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Sample records for neuroendocrine tumors carcinoids

  1. Pulmonary neuroendocrine (carcinoid) tumors

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

    2015-01-01

    BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS: Bibliographical searches were...... 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...

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

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    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.......03). However, the number of removed lymph nodes were insufficient for definitive determination of the prognostic impact of node metastases. Regarding the revised diagnoses, a significant difference in survival between typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma and small cell...

  3. Carcinoid Tumor: Frequently Asked Questions

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    ... serotonin is made and is also a useful marker sometimes. Carcinoid Heart Disease How do carcinoids in the liver affect heart ... many cases it can be supplemented by other markers which should have been ... heart disease in patients with functioning tumors.In other neuroendocrine ...

  4. A Rare Primary Neuroendocrine Tumor (Typical Carcinoid of the Sublingual Gland

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    Kenji Yamagata

    2016-01-01

    Full Text Available A typical carcinoid is extremely rare in the oral cavity. We here present a case of a typical carcinoid arising in the sublingual gland of a 62-year-old woman. The tumor was removed by primary excision with 10 mm surgical margins and submandibular dissection. Examination of the tumor showed medium-sized tumor cells that were positive for CD56 and chromogranin A, with no necrosis, and with a mitotic count less than 1/10 HPF. A pathological diagnosis of typical carcinoid was made from both morphological and immunological examinations. One year after excision surgery, there was no tumor recurrence or neck metastasis.

  5. Carcinoid Tumors

    Science.gov (United States)

    ... cell functions and some hormone-producing endocrine cell functions. Some hormones that are produced by neuroendocrine cells are cortisol, histamine, insulin and serotonin. Risk factors Factors that increase the ...

  6. Infection with multidrug-resistant Campylobacter coli mimicking recurrence of carcinoid syndrome: a case report of a neuroendocrine tumor patient with repeated diarrhea.

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    Lagler, Heimo; Kiesewetter, Barbara; Raderer, Markus

    2016-08-12

    Campylobacteriosis caused by Gram-negative bacteria of the genus Campylobacter (mainly C. jejuni and C. coli) is one of the most common gastrointestinal zoonotic infections with increased incidence in humans worldwide. The typical symptoms are severe abdominal cramps, diarrhea and sometimes fever. The clinical course of Campylobacter infection is mainly mild and after one week self-limiting, but can take several weeks in some rare cases. However, patients with neuroendocrine tumors in the gastrointestinal tract, a neoplasm of enterochromaffin/neuroendocrine cell origin, can develop severe diarrhea during progression of tumor growth caused by hormonal excess due to the tumor. Both diseases have very similar clinical symptoms and this case report elaborates the differences. So far it is known in the literature that the clinical symptoms of campylobacteriosis can mimic appendicitis or acute colitis of inflammatory bowel disease but a mimicking of recurrence of carcinoid syndrome in a patient with neuroendocrine tumor is not reported. A 72-year-old man with already diagnosed and treated metastatic neuroendocrine tumor of the terminal ileum (G1 rated, Ki-67 index 1 %) was again suffering from increasing diarrhea, abdominal cramps and weight lost. These symptoms were similar to the initial symptoms due to the tumor which improved at the time after total resection of the primary in the terminal ileum and regular therapy with long-acting release depot octreotide intramuscularly. As progression/tachyphylaxis in symptomatic patients with carcinoid syndrome undergoing therapy, reassessment of disease and analysis of tumor markers was initiated, and the interval of intramuscular injections was shortened. Radiological findings and tumor marker levels disclosed no evidence of neuroendocrine tumor progression and the symptoms continued. After 4 weeks with symptoms the patient developed additionally fever. Due to impaired renal function and elevated signs of systemic

  7. Primary hepatic carcinoid tumor

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    Gao Jinbo

    2011-11-01

    Full Text Available Abstract Primary hepatic carcinoid tumor is rare and poses a challenge for diagnosis and management. We presented a case of primary hepatic carcinoid tumor in a 53-year-old female with a complaint of right upper abdominal pain. Computer tomography scans revealed a hypervascular mass in segment 4 of the liver. An ultrasonography-guided biopsy showed a carcinoid tumor. No other lesions were found by the radiological investigations. Surgery resection was performed and histopathological examination revealed a primary hepatic carcinoid tumor. Three years later, recurrence was found and transcatheter arterial chemoembolization was performed. After transcatheter arterial chemoembolization, the patient has been free of symptom and had no radiological disease progression for over 6 months. Surgical resection combination with transcatheter arterial chemoembolization is effective to offer excellent palliation.

  8. Predicting neuroendocrine tumor (carcinoid) neoplasia using gene expression profiling and supervised machine learning.

    Science.gov (United States)

    Drozdov, Ignat; Kidd, Mark; Nadler, Boaz; Camp, Robert L; Mane, Shrikant M; Hauso, Oyvind; Gustafsson, Bjorn I; Modlin, Irvin M

    2009-04-15

    A more accurate taxonomy of small intestinal (SI) neuroendocrine tumors (NETs) is necessary to accurately predict tumor behavior and prognosis and to define therapeutic strategy. In this study, the authors identified a panel of such markers that have been implicated in tumorigenicity, metastasis, and hormone production and hypothesized that transcript levels of the genes melanoma antigen family D2 (MAGE-D2), metastasis-associated 1 (MTA1), nucleosome assembly protein 1-like (NAP1L1), Ki-67 (a marker of proliferation), survivin, frizzled homolog 7 (FZD7), the Kiss1 metastasis suppressor (Kiss1), neuropilin 2 (NRP2), and chromogranin A (CgA) could be used to define primary SI NETs and to predict the development of metastases. Seventy-three clinically and World Health Organization pathologically classified NET samples (primary tumor, n = 44 samples; liver metastases, n = 29 samples) and 30 normal human enterochromaffin (EC) cell preparations were analyzed using real-time polymerase chain reaction. Transcript levels were normalized to 3 NET housekeeping genes (asparagine-linked glycosylation 9 or ALG9, transcription factor CP2 or TFCP2, and zinc finger protein 410 or ZNF410) using geNorm analysis. A predictive gene-based model was constructed using supervised learning algorithms from the transcript expression levels. Primary SI NETs could be differentiated from normal human EC cell preparations with 100% specificity and 92% sensitivity. Well differentiated NETs (WDNETs), well differentiated neuroendocrine carcinomas, and poorly differentiated NETs (PDNETs) were classified with a specificity of 78%, 78%, and 71%, respectively; whereas poorly differentiated neuroendocrine carcinomas were misclassified as either WDNETs or PDNETs. Metastases were predicted in all cases with 100% sensitivity and specificity. The current results indicated that gene expression profiling and supervised machine learning can be used to classify SI NET subtypes and accurately predict metastasis

  9. Primary carcinoid tumors of the liver

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    Olichney John

    2008-08-01

    Full Text Available Abstract Background Primary carcinoid tumors of the liver are uncommon and rarely symptomatic. The diagnosis of primary hepatic etiology requires rigorous workup and continued surveillance to exclude a missed primary. Case Presentation We present a case of a 62-year-old female with a primary hepatic carcinoid tumor successfully resected, now with three years of disease-free follow-up. We present a review of the current literature regarding the diagnosis, pathology, management, and natural history of this disease entity. Conclusion Primary carcinoid tumors of the liver are rare, therefore classifying their nature as primary hepatic in nature requires extensive workup and prolonged follow-up. All neuroendocrine tumors have an inherent malignant potential that must be recognized. Management remains surgical resection, with several alternative options available for non-resectable tumors and severe symptoms. The risk of recurrence of primary hepatic carcinoid tumors after resection remains unknown.

  10. Tumor carcinoide apendicular Appendiceal carcinoid tumor

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    Julio Vázquez Palanco

    2008-12-01

    Full Text Available El objetivo de este trabajo fue dar a conocer un interesante caso de tumor carcinoide que se presentó con cuadro clínico de apendicitis aguda. El paciente fue un varón de 8 años de edad, al cual se realizó apendicectomía a causa de una apendicitis aguda. El resultado anatomopatológico confirmó un tumor de células endocrinas (argentafinoma, tumor carcinoide en el tercio distal del órgano, que infiltraba hasta la serosa, y apendicitis aguda supurada. El paciente fue enviado a un servicio de oncohematología para tratamiento oncoespecífico. Por lo inusual de estos tumores en edades tempranas y por lo que puede representar para el niño una conducta no consecuente, decidimos presentar este caso a la comunidad científica nacional e internacional. Es extremadamente importante el seguimiento de los pacientes con apendicitis aguda y de las conclusiones del examen histológico, por lo que puede representar para el niño una conducta inadecuada en una situación como esta.The objective of this paper was to make known an interesting case of carcinoid tumor that presented a clinical picture of acute appendicitis.The patient was an eight-year-old boy that underwent appendectomy due to an acute appendicitis. The anatomopathological report confirmed an endocrine cell tumor (argentaffinoma, carcinoid tumor in the distal third of the organ that infiltrated up to the serosa, and acute suppurative appendicitis. The patient was referred to an oncohematology service for oncospecific treatment. As it is a rare tumor at early ages, and taking into account what a inconsequent behavior may represent for the child, it was decided to present this case to the national and international scientific community. The follow-up of the patients with acute appendicitis and of the conclusions of the histological examination is extremely important considering what an inadequate conduct may represent for the child in a situation like this.

  11. Telotristat ethyl: proof of principle and the first oral agent in the management of well-differentiated metastatic neuroendocrine tumor and carcinoid syndrome diarrhea.

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    Masab, Muhammad; Saif, Muhammad Wasif

    2017-12-01

    Metastatic neuroendocrine tumors (NETs) are associated with carcinoid syndrome that is typically characterized by diarrhea, cutaneous flushing and bronchospasm. Treatment with somatostatin analogues (SSA) improves the symptom burden but a significant proportion of patients stop responding to SSA therapy eventually. Novel agents with the potential to effectively control the symptoms are urgently needed. This article reviews an in-depth analysis of the phase I-III clinical trials determining the clinical rationale for the use of tryptophan hydroxylase inhibitor, telotristat ethyl in patients with well-differentiated metastatic NETs and uncontrolled carcinoid syndrome. Telotristat ethyl has already been approved for the treatment of inadequately controlled carcinoid syndrome symptoms in metastatic NET patients on SSA therapy. Results from multiple phase I-III clinical studies of telotristat ethyl therapy have reported a significant decrease in the daily bowel movement frequency, increase in quality of life and the subsequent decrease in annual health costs related to carcinoid syndrome symptoms in NET patients. The associated decrease in urinary 5-hydroxyindoleacetic acid (u5-HIAA) provides evidence that telotristat ethyl effectively decreases serotonin production, and therefore, offers a rationale to investigate this agent to mitigate serotonin-mediated complications in this patient population, especially cardiac valvular disease or mesenteric fibrosis.

  12. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

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    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  13. Neuroendocrine Tumors of the Lung

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    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.

  14. Primary renal carcinoid tumor: A radiologic review

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    Leslie Lamb, MD, Msc, Bsc

    2014-01-01

    Full Text Available Carcinoid tumor is the classic famous anonym of neuroendocrine neoplasms. Primary renal carcinoid tumors are extremely rare, first described by Resnick and colleagues in 1966, with fewer than a total of 100 cases reported in the literature. Thus, given the paucity of cases, the clinical and histological behavior is not well understood, impairing the ability to predict prognosis. Computed tomography and (occasionally octreotide studies are used in the diagnosis and followup of these rare entites. A review of 85 cases in the literature shows that no distinctive imaging features differentiate them from other primary renal masses. The lesions tend to demonstrate a hypodense appearance and do not usually enhance in the arterial phases, but can occasionally calcify. Octreotide scans do not seem to help in the diagnosis; however, they are more commonly used in the postoperative followup. In addition, we report a new case of primary renal carcinoid in a horseshoe kidney.

  15. The Rare Malignancy of the Hepatobiliary System: Ampullary Carcinoid Tumor

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    Mustafa Ozsoy

    2011-01-01

    Full Text Available Introduction. Carcinoid tumors are low-grade tumors originating from endoderm and mostly involving the gastrointestinal system. However; they may be seen in any site within the gastrointestinal system. Case Presentation. A 69-year-old female patient. The results of blood tests were observed to be consistent with obstructive jaundice. A mass appearance was not encountered on tomographic examination. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in diagnostic endoscopy. Pylorus—preserving pancreaticoduodenectomy surgical procedure was applied. On pathological examination of the mass, a tumoral mass was detected in ampulla vateri localization, 1.5 × 1 × 0.8 cm in size, which, in immunohistochemical staining, was evaluated as a neuroendocrine tumor. Also, Metastasis was observed. Conclusion. The rarest type of carcinoid tumor is ampullary located carcinoid tumor, and tumor size is not a reliable indicator for tumor aggressivity in ampullary carcinoid tumors.

  16. Primary ovarian carcinoid tumor with luteinized stromal cells.

    Science.gov (United States)

    Engohan-Aloghe, Corinne; Buxant, F; Noël, J C

    2009-07-01

    Primary ovarian carcinoid tumors are rare. Distinct histologic patterns have been described in the literature as insular, trabecular, mucinous and mixed types. We describe a case of 71-year-old woman diagnosed with a left ovarian tumor. Frozen section examination identified the mass as a sex-cord stromal tumor. The surgically resected tumor was diagnosed as an insular carcinoid tumor with unusual luteinized stromal cells. Histologic diagnosis complied with results acquired by immunohistochemical with positivity of tumor cells for neuroendocrine markers and positivity of luteinized stromal cells for alpha-inhibin, calretinin and Melan A. Ovarian carcinoid tumor can be extremely heterogeneous. The purpose of our report was to show that the ovarian carcinoid tumor can be associated with stromal luteinization, mimicking a sex-cord stromal tumor.

  17. Cowden Syndrome and Concomitant Pulmonary Neuroendocrine Tumor

    DEFF Research Database (Denmark)

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

    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 Cowden Syndrome and neuroendocrine tumors has previously been described. We present two cases of Cowden...

  18. Carcinoid Syndrome and Carcinoid Heart Disease as Manifestations of Non-Metastatic Ovarian Neuroendocrine Tumour

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    Joana Simões-Pereira

    2017-05-01

    Full Text Available The carcinoid syndrome is rare but it is associated with carcinoid heart disease in more than a half of the cases. Carcinoid heart disease is typically characterised by morphological and functional modifications of right-sided valves. Its aetiology is probable multifactorial but serotonin appears to play a key role in the development of this valvular disease. Unlike gastrointestinal neuroendocrine tumours, ovarian neuroendocrine tumours can present with carcinoid syndrome and carcinoid heart disease in the absence of liver metastases; such ovarian neuroendocrine tumours are a unique clinical entity. The additional burden of cardiac impairment in these patients represents a significant reduction in survival. Early recognition and surgical valve replacement before advanced heart failure is established may improve the clinical outcome. We report the case of a woman with an ovarian neuroendocrine tumour and highly symptomatic carcinoid heart disease who was submitted to tumour resection followed by valvuloplasty. She demonstrated an outstanding clinical improvement and has remained free of tumour and symptomatology.

  19. Phase III study of pasireotide long-acting release in patients with metastatic neuroendocrine tumors and carcinoid symptoms refractory to available somatostatin analogues

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    Wolin EM

    2015-09-01

    : In a randomized, double-blind, Phase III study, we compared pasireotide long-acting release (pasireotide LAR with octreotide long-acting repeatable (octreotide LAR in managing carcinoid symptoms refractory to first-generation somatostatin analogues. Adults with carcinoid tumors of the digestive tract were randomly assigned (1:1 to receive pasireotide LAR (60 mg or octreotide LAR (40 mg every 28 days. Primary outcome was symptom control based on frequency of bowel movements and flushing episodes. Objective tumor response was a secondary outcome. Progression-free survival (PFS was calculated in a post hoc analysis. Adverse events were recorded. At the time of a planned interim analysis, the data monitoring committee recommended halting the study because of a low predictive probability of showing superiority of pasireotide over octreotide for symptom control (n=43 pasireotide LAR, 20.9%; n=45 octreotide LAR, 26.7%; odds ratio, 0.73; 95% confidence interval [CI], 0.27–1.97; P=0.53. Tumor control rate at month 6 was 62.7% with pasireotide and 46.2% with octreotide (odds ratio, 1.96; 95% CI, 0.89–4.32; P=0.09. Median (95% CI PFS was 11.8 months (11.0 – not reached with pasireotide versus 6.8 months (5.6 – not reached with octreotide (hazard ratio, 0.46; 95% CI, 0.20–0.98; P=0.045. The most frequent drug-related adverse events (pasireotide vs octreotide included hyperglycemia (28.3% vs 5.3%, fatigue (11.3% vs 3.5%, and nausea (9.4% vs 0%. We conclude that, among patients with carcinoid symptoms refractory to available somatostatin analogues, similar proportions of patients receiving pasireotide LAR or octreotide LAR achieved symptom control at month 6. Pasireotide LAR showed a trend toward higher tumor control rate at month 6, although it was statistically not significant, and was associated with a longer PFS than octreotide LAR. Keywords: neuroendocrine tumors, carcinoid syndrome, somatostatin analogues, pasireotide, symptom control, progression

  20. Management of appendiceal carcinoid tumors in children.

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    Fallon, Sara C; Hicks, M John; Carpenter, Jennifer L; Vasudevan, Sanjeev A; Nuchtern, Jed G; Cass, Darrell L

    2015-10-01

    Appendiceal carcinoid tumors, also know as well-differentiated neuroendocrine neoplasms, are rare lesions detected incidentally after appendectomy in children. There are limited data about the natural history of these tumors, and guidelines regarding family counseling and need for additional surgery or follow-up imaging are not established in the pediatric age group. The purpose of this study was to review our institutional experience with appendiceal carcinoid tumors to provide data that might improve management. After institutional review board approval, the charts of all patients treated at our institution for an appendiceal carcinoid tumor between 2002 and 2014 were reviewed. Data collected included patient demographics, pathologic details, postoperative management, and follow-up information. Descriptive analyses were performed. Twenty-eight patients were identified, which represents an incidence of 0.2% of children undergoing appendectomy during that time interval. The mean age at surgery was 13.8 ± 2.1 y; 54% were females. Two patients had symptoms suspicious for carcinoid syndrome at presentation, though none had evidence of metastatic disease. The mean tumor size was 0.73 ± 0.4 cm. Five patients (18%) underwent subsequent ileocecectomy or right hemicolectomy because of pathologic findings of invasion of the mesoappendix (n = 4) or lymphovascular invasion and subserosal extension (n = 1), two of whom had residual disease in the resected specimen (one in a lymph node). No recurrences have been detected at mean follow-up of 1.8 y. Appendiceal carcinoid tumors are discovered incidentally in about 0.2% of children undergoing appendectomy. Based on findings from a large contemporary series, we can conclude that these tumors are generally small and demonstrate lymphovascular invasion or mesenteric extension in fewer than 20% of cases. Prospective, multicenter studies are necessary to better define the indication for ileocecectomy and follow-up imaging

  1. [Obscure digestive bleeding by ileal carcinoid tumor].

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    Nelly Manrique, María; Frisancho, Oscar; Zumaeta, Eduardo; Palomino, Américo; Rodriguez, César

    2011-01-01

    The patient is an 82 year-old female with a history of osteoarthritis, hypothyroidism and anemia for 14 years (receiving blood transfusions). She was admited to our hospital with a nine months history of malaise, anorexia, fatigue and weakness, associated with intermitten episodes of abdominal pain. She was diagnosed anemia and occult blood positive stools. Physical examination revealed a patient in generally fair condition, obese, with mild edema of lower limbs, no changes in the evaluation of chest, cardiovascular, abdomen, etc. Laboratory data was unremarkable, except for iron deficiency anemia. The upper endoscopy showed duodenal ulcer scar, fundic polyposis and chronic gastritis. Colonoscopy revealed some diverticula, a small sessile polyp and internal hemorrhoids. The diagnosis of obscure gastrointestinal bleeding was made. The CT scan of the abdomen showed gallstones and fatty liver; a radiograph of intestinal transit detected a lesion apparently protruded intestinal loop for distal jejunum; enteroscopy was performed (with one team ball) anterograde and retrograde achieving assess distal jejunum and distal ileum without observing any injuries. The study of capsule endoscopy showed a polypoid tumor intestinal with evidence of having bleeding. Surgery detected the tumor in proximal ileum. The surgical specimen findings showed three tumors 0.7 mm, 10 mm and 15 mm on the proximal ileum. The microscopic examination revealed that these lesions were neuroendocrine tumors (carcinoid). The Ileal carcinoid tumor may rarely presented with obscure gastrointestinal bleeding.

  2. Neuroendocrine Tumor: Statistics

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    ... Tumor > Neuroendocrine Tumor: Statistics Request Permissions Neuroendocrine Tumor: Statistics Approved by the Cancer.Net Editorial Board , 11/ ... the body. It is important to remember that statistics on the survival rates for people with a ...

  3. Nuclear Medicine diagnosis and therapy of neuroendocrine tumors of the gastrointestinal tract, including carcinoids; Nuklearmedizinische Diagnostik und Therapie neuroendokriner Tumoren des Gastrointestinaltraktes einschliesslich des Karzinoides

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    Behr, T.M.; Gotthardt, M.; Behe, M. [Klinik fuer Nuklearmedizin der Phillipps-Univ. Marburg (Germany); Kann, P.H. [Bereich fuer Endokrinologie and Diabetologie der Phillipps-Univ. Marburg (Germany); Arnold, R. [Klinik fuer Gastroenterologie, Stoffwechsel, Endokrinologie der Phillipps-Univ. Marburg (Germany)

    2003-06-01

    Neuroendocrine tumors of the gastrointestinal tract are the special domain of Nuclear Medical diagnosis and therapy, especially since they have been recognized as overexpressing receptors for regulatory peptides. Regulatory peptides are small, readily diffusible and potent natural substances with a wide spectrum of receptor-mediated actions. High affinity receptors are reliably (over-) expressed on a variety of tumors, and these receptors represent novel molecular targets for tumor diagnosis and therapy. Whereas the historically more ancient MIBG scintigraphy showed only limited sensitivity and therapeutic efficacy, somatostatin receptor scintigraphy has revolutionized the staging of gastro-enteropancreatic tumors. Physiologically, these peptides bind to G-protein associated receptors in the cell membranes. Historically, somatostatin analogues are the first class of receptor-binding peptides with a broader field of clinical applications. In-111-DTPA-[D-Phe1]-octreotide is the first and only radiopeptide having gained approval by the respective regulatory agencies in Europe and the United States of America. Extensive clinical studies with several thousands of patients were able to show that the main application of somatostatin receptor scintigraphy lies in the detection and the staging of gastroenteropancreatic neuro-endocrine tumors (carcinoids and others). In these, radiolabeled octreotide is superior to all other forms or methods of staging. A variety of novel radiolabeled regulatory peptides is in development, binding to other, novel receptor types. Radiolabeled vasoactive intestinal peptide (VIP), gastrin and cholecystokinin derivatives, gastrin-releasing peptide/bombesin, neurotensin, substance P, glucagon-like peptide-1 (GLP-1) analogues and potentially also pan-somatostatin receptor ligands stay in differently developed stages of their pre-clinical or even clinical testing. Radiolalebeled regulatory peptides have opened new horizons in Nuclear oncology for

  4. Bronchial carcinoid tumors: A rare malignant tumor

    African Journals Online (AJOL)

    2015-02-03

    Feb 3, 2015 ... Nigerian Journal of Clinical Practice • Sep-Oct 2015 • Vol 18 • Issue 5. Abstract. Bronchial carcinoid tumors (BCTs) are an uncommon group of lung tumors. They commonly affect the young adults and the middle aged, the same age group affected by other more common chronic lung conditions such as ...

  5. Carcinoid tumors: Challenges and considerations during anesthetic management

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    Sukhminder Jit Singh Bajwa

    2015-01-01

    Full Text Available Carcinoid tumors are rare, slow-growing neoplasms of neuroendocrine tissues from enterochromaffin or kulchitsky cells, which have the potential to metastasize. The mediators released from these tumors when bypass the hepatic metabolism, can lead to the possible development of carcinoid syndrome. This is a life-threatening complication, which can lead to profound hemodynamic instability, especially in a peri-operative period, when the patient is exposed to various types of noxious stimuli. Off late, use of octreotide, a synthetic analog of somatostatin, has significantly reduced the peri-operative morbidity and mortality. The current review discusses the various anesthetic challenges and considerations during peri-operative management of carcinoid tumors.

  6. Metastatic Carcinoid Tumor Presenting As Right Sided Heart Failure

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    Martinez-Quintana, Efren; Avila-Gonzalez, Maria Del Mar; Suarez-Castellano, Laura; Rodriguez-Gonzalez, Fayna

    2013-01-01

    Carcinoid tumor is a slow-growing type of neuroendocrine tumor, originating in the enterochromaffin cells and secreting mainly serotonin. The diagnosis is based on clinical symptoms, hormone levels, radiological and nuclear imaging, and histological confirmation. The clinical symptoms are characterized by flushing, diarrhea, abdominal pain, telangiectasia and/or bronchoconstriction. However, most patients have metastatic disease at diagnosis because the clinic goes unnoticed or are ascribed to other abdominal conditions. We report the clinical symptoms, hormone levels, radiological and nuclear imaging, histological diagnosis, treatment and evaluation of a 44-year-old female patient with congestive heart failure secondary to carcinoid heart disease in the context of liver metastases of an ileum carcinoid tumor. PMID:23825984

  7. Tumor Carcinoide Gástrico.

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    Haydelisis Peraza González

    2015-12-01

    Full Text Available Las neoplasias endocrinas se originan en las células del sistema neuroendocrino, también afectan al tubo digestivo; dentro de ellas, el tumor carcinoide gástrico es poco frecuente. El objetivo de la publicación es mostrar la situación de una paciente femenina que presentó características clínicas, endoscópicas, histológicas e inmunohistoquímica de esta variedad de tumor gástrico. Paciente femenina de 45 años de edad con antecedentes de salud, referida de su área de salud al Departamento de Gastroenterología, por presentar dolor en epigastrio, regurgitaciones, acidez y cifras bajas de hemoglobina. Se le diagnosticó pólipo gástrico erosionado a través de estudio endoscópico superior, se realizó estudio histológico y se aplicó técnica de inmunohistoquímica, cuyo diagnóstico definitivo fue un tumor carcinoide gástrico, y se le efectuó una gastrectomía subtotal ampliada, con evolución satisfactoria. El tumor carcinoide gástrico es una neoplasia no habitual, cuyo tratamiento de elección es quirúrgico, donde la supervivencia y calidad de vida del paciente depende del tamaño, la localización, infiltración y presencia de metástasis del mismo.

  8. Carcinoid Tumor in Accidental, Asymptomatic Meckel's Diverticulum

    African Journals Online (AJOL)

    carcinoid tumors.[1] We have found no report in the literature where it was found accidentally. Carcinoid tumors in the gastrointestinal tract arise from amine precursor uptake and decarboxylation cells ... Following blunt abdominal injury she was admitted due to lack of ... infiltrated the muscle layer of the bowel, but no further.

  9. Endoscopic Management of a Primary Duodenal Carcinoid Tumor

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    Albin Abraham

    2012-03-01

    Full Text Available Carcinoids are rare, slow-growing tumors originating from a variety of different neuroendocrine cell types. They are identified histologically by their affinity for silver salts and by positive reactions to neuroendocrine markers such as neuron-specific enolase, synaptophysin and chromogranin. They can present with various clinical symptoms and are difficult to diagnose. We present the case of a 43-year-old woman who was referred for evaluation of anemia. Upper endoscopy showed a duodenal bulb mass around 1 cm in size. Histopathological and immunohistochemistry staining were consistent with the diagnosis of a carcinoid tumor. Further imaging and endoscopic studies showed no other synchronous carcinoid lesions. Endoscopic ultrasound (EUS revealed a 1 cm lesion confined to the mucosa and no local lymphadenopathy. Successful endoscopic mucosal resection of the mass was performed. Follow-up surveillance 6 months later with EUS and Octreoscan revealed no new lesions suggestive of recurrence. No consensus guidelines exist for the endoscopic management of duodenal carcinoid tumors. However, endoscopic resection is safe and preferred for tumors measuring 1 cm or less with no evidence of invasion of the muscularis layer.

  10. Laser excision of a typical carcinoid tumor of the larynx: a case report.

    Science.gov (United States)

    Cevizci, Raşit; Karakullukçu, Barış; van den Brekel, Michiel W M; Balm, Alfons J

    2010-01-01

    Neuroendocrine carcinomas of the larynx include a range of rare tumors which have variable biologic behavior, affecting treatment and prognosis. Among these, typical carcinoid tumors are the least common type. Prognosis of typical carcinoid tumor is better than atypical carcinoid tumor and small cell carcinoma of the larynx. Conservation surgery is the preferred treatment modality. Transoral CO2 laser surgery can be a good alternative for appropriate cases because of the functional results and less morbidity. In this article, a 71-year-old female presented with complaints of feeling a mass during swallowing. Fiberoptic examination of the larynx revealed a mass located on the right aryepiglottic fold and biopsy revealed the tumor as a typical carcinoid tumor. We describe CO2 laser excision of a typical carcinoid tumor of the larynx in this case report.

  11. Tumor carcinoide e sequestro pulmonar Carcinoid tumor and pulmonary sequestration

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    Fernando Luiz Westphal

    2012-02-01

    Full Text Available O sequestro pulmonar é definido como uma massa de tecido pulmonar separada da árvore traqueobrônquica e irrigada por uma artéria sistêmica anômala. Sua associação com neoplasias pulmonares é rara. Relatamos o caso de uma paciente de 39 anos com o diagnóstico de tumor carcinoide localizado no brônquio intermediário, associado a alterações caracterizadas como bronquiectasias em lobo inferior direito. A paciente foi submetida à toracotomia para ressecção da área acometida e, durante a cirurgia, apresentou hemorragia importante decorrente da transecção da artéria anômala que nutria o sequestro pulmonar intralobar localizado em lobo inferior direito, não identificado nos exames pré-operatórios.Pulmonary sequestration is defined as a mass of lung tissue separated from the tracheobronchial tree and irrigated by an anomalous systemic artery. It is rarely seen in conjunction with lung neoplasms. We report the case of a 39-year-old female patient diagnosed with a carcinoid tumor, located in the intermediate bronchus and accompanied by bronchiectasis in the right lower lobe. The patient underwent thoracotomy for the resection of the affected area. During surgery, she presented with significant hemorrhage resulting from the transection of the anomalous artery that irrigated an intralobar pulmonary sequestration, which was located in right lower lobe and had not been identified in pre-operative examinations.

  12. Primary synchronous mesenteric neuroendocrine tumors: Report of a rare case with review of literature

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    Sulata Manjunath Kamath

    2015-01-01

    Full Text Available Most neuroendocrine tumors of the gastrointestinal tract are traditionally termed "carcinoid tumors." More than 90% of all gastrointestinal carcinoids are located in the appendix, small intestine, rectum, and mesenteric carcinoids are rare. Even when invasive, most carcinoids are relatively indolent and display minimal histological pleomorphism. A minority of these tumors is clinically more aggressive and has a less differentiated histological pattern. Carcinoid tumors of the intestine frequently invade the mesentery, but a primary carcinoid of the mesentery is extremely rare. Mesenteric carcinoid tumors can go unrecognized due to nonspecific symptoms. We report an unusual case of two large primary mesenteric carcinoid tumors in a 38-year-old male who had excellent recovery following surgery. A complete histopathologic, immunohistochemical, and radiologic workup enabled correct diagnosis in this case.

  13. Midgut neuroendocrine tumor presenting with acute intestinal ischemia.

    Science.gov (United States)

    Mantzoros, Ioannis; Savvala, Natalia Antigoni; Ioannidis, Orestis; Parpoudi, Styliani; Loutzidou, Lydia; Kyriakidou, Despoina; Cheva, Angeliki; Intzos, Vasileios; Tsalis, Konstantinos

    2017-12-07

    Neuroendocrine tumors represent a heterogeneous group of neoplasms that arise from neuroendocrine cells and secrete various peptides and bioamines. While gastrointestinal neuroendocrine tumors, commonly called carcinoids, account for about 2/3 of all neuroendocrine tumors, they are relatively rare. Small intestine neuroendocrine tumors originate from intestinal enterochromaffin cells and represent about 1/4 of small intestine neoplasms. They can be asymptomatic or cause nonspecific symptoms, which usually leads to a delayed diagnosis. Imaging modalities can aid diagnosis and surgery remains the mainstay of treatment. We present a case of a jejunal neuroendocrine tumor that caused nonspecific symptoms for about 1 year before manifesting with acute mesenteric ischemia. Abdominal X-rays revealed pneumatosis intestinalis and an abdominal ultrasound and computed tomography confirmed the diagnosis. The patient was submitted to segmental enterectomy. Histopathological study demonstrated a neuroendocrine tumor with perineural and arterial infiltration and lymph node metastasis. The postoperative course was uneventful and the patient denied any adjuvant treatment.

  14. Current Concepts on Gastric Carcinoid Tumors

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    George C. Nikou

    2012-01-01

    Full Text Available Gastric carcinoid tumors (GCs are rare lesions representing less than 10% of carcinoid tumors and less than 1% of all stomach neoplasms. There are three distinct types of gastric carcinoids; type I includes the vast majority (70–85% of these neoplasms that are closely linked to chronic atrophic gastritis. Type II which accounts for 5–10 %, is associated with Zollinger-Ellison syndrome and often occurs in the context of multiple endocrine neoplasia type 1. Type III, finally, represents 15–25% of gastric carcinoids and is characterized by a far more aggressive course. The optimal clinical approach to GCs remains to be elucidated, depending upon type, size, and number of carcinoids. While there is universal agreement about the surgical treatment of type III GCs, current options for type I and II include simple surveillance, endoscopic polypectomy, surgical excision associated with or without surgical antrectomy, or total gastrectomy. Moreover, the introduction of somatostatin analogues could represent another therapeutic option.

  15. GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS ...

    African Journals Online (AJOL)

    INTRODUCTION. Neuroendocrine tumors comprise heterogeneous group of neoplasms which originate from endocrine cells, both within endocrine organs and within the cells of diffuse endocrine system. These tumors have vari- able clinical behavior ranging from well-differentiated, slow growing tumors to ...

  16. Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor

    Science.gov (United States)

    2011-01-01

    Background Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia. Case Presentation We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors. Conclusions Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root. PMID:21281518

  17. Partial abdominal evisceration and intestinal autotransplantation to resect a mesenteric carcinoid tumor

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    Cosimi A Benedict

    2011-01-01

    Full Text Available Abstract Background Midgut carcinoids are neuroendocrine tumors that commonly metastasize to the intestinal mesentery, where they predispose to intestinal obstruction, ischemia and/or congestion. Because of their location, many mesenteric carcinoid tumors are deemed unresectable due to the risk of uncontrollable bleeding and prolonged intestinal ischemia. Case Presentation We report the case of a 60-year-old male with a mesenteric carcinoid tumor obstructing his superior mesenteric vein, resulting in intestinal varices and severe recurrent GI bleeds. While his tumor was thought to be unresectable by conventional techniques, it was successfully resected using intestinal autotransplantation to safely gain access to the tumor. This case is the first described application of this technique to carcinoid tumors. Conclusions Intestinal autotransplantation can be utilized to safely resect mesenteric carcinoid tumors from patients who were not previously thought to be surgical candidates. We review the literature concerning both carcinoid metastases to the intestinal mesentery and the use of intestinal autotransplantation to treat lesions involving the mesenteric root.

  18. Atypical carcinoid and large cell neuroendocrine carcinoma of the lung: a proteomic dataset from formalin-fixed archival samples

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    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.

  19. Secretagogin is a novel marker for neuroendocrine differentiation

    DEFF Research Database (Denmark)

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

    2005-01-01

    , 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...

  20. Surgical treatment of a rare primary renal carcinoid tumor with liver metastasis

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    Rowland Randall G

    2008-04-01

    Full Text Available Abstract Background Carcinoid tumors are characteristically low grade malignant neoplasms with neuroendocrine differentiation that arise in various body sites, most commonly the lung and gastrointestinal tract, but less frequently the kidneys, breasts, ovaries, testes, prostate and other locations. We report a case of a carcinoid of renal origin with synchronous single liver metastases on radiological studies. Case presentation A 45 year-old patient who presented with abdominal pain was found on CT scan to have lesions in the right ovary, right kidney, and left hepatic lobe. CA-125, CEA, and CA 19-9 were within normal limits, as were preoperative liver function tests and renal function. Biopsy of the liver mass demonstrated metastatic neuroendocrine tumor. At laparotomy, the patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, radical right nephrectomy with lymphadenectomy, and left hepatectomy. Pathology evaluation reported a right ovarian borderline serous tumor, well-differentiated neuroendocrine carcinoma of the kidney (carcinoid with 2 positive retroperitoneal lymph nodes, and a single liver metastasis. Immunohistochemistry revealed that this lesion was positive for synaptophysin and CD56, but negative for chromogranin as well as CD10, CD7, and CD20, consistent with a well-differentiated neuroendocrine tumor. She is doing well one year after her initial surgery, with no evidence of tumor recurrence. Conclusion Early surgical intervention, together with careful surveillance and follow-up, can achieve successful long-term outcomes in patients with this rare malignancy.

  1. Neuroendocrine Tumor, diagnostic difficulties

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    Pedro Oliveira

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH secretion is a rare disease. A 51 years old woman, with a Cushing syndrome secondary to ectopic ACTH secretion, diagnosed in 2009, with mediastinal lymphadenopathy, whose biopsy was compatible with lung small cell carcinoma, staged as IIIB using TNM classification. No other lesions were found in patient study. The patient was submitted to chemotherapy, associated to ketoconazole 200 mg twice daily, with partial remission of both conditions. Three years later was admitted with an aggravation of Cushing syndrome. There was no evidence of progression of pulmonary disease. A cystic lesion in the pancreatic uncinated process was found by abdominal CT scan and with avid uptake by DOTANOC PET discreet in anterior mediastinal lymphadenopathy. Biopsy of pancreatic mass revealed a neuroendocrine tumor. Pulmonary masses were biopsied again and was in favor of neuroendocrine tumor. It was assumed the diagnosis of pancreatic neuroendocrine tumor with mediastinal metastasis. The patient initiated lanreotid (120 mg, monthly, subcutaneous in association with ketoconazole. After 5 months of therapy, patient died with sepsis secondary to pneumonia. Neuroendocrine tumours are rare, difficult to diagnose and with poor prognosis when associated with ectopic ACTH secreting Cushing syndrome.

  2. Atelectasis in pediatrics: a case of carcinoid tumor.

    Science.gov (United States)

    Guerreiro, Cláudia Vaz; Ornelas, Paula; Pereira, Luísa; Abecasis, Nuno; Almodovar, Maria Teresa

    2017-10-03

    Carcinoid pulmonary tumors occur in the fourth to sixth decades of life. Usually, typical carcinoid arise a decade earlier when compared to atypical carcinoid (45 years and 55 years, respectively). Typical carcinoid tumors are the most common primary lung neoplasm in children and late adolescents, but there are less than 40 cases described in the literature. The clinical presentation is nonspecific and usually the symptoms are due to bronchial obstruction, sometimes with recurrent pneumonia. Its rarity may delay diagnosis but in most cases a favorable course after treatment is observed. The authors describe the case of a 13-year-old girl diagnosed with a carcinoid tumor located on the intermediate bronchus. The treatment approach included endoscopic laser resection, for obstruction resolution, followed by a right inferior bilobectomy with mediastinal lymph node dissection as definitive treatment. Histopathology confirmed a typical carcinoid tumor with mediastinal ipsilateral lymph node involvement.

  3. Bronchial carcinoid tumors: A rare malignant tumor | Orakwe ...

    African Journals Online (AJOL)

    Bronchial carcinoid tumors (BCTs) are an uncommon group of lung tumors. They commonly affect the young adults and the middle aged, the same age group affected by other more common chronic lung conditions such as pulmonary tuberculosis. Diagnosis is commonly missed or delayed due to a low index of suspicion.

  4. Neuroendocrine tumors in the urinary bladder: a literature review

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    Monika Ulamec

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs can be found in most organs, as well as in the urinary bladder. Some of the clinical and pathologic features of these tumors may be characteristic of the organ of origin, but most of the properties are shared by neuroendocrine neoplasms regardless of their anatomic site. In the bladder, NETs comprise less than 1% of all bladder tumors and can be found in a pure form or intermixed with urothelial carcinoma and its variants. Bladder NETs are classified into 2 subtypes: carcinoid tumor and neuroendocrine carcinoma, which is further subdivided into small cell and large cell neuroendocrine carcinoma. Characteristics of bladder NETs and its differential diagnosis are discussed herein.

  5. NEW CLASSIFICATION AND DIAGNOSIS OF APPENDICEAL CARCINOID TUMORS

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    Vuka Katić

    2012-03-01

    Full Text Available Carcinoid tumours are rare lesions that belong to the APUDoma category having the capacity of Amine Precursor Uptake and Decarboxylase. Gastrointestinal system comprises 90% of all carcinoids in the body and they are the most common type of primary malignant lesions of the appendix. New WHO classification of gastrointestinal carcinoids, diagnostic dilemmas of some carcinoid variants and, sometimes unpredictable prognosis are the reasons for the following study: clinical, macro- and microscopical as well as cytochemical and immunocytochemical examination of the vermiform appendix carcinoids, surgically removed from 16 patients. The appendectomy was induced by acute appendicitis or tumorous mass, without carcinoid syndrome. After two-day fixation in 10% formaldehyde, routinelly processed and embedded in paraffin, laboratory sections were stained with H&E, Fontana-Masson’s, Grimelius’, FIF and ABPAS methods. ABC method has been used for immunohistochemical examination. The antibodies for Chromogranin A, NSE, Synaptophysin, Cytokeratin 7, S-100 protein, Ki67 and CEA (primary antibodies and ABC (secondary antibody (Dako Kopenhagen were tested. The patients had no carcinoid syndrome. The most frequent was classic appendiceal carcinoid, well differentiated - NETG1 (8 cases, without metastases; goblet cell carcinoids were rare (3 cases, one case with liver metastases. The second case of goblet cell carcinoid was associated with cystadenoma papillare mucinosum, complicated by pseudomixoma peritonei and the third case was limited only to appendiceal wall. The patient with liver metastases died five months after appendectomy. The patient with goblet cell carcinoid associated with papillary mucinous cystadenoma and complicated by pseudomixoma peritonei had re-operation with both partial cecal and right ovarial resection, associated with washing the peritoneal cavity. The patient was feeling well during six years from the second operation. Based on our

  6. Incidental Primary Intradural Carcinoid Tumor in a Patient with Lumbar Radiculopathy.

    Science.gov (United States)

    Koustais, Stavros; O'Halloran, Philip J; Hassan, Alfrazdaq; Brett, Francesca; Young, Steven

    2017-09-01

    Carcinoid tumors are neuroendocrine neoplasms derived from enterochromaffin cells. Central nervous system involvement is rare. The reported cases include metastases to brain or spinal cord, and primary skeletal or extradural disease resulting in compressive myeloradiculopathy. There are 2 previously reported cases of primary intradural extramedullary carcinoid tumor, presenting with compressive symptoms. We report the first case of primary incidental intradural extramedullary carcinoid tumor. A 68-year-old man was complaining of a 2-month history of left-sided back pain and sciatica; however, he presented with acutely worse symptoms of severe left sciatica. There was no sphincter dysfunction nor power deficit on examination. A magnetic resonance imaging (MRI) scan of the lumbar spine revealed an L4-5 central disk protrusion causing left L5 nerve root compression, and a heterogeneous enhancing intradural mass at the L2-3 level displacing the cauda equina. An L4-5 microdiscectomy followed by an L2-3 laminectomy and resection of the intradural mass was performed. There was a postoperative left S1 paresthesia that was managed medically; however, the postoperative period was unremarkable. A postoperative MRI of the lumbar spine showed complete resection of the mass. A staging scan revealed an incidental thyroid nodule; however, there was no other disease burden. Histopathology of the resected specimen revealed a primary spinal carcinoid tumor. To our knowledge, this is the first reported case of incidental primary intradural spinal carcinoid tumor. Even though intradural spinal carcinoid tumors are exceedingly rare, they should be included in the differential diagnosis of enhancing intradural lesions. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Midgut carcinoids; surgical aspects, biogenic amines and vascular effects

    NARCIS (Netherlands)

    Vries, Harry de

    2006-01-01

    General introduction Carcinoids are rare slowly growing, neuroendocrine tumors. In 1907 Obendorfer was the first to use the term carcinoid (Karzinoide)1. He described an ileal tumor with a much slower progression than expected from denocarcinomas. The traditional classification of the carcinoids

  8. Isolated carcinoid tumor metastatic to the thyroid gland: report of a case initially diagnosed by fine needle aspiration cytology.

    Science.gov (United States)

    Maly, Alexander; Meir, Karen; Maly, Bella

    2006-01-01

    Neuroendocrine tumor metastatic to the thyroid gland is rare and may be difficult to differentiate from primary thyroid neuroendocrine tumors, such as medullary thyroid carcinoma (M/ITC). This report describes an unusual case of bronchial carcinoid metastatic to the thyroid diagnosed by fine needle aspiration cytology (FNAC). A 42-year-old woman with an undiagnosed bronchial carcinoid tumor presented to our clinic with a solitary nodule in the thyroid gland. FNAC of the nodule showed loosely cohesive groups of cuboidal tumor cells with scant, slightly granular cytoplasm; centrally located nuclei with a coarsely granular, salt-and-pepper chromatin pattern and inconspicuous nucleoli. Immunocytochemically the tumor cells were positive for neuron-specific enolase, chromogranin and synaptophysin and negative for thyroglobulin, calcitonin and carcinoembryonic antigen. The cytologic diagnosis of a metastatic neuroendocrine carcinoma was confirmed histologically. Metastasis to the thyroid gland may pose a diagnostic problem, particularly with tumors of neuroendocrine origin, as these have similar cytologic features in various organs. The correct preoperative cytologic diagnosis of metastatic carcinoid tumor in patients without a prior history of cancer and differential diagnosis with MTC are crucial because prognosis, workup and treatment are different in each.

  9. [Retrospective evaluation of carcinoid tumors of the appendix in children].

    Science.gov (United States)

    San Vicente, B; Bardají, C; Rigol, S; Obiols, P; Melo, M; Bella, R

    2009-04-01

    Carcinoids of the appendix are rare in children. Usually diagnosed incidentally on histologic investigation following appendectomy for acute apendicitis. To investigate the significance of the diagnosis of appendiceal carcinoid tumors in children, we conducted a retrospective study in our institution. Between 1990 and 2007 a total of 1158 appendectomy were done. In four patients the diagnosis was appendiceal carcinoid. We studied treatment, follow-up and prognosis of this patients. Indicacion for appendectomy was acute pain in lower right quadrant. The median tumor diameter was lower than 1 cm and the appropriate treatment was appendectomy. The prognosis was excellent in all the patients.

  10. Multiple synchronous bronchial carcinoid tumors: report of a case.

    Science.gov (United States)

    Camargo, S M; Machuca, T N; Moreira, A L S; Schio, S M; Moreira, J S; Camargo, J J P

    2009-02-01

    Peripheral bronchial carcinoids are uncommon. Their presentation as synchronous tumors is rare and limited to anecdotal cases.We report the case of a 62-year-old female with the radiological finding of multiple bilateral nodular lesions. Bilateral sequential thoracotomies were performed and all three nodules were treated by sublobar resections. Pathological examination revealed all specimens to be carcinoid tumors and subsequent investigation confirmed the lung as the primary site. A review of previous cases of multiple carcinoids is presented and the particularities of their management are discussed.

  11. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

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    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

  12. Tumor carcinoide de apéndice cecal Carcinoid tumor of the cecal appendix

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    Gilberto Collazo Mauri

    2012-12-01

    Full Text Available El tumor carcinoide de apéndice cecal es el más frecuente de todos los tumores apendiculares y generalmente no presentan manifestaciones clínicas. El objetivo de este trabajo fue dar a conocer un interesante caso de tumor carcinoide en una paciente de 26 años de edad cuyo cuadro clínico se interpretó como una apendicitis subaguda. Se indicó tratamiento con antibióticoterapia y hospitalización. La evolución fue satisfactoria. Se da el alta a los 10 días, con ausencia de la tumoración abdominal tanto clínica como ecográficamente. A los 3 meses se decide la operación y se realiza apendicectomía cecal, y se recibe como resultado de anatomía patológica argentafinoma del tercio distal del apéndice cecal con infiltración de la mucosa. Se interconsultó con oncología y se realizó seguimiento. La paciente se ha mantenido durante 10 años con evolución satisfactoria, libre de enfermedad. Los exámenes de ultrasonido y tomografía axial computarizada anual informan ausencia de adenopatías regionales y de metástasis hepática.The carcinoid tumors of the cecal appendix are the most frequent of all appendicular tumors, with no clinical manifestations in general. The general objective of this paper was to present an interesting case of carcinoid tumor found in a 26 years-old woman, whose clinical picture was diagnosed as subacute appendicitis. She was hospitalized and treated with antibiotics with good recovery and discharged 10 days later. She had no abdominal tumors confirmed clinically and echographically at that time. Three months later, the patient was operated on and underwent cecal appendicectomy. The pathological anatomy analysis yielded argentaffinoma in the distal third of the cecal appendix with mucosal infiltration. She was referred to the oncology service to be followed up. She has been free from any complication with good recovery for 10 years. The annual ultrasound and the CT scan show that there is neither regional

  13. [Multifocal carcinoid of the stomach].

    Science.gov (United States)

    Poletti, E M; Guffanti Pesenti, G; Giovanelli, A; Farina, C; Vescovi, L; Ghislandi, R; Sonzogni, A

    1996-05-01

    Carcinoid tumors are among the most frequently reported neuroendocrine neoplasms of the gastroenteropancreatic system. They occur more commonly as benign diseases but malignant ones can also be found. Gastric carcinoid is an uncommon pathology which accusin 2% of the carcinoid tumors of various districts and 0.5% of the gastric carcinomas. The authors report a case of gastric malignant multifocal carcinoid, diagnosed in a 63 year-old female patient. Diagnosis was confirmed at histologic analysis of the operating piece. The aim of this paper has been to review the frequency, prognosis and treatment of this neoplasm in the literature.

  14. Clear cell carcinoid tumor of the distal common bile duct

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    Tsukada Katsuhiko

    2007-01-01

    Full Text Available Abstract Background Carcinoid tumors rarely arise in the extrahepatic bile duct and can be difficult to distinguish from carcinoma. There are no reports of clear cell carcinoid (CCC tumors in the distal bile duct (DBD to the best of our knowledge. Herein, we report a CCC tumor in the DBD and review the literature concerning extrahepatic bile duct carcinoid tumors. Case presentation A 73-old man presented with fever and occult obstructive jaundice. Ultrasonography, computed tomography (CT and magnetic resonance cholangiopancreaticography (MRCP demonstrated a nodular tumor projection in the DBD without regional lymph node swelling. Under suspicion of carcinoma, we resected the head of the pancreas along with 2nd portion duodenectomy and a lymph node dissection. The surgical specimen showed a golden yellow polypoid tumor in the DBD (0.8 × 0.6 × 0.5 cm in size. The lesion was composed of clear polygonal cells arranged in nests and a trabecular pattern. The tumor invaded through the wall into the fibromuscular layer. Immunohistochemical stains showed that neoplastic cells were positive for neuron-specific enolase (NSE, chromogranin A, synaptophysin, and pancreatic polypeptide and negative for inhibin, keratin, CD56, serotonin, gastrin and somatostatin. The postoperative course was uneventful and he is living well without relapse 12 months after surgery. Conclusion Given the preoperative difficulty in differentiating carcinoid from carcinoma, the pancreaticoduodenectomy is an appropriate treatment choice for carcinoid tumors located within the intra-pancreatic bile duct.

  15. Abdominal surgery in patients with midgut carcinoid tumors. [Preoperative radiology

    Energy Technology Data Exchange (ETDEWEB)

    Aakerstroem, G.; Makridis, C.; Johansson, H. (Uppsala Univ. Hospital (Sweden). Dept. of Surgery)

    1991-01-01

    In patients with midgut carcinoid tumors a curative, radical tumor removal should be attempted when possible. As these tumors are generally malignant, irrespective of size, the radical surgery implies that intestinal resection for excision of a primary tumor should be combined with an extended mesenteric resection. When the patients present with the carcinoid syndrome the disease is, with few exceptions, too advanced for curative surgery. However, surgery often has to be performed also in patients with the advanced carcinoids. Patients with more extensive disease may thus benefit from surgical debulking of large mesenteric or hepatic metastases. Moreover, when the patients present with abdominal symptoms it is important to exclude a threatening major abdominal complication such as intestinal obstruction or ischemia. As these complications may cause malnutrion and deterioration, it is important to treat them properly, sometimes by repeated surgery. (orig.).

  16. Surgical treatment of bronchial carcinoid tumors: a single-center experience.

    Science.gov (United States)

    Machuca, Tiago Noguchi; Cardoso, Paulo Francisco Guerreiro; Camargo, Spencer Marcantonio; Signori, Leonardo; Andrade, Cristiano Feijó; Moreira, Ana Luiza Schneider; Moreira, José da Silva; Felicetti, José Carlos; Camargo, José Jesus

    2010-11-01

    Bronchial carcinoid is an infrequent neoplasm with a neuroendocrine differentiation. Surgical treatment is the gold standard therapy, with procedures varying from sublobar resections to complex lung sparing broncoplastic procedures. This study evaluates the results of surgical treatment of bronchial carcinoids and its prognostic factors. Retrospective review of 126 consecutive patients who underwent surgical treatment for bronchial carcinoid tumors between December 1974 and July 2007. There were 70 females (55%) and the mean age was 46 years, ranging from 17 to 81 years. Upon clinical presentation, 38 patients (30%) have had recurrent respiratory tract infection, 31 (24%) cough, 16 (12%) chest pain and 25 (20%) were asymptomatic. Preoperative bronchoscopic diagnosis was obtained in 74 cases (58.7%). The procedures performed were: 19 sublobar resections (14,9%), 58 lobectomies (46%), 8 bilobectomies (6.3%), 6 pneumonectomies (4.7%), 2 sleeve segmentectomies (1.5%), 26 sleeve lobectomies (20.6%) and 9 bronchoplastic procedures without lung resection (7.1%). Operative mortality was 1.5% (n = 2) and morbidity was 25.8% (n=32), including 12 respiratory tract infections and 4 reinterventions due to bleeding (3) and pleural empyema (1). Among the 112 patients available for follow-up, the overall survival at 3, 5 and 10 years was 89.2%, 85.5% and 79.8%, respectively. Five and 10-year survival for typical and atypical carcinoids were 91, 89% and 56, 47%, respectively. Overall disease-free survival at 5 years was 91.9% Statistical analysis showed that overall disease-free survival correlated with histology--typical vs. atypical--(p = 0.04) and stage (p = 0.02). Surgery provides safe and adequate treatment to bronchial carcinoid tumors. Histology and stage were the main prognostic factors. Copyright © 2010. Published by Elsevier Ireland Ltd.

  17. Goblet cell carcinoid in a patient with neurofibromatosis type 1-a rare combination

    DEFF Research Database (Denmark)

    Gregersen, Tine; Holt, Nanna; Gronbaek, Henning

    2012-01-01

    Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients...... with neurofibromatosis type 1 have an increased incidence of typical neuroendocrine tumors, but it is unknown if this is the case with goblet cell carcinoids. We describe a patient with both neurofibromatosis type 1 and goblet cell carcinoid, that according to literature would occur in 0.00017 per million per year....... This may suggest a previously unknown association between neurofibromatosis type 1 and goblet cell carcinoids....

  18. The CCK(2) receptor antagonist, YF476, inhibits Mastomys ECL cell hyperplasia and gastric carcinoid tumor development.

    Science.gov (United States)

    Kidd, M; Siddique, Z-L; Drozdov, I; Gustafsson, B I; Camp, R L; Black, J W; Boyce, M; Modlin, I M

    2010-06-08

    YF476 is a potent and highly selective cholecystokin 2 (CCK(2)) receptor antagonist of the benzodiazepine class. It inhibits gastric neuroendocrine enterochromaffin-like (ECL) cell secretion, proliferation and spontaneous formation of gastric neuroendocrine tumors (carcinoids) in cotton rats. The Mastomys rodent species exhibits a genetic predisposition to gastric ECL neuroendocrine tumor formation which can be accelerated by acid suppression and induction of hypergastrinemia. In this respect, it mimics the human condition of atrophic gastritis, hypergastrinemia and gastric carcinoid development. We investigated whether YF476 could inhibit acid suppression-induced ECL cell hyperplasia and neoplasia in this model. In addition, we examined whether YF476 could reverse established ECL cell hyperplasia and neoplasia. Targeting the CCK(2) receptor during Loxtidine-induced hypergastrinemia resulted in a reduction in ECL cell secretion (plasma and mucosal histamine, and histidine decarboxylase (HDC) transcripts, pdevelopement of gastric ECL cell carcinoids in long-term acid suppressed Mastomys. Variable importance analysis using a logistic multinomial regression model indicated the effects of YF476 were specific to the ECL cell and alterations in ECL cell function reflected inhibition of transcripts for HDC, Chromogranin A (CgA), CCK(2) and the autocrine growth factor, CTGF. We conclude that specifically targeting the CCK(2) receptor inhibits gastrin-mediated ECL cell secretion and ECL cell proliferation and tumor development in vivo. Copyright 2010 Elsevier B.V. All rights reserved.

  19. Functional imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Loft, Annika

    2010-01-01

    UNLABELLED: Functional techniques are playing a pivotal role in the imaging of cancer today. Our aim was to compare, on a head-to-head basis, 3 functional imaging techniques in patients with histologically verified neuroendocrine tumors: somatostatin receptor scintigraphy (SRS) with (111)In......-diethylenetriaminepentaacetic acid-octreotide, scintigraphy with (123)I-metaiodobenzylguanidine (MIBG), and (18)F-FDG PET. METHODS: Ninety-six prospectively enrolled patients with neuroendocrine tumors underwent SRS, (123)I-MIBG scintigraphy, and (18)F-FDG PET on average within 40 d. The functional images were fused with low......-positive, of which 3 were also (123)I-MIBG scintigraphy-positive, giving a combined overall sensitivity of 96%. SRS also exceeded (123)I-MIBG scintigraphy and (18)F-FDG PET based on the number of lesions detected (393, 185, and 225, respectively) and tumor subtypes. (123)I-MIBG scintigraphy was superior to (18)F...

  20. The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features.

    Science.gov (United States)

    Herrera-Martínez, Aura D; Gahete, Manuel D; Sánchez-Sánchez, Rafael; Salas, Rosa Ortega; Serrano-Blanch, Raquel; Salvatierra, Ángel; Hofland, Leo J; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

    2017-07-01

    Lung carcinoids (LCs) are rare tumors that comprise 1-5% of lung malignancies but represent 20-30% of neuroendocrine tumors. Their incidence is progressively increasing and a better characterization of these tumors is required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of various endocrine-related cancers, wherein they may become useful diagnostic, prognostic and therapeutic biomarkers. We aimed to evaluate the expression levels of ghrelin and SST/CORT system components in LCs, as well as to explore their putative relationship with histological/clinical characteristics. An observational retrospective study was performed; 75 LC patients with clinical/histological characteristics were included. Samples from 46 patients were processed to isolate mRNA from tumor and adjacent non-tumor region, and the expression levels of SST/CORT and ghrelin systems components, determined by quantitative-PCR, were compared to those of 7 normal lung tissues. Patient cohort was characterized by mean age 53±15 years, 48% males, 34% with tobacco exposure; 71.4/28.6% typical/atypical carcinoids, 21.7% incidental tumors, 4.3% functioning tumors, 17.7% with metastasis. SST/CORT and ghrelin system components were expressed at variable levels in a high proportion of tumors, as well as in adjacent non-tumor tissues, while a lower proportion of normal lung samples also expressed these molecules. A gradation was observed from normal non-neoplastic lung tissues, non-tumor adjacent tissue and LCs, being SST, sst4, sst5, GHS-R1a and GHS-R1b overexpressed in tumor tissue compared to normal tissue. Importantly, several SST/CORT and ghrelin system components displayed significant correlations with relevant clinical parameters, such as necrosis, peritumoral and vascular invasion, or metastasis. Altogether, these data reveal a prominent, widespread expression of key SST/CORT/ghrelin system components in LCs, where they display

  1. 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

    .027). CONCLUSION: Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders...

  2. Paraneoplastic neuromyelitis optica spectrum disorder associated with stomach carcinoid tumor.

    Science.gov (United States)

    Al-Harbi, Talal; Al-Sarawi, Adnan; Binfalah, Mohamed; Dermime, Said

    2014-09-01

    Neuromyelitis optica (NMO), or Devic's syndrome, is an autoimmune central nervous system demyelinating disorder primarily affecting the spinal cord and the optic nerves. It is characterized by the presence of NMO antibodies, alongside clinical and radiological findings. NMO and NMO-spectrum disorders (NMO-SD) have been reported in autoimmune disorders, and are infrequently described as a paraneoplastic syndrome with cancers of lung, breast, and carcinoid tumors of the thyroid. We report a patient who presented with severe vomiting, blurring of vision, vertigo, diplopia, left hemiparesis and hemisensory loss and ataxia. She was found to have a longitudinally-extensive demyelinating lesion extending from the medulla to the upper cervical spinal cord on MRI. Her gastric endoscopy revealed carcinoid tumor of the stomach, and classic paraneoplastic antibodies in the serum were negative. She had extremely high serum gastrin level and high titer of NMO IgG autoantibody. The patient made an excellent recovery with tumor resection and immunotherapy, with both clinical and radiological improvement. On rare instances, NMO or NMO-SD may present as a paraneoplastic neurological syndrome associated with carcinoid tumor of the stomach. Copyright © 2014 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  3. Diffuse Neuroendocrine Cell Hyperplasia: Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Cevriye Cansız Ersöz

    2016-01-01

    Full Text Available Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH is a rare pulmonary disorder characterised by a proliferation of neuroendocrine cells within the lung. It is believed that a minority of the patients with DIPNECH can develop carcinoid tumors. Here, we report two new cases of DIPNECH with coexisting carcinoid tumors.

  4. Pulmonary neuroendocrine tumor in a female wolf (Canis lupus lupus).

    Science.gov (United States)

    Shiraki, Ayako; Yoshida, Toshinori; Kawashima, Masahi; Murayama, Hirotada; Nagahara, Rei; Ito, Nanao; Shibutani, Makoto

    2017-03-23

    A 17-year-old female wolf (Canis lupus lupus) had a right lung mass that was adhered to the thoracic cavity. Histopathological examination revealed that the mass consisted of sheets, cord or ribbon-like structures of monotonous, small, cuboidal cells with round, oval or short-spindle nuclei and scant clear cytoplasm, demarcated by a fine fibrovascular stroma. Focal necrosis, congestion and thrombi were observed. Immunohistochemically, the tumor cells diffusely expressed cytokeratin AE1/AE3, and some expressed chromogranin A, neural cell adhesion molecule (CD56) and thyroid transcription factor-1. The number of proliferating cell nuclear antigen-positive tumor cells was low. A diagnosis of pulmonary neuroendocrine tumor was based on the resemblance to carcinoids.

  5. Differential expression of the PTEN tumor suppressor protein in fetal and adult neuroendocrine tissues and tumors: progressive loss of PTEN expression in poorly differentiated neuroendocrine neoplasms.

    Science.gov (United States)

    Wang, Luoquan; Ignat, Ana; Axiotis, Constantine A

    2002-06-01

    Genetic alteration and loss of expression of tumor suppressor gene PTEN has been found in carcinomas of the breast, prostate, and endometrium, as well as in gliomas. PTEN expression in neural crest/neuroendocrine (NC/NE) tissues and in neoplasms has not been reported. This study examines PTEN expression in embryonal, fetal, and adult tissues by immunohistochemistry. The authors found high PTEN expression in embryonal, fetal, and adult NC/NE tissues. The authors also study the PTEN expression in NC/NE neoplasms (N = 37), including 5 melanocytic nevi, 2 melanomas, 9 carcinoids, 2 moderately differentiated neuroendocrine carcinomas, 13 poorly differentiated neuroendocrine carcinomas, 2 paragangliomas, 2 pheochromocytomas, 2 medullary thyroid carcinomas, and 1 neuroblastoma. All carcinoid tumors and melanocytic nevi showed moderate or strong immunostaining for PTEN. In contrast, the majority of poorly differentiated neuroendocrine carcinomas (7 of 13) were negative for PTEN (54%); the remainder showed diminished reactivity. The two melanomas studied were also negative for PTEN immunostaining. The paragangliomas, pheochromocytomas, medullary thyroid carcinomas, and neuroblastoma all showed a strong PTEN stain. The authors postulate that PTEN is a differentiation marker for NC/NE tissue and tumors and that loss of PTEN expression may represent an important step in the progression of NE tumors.

  6. Pitfalls in the diagnosis of neuroendocrine tumors: atypical clinical and radiological findings as cause of medical mistakes.

    Science.gov (United States)

    Bajetta, Emilio; Catena, Laura; Ducceschi, Monika; Pusceddu, Sara; Milione, Massimo; Maccauro, Marco; Bajetta, Roberto; Procopio, Giuseppe; Buzzoni, Roberto; Formisano, Barbara; Di Guardo, Lorenza; Platania, Marco

    2009-01-01

    Carcinoids are infrequent neoplasms arising from neuroendocrine cells. Due to blurred symptoms and the presence of equivocal diagnostic findings, these tumors are sometimes misdiagnosed. Therefore, increased rates of false neuroendocrine tumors represent an emerging problem in clinical practice. Our aim is to alert clinicians on this matter by supplying them with useful warnings. In the specialized neuroendocrine tumor study Center Centro di Riferimento per lo Studio e la Cura dei Carcinoidi e dei Tumori Neuroendocrini (Ce.Ri.Ca), some patients highly suspected to have a neuroendocrine tumor have been recognized as having false neuroendocrine tumors. The related clinical and instrumental findings leading to a previous wrong neuroendocrine tumor diagnosis are reported. From July 2006 to December 2008, 88 consecutive cases of neuroendocrine tumors (Nets) were referred at Ce.Ri.Ca. In the former group, 8 cases of false Nets were discovered while in the remaining 80 cases a correct Net diagnosis was carried out. Watchful differential diagnoses and skill appraisal of laboratory investigations resulted in: chronic atrophic gastritis with enterochromaffin-like cell hyperplasia (4 cases), estrogen-deprivation syndrome (1), hypochondriac disorder (1), metabolic syndrome (1), and sarcoidosis (1). Neuroendocrine tumors are still relatively known clinical entities. To discriminate false neuroendocrine tumors from neuroendocrine tumors requires a good expertise and a large daily practice with the disease. Good knowledge and skillfulness in identifying biochemical alterations and false radiological positive results could avoid both patient inconvenience and very expensive workup. The importance of a multidisciplinary approach in specialized centers is emphasized.

  7. Marital Status and Survival in Patients with Carcinoid Tumors

    Directory of Open Access Journals (Sweden)

    Erin K. Greenleaf

    2016-01-01

    Full Text Available Background Marital status is a known prognostic factor in overall and disease-specific survival in several types of cancer. The impact of marital status on survival in patients with carcinoid tumors remains unknown. We hypothesized that married patients have higher rates of survival than similar unmarried patients with carcinoid tumors. Methods Using the Surveillance, Epidemiology, and End Results database, we identified 23,126 people diagnosed with a carcinoid tumor between 2000 and 2011 and stratified them according to marital status. Univariate and multivariable analyses were performed to compare the characteristics and outcomes between patient cohorts. Overall and cancer-related survival were analyzed using the Kaplan–Meier method. Multivariable survival analyses were performed using Cox proportional hazards models (hazards ratio [HR], controlling for demographics and tumor-related and treatment-related variables. Propensity score analysis was performed to determine surgical intervention distributions among married and unmarried (ie, single, separated, divorced, widowed patients. Results Marital status was significantly related to both overall and cancer-related survival in patients with carcinoid tumors. Divorced and widowed patients had worse overall survival (HR, 1.33 [95% confidence interval {CI}, 1.08–1.33] and 1.34 [95% CI, 1.22–1.46], respectively and cancer-related survival (HR, 1.15 [95% CI, 1.00–1.31] and 1.15 [95% CI, 1.03–1.29], respectively than married patients over five years. Single and separated patients had worse overall survival (HR, 1.20 [95% CI, 1.08–1.33] and 1.62 [95% CI, 1.25–2.11], respectively than married patients over five years, but not worse cancer-related survival. Unmarried patients were more likely than matched married patients to undergo definitive surgical intervention (62.67% vs 53.11%, respectively, P < 0.0001. Conclusions Even after controlling for other prognostic factors, married patients

  8. Massive parallel sequencing and digital gene expression analysis reveals potential mechanisms to overcome therapy resistance in pulmonary neuroendocrine tumors.

    Science.gov (United States)

    Walter, Robert Fred Henry; Vollbrecht, Claudia; Christoph, Daniel; Werner, Robert; Schmeller, Jan; Flom, Elena; Trakada, Georgia; Rapti, Aggeliki; Adamidis, Vasilis; Hohenforst-Schmidt, Wolfgang; Kollmeier, Jens; Mairinger, Thomas; Wohlschlaeger, Jeremias; Zarogoulidis, Paul; Porpodis, Konstantinos; Schmidt, Kurt Werner; Mairinger, Fabian Dominik

    2016-01-01

    Background : Lung cancer is the leading cause of cancer-related deaths worldwide. 25% show neuroendocrine differentiation (typical/atypical carcinoids, large-/small-cell neuroendocrine carcinomas). Carcinoids present with long survival rates, but metastatic carcinoids correlate with decreased survival and are commonly insensitive to standard chemotherapy or radiation. Therefore, novel therapeutic strategies are urgently needed. Material and methods : 70 representative tumor specimens were used for next-generation sequencing analysis of 14 genes related to therapy response. Additionally, mRNA-expression profiles of 60 matching samples were determined for 13 selected drug targets by using the NanoString nCounter technology. Results : A number of features known to sensitize tumors for different targeted therapies could be identified, which hopefully improve the clinical management of this subgroup of lung neoplasias. In particular, EGFR expression was observed in the investigated tumors in a noteworthy manner. Additionally, MDM2 was strongly expressed in the majority of all samples whereas the expression of its physiological inhibitor, CDKN2A , was nearly absent in all low-grade tumors. TP53 showed a high frequency of variants in high-grade tumors but mutations were rare in carcinoids. Conclusion : Based on our results, therapeutic approaches with MDM2-inhibitors and monoclonal anti-EGFR antibodies may be promising in pulmonary carcinoid tumors.

  9. Tumor de colisión periampular Collision tumor of the ampulla of Vater: Carcinoid and adenocarcinoma

    Directory of Open Access Journals (Sweden)

    J. Ferrando Marco

    2007-04-01

    Full Text Available Presentamos un caso de tumor de colisión periampular en el que coexisten un tumor carcinoide de pared duodenal y un adenocarcinoma de cabeza de páncreas. El paciente era un varón de 64 años con historia reciente de diarreas al que se diagnosticó una ictericia obstructiva. Histopatológicamente el tumor resecado mostraba dos neoplasias independientes. Una de ellas constituida por cordones sólidos de células neuroendocrinas que afectaba pared duodenal. La otra está formada por un adenocarcinoma bien diferenciado procedente del páncreas. Ambas neoplasias fueron confirmadas inmunohistoquímicamente. Según la literatura anglosajona revisada tan sólo hemos encontrado seis casos de esta rara coexistencia neoplásica.We report the case of a periampullary collision tumor, in which a duodenal-wall carcinoid and an adenocarcinoma of the head of the pancreas coexisted. We describe the case of a 64-year-old man with a recent history of diarrhea, who was diagnosed with obstructive jaundice. A duodeno-pancreatectomy was performed, and the specimen showed two independent neoplasms in the histopathologic study. Solid cords and nests of neuroendocrine cells in the duodenal wall formed the carcinoid tumor, whereas the other neoplasm was made up of a well-differentiated adenocarcinoma of the pancreas. Both were confirmed by immunohistochemical analysis. According to the literature reviewed, this is the sixth reported case of this rare neoplastic association.

  10. Octreotide long-acting repeatable in the treatment of neuroendocrine tumors: patient selection and perspectives

    Directory of Open Access Journals (Sweden)

    Yau H

    2017-12-01

    Full Text Available Hanford Yau,1 Mustafa Kinaan,2 Suzanne L Quinn,3 Andreas G Moraitis3 1Division of Endocrinology, Diabetes, and Metabolism, University of California, San Francisco (Fresno Division, Fresno, CA, USA; 2Division of Internal Medicine, University of Central Florida College of Medicine, Orlando, FL, USA; 3Division of Endocrinology, Diabetes, and Metabolism, Orlando VA Medical Center, Orlando, FL, USA Abstract: Over the past three decades, the incidence and prevalence of neuroendocrine tumors have gradually increased. Due to the slow-growing nature of these tumors, most cases are diagnosed at advanced stages. Prognosis and survival are associated with location of primary lesion, biochemical functional status, differentiation, initial staging, and response to therapy. Octreotide, the first synthetic somatostatin analog, was initially used for the management of gastrointestinal symptoms associated with functional carcinoid tumors. Its commercial development over time led to long-acting repeatable octreotide acetate, a long-acting version that provided greater administration convenience. Recent research demonstrates that octreotide’s efficacy has evolved beyond symptomatic management to targeted therapy with antitumoral effects. This review examines the history and development of octreotide, provides a synopsis on the classification, grading, and staging of neuroendocrine tumors, and reviews the evidence of long-acting repeatable octreotide acetate as monotherapy and in combination with other treatment modalities in the management of non-pituitary neuroendocrine tumors with special attention to recent high-quality Phase III trials. Keywords: carcinoid, everolimus, neuroendocrine tumor, octreotide LAR, somatostatin analog, ITMO, NETTER-1, PROMID, RADIANT-2

  11. Ectopic Cushing syndrome associated with thymic carcinoid tumor as the first presentation of MEN1 syndrome-report of a family with MEN1 gene mutation.

    Science.gov (United States)

    Hasani-Ranjbar, Shirin; Rahmanian, Masoud; Ebrahim-Habibi, Azadeh; Soltani, Akbar; Soltanzade, Akbar; Mahrampour, Elnaz; Amoli, Mahsa M

    2014-06-01

    Multiple endocrine neoplasia type 1(MEN1) is an autosomal dominant syndrome. Although thymic carcinoid tumor is recognized as a part of MEN1 syndrome but functioning thymic carcinoid tumor as the first presentation of the MEN1 seems to be very rare. In this report, we present a 29-year-old male who developed ectopic Cushing syndrome secondary to thymic carcinoid tumor and was diagnosed as MEN1 syndrome 2 years later. Further evaluation revealed the presence of carcinoid tumor and other MEN 1 manifestations in several other member of family. Genetic evaluation showed presence of a previously reported mutation in exon 10(R527X) of MEN1 gene in these patients. This presentation showed that thymic neuroendocrine tumor could be the first manifestation of the MEN1 syndrome and it might be diagnosed as a dominant manifestation of this syndrome in a family. We suggest biochemical or genetic screening for MEN-1 syndrome for patients with thymic carcinoid.

  12. A NEW INCOME IN PEDIATRIC PATHOLOGY: GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS. PART I: PANCREATIC TUMORS

    Directory of Open Access Journals (Sweden)

    Smaranda DIACONESCU

    2013-03-01

    Full Text Available Gastroenteropancreatic neuroendocrine tumors (GEP NET represent a heterogenous group of neoplasms: carcinoids (serotoninomas and gastroenteropancreatic (insulinomas, gastrinomas, VIPomas, glucagonomas, somatostatinomas respectively, unified by their origin (neuroendocrine cells, histology and immunohistochemical profile. Unlike their frequency in adults, the rarity of these lesions in childhood makes difficult their early diagnosis. Many tumors can be asymptomatic or may show non-specific features, the diagnosis being nevertheless based on clinical signs, dosage of hormonal specific peptides, nuclear medicine imaging and pathology confirmation. Baseline tests should also include chromogranine A and sinaptophysine. Localising studies comprise CT, MRI, somatostatine receptor scintigraphy and ultrasonography completed by endoscopy. Surgery is the mainstay therapy of GEP NET, as a complete removal can potentially cure the disease; debulking and metastasis surgery, together with adjuvant medical therapy can alleviate some symptoms, sometimes for a long period. Survival is variable, depending on tumour’s type, stage, histology and also on the completeness of the treatment.

  13. Ileal neuroendocrine tumors and heart: not only valvular consequences.

    Science.gov (United States)

    Calissendorff, Jan; Maret, Eva; Sundin, Anders; Falhammar, Henrik

    2015-04-01

    Ileal neuroendocrine tumors (NETs) often progress slowly, but because of their generally nonspecific symptoms, they have often metastasized to local lymph nodes and to the liver by the time the patient presents. Biochemically, most of these patients have increased levels of whole blood serotonin, urinary 5-hydroxyindoleacetic acid, and chromogranin A. Imaging work-up generally comprises computed tomography or magnetic resonance imaging and somatostatin receptor scintigraphy, or in recent years positron emission tomography with 68Ga-labeled somatostatin analogs, allowing for detection of even sub-cm lesions. Carcinoid heart disease with affected leaflets, mainly to the right side of the heart, is a well-known complication and patients routinely undergo echocardiography to diagnose and monitor this. Multitasking surgery is currently recognized as first-line treatment for ileal NETs with metastases and carcinoid heart disease. Open heart surgery and valve replacement are advocated in patients with valvular disease and progressive heart failure. When valvulopathy in the tricuspid valve results in right-sided heart failure, a sequential approach, performing valve replacement first before intra-abdominal tumor-reductive procedures are conducted, reduces the risk of bleeding. Metastases to the myocardium from ileal NETs are seen in heart metastases are detected, with the addition of diuretics and fluid restriction in cases of heart failure. Myocardial metastases are rarely treated by surgical resection.

  14. 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.

  15. [EGFR-expression in pulmonary neuroendocrine cell hyperplasia].

    Science.gov (United States)

    Kuhnen, C; Winter, B U

    2006-03-01

    15 cases of pulmonary neuroendocrine cell hyperplasia (carcinoid-tumorlets, diffuse idiopathic pulmonary neuroendocrine cell hyperplasia/DIPNECH) and 20 neuroendocrine pulmonary tumors (10 carcinoid tumors, 5 large cell neuroendocrine, and 5 small cell neuroendocrine lung carcinomas) were immunohistochemically analyzed for the expression of epidermal growth factor receptor (EGFR, = HER-1). All cases of neuroendocrine cell hyperplasia exhibited a maximum EGFR expression (score 3 in 100% of cells) showing predominantly membranous, partly cytoplasmic staining. 4 ot the 10 carcinoid tumors were strongly positive for EGFR, whereas the other 6 were EGFR-negative. A total of 90% of large cell neuroendocrine and small cell neuroendocrine carcinomas were negative for EGFR. Overexpression of EGFR in pulmonary neuroendocrine cell hyperplasia might be significant for the pathogenesis of these lesions. As DIPNECH is characterized by clinical signs and symptoms including mild cough and obstructive functional impairment, a specific antagonistic therapeutic trial could aim at blocking EGFR/HER-1 or its subsequent signal transduction pathway.

  16. 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.)

  17. Neuroendocrine tumors of the lung: major radiologic findings in a series of 22 histopathologically confirmed cases

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Marcel Koenigkam, E-mail: marcelk46@yahoo.com.br [Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (HCFMRP-USP), SP (Brazil); Department of Diagnostic and Interventional Radiology, Heidelberg University (Germany); Barreto, Andre Rodrigues Facanha [Clinica Radius, Clinica Sao Carlos Imagem and Santa Casa de Misericordia de Fortaleza, Fortaleza, CE (Brazil); Chagas Neto, Francisco Abaete [Program of Health Sciences Applied to the Locomotor System - Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRP-USP), Ribeirao Preto, SP (Brazil); Muglia, Valdair Francisco; Elias Junior, Jorge [Division of Radiology, Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo (FMRPUSP), Ribeirao Preto, SP (Brazil)

    2012-07-15

    Objective: To describe key imaging findings in a series of cases of primary neuroendocrine tumors of the lung (NTLs), with emphasis on computed tomography changes. Materials And Methods: Imaging studies of 22 patients (12 men, mean age 60 years) with histopathologically confirmed diagnosis, evaluated in the author's institution during the last five years were retrospectively reviewed by two radiologists, with findings being consensually described focusing on changes observed at computed tomography. Results: The authors have described five typical carcinoids, three atypical carcinoids, three large-cell neuroendocrine carcinomas (LCNCs), and 11 small-cell lung cancers (SCLCs). Only one typical carcinoid presented the characteristic appearance of central endobronchial nodule with distal pulmonary atelectasis, while the others were pulmonary nodules or masses. The atypical carcinoids corresponded to peripheral heterogeneous masses. One out of the three LCNCs was a peripheral homogeneous mass, while the others were ill-defined and heterogeneous. The 11 SCLCs corresponded to central, infiltrating and heterogeneous masses with secondary pleuropulmonary changes. Calcifications were absent both in LGNCs and SCLCs. Metastases were found initially and also at follow-up of all the cases of LCNCs and SCLCs. Conclusion: Although some imaging features may be similar, radiologic findings considered together with clinical information may play a relevant role in the differentiation of histological types of NTLs. (author)

  18. Combined adenocarcinoma-carcinoid tumor of transverse colon

    Directory of Open Access Journals (Sweden)

    Prosanta Kumar Bhattacharjee

    2013-01-01

    Full Text Available A 65-year-old male presented with painless hematochezia associated with episodic cramps in upper abdomen, watery diarrhea, and a slowly growing mass in upper abdomen. Examination revealed a firm 6 x 5 cm, intra-abdominal, epigastric mass. Colonoscopy up to 90 cm showed a stenosing, ulcero-proliferative lesion in the transverse colon. No synchronous lesion was detected. Biopsy revealed mucin secreting adenocarcinoma. Exploration showed the growth involving the transverse colon proximal to the splenic flexure with a part of ileum, approximately three feet proximal to ileo-caecal junction, adherent to it. No significant mesenteric lymph node enlargement was evident. The patient underwent resection of the growth along with the segment of adherent ileum. Continuity was re-established by a colo-colic and ileo-ileal anastomosis respectively. Patient received adjuvant chemotherapy. Post-operative histopathology demonstrated a composite histological pattern with an admixture of carcinoid tumor and adenocarcinoma, invasion of ileal serosa and adenocarcinomatous deposits in mesocolic lymph nodes, the tumor staging being (T4, N0, M0/Stage II for carcinoid and (T4, N1, M0/Stage III for adenocarcinoma. Patient was followed-up for a year and was doing well without any evidence of recurrence.

  19. Contemporary nuclear medicine diagnostics of neuroendocrine tumors

    OpenAIRE

    Todorović-Tirnanić Mila; Artiko Vera; Pavlović Smiljana; Šobić-Šaranović Dragana; Obradović Vladimir

    2015-01-01

    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 a...

  20. Tumores carcinoides del pulmón: presentación de un caso Lung carcinoid tumors: a case report

    Directory of Open Access Journals (Sweden)

    Juan Carlos Collado Otero

    2007-12-01

    Full Text Available Se presenta el caso de un paciente de 35 años de edad, que acudió a nuestro instituto después de habérsele practicado, hace 6 años en otro hospital, una lobectomía inferior derecha, tras el diagnóstico de hemangioma pulmonar derecho. En esta oportunidad se ingresa nuevamente para estudiar la reaparición de una sombra pulmonar parahiliar derecha. Presentó hemoptisis masiva y se le realizó una neumonectomía derecha de urgencia. El resultado de la biopsia confirmó como diagnóstico definitivo un tumor carcinoide bronquial. Se revisó la literatura que versa sobre las características clínicas, radiológicas y anatomopatológicas de esta enfermedad.The case of a 35-year-old patient that came to our institute after having been diagnosed right lung hemangioma and having undergone a right inferior lobectomy in another hospital 6 years ago was presented. In this opportunity, she was admitted again to study the reappearance of a right parahiliar lung shadow. She presented massive hemoptisis, and an emergency right pneumonectomy was performed. The result of the biopsy confirmed a bronchial carcinoid tumor as a definitive diagnosis. The literatute that makes reference to the clinical, radiological and anatomopathological characteristics of this disease was reviewed.

  1. Metastatic appendiceal goblet cell carcinoid masquerading as mucinous adenocarcinoma in effusion cytology: A diagnostic pitfall

    Directory of Open Access Journals (Sweden)

    Anuja Gupta

    2013-01-01

    Full Text Available Goblet cell carcinoids are rare tumors of appendix having a mixed phenotype, with partial neuroendocrine differentiation and intestinal type goblet cell morphology. The reported incidence of this tumor is still limited. Till now, only two cases of metastatic goblet cell appendiceal carcinoid on effusion cytology have been reported in literature. We describe the clinico-pathological details and lay stress on fluid cytology of metastatic goblet cell carcinoid to ascitic fluid.

  2. SEROTONIN, CATECHOLAMINES, HISTAMINE, AND THEIR METABOLITES IN URINE, PLATELETS, AND TUMOR-TISSUE OF PATIENTS WITH CARCINOID-TUMORS

    NARCIS (Netherlands)

    KEMA, IP; DEVRIES, EGE; SLOOFF, MJH; BIESMA, B; MUSKIET, FAJ

    We monitored long-term (median 11 months) concentrations of platelet serotonin and urinary serotonin, 5-hydroxyindoleacetic acid, and seven catecholamine metabolites in 44 patients with carcinoid tumors. Tumor serotonin and catecholamine contents (11 patients) and urinary histamine and

  3. Carcinoid tumor associated with adjacent dysplastic columnar epithelium in the renal pelvis: A case report and literature review.

    Science.gov (United States)

    Kim, Sung Sun; Choi, Chan; Kang, Taek Won; Choi, Yoo Duk

    2016-01-01

    Carcinoid tumors are well documented in the pulmonary and gastrointestinal systems, but very rare in the urinary tract, especially in the renal pelvis. We report on a 60-year-old female patient who presented with left flank pain and fever. Abdominal computed tomography demonstrated a heterogeneously enhancing mass in the left renal pelvis and a stone at the left proximal ureter. Multiple parenchymal lesions were also observed, which were identified as uneven caliectasis displaying air-fluid levels and renal parenchymal atrophy. The patient underwent simple nephro-ureterectomy. Macroscopically, a polypoid mass was observed in the renal pelvis. Microscopically, the tumor revealed acinar, tubular, and solid pattern and was composed of small, monotonous and hyperchromatic cells. Lining epithelia in renal pelvis and ureter revealed columnar epithelia with dysplastic change. The tumor cells were positive for chromogranin A, synaptophysin, CD56, and focally positive for cytokeratin. Immunohistochemical staining of synaptophysin and chromogranin A highlighted the neuroendocrine cells in the columnar epithelium. Ki-67 (1:50; MIB-1) labeling index was less than 1% in the area with highest uptake. We report here a case of carcinoid tumor of the renal pelvis that was associated with adjacent dysplastic columnar epithelium. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

  4. 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.

  5. Medical Treatment of Gastroenteropancreatic Neuroendocrine Tumors

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    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.

  6. 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.

  7. PET/CT in Neuroendocrine Tumors.

    Science.gov (United States)

    Castellucci, Paolo; Ambrosini, Valentina; Montini, Giancarlo

    2008-04-01

    Neuroendocrine tumors (NETs) are a rare group of neoplasms that originate from pluripotent stem cells or differentiated neuroendocrine cells, mostly localized in the bronchus, lungs, or gastroenteropancreatic tract. This issue reviews the results achieved with PET. The potential applications of the most commonly used receptor or metabolic positron-emitter radiopharmaceuticals in the field of NET to stage or restage disease, to detect unknown primary tumor, and to assess and monitor therapy response to different kind of treatments are analyzed. Copyright © 2008 Elsevier Inc. All rights reserved.

  8. CD200 Expression in Neuroendocrine Neoplasms.

    Science.gov (United States)

    Love, Jason E; Thompson, Kimberly; Kilgore, Mark R; Westerhoff, Maria; Murphy, Claire E; Papanicolau-Sengos, Antonios; McCormick, Kinsey A; Shankaran, Veena; Vandeven, Natalie; Miller, Faith; Blom, Astrid; Nghiem, Paul T; Kussick, Steven J

    2017-09-01

    CD200 expression has been well studied in hematopoietic malignancies; however, CD200 expression has not been well-characterized in neuroendocrine neoplasms. We examined CD200 expression in 391 neuroendocrine neoplasms from various anatomic sites. Tissue blocks containing pulmonary small cell carcinoma, pulmonary carcinoid, large cell neuroendocrine carcinoma, pancreatic neuroendocrine tumor, gastrointestinal carcinoid, and Merkel cell carcinoma were evaluated for CD200 expression by immunohistochemistry. A set of nonneuroendocrine carcinomas was stained for comparison. CD200 was expressed in 87% of the neuroendocrine neoplasms studied, including 60 of 72 (83%) pulmonary small cell carcinomas, 15 of 22 (68%) pulmonary carcinoids, three of four (75%) pulmonary large cell neuroendocrine carcinomas, 125 of 146 (86%) Merkel cell carcinomas, 79 of 83 (95%) gastrointestinal luminal carcinoids, and 56 of 60 (93%) pancreatic neuroendocrine tumors. Thirty-two of 157 (20%) nonneuroendocrine carcinomas expressed CD200. In gastrointestinal carcinoid and pancreatic neuroendocrine neoplasms, CD200 negativity correlated with higher grade. CD200 is a relatively sensitive marker of neuroendocrine neoplasms and represents a potential therapeutic target in these difficult-to-treat malignancies.

  9. Endoscopic ultrasound-assisted endoscopic resection of carcinoid tumors of the gastrointestinal tract Resección endoscópica asistida por ecoendoscopia de tumores carcinoides del aparato digestivo

    Directory of Open Access Journals (Sweden)

    D. Martínez-Ares

    2004-12-01

    Full Text Available Introduction: usually found in the gastrointestinal tract, carcinoids are the most frequent neuroendocrine tumors. Most of these lesions are located in areas that are difficult to access using conventional endoscopy (small intestine and appendix; carcinoid tumors found in the gastroduodenal tract and in the large intestine can be studied endoscopically; in these cases, if localized disease is confirmed, local treatment by endoscopic resection may be the treatment of choice. Since endoscopic ultrasonography has been shown to be the technique of choice for the study of tumors exhibiting submucosal growth, the selection of patients who are candidates for a safe and effective local resection should be based on this technique. Patients and method: we selected patients with gastrointestinal carcinoid tumors who were endoscopically treated between 1997 and 2002. Those patients with tumors measuring less than 10 mm, which had not penetrated the muscularis propria, and those with localized disease were considered candidates for endoscopic resection. The endpoints of this study were to assess the effectiveness (complete resection and safety (complications of the technique. Follow-up consisted of eschar biopsies performed one month and twelve months after the resection. Results: during the aforementioned period, we resected endoscopically 24 tumors in 21 patients (mean age: 51.7 years; 71.5% males. Most lesions were incidental discoveries made during examinations indicated for other reasons. Resection was indicated in most cases as a result of the suspected presence of a carcinoid tumor after endoscopic ultrasonography. Endoscopic ultrasonography also enabled us to clearly identify the layer where the lesion had originated, as well as the size of the lesion. The carcinoid tumor was removed in 13 cases (54.2% by using the conventional snare polypectomy technique, in 9 cases (37.5% assisted by a submucosal injection of saline solution and/or adrenaline, and

  10. Ectopic ACTH-Dependent Cushing’s Syndrome Caused by Bronchial Carcinoid

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    P.M. Liashuk

    2015-11-01

    Full Text Available The article presents the concept of ectopic ACTH-secreting tumors of the neuroendocrine system. There was described a rare case of ectopic ACTH-dependent Cushing’s syndrome caused by bronchial carcinoid, in the clinical pattern of which, along with typical symptoms, thromboembolic syndrome dominated. Surgical removal of bronchial carcinoid led to regression of cushingoid and other symptoms.

  11. Incidental neuroendocrine tumor of the appendiceal base less ...

    African Journals Online (AJOL)

    Incidental neuroendocrine tumor of the appendiceal base less than20 mm in diameter: is appendectomy enough? Landolsi Sana, Mannai Saber. Abstract. The appendixis the second primary site for neuroendocrine tumors. The management of incidentelly discovered neuroendocrine tumor of the appendiceal base less ...

  12. Collision tumor of the appendix: mucinous cystadenoma and carcinoid. A case report.

    Science.gov (United States)

    Dellaportas, D; Vlahos, Nf; Polymeneas, G; Gkiokas, G; Dastamani, C; Carvounis, E; Theodosopoulos, T

    2014-01-01

    Mucinous cystadenoma is the most common of benign neoplasms of the appendix and carcinoid is the most common type of primary malignant lesions of the appendix.We report a rare case of a 57-year-old female with combined mucinous cystadenoma and carcinoid tumor of the appendix.Dual carcinoid and epithelial neoplasia is a rare occurrence in the appendix. A 57-year-old Caucasian woman presented after incidentally palpating a mass on her right iliac fossa. Imaging modalities revealed a cystic tumor in the right iliac fossa with a diameter of about 8 cm, originating either from the right ovary or the appendix. She underwent laparoscopic surgical exploration, which revealed appendiceal mucocele and appendicectomy was finally performed as well as excision of a right ovarian cyst. Pathological examination showed acollision tumor consisting of mucinous cystadenoma and carcinoid tumor of the appendix. Because of the size and extension of the carcinoid tumor, which the pathology report revealed, she underwent re-exploration and laparoscopic right colectomy. Mucinous cystadenoma is rare, but it is the commonest of benign appendiceal tumours accounting for 0.6% of appendectomy specimens. It can present as appendicitis,mucocele or if the tumour ruptures, as pseudomyxomaperitonei. On the other hand, carcinoid is the most common type of primary malignant lesion of the appendix and 0.3-0.9%of appendectomy specimens, with small predominance in female patients. Rare cases of mucinous cystadenomas of the appendix coexisting with carcinoid tumors were reported before, but in our case it was a collision tumor with no transitional zone between them. Also, the clinical presentation of our patient and the differential diagnosis of ovarian lesions from appendiceal tumors is worth being mentioned. Celsius.

  13. FDA Approves Lutathera for Neuroendocrine Tumors

    Science.gov (United States)

    FDA has approved Lutathera® for some people with neuroendocrine tumors (NETs) that affect the digestive tract. On January 29, FDA approved Lutathera® for adult patients with advanced NETs that affect the pancreas or gastrointestinal tract, known as GEP-NETs.

  14. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    Pancreatic neuroendocrine tumors (PNET) are increasingly being discovered. A case of PNET diagnosed and treated during the management of acute appendicitis is presented and discussed. The importance of imaging modalities in patients with acute abdominal pain is emphasized. To the best our knowledge, this is the ...

  15. Nuclear Medicine Imaging of Neuroendocrine Tumors

    NARCIS (Netherlands)

    Brabander, Tessa; Kwekkeboom, Dik J.; Feelders, Richard A.; Brouwers, Adrienne H.; Teunissen, Jaap J. M.; Papotti, M; DeHerder, WW

    2015-01-01

    An important role is reserved for nuclear imaging techniques in the imaging of neuroendocrine tumors (NETs). Somatostatin receptor scintigraphy (SRS) with In-111-DTPA-octreotide is currently the most important tracer in the diagnosis, staging and selection for peptide receptor radionuclide therapy

  16. Other PET tracers for neuroendocrine tumors

    NARCIS (Netherlands)

    Koopmans, Klaas Pieter; Glaudemans, Andor W J M

    In this article the applicability of (124)I-MIBG and (11)C-5-HTP PET for the detection of abdominal gastro-enteropancreatic neuroendocrine tumors is discussed. (124)I-MIBG is a positron-emitting variant of (123)I-MIBG and therefore suited for PET imaging. Due to the better intrinsic characteristics

  17. Intestinal neuroendocrine tumor in a patient with pituitary adenoma. A case report and review of the current screening recommendations

    Directory of Open Access Journals (Sweden)

    Boutros Cherif

    2007-11-01

    Full Text Available Abstract Introduction Multiple endocrine neoplasia type 1 (MEN-1 patients are prone to develop carcinoid tumors. Few cases report the development of gastrointestinal carcinoid tumors in patients with MEN-1 syndrome related tumors. This is the first paper to report the occurrence of an intestinal carcinoid tumour in association with a pituitary adenoma. Case presentation A sixty eight year old female presented with intestinal obstruction four years after transphenoidal pituitary resection for pituitary adenoma. During surgical exploration and lysis of adhesions, we accidentally discovered an intestinal carcinoid tumour. Resection of the involved small bowel segment and the draining lymph nodes was undertaken. Postoperative follow up showed no biochemical or radiological evidence of residual tumor. Neuroendocrine tumors (NETs may occur as part of familial endocrine cancer syndromes including MEN-1. It is recommended that clinicians search thoroughly for MEN-1 in patients presented with NETs, however, there is no current consensus for screening patients suspected to have MEN-1 to rule out NET. Conclusion We recommend screening patients suspected to have any familial type of endocrine tumors for the presence of NET.

  18. Reproductive disturbances in multiple neuroendocrine tumor syndromes.

    Science.gov (United States)

    Lytras, Aristides; Tolis, George

    2009-12-01

    In the context of multiple neuroendocrine tumor syndromes, reproductive abnormalities may occur via a number of different mechanisms, such as hyperprolactinemia, increased GH/IGF-1 levels, hypogonadotropic hypogonadism, hypercortisolism, hyperandrogenism, hyperthyroidism, gonadotropin hypersecretion, as well as, tumorigenesis or functional disturbances in gonads or other reproductive organs. Precocious puberty and/or male feminization is a feature of McCune-Albright syndrome (MAS), neurofibromatosis type 1 (NF1), Carney complex (CNC), and Peutz-Jeghers syndrome (PJS), while sperm maturation and ovulation defects have been described in MAS and CNC. Although tumorigenesis of reproductive organs due to a multiple neuroendocrine tumor syndrome is very rare, certain lesions are characteristic and very unusual in the general population. Awareness leading to their recognition is important especially when other endocrine abnormalities coexist, as occasionally they may even be the first manifestation of a syndrome. Lesions such as certain types of ovarian cysts (MAS, CNC), pseudogynecomastia due to neurofibromas of the nipple-areola area (NF1), breast disease (CNC and Cowden disease (CD)), cysts and 'hypernephroid' tumors of the epididymis or bilateral papillary cystadenomas (mesosalpinx cysts) and endometrioid cystadenomas of the broad ligament (von Hippel-Lindau disease), testicular Sertoli calcifying tumors (CNC, PJS) monolateral or bilateral macroochidism and microlithiasis (MAS) may offer diagnostic clues. In addition, multiple neuroendocrine tumor syndromes may be complicated by reproductive malignancies including ovarian cancer in CNC, breast and endometrial cancer in CD, breast malignancies in NF1, and malignant sex-cord stromal tumors in PJS.

  19. Neuroendocrine tumors of the pancreas.

    LENUS (Irish Health Repository)

    Davies, Karen

    2009-04-01

    Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

  20. Neuroendocrine tumors of the pancreas.

    LENUS (Irish Health Repository)

    Davies, Karen

    2012-02-01

    Pancreatic endocrine tumors are rare neoplasms accounting for less than 5% of pancreatic malignancies. They are broadly classified into either functioning tumors (insulinomas, gastrinomas, glucagonomas, VIPomas, and somatostatinomas) or nonfunctioning tumors. The diagnosis of these tumors is difficult and requires a careful history and examination combined with laboratory tests and radiologic imaging. Signs and symptoms are usually related to hormone hypersecretion in the case of functioning tumors and to tumor size or metastases with nonfunctioning tumors. Surgical resection remains the treatment of choice even in the face of metastatic disease. Further development of novel diagnostic and treatment modalities offers potential to greatly improve quality of life and prolong disease-free survival for patients with pancreatic endocrine tumors.

  1. INSM1 Demonstrates Superior Performance to the Individual and Combined Use of Synaptophysin, Chromogranin and CD56 for Diagnosing Neuroendocrine Tumors of the Thoracic Cavity.

    Science.gov (United States)

    Rooper, Lisa M; Sharma, Rajni; Li, Qing Kay; Illei, Peter B; Westra, William H

    2017-11-01

    Despite the importance of recognizing neuroendocrine differentiation when diagnosing tumors of the thoracic cavity, the sensitivity of traditional neuroendocrine markers is suboptimal, particularly for high-grade neuroendocrine carcinomas such as small cell lung carcinoma and large cell neuroendocrine carcinoma. To increase sensitivity, neuroendocrine markers are routinely ordered as panels of multiple immunostains where any single positive marker is regarded as sufficient evidence of neuroendocrine differentiation. Insulinoma-associated protein 1 (INSM1) is a well-validated transcription factor of neuroendocrine differentiation that has only recently been evaluated for diagnostic use. We performed INSM1 immunohistochemistry on a large series of thoracic neuroendocrine and non-neuroendocrine tumors and compared its performance to synaptophysin, chromogranin, and CD56. INSM1 was positive in 94.9% of small cell lung carcinomas and 91.3% of large cell neuroendocrine carcinomas, compared with 74.4% and 78.3% with the combined panel of traditional markers. INSM1 also stained all (100%) of the atypical carcinoids, typical carcinoids and mediastinal paragangliomas, but only 3.3% of adenocarcinomas and 4.2% of squamous cell carcinomas. Overall, INSM1 demonstrated a sensitivity of 96.4% across all grades of thoracic neuroendocrine tumors, significantly more than the 87.4% using the panel of traditional markers (P=0.02). INSM1 is sufficiently sensitive and specific to serve as a standalone first-line marker of neuroendocrine differentiation. A more restrained approach to immunohistochemical analysis of small thoracic biopsies is appropriate given the expanding demand on this limited material for therapeutic biomarker analysis.

  2. A case of typical pulmonary carcinoid tumor treated with bronchoscopic therapy followed by lobectomy

    Directory of Open Access Journals (Sweden)

    Porpodis K

    2012-02-01

    Full Text Available Konstantinos Porpodis1, Michael Karanikas2, Paul Zarogoulidis1, Theodoros Kontakiotis1, Alexandros Mitrakas2, Agisilaos Esebidis2, Maria Konoglou3, Kalliopi Domvri1, Alkis Iordanidis4, Nikolaos Katsikogiannis5, Nikolaos Courcoutsakis4, Konstantinos Zarogoulidis11Pulmonary Department, "G Papanikolaou" General Hospital, Aristotle University of Thessaloniki, Greece; 21st University Surgery Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 31st Pulmonary Department, "G Papanikolaou" General Hospital, Thessaloniki, Greece; 4Radiology Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Greece; 5Surgery Department (NHS, University General Hospital of Alexandroupolis, GreeceAbstract: Carcinoid bronchopulmonary tumors represent approximately 25% of all carcinoid tumors and 1%–2% of all lung neoplasms. The most common symptoms are: persistent cough, asthma-like wheezing, chest pain, dyspnea, hemoptysis and obstructive pneumonitis. We present a case of a young adult diagnosed with a typical carcinoid tumor. The diagnosis was established on the basis of imaging examination and bronchoscopic biopsy. The patient was treated with bronchoscopic electrocautery therapy to relieve the obstructed airway, followed by surgical lobectomy in order to entirely remove the exophytic damage. This approach was not only a palliative management to bronchial obstruction but also avoided pneumonectomy. Recent studies support the use of such interventional resection methods, as they may result in a more conservative surgical resection.Keywords: carcinoid tumor, typical lung carcinoid, therapeutic bronchoscopy, surgical resection

  3. Concordance in the neuroendocrine tumors between scintigraphy with pentetreotide labelled with indium 111 and morphological imaging; Concordance dans les tumeurs neuroendocrines entre la scintigraphie au pentetreotide marque a l'indium 111 et l'imagerie morphologique

    Energy Technology Data Exchange (ETDEWEB)

    Elkadri, N.; Sellem, A.; El Ajmi, W.; Meddeb, I.; Hammami, H. [Hopital militaire de Tunis, Service de medecine nucleaire (Tunisia); Rejeb, O.; Slimene, H. [Hopital La Rabta, service d' endocrinologie, Tunis (Tunisia)

    2010-07-01

    Assess the consistency in the exploration of neuroendocrine tumors between pentetreotide scintigraphy labeled with {sup 111}In (octreoscan) and morphological imaging by CT and / or magnetic resonance imaging (CT and / or MRI). Conclusions: The association between Octreoscan and morphologic imaging (CT and / or MRI) allows a more complete assessment of the lesions of neuroendocrine tumors. Octreoscan is probably not indicated in cases of carcinoid syndrome with a positive urine assay for 5-hydroxy-indole-acetic acid (5-H.I.A.A.) and without hepatic localization in morphological imaging.Scintigraphy with depreotide labelled with {sup 99m}Tc would be probably more appropriate. (N.C.)

  4. A Remarkable Improvement of Patients with Idiopathic Thrombocytopenic Purpura after appendectomy including Carcinoid tumor

    Directory of Open Access Journals (Sweden)

    Hamidreza Alizadeh-Otaghvar

    2011-09-01

    Full Text Available The assistance of chronic idiopathic thrombocytopenic purpura and appendiceal carcinoid tumor is so rare and has not been reported before .we present here in a 11 year old boy that is the known case of chronic idiopathic thrombocytopenic purpura (with the platelet count of 20000 when admitted. He reffered due to anorexia, pain and tenderness of right lower quadrant of abdomen and vomiting. He also had leukocytosis and abdominal free fluid in sonographic report. These findings suggested the diagnosis of acute appendicitis and the patient underwent appendectomy, after the operation, the platelet count became normal. The pathologic report of the specimen of the appendix was carcinoid tumor. Now the question is whether the appendiceal carcinoid tumor can be the reason of symptoms of chronic idiopathic.

  5. 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...

  6. Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Morgan, Rosemary E; Pommier, SuEllen J; Pommier, Rodney F

    2017-11-02

    Recently, there has been a move toward decreasing the threshold for liver debulking for metastatic carcinoid tumors from 90% to 70%. The debulking threshold and factors that predict outcomes of liver debulking operations specifically among pancreatic neuroendocrine tumors are not well defined. Records of patients with pancreatic neuroendocrine tumors undergoing liver debulking with a threshold of 70% from 2006 to 2016 were reviewed. Extrahepatic metastases and positive margins by enucleation were allowed. Liver progression-free survival and overall survival were calculated by the Kaplan-Meier method for various factors and compared by log-rank. Factors also were correlated with liver progression-free survival and overall survival by multivariate regression analyses. Forty-two patients underwent 44 operations, of which 24 resulted in 100% debulking, 12 resulted in ≥90% debulking, and 8 resulted in ≥70% debulking. Median liver progression-free survival was 11 months. The 5-year overall survival rate was 81%. There were no significant differences in outcome based on percent debulked. Only liver metastasis ≥5 cm correlated with liver progression-free survival and overall survival. Consideration should be given to expanding the criteria for liver debulking in pancreatic neuroendocrine tumors to include a new threshold of >70% debulking, intermediate grade tumors, positive margins, and extrahepatic metastases; these criteria yield results indistinguishable from complete resection. Using these expanded criteria will increase the number of patients eligible for an operation and maintain high survival rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A Case of Early-Stage Ovarian Carcinoid Tumor Metastasized to the Liver

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    Seiji Kanayama

    2012-01-01

    Full Text Available We report a case of ovarian carcinoid tumor that recurred with multiple liver metastases and was successfully treated with chemoembolization. A 76-year-old woman was admitted to our hospital presented with abdominal distension and abnormal uterine bleeding for about 6 months. She presented with hyperestrogenic and androgenic manifestations such as vaginal bleeding with endometrial hyperplasia and hirsutism. Magnetic resonance (MR imaging revealed a large solid and cystic ovarian tumor of 17 cm at maximum diameter. On the basis of the clinical diagnosis of sex cord stromal tumor containing a mature cystic teratoma, she underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The pathology report revealed that the mass in the left ovary was a carcinoid tumor, insular type, with mature cystic teratoma. Two years after surgical treatment, multiple liver metastases were revealed by abdominal CT. Hepatic arterial infusion of cisplatin was performed for 2 courses, and multiple metastatic nodules have remarkably reduced. No established chemotherapy or radiation therapy treatments are currently available for recurrent or advanced carcinoid tumors. Our paper suggests that chemoembolization with cisplatin may be effective in treatment of patients with multiple liver metastases of ovarian carcinoid tumor.

  8. Acromegaly due to GHRH-secreting large bronchial carcinoid. Complete recovery following tumor surgery.

    Science.gov (United States)

    Bolanowski, M; Schopohl, J; Marciniak, M; Rzeszutko, M; Zatonska, K; Daroszewski, J; Milewicz, A; Malczewska, J; Badowski, R

    2002-06-01

    A case of acromegaly, secondary to GHRH secretion by a large bronchial carcinoid is reported. A 61-year-old woman presented with typical symptoms and signs of acromegaly for at least 10 years. She suffered from recurrent pneumonias, but repeated chest X-ray examinations failed to demonstrate the bronchial tumor. The diagnosis was confirmed by elevated GH, IGF-1 and GHRH secretion. We have shown an enlarged pituitary gland without focal lesions together with a cerebral meningioma on MRI and the presence of a bronchial carcinoid tumor. The latter was confirmed by histology carried out after bronchoscopy and tumor excision. We observed partial suppression of GH secretion following short-term oral bromocriptine administration in this patient. Surgical removal of the carcinoid tumor resulted in a complete clinical, hormonal and radiological cure of acromegaly. This case of acromegaly due to ectopic GHRH secretion by bronchial carcinoid differs from others described in the literature by an atypical large tumor size, the suppression of elevated GH secretion by oral bromocriptine and a concomitant meningioma.

  9. Reversible right-sided heart failure secondary to carcinoid crisis.

    Science.gov (United States)

    Soto Herrera, Mariana; Restrepo, José A; Díaz, Jesús H; Ramos, Andrés; Felipe Buitrago, Andrés; Gómez Mejía, Mabel

    2013-01-01

    Carcinoid crisis is an infrequent and little-described complication of neuroendocrine tumors that can be life threatening. It may develop during induction of anesthesia, intraoperatively, during tumor manipulation and arterial embolization, or even spontaneously. The massive release of neuroendocrine substances can lead to potentially fatal complications. Somatostatin analogs inhibit the release of these substances and are the mainstay of treatment. The following case report describes a patient with reversible acute right-sided heart failure posterior to hepatic artery embolization.

  10. Meta-iodobenzyl guanidine for detection and staging of neuroendocrine tumors

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    Pryma, Daniel [Nuclear Medicine and Clinical Molecular Imaging Division, University of Pennsylvania, Philadelphia, PA 19105 (United States); Divgi, Chaitanya [Nuclear Medicine and Clinical Molecular Imaging Division, University of Pennsylvania, Philadelphia, PA 19105 (United States)], E-mail: chaitanya.divgi@uphs.upenn.edu

    2008-08-15

    Gastroenteropancreatic neuroendocrine tumors (GEP-NET) are slow-growing neoplasms that arise from the neuroendocrine system of the gastrointestinal tract and pancreas. These may be classified based on location into the following: pheochromocytomas and parangangliomas; carcinoids; and pancreatic endocrine tumors. The majority of these tumors are nonfunctional, and thus, molecular imaging methods are critical in detection and staging of disease. Meta-iodobenzyl guanidine (MIBG) is a norepinephrine analog taken up by norepinephrine transporters that are overexpressed in the majority of GEP-NET. Radioactive MIBG can be used to image GEP-NET. The isotopes suitable for imaging include iodine-123 and iodine-131, using single-photon cameras, and iodine-124, using positron emission tomography (PET). Imaging is usually carried out a day or more after administration of the radiotracer, and serial and tomographic imaging may be necessary for optimal delineation. MIBG imaging is more useful for detecting pheochromocytoma, with reported accuracies greater than 80%, than for detecting carcinoid tumors, where the accuracy has been {approx}70% and is reportedly higher in mid-gut tumors. MIBG imaging has been invaluable in the accurate staging of children with neuroblastoma, a lethal childhood tumor of the sympathetic nervous system. An important application of MIBG imaging is to demonstrate targeting of therapeutic I-131 MIBG. Imaging is thus useful in the detection of disease as well as in the demonstration of adequate targeting for therapy - either qualitatively or quantitatively with dosimetry. The latter will probably be feasible with PET using isotopes like iodine-124, and perhaps with single photon emission computed tomography/computed tomography. Imaging with MIBG will continue to be the mainstay for detection and staging of GEP-NET. More importantly, perhaps, imaging with MIBG will form part of an imaging continuum, including assessment of glycolytic rate and somatostatin

  11. Tumor carcinoide de la apéndice cecal: Reporte de cuatro casos en la Clínica Carlos Ardila Lülle, Floridablanca, Colombia Carcinoid tumor of the cecal appendix: A report of four cases in the Clinica Carlos Ardila Lulle, Floridablanca, Colombia

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    Julio Cesar Mantilla

    2011-08-01

    appendicectomies and occur most often in women between the fourth o fifth decade of life. Usually these are small lesions diagnosed after appendicectomy. Methodology: This work belongs to a description of cases of carcinoid tumor of cecal appendix, conduced in the MEGA anatomic pathology laboratory of Carlos Ardila Lulle Clinic (CAL, wich includes protocols review of surgical specimens analized between January 1, 2000 and December 31, 2010. Results: During the proposed period are four cases of carcinoid tumor confined to the cecal appendix in four young women. Three of the lesions have the A histological type or insular pattern, and the remainder have the B histological type or trabecular pattern, in all cases documented reactivity with silver salts with Masson-Fontana stain and all four were found positive with the neuroendocrine marker chromogragin. Conclusion: The carcinoid tumors of the apenddix are lesions of neuroendocrine origen, most of them located at the tip of the organ, and having a indolent clinical course; however some of these tumors have an aggressive behavior, which depends on its size and the mitotic activity of its cells, that's the reason why the diagnostic evaluation of neuroendocrine markers like chromogranin, and Ki67 (proliferation cell index are recommended. Salud UIS 2011; 43 (2: 203-210

  12. Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature

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    Demirci Ilhan; Herold Susanne; Kopp Andreas; Flaßhove Michael; Klosterhalfen Bernd; Janßen Hermann

    2012-01-01

    Abstract Background Overdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, applicati...

  13. Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

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    Norio Yokoigawa

    2009-04-01

    Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

  14. 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)

    2017-01-05

    Poorly Differentiated Malignant 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.)

  15. Management of neuroendocrine tumors of unknown primary.

    Science.gov (United States)

    Alexandraki, Krystallenia; Angelousi, Anna; Boutzios, Georgios; Kyriakopoulos, Georgios; Rontogianni, Dimitra; Kaltsas, Gregory

    2017-12-04

    Neuroendocrine neoplams (NENs) are mostly relatively indolent malignancies but a significant number have metastatic disease at diagnosis mainly to the liver. Although in the majority of such cases the primary origin of the tumor can be identified, in approximately 11-22% no primary tumor is found and such cases are designated as NENs of unknown primary origin (UPO). This has significant therapeutic implications with respect to potentially resectable hepatic disease and/or application of appropriate medical therapy, either chemotherapeutic agents or targeted treatment, as the response to various treatments varies according to the origin of the primary tumor. This lack of tumor specific orientated treatment may also account for the relatively poorer prognosis of NENs of UPO compared to metastatic NENs with a known primary site. In the majority of cases the primary tumors are located in the small bowel and the lung, but a number may still elude detection. Occasionally the presence of a functional syndrome may direct to the specific tissue of origin but in the majority of cases a number of biochemical, imaging, histopathological and molecular modalities are utilized to help identify the primary origin of the tumor and direct treatment accordingly. Several diagnostic algorithms have recently been developed to help localize an occult primary tumor; however, in a number of cases no lesion is identified even after prolonged follow-up. It is expected that the delineation of the molecular signature of the different NENs may help identify such cases and provide appropriate treatment.

  16. The clinical value of scintigraphy of neuroendocrine tumors using (99m)Tc-HYNIC-TOC.

    Science.gov (United States)

    Artiko, V; Sobic-Saranovic, D; Pavlovic, S; Petrovic, M; Zuvela, M; Antic, A; Matic, S; Odalovic, S; Petrovic, N; Milovanovic, A; Obradovic, V

    2012-01-01

    To assess the value of whole body scintigraphy using (99m)Tc-HYNIC-TOC (Tektrotyd) and with single photon emission computerized tomography (SPECT) in the detection of primary and metastatic neuroendocrine tumors (NETs). Thirty patients with different neuroendocrine tumors, mainly gastroenteropancreatic (GEP), were investigated. Whole body scintigraphy was performed 2 h (if necessary 10 min and 24h) after i.v. administration of 740 Mbq (99m)Tc-Tektrotyd, Polatom. In cases of unclear findings obtained by whole body scintigraphy, investigation was followed by SPECT. From 12 patients with NETs of unknown origin, there were 10 true positive (TP), and 2 false negative (FN) findings. Diagnosis was made with SPECT in 6 patients. From 8 patients with gut carcinoids, there were 4 TP, 2 true negative (TN), one FN, and one false positive (FP) finding. Diagnosis was made with SPECT in 2 patients. From 7 patients with neuroendocrine pancreatic carcinomas there were 4 TP and 3 TN findings. Diagnosis was made with SPECT in 2 patients. From 3 patients with gastrinomas there were 2 TP findings and one TN findings. Diagnosis was made with SPECT findings in 2 patients. Sensitivity of (99m)Tc-HYNIC-TOC was 87%, specificity 86%, positive predictive value 95%, negative predictive value 67% and accuracy 87%. We concluded that scintigraphy with (99m)Tc-Tektrotyd is an useful method for diagnosis, staging and follow up of the patients with NETs.

  17. Gastric non-secreting neuroendocrine tumor and hypochlorhydria-related hypergastrinemia: a case report.

    Science.gov (United States)

    Biolato, Marco; Alfieri, Sergio; Ianiro, Gianluca; Pizzoferrato, Marco; Gasbarrini, Giovanni

    2013-02-22

    Zollinger-Ellison syndrome is characterized by recurrent peptic ulcers and diarrhea that result from gastrin-secreting neuroendocrine tumors of the gastrointestinal tract; nevertheless, severe hypergastrinemia may also have alternative pathogenetic explanations. A 61-year-old woman of Caucasian origin presented with a history of epigastric pain and early satiety, severe hypergastrinemia (approximately 2000 pg/mL) and a neuroendocrine polyp in the corpus of her stomach. Chronic atrophic gastritis and intestinal metaplasia was present, but she denied use of acid suppressant drugs and the results of tests for Helicobacter pylori as well as gastric parietal cell and intrinsic factor antibodies were negative. She underwent a radical gastric tangential resection. Six months later, serum gastrin was still elevated despite lack of recurrence of tumor. The clinical picture was suggestive for a hypochlorhydria-related hypergastrinemia with subsequent development of a non-secreting carcinoid. We suggest a periodic endoscopic follow-up in patients with severe hypochlorhydria-related hypergastrinemia in order to earlier detect neuroendocrine polyps.

  18. Primary carcinoid tumor of the kidney with estrogen and progesterone receptor expression

    Science.gov (United States)

    LIN, CHUNHUA; WU, JITAO; GAO, ZHENLI; QU, GUIMEI; WANG, WEI; YU, GUOHUA

    2015-01-01

    Primary carcinoid tumors are uncommon neoplasms in the kidney. The current study presents a case of primary carcinoid tumor of the kidney in a 49-year-old female who suffered from painless gross hematuria for half a month. Left hydronephrosis, a horseshoe kidney and a space-occupying lesion of the left ureter were found by abdominal computed tomography scans and ultrasonic testing. Surgery was performed and an oval tumor was found under the left ureter; the tumor and left kidney were excised completely. The neoplasm was composed of solid nests of cells, trabeculae, adenoid structures and anastomosing cords in a loose and myxoid background. The tumor cells, which were consistent in volume, exhibited centrally oval nuclei with inconspicuous nucleoli, and eosinophilic finely granular cytoplasm. Upon immunohistochemical staining, the neoplastic cells were positive for AE1/AE3, vimentin, synaptophysin, chromogranin A, estrogen receptor and progesterone receptor, while being negative for epithelial membrane antigen, inhibin A, cluster of differentiation (CD)99, S-100 and CD10. Based on the histological characteristics, a diagnosis of primary carcinoid tumor of the left kidney was formed. The patient did not receive further treatment. The total follow-up period was 18 months after the surgery and repeated imaging examinations every 6 months revealed no recurrence. PMID:26171049

  19. CLINICAL VALUE OF CHROMOGRANIN A IN GASTROENTEROPANCREATIC NEUROENDOCRINE TUMORS

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    N. V. Lyubimova

    2015-01-01

    Full Text Available Background: Neuroendocrine tumors (NET is a heterogeneous group of neoplasms characterized by hypersecretion of biologically active sub- stances that manifests by specific syndromes and determines the clinical course of the disease. The most common NET types are those of gastrointestinal tract. The obligatory biochemical marker used in the examination of NET patients is chromogranin A (CgA.Aim: Evaluation of the CgA value for diagnostics and monitoring of gastrointestinal NETs.Materials and methods: A comparative study of plasma CgA levels was performed in 146 patients with gastroenteropancreatic neuroendocrine tu- mors and 66 healthy individuals using the enzyme immunoassay “Chromogranin A ELISA kit” (Dako A/S, Denmark.Results: CgA levels were significantly higher in patients with NETs of all localizations, such as pancreas, stomach, gut, small and large bowel, than in the healthy subjects (р < 0.000001. In NET patients, CgA secretion was highly variable, with the highest value in the group of patients with gastric NETs (102000 U/l. The highest CgA medians were detected in patients with small intestinal (183.9 U/l, colon (148.4 U/l and pancreatic (135.9 U/l NETs. There was an association between CgA secretion and extension or activity of NETs, with the highest median values in patients with hepatic metastases (395 U/l and those with carcinoid syndrome (352 U/l. The clinical significance of CgA as a NET marker was assessed using the cut-off value of 33 U/l, calculated according to the results in the control group. Overall diagnostic sensitivity of CgA in NET patients was high (85.8% with a specificity of 98.5%. Conclusion: The results obtained confirm a high sensitivity of CgA as a NET marker whose determination helps to improve accuracy of diagnostics and to assess NET prevalence.

  20. Identification of deregulation of apoptosis and cell cycle in neuroendocrine tumors of the lung via NanoString nCounter expression analysis.

    Science.gov (United States)

    Walter, Robert Fred Henry; Werner, Robert; Ting, Saskia; Vollbrecht, Claudia; Theegarten, Dirk; Christoph, Daniel Christian; Schmid, Kurt Werner; Wohlschlaeger, Jeremias; Mairinger, Fabian Dominik

    2015-09-22

    Neuroendocrine tumors of the lung comprise typical (TC) and atypical carcinoids (AC), large-cell neuroendocrine cancer (LCNEC) and small-cell lung cancer (SCLC). Cell cycle and apoptosis are key pathways of multicellular homeostasis and deregulation of these pathways is associated with cancerogenesis. Sixty representative FFPE-specimens (16 TC, 13 AC, 16 LCNEC and 15 SCLC) were used for mRNA expression analysis using the NanoString technique. Eight genes related to apoptosis and ten genes regulating key points of cell cycle were investigated. ASCL1, BCL2, CASP8, CCNE1, CDK1, CDK2, CDKN1A and CDKN2A showed lower expression in carcinoids compared to carcinomas. In contrast, CCNE1 and CDK6 showed elevated expression in carcinoids compared to carcinomas. The calculated BCL2/BAX ratio showed increasing values from TC to SCLC. Between SCLC and LCNEC CDK2, CDKN1B, CDKN2A and PNN expression was significantly different with higher expression in SCLC. Carcinoids have increased CDK4/6 and CCND1 expression controlling RB1 phosphorylation via this signaling cascade. CDK2 and CCNE1 were increased in carcinomas showing that these use the opposite way to control RB1. BAX and BCL2 are antagonists in regulating apoptosis. BCL2 expression increased over BAX expression with increasing malignancy of the tumor from TC to SCLC.

  1. Neuroendocrine tumor of the inguinal node: A very rare presentation

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    Niharika Bisht

    2017-12-01

    Full Text Available Neuroendocrine tumors are a broad family of tumors arising most commonly in the gastrointestinal tract and the bronchus pulmonary tree. The other common sounds are the parathyroid, pituitary and adrenal gland. Inguinal node as a primary presentation of a neuroendocrine tumor is an extremely rare presentation. We present the case of a 43-year-old-male who presented with the complaints of an inguinal node swelling without any other symptoms and on further evaluation was diagnosed to have a non-metastatic neuroendocrine tumor of the inguinal node. He was treated with a combination of chemotherapy and surgery and is presently awaiting completion chemotherapy.

  2. Neuroendocrine tumor presenting like lymphoma: a case report

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    Vincenzi Bruno

    2011-10-01

    Full Text Available Abstract Introduction Neuroendocrine tumors are a rare but diverse group of malignancies that arise in a wide range of organ systems, including the mediastinum. Differential diagnosis includes other masses arising in the middle mediastinum such as lymphoma, pericardial, bronchogenic and enteric cysts, metastatic tumors, xanthogranuloma, systemic granuloma, diaphragmatic hernia, meningocele and paravertebral abscess. Case presentation We present a case of 42-year-old Caucasian man with a neuroendocrine tumor of the middle-posterior mediastinum and liver metastases, which resembled a lymphoma on magnetic resonance imaging. Conclusion The differential diagnosis in patients with mediastinal masses and liver lesions should include neuroendocrine tumor.

  3. CARCINOID TUMOR OF THE DUODENUM: a rare tumor at an unusual site. Case series from a single institution

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    Jaques WAISBERG

    2013-03-01

    Full Text Available Context Duodenal carcinoids are extremely rare, and their characteristics and biological behavior have not been fully elucidated. Objective To analyze the clinicopathological characteristics of patients with resected duodenal carcinoids. Methods Twenty patients (12 females and 8 males were investigated. Their average age was 66.4 ± 5.8 years old (43 to 88 years old. The data corresponding to the clinical picture, diagnosis, treatment, and prognosis of patients with duodenal carcinoid tumors subjected to resection over a period of 18 years (1993-2011 were analyzed. Results The most common symptoms were dyspepsia (50% and epigastric pain (45% followed by weight loss (10% and vomiting (5%. Carcinoid syndrome was not observed in any patient. The lesion was located on the first part of the duodenum in 15 (75% patients, the second part in 4 (20% patients, and the third part in 1 (5% patient. The diagnosis of a carcinoid tumor was established through an endoscopic excision biopsy in 19 (95% patients and an histopathological examination of the surgical specimen in 1 (5% patient. The average tumor size was 1.1 cm ± 0.4 cm (0.3 cm to 6.0 cm. Nineteen (95% patients were initially treated by endoscopic resection of the duodenal lesion. One patient (5%, whose tumor was on the third part of the duodenum underwent a duodenectomy of the third and fourth duodenal parts and duodenojejunal anastomosis. The duodenal carcinoid resection margin was involved in four (20% patients. Four (20% patients were subjected to a partial gastrectomy to fully remove the lesion. The tumor was restricted to the submucosal layer in 16 (80% cases, and it penetrated into the muscular layer in 4 (20% cases. All patients exhibited positive chromogranin A, neuron-specific enolase, and/or synaptophysin immunostaining. The average duration of the follow-up period was 39.6 months (3 to 96 months. Twelve (60% of the 20 cases in this series are alive without any evidence of active

  4. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

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    Tonelli, Francesco, E-mail: f.tonelli@dfc.unifi.it; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)

    2012-05-07

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  5. Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease.

    Science.gov (United States)

    Hendifar, Andrew E; Marchevsky, Alberto M; Tuli, Richard

    2017-03-01

    Neuroendocrine tumors (NETs) comprise a heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, most commonly originating from the lungs and gastrointestinal tract. Lung NETs can be classified as well differentiated (low-grade typical carcinoids [TCs] and intermediate-grade atypical carcinoids [ACs]) and poorly differentiated (high-grade large cell neuroendocrine carcinoma or SCLC). The incidence of these tumors is increasing, but disease awareness remains low among thoracic specialists, who are often involved in the diagnosis and early treatment for these patients. An accurate and timely diagnosis can ensure the implementation of appropriate treatment and have a substantial impact on prognosis. However, lung NET classification and diagnosis, particularly for TCs/ACs, are complicated by several factors, including a variable natural history and nonspecific symptoms. Surgery remains the only curative option for TCs/ACs, but there is a lack of consensus between lung NET management guidelines regarding optimal treatment approaches in the unresectable/metastatic setting on account of the limited availability of high-level clinical evidence. As a result, a multidisciplinary approach to management of lung NETs is required to ensure a consistent and optimal level of care. RADIANT-4 is the first phase III trial involving a large subpopulation of patients with advanced well-differentiated lung NETs to report reductions in the risk for disease progression and death with everolimus over placebo. This led to the recent U.S. approval of everolimus-the first agent approved for advanced lung TCs/ACs. To further improve evidence-based care, additional randomized controlled trials in patients with lung carcinoids are needed. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

  6. Carcinoid heart disease.

    Science.gov (United States)

    Hassan, Saamir A; Banchs, Jose; Iliescu, Cezar; Dasari, Arvind; Lopez-Mattei, Juan; Yusuf, Syed Wamique

    2017-10-01

    Rare neuroendocrine tumours (NETs) that most commonly arise in the gastrointestinal tract can lead to carcinoid syndrome and carcinoid heart disease. Patients with carcinoid syndrome present with vasomotor changes, hypermotility of the gastrointestinal system, hypotension and bronchospasm. Medical therapy for carcinoid syndrome, typically with somatostatin analogues, can help control symptoms, inhibit tumour progression and prolong survival. Carcinoid heart disease occurs in more than 50% of these patients and is the initial presentation of carcinoid syndrome in up to 20% of patients. Carcinoid heart disease has characteristic findings of plaque-like deposits composed of smooth muscle cells, myofibroblasts, extracellular matrix and an overlying endothelial layer which can lead to valve dysfunction. Valvular dysfunction can lead to oedema, ascites and right-sided heart failure. Medical therapy of carcinoid heart disease is limited to symptom control and palliation. Valve surgery for carcinoid heart disease should be considered for symptomatic patients with controlled metastatic carcinoid syndrome. A multidisciplinary approach is needed to guide optimal management. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Synchronous Adenocarcinoma of the Colon and Rectal Carcinoid

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    Vamshidhar Vootla

    2016-10-01

    Full Text Available Primary colonic adenocarcinoma and synchronous rectal carcinoids are rare tumors. Whenever a synchronous tumor with a nonmetastatic carcinoid component is encountered, its prognosis is determined by the associate malignancy. The discovery of an asymptomatic gastrointestinal carcinoid during the operative treatment of another malignancy will usually only require resection without additional treatment and will have little effect on the prognosis of the individual. This article reports a synchronous rectal carcinoid in a patient with hepatic flexure adenocarcinoma. We present a case of a 46-year-old Hispanic woman with a history of hypothyroidism, uterine fibroids and hypercholesterolemia presenting with a 2-week history of intermittent abdominal pain, mainly in the right upper quadrant. She had no family history of cancers. Physical examination was significant for pallor. Laboratory findings showed microcytic anemia with a hemoglobin of 6.6 g/dl. CT abdomen showed circumferential wall thickening in the ascending colon near the hepatic flexure and pulmonary nodules. Colonoscopy showed hepatic flexure mass and rectal nodule which were biopsied. Pathology showed a moderately differentiated invasive adenocarcinoma of the colon (hepatic flexure mass and a low-grade neuroendocrine neoplasm (carcinoid of rectum. The patient underwent laparoscopic right hemicolectomy and chemotherapy. In patients diagnosed with adenocarcinoma of the colon and rectum, carcinoids could be missed due to their submucosal location, multicentricity and indolent growth pattern. Studies suggest a closer surveillance of the GI tract for noncarcinoid synchronous malignancy when a carcinoid tumor is detected and vice versa.

  8. CARCINOID TUMOR OF THE DUODENUM: a rare tumor at an unusual site. Case series from a single institution

    Directory of Open Access Journals (Sweden)

    Jaques WAISBERG

    2013-03-01

    Full Text Available Context Duodenal carcinoids are extremely rare, and their characteristics and biological behavior have not been fully elucidated. Objective To analyze the clinicopathological characteristics of patients with resected duodenal carcinoids. Methods Twenty patients (12 females and 8 males were investigated. Their average age was 66.4 ± 5.8 years old (43 to 88 years old. The data corresponding to the clinical picture, diagnosis, treatment, and prognosis of patients with duodenal carcinoid tumors subjected to resection over a period of 18 years (1993-2011 were analyzed. Results The most common symptoms were dyspepsia (50% and epigastric pain (45% followed by weight loss (10% and vomiting (5%. Carcinoid syndrome was not observed in any patient. The lesion was located on the first part of the duodenum in 15 (75% patients, the second part in 4 (20% patients, and the third part in 1 (5% patient. The diagnosis of a carcinoid tumor was established through an endoscopic excision biopsy in 19 (95% patients and an histopathological examination of the surgical specimen in 1 (5% patient. The average tumor size was 1.1 cm ± 0.4 cm (0.3 cm to 6.0 cm. Nineteen (95% patients were initially treated by endoscopic resection of the duodenal lesion. One patient (5%, whose tumor was on the third part of the duodenum underwent a duodenectomy of the third and fourth duodenal parts and duodenojejunal anastomosis. The duodenal carcinoid resection margin was involved in four (20% patients. Four (20% patients were subjected to a partial gastrectomy to fully remove the lesion. The tumor was restricted to the submucosal layer in 16 (80% cases, and it penetrated into the muscular layer in 4 (20% cases. All patients exhibited positive chromogranin A, neuron-specific enolase, and/or synaptophysin immunostaining. The average duration of the follow-up period was 39.6 months (3 to 96 months. Twelve (60% of the 20 cases in this series are alive without any evidence of active

  9. Ependymoma and Carcinoid Tumor Associated with Ovarian Mature Cystic Teratoma in a Patient with Multiple Endocrine Neoplasia I

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    Reed Spaulding

    2014-01-01

    Full Text Available Ovarian teratomas rarely undergo new neoplastic transformation and account for a small percentage of malignant ovarian germ cell neoplasms. Here we report a case of a 51-year-old woman with multiple endocrine neoplasia type I (MEN I who was found to have an ependymoma and neuroendocrine tumor (trabecular carcinoid associated with mature cystic teratoma of her left ovary. The ependymoma component displayed cells with round nuclei and occasional small nucleoli which were focally arranged in perivascular pseudorosettes and true rosettes. Rare mitoses were identified. No necrosis was present. Immunohistochemical staining was positive for S-100 and GFAP. The Ki67 proliferation index was very low (2-3%. In contrast, the endocrine tumor component was composed of small uniform cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Immunohistochemical staining was positive for synaptophysin and focally positive for chromogranin. This rare case illustrates that MEN I may have an influence on the pathogenesis of ovarian teratomas as they undergo malignant transformation.

  10. 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...

  11. Benign gastric neuroendocrine tumors in three snow leopards (Panthera uncia).

    Science.gov (United States)

    Dobson, Elizabeth C; Naydan, Dianne K; Raphael, Bonnie L; McAloose, Denise

    2013-06-01

    Neuroendocrine tumors are relatively rare neoplasms arising from neuroendocrine cells that are distributed throughout the body and are predominant in the gastrointestinal tract. This report describes benign, well-differentiated gastric neuroendocrine tumors in three captive snow leopards (Panthera uncia). All tumors were well circumscribed, were within the gastric mucosa or submucosa, and had histologic and immunohistochemical features of neuroendocrine tumors. Histologic features included packeted cuboidal to columnar epithelial cells that were arranged in palisades or pseudorosettes and contained finely granular cellular cytoplasm with centrally placed, round nuclei. Cytoplasmic granules of neoplastic cells strongly expressed chromogranin A, variably expressed neuron-specific enolase, and did not express synaptophysin or gastrin. Each leopard died or was euthanatized for reasons unrelated to its tumor.

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

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    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.

  13. Targeted Therapies Improve Survival for Patients with Pancreatic Neuroendocrine Tumors

    Science.gov (United States)

    In 2011, based on initial findings from two clinical trials, the Food and Drug Administration approved sunitinib and everolimus for patients with pancreatic neuroendocrine tumors. Updated results from the everolimus trial were published in September 2016.

  14. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  15. Mature Ovarian Teratoma with Carcinoid Tumor in a 28-Year-Old Patient

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    Stamatios Petousis

    2013-01-01

    Full Text Available Introduction. Coexistence of carcinoid tumor inside a mature cystic teratoma is an extremely rare phenomenon, especially in young women. We present the case of a 28-year-old woman diagnosed with a right ovarian carcinoid and treated uneventfully with conservative surgical approach. Case Report. A 28-year-old woman, gravid 0, parity 0, presented to our department for her annual gynecological examination and Pap smear test. During her examination, a mobile cystic mass was detected in the right lower abdomen. Ultrasound indicated a right ovarian mass 10.5 × 6.3 cm, confirmed by CT scan. Further investigation revealed AFP levels (1539 ng/mL. The ovarian mass was excised by laparoscopy, leaving intact the remaining right ovary. Frozen sections showed a mature cystic teratoma. However, paraffin sections revealed the presence of a small carcinoid within the teratoma’s gastric-type mucosa. The patient was set to a close followup. Nine months postoperatively, ultrasound pelvis imaging and CT scan of the abdomen as well as serum tumor markers have shown no evidence of recurrence disease. Conclusion. Despite the weak evidence, fertility spare surgical approach for women wanting to preserve their genital tract might be a reasonable option.

  16. Prognostic Impact of DNA-Image-Cytometry in Neuroendocrine (Carcinoid Tumours

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    H. Raatz

    2004-01-01

    Full Text Available Establishing prognosis proves particularly difficult with neuroendocrine tumours (NETs as a benign looking histology can be associated with a malignant behaviour. In order to identify prognostic factors we examined 44 gastrointestinal and pulmonary, paraffin‐embedded NETs histologically and immunohistochemically. DNA‐image‐cytometry was used to examine 40 of these. We found that poor differentiation (corresponding to a Soga and Tazawa type D and infiltrative growth correlated with a poorer prognosis. Moreover, parameters determined by diagnostic DNA cytometry like the 5c‐exceeding rate, the 2c‐deviation index, DNA‐grade of malignancy, DNA‐entropy and the type of DNA histogram were found to be of prognostic relevance. Morphometric parameters like the form factor and the mean nuclear area were relevant for survival, tumour recurrence and metastasis. However, in the multivariate analysis the only independent risk factor was the histological differentiation. The 5c‐exceeding rate is a good objective risk factor, which can be used particularly in cases in which only a fine needle biopsie is available. Direct comparison of the histology and the 5c‐exceeding rate in the multivariate analysis suggests that the 5c‐exceeding rate taken as sole prognostic factor might be of higher prognostic relevance than the histology but larger studies are needed to confirm this.

  17. Primary carcinoid tumor arising within mature teratoma of the kidney: report of a rare entity and review of the literature

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    Parwani Anil V

    2007-05-01

    Full Text Available Abstract Background Primary carcinoid tumor arising within mature teratoma of the kidney is extremely rare, and their clinicopathologic features are not well described. Our objective was to further define the clinical features and pathologic spectra of primary carcinoid tumor arising within mature teratoma of the kidney. Methods Six previously reported case reports were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews was performed. We also searched the electronic medical archival records of our institution and identified one additional unreported case. Data were extracted on the demographics, predisposing factors, clinical presentation, radiographic features, gross pathology, microscopic pathology, immunophenotype, therapy, and outcome of each of these seven cases. Results Primary carcinoid tumor arising within mature teratoma of the kidney was found at a mean age of 41.4 years. Of the 7 cases, 3 were female and 4 were male. Two of the 7 cases (28.6% were associated with horseshoe kidney. It typically presented with abdominal pain without carcinoid syndrome. It typical radiologic appearance was well circumscribed partly calcified Bosniak II-III lesion. Histologically, the carcinoid tumor showed monotonous small round cells arranged in classic anastomosing cords/ribbons intermixed with solid nests. Surgery was curative, no additional treatment was required, no local recurrences occurred, and no metastases occurred in all 7 cases. The 3 cases with available outcome data were alive at the time of publication of their respective cases (mean, 5 months. Conclusion Primary carcinoid tumor arising within mature teratoma of the kidney is a rare tumor that typically presents with abdominal pain without carcinoid syndrome. It is not associated with local recurrence and metastasis, is surgically curable, and has excellent prognosis.

  18. Carcinoid-syndrome: recent advances, current status and controversies.

    Science.gov (United States)

    Ito, Tetsuhide; Lee, Lingaku; Jensen, Robert T

    2018-02-01

    To review recent advances and controversies in all aspects of carcinoid-syndrome. Over the last few years there have been a number of advances in all aspects of carcinoid syndrome as well as new therapies. These include new studies on its epidemiology which demonstrate it is increasing in frequency; increasing insights into the pathogenesis of its various clinical manifestations and into its natural history: definition of prognostic factors; new methods to verify its presence; the development of new drugs to treat its various manifestations, both initially and in somatostatin-refractory cases; and an increased understanding of the pathogenesis, natural history and management of carcinoid heart disease. These advances have generated several controversies and these are also reviewed. There have been numerous advances in all aspects of the carcinoid-syndrome, which is the most common functional syndrome neuroendocrine tumors produce. These advances are leading to new approaches to the management of these patients and in some cases to new controversies.

  19. Diverticulitis of the appendix as debut of appendicular cystadenoma and carcinoid tumor.

    Science.gov (United States)

    Fernández Gómez-Cruzado, Laura; Prieto Calvo, Mikel; Pérez González, Christian; Larrea Oleaga, Jasone

    2017-02-01

    Appendiceal diverticulosis is a rare condition with a frequency of 0.004% to 2.1%, and is sometimes an occasional finding during anatomopathologic study of the surgical specimen. It may be presented acutely as a right lower quadrant pain, similar to acute appendicitis for which differential diagnosis must be carried out, and it is associated with appendicular tumors. We report a case of diverticulitis of the appendix as debut of appendicular cystadenoma and carcinoid tumor with representative iconography, being unusual the association of both diseases and even more its preoperative diagnosis.

  20. Minimally invasive surgery for resection of duodenal carcinoid tumors: endoscopic full-thickness resection under laparoscopic observation.

    Science.gov (United States)

    Tsujimoto, Hironori; Ichikura, Takashi; Nagao, Shigeaki; Sato, Tomoki; Ono, Satoshi; Aiko, Satoshi; Hiraki, Shuichi; Yaguchi, Yoshihisa; Sakamoto, Naoko; Tanimizu, Takemaru; Yamamoto, Junji; Hase, Kazuo

    2010-02-01

    Carcinoid tumors of the duodenum are rare, and the most effective treatment for duodenal carcinoid tumors remains debatable. Because carcinoid tumors of the gastrointestinal tract tend to spread to the submucosal layer even during the early stages of the disease, the possibility of tumor seeding in the vertical margin of the tumor cannot be eliminated by conventional endoscopic mucosal resection (EMR). In addition, because the duodenal wall is thinner than the gastric wall, EMR performed for duodenal lesions may be associated with a high risk of accidental perforation. In this article, we introduce a minimally invasive endoscopic full-thickness resection technique after laparoscopic repair for the local resection of duodenal carcinoid tumors. Under general anesthesia, after the duodenum was mobilized laparoscopically, the duodenal serosa at the site of the lesion was suctioned under laparoscopic observation, and full-thickness resection of the duodenum was performed using a cap-fitted endoscope, i.e., EMR-c, without injecting hypertonic saline-epinephrine. The sample was retrieved endoscopically after resection. After confirming that the full-thickness resection of the duodenal wall with enough surgical margins was achieved and that there was no active bleeding, the wound was sutured by the laparoscopic hand-suturing technique. We have performed this surgical procedure in two cases of duodenal carcinoid tumor. The mean operation time was 116 +/- 14 minutes, and the estimated blood loss was 2.5 +/- 0.5 ml. The postoperative courses were uneventful in both cases. The technique of endoscopic full-thickness resection of gastrointestinal tract under laparoscopic observation is a safe, simple, and can be radical surgical procedure for a small duodenal carcinoid tumor. This surgical procedure may be applicable in the case of other gastrointestinal tumors.

  1. Small neuroendocrine tumor of the duodenal bulb: Endoscopic submucosal dissection, laparoscopic and endoscopic cooperative surgery or surgery?

    Directory of Open Access Journals (Sweden)

    Nikolaos V Chrysanthos

    2016-01-01

    Full Text Available Neuroendocrine neoplasms of the gastric tube are less common than adenocarcinomas. Topography includes stomach, small intestine, Vater ampulla, and gross intestine. They are graded as neuroendocrine tumors grade I and II (NETs GI and GII and neuroendocrine carcinomas GIII based on Ki-67 index and mitotic count. [1] Endoscopic treatment for GI NETs ≤1 cm that does not extend beyond the submucosal layer and does not demonstrate lymph node metastasis is recommended. Tumors ≥2 cm, with lymph node metastasis, are indicated for surgical treatment. The treatment strategy for tumors between 10 and 20 mm in size remains controversial. [2] We present a rare case of a 60-year-old male patient with end-stage renal failure who underwent a screening pretransplantation endoscopic control. Colonoscopy had no pathological findings. Gastroscopy reveals an abnormal mucosa in the anterior upper part of the duodenal bulb that was described as a micronodular mucosa and a central nodule of 6 mm with erythematous mucosa. Histology of the micronodular mucosa reveals a heterotopic gastric mucosa and a small hyperplastic polyp. Biopsies from the nodule reveal a carcinoid tumor (NET GI. Immunohistochemistry: Positive chromogranin levels, low mitotic index (1/10 HPF, and Ki-67 index 2 cm and those of the duodenal bulb with histological extensions and the lack of assessing depth invasion.

  2. [The role of endoscopy in gastroenteropancreatic neuroendocrine tumors].

    Science.gov (United States)

    Magno, L; Sivero, L; Napolitano, V; Ruggiero, S; Fontanarosa, G; Massa, S

    2010-01-01

    Versione italiana Riassunto: Il ruolo dell'endoscopia nei tumori neuroendocrini gastroenteropancreatici. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa I tumori neuroendocrini (NET) gastro-entero-pancreatici (GEP) sono neoplasie rare che originano dalle cellule neuroendocrine del tubo digerente e del pancreas. L'endoscopia digestiva e l'ecoendoscopia rivestono un ruolo importante nella diagnosi, stadiazione e sorveglianza dei pazienti con NET. Inoltre, in casi selezionati, le tecniche endoscopiche operative consentono il trattamento di queste neoplasie in fase precoce. English version Summary: The role of endoscopy in gastroenteropancreatic neuroendocrine tumors. L. Magno, L. Sivero, V. Napolitano, S. Ruggiero, G. Fontanarosa, S. Massa Gastroenteropancreatic (GEP) neuroendocrine tumors (NET) are rare neoplasia arisen from neuroendocrine cells present in the gut mucosa and pancreas. Digestive endoscopy and endoscopic ultrasonography play a relevant role in NET diagnosis, stadiation and surveillance. Moreover, in selected patients, surgical endoscopy allows the tratment of these cancers at an early stage.

  3. Ectopic adrenocorticotropic hormone syndrome in a case of duodenal neuroendocrine tumor presenting with liver metastasis

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    J Khare

    2018-01-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is an uncommon disorder and comprises about 15% of all patients with Cushing's syndrome (CS. Duodenal carcinoids are rare, indolent tumors usually associated with a benign progression. We hereby report a rare case of CS resulting from ectopic ACTH secretion from a duodenal neuroendocrine tumor (NET presenting with liver metastasis. A 37-year-old female presented with abdominal discomfort and dyspepsia of 1-month duration. Ultrasound abdomen suggested a well-defined hypoechoic lesion in the left lobe of the liver, suggestive of neoplasia. On clinical examination, she had Cushingoid features and persistent hypokalemia. Midnight ACTH and cortisol levels were grossly elevated at 1027 pg/ml (n < 46 pg/ml and 87.56 μg/dl (n < 7.5 μg/ml, respectively. Both overnight and high-dose dexamethasone suppression test confirmed nonsuppressed cortisol levels - 86.04 and 84.42 μg/dl (n < 1.8 μg/ml, respectively. Magnetic resonance imaging brain showed a structurally normal pituitary gland. Computed tomography scan of the abdomen revealed hepatic lesion with bilateral adrenal enlargement. A diagnosis of ectopic ACTH-dependent CS was made. Intraoperatively, a duodenal lesion of 0.5 cm × 0.5 cm was identified alongside an 8 cm × 6 cm exophytic lesion in segment IV of the liver. Frozen section of the duodenal lesion was positive for NET. She underwent a Whipple's surgery, cholecystectomy, and left hepatic lobectomy. Postoperatively, she showed clinical and biochemical remission. Herewith, we report the third case of duodenal carcinoid tumor presenting as ectopic ACTH syndrome and the first with liver metastasis.

  4. BIOCHEMICAL MARKERS IN SERUM AND URINE IN THE WORKUP OF PATIENTS WITH NEUROENDOCRINE TUMORS

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    N. V. Lyubimova

    2016-01-01

    Full Text Available This review summarizes current data on neuroendocrine tumors (NET, which, unlike other neoplasms, are able to produce biologically active substances (hormones, vasoactive peptides, amines. It is exactly their main characteristic that allows to unify this heterogeneous group and that may determine their clinical course. We present integrated recommendations for biochemical diagnosis and confirmation of over-secretion syndromes based on a  panel assessment of NET biochemical markers. Data from the literature are reviewed on evaluation of clinical significance of generic and specific NET markers, as well as the results of the studies performed by the authors themselves. Three hundred and thirty patients were examined with NETs of various localization (pancreas, stomach, small intestine and large intestine, lungs and with metastatic NET disease with unknown primary location, who were treated in the N.N. Blokhin Russian Cancer Research Center. The control group included 115 healthy individuals. Before and during the treatment, plasma and serum chromogranin A (CgA and serotonin levels, as well as 5-hydroxyindoleacetic acid (5-HIAA in a  24-hour urine sample were measured with standardized immunoenzyme plate-based assays (“Chromogranin A ELISA kit”, Dako A/S; “Serotonin ELISA and 5-HIAA ELISA”, IBL International GMBH. We evaluated clinical importance of CgA as a generic NET marker, as well as that of serotonin and its metabolite 5-HIAA as specific markers of the carcinoid syndrome. CgA was shown to be the most efficient biochemical marker for diagnosis, assessment of prevalence and monitoring of NETs. CgA has a  high diagnostic sensitivity (63.4 to 88.9% in various NETs. An association between CgA secretion and prevalence and biological activity of the tumor was confirmed. CgA measurement is particularly important in functionally inactive tumors, where serotonin and 5-HIAA have lower sensitivity, being specific markers of the carcinoid

  5. Usefulness of endoscopic ultrasonography (EUS for selecting carcinoid tumors as candidates to endoscopic resection Utilidad de la ultrasonografía endoscópica (USE para seleccionar tumores carcinoides como candidatos a una resección endoscópica

    Directory of Open Access Journals (Sweden)

    M. J. Varas

    2010-10-01

    Full Text Available Introduction: carcinoid tumors (CTs represent the most common type of neuroendocrine tumors (NETs. Digestive CTs in the gastroduodenal and colorectal tracts may be assessed using endoscopy and echoendoscopy or endoscopic ultrasonography (EUS with the goal of attempting local resection with curative intent without having recourse to surgery. Objective: endpoints in this study included: - Assessing the usefulness of EUS for selecting CTs as candidates to endoscopic excision. - Assessing the effectiveness of local resection (complete carcinoid resection and the safety (complications of the technique involved. Patients and methods: our series included 18 patients (12 males and 6 females with 23 tumors. Sixteen patients (10 males and 6 females were selected, with age ranging from 40 to 81 years (mean: 57 years, biopsied, endoscopically treated digestive carcinoid tumors, and a previous negative extension study. Twenty-one 2-to-20-mm (mean size 8 mm tumors were resected in 23 procedures. After endoscopy plus biopsy and echoendoscopy (EUS, excision was carried out with conventional polypectomy snare mucosectomy and submucosal injection with saline and/or adrenaline in most cases (15, and mucosectomy technique following lesion ligation with elastic bands for six cases. Two cases underwent transanal endoscopic surgery (TEM, one of them following non-curative polypectomy. A total of 23 local procedures were performed with the key goal of assessing efficacy (complete resection: CR and safety (complications. Results: there were no severe complications except for the last gastric mucosectomy for a 6-mm carcinoid, where a miniperforation occurred that was solved by using 3 clips (1/23: 4.3%. EUS sensitivity was 94%. Complete resection was 90.5% (19/21. Conclusions: the endoscopic mucosal resection of selected carcinoid tumors is a safe, effective technique. EUS is the technique of choice to select patients eligible for endoscopic resection (carcinoids smaller

  6. Surgical Treatment of an Isolated Metastatic Myocardial Neuroendocrine Tumor.

    Science.gov (United States)

    Caldeira, Christiano C B; Sayad, Dany; Strosberg, Jonathan; Faber, Cristiano; Saouma, Samer; Michaud, Tabitha

    2016-02-01

    We describe a patient diagnosed with a neuroendocrine tumor of the small intestine metastatic to the heart who underwent successful cardiac metastasectomy. The tumor was located on the right ventricle free wall, obstructing the right ventricular outflow tract. There was no valvular involvement. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. A novel approach in the treatment of neuroendocrine gastrointestinal tumors: Additive antiproliferative effects of interferon-γ and meta-iodobenzylguanidine

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    Ahnert-Hilger Gudrun

    2004-05-01

    Full Text Available Abstract Background Therapeutic options to effectively inhibit growth and spread of neuroendocrine gastrointestinal tumors are still limited. As both meta-iodobenzylguanidine (MIBG and interferon-γ (IFNγ cause antineoplastic effects in neuroendocrine gastrointestinal tumor cells, we investigated the antiproliferative effects of the combination of IFNγ and non-radiolabeled MIBG in neuroendocrine gut STC-1 and pancreatic carcinoid BON tumor cells. Methods and results IFNγ receptors were expressed in both models. IFNγ dose- and time-dependently inhibited the growth of both STC-1 and of BON tumor cells with IC50-values of 95 ± 15 U/ml and 135 ± 10 U/ml, respectively. Above 10 U/ml IFNγ induced apoptosis-specific caspase-3 activity in a time-dependent manner in either cell line and caused a dose-dependent arrest in the S-phase of the cell cycle. Furthermore, IFNγ induced cytotoxic effects in NE tumor cells. The NE tumor-targeted drug MIBG is selectively taken up via norepinephrine transporters, thereby specifically inhibiting growth in NE tumor cells. Intriguingly, IFNγ treatment induced an upregulation of norepinephrine transporter expression in neuroendocrine tumors cells, as determined by semi-quantitative RT-PCR. Co-application of sub-IC50 concentrations of IFNγ and MIBG led to additive growth inhibitory effects, which were mainly due to increased cytotoxicity and S-phase arrest of the cell cycle. Conclusion Our data show that IFNγ exerts antiproliferative effects on neuroendocrine gastrointestinal tumor cells by inducing cell cycle arrest, apoptosis and cytotoxicity. The combination of IFNγ with the NE tumor-targeted agent MIBG leads to effective growth control at reduced doses of either drug. Thus, the administration of IFNγ alone and more so, in combination with MIBG, is a promising novel approach in the treatment of neuroendocrine gastrointestinal tumors.

  8. Endobronchial Carcinoid and Concurrent Carcinoid Syndrome in an Adolescent Female

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    Jonathan D. Cogen

    2016-01-01

    Full Text Available Endobronchial carcinoid tumors are the most common intrabronchial tumors in children and adolescents. Common signs and symptoms include persistent cough and wheezing not responsive to bronchodilators, hemoptysis, and recurrent fever. Diagnosis is frequently made by imaging and direct visualization with flexible bronchoscopy; surgery remains the gold standard treatment, and lung-sparing resections should be performed whenever possible. Though carcinoid syndrome—characterized by flushing, palpitations, wheezing, shortness of breath, and diarrhea—has been found in association with adult bronchial carcinoid tumors, to our knowledge only one previous study has reported the presence of carcinoid syndrome in a pediatric patient with an endobronchial carcinoid. Here, we report a case of a 14-year-old girl with chronic cough found to have an endobronchial carcinoid tumor and signs and symptoms consistent with carcinoid syndrome.

  9. ERCC1 and Ki67 in Small Cell Lung Carcinoma and Other Neuroendocrine Tumors of the Lung Distribution and Impact on Survival

    DEFF Research Database (Denmark)

    Skov, Birgit Guldhammer; Holm, B.; Erreboe, A.

    2010-01-01

    ), typical carcinoid (TC), atypical carcinoid (AC), and large cell neuroendocrine carcinoma (LCNEC) were determined. Materials and Methods: We included a consecutive series of 186 patients with SCLC treated with platinum-based chemotherapy and surgically treated patients with TC (n = 48), AC (n = 15......) and LCNEC (n = 27). ERCC1 and Ki 67 were measured by immunohistochemistry and scored using published criteria. Results: The expression of ERCC1 was different among the different tumor types (p disease as well as extensive disease SCLC, no association of ERCC1 expression.......001). The difference between TC and AC was significant (p = 0.02), as was the difference between low grade (TC + AC) and high grade NE (LCNEC + SCLC) (p treated...

  10. Goblet cell carcinoids

    DEFF Research Database (Denmark)

    Olsen, Ingrid Holst; Holt, Nanna; Langer, Seppo W

    2015-01-01

    BACKGROUND: Appendiceal goblet cell carcinoids (GCCs) exhibit neuroendocrine and adenocarcinoma features. PATIENTS AND METHODS: Analysis of demography, pathology, prognostic markers, treatment and survival in 83 GCC patients (f/m: 56/27) diagnosed 1992-2013. RESULTS: Median age for f/m was 59...

  11. Everolimus Effect on Gastrin and Glucagon in Pancreatic Neuroendocrine Tumors

    NARCIS (Netherlands)

    Pavel, Marianne E.; Chen, David; He, Wei; Cushman, Stephanie; Voi, Maurizio; de Vries, Elisabeth G. E.; Baudin, Eric; Yao, James C.

    Objectives: The pharmacodynamic effects of everolimus on gastrointestinal hormone levels have not been described in patients with pancreatic neuroendocrine tumors (pNETs). We report the effects of everolimus on gastrin and glucagon levels in patients with progressive pNETin RADIANT-1 (a single-arm

  12. High expression of dopamine receptor subtype 2 in a large series of neuroendocrine tumors.

    Science.gov (United States)

    Grossrubatscher, Erika; Veronese, Silvio; Ciaramella, Paolo Dalino; Pugliese, Raffaele; Boniardi, Marco; De Carlis, Luciano; Torre, Massimo; Ravini, Mario; Gambacorta, Marcello; Loli, Paola

    2008-12-01

    To evaluate by immumohistochemistry the presence of DR subtype 2 (D2R) in well differentiated NETs of different sites and in normal islet cells. Recent data in vitro and in vivo support that dopaminergic drugs might exert an inhibitory effect on hormone secretion and, possibly, on tumor growth in neuroendocrine tumors (NET)s. Their potential therapeutic role needs the demonstration of dopamine receptors (DR) in tumor cells. Little is known on the expression of DR in NETs. 85% of samples (100% of bronchial carcinoids and 93% of islet cell tumors) showed positivity for D2R; intensity of immunoreaction in NETs was similar or higher than in pituitary (54% and respectively 31% of cases). D2R positivity in more than 70% of tumor cells was observed in 46% of samples. Same intensity of D2R-immunoreactivity was found in pituitary and normal islet cells. No differences in D2R expression were recorded on considering tumor grading, size, proliferative activity, presence of metastases, endocrine activity and gender. A significant difference (62.5% vs 96.4%, p = 0.039) was observed in the prevalence of D2R expression between patients with more aggressive tumors and patients without recurrence/progression of disease during follow-up. 46 NET samples from 44 patients and normal endocrine pancreatic tissue were studied. D2R-staining was performed on NETs and compared with six non-secreting pituitary adenomas and related to clinical-pathological data. The present data demonstrate a high expression of D2R in NETs; this finding is of clinical relevance in view of the potential role of dopaminergic drugs in inhibiting secretion and/or cell proliferation in NETs.

  13. [Surgical treatment of gastroentero-pancreatic neuroendocrine tumor].

    Science.gov (United States)

    Ohtsuka, Takao; Takahata, Shunichi; Ueda, Junji; Ueki, Takashi; Nagai, Eishi; Mizumoto, Kazuhiro; Shimizu, Shuji; Tanaka, Masao

    2013-07-01

    The treatment of choice for gastroentero-pancreatic neuroendocrine tumor(NET)is resection. Because it is difficult to determine the histological grade of NET before operation, the treatment strategy is usually made based on an imaging study including the tumor's size. Some selected gastrointestinal NETs are indicated for endoscopic resection, while others are resected surgically with lymph node dissection. The types of resections for pancreatic NETs vary from enucleation to pancreatectomy with or without regional lymph node dissection, based on the type of excessive hormone, tumor size, distance from the main pancreatic duct, and the presence of type 1 multiple endocrine neoplasia. Hepatic metastases are also resected, if indicated, and even in patients having unresectable metastatic lesions, multidisciplinary therapy including reduction surgery of over 90% of tumor volume might lead to a favorable prognosis. Postoperative adjuvant therapy is recommended for neuroendocrine carcinoma, while there is no evidence to support adjuvant therapy for curatively resected well-differentiated NET.

  14. Insulinoma and gastrinoma syndromes from a single intrapancreatic neuroendocrine tumor.

    Science.gov (United States)

    Lodish, Maya B; Powell, Anathea C; Abu-Asab, Mones; Cochran, Craig; Lenz, Petra; Libutti, Steven K; Pingpank, James F; Tsokos, Maria; Gorden, Phillip

    2008-04-01

    The insulinoma syndrome is marked by fasting hypoglycemia and inappropriate elevations of insulin. The gastrinoma syndrome is characterized by hypergastrinemia, ulcer disease, and/or diarrhea. Rarely, insulinoma and gastrinoma coexist in the same patient simultaneously. Our objective was to determine the cause of a patient's hypoglycemic episodes and peptic ulcer disease. This is a clinical case report from the Clinical Research Center of the National Institutes of Health. One patient with hypoglycemic episodes and peptic ulcer disease had a surgical resection of neuroendocrine tumor. The patient was found to have a single tumor cosecreting both insulin and gastrin. Resection of this single tumor was curative. A single pancreatic neuroendocrine tumor may lead to the expression of both the hyperinsulinemic and hypergastrinemic syndromes.

  15. Expression of developing neural transcription factors in diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH).

    Science.gov (United States)

    Escudero, Antonio García; Zarco, Enrique Rodríguez; Arjona, Juan Carlos Girón; Moreno, María José Ríos; Rodríguez, Katherine Gallardo; Benítez, Ana Vallejo; Cámpora, Ricardo González

    2016-09-01

    DIPNECH is characterized by neuroendocrine cell hyperplasia, tumorlets, and eventually carcinoid tumors. Although it is regarded by some authors as a preneoplastic condition, this issue is controversial. New pathologic criteria have recently been proposed for the diagnosis of DIPNECH, and a subgroup of carcinoid tumors expressing developing neural transcription factors (DNTFs), with clinicopathologic features similar to those of DIPNECH, has been recognized. This paper reports on the clinical and pathological findings in three cases of DIPNECH and investigates the expression of three DNTFs (TTF1, ASCL1, and POU3F2). All patients were female, with a mean age of 63 years, and all lesions were located in the periphery of the lung. In two cases, typical carcinoids were associated with a spindle-cell component. All neuroendocrine proliferations were DNTF positive. The morphologic (spindle-cell component), phenotypic (DNTF expression), and clinicopathologic (peripheral tumors, female predominance) similarities suggest that DIPNECH may be a preneoplastic lesion for peripheral carcinoids.

  16. Goblet Cell Carcinoids of the Appendix

    Directory of Open Access Journals (Sweden)

    Nanna Holt

    2013-01-01

    Full Text Available Goblet cell carcinoid (GCC tumors are a rare subgroup of neuroendocrine tumors almost exclusively originating in the appendix. The tumor most often presents in the fifth or sixth decade with a clinical picture of appendicitis or in advanced cases an abdominal mass associated with abdominal pain. Histologically tumors are most often positive for chromogranin A and synaptophysin, however, less homogenous than for classic appendix carcinoids. The malignant potential is higher than that for the classic appendix carcinoids due to local spread and distant metastases at diagnosis and the proliferation markers (Ki67 index may determine prognosis. Octreotide receptor scintigraphy is usually negative while CT/MRI scans may be useful. Chromogranin A is usually negative and other biomarkers related to the mucinous component or the tumor (CEA, CA-19-9, and CA-125 may be used. Surgery is the main treatment with appendectomy and right hemicolectomy while patients with disseminated disease should be treated with chemotherapy. Overall 5-year survival is approximately 75%. The diagnosis and treatment of GCC tumorss should be restricted to high volume NET centers in order to accumulate knowledge and improve survival in GCC NET patients. The aim of this paper is to update on epidemiology, clinical presentation, and diagnostic markers including Ki67 index, treatment, and survival.

  17. Patients with carcinoid syndrome exhibit symptoms of aggressive impulse dysregulation

    NARCIS (Netherlands)

    Russo, S; Boon, JC; Kema, IP; Willemse, PHB; den Boer, JA; Korf, J; de Vries, EGE

    2004-01-01

    Objective: Carcinoid tumors can produce excessive amounts of biogenic amines, notably serotonin. We assessed psychiatric symptoms in carcinoid patients and peripheral metabolism of tryptophan, the precursor of serotonin. Methods: Twenty consecutive patients with carcinoid syndrome underwent a

  18. Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature.

    Science.gov (United States)

    Demirci, Ilhan; Herold, Susanne; Kopp, Andreas; Flaßhove, Michael; Klosterhalfen, Bernd; Janßen, Hermann

    2012-01-23

    Overdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, application of leuprolide and the Raf-1/MEK/ERK-1/2-pathway. Therefore, we examined GnrH receptor status in the examined specimen. In 2010 a 77 year-old male patient was shown to have a tumor mass of about 1.7 cm diameter in the inferior lobe of the left lung. Since 2005, this tumor had hitherto been known and showed no progression in size. The patient suffered from prostate cancer 4 years ago and was treated with TUR-P, radiation therapy and the application of leuprolide. We conducted an explorative thoracotomy with atypical segment resection. The first histological diagnosis was a metastasis of prostate cancer with lymphangiosis carcinomatosa. After several immunohistochemical stainings, the diagnosis was changed to adenocarcinoma of the lung. We conducted a re-thoracotomy with lobectomy and systematic lymphadenectomy 12 days later. The tumor stage was pT1 N0 MX G2 L1 V0 R0. Further immunohistochemical studies were performed. We received the results 15 days after the last operation. The diagnosis was ultimately changed to typical carcinoid tumor without any signs of lymphatic vessel invasion. The patient recovered well from surgery, but still suffers from dyspnea and lack of physical performance. Lung function testing revealed no evidence of impairment. The use of several immunohistochemical markers, careful evaluation of hematoxylin-eosin sections and the Ki-67 labelling index are important tools in discriminating between carcinoids and other bronchopulmonary carcinomas. Although we could not detect Gnr

  19. Overdiagnosis of a typical carcinoid tumor as an adenocarcinoma of the lung: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Demirci Ilhan

    2012-01-01

    Full Text Available Abstract Background Overdiagnosis of bronchopulmonary carcinoid tumors together with overtreatment can cause serious postoperative consequences for the patient. We report of a patient with a typical bronchopulmonary carcinoid tumor, which was initially misdiagnosed and treated as an adenocarcinoma of the lung. GnrH receptors and the associated Raf-1/MEK/ERK-1/2-pathway are potential targets for analogs in cancer treatment. We suspected a correlation between the lack of tumor growth, application of leuprolide and the Raf-1/MEK/ERK-1/2-pathway. Therefore, we examined GnrH receptor status in the examined specimen. Case presentation In 2010 a 77 year-old male patient was shown to have a tumor mass of about 1.7 cm diameter in the inferior lobe of the left lung. Since 2005, this tumor had hitherto been known and showed no progression in size. The patient suffered from prostate cancer 4 years ago and was treated with TUR-P, radiation therapy and the application of leuprolide. We conducted an explorative thoracotomy with atypical segment resection. The first histological diagnosis was a metastasis of prostate cancer with lymphangiosis carcinomatosa. After several immunohistochemical stainings, the diagnosis was changed to adenocarcinoma of the lung. We conducted a re-thoracotomy with lobectomy and systematic lymphadenectomy 12 days later. The tumor stage was pT1 N0 MX G2 L1 V0 R0. Further immunohistochemical studies were performed. We received the results 15 days after the last operation. The diagnosis was ultimately changed to typical carcinoid tumor without any signs of lymphatic vessel invasion. The patient recovered well from surgery, but still suffers from dyspnea and lack of physical performance. Lung function testing revealed no evidence of impairment. Conclusion The use of several immunohistochemical markers, careful evaluation of hematoxylin-eosin sections and the Ki-67 labelling index are important tools in discriminating between carcinoids

  20. Growth hormone-releasing hormone-producing pancreatic neuroendocrine tumor in a multiple endocrine neoplasia type 1 family with an uncommon phenotype.

    Science.gov (United States)

    Sala, Elisa; Ferrante, Emanuele; Verrua, Elisa; Malchiodi, Elena; Mantovani, Giovanna; Filopanti, Marcello; Ferrero, Stefano; Pietrabissa, Andrea; Vanoli, Alessandro; La Rosa, Stefano; Zatelli, Maria C; Beck-Peccoz, Paolo; Verga, Uberta

    2013-07-01

    The objective of this study was to describe a multiple endocrine neoplasia type 1 (MEN1) family characterized by primary hyperparathyroidism, in association with acromegaly because of ectopic growth hormone-releasing hormone (GHRH) secretion by a pancreatic neuroendocrine tumor in a young man and with a bronchial carcinoid in his mother. We investigate the clinical, radiological imaging, histopathologic findings, and therapy. An 18-year-old man successfully underwent subtotal parathyroidectomy for primary hyperparathyroidism. A subsequent genetic analysis showed a MEN1 gene mutation. Three years later, acromegaly because of ectopic GHRH secretion was diagnosed (pituitary MRI negative and elevated GHRH levels). A search for an ectopic tumor was unsuccessful and somatostatin analog therapy was started. Successively, scintigraphy with somatostatin analogs (68-Ga-DOTATOC-PET) showed three focal areas in the pancreatic tail. Distal pancreatectomy showed multiple pancreatic neuroendocrine tumors and hormonal status was normalized. Afterwards, the evaluation of the patient's mother, carrying the same mutation, indicated a primary hyperparathyroidism and a 4 cm lung mass. The patient underwent subtotal pneumonectomy and the histological analysis was consistent with the diagnosis of a typical bronchial carcinoid. In conclusion, an atypical phenotype may be recorded in MEN1 families, thus emphasizing the importance of the new imaging and surgical techniques in the diagnosis and treatment of such a rare disease.

  1. Identification of a novel Raf-1 pathway activator that inhibits gastrointestinal carcinoid cell growth

    Science.gov (United States)

    Cook, Mackenzie R.; Pinchot, Scott N.; Jaskula-Sztul, Renata; Luo, Jie; Kunnimalaiyaan, Muthusamy; Chen, Herbert

    2010-01-01

    Carcinoids are neuroendocrine tumors (NETs) that secrete hormones, including serotonin, resulting in the malignant carcinoid syndrome. In addition to the significant morbidity associated with the syndrome, carcinoids are frequently metastatic at diagnosis and untreated mortality at 5 years tops 70%. Surgery is the only curative option and the need for other therapies is clear. We have previously shown that activation of Raf-1 inhibits carcinoid cell proliferation. We investigated the ability of Leflunomide (LFN), an FDA approved medication for the treatment of rheumatoid arthritis, and its active metabolite Teriflunomide (TFN) as a potential anti-NET treatment. LFN and TFN inhibit the in vitro proliferation of gastrointestinal carcinoid cells and induce G2/M phase arrest. Daily oral gavage of nude mice with subcutaneous xenografted carcinoid tumors confirms that LFN can inhibit NET growth in vivo. Treatment with TFN suppresses the cellular levels of serotonin and chromogranin A, a glycopeptide co-secreted with bioactive hormones. Additionally TFN reduces the level of Achaete-Scute Complex-Like 1 (ASCL1), a NET marker correlated with survival. These effects are associated with the activation of the Raf-1/MEK/ERK1/2 pathway and blockade of MEK signaling reversed the effects of TFN on markers of the cell cycle and ASCL1 expression. In summary, LFN and TFN inhibit carcinoid cell proliferation in vitro and in vivo and alter the expression of NET markers. This compound thus represents an attractive target for further clinical investigation. PMID:20103603

  2. The role of 68Ga-DOTA-NOC PET/CT in evaluating neuroendocrine tumors: real-world experience from two large neuroendocrine tumor centers.

    Science.gov (United States)

    Haidar, Mohamad; Shamseddine, Ali; Panagiotidis, Emmanouil; Jreige, Mario; Mukherji, Deborah; Assi, Rita; Abousaid, Rayan; Ibrahim, Toni; Haddad, Marwan M; Vinjamuri, Sobhan

    2017-02-01

    Our aim was to assess the role of Ga-DOTA-NOC PET/CT as a tool for the management of neuroendocrine tumors (NETs), evaluating the clinical impact on patients from two large NET centers in different geopolitical settings. This is a retrospective study of patients with NETs who underwent Ga-DOTA-NOC PET/CT at Royal Liverpool University Hospital (UK) and at Mount Lebanon Hospital (Lebanon). Indications for imaging and findings of the PET/CT along with demographic and clinical outcome data were recorded and evaluated. Four hundred and forty-five patients fulfilled the inclusion criteria, with a median age at the time of diagnosis of 56 (range: 3-90) years; 248 (55.7%) patients were male.Ga-DOTA-NOC PET/CT was indicated for staging in 193 (43.4%) patients, for diagnosis in 124 (27.9%) patients, for follow-up in 97 (21.7%) patients, and for identification of a primary NET site in 31 (7%) patients.One hundred and four (27.9%) patients underwent Ga-DOTA-NOC PET/CT for the primary diagnosis of NET, of whom 66 (52.7%) patients presented with a clinical suspicion of NET, 10 (8.3%) patients presented with a biochemical suspicion of NET only, and 48 (38.8%) patients presented with a suspicious NET lesion discovered on another imaging modality. The most common clinical presentation was typical carcinoid syndrome [4 (33%) patients].Results on the basis of histology were used as the gold standard for the diagnosis in 57% of patients and the remaining on the basis of follow-up as per established clinical consensus. Sensitivity, specificity, negative-predictive value, and positive-predictive value of PET/CT were 87.1, 97.7, 79.6, and 98.7%, respectively, for the entire sample. Accuracy was measured using the receiver operating characteristic curve analysis with an area under the curve of 0.924 (95% confidence interval: 0.874-0.974). Ga-DOTA-NOC PET/CT is a highly sensitive and specific study for the diagnosis and follow-up of patients with neuroendocrine tumors. These results

  3. Image Findings of a Rare Case of Neuroendocrine Tumor Metastatic to Orbital Extraocular Muscle in Gallium-68 DOTANOC Positron Emission Tomography/Computed Tomography and Therapy with Lutetium-177 DOTATATE.

    Science.gov (United States)

    Kamaleshwaran, Koramadai Karuppusamy; Joseph, Jephy; Upadhya, Indra; Shinto, Ajit Sugunan

    2017-01-01

    Metastatic tumor is one of several etiologies of space-occupying masses in the orbit that accounts for 1-13% of all orbital masses. In the adult patient population, breast cancer is the most common tumor to metastasize to the orbit, followed by metastasis from the lung, prostate, and gastrointestinal tract. Carcinoid tumors are rare neuroendocrine neoplasms derived from enterochromaffin cells, which are found primarily in the gastrointestinal tract and bronchial tree. Liver metastases are the classic presentation of distant disease. Although rare, metastatic carcinoid to the extraocular muscles (EOMs) has been relatively well described in both retrospective case reports and clinical series in the ophthalmology literature, but not in nuclear medicine. Positron emission tomography/computed tomography (PET/CT) using Ga-68-labeled somatostatin-analogues have shown superiority over other modalities for imaging of Neuroendocrine tumor We describe a case of bilateral EOM metastasis from carcinoid lung in Ga-68 DOTANOC PET/CT and treatment with Lu -177 DOTATATE.

  4. Management and disease outcome of type I gastric neuroendocrine tumors: the Mount Sinai experience.

    Science.gov (United States)

    Chen, William C; Warner, Richard R P; Ward, Stephen C; Harpaz, Noam; Divino, Celia M; Itzkowitz, Steven H; Kim, Michelle K

    2015-04-01

    The incidence of gastric neuroendocrine tumors (NETs) has increased tenfold since the 1970s. Our aim was to describe the clinicopathologic profile, management, and outcomes of type I gastric NETs at The Mount Sinai Hospital. From existing databases of the Mount Sinai Division of Gastrointestinal Pathology and the Carcinoid Cancer Foundation, we identified 56 patients with type I gastric NETs seen at The Mount Sinai Hospital from 1993 to 2012. We generated a comprehensive dataset encompassing demographic, clinical, endoscopic, and pathologic factors. Survival information was determined from medical records and the Social Security Death Index. Tumor-node-metastasis staging was conducted, and tumors were graded based on mitotic counts and Ki67 index. Median NET size was 3.0 mm; 55.8 % displayed multifocal disease. Stages I, II, III, and IV disease were observed in 83.8, 10.8, 5.4, and 0 %, respectively. Tumors were either low (69.7 %) or intermediate (30.3 %) grade. Furthermore, 3.6 % of patients developed gastric dysplasia, and 5.5 % had gastric adenocarcinoma. Patients underwent endoscopy every 15 months, while 28.6 % underwent polypectomy, 32.7 % somatostatin therapy, and 46.4 % surgical resection. 5- and 10-year disease-specific survival was 100 %. Most patients received annual endoscopic surveillance, with a minority undergoing surgical resection, though outcomes remained excellent independent of therapeutic approach. We identified a very low but real rate of loco-regional spread, despite the generally indolent behavior of type I gastric NETs. Several patients demonstrated concurrent dysplasia or adenocarcinoma, underscoring the efficacy of regular endoscopic management not only for gastric NETs, but also for dysplasia and adenocarcinoma.

  5. 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.

  6. Single-institution experience of radioembolization with yttrium-90 microspheres for unresectable metastatic neuroendocrine liver tumors.

    Science.gov (United States)

    Jia, Zhongzhi; Paz-Fumagalli, Ricardo; Frey, Gregory; Sella, David M; McKinney, J Mark; Wang, Weiping

    2017-09-01

    The aim of this study was to assess the effectiveness of yttrium-90 ((90) Y) microspheres for the treatment of unresectable metastatic liver neuroendocrine tumors (NET). From February 2006 to September 2015, 36 patients (19 male and 17 female, age 63.6 ± 9.4 years) who underwent (90) Y therapy for unresectable liver metastases of NET were included and analyzed retrospectively. All patients received a variety of treatments before (90) Y therapy. The radiological response, symptoms improvement of carcinoid syndrome, tumor marker changes, complications, side effects/toxicity, survival, and factors related to survival were evaluated and analyzed. Of the 36 patients, the mean delivered dose of (90) Y was 1.8 ± 0.7 GBq with a total of 40 treatments. Overall disease control rate was 88.9% (32/36) at 3 months following therapy. In 16 patients with carcinoid syndrome, 15 (93.8%) patients had symptomatic improvement. Tumor marker response (5-hydroxyindoleacetic acid [n = 7] and chromogranin A [n = 13]) at 3 months after treatment were as follows: none (n = 0, 4), partial (n = 6, 7), and complete (n = 1, 2). Radiation-induced gastrointestinal ulcers (n = 2, 5.6%) were identified. Side effects included fatigue (n = 31, 86.1%), anorexia (n = 26, 72.2%), nausea (n = 15, 41.7%), vomiting (n = 14, 38.9%), abdominal pain (n = 10, 27.8%), and fever (n = 8, 22.2%). The mean follow-up was 27.0 ± 16.4 months, with a median survival of 41.0 months. Child-Pugh classification (P = 0.008) and lymph node metastases (P = 0.045) had statistically significant influence on overall survival. Yttrium-90 radioembolization can be effective in the treatment of unresectable liver metastases of NET who failed to respond to other treatments. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  7. A Case of Pulmonary Carcinoid Tumor with a Superimposed Aspergilloma Presenting As a Covert Ectopic Adrenocorticotropic Hormone Syndrome

    Directory of Open Access Journals (Sweden)

    Kyoung Jin Kim

    2017-06-01

    Full Text Available Ectopic adrenocorticotropic hormone (ACTH syndrome is a challenging diagnosis only responsible for approximately 10% of Cushing syndrome cases. It has been associated with a variety of benign and malignant tumors including a carcinoid tumor accompanied by aspergilloma in our case that was significantly difficult to be detected. We report a patient over 70 years old with uncontrolled hypertension and hypokalemia presenting with generalized edema. Laboratory results revealed ACTH-dependent Cushing syndrome, but imaging studies did not show any discrete lesions secreting ACTH. The petrosal to peripheral ACTH gradient resulted in no evidence of pituitary adenoma. As the only lesion suspicious for ectopic ACTH secretion was a right lower round cystic lesion that did not appear to be a carcinoid tumor on computed tomography scan of the chest, the patient underwent video-assisted thoracic surgical resection to provide a definitive diagnosis. The final diagnosis was a small ectopic ACTH-secreting carcinoid tumor with unusual superimposed aspergilloma in the periphery of the lung. Postoperatively, the abnormal endocrine levels were normalized, and all of the clinical symptoms and signs were ameliorated. This is an informative case of ectopic ACTH syndrome (EAS that was the cause of hypokalemia, hypertension, metabolic alkalosis, and hypercortisolism despite its poorly specific cushingoid morphology and uncommon imaging findings. Therefore, we recommend that clinicians investigate any possible lesion as a potential source of EAS.

  8. Massive gastrointestinal bleed due to multiple gastric neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Vishal Sharma

    2015-01-01

    Full Text Available Gastric neuroendocrine tumors (G-NETs are uncommon lesions which are usually diagnosed on histological evaluation of gastric polyps. These may occur sporadically or due to hypergastrinemia in the setting of atrophic gastritis or Zollinger-Ellison Syndrome. Large lesions may ulcerate and result in gastrointestinal bleeding. However, massive gastrointestinal bleeding is rare in patients with NETs. We report a 60-year-old lady who presented with massive gastrointestinal bleeding due to multiple G-NETs.

  9. Divergent management strategies for typical versus atypical carcinoid tumors of the thoracic cavity.

    Science.gov (United States)

    Okoye, Christian C; Jablons, David M; Jahan, Thierry M; Kukreja, Jasleen; Cardozo, Shayne; Yom, Sue S

    2014-08-01

    At our institution, limited surgical techniques are reserved only for suspected typical carcinoids, and nodal dissection and multimodality therapy are frequently used for atypical carcinoids. We describe the results of these differing management strategies based on initial clinicopathologic characteristics. Retrospective review of patients treated for thoracic carcinoid from 1995 to 2009. Information was abstracted concerning surgical and nonsurgical treatments, pathology results, and outcomes. Event-free and survival endpoints were compared. The median follow-up was 5.0 years (range, 0.5 to 17.4 y). Fifty-two patients underwent resection. The 5-year event-free survival for typical carcinoid patients was 88.2%. Atypical carcinoids had a tendency for nodal involvement (50% vs. 15%) and greater likelihood for disease recurrence, with a 5-year event-free survival of 50%. These data support the appropriateness of divergent management strategies for typical versus atypical bronchial carcinoids. We propose the following: (1) nonanatomic resection is acceptable only for peripheral typical carcinoids; (2) extended mediastinal dissection should be limited to central presentations, clinically aggressive, or atypical carcinoids; (3) atypical histology, especially with nodal involvement, is prognostic for recurrence and metastasis; (4) nonsurgical therapies only rarely achieve long-term freedom from disease.

  10. Cecal Carcinoid Tumor in a Nigerian Man: A Case Report and ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... [5,6] The release of serotonin and other vasoactive substances into the systemic circulation is thought to cause the carcinoid syndrome, the manifestations of which are episodic flushing, wheezing, diarrhea, and eventual right-sided valvular heart disease.[5] This constellation of symptoms is called carcinoid ...

  11. 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. Copyright © 2012 S. Karger AG, Basel.

  12. Transcatheter arterial embolization with trisacryl gelatin microspheres (Embosphere® leads to life-threatening tumor lysis syndrome in a rectal carcinoid patient with hepatic metastases

    Directory of Open Access Journals (Sweden)

    Yuan-Hao Lo

    2012-11-01

    Full Text Available The incidence of gastrointestinal carcinoids appears to be increasing, and the rectum is the third most common location. Transcatheter arterial embolization (TAE with trisacryl gelatin microspheres (Embosphere® has been reported as an effective method for hepatic metastases of rectal carcinoids. Complications are uncommon and usually of minor consequence. We report an unusual case of a 34-year-old man with tumor lysis syndrome following TAE with Embosphere® in a patient with multiple hepatic metastases of a rectal carcinoid. Early detection and effective treatment are essential for this rare but potentially catastrophic complication.

  13. The term "carcinoid" is a misnomer: the evidence based on local invasion

    Directory of Open Access Journals (Sweden)

    Soga Jun

    2009-02-01

    Full Text Available Abstract Background Since Oberndorfer proposed the term "carcinoid" in 1907, over 100 years have passed. This attractive term was initially proposed for 6 cases of his own experience with 12 submucosal lesions in the small intestine. Oberndorfer summarized the characteristic features of these lesions as follows: (1 small in size and often multiple, (2 histologically undifferentiated with a suggestion of gland-formation, (3 well-defined without any tendency to infiltrate the surroundings, (4 no metastases, and (5 apparently slow-growing reaching no significant size with a seemingly harmless nature. Review This article stresses the malignant nature of "carcinoid" on the basis of local invasion prior to metastases in the first two sessions, (1 with Oberndorfer's original diagram, and (2 with an experimental observation on extraglandular microcarcinoid in a form of "budding". Next, (3 a statistical comparison between a carcinoid group and a non-carcinoid ordinary carcinoma group is introduced on metastasis rates at an early stage with two prescribed factors of the depth of invasion restricted within the submucosa (sm-lesion and a small tumor size category of 1 cm to 2 cm: the carcinoid group exhibited metastasis rates higher than those in the ordinary carcinoma group when calculated in the stomach and rectum. In the author's experience, "carcinoids" are malignant not only in the gastrointestinal tract but also in the other sites on the basis of local invasion. Lastly, (4 discussion on the terminology of "carcinoid" as a misnomer is carried out. Adequate terms referring to the entity of this malignant tumor group are discussed. One of the most adequate and brief terms for "carcinoid" that is included now in neuroendocrine tumor group would be "endocrinocarcinoma" as per the author's proposal, followed by NEC (neuroendocrinocarcinoma or GEC (gut endocrinocarcinoma. Conclusion The term "carcinoid" is a misnomer that can be confirmed on the basis of

  14. A pancreatic neuroendocrine tumor diagnosed during the ...

    African Journals Online (AJOL)

    necrosis. Immunohistochemically, the tumor showed positivity for synaptophysin and chromogranin A, and the expression of Ki-67 was found to be lower than 1%. The patient had an uneventful postoperative course. At present, he is being followed up by both us and the pediatric oncology department, and has no evidence ...

  15. Treatment of pancreatic neuroendocrine tumor with liver metastases

    Directory of Open Access Journals (Sweden)

    LI Zhao

    2015-05-01

    Full Text Available Pancreatic neuroendocrine tumor (pNET is a rare type of pancreatic tumors. The incidence of pNET shows a gradually increasing trend in recent years. The most common organ of distant metastases is the liver. Surgical resection is still the optimal treatment for resectable, well-differentiated liver metastases with no evidence of extrahepatic spread. For unresectable patients, a combination of multiple modalities, such as transarterial chemoembolization, radiofrequency ablation, systemic chemotherapy, and molecular targeted therapy, can prolong the survival time of patients. Liver transplantation should be strictly evaluated on an individual basis.

  16. Surgical Management of Small Bowel Neuroendocrine Tumors: Specific Requirements and Their Impact on Staging and Prognosis.

    Science.gov (United States)

    Pasquer, Arnaud; Walter, Thomas; Hervieu, Valérie; Forestier, Julien; Scoazec, Jean-Yves; Lombard-Bohas, Catherine; Poncet, Gilles

    2015-12-01

    Small bowel neuroendocrine tumors (SB-NETs) are characterized by two main features: they usually are metastatic at diagnosis and multiple in 30 % of cases. As such, SB-NETs require specific surgical management. This retrospective study examined local recurrence, survival, and prognosis of SB-NETs after adapted surgery. All consecutive patients with SB-NETs who underwent resection of at least one primary tumor between 1 January 2000 and 1 January 2013 were analyzed. The preoperative morphologic workup, histologic classification, and metastatic lymph node (LN) ratio (LNs involved/removed) were recorded. The study enrolled 107 patients, 35 (33 %) of whom had multiple SB-NETs (range 1-44; mean 3.1). Preoperative imaging and perioperative surgical examination missed 61 and 33 % of SB-NETs, respectively, in contrast to pathologic examination. Of the 107 patients, 43 % had carcinoid syndrome, 70 % had metastatic disease, and 90 % had LN involvement. The median number of LNs retrieved was 12 (range 1-69). The LN ratio (LNs involved/removed) was 0.25. The highest tumoral grades were G1 (in 61 % of patients) and G2 (in 37 % of patients). Of the 107 patients, 13 (12 %) had local LN recurrence. The rate of LN recurrence-free survival at 5 years was 88 %. The median overall survival (OS) time was 128 months (range 91-165 months). In the multivariate analysis, high chromogranin A (CgA) levels and peritoneal carcinomatosis were significantly associated with shorter OS. Systematic palpation of the entire small bowel detects more multiple NETs than preoperative imaging. Systematic surgery with extensive LN resection is associated with low local recurrence. High CgA levels and carcinomatosis are linked with shorter survival.

  17. Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence-based medicine - A Scandinavian view.

    Science.gov (United States)

    Öberg, Kjell

    2015-06-01

    Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with variable clinical expression and progression. The primary tumors most frequently occur in the lungs, intestine and the pancreas. The NET incidence is approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per year. A NET may be functioning with symptoms related to hormone overproduction or non-functioning, not presenting any hormone-related symptoms. From the early 1980s and onwards, Uppsala University Hospital has contributed significantly to diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones and peptides and molecular imaging. On the therapeutic side, treatments with cytotoxics as well as biologicals such as, somatostatin analogs and interferons have been evaluated. We have furthermore been involved in important phase III trials for registration of so called, new targeted agents such as, RADIANT-3 and RADIANT-2. Our group were also the first to localize the gene for MEN I on chromosome 11 locus q13. Most recent developments have been the establishments of new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for treatment of most NETs has been developed and is ready for the clinic. Furthermore, we have been involved in establishing Nordic and international collaborations. Today, NETs is an area with rapid development and recognized by international organizations at conferences, with large attendance. The Nordic countries continue to be significant contributors to the field.

  18. Local treatment in unresectable hepatic metastases of carcinoid tumors: Experiences with hepatic artery embolization and radiofrequency ablation

    Directory of Open Access Journals (Sweden)

    van Coevorden Frits

    2005-11-01

    Full Text Available Abstract Background Hepatic metastases of carcinoid tumors cause incapacitating symptoms, but are usually diffuse and therefore unresectable. In this article we evaluate our experiences with local treatment techniques in the management of carcinoid patients with hepatic metastases and failing systemic treatment. Methods Fifteen consecutive carcinoid patients (11 men and 4 women; median age 60 years; range 45–71 years were treated with either hepatic artery embolization (HAE with Ivalon particles or radiofrequency ablation (RFA (percutaneously or intra-operatively. Follow-up evaluation was performed by CT scan and 24-hours urinary 5-HIAA excretions. Results A total of 18 HAE's was performed in 13 patients, while 10 lesions in 3 patients were treated with RFA. Median follow-up was 12.5 months (2 – 25 months. Median duration of symptoms was 22 months (8 – 193 months. Median overall decrease of 5-HIAA excretion 2 months after HAE was 32% with tumor regression on CT-scan in 4 patients (30% and improvement of symptoms with a median duration of 15 months in 3 of them (23%. Embolization led to fatal hepatic failure in one patient. The 3 patients treated with RFA showed a decrease of urinary 5-HIAA values of 34, 81 and 93% respectively, with tumor regression in all of them. Improvement of symptoms was reported in 2 patients up to 25 months. Conclusion Liver embolization performed late in the clinical course had limited effect on symptoms and biochemical and radiological parameters. First experiences with RFA are favorable and might encourage to apply RFA more widely in metastatic carcinoid.

  19. PET tracer for imaging of neuroendocrine tumors

    DEFF Research Database (Denmark)

    2013-01-01

    There is provided a radiolabelled peptide-based compound for diagnostic imaging using positron emission tomography (PET). The compound may thus be used for diagnosis of malignant diseases. The compound is particularly useful for imaging of somatostatin overexpression in tumors, wherein the compound...... is capable of being imaged by PET when administered with a target dose in the range of 150-350 MBq, such as 150-250 MBq, preferable in the range of 191-210 MBq....

  20. Driver gene mutations of non-small-cell lung cancer are rare in primary carcinoids of the lung: NGS study by ion Torrent.

    Science.gov (United States)

    Armengol, Gemma; Sarhadi, Virinder Kaur; Rönty, Mikko; Tikkanen, Milja; Knuuttila, Aija; Knuutila, Sakari

    2015-04-01

    Lung carcinoids are rare neuroendocrine tumors of the lung. Very little is known about the genetic background of these tumors. We applied Ion Torrent Ampliseq next-generation technology to study hotspot mutations of 22 lung cancer-related genes from typical and atypical lung carcinoid tumors. DNA isolated from 25 formalin-fixed, paraffin-embedded carcinoid tumors were amplified to prepare barcoded libraries covering 507 mutations included in 90 amplicons. The libraries were pooled, purified, enriched, and sequenced on ion personal genome machine. The sequences were aligned and checked for known and novel variations using Torrent Suite Software v.4.0.2. One out of 25 patients had mutations in the targeted regions sequenced. This patient had mutations in BRAF, SMAD4, PIK3CA, and KRAS. All these mutations were confirmed as somatic and are previously known mutations. In summary, mutations in genes commonly mutated in non-small-cell lung cancer are not common in lung carcinoids.

  1. Tracer development for detection and characterization of neuroendocrine tumors with PET

    NARCIS (Netherlands)

    Neels, Olivier Christiaan

    2008-01-01

    Neuroendocrine tumors are slowly growing tumors which originate from neuroendocrine cells. These tumors can secrete several products. In case of overproduction of serotonin, symptoms such as flushing, diarrhea and right-sided heart disease can occur. Next to serotonin, other well known products are

  2. Spectrum of malignant somatostatin-producing neuroendocrine tumors.

    Science.gov (United States)

    Moayedoddin, Baback; Booya, Fargol; Wermers, Robert A; Lloyd, Ricardo V; Rubin, Joseph; Thompson, Geoffrey B; Fatourechi, Vahab

    2006-01-01

    To evaluate the clinical manifestations and outcome of patients with somatostatinomas--rare neuroendocrine tumors of pancreaticoduodenal origin. We searched the medical archives and tumor registry of our institution for somatostatinomas or somatostatin-staining tumors for the 12-year period from January 1990 to February 2002. In addition, we reviewed laboratory databases for patients who had an elevated serum somatostatin level. Patients with a neuroendocrine tumor and an elevated serum somatostatin level or somatostatin-positive tumor immunostaining were included in this study. Eleven patients qualified (9 men and 2 women; median age at diagnosis, 45 years; age range, 22 to 73). The diagnosis of a somatostatinoma was made by immunostaining of the tumor in 9 patients and by finding elevated serum somatostatin levels in 2. Five primary tumors were of duodenal and 6 of pancreatic origin. Psammoma body formation and association with neurofibromatosis were seen only in the duodenal tumors. The known primary tumor sizes varied from 2 to 6 cm. Liver metastatic lesions were present in 6 patients, abdominal lymph node involvement was found in 10 patients, and lung, spleen, and ovarian metastatic involvement was noted in 1 patient each. Diabetes was present in 4 patients (36%) and cholelithiasis in 7 (64%). The presence of a mass led to the diagnosis in most patients with primary duodenal tumors, whereas patients with pancreatic tumors were more likely to have endocrine manifestations. A Whipple procedure was performed in 6 patients, distal pancreatectomy in 3, hepatic artery embolization or ligation in 3, and partial hepatectomy in 1. Cancer-related death occurred in 4 patients, 1 to 8 years after diagnosis (median, 4.5 years). At last follow-up, 2 patients were alive without evidence of disease (8 and 10 years after diagnosis), and 3 were alive with liver metastatic lesions. The status of 2 patients was unclear. Somatostatinomas occurred with approximately equal frequency

  3. IMPROVED DIAGNOSIS OF CARCINOID-TUMORS BY MEASUREMENT OF PLATELET SEROTONIN

    NARCIS (Netherlands)

    KEMA, IP; DEVRIES, EGE; SCHELLINGS, AMJ; POSTMUS, PE; MUSKIET, FAJ

    Carcinoid patients are diagnosed biochemically on the basis of increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA); urinary and platelet serotonin concentrations are considered to provide complementary information. Using established HPLC methods with fluorometric detection, we

  4. Tumores carcinoides del apéndice. Presentación de caso.

    Directory of Open Access Journals (Sweden)

    Zaymar Haber Ané

    2015-09-01

    Full Text Available Se realizó un estudio descriptivo para caracterizar la evolución de seis pacientes con impresión diagnóstica de apendicitis y diagnóstico definitivo de tumor carcinoide, asistidos en el Hospital General Docente de Guantánamo “Dr. Agostinho Neto”, enero -marzo 2013. Se informa el caso de los pacientes: 3 femeninas y 3 masculinos con edades promedio entre 20 y 50 años, antecedentes de salud aparente y cuadro clínico de dolor abdominal intenso asociado o no a otro síntoma general, al examen físico se constata abdomen doloroso en fosa iliaca derecha, reacción peritoneal, signo de Blumberg positivo, ligero tinte ictérico y taquicardia. Los estudios de ultrasonido revelan la asociación en uno de los casos con quiste de ovario. Son admitidos en el hospital evolucionando favorablemente. Se identifican y describen en biopsia por parafina los componentes morfológicos de esta entidad y se realiza revisión de la literatura concerniente.

  5. [Unilateral hyperlucent lung induced by a carcinoid tumor: comments on the differential diagnosis and mechanisms of hypoperfusion].

    Science.gov (United States)

    Schmitz, N; Bugnet, A-S; Demian, M; Massard, G; De Blay, F; Pauli, G

    2005-04-01

    We report the case of a 35-year-old woman in whom a systematic thoracic x-ray led to the diagnosis of unilateral hyperlucent lung due to a carcinoid tumor obstructing the main left bronchus almost completely. Injected computed tomography permitted diagnosis of left lung hypoperfusion and visualization of the tumor. After enlarged inferior left lobar resection, normal perfusion was observed six months later on the isotopic lung perfusion scan. Other reported causes of unilateral hyperlucent lung are discussed as well as pathophysiological mechanisms of lung hypoperfusion and hypoxic vasoconstriction.

  6. The Association of a Panel of Biomarkers with the Presence and Severity of Carcinoid Heart Disease: A Cross-Sectional Study

    Science.gov (United States)

    Dobson, Rebecca; Burgess, Malcolm I.; Banks, Melissa; Pritchard, D. Mark; Vora, Jiten; Valle, Juan W.; Wong, Christopher; Chadwick, Carrie; George, Keith; Keevil, Brian; Adaway, Joanne; Ardill, Joy E. S.; Anthoney, Alan; Hofmann, Uschi; Poston, Graeme J.; Cuthbertson, Daniel J.

    2013-01-01

    Purpose Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors. Patients and methods A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009–October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP). Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA). Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker. Results A total of 187 patients were identified of whom 37 (20%) had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74–0.90, p<0.0001) and 5HIAA 0.85 (95% confidence interval 0.78–0.92, p<0.0001]. NT-proBNP was moderately correlated (r = 0.48, p<0.001) whereas plasma 5HIAA was only weakly correlated (r = 0.34, p<0.001) with the echocardiographic severity score. Conclusion NT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity. PMID:24069222

  7. The association of a panel of biomarkers with the presence and severity of carcinoid heart disease: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Rebecca Dobson

    Full Text Available PURPOSE: Metastatic neuroendocrine tumors secrete serotonin and other vasoactive substances that are responsible for carcinoid syndrome and carcinoid heart disease. We sought to evaluate the discriminatory utility of diagnostic biomarkers in determining the presence and severity of carcinoid heart disease in patients with metastatic neuroendocrine tumors. PATIENTS AND METHODS: A cross-sectional study of patients with neuroendocrine tumors with documented liver metastases and/or carcinoid syndrome between April 2009-October 2012 in 5 tertiary referral centers. Serum was analyzed for Chromogranin A, Chromogranin B and N-terminal pro Brain Natriuretic Peptide (NT-proBNP. Plasma was analyzed for Neurokinin A and 5-Hydroxyindoleacetic acid (5HIAA. Echocardiography was used to determine the presence and severity of carcinoid heart disease. Non-parametric receiver operating characteristic curves were constructed for biomarkers, and the area under the curve determined. The severity of cardiac involvement was correlated with the concentration of each biomarker. RESULTS: A total of 187 patients were identified of whom 37 (20% had carcinoid heart disease. Significantly higher median values of all biomarkers were found in the patients with cardiac involvement. NT-proBNP and plasma 5HIAA had the highest areas under the curve for the prediction of carcinoid heart disease [NT-proBNP 0.82 (95% confidence interval 0.74-0.90, p<0.0001 and 5HIAA 0.85 (95% confidence interval 0.78-0.92, p<0.0001]. NT-proBNP was moderately correlated (r = 0.48, p<0.001 whereas plasma 5HIAA was only weakly correlated (r = 0.34, p<0.001 with the echocardiographic severity score. CONCLUSION: NT-proBNP and plasma 5HIAA are both sensitive and specific biomarkers for the presence of carcinoid heart disease whereas only NT-proBNP is moderately correlated with disease severity.

  8. 18F-FDG and 18F-FLT-PET imaging for monitoring everolimus effect on tumor-growth in neuroendocrine tumors: studies in human tumor xenografts in mice.

    Directory of Open Access Journals (Sweden)

    Camilla Bardram Johnbeck

    Full Text Available 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 and evaluated the performance of 18F-FDG and the proliferation tracer 18F-FLT for treatment response assessment by PET imaging.The effect of everolimus on the human carcinoid cell line H727 was examined in vitro with the MTT assay and in vivo on H727 xenograft tumors. The mice were scanned at baseline with 18F-FDG or 18F-FLT and then treated with either placebo or everolimus (5 mg/kg daily for 10 days. PET/CT scans were repeated at day 1,3 and 10.Everolimus showed significant inhibition of H727 cell proliferation in vitro at concentrations above 1 nM. In vivo tumor volumes measured relative to baseline were significantly lower in the everolimus group compared to the control group at day 3 (126±6% vs. 152±6%; p = 0.016, day 7 (164±7% vs. 226±13%; p<0.001 and at day 10 (194±10% vs. 281±18%; p<0.001. Uptake of 18F-FDG and 18F-FLT showed little differences between control and treatment groups, but individual mean uptake of 18F-FDG at day 3 correlated with tumor growth day 10 (r2 = 0.45; P = 0.034, 18F-FLT mean uptake at day 1 correlated with tumor growth day 7 (r2 = 0.63; P = 0.019 and at day 3 18F-FLT correlated with tumor growth day 7 (r2 = 0.87; P<0.001 and day 10 (r2 = 0.58; P = 0.027.Everolimus was effective in vitro and in vivo in human xenografts lung carcinoid NETs and especially early 18F-FLT uptake predicted subsequent tumor growth. We suggest that 18F-FLT PET can be used for tailoring therapy for neuroendocrine tumor patients through early identification of responders and non-responders.

  9. Variable picture of gastric carcinoids

    Energy Technology Data Exchange (ETDEWEB)

    Kuyer, P.P.; Rosenbusch, G.; Yap, S.H.; Boer, H.H.M. de

    1987-02-01

    Carcinoids are endocrine tumors which develop from enterochromaffin cells and will be found in more than 80% in the gastrointestinal tract. Only 2-3% of these carcinoids is located in the stomach. The rarity of their occurrence and the wide variety of radiographic features (intramural defects, multiple gastric polyps, large gastric ulcers and polypoid intraluminal lesions) make their recognition difficult. We report 3 cases of gastric carcinoid, one of them presented with pernicious anemia, which has been reported more frequently in literature. One patient showed the unusual combination of adenocarcinoma and a carcinoid with a stalk in the stomach.

  10. [Radioguided surgery in neuroendocrine tumors. A review of the literature].

    Science.gov (United States)

    García-Talavera, P; Ruano, R; Rioja, M E; Cordero, J M; Razola, P; Vidal-Sicart, S

    2014-01-01

    Radioguided surgery can be a useful technique in the localization of neuroendocrine tumors. It detects more and smaller lesions compared to pre-surgical imaging and intraoperative digital palpation by the surgeon. It detects residual lesions and also indicates the shortest access route to the lesion. Nevertheless, its use has not become widespread because of technical difficulties. There is a limited number of published series, a lack of standardized protocol because of the great variability regarding type of radiopharmaceutical, dose of radiotracer, timing between injection and surgery. In this paper, we review these issues, describing the experience of different authors in diverse tumors. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

  11. Down-Regulation of miR-129-5p and the let-7 Family in Neuroendocrine Tumors and Metastases Leads to Up-Regulation of Their Targets Egr1, G3bp1, Hmga2 and Bach1

    DEFF Research Database (Denmark)

    Dossing, Kristina B. V.; Binderup, Tina; Kaczkowski, Bogumil

    2014-01-01

    by miR-129-5p. let-7 overexpression inhibited growth of carcinoid cell lines, and let-7 inhibition increased protein content of the transcription factor BACH1 and its targets MMP1 and HMGA2, all known to promote bone metastases. Immunohistochemistry analysis revealed that let-7 targets are highly...... and an intestinal carcinoid cell line. Analysis of mRNA expression changes identified EGR1 and G3BP1 as miR-129-5p targets. They were validated by luciferase assay and western blotting, and found robustly expressed in NETs by immunohistochemistry. Knockdown of EGR1 and G3BP1 mimicked the growth inhibition induced...... expressed in NETs and metastases. We found down-regulation of miR-129-5p and the let-7 family, and identified new neuroendocrine specific targets for these miRNAs, which contributes to the growth and metastatic potential of these tumors....

  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. © 2016 Society for Endocrinology.

  13. Synchronous primary carcinoid tumor and primary adenocarcinoma arising within mature cystic teratoma of horseshoe kidney: a unique case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Perepletchikov Aleksandr M

    2009-06-01

    Full Text Available Abstract Background Malignant transformation of mature cystic teratoma is a rare complication. While any of the constituent tissues of a teratoma has the potential to undergo malignant transformation, squamous cell carcinoma is the most commonly associated malignancy. Renal carcinoid tumors are rare and frequently associated with horseshoe kidney and renal teratoma. Renal teratoma rarely presents together with carcinoid tumor or adenocarcinoma. To the best of our knowledge, there has never been a report of renal teratoma coexisting with both carcinoid tumor and adenocarcinoma. Methods Here, we present a unique and first case of synchronous primary carcinoid tumor and moderately differentiated adenocarcinoma arising within mature cystic teratoma of horseshoe kidney in a 50-year-old female. Lumbar spine X-ray, done for her complaint of progressive chronic low back pain, accidentally found a large calcification overlying the lower pole of the right kidney. Further radiologic studies revealed horseshoe kidney and a large multiseptated cystic lesion immediately anterior to the right renal pelvis with central calcification and peripheral enhancement. She underwent right partial nephrectomy. Results Macroscopically, the encapsulated complex solid and multiloculated cystic tumor with large calcification, focal thickened walls and filled with yellow-tan gelatinous material. Microscopically, the tumor showed coexistent mature cystic teratoma, moderately differentiated adenocarcinoma and carcinoid tumor. Immunohistochemically, alpha-methylacyl-coenzyme A-racemase, calretinin, CD10 and thyroid transcription factor-1 were negative in all the three components of the tumor. The teratomatous cysts lined by ciliated epithelium showed strong staining for cytokeratin 7 and pancytokeratin, and those lined by colonic-like epithelium showed strong staining for CDX2, cytokeratin 20 and pancytokeratin, but both were negative for calretinin. Additionally, the

  14. Thymic and Bronchial Carcinoid Tumors in Multiple Endocrine Neoplasia Type 1: The Mayo Clinic Experience from 1977 to 2013.

    Science.gov (United States)

    Singh Ospina, Naykky; Thompson, Geoffrey B; C Nichols, Francis; Cassivi, Stephen D; Young, William F

    2015-12-01

    The clinical features of thymic carcinoid (TC) and bronchial carcinoid (BC) tumors as part of multiple endocrine neoplasia type 1 (MEN1) have been rarely described and their importance in clinical practice is debated. The objective of this study was to describe the clinical presentation and outcome of this uncommon manifestation of MEN1 in a tertiary care center setting. We present the clinical features of patients with MEN1 and either TC or BC evaluated at the Mayo Clinic from 1977 to 2013. A total of 348 patients with MEN1 were evaluated and the prevalence of TC was 2.0% (n = 7) and of BC 4.9% (n = 17). The majority of the patients with BC were men (61%) diagnosed on routine screening (77%) and BC was not the confirmed cause of death in any patient. In contrast, TC patients were all men and during follow-up 43% died due to TC complications. We conclude that TC and BC tumors are uncommon, but important components of MEN1. BC were most commonly diagnosed during routine screening and associated with an indolent course. TC were predominantly seen in men and associated with a more aggressive behavior.

  15. Carcinoid heart disease

    Directory of Open Access Journals (Sweden)

    Stephen A. Geller

    2013-04-01

    Full Text Available The images are of the tricuspid valve and the pulmonic valve from the autopsy of a patient with mid-gut neuroendocrine carcinoma, carcinoid pattern, extensively metastatic to the liver. The patient had typical “carcinoid syndrome,” including clinical evidence of tricuspid and pulmonic stenosis and insufficiency. The tricuspid valve (left shows slight retraction and distortion by the overlying endothelial deposition of plaque composed of acid mucopolysaccharide-rich matrix with varying amounts of smooth muscle cells and collagen fibers. The plaque material causes partial coalescence of chordae tendinae with effacement of the usual delicate strands. The pulmonic valve (right shows more marked distortion with shrinkage and obliteration of cusps and coalescence at the commissures. Beneath the plaque the valves are intact.

  16. Lanreotide autogel every 6 weeks compared with Lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a Phase III Study.

    Science.gov (United States)

    Bajetta, Emilio; Procopio, Giuseppe; Catena, Laura; Martinetti, Antonia; De Dosso, Sara; Ricci, Sergio; Lecchi, Alberto S; Boscani, Paolo F; Iacobelli, Stefano; Carteni, Giacomo; De Braud, Filippo; Loli, Paola; Tartaglia, Andreas; Bajetta, Roberto; Ferrari, Leonardo

    2006-11-15

    The noninferiority of a 6-week dosing schedule of lanreotide Autogel (Lan ATG) at a dose of 120 mg compared with a 3-week dosing schedule of lanreotide microparticles (Lan MP) at a dose of 60 mg was investigated in patients with neuroendocrine tumors (NET). Patients who had sporadic, well differentiated NET with a low grade of malignancy were recruited for this open-label, Phase III, multicenter trial. Patients were randomized to receive either 3 deep subcutaneous injections of Lan ATG (120 mg, every 6 weeks) or 6 intramuscular injections of Lan MP (60 mg, every 3 weeks). Tumor markers, tumor size, and symptoms were assessed between baseline and Week 18. Success was classified as a response that ranged from disappearance to an increase <25% in tumor marker, tumor size, or symptom frequency. Sixty patients were randomized, and 46 patients completed the study. Both for tumor markers and for tumor size, Lan ATG was not inferior to Lan MP (55% and 59% of patients responded on tumor markers, respectively; 68% and 66% of patients responded on tumor size, respectively). There were too few symptomatic patients to compare carcinoid symptoms. Both treatments were tolerated well, and no safety concerns were identified. Lan ATG at a dose of 120 mg every 6 weeks was as effective for controlling NET as Lan MP at a dose of 60 mg every 3 weeks.

  17. Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum.

    Science.gov (United States)

    Niemeijer, Nicolasine D; Papathomas, Thomas G; Korpershoek, Esther; de Krijger, Ronald R; Oudijk, Lindsey; Morreau, Hans; Bayley, Jean-Pierre; Hes, Frederik J; Jansen, Jeroen C; Dinjens, Winand N M; Corssmit, Eleonora P M

    2015-10-01

    Mutations in genes encoding the subunits of succinate dehydrogenase (SDH) can lead to pheochromocytoma/paraganglioma formation. However, SDH mutations have also been linked to nonparaganglionic tumors. The objective was to investigate which nonparaganglionic tumors belong to the SDH-associated tumor spectrum. This was a retrospective cohort study. The setting was a tertiary referral center. Patients included all consecutive SDHA/SDHB/SDHC and SDHD mutation carriers followed at the Department of Endocrinology of the Leiden University Medical Center who were affected by non-pheochromocytoma/paraganglioma solid tumors. Main outcome measures were SDHA/SDHB immunohistochemistry, mutation analysis, and loss of heterozygosity analysis of the involved SDH-encoding genes. Twenty-five of 35 tumors (from 26 patients) showed positive staining on SDHB and SDHA immunohistochemistry. Eight tumors showed negative staining for SDHB and positive staining for SDHA: a pancreatic neuroendocrine tumor, a macroprolactinoma, two gastric gastrointestinal stromal tumors, an abdominal ganglioneuroma, and three renal cell carcinomas. With the exception of the abdominal ganglioneuroma, loss of heterozygosity was detected in all tumors. A prolactinoma in a patient with a germline SDHA mutation was the only tumor immunonegative for both SDHA and SDHB. Sanger sequencing of this tumor revealed a somatic mutation (p.D38V) as a likely second hit leading to biallelic inactivation of SDHA. One tumor (breast cancer) showed heterogeneous SDHB staining, positive SDHA staining, and retention of heterozygosity. This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal stromal tumors. Furthermore, our results indicate that pancreatic neuroendocrine tumor also falls within the SDH-related tumor spectrum.

  18. The predictive value of mean platelet volume, plateletcrit and red cell distribution width in the differentiation of autoimmune gastritis patients with and without type I gastric carcinoid tumors.

    Science.gov (United States)

    Tüzün, Ali; Keskin, Onur; Yakut, Mustafa; Kalkan, Cagdas; Soykan, Irfan

    2014-01-01

    Autoimmune gastritis is an autoimmune and inflammatory condition that may predispose to gastric carcinoid tumors or adenocarcinomas. The early diagnosis of these tumors is important in order to decrease morbidity and mortality. Platelet indices such as mean platelet volume and plateletcrit levels increase in inflammatory, infectious and malign conditions. The primary aim of this study was to explore wheter platelet indices and red cell distribution width have any predictive role in the discrimination of autoimmune gastritis patients with and without gastric carcinoid tumors. Also secondary aim of this study was to investigate whether any changes exist betwenn autoimmune gastritis and functional dyspepsia patients by means of platelet indices. Plateletcrit (0.22 ± 0.06 vs. 0.20 ± 0.03%, p gastritis patients compared to control group. Receiver operating curve analysis suggested that optimum plateletcrit cut-off point was 0.20% (AUC: 0.646), and 13.95% as the cut off value for red cell distribution width (AUC: 0.860). Although plateletcrit (0.22 ± 0.06 vs. 0.21 ± 0.04%, p = 0.220) and mean platelet volume (8.94 ± 1.44 vs. 8.68 ± 0.89 fl, p = 0.265) were higher in autoimmune gastritis patients without carcinoid tumor compared to patients with carcinoid tumors, these parameters were not statistically significant. Changes in plateletcrit and red cell distribution width values may be used as a marker in the discrimination of autoimmune gastritis and fucntional dyspepsia patients but not useful in patients with gastric carcinoid tumor type I.

  19. An unusual association of neuroendocrine tumors in MEN 1A.

    Science.gov (United States)

    Varsavsky, Mariela; Reyes-García, Rebeca; Alonso García, Guillermo; Muñoz-Torres, Manuel

    2012-09-01

    Multiple Endocrine Neoplasia type 1 is an autonomic dominant disease with a high degree of penetrance. It is characterized by combinations of over 20 different endocrine and nonendocrine tumors. A 25-year-old woman was referred for 1 year-evolution amenorrhea and bilateral galactorrhea. She also had fasting hypoglycaemia and hypercalcemia, and she was diagnosed of Multiple Endocrine Neoplasia type 1A. Resection of three parathyroid glands was performed showing hyperplasia of principal cells. Post-parathyroidectomy serum levels of calcium and intact PTH were normal but 3 years later serum calcium levels rose again. A 99mTc-sestamibi scan showed increased uptake in the low right area compatible with adenoma. After biochemical test showing probable insulinoma, somatostatin receptor scintigraphy showed a focal captation in head and body of pancreas. MRI found two nodules in the same localization. An antral gastrectomy, total pancreatoduodenectomy, colecistectomy and truncal vagotomy was performed and histopathologic examination revealed a combination of neuroendocrine tumors: gastrinomas, somastotinomas, glucagonomas and insulinomas. After surgery she started with tingling in fingers, toes and lips, and calcium levels was 5.9 mg/dl and PTH intact 3 pg/ml. A new 99m Tc-sestamibi scan showed no captation and cervical ultrasonography was normal. Now, 2 years later, she continues with normal calcium and i-PTH levels. This report represents an unusual case of MEN 1A with association of insulinomas, gastrinomas glucagonomas and somatostatinomas in the same patient.

  20. Genetic and molecular coordinates of neuroendocrine lung tumors, with emphasis on small-cell lung carcinomas

    National Research Council Canada - National Science Library

    Koutsami, Marilena K; Doussis-Anagnostopoulou, Ipatia; Papavassiliou, Athanasios G; Gorgoulis, Vassilis G

    2002-01-01

    .... Current information on established and putative diagnostic and prognostic markers of neuroendocrine tumors are evaluated, with a special reference to small-cell lung carcinoma, due to its higher...

  1. Distinguishing carcinoid tumor from small cell carcinoma of the lung: correlating cytologic features and performance in the College of American Pathologists Non-Gynecologic Cytology Program.

    Science.gov (United States)

    Renshaw, Andrew A; Haja, Jennifer; Lozano, Richard L; Wilbur, David C

    2005-05-01

    The cytologic features of carcinoid tumor of the lung are well described. Nevertheless, some carcinoids may be difficult to distinguish from small cell carcinomas. To correlate the cytologic features of individual cases of carcinoid tumor of the lung in fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program with the frequency of misclassification as small cell carcinoma. We reviewed 1100 interpretations from 26 different cases of carcinoid tumor in lung fine-needle aspiration specimens in the College of American Pathologists Non-Gynecologic Cytology Program and correlated the cytologic features with the performance in the program. Cases were divided into those that were frequently misclassified as small cell carcinoma (at least 20% of the responses, 19 cases) and those that were infrequently misclassified as small cell carcinoma (cytologic features that might be responsible for misclassification as small cell carcinoma. All 7 cases that were infrequently misclassified consisted of numerous monotonous well-preserved tumor cells that were either entirely round or were a mixture of round and spindle-shaped cells. Six of 7 cases showed a prominent streaming vascular pattern with tumor cells attached to the endothelial cell core. In contrast, cases that were frequently misclassified had 1 of 6 patterns that were not seen in cases that were rarely misclassified. These 6 patterns were: (1) poorly preserved and pale-staining cells with fine chromatin and a suggestion of molding (5 cases); (2) numerous large, well-preserved, spindle-shaped cells (2 cases); (3) numerous cells varying markedly in both size and shape (both round and spindle-shaped cells), with a common finding of degenerated, smudgy, small round and spindle-shaped cells (9 cases); (4) hypocellular specimens (8 cases); (5) obscuration of cells by blood (2 cases); and (6) tumor cells present predominantly in groups, with few isolated cells (8 cases). In none of

  2. Endoscopic treatment of sporadic small duodenal and ampullary neuroendocrine tumors.

    Science.gov (United States)

    Gincul, Rodica; Ponchon, Thierry; Napoleon, Bertrand; Scoazec, Jean-Yves; Guillaud, Olivier; Saurin, Jean-Christophe; Ciocirlan, Mihai; Lepilliez, Vincent; Pioche, Mathieu; Lefort, Christine; Adham, Mustapha; Pialat, Jean; Chayvialle, Jean-Alain; Walter, Thomas

    2016-11-01

    Background and study aim: As duodenal neuroendocrine tumors (NETs) are rare, their optimal management has not been clearly established. The aim of this study was to evaluate the feasibility and outcome of endoscopic treatment of duodenal NETs. Patients and methods: We reviewed the files of all patients who underwent endoscopic resection of a sporadic duodenal or ampullary NET between 1996 and 2014 at two centers. Results: A total of 29 patients with 32 uT1N0M0 NETs < 20 mm were included. Treatment consisted of endoscopic mucosal resection in 19 cases, and cap aspiration in 13 cases. Prior submucosal saline injection was used in 15 cases. Mortality was 3 % (one severe bleeding). Morbidity was 38 % (11/29). At post-resection analysis, mean tumor size was 8.9 mm (range 3 - 17 mm), 29 lesions were stage pT1, one was pT2, and 2 were pTx because of piecemeal resection. All NETs were well differentiated. A total of 27 lesions were classified as grade 1 and 5 were grade 2. The resection was R0, R1, and Rx for 16, 14, and 2 lesions, respectively. Three R1 patients underwent additional surgical treatment, with no residual tumor on the surgical specimen but with positive metastatic lymph nodes in two cases. One patient was lost to follow-up. Finally, 24 patients were included in the follow-up analysis. The median follow-up period was 56 months (range 6 - 175 months). Two patients presented a tumor recurrence during the follow-up period. Conclusions: Endoscopic treatment of small duodenal NETs was associated with significant morbidity, a difficulty in obtaining an R0 specimen, and the risk of lymph node metastasis. Nevertheless, it represents an interesting alternative in small grade 1 duodenal lesions and in patients at high surgical risk. © Georg Thieme Verlag KG Stuttgart · New York.

  3. A Rare Combination of Ovarian and Uterine Leiomyomas with Goblet Cell Carcinoid of the Appendix

    Directory of Open Access Journals (Sweden)

    Abdulrahman F. Al-Shaikh

    2015-01-01

    Full Text Available We present a case of the rare combination of unilateral ovarian leiomyoma, uterine leiomyoma, and goblet cell carcinoid tumor of the appendix in a premenopausal woman who presented with right iliac pain. Immunohistochemistry study for desmin (muscle marker and chromogranin and synaptophysin (neuroendocrine markers confirmed immunophenotyping origin. Interestingly, both tumors showed positive reaction for estrogen receptor. To our knowledge, such a combination has not been reported previously in the literature. In this paper, the pathogenesis and differential diagnosis of both types of tumors are discussed.

  4. A Study of Appendiceal Crypt Cell Adenocarcinoma (So-Called Goblet Cell Carcinoid and Its Related Adenocarcinoma).

    Science.gov (United States)

    Nonaka, Daisuke; Papaxoinis, George; Lamarca, Angela; Fulford, Paul; Valle, Juan; Chakrabarty, Bipasha

    2017-08-17

    Goblet cell carcinoids (GCCs) of the appendix are rare tumors, characterized by a carcinoid-like organoid growth pattern. Despite the term carcinoid, neuroendocrine features are inconspicuous, and its behavior is distinct from carcinoid. Its high grade counterpart is designated as adenocarcinoma ex GCC. We conducted a retrospective study of 105 tumors to find prognostic values of a variety of clinico-pathologic features. The tumors were subclassified as low grade, equivalent to classic type, and high grade, defined as loss of organoid pattern, and a proportion (%) of low and high grades were documented in each tumor. Correlations between survival and various clinico-pathologic parameters were investigated. One-third were pure low grade while the remainder contained variable high grade component ranging 5-95%. Neuroendocrine cell component ranged 0-90% (median 5) while mucus cell component ranged 5-100% (median 70). By univariate analysis, size, stage, high grade component, nuclear grade, surgery and chemotherapy correlated with cancer-related survival (CSS), and by multivariate analysis, stage (P=.001), high grade component (P=.008) and tumor size (P=.005) correlated with CSS. There was significant difference in CSS when the cases were grouped in high grade component <40%, 40-90 and ≤90% (P<.001). Our results indicate that staging and proportion of high grade histology may provide important prognostic information. Neuroendocrine component was insignificant in both low and high grade areas. In light of our findings, this tumor type is best regarded as a variant of adenocarcinoma, and the term crypt cell adenocarcinoma more appropriately reflects the nature and origin of this tumor group. Copyright © 2017. Published by Elsevier Inc.

  5. Regional Gastrointestinal Transit Times in Patients With Carcinoid Diarrhea: Assessment With the Novel 3D-Transit System

    DEFF Research Database (Denmark)

    Gregersen, Tine; Haase, Anne-Mette; Schlageter, Vincent

    2015-01-01

    BACKGROUND/AIMS: The paucity of knowledge regarding gastrointestinal motility in patients with neuroendocrine tumors and carcinoid diarrhea re-stricts targeted treatment. 3D-Transit is a novel, minimally invasive, ambulatory method for description of gastrointestinal motility. The system has...... not yet been evaluated in any group of patients. We aimed to test the performance of 3D-Transit in patients with carcinoid diarrhea and to compare the patients' regional gastrointestinal transit times (GITT) and colonic motility patterns with those of healthy subjects. METHODS: Fifteen healthy volunteers...... = 0.045). CONCLUSIONS: Three-dimensional Transit allows assessment of regional GITT in patients with diarrhea. Patients with carcinoid diarrhea have faster than normal gastrointestinal transit due to faster small intestinal and colorectal transit times. The latter is caused by an increased frequency...

  6. Lu-177 DOTATATE dosimetry for neuroendocrine tumor: single center experience

    Science.gov (United States)

    Said, MA; Masud, MA; Zaini, MZ; Salleh, RA; Lee, BN; Zainon, R.

    2017-05-01

    Lu-177 labelled with DOTATE is widely acceptable to treat Neuroendocrine Tumor (NET) disease and it better improvement of quality of patients’ life since few years ago. However, the radionuclide toxicity becomes the main limitation of the (NET) treatment. Therefore, we performed a pilot study aimed to estimate radiation absorbed doses to dose-limiting organs to develop a systemic therapy with Lu-177 in NET patients. In this study, five set of planar whole body images was acquired every 0.5 hour, 4 hours, 24 hours, 48 hours and 72 hours after Lu-177 administrations. The planar image acquisition was done using Philip Brightview X with Medium Energy General Purpose Collimator (MEGP) collimator. All patients’ images in Conjugate View (CV) format were transferred into PMOD 3.7 Software for Region of Interest (ROI) analysis. The ROI were drawn at selected organs such as kidneys, liver, spleen and bladder. This study found that the mean absorbed dose for kidneys 0.62 ± 0.26 Gy/GBq, liver 0.63 ± 0.28 Gy/GBq, spleen 0.83 ± 0.73 Gy/GBq and bladder 0.14 ± 0.07 Gy/GBq. The radionuclide kinetic for the whole body 99.7 ± 0.1 percent at 0.5 hours, 79.5 ± 10.7 percent at 4 hours, 56.6 ± 10.3 percent at 24 hours, 43.2 ± 7.9 percent at 48 hours and 37.1 ± 9.0 percent at 72 hours. This study verifies that this planar quantitative method able to determine organ at risk and the result line with other published data.

  7. High grade neuroendocrine lung tumors: pathological characteristics, surgical management and prognostic implications.

    Science.gov (United States)

    Grand, Bertrand; Cazes, Aurélie; Mordant, Pierre; Foucault, Christophe; Dujon, Antoine; Guillevin, Elizabeth Fabre; Barthes, Françoise Le Pimpec; Riquet, Marc

    2013-09-01

    Among non-small cell lung cancers (NSCLC), large cell carcinoma (LCC) is credited of significant adverse prognosis. Its neuroendocrine subtype has even a poorer diagnosis, with long-term survival similar to small cell lung cancer (SCLC). Our purpose was to review the surgical characteristics of those tumors. The clinical records of patients who underwent surgery for lung cancer in two French centers from 1980 to 2009 were retrospectively reviewed. We more particularly focused on patients with LCC or with high grade neuroendocrine lung tumors. High grade neuroendocrine tumors were classified as pure large cell neuroendocrine carcinoma (pure LCNEC), NSCLC combined with LCNEC (combined LCNEC), and SCLC combined with LCNEC (combined SCLC). There were 470 LCC and 155 high grade neuroendocrine lung tumors, with no difference concerning gender, mean age, smoking habits. There were significantly more exploratory thoracotomies in LCC, and more frequent postoperative complications in high grade neuroendocrine lung tumors. Pathologic TNM and 5-year survival rates were similar, with 5-year ranging from 34.3% to 37.6% for high grade neuroendocrine lung tumors and LCC, respectively. Induction and adjuvant therapy were not associated with an improved prognosis. The subgroups of LCNEC (pure NE, combined NE) and combined SCLC behaved similarly, except visceral pleura invasion, which proved more frequent in combined NE and less frequent in combined SCLC. Survival analysis showed a trend toward a lower 5-year survival in case of combined SCLC. Therefore, LCC, LCNEC and combined SCLC share the same poor prognosis, but surgical resection is associated with long-term survival in about one third of patients. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Endoscopic diagnosis and treatment of neuroendocrine tumors of the digestive system

    Directory of Open Access Journals (Sweden)

    Sivero Luigi

    2016-01-01

    Full Text Available The authors evaluated the role of endoscopic techniques in the diagnosis and in the potential treatment of neuroendocrine tumors (NET localized in the gastro-entero-pancreatic system, on the basis of their experience and of the international literature. NET are rare tumors that arise from neuroendocrine cells of the gastrointestinal tract and pancreas. It is a possibility that both the digestive endoscopy and EUS play an important role in the diagnosis, staging and surveillance of this disease. In some cases, especially in the early stages, surgical endoscopy allows the treatment of such tumors.

  9. Multiple rectal carcinoids with diffuse ganglioneuromatosis

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    Kosaka Taiichiro

    2007-02-01

    Full Text Available Abstract Background Rectal carcinoids comprise only about 1% of all anorectal neoplasms. In addition, ganglioneuroma of the gastrointestinal tract is a rare tumor composed ganglion cells, nerve fibers, and supporting cells. Multiple carcinoid tumors with diffuse ganglioneuromatosis limited to the rectum are quite unusual. Case presentation A 69-year-old man was referred to us because of about 100 small submucosal rectal tumors. He underwent abdominoperineal resection. Pathology revealed carcinoid tumors for about 30 submucosal nodules and diffuse ganglioneuromotosis. To date (6 months later he remains well with no recurrence. Conclusion Although the optimal treatment for the multiple rectal carcinoids remains to be clearly established, it is believed that not all patients with multiple rectal carcinoids (measuring less than 1 cm in diameter need to have a radical operation. However, the treatment plan for each case should be individualized and a careful follow-up is mandatory.

  10. The combination of neuroendocrine tumor and mucinous neoplasm of the appendix: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Suh, Hie Bum; Lee, Nam Kyung; Kim, Suk; Park, Won Young; Kim, Jae Hun [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of)

    2014-05-15

    Primary neoplasm of the appendix is an uncommon pathology, representing 0.5-1% of all appendix specimens. Especially, simultaneous occurrence of two tumors of the appendix was rarely documented. We report a case of the concomitant neuroendocrine tumor and the mucinous neoplasm of the appendix on abdominal computed tomography, in a 62-year-old female who came for a check-up.

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

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    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.

  12. Carcinoid Cancer Foundation

    Science.gov (United States)

    ... to-Understanding.pdf . New England Journal of Medicine Publishes Article on PRRT Clinical Study for Neuroendocrine Tumors ... NY 10605 1-888-722-3132 Disclaimer Privacy Policy Copyright Information

  13. Alternative polyadenylation of tumor suppressor genes in small intestinal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Rehfeld, Anders Aagaard; Plass, Mireya; Døssing, Kristina

    2014-01-01

    The tumorigenesis of small intestinal neuroendocrine tumors (SI-NETs) is poorly understood. Recent studies have associated alternative polyadenylation (APA) with proliferation, cell transformation, and cancer. Polyadenylation is the process in which the pre-messenger RNA is cleaved at a polyA site...... and a polyA tail is added. Genes with two or more polyA sites can undergo APA. This produces two or more distinct mRNA isoforms with different 3' untranslated regions. Additionally, APA can also produce mRNAs containing different 3'-terminal coding regions. Therefore, APA alters both the repertoire...... and the expression level of proteins. Here, we used high-throughput sequencing data to map polyA sites and characterize polyadenylation genome-wide in three SI-NETs and a reference sample. In the tumors, 16 genes showed significant changes of APA pattern, which lead to either the 3' truncation of mRNA coding regions...

  14. Neuroendocrine tumors: fascination and infrequency Tumores neuroendocrinos: fascinación e infrecuencia

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    M. J. Varas Lorenzo

    2009-03-01

    Full Text Available In this article, I review and update of gastro-entero-pancreatic neuroendocrine tumors, which so much fascination have risen among healthcare providers on grounds of their infrequency, hormonal syndromes, and high survival rate, is performed based on references from the past fifteen years.Se efectúa una revisión y puesta al día, basándose en citas bibliográficas de los últimos quince años, de los tumores neuroendocrinos gastroenteropancreáticos, que tanta fascinación han provocado en el estamento médico por su infrecuencia, síndromes hormonales y supervivencia elevada.

  15. Randomized crossover study in patients with neuroendocrine tumors to assess patient preference for lanreotide Autogel® given by either self/partner or a health care professional

    Directory of Open Access Journals (Sweden)

    Johanson V

    2012-10-01

    /partner or health care professionals was measured, as well as efficacy, safety, and health care resource utilization (both direct and indirect costs.Results: Of 25 evaluable patients, 22 (88% preferred self/partner injections, mainly because they experienced increased independence. Based on all patients asked to participate (n = 62, 35% preferred self/partner injections on a regular basis. There was no difference in efficacy or safety between the two administration blocks.Conclusion: Many patients with neuroendocrine tumors prefer self/partner injection of lanreotide Autogel, and are able to self/partner inject without any impact on efficacy or safety. This administration method seems to provide a good alternative for suitable patients to increase patient independence and reduce the number of clinic visits.Keywords: neuroendocrine tumors, carcinoid syndrome, self administration, somatostatin analogs, lanreotide

  16. A massive hepatic tumor demonstrating hepatocellular, cholangiocarcinoma and neuroendocrine lineages: A case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Rachel E. Beard

    2017-01-01

    Conclusion: This is one of the only reports of a hepatic tumor arising from hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine lineages. Increased awareness of this tumor type may optimize improve future management.

  17. Diagnosis and Treatment of Gastroenteropancreatic Neuroendocrine Tumors: Current Data on a Prospectively Collected, Retrospectively Analyzed Clinical Multicenter Investigation

    OpenAIRE

    Niederle, Martin B.; Niederle, Bruno

    2011-01-01

    Clinical information concerning diagnosis, symptoms, and treatment of 277 patients with gastrointestinal neuroendocrine tumors (including pancreatic tumors) diagnosed prospectively within 1 year were analyzed. Endoscopic and surgical techniques are the key to both correct diagnosis and effective treatment.

  18. Assessment of intracranial metastases from neuroendocrine tumors/carcinoma

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    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.

  19. Grade Increases in Gastroenteropancreatic Neuroendocrine Tumor Metastases Compared to the Primary Tumor.

    Science.gov (United States)

    Grillo, Federica; Albertelli, Manuela; Brisigotti, Maria Pia; Borra, Tiziana; Boschetti, Mara; Fiocca, Roberto; Ferone, Diego; Mastracci, Luca

    2016-01-01

    The neuroendocrine tumor (NET) proliferation-based grading system (ENETS/WHO) for gastroenteropancreatic (GEP) tumors has proved reliable for prognostic stratification. To date, concerns exist regarding Ki-67 heterogeneity within the tumor and little is known on whether grade varies between primary and secondary sites. As tumor heterogeneity may have a significant impact on clinical management, our aim was to retrospectively evaluate Ki-67 on a series of GEP NETs in order to establish whether there is variability in different samples of the same lesion or between primary and metastatic disease (local/distant, synchronous/metachronous). Sixty patients with multiple samples of tumor were accrued from a total of 338 GEP NETs; 44 of them also had tissue from local/distant metastases and a further 5 had multiple metastatic foci from unknown primary tumors. Immunohistochemistry for Ki-67 was performed on all paraffin blocks from both primary and metastatic tumors. Intratumor Ki-67 heterogeneity sufficient to change grade at first diagnosis was seen in 3/60 cases (5%). Out of 49 patients with primary NETs and/or multiple metastases, discrepancy in grade between sites was identified in 19 (39%) cases and in particular in 11/47 (23%) and in 10/12 (83%) patients with synchronous and metachronous metastases, respectively (p = 0.0002). Change in grade was more frequent in distant compared to locoregional metastases (p = 0.024) and in particular in distant sites other than the liver (p = 0.006). NETs show frequent differences in grade between primary sites and their synchronous/metachronous metastases; assessment of Ki-67 at all sites may prove to be significant for patient management. © 2015 S. Karger AG, Basel.

  20. Occurrence of second primary malignancies in patients with neuroendocrine tumors of the digestive tract and pancreas

    NARCIS (Netherlands)

    K. Kamp (Kimberly); 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

  1. Neuroendocrine tumor of the appendix inside an incarcerated Amyand’s hernia

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    Khaled Y. Elbanna

    2015-01-01

    An incidental finding of neuroendocrine tumor of the appendix in a patient with s hernia is extremely rare. A high index of suspicion is the key to diagnose such a coincidence in order to safely and optimally treat such a condition.

  2. Niacin (Vitamin B-3) Supplementation in Patients with Serotonin-Producing Neuroendocrine Tumor

    NARCIS (Netherlands)

    Bouma, Grietje; van Faassen, Martijn; Kats-Ugurlu, Gursah; Vries, de Elisabeth G. E.; Kema, Ido P.; Walenkamp, Annemiek M. E.

    2016-01-01

    BACKGROUND/AIMS: Tryptophan is the precursor of serotonin and niacin (vitamin B3). The latter is critical for normal cellular metabolism. Tryptophan and niacin can be deficient in patients with serotonin producing neuroendocrine tumors (NETs). Niacin deficiency can lead to severe symptoms including

  3. Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Knigge, Ulrich

    2015-01-01

    Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when...

  4. Collision tumor in form of primary adenocarcinoma and neuroendocrine carcinoma of the duodenum

    Directory of Open Access Journals (Sweden)

    Roderich E. Schwarz

    2012-04-01

    Full Text Available Collision tumor is a rare phenomenon characterized by coexistence of completely distinct and independent tumors at the same body location. Collision tumors have been reported in different sites. However, they are extremely uncommon in the duodenum. We report the case of a 52-year old man with a collision tumor in the third portion of the duodenum with two distinct tumors of primary adenocarcinoma and neuroendocrine carcinoma, and both tumors coexisting within a single metastatic lymph node. Immunohistochemistry studies were performed to conclude that this was a case of collision cancer. To the best of our knowledge, this is the first collision tumor case reported to date at this location, and the first report of lymph node with a collision metastasis from a collision tumor. Such tumor is very rare and may thus provide diagnostic challenges. This report also provides a review of other cases on duodenal collision tumors.

  5. Quantitative gene-expression of the tumor angiogenesis markers vascular endothelial growth factor, integrin alphaV and integrin beta3 in human neuroendocrine tumors

    DEFF Research Database (Denmark)

    Oxboel, Jytte; Binderup, Tina; Knigge, Ulrich

    2009-01-01

    compared to both colorectal liver metastases (p=0.10) and normal liver tissue (p=0.06). In neuroendocrine tumors, gene-expression was highly variable of VEGF (530-fold), integrin alphaV (23-fold) and integrin beta3 (106-fold). Quantitative gene-expression levels of the key angiogenesis molecules VEGF......, in neuroendocrine tumors. We used quantitative real-time PCR for measuring mRNA gene-expression of vascular endothelial growth factor (VEGF), integrin alphaV, and integrin beta3, and CD34 for a group of patients with neuroendocrine tumors (n=13). Tissue from patients with colorectal cancer liver metastases (n=14......) and normal liver tissues (n=16) was used as control. We found a lower mRNA level of VEGF in neuroendocrine tumors compared to both colorectal liver metastases (pbeta3 there was also a borderline significant lower level of mRNA in neuroendocrine tumors...

  6. [Neuroendocrine tumors of digestive system: morphologic spectrum and cell proliferation (Ki67 index)].

    Science.gov (United States)

    Delektorskaia, V V; Kushliskiĭ, N E

    2013-01-01

    This review deals with the analysis of up-to-date concepts ofdiferent types of human neuroendocrine tumors of the digestive system. It summarizes the information on the specifics of recent histological classifications and criteria of morphological diagnosis accounting histological, ultrastructural and immunohistochemical parameters. Current issues of the nomenclature as well as various systems of grading and staging are discussed. In the light of these criteria the results of the own research clinical value of the determination of cell proliferation in primary and metastatic gastroenteropancreatic neuroendocrine neoplasms on the basis of evaluation of the Ki67 antigen expression are also presented.

  7. Successful application of technetium-99m-labeled octreotide acetate scintigraphy in the detection of ectopic adrenocorticotropin-producing bronchial carcinoid lung tumor: a case report

    Directory of Open Access Journals (Sweden)

    Fallahi Babak

    2010-10-01

    Full Text Available Abstract Introduction The diagnostic efficacy of somatostatin receptor scintigraphy labeling with 111 indium in the localization of tumors has been assessed in a limited number of patients with contradictory outcomes. Here, we describe the case of a patient with an ectopic adrenocorticotropic hormone-producing bronchial carcinoid tumor diagnosed preoperatively using technetium-99m-labeled octreotide acetate scintigraphy. Case presentation A 29-year-old Asian man presented to our hospital with the typical clinical features of Cushing's syndrome, which he had had for a duration of 18 months. The results of a biochemical evaluation revealed he had adrenocorticotropic hormone-dependent Cushing's syndrome. The results of a spiral abdominal computed tomography scan showed he had bilateral adrenal hypertrophy. A magnetic resonance image of the patient's brain showed he had a normal hypophysis. Whole body technetium-99m-labeled octreotide acetate scintigraphy was performed to check for the presence of an ectopic adrenocorticotropic hormone-producing tumor. The scan results showed a small focal increase in uptake in the lower lobe of our patient's right lung, just above his diaphragm. A spiral chest computed tomography scan also revealed a small non-specific lesion in the same region. A transthoracic biopsy was then performed. Pathological evaluation confirmed the diagnosis of a carcinoid tumor, of the adrenocorticotropic hormone-producing type. After surgical removal, the patient's symptoms resolved and significant clinical improvement was achieved. Conclusions This case report shows that technetium-99m-labeled octreotide acetate scintigraphy can effectively detect an ectopic adrenocorticotropic hormone-producing bronchial carcinoid.

  8. Tumor thrombosis: a peculiar finding associated with pancreatic neuroendocrine neoplasms. A pictorial essay.

    Science.gov (United States)

    De Robertis, Riccardo; Paiella, Salvatore; Cardobi, Nicolò; Landoni, Luca; Tinazzi Martini, Paolo; Ortolani, Silvia; De Marchi, Giulia; Gobbo, Stefano; Giardino, Alessandro; Butturini, Giovanni; Tortora, Giampaolo; Bassi, Claudio; D'Onofrio, Mirko

    2017-07-04

    While abutment, encasement or vessel occlusion are identified in most patients with a pancreatic tumor, tumor thrombosis is an uncommon finding. In particular, there are no description in the literature of tumor thrombosis associated with ductal adenocarcinoma, the most common pancreatic tumor. On the other hand, surgical series reveal that tumor thrombosis is associated with about 5% of pancreatic neuroendocrine neoplasms (PanNENs), and literature data suggest that this finding is frequently underreported on pre-operative imaging examinations. Tumor thrombosis may be clinically relevant, causing splenoportomesenteric hypertension, possibly responsible for life-threatening upper gastrointestinal bleeding. Bland thrombosis caused by direct infiltration of peri-pancreatic vessels frequently determines surgical unresectability, even in neuroendocrine tumors; on the opposite, tumor thrombosis associated with PanNENs do not exclude surgery per se, even though both morbidity and mortality can be increased by such condition. Considering the favorable prognosis of PanNENs and the frequent need to treat tumor thrombosis in order to prevent complications or to relieve symptoms, it is of paramount importance for radiologists the knowledge of the variety of findings associated with tumor thrombosis in PanNENs.

  9. 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.)

  10. Cytologic and immunohistochemical characterization of a lung carcinoid in a dog.

    Science.gov (United States)

    Choi, Ul Soo; Alleman, A Rick; Choi, Ji-Hye; Kim, Hyun Wook; Youn, Hee-Jeong; Lee, Chang Woo

    2008-06-01

    An 11-year-old neutered male Yorkshire Terrier was presented to the Haemaru Referral Animal Hospital with a history of unresponsive tracheal collapse and an incidental finding of a lung nodule in the left caudal lung lobe on radiography. Thorough physical examination and imaging studies revealed no other masses. Cytologic examination of C-arm mobile fluoroscopy-guided fine-needle aspirates revealed numerous free nuclei and a low number of small round cells with moderate to abundant pale basophilic cytoplasm. Some cells contained indistinct basophilic granules in their cytoplasm, and extracellular pink material was noted. A caudal lung lobectomy was performed, and histologic evaluation of the mass revealed round to polygonal cells with abundant eosinophilic granular cytoplasm and round nuclei with mild anisokaryosis and 0-3 mitotic figures per high-power field. Cells were arranged in packets separated by fine fibrovascular stroma, suggestive of a pulmonary neuroendocrine neoplasm, specifically a carcinoma/carcinoid. The cells were immunoreactive for chromogranin A and neuron-specific enolase, and negative for cytokeratin, synaptophysin, calcitonin, thyroglobulin, parathyroid hormone, CD79a, light lambda, and vimentin. With these findings the tumor was diagnosed as a primary lung carcinoid. Eleven months after resection, there was no evidence of tumor regrowth or metastasis. The absence of necrosis, few mitotic figures, minimal pleomorphism, and benign behavior of this tumor resembled those of a typical carcinoid in humans.

  11. Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival

    National Research Council Canada - National Science Library

    Gupta, Sanjay; Johnson, Marcella M; Murthy, Ravi; Ahrar, Kamran; Wallace, Michael J; Madoff, David C; McRae, Stephen E; Hicks, Marshall E; Rao, Sujaya; Vauthey, Jean-Nicolas; Ajani, Jaffer A; Yao, James C

    2005-01-01

    The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE...

  12. The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients

    DEFF Research Database (Denmark)

    Rehfeld, Jens F; Federspiel, Birgitte; Agersnap, Mikkel

    2016-01-01

    OBJECTIVE: Neuroendocrine tumors in the pancreas and the gastrointestinal tract may secrete hormones which cause specific syndromes. Well-known examples are gastrinomas, glucagonomas, and insulinomas. Cholecystokinin-producing tumors (CCKomas) have been induced experimentally in rats, but a CCKoma...... attacks from a contracted gallbladder. The CCK concentrations in plasma were not affected by resection of the pancreatic tumor, but decreased to normal after hemihepatectomy with removal of the metastases. CONCLUSION: A CCKoma syndrome with severe hypersecretion of CCK exists in man. The duodenal ulcer...

  13. Association between pernicious anemia and gastric carcinoid tumor: a report of a clinical case

    OpenAIRE

    de Carvalho, R.; Leichsenring, C; Félix, J; Gomes, F.; Manso, RT; Geraldes, V.; Cuña, L; Branquinho, F; Perloiro, MC

    2010-01-01

    Os tumores carcinóides gástricos são raros, representando ≤ 1% dos tumores gástricos e 8,7% de todos os carcinóides gastrentestinais. Os autores descrevem o caso clínico de uma mulher de 32 anos admitida por anemia macrocítica, e cuja investigação etiológica revelou tratar-se de uma anemia perniciosa (AP). Realizou uma endoscopia digestiva alta (EDA), onde se encontraram 6 nódulos bem delimitados no corpo e fundo gástricos. O resultado histopatológico foi consistente com o diagnóstic...

  14. Evaluation of neuroendocrine tumors with 99mTc-EDDA/HYNIC TOC.

    Science.gov (United States)

    Artiko, Vera; Afgan, Aida; Petrović, Jelena; Radović, Branislava; Petrović, Nebojša; Vlajković, Marina; Šobić-Šaranović, Dragana; Obradović, Vladimir

    2016-01-01

    This paper is the short review of our preliminary results obtained with 99mTc-EDDA/HYNIC-TOC. The total of 495 patients with different neuroendocrine tumors were investigated during last few years. There have been 334 true positive (TP), 73 true negative (TN), 6 false positive (FP) and 82 false negative findings (FN). Diagnosis was made according to SPECT findings in 122 patients (25%). The mean T/NT ratio for TP cases was significantly higher (p Tektrotyd is a useful method for diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors. SPECT had important role in diagnosis. It is also helpful in the appropriate choice of the therapy, including the peptide receptor radionuclide therapy. In the absence of 68Ga-labeled peptides and PET/CT, the special emphasize should be given to application of SPECT/CT as well as to the radioguided surgery.

  15. ASCL1 and NEUROD1 Reveal Heterogeneity in Pulmonary Neuroendocrine Tumors and Regulate Distinct Genetic Programs

    Directory of Open Access Journals (Sweden)

    Mark D. Borromeo

    2016-08-01

    Full Text Available Small cell lung carcinoma (SCLC is a high-grade pulmonary neuroendocrine tumor. The transcription factors ASCL1 and NEUROD1 play crucial roles in promoting malignant behavior and survival of human SCLC cell lines. Here, we find that ASCL1 and NEUROD1 identify heterogeneity in SCLC, bind distinct genomic loci, and regulate mostly distinct genes. ASCL1, but not NEUROD1, is present in mouse pulmonary neuroendocrine cells, and only ASCL1 is required in vivo for tumor formation in mouse models of SCLC. ASCL1 targets oncogenic genes including MYCL1, RET, SOX2, and NFIB while NEUROD1 targets MYC. ASCL1 and NEUROD1 regulate different genes that commonly contribute to neuronal function. ASCL1 also regulates multiple genes in the NOTCH pathway including DLL3. Together, ASCL1 and NEUROD1 distinguish heterogeneity in SCLC with distinct genomic landscapes and distinct gene expression programs.

  16. Ectopic Cushing and other paraneoplastic syndromes in thoracic neuroendocrine tumors.

    Science.gov (United States)

    Ferone, Diego; Albertelli, Manuela

    2014-08-01

    Overproduction of corticotropin by the pituitary gland or extrapituitary tumors leads to hypercortisolism or Cushing syndrome. Diagnosis of suspected Cushing syndrome involves 3 major steps: confirmation of hypercortisolism, differentiation between corticotropin-independent and corticotropin-dependent causes of Cushing syndrome, and distinction between pituitary and ectopic corticotropin production. A definitive diagnosis of ectopic corticotropin secretion requires stringent criteria, including reversal of the clinical picture after resection of the tumor and/or demonstration of corticotropin immunohistochemical staining within the tumor tissue. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. The Thyro-Gastric syndrome: from thyroid autoimmunity to neuroendocrine gastric tumors

    OpenAIRE

    VALDES SOCIN, Hernan Gonzalo; Beckers, Albert

    2011-01-01

    THE THYRO-GASTRIC SYNDROME: FROM THYROID AUTOIMMUNITY TO NEUROENDOCRINE GASTRIC TUMORS. In 1849, Prof Addison described a fatal case of anemia, or anemia perniciosa. Dr Biermer expanded this original description in 1872. Nowadays, this pathological condition associating a megaloglastic anemia associated with a metabolic polyneuropathy is recognized as Biermer disease. Biermer anemia or anemia perniciosa and its associated polyneuropathy are the consequence of vitamine B12 malabsorpti...

  18. 99mTc-HYNIC-TOC imaging in the evaluation of pancreatic masses which are potential neuroendocrine tumors.

    Science.gov (United States)

    Qiao, Zhen; Zhang, Jingjing; Jin, Xiaona; Huo, Li; Zhu, Zhaohui; Xing, Haiqun; Li, Fang

    2015-05-01

    The aim of this investigation was to determine the accuracy of the findings and the diagnoses of Tc-hydrazinonicotinyl-Tyr3-octreotide scan (Tc-HYNIC-TOC imaging) in patients with pancreatic masses which were potential neuroendocrine tumors. Records of total 20 patients with pancreatic masses were retrospectively reviewed. All of the patients had been revealed by abdominal contrast CT and possibility of neuroendocrine tumors could not be excluded by CT imaging before Tc-HYNIC-TOC imaging. Tc-HYNIC-TOC imaging was performed at 1 and 4 hours post-tracer injection, and SPECT/CT images of the abdomen were also acquired. The image findings were compared to final diagnoses which were made from pathological examination. Among all 20 pancreatic masses evaluated, there were 16 malignant lesions which included 1 ductal adenocarcinoma and 15 neuroendocrine tumors. Tc-HYNIC-TOC imaging identified 14 of 15 pancreatic neuroendocrine tumors and excluded 4 of 5 lesions which were not neuroendocrine tumors. The overall sensitivity, specificity, and accuracy was therefore 93.3% (14 of 15), 80% (4 of 5), and 90.0% (18 of 20), respectively, in our patient population. Tc-HYNIC-TOC imaging provides reasonable accuracy in the evaluation pancreatic mass suspected to be neuroendocrine tumors.

  19. 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.

  20. Occult Primary Neuroendocrine Tumor Metastasis to the Breast Detected on Screening Mammogram

    Directory of Open Access Journals (Sweden)

    Fabiana Policeni

    2016-01-01

    Full Text Available Metastatic tumors are rare in the breast. Well-differentiated neuroendocrine tumors (WDNETs are slow-growing neoplasms that arise from neuroendocrine cells, particularly in the gastrointestinal tract and bronchial tree. Metastatic WDNET to the breast is a rare entity. We present a case report of ileal WDNET metastatic to the breast which was initially identified as a small mass in the patient′s left breast on screening mammography. Targeted ultrasound identified a suspicious mass, and ultrasound-guided percutaneous core biopsy was performed. Pathology revealed metastatic WDNET. Breast magnetic resonance imaging (MRI was then performed and demonstrated left axillary Level 2 lymphadenopathy, and liver lesions were suspicious for metastasis. The patient underwent abdominal computed tomography (CT to evaluate for distant metastatic disease. A spiculated mass was found near the ileocecal valve, suggestive of primary ileal WDNET. In addition, CT identified multiple liver lesions, most compatible with metastasis. Indium 111 OctreoScan confirmed radiotracer uptake in the ileum consistent with primary neuroendocrine tumor. In this report, we review the imaging characteristics of metastatic WDNET to the breast by different imaging modalities including mammogram, ultrasound, and breast MRI.

  1. Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms

    NARCIS (Netherlands)

    Wymenga, ANM; Eriksson, B; Salmela, PI; Jacobsen, MB; Van Cutsem, EJDG; Fiasse, RH; Valimaki, MJ; Renstrup, J; de Vries, EGE; Oberg, KE

    Purpose: To evaluate the prolonged release (PR) of the long-acting somatostatin analog lanreotide in patients with gastrointestinal neuroendocrine tumors and its effect on hormone-related symptomatology, tumor markers, tumor size, tolerability, and quality of life (QOL), Patients and Methods:

  2. Neuroendocrine Tumor, Well Differentiated, of the Breast: A Relatively High-Grade Case in the Histological Subtype

    Directory of Open Access Journals (Sweden)

    Shogo Tajima

    2013-01-01

    Full Text Available Primary neuroendocrine carcinoma of the breast is a rare entity, comprising <1% of breast carcinomas. Described here is the case of a 78-year-old woman who developed an invasive tumor in the left breast measuring 2.0 cm x 1.5 cm x 1.2 cm. The tumor was composed of only endocrine elements in the invasive part. It infiltrated in a nested fashion with no tubular formation. Intraductal components were present both inside and outside of the invasive portion. Almost all carcinoma cells consisting of invasive and intraductal parts were positive for synaptophysin and neuron-specific enolase. According to the World Health Organization classification 2012, this tumor was subclassified as neuroendocrine tumor, well-differentiated. Among the subgroup, this tumor was relatively high-grade because it was grade 3 tumor with a few mitotic figures. Vascular and lymphatic permeation and lymph node metastases were noted. In the lymph nodes, the morphology of the tumor was similar to the primary site. No distant metastasis and no relapse was seen for one year after surgery. The prognosis of neuroendocrine carcinomas is thought to be worse than invasive mammary carcinomas, not otherwise specified. Therefore, immunohistochemistry for neuroendocrine markers is important in the routine practice to prevent overlooking neuroendocrine carcinomas.

  3. Global gene expression in neuroendocrine tumors from patients with the MEN1 syndrome

    Directory of Open Access Journals (Sweden)

    Laramie Jason M

    2005-02-01

    Full Text Available Abstract Background Multiple Endocrine Neoplasia type 1 (MEN1, OMIM 131100 is an autosomal dominant disorder characterized by endocrine tumors of the parathyroids, pancreatic islets and pituitary. The disease is caused by the functional loss of the tumor suppressor protein menin, coded by the MEN1 gene. The protein sequence has no significant homology to known consensus motifs. In vitro studies have shown menin binding to JunD, Pem, Smad3, NF-kappaB, nm23H1, and RPA2 proteins. However, none of these binding studies have led to a convincing theory of how loss-of-menin leads to neoplasia. Results Global gene expression studies on eight neuroendocrine tumors from MEN1 patients and 4 normal islet controls was performed utilizing Affymetrix U95Av2 chips. Overall hierarchical clustering placed all tumors in one group separate from the group of normal islets. Within the group of tumors, those of the same type were mostly clustered together. The clustering analysis also revealed 19 apoptosis-related genes that were under-expressed in the group of tumors. There were 193 genes that were increased/decreased by at least 2-fold in the tumors relative to the normal islets and that had a t-test significance value of p Conclusion This is the first analysis of global gene expression in MEN1-associated neuroendocrine tumors. Many genes were identified which were differentially expressed in neuroendocrine tumors arising in patients with the MEN1 syndrome, as compared with normal human islet cells. The expression of a group of apoptosis-related genes was significantly suppressed, suggesting that these genes may play crucial roles in tumorigenesis in this syndrome. We identified a number of genes which are attractive candidates for further investigation into the mechanisms by which menin loss causes tumors in pancreatic islets. Of particular interest are: FGF9 which may stimulate the growth of prostate cancer, brain cancer and endometrium; and IER3 (IEX-1, PHLDA2

  4. Neuroendocrine tumors of the pancreas; Multimodale Bildgebung bei neuroendokrinen Tumoren des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Holzapfel, Konstantin; Rummeny, Ernst J. [Technische Univ. Muenchen (Germany). Inst. fuer Radiologie; Gaertner, Florian C. [Technische Univ. Muenchen (Germany). Nuklearmedizinische Klinik

    2011-12-15

    Neuroendocrine tumors (NET) of the pancreas are rare entities. Functioning tumors tend to present early with specific symptoms and typical abnormalities in laboratory values. In contrast, non-functioning NET are often diagnosed with delay and become evident by tumor-related symptoms like pain, weight-loss or jaundice. The role of imaging is to localize and delineate the primary tumor and to detect metastases. In the diagnosis of NET radiologic techniques like computed tomography (CT) and magnetic resonance imaging (MRI) are applied. In certain cases nuclear medicine techniques like somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using radioactively labelled somatostatin analogues are used. The present article reviews characteristic imaging findings of both functioning and non-functioning NET of the pancreas. (orig.)

  5. Optimal Lymphadenectomy in Small Bowel Neuroendocrine Tumors: Analysis of the NCDB.

    Science.gov (United States)

    Motz, Benjamin M; Lorimer, Patrick D; Boselli, Danielle; Hill, Joshua S; Salo, Jonathan C

    2017-08-17

    Current National Comprehensive Cancer Network guidelines for resectable small bowel neuroendocrine tumors (NETs) recommend regional lymphadenectomy. However, no consensus exists on the optimal nodal harvest. The National Cancer Database was queried for patients with resectable small bowel NETs (1998-2013). Patients with metastatic disease and missing lymph node harvest data were excluded. We performed logistic regression of factors determining nodal positivity and multivariable survival analyses. Of 11,852 patients, 81.8% underwent lymphadenectomy. 79.3% were node positive (N+) and 46.9% of patients had tumors < 1 cm. Independent predictors of N+ were large tumor size, ileal location, and neuroendocrine carcinoma histology. Logistic regression found no difference between observed and expected proportions of N+ patients with lymphadenectomy greater than or equal to eight nodes. Lower metastatic node ratio predicted improved survival on multivariable analysis and is associated with high-volume institutions. Small bowel NETs have high rates of nodal metastasis, even in patients with small tumors, and many patients do not undergo lymphadenectomy despite the clear benefit. Lymphadenectomy of eight nodes is optimal to identify N+ patients. Additionally, minimizing metastatic node ratio with complete regional lymphadenectomy is associated with improved survival in these patients.

  6. Duodenal neuroendocrine tumor and the onset of severe diabetes mellitus in a US veteran

    Directory of Open Access Journals (Sweden)

    Lauren Murray

    2016-01-01

    Full Text Available Objective: Neuroendocrine tumors are neoplasms derived from endocrine cells, most commonly occurring in the gastrointestinal tract. Duodenal neuroendocrine tumors are rare tumors averaging 1.2–1.5 cm, and most are asymptomatic. Common presentation is abdominal pain, upper gastrointestinal bleed, constipation, anemia, and jaundice. Methods: An adult, Black, male patient with newly diagnosed diabetes mellitus presented to the emergency department with elevated liver function test and fatigue. Results: Magnetic resonance cholangiopancreatography demonstrated a large obstructing mass (3.6 cm × 4.4 cm × 3 cm within the second and third portions of the duodenum at the ampulla. Esophagogastroduodenoscopy demonstrated an ulcerated duodenal mass that was biopsied. Immunohistochemical stains were positive for synaptophysin, chromogranin B, and CK7. Chromogranin A was in normal range. Post-Whipple procedure demonstrated a 5.5 cm × 4.1 cm × 2.9 cm duodenal mass with invasion of the subserosal tissue of the small intestine, a mitotic rate of 2 per high-power field, and antigen Ki-67 of 2%–5%. Conclusion: This case raises the question as to if the patient developed diabetes mellitus due to the tumor size and location or if the new onset of diabetes was coincidental. This case also demonstrates the importance of a proficient history and physical.

  7. Profiling of metastatic small intestine neuroendocrine tumors reveals characteristic miRNAs detectable in plasma.

    Science.gov (United States)

    Bowden, Michaela; Zhou, Chensheng W; Zhang, Sui; Brais, Lauren; Rossi, Ashley; Naudin, Laurent; Thiagalingam, Arunthi; Sicinska, Ewa; Kulke, Matthew H

    2017-08-15

    Current diagnostic and prognostic blood-based biomarkers for neuroendocrine tumors are limited. MiRNAs have tumor-specific expression patterns, are relatively stable, and can be measured in patient blood specimens. We performed a multi-stage study to identify and validate characteristic circulating miRNAs in patients with metastatic small intestine neuroendocrine tumors, and to assess associations between miRNA levels and survival. Using a 742-miRNA panel, we identified candidate miRNAs similarly expressed in 19 small intestine neuroendocrine tumors and matched plasma samples. We refined our panel in an independent cohort of plasma samples from 40 patients with metastatic small intestine NET and 40 controls, and then validated this panel in a second, large cohort of 120 patients with metastatic small intestine NET and 120 independent controls. miRNA profiling of 19 matched small intestine neuroendocrine tumors and matched plasma samples revealed 31 candidate miRNAs similarly expressed in both tissue and plasma. We evaluated expression of these 31 candidate miRNAs in 40 independent cases and 40 normal controls, and identified 4 miRNAs (miR-21-5p, miR-22-3p, miR-29b-3p, and miR-150-5p) that were differently expressed in cases and controls (p<0.05). We validated these 4 miRNAs in a separate, larger panel of 120 cases and 120 controls. We confirmed that high circulating levels of miR-22-3p (p<0.0001), high levels of miR 21-5p, and low levels of miR-150-5p (p=0.027) were associated with the presence of metastatic small intestine NET. While levels of 29b-3p were lower in cases than in controls in both the initial cohort and the validation cohort, the difference in the validation cohort did not reach statistical significance. We further found that high levels of circulating miR-21-5p, high levels of circulating miR-22-3p and low levels of circulating miR-150-5p were each independently associated with shorter overall survival. A combined analysis using all three markers

  8. 68Ga-DOTA-NOC PET/CT imaging of neuroendocrine tumors: comparison with ¹¹¹In-DTPA-octreotide (OctreoScan®).

    Science.gov (United States)

    Krausz, Yodphat; Freedman, Nanette; Rubinstein, Rina; Lavie, Efraim; Orevi, Marina; Tshori, Sagi; Salmon, Asher; Glaser, Benjamin; Chisin, Roland; Mishani, Eyal; J Gross, David

    2011-06-01

    Recent data have indicated that ⁶⁸Ga-DOTA-NOC positron emission tomography/X-ray computed tomography (PET/CT) may yield improved images in a shorter acquisition protocol than ¹¹¹In-DTPA-octreotide (OctreoScan®, OCT). Therefore, we performed a prospective comparison of ⁶⁸Ga-DOTA-NOC and OCT for the detection of neuroendocrine tumors (NETs). Nineteen patients (eight carcinoid, nine pancreatic NETs, and two NE carcinoma of unknown origin) with previous positive OCT scans underwent ⁶⁸Ga-DOTA-NOC PET/CT and OCT single-photon emission computed tomography imaging for staging or follow-up. Findings were compared by region and verified with conventional imaging. All images of both modalities demonstrated focal uptake, often at multiple sites. ⁶⁸Ga-DOTA-NOC images were clearer than OCT images, facilitating interpretation. Similar foci were identified with both modalities in 41 regions, with additional foci on ⁶⁸Ga-DOTA-NOC in 21 and on OCT in 15 regions. CT, magnetic resonance imaging, or ultrasound confirmed the concordant findings in 31 of 41 regions and findings seen with ⁶⁸Ga-DOTA-NOC only in 15 of 21 regions. Findings seen with OCT only were less clear and were only confirmed in 4 of 15 regions. ⁶⁸Ga-DOTA-NOC had impact on staging in four patients and on management in three patients. Although ⁶⁸Ga-DOTA-NOC and OCT images were similar, in this study, ⁶⁸Ga-DOTA-NOC demonstrated more true positive tumor foci and was better tolerated by patients. This direct comparison supports replacement of OCT with ⁶⁸Ga-DOTA-NOC-PET/CT in the evaluation of NETs.

  9. A case of pancreatic neuroendocrine tumor in a patient with neurofibromatosis-1

    Directory of Open Access Journals (Sweden)

    Nishi Takeshi

    2012-07-01

    Full Text Available Abstract Patients with neurofibromatosis-1 (NF-1 sometime develop neuroendocrine tumors (NET. Although these NETs usually occur in the duodenum or peri-ampullary region, they occasionally grow in the pancreas (PNET. A 62-year-old man with NF-1 had mild liver dysfunction and was admitted to our hospital for further examination. An abdominal contrast-enhanced computed tomography scan demonstrated a 30-mm tumor in the head of the pancreas. The scan showed an invasion of the tumor into the duodenum, and biopsy under an endoscopic ultrasonography indicated that the tumor was a NET. A subtotal stomach-preserving pancreaticoduodenectomy was performed. Macroscopically, the pancreatic tumor was white and elastic hard. Microscopically, tumor cells were composed of ribbons, cords, and solid nests with an acinus-like structure. The tumor was diagnosed as NET G2 according to the WHO classification (2010. The product of theNF-1 gene, i.e., neurofibromin, was weakly positive in the tumor cells, suggesting that the tumor was induced by a mutation in the NF-1 gene. This is the seventh case of PNET arising in NF-1 patients worldwide.

  10. Evaluation of {sup 68}Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1

    Energy Technology Data Exchange (ETDEWEB)

    Morgat, Clement; Mazere, Joachim; Hindie, Elif; Fernandez, Philippe [CNRS, INCIA, Bordeaux (France); University of Bordeaux, INCIA, Bordeaux (France); University Hospital of Bordeaux, Department of Nuclear Medicine, Bordeaux (France); Velayoudom-Cephise, Fritz-Line; Nunes, Marie-Laure; Tabarin, Antoine [USN Haut-Leveque, Department of Endocrinology, Pessac (France); Schwartz, Paul; Guyot, Martine [University Hospital of Bordeaux, Department of Nuclear Medicine, Bordeaux (France); Gaye, Delphine [University Hospital of Bordeaux, Department of Radiology, Pessac (France); Vimont, Delphine; Schulz, Juergen [CNRS, INCIA, Bordeaux (France); University of Bordeaux, INCIA, Bordeaux (France); Smith, Denis [University Hospital of Bordeaux, Department of Oncology, Bordeaux (France)

    2016-07-15

    Somatostatin receptor scintigraphy with {sup 111}In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with {sup 68}Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. To compare the performances of {sup 68}Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. Single-institution prospective comparative study Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent {sup 68}Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, {sup 18}F-2-fluoro-deoxy-d-glucose ({sup 18}F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. The sensitivity of {sup 68}Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p < 0.0001). All the true-positive lesions detected by SRS were also depicted on {sup 68}Ga-DOTA-TOC PET/CT. {sup 68}Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p < 0.03). False negatives of {sup 68}Ga-DOTA-TOC PET/CT included small dpNETs (<10 mm) and {sup 18}F-FDG PET/CT positive aggressive dpNETs. No false positives were recorded. In addition, whole-body mapping with {sup 68}Ga-DOTA-TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. Owing to higher diagnostic performance, {sup 68}Ga-DOTA-TOC PET/CT (or alternative {sup 68}Ga-labeled somatostatin analogues

  11. Evaluation of (68)Ga-DOTA-TOC PET/CT for the detection of duodenopancreatic neuroendocrine tumors in patients with MEN1.

    Science.gov (United States)

    Morgat, Clément; Vélayoudom-Céphise, Fritz-Line; Schwartz, Paul; Guyot, Martine; Gaye, Delphine; Vimont, Delphine; Schulz, Jürgen; Mazère, Joachim; Nunes, Marie-Laure; Smith, Denis; Hindié, Elif; Fernandez, Philippe; Tabarin, Antoine

    2016-07-01

    Somatostatin receptor scintigraphy with (111)In-pentetreotide (SRS) is used to detect duodenopancreatic neuroendocrine tumors (dpNETs) in multiple endocrine neoplasia type 1 (MEN1). However, SRS has limited sensitivity for this purpose. Positron emission tomography/computed tomography (PET/CT) with (68)Ga-DOTA-TOC has a higher rate of sporadic dpNETs detection than SRS but there is little data for dpNETs detection in MEN1. To compare the performances of (68)Ga-DOTA-TOC PET/CT, SRS and contrast-enhanced computed tomography (CE-CT) to diagnose dpNETs in MEN1. Single-institution prospective comparative study Nineteen consecutive MEN1 patients (aged 47 ± 13 years) underwent (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT within 2 months in random order. Blinded readings of images were performed separately by experienced physicians. Unblinded analysis of CE-CT, combined with additional magnetic resonance imaging, endoscopic-ultrasound, (18)F-2-fluoro-deoxy-D-glucose ((18)F-FDG) PET/CT or histopathology results served as reference standard for dpNETs diagnosis. The sensitivity of (68)Ga-DOTA-TOC PET/CT, SRS, and CE-CT was 76, 20, and 60 %, respectively (p TOC PET/CT. (68)Ga-DOTA-TOC PET/CT detected lesions of smaller size than SRS (10.7 ± 7.6 and 15.2 ± 5.9 mm, respectively, p TOC PET/CT included small dpNETs (TOC PET/CT identified extra-abdominal MEN1-related tumors including one neuroendocrine thymic carcinoma identified by the three imaging procedures, one bronchial carcinoid undetected by CE-CT and three meningiomas undetected by SRS. Owing to higher diagnostic performance, (68)Ga-DOTA-TOC PET/CT (or alternative (68)Ga-labeled somatostatin analogues) should replace (111)In-pentetreotide in the investigation of MEN1 patients.

  12. Assessment of disease aggression in cystic pancreatic neuroendocrine tumors: A CT and pathology correlation study.

    Science.gov (United States)

    Yano, Motoyo; Misra, Sunil; Salter, Amber; Carpenter, Danielle H

    There are inconsistencies in the literature regarding the clinical significance of cystic components in pancreatic neuroendocrine tumors (NET). This may be related to differences in the identification of cystic NET through imaging and/or pathology. Tumors may also be microscopically or macroscopically cystic. Our primary objective is to determine radiology-pathology correlation for the identification of cystic components. Our secondary objective is to determine if cystic components are associated with indices of tumor aggression. 60 tumors with correlative surgical pathology were assessed retrospectively for cystic components on CT and pathology. Tumor was categorized as solid or cystic on CT and pathology. If cystic on pathology, cystic components were categorized as macroscopic or microscopic. Cystic components were estimated as disease aggression. Associations were tested with Chi square/Fisher's exact test and differences were tested with t-test/Wilcoxon rank sums test. There is moderate agreement between CT and histology for presence of cystic components. Discrepancies were mostly attributable to the presence of microscopic cystic components in tumors appearing solid on CT. There was no difference in size between cystic and solid tumors on CT or pathology. No association between CT-determined cystic components and tumor grade was found. Tumors with cystic components (cystic by CT, and macroscopically cystic by pathology) demonstrated less association with metastases than solid tumors. Cystic components, comprising ≥50% of the tumor by CT and observed macroscopically on pathology, are associated with less aggressive disease. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  13. Neuroendocrine tumors of the gastrointestinal tract; Multimodale Bildgebung neuroendokriner Tumoren des Gastrointestinaltrakts

    Energy Technology Data Exchange (ETDEWEB)

    Holzapfel, Konstantin; Eiber, Matthias; Rummeny, Ernst J. [Klinikum rechts der Isar der Technischen Univ. Muenchen (Germany). Inst. fuer Radiologie; Gaertner, Florian C. [Bonn Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2014-03-15

    Neuroendocrine tumors (neuroendokrine Tumoren) are rare entities. They can be found in all organs and show substantial biologic heterogeneity depending on involved organ, clinical symptoms and histopathologic morphology. Involvement of organs like larynx, cervix uteri, ovary, gallbladder, liver or kidney is extensively rare. The majority of neuroendokrine Tumoren are found in gastrointestinal tract and lung and are classified as neuroendokrine Tumoren of foregut (stomach, duodenum, pancreas, lung), midgut (jejunum, ileum, appendix, right side of the colon) and hindgut (left side of the colon, rectum). The role of imaging is to localize and delineate the primary tumor and to detect metastases. In the diagnosis of neuroendokrine Tumoren radiologic techniques like computed tomography (CT) and magnetic resonance imaging (MRI) are applied. In certain cases nuclear medicine techniques like somatostatin receptor scintigraphy (SRS) and positron emission tomography (PET) using radioactively labelled somatostatin analogues are used. The present article reviews characteristic imaging findings of neuroendokrine Tumoren of the gastrointestinal tract. (orig.)

  14. Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia of the Lung (DIPNECH): Current Best Evidence.

    Science.gov (United States)

    Wirtschafter, Eric; Walts, Ann E; Liu, Sandy T; Marchevsky, Alberto M

    2015-10-01

    Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is recognized as a preneoplastic condition by the World Health Organization. We reviewed our experience with 30 patients and performed a systematic review of the English literature to collect best evidence on the clinical features and disease course in 169 additional patients. Some patients presented with one or more carcinoid tumors associated with multiple small pulmonary nodules on imaging studies and showed DIPNECH as a somewhat unexpected pathologic finding. Others presented with multiple small pulmonary nodules that raised suspicion of metastatic disease on imaging. A third subset was presented with previously unexplained respiratory symptoms. In most patients, DIPNECH was associated with a good prognosis, with chronological progression into a subsequent carcinoid tumor noted in only one patient and death attributed directly to DIPNECH in only two patients. There is no best evidence to support the use of octreotide, steroids, or bronchodilators in DIPNECH patients.

  15. Gastric Carcinoid and Obesity: Association or Coincidence? Report of Two Cases and Literature Review

    Directory of Open Access Journals (Sweden)

    Obaid Al-Harbi

    2013-01-01

    Full Text Available Bariatric surgery is a prevalent procedure due to the high incidence of obesity and comorbidities. Upper gastrointestinal endoscopy is one of the procedures used to evaluate the patient before surgery. However, its role is questionable. The incidental findings during endoscopy are variable including inflammatory diseases, and ulcers, and epithelial and stromal tumors. Herein a report of two obese sisters with incidental gastric carcinoids was diagnosed in prebariatric surgery endoscopy. Case Summary. 35- and 41-year-old female patients presented with obesity and BMI of 102 and 46 kg/m2, respectively. Both patients underwent upper gastrointestinal endoscopy as part of presurgical evaluation. Multiple polyps were indentified in both patients, and biopsy was taken. Histological examination revealed tumors that were formed by nests of epithelial cells. The cells have eosinophilic cytoplasm and monomorphic nuclei, typical morphology of neuroendocrine tumors. Conclusions. (1 Upper gastrointestinal endoscopy is an important procedure for prebariatric surgery evaluation. (2 Gastric carcinoid is a rare tumor with higher incidence among obese patients.

  16. Tumor neuroendocrino ileal con síndrome carcinoide, patología de difícil diagnóstico y pronóstico variable

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    Gonzalo Miranda

    2015-04-01

    Full Text Available Los tumores neuroendocrinos (TNE presentan dificultad en el diagnóstico por sus síntomas inespecíficos y el manejo es un reto. Se presenta el caso de un varón de 78 años de edad, con dolor crónico en hemiabdomen superior. Ingresó a emergencia con obstrucción intestinal y síntomas de síndrome carcinoide (SC. En cirugía se resecó tumor ileal con resultado anatomopatológico de tumor neuroendocrino, cromogranina positivo, índice proliferativo ki 67 de 2 a 3%. El paciente continuó con síntomas de SC, altos niveles de 5-HIA, metástasis hepáticas en RMN. Se inició octreotide con adecuada respuesta clínica. La experiencia con el presente caso indica estar alerta con los síntomas de TNE funcionantes, debido al aumento en su incidencia. Es de utilidad solicitar marcadores inmunohistoquimicos. La identificación de un TNE con índice de mitosis y proliferación bajo indica buen pronóstico.

  17. Pancreatic neuroendocrine neoplasms: Correlation between MR features and pathological tumor grades.

    Science.gov (United States)

    Jin, Feng; Wang, Kai; Qin, Ting-Ting; Li, Xin; Guo, Feng; Ma, Gui-Na; Hu, Xue-Han; Han, Ping

    2017-08-01

    This study investigated the accuracy of MRI features in differentiating the pathological grades of pancreatic neuroendocrine neoplasms (PNENs). A total of 31 PNENs patients were retrospectively evaluated, including 19 cases in grade 1, 5 in grade 2, and 7 in grade 3. Plain and contrastenhanced MRI was performed on all patients. MRI features including tumor size, margin, signal intensity, enhancement patterns, degenerative changes, duct dilatation and metastasis were analyzed. Chi square tests, Fisher's exact tests, one-way ANOVA and ROC analysis were conducted to assess the associations between MRI features and different tumor grades. It was found that patients with older age, tumors with higher TNM stage and without hormonal syndrome had higher grade of PNETs (all Pgrades (all Pgrade 3 from grade 1 and grade 2 tumors. Features of peripancreatic tissue or vascular invasion, and distant metastasis showed high specificity but relatively low sensitivity. In conclusion, larger size, poorlydefined margin, heterogeneous enhanced pattern during arterial phase, duct dilatation and the presence of metastases are common features of higher grade PNENs. Plain and contrast-enhanced MRI provides the ability to differentiate tumors with different pathological grades.

  18. Gastrointestinal neuroendocrine tumors: Searching the optimal treatment strategy--A literature review.

    Science.gov (United States)

    Berardi, Rossana; Rinaldi, Silvia; Torniai, Mariangela; Morgese, Francesca; Partelli, Stefano; Caramanti, Miriam; Onofri, Azzurra; Polenta, Vanessa; Pagliaretta, Silvia; Falconi, Massimo; Cascinu, Stefano

    2016-02-01

    Neuroendocrine tumors of the gastro-entero-pancreatic system (GEP-NETs) are a heterogeneous group of neoplasms, with different malignant potential and behavior. Many treatment options are available. Surgery should be considered for localized tumors and in some selected cases of metastatic disease. Somatostatin analogs, useful for symptoms control in functioning tumors, are also effective to inhibit tumor progression in specific settings. The multi-TKI sunitinib and of the mTOR-inhibitor everolimus are efficacy for metastatic pancreatic NET (P-NET) treatment. Chemotherapy is generally used in symptomatic and progressive NETs. Peptide receptor radionuclide therapy (PRRT) should be recommended after failure of medical therapy. For tumors confined to the liver ablative techniques should be considered. Nevertheless a shared therapeutic sequence for GEP-NET treatment still does not exist. In this review, we analyzed available data trying to identify the better treatment strategy and to suggest potential therapeutic algorithms distinguishing P-NETs from gastrointestinal NETs (GI-NETs). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Synchronous neuroendocrine tumors in both the pancreas and ileum: A case report.

    Science.gov (United States)

    Tsunenari, Takazumi; Aosasa, Suefumi; Ogata, Sho; Hoshikawa, Mayumi; Nishikawa, Makoto; Noro, Takuji; Shinto, Eiji; Tsujimoto, Hironori; Ueno, Hideki; Hamabe, Fumiko; Shinmoto, Hiroshi; Hase, Kazuo; Yamamoto, Junji

    2016-01-01

    Although it is well-known that in multiple endocrine neoplasia type 1 (MEN 1) disease, multiple endocrine lesions frequently occur, synchronous or metachronous neuroendocrine tumors (NETs) in non-MEN 1 patients are extremely rare. An asymptomatic 72-year-old woman with an ileal NET was referred to our hospital. Abdominal computed tomography revealed another circular tumor within the pancreatic head. She was classified as a non-MEN 1 patient. An operative procedure was performed with a preoperative diagnosis of synchronous NET, which was confirmed by pathological examination. Both morphologic and immunophenotypic findings were different between in the ileum and pancreas. Therefore, it was reasonable to consider that both tumors were primary tumors. The synchronous occurrence of these tumors is unusual, and it may be considered as a chance occurrence. We here report the first case of synchronous pancreatic NET and ileal NET in a non-MEN 1 patient. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Somatic Mutations and Genetic Heterogeneity at the CDKN1B Locus in Small Intestinal Neuroendocrine Tumors.

    Science.gov (United States)

    Crona, Joakim; Gustavsson, Tobias; Norlén, Olov; Edfeldt, Katarina; Åkerström, Tobias; Westin, Gunnar; Hellman, Per; Björklund, Peyman; Stålberg, Peter

    2015-12-01

    Until recently, the genetic landscape of small intestinal neuroendocrine tumors (SI-NETs) was limited to recurrent copy number alterations, most commonly a loss on chromosome 18. Intertumor heterogeneity with nonconcordant genotype in paired primary and metastatic lesions also is described, further contributing to the difficulty of unraveling the genetic enigma of SI-NETs. A recent study analyzing 55 SI-NET exomes nominated CDKN1B (p27) as a haploinsufficient tumor suppressor gene. This study aimed to determine the frequency of CDKN1B inactivation and to investigate genotype-phenotype correlations. It investigated 362 tumors from 200 patients. All samples were resequenced for mutations in CDKN1B using automated Sanger sequencing. The expression of p27 was investigated in 12 CDKN1B mutant and nine wild type tumors. Some 8.5 % (17/200) of patients had tumors with pathogenic mutations in CDKN1B including 13 insertion deletions, four nonsense variants, and one stop-loss variant. All variants with available nontumoral DNA were classified as somatic. Inter- and intratumor heterogeneity at the CDKN1B locus was detected respectively in six of ten and two of ten patients. Patients with CDKN1B mutated tumors had both heterogeneous disease presentation and diverse prognosis. Expression of the p27 protein did not correlate with CDKN1B mutation status, and no differences in the clinical characteristics between CDKN1B mutated and CDKN1B wild type tumor carriers were found. This study corroborates the finding of CDKN1B as a potential haplo-insufficient tumor suppressor gene characterized by inter- and intratumor heterogeneity in SI-NETs.

  2. Functional malignant cell heterogeneity in pancreatic neuroendocrine tumors revealed by targeting of PDGF-DD.

    Science.gov (United States)

    Cortez, Eliane; Gladh, Hanna; Braun, Sebastian; Bocci, Matteo; Cordero, Eugenia; Björkström, Niklas K; Miyazaki, Hideki; Michael, Iacovos P; Eriksson, Ulf; Folestad, Erika; Pietras, Kristian

    2016-02-16

    Intratumoral heterogeneity is an inherent feature of most human cancers and has profound implications for cancer therapy. As a result, there is an emergent need to explore previously unmapped mechanisms regulating distinct subpopulations of tumor cells and to understand their contribution to tumor progression and treatment response. Aberrant platelet-derived growth factor receptor beta (PDGFRβ) signaling in cancer has motivated the development of several antagonists currently in clinical use, including imatinib, sunitinib, and sorafenib. The discovery of a novel ligand for PDGFRβ, platelet-derived growth factor (PDGF)-DD, opened the possibility of a previously unidentified signaling pathway involved in tumor development. However, the precise function of PDGF-DD in tumor growth and invasion remains elusive. Here, making use of a newly generated Pdgfd knockout mouse, we reveal a functionally important malignant cell heterogeneity modulated by PDGF-DD signaling in pancreatic neuroendocrine tumors (PanNET). Our analyses demonstrate that tumor growth was delayed in the absence of signaling by PDGF-DD. Surprisingly, ablation of PDGF-DD did not affect the vasculature or stroma of PanNET; instead, we found that PDGF-DD stimulated bulk tumor cell proliferation by induction of paracrine mitogenic signaling between heterogeneous malignant cell clones, some of which expressed PDGFRβ. The presence of a subclonal population of tumor cells characterized by PDGFRβ expression was further validated in a cohort of human PanNET. In conclusion, we demonstrate a previously unrecognized heterogeneity in PanNET characterized by signaling through the PDGF-DD/PDGFRβ axis.

  3. Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman

    Directory of Open Access Journals (Sweden)

    Elham S. Al-Risi

    2017-09-01

    Full Text Available Objectives: To evaluate the significance of serum chromogranin A (CgA status in patients with and without different neuroendocrine tumors (NETs by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. Methods: We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014. During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11–86 years and mean±standard deviation (SD 44.0±18.0 years, were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. Results: Of the 302 CgA tests reviewed, 197 (65.2% were within the quoted normal range; however, 105 (34.8% had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5% had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3% patients with CgA > 22 IU/L (83.0±116.0 IU/L who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus. Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L. The overall clinical sensitivity of CgA in the

  4. Chromogranin A as a Biochemical Marker for Neuroendocrine Tumors: A Single Center Experience at Royal Hospital, Oman.

    Science.gov (United States)

    Al-Risi, Elham S; Al-Essry, Fatma S; Mula-Abed, Waad-Allah S

    2017-09-01

    To evaluate the significance of serum chromogranin A (CgA) status in patients with and without different neuroendocrine tumors (NETs) by conducting a retrospective assessment of the diagnostic utility and limitations of CgA as a biomarker for NETs in a tertiary care hospital in Oman. We conducted a retrospective analysis of CgA requests referred to the Clinical Biochemistry Laboratory, Royal Hospital, Oman over a 24-month period (April 2012 to March 2014). During this time, 302 CgA tests for 270 patients (119 males and 151 females; age range 11-86 years and mean±standard deviation (SD) 44.0±18.0 years), were requested. Of these CgA tests, 245 tests were performed for 245 patients investigated for the diagnosis of NETs, and 57 CgA tests were performed for 25 patients with diagnosed NETs who were undergoing follow-up. Serum CgA levels were analyzed using the enzyme-linked immunosorbent assay based on a cut-off value of 22 IU/L. Of the 302 CgA tests reviewed, 197 (65.2%) were within the quoted normal range; however, 105 (34.8%) had CgA > 22 IU/L. Of the 245 patients with first-line CgA, 38 patients (15.5%) had NET that included carcinoid, pheochromocytoma, pancreatic NET, adrenal adenoma, prostatic adenocarcinoma, gastrointestinal NET, medullary thyroid carcinoma, Schwannoma, lung small cell carcinoma, parathyroid adenoma, and pituitary macroadenoma. The mean±SD of CgA in these patients with NETs was 205.0±172.0 IU/L. Meanwhile, there were 45 (18.3%) patients with CgA > 22 IU/L (83.0±116.0 IU/L) who did not have NETs. The conditions/diseases included: essential hypertension, chronic kidney disease, heart failure, peptic ulcer, chronic diarrhea, use of proton pump inhibitors, and other chronic diseases (hypothyroidism, asthma, diabetes mellitus). Of the 25 patients with known NET who were followed-up, there were 57 CgA results (29 with CgA ≤ 22 IU/L and 28 with CgA > 22 IU/L). The overall clinical sensitivity of CgA in the diagnosis of NETs was 84.2%, overall

  5. Sister Mary Joseph Nodules on 99mTc HYNIC-TOC scintigraphy in patients with neuroendocrine tumors.

    Science.gov (United States)

    Jing, Hongli; Zhang, Yingqiang; Li, Fang

    2015-02-01

    A Sister Mary Joseph nodule represents an umbilical metastasis, which is more commonly caused by a primary malignancy in gastrointestinal tract or from reproductive system. We report Sister Mary Joseph nodules caused by neuroendocrine tumor and revealed on Tc HYNIC-TOC scintigraphy.

  6. Web-based information and support for patients with a newly diagnosed neuroendocrine tumor : A feasibility study

    NARCIS (Netherlands)

    Bouma, Grietje; de Hosson, Lotte D; van Woerkom, Claudia E; van Essen, Hennie; de Bock, Geertruida H; Admiraal, Jolien M; Reyners, Anna K L; Walenkamp, Annemiek M E

    Purpose: Patients with a neuroendocrine tumor (NET) frequently experience physical and psychosocial complaints. Novel strategies to provide information to optimize supportive care in these patients are of interest. The aim of this study was to examine whether the use of a web-based system consisting

  7. Different expression of EZH2, BMI1 and Ki67 in low and high grade neuroendocrine tumors of the lung

    DEFF Research Database (Denmark)

    Bondgaard, Anna-Louise Reinert Ørsum; Poulsen, Thomas Tuxen; Poulsen, Hans Skovgaard

    2012-01-01

    Enhancer of Zeste Homolog 2 (EZH2) and B lymphoma Mo-MLV Insertion region 1 polycomb ring finger (BMI1) are involved in malignant transformation of many human carcinomas. Still, in neuroendocrine tumors of the lung (NELT) their expression pattern is largely unknown. This study evaluated...

  8. Neuroendocrine Carcinoma: Immunohistochemistry Department Of Cancer Institute 1996 - 2000

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    Yazdani F

    2003-07-01

    Full Text Available Dispersed neuroendocrine system (D.N.S consists of a wide variety of cells that are present in the central and peripheral nervous system and in many classic endocrine organs and different tissues such as respiratory and gastrointestinal tracts, skin, prostate, breast and also their neoplasm show neuroendocrine differentiation by electron microscopy, immunohistochemistry or biochemical techniques:"nMaterials and Methods: The present study has been carried out by case-series method in order to evaluating the characteristics of all types of neuroendocrine carcinoma: different anatomical locations during 5 years period in immunohistochemistry department of cancer institute."nResults: The diagnosis of 109 cases of neuroendocrine carcinoma consisting of neuroendocrine carcinoma, small cell carcinoma, medullary carcinoma of thyroid, carcinoid tumor and merkel cell carcinoma are confirmed that among them the most common diagnosis was related to neuroendocrine carcinoma (50.5 percent. The most prevalent age group was 40-49 years and male to female distribution were 56 percent and 44 percent respectively. Anatomical distribution of tumor show that about 30 percent of cases were metastatic carcinoma, 30 percent in thyroid, respiratory tract and head and neck region and remainder in a variety of tissues. In over 50 percent of cases one of endocrinoid patterns as trabecular, organoid or mixed of them were seen."nConclusion: Immunohistochemically N.S.E (Neuron Specific Enolase show high sensitivity with 96 percent positive reaction and more specific endocrine markers as chromogranin A in 80 percent and synaptophysin only in 24 percent because of lesser application of the latter. Also epithelial markers such as cytokeratin and E.M.A."n(Epithelial Membrane Antigen were positive in 69 percent and 74 percent respectively. Mean survival rate of all neuroendocrine carcinoma reached to 4.8 years with lowest survival of 4.3 years among small cell carcinoma and

  9. GEP-NETS update: a review on surgery of gastro-entero-pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Partelli, Stefano; Maurizi, Angela; Tamburrino, Domenico; Baldoni, Andrea; Polenta, Vanessa; Crippa, Stefano; Falconi, Massimo

    2014-10-01

    The incidence of neuroendocrine tumors (NETs) has increased in the last decades. Surgical treatment encompasses a panel of approaches ranging from conservative procedures to extended surgical resection. Tumor size and localization usually represent the main drivers in the choice of the most appropriate surgical resection. In the presence of small (<2 cm) and asymptomatic nonfunctioning NETs, a conservative treatment is usually recommended. For localized NETs measuring above 2 cm, surgical resection represents the cornerstone in the management of these tumors. As they are relatively biologically indolent, an extended resection is often justified also in the presence of advanced NETs. Surgical options for NET liver metastases range from limited resection up to liver transplantation. Surgical choices for metastatic NETs need to consider the extent of disease, the grade of tumor, and the presence of extra-abdominal disease. Any surgical procedures should always be balanced with the benefit of survival or relieving symptoms and patients' comorbidities. © 2014 European Society of Endocrinology.

  10. GLP1 and glucagon co-secreting pancreatic neuroendocrine tumor presenting as hypoglycemia after gastric bypass

    DEFF Research Database (Denmark)

    Guimarães, Marta; Rodrigues, Pedro; Pereira, Sofia S

    2015-01-01

    Post-prandial hypoglycemia is frequently found after bariatric surgery. Although rare, pancreatic neuroendocrine tumors (pNET), which occasionally are mixed hormone secreting, can lead to atypical clinical manifestations, including reactive hypoglycemia. Two years after gastric bypass surgery...... to the post-bariatric surgery hypoglycemia patient. LEARNING POINTS: pNETs can be multihormonal-secreting, leading to atypical clinical manifestations.Reactive hypoglycemic episodes are frequent after gastric bypass.pNETs should be considered in the differential diagnosis of hypoglycemia after bariatric...... (471 pmol/g), insulin (139 pmol/g) and somatostatin (23 pmol/g). This is the first report of a GLP1 and glucagon co-secreting pNET presenting as hypoglycemia after gastric bypass surgery. Although pNET are rare, they should be considered in the differential diagnosis of the clinical approach...

  11. Pitfalls in the diagnosis of carcinoid syndrome

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    Dorota Kaczmarska-Turek

    2016-06-01

    Full Text Available Background . Carcinoid syndrome (CS is a rare syndrome, most commonly associated with neuroendocrine neoplasms (NEN s of the small intestine. Carcinoid syndrome consists of diarrhea, vomiting, abdominal pain, cutaneous flushing, teleangiectasias, bronchoconstriction and increased perspiration. Diagnosis of carcinoid syndrome remains a challenge and it is often delayed. Objectives . The aim of this study was to characterize patients with CS and define the most sensitive, primary diagnostic tools for CS . Material and methods. 26 consecutive patients admitted to the Department because of carcinoid-like symptoms. Diagnosis of CS was based on clinical findings and laboratory data (levels of 5-hydroxyindoloacetic acid. Diagnosis of NEN was based on laboratory findings, imaging studies (US , CT , Gallium-68-DOTA TATE PET -CT and histopathological analysis. CS due to NEN was diagnosed in 16 subjects (NEN –CS . Results . The most common symptoms in non-NEN were increased perspiration, flushes and diarrhea. CgA was elevated (40%; n = 4 in this group. However, elevated levels of 5-HIAA and liver lesions were not presented. In the NEN –CS symptoms were reported more often: flush (93.7%; n = 15, diarrhea (87.5%; n = 14, abdominal pain and teleangiectasis (81.2%; n = 13. Elevated CgA and 5-HIAA were noted in 87.5% (n = 14 and 81.2% (n = 13 respectively. US and CT revealed liver metastases in all patients. The mean duration of symptoms before diagnosis was 28.6 months. Conclusions . The combination of several symptoms of carcinoid syndrome and liver lesion in easily available abdominal imaging (US and/or CT should prompt physicians to quick referral to centres specialized in the diagnosis and treatment of NEN.

  12. Twenty years of gastroenteropancreatic neuroendocrine tumors: is reclassification worthwhile and feasible?

    Science.gov (United States)

    Grillo, Federica; Albertelli, Manuela; Annunziata, Francesca; Boschetti, Mara; Caff, Andrea; Pigozzi, Simona; Ferone, Diego; Mastracci, Luca

    2016-07-01

    Gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) are rare neoplasms with heterogeneous clinical behavior and potential long-term survival. In 2006/2007, the European Neuroendocrine Tumors Society introduced an important parameter, grade (based on mitoses and Ki-67 proliferation rate), which became part of the latest 2010-WHO classification. Since this is an important tool in the choice of therapeutic algorithm of patients with NETs, our aim was to audit whether retrospective reclassification is possible and feasible and correlate pathological findings with survival. From the histopathology archive, 338 GEP-NETs (1994-2014) were identified, of which 250 were diagnosed pre-2010 and 80 of these have needed, up till now, classification (morphology and grade-mitotic count/Ki-67). Morphology was well differentiated (WD) in 74 cases while only 6 cases were poorly differentiated (PD). Grade was reclassified: G1-45 cases (56 %); G2-28 cases (35 %); G3-7 cases (9 %). Overall survival (OS) in WD NETs was strikingly better compared to PD neoplasms. Differences in OS between grade were statistically significant (p < 0.0001) and, in particular, grade identified a subgroup of patients with WD lesions but with less favorable clinical behavior (OS at 5 years: G1-89 %; G2-48 %; G3-0 %; G1 vs G2 p = 0.03). Feasibility analysis quantified time for reclassification to be between 45 and 64 min/case. Our series confirms the importance of grade in prognostic stratification and underlines that reclassification is feasible, and may prove worthwhile in patient management, especially in view of the potential long survival of patients with NETs and risk of use of inappropriate therapies.

  13. The identification of gut neuroendocrine tumor disease by multiple synchronous transcript analysis in blood.

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    Irvin M Modlin

    Full Text Available Gastroenteropancreatic (GEP neuroendocrine neoplasms (NENs are increasing in both incidence and prevalence. A delay in correct diagnosis is common for these lesions. This reflects the absence of specific blood biomarkers to detect NENs. Measurement of the neuroendocrine secretory peptide Chromogranin A (CgA is used, but is a single value, is non-specific and assay data are highly variable. To facilitate tumor detection, we developed a multi-transcript molecular signature for PCR-based blood analysis. NEN transcripts were identified by computational analysis of 3 microarray datasets: NEN tissue (n = 15, NEN peripheral blood (n = 7, and adenocarcinoma (n = 363 tumors. The candidate gene signature was examined in 130 blood samples (NENs: n = 63 and validated in two independent sets (Set 1 [n = 115, NENs: n = 72]; Set 2 [n = 120, NENs: n = 58]. Comparison with CgA (ELISA was undertaken in 176 samples (NENs: n = 81. 51 significantly elevated transcript markers were identified. Gene-based classifiers detected NENs in independent sets with high sensitivity (85-98%, specificity (93-97%, PPV (95-96% and NPV (87-98%. The AUC for the NEN gene-based classifiers was 0.95-0.98 compared to 0.64 for CgA (Z-statistic 6.97-11.42, p90%, identifies pancreatic and gastrointestinal NENs with similar efficacy, and confirms GEP-NENs when CgA levels are low. The panel is significantly more accurate than the CgA assay. This reflects its utility to identify multiple diverse biological components of NENs. Application of this sensitive and specific PCR-based blood test to NENs will allow accurate detection of disease, and potentially define disease progress enabling monitoring of treatment efficacy.

  14. {sup 68}Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Pettinato, C.; Sarnelli, A.; Di Donna, M.; Civollani, S.; Marengo, M.; Bergamini, C. [A.O. S. Orsola-Malpighi, Health Physics, Bologna (Italy); Nanni, C.; Montini, G.; Di Pierro, D. [A.O. S. Orsola-Malpighi, Nuclear Medicine, Bologna (Italy); Ferrari, M. [European Institute of Oncology, Health Physics, Milano (Italy)

    2008-01-15

    The aim of this work was the evaluation of biodistribution and radiation dosimetry of {sup 68}Ga-DOTANOC in patients affected by neuroendocrine tumors. We enrolled nine patients (six male and three female) affected by different types of neuroendocrine tumors (NETs). Each patient underwent four whole body positron emission tomography (PET) scans, respectively, at 5, 20, 60, and 120 min after the intravenous injection of about 185 MBq of {sup 68}Ga-DOTANOC. Blood and urine samples were taken at different time points post injection: respectively, at about 5, 18, 40, 60, and 120 min for blood and every 40-50 min from injection time up to 4 h for urine. The organs involved in the dosimetric evaluations were liver, heart, spleen, kidneys, lungs, pituitary gland, and urinary bladder. Dosimetric evaluations were done using the OLINDA/EXM 1.0 software. A physiological uptake of {sup 68}Ga-DOTANOC was seen in all patients in the pituitary gland, the spleen, the liver, and the urinary tract (kidneys and urinary bladder). Organs with the highest absorbed doses were kidneys (9.0 E-02{+-}3.2 E-02 mSv/Mq). The mean effective dose equivalent (EDE) was 2.5 E-02{+-}4.6 E-03 mSv/MBq. The excretion of the compound was principally via urine, giving dose to the kidney and the urinary bladder wall. As SSTR2 is the most frequently expressed somatostatin receptor and {sup 68}Ga-DOTANOC has high affinity to it, this compound might play an important role in PET oncology in the future. The dosimetric evaluation carried out by our team demonstrated that {sup 68}Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds. (orig.)

  15. Association between ABO blood types and sporadic pancreatic neuroendocrine tumors in the Chinese Han population.

    Science.gov (United States)

    Ben, Qiwen; Liu, Jun; Wang, Weiyi; Guo, Fang; Yao, Weiyan; Zhong, Jie; Yuan, Yaozong

    2017-08-15

    Although the relationship between non-O blood types and the risk of exocrine pancreatic cancer has been demonstrated, the association between ABO blood types and sporadic pancreatic neuroendocrine tumor (PNET) has not been reported thus far. This hospital-based, case-control study included 387 patients with PNET and 542 age- and sex-matched controls. Unconditional multivariable logistic regression analysis was performed to estimate the adjusted odds ratios (AORs) and 95% confidence intervals (CIs). The relationship between ABO blood types and clinicopathologic features was also analyzed. After adjusting for age, sex, smoking status, alcohol drinking, and first-degree family history of any cancer, the AORs (95% CI) of functional PNET were 0.87 (0.59-1.28) for blood type A, 0.86 (0.58-1.28) for blood type B, and 0.71 (0.39-1.26) for blood type AB compared with subjects with blood type O. A similar ABO blood-type distribution was observed among cases with non-functional PNETs compared with controls. On comparing blood type B with non-B blood type, cases with non-functional PNETs had marginally higher rates of lymph node invasion (P = 0.047), distant metastasis (P = 0.044), and advanced European Neuroendocrine Tumor Society Stage (P = 0.040). There is no association between the ABO blood group and the development of functional and non-functional PNETs. The ABO blood types are not associated with the clinicopathologic features in patients with functional and non-functional PNETs.

  16. Succinate dehydrogenase (SDH)-deficient pancreatic neuroendocrine tumor expands the SDH-related tumor spectrum

    NARCIS (Netherlands)

    Niemeijer, Nicolasine D.; Papathomas, Thomas G.; Korpershoek, Esther; De Krijger, Ronald R.; Oudijk, Lindsey; Morreau, Hans; Bayley, Jean Pierre; Hes, Frederik J.; Jansen, Jeroen C.; Dinjens, Winand N M; Corssmit, Eleonora P M

    2015-01-01

    Context: Mutations in genes encoding the subunits of succinate dehydrogenase (SDH) can lead to pheochromocytoma/paraganglioma formation. However, SDH mutations have also been linked to nonparaganglionic tumors. Objective: The objective was to investigate which nonparaganglionic tumors belong to the

  17. Neuroendocrine tumors of the large intestine: clinicopathological features and predictive factors of lymph node metastasis

    Directory of Open Access Journals (Sweden)

    Motohiro Kojima

    2016-07-01

    Full Text Available A new histological classification of neuroendocrine tumors (NET was established in WHO 2010. ENET and NCCN proposed treatment algorithms for colorectal NET. Retrospective study of NET of the large intestine (colorectal and appendiceal NET was performed among institutions allied with the Japanese Society for Cancer of the Colon and Rectum, and 760 neuroendocrine tumors from 2001 to 2011 were re-assessed using WHO 2010 criteria to elucidate the clinicopathological features of NET in the large intestine. Next, the clinicopathological relationship with lymph node metastasis was analyzed to predict lymph node metastasis in locally resected rectal NET. The primary site was rectum in 718/760 cases (94.5%, colon in 30/760 cases (3.9%, and appendix in 12/760 cases (1.6%. Patients were predominantly men (61.6% with a mean age of 58.7 years old. Tumor size was less than 10 mm in 65.4% of cases. Proportions of NET G1, G2, G3, and MANEC were 88.4%, 6.3%, 3.9%, and 1.3%, respectively. Of the 760 tumors, 468 were locally resected, and 292 were surgically resected with lymph node dissection. Rectal NET showed a higher proportion of NET G1, and colonic and appendiceal NET was more commonly G3 and MANEC. Of the 292 surgically resected cases, 233 NET G1 and G2 located in the rectum were used for the prediction of lymph node metastasis. Lymphatic and blood vessel invasion were independent predictive factors of lymph node metastasis. NET G2 cases showed more frequent lymph node metastasis than that seen in NET G1 cases, but this was not an independent predictor of lymph node metastasis. Of the 98 surgically resected cases less than 10 mm in size, we found 9 cases with lymph node metastasis (9.2%. All cases were NET G1, and 8 of 9 cases were positive either for lymphatic invasion or blood vessel invasion. Using the WHO classification, we found NET in the large intestine showed a tumor-site–dependent variety of histological and clinicopathological features. Risk of

  18. Epithelial-Mesenchymal Transition Is a Critical Step in Tumorgenesis of Pancreatic Neuroendocrine Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Fendrich, Volker, E-mail: fendrich@med.uni-marburg.de; Maschuw, Katja; Waldmann, Jens [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Buchholz, Malte [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Rehm, Johannes [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Gress, Thomas M. [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany); Bartsch, Detlef K. [Department of Surgery, Philipps University Marburg, Baldingerstraße, Marburg D-35043 (Germany); König, Alexander [Department of Gastroenterology and Endocrinology, Philipps-University Marburg, Baldingerstraße, Marburg D-35043 (Germany)

    2012-03-08

    The transcription factors Snail, Slug and Twist repress E-cadherin and induce epithelial-mesenchymal transition (EMT), a process exploited by invasive cancer cells. In this study, we evaluated the role of EMT in the tumorgenesis of neuroendocrine tumors of the pancreas (PNETs) in vitro, in vivo and human tumor specimen. Expression of EMT markers was analyzed using immunohistochemistry and real-time PCR. For in vitro studies, BON-1 cells were analyzed regarding expression of EMT markers before and after transfection with siRNA against Slug or Snail, and cell aggregation assays were performed. To asses in vivo effects, Rip1Tag2 mice were treated with vehicle or the snail-inhibitor polythlylenglykol from week 5-10 of age. The resected pancreata were evaluated by weight, tumor cell proliferation and apoptosis. Snail and Twist was expressed in 61 % and 64% of PNETs. This was associated with loss of E-cadherin. RT-PCR revealed conservation of the EMT markers Slug and Snail in BON-1 cells. Transfection with siRNA against Slug was associated with upregulation of E-cadherin, enhanced cell-cell adhesion and inhibition of cell proliferation. Snail-inhibition in vivo by PEG was associated with increased apoptosis, decreased tumor cell proliferation and dramatic reduced tumor volume in Rip1Tag2 mice. The presented data show that EMT plays a key role in tumorgenesis of PNETs. The activation of Snail in a considerable subset of human PNETs and the successful effect of Snail inhibition by PEG in islet cell tumors of transgenic mice provides first evidence of Snail as a drug target in PNETs.

  19. NEUROECTODERMAL TUMORS OF THE PERIPHERAL AND THE CENTRAL-NERVOUS-SYSTEM SHARE NEUROENDOCRINE N-CAM-RELATED ANTIGENS WITH SMALL-CELL LUNG CARCINOMAS

    NARCIS (Netherlands)

    MOLENAAR, WM; DELEIJ, L; TROJANOWSKI, JQ

    1991-01-01

    The current study describes the presence of neuroendocrine antigens of peripheral and central neural tumors using eight monoclonal antibodies raised to small cell lung carcinoma (SCLC), which recognize "neural/neuroendocrine" or "neural" antigens, as defined by their reaction pattern in normal

  20. Pancreatic splenosis mimicking neuroendocrine tumors: microhistological diagnosis by endoscopic ultrasound guided fine needle aspiration.

    Science.gov (United States)

    Ardengh, José Celso; Lopes, César Vivian; Kemp, Rafael; Lima-Filho, Eder Rios; Venco, Filadelfo; Santos, José Sebastião dos

    2013-01-01

    Pancreatic splenosis is a benign condition which can mimic a pancreatic neoplasm. To describe the role of the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic nodules suspicious for pancreatic splenosis. From 1997 to 2011, patients with pancreatic solid tumors suspicious for splenosis by computed tomography and/or magnetic resonance imaging were referred to EUS-FNA. Those cases with pancreatic splenosis confirmed by EUS-FNA or surgery were included. Endosonographic findings and clinicopathologic features were also analysed. A total of 2,060 patients with pancreatic solid tumors underwent EUS-FNA. Fourteen (0.6%) cases with pancreatic splenosis were found. After applying exclusion criteria, 11 patients were selected. Most patients were male (7), young (mean age: 42 years) and asymptomatic (8). Endoscopic ultrasound imaging alone suspected pancreatic splenosis in 6 cases, and neuroendocrine tumors in 5 cases. Pancreatic splenosis was found most commonly in the tail, was round, hypoechoic, with homogeneous pattern, regular borders, and with scintigraphy negative for somatostatin receptors. The average diameter of these nodules identified by endoscopic ultrasound was 2.15 cm. Microhistology obtained by EUS-FNA confirmed the diagnosis in 9/10 patients. Pancreatic splenosis can be diagnosed by EUS-FNA. Microhistology prevents unnecessary surgeries, and reassures asymptomatic patients with hypoechoic, homogeneous, and well circumscribed pancreatic nodules.

  1. PANCREATIC SPLENOSIS MIMICKING NEUROENDOCRINE TUMORS: microhistological diagnosis by endoscopic ultrasound guided fine needle aspiration

    Directory of Open Access Journals (Sweden)

    Jose Celso ARDENGH

    2013-03-01

    Full Text Available Context Pancreatic splenosis is a benign condition which can mimic a pancreatic neoplasm. Objective To describe the role of the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA of pancreatic nodules suspicious for pancreatic splenosis. Method From 1997 to 2011, patients with pancreatic solid tumors suspicious for splenosis by computed tomography and/or magnetic resonance imaging were referred to EUS-FNA. Those cases with pancreatic splenosis confirmed by EUS-FNA or surgery were included. Endosonographic findings and clinicopathologic features were also analysed. Results A total of 2,060 patients with pancreatic solid tumors underwent EUS-FNA. Fourteen (0.6% cases with pancreatic splenosis were found. After applying exclusion criteria, 11 patients were selected. Most patients were male (7, young (mean age: 42 years and asymptomatic (8. Endoscopic ultrasound imaging alone suspected pancreatic splenosis in 6 cases, and neuroendocrine tumors in 5 cases. Pancreatic splenosis was found most commonly in the tail, was round, hypoechoic, with homogeneous pattern, regular borders, and with scintigraphy negative for somatostatin receptors. The average diameter of these nodules identified by endoscopic ultrasound was 2.15 cm. Microhistology obtained by EUS-FNA confirmed the diagnosis in 9/10 patients. Conclusion Pancreatic splenosis can be diagnosed by EUS-FNA. Microhistology prevents unnecessary surgeries, and reassures asymptomatic patients with hypoechoic, homogeneous, and well circumscribed pancreatic nodules.

  2. Neuroendocrine Tumors in the Stomach, Duodenum, and Pancreas Accompanied by Novel MEN1 Gene Mutation.

    Science.gov (United States)

    Yang, Min A; Lee, Woong Ki; Shin, Hong Shik; Park, Sung Hyun; Kim, Byung Sun; Kim, Ji Woong; Cho, Jin Woong; Yun, So Hee

    2017-03-25

    Multiple endocrine neoplasia type 1 (MEN1) syndrome is a relatively rare disease, characterized by the occurrence of multiple endocrine tumors in the parathyroid and pituitary glands as well as the pancreas. Here, we report a case of MEN1 with neuroendocrine tumors (NETs) in the stomach, duodenum, and pancreas. A 53-year-old man visited our hospital to manage gastric NET. Five years prior to his visit, he had undergone surgery for incidental meningioma. His brother had pancreatic nodules and a history of surgery for adrenal adenoma. His brother's daughter also had pancreatic nodules, but had not undergone surgery. The lesion was treated by endoscopic submucosal dissection and diagnosed as a grade 1 NET. Another small NET was detected in the second duodenal portion, resected by endoscopic submucosal dissection, which was also diagnosed as a grade 1 NET. During evaluation, three nodules were detected in the pancreas, and no evidence of pituitary, parathyroid tumors, or metastasis was observed. After surgery, the pancreatic lesions were diagnosed as NETs, with the same immunohistochemical patterns as those of the stomach and duodenum. Genetic testing was performed, and a heterozygous mutation was detected in the MEN1 gene, which is located on 11q13.

  3. Clinical and functional implication of the components of somatostatin system in gastroenteropancreatic neuroendocrine tumors.

    Science.gov (United States)

    Herrera-Martínez, Aura D; Gahete, Manuel D; Pedraza-Arevalo, Sergio; Sánchez-Sánchez, Rafael; Ortega-Salas, Rosa; Serrano-Blanch, Raquel; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

    2018-02-01

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) comprise a heterogeneous group of malignancies often presenting with metastasis at diagnosis and whose clinical outcome is difficult to predict. Somatostatin (SST) analogs (SSAs) provide a valuable pharmacological tool to palliate hormonal symptoms, and control progression in some NETs. However, many patients do not respond to SSAs or develop resistance, and there are many uncertainties regarding pathophysiology of SST and its receptors (sst1-sst5) in GEP-NETs. The expression of SST system components in GEP-NETs was determined, compared with that of non-tumor adjacent and normal tissues and correlated with clinical and histological characteristics. Specifically, 58 patients with GEP-NETs and 14 normal samples were included. Cell viability in NET cell lines was determined in response to specific SSAs. Normal samples and non-tumor adjacent tissues presented a similar expression profile, with appreciable expression of sst2 and sst3, and a lower expression of the other receptors. In contrast, cortistatin, sst1, sst4, and sst5 were overexpressed in tumors, while sst3 and sst4 seemed overexpressed in less differentiated tumors. Some SST system components were related to vascular/nerve invasion and metastasis. In vitro, sst1 and sst3 agonists reduced viability in BON-1 cells, while they, similar to octreotide and pasireotide, increased viability in QGP-1 cells. These results provide novel information on SST system pathophysiology in GEP-NETs, including relevant associations with clinical-histological parameters, which might help to better understand the intrinsic heterogeneity of NETs and to identify novel biomarkers and/or targets with potential prognostic and/or therapeutic value for GEP-NETs patients.

  4. Characteristic imaging features of carcinoid tumors of the small bowel in MR enteroclysis; Morphologisches Erscheinungsbild neuroendokriner Tumoren des Duenndarms im MR-Enteroklysma

    Energy Technology Data Exchange (ETDEWEB)

    Schmid-Tannwald, C.; Zech, C.J.; Panteleon, A.; Sommer, W.H.; Herrmann, K.A. [Klinikum Grosshadern der Ludwig-Maxilimians-Universitaet Muenchen, Institut fuer Klinische Radiologie, Muenchen (Germany); Auernhammer, C. [Klinikum Grosshadern der Ludwig-Maximilians-Universitaet Muenchen, Medizinische Klinik II, Muenchen (Germany)

    2009-03-15

    To determine the value of MR enteroclysis (MRE) in the localization and characterization of primary carcinoid tumors of the small bowel and to describe typical imaging features. Twenty patients with suspicion of primary small bowel carcinoid tumors (pCT) were recruited to undergo MRE following nasojejunal intubation and small bowel filling with 2.5 l of 0.5% methylcellulose solution under MR fluoroscopic guidance. MRE was performed on a 1.5 T MR scanner including T2w SSFSE, SSFP and contrast enhanced T1w GRE sequences with fat saturation. Fifteen patients, who subsequently had surgery for resection of their pCT, were retrospectively included in the study. All MRE were analyzed as for the presence, location, number, size, multiplicity and morphologic appearance of the pCT by two board certified radiologists in consensus. The conspicuity of the tumors was rated for each sequence type separately, according to a 4-point rating scale. Signal intensity measurements were performed in tumor and muscle. The presence of desmoplastic reaction, vascular involvement and lymph node metastases was also analyzed. pCT were correctly identified and localized in 14/15 patients. Due to their hyperenhancement tumors was best detected on contrast-enhanced T1w fat saturated GRE sequences. SSFSE was clearly inferior with the tumors being either hyperintense or isointense to muscle. pCT appeared as nodular intraluminal masses in 40% of the cases, as focal wall thickening in 33.3% and in 20% with both. Mean size was 25 (7-46 mm) with a tendency to smaller size for ileal tumors. MRE failed to depict superficial micronodular peritoneal spread in one patient. Desmoplastic reaction was observed in 73.3% of the cases with mesenteric masses exhibiting lower signal than the pCT due to fibrotic changes. MRE is a valuable method for the detection and localization of primary carcinoid tumors, provided that appropriate bowel distension is achieved. Various characteristic morphologic features could be

  5. Chromogranin A as Serum Marker for Gastroenteropancreatic Neuroendocrine Tumors: A Single Center Experience and Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Nölting, Svenja; Kuttner, Axel [Department of Internal Medicine II, Campus Grosshadern, University-Hospital of the Ludwig-Maximilians-University of Munich, Munich 81377 (Germany); Lauseker, Michael [Institute of Medical Informatics, Biometry and Epidemiology, University of Munich, Munich 81377 (Germany); Vogeser, Michael [Department of Clinical Chemistry, Campus Grosshadern, University-Hospital of the Ludwig-Maximilian-University of Munich, Munich 81377 (Germany); Haug, Alexander [Clinic of Nuclear Medicine, Campus Grosshadern, University-Hospital of the Ludwig-Maximilian-University of Munich, Munich 81377 (Germany); Herrmann, Karin A. [Institute of Radiology, Campus Grosshadern, University-Hospital of the Ludwig-Maximilian-University of Munich, Munich 81377 (Germany); Hoffmann, Johannes N. [Department of Surgery, Campus Grosshadern, University-Hospital of the Ludwig-Maximilians-University of Munich, Munich 81377 (Germany); Spitzweg, Christine; Göke, Burkhard; Auernhammer, Christoph J., E-mail: christoph.auernhammer@med.uni-muenchen.de [Department of Internal Medicine II, Campus Grosshadern, University-Hospital of the Ludwig-Maximilians-University of Munich, Munich 81377 (Germany)

    2012-02-15

    The aim of this study was to assess the clinical sensitivities of the tumor markers chromogranin A (CgA), urinary 5-hydroxyindoleacetic acid (5-HIAA) and alkaline phosphatase (AP) in neuroendocrine tumors (NETs) of the GastroEnteroPancreatic-(GEP-) system depending on tumor primary location and metastatic spread. In a retrospective single-center series, sensitivities were evaluated in serum samples from 110 patients with midgut (n = 62) and pancreatic (n = 48) NETs. CgA levels were analyzed by a commercially-available immunoradiometric assay (CIS-bio) during routine follow-up in the years 2000–2009. CgA showed a higher sensitivity for midgut (68%) than pancreatic (54%) NETs. A higher CgA sensitivity and significantly higher median CgA values were found in patients with liver metastases than in those without, and in patients with hepatic and additionally extra-hepatic metastases than in those with hepatic and nodal metastases alone, respectively. We found an overall sensitivity for elevated 5HIAA excretion of 69% for midgut NETs and a significant correlation between median CgA and 5-HIAA values. The sensitivity of AP and the correlations of AP/CgA-data-pairs were low in both midgut and pancreatic NETs, although highest for metastatic pancreatic NETs. The sensitivity of CgA measurement depends on the NET primary location and spread of disease. 5-HIAA and CgA showed comparable sensitivity in midgut NETs, while AP does not seem to be useful as a tumor marker in GEP-NETs.

  6. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Barbara Seroczyńska

    2013-10-01

    Full Text Available 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 diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL−1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1–300 ng mL−1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  7. Blood and tissue neuroendocrine tumor gene cluster analysis correlate, define hallmarks and predict disease status.

    Science.gov (United States)

    Kidd, Mark; Drozdov, Ignat; Modlin, Irvin

    2015-08-01

    A multianalyte algorithmic assay (MAAA) identifies circulating neuroendocrine tumor (NET) transcripts (n=51) with a sensitivity/specificity of 98%/97%. We evaluated whether blood measurements correlated with tumor tissue transcript analysis. The latter were segregated into gene clusters (GC) that defined clinical 'hallmarks' of neoplasia. A MAAA/cluster integrated algorithm (CIA) was developed as a predictive activity index to define tumor behavior and outcome. We evaluated three groups. Group 1: publically available NET transcriptome databases (n=15; GeneProfiler). Group 2: prospectively collected tumors and matched blood samples (n=22; qRT-PCR). Group 3: prospective clinical blood samples, n=159: stable disease (SD): n=111 and progressive disease (PD): n=48. Regulatory network analysis, linear modeling, principal component analysis (PCA), and receiver operating characteristic analyses were used to delineate neoplasia 'hallmarks' and assess GC predictive utility. Our results demonstrated: group 1: NET transcriptomes identified (92%) genes elevated. Group 2: 98% genes elevated by qPCR (fold change >2, Pgenes defined nine omic clusters (SSTRome, proliferome, signalome, metabolome, secretome, epigenome, plurome, and apoptome). Group 3: six clusters (SSTRome, proliferome, metabolome, secretome, epigenome, and plurome) differentiated SD from PD (area under the curve (AUC)=0.81). Integration with blood-algorithm amplified the AUC to 0.92±0.02 for differentiating PD and SD. The CIA defined a significantly lower SD score (34.1±2.6%) than in PD (84±2.8%, P92%. Blood transcript measurement predicts NET activity. © 2015 Society for Endocrinology.

  8. Initial impact of a systematic multidisciplinary approach on the management of patients with gastroenteropancreatic neuroendocrine tumor.

    LENUS (Irish Health Repository)

    Tamagno, Gianluca

    2013-10-01

    According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

  9. Identification of candidate serum proteins for classifying well-differentiated small intestinal neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Spyros Darmanis

    Full Text Available BACKGROUND: Patients with well-differentiated small intestine neuroendocrine tumors (WD-SI-NETs are most often diagnosed at a metastatic stage of disease, which reduces possibilities for a curative treatment. Thus new approaches for earlier detection and improved monitoring of the disease are required. MATERIALS AND METHODS: Suspension bead arrays targeting 124 unique proteins with antibodies from the Human Protein Atlas were used to profile biotinylated serum samples. Discoveries from a cohort of 77 individuals were followed up in a cohort of 132 individuals both including healthy controls as well as patients with untreated primary WD-SI-NETs, lymph node metastases and liver metastases. RESULTS: A set of 20 antibodies suggested promising proteins for further verification based on technically verified statistical significance. Proceeding, we assessed the classification performance in an independent cohort of patient serum, achieving, classification accuracy of up to 85% with different subsets of antibodies in respective pairwise group comparisons. The protein profiles of nine targets, namely IGFBP2, IGF1, SHKBP1, ETS1, IL1α, STX2, MAML3, EGR3 and XIAP were verified as significant contributors to tumor classification. CONCLUSIONS: We propose new potential protein biomarker candidates for classifying WD-SI-NETs at different stage of disease. Further evaluation of these proteins in larger sample sets and with alternative approaches is needed in order to further improve our understanding of their functional relation to WD-SI-NETs and their eventual use in diagnostics.

  10. 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, this t...

  11. Colonic carcinoid tumors: a clinicopathologic study of 23 patients from a single institution Tumores carcinóides do cólon: estudo clinicopatológico de 23 doentes de uma única instituição

    Directory of Open Access Journals (Sweden)

    Daniel Reis Waisberg

    2009-12-01

    Full Text Available CONTEXT: Colonic carcinoids, excluding those arising in the appendix, have proved to be extremely rare. Due to their rarity, the characteristics and behavior of this unusual malignancy remain unclear. OBJECTIVE: To review the clinicopathologic features of patients operated on carcinoid tumors of the colon. METHODS: Twenty-three patients (12 males and 11 females were operated on colonic carcinoids. The mean age of the patients was 63.0 ± 12.9 years (42 to 85 years. The clinical and histopathological data of patients who were pathologically diagnosed as having carcinoid tumors and submitted to surgical treatment over a 30-year period (1977-2007 were gathered. Actuarial patient survival was estimated using the Kaplan-Meier method, with carcinoid-specific death as the outcome. RESULTS: The mean time elapsed between onset of symptoms and surgical treatment was 8.3 months (1.5 to 20 months. The most frequent symptoms or signs encountered were abdominal pain followed by anorexia or weight loss, diarrhea, abdominal tenderness, palpable abdominal mass, and rectal bleeding. No carcinoid syndrome was noted. The lesion was located in the cecum in 16 (69.6% patients, in the sigmoid in 3 patients (13.0%, in the ascending colon in 3 patients (13.0%, and in the transverse colon in one patient (4.3%. Twenty-one (91.3% patients were operated on curative intent. Spreading of the disease to the liver and peritoneum was found in two (8.7% patients who submitted to intestinal bypass. The mean size of the largest mass was 3.7 ± 1.2 cm (1.5 to 6.2 cm. There were multiple (two or more lesions in three cases (13.0%. In the resected cases, the lymph nodes were compromised in 10 patients (47.6% and disease-free in 11 (52.4%. Venous invasion and neural infiltration were both present in five (23.8% patients. The tumors had penetrated the muscularis propria in all resected cases. Four (17.4% patients had a second non-carcinoid primary tumor. Three (13.0% patients died due

  12. A short history of neuroendocrine tumours and their peptide hormones

    DEFF Research Database (Denmark)

    de Herder, Wouter W; Rehfeld, Jens F; Kidd, Mark

    2016-01-01

    The discovery of neuroendocrine tumours of the gastrointestinal tract and pancreas started in 1870, when Rudolf Heidenhain discovered the neuroendocrine cells, which can lead to the development of these tumours. Siegfried Oberndorfer was the first to introduce the term carcinoid in 1907. The panc...

  13. 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

  14. A clinical and radiological objective tumor response with somatostatin analogs (SSA in well-differentiated neuroendocrine metastatic tumor of the ileum: a case report

    Directory of Open Access Journals (Sweden)

    De Divitiis C

    2015-03-01

    Full Text Available Chiara De Divitiis,1 Claudia von Arx,2 Roberto Carbone,3 Fabiana Tatangelo,4 Elena di Girolamo,5 Giovanni Maria Romano,1 Alessandro Ottaiano,1 Elisabetta de Lutio di Castelguidone,3 Rosario Vincenzo Iaffaioli,1 Salvatore Tafuto1 On behalf of the European Neuroendocrine Tumor Society (ENETS Center of Excellence Multidisciplinary Group for Neuroendocrine Tumors in Naples (Italy 1Department of Abdominal Oncology, National Cancer Institute “Fondazione G. Pascale”, Naples, Italy; 2Department of Clinical Medicine and Surgery, “Federico II” University, Naples, Italy; 3Department of Radiology, 4Department of Pathology, 5Department of Endoscopy, National Cancer Institute “Fondazione G Pascale”, Naples, Italy Abstract: Somatostatin analogs (SSAs are typically used to treat the symptoms caused by neuroendocrine tumors (NETs, but they are not used as the primary treatment to induce tumor shrinkage. We report a case of a 63-year-old woman with a symptomatic metastatic NET of the ileum. Complete symptomatic response was achieved after 1 month of treatment with SSAs. In addition, there was an objective response in the liver, with the disappearance of secondary lesions noted on computed tomography scan after 3 months of octreotide treatment. Our experience suggests that SSAs could be useful for downstaging and/or downsizing well-differentiated NETs, and they could allow surgery to be performed. Such presurgery therapy could be a promising tool in the management of patients with initially inoperable NETs. Keywords: neuroendocrine tumor, somatostatin analogs, octreotide, metastatic tumor of the ileum, radiological tumor response

  15. Splenosis Mimicking Relapse of a Neuroendocrine Tumor at Gallium-68-DOTATOC PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Treglia, Giorgio; Luca, Giovanella [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland); Barbara, Muoio; Carmelo, Caldarella [Catholic Univ., Rome (Italy)

    2014-06-15

    A 48-year-old female patient underwent splenopancreasectomy for a 4-cm pancreatic neuroendocrine tumor (pNET), grade G2, located in the pancreatic tail. One year after surgery, the patient presented an increased serum level of the tumor marker chromogranin A (value: 160 U/l). Therefore, she underwent somatostatin receptor PET/CT using gallium-68-DOTATOC for restaging. This imaging method showed a focal area of increased radiopharmaceutical uptake corresponding to a 2.5-cm nodule located in the left superior abdomen near a clip from the previous surgery, suggesting a possible relapse of pNET. Based on this PET/CT finding, the patient underwent ultrasonography-guided core biopsy of this nodule. Histology did not reveal findings suggestive of pNET but identified spleen tissue most likely caused by splenosis accidentally seeded at the previous operation. It is likely that the increased serum level of the tumor marker chromogranin A was due to the chronic proton-pump inhibitors use. Somatostatin receptor PET/CT is an accurate imaging method for staging and restaging pNET, presenting high sensitivity and specificity in this setting. Nevertheless, possible sources of false-negative and -positive findings with this method should be taken into account. Inflammatory lesions represent the most frequent causes of false-positive findings for pNET at somatostatin receptor imaging because inflammatory cellsmay overexpress somatostatin receptors on their cell surface. In our case, we showed that splenosis may represent a possible cause of false-positive findings for pNET relapse due to the physiological uptake of somatostatin analogs by the spleen tissue.

  16. Molecular Imaging Radiotherapy: Theranostics for Personalized Patient Management of Neuroendocrine Tumors (NETs).

    Science.gov (United States)

    Oberg, Kjell

    2012-01-01

    Neuroendocrine tumors (NETs) possess unique features including expression of peptide hormone receptors as well as the capacity to concentrate and take up precursor forms of amines and peptides making hormones that are stored in secretory granules within the tumor cells (APUD). The expression of somatostatin receptors on tumor cells have been widely explored during the last two decades starting with (111)In-DTPA-Octreotide as an imaging agent followed by (68)Ga-DOTATOC/TATE positron emission tomography scanning. The new generation of treatment includes (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE/DOTANOC treatment of various subtypes of NETs. The objective response rate by these types of PRRT is in the range of 30-45% objective responses with 5-10% grade 3/4 toxicity mainly hematologic and renal toxicity. The APUD mechanism is another unique feature of NETs which have generated an interest over the last two decades to develop specific tracers including (11)C-5HTP, (18)F-DOPA and (11)C-hydroxyefedrin. These radioactive tracers have been developed in centres with specific interest in NETs and are not available everywhere. (111)In-DTPA-Octreotide is still the working horse in diagnosis and staging of metastatic NETs, but will in the future be replaced by (68)Ga-DOTATOC/DOTATATE PET/CT scanning which provide higher sensitivity and specificity and is also more convenient for the patient because it is a one-stop-procedure. Both (90)Yttrium-DOTATOC/DOTATATE as well as (177)Lutetium-DOTATOC/DOTATATE are important new therapies for malignant metastatic NETs. However, the precise role in the treatment algorithm has to be determined in forthcoming randomized trials.

  17. Analysis of 320 gastroenteropancreatic neuroendocrine tumors identifies TS expression as independent biomarker for survival.

    Science.gov (United States)

    Lee, Hye Seung; Chen, Min; Kim, Ji Hun; Kim, Woo Ho; Ahn, Soyeon; Maeng, Kyungah; Allegra, Carmen J; Kaye, Frederic J; Hochwald, Steven N; Zajac-Kaye, Maria

    2014-07-01

    Thymidylate synthase (TS), a critical enzyme for DNA synthesis and repair, is both a potential tumor prognostic biomarker as well as a tumorigenic oncogene in animal models. We have now studied the clinical implications of TS expression in gastroenteropancreatic (GEP) neuroendocrine tumors (NETs) and compared these results to other cell cycle biomarker genes. Protein tissue arrays were used to study TS, Ki-67, Rb, pRb, E2F1, p18, p21, p27 and menin expression in 320 human GEP-NETs samples. Immunohistochemical expression was correlated with univariate and multivariate predictors of survival utilizing Kaplan Meier and Cox proportional hazards models. Real time RT-PCR was used to validate these findings. We found that 78 of 320 GEP-NETs (24.4%) expressed TS. NETs arising in the colon, stomach and pancreas showed the highest expression of TS (47.4%, 42.6% and 37.3%, respectively), whereas NETs of the appendix, rectum and duodenum displayed low TS expression (3.3%, 12.9% and 15.4%, respectively). TS expression in GEP-NETs was associated with poorly differentiated endocrine carcinoma, angiolymphatic invasion, lymph node metastasis and distant metastasis (p TS-positive NETs had markedly worse outcomes than TS-negative NETs as shown by univariate (p TS-positive patients that received chemotherapy (p = 0.015). In conclusion, TS protein expression was an independent prognostic biomarker for GEP-NETs. The strong association of increased TS expression with aggressive disease and early death supports the role of TS as a cancer promoting agent in these tumors. © 2013 UICC.

  18. Quantitative gene expression of somatostatin receptors and noradrenaline transporter underlying scintigraphic results in patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Mellon Mogensen, Anne

    2008-01-01

    AIM: To measure, by a quantitative approach, the gene expression underlying the results of somatostatin receptor (sst) scintigraphy ((111)In-DTPA-octreotide) and noradrenaline transporter (NAT) scintigraphy ((123)I-MIBG) in patients with neuroendocrine (NE) tumors. METHODS: The gene expression of...... to achieve a better understanding of the link between them, which in turn could aid in planning and development of noninvasive molecular imaging of key molecular processes....

  19. Improved Benefit of SPECT/CT Compared to SPECT Alone for the Accurate Localization of Endocrine and Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Gonca G. Bural

    2012-12-01

    Full Text Available Objective: To assess the clinical utility of SPECT/ CT in subjects with endocrine and neuroendocrine tumors compared to SPECT alone. Material and Methods: 48 subjects (31 women;17 men; mean age 54±11 with clinical suspicion or diagnosis of endocrine and neuroendocrine tumor had 50 SPECT/CT scans (32 Tc-99m MIBI, 5 post treatment I-131, 8 In-111 Pentetreotide, and 5 I-123 MIBG. SPECT alone findings were compared to SPECT/CT and to pathology or radiological follow up. Results: From the 32 Tc-99m MIBI scans, SPECT accurately localized the lesion in 22 positive subjects while SPECT/CT did in 31 subjects. Parathyroid lesions not seen on SPECT alone were smaller than 10 mm. In five post treatment I-131 scans, SPECT alone neither characterized, nor localized any lesions accurately. SPECT/CT revealed 3 benign etiologies, a metastatic lymph node, and one equivocal lesion. In 8 In-111 Pentetreotide scans, SPECT alone could not localize primary or metastatic lesions in 6 subjects all of which were localized with SPECT/CT. In five I-123 MIBG scans, SPECT alone could not detect a 1.1 cm adrenal lesion or correctly characterize normal physiologic adrenal uptake in consecutive scans of the same patient with prior history of adrenelectomy, all of which were correctly localized and characterized with SPECT/CT. Conclusion: SPECT/CT is superior to SPECT alone in the assessment of endocrine and neuroendocrine tumors. It is better in lesion localization and lesion characterization leading to a decrease in the number of equivocal findings. SPECT/CT should be included in the clinical work up of all patients with diagnosis or suspicion of endocrine and neuroendocrine tumors. (MIRT 2012;21:91-96

  20. Treatment Outcomes, Growth Height, and Neuroendocrine Functions in Patients With Intracranial Germ Cell Tumors Treated With Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Odagiri, Kazumasa, E-mail: t086016a@yokohama-cu.ac.jp [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Omura, Motoko [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Hata, Masaharu [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan); Aida, Noriko; Niwa, Tetsu [Department of Radiology, Kanagawa Children' s Medical Center, Yokohama (Japan); Ogino, Ichiro [Department of Radiology, Yokohama City University Medical Center, Yokohama (Japan); Kigasawa, Hisato [Division of Hemato-oncology/Regeneration Medicine, Kanagawa Children' s Medical Center, Yokohama (Japan); Ito, Susumu [Department of Neurosurgery, Kanagawa Children' s Medical Center, Yokohama (Japan); Adachi, Masataka [Department of Endocrinology, Kanagawa Children' s Medical Center, Yokohama (Japan); Inoue, Tomio [Department of Radiology, Yokohama City University Graduate School of Medicine, Yokohama (Japan)

    2012-11-01

    Purpose: We carried out a retrospective review of patients receiving chemoradiation therapy (CRT) for intracranial germ cell tumor (GCT) using a lower dose than those previously reported. To identify an optimal GCT treatment strategy, we evaluated treatment outcomes, growth height, and neuroendocrine functions. Methods and Materials: Twenty-two patients with GCT, including 4 patients with nongerminomatous GCT (NGGCT) were treated with CRT. The median age at initial diagnosis was 11.5 years (range, 6-19 years). Seventeen patients initially received whole brain irradiation (median dose, 19.8 Gy), and 5 patients, including 4 with NGGCT, received craniospinal irradiation (median dose, 30.6 Gy). The median radiation doses delivered to the primary site were 36 Gy for pure germinoma and 45 Gy for NGGCT. Seventeen patients had tumors adjacent to the hypothalamic-pituitary axis (HPA), and 5 had tumors away from the HPA. Results: The median follow-up time was 72 months (range, 18-203 months). The rates of both disease-free survival and overall survival were 100%. The standard deviation scores (SDSs) of final heights recorded at the last assessment tended to be lower than those at initial diagnosis. Even in all 5 patients with tumors located away from the HPA, final height SDSs decreased (p = 0.018). In 16 patients with tumors adjacent to the HPA, 8 showed metabolic changes suggestive of hypothalamic obesity and/or growth hormone deficiency, and 13 had other pituitary hormone deficiencies. In contrast, 4 of 5 patients with tumors away from the HPA did not show any neuroendocrine dysfunctions except for a tendency to short stature. Conclusions: CRT for GCT using limited radiation doses resulted in excellent treatment outcomes. Even after limited radiation doses, insufficient growth height was often observed that was independent of tumor location. Our study suggests that close follow-up of neuroendocrine functions, including growth hormone, is essential for all patients with

  1. Management Options for Advanced Low or Intermediate Grade Gastroenteropancreatic Neuroendocrine Tumors: Review of Recent Literature

    Directory of Open Access Journals (Sweden)

    Vladimir Neychev

    2017-01-01

    Full Text Available Our understanding of the biology, genetics, and natural history of neuroendocrine tumors (NETs of the gastrointestinal tract and pancreas has improved considerably in the last several decades and the spectrum of available therapeutic options is rapidly expanding. The management of patients with metastatic low or intermediate grade NETs has been revolutionized by the development of new treatment strategies such as molecular targeting therapies with everolimus and sunitinib, somatostatin analogs, tryptophan hydroxylase inhibitors, and peptide receptor radionuclide therapy that can be used alone or as a multimodal approach with or without surgery. To further define and clarify the utility, appropriateness, and the sequence of the growing list of available therapies for this patient population will require more high level evidence; however, data from well-designed randomized phase III clinical trials is rapidly accumulating that will further stimulate development of new management strategies. It is therefore important to thoroughly review emerging evidence and report major findings in frequent updates, which will expand our knowledge and contribute to a better understanding, characterization, and management of advanced NETs.

  2. Trends of Incidence and Survival of Gastrointestinal Neuroendocrine Tumors in the United States: A Seer Analysis

    Directory of Open Access Journals (Sweden)

    Vassiliki L. Tsikitis, Betsy C. Wertheim, Marlon A. Guerrero

    2012-01-01

    Full Text Available OBJECTIVES: To examine trends in detection and survival of hollow viscus gastrointestinal neuroendocrine tumors (NETs across time and geographic regions of the U.S.METHODS: We used the Surveillance, Epidemiology and End Results (SEER database to investigate 19,669 individuals with newly diagnosed gastrointestinal NETs. Trends in incidence were tested using Poisson regression. Cox proportional hazards regression was used to examine survival.RESULTS: Incidence increased over time for NETs of all gastrointestinal sites (all P < 0.001, except appendix. Rates have risen faster for NETs of the small intestine and rectum than stomach and colon. Rectal NETs were detected at a faster pace among blacks than whites (P < 0.001 and slower in the East than other regions (P < 0.001. We observed that appendiceal and rectal NETs carry the best prognosis and survival of small intestinal and colon NETs has improved for both men and women. Colon NETs showed different temporal trends in survival according to geographic region (Pinteraction = 0.028. Improved prognosis was more consistent across the country for small intestinal NETs.CONCLUSIONS: Incidence of gastrointestinal NETs has increased, accompanied by inconsistently improved survival for different anatomic sites among certain groups defined by race and geographic region.

  3. Pancreatic neuroendocrine cell tumor secreting parathyroid hormone-related protein and gastrin: Report of a case.

    Science.gov (United States)

    Morita, Yoshifumi; Suzuki, Shohachi; Sakaguchi, Takanori; Oishi, Kosuke; Suzuki, Atsushi; Fukumoto, Kazuhiko; Inaba, Keisuke; Baba, Satoshi; Takehara, Yasuo; Konno, Hiroyuki

    2010-12-01

    This report presents a case of pancreatic neuroendocrine cell carcinoma with multiple liver metastases secreting gastrin and parathyroid hormone-related protein (PTHrP) related to lumbar bone fracture and hypercalcemia. A 58-year-old woman visited an affiliated hospital with a chief complaint of lumbago without any evidence of trauma. She was diagnosed with hepatic dysfunction and hypercalcemia as well as multiple lumbar compression fractures without osteolytic lesions. Abdominal computed tomography (CT) showed a hypervascular mass in the pancreatic tail and multiple liver tumors. Duodenal ulcers were found with gastrointestinal endoscopy. There was a marked increase in the serum gastrin level. She was diagnosed as gastrinoma with multiple liver metastases and was admitted to the hospital. She had an increase in serum PTHrP level without the elevation of intact parathyroid hormone at the time of admission. She underwent an extended right hepatectomy in addition to a distal pancreatectomy with a regional lymphadenectomy and splenectomy. The postoperative course was uneventful, and serum gastrin and PTHrP activities reduced to normal levels. She remained symptom-free, and serum calcium, gastrin, and PTHrP levels remain within the normal ranges 19 months after surgery without adjuvant therapy.

  4. ⁶⁸Ga-DOTA-TOC-PET/CT detects heart metastases from ileal neuroendocrine tumors.

    Science.gov (United States)

    Calissendorff, Jan; Sundin, Anders; Falhammar, Henrik

    2014-09-01

    Metastases from ileal neuroendocrine tumors (NETs) to the myocardium are rare and generally seen in patients with widespread metastatic NET disease. The objectives of this investigation were to describe the frequency of intracardiac metastases in ileal NET patients examined by (68)Ga-DOTA-TOC-PET/CT and to describe the cases in detail. All (68)Ga-DOTA-TOC-PET/CT examinations performed at the Karolinska University Hospital since 2010 until April 2012 were reviewed. In all, 128 out of 337 examinations were in patients with ileal NETs. Four patients had seven myocardiac metastases, yielding a frequency of 4.3 % in patients with ileal NETs. One patient had cardiac surgery while three were treated with somatostatin analogs. The cardiac metastases did not affect the patients' activity of daily life. (68)Ga-DOTA-TOC-PET/CT is an established imaging modality in identifying cardiac metastases in ileal NETs. Prospective studies are needed to confirm the true clinical value of (68)Ga-DOTA-TOC-PET/CT in detecting cardiac metastases in both ileal and non-ileal NETs.

  5. Risk factors for pancreatic neuroendocrine tumors: a clinic-based case-control study.

    Science.gov (United States)

    Halfdanarson, Thorvardur R; Bamlet, William R; McWilliams, Robert R; Hobday, Timothy J; Burch, Patrick A; Rabe, Kari G; Petersen, Gloria M

    2014-11-01

    Pancreatic neuroendocrine tumors (PNETs) are uncommon, and little is known about their risk factors and association with other cancers. We evaluated whether the following risk factors known to be associated with pancreatic adenocarcinoma are also associated with PNETs: smoking, alcohol use, family history of PNET, and other cancers, and personal history of diabetes as potential risk factors. Patients with PNETs seen at Mayo Clinic Rochester between 2000 and 2011 were compared with controls seen for a general medical evaluation. Patients and controls completed the same questionnaires. After excluding insulinoma and high-grade PNETs, 355 cases were evaluated, and 309 were matched to 602 controls (2:1) on age, sex, and region of residence. Personal smoking history was not associated with PNETs. Alcohol use was less common among cases (54% vs 67%, P cancer (P = 0.02), ovarian cancer (P = 0.04), and gastric cancer (P = 0.01). There was no association with other cancers in family members. Diabetes was more commonly reported by cases than controls (19% vs 11%, P associated with pancreatic adenocarcinoma are not risk factors for PNETs.

  6. Perfusion CT Changes in Liver Metastases from Pancreatic Neuroendocrine Tumors During Everolimus Treatment.

    Science.gov (United States)

    D'Onofrio, Mirko; Cingarlini, Sara; Ortolani, Silvia; Crosara, Stefano; DE Robertis, Riccardo; Vallerio, Paola; Grego, Elisabetta; Ciaravino, Valentina; Ruzzenente, Andrea; Landoni, Luca; Scarpa, Aldo; Bassi, Claudio; Tortora, Giampaolo

    2017-03-01

    To evaluate modifications of perfusional parameters assessed by perfusion computed tomography (P-CT) of liver metastases (LM) from pancreatic neuroendocrine tumors (PanNETs) during everolimus treatment. All patients with LMs from G1-2 PanNETs undergoing everolimus treatment between January 2013 and January 2015 were prospectively evaluated with P-CT at baseline, and after 2 and 4 months of therapy. Size, perfusion, blood volume (BV), peak enhancement intensity (PEI) and time to peak for each lesion were calculated. A total of 33 LMs in nine patients with G1-2 PanNETs were prospectively evaluated: 23/33 (69.7%) were responders, 10/33 (30.3%) were non-responders. Among perfusional parameters, only numerical peak enhancement intensity values significantly differed between the two groups at baseline (p=0.043). BV increase was the most significant perfusional modification identifying responding lesions, even at an early stage of treatment, with a high positive predictive value (89.47%). P-CT seems to be useful for prediction of response to everolimus of LMs from PanNETs. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. A Delphic consensus assessment: imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

    Directory of Open Access Journals (Sweden)

    Kjell Oberg

    2016-09-01

    Full Text Available The complexity of the clinical management of neuroendocrine neoplasia (NEN is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease, resolution inadequacies and inter-/intra-facility device variability and that RECIST (Response Evaluation Criteria in Solid Tumors criteria are not optimal for NEN. Limitations of currently used biomarkers are that they are secretory biomarkers (chromogranin A, serotonin, neuron-specific enolase and pancreastatin; monoanalyte measurements; and lack sensitivity, specificity and predictive capacity. None of them meet the NIH metrics for clinical usage. A multinational, multidisciplinary Delphi consensus meeting of NEN experts (n = 33 assessed current imaging strategies and biomarkers in NEN management. Consensus (>75% was achieved for 78% of the 142 questions. The panel concluded that morphological imaging has a diagnostic value. However, both imaging and current single-analyte biomarkers exhibit substantial limitations in measuring the disease status and predicting the therapeutic efficacy. RECIST remains suboptimal as a metric. A critical unmet need is the development of a clinico-biological tool to provide enhanced information regarding precise disease status and treatment response. The group considered that circulating RNA was better than current general NEN biomarkers and preliminary clinical data were considered promising. It was resolved that circulating multianalyte mRNA (NETest had clinical utility in both diagnosis and monitoring disease status and therapeutic efficacy. Overall, it was concluded that a combination of tumor spatial and functional imaging with circulating transcripts (mRNA would represent the future strategy for real-time monitoring of disease progress and therapeutic efficacy.

  8. Perifosine-mediated Akt inhibition in neuroendocrine tumor cells: role of specific Akt isoforms.

    Science.gov (United States)

    Zitzmann, Kathrin; Vlotides, George; Brand, Stephan; Lahm, Harald; Spöttl, Gerald; Göke, Burkhard; Auernhammer, Christoph J

    2012-06-01

    The majority of neuroendocrine tumors (NETs) of the gastroenteropancreatic system show aberrant Akt activity. Several inhibitors of the phosphoinositide 3-kinase (PI(3)K)-Akt-mTOR signaling pathway are currently being evaluated in clinical phase II and III studies for the treatment of NETs with promising results. However, the molecular mechanisms and particularly the role of different Akt isoforms in NET signaling are not fully understood. In this study, we examine the effect of Akt inhibition on NET cells of heterogeneous origin. We show that the Akt inhibitor perifosine effectively inhibits Akt phosphorylation and cell viability in human pancreatic (BON1), bronchus (NCI-H727), and midgut (GOT1) NET cells. Perifosine treatment suppressed the phosphorylation of Akt downstream targets such as GSK3α/β, MDM2, and p70S6K and induced apoptosis. To further investigate the role of individual Akt isoforms for NET cell function, we specifically blocked Akt1, Akt2, and Akt3 via siRNA transfection. In contrast to Akt2 knockdown, knockdown of Akt isoforms 1 and 3 decreased phosphorylation levels of GSK3α/β, MDM2, and p70S6K and suppressed NET cell viability and colony-forming capacity. The inhibitory effect of simultaneous downregulation of Akt1 and Akt3 on tumor cell viability was significantly stronger than that caused by downregulation of all Akt isoforms, suggesting a particular role for Akt1 and Akt3 in NET signaling. Akt3 siRNA-induced apoptosis while all three isoform-specific siRNAs impaired BON1 cell invasion. Together, our data demonstrate potent antitumor effects of the pan-Akt inhibitor perifosine on NET cells in vitro and suggest that selective targeting of Akt1 and/or Akt3 might improve the therapeutic potential of Akt inhibition in NET disease.

  9. Current size criteria for the management of neuroendocrine tumors of the appendix: are they valid? Clinical experience and review of the literature.

    Science.gov (United States)

    Grozinsky-Glasberg, S; Alexandraki, K I; Barak, D; Doviner, V; Reissman, P; Kaltsas, G A; Gross, D J

    2013-01-01

    We evaluated the latest pathological criteria for completion right hemicolectomy (RHC) in patients with appendiceal neuroendocrine tumors (ANETs) with emphasis on the size of the primary tumor. Data of 28 consecutive patients who underwent RHC for ANETs in three tertiary hospitals were reviewed retrospectively to assess the indications for completion RHC. 10/28 patients were found to have residual disease (36%). In 8/28 patients (29%), the tumor diameter was European Neuroendocrine Tumor Society criteria for RHC, residual disease may be missed in 18% of ANET patients. Copyright © 2012 S. Karger AG, Basel.

  10. The frequency of neuroendocrine cell hyperplasia in patients with pulmonary neuroendocrine tumours and non-neuroendocrine cell carcinomas.

    Science.gov (United States)

    Rizvi, Selim M H; Goodwill, Joseph; Lim, Eric; Yap, Yoong K; Wells, Athol U; Hansell, David M; Davis, Peter; Selim, Abdel-Ghani; Abdel-Ghani, Syed; Goldstraw, Peter; Nicholson, Andrew G

    2009-09-01

    To evaluate the frequency of neuroendocrine cell hyperplasia (NEH) in resected neuroendocrine tumours and non-neuroendocrine cell carcinomas and to study its relationship to selected clinical parameters. Random blocks without tumour from resected typical carcinoids (TCs, n = 46), atypical carcinoids (ACs, n = 14), large cell neuroendocrine carcinomas (LCNECs, n = 18), small cell carcinomas (SCLCs, n = 22), adenocarcinomas (ADENOs, n = 26) and squamous cell carcinomas (SCCs, n = 18) were stained for CD56 and evaluated for linear proliferations, cell aggregates (>4 CD56+ cells), and tumourlets (<5 mm with basement membrane invasion). There was a statistically significant difference between the frequency of NEH in all neuroendocrine tumours (TC/AC/LCNEC/SCLC, 35/100, 35%) (P = 0.009) when compared with non-neuroendocrine carcinomas (ADENO/SCC, 6/44, 14%) and in the frequency of NEH in TC (21/46, 46%) versus all other tumours (AC/LCNEC/SCLC/SCC/ADENO, 20/98, 20%) (P = 0.001). There was increased frequency of NEH in peripheral TCs (8/13, 62%) compared with central TCs (14/33, 43%) (P = 0.33). There was no association between smoking history and NEH. Clinical and imaging data showed no evidence of an increased frequency of obliterative bronchiolitis in patients with NEH. NEH is significantly increased in the background lung of neuroendocrine tumours when compared with non-neuroendocrine carcinomas, supportive data for NEH having neoplastic potential.

  11. Risk factors for aggressive nonfunctional pancreatic neuroendocrine tumors and the role of endoscopic ultrasound guided fine-needle aspiration

    Science.gov (United States)

    Ende, Alexander R.; Sedarat, Alireza; Shah, Pari; Jhala, Nirag; Fraker, Douglas L.; Drebin, Jeffrey A.; Metz, David C.; Kochman, Michael L.

    2016-01-01

    Background: Nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) are increasingly being diagnosed but management, especially of small tumors, remains a clinical dilemma. Endoscopic ultrasound guided fine-needle aspiration (EUS-FNA) is now routinely used for diagnosis of pancreatic neuroendocrine tumors (pNETs) but has not been well studied as a tool for identifying aggressive disease. Materials and Methods: A systematic search of the cytology database identified all patients at our center who underwent EUS-FNA from 1999 through 2011 and were diagnosed with NF-pNET. Results: A total of 50 patients were identified. Though patients with metastatic disease had a mean tumor size of 40 mm compared to 25 mm in patients without metastatic disease (P = 0.04), we also identified several patients with tumors 20 mm (P = 0.13). Using receiver operating characteristic (ROC) analysis, we found that using a cutoff point of 20 mm only led to a sensitivity of 85% in screening for metastases, while lowering the cutoff point to 18 mm allowed for a sensitivity of 95%. Conclusion: Currently, guidelines suggest that only patients with tumors greater than 20 mm undergo surgical resection, as tumors less than this size are thought to have low risk of metastases. Our analysis suggests that these recommendations could lead to undertreating patients with small tumors. Tumor size alone may be inadequate as a marker for aggressive NF-pNETs. Given this, other risk factors for aggressive pNETs should be studied to help identify the patients most likely to benefit from surgery. PMID:26879167

  12. A Delphic consensus assessment : imaging and biomarkers in gastroenteropancreatic neuroendocrine tumor disease management

    NARCIS (Netherlands)

    Oberg, Kjell; Krenning, Eric; Sundin, Anders; Bodei, Lisa; Kidd, Mark; Tesselaar, Margot; Ambrosini, Valentina; Baum, Richard P.; Kulke, Matthew; Pavel, Marianne; Cwikla, Jaroslaw; Drozdov, Ignat; Falconi, Massimo; Fazio, Nicola; Frilling, Andrea; Jensen, Robert; Koopmans, Klaus; Korse, Tiny; Kwekkeboom, Dik; Maecke, Helmut; Paganelli, Giovanni; Salazar, Ramon; Severi, Stefano; Strosberg, Jonathan; Prasad, Vikas; Scarpa, Aldo; Grossman, Ashley; Walenkamp, Annemiek; Cives, Mauro; Virgolini, Irene; Kjaer, Andreas; Modlin, Irvin M.

    2016-01-01

    The complexity of the clinical management of neuroendocrine neoplasia (NEN) is exacerbated by limitations in imaging modalities and a paucity of clinically useful biomarkers. Limitations in currently available imaging modalities reflect difficulties in measuring an intrinsically indolent disease,

  13. Computed tomography and magnetic resonance imaging features of lipid-rich neuroendocrine tumors of the pancreas

    Science.gov (United States)

    Fukukura, Yoshihiko; Shindo, Toshikazu; Higashi, Michiyo; Takumi, Koji; Umanodan, Tomokazu; Yoneyama, Tomohide; Yoshiura, Takashi

    2015-01-01

    AIM: To clarify the computed tomography (CT) and magnetic resonance imaging (MRI) characteristics of lipid-rich pancreatic neuroendocrine tumors (PanNETs). METHODS: Enhanced CT and MRI performed before pancreatectomy in 29 patients with 34 histologically-confirmed PanNETs was retrospectively reviewed. Tumor attenuation on CT and signal intensities on conventional (T1- and T2-weighted) and chemical shift MRI were qualitatively analyzed and compared alongside adipose differentiation-related protein (ADRP) immunostaining (ADRP-positive: lipid-rich; ADRP-negative: non-lipid-rich) results using Fisher’s exact test or the Mann-Whitney U test. Signal intensity index on chemical shift MRI was quantitatively assessed. RESULTS: There were 15 lipid-rich PanNETs (44.1%) in 12 patients (41.4%). Tumor attenuation during the early, portal venous, and delayed phases of enhanced CT (P = 0.888, 0.443, and 0.359, respectively) and signal intensities on conventional MRI (P = 0.698 and 0.798, respectively) were not significantly different between lipid-rich and non-lipid-rich PanNETs. Four of the 15 lipid-rich PanNETs exhibited high signal intensity on subtraction chemical shift MRI, and the association of high signal intensity on subtraction imaging with lipid-rich PanNETs was significant (4 of 15 lipid-rich PanNETs, 26.73%, vs 0 of 19 non-lipid-rich PanNETs, 0%, P = 0.029). Lipid-rich PanNETs showed a significantly higher signal intensity index than non-lipid-rich PanNETs (0.6% ± 14.1% vs -10.4% ± 14.4%, P = 0.004). Eight of 15 lipid-rich PanNETs, vs 0 of 19 non-lipid-rich PanNETs, had positive signal intensity index values in concordance with lipid contents. CONCLUSION: CT contrast enhancement and conventional MR signal intensities are similar in lipid-rich and non-lipid-rich PanNETs. Chemical shift MRI can demonstrate cytoplasmic lipids in PanNETs. PMID:26379406

  14. Neuroendocrine tumor recurrence: diagnosis with 68Ga-DOTATATE PET/CT.

    Science.gov (United States)

    Haug, Alexander R; Cindea-Drimus, Ramona; Auernhammer, Christoph J; Reincke, Martin; Beuschlein, Felix; Wängler, Björn; Uebleis, Christopher; Schmidt, Gerwin P; Spitzweg, Christine; Bartenstein, Peter; Hacker, Marcus

    2014-02-01

    To evaluate diagnostic performance of gallium 68-tetraazacyclododecane tetraacetic acid-octreotate ((68)Ga-DOTATATE) in detection of recurrent neuroendocrine tumors (NETs). Approval was waived by the local ethics committee for this retrospective study. Between 2007 and 2011, 63 patients (mean age, 58 years) were examined with (68)Ga-DOTATATE positron emission tomography (PET)/computed tomography (CT) after primary NET curative resection. Reasons for PET/CT were regular follow-up examinations (n = 30), increased plasma levels of tumor markers (n = 27), or clinical suspicion of recurrence (n = 6). Final diagnosis was determined with histopathologic verification (n = 25) or clinical follow-up (n = 38). PET/CT scans were evaluated in consensus by two readers without blinding to clinical information and independently by two readers with blinding. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Final diagnosis of NET recurrence was determined in 29 patients. In three other patients, tumors of nonneuroendocrine origin were diagnosed. (68)Ga-DOTATATE PET/CT helped identify NET recurrence in 26 of 29 patients (sensitivity, 90%) and exclude presence of recurrent NET in 28 of 34 patients (specificity, 82% ). PET/CT provided false-positive and false-negative results in six and three patients (PPV, 81% [26 of 32]; NPV, 90% [28 of 31]; accuracy, 86% [54 of 63]). In gastroenteropancreatic NET (n = 45), sensitivity was 94% (17 of 18); specificity was 89% (24 of 27); PPV was 85% (17 of 20); NPV was 96% (24 of 25); and accuracy was 91% (41 of 45). Two blinded readers achieved sensitivity of 79% (23 of 29) and 76% (22 of 29); specificity of 85% (29 of 34) and 94% (32 of 34) (κ = 0.80); and accuracy of 83% and 86%. (68)Ga-DOTATATE PET/CT is accurate in detection of recurrent NET. Blinded PET/CT review markedly decreased sensitivity, underlining importance of considering clinical parameters in NET recurrence. Present

  15. Metastatic Neuroendocrine Carcinoma of the Breast Identified by Tc-99m-HYNIC-TOC SPECT/CT: A Rare Case Report.

    Science.gov (United States)

    Claimon, Apichaya; Chuthapisith, Suebwong; Samarnthai, Norasate; Pusuwan, Pawana

    2015-08-01

    The authors reported an uncommon presentation of metastatic neuroendocrine carcinoma to the breast detected by Tc-99m-HYNIC-TOC SPECT/CT in a 49 years old woman who, previously, had carcinoid tumor of left main bronchus and invasive ductal carcinoma of the right breast. Later, the patient developed left breast mass. Core needle biopsy of the mass revealed poorly differentiated invasive ductal carcinoma. The disease remained stable for 12 years without any treatment on that left breast (due to patient's rejection). On the later investigation using Tc-99m-HYNIC-TOC scintigraphy examination, rather than invasive ductal carcinoma, metastatic neuroendocrine cancer was suggested. The final diagnosis was confirmed by pathological examination after surgical excision. Multiple metastatic lesions of neuroendocrine carcinoma at lung, liver, ovaries, and bones were also depicted. Due to the good behavior of the disease, patient had been doing well for eight months, without specific treatment. This report confirmed the advantage and the accuracy of Tc-99m-HYNIC-TOC scintigraphy in detection of neuroendocrine carcinoma. Furthermore, metastatic neuroendocrine tumor should be in differential diagnosis for patient with breast mass together with history of neuroendocrine tumor

  16. Clinical application of SPECT-CT with 99mTc-Tektrotyd in bronchial and thymic neuroendocrine tumors (NETs).

    Science.gov (United States)

    Sergieva, Sonya; Robev, Bozhil; Dimcheva, Milena; Fakirova, Albena; Hristoskova, Radka

    2016-01-01

    Neuroendocrine tumors (NETs) of the thorax including bronchial and thymic tumors belong to foregut NETs. Limited loco-regional thoracic NETs can be resected with surgery, but in extensive metastatic disease the treatment is mainly palliative. A high incidence and density of somatostatin receptors (SSTR2, SSTR3, and SSTR5) are found in thoracic NETs. The purpose of this study was to evaluate the role of SPECT-CT somatostatin receptor scintigraphy (SRS) with 99mTc-Tektrotyd for imaging, staging and follow up of patients with bronchial and thymic neuroendocrine tumors. Forty-one patients with thoracic tumors with neuroendocrine differentiation were studied. Sixty-eight examinations including SPECT-CT studies of the neck and chest and/or abdomen and pelvis were carried out 2-4 hrs. post i.v. administration of aver-age 740 MBq activity dose of 99mTc-EDDA/HYNIC-TOC (Tektrotyd, Polatom). In all 41 investigated patients we obtained 81.25% (13/16), 88% (22/25) and 85.36% (35/41) of sensitivity, specificity and accuracy of this diagnostic approach, respectively. Somatostatin-receptor scintigraphy correctly identified all primary NETs located in the lungs and thymus. SPECT-CT studies with 99mTc-EDDA/HYNIC-TOC resulted in exact pre-surgical and pre-treatment N/M staging of bronchial and thymic NETs, except 2 cases with multiple hepatic metastases and 1 with massive suprarenal metastasis. It can be concluded that SPECT-CT with 99mTc-EDDA/HYNIC-TOC is a valuable tool for staging and follow-up of patients with thoracic NETs.

  17. mTOR inhibitors response and mTOR pathway in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Falletta, Simona; Partelli, Stefano; Rubini, Corrado; Nann, Dominik; Doria, Andrea; Marinoni, Ilaria; Polenta, Vanessa; Di Pasquale, Carmelina; Degli Uberti, Ettore; Perren, Aurel; Falconi, Massimo; Zatelli, Maria Chiara

    2016-11-01

    Medical therapy of pancreatic neuroendocrine tumors (P-NET) may take advantage of Everolimus treatment. However, the extent of therapeutic response cannot be predicted. This study was aimed to identify the possible predictive markers of response to Everolimus in P-NET. We found that Everolimus reduced the cell viability and induced apoptosis in primary cultures of 6 P-NET (P-NET-R), where the proliferative and antiapoptotic effects of IGF1 were blocked by Everolimus. On the contrary, 14 P-NET primary cultures (P-NET-NR) were resistant to Everolimus and IGF1, suggesting an involvement of PI3K/AKT/mTOR pathway in the mechanism of resistance. The response to Everolimus in vitro was associated with an active AKT/mTOR pathway and seemed to be associated with a greater clinical aggressiveness. In addition, a patient sensitive to Everolimus in vitro was sensitive to this drug in vivo also and showed a positive p-AKT immunohistochemistry (IHC) at tissue level. Similarly, a patient resistant to Everolimus treatment after surgery was not sensitive to the drug in vitro and had a negative p-AKT IHC staining. Therefore, present data confirm that P-NET primary cultures may be considered a model for testing medical treatment efficacy and that IHC characterization of p-AKT might help in identifying human P-NET who can benefit from Everolimus treatment. These data encourage conducting a prospective multicenter study involving different groups of P-NET patients treated with Everolimus. © 2016 Society for Endocrinology.

  18. Somatostatin receptor immunohistochemistry in neuroendocrine tumors: comparison between manual and automated evaluation

    Science.gov (United States)

    Daniel, Kaemmerer; Maria, Athelogou; Amelie, Lupp; Isabell, Lenhardt; Stefan, Schulz; Luisa, Peter; Merten, Hommann; Vikas, Prasad; Gerd, Binnig; Paul, Baum Richard

    2014-01-01

    Background: Manual evaluation of somatostatin receptor (SSTR) immunohistochemistry (IHC) is a time-consuming and cost-intensive procedure. Aim of the study was to compare manual evaluation of SSTR subtype IHC to an automated software-based analysis, and to in-vivo imaging by SSTR-based PET/CT. Methods: We examined 25 gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients and correlated their in-vivo SSTR-PET/CT data (determined by the standardized uptake values SUVmax,-mean) with the corresponding ex-vivo IHC data of SSTR subtype (1, 2A, 4, 5) expression. Exactly the same lesions were imaged by PET/CT, resected and analyzed by IHC in each patient. After manual evaluation, the IHC slides were digitized and automatically evaluated for SSTR expression by Definiens XD software. A virtual IHC score “BB1” was created for comparing the manual and automated analysis of SSTR expression. Results: BB1 showed a significant correlation with the corresponding conventionally determined Her2/neu score of the SSTR-subtypes 2A (rs: 0.57), 4 (rs: 0.44) and 5 (rs: 0.43). BB1 of SSTR2A also significantly correlated with the SUVmax (rs: 0.41) and the SUVmean (rs: 0.50). Likewise, a significant correlation was seen between the conventionally evaluated SSTR2A status and the SUVmax (rs: 0.42) and SUVmean (rs: 0.62).Conclusion: Our data demonstrate that the evaluation of the SSTR status by automated analysis (BB1 score), using digitized histopathology slides (“virtual microscopy”), corresponds well with the SSTR2A, 4 and 5 expression as determined by conventional manual histopathology. The BB1 score also exhibited a significant association to the SSTR-PET/CT data in accordance with the high affinity profile of the SSTR analogues used for imaging. PMID:25197368

  19. Multimodality Management of "Borderline Resectable" Pancreatic Neuroendocrine Tumors: Report of a Single-Institution Experience.

    Science.gov (United States)

    Ambe, Chenwi M; Nguyen, Phuong; Centeno, Barbara A; Choi, Junsung; Strosberg, Jonathan; Kvols, Larry; Hodul, Pamela; Hoffe, Sarah; Malafa, Mokenge P

    2017-01-01

    Pancreatic neuroendocrine tumors (PanNETs) constitute approximately 3% of pancreatic neoplasms. Like patients with pancreatic ductal adenocarcinoma (PDAC), some of these patients present with "borderline resectable disease." For these patients, an optimal treatment approach is lacking. We report our institution's experience with borderline resectable PanNETs using multimodality treatment. We identified patients with borderline resectable PanNETs who had received neoadjuvant therapy at our institution between 2000 and 2013. The definition of borderline resectability was based on National Comprehensive Cancer Network criteria for PDAC. Neoadjuvant regimen, radiographic response, pathologic response, surgical margins, nodal retrieval, number of positive nodes, and recurrence were documented. Statistics were descriptive. Of 112 patients who underwent surgical resection for PanNETs during the study period, 23 received neoadjuvant therapy, 6 of whom met all inclusion criteria and had borderline resectable disease. These 6 patients received at least 1 cycle of temozolomide and capecitabine, with 3 also receiving radiation. All had radiographic evidence of treatment response. Four (67%) had negative-margin resections. Four patients had histologic evidence of a moderate response. Follow-up (3.0-4.3 years) indicated that all patients were alive, with 5/6 free of disease (1 patient with metastatic disease still on treatment without progression). A multimodality treatment strategy (neoadjuvant temozolomide and capecitabine ± radiation) can be successfully applied to patients with PanNETs who meet NCCN borderline resectable criteria for PDAC. To our knowledge, this is the first report of the use of a multimodality protocol in the treatment of patients with borderline resectable PanNETs.

  20. Immune Reactivity and Pseudoprogression or Tumor Flare in a Serially Biopsied Neuroendocrine Patient Treated with the Epigenetic Agent RRx-001

    Directory of Open Access Journals (Sweden)

    Corey A. Carter

    2016-03-01

    Full Text Available Neuroendocrine tumors (NETs are grouped together as a single class on the basis of histologic appearance, immunoreactivity for the neuroendocrine markers chromogranin A and synaptophysin, and potential secretion of hormones, neurotransmitters, neuromodulators and neuropeptides. Nevertheless, despite these common characteristics, NETs differ widely in terms of their natural histories: high-grade NETs are clinically aggressive and, like small cell lung cancer, which they most closely resemble, tend to respond to cisplatin and etoposide. In contrast, low-grade NETs, which as a rule progress and behave indolently, do not. In either case, the treatment strategy, apart from potentially curative surgical resection, is very poorly defined. This report describes the case of a 28-year-old white male with a diagnosis of high-grade NET of undetermined primary site metastatic to the lymph nodes, skin and paraspinal soft tissues, treated with the experimental anticancer agent RRx-001, in the context of a phase II clinical trial called TRIPLE THREAT (NCT02489903; serial sampling of tumor material through repeat biopsies demonstrated an intratumoral inflammatory response, including the amplification of infiltrating T cells, which correlated with clinical and symptomatic benefit. This case suggests that pseudoprogression or RRx-001-induced enlargement of tumor lesions, which has been previously described for several RRx-001-treated patients, is the result of tumoral lymphocyte infiltration.

  1. PANCREATIC SPLENOSIS MIMICKING NEUROENDOCRINE TUMORS: microhistological diagnosis by endoscopic ultrasound guided fine needle aspiration

    Directory of Open Access Journals (Sweden)

    José Celso ARDENGH

    2013-03-01

    Full Text Available Context Pancreatic splenosis is a benign condition which can mimic a pancreatic neoplasm. Objective To describe the role of the endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA of pancreatic nodules suspicious for pancreatic splenosis. Method From 1997 to 2011, patients with pancreatic solid tumors suspicious for splenosis by computed tomography and/or magnetic resonance imaging were referred to EUS-FNA. Those cases with pancreatic splenosis confirmed by EUS-FNA or surgery were included. Endosonographic findings and clinicopathologic features were also analysed. Results A total of 2,060 patients with pancreatic solid tumors underwent EUS-FNA. Fourteen (0.6% cases with pancreatic splenosis were found. After applying exclusion criteria, 11 patients were selected. Most patients were male (7, young (mean age: 42 years and asymptomatic (8. Endoscopic ultrasound imaging alone suspected pancreatic splenosis in 6 cases, and neuroendocrine tumors in 5 cases. Pancreatic splenosis was found most commonly in the tail, was round, hypoechoic, with homogeneous pattern, regular borders, and with scintigraphy negative for somatostatin receptors. The average diameter of these nodules identified by endoscopic ultrasound was 2.15 cm. Microhistology obtained by EUS-FNA confirmed the diagnosis in 9/10 patients. Conclusion Pancreatic splenosis can be diagnosed by EUS-FNA. Microhistology prevents unnecessary surgeries, and reassures asymptomatic patients with hypoechoic, homogeneous, and well circumscribed pancreatic nodules. Contexto A esplenose pancreática é uma afecção benigna que pode mimetizar uma neoplasia pancreática. Objetivo Descrever o papel da ecoendoscopia associada à punção aspirativa com agulha fina ecoguiada (EE-PAAF dos nódulos de pâncreas suspeitos de esplenose pancreática. Método De 1997 a 2011, pacientes com tumores sólidos de pâncreas sugestivos de esplenose pancreática, conforme achados de exames de imagem por

  2. Use of radioguided surgery with [111In]-pentetreotide in the management of an ACTH-secreting bronchial carcinoid causing ectopic Cushing's syndrome.

    Science.gov (United States)

    Grossrubatscher, E; Vignati, F; Dalino, P; Possa, M; Belloni, P A; Vanzulli, A; Bramerio, M; Marocchi, A; Rossetti, O; Zurleni, F; Loli, P

    2005-01-01

    Intraoperative [111In]-pentetreotide scintigraphy with a hand-held gamma detector probe has recently been proposed to increase the intraoperative detection rate of small neuroendocrine tumors and their metastases. We report a case of a 28-yr-old woman with ectopic Cushing's syndrome due to an ACTH-secreting bronchial carcinoid, in whom the use of radioguided surgery improved disease management. At presentation, radiolabeled pentetreotide scintigraphy was the only procedure able to detect the ectopic source of ACTH. After radiologic confirmation, the patient underwent removal of a bronchial carcinoid, with disease persistence. After surgery, pentetreotide scintigraphy showed pathologic uptake in the mediastinum not previously detected at surgery and only subsequently confirmed by radiologic studies. Despite a second thoracic exploration, hormonal, scintigraphic, and radiological evidence of residual disease persisted. Radioguided surgery was then performed using a hand-held gamma probe 48 h after iv administration of a tracer dose of radiolabeled [111In-DTPA-D-Phe1]-pentetreotide, which permitted detection and removal of multiple residual mediastinal lymph node metastases. Clinical and radiologic cure, with no evidence of tracer uptake at pentetreotide scintigraphy, was subsequently observed. The use of an intraoperative gamma counter appears a promising procedure in the management of metastatic ACTH-secreting bronchial carcinoids.

  3. Neuroendocrine tumor imaging with 68Ga-DOTA-NOC: physiologic and benign variants.

    Science.gov (United States)

    Kagna, Olga; Pirmisashvili, Natalia; Tshori, Sagi; Freedman, Nanette; Israel, Ora; Krausz, Yodphat

    2014-12-01

    Imaging with (68)Ga-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-octreotide analogs has become an important modality in patients with neuroendocrine tumors (NETs). In addition to high uptake in NET lesions, prominent physiologic radiotracer activity has been reported in the pituitary gland, pancreas, adrenal glands, liver, and spleen, and faint activity has been reported in the thyroid and gastrointestinal tract. This article describes previously unknown sites of 68Ga-DOTA-1-NaI3-octreotide (NOC) uptake unrelated to NETs. One hundred eighty-two patients (96 female and 86 male patients; age range, 4-89 years) with documented (n=156) or suspected (n=26) NETs underwent 207 68Ga-DOTA-NOC PET/CT studies. Studies were retrospectively reviewed for the presence, intensity, and localization of foci of increased uptake that were further correlated with findings on additional imaging studies and clinical follow-up for a period of 4-32 months. Uptake of 68Ga-DOTA-NOC not identified as NET or known physiologic activity was detected in 297 sites with confirmation in 149 of 207 studies (72%). The most common location of non-NET-related 68Ga-DOTA-NOC-avid sites was in small lymph nodes, followed by prostate, uterus, breasts, lungs, brown fat, musculoskeletal system, and other sites, including oropharynx, pineal body, thymus, aortic plaque, genitalia, surgical bed, and subcutaneous granuloma. Intensity of uptake in non-NET-related 68Ga-DOTA-NOC-avid sites ranged in maximum standardized uptake value from 0.8 to 10.5. Previously unreported benign sites of 68Ga-DOTA-NOC uptake were found in the majority of studies, suggesting the presence of somatostatin receptors in physiologic variants or processes with no evidence of tumor. Knowledge of increased tracer uptake in non-NET-related sites is important for accurate interpretation and for avoiding potential pitfalls of 68Ga-DOTA-NOC PET/CT.

  4. Synchronous Quadruple Primary Neoplasms: Colon Adenocarcinoma, Collision Tumor of Neuroendocrine Tumor and Schwann Cell Hamartoma and Sessile Serrated Adenoma of the Appendix.

    Science.gov (United States)

    Meeks, Marshall W; Grace, Shane; Chen, Yongxin; Petterchak, James; Bolesta, Edward; Zhou, Yihua; Lai, Jin-Ping

    2016-08-01

    Quadruple synchronous primary neoplasms are very rare with only three cases reported in the English-speaking literature to date. Collision tumors are also rare entities, especially of the appendix. We herein report a case of synchronous quadruple primary neoplasm in a 95-year-old female. She was diagnosed with colon adenocarcinoma, sessile serrated adenoma of the appendix and a collision tumor composed of a well-differentiated neuroendocrine tumor and Schwann cell hamartoma. Histological examination and immunohistochemistry supported these four lesions as separate entities. This case is unique because we report the diagnosis of quadruple synchronous primary, an extremely rare occurrence, in addition to a collision tumor of the appendix. We also provide a review of the literature for synchronous neoplasms and collision tumors. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  5. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  6. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...... treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy....

  7. Use of Ga-68 DOTATATE PET/CT to confirm portal vein tumor thrombosis in a patient with pancreatic neuroendocrine tumor.

    Science.gov (United States)

    Lim, Tze Chwan; Tan, Eik Hock; Zaheer, Sumbul

    2011-06-01

    A 37-year-old man complained of increasing severity and frequency of abdominal pain over a 2-year period. Initial contrast-enhanced computed tomography of the abdomen demonstrated diffuse enlargement of the pancreas associated with a filling defect in the portal vein, splenomegaly with wedge-shaped peripheral splenic hypodensities and multiple hepatic hypodensities. Findings were suggestive of a pancreatic malignancy complicated by hepatic metastases, splenic infarcts, and portal vein thrombosis. We describe the use of gallium-68 DOTA-DPhe1, Tyr3-octreotate positron emission tomography/computed tomography (Ga-68 DOTATATE PET/CT) in confirming the diagnosis of a pancreatic neuroendocrine tumor with portal vein tumor thrombosis.

  8. Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

    Science.gov (United States)

    Hope, Thomas A; Pampaloni, Miguel Hernandez; Nakakura, Eric; VanBrocklin, Henry; Slater, James; Jivan, Salma; Aparici, Carina Mari; Yee, Judy; Bergsland, Emily

    2015-08-01

    To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

  9. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Directory of Open Access Journals (Sweden)

    Severi S

    2017-01-01

    Full Text Available Stefano Severi,1 Ilaria Grassi,1 Silvia Nicolini,1 Maddalena Sansovini,1 Alberto Bongiovanni,2 Giovanni Paganelli1 1Nuclear Medicine Unit, 2Osteoncology and Rare Tumors Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST IRCCS, Meldola, Italy Abstract: Peptide receptor radionuclide therapy (PRRT, developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate. These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide and peptide receptor affinity (due to the analog but share the common characteristic of binding specific membrane somatostatin receptors that are (generally overexpressed in neuroendocrine neoplasms (NENs and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs] and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs. They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases. Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon. Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors

  10. High-Dose Lanreotide in the Treatment of Poorly Differentiated Pancreatic Neuroendocrine Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Frank Van Fraeyenhove

    2014-03-01

    Full Text Available Pancreatic neuroendocrine tumors (NETs, including poorly differentiated carcinomas (NECs, are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel®. In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0. Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

  11. A novel injectable formulation of 6-fluoro-l-DOPA imaging agent for diagnosis of neuroendocrine tumors and Parkinson's disease.

    Science.gov (United States)

    Trapani, Adriana; Tricarico, Domenico; Mele, Antonietta; Maqoud, Fatima; Mandracchia, Delia; Vitale, Paola; Capriati, Vito; Trapani, Giuseppe; Dimiccoli, Vincenzo; Tolomeo, Anna; Scilimati, Antonio

    2017-03-15

    Two [19F]F-l-DOPA (F-DOPA) new β-cyclodextrin (CD)-based dosage forms (FA and FB, respectively) have been studied and their physico-chemical and pharmacological features determined to overcome the administration site reactions showed by the currently used [18F]F-l-DOPA formulation (IASOdopa(®)) to perform PET-CT diagnosis in oncology (neuroendocrine tumors) and neurological (Parkinson's disease) field. Chemical stability of FA and FB was found to be longer than IASOdopa(®) by adding the thiol-antioxidant agent, L-Cysteine. (1)H and (19)F NMR investigations suggest the formation of an inclusion complex of F-DOPA with β-CD. In vitro experiments on the effects of FA and FB on mouse skeletal muscle fibers and on the human neuroblastoma SH-SY5Y and embryonal kidney tsA201 cell lines viability showed that FA was the most performant formulation compared to F-DOPA solutions. In vivo tolerability tests of FA on adult male rat showed no significant effects on body weight and no change in their dried organs weight. In addition, their metabolic and physiological parameters were not affected. In conclusion, [18F]F-l-DOPA, formulated as FA, constitutes a promising dosage form for PET-CT diagnosis of both neuroendocrine tumors and Parkinson's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Retrosternal goiter and thymic carcinoid: A rare co-existence

    Directory of Open Access Journals (Sweden)

    Abdulsalam Yaseen Taha

    2017-12-01

    Full Text Available Retrosternal goiter is diagnosed when more than 50% of the thyroid gland extends below the thoracic inlet. Surgery is the treatment of choice. Carcinoid tumor of thymus gland is very rare. Although both conditions develop in the anterior mediastinum, literature search revealed no patient having both lesions at the same time. Reported herein, is a 55-year old Iraqi man with retrosternal multinodular goiter and a localized solitary primary thymic carcinoid. Thymic tumor was simultaneously removed along right thyroid lobectomy via median sternotomy extended to the neck. Early outcome was good. The patient had no evidence of recurrence after surgery.

  13. Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas: Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region.

    Science.gov (United States)

    Casar-Borota, Olivera; Botling, Johan; Granberg, Dan; Stigare, Jerker; Wikström, Johan; Boldt, Henning Bünsow; Kristensen, Bjarne Winther; Pontén, Fredrik; Trouillas, Jacqueline

    2017-09-01

    Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.

  14. 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.

  15. KI-67 heterogeneity in well differentiated gastro-entero-pancreatic neuroendocrine tumors: when is biopsy reliable for grade assessment?

    Science.gov (United States)

    Grillo, Federica; Valle, Luca; Ferone, Diego; Albertelli, Manuela; Brisigotti, Maria Pia; Cittadini, Giuseppe; Vanoli, Alessandro; Fiocca, Roberto; Mastracci, Luca

    2017-09-01

    Ki-67 heterogeneity can impact on gastroenteropancreatic neuroendocrine tumor grade assignment, especially when tissue is scarce. This work is aimed at devising adequacy criteria for grade assessment in biopsy specimens. To analyze the impact of biopsy size on reliability, 360 virtual biopsies of different thickness and lengths were constructed. Furthermore, to estimate the mean amount of non-neoplastic tissue component present in biopsies, 28 real biopsies were collected, the non-neoplastic components (fibrosis and inflammation) quantified and the effective area of neoplastic tissue calculated for each biopsy. Heterogeneity of Ki-67 distribution, G2 tumors and biopsy size all play an important role in reducing the reliability of biopsy samples in Ki-67-based grade assignment. In particular in G2 cases, 59.9% of virtual biopsies downgraded the tumor and the smaller the biopsy, the more frequent downgrading occurs. In real biopsies the presence of non-neoplastic tissue reduced the available total area by a mean of 20%. By coupling the results from these two different approaches we show that both biopsy size and non-neoplastic component must be taken into account for biopsy adequacy. In particular, we can speculate that if the minimum biopsy area, necessary to confidently (80% concordance) grade gastro-entero-pancreatic neuroendocrine tumors on virtual biopsies ranges between 15 and 30 mm2, and if real biopsies are on average composed of only 80% of neoplastic tissue, then biopsies with a surface area not <12 mm2 should be performed; using 18G needles, this corresponds to a minimum total length of 15 mm.

  16. Identifying and Prioritizing Gaps in Neuroendocrine Tumor Research: A Modified Delphi Process With Patients and Health Care Providers to Set the Research Action Plan for the Newly Formed Commonwealth Neuroendocrine Tumor Collaboration

    Directory of Open Access Journals (Sweden)

    Eva Segelov

    2017-08-01

    Full Text Available Purpose: Neuroendocrine tumors (NETs are a diverse group of malignancies that pose challenges common to all rare tumors. The Commonwealth Neuroendocrine Tumor Collaboration (CommNETS was established in 2015 to enhance outcomes for patients with NETs in Canada, Australia, and New Zealand. A modified Delphi process was undertaken involving patients, clinicians, and researchers to identify gaps in NETs research to produce a comprehensive and defensible research action plan. Methods: A three-round modified Delphi process was undertaken with larger representation than usual for medical consensus processes. Patient/advocate and health care provider/researcher expert panels undertook Round 1, which canvassed 17 research priorities and 42 potential topics; in Round 2, these priorities were ranked. Round 3 comprised a face-to-face meeting to generate final consensus rankings and formulate the research action plan. Results: The Delphi groups consisted of 203 participants in Round 1 (64% health care providers/researchers, 36% patient/advocates; 52% Canadian, 32% Australian, and 17% New Zealander, of whom 132 participated in Round 2. The top eight priorities were biomarker development; peptide receptor radionuclide therapy optimization; trials of new agents in advanced NETs; functional imaging; sequencing therapies for metastatic NETs, including development of validated surrogate end points for studies; pathologic classification; early diagnosis; interventional therapeutics; and curative surgery. Two major areas were ranked significantly higher by patients/advocates: early diagnosis and curative surgery. Six CommNETS working parties were established. Conclusion: This modified Delphi process resulted in a well-founded set of research priorities for the newly formed CommNETS collaboration by involving a large, diverse group of stakeholders. This approach to setting a research agenda for a new collaborative group should be adopted to ensure that research plans

  17. Rectal carcinoids: a systematic review.

    LENUS (Irish Health Repository)

    McDermott, Frank D

    2014-07-01

    Rectal carcinoids are increasing in incidence worldwide. Frequently thought of as a relatively benign condition, there are limited data regarding optimal treatment strategies for both localized and more advanced disease. The aim of this study was to summarize published experiences with rectal carcinoids and to present the most current data.

  18. The value of 68Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature

    Science.gov (United States)

    Mojtahedi, Alireza; Thamake, Sanjay; Tworowska, Izabela; Ranganathan, David; Delpassand, Ebrahim S

    2014-01-01

    Neuroendocrine tumors (NETs) are rare group of neoplasms arising from nervous and endocrine systems. Somatostatin analogue imaging is a functional imaging modality of choice for evaluating the NETs. Recent availability of positron emitting radioisotope labeled somatostatin analogues to image neuroendocrine cancers, has raised the interests to use this new imaging modality in management of patients with NETs. 68Ga-DOTATATE PET/CT has demonstrated superiority in lesion detection compared to Octreoscan, MIBG scintigraphy and MRI. In this article, we reviewed the published studies evaluating the role of 68Ga-DOTATATE PET in diagnosis and management of patients with neuroendocrine tumors and comparing it to current FDA approved imaging modalities including Octreoscan, MIBG scintigraphy, 18F FDG PET/CT, CT and MRI. PMID:25143861

  19. The value of (68)Ga-DOTATATE PET/CT in diagnosis and management of neuroendocrine tumors compared to current FDA approved imaging modalities: a review of literature.

    Science.gov (United States)

    Mojtahedi, Alireza; Thamake, Sanjay; Tworowska, Izabela; Ranganathan, David; Delpassand, Ebrahim S

    2014-01-01

    Neuroendocrine tumors (NETs) are rare group of neoplasms arising from nervous and endocrine systems. Somatostatin analogue imaging is a functional imaging modality of choice for evaluating the NETs. Recent availability of positron emitting radioisotope labeled somatostatin analogues to image neuroendocrine cancers, has raised the interests to use this new imaging modality in management of patients with NETs. (68)Ga-DOTATATE PET/CT has demonstrated superiority in lesion detection compared to Octreoscan, MIBG scintigraphy and MRI. In this article, we reviewed the published studies evaluating the role of (68)Ga-DOTATATE PET in diagnosis and management of patients with neuroendocrine tumors and comparing it to current FDA approved imaging modalities including Octreoscan, MIBG scintigraphy, (18)F FDG PET/CT, CT and MRI.

  20. Stages of Gastrointestinal Carcinoid Tumors

    Science.gov (United States)

    ... include the following: Redness or a feeling of warmth in the face and neck. Abdominal pain. Feeling ... is checked to measure the amounts of certain substances, such as hormones, released into the blood by ...

  1. Sexual dimorphism of liver metastasis by murine pancreatic neuroendocrine tumors is affected by expression of complement C5.

    Science.gov (United States)

    Contractor, Tanupriya; Kobayashi, Shinta; da Silva, Edaise; Clausen, Richard; Chan, Chang; Vosburgh, Evan; Tang, Laura H; Levine, Arnold J; Harris, Chris R

    2016-05-24

    In a mouse model for neuroendocrine tumors of the pancreas (PanNETs), liver metastasis occurred at a higher frequency in males. Male mice also had higher serum and intratumoral levels of the innate immunity protein complement C5. In mice that lost the ability to express complement C5, there was a lower frequency of metastasis, and males no longer had a higher frequency of metastasis than females. Treatment with PMX53, a small molecule antagonist of C5aR1/CD88, the receptor for complement C5a, also reduced metastasis. Mice lacking a functional gene for complement C5 had smaller primary tumors, which were less invasive and lacked the CD68+ macrophages that have previously been associated with metastasis in this type of tumor. This is the first report of a gene that causes sexual dimorphism of metastasis in a mouse model. In the human disease, which also shows sexual dimorphism for metastasis, clinically advanced tumors expressed more complement C5 than less advanced tumors.

  2. Endoscopic therapy of rectal carcinoid: a report of 27 cases

    Directory of Open Access Journals (Sweden)

    Zhi-feng ZHAO

    2011-06-01

    Full Text Available Objective To assess the effect of treatment of rectal carcinoid tumors through endoscopy.Methods Endoscopic dissection was performed for patients during Jun.2005 to Dec.2009,in whom an elevated lesion in rectal mucosa as seen through colonoscopy,and highly suspected to be rectal carcinoid by endoscopic ultrasound(EUS,with the diameter of the lesion smaller than 1.0cm,was excised through endoscope.After being proved to be totally excised,endoscopic biopsy was performed at 4 to 6 sites along borderline of the tumor.Accurate rate of EUS was evaluated by postoperative pathology.Invasion and entirety of excised tumor were analyzed by pathological examination.Colonoscopy and liver ultrasound were carried out one time every half a year during the follow-up.Results 27 patients with elevated lesion in rectal mucosa were investigated.Rectal carcinoid was highly suspected in these patients and met the indication for endoscopic excision.The elevated lesion in rectal mucosa was excised successfully by endoscopy in all cases.Postoperative pathology confirmed that corvect diagnosis of rectal carcinoid was 92.6%(25/27.Interstitialoma was found in 1 patient,and granular cell tumor in another patient.All the 25 patients with rectal carcinoid were followed up with an average follow-up time of 33.7±12.5 months.Metastases and recurrence had not been found.Conclusions EUS has a good diagnostic specificity in the elevated lesion of rectal mucosa,and can accurately assess the indication of endoscopic excision.Endoscopic excision is a safe and effective method for rectal carcinoid which is smaller than 1.0 cm.

  3. Pancreatic neuroendocrine tumor with complete replacement of the pancreas by serous cystic neoplasms in a patient with von Hippel-Lindau disease: a case report.

    Science.gov (United States)

    Maeda, Shimpei; Motoi, Fuyuhiko; Oana, Shuhei; Ariake, Kyohei; Mizuma, Masamichi; Morikawa, Takanori; Hayashi, Hiroki; Nakagawa, Kei; Kamei, Takashi; Naitoh, Takeshi; Unno, Michiaki

    2017-09-25

    von Hippel-Lindau disease is a dominantly inherited multi-system syndrome with neoplastic hallmarks. Pancreatic lesions associated with von Hippel-Lindau include serous cystic neoplasms, simple cysts, and neuroendocrine tumors. The combination of pancreatic neuroendocrine tumors and serous cystic neoplasms is relatively rare, and the surgical treatment of these lesions must consider both preservation of pancreatic function and oncological clearance. We report a patient with von Hippel-Lindau disease successfully treated with pancreas-sparing resection of a pancreatic neuroendocrine tumor where the pancreas had been completely replaced by serous cystic neoplasms, in which pancreatic function was preserved. A 39-year-old female with von Hippel-Lindau disease was referred to our institution for treatment of a pancreatic neuroendocrine tumor. Abdominal computed tomography demonstrated a well-enhanced mass, 4 cm in diameter in the tail of the pancreas, and two multilocular tumors with several calcifications, 5 cm in diameter, in the head of the pancreas. There was complete replacement of the pancreas by multiple cystic lesions with diameters ranging from 1 to 3 cm. Magnetic resonance cholangiopancreatography showed innumerable cystic lesions on the whole pancreas and no detectable main pancreatic duct. Endoscopic ultrasound-guided fine-needle aspiration of the mass in the pancreatic tail showed characteristic features of a neuroendocrine tumor. A diagnosis of pancreatic neuroendocrine tumor in the tail of the pancreas and mixed-type serous cystic neoplasms replacing the whole pancreas was made and she underwent distal pancreatectomy while avoiding total pancreatectomy. The stump of the pancreas was sutured as firm as possible using a fish-mouth closure. The patient made a good recovery and was discharged on postoperative day 9. She is currently alive and well with no symptoms of endocrine or exocrine pancreatic insufficiency 8 months after surgery. A pancreas

  4. Expression of estrogen-induced genes and estrogen receptor β in pancreatic neuroendocrine tumors: implications for targeted therapy.

    Science.gov (United States)

    Estrella, Jeannelyn S; Ma, Ly T; Milton, Denái R; Yao, James C; Wang, Huamin; Rashid, Asif; Broaddus, Russell R

    2014-10-01

    The indolent nature and expression of progesterone receptor (PR), a well-known estrogen-induced gene, in a subset of pancreatic neuroendocrine tumors (PanNETs), raise the possibility of hormonal regulation in these tumors. Immunohistochemical expression of estrogen receptors (ERs) α and β as well as messenger RNA expression of estrogen-induced genes (PR, EIG121, IGF-1, IGF-1R, sFRP1, and sFRP4) by quantitative reverse transcription-polymerase chain reaction were examined in 131 World Health Organization grade G1 and G2 PanNETs and correlated their expression with clinicopathological features. Thirty-nine PanNETs (30%) showed high positive ERβ staining, and 87 cases (66%) had low positive ERβ staining; only 5 cases (4%) had no nuclear staining. Pancreatic neuroendocrine tumors with small size (P = 0.02), low World Health Organization grade (P = 0.02), and low American Joint Committee on Cancer stage (P = 0.006) more frequently showed high positive ERβ staining. Among the estrogen-induced genes studied, PanNETs had significantly higher expression of PR, EIG121, IGF-1, sFRP1, and sFRP4 compared with normal pancreas, independent of age or sex. High positive ERβ staining was associated with an increased expression of PR (P < 0.001) and EIG121 (P = 0.02). Our study showed that PanNETs with favorable prognostic features have higher ERβ expression, which is associated with up-regulated PR and EIG121 messenger RNA expression. Estrogen regulation in PanNETs could potentially help in risk stratification and provide a rational target for novel treatment strategies.

  5. Estimation of optical properties of neuroendocrine pancreas tumor with double-integrating-sphere system and inverse Monte Carlo model.

    Science.gov (United States)

    Saccomandi, Paola; Larocca, Enza Stefania; Rendina, Veneranda; Schena, Emiliano; D'Ambrosio, Roberto; Crescenzi, Anna; Di Matteo, Francesco Maria; Silvestri, Sergio

    2016-08-01

    The investigation of laser-tissue interaction is crucial for diagnostics and therapeutics. In particular, the estimation of tissue optical properties allows developing predictive models for defining organ-specific treatment planning tool. With regard to laser ablation (LA), optical properties are among the main responsible for the therapy efficacy, as they globally affect the heating process of the tissue, due to its capability to absorb and scatter laser energy. The recent introduction of LA for pancreatic tumor treatment in clinical studies has fostered the need to assess the laser-pancreas interaction and hence to find its optical properties in the wavelength of interest. This work aims at estimating optical properties (i.e., absorption, μ a , scattering, μ s , anisotropy, g, coefficients) of neuroendocrine pancreas tumor at 1064 nm. Experiments were performed using two popular sample storage methods; the optical properties of frozen and paraffin-embedded neuroendocrine tumor of the pancreas are estimated by employing a double-integrating-sphere system and inverse Monte Carlo algorithm. Results show that paraffin-embedded tissue is characterized by absorption and scattering coefficients significantly higher than frozen samples (μ a of 56 cm(-1) vs 0.9 cm(-1), μ s of 539 cm(-1) vs 130 cm(-1), respectively). Simulations show that such different optical features strongly influence the pancreas temperature distribution during LA. This result may affect the prediction of therapeutic outcome. Therefore, the choice of the appropriate preparation technique of samples for optical property estimation is crucial for the performances of the mathematical models which predict LA thermal outcome on the tissue and lead the selection of optimal LA settings.

  6. Inhibition of mTOR's Catalytic Site by PKI-587 Is a Promising Therapeutic Option for Gastroenteropancreatic Neuroendocrine Tumor Disease.

    Science.gov (United States)

    Freitag, Helma; Christen, Friederike; Lewens, Florentine; Grass, Irina; Briest, Franziska; Iwaszkiewicz, Sara; Siegmund, Britta; Grabowski, Patricia

    2017-01-01

    The characteristic clinical heterogeneity and mostly slow-growing behavior of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) cause problems in finding appropriate treatments. Thus, the current therapy options are not satisfactory. PKI-587 is a highly potent, novel dual inhibitor of PI3K and mTORC1/C2. We assessed the effects of PKI-587 in different GEP-NEN tumor models, including the poorly differentiated cell line LCC-18, and compared them with those of the established mTORC1 inhibitor everolimus. We treated BON, QGP-1, KRJ-I, and LCC-18 cell lines with increasing concentrations of the inhibitor PKI-587, and compared the results with those of everolimus and DMSO. We assessed the impact of the treatments on viability (WST-1 assay), on apoptotic processes (caspase 3/7 assay, JC-1), and on cell cycle regulation (flow cytometry). We determined alterations in signaling mediators by phosphor-specific Western blot analysis and conducted multiplexed gene expression analysis (nCounter® technology). In all cell lines, PKI-587 dose-dependently inhibited proliferation, whereas everolimus was less effective. Treatment with PKI-587 led to cell cycle arrest and induction of apoptosis and successfully suppressed activity of the direct mTORC1 target 4E-BP1, a crucial factor for tumor genesis only partially inhibited by everolimus. Gene expression analyses revealed relevant changes of RAS, MAPK, STAT, and PI3K pathway genes after treatment. Treatment-dependent and cell line-characteristic effects on AKT/Rb/E2F signaling regarding cell cycle control and apoptosis are extensively discussed in this paper. PI3K/mTOR dual targeting is a promising new therapeutic approach in neuroendocrine tumor disease that should be evaluated in further clinical trials. © 2016 The Author(s) Published by S. Karger AG, Basel.

  7. Prognostic value of WHO grade in pancreatic neuro-endocrine tumors in Multiple Endocrine Neoplasia type 1 : Results from the DutchMEN1 Study Group

    NARCIS (Netherlands)

    Conemans, Elfi B.; Brosens, Lodewijk A. A.; Raicu-Ionita, Gabriela M.; Pieterman, Carolina R. C.; de Herder, Wouter W.; Dekkers, Olaf M.; Hermus, Ad R.; van der Horst-Schrivers, Anouk N.; Bisschop, Peter H.; Havekes, Bas; Drent, Madeleine L.; Timmers, H. Th Marc; Offerhaus, G. Johan; Valk, Gerlof D.; Vriens, Menno R.

    2017-01-01

    Background: The prognostic value of WHO grade in pancreatic neuroendocrine tumors (PanNETs) in patients with Multiple Endocrine Neoplasia Type 1 (MEN1) is unknown. Methods: We performed a cohort study using the Dutch National MEN1 database, which includes >90% of the Dutch MEN1 population with data

  8. Improved safety and efficacy of 213Bi-DOTATATE-targeted alpha therapy of somatostatin receptor-expressing neuroendocrine tumors in mice pre-treated with l-lysine

    NARCIS (Netherlands)

    H.S. Chan (Ho Sze); M. Konijnenberg (Mark); Daniels, T. (Tamara); Nysus, M. (Monique); Makvandi, M. (Mehran); E. de Blois (Erik); W.A.P. Breeman (Wouter); Atcher, R.W. (Robert W.); M. de Jong (Marcel); J.P. Norenberg (Jeffrey)

    2016-01-01

    textabstractBackground: Targeted alpha therapy (TAT) offers advantages over current β-emitting conjugates for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. PRRT with 177Lu-DOTATATE or 90Y-DOTATOC has shown dose-limiting nephrotoxicity due to radiopeptide retention in the

  9. Patient-reported outcomes with lanreotide Autogel/Depot for carcinoid syndrome: An international observational study.

    Science.gov (United States)

    Ruszniewski, Philippe; Valle, Juan W; Lombard-Bohas, Catherine; Cuthbertson, Daniel J; Perros, Petros; Holubec, Luboš; Delle Fave, Gianfranco; Smith, Denis; Niccoli, Patricia; Maisonobe, Pascal; Atlan, Philippe; Caplin, Martyn E

    2016-05-01

    Lanreotide Autogel/Depot effectively controls symptoms in patients with carcinoid syndrome associated with neuroendocrine tumours. Data on patient-reported outcomes are sparse. To evaluate the effect of lanreotide on patient-reported outcomes (PROs) with carcinoid syndrome. This was an international, open-label, observational study of adults with neuroendocrine tumours and history of diarrhoea, receiving lanreotide for >3 months for relief of carcinoid syndrome symptoms. The primary PRO measure was satisfaction with diarrhoea control. Secondary PRO measures included severity, change in symptoms and impact on daily life of diarrhoea; and patient satisfaction with flushing control. Of 273 patients enrolled, 76% were 'completely' or 'rather' satisfied with diarrhoea control; 79% reported improvement in diarrhoea with lanreotide. The proportion of patients with 'mild', 'minimal', or 'no diarrhoea' increased from 33% before treatment to 75% during treatment; 75% were unconcerned about the impact of diarrhoea on daily life. Satisfaction with flushing control amongst patients with significant flushing at treatment initiation was 73%. Lanreotide treatment was associated with improvements in symptoms as well as a range of PROs in patients with neuroendocrine tumours and carcinoid syndrome (ClinicalTrials.gov: NCT01234168). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Transfusion free radical antegrade modular pancreaticosplenectomy of metastatic neuroendocrine tumor of the pancreas in Jehovah's Witness patient.

    Science.gov (United States)

    Jeon, Young Bae; Yun, Sangchul; Choi, Dongho

    2015-02-01

    In a popular sense, Jehovah's Witnesses (JW) have their creeds, one of which is refusal of blood transfusion. Such refusal may impinge on their proper management, especially in critical situations. We present a case of successful bloodless multimodality therapy, which was performed for a JW. The patient was a 49-year-old woman and JW who had general weakness 7 days before admission. She was diagnosed with a pancreatic neuroendocrine tumor (PNET) with hepatic metastases. Transcatheter arterial chemoembolization and Sandostatin LAR injection were performed, and then she was given a transfusion-free Radical antegrade modular pancreatosplenectomy sequentially. We gave recombinant human erythropoietin and iron hydroxide sucrose complex daily for five days after surgery. She was discharged at postoperative day 12 without any surgical complications. Multimodality therapy is very important for optimal treatment of PNET. Along with intimate interdepartmental cooperation, careful patient selection and appropriate perioperative management could possibly enhance the surgical outcome.

  11. Gene Expression of Glucose Transporter 1 (GLUT1), Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors

    DEFF Research Database (Denmark)

    Binderup, Tina; Knigge, Ulrich; Federspiel, Birgitte Hartnack

    2013-01-01

    Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs) and hexokinases (HKs), which can be imaged by (18)F-Fluorodeoxyglucose-positron emission tomography (FDG-PET). The aim of the present study was to investigate the expression of glycolysis......-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs) in comparison with 14 colorectal...... adenocarcinomas (CRAs). The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38%) compared to CRAs (86%), P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0...

  12. Carcinoids of the stomach and the duodenum with atrophic gastritis ...

    African Journals Online (AJOL)

    Multifocal tumors were observed in the setting of endocrine cell hyperplasia and atrophic gastritis. Investigations:CT scan,MRI, somatostatin receptor scintigraphy, EGD, endoscopic ultrasonography and gastric analysis. Diagnosis: Carcinoids of the stomach and duodenum with atrophic gastritis and ZES accompanied by ...

  13. Síndrome carcinoide cardiaco

    OpenAIRE

    Luis Alberto Laínez-Sánchez; Lidiette Esquivel-Alfaro

    2013-01-01

    El síndrome carcinoide cardiaco es una patología muy infrecuente que ocurre en el 50% de los pacientes con síndrome carcinoide maligno, y es caracterizado por la fibrosis de las válvulas tricúspide y pulmonar, así como del endocardio ventricular derecho, lo cual puede provocar una insuficiencia cardiaca derecha, que repercute directamente en el pronóstico de estos pacientes. Se reporta el caso de un masculino de 29 años, portador de síndrome carcinoide con metástasis hepáticas, referido para ...

  14. Syndromic versus non-syndromic sporadic gastrin-producing neuroendocrine tumors of the duodenum: comparison of pathological features and biological behavior.

    Science.gov (United States)

    Rosentraeger, M Johannes; Garbrecht, Nele; Anlauf, Martin; Raffel, Andreas; Knoefel, Wolfram T; Wiedenmann, Bertram; Klöppel, Günter

    2016-03-01

    Sporadic gastrin-producing neuroendocrine tumors of the duodenum present either with the Zollinger-Ellison syndrome (ZES) or with unspecific symptoms. While syndromic gastrin-producing neuroendocrine tumors often show metastases at the time of diagnosis, those without a syndrome do not. The aim of the study was to search for clinicopathological features that may distinguish the two categories of gastrin-producing duodenal tumors. In a retrospective study, we analyzed the clinical and pathological data in a series of 41 patients with syndromic (i.e., gastrinomas) or non-syndromic duodenal gastrin-producing neuroendocrine tumors (ns-gas-NETs). Twenty-four (59 %) of the 41 patients had tumors that were associated with a ZES and were classified as gastrinomas. These tumors showed a higher Ki-67 index than that of the ns-gas-NETs (1.74 vs. 0.85 %, p = 0.012). In addition, they had more lymph node metastases (75 vs. 6 %, p gastrin-producing duodenal NETs may be cured by complete endoscopical removal.

  15. Secondary cancers after a lung carcinoid primary: a population-based analysis.

    Science.gov (United States)

    Cote, M L; Wenzlaff, A S; Philip, P A; Schwartz, A G

    2006-06-01

    Carcinoid tumors of the lung were first described in 1937, yet little is known about their etiology. The aim of the present investigation was to determine if there was excess risk of secondary cancers in a population-based sample after a lung carcinoid tumor diagnosis which may provide insight to the etiology. Subjects were 1882 cases diagnosed with carcinoid tumors of the lung between 1988 and 2000 whose information was obtained from the Surveillance, Epidemiology and End Results (SEER) Program database. Standardized incidence ratios were calculated by dividing the observed number of second primary cancers by the expected number of cancers. Excess risk of breast cancer was seen following diagnosis of a carcinoid tumor (SIR=1.80 95% CI 1.22-2.55). When stratified by time after diagnosis, excess risk of breast cancers in women was seen in the first 5 years after carcinoid diagnosis (SIR=1.68 95% CI 1.08-2.50) but fewer than expected breast cancers were diagnosed greater than 5 years after carcinoid diagnosis (SIR=0.29 95% CI 0.09-0.68). Prostate cancers also occurred 2.8 times more often than expected (95% CI 1.66-4.43), with risk being elevated only in the first 5 years post-carcinoid diagnosis. Development of lung carcinoids may be the result of genetic predisposition or environmental exposures, particularly those that are hormonally related. The role of genetics and sex hormones in lung carcinoid development, as well as the identification of other risk factors, should be explored.

  16. Metastatic Midgut Carcinoid in the Myocardium.

    Science.gov (United States)

    Bukowczan, Jakub; Lois, Konstantinos B; Skinner, Jane; Petrides, George; James, Robert Andrew; Perros, Petros

    2015-09-01

    Metastasis of neuroendocrine tumor to the myocardium is rare. We present a case of 64-year-old woman, who presented initially with abdominal pain and large adnexal mass. The image-guided biopsy showed low-grade neuroendocrine tumor with Ki67 less than 2% within the ovarian tissue. CT staging revealed bilateral adnexal masses, liver metastases, and primary lesion in the terminal ileum. Octreoscan showed marked tracer uptake within the lower esophagus not related to obvious mass on CT scan; the echocardiography confirmed the presence of a 2.7 cm LV/LA mass. In this case, close correlation between ECHO and the octreoscan obviated need for myocardial biopsy.

  17. Phase III Prospective Randomized Comparison Trial of Depot Octreotide Plus Interferon Alfa-2b Versus Depot Octreotide Plus Bevacizumab in Patients With Advanced Carcinoid Tumors: SWOG S0518.

    Science.gov (United States)

    Yao, James C; Guthrie, Katherine A; Moran, Cesar; Strosberg, Jonathan R; Kulke, Matthew H; Chan, Jennifer A; LoConte, Noelle; McWilliams, Robert R; Wolin, Edward M; Mattar, Bassam; McDonough, Shannon; Chen, Helen; Blanke, Charles D; Hochster, Howard S

    2017-05-20

    Purpose Treatment options for neuroendocrine tumors (NETs) remain limited. This trial assessed the progression-free survival (PFS) of bevacizumab or interferon alfa-2b (IFN-α-2b) added to octreotide among patients with advanced NETs. Patients and Methods Southwest Oncology Group (SWOG) S0518, a phase III study conducted in a US cooperative group system, enrolled patients with advanced grades 1 and 2 NETs with progressive disease or other poor prognostic features. Patients were randomly assigned to treatment with octreotide LAR 20 mg every 21 days with either bevacizumab 15 mg/kg every 21 days or 5 million units of IFN-α-2b three times per week. The primary end point was centrally assessed PFS. This trial is registered with ClinicalTrials.gov as NCT00569127. Results A total of 427 patients was enrolled, of whom 214 were allocated to bevacizumab and 213 to IFN-α-2b. The median PFS by central review was 16.6 months (95% CI, 12.9 to 19.6 months) in the bevacizumab arm and was 15.4 months (95% CI, 9.6 to 18.6 months) in the IFN arm (hazard ratio [HR], 0.93; 95% CI, 0.73 to 1.18; P = .55). By site review, the median PFS times were 15.4 months (95% CI, 12.6 to 17.2 months) for bevacizumab and 10.6 months (95% CI, 8.5 to 14.4 months) for interferon (HR, 0.90; 95% CI, 0.72 to 1.12; P = .33). Time to treatment failure was longer with bevacizumab than with IFN (HR, 0.72; 95% CI, 0.58 to 0.89; P = .003). Confirmed radiologic response rates were 12% (95% CI, 8% to 18%) for bevacizumab and 4% (95% CI, 2% to 8%) for IFN. Common adverse events with bevacizumab and octreotide included hypertension (32%), proteinuria (9%), and fatigue (7%); with IFN and octreotide, they included fatigue (27%), neutropenia (12%), and nausea (6%). Conclusion No significant differences in PFS were observed between the bevacizumab and IFN arms, which suggests that these agents have similar antitumor activity among patients with advanced NETs.

  18. Preoperative Imaging Overestimates the Tumor Size in Pancreatic Neuroendocrine Neoplasms Associated with Multiple Endocrine Neoplasia Type 1.

    Science.gov (United States)

    Polenta, V; Slater, E P; Kann, P H; Albers, M B; Manoharan, J; Ramaswamy, A; Mahnken, A H; Bartsch, D K

    2017-10-26

    Radiological tumor size of non-functioning pancreatic neuroendocrine neoplasms (Nf-pNENs) associated with multiple endocrine neoplasia type 1 (MEN1) is a crucial parameter to indicate surgery. The aim of this study was to compare radiological size (RS) and pathologic size (PS) of MEN1 associated with pNENs. Prospectively collected data of MEN1 patients who underwent pancreatic resections for pNENs were retrospectively analyzed. RS was defined as the largest tumor diameter measured on endoscopic ultrasound (EUS), magnetic resonance imaging (MRI) or computed tomography (CT). PS was defined as the largest tumor diameter on pathological analysis. Student's t test and linear regression analysis were used to compare the median RS and PS. p  20 mm had in reality a PS < 20 mm. MRI was the imaging technique that best correlated with PS in the total cohort (r = 0.8; p < 0.0001), whereas EUS was the best correlating imaging tool in pNENs < 20 mm (r = 0.5; p = 0.0001). Preoperative imaging, especially EUS, frequently overestimates the size of MEN1-pNENs, especially those with a PS < 20 mm. This should be considered when indicating surgery in MEN1 patients with small Nf-pNENs.

  19. Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study.

    Science.gov (United States)

    Naswa, Niraj; Sharma, Punit; Kumar, Abhishek; Nazar, Aftab Hasan; Kumar, Rakesh; Chumber, Sunil; Bal, Chandrashekhar

    2011-11-01

    The objective of this study was to evaluate the role of (68)Ga-labeled [1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid]-1-NaI(3)-octreotide (DOTA-NOC) PET/CT in the diagnosis and management of gastroenteropancreatic neuroendocrine tumors (NETs). One hundred nine patients (median age, 50 years) with gastroenteropancreatic NETs underwent (68)Ga-DOTA-NOC PET/CT. PET/CT was performed after injection of 132-222 MBq (4-6 mCi) of (68)Ga-DOTA-NOC. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as quantitatively (maximum standardized uptake value [SUV(max)]). Results of PET/CT were compared with the results of conventional imaging. Histopathology results, when available, and follow-up PET/CT or conventional imaging with biochemical markers were considered to be the reference standards. Gallium-68-DOTA-NOC PET/CT showed sensitivity and specificity of 78.3% and 92.5%, respectively, for primary tumor and 97.4% and 100% for metastases. It was better than a conventional imaging modality for the detection of both primary tumor (p NOC PET/CT appears to be a highly sensitive and specific modality for the detection of gastroenteropancreatic NET. It is better than conventional imaging for the evaluation of gastroenteropancreatic NETs and can have a significant impact on patient management.

  20. A rare case of an ACTH/CRH co-secreting midgut neuroendocrine tumor mimicking Cushing’s disease

    Directory of Open Access Journals (Sweden)

    Regina Streuli

    2017-06-01

    Full Text Available Ectopic ACTH/CRH co-secreting tumors are a very rare cause of Cushing’s syndrome and only a few cases have been reported in the literature. Differentiating between Cushing’s disease and ectopic Cushing’s syndrome may be particularly difficult if predominant ectopic CRH secretion leads to pituitary corticotroph hyperplasia that may mimic Cushing’s disease during dynamic testing with both dexamethasone and CRH as well as bilateral inferior petrosal sinus sampling (BIPSS. We present the case of a 24-year-old man diagnosed with ACTH-dependent Cushing’s syndrome caused by an ACTH/CRH co-secreting midgut NET. Both high-dose dexamethasone testing and BIPSS suggested Cushing’s disease. However, the clinical presentation with a rather rapid onset of cushingoid features, hyperpigmentation and hypokalemia led to the consideration of ectopic ACTH/CRH-secretion and prompted a further workup. Computed tomography (CT of the abdomen revealed a cecal mass which was identified as a predominantly CRH-secreting neuroendocrine tumor. To the best of our knowledge, this is the first reported case of an ACTH/CRH co-secreting tumor of the cecum presenting with biochemical features suggestive of Cushing’s disease.

  1. Application of analytic methodologies for image quantification in neuroendocrine tumor therapy with {sup 177}Lu-DOTA

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, T.T.A.; Oliveira, S.M.V. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marco, L.; Mamede, M., E-mail: tadeukubo@gmail.com [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil)

    2012-07-01

    Neuroendocrine tumors have annual incidence of 1 to 2 cases per one hundred thousand inhabitants. The {sup 177}Lu-DOTA-octreotate treatments in 3 or 4 cycles has been effective in controlling disease progression and, in some cases, promote tumor remission. To estimate radiation side effects in healthy organs, image quantification techniques have been broadcast for individualized patient dosimetry. In this paper, image data processing methods are presented to allowing comparisons between different image conjugate views, combined with attenuation correction and system sensitivity. Images were acquired 24, 72 and 192 h after administration of 74 GBq of {sup 177}Lu-DOTA using a dual-head gamma camera detection system and they were evaluated with ImageJ software. 4 female patients underwent to two cycles of treatment. The kidneys, liver and whole-body regions of interest were separately assessed by 4 techniques for counts method and 12 techniques for pixel intensity method, considering the main photopeak separately and aided by the attenuation correction map and adjacent windows to photopeak energy. The pixel intensity method was combined with mathematical correction for pixels with null value. The results obtained by the two methods were strongly correlated (r>0.9) (p<0.001). The paired t-test accepted the null hypothesis of compatibility between the two methods (with and without attenuation correction map) (p<0.05), but rejected it when the adjacent windows were combined. No significant tumor reduction (p>0.05) was found between the treatment cycles. In conclusion, the pixel intensity method is faster and allows macros, minimizing operator error, and may optimize dosimetry in tumor therapies with {sup 177}Lu-DOTA-octreotate. (author)

  2. Primary intracranial neuroendocrine tumor with ectopic adrenocorticotropic hormone syndrome: A rare and complicated case report and literature review.

    Science.gov (United States)

    Liu, Hailong; Zhang, Mingshan; Wang, Xuan; Qu, Yanming; Zhang, Hongwei; Yu, Chunjiang

    2016-07-01

    Neuroendocrine tumors (NETs) and ectopic adrenocorticotropic hormone (ACTH) syndrome are frequent in adult patients. However, primary intracranial NETs, exhibiting immunonegativity for ACTH, high serum ACTH level and treated with anterior skull base reconstruction, are rare and complicated. We herein present a case of a primary intracranial NET immunonegative for ACTH, resulting in ectopic ACTH syndrome. A 40-year-old woman presented with intermittent rhinorrhea, rapid weight gain, polydipsia, polyuria, hypertension, dimness, bilateral exophthalmus, diminution of vision in the left eye and pigmentation of the skin of the face and trunk. Computed tomography (CT) and magnetic resonance imaging scans revealed a sizeable enhancing tumor in the anterior cranial fossa, which infiltrated the sphenoid and ethmoid sinuses bilaterally, the left maxillary sinus and the nasal cavity. Abdominal CT scans revealed bilateral adrenal hyperplasia. The biochemical findings included hypokalemia and high glucose, cortisol, plasma ACTH, 24-h urinary free cortisol and testosterone levels. The neoplasm was exposed through a right frontal craniotomy, while anterior skull base reconstruction was performed during surgery. The intracranial surgery achieved gross removal of the tumor; however, part of the tumor remained in the nasal cavity. Histopathological examination of the surgical specimen confirmed the diagnosis of a low-grade small-cell NET, exhibiting immunonegativity for ACTH. A postoperative abdominal CT scan demonstrated bilateral regression of the adrenal gland hyperplasia and the serum ACTH level returned to normal after 16 days. To the best of our knowledge, there are no previous reports of primary intracranial NETs, immunohistochemically negative for ACTH, resulting in ectopic ACTH syndrome.

  3. Two childhood pheochromocytoma cases due to von Hippel -Lindau disease, one associated with pancreatic neuroendocrine tumor; a rare manifestation.

    Science.gov (United States)

    Dağdeviren Çakır, Aydilek; Turan, Hande; Aykut, Ayça; Durmaz, Asude; Ercan, Oya; Evliyaoğlu, Olcay

    2017-10-12

    (VHL) disease is an autosomal dominantly inherited disorder characterized by hemangioblastomas of retina and central nervous system (CNS); renal cysts, clear cell carcinoma; PCC; endolymphatic sac tumors; cystadenomas of the epididymis in males, broad ligament of uterus in females; pancreatic cysts, cystadenomas and neuroendocrine tumors. We here report two cases of VHL disease presented with PCC as the first manifestation. Hemangioblastoma of CNS in the first case and PNET in the second case developed during follow- up and led to the diagnosis of VHL disease. Genetic analyses of cases revealed p.Arg161Gln (c.482G>A) and p.Leu129Pro(c.386T>G) heterozygous missense mutation in VHL gene, respectively. In children, PCC may be the only and/or initial manifestation of the disease with delayed manifestations of the syndrome in other organs. PNET is a very rare manifestation of VHL disease. To best of our knowledge, this is the second case in literature, presenting with combination of PNET and bilateral PCC as components of childhood VHL disease. Pediatric patients diagnosed with PCC should be investigated for the genetic causes especially for VHL.

  4. Primary atypical carcinoid of the parietal pleura expressing KIT.

    Science.gov (United States)

    Terada, Tadashi

    2014-01-01

    The author reports an extremely rare case of atypical carcinoid of the pleura expressing KIT. An 81-year-old Japanese man with emphysema was found to have a mass (3×3×2 cm) in the left parietal pleura by various imaging modalities. Video-assisted tumorectomy was performed, but could not excise it completely. Histologically, the tumor was composed of atypical cells arranged in trabecular, ribbon-like, and rosette patterns. Mitotic figures and necrosis were present. The tumor cells were argyrophil. Immunohistochemically, the tumor cells were positive for pancytokeratins, cytokeratin (CK) 18, chromogranin (focal), p53, KIT, and Ki67 (labeling=17%). In contrast, the tumor cells were negative for CK5/6, CK7, CK19, CK20, CK34βE12, epithelial membrane antigen, vimentin, S100-protein, α-smooth muscle actin, desmin, CEA, TTF-1, CDX-2, AFP, HepPar-1, synaptophysin, CD56, CA19-9, CD15, neuron specific enolase, serotonin, CD34, platelet-derived growth factor-α, calretinin, thrombomodulin, WT-1, B72.3, and D2-40. The pathologic diagnosis was atypical carcinoid of the pleura. The patient was examined by whole body computed tomography, magnetic resonance imaging, and positron emission tomography, but there were no tumors other than the pleural tumor. Endoscopic examinations including upper and lower gastrointestinal tract revealed no tumors. Therefore, the pleural tumor was thought to be primary. Ten months later, the patient developed metastatic lesions in the vertebular and femoral bones, and died of respiratory failure. Autopsy was not performed. To the best of the author's knowledge, there are no cases of primary carcinoid in the pleura in the English literature. This case is also interesting in that the atypical carcinoid expressed KIT.

  5. Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine.

    Science.gov (United States)

    Levine, Rachel; Krenning, Eric P

    2017-09-01

    In nuclear medicine, the term theranostics describes the combination of therapy and diagnostic imaging. In practice, this concept dates back more than 50 years; however, among the most successful examples of theranostics are peptide receptor scintigraphy and peptide receptor radionuclide therapy of neuroendocrine tumors. The development of these modalities through the radiolabeling of somatostatin analogs with various radionuclides has led to a revolution in patient management and established a foundation for expansion of the theranostic principle into other oncology indications. This article provides a review of the evolution and development of the theranostic radionuclide approach to the management of neuroendocrine tumors, as described by the inventor of this technique, Eric P. Krenning, in an interview with Rachel Levine. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  6. Primary Renal Carcinoid - A Case Report

    LENUS (Irish Health Repository)

    O’Sullivan, M

    2018-01-01

    Carcinoid tumours in the abdomen are uncommon, but typically occur in the gastrointestinal tract. Primary renal carcinoid is an extremely rare tumour, poorly described in the literature. We describe an unusual case where an atypical renal mass on imaging led to a preoperative diagnosis of renal carcinoid on imaging guiding biopsy.

  7. Goblet cell carcinoid of the appendix

    Directory of Open Access Journals (Sweden)

    Pahlavan Payam S

    2005-06-01

    Full Text Available Abstract Background Goblet cell carcinoid (GCC of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management. Methods Published studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix. Results Based on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable

  8. Evaluation of the WHO 2010 grading and AJCC/UICC staging systems in prognostic behavior of intestinal neuroendocrine tumors.

    Directory of Open Access Journals (Sweden)

    Paula B Araujo

    Full Text Available BACKGROUND: The increasing incidence and heterogeneous behavior of intestinal neuroendocrine tumors (iNETs pose a clinicopathological challenge. Our goal was to decribe the prognostic value of the new WHO 2010 grading and the AJCC/UICC TNM staging systems for iNETs. Moreover, outcomes of patients treated with somatostatin analogs were assessed. METHODS: We collected epidemiological and clinicopathological data from 93 patients with histologically proven iNETs including progression and survival outcomes. The WHO 2010 grading and the AJCC/UICC TNM staging systems were applied for all cases. RECIST criteria were used to define progression. Kaplan-Meier analyses for progression free survival (PFS and overall survival (OS were performed. RESULTS: Mean follow-up was 58.6 months (4-213 months. WHO 2010 grading yielded PFS and disease-specific OS of 125.0 and 165.8 months for grade 1 (G1, 100.0 and 144.2 months for G2 and 15.0 and 15.8 months for G3 tumors (p = 0.004 and p = 0.001. Using AJCC staging, patients with stage I and II tumors had no progression and no deaths. Stage III and IV patients demonstrated PFS of 138.4 and 84.7 months (p = 0.003 and disease-specific OS of 210.0 and 112.8 months (p = 0.017. AJCC staging also provided informative PFS (91.2 vs. 50.0 months, p = 0.004 and OS (112.3 vs. 80.0 months, p = 0.005 measures with somatostatin analog use in stage IV patients. CONCLUSION: Our findings underscore the complementarity of WHO 2010 and AJCC classifications in providing better estimates of iNETS disease outcomes and extend the evidence for somatostatin analog benefit in patients with metastatic disease.

  9. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    OpenAIRE

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were conside...

  10. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome

    OpenAIRE

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also gi...

  11. Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

    Energy Technology Data Exchange (ETDEWEB)

    Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

    2017-01-15

    PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

  12. Biodistribution of the Ga-68 labeled somatostatin analogue DOTA-NOC in patients with neuroendocrine tumors: characterization of uptake in normal organs and tumor lesions.

    Science.gov (United States)

    Prasad, V; Baum, R P

    2010-02-01

    The aim of the study was 1) to determine the normal biodistribution of radiolabeled somatostatin analogue (68)Ga DOTA-NOC; 2) to establish the range of its uptake in liver, bone and lymph node metastases in patients with NET, 3) to establish the cut-off value for differentiating between physiological uptake and tumor related sstr expression in the processus uncinatus of pancreas. Maximum standardized uptake values (SUV(max)) of (68)Ga DOTA-NOC were determined in normal organs of 89 NET patients undergoing receptor PET/CT. In addition, SUV(max) of primary pancreatic neuroendocrine tumors (pNET), liver, bone and lymph node metastases were evaluated. SUV(max) (mean + or - standard deviation) were determined in: pituitary gland 2.6 + or - 1.3, thyroid: 3.4 + or - 1.4, lung: 0.9 + or - 0.8, normal liver: 6.9 + or - 2 , spleen: 22.0 + or - 10.0, adrenal 6.0 + or - 2.5, kidney: 12.9 + or - 3.8, gastrointestinal tract 2.3 + or - 1.0, gluteal muscle:1.0 + or - 0.3, femur 0.8 + or - 0.3, blood pool 2.6 + or - 1.2 and processus uncinatus of pancreas 5.8 + or - 2.0. SUV(max) of (68)Ga DOTA-NOC was 19.6 + or - 13.4 (N.=200) in liver metastases, 12.5 + or - 10 (N.=67) in lymph nodes metastasis, 9.5 + or - 6.0 (N.=78) in bone lesions, and 20.8 + or - 10.8 (N.=26) in pancreatic neuroendocrine primary tumors. Target to non target (T/NT) ratios were 3.4 + or - 2.3 for liver metastases (with normal There is a broad range of sstr expression in metastastic lesions and in pNET. The splenic uptake of (68)Ga DOTA-NOC is highly variable. (68)Ga DOTA-NOC is an excellent tracer for imaging somatostatin receptor positive tumors, which, due to the high target to non-target ratios, allows the detection of very small lesions, especially of lymph node and bone metastases.

  13. ACTH-producing neuroendocrine tumor of thymus with recurrences. Clinical case

    Directory of Open Access Journals (Sweden)

    E A Dobreva

    2015-06-01

    Full Text Available One of the most difficult in diagnostic and treatment options for endogenous Cushing is the ectopic ACTH syndrome, which causes the development of tumors of different histogenesis localization producing adrenocorticotropic hormone (ACTH, and much less - corticotropin hormone (CRH. ACTH-secreting tumors varied in location, morphological structure and the degree of malignancy. Most of these tumors are characterized by an aggressive course with a propensity to metastasize and relapse. The article presents data of the prevalence, pathogenesis of ectopic ACTH tumors localized in the thymus, analyzis of clinical, morphological features, the methods of diagnosis and treatment. Based on the current literature, the world and our own experience on the diagnosis and treatment of patients with ectopic ACTH syndrome with localization of hormone production in the thymus, we want to highlight the current state of the problem in order to create the most efficient algorithm for diagnostic search and treatment of this difficult group of patients.

  14. Clinical features of choroidal metastases from carcinoid tumour.

    Science.gov (United States)

    She, Huaning; Zheng, Yuping; Wang, Xiaohua; Quan, Yanlong; Sun, Naixue

    2004-03-01

    To report ophthalmologic and angiographic features of choroidal metastases from carcinoid tumor and analyze their common clinical manifestation. Ophthalmologic examinations and fundus fluorescein angiography (FFA) were performed in 30 patients suffered from carcinoid tumor, and four patients diagnosed of breast cancer (2 cases), lung cancer (1 case) and maxillary sinus cancer (1 case) were confirmed with choroidal metastases. Choroidal metastases were found as the initial manifestations of the malignant tumors on 2 patients whose initial and chief complaints were decreasing vision, their fundus lesions were mainly presented in the posterior pole and FFA showed high density of fluorescence of the lesions. This study indicated choroidal metastasis might be the first sign of metastases for patients with cancer. For patients with unknown metastasic cancers, examinations of the choroids may be useful for diagnosis and prognosis.

  15. Chromogranin A is a sensitive marker of progression or regression in ileo-cecal neuroendocrine tumors

    DEFF Research Database (Denmark)

    Jensen, Kenneth Højsgaard; Hilsted, Linda; Jensen, Claus Verner

    2013-01-01

    on the ROC curves a cutoff value of 25% change was selected to discriminate between increased, decreased, or unchanged CgA concentrations in plasma, using a sensitive radioimmunoassay with well-defined epitope specificity. Results. In the 97 events showing tumor progression diagnostic sensitivity...... and specificity of an increased CgA concentration were 86% and 86%, respectively. The positive and negative predictive values were 64% and 85%, respectively. In the 279 events with unchanged tumor size the diagnostic sensitivity and specificity of an unchanged CgA concentration were 73% and 86%, and the positive...... and negative predictive values were 91% and 63%, respectively. In the 50 events showing tumor regression, diagnostic sensitivity and specificity of a decrease in CgA concentration were 78% and 91%, the positive and negative predictive values being 55% and 97%. Conclusions. CgA concentrations in plasma have...

  16. Optimizing MIBG therapy of neuroendocrine tumors: preclinical evidence of dose maximization and synergy

    Energy Technology Data Exchange (ETDEWEB)

    Mairs, Rob J. [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)], E-mail: r.mairs@beatson.gla.ac.uk; Boyd, Marie [Department of Radiation Oncology, University of Glasgow, Glasgow (United Kingdom)

    2008-08-15

    [{sup 131}I]meta-Iodobenzylguanidine ([{sup 131}I]MIBG) has been used for the therapy of tumors of neuroectodermal origin since the 1980s. Its role in the management of these malignancies remains controversial because of the large variation in response rates. Appreciation of the mode of conveyance of [{sup 131}I]MIBG via the noradrenaline transporter into malignant cells and of factors that influence the activity of the uptake mechanism has indicated various ways in which the effectiveness of this type of targeted radiotherapy may be improved. Experimental observations indicate that radiolabeling of MIBG to high specific activity reduced the amount of cold competitor, thereby increasing tumor dose and minimizing pressor effects. We observed supra-additive tumor cell kill and inhibition of tumor growth following combined topotecan and [{sup 131}I]MIBG treatment. The improved efficacy is related to topotecan's increased disruption of DNA repair. Radiation damage to targeted tumors may also be enhanced by the use of the {alpha}-particle emitter [{sup 211}At]astatine rather than {sup 131}I as radiolabel. Furthermore, recent experimental findings indicate that [{sup 123}I]MIBG may have therapeutic potential over and above its utility as an imaging agent. It has recently been demonstrated that potent cytotoxic bystander effects were induced by the intracellular concentration of [{sup 131}I]MIBG, [{sup 123}I]MIBG or meta-[{sup 211}At]astatobenzylguanidine. Identification of the nature of bystander factors could be exploited to maximize the specificity and potency of MIBG-targeted radiotherapy. By employing a range of strategies, there are good prospects for the improvement of the [{sup 131}I]MIBG therapy of neuroectodermal tumors.

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

    DEFF Research Database (Denmark)

    Christensen, Lene Svendstrup; 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....

  18. Synergistic effect of pasireotide and teriflunomide in carcinoids in vitro.

    Science.gov (United States)

    Somnay, Yash; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2013-01-01

    Somatostatin (SST) analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation may potentiate the anti-tumor effects of SST analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic with SST analogs such as pasireotide (SOM230), which may be more effective than others in its class given its elevated receptor affinity and broader binding spectrum. Here, we investigate the effects of SOM230 in combination with teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a combination. Cell proliferation was measured using a rapid colorimetric assay. Western analysis was performed to analyze expression levels of achaete-scute complex-like 1 (ASCL1), chromogranin A (CgA), phosphorylated and total ERK1/2, and markers for apoptosis. Combination treatment with SOM230 and TFN reduced cell growth beyond the additive effect of either drug alone. Combination indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA expression beyond the additive effect of either drug alone. Furthermore, it increased levels of phosphorylated ERK1/2, cleaved poly(ADP)-ribose polymerase and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated phosphorylated ERK1/2 expression following combination therapy may underlie the synergistic interaction between the two drugs. Since efficacy is achieved at lower doses, combination therapy may palliate symptoms at low toxicity levels. Because each drug has already been evaluated in clinical trials, combinatorial drug trials are warranted. Copyright © 2012 S. Karger AG, Basel.

  19. Occupational doses in neuroendocrine tumors by using {sup 177}Lu DOTATATE; Doses ocupacionais em tratamento de tumores neuroendocrinos utilizando {sup 17'}7Lu DOTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de, E-mail: gustavo@ird.gov.b, E-mail: lidia@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-10-26

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of {sup 177}Lu 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 {mu}Sv to 450 {mu}Sv, 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 {mu}Sv/h

  20. Long-Term Disease Control of a Pancreatic Neuroendocrine Tumor with Lanreotide Autogel®: A Case Report

    Directory of Open Access Journals (Sweden)

    Willem Lybaert

    2014-09-01

    Full Text Available The CLARINET study (ClinicalTrials.gov: NCT00353496 showed that somatostatin analogs are able to stabilize tumor growth in patients with intestinal and pancreatic neuroendocrine tumors (NETs. Here, we present a case of NET originating from the pancreatic tail that was treated with lanreotide Autogel®. A 60-year-old patient underwent resection of a pancreatic NET with splenectomy and distal pancreatectomy. Four months after surgery, there was an increase in chromogranin A levels, along with a hypercaptating lesion of approximately 3.5 cm at the residual part of the pancreatic corpus. Treatment with 30 mg monthly-administered octreotide long-acting release (LAR was initiated. After 3 months of treatment, a control CT scan revealed diffuse metastases in the liver, although the patient presented no symptoms and liver tests were normal. Due to difficulties with the administration of octreotide LAR, treatment was switched to lanreotide Autogel® 120 mg, administered as monthly deep-subcutaneous injections. Progression-free survival, as shown by 3-monthly CT scans, was obtained for 2 years without the need to increase the lanreotide Autogel® dose, and the patient reported no side effects. After these 2 years, deterioration of the patient's clinical status and weight loss were observed, along with increased size of the liver lesions and appearance of peritoneal metastases. Chemotherapy treatment with cisplatinum-etoposide was initiated, while the lanreotide Autogel® injections were continued. After three chemotherapy cycles, a rapid decline in the patient's quality of life was noted, and she requested discontinuation of the chemotherapy and lanreotide injections. One month later, the patient died due to clinical progressive disease.

  1. Evaluation of the risk factors associated with rectal neuroendocrine tumors: a big data analytic study from a health screening center.

    Science.gov (United States)

    Pyo, Jeung Hui; Hong, Sung Noh; Min, Byung-Hoon; Lee, Jun Haeng; Chang, Dong Kyung; Rhee, Poong-Lyul; Kim, Jae Jun; Choi, Sun Kyu; Jung, Sin-Ho; Son, Hee Jung; Kim, Young-Ho

    2016-12-01

    Rectal neuroendocrine tumor (NET) is the most common NET in Asia. The risk factors associated with rectal NETs are unclear because of the overall low incidence rate of these tumors and the associated difficulty in conducting large epidemiological studies on rare cases. The aim of this study was to exploit the benefits of big data analytics to assess the risk factors associated with rectal NET. A retrospective case-control study was conducted, including 102 patients with histologically confirmed rectal NETs and 52,583 healthy controls who underwent screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea between January 2002 and December 2012. Information on different risk factors was collected and logistic regression analysis applied to identify predictive factors. Four factors were significantly associated with rectal NET: higher levels of cholesterol [odds ratio (OR) = 1.007, 95 % confidence interval (CI), 1.001-1.013, p = 0.016] and ferritin (OR = 1.502, 95 % CI, 1.167-1.935, p = 0.002), presence of metabolic syndrome (OR = 1.768, 95 % CI, 1.071-2.918, p = 0.026), and family history of cancer among first-degree relatives (OR = 1.664, 95 % CI, 1.019-2.718, p = 0.042). The findings of our study demonstrate the benefits of using big data analytics for research and clinical risk factor studies. Specifically, in this study, this analytical method was applied to identify higher levels of serum cholesterol and ferritin, metabolic syndrome, and family history of cancer as factors that may explain the increasing incidence and prevalence of rectal NET.

  2. 1α,25(OH)2D3Analog, MART-10, Inhibits Neuroendocrine Tumor Cell Metastasis After VEGF-A Stimulation.

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Chun-Nan; Pang, Jong-Hwei S; Hsu, Jun-Te; Yeh, Ta-Sen; Chen, Li-Wei; Kuo, Sheng-Fong; Takano, Masashi; Chen, Tai C; Kittaka, Atsushi; Hsieh, Po-Jen; Juang, Horng-Heng

    2017-11-01

    Pancreatic neuroendocrine tumors (PanNETs) are usually diagnosed in an advanced stage. Most patients with PanNETs die of metastasis. Vascular endothelial growth factor-A (VEGF-A) is a strong stimulator of angiogenesis and tumor metastasis. We aimed to investigate the effect of MART-10 [19-nor-2α-(3-hydroxypropyl)-1α,25(OH) 2 D 3 ], a 1α,25-dihydroxy-vitamin D3 (1α,25(OH) 2 D 3 ) analog, on PanNET cell metastasis after VEGF-A stimulation. Migration and invasion assays, western blot, and immunofluorescent staining were applied in this study. VEGF-A increased PanNET cell migration and invasion, which was attenuated by 1α,25(OH) 2 D 3 and MART-10. VEGF-A treatment stimulated epithelial-mesenchymal transition (EMT) of PanNET cells. During this process, expression of snail family transcriptional repressor 1 and 2, and fibronectin was up-regulated. 1α,25(OH) 2 D 3 and MART-10 counteracted VEGF-A-induced EMT. In addition, expression of neuropilin 1, a key protein in VEGF-A signaling, was down-regulated by 1α,25(OH) 2 D 3 and MART-10. Furthermore, synthesis of F-actin was increased by VEGF-A and reduced by 1α,25(OH) 2 D 3 and MART-10. Our data indicate that MART-10 could be deemed a promising drug for PanNET treatment. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  3. Bronchial carcinoid in college freshman with persistent focal wheeze.

    Science.gov (United States)

    Holzer, Rena; Rosen, Dennis

    2013-12-01

    To bring attention to a rare diagnosis in the pediatric population that is in the differential diagnosis for not well-controlled asthma. Case presentation. Pulmonary carcinoid tumors are rare and usually present late in adolescence. Most of these tumors are located in the proximal airways and symptoms may be similar to those of asthma including cough, wheeze, chest pain, or recurrent pneumonia. Bronchial carcinoid should be in the differential diagnosis for adolescents with difficult to control asthma, who have symptoms including chronic cough and focal wheeze. Referral to a pulmonary specialist should be considered to help work up the differential diagnoses. ©2013 The Author(s) ©2013 American Association of Nurse Practitioners.

  4. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  5. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  6. EVALUATION OF LANREOTIDE DEPOT/AUTOGEL EFFICACY AND SAFETY AS A CARCINOID SYNDROME TREATMENT (ELECT): A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL.

    Science.gov (United States)

    Vinik, Aaron I; Wolin, Edward M; Liyanage, Nilani; Gomez-Panzani, Edda; Fisher, George A

    2016-09-01

    To evaluate the efficacy and safety of lanreotide depot/autogel 120 mg for the control of carcinoid syndrome (CS) symptoms in patients with neuroendocrine tumors (NETs). This was a 16-week, randomized, double-blind, phase 3 trial (Clinicaltrials.gov: NCT00774930). Patients with/without prior somatostatin analog (SSA) use were randomized to lanreotide depot/autogel 120 mg or placebo every 4 weeks, with access to short-acting octreotide as rescue medication. The primary endpoint was the percentage of days in which short-acting octreotide was used, which was assessed from daily diaries using an analysis of covariance including the stratification variables baseline short-acting octreotide use and frequency of diarrhea/flushing. The proportions of patients experiencing treatment success was a supportive analysis. Adverse events were recorded at all visits. A total of 115 patients were enrolled (lanreotide, n = 59; placebo, n = 56). The adjusted mean (95% confidence interval [CI]) percentage of days with rescue octreotide use (primary endpoint) was significantly lower in the lanreotide (33.7%; 95% CI, 25.0%-42.4%) versus the placebo group (48.5%; 95% CI, 39.6%-57.4%), representing an absolute difference of -14.8% (95% CI, -26.8% to -2.8%; P = .017). The odds ratio of full/partial treatment success (≤3 days short-acting octreotide use weeks 12 to 15) was significantly greater with lanreotide than placebo (2.4; 95% CI, 1.1-5.3; P = .036). No new safety concerns were identified, and lanreotide was well tolerated. Lanreotide depot/autogel is effective for the control of CS symptoms in patients (SSA-naïve or experienced) with NETs. AE = adverse event BMI = body mass index CS = carcinoid syndrome ELECT = Evaluating Lanreotide Efficacy and safety as a Carcinoid-syndrome Treatment HRQoL = health-related quality of life LTOLE = long-term open-label extension NET = neuroendocrine tumor OL = open label SSA = somatostatin analog.

  7. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    Science.gov (United States)

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-01-01

    Abstract The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No

  8. Sexual function in patients with metastatic midgut carcinoid tumours

    NARCIS (Netherlands)

    van der Horst-Schrivers, Anouk N. A.; van Ieperen, Ellen; Wymenga, A. N. Machteld; Boezen, H. Marike; Weijmar-Schultz, Willibrord C. M.; Kema, Ido P.; Meijer, Wim G.; de Herder, Wouter W.; Willemse, Pax H. B.; Links, Thera P.; de Vries, Elisabeth G. E.

    2009-01-01

    Background: Sexual dysfunction is a poorly studied aspect of quality of life in patients with midgut carcinoid tumours. We investigated whether carcinoid patients experience sexual problems. Methods: Patients with metastatic midgut carcinoid tumours filled in a validated questionnaire for sexual

  9. Automatic and manual image fusion of 111 In-pentetreotide SPECT and diagnostic CT in neuroendocrine tumor imaging - An evaluation

    Directory of Open Access Journals (Sweden)

    Hedlund Elisabeth

    2010-01-01

    Full Text Available In the clinical diagnosis of neuroendocrine tumors (NET, the results of examinations, such as high-resolution computed tomography (CT and single photon computerized tomography (SPECT, have conventionally been interpreted separately. The aim of the present study was to evaluate Hermes Multimodality™ 5.0 H Image Fusion software-based automatic and manual image fusion of SPECT and CT for the localization of NET lesions. Out of 34 NET patients who were examined by means of somatostatin receptor scintigraphy (SRS with 111In- pentetreotide along with SPECT, 22 patients had a CT examination of the abdomen, which was used in the fusion analysis. SPECT and CT data were fused using software with a registration algorithm based on normalized mutual information. The criteria for acceptable fusion were established at a maximum cranial or caudal dislocation of 25 mm between the images and at a reasonable consensus (in order of less than 1 cm between outline of the reference organs. The automatic fusion was acceptable in 13 of the 22 examinations, whereas 9 fusions were not. However all the 22 examinations were acceptable at the manual fusion. The result of automatic fusion was better when the slice thickness of 5 mm was applied at CT examination, when the number of slices was below 100 in CT data and when both examinations included uptakes of pathological lesions. Retrospective manual image fusion of SPECT and CT is a relatively inexpensive but reliable method to be used in NET imaging. Automatic image fusion with specified software of SPECT and CT acts better when the number of CT slices is reduced to the SPECT volume and when corresponding pathological lesions appear at both SPECT and CT examinations.

  10. A lymph node ratio-based staging model is superior to the current staging system for pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Gaitanidis, Apostolos; Patel, Dhaval; Nilubol, Naris; Tirosh, Amit; Kebebew, Electron

    2017-10-20

    The incidence of pancreatic neuroendocrine tumors (PNETs) is increasing. Current staging systems include nodal positivity, but the association of lymph node status and worse survival is controversial. The study aim was to determine the prognostic significance of lymph node ratio (LNR) and compare it to nodal positivity for PNET. A retrospective analysis of the Surveillance Epidemiology End Results (SEER) database between 2004 and 2011 was performed in patients who underwent a pancreatectomy with lymphadenectomy. The primary outcome was disease-specific survival (DSS). Staging models were compared using Akaike Information Criterion (AIC), Bayesian Information Criterion (BIC), corrected AIC (AICc) and Harrell's c-statistic. Of the 896 patients analyzed, T stage, N stage, distant metastasis, grade, extent of resection, sex, age ≥57 years were significantly associated with worse DSS on univariate analysis. On multivariate analysis, age ≥57 (HR 1.75, 95% CI: 1.12-2.74, p=0.015), male sex (HR 1.58, 95% CI: 1.01-2.48, p=0.046), grade (poorly differentiated/undifferentiated: HR 7.59, 95% CI: 4.71-12.23, p<0.001), distant metastases (HR 2.45, 95% CI: 1.58-3.79, p<0.001), partial pancreatectomy (HR 2.55, 95% CI: 1.2-5.4, p=0.015) were associated with worse DSS. Stepwise analysis identified several LNR cut-offs to be independently associated with worse DSS. Comparison between staging models constructed based on these LNR cut-offs and the AJCC 8th edition staging system revealed that a model based on LNR ≥0.5 was superior. LNR ≥0.5 is independently associated with worse DSS. A staging system with LNR ≥0.5 was superior to the current AJCC 8th edition staging system.

  11. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2017-12-08

    Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Dermoid Cyst; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Ovarian Transitional Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous

  12. Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion.

    Science.gov (United States)

    Tanke, Marit A C; Kema, Ido P; Dijck-Brouwer, Janneke; Doornbos, Bennard; De Vries, Elisabeth G E; Korf, Jakob

    2008-10-01

    Previously we observed in patients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan resulted in higher stress responses and higher corticosterone production. Here we tested in carcinoid patients whether tryptophan depletion due to tumor 5-HT overproduction is associated with high cortisol production. Urinary excretion of cortisol, serotonin, 5-hydroxyindole acetic acid (the main metabolite of serotonin a marker of tumor activity), plasma levels of tryptophan and platelet content of serotonin (index of peripheral serotonin synthesis) were determined in metastatic midgut carcinoid patients. Patients (N = 25) were divided into two groups based on their plasma tryptophan levels ( or = 49 micromol/l, n = 13). Carcinoid patients with low plasma tryptophan levels had significantly higher urinary excretion of free cortisol (p < 0.01), independent of tumor activity. The inter-individual differences in the low tryptophan group, however, were substantial. In a subgroup of the patients suffering from metastatic carcinoid disease the cerebral access of plasma tryptophan is impaired, thus rendering cerebral serotonin neurotransmission suboptimal and leading to hypercortisolism. The present study provides further support to the idea that low serotonergic function is a risk for developing stress-associated psychopathology.

  13. Feasibility of Radio-Guided Surgery with ⁶⁸Gallium-DOTATATE in Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors.

    Science.gov (United States)

    Sadowski, Samira M; Millo, Corina; Neychev, Vladimir; Aufforth, Rachel; Keutgen, Xavier; Glanville, Joanne; Alimchandani, Meghna; Nilubol, Naris; Herscovitch, Peter; Quezado, Martha; Kebebew, Electron

    2015-12-01

    Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEPNETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as (68)Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using (68)Ga-DOTATATE in patients with primary and recurrent GEPNETs. Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with (68)Ga-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed. The median decay corrected target count rate was 172.6 (range 28.15-2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6-43.56). The median lesion size was 1.55 (range 0.5-15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUVmax) of the lesions and TBR (Spearman r = - 0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUVmax and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6-40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS. Our study shows that RGS with (68)Ga-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with (68)Ga-DOTATATE.

  14. Atypical lung carcinoid metastasis to the pituitary gland

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    Xiao-ling YAN

    2017-09-01

    Full Text Available Objective To study clinicopathological features, diagnosis and differential diagnosis of atypical lung carcinoid metastasis to the pituitary gland based on clinical data of one patient. Methods and Results A 81-year-old female presented headache and sudden blindness, and head MRI showed that there was a lesion at the saddle area. The tumor was detected at intrasellar and in grayish red during surgery. The diameter of tumor was 2 cm. The tumor was soft with no envelop at and well-defined margins, and insufficiency in blood supply. The tumor was removed completely along its edge. Under optical microscopy, the tumor was consisted of small round cells of the same size. Tumor cells were distributed around blood vessels in a nest manner or diffuse manner with brisk mitotic activity and focal necrosis. By using immunohistochemical staining, the tumor cells were diffusely positive for synaptophysin (Syn, CD56 and thyoid transcription factor - 1 (TTF - 1, focal positive for cytokeratin (CK and P53, and negative for growth hormone (GH, prolactin (PRL, adrenocorticotropic hormone (ACTH, follicle stimulating hormone (FSH, thyroid stimulating hormone (TSH, luteinizing hormone (LH, S-100 protein (S-100, thyroglobulin (TG and calcitonin. Ki?67 labeling index was about 33%. Conclusions Pituitary metastasis is a rare tumor, and only a few cases of atypical lung carcinoid metastasis to the pituitary gland have been reported. Definite diagnosis could be made by history, typical histopathological characteristics and immunohistochemical expressions. DOI: 10.3969/j.issn.1672-6731.2017.09.010

  15. Is there still a place for conventional somatostatin scintigraphy in the carcinoid tumours in the era of PET?; Y a t-il encore de la place pour la scintigraphie conventionnelle aux recepteurs de la somatostatine dans les tumeurs carcinoides a l'ere de la TEP?

    Energy Technology Data Exchange (ETDEWEB)

    Chatti, K.; Guezguez, M.; Chhoumi, M.; Sfar, R.; Nouira, M.; Fredj, M.B.; Essabbah, H. [CHU de Sahloul, EPS Sahloul, Service de Medecine Nucleaire, Sahloul (Tunisia)

    2009-10-15

    Our aim is to discuss, based on literature data, whether or not there is still a place for conventional somatostatin receptor scintigraphy (C-S.R.S.) in the exploration of carcinoid tumours (C.T.) in the era of PET. Methods Bibliography was obtained by an interrogation of database: PubMed and Cochrane for the last 10 years. Keywords used were 'neuroendocrine tumors', 'carcinoid tumors, 'pentetreotide', 'somatostatin', '{sup 68}gallium' and '{sup 111}indium'. Results C-S.R.S. visualized local or distant metastasis, with a sensitivity reaching 90% when size lesion is greater than 1 cm. It was more sensitive than morphologic exams in the detection of the primary lesion as well as the metastases and recurrent lesions. C-S.R.S. had modified the therapeutic strategy in 21 to 53% of patients. It had determined resectability criteria and had predicted somatostatin analogue treatment efficiency. Furthermore, C-S.R.S. was very useful in the follow-up of these tumours, mainly in the early detection of postoperative residues and recurrence. Recently, {sup 68}Ga-DOTA-TOC PET had been used in some centers. According to many authors, it was superior to C-S.R.S. for the detection of C.T. localization in the lung and skeleton and was similar for the detection of CT localization in liver and brain. According to these authors, {sup 68}Ga-DOTA-TOC PET had evidenced lesions than C-S.R.S.; nevertheless, there is always a global similar sensitivity in carcinoid tumours. Conclusion {sup 68}Ga-DOTA-TOC PET is surely more advantageous in guiding clinical management and follow-up, yet this imaging modality is expensive and not widespread. Nevertheless, C-S.R.S., which is cheaper, is an accurate technique in carcinoid tumours. Furthermore, if C-S.R.S. proves negative, {sup 68}Ga-DOTA-TOC PET should be indicated. (authors)

  16. Diagnostic role of Gallium-68 DOTATOC and Gallium-68 DOTATATE PET in patients with neuroendocrine tumors: a meta-analysis.

    Science.gov (United States)

    Yang, Jigang; Kan, Ying; Ge, Benjamin H; Yuan, Leilei; Li, Chunlin; Zhao, Wenrui

    2014-05-01

    Gallium-68 somatostatin receptor positron emission tomography (PET) has been used in the diagnosis of neuroendocrine tumors (NETs). The compounds often used in molecular imaging of NETs with PET are 68Ga-DOTATOC, 68Ga-DOTATATE, and 68Ga-DOTANOC. There is varying affinity to different somatostatin receptors. To systematically review and perform a meta-analysis of published data regarding the diagnostic role of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. A comprehensive literature search of studies published through 30 April 2013 regarding 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs was performed using the PubMed/MEDLINE, Embase, and Scopus databases. Pooled sensitivity and specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs were calculated. The area under the receiver-operating characteristic (ROC) curve was calculated to measure the accuracy of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs. Ten studies comprising 416 patients with NETs were included in this meta-analysis. The pooled sensitivity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in the diagnosis of NETs calculated on a per-patient-based analysis was 93% (95% confidence interval [CI] 89-96%) and 96% (95% CI 91-99%). The pooled specificity of 68Ga-DOTATOC and 68Ga-DOTATATE PET in diagnosing NETs was 85% (95% CI 74-93%) and 100% (95% CI 82-100%). The area under the ROC curve of 68Ga-DOTATOC and 68Ga-DOTATATE PET was 0.96 and 0.98, respectively, on a per-patient-based analysis. The molecular imaging agents 68Ga-DOTATOC and 68Ga-DOTATATE demonstrated high sensitivity and specificity in the diagnosis of NETs on PET scan. Although both are accurate tools in the diagnosis of NETs, 68Ga-DOTATATE PET may be more sensitive and specific than 68Ga-DOTATOC PET scan.

  17. Specificity and sensitivity of ⁹⁹mTc-EDDA/HYNIC-Tyr³-octreotide (⁹⁹mTc-TOC) for imaging neuroendocrine tumors.

    Science.gov (United States)

    Sepúlveda-Méndez, Jesús; de Murphy, Consuelo Arteaga; Pedraza-López, Martha; Murphy-Stack, Eduardo; Rojas-Bautista, Juan Carlos; González-Treviño, Ofelia

    2012-01-01

    Gastroenteropancreatic neuroendocrine tumors (NETs) are cancers originating from neuroendocrine organs such as the pancreas, pituitary, thyroid, and adrenal glands and tumors arising from the diffuse neuroendocrine cells that are widely distributed throughout the body. NETs express somatostatin (SS) and contain a high density of SS receptors; therefore, they can be specifically targeted with SS-based radiopharmaceuticals. The aim of this research was to determine the validity in terms of specificity, sensitivity, and the agreement beyond chance with the biopsy (gold standard) of the ⁹⁹mTc-EDDA-HYNIC-Tyr³octreotide (⁹⁹mTc-TOC) to image and localize NETs and their metastases. Freeze-dried kits containing 0.0125 mg HYNIC-octreotide and co-ligands were easily labeled and quality controlled within the hospital radiopharmacy. Fifty-six consecutive Mexican patients with a previous presumptive diagnosis of NETs underwent several clinical and laboratory studies and were referred to the Nuclear Medicine Department for a routine scan with ⁹⁹mTc-TOC. The patients were injected with 500-600 MBq ⁹⁹mTc-TOC, and whole-body images were obtained 2 h later with a SPECT or a SPECT/CT camera. Two nuclear medicine physicians observed the images and classified them as 17 negative and 39 positive. After correlating the image of each patient with our 'gold standard' (biopsy, clinical history, morphological images, and tumor marker assays), the ⁹⁹mTc-TOC images were classified by the same two physicians as 12 true negatives, five false negatives, 38 true positives and one false positive. The validity of ⁹⁹mTc-TOC in terms of relative frequencies with corresponding 95% confidence intervals were as follows: 92.3% (64-100%) specificity; 88.4% (78-97%) sensitivity; and the agreement beyond chance was 73% (60-84%). The positive predictive value was 97.4% (87-100%); the negative predicted value was 70.6% (48-93%); the accuracy was 89.3% (89-97%); and the prevalence was 76

  18. Pancreatic Neuroendocrine Tumors (PNETs)

    Science.gov (United States)

    ... Stories Our signature PurpleStride run/walk events raise spirits, awareness and funds in communities nationwide. FIND YOUR ... two main pancreatic hormones. Insulin lowers blood sugar levels, while glucagon raises blood sugar levels. Together, these ...

  19. PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

    Directory of Open Access Journals (Sweden)

    Geetanjali Arora

    Full Text Available BACKGROUND: Peptide receptor radionuclide therapy (PRRT, employed for treatment of neuroendocrine tumors (NETs is based on over-expression of Somatostatin Receptors (SSTRs on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177Lu-DOTATATE loaded PLGA nanoparticles (NPs were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS: DOTATATE was labeled with Lutetium-177 ((177Lu (labeling efficiency 98%; R(f∼0.8. Polyethylene Glycol (PEG coated (177Lu-DOTATATE-PLGA NPs (50:50 and 75:25 formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated and 303.8±67.2 and 494.3±71.8 nm (coated for PLGA(50:50 and PLGA(75:25 respectively. Encapsulation efficiency (EE and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25 were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated and 65.385±5.67% & 58.495±5.35% (coated. NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177Lu-DOTATATE and (177Lu-DOTATATE-NP (uncoated and PEG-coated by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177Lu-DOTATATE-NP. The high liver uptake with uncoated (177Lu-DOTATATE-NP (13.68±3.08% ID/g, reduced to 7.20±2.04%ID/g (p = 0.02 with PEG coating. CONCLUSION: PLGA NPs were easily formulated and modified for desired release properties. PLGA

  20. A pictoral review on somatostatin receptor scintigraphy in neuroendocrine tumors: The role of multimodality imaging with SRS and GLUT receptor imaging with FDG PET-CT

    Directory of Open Access Journals (Sweden)

    Sneha Shah

    2012-01-01

    Full Text Available Somatostatin receptor scintigraphy is considered as a comprehensive imaging modality for many neuroendocrine tumors. Multiple radiotracers using combinations of gamma or positron emitting radionuclides and tracers are now available. Newer radiopharmaceuticals using 99m Tc labeled with TOC, TATE, NOC are good alternatives to the 68 - Gallium radiotracers where the PET facility is not available. The pictoral depicts the role of SRS using 99m TC - HYNIC -TOC radiotracers in staging and treatment planning of NETs. Characterization of the tumor biology using combined SRS and FDG PET/CT is also demonstrated with a proposed categorization method. The emerging role of SRS in tailored targeted radionuclide therapy is outlined in brief.

  1. The utility of (68)Ga-DOTATATE positron-emission tomography/computed tomography in the diagnosis, management, follow-up and prognosis of neuroendocrine tumors.

    Science.gov (United States)

    Tirosh, Amit; Kebebew, Electron

    2017-10-26

    Neuroendocrine tumors (NETs) are rare neoplasms that emerge mainly from the GI tract, pancreas and respiratory tract. The incidence of NETs has increased more than sixfold in the last decades. NETs typically express somatostatin receptors on their cell surface, which can be targeted by 'cold' somatostatin analogs for therapy or by 'hot' radiolabeled somatostatin analogs for tumor localization and treatment. 68-Gallium-DOTA peptides (DOTATATE, DOTATOC, DOTANOC) positron emission tomography/computed tomography is a highly accurate imaging modality for NETs that has been found to be more sensitive for NET detection than other imaging modalities. In the current review, we will discuss the clinical utility of 68-Gallium-DOTATATE positron emission tomography/computed tomography for the diagnosis and management of patients with NETs.

  2. Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Giesel, F.L., E-mail: f.giesel@dkfz.de [Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg (Germany); Kratochwil, C., E-mail: Clemens.kratochwil@t-online.de [Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg (Germany); Mehndiratta, A., E-mail: dramit.mehndiratta@gmail.com [Keble College, Institute of Biomedical Engineering, University of Oxford, Parks Road, Oxford OX13PG (United Kingdom); Wulfert, S., E-mail: sarah.wulfert@googlemail.com [Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg (Germany); Moltz, J.H., E-mail: Jan.Moltz@mevis.fraunhofer.de [Fraunhofer MEVIS, Bremen (Germany); Zechmann, C.M., E-mail: christian.zechmann@med.uni-heidelberg.de [Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg (Germany); Kauczor, H.U., E-mail: Hans-ulrich.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University of Heidelberg, INF 110, 69120 Heidelberg (Germany); Haberkorn, U., E-mail: uwe.haberkorn@med.uni-heidelberg.de [Department of Nuclear Medicine, University Hospital Heidelberg, INF 400, 69120 Heidelberg (Germany); Ley, S., E-mail: ley@gmx.de [Department of Diagnostic and Interventional Radiology, University of Heidelberg, INF 110, 69120 Heidelberg (Germany); Department of Medical Imaging, Toronto General Hospital (Canada)

    2012-10-15

    Purpose: We evaluated the rate of successful characterization of gastroenteropancreatic neuroendocrine tumors (NETs) present with an increased somatostatin receptor, comparing CE-CT with CE-MRI, each in correlation with DOTATOC-PET. Methods and materials: 8 patients with GEP-NET were imaged using CE-MRI (Gd-EOB-DTPA), CE-CT (Imeron 400) and DOTATOC-PET. Contrast-enhancement of normal liver-tissue and metastasis was quantified with ROI-technique. Tumor delineation was assessed with visual-score in blind-read-analysis by two experienced radiologists. Results: Out of 40 liver metastases in patients with NETs, all were detected by CE-MRI and the lesion extent could be adequately assessed, whereas CT failed to detect 20% of all metastases. The blind-read-score of CT in arterial and portal phase was median −0.65 and −1.4, respectively, and 2.7 for delayed-MRI. The quantitative ROI-analysis presented an improved contrast-enhancement-ratio with a median of 1.2, 1.6 and 3.3 for CE-CT arterial, portal-phase and delayed-MRI respectively. Conclusion: Late CE-MRI was superior to CE-CT in providing additionally morphologic characterization and exact lesion extension of hepatic metastases from neuroendocrine tumor detected with DOTATOC-PET. Therefore, late enhanced Gd-EOB-DTPA-MRI seems to be the adequate imaging modality for combination with DOTATOC-PET to provide complementary (macroscopic and molecular) tumor characterization in hepatic metastasized NETs.

  3. Aromatic L-amino acid decarboxylase (AAAD) inhibitors as carcinoid tumor-imaging agents: synthesis of {sup 18}F-labeled {alpha}-fluoromethyl-6-fluoro-m-tyrosine (FM-6-FmT)

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    Murali, D.; Flores, L.G.; Roberts, A.D.; Nickles, R.J.; DeJesus, O.T. E-mail: odejesus@wisc.edu

    2003-10-01

    The aromatic L-amino acid decarboxylase (AAAD) enzyme is significantly upregulated in neuroendocrine tumors and, thus, would be a good target for PET imaging agents. {alpha}-fluoromethyl-DOPA (FMDOPA) is one of the most potent irreversible AAAD inhibitor and its non-catechol derivative, {alpha}-fluoromethyl-m-tyrosine (FMmT), is a promising AAAD imaging agent. We synthesized FMmT and its direct electrophilic fluorination provided a mixture of products identified by NMR analysis after HPLC purification as 6-fluoro-, 2-fluoro- and 2,6-difluoro-derivatives of FMmT. Using rat striatal homogenates, {alpha}-fluoromethyl-6-fluoro-m-tyrosine (FM-6-FmT) was found to have AAAD inhibitory activity comparable to that of FMDOPA. Electrophilic radiofluorination of FMmT using [{sup 18}F]AcOF gave {sup 18}F labeled 6-fluoro-, 2-fluoro- and 2,6-difluoro-FMmT derivatives in 22.0%, 21.9% and 8.5% radiochemical yields, respectively. Based on its proposed mechanism of inhibition, FM-6-[{sup 18}F]FmT is expected to irreversibly bind to AAAD and, hence, could be used as a PET agent to image tumors of endocrine origin containing high concentrations of AAAD. Since FM-6-FmT lacks the catechol moiety, it is expected to be better than FMDOPA since it is not a substrate for catechol-O-methyltransferase.

  4. The value of somatostatin receptor imaging with In-111 Octreotide and/or Ga-68 DOTATATE in localizing Ectopic ACTH producing tumors.

    Science.gov (United States)

    Özkan, Zeynep Gözde; Kuyumcu, Serkan; Balköse, Deniz; Ozkan, Berker; Aksakal, Nihat; Yılmaz, Ebru; Sanlı, Yasemin; Türkmen, Cüneyt; Aral, Ferihan; Adalet, Işik

    2013-08-01

    We aimed to evaluate the value of somatostatin receptor imaging (SRI) with In-111 octreotide and Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. Nineteen patients who had In-111 octreotide somatostatin receptor scintigraphy (SRS) and/or Ga-68 DOTATATE PET-CT to localize ectopic ACTH producing tumors between the years 2000 and 2012 were included retrospectively in our study. The results of SRI were compared with clinical onset, radiological findings and surgical data of the patients. Sixteen In-111 octreotide SRS and five Ga-68 DOTATATE PET-CT were performed in 19 patients. In eight out of 19 patients, ectopic ACTH secretion site could be detected. In five patients, SRS showed pathologic uptake. In four of these patients, surgery revealed pulmonary carcinoid tumors and in one patient pancreatic neuroendocrine tumor. In one patient, Ga-68 DOTATATE PET-CT revealed pathologic uptake in lung nodule which came out to be pulmonary carcinoid tumor. In another patient who had resection of metastases of atypical carcinoid tumor prior to scans, new metastatic foci were detected both with SRS and Ga-68 DOTATATE PET-CT imaging. In one patient, although SRS was negative, CT which was performed three years later showed a lung nodule diagnosed as pulmonary carcinoid tumor. In 11 patients, ectopic ACTH secretion site could not be detected. In 10 of those patients, scintigraphic and radiological imaging did not show any lesions and in one patient, Ga-68 DOTATATE PET-CT was false positive. SRI has a complementary role with radiological imaging in localizing ectopic ACTH secretion sites. PET-CT imaging with Ga-68 peptide conjugates is a promising new modality for this indication. None declared.

  5. The Value of Somatostatin Receptor Imaging with In-111 Octreotide and/or Ga-68 DOTATATE in Localizing Ectopic ACTH Producing Tumors

    Directory of Open Access Journals (Sweden)

    Zeynep Gözde Özkan

    2013-08-01

    Full Text Available Objective: We aimed to evaluate the value of somatostatin receptor imaging (SRI with In-111 octreotide and Ga-68 DOTATATE in localizing ectopic ACTH producing tumors. Methods: Nineteen patients who had In-111 octreotide somatostatin receptor scintigraphy (SRS and/or Ga-68 DOTATATE PET-CT to localize ectopic ACTH producing tumors between the years 2000 and 2012 were included retrospectively in our study. The results of SRI were compared with clinical onset, radiological findings and surgical data of the patients. Results: Sixteen In-111 octreotide SRS and five Ga-68 DOTATATE PET-CT were performed in 19 patients. In eight out of 19 patients, ectopic ACTH secretion site could be detected. In five patients, SRS showed pathologic uptake. In four of these patients, surgery revealed pulmonary carcinoid tumors and in one patient pancreatic neuroendocrine tumor. In one patient, Ga-68 DOTATATE PET-CT revealed pathologic uptake in lung nodule which came out to be pulmonary carcinoid tumor. In another patient who had resection of metastases of atypical carcinoid tumor prior to scans, new metastatic foci were detected both with SRS and Ga-68 DOTATATE PET-CT imaging. In one patient, although SRS was negative, CT which was performed three years later showed a lung nodule diagnosed as pulmonary carcinoid tumor. In 11 patients, ectopic ACTH secretion site could not be detected. In 10 of those patients, scintigraphic and radiological imaging did not show any lesions and in one patient, Ga-68 DOTATATE PET-CT was false positive. Conclusion: SRI has a complementary role with radiological imaging in localizing ectopic ACTH secretion sites. PET-CT imaging with Ga-68 peptide conjugates is a promising new modality for this indication.

  6. Chemoembolization of Neuroendocrine Liver Metastases Using Streptozocin and Tris-acryl Microspheres: Embozar (EMBOsphere + ZAnosaR) Study

    Energy Technology Data Exchange (ETDEWEB)

    Pelage, Jean-Pierre, E-mail: pelage-jp@chu-caen.fr; Fohlen, Audrey [Caen University and Medical Center, Department of Diagnostic Imaging and Interventional Radiology (France); Mitry, Emmanuel [Hopital Ambroise Pare, Department of Hepatogastroenterology and Oncology (France); Lagrange, Christine [Hopital Ambroise Pare, Department of Radiology (France); Beauchet, Alain [Hopital Ambroise Pare, Department of Biostatistics and Public Health (France); Rougier, Philippe [Hopital Ambroise Pare, Department of Hepatogastroenterology and Oncology (France)

    2017-03-15

    PurposeThe purpose of this prospective observational study was to evaluate the efficacy and tolerability of transarterial chemoembolization (TACE) for neuroendocrine liver metastases using a combination of streptozocin, Lipiodol, and tris-acryl microspheres.Patients and MethodsA total of 16 men and 9 women aged 59.6 ± 11.3 years, all with predominant liver disease, underwent 54 courses of TACE using an emulsion of 1.5 g of streptozocin and 10 ml of Lipiodol. Additional embolization was performed using 300–500 µm tris-acryl microspheres. Morphological response was evaluated using the RECIST criteria on multi-detector computed tomography or MRI. Clinical efficacy was evaluated particularly in patients with carcinoid syndrome.ResultsThe primary tumor was located in the small bowel or pancreas in 21 (84%) patients. Eleven (44%) patients presented with a carcinoid syndrome. Nineteen (76%) patients presented with more than 10 liver nodules. One delayed case of ischemic cholecystitis was treated conservatively. After a median follow-up of 36.1 months, 1 (4%) patient had a complete response, 12 (48%) patients had a partial response, and 7 (28%) patients had a stable disease corresponding to a disease control rate of 80%. All patients with carcinoid syndrome had significant improvement. Median time to progression was 18.8 months and overall survival was 100, 100, and 92% at 1, 2, and 3 years, respectively. Seven patients presented with extrahepatic progression with abdominal lymphadenopathies or metastases to the brain, ovary, adrenal gland, or lung.ConclusionOptimized TACE using a combination of streptozocin, Lipiodol, and tris-acryl microspheres is effective and well tolerated.

  7. Somatostatin-based Radiopeptide Therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in Neuroendocrine Tumors

    OpenAIRE

    Romer A Seiler D Marincek N Brunner P Koller MT Ng QK Maecke HR Muller-Brand J Rochlitz C B; riel M and Walter MA

    2014-01-01

    PURPOSE: Somatostatin based radiopeptide treatment is generally performed using the ß emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y DOTA] TOC or [(177)Lu DOTA] TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were emplo...

  8. An elevated serum alkaline phosphatase level in hepatic metastases of grade 1 and 2 gastrointestinal neuroendocrine tumors is unusual and of prognostic value.

    Science.gov (United States)

    Andriantsoa, Maeva; Hoibian, Solene; Autret, Aurelie; Gilabert, Marine; Sarran, Anthony; Niccoli, Patricia; Raoul, Jean-Luc

    2017-01-01

    In our clinical practice we have observed that despite a high hepatic metastatic tumor burden, serum alkaline phosphatase (AP) levels are frequently normal in cases of metastatic neuroendocrine tumor (NET). We retrospectively reviewed the records of patients with grade 1 and 2 NETs with liver metastases but without bone metastases seen at our institution in 2013. In total, 49 patients were included (22 female), with a median age of 60 years (range: 28 to 84 years). The primary tumors were located in the duodenum/pancreas (n = 29), small bowel (n = 17) or colon/rectum (n = 3); 10 cases were grade 1 and 39 grade 2. Hepatic involvement was bulky, with more than 10 lesions in 23 patients and a tumor burden above 10% of the liver volume in 26 patients. Serum AP levels were elevated (≥ upper limit of normal (ULN)) in 16 patients. In multiparametric analysis, elevated serum AP levels were not associated with the primary site, grade, or number or volume of metastases. In multiparametric analysis, progression-free survival was only correlated with grade (p = 0.010) and AP level (p = 0.017). Serum AP levels are frequently normal in liver metastases from NET, even in the event of a major tumor burden, and the serum AP level can be of prognostic value.

  9. The Evolution of Surgical Strategies for Pancreatic Neuroendocrine Tumors (Pan-NENs): Time-trend and Outcome Analysis From 587 Consecutive Resections at a High-volume Institution.

    Science.gov (United States)

    Landoni, Luca; Marchegiani, Giovanni; Pollini, Tommaso; Cingarlini, Sara; D'Onofrio, Mirko; Capelli, Paola; De Robertis, Riccardo; Davì, Maria V; Amodio, Antonio; Impellizzeri, Harmony; Malpaga, Anna; Miotto, Marco; Boninsegna, Letizia; Crepaz, Lorenzo; Nessi, Chiara; Zingaretti, Caterina C; Paiella, Salvatore; Esposito, Alessandro; Casetti, Luca; Malleo, Giuseppe; Tuveri, Massimiliano; Butturini, Giovanni; Salvia, Roberto; Scarpa, Aldo; Falconi, Massimo; Bassi, Claudio

    2017-11-16

    The objective of the present analysis is 2-fold: first, to define the evolution of time trends on the surgical approach to pancreatic neuroendocrine neoplasms (Pan-NENs); second, to perform a complete analysis of the predictors of oncologic outcome. Reflecting their rarity and heterogeneity, Pan-NENs represent a clinical dilemma. In particular, there is a scarcity of data regarding their long-term follow-up after surgical resection. From the Institutional Pan-NEN database, 587 resected cases from 1990 to 2015 were extracted. The time span was arbitrarily divided into 3 discrete clusters enabling a balanced comparison between patient groups. Analyses for predictors of recurrence and survival were performed, together with conditional survival analyses. Among the 587 resected Pan-NENs, 75% were nonfunctioning tumors, and 5% were syndrome-associated tumors. The mean age was 54 years (±14 years), and 51% of the patients were female. The median tumor size was 20 mm (range 4 to 140), 62% were G1, 32% were G2, and 4% were G3 tumors. Time trends analysis revealed that the number of resected Pan-NENs constantly increased, while the size (from 25 to 20 mm) and G1 proportion (from 65% to 49%) decreased during the study period. After a mean follow-up of 75 months, recurrence analysis revealed that nonfunctioning tumors, tumor grade, N1 status, and vascular invasion were all independent predictors of recurrence. Regardless of size, G1 nonfunctioning tumors with no nodal involvement and vascular invasion had a negligible risk of recurrence at 5 years. Pan-NENs have been increasingly diagnosed and resected during the last 3 decades, revealing reliable predictors of outcome. Functioning and nodal status, tumor grade, and vascular invasion accurately predict survival and recurrence with resulting implications for patient follow-up.

  10. Functional imaging of malignant paragangliomas and carcinoid tumours

    Energy Technology Data Exchange (ETDEWEB)

    Le Rest, C.; Bomanji, J.B.; Costa, D.C.; Townsend, C.E.; Visvikis, D.; Ell, P.J. [Middlesex Hospital, London (United Kingdom). Inst. of Nuclear Medicine

    2001-04-01

    Complete staging is mandatory for the management and therapy of neuroendocrine tumours. Various radiotracers are available but the best imaging strategy has yet to be defined. In this study we retrospectively compared {sup 123}I-MIBG, {sup 111}In-[D-Phe{sup 1}]-DTPA-octreotide and {sup 18}F-FDG (PET) imaging in 15 patients with metastatic neuroendocrine tumours (11 carcinoid tumours, 4 paragangliomas). Planar images were acquired 1, 4, 24 and 48 h following the injection of {sup 111}In-[D-Phe{sup 1}]-DTPA-octreotide and {sup 123}I-MIBG. Whole-body PET scans were performed 45 min after injection of {sup 18}F-FDG. {sup 111}In-[D-Phe{sup 1}]-DTPA-octreotide was positive in 11/15 patients and identified 44 lesions, {sup 18}F-FDG PET was positive in 11/15 patients and identified 107 lesions and {sup 123}I-MIBG was positive in 8/15 patients and identified 67 lesions. No single scintigraphic technique identified all metastatic sites. In one patient all studies were negative. {sup 18}F-FDG PET identified more abnormal sites than the other two modalities. Combination of all three imaging modalities with X-ray CT helps to provide a more comprehensive map of the disease. (orig.)

  11. Quadruple valve involvement in a patient with severe carcinoid heart disease.

    Science.gov (United States)

    Chiappini, Bruno; Noirhomme, Philippe; Verhelst, Robert; El Khoury, Gebrine

    2006-01-01

    We report on the case of a 48-year-old male patient suffering from a severe carcinoid heart disease with involvement of the four valves. The primary carcinoid tumor was diagnosed in the ileum. The patient developed a moderate stenosis and severe insufficiency of the tricuspid valve, a severe insufficiency of the pulmonary valve, and a moderate insufficiency of the mitral and aortic valves. Ultimately, a stentless pulmonary valve replacement was performed, as well as a tricuspid valve replacement with a pericardial prosthesis and aortic and mitral valve plasty. The patient recovered well and he was discharged from hospital on day 10.

  12. Left upper lobectomy with bronchoplasty in uniportal video-assisted thoracic surgery for bronchial carcinoid.

    Science.gov (United States)

    Zhang, Zhi; Yuan, Fangliang; Yin, Rong; Xu, Lin

    2016-01-01

    A 36-year-old male smoker presented with a bronchial carcinoid in the left upper lobe (LUL) associated with bronchial occlusion of the LUL bronchus. A left upper lobectomy with bronchoplasty was performed through a 3.5 cm single-incision in video-assisted thoracic surgery (VATS). The procedure was successful and the recovery uneventful. Pathological examination revealed a carcinoid tumor with no lymph node involvement (T1bN0M0). The follow-up bronchoscopy and computed tomography (CT) scan confirmed no stenosis and no signs of recurrence.

  13. Comparison of applied dose and image quality in staging CT of neuroendocrine tumor patients using standard filtered back projection and adaptive statistical iterative reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Böning, G., E-mail: georg.boening@charite.de [Department of Radiology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany); Schäfer, M.; Grupp, U. [Department of Radiology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany); Kaul, D. [Department of Radiation Oncology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany); Kahn, J. [Department of Radiology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany); Pavel, M. [Department of Gastroenterology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany); Maurer, M.; Denecke, T.; Hamm, B.; Streitparth, F. [Department of Radiology, Charité, Humboldt-University Medical School, Charitéplatz 1, 10117 Berlin (Germany)

    2015-08-15

    Highlights: • Iterative reconstruction (IR) in staging CT provides equal objective image quality compared to filtered back projection (FBP). • IR delivers excellent subjective quality and reduces effective dose compared to FBP. • In patients with neuroendocrine tumor (NET) or may other hypervascular abdominal tumors IR can be used without scarifying diagnostic confidence. - Abstract: Objective: To investigate whether dose reduction via adaptive statistical iterative reconstruction (ASIR) affects image quality and diagnostic accuracy in neuroendocrine tumor (NET) staging. Methods: A total of 28 NET patients were enrolled in the study. Inclusion criteria were histologically proven NET and visible tumor in abdominal computed tomography (CT). In an intraindividual study design, the patients underwent a baseline CT (filtered back projection, FBP) and follow-up CT (ASIR 40%) using matched scan parameters. Image quality was assessed subjectively using a 5-grade scoring system and objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNRs). Applied volume computed tomography dose index (CTDI{sub vol}) of each scan was taken from the dose report. Results: ASIR 40% significantly reduced CTDI{sub vol} (10.17 ± 3.06 mGy [FBP], 6.34 ± 2.25 mGy [ASIR] (p < 0.001) by 37.6% and significantly increased CNRs (complete tumor-to-liver, 2.76 ± 1.87 [FBP], 3.2 ± 2.32 [ASIR]) (p < 0.05) (complete tumor-to-muscle, 2.74 ± 2.67 [FBP], 4.31 ± 4.61 [ASIR]) (p < 0.05) compared to FBP. Subjective scoring revealed no significant changes for diagnostic confidence (5.0 ± 0 [FBP], 5.0 ± 0 [ASIR]), visibility of suspicious lesion (4.8 ± 0.5 [FBP], 4.8 ± 0.5 [ASIR]) and artifacts (5.0 ± 0 [FBP], 5.0 ± 0 [ASIR]). ASIR 40% significantly decreased scores for noise (4.3 ± 0.6 [FBP], 4.0 ± 0.8 [ASIR]) (p < 0.05), contrast (4.4 ± 0.6 [FBP], 4.1 ± 0.8 [ASIR]) (p < 0.001) and visibility of small structures (4.5 ± 0.7 [FBP], 4.3 ± 0.8 [ASIR]) (p < 0

  14. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters.

    Science.gov (United States)

    Luque, Raul M; Sampedro-Nuñez, Miguel; Gahete, Manuel D; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D; Castaño, Justo P; Marazuela, Mónica

    2015-08-14

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value.

  15. In1-ghrelin, a splice variant of ghrelin gene, is associated with the evolution and aggressiveness of human neuroendocrine tumors: Evidence from clinical, cellular and molecular parameters

    Science.gov (United States)

    Gahete, Manuel D.; Ramos-Levi, Ana; Ibáñez-Costa, Alejandro; Rivero-Cortés, Esther; Serrano-Somavilla, Ana; Adrados, Magdalena; Culler, Michael D.; Castaño, Justo P.; Marazuela, Mónica

    2015-01-01

    Ghrelin system comprises a complex family of peptides, receptors (GHSRs), and modifying enzymes [e.g. ghrelin-O-acyl-transferase (GOAT)] that control multiple pathophysiological processes. Aberrant alternative splicing is an emerging cancer hallmark that generates altered proteins with tumorigenic capacity. Indeed, In1-ghrelin and truncated-GHSR1b splicing variants can promote development/progression of certain endocrine-related cancers. Here, we determined the expression levels of key ghrelin system components in neuroendocrine tumor (NETs) and explored their potential functional role. Twenty-six patients with NETs were prospectively/retrospectively studied [72 samples from primary and metastatic tissues (30 normal/42 tumors)] and clinical data were obtained. The role of In1-ghrelin in aggressiveness was studied in vitro using NET cell lines (BON-1/QGP-1). In1-ghrelin, GOAT and GHSR1a/1b expression levels were elevated in tumoral compared to normal/adjacent tissues. Moreover, In1-ghrelin, GOAT, and GHSR1b expression levels were positively correlated within tumoral, but not within normal/adjacent samples, and were higher in patients with progressive vs. with stable/cured disease. Finally, In1-ghrelin increased aggressiveness (e.g. proliferation/migration) of NET cells. Altogether, our data strongly suggests a potential implication of ghrelin system in the pathogenesis and/or clinical outcome of NETs, and warrant further studies on their possible value for the future development of molecular biomarkers with diagnostic/prognostic/therapeutic value. PMID:26124083

  16. Tc-99m-EDDA-HYNIC-TOC somatostatin receptor scintigraphy in patients with carcinoids

    Directory of Open Access Journals (Sweden)

    Vlajković Marina

    2014-11-01

    Full Text Available The aim of this paper is to determine the influence of Ki-67 proliferation index on somatostatin receptor scintigraphy (SSRS with Tc-99m-EDDA-HYNIC-TOC (Tc-99m-Tektrotyd somatostatin analogue in patients with carcinoid tumors. Sixty-one patients (31 female, 30 male; age range: 33-76 years were examined: 13 patients highly suspected of having a carcinoid, and 48 patients who had undergone the surgical removal of the tumor. Whole body SSRS at 4 h postinjection, spot scintigrams and SPECT of the selected regions were obtained for all patients. Tc-99m-Tektrotyd scintigraphy was classified as true positive in 26 out of 30 and true negative in 24 out of 28 patients. The sensitivity of Tc-99mTc-Tektrotyd scintigraphy was found to be as high as 94.74% in the group of patients with low mitotic index Ki67 (20%. The likelihood of Tc-99m-Tektrotyd scan being positive when a carcinoid is present was found to be inversely proportional to the value of Ki67 proliferation index. The results showed that Tc-99m-Tektrotyd SSRS is a sensitive method for diagnosing and staging patients with well-differentiated carcinoid tumors. However, in poorly differentiated tumors with high Ki67 proliferation index, additional analyses are necessary for precise staging.

  17. Low plasma tryptophan in carcinoid patients is associated with increased urinary cortisol excretion

    NARCIS (Netherlands)

    Tanke, Marit A. C.; Kema, Ido P.; Dijck-Brouwer, Janneke; Doornbos, Bennard; De Vries, Elisabeth G. E.; Korf, Jakob

    2008-01-01

    Background: Previously we observed inpatients suffering from a metastatic carcinoid tumor that irritability, aggression and lack of impulse control are associated with Low levels of plasma tryptophan and presumably with low brain serotonin function. In rats we showed that a diet of low tryptophan

  18. 64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin αvβ3 Expression in Human Neuroendocrine Tumor Xenografts

    DEFF Research Database (Denmark)

    Oxbøl, Jytte; Schjøth-Eskesen, Christina; El Ali, Henrik H.

    2012-01-01

    Purpose. The purpose of this paper is to evaluate a new PET tracer (64)Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures. Nude mice with human neuroendocrine tumor xenografts (H...... human radiation-absorbed doses were estimated using OLINDA/EXM. Results. Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin α(V) R = 0.76, integrin β(3) R = 0.75 and VEGF-A R = 0.81 (all P body effective dose for humans...... was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion. (64)Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use....

  19. Expression of aldo-keto reductase family 1 member C3 (AKR1C3) in neuroendocrine tumors & adenocarcinomas of pancreas, gastrointestinal tract, and lung.

    Science.gov (United States)

    Chang, Theodore S; Lin, Hsueh-Kung; Rogers, Kyle A; Brame, Lacy S; Yeh, Matthew M; Yang, Qing; Fung, Kar-Ming

    2013-01-01

    Human aldo-keto reductase family 1 member C3 (AKR1C3) was initially identified as an enzyme in reducing 5α-dihydrotestosterone (5α-DHT) to 5α-androstane-3α, 17β-diol (3α-diol) and oxidizing 3α-diol to androsterone. It was subsequently demonstrated to possess ketosteroid reductase activity in metabolizing other steroids including estrogen and progesterone, 11-ketoprostaglandin reductase activity in metabolizing prostaglandins, and dihydrodiol dehydrogenase x (DDx) activity in metabolizing xenobiotics. AKR1C3 was demonstrated in sex hormone-dependent tissues including testis, breast, endometrium, and prostate; in sex hormone-independent tissues including kidney and urothelium. Our previous study described the expression of AKR1C3 in squamous cell carcinoma and adenocarcinoma but not in small cell carcinoma. In this report, we studied the expression of AKR1C3 in normal tissue, adenocarcinomas (43 cases) and neuroendocrine (NE) tumors (40 cases) arising from the aerodigestive tract and pancreas. We demonstrated wide expression of AKR1C3 in superficially located mucosal cells, but not in NE cells. AKR1C3-positive immunoreactivity was detected in 38 cases (88.4%) of adenocarcinoma, but only in 7 cases (17.5%) of NE tumors in all cases. All NE tumors arising from the pancreas and appendix and most tumors from the colon and lung were negative. The highest ratio of positive AKR1C3 in NE tumors was found in tumors arising from the small intestine (50%). These results raise the question of AKR1C3's role in the biology of normal mucosal epithelia and tumors. In addition, AKR1C3 may be a useful adjunct marker for the exclusion of the NE phenotype in diagnostic pathology.

  20. Pancreatic neuroendocrine tumors containing areas of iso- or hypoattenuation in dynamic contrast-enhanced computed tomography: Spectrum of imaging findings and pathological grading.

    Science.gov (United States)

    Hyodo, Ryota; Suzuki, Kojiro; Ogawa, Hiroshi; Komada, Tomohiro; Naganawa, Shinji

    2015-11-01

    To evaluate dynamic contrast-enhanced computed tomography (CT) features of pancreatic neuroendocrine tumors (PNETs) containing areas of iso- or hypoattenuation and the relationship with pathological grading. Between June 2006 and March 2014, 61 PNETs in 58 consecutive patients (29 male, 29 female; median-age 55 years), which were surgically diagnosed, underwent preoperative dynamic contrast-enhanced CT. PNETs were classified based on contrast enhancement patterns in the pancreatic phase: iso/hypo-PNETs were defined as tumors containing areas of iso- or hypoattenuation except for cystic components, and hyper-PNETs were tumors showing hyperattenuation over the whole area. CT findings and contrast-enhancement patterns of the tumors were evaluated retrospectively by two radiologists and compared with the pathological grading. Iso/hypo-PNETs comprised 26 tumors, and hyper-PNETs comprised 35 tumors. Not only hyper-PNETs but also most iso/hypo-PNETs showed peak enhancement in the pancreatic phase and a washout from the portal venous phase to the delayed phase. Iso/hypo-PNETs showed larger tumor size than the hyper-PNETs (mean, 3.7 cm vs. 1.6 cm; PIso/hypo-PNETs also showed significantly higher pathological grading (WHO 2010 classification; iso/hypo, G1=14, G2=11, G3=1; hyper, G1=34, G2=1; Piso/hypo-areas showed a rapid enhancement pattern as well as hyper-PNETs, various radiological features and higher malignant potential. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  1. Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report

    Directory of Open Access Journals (Sweden)

    Karakaş Barış R

    2010-12-01

    Full Text Available Abstract Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

  2. Head-to-head comparison of 64Cu-DOTATATE and 68Ga -DOTATOC PET/CT: a prospective study of 59 patients with neuroendocrine tumors

    DEFF Research Database (Denmark)

    Johnbeck, C.B.; Knigge, U.; Loft, A.

    2016-01-01

    lesions in 13 and 3 patients, respectively. All patients with additional lesions also had concordant lesions found by both scans. Conclusions Although patient based sensitivity was the same for 64Cu-DOTATATE and 68Ga-DOTATOC in this cohort, more lesions were found by 64Cu-DOTATATE. Furthermore the shelve......Somatostatin receptor imaging is a valuable tool in the diagnosis, follow-up and treatment planning of neuroendocrine tumor (NET) patients. Positron emission tomography (PET) based tracers using 68Ga as the radioisotope have in most centers replaced single-photon emission tomography (SPECT) based...... tracers as the gold standard. 64Cu-DOTATATE is a new PET tracer that has been shown to be far superior compared to the SPECT tracer 111In-DTPA-octreotide. Due to advantages of 64Cu compared to 68Ga, we hypothesize that the tracer could have a higher sensitivity than 68Ga-based tracers. To test...

  3. Diabetes, smoking, alcohol use, and family history of cancer as risk factors for pancreatic neuroendocrine tumors: a systematic review and meta-analysis.

    Science.gov (United States)

    Haugvik, Sven-Petter; Hedenström, Per; Korsæth, Emilie; Valente, Roberto; Hayes, Alastair; Siuka, Darko; Maisonneuve, Patrick; Gladhaug, Ivar Prydz; Lindkvist, Björn; Capurso, Gabriele

    2015-01-01

    Risk factors for pancreatic neuroendocrine tumors (PNETs) are not well understood. The aim of this systematic review was to assess if diabetes mellitus, smoking, alcohol use, and family history of cancer are risk factors for PNETs. MEDLINE and abstracts from the European and North American Neuroendocrine Tumor Societies (ENETS and NANETS) were searched for studies published until October 2013. Eligible studies were selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Five studies evaluating 4 individual populations were included (study accrual period 2000-2011) into the meta-analysis, involving 827 cases (range 160-309 per study) and 2,407 controls (range 233-924 per study). All studies had a case-control design and described regional series. The pooled adjusted odds ratio was 2.74 (95% CI: 1.63-4.62; p alcohol use, 2.72 (95% CI: 1.25-5.91; p = 0.01; I(2) = 57.8%) for heavy alcohol use, and 2.16 (95% CI: 1.64-2.85; p cancer. Diabetes mellitus and first-degree family history of cancer are associated with an increased risk of sporadic PNET. There was also a trend for diagnosis of sporadic PNET associated with heavy smoking. Alcohol use may be a risk factor for PNET, but there was considerable heterogeneity in the meta-analysis. These results suggest the need for a larger, homogeneous, international study for the clarification of risk factors for the occurrence of PNET. © 2015 S. Karger AG, Basel.

  4. Improved kit formulation for preparation of (99m)Tc-HYNIC-TOC: results of preliminary clinical evaluation in imaging patients with neuroendocrine tumors.

    Science.gov (United States)

    Korde, Aruna; Mallia, Madhava; Shinto, Ajit; Sarma, H D; Samuel, Grace; Banerjee, Sharmila

    2014-11-01

    (99m)Tc-HYNIC-TOC is a cost-effective and logistically viable agent for scintigraphy of neuroendocrine tumors overexpressing somatostatin receptors as compared with [(111)In-DTPA-D-Phe(1)] Octreotide (Octreoscan(®)). Several studies have been reported, wherein the efficacy of this agent is demonstrated. In the present article, the authors report the preparation of a single-vial HYNIC-TOC kit suitable for the preparation of 4-5 patient doses (15 mCi/patient) of (99m)Tc-HYNIC-TOC. The kits were tested for sterility and bacterial endotoxins to assure safety of the product. A significant modification in this kit is the inclusion of buffer in the kit itself, unlike in commercially available kits where the buffer solution has to be added during preparation. (99m)Tc-HYNIC-TOC was prepared by adding 20-80 mCi (740-2960 MBq) of freshly eluted Na(99m)TcO4 in 1-3 mL of sterile saline directly into the kit vial and heating the vial in a water bath at 100°C for 20 minutes. The labeling yield and radiochemical purity of (99m)Tc-HYNIC-TOC, prepared using the lyophilized cold kit, were consistently >90%. The kits were evaluated over a period of 9 months and found to be stable when stored at -20°C. Limited clinical studies performed with the (99m)Tc-HYNIC-TOC, formulated using the kit, showed adequate sensitivity and specificity for the detection of gasteroenteropancreatic neuroendocrine tumors.

  5. Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

    Science.gov (United States)

    Nocuń, Anna; Chrapko, Beata; Gołębiewska, Renata; Stefaniak, Bogusław; Czekajska-Chehab, Elżbieta

    2011-06-01

    Large cell pulmonary neuroendocrine carcinoma (LCNEC) is a poorly differentiated and high-grade neoplasm. It is positioned between an atypical carcinoid and small cell neuroendocrine carcinoma of the lung in a distinct family of pulmonary neuroendocrine tumors. The aim of our study was to detect somatostatin receptors in this uncommon malignancy and to evaluate the sensitivity of somatostatin receptor scintigraphy (SRS) in LCNEC staging. We analyzed data of 26 patients (mean age: 61.5±7.9 years) with histologically confirmed diagnosis of LCNEC, including 18 cases not treated surgically and eight patients after the resection of the primary tumor. SRS was carried out with technetium-99m ethylene diamine-diacetic acid/hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC). A visual analysis of scintigraphic images was done with reference to conventional imaging modalities (computed tomography and bone sicintigraphy). SRS sensitivity for the detection of primary lesions, supradiaphragmatic metastases, and infradiaphragmatic metastases was 100, 83.3%, and 0%, respectively. Five out of 13 metastases to the liver appeared on SRS as photopenic foci, visible on the background of physiological hepatic activity. Only one of the nine metastases to the skeletal system was found by SRS with sensitivity as low as 11.1%. The overall SRS sensitivity for the detection of secondary lesions and of all lesions was 54.8 and 62.2%, respectively. Within a rather large series of LCNEC, the primary tumor showed an uptake of Tc-TOC in all cases, whereas some metastases did show Tc-TOC uptake and some others did not.

  6. Large cell neuroendocrine carcinoma originating from the uterine endometrium: a report on magnetic resonance features of 2 cases with very rare and aggressive tumor

    Directory of Open Access Journals (Sweden)

    Natsuko Makihara

    2012-06-01

    Full Text Available Neuroendocrine carcinomas (NEC of the female genital tract are aggressive and uncommon tumors, which usually involve the uterine cervix and ovary, and are seen very rarely in the endometrium. Only less than 10 cases of large cell NEC (LCNEC of the endometrium have been reported in the literature and their radiological findings are not well described. We report here two cases of pathologically proven LCNEC of the uterine endometrium. In both cases, the uterine body was enlarged and the tumor occupied part of the uterine cavity. Endometrial mass exhibited heterogeneous high intensity on T2-weighted magnetic resonance (MR images, and diffusion-weighted MR images revealed high intensity throughout the tumor, consistent with malignancy. LCNEC is a highly malignant neoplasm without particular findings in terms of diagnostic imaging and pathology, so its preoperative definitive diagnosis is very difficult. However, when laboratory test, pathologic diagnosis and MR imaging suggest a poorly differentiated uterine malignancy, positron emission tomography-computed tomography scan should be performed as a general assessment to help with diagnosis.

  7. Study of Efficacy and Safety of PDR001 in Patients With Advanced or Metastatic, Well-differentiated, Non-functional Neuroendocrine Tumors of Pancreatic, Gastrointestinal (GI), or Thoracic Origin or Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma (GEP-NEC)

    Science.gov (United States)

    2017-11-15

    Well-differentiated Non-functional NET of Thoracic Origin; Well-differentiated Non-functional NET of Gastrointestinal Origin; Well-differentiated Non-functional NET of Pancreatic Origin; Poorly-differentiated Gastroenteropancreatic Neuroendocrine Carcinoma

  8. Presence of sst5TMD4, a truncated splice variant of the somatostatin receptor subtype 5, is associated to features of increased aggressiveness in pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Sampedro-Núñez, Miguel; Luque, Raúl M; Ramos-Levi, Ana M; Gahete, Manuel D; Serrano-Somavilla, Ana; Villa-Osaba, Alicia; Adrados, Magdalena; Ibáñez-Costa, Alejandro; Martín-Pérez, Elena; Culler, Michael D; Marazuela, Mónica; Castaño, Justo P

    2016-02-09

    Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare and heterogeneous tumors, and their biological behavior is not well known. We studied the presence and potential functional roles of somatostatin receptors (sst1-5), focusing particularly on the truncated variants (sst5TMD4, sst5TMD5) and on their relationships with the angiogenic system (Ang/Tie-2 and VEGF) in human GEP-NETs. We evaluated 42 tumor tissue samples (26 primary/16 metastatic) from 26 patients with GEP-NETs, and 30 non-tumoral tissues (26 from adjacent non-tumor regions and 4 from normal controls) from a single center. Expression of sst1-5, sst5TMD4, sst5TMD5, Ang1-2, Tie-2 and VEGF was analyzed using real-time qPCR, immunofluorescence and immunohistochemistry. Expression levels were associated with tumor characteristics and clinical outcomes. Functional role of sst5TMD4 was analyzed in GEP-NET cell lines. sst1 exhibited the highest expression in GEP-NET, whilst sst2 was the most frequently observed sst-subtype (90.2%). Expression levels of sst1, sst2, sst3, sst5TMD4, and sst5TMD5 were significantly higher in tumor tissues compared to their adjacent non-tumoral tissue. Lymph-node metastases expressed higher levels of sst5TMD4 than in its corresponding primary tumor tissue. sst5TMD4 was also significantly higher in intestinal tumor tissues from patients with residual disease of intestinal origin compared to those with non-residual disease. Functional assays demonstrated that the presence of sst5TMD4 was associated to enhanced malignant features in GEP-NET cells. Angiogenic markers correlated positively with sst5TMD4, which was confirmed by immunohistochemical/fluorescence studies. sst5TMD4 is overexpressed in GEP-NETs and is associated to enhanced aggressiveness, suggesting its potential value as biomarker and target in GEP-NETs.

  9. Comparative evaluation of three proliferation markers, Ki-67, TOP2A, and RacGAP1, in bronchopulmonary neuroendocrine neoplasms: Issues and prospects.

    Science.gov (United States)

    Neubauer, Elisa; Wirtz, Ralph M; Kaemmerer, Daniel; Athelogou, Maria; Schmidt, Lydia; Sänger, Jörg; Lupp, Amelie

    2016-07-05

    The classification of bronchopulmonary neuroendocrine neoplasms (BP-NEN) into four tumor entities (typical carcinoids (TC), atypical carcinoids (AC), small cell lung cancers (SCLC), large cell neuroendocrine lung carcinomas (LCNEC)) is difficult to perform accurately, but important for prognostic statements and therapeutic management decisions. In this regard, we compared the expression of three proliferation markers, Ki-67, Topoisomerase II alpha (TOP2A), and RacGAP1, in a series of tumor samples from 104 BP-NEN patients (24 TC, 21 AC, 52 SCLC, 7 LCNEC) using different evaluation methods (immunohistochemistry (IHC): Average evaluation, Hotspot evaluation, digital image analysis; RT-qPCR).The results indicated that all three markers had increased protein and mRNA expression with poorer differentiation and correlated well with each other, as well as with grading, staging, and poor survival. Compared with Ki-67 and TOP2A, RacGAP1 allowed for a clearer prognostic statement. The cut-off limits obtained for Ki-67-Average (IHC) were TC-AC 1.5, AC-SCLC 19, and AC-LCNEC 23.5. The Hotspot evaluation generated equal to higher, the digital image analysis generally lower between-entity cut-off limits.All three markers enabled a clear-cut differentiation between the BP-NEN entities, and all methods evaluated were suitable for marker assessment. However, to define optimal cut-off limits, the Ki-67 evaluation methods should be standardized. RacGAP1 appeared to be a new marker with great potential.

  10. Karcinoide tumorer og gobletcelle-karcinoide tumorer i appendix

    DEFF Research Database (Denmark)

    Knigge, Ulrich; Hansen, Carsten Palnaes

    2010-01-01

    Appendiceial carcinoid tumors (CAT) and goblet cell carcinoids (GCCAT) are rare. Most are asymptomatic and found after appendectomy. Metastases to regional nodes are seen in 10% of CATs larger than two cm. Ovarian or peritoneal metastases are seen in 20% of all GCCATs. Further surgical treatments...

  11. Carcinoid Tumor in Accidental, Asymptomatic Meckel's Diverticulum ...

    African Journals Online (AJOL)

    Although Meckel's diverticulum is the most common congenital gastrointestinal disorder, it is controversial whether asymptomatic diverticula in adults should be respected. The authors report the case of a patient who was operated due to ileus caused by adhesions and a Meckel's diverticulum without any sign of ...

  12. General Information about Gastrointestinal Carcinoid Tumors

    Science.gov (United States)

    ... include the following: Redness or a feeling of warmth in the face and neck. Abdominal pain. Feeling ... is checked to measure the amounts of certain substances, such as hormones, released into the blood by ...

  13. Treatment Options for Gastrointestinal Carcinoid Tumors

    Science.gov (United States)

    ... include the following: Redness or a feeling of warmth in the face and neck. Abdominal pain. Feeling ... is checked to measure the amounts of certain substances, such as hormones, released into the blood by ...

  14. Treatment Option Overview (Gastrointestinal Carcinoid Tumors)

    Science.gov (United States)

    ... include the following: Redness or a feeling of warmth in the face and neck. Abdominal pain. Feeling ... is checked to measure the amounts of certain substances, such as hormones, released into the blood by ...

  15. The Impact of Somatostatin Receptor-Directed PET/CT on the Management of Patients with Neuroendocrine Tumor: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Barrio, Martin; Czernin, Johannes; Fanti, Stefano; Ambrosini, Valentina; Binse, Ina; Du, Lin; Eiber, Matthias; Herrmann, Ken; Fendler, Wolfgang P

    2017-05-01

    Somatostatin receptor (SSTR) imaging is widely used for guiding the management of neuroendocrine tumor (NET) patients. 68 Ga-DOTATATE approval by the U.S. Food and Drug Administration has triggered widespread clinical interest in SSTR PET/CT throughout the United States. Here, we performed a systematic review and meta-analysis to evaluate the impact of SSTR PET/CT on the management of patients with NETs. Methods: A comprehensive literature search was performed using The National Center for Biotechnology Information PubMed online database, applying the following key words: "management" AND "PET" AND "neuroendocrine". Fourteen of 190 studies were deemed suitable based on the following inclusion criteria: original research, cohort study, number of patients 10 or more, and reported change in management after SSTR PET/CT. Change in management across studies was determined by a random-effects model. Results: A total of 1,561 patients were included. Overall, change in management occurred in 44% (range, 16%-71%) of NET patients after SSTR PET/CT. In 4 of 14 studies, SSTR PET/CT was performed after an 111 In-Octreotide scan. In this subgroup, additional information by SSTR PET/CT led to a change in management in 39% (range, 16%-71%) of patients. Seven of 14 studies differentiated between inter- and intramodality changes, with most changes being intermodality (77%; intramodality, 23%). Conclusion: The management was changed in more than one third of patients undergoing SSTR PET/CT even when performed after an 111 In-Octreotide scan. Intermodality changes were 3 times more likely than intramodality changes, underlining the clinical impact of SSTR PET/CT. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  16. Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study.

    Science.gov (United States)

    Ballal, Sanjana; Yadav, Madhav P; Damle, Nishikant A; Sahoo, Ranjit K; Bal, Chandrasekhar

    2017-11-01

    The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors. One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively. There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/μL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression. Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

  17. The prognostic and predictive value of sstr{sub 2}-immunohistochemistry and sstr{sub 2}-targeted imaging in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Brunner, Philippe [University Hospital Basel, Institute of Pathology (Switzerland); University Hospital Basel, Institute of Nuclear Medicine (Switzerland); Joerg, Ann-Catherine; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine (Switzerland); Glatz, Katharina; Bubendorf, Lukas [University Hospital Basel, Institute of Pathology (Switzerland); Radojewski, Piotr; Umlauft, Maria; Spanjol, Petar-Marko; Krause, Thomas; Dumont, Rebecca A.; Walter, Martin A. [University Hospital Bern, Institute of Nuclear Medicine (Switzerland); Marincek, Nicolas [University Hospital Basel, Institute of Nuclear Medicine (Switzerland); University Hospital Bern, Institute of Nuclear Medicine (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry (Switzerland); Briel, Matthias [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schmitt, Anja; Perren, Aurel [University Bern, Institute of Pathology, Bern (Switzerland)

    2017-03-15

    Our aim was to assess the prognostic and predictive value of somatostatin receptor 2 (sstr{sub 2}) in neuroendocrine tumors (NETs). We established a tissue microarray and imaging database from NET patients that received sstr{sub 2}-targeted radiopeptide therapy with yttrium-90-DOTATOC, lutetium-177-DOTATOC or alternative treatment. We used univariate and multivariate analyses to identify prognostic and predictive markers for overall survival, including sstr{sub 2}-imaging and sstr{sub 2}-immunohistochemistry. We included a total of 279 patients. In these patients, sstr{sub 2}-immunohistochemistry was an independent prognostic marker for overall survival (HR: 0.82, 95 % CI: 0.67 - 0.99, n = 279, p = 0.037). In DOTATOC patients, sstr{sub 2}-expression on immunohistochemistry correlated with tumor uptake on sstr{sub 2}-imaging (n = 170, p < 0.001); however, sstr{sub 2}-imaging showed a higher prognostic accuracy (positive predictive value: +27 %, 95 % CI: 3 - 56 %, p = 0.025). Sstr{sub 2}-expression did not predict a benefit of DOTATOC over alternative treatment (p = 0.93). Our results suggest sstr{sub 2} as an independent prognostic marker in NETs. Sstr{sub 2}-immunohistochemistry correlates with sstr{sub 2}-imaging; however, sstr{sub 2}-imaging is more accurate for determining the individual prognosis. (orig.)

  18. Management of occult adrenocorticotropin-secreting bronchial carcinoids: limits of endocrine testing and imaging techniques.

    Science.gov (United States)

    Loli, P; Vignati, F; Grossrubatscher, E; Dalino, P; Possa, M; Zurleni, F; Lomuscio, G; Rossetti, O; Ravini, M; Vanzulli, A; Bacchetta, C; Galli, C; Valente, D

    2003-03-01

    The differential diagnosis and the identification of the source of ACTH in occult ectopic Cushing's syndrome due to a bronchial carcinoid still represents a challenge for the endocrinologist. We report our experience in six patients with occult bronchial carcinoid in whom extensive hormonal, imaging, and scintigraphic evaluation was performed. All patients presented with hypercortisolism associated with high plasma ACTH values. The CRH test and high dose dexamethasone suppression test suggested an ectopic source of ACTH in three of six patients. During bilateral inferior petrosal sinus sampling, none of the patients showed a central to peripheral ACTH gradient. At the time of diagnosis, none of the patients had radiological evidence of the ectopic source of ACTH, whereas pentetreotide scintigraphy identified the lesion in two of four patients. Finally, a chest computed tomography scan revealed the presence of a bronchial lesion in all patients, and pentetreotide scintigraphy identified four of six lesions. In all patients a bronchial carcinoid was found and removed. In one patient with scintigraphic evidence of residual disease after two operations, radioguided surgery, using a hand-held gamma probe after iv administration of radiolabeled pentetreotide, was performed; this allowed detection and removal of residual multiple mediastinal lymph node metastases. In conclusion, our data show that there is not a single endocrine test or imaging procedure accurate enough to diagnose and localize occult ectopic ACTH-secreting bronchial carcinoids. Radioguided surgery appears to be promising in the presence of multiple tumor foci and previous incomplete removal of the tumor.

  19. Performance of 177Lu-DOTATATE-based peptide receptor radionuclide therapy in metastatic gastroenteropancreatic neuroendocrine tumor: a multiparametric response evaluation correlating with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics.

    Science.gov (United States)

    Thapa, Pradeep; Ranade, Rohit; Ostwal, Vikas; Shrikhande, Shailesh V; Goel, Mahesh; Basu, Sandip

    2016-10-01

    To assess the performance of Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in metastatic gastroenteropancreatic neuroendocrine tumor (GEP-NET) and correlate it with primary tumor site, tumor proliferation index, and dual tracer imaging characteristics. Fifty patients (M : F 33 : 17, age: 26-71 years) with histopathologically confirmed metastatic/inoperable NETs who had undergone at least three cycles of PRRT with Lu-DOTATATE were included in the analysis. As part of the pretreatment evaluation, they underwent either Tc-HYNIC TOC (n=40)/Ga-DOTATATE PET (n=10) or fluorine-18-fluorodeoxyglucose (F-FDG) PET-computed tomography (CT). Response was assessed after three and five cycles PRRT on the basis of three parameters: (a) symptomatic and subjective scale, (b) biochemical tumor marker level, and (c) objective imaging (F-FDG/Ga DOTATATE PET/CT, Tc-HYNIC TOC, ceCT), and was categorized using predefined criteria (detailed in methods). Stable disease on imaging assessment with response on symptomatic or biochemical tumor marker scales or both were included in the responder group. The study population was broadly classified into (a) metastatic GEP-NET with known primary (n=43 i.e. 86%), which was further subclassified according to the site of primary and (b) those with unknown primary (n=7 i.e. 14%). Symptomatic response: 96% of patients showed a symptomatic response or improvement in health-related quality of life, irrespective of tumor proliferation index, dual tracer imaging characteristics, and response or progression of disease in the scan. Biochemical tumor marker response: 83% of scan responders showed a decrease, 10% showed a stable value, and 7% showed an increase in tumor marker levels. Among the scan nonresponders, 67% patients showed a corresponding increase in the tumor marker level, 22% patient showed a decrease, whereas 11% showed stable values. Scan response: 31 out of total 50 patients (62%) showed a partial scan response with either a

  20. Role of hepatic resection for patients with carcinoid heart disease

    DEFF Research Database (Denmark)

    Bernheim, A.M.; Connolly, H.M.; Rubin, J.

    2008-01-01

    OBJECTIVE: To evaluate the effects of resection of hepatic carcinoid metastases on progression and prognosis of carcinoid heart disease. PATIENTS AND METHODS: From our database of 265 consecutive patients diagnosed as having carcinoid heart disease from January 1, 1980, through December 31, 2005,...

  1. Carcinoid heart disease secondary to ovarian tumour: a logical ...

    African Journals Online (AJOL)

    There are only few reported cases of carcinoid heart disease caused by ovarian tumours. The main cause of morbidity and mortality in these patients is right heart failure. Most cases of carcinoid heart disease have liver metastases and undergo cardiac surgery, followed by liver resection. Ovarian carcinoids cause heart ...

  2. Study on histogenesis of enterochromaffin-like carcinoid in autoimmune atrophic gastritis associated with pernicious anemia

    Directory of Open Access Journals (Sweden)

    Mačukanović-Golubović Lana

    2007-01-01

    Full Text Available Background/Aim. Autoimmune atrophic fundic gastritis induces the pernicious anemia (PA, as well as the changes in both epithelium and endocrine cells of gastric mucosa. The most important complications are: achlorhydria, hypergastrinemia, gastric cancer and enterochromaffin-like ( ECL carcinoid. The aim of this study was to examine ECL carcinoid histogenesis in A-gastritis associated with PA. Methods. During the period from 2000−2006, 65 patients with PA and 30 patients of the control group were examined. Histopathological examination was done in endoscopical biopsies of gastric mucosa fixed in 10% formaldehyde. Paraffin sections were stained with classic hematoxylin-eosin (HE; histochemical AB-PAS (pH 2.5, cytochemical argyrophilic Servier-Munger′s and immunocytochemical PAP methods for G cell identification and chromogranin A antibodies - specific marker for neuroendocrine ECL cells. Both G and ECL cells were counted per 20 fields, of surface 0.0245312 mm2 by a field. Basal gastrin serum levels were also examined by using radioimmunoassay (RIA method. The obtained results were statisticaly calculated by using Student΄s t test. Results. Marked antral G cell hyperplasia associated with corporal ECL hyperplasia was found. ECL cell hyperplasia was of simplex, linear, adenomatoid type to the pattern of intramucous ECL cell carcinoid. An average number of G cells was statistically significant in the patients with PA as compared to the control group (p < 0.05 as well as an average number of ECL cells. Conclusion. We concluded that antral G cell hyperplasia accompanied by gastrinemia induces ECL hyperplasia and ECL corporal carcinoid in A-gastritis and that their histogenesis develops trough simple, linear and adenomatoide hyperplasia. .

  3. [Neuroendocrine neoplasms of the breast].

    Science.gov (United States)

    Anlauf, M; Neumann, M; Bomberg, S; Luczak, K; Heikaus, S; Gustmann, C; Antke, C; Ezziddin, S; Fottner, C; Pavel, M; Pape, U-F; Rinke, A; Lahner, H; Schott, M; Cremer, B; Hörsch, D; Baum, R P; Groh, U; Alkatout, I; Rudlowski, C; Scheler, P; Zirbes, T K; Hoffmann, J; Fehm, T; Gabbert, H E; Baldus, S E

    2015-05-01

    Neuroendocrine neoplasms (NEN) of the breast are specific tumor entities. According to the literature up to 5% of breast neoplasms are malignant epithelial neoplasms of the breast. They are defined by a neuroendocrine (NE) architecture and cytology combined with an expression of the neuroendocrine vesicle markers chromogranin A and/or synaptophysin. The diagnosis is supplemented by the receptor status and the proliferative activity. According to the World Health Organization (WHO) classification of 2012 the following groups of NEN are distinguished: (1) invasive breast carcinoma with NE differentiation, (2) well-differentiated neuroendocrine tumor (NET) and (3) poorly differentiated small cell carcinoma (NEC). This review article focuses on (1) the definition and basic principles of diagnostics, (2) the history, nomenclature and WHO classification from 2003 and 2012, (3) the frequency of breast NEN, (4) the hereditary background and functional activity, (5) the expression of receptors and (6) the possible clinical implications. In addition, the first results of a retrospective single center study (n = 465 patients with breast cancer over a time period of 4 years) on the frequency of NEN of the breast at the Breast Center of the University Hospital Düsseldorf are presented. In this study a frequency of 4.5% of NEN was found based on a diagnostic cut-off of > 50% Chromogranin A and/or synaptophysin positive tumor cells.

  4. SOX4, SOX11 and PAX6 mRNA expression was identified as a (prognostic) marker for the aggressiveness of neuroendocrine tumors of the lung by using next-generation expression analysis (NanoString).

    Science.gov (United States)

    Walter, Robert Fred Henry; Mairinger, Fabian Dominik; Werner, Robert; Ting, Saskia; Vollbrecht, Claudia; Theegarten, Dirk; Christoph, Daniel Christian; Zarogoulidis, Konstantinos; Schmid, Kurt Werner; Zarogoulidis, Paul; Wohlschlaeger, Jeremias

    2015-01-01

    Neuroendocrine tumors of the lung (NELC) account for 25% of all lung cancer cases and transcription factors may drive dedifferentiation of these tumors. This study was conducted to identify supportive diagnostic and prognostic biomarkers. A total of 16 TC, 13 AC, 16 large cell neuroendocrine carcinomas and 15 small cell lung cancer were investigated for the mRNA expression of 11 transcription factors and related genes (MYB, MYBBP1A, OCT4, PAX6, PCDHB, RBP1, SDCBP, SOX2, SOX4, SOX11, TEAD2). SOX4 (p = 0.0002), SOX11 (p < 0.0001) and PAX6 (p = 0.0002) were significant for tumor type. Elevated PAX6 and SOX11 expression correlated with poor outcome in large cell neuroendocrine carcinomas and small cell lung cancer (p < 0.0001 and p = 0.0232, respectively) based on survival data of 34 patients (57%). Aggressiveness of NELC correlated with increasing expression of transcription factors. SOX11 seems to be a highly valuable diagnostic and prognostic marker for aggressive NELC.

  5. The Synergistic Effect of Pasireotide and Teriflunomide in Carcinoids in vitro

    Science.gov (United States)

    Somnay, Yash; Chen, Herbert; Kunnimalaiyaan, Muthusamy

    2012-01-01

    Background/Aim Somatostatin analogs are mainstay for controlling tumor proliferation and hormone secretion in carcinoid patients. Recent data suggest that ERK1/2 phosphorylation may potentiate the anti-tumor effects of somatostatin analogs in carcinoids. Additionally, ERK1/2 phosphorylating agents have been shown to suppress biomarker expression in carcinoids. Thus, Raf-1/MEK/ERK1/2 pathway activating drugs may be synergistic with somatostatin analogs such as Pasireotide (SOM230), which may be more effective than others in its class given its elevated receptor affinity and broader binding spectrum. Here, we investigate the effects of SOM230 in combination with Teriflunomide (TFN), a Raf-1 activator, in a human carcinoid cell line. Methods Human pancreatic carcinoid cells (BON) were incubated in TFN, SOM230 or a combination. Cell proliferation was measured using a rapid colorimetric assay. Western analysis was performed to analyze expression levels of achaete-scute complex-like1 (ASCL1), Chromogranin A (CgA), phosphorylated and total ERK1/2, and markers for apoptosis. Results Combination treatment with SOM230 and TFN reduced cell growth beyond the additive effect of either drug alone. Combination indices (CI) fell below 1, thus quantifiably verifying synergy between both drugs as per the Chou-Talalay CI scale. Combined treatment also reduced ASCL1 and CgA expression beyond the additive effect of either drug alone. Furthermore, it increased levels of phosphorylated ERK1/2, cleaved PARP and caspase-3, and reduced levels of anti-apoptotic biomarkers. Elevated phosphorylated ERK1/2 expression following combination therapy may underlie the synergistic interaction between the two drugs. Conclusion Since efficacy is achieved at lower doses, combination therapy may palliate symptoms at low toxicity levels. Because each drug has already been evaluated in clinical trials, combinatorial drug trials are warranted. PMID:22965070

  6. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  7. Compensatory activation of Akt in response to mTOR and Raf inhibitors - a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease.

    Science.gov (United States)

    Zitzmann, Kathrin; Rüden, Janina von; Brand, Stephan; Göke, Burkhard; Lichtl, Jennifer; Spöttl, Gerald; Auernhammer, Christoph J

    2010-09-01

    Several studies have established a link between aberrant PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling and neuroendocrine tumor disease. In this study, we comparatively investigate the antitumor potential of novel small-molecule inhibitors targeting mTOR (RAD001), mTOR/PI(3)K (NVP-BEZ235) and Raf (Raf265) on human NET cell lines of heterogeneous origin. All inhibitors induced potent antitumor effects which involved the induction of apoptosis and G0/G1 arrest. However, the dual mTOR/PI(3)K inhibitor NVP-BEZ235 was more efficient compared to the single mTOR inhibitor RAD001. Consistently, NVP-BEZ235 prevented the negative feedback activation of Akt as observed after treatment with RAD001. Raf265 inhibited Erk1/2 phosphorylation but strongly induced Akt phosphorylation and VEGF secretion, suggesting the existence of a compensatory feedback loop on PI3K-Akt signaling. Finally, combined treatment with RAD001 or NVP-BEZ235 and Raf265 was more efficient than single treatment with either kinase inhibitor. Together, our data provide a rationale for dual targeting of PI(3)K-Akt-mTOR- and Ras-Raf-MEK-Erk1/2 signaling in NET disease. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  8. Dual tracer functional imaging of gastroenteropancreatic neuroendocrine tumors using 68Ga-DOTA-NOC PET-CT and 18F-FDG PET-CT: competitive or complimentary?

    Science.gov (United States)

    Naswa, Niraj; Sharma, Punit; Gupta, Santosh Kumar; Karunanithi, Sellam; Reddy, Rama Mohan; Patnecha, Manish; Lata, Sneh; Kumar, Rakesh; Malhotra, Arun; Bal, Chandrasekhar

    2014-01-01

    This study aimed to compare the diagnostic performance of Ga-DOTANOC PET/CT with F-FDG PET/CT in the patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Data of 51 patients with definite histological diagnosis of GEP-NET who underwent both Ga-DOTA-NOC PET-CT and F-FDG PET-CT within a span of 15 days were selected for this retrospective analysis. Sensitivity, specificity, and predictive values were calculated for Ga-DOTA-NOC PET-CT and F-FDG PET-CT, and results were compared both on patientwise and regionwise analysis. Ga-DOTA-NOC PET-CT is superior to F-FDG PET-CT on patientwise analysis (P NOC PET-CT is superior to F-FDG PET-CT only for lymph node metastases (P NOC PET-CT detected more liver and skeletal lesions compared with F-FDG PET-CT, the difference was not statistically significant. In addition, the results of combined imaging helped in selecting candidates who would undergo the appropriate mode of treatment, whether octreotide therapy or conventional chemotherapy Ga-DOTA-NOC PET-CT seems to be superior to F-FDG PET-CT for imaging GEP-NETs. However, their role seems to be complementary because combination of Ga-DOTA-NOC PET-CT and F-FDG PET-CT in such patients helps demonstrate the total disease burden and segregate them to proper therapeutic groups.

  9. Improvement in Stress, General Self-Efficacy, and Health Related Quality of Life following Patient Education for Patients with Neuroendocrine Tumors: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Trude Haugland

    2013-01-01

    Full Text Available The purpose of the study was to evaluate changes in general self-efficacy, health related quality of life (HRQoL, and stress among patients with neuroendocrine tumors (NET following a multidisciplinary educational intervention. Forty-one patients were enrolled in this exploratory pilot study. A total of 37 patients completed the full 26-week intervention based on the principles of self-efficacy. General self-efficacy was measured by the General Self-Efficacy Scale, HRQoL was measured with the SF-36, and stress was measured with the Impact of Event Scale. Mixed effect models were used to evaluate changes in general self-efficacy, mental and physical components of HRQoL, and stress adjusting for demographic and clinical variables. Results showed significant improvements in patients’ general self-efficacy (β = 0.71; P<0.05, physical component scores of HRQoL (β = 3.09; P<0.01, and stress (β=-2.10, P=0.008. Findings suggest that patients with NET have the capacity to improve their ability to cope with their disease, problem-solve, improve their physical status, and reduce their stress following an educational intervention based on the principles of self-efficacy. These preliminary data provide a basis for future randomized controlled trials to test interventions to improve HRQoL for patients with NET.

  10. The selective PI3Kα inhibitor BYL719 as a novel therapeutic option for neuroendocrine tumors: Results from multiple cell line models.

    Directory of Open Access Journals (Sweden)

    Svenja Nölting

    Full Text Available The therapeutic options for metastatic neuroendocrine tumors (NETs are limited. As PI3K signaling is often activated in NETs, we have assessed the effects of selective PI3Kp110α inhibition by the novel agent BYL719 on cell viability, colony formation, apoptosis, cell cycle, signaling pathways, differentiation and secretion in pancreatic (BON-1, QGP-1 and pulmonary (H727 NET cell lines.Cell viability was investigated by WST-1 assay, colony formation by clonogenic assay, apoptosis by caspase3/7 assay, the cell cycle by FACS, cell signaling by Western blot analysis, expression of chromogranin A and somatostatin receptors 1/2/5 by RT-qPCR, and chromogranin A secretion by ELISA.BYL719 dose-dependently decreased cell viability and colony formation with the highest sensitivity in BON-1, followed by H727, and lowest sensitivity in QGP-1 cells. BYL719 induced apoptosis and G0/G1 cell cycle arrest associated with increased p27 expression. Western blots showed inhibition of PI3K downstream targets to a varying degree in the different cell lines, but IGF1R activation. The most sensitive BON-1 cells displayed a significant, and H727 cells a non-significant, GSK3 inhibition after BYL719 treatment, but these effects do not appear to be mediated through the IGF1R. In contrast, the most resistant QGP-1 cells showed no GSK3 inhibition, but a modest activation, which would partially counteract the other anti-proliferative effects. Accordingly, BYL719 enhanced neuroendocrine differentiation with the strongest effect in BON-1, followed by H727 cells indicated by induction of chromogranin A and somatostatin receptor 1/2 mRNA-synthesis, but not in QGP-1 cells. In BON-1 and QGP-1 cells, the BYL719/everolimus combination was synergistic through simultaneous AKT/mTORC1 inhibition, and significantly increased somatostatin receptor 2 transcription compared to each drug separately.Our results suggest that the agent BYL719 could be a novel therapeutic approach to the

  11. Comparison of applied dose and image quality in staging CT of neuroendocrine tumor patients using standard filtered back projection and adaptive statistical iterative reconstruction.

    Science.gov (United States)

    Böning, G; Schäfer, M; Grupp, U; Kaul, D; Kahn, J; Pavel, M; Maurer, M; Denecke, T; Hamm, B; Streitparth, F

    2015-08-01

    To investigate whether dose reduction via adaptive statistical iterative reconstruction (ASIR) affects image quality and diagnostic accuracy in neuroendocrine tumor (NET) staging. A total of 28 NET patients were enrolled in the study. Inclusion criteria were histologically proven NET and visible tumor in abdominal computed tomography (CT). In an intraindividual study design, the patients underwent a baseline CT (filtered back projection, FBP) and follow-up CT (ASIR 40%) using matched scan parameters. Image quality was assessed subjectively using a 5-grade scoring system and objectively by determining signal-to-noise ratio (SNR) and contrast-to-noise ratios (CNRs). Applied volume computed tomography dose index (CTDIvol) of each scan was taken from the dose report. ASIR 40% significantly reduced CTDIvol (10.17±3.06mGy [FBP], 6.34±2.25mGy [ASIR] (pASIR]) (pASIR]) (pASIR]), visibility of suspicious lesion (4.8±0.5 [FBP], 4.8±0.5 [ASIR]) and artifacts (5.0±0 [FBP], 5.0±0 [ASIR]). ASIR 40% significantly decreased scores for noise (4.3±0.6 [FBP], 4.0±0.8 [ASIR]) (pASIR]) (pASIR]) (pASIR can be used to reduce radiation dose without sacrificing image quality and diagnostic confidence in staging CT of NET patients. This may be beneficial for patients with frequent follow-up and significant cumulative radiation exposure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Gene Expression of Glucose Transporter 1 (GLUT1, Hexokinase 1 and Hexokinase 2 in Gastroenteropancreatic Neuroendocrine Tumors: Correlation with F-18-fluorodeoxyglucose Positron Emission Tomography and Cellular Proliferation

    Directory of Open Access Journals (Sweden)

    Andreas Kjaer

    2013-10-01

    Full Text Available Neoplastic tissue exhibits high glucose utilization and over-expression of glucose transporters (GLUTs and hexokinases (HKs, which can be imaged by 18F-Fluorodeoxyglucose-positron emission tomography (FDG-PET. The aim of the present study was to investigate the expression of glycolysis-associated genes and to compare this with FDG-PET imaging as well as with the cellular proliferation index in two cancer entities with different malignant potential. Using real-time PCR, gene expression of GLUT1, HK1 and HK2 were studied in 34 neuroendocrine tumors (NETs in comparison with 14 colorectal adenocarcinomas (CRAs. The Ki67 proliferation index and, when available, FDG-PET imaging was compared with gene expression. Overexpression of GLUT1 gene expression was less frequent in NETs (38% compared to CRAs (86%, P = 0.004. HK1 was overexpressed in 41% and 71% of NETs and CRAs, respectively (P = 0.111 and HK2 was overexpressed in 50% and 64% of NETs and CRAs, respectively (P = 0.53. There was a significant correlation between the Ki67 proliferation index and GLUT1 gene expression for the NETs (R = 0.34, P = 0.047, but no correlation with the hexokinases. FDG-PET identified foci in significantly fewer NETs (36% than CRAs (86%, (P = 0.04. The gene expression results, with less frequent GLUT1 and HK1 upregulation in NETs, confirmed the lower metabolic activity of NETs compared to the more aggressive CRAs. In accordance with this, fewer NETs were FDG-PET positive compared to CRA tumors and FDG uptake correlated with GLUT1 gene expression.

  13. 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 (Roger); 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

  14. Neuroendokrine Tumore (NET des Gastrointestinaltraktes: Nuklearmedizinische Optionen in Diagnose und Therapie // Neuroendocrine Tumours (NET of the Gastrointestinal Tract: Nuclear Medicine Methods in Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Gabriel M

    2017-01-01

    Full Text Available In the diagnosis of tumours of neuroendocrine origin PET-CT plays a central role using 68Ga-DOTA-conjugated peptides. In addition to primary diagnosis with clinical and biochemical suspicion, this diagnostic procedure also is essential for staging and further therapy decision, showing in many cases better diagnostic performance than radiological cross-sectional imaging. The detection of unexpected lesions changes therapy management in about one-third of cases. In addition, the 18F-FDG, which is mainly used in non-neuroendocrine tumours, can be an option in poorly differentiated neuroendocrine tumours (NET and, to a certain extent, for estimation of prognosis.br New findings in a prospective randomized multicentre study (NETTER-1 Phase III study strongly confirm the efficacy and safety of radionuclide peptide therapy (PRRT using 177Lu-DOTATATE (Lutathera®. It has been used in several European and US centers including a total of 230 patients with a grade 1–2 midgut tumours. It is evident from the data so far that patients with advanced midgut NETs who are treated with Lutathera have a statistically significantly longer PFS and the OS might be also positively influenced. Although no comparable prospective ranomized study is available for 90Y-DOTA-TOC so far, a comparable therapy efficiency and also good tolerability can be assumed for this compound as indicated by numerous monocentric studies with an overall high number of patients being treated.br In patients with preferential hepatic involvement, the selective internal radiotherapy (SIRT, also called radioembolisation, represents a possible alternative for the local intrahepatic radiation treatment of liver metastases.br bKurzfassung:/b Bei der Diagnose von Tumoren neuroendokrinen Ursprungs spielt die PET-CT mittels 68Ga-DOTA-konjugierter Peptide eine zentrale Rolle. Neben der Primärdiagnose bei klinischem und biochemischem Verdacht erweist sich dieses Diagnoseverfahren auch bei der

  15. Peptide Receptor Radionuclide Therapy with177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

    Science.gov (United States)

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was

  16. Is there a role for near-infrared technology in laparoscopic resection of pancreatic neuroendocrine tumors? Results of the COLPAN "colour-and-resect the pancreas" study.

    Science.gov (United States)

    Paiella, Salvatore; De Pastena, Matteo; Landoni, Luca; Esposito, Alessandro; Casetti, Luca; Miotto, Marco; Ramera, Marco; Salvia, Roberto; Secchettin, Erica; Bonamini, Deborah; Manzini, Gessica; D'Onofrio, Mirko; Marchegiani, Giovanni; Bassi, Claudio

    2017-11-01

    The intraoperative identification of pancreatic neuroendocrine tumors (PanNETs) is of utmost importance to drive their laparoscopic resection. Near-infrared (NIR) surgery has emerged as a new technique for localizing tumors or neoplastic tissue. This study aimed to explore the results of the application of NIR in the laparoscopic resection of PanNETs. Per protocol we enrolled ten subjects undergoing laparoscopic pancreatic surgery for PanNET from March 2016 to October 2016. During surgery, the patients were injected with indocyanine green dye (ICG, 25 mg given in 5 boli of 5 mg each). The switch-activation of NIR was performed to identify PanNETs. An ex-post analysis of the images was realized using ImageJ Software® to calculate the fluorescence signal. NIR imaging identified all ten PanNETs. Nine (90%) laparoscopic distal pancreatectomy with splenectomy and one (10%) laparoscopic enucleation were performed. The mean maximum tumor dimension was 2.4 cm (range 1-4 cm). Eight non-functioning PanNETs (80%) and two insulinomas (20%) were found at the final pathology. Nine out of ten (90%) PanNETs were detected after the second ICG bolus. The mean latency time was 80 s and the mean visibility time was 220 s. The peak of tumor visualization was reached 20 min after the last bolus. This finding was confirmed by the ex-post analysis of the fluorescence signal (mean signal-to-background ratio of 7.7, p = 0.001). NIR identified two additional lesions, which turned out to be normal lymph nodes at final pathology. A fluorescent signal was identified at the bed of the enucleation, and thus, a further exeresis was performed and final pathology revealed that is was residual neoplastic tissue. This explorative study shows that NIR with ICG can have a role in laparoscopic pancreatic resection of PanNETs. Further studies are needed to assess the proper setting and role of this new and promising technology.

  17. Cushing’s like syndrome in typical bronchial carcinoid a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Ilaria Pedicelli

    2016-01-01

    Full Text Available Cushing’s syndrome occurred in 1–5% of cases of bronchial carcinoids. In this paper we describe a case of typical bronchial carcinoid in a nonsmoker young male with clinical manifestations mimicking a Cushing’s syndrome. The patient performed chest radiograph and computed tomography. Fiberoptic bronchoscopy revealed the presence of an endobronchial mass occluding the bronchus intermedius. A rigid bronchoscopy was necessary for the conclusive diagnosis and for partial resection of the intraluminal tumor. Despite of the presence of Cushingoid features, the normal blood levels of ACTH and cortisol excluded the coexistence of a Cushing’s syndrome.

  18. [Bronchial carcinoid discovered due to repeated pneumonia in the lingular division of the left lung; report of a case].

    Science.gov (United States)

    Hashimoto, Hiroshi; Oshika, Yoshiro; Obara, Kiyohaya; Nakagishi, Yoshinori; Shoko, Tanaka; Tanaka, Yoshiaki; Sato, Kimiya; Matsukuma, Susumu; Ozeki, Yuichi

    2010-09-01

    Bronchial carcinoids are relatively rare, low-grade malignancies. Here we report a case of a bronchial carcinoid found by repeated pneumonia in the lingular division of the left lung. A 34-year-old man was referred to our hospital because of an abnormal shadow detected in an annual checkup. A chest computed tomography (CT) showed an infiltrative shadow in the lingular division. Two months later, a follow-up CT showed the shadow had remarkably improved. Two years after the 1st detection, an annual checkup revealed an abnormal shadow in the same lesion again. A chest CT showed not only an infiltrative shadow in the lingular division, but also a solid mass with calcification in the lingular bronchus. A bronchoscopy revealed an obstruction of the left upper lobe bronchus by a vascularized polypoid tumor. A transbronchial biopsy indicated a presence of a carcinoid, and a resection of the left upper lobe was performed. A histopathological examination showed that it was a typical carcinoid. The patient has been free of recurrence for 2 years since surgery. This is a case with repeated pneumonia and atelectasis caused by a bronchial carcinoid.

  19. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids: Case Report and Review of the Literature.

    Science.gov (United States)

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-02-01

    The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No optimal

  20. Clinical PET of Neuroendocrine Tumors Using 64Cu-DOTATATE: First-in-Humans Study

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Knigge, Ulrich Peter; Mortensen, Jann

    2012-01-01

    The use of positron emitter–labeled compounds for somatostatin receptor imaging (SRI) has become attractive because of the prospect of improved spatial resolution, accelerated imaging procedures, and the ability to quantify tissue radioactivity concentrations. This paper provides results from first...... performance of 64Cu-DOTATATE with respect to lesion detection was compared with conventional SRI. Results: SRI with 64Cu-DOTATATE produced images of excellent quality and high spatial resolution. Images were characterized by high and stable tumor-to-background ratios over an imaging time window of at least 3...

  1. The role of combined Ga-DOTANOC and (18)FDG PET/CT in the management of patients with pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Partelli, Stefano; Rinzivillo, Maria; Maurizi, Angela; Panzuto, Francesco; Salgarello, Matteo; Polenta, Vanessa; Delle Fave, Gianfranco; Falconi, Massimo

    2014-01-01

    The aim of this study was to evaluate the effect of combined (68)Ga and (18)F-FDG PET/CT on treatment management for patients with pancreatic neuroendocrine tumor (PNET). Between January 2012 and April 2014, 49 consecutive patients with a cytologically and/or histologically proven diagnosis of PNET underwent combined (68)Ga and (18)FDG PET/CT on the same day. The study group consisted of 21 males and 28 females with a median age of 59 years. Disease detection was achieved in 48 out of the 49 cases with (68)Ga imaging, and in 36 of the 49 cases with (18)FDG PET/CT. These results corresponded to sensitivities of 98% for (68)Ga versus 73% for (18)FDG PET/CT. Patients with NET-G1/NET-G2 had a positive (68)Ga and negative (18)FDG PET/CT in 13 cases, whereas both (68)Ga and (18)FDG PET/CT were positive in 27 cases. Patients with NEC-G3 were positive by both (68)Ga and (18)FDG PET/CT in 7 cases and positive only by (18)FDG in 1 case. Another NEC-G3 patient was only positive by (68)Ga PET/CT. The median Ki67 was 7% for (68)Ga PET/CT-positive tumors and 10% for tumors with both (68)Ga and (18)FDG PET/CT positivity (p = 0.130). Half of the patients with a prevalent uptake of (18)FDG (n = 7) had an NEC-G3 compared with 12% of patients with a prevalent uptake of (68)Ga (p = 0.012). There were no significant differences between patients with positive (68)Ga and those with positive (18)FDG with regards to treatment choice. The association of (18)FDG slightly increases sensitivity of (68)Ga PET/CT alone in the diagnosis of PNET. A combined dual tracer PET/CT does not influence the choice of treatment strategy.

  2. Budget impact of everolimus for the treatment of progressive, well-differentiated, non-functional neuroendocrine tumors of gastrointestinal or lung origin that are advanced or metastatic.

    Science.gov (United States)

    Rose, Darya B; Nellesen, Dave; Neary, Maureen P; Cai, Beilei

    2017-04-01

    Advanced neuroendocrine tumors (NETs) are a rare malignancy with considerable need for effective therapies. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in 2016 for treatment of adults with progressive, well-differentiated, non-functional NETs of gastrointestinal (GI) or lung origin that are unresectable, locally advanced, or metastatic. To assess the 3-year budget impact for a typical US health plan following availability of everolimus for treatment of GI and lung NETs. Methods An economic model was developed that considered two perspectives: an entire health plan and a pharmacy budget. The total budget impact included costs of drug therapies, administration, hospitalizations, physician visits, monitoring, and adverse events (AEs). The pharmacy model only considered drug costs. In a US health plan with 1 million members, the model estimated 66 patients with well-differentiated, non-functional, and advanced or metastatic GI NETs and 20 with lung NETs undergoing treatment each year. Total budget impact in the first through third year after FDA approval ranged from $0.0568-$