - Highlights: • Caffeine-induced neuroendocrine metabolic programming of HPA has hereditary effect. • Caffeine

  16. Neuroendocrine liver metastases: Contributions of endoscopy and surgery to primary tumor search

    Institute of Scientific and Technical Information of China (English)

    Herwig Cerwenka

    2012-01-01

    Neuroendocrine tumors (NETs) are diagnosed with increasing frequency and patients often present with liver metastases at the time of diagnosis.Apart from treatment of the metastases,resection of the primary tumor at an early phase is recommended to prevent complications,although it may be difficult to locate,especially in patients with functionally inactive NETs.Small and multifocal tumors in the jejunum and ileum represent a particular challenge.Primary hepatic neuroendocrine carcinoma is extremely rare and is diagnosed only after exclusion of other primary tumors.Therefore,some uncertainty may remain,as small non-hepatic primary tumors may escape detection.Diagnostic work-up in these patients includes biochemical assays and imaging modalities (also comprising specific techniques of scintigraphy and positron emission tomography).This editorial highlights the contributions of endoscopy and operative exploration to the search for the primary tumor.Besides esophagogastro-duodenoscopy,endoscopic ultrasonography,colonoscopy and bronchoscopy,special endoscopic techniques such as balloon enteroscopy or capsule endoscopy are used with growing experience.Compared with balloon enteroscopy,capsule endoscopy is noninvasive and better tolerated,but it cannot localize a lesion precisely and does not allow biopsy or removal of lesions.Before proceeding to surgery,a discussion of the findings by a tumor board should be a standard procedure.Improvements in diagnostic tools have created new perspectives for the detection of obscure primary tumors in patients with neuroendocrine liver metastases,and these searches are best coordinated by a multidisciplinary team.

  17. Stress and affective disorders: animal models elucidating the molecular basis of neuroendocrine-behavior interactions.

    Science.gov (United States)

    Touma, C

    2011-05-01

    Profound dysfunctions in several neuroendocrine systems have been described in patients suffering from affective disorders such as major depression. In order to elucidate the mechanisms underlying these functional alterations, animal models including mice genetically modified by either direct gene-targeting or by selective breeding approaches have been used exceedingly, revealing valuable insights into neuroendocrine pathways conserved between rodents and men. This review focuses on altered function and regulation of the hypothalamic-pituitary-adrenocortical axis, including its involvement in emotionality and stress responsiveness. In this context, the corticotropin-releasing hormone system and disturbances in glucocorticoid receptor signaling seem to be of central importance. However, changes in the expression and release patterns of vasopressin, dopamine and serotonin have also been shown to contribute to variation in emotionality, stress coping, cognitive functions and social behaviors. Affective disorders show a high degree of complexity, involving a multitude of molecular, neuroendocrine, and behavioral alterations as well as an intense gene-environment interaction, making it difficult to dissociate the primary causes from secondary consequences of the disease. Thus, interdisciplinary research, as applied in the emerging field of systems biology, involving adequate animal models and combined methodologies can significantly contribute to our understanding regarding the transmission of genetic predispositions into clinically relevant endophenotypes. It is only with deep insight into the mechanisms by which the stress hormone systems are regulated that novel treatment strategies and promising targets for therapeutic interventions can be developed in the future. Such in-depth understanding is ultimately essential to realizing our goal of predictive, preventive, and personalized medicine. PMID:21544741

  18. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles.

    Science.gov (United States)

    Grippo, Angela J; Gerena, Davida; Huang, Jonathan; Kumar, Narmda; Shah, Maulin; Ughreja, Raj; Carter, C Sue

    2007-01-01

    Supportive social interactions may be protective against stressors and certain mental and physical illness, while social isolation may be a powerful stressor. Prairie voles are socially monogamous rodents that model some of the behavioral and physiological traits displayed by humans, including sensitivity to social isolation. Neuroendocrine and behavioral parameters, selected for their relevance to stress and depression, were measured in adult female and male prairie voles following 4 weeks of social isolation versus paired housing. In Experiment 1, oxytocin-immunoreactive cell density was higher in the hypothalamic paraventricular nucleus (PVN) and plasma oxytocin was elevated in isolated females, but not in males. In Experiment 2, sucrose intake, used as an operational definition of hedonia, was reduced in both sexes following 4 weeks of isolation. Animals then received a resident-intruder test, and were sacrificed either 10 min later for the analysis of circulating hormones and peptides, or 2h later to examine neural activation, indexed by c-Fos expression in PVN cells immunoreactive for oxytocin or corticotropin-releasing factor (CRF). Compared to paired animals, plasma oxytocin, ACTH and corticosterone were elevated in isolated females and plasma oxytocin was elevated in isolated males, following the resident-intruder test. The proportion of cells double-labeled for c-Fos and oxytocin or c-Fos and CRF was elevated in isolated females, and the proportion of cells double-labeled for c-Fos and oxytocin was elevated in isolated males following this test. These findings suggest that social isolation induces behavioral and neuroendocrine responses relevant to depression in male and female prairie voles, although neuroendocrine responses in females may be especially sensitive to isolation. PMID:17825994

  19. Kinome sequencing reveals RET G691S polymorphism in human neuroendocrine lung cancer cell lines

    OpenAIRE

    Sosonkina, Nadiya; HONG, SEUNG-KEUN; Starenki, Dmytro; Park, Jong-In

    2014-01-01

    Neuroendocrine (NE) lung tumors comprise 20–25% of all invasive lung malignancies. Currently, no effective treatments are available to cure these tumors, and it is necessary to identify a molecular alteration(s) that characterizes NE lung tumor cells. We aimed to identify a kinase mutation(s) associated with NE lung tumor by screening 517 kinase-encoding genes in human lung cancer cell lines. Our next-generation sequencing analysis of six NE lung tumor cell lines (four small cell lung cancer ...

  20. Radioembolization for Neuroendocrine Liver Metastases: Safety, Imaging, and Long-Term Outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Memon, Khairuddin; Lewandowski, Robert J. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Mulcahy, Mary F. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Riaz, Ahsun; Ryu, Robert K.; Sato, Kent T.; Gupta, Ramona; Nikolaidis, Paul; Miller, Frank H.; Yaghmai, Vahid; Gates, Vanessa L.; Atassi, Bassel [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Newman, Steven [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Omary, Reed A. [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Benson, Al B. [Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Salem, Riad, E-mail: r-salem@northwestern.edu [Department of Radiology, Section of Interventional Radiology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States); Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL (United States)

    2012-07-01

    Purpose: To present long-term outcomes on the safety and efficacy of Yttrium-90 radioembolization in the treatment of unresectable hepatic neuroendocrine metastases refractory to standard-of-care therapy. Methods and Materials: This study was approved by our institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Forty patients with hepatic neuroendocrine metastases were treated with {sup 90}Y radioembolization at a single center. Toxicity was assessed using National Cancer Institute Common Terminology Criteria v3.0. Response to therapy was assessed by World Health Organization (WHO) guidelines for size and European Association for the Study of the Liver disease (EASL) guidelines for necrosis. Time to response and overall survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed. Results: The median dose was 113 Gy (29-299 Gy). Clinical toxicities included fatigue (63%), nausea/vomiting (40%), abdominal pain (18%), fever (8%), diarrhea and weight loss (5%); Grade 3 and 4 bilirubin toxicities were experienced by 2 patients and 1 patient, respectively. Different responses were noted by WHO (complete response, 1.2%; partial response, 62.7%) and EASL (complete response, 20.5%; partial response, 43.4%). Median time to response was 4 and 4.9 months by lesion and patient, respectively. The 1-, 2-, and 3-year overall survival rates were 72.5%, 62.5%, and 45%, respectively. Eastern Cooperative Oncology Group (ECOG) performance score 0 (p < 0.0001), tumor burden {<=}25% (p = 0.0019), albumin {>=}3.5 g/dL (p = 0.017), and bilirubin {<=}1.2 mg/dL (p = 0.002) prognosticated survival on univariate analysis; only ECOG performance score 0 and bilirubin {<=}1.2 mg/dL prognosticated better survival outcome on multivariate analysis (p = 0.0001 and p = 0.02). Conclusion: Yttrium-90 therapy for hepatic neuroendocrine metastases leads to satisfactory tumor response and patient survival

  1. L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

    Institute of Scientific and Technical Information of China (English)

    Zhihua Wang; Jinghua Li; Zhiming Wang; Lingyan Xue; Yi Zhang; Yingjie Chen; Jun Su; Zhongming Li

    2012-01-01

    Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

  2. Neuroendocrine-immune and metabolic accompaniments of cholecystokinetic effects of balneotherapy on SPA Truskavets’

    OpenAIRE

    Marfiyan, O M; Korolyshyn, T A; Barylyak, L G; Kovbasnyuk, M M; Yavors’kyi, O V; Zukow, W; Popovych, I L

    2015-01-01

    Marfiyan O M, Korolyshyn T A, Barylyak L G, Kovbasnyuk M M, Yavors’kyi O V, Zukow W, Popovych I L. Neuroendocrine-immune and metabolic accompaniments of cholecystokinetic effects of balneotherapy on SPA Truskavets’. Journal of Education, Health and Sport. 2015;5(5):21-30. ISSN 2391-8306. DOI: 10.5281/zenodo.17307 http://ojs.ukw.edu.pl/index.php/johs/article/view/2015%3B5%285%29%3A21-30 https://pbn.nauka.gov.pl/works/556532 http://dx.doi.org/10.5281/zenodo.17307 For...

  3. Chromogranin A as a Marker for Diagnosis, Treatment, and Survival in Patients With Gastroenteropancreatic Neuroendocrine Neoplasm

    OpenAIRE

    Wang, Yu-Hong; Yang, Qiu-chen; Lin, Yuan; Xue, Ling; Chen, Min-hu; Chen, Jie

    2014-01-01

    Abstract Chromogranin A (CgA) not only plays an important role in pathologic diagnosis, but is also used as a circulating biomarker in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). However, the relationship between immunohistochemistry (IHC) expression and serum levels of CgA has not been investigated. The value of CgA for evaluating treatment response and prognosis is still not well understood. We conducted this study to assess the significance of CgA in GEP-NEN in ...

  4. Malignant Neuroendocrine Tumour (Carcinoid) of the Spleen in an African Pygmy Hedgehog (Atelerix albiventris).

    Science.gov (United States)

    Lowden, L R; Davies, J L

    2016-07-01

    A malignant neuroendocrine tumour (carcinoid) of the spleen was diagnosed on post-mortem examination of a 3-year-old, male African pygmy hedgehog (Atelerix albiventris). The animal presented with a history of inappetence, weight loss, lethargy, a wide-based gait and a palpable abdominal mass. The gross pathological, histopathological, histochemical and immunohistochemical findings are described. Primary splenic carcinoids are reported rarely in the human medical literature and this is believed to be the first report in a non-human animal. PMID:27212029

  5. Progression after spontaneous regression in lung large cell neuroendocrine carcinoma: Report of a curative resection

    OpenAIRE

    Tomizawa, Kenji; Suda, Kenichi; Takemoto, Toshiki; Iwasaki, Takuya; Sakaguchi, Masahiro; Kuwano, Hiroyuki; Mitsudomi, Tetsuya

    2015-01-01

    We present the first reported case of lung large cell neuroendocrine carcinoma (LCNEC) with spontaneous regression followed by progression. An 85-year-old woman presented with a 2.8-cm nodule in the right upper lung lobe on chest computed tomography. After four months, the tumor decreased to 1.8 cm and remained unchanged in size for the next three months, but it grew to 8.6 cm and invaded the mediastinal fat tissue after approximately one year. Ultrasound echo-guided percutaneous biopsy revea...

  6. Octreotide acetate long-acting release in treatment of pancreatic neuroendocrine tumors

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shi; LI Yu-xiu; LI Nai-shi; LI Wen-hui; ZHU Hui-juan; GU Feng; WANG Heng

    2009-01-01

    @@ Pancreatic neuroendocrine tumours are uncommon neoplasms of the pancreas, accounting for around 2% of all primary pancreatic tumors,1 This specific group of tumours includes insulinoma, gastrinoma, glucagonoma,VIPoma, somatostatinoma and others.2 They may cause a clinical syndrome due to hormone overproduction. These tumours tend to be less aggressive than pancreatic adenocarcinoma, however, more than 50% of them have metastasized to the liver at the time of diagnosis.3 Under this circumstance, surgery is impossible to resect all metastases. Thus other various medical measures have been explored in the treatment of these tumors.

  7. Quantitative evaluation of integrated neuroendocrine and immune responses to chronic stress in rats male

    OpenAIRE

    Polovynko, Іlona S; Zajats, Lyubomyr М; Zukow, Walery; Yanchij, Roman I; Popovych, Іgor L

    2016-01-01

    Polovynko Іlona S, Zajats Lyubomyr М, Zukow Walery, Yanchij Roman I, Popovych Іgor L. Quantitative evaluation of integrated neuroendocrine and immune responses to chronic stress in rats male. Journal of Education, Health and Sport. 2016;6(8):154-166. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.60023 http://ojs.ukw.edu.pl/index.php/johs/article/view/3745       The journal has had 7 points in Ministry of Science and Higher Education parametric evalua...

  8. Fish as models for the neuroendocrine regulation of reproduction and growth.

    Science.gov (United States)

    Blázquez, M; Bosma, P T; Fraser, E J; Van Look, K J; Trudeau, V L

    1998-06-01

    Models are essential for the full understanding of neuroendocrine control processes. In this regard fish offer a rich source of biological material. They have diverse growth and reproductive strategies, inhabiting most of the Earth's aquatic ecological niches. Fish possess many of the common vertebrate features but also offer several unique aspects to allow the biologist easy access to the study of hypothalamic and pituitary function. Several key examples of how teleosts, or the bony fish, can offer insight into fundamental mechanisms of vertebrate sex differentiation, growth and reproduction are reviewed. PMID:9827007

  9. Cutaneous Neuroendocrine Carcinoma of the External Auditory Canal: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yi-Ke Li

    2012-01-01

    Full Text Available Cutaneous neuroendocrine carcinoma (cNEC is rarely seen in the external ear. In this paper, we newly describe a patient with cNEC in his right external auditory canal, followed by a further discussion on the clinical features, diagnosis, and treatments of cNEC of the external ear. A review of the literature showed that cNEC of the external auditory canal generally presents as asymptomatic and that pathology yields the most confirmative diagnosis. A wide resection with adjuvant radiotherapy and chemotherapy is recommended. The overall prognosis of this condition is poor.

  10. [Microbial endocrinology: impact of interactions between microbes and neuroendocrine hormones on infection--a review].

    Science.gov (United States)

    Xu, Fuzhou; Wu, Cun; Lin, Jun

    2013-09-01

    Microbial endocrinology is a crossdisciplinary field representing the intersection of microbiology with mammalian endocrinology and neurophysiology. In this review, effects of catecholamine on bacteria were used as an example to demonstrate the interactions between microbes and neuroendocrine hormones. Catecholamine modulates bacterial infectivity by stimulation of bacteria growth and augmentation of host tissue attachment and invasion. Moreover, the bacterial adrenergic receptors recognized by catecholamine and its relationship with quorum sensing signals were also addressed. This review will be helpful for understanding the interactions between microorganism and host as well as health breeding and food safety in animal industries.

  11. Comparison of abdominal MRI with diffusion-weighted imaging to {sup 68}Ga-DOTATATE PET/CT in detection of neuroendocrine tumors of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Schmid-Tannwald, Christine; Schmid-Tannwald, Christoph M.; Neumann, Ralph; Nikolaou, Konstantin; Schramm, Nicolai; Reiser, Maximilian F.; Rist, Carsten [Ludwig Maximilians University Hospital Munich, Institute for Clinical Radiology, Munich (Germany); Morelli, John N. [Scott and White Hospital Temple, Department of Radiology, Temple, TX (United States); Haug, Alexander R.; Jansen, Nathalie [Ludwig Maximilians University Hospital Munich, Department of Nuclear Medicine, Munich (Germany)

    2013-06-15

    The aim of the study was to evaluate contrast-enhanced MRI, diffusion-weighted MRI (DW MRI), and {sup 68}Ga-DOTATATE positron emission tomography (PET)/CT in the detection of intermediate to well-differentiated neuroendocrine tumors (NET) of the pancreas. Eighteen patients with pathologically proven pancreatic NET who underwent MRI including DW MRI and PET/CT within 6 weeks of each other were included in this retrospective study. Two radiologists evaluated T2-weighted (T2w), T2w + DW MRI, T2w + contrast-enhanced T1-weighted (CE T1w) MR images, and PET/CT for NET detection. The sensitivity and level of diagnostic confidence were compared among modalities using McNemar's test and a Wilcoxon signed rank test. Apparent diffusion coefficients (ADC) of pancreatic NETs and normal pancreatic tissue were compared with Student's t test. Of the NETs, 8/23 (34.8 %) and 9/23 (39.1 %) were detected on T2w images by observers 1 and 2, respectively. Detection rates improved significantly by combining T2w images with DW MRI (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05) or CE T1w images (observer 1: 14/23 = 61 %; observer 2: 15/23 = 65.2 %; p < 0.05). Detection rates of pancreatic NET with PET/CT (both observers: 23/23 = 100 %) were statistically significantly higher than with MRI (p < 0.05). The mean ADC value of NET (1.02 {+-} 0.26 x 10{sup -3} mm{sup 2}/s) was statistically significantly lower than that of normal pancreatic tissue (1.48 {+-} 0.39 x 10{sup -3} mm{sup 2}/s). DW MRI is a valuable adjunct to T2w imaging and comparable to CE T1w imaging in pancreatic NET detection, quantitatively differentiating between NET and normal pancreatic tissue with ADC measurements. {sup 68}Ga-DOTATATE PET/CT is more sensitive than MRI in the detection of pancreatic NET. (orig.)

  12. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

    Science.gov (United States)

    Tanca, Alessandro; Addis, Maria Filippa; Pisanu, Salvatore; Abbondio, Marcello; Pagnozzi, Daniela; Eccher, Albino; Rindi, Guido; Cossu-Rocca, Paolo; Uzzau, Sergio; Fanciulli, Giuseppe

    2016-01-01

    Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375. PMID:27054153

  13. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples.

    Science.gov (United States)

    Tanca, Alessandro; Addis, Maria Filippa; Pisanu, Salvatore; Abbondio, Marcello; Pagnozzi, Daniela; Eccher, Albino; Rindi, Guido; Cossu-Rocca, Paolo; Uzzau, Sergio; Fanciulli, Giuseppe

    2016-06-01

    Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs). Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375.

  14. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

    Directory of Open Access Journals (Sweden)

    Alessandro Tanca

    2016-06-01

    Full Text Available Here we present a dataset generated using formalin-fixed paraffin-embedded archival samples from two rare lung neuroendocrine tumor subtypes (namely, two atypical carcinoids, ACs, and two large-cell neuroendocrine carcinomas, LCNECs. Samples were subjected to a shotgun proteomics pipeline, comprising full-length protein extraction, SDS removal through spin columns, in solution trypsin digestion, long gradient liquid chromatography peptide separation and LTQ-Orbitrap mass spectrometry analysis. A total of 1260 and 2436 proteins were identified in the AC and LCNEC samples, respectively, with FDR <1%. MS data are available in the PeptideAtlas repository at http://www.peptideatlas.org/PASS/PASS00375.

  15. Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder.

    Science.gov (United States)

    Tanriverdi, Fatih; Kelestimur, Fahrettin

    2015-04-28

    Traumatic brain injury (TBI) is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.

  16. Neuroendocrine Disturbances after Brain Damage: An Important and Often Undiagnosed Disorder

    Directory of Open Access Journals (Sweden)

    Fatih Tanriverdi

    2015-04-01

    Full Text Available Traumatic brain injury (TBI is a common and significant public health problem all over the world. Until recently, TBI has been recognized as an uncommon cause of hypopituitarism. The studies conducted during the last 15 years revealed that TBI is a serious cause of hypopituitarism. Although the underlying pathophysiology has not yet been fully clarified, new data indicate that genetic predisposition, autoimmunity and neuroinflammatory changes may play a role in the development of hypopituitarism. Combative sports, including boxing and kickboxing, both of which are characterized by chronic repetitive head trauma, have been shown as new causes of neuroendocrine abnormalities, mainly hypopituitarism, for the first time during the last 10 years. Most patients with TBI-induced pituitary dysfunction remain undiagnosed and untreated because of the non-specific and subtle clinical manifestations of hypopituitarism. Replacement of the deficient hormones, of which GH is the commonest hormone lost, may not only reverse the clinical manifestations and neurocognitive dysfunction, but may also help posttraumatic disabled patients resistant to classical treatment who have undiagnosed hypopituitarism and GH deficiency in particular. Therefore, early diagnosis, which depends on the awareness of TBI as a cause of neuroendocrine abnormalities among the medical community, is crucially important.

  17. Neuroendocrine differentiated breast carcinoma: imaging features correlated with clinical and histopathological findings

    Energy Technology Data Exchange (ETDEWEB)

    Guenhan-Bilgen, Isil; Ustuen, Esin Emin; Memis, Aysenur [Department of Radiology, Ege University Hospital, Bornova, 35100 Izmir (Turkey); Zekioglu, Osman; Erhan, Yildiz [Department of Pathology, Ege University Hospital, Bornova, 35100 Izmir (Turkey)

    2003-04-01

    The aim of this study was to describe the imaging features of neuroendocrine differentiated breast carcinoma (NEDBC) and to correlate the radiological findings with the clinical and histopathological findings. A retrospective review of the mammograms of 1845 histopathologically proven breast cancer cases revealed five NEDBC. The clinical, imaging, and histopathological findings were analyzed. On mammography, a high-density mass was seen in all patients. The shape of the mass was round in 4 and irregular in 1 patient. The margins were spiculated in 2, indistinct in 1, microlobulated in 1, and partially obscured in 1 patient. On sonography, 4 patients had homogeneously hypoechoic masses with normal sound transmission. In 1 patient the mass was heterogeneously hypoechoic with mild posterior acoustic enhancement. The margins were microlobulated in 2, irregular in 2, and well-circumscribed in 1 patient. Neuroendocrine differentiated breast carcinoma should be included in the differential diagnosis of mammographically dense, round masses with predominantly spiculated or lobulated margins. Sonographically, they mostly present as irregular or microlobulated, homogeneously hypoechoic masses with normal sound transmission. (orig.)

  18. Doublecortin-like kinase 1 expression associates with breast cancer with neuroendocrine differentiation.

    Science.gov (United States)

    Liu, Yu-Hong; Tsang, Julia Y S; Ni, Yun-Bi; Hlaing, Thazin; Chan, Siu-Ki; Chan, Kui-Fat; Ko, Chun-Wai; Mujtaba, S Shafaq; Tse, Gary M

    2016-01-12

    Doublecortin-like kinase 1 (DCLK1), a microtubule associated kinase, has recently been proposed to be a putative marker for stemness and adverse prognosis in gastrointestinal cancers. However, it is not clear whether the protein also plays similar roles in breast cancer. Here, the expression of DCLK1 was analyzed in a large cohort of invasive breast cancers (IBC) by immunohistochemistry. DCKL1 was associated with favorable clinico-pathologic features, namely lower histologic grade, absence of lymphovascular invasion, fibrotic focus, necrosis and lower pN stage (p≤0.045). Additionally, independent significant correlations were found with estrogen receptor and neuroendocrine markers (p ≤0.019), implicating its relationship with IBC with neuroendocrine differentiation (IBC-NED). In the current cohort, IBC-NED showed worse outcome than luminal cancers without NED (hazard ratio=1.756, p=0.041). Interestingly, within the IBC-NED group, DCLK1 was found to be a good prognostic factor (hazard ratio =0.288, p=0.011). These findings were in contrast to those in gastrointestinal cancers, suggesting different functional roles of DCLK1 in different types of cancers. In clinical practice, NED is not routinely assessed; thus IBC-NED are not well studied. Its poor outcome and significant heterogeneity warrants more attention. DCLK1 expression could aid in the prognostication and management of this special cancer subtype. PMID:26621833

  19. Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

    Directory of Open Access Journals (Sweden)

    Laurent Kappeler

    2008-10-01

    Full Text Available Mutations that decrease insulin-like growth factor (IGF and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan.

  20. Primary hyperparathyroidism, adrenal tumors and neuroendocrine tumors of the pancreas - clinical diagnosis and imaging requirements

    International Nuclear Information System (INIS)

    Diseases of the parathyroids, the adrenals and of neuroendocrine tumors of the pancreas are primarily diagnosed by clinical and endocrinological evaluation.The requirements concerning various imaging techniques and their relative importance in localization strategies of the different tumors are complex. Current literature search, using PubMed. Evaluation of primary hyperparathyroidism requires bone densitometry by DXA and search for nephrolithiasis by ultrasound or native CT examination.While ultrasound of the thyroid and parathyroids seems useful before any parathyroid surgery,more extensive preoperative localization strategies (sestamibi scintigraphy, MRI) should be restricted to minimal invasive parathyroid surgery or re-operations.For adrenal tumors CT and MRI are of similar diagnostic value. Imaging of pheochromocytomas should be completed by MIBG scintigraphy. Each adrenal incidentaloma requires an endocrinological work-up.A fine-needle aspiration or core needle biopsy of an adrenal tumor is rarely indicated.Before adrenal biopsy a pheochromocytoma has to be excluded.Successful localization strategies for neuroendocrine tumors of the pancreas include somatostatin receptor scintigraphy, endoscopic ultrasound and MRI.Discussion Specific localization strategies have been established for the aforementioned tumors.The continuous progress of different imaging techniques requires a regular reevaluation of these localization strategies. (orig.)