Palatine Tonsillar Metastasis of Small-Cell Neuroendocrine Carcinoma from the Lung Detected by FDG-PET/CT After Tonsillectomy: A Case Report

International Nuclear Information System (INIS)

Chen, Xiao-Hong; Bao, Yang-Yang; Zhou, Shui-Hong; Wang, Qin-Ying; Zhao, Kui

2013-01-01

Metastasis from a malignant tumor to the palatine tonsils is rare, accounting for only 0.8% of all tonsillar tumors, with only 100 cases reported in the English-language literature. Various malignant lung carcinomas may metastasize to the tonsils. A few cases of tonsillar metastasis from neuroendocrine lung carcinoma have been reported. A 67-year-old female underwent a right tonsillectomy because of a sore throat and an enlarged right tonsil. The postoperative pathology showed right tonsillar small cell neuroendocrine carcinoma (SCNC). Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) demonstrated metabolic activity in the lower lobe of the right lung. In addition, hypermetabolic foci were noted in the lymph nodes of the right neck and mediastinum. A needle biopsy of the pulmonary mass showed SCNC. The patient received chemotherapy and died of multiple distant metastases after 6 months. This is the first report using PET/CT to evaluate tonsillar metastasis from lung SCNC

Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors

International Nuclear Information System (INIS)

Lamberts, S.W.J.; Reubi, J.C.; Krenning, E.P.

1993-01-01

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers. (orig.)

Validation of somatostatin receptor scintigraphy in the localization of neuroendocrine tumors

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Lamberts, S.W.J. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland)); Reubi, J.C. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland)); Krenning, E.P. (Depts. of Medicine and Nuclear Medicine, Erasmus Univ., Rotterdam (Netherlands) Div. of Cell Biology and Experimental Cancer Research, Institution of Pathology, Bern Univ. (Switzerland))

1993-01-01

Somatostatin analogs are used in the control of hormonal hypersecretion and tumor growth of patients with acromegaly, islet cell carcinomas and carcinoids. Recently we showed that somatostatin receptor positive tumors can be visualized in vivo after the administration of radionuclide-labeled somatostatin analogs. Receptor imaging was positive in 18/21 islet cell tumors, 32/37 carcinoids, 26/28 paragangliomas, 9/14 medullary thyroid carcinomas, and 5/7 small cell lung cancers. Somatostatin receptor imaging is an easy, harmless and painless diagnostic method. It localizes multiple and/or metastatic tumors, predicts the successful control of hormonal hypersecretion by octreotide and seems to be of prognostic value in certain types of cancer. This scintigraphic method might help in patient selection for clinical trials with somatostatin analogs in the treatment of neuroendocrine cancers. (orig.).

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...... these PET tracers further....

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.

Tumors of the endocrine/neuroendocrine system: an overview.

Science.gov (United States)

Erlandson, R A; Nesland, J M

1994-01-01

For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

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

Science.gov (United States)

2017-09-26

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

[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.

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.

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

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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.)

WHO Grade 2 Neuroendocrine Tumor in a 15-Year-Old Male: A Case Report and Literature Review

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Eric Johannesen

2014-01-01

Full Text Available Neuroendocrine tumors, distinguished from adenocarcinomas by their neuroendocrine differentiation, are the most common pediatric epithelial malignancy that most often occurs in the appendix. In 2010, the WHO classified neuroendocrine neoplasms into three grades based on morphology, mitotic count, and Ki67 proliferation index. A 15-year-old male with a history of anemia and failure to thrive was diagnosed with a well-differentiated neuroendocrine tumor in the jejunum that invaded into the subserosal soft tissue and metastasized to four lymph nodes. Pediatric neuroendocrine tumors frequently arise within hereditary tumor syndromes with pancreatic neuroendocrine tumors being the most common. Several studies also indicate an elevated risk of small intestinal neuroendocrine tumors in which children born to a parent with a history of neuroendocrine tumors in the small intestine have a significant increased risk of developing one.

[Neuroendocrine tumors of gastrointestinal tract: the paradigm that lasts].

Science.gov (United States)

Bjelović, Milos M; Babić, Tamara D

2013-01-01

Historically, the tumors that were morphologically different and clinically less agressive than the more common gastrointestinal adenocarcinomas were clasified under carcinoid tumors. However, the development of molecular biology tehniques revealed the heterogeneity of these tumors on cellular and subcellular level and ther different biological behaviour. Neuroendocrine tumors of gastrointestinal tract originated from neuroendocrine cells scaterred across the gastrointestinal mucosa. As a result these tumors were capable of secreting many different neurotransmiters, which may or may not be biologically active. The incidence of gastrointestinal NETs has been incresing over the last 2 to 3 decades. Patients often presented with vague, nonspecific symptoms which resulted in delayed diagnosis and adequate treatment. In this article, we discuss the nature of gastrointestinal NETs, clinical presentation, treatment options and prognosis.

Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

Science.gov (United States)

Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

2015-06-01

A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

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

Calcification in large cell neuroendocrine carcinoma of the lung

International Nuclear Information System (INIS)

Takamochi, Kazuya; Yokose, Tomoyuki; Ochiai, Atsushi; Yoshida, Junji; Nishimura, Mitsuyo; Ohmatsu, Hironobu; Nagai, Kanji; Nishiwaki, Yutaka

2003-01-01

The aim was to investigate the prevalence of intratumoral calcification in large cell neuroendocrine carcinoma (LCNEC) and to review computed tomography (CT) and histological findings. From August 1992 through March 2000, 35 out of 1183 surgically resected lung cancer patients were histologically diagnosed as having LCNEC at our institute. We reviewed the pain radiographs and CT scans of these 35 LCNEC patients. In LCNEC cases with intratumoral calcification, we examined the size, number, distribution and pattern of intratumoral calcifications visible on the CT scans and the histological features. Three cases (9%) exhibited calcification. The calcifications were recognized by CT scans alone. The CT scans showed punctate or eccentric intratumoral calcifications, which are considered to be a malignant feature, in all three cases. In two cases, the calcifications were histologically confirmed to be located within the necrotic areas of a tumor nest. We found three LCNEC cases with intratumoral calcification. The prevalence of LCNEC calcification was similar to that in previous reports on lung cancer. The mechanism of the intratumoral calcification in our LCNEC cases is speculated to be dystrophic calcification. (author)

Neuroendocrine tumors of the pancreas

International Nuclear Information System (INIS)

Holzapfel, Konstantin; Rummeny, Ernst J.; Gaertner, Florian C.

2011-01-01

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.)

Everolimus for Advanced Pancreatic Neuroendocrine Tumors.

NARCIS (Netherlands)

Yao, James C.; Shah, Manisha H.; Ito, Tetsuhide; Bohas, Catherine Lombard; Wolin, Edward M.; Van Cutsem, Eric; Hobday, Timothy J.; Okusaka, Takuji; Capdevila, Jaume; de Vries, Elisabeth G. E.; Tomassetti, Paola; Pavel, Marianne E.; Hoosen, Sakina; Haas, Tomas; Lincy, Jeremie; Lebwohl, David; Oberg, Kjell

2011-01-01

Background: Everolimus, an oral inhibitor of mammalian target of rapamycin (mTOR), has shown antitumor activity in patients with advanced pancreatic neuroendocrine tumors, in two phase 2 studies. We evaluated the agent in a prospective, randomized, phase 3 study. Methods: We randomly assigned 410

Cystic pancreatic neuroendocrine tumors (cPNETs: a systematic review and meta-analysis of case series

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Luis Hurtado-Pardo

Full Text Available Cystic pancreatic neuroendocrine tumors represent 13% of all neuroendocrine tumors. The aim of this study is to analyze the phenotype and biologic behavior of resected cystic neuroendocrine tumors. A systematic review and meta-analysis were conducted until September 2016 using a search in Medline, Scopus, and EMBASE with the terms "cystic pancreatic endocrine neoplasm", "cystic islets tumors" and "cystic islets neoplasms". From the 795 citations recovered 80 studies reporting on 431 patients were selected. 87.1% (n = 387 were sporadic tumors and 10.3% (n = 40 corresponded to multiple endocrine neoplasia type 1. Were diagnosed incidentally 44.6% (n = 135. Cytology was found to have a sensitivity of 78.5%. Were non-functional tumors 85% (n = 338, and among the functional tumors, insulinoma was the most frequent. According to the European Neuroendocrine Tumor Society staging, 87.8% were limited to the pancreas (I-IIb, and 12.2% were advanced (III-IV. Disease-free survival at 5 years in stages (I-IIIa and (IIIb-IV was 91.5% and 54.2%, respectively; and was significantly lower (p = 0.0001 in functional tumors. In patients with multiple endocrine neoplasia there was a higher incidence of functional (62.5% and multifocal (28.1% tumors. Disease-free survival at 5 and 10 years was 60%. Cystic pancreatic neuroendocrine tumors exhibit phenotypical characteristics which are different to those of solid neuroendocrine tumors.

Advances in the treatment of gastroenteropancreatic neuroendocrine tumors

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Pamela L Kunz

2010-06-01

Full Text Available Pamela L Kunz, George A FisherStanford University Medical Center, CA, USAAbstract: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs are a rare and heterogeneous class of neoplasms. While surgical resection is the mainstay of treatment, non-surgical therapies play a role in the setting of unresectable and metastatic disease. The goals of medical therapy are directed both at alleviating symptoms of peptide release and shrinking tumor mass. Biotherapies such as somatostatin analogs and interferon can decrease the secretion of peptides and inhibit their end-organ effects. A second objective for treatment of unresectable GEP-NETs is limiting tumor growth. Options for limiting tumor growth include somatostatin analogs, systemic chemotherapy, locoregional therapies, ionizing radiation, external beam radiation, and newer targeted agents. In particular, angiogenesis inhibitors, tyrosine kinase inhibitors, and mTOR inhibitors have shown early promising results. The rarity of these tumors, their resistance to standard chemotherapy, and the excellent performance status of most of these patients, make a strong argument for consideration of novel therapeutic trials.Keywords: neuroendocrine, gastroenteropancreatic, carcinoid, somatostatin

Specific targeting for the treatment of neuroendocrine tumors

International Nuclear Information System (INIS)

Hoefnagel, C.A.

2003-01-01

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

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

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...

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.

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

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Surlin Valeriu

2012-09-01

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

18F-FDG and 18F-FLT-PET Imaging for Monitoring Everolimus Effect on Tumor-Growth in Neuroendocrine Tumors

DEFF Research Database (Denmark)

Johnbeck, Camilla Bardram; Munk Jensen, Mette; Nielsen, Carsten Haagen

2014-01-01

INTRODUCTION: The mTOR inhibitor everolimus has shown promising results in some but not all neuroendocrine tumors. Therefore, early assessment of treatment response would be beneficial. In this study, we investigated the in vivo and in vitro treatment effect of everolimus in neuroendocrine tumors...

Radiosensitivity related to neuroendocrine and endodermal differentation in lung carcinoma lines

International Nuclear Information System (INIS)

Duchesne, G.; Casoni, A.; Pera, M.

1988-01-01

A panel of human lung carcinoma lines was studied with respect to hormone production and intermediate filament expression to distinguish between endodermal and neuroendocrine differentation. An index of the degree of neuroendocrine differentiation of each line was derived from the presence or absence of hormone production, cytokeratins, neurofilaments and an embryonic endodermal cell marker, which allowed identification of three groups showing high, intermediate or low neuroendocrine expression. This grouping correlated well with the in vitro radiosensitivity of the lines, those expressing pure neuroendocrine features being significantly more radiosensitive than those with an endodermal phenotype, with the intermediate group having intermediate sensitivity. Use of such an index might predict those patients likely to benefit from the use of radiotherapy in their management. 30 refs.; 3 figs.; 3 tabs

Chronic diarrhea as presenting symptom for a metastasic neuroendocrine tumor

International Nuclear Information System (INIS)

Hani A, Albis Cecilia; Garcia A, Jairo Alberto

2007-01-01

We describe the clinical case of a 74 years old female patient presenting with a watery diarrhea syndrome, having severe hypokalaemia and liver metastases. In her necropsy a pancreatic neuroendocrine tumor was found. We present a literature review about pancreas neuroendocrine tumours, focusing in the VIPoma, which may correspond with the clinical features of this particular patient

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.

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 ...

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

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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.

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor

International Nuclear Information System (INIS)

Panda, D.; Aggarwal, M.; Kumar, S.; Mukund, A.; Baghmar, S.; Yadav, V.

2016-01-01

We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD)

Diagnosis, treatment and prognosis of neuroendocrine tumor in stomach and duodenum

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Xiang-yao WANG

2016-04-01

Full Text Available Objective 　To investigate the clinicopathological characteristics and prognosis of patients with neuroendocrine tumor in stomach and duodenum for early diagnosis. Methods 　The clinical, endoscopic and pathological data of 20 patients admitted to the PLA General Hospital from Jan. 2012 to Jan. 2015 and diagnosed as gastric and duodenal neuroendocrine tumor were collected for retrospective analysis. The histopathological classification of the disease was made according to the WHO 2010 Classification of the Neuroendocrine Neoplasms. Result 　Ten male and 10 female patients aged between 35 and 77 (mean 55.5±10.6 years old were recruited in the present study. Tumor located in the stomach in 13 cases, and in duodenum in 7 cases. The maximum diameter of the tumor was 0.2-2.5cm. Endoscopic features included polypoid protrusion, hemispheric submucosal protrusion, and mucosal erosion. All the patients were treated endoscopically, among them, four patients were treated with electrocoagulation and electrosection, 10 by endoscopic resection (EMR, and 6 by endoscopic submucosal dissection (ESD. In one patient, surgical excision was done after ESD. Biopsy under gastroscopy and endoscopic ultrasonography were conducive to the diagnosis and treatment. According to the histopathological classification, 19 cases were classified as NET grade 1, and another one as NET grade 2. The follow-up study showed no metastasis and recurrence. Conclusions 　The early diagnosis and treatment for gastric and duodenal neuroendocrine tumor can lead to satisfactory results. DOI: 10.11855/j.issn.0577-7402.2016.03.12

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 ...

Neuroendocrine tumor of vulva: A case report and review of literature

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Sheikh Zahoor

2010-01-01

Full Text Available Neuroendocrine tumor (Merkel cell carcinoma-MCC of the vulva is a very rare entity with less than 15 cases reported in the English literature. It is known for its aggressive behaviour and propensity for early dissemination. The actual cell of origin and etiology of this disease is controversial. In absence of any definite guidelines for management (due to its rarity, extrapolation of data from extra-vulvar MCC seems logical. We present a case of vulvar neuroendocrine tumor who presented at a locally advanced stage.

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor

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Dipanjan Panda

2016-06-01

Full Text Available We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET; diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT; and successfully treated with percutaneous transhepatic biliary drainage (PTBD.

PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

International Nuclear Information System (INIS)

Makinoshima, Hideki; Ishii, Genichiro; Kojima, Motohiro; Fujii, Satoshi; Higuchi, Youichi; Kuwata, Takeshi; Ochiai, Atsushi

2012-01-01

Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease. We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines. Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model. PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs

Place of surgical resection in the treatment strategy of gastrointestinal neuroendocrine tumors.

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Gaujoux, Sébastien; Sauvanet, Alain; Belghiti, Jacques

2012-09-01

Neuroendocrine tumors (NET) are usually slow-growing neoplasms carrying an overall favorable prognosis. Surgery, from resection to transplantation, remains the only potential curative option for these patients, and should always be considered. Nevertheless, because of very few randomized controlled trials available, the optimal treatment for these patients remains controversial, especially regarding the place of surgery. We herein discuss the place of surgical resection in the treatment strategy in neuroendocrine tumors of the digestive tract.

Diagnosis and Management of Upper Gastrointestinal Neuroendocrine Tumors

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Jun Liong Chin

2017-11-01

Full Text Available Upper gastrointestinal neuroendocrine tumors (NETs are rare tumors which are increasingly recognised by practising endoscopists. After confirmation by endoscopic biopsies of these focal lesions, many questions may arise. As NETs are less frequently encountered compared to other malignancies or gastrointestinal pathology, many endoscopists may not fully understand the natural history, diagnosis and management of these tumors. In this review, we aim to update the practising endoscopist on the key clinical features and management of patients with upper gastrointestinal NET.

68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

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Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

2017-06-01

Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

Pathological characteristics and clinical specifications in gastroenteropancreatic neuroendocrine tumors: a study of 68 cases.

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Stoica-Mustafa, Elena; Pechianu, C; Iorgescu, Andreea; Hortopan, Monica; Dima, Simona Olimpia; Tomulescu, V; Dumitraşcu, T; Ungureanu, C; Andronesi, D; Popescu, I; Herlea, V

2012-01-01

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a group of tumors, having their origin in cells of diffuse endocrine system, with particular clinical course, diagnosis and treatment. In our study, were included 68 patients with neuroendocrine digestive tumors admitted, diagnosed and treated in Fundeni Clinical Institute, Bucharest, in the last ten years--2000-2010 (retrospective study). Thirty-three (49%) patients were males, 35 (51%) females, and the main age was 58.9 years. In 62 (90.3%) cases was possible to find the primary tumor. The examined tumors had different localizations: pancreas--32 (47.04%) cases (head--17 (24.99%) cases, and body and tail--15 (22.05%) cases), stomach--7 (10.29%) cases, small intestine--7 (10.29%) cases, 6 (8.82%) cases--unknown primary site (diagnosis was established on metastases), right colon--6 (8.82%) cases, liver--6 (8.82%) cases, rectum--2 (2.94%) cases, and retroperitoneum--2 (2.94%) cases. Microscopic examination revealed 59 (86.8%) malignant tumors and 9 (13.2%) benign tumors. Using WHO 2000 Classification, 28 cases of malignant tumors were well-differentiated neuroendocrine carcinomas, and 31 cases were poor differentiated neuroendocrine carcinomas. From malignant cases, 25 (42.3%) have distant metastases and 15 (25.9%) lymph node metastases. Cases of gastroenteropancreatic neuroendocrine tumors included in our study had clinical and histopathological features in correspondence with data from literature--slight predominance in women, predominance in 5th and 6th decades of life, the most frequent localizations were at pancreatic level--both head and body and tail, but the rarest were in colon and retroperitoneum. Most of the cases studied, were malignant tumors, from these more than a half were poor differentiated, and a quarter of them having lymph node or distant metastases.

Amenorrhea as a rare drug-related adverse event associated with everolimus for pancreatic neuroendocrine tumors.

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Kawaguchi, Yoshiaki; Maruno, Atsuko; Kawashima, Yohei; Ito, Hiroyuki; Ogawa, Masami; Mine, Tetsuya

2014-11-14

The patient was an asymptomatic 43-year-old woman. Abdominal ultrasonography and enhanced computed tomography showed a tumor lesion accompanied by multiple cystic changes in the liver and the pancreatic tail. Endoscopic ultrasound-fine needle aspiration was performed on the pancreatic tumor lesion and revealed pancreatic neuroendocrine tumor (PNET). As it was unresectable due to multiple liver metastases, the decision was made to initiate treatment with everolimus and transcatheter arterial chemoembolization. The patient ceased menstruating after the start of everolimus administration. When the administration was discontinued due to interstitial lung disease, menstruation resumed, but then again stopped with everolimus resumption. An association between everolimus and amenorrhea was highly suspected. Amenorrhea occurred as a rare adverse event of everolimus. As the younger women might be included in PNETs patients, we should put this adverse event into consideration.

Retrospective review of 21 cases of neuroendocrine tumors and review of literature

International Nuclear Information System (INIS)

Ferrari, A.; Alonso, S.; Cordoba, A.; Vazquez, A.

2010-01-01

Objective: literature review and case histories. Neuroendocrine tumors (Nets) are considered rare and comprise a group very heterogeneous with different prognosis and evolution. They represent less than 1% of all malignant tumors and most originate from the gastrointestinal tract in enterocromoafines cells are widely distributed in the same: in the stomach, duodenum, pancreas, small, colon and rectum. Carcinoid tumors Gastrointestinal represent over 70% of all tumors (Nets) in humans. And frequently they are finding their debut as disseminated disease, coinciding our review. 21 records were retrospectively analyzed between 1995 and June 2010. No significant difference in gender, of these 9 patients were 12 female and male sex. Ages ranged from 36 years to 83 years, with an average of 63 years. The locations were distributed as follows: 6 patients with small bowel tumor, 2 with blind tumor, 2 esophageal tumor , 1 patient with pancreatic tumor, 1 patient with stomach tumor, 2 patients with retroperitoneal disease in which failed to define the primary, 2 patients with tumor in breast, 3 patients with lung tumor, 1 patient with piriform sinus tumor and 1 patient with parotid tumor. Of the 21 patients, only 4 sometime had functional syndrome characterized by diarrhea and flushing. The treatments that received these patients were also very heterogeneous. From these patients, only one died in 2008 and the others are still alive, some in control and other treatment. Because of the number of patients seen and the therapeutic variability the statistical analysis no was done

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

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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.

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

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

2003-09-01

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

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

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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.

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

, 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...... 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......Anti-angiogenesis treatment is a promising new therapy for cancer that recently has also been suggested for patients with neuroendocrine tumors. The aim of the present study was therefore to investigate the level of tumor angiogenesis, and thereby the molecular basis for anti-angiogenesis treatment...

IMMUNOHISTOCHEMICAL DETERMINATION OF EXPRESSION OF SOMATOSTATIN RECEPTORS TYPES 1, 2A, 3 AND 5 IN NEUROENDOCRINE TUMORS OF VARIOUS LOCALIZATION AND GRADE

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L. E. Gurevich

2016-01-01

Full Text Available Background: Prediction of clinical benefits of somatostatin analogues in patients with neuroendocrine tumors (NET is very important prior to their administration. Data on immunohistochemical assessment of the expression of somatostatin receptors (SSR of various types, obtained from large samples of NET with various localization, functional activity and degree of malignancy, are scarce; therefore, the study was aimed at assessment of the latter.Materials and methods: We performed an immunohistochemical study with antibodies to SSR1, 2A, 3 and 5  types on tissue samples obtained during diagnostic and intra-operative biopsies from 399 NETs: 168 from pancreas, 120 from gastrointestinal tract (stomach, 48, from small intestine, 39, 14 of which being from duodenum; appendix, 6, colon and the rectum, 15 and 12, respectively, 84 from lung, 6 from thymus/mediastinum, and 21 from NET metastases of unknown primary localization.Results: Very high levels expression of receptors SSR2A preferentially binding to somatostatin analogues, which are currently used in clinical practice, were detected in the small intestine NETs (22/25, 88%, appendix (5/6, 83.3%, colon (10/15, 66.7%, thymus (4/6, 66.7%, atypical carcinoids of the lung (10/15, 66.7%, stomach (27/41, 65.8% and pancreas (105/165, 63.6%. The lowest expression was found in rectal NETs (5/12, 41.7% and small and large cell neuroendocrine lung carcinomas (20, 11.1%. Among functioning NETs, the highest level of SSR2A was found in gastrinomas (18/19, 94.7%, glucagonomas (15/16, 93.8%, small intestine carcinoids (31/35, 88.6%, and somatostatinomas (2/3, 66.7%. The lowest expression was detected in ACTH secreting tumors with Cushing's syndrome (11/12, 50%, and in insulinomas (34/69, 49.3%. SSR2A expression in functionally inactive pancreatic NETs was significantly higher than in insulinomas (57/82, 34/69 vs 69.5 and 49.3%, respectively. SSR2A expression was associated with the degree of malignancy and is

Calcitonin-producing well-differentiated neuroendocrine carcinoma (carcinoid tumor of the urinary bladder: case report

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De Rosa Gaetano

2005-07-01

Full Text Available Abstract Background The occurrence of calcitonin-secreting primary carcinoid tumor of the urinary bladder is extremely rare. Case presentation The case of a 68-year-old male with carcinoid tumor arising in the urinary bladder is presented. Transurethral resection of a polypoid small tumor 0.4 cm in diameter was performed. Immunohistochemical study using neuroendocrine markers allowed a straightforward diagnosis of a low-grade neuroendocrine carcinoma (carcinoid tumor of the urinary bladder. Immunohistochemistry demonstrated calcitonin immunoreactivity in the most of the tumor cells. Conclusion This tumor shows specific clinical, macroscopical and histological features and must be considered in the differential diagnosis of bladder neoplasms.

Primary hyperparathyroidism, adrenal tumors and neuroendocrine tumors of the pancreas - clinical diagnosis and imaging requirements

International Nuclear Information System (INIS)

Auernhammer, C.J.; Engelhardt, D.; Goeke, B.

2003-01-01

Diseases of the parathyroids, the adrenals and of neuroendocrine tumors of the pancreas are primarily diagnosed by clinical and endocrinological evaluation.The requirements concerning various imaging techniques and their relative importance in localization strategies of the different tumors are complex. Current literature search, using PubMed. Evaluation of primary hyperparathyroidism requires bone densitometry by DXA and search for nephrolithiasis by ultrasound or native CT examination.While ultrasound of the thyroid and parathyroids seems useful before any parathyroid surgery,more extensive preoperative localization strategies (sestamibi scintigraphy, MRI) should be restricted to minimal invasive parathyroid surgery or re-operations.For adrenal tumors CT and MRI are of similar diagnostic value. Imaging of pheochromocytomas should be completed by MIBG scintigraphy. Each adrenal incidentaloma requires an endocrinological work-up.A fine-needle aspiration or core needle biopsy of an adrenal tumor is rarely indicated.Before adrenal biopsy a pheochromocytoma has to be excluded.Successful localization strategies for neuroendocrine tumors of the pancreas include somatostatin receptor scintigraphy, endoscopic ultrasound and MRI.Discussion Specific localization strategies have been established for the aforementioned tumors.The continuous progress of different imaging techniques requires a regular reevaluation of these localization strategies. (orig.) [de

Clinical relevance of F-18 FDG PET for imaging of neuroendocrine tumors

International Nuclear Information System (INIS)

Adams, S.; Baum, R.P.; Hoer, G.

2001-01-01

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

Neuroendocrine tumors: a review of the clinical aspects, diagnosis and treatment

International Nuclear Information System (INIS)

Rodriguez Fernandez, Lisbet; Hernandez Yero, Arturo; Pina Rivera, Yordanka; Yanes Quesada, Marelys

2008-01-01

The study of neuroendocrine tumors has been object of interests by medical science. Different methods have been developed for their diagnosis, treatment and prognosis, each of them with its advantages and inconveniences. The published results are based on the experience of other countries, and it would be very useful to apply them in our country to get closer to the real incidence of these tumors in our environment and to have an adequate treatment of the patients affected with this disease. The objective of this paper is to offer a view of the current trends as regards the clinical aspects, the diagnosis and treatment of the neuroendocrine tumors that serves as a working tool for medical practice and for the teaching activity of the physicians related to this topic

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

Broncho-biliary fistula secondary to biliary obstruction and lung abscess in a patient with pancreatic neuro-endocrine tumor.

Science.gov (United States)

Panda, Dipanjan; Aggarwal, Mayank; Yadav, Vikas; Kumar, Sachin; Mukund, Amar; Baghmar, Saphalta

2016-06-01

We present a case report of broncho-biliary fistula that developed due to the blockage of biliary stent placed during the management of pancreatic neuroendocrine tumor (pNET); diagnosed on high clinical suspicion, percutaneous cholangiogram and contrast enhanced computed tomography (CECT); and successfully treated with percutaneous transhepatic biliary drainage (PTBD). Copyright © 2016 National Cancer Institute, Cairo University. Production and hosting by Elsevier B.V. All rights reserved.

(CT, MRI, USG) radiological diagnostics of neuroendocrine tumors

International Nuclear Information System (INIS)

Cwikla, J.; Furmanek, M.; Walecki, J.; Sankowski, A.; Pawlowska-Detko, A.

2007-01-01

Neuroendocrine tumors (NET) consists of a heterogeneneous group of neoplasma, that are able to express cell membrane neuroamine uptake mechanisms and/or specific receptors, which can be used in the localization and treatment of these tumours. Conventionally NETs may present with a wide variety of functional or nonfuctional endocrinesyndromes and may be familial and have other associated tumors, also they have different histology and prognosis. They originate from endocrine glands such as the pituitary, the parathyroids, and the neuroendocrine) adrenal, as well as endocrine islets within glandular tissue (thyroid or pancreatic) and cells dispersed between exocrine cells, such as endocrine cells of the digestive system (gastroenteropancreatic GEP-NET0 and respiratory tracts. GEp-NET are the the most common including more 70% of all NETs. Imaging modalities and assessment of specific tumors markers offers high sensitivity in establishing the diagnosis and can also have pronostic significance. One of most important single imaging techniques in terms of initial identification and staging o GET-NET are CT and somatostatin receptor scintigraphy (SRS). Other investigation like magnetic resonance imaging (MRI), endoscopic (EUS) are used for the precise localization of GEP-NET. Another techniques including functional approach 123 I MIBG (meta-iodobenzylguanidine scintigraphy) and FDG PET.Important using of imaging approach is monitoring of response on treatment. (author)

Neuroendocrine tumors of the gastrointestinal tract: Case reports and literature review

Institute of Scientific and Technical Information of China (English)

William; J; Salyers; Kenneth; J; Vega; Juan; Carlos; Munoz; Bruce; W; Trotman; Silvio; S; Tanev

2014-01-01

Neuroendocrine tumors(NET)previously called carcinoid tumors are neoplasms of enterochromaffin/neuroendocrine cell origin which display neurosecretory capacity that may result in the carcinoid syndrome.The annual incidence of patients with NET is 8.4 per 100000;yet many NET remain asymptomatic and clinically undetected.A majority of NET follows a benign course;however,some will display malignant characteristics.NET most commonly occur in the gastrointestinal tract(67%)and bronchopulmonary system(25%).Gastrointestinal NET occur within the stomach,small intestine,liver,and rectum.We report a retrospective study of 11 subjects:Eight with benign carcinoid tumors:duodenal bulb(n=2),terminal ileum(n=1),sigmoid colon(n=2),and rectum(n=3);three with malignant carcinoid:liver(n=1)and intra-abdominal site(n=2).The diagnosis,endoscopic images,outcome,treatment and review of the literature are presented.

Morbidity and mortality of aggressive resection in patients with advanced neuroendocrine tumors.

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Norton, Jeffrey A; Kivlen, Maryann; Li, Michelle; Schneider, Darren; Chuter, Timothy; Jensen, Robert T

2003-08-01

There is considerable controversy about the treatment of patients with malignant advanced neuroendocrine tumors of the pancreas and duodenum. Aggressive surgery remains a potentially efficacious antitumor therapy but is rarely performed because of its possible morbidity and mortality. Aggressive resection of advanced neuroendocrine tumors can be performed with acceptable morbidity and mortality rates and may lead to extended survival. The medical records of patients with advanced neuroendocrine tumors who underwent surgery between 1997 and 2002 by a single surgeon at the University of California, San Francisco, were reviewed in an institutional review board-approved protocol. Surgical procedure, pathologic characteristics, complications, mortality rates, and disease-free and overall survival rates were recorded. Disease-free survival was defined as no tumor identified on radiological imaging studies and no detectable abnormal hormone levels. Proportions were compared statistically using the Fisher exact test. Kaplan-Meier curves were used to estimate survival rates. Twenty patients were identified (11 men and 9 women). Of these, 10 (50%) had gastrinoma, 1 had insulinoma, and the remainder had nonfunctional tumors; 2 had multiple endocrine neoplasia type 1, and 1 had von Hippel-Lindau disease. The mean age was 55 years (range, 34-72 years). In 10 patients (50%), tumors were thought to be unresectable according to radiological imaging studies because of multiple bilobar liver metastases (n = 6), superior mesenteric vein invasion (n = 3), and extensive nodal metastases (n = 1). Tumors were completely removed in 15 patients (75%). Surgical procedures included 8 proximal pancreatectomies (pancreatoduodenectomy or whipple procedure), 3 total pancreatectomies, 9 distal pancreatectomies, and 3 tumor enucleations from the pancreatic head. Superior mesenteric vein reconstruction was done in 3 patients. Liver resections were done in 6 patients, and an extended periaortic node

Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

Science.gov (United States)

2018-05-14

Acinar Cell Carcinoma; Adenoid Cystic 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; Desmoid-Type Fibromatosis; 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; Gastrointestinal Stromal Tumor; 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; Metaplastic Breast Carcinoma; 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

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

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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 < 0.01) on SPECT (3.12 ± 1.13) than on whole body scan (2.2 ± 0.75). According to our results, overall sensitivity of the method is 80%, specificity 92%, positive predictive value 98%, negative predictive value 47% and accuracy 82%. Fifteen TP patients underwent therapy with 90Y-DOTATATE. Scintigraphy of neuroendocrine tumors with 99mTc-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.

Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

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Vinik, Aaron I; Chaya, Celine

2016-02-01

Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Treatment of pancreatic neuroendocrine tumor with liver metastases

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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.

Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature

Institute of Scientific and Technical Information of China (English)

Wojciech C Blonski; K Rajender Reddy; Abraham Shaked; Evan Siegelman; David C Metz

2005-01-01

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases,alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocinbased chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived.Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver.However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

Neuroendocrine carcinomas of the lung

International Nuclear Information System (INIS)

Forster, B.B.; Muller, N.L.; Miller, R.R.; Nelems, B.; Evans, K.G.

1988-01-01

Neuroendocrine lung carcinomas may be classified as Kulchitzky cell carcinoma (KCC) I (classic carcinoids), II (atypical carcinoids), and III (small cell carcinomas). The authors reviewed the clinical, CT, and pathologic findings in 31 patients with KCC. KCC I occurred mainly in younger nonsmoking women, and on CT were small (1.8 cm average diameter) and showed lymphadenopathy in one of ten patients. KCC II were found mainly in older smoking men and were larger (3.9 cm, P < .001), and four of ten patients had lymphadenopathy. KCC III occurred in older smoking men and were large (4.2 cm), and 11 of 11 patients had lymphadenopathy. Sputum cytology and percutaneous and bronchoscopic biopsy were often nondiagnostic or misleading. The authors conclude that chest CT provides additional discriminating information in the preoperative diagnosis of KCC

Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Intraoperative use of gamma-detecting probes to localize neuroendocrine tumor

International Nuclear Information System (INIS)

Adams, S.; Baum, R.P.

2000-01-01

Neuroendocrine tumors are characterized by the expression of different peptides and biogenic amines. These rare tumors tend to grow slowly and are notoriously difficult to localize, at least in the early stages. Surgical removal is the only definitive therapeutic option for neuroendocrine tumors and relief from hyper functional status. The effectiveness of surgical treatment is invariably dependent upon the complete surgical excision of all tumor tissue, because microscopic and occult disease not readily seen by the surgeon may remain in sit, leading to shortened survival. Radio guided surgery (RGS) is an intraoperative technique that enables the surgeon to localize radiolabelled tissue based on the characteristics of the various tissues. For imaging recurrent MTC (Medullary Thyroid Cancer) many radiopharmaceuticals have been used to visualize tumor sites, but none of them has shown excellent sensitivity. Preoperative somatostatin receptor scintigraphy and intraoperative RGS in patients with recurrent MTC demonstrate only part of the tumor sites and cannot visualize small tumor sites (less than 10 mm). In patients with recurrent MTC, intraoperative gamma probe examination is able to localize over 30% more tumor lesions when compared with conventional preoperative imaging modalities and surgical findings. In addition to scintigraphy of the adrenal glands by precursors of adrenal hormones, imaging with a radiolabelled somatostatin analogue is possible; however ( 111 In-DTPA-D-Phe 1 )-pentetreotide is not specific for any adrenal disease or function and the relatively high radioligand accumulation in the kidneys limited the use for detection of tumors in the area of the adrenal glands

Intraoperative use of gamma-detecting probes to localize neuroendocrine tumor

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Adams, S. [Johann Wolfgang Goethe Univ., Frankfurt/Main (Germany). Medical Center, Dept. of Nuclear Medicine; Baum, R.P. [Zentralklinik Bad Berka GmbH, Bad Berka (Germany). Clinic of Nuclear Medicine/PET Center

2000-03-01

Neuroendocrine tumors are characterized by the expression of different peptides and biogenic amines. These rare tumors tend to grow slowly and are notoriously difficult to localize, at least in the early stages. Surgical removal is the only definitive therapeutic option for neuroendocrine tumors and relief from hyper functional status. The effectiveness of surgical treatment is invariably dependent upon the complete surgical excision of all tumor tissue, because microscopic and occult disease not readily seen by the surgeon may remain in sit, leading to shortened survival. Radio guided surgery (RGS) is an intraoperative technique that enables the surgeon to localize radiolabelled tissue based on the characteristics of the various tissues. For imaging recurrent MTC (Medullary Thyroid Cancer) many radiopharmaceuticals have been used to visualize tumor sites, but none of them has shown excellent sensitivity. Preoperative somatostatin receptor scintigraphy and intraoperative RGS in patients with recurrent MTC demonstrate only part of the tumor sites and cannot visualize small tumor sites (less than 10 mm). In patients with recurrent MTC, intraoperative gamma probe examination is able to localize over 30% more tumor lesions when compared with conventional preoperative imaging modalities and surgical findings. In addition to scintigraphy of the adrenal glands by precursors of adrenal hormones, imaging with a radiolabelled somatostatin analogue is possible; however ({sup 111}In-DTPA-D-Phe{sup 1})-pentetreotide is not specific for any adrenal disease or function and the relatively high radioligand accumulation in the kidneys limited the use for detection of tumors in the area of the adrenal glands.

[Diagnosis and surgical management in gastrointestinal neuroendocrine tumors].

Science.gov (United States)

Tomulescu, V; Stănciulea, O; Dima, S; Herlea, V; Stoica Mustafa, E; Dumitraşcu, T; Pechianu, C; Popescu, I

2011-01-01

Neuroendocrine tumors, known as carcinoid tumors constitute a heterogeneous group of neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause specific clinical syndromes. Assessment of specific or general tumors markers offers high sensitivity in establishing the diagnosis and they also have prognostic significance. Management strategies include curative surgery, whenever possible-that can be rarely achieved, palliative surgery, chemotherapy, radiologic therapy, such as radiofrequency ablation and chemoembolisations and somatostatin analogues therapy in order to control the symptoms. The aim of this paper is to review recent publications in this field and to give recommendations that take into account current advances in order to facilitate improvement in management and outcome.

Labeling of the peptide DOTA-tyr3-octreotate with radioiodine and biodistribution and AR42J neuroendocrine tumor affinity study in mice

International Nuclear Information System (INIS)

Nagamati, Lucio Takeshi

2006-01-01

Neuroendocrine tumors are rare and affect mainly the gastrointestinal tract but other systems are also affected like the skin, lungs and the nervous system. They are rich in type 2 somatostatin (SM) receptors (SSTR2) and may secrete hormones in excess. Synthetic SM derivative peptides are of great utility because presented bigger half life when compared to SM and can be used to clinical improvement of these patients due to its tumoral inhibitory action. The labeling of these peptides with radioisotopes allowed the acquisition of images with favourable cost-efficiency relationship and use in therapy. The peptide, DOTATyr3- octreotate (DOTATATE), has much more affinity for the SSTR2 receptor than the peptide commercially used nowadays, is easily radioiodinated and has a favourable biodistribution for diagnosis and treatment due to the presence of the chelator DOTA. We have studied the influence of various factors on the radiochemical purity of the labeled compound as labeling stability, absorbed dose estimation and biodistribution in normal and AR42J cell tumor-bearing Swiss and Nude mice. We observed easy and stable peptide radioiodination at peptide/radioiodine ( 131 I) ratio of 2.73 that produced a radiochemical species with retention time of 22.7 minutes at high performance liquid chromatography and presented a favourable biodistribution and dosimetry for imaging and therapy of patients with neuroendocrine tumors, just the opposite result observed the radioiodinated compounds without a chelator as described in the literature. Other molar peptide/radioiodine ratios did not showed good results, with various radiochemical species and unfavourable biodistribution. A possible dosimetric study in patients with neuroendocrine tumors may be carried out in the near future. (author)

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.

Neuroendocrine tumors of colon and rectum: validation of clinical and prognostic values of the World Health Organization 2010 grading classifications and European Neuroendocrine Tumor Society staging systems.

Science.gov (United States)

Shen, Chaoyong; Yin, Yuan; Chen, Huijiao; Tang, Sumin; Yin, Xiaonan; Zhou, Zongguang; Zhang, Bo; Chen, Zhixin

2017-03-28

This study evaluated and compared the clinical and prognostic values of the grading criteria used by the World Health Organization (WHO) and the European Neuroendocrine Tumors Society (ENETS). Moreover, this work assessed the current best prognostic model for colorectal neuroendocrine tumors (CRNETs). The 2010 WHO classifications and the ENETS systems can both stratify the patients into prognostic groups, although the 2010 WHO criteria is more applicable to CRNET patients. Along with tumor location, the 2010 WHO criteria are important independent prognostic parameters for CRNETs in both univariate and multivariate analyses through Cox regression (P<0.05). Data from 192 consecutive patients histopathologically diagnosed with CRNETs and had undergone surgical resection from January 2009 to May 2016 in a single center were retrospectively analyzed. Findings suggest that the WHO classifications are superior over the ENETS classification system in predicting the prognosis of CRNETs. Additionally, the WHO classifications can be widely used in clinical practice.

Peptide receptor radionuclide therapy for neuroendocrine tumors in Germany: first results of a multi-institutional cancer registry.

Science.gov (United States)

Hörsch, Dieter; Ezziddin, Samer; Haug, Alexander; Gratz, Klaus Friedrich; Dunkelmann, Simone; Krause, Bernd Joachim; Schümichen, Carl; Bengel, Frank M; Knapp, Wolfram H; Bartenstein, Peter; Biersack, Hans-Jürgen; Plöckinger, Ursula; Schwartz-Fuchs, Sabine; Baum, R P

2013-01-01

Peptide receptor radionuclide therapy is an effective treatment option for patients with well-differentiated somatostatin receptor-expressing neuroendocrine tumors. However, published data result mainly from retrospective monocentric studies. We initiated a multi-institutional, prospective, board-reviewed registry for patients treated with peptide receptor radionuclide therapy in Germany in 2009. In five centers, 297 patients were registered. Primary tumors were mainly derived from pancreas (117/297) and small intestine (80/297), whereas 56 were of unknown primary. Most tumors were well differentiated with median Ki67 proliferation rate of 5% (range 0.9-70%). Peptide receptor radionuclide therapy was performed using mainly yttrium-90 and/or lutetium-177 as radionuclides in 1-8 cycles. Mean overall survival was estimated at 213 months with follow-up between 1 and 230 months after initial diagnosis, and 87 months with follow-up between 1 and 92 months after start of peptide receptor radionuclide therapy. Median overall survival was not yet reached. Subgroup analysis demonstrated that best results were obtained in neuroendocrine tumors with proliferation rate below 20%. Our results indicate that peptide receptor radionuclide therapy is an effective treatment for well- and moderately differentiated neuroendocrine tumors irrespective of previous therapies and should be regarded as one of the primary treatment options for patients with somatostatin receptor-expressing neuroendocrine tumors.

Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

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Robert Grützmann

2010-11-01

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

Molecular Pathogenesis of Pancreatic Neuroendocrine Tumors

International Nuclear Information System (INIS)

Ehehalt, Florian; Franke, Ellen; Pilarsky, Christian; Grützmann, Robert

2010-01-01

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

The axon guidance molecule semaphorin 3F is a negative regulator of tumor progression and proliferation in ileal neuroendocrine tumors

Science.gov (United States)

Vercherat, Cécile; Blanc, Martine; Lepinasse, Florian; Gadot, Nicolas; Couderc, Christophe; Poncet, Gilles; Walter, Thomas; Joly, Marie-Odile; Hervieu, Valérie; Scoazec, Jean-Yves; Roche, Colette

2015-01-01

Gastro-intestinal neuroendocrine tumors (GI-NETs) are rare neoplasms, frequently metastatic, raising difficult clinical and therapeutic challenges due to a poor knowledge of their biology. As neuroendocrine cells express both epithelial and neural cell markers, we studied the possible involvement in GI-NETs of axon guidance molecules, which have been shown to decrease tumor cell proliferation and metastatic dissemination in several tumor types. We focused on the role of Semaphorin 3F (SEMA3F) in ileal NETs, one of the most frequent subtypes of GI-NETs. SEMA3F expression was detected in normal neuroendocrine cells but was lost in most of human primary tumors and all their metastases. SEMA3F loss of expression was associated with promoter gene methylation. After increasing endogenous SEMA3F levels through stable transfection, enteroendocrine cell lines STC-1 and GluTag showed a reduced proliferation rate in vitro. In two different xenograft mouse models, SEMA3F-overexpressing cells exhibited a reduced ability to form tumors and a hampered liver dissemination potential in vivo. This resulted, at least in part, from the inhibition of mTOR and MAPK signaling pathways. This study demonstrates an anti-tumoral role of SEMA3F in ileal NETs. We thus suggest that SEMA3F and/or its cellular signaling pathway could represent a target for ileal NET therapy. PMID:26447612

Salvage treatment after r-interferon α-2a in advanced neuroendocrine tumors

International Nuclear Information System (INIS)

Zilembo, N.; Buzzoni, R.; Bajetta, E.; Di Bartolomeo, M.; De Braud, F.; Castellani, R.; Maffioli, L.; Celio, L.; Villa, E.; Lorusso, V.; Fosser, V.; Buzzi, F.

1993-01-01

The use of interferon (IFN) in neuroendocrine advanced tumors has achieved control of hormonal symptoms but low objective tumor response rate. In patients resistant to, or failing on, IFN a second line treatment may be required. Seventeen patients having received recombinant IFN α-2a as last treatment entered the study. There were 12 carcinoids, 3 medullary thyroid carcinomas, one Merkel cell carcinoma, and one neuroendocrine pancreatic tumor. Two different treatments were used: one radiometabolic therapy with metaiodobenzylguanidine (MIBG) in 3 patients with high MIBG uptake and one polychemotherapy regimen, including streptozotocin 500 mg/m 2 intravenously days 1, 2, 3 and epirubicin 75 mg/m 2 intravenously day 1, in the remaining 14 patients. Stable disease with relief of symptoms and tumor marker reduction was obtained in two patients receiving MIGB therapy, whereas the third patient had progressive disease. In the chemotherapy group only one partial response was obtained and neither tumor marker reduction nor subjective improvement were seen. Our second-line treatment was not especially effective but may be considered for rapidly progressive and/or symptomatic disease. The radiometabolic therapy appears promising in symptomatic patients with small tumor burden whereas our chemotherapy regimen appears ineffective. (orig.)

A Case of High-Grade Neuroendocrine Carcinoma That Improved with Bevacizumab plus Modified FOLFOX6 as the Fourth-Line Chemotherapy

Directory of Open Access Journals (Sweden)

Satoshi Takeuchi

2011-05-01

Full Text Available High-grade neuroendocrine carcinoma differs from usual neuroendocrine carcinoma, and its prognosis is dismal. In this case report, a case of high-grade neuroendocrine carcinoma that improved with bevacizumab plus modified FOLFOX6 as the fourth-line chemotherapy is presented. A 29-year-old male with a huge liver tumor was diagnosed with high-grade neuroendocrine carcinoma originating from the liver. Multiple liver and bone metastases were found one month after surgery. He was treated with three chemotherapy regimens used for the management of small-cell lung cancer with extensive disease. However, none of them could be maintained because of tumor progression. He was then treated with bevacizumab plus modified FOLFOX6 as the fourth-line regimen. Dramatic tumor shrinkage was obtained, and a partial response was achieved. This case suggests that high-grade neuroendocrine carcinoma can be treated with bevacizumab in combination with cytotoxic chemotherapy.

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.

Multidetector Computed Tomography and Neuroendocrine Pancreaticoduodenal Tumors

International Nuclear Information System (INIS)

Rappeport, E.D.; Palnaes Hansen, C.; Kjaer, A.; Knigge, U.

2006-01-01

Purpose: To investigate the accuracy of dedicated pancreatic multidetector computed tomography (MDCT) in the diagnosis of neuroendocrine pancreaticoduodenal tumors (NPTs). Material and Methods: MDCT and other imaging studies in patients with suspected NPTs were identified. Thirty dedicated MDCT studies were done in 23 patients. Fourteen patients (16 operations) subsequently had surgery. Imaging reports were reviewed and findings compared with surgical findings and findings in other imaging studies. Results: Patients with surgery : 19 NPTs (16 extrapancreatic gastrinomas and 3 pancreatic NPTs) were identified at surgery. MDCT identified 16 and somatostatin receptor scintigraphy (SRS) 11 out of 19 tumors. Endoscopic ultrasound detected 11 out of 14 NPTs. Patients without surgery : In 4 out of 9 patients, no NPTs were identified at MDCT. Conclusion: Dedicated MDCT of the pancreas can identify many NPTs, including small duodenal and periduodenal tumors, and the detection rate is better than reported in the older literature on CT

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

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

2012-08-16

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

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

International Nuclear Information System (INIS)

Milione, Massimo; Pusceddu, Sara; Gasparini, Patrizia; Melotti, Flavia; Maisonneuve, Patrick; Mazzaferro, Vincenzo; Braud, Filippo G. de; Pelosi, Giuseppe

2012-01-01

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

68Ga-DOTANOC: biodistribution and dosimetry in patients affected by neuroendocrine tumors

International Nuclear Information System (INIS)

Pettinato, C.; Sarnelli, A.; Di Donna, M.; Civollani, S.; Marengo, M.; Bergamini, C.; Nanni, C.; Montini, G.; Di Pierro, D.; Ferrari, M.

2008-01-01

The aim of this work was the evaluation of biodistribution and radiation dosimetry of 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 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 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 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 68 Ga-DOTANOC delivers a dose to organs comparable to, and even lower than, analogous diagnostic compounds. (orig.)

Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases.

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Alejo, Maria; Alemany, Laia; Clavero, Omar; Quiros, Beatriz; Vighi, Susana; Seoud, Muhieddine; Cheng-Yang, Chou; Garland, Suzanne M; Juanpere, Nuria; Lloreta, Josep; Tous, Sara; Klaustermeier, Jo Ellen; Quint, Wim; Bosch, F Xavier; de Sanjosé, Silvia; Lloveras, Belen

2018-06-01

Neuroendocrine tumors (NET) of the cervix are rare tumors with a very aggressive course. The human papillomavirus (HPV) has been linked to its etiology. The objective of this study is to describe HPV prevalence and genotype distribution of NET. Forty-nine tumors with histological neuroendocrine features were identified among 10,575 invasive cervical cancer (ICC) cases from an international study. HPV DNA detection was done using SPF10/DEIA /LiPA 25 system. Immunohistochemical (IHC) staining for neuroendocrine markers (chromogranin A, synaptophysin, CD56) and for p16 INK4a as a surrogate for HPV transforming infection was performed. In 13 samples with negative IHC for all 3 neuroendocrine markers studied, it was possible to conduct electron microscopy (EM). NET represented 0.5% of the total ICC series and HPV was detected in 42 out of 49 samples (85.7%, 95%CI:72.8%,94.1%). HPV16 was the predominant type (54.8%), followed by HPV18 (40.5%). p16 INK4a overexpression was observed in 38/44 cases (86.4%). Neuroendocrine IHC markers could be demonstrated in 24/37 (64.9%) cases. EM identified neuroendocrine granules in 8 samples with negative IHC markers. Our data confirms the association of cervical NET with HPV and p16 INK4a overexpression. Specifically, HPV16 and 18 accounted together for over 95% of the HPV positive cases. Current HPV vaccines could largely prevent these aggressive tumors. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Should patients with laryngeal small cell neuroendocrine carcinoma receive prophylactic cranial irradiation?

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Coca-Pelaz, Andres; Devaney, Kenneth O.; Rodrigo, Juan P.; Halmos, Gyorgy B.; Strojan, Primoz; Mendenhall, William M.; Eisbruch, Avraham; Smee, Robert; Kusafuka, Kimihide; Rinaldo, Alessandra; Ferlito, Alfio

2016-01-01

While small cell neuroendocrine carcinomas (SCNCs) most often arise in the lung, extrapulmonary SCNCs arise in a variety of locations-including the head and neck region. In particular, laryngeal SCNCs-while rare tumors-are nevertheless recognized as distinct lesions. The rarity of laryngeal SCNC

18F-fluorodeoxyglucose positron emission tomography predicts survival of patients with neuroendocrine tumors

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Binderup, Tina; Knigge, Ulrich; Loft, Annika

2010-01-01

PURPOSE: (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) is currently not used on a routine basis for imaging of neuroendocrine (NE) tumors. The aim of this study was to investigate the prognostic value of FDG-PET in patients with NE tumors. EXPERIMENTAL DESIGN: Ninety...

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

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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

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.

Alternative Polyadenylation of Tumor Suppressor Genes in Small Intestinal Neuroendocrine Tumors

OpenAIRE

Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

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 pro...

F-18 FDG PET/CT imaging of primary hepatic neuroendocrine tumor

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Katsuya Mitamura

2015-01-01

Full Text Available Primary hepatic neuroendocrine tumors (PHNETs are extremely rare neoplasms. Herein, we report a case of a 70-year-old man with a hepatic mass. The non-contrast computed tomography (CT image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F18- fluorodeoxyglucose (18F-FDG positron emission tomography (PET and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body 18F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1. The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by 18F-FDG PET imaging.

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.

Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

International Nuclear Information System (INIS)

Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

2012-01-01

The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

Radiofrequency Ablation of Lung Tumors

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... News Physician Resources Professions Site Index A-Z Radiofrequency Ablation (RFA) / Microwave Ablation (MWA) of Lung Tumors ... and Microwave Ablation of Lung Tumors? What are Radiofrequency and Microwave Ablation of Lung Tumors? Radiofrequency ablation, ...

CT imaging findings of neuroendocrine tumor arising from tailgut cyst: a case report

International Nuclear Information System (INIS)

Aydin, N.; Kara, T.; Kebapci, M.

2012-01-01

Full text: Introduction: We present a case of neuroendocrine tumor which is arisen from a tailgut cyst in a middle aged woman with its computed tomography (CT) imaging findings. Objective and tasks:The tailgut normally involutes by the eighth week of gestational age. If a tailgut rest proceeds, it may give rise to a tailgut cyst in the presacral space. Malign transformation of the tailgut cyst is very rare. Material and methods: A 35-year-old woman with a history of endometriosis admitted to our hospital for her routine control.An ultrasonography examination and contrast medium enhanced tomography of the abdomen and pelvis were performed. Results: CT showed multiple well-defined solid heterogen masses in presacral space. The patient underwent surgery. Pathology was reported as neuroendocrine tumor arising within tailgut cyst. Conclusion: Adenocarcinoma, neuroendocrine carcinoma, and sarcoma developing within the tailgut cyst has been reported. CT shows well-marginated presacral mass.If concurrent malignant transformation occurs, CT shows loss of margins and involvement of adjacent structures.Diagnosis of tailgut cyst is important because of it's malignant potential

Severe Unresponsive Hypoglycemia Associated with Neuroendocrine Tumor of Unknown Primary Site - 18 Years after Rectal Cancer Surgery. Case Report.

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Rusu, Octavia Cristina; Costea, Radu Virgil; Popa, Cristian Constantin; Iliesiu, Andreea; Dumitru, Adrian; Becheanu, Gabriel; Neagu, Stefan Ilie

2015-09-01

Neuroendocrine tumors are derived from cells that have the unique ability to synthesize, store and secrete a variety of metabolically active substances, peptides and amines, characteristic of the tissue of origin, which can cause distinct clinical syndromes. We present the case of a 58-year-old patient diagnosed and surgically treated in January 1996 for stage III inferior rectal cancer, who was readmitted after 18 years presenting persistent diarrheic syndrome and asthenia. Investigations performed (abdominal CT) showed multiple liver metastases, initially suspected as being related to the rectal cancer. Biopsy of liver metastases and pathological and immunohistochemical analysis demonstrated the neuroendocrine origin (moderately differentiated neuroendocrine tumor). Seven months after the identification of liver metastases and after initiation of oncological therapy with Interferon and Somatostatin, the patient presented severe hypoglycemia (serum glucose 13-70 mg/dl) proved to be due to insulin-like factors (serum insulin level 64.9 ìU/ml) secreted by metastases. Due to the aggressive evolution of neuroendocrine tumor, with multiple episodes of severe hypoglycemia, resistant to treatment, the patient died approximately one month after the occurrence of hypoglycemic episodes. Despite comprehensive tests (abdominal CT scan, colonoscopy, bone scintigraphy and PET/CT), the primary site of the neuroendocrine tumors remained unknown.

Neuroendocrine tumor of the skin of head and neck

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Stošić Srboljub

2005-01-01

Full Text Available Background. Merkel cell carcinom is a rare neuroendrocine tumor of skin which manifests it self through aggressive growth and early regional metastasis. It develops mainly in older population. Locally, the tumor spreads intracutaneously. Case report. We showed two cases (females of 89 and 70 years old hospitalized within the last two years. The first patient was treated surgically three times. After the surgery, the patient was treated with radio therapy, and died 3 years from the beginning of the treatment. The second patient with this neuroendocrine tumor with the high malignancy potential and huge regional metastasis, was treated surgically, and died a month and a half after the operation. Conclusion. These two cases confirmed the aggressive and recidivant growth of this tumor with the difficult pathologic investigation, and the extremely bad prognosis inspite of the treatment.

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

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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

Nationwide multicenter study on the management of pulmonary neuroendocrine (carcinoid tumors

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Samira M Sadowski

2017-12-01

Full Text Available Background and aim: To analyze the management and outcome of patients with primary typical (TC and atypical lung carcinoids (AC in Switzerland. Methods: Retrospective analysis of patients selected from a neuroendocrine tumor (NET registry. Patients were divided into TC and AC according to pathology reports, and surgical procedures were grouped as wedge/segmentectomy, lobectomy/bilobectomy and pneumectomy. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Results: Over 7 years, 113 pulmonary carcinoids (61.9% females, mean age 59.4 years were included from 19 hospitals, with pathology data on Ki67 and necrosis incomplete in 16 cases. Eighty-three TC and 14 AC underwent surgical resection with a primary tumor size of median 14.5 (range 1–80 mm and diagnosis was established in 55.8% at surgery. Mean follow-up was 30.2 ± 23.1 months. Lobectomy was performed in 54.2% and wedge resection in 17.7% of cases. Six patients received additional systemic therapy. There was a trend for larger primary lesion size and a significantly higher rate of N2–N3 status in AC. Mean survival tended to be increased in patients with TC compared to AC (86.1 vs 48.4 months, P = 0.06 and mean disease-free interval after surgical resection was 74.1 and 48.3 months for TC and AC, respectively (P = 0.74. Conclusion: AC of the lung has a more malignant behavior and a trend to a worse outcome. The results of this registry reinforce the need for standardized histological diagnosis and inter-disciplinary therapeutic decision making to improve the quality of care of patients with TC and AC.

Five year remission of GHRH secreting bronchial neuroendocrine tumor with symptoms of acromegaly. Utility of chromogranin A in the monitoring of the disease

International Nuclear Information System (INIS)

Bolanowski, M.; Zatonska, K.; Kos-Kudla, B.; Rzeszutko, M.; Marciniak, M.

2006-01-01

Acromegaly is usually caused by excess GH (growth hormone) secretion by pituitary adenoma. Extremely rare (< 1% of cases) acromegaly can be a result of ectopic GHRH (growth hormone releasing hormone) secretion by bronchial tubes, lung, pancreatic or intestinal tumor. The aim of this description is to present the case of successfully treated acromegaly caused by ectopic GHRH secretion by bronchial neuroendocrine tumor and the usefulness of chromogranin A assay in the disease monitoring. The diagnosis of acromegaly in 61-year old woman was based on typical clinical picture and elevated GH and IGF-1(insulin-like growth factor-1) levels. MRI (magnetic resonance imaging) images revealed no tumor in the pituitary but only the pituitary enlargement. Moreover, the right lung tumor (10 cm size) and elevated GHRH level were documented. The secretion of GH, IGF-1 and GHRH were normalized and progression of acromegaly was stopped after the carcinoid tumor surgery. Currently, 5 year after surgery, acromegaly is still in the remission, as the normal levels of GH, IGF-1, chromogranin A and normal chest and pituitary images confirm. The authors emphasize usefulness of measurement of chromogranin A concentration for the evaluation of the tumor remission in case the routine GHRH assay is not accessible. (authors)

Neuroendocrine tumors of the gallbladder: a case report and review of the literature

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Mezi Silvia

2011-07-01

Full Text Available Abstract Introduction Primary gallbladder neuroendocrine tumors are extremely rare, representing 0.2% of all neuroendocrine tumors. The diagnosis is incidental in most cases. Case presentation We describe the case of a 57-year-old Caucasian man who underwent laparoscopic cholecystectomy for the evaluation of a gallbladder polyp that had been incidentally detected by ultasonography. Histologically, his lesion was composed of monomorphic cells that contained small round nuclei and that were organized in small nodular, trabecular, and acinar structures. His cells were positive for chromogranin A and synaptophysin, and a diagnosis of "typical" carcinoid of the gallbladder was made. His post-operative computerized axial tomography, 111In-pentetreotide scintigraphy, and hormone-specific marker results were negative. He is disease-free 45 months after surgical treatment. Conclusions Characteristic pathological findings of the gallbladder neuroendocrine tumors predict the prognosis. Whereas classical carcinoids of the gallbladder only rarely have a metastatic or invasive phenotype, the "atypical" variants are more aggressive and are associated with a poorer prognosis. Given the difficulty in distinguishing between benign and malignant lesions in the pre-surgical setting, we tend to consider each polypoid-like lesion of the gallbladder to be a high-risk lesion if it is larger than 1 cm and, as a result, to emphasize the need for cholecystectomy in all cases, relying on the pathological and immunohistochemistry analyses for the final diagnosis.

Critical appraisal of the role of everolimus in advanced neuroendocrine tumors of pancreatic origin

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Mulet-Margalef N

2012-09-01

Full Text Available Núria Mulet-Margalef, Jaume CapdevilaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, SpainAbstract: For many years, the treatment of advanced pancreatic neuroendocrine tumors (pNETs has been limited almost entirely to somatostatin analogs and streptozocin-based chemotherapy, with modest benefit. Increasing knowledge of the biologic features of pNETs has allowed the design of molecular-based clinical trials, which have taken a step forward in the management of these tumors. In this review, we discuss the molecular rationale for the development of everolimus for patients with advanced pNETs, critically review the clinical data obtained by the main studies in this setting, and discuss essential considerations based on recent findings in pNET biology for future drug development involving the phosphatidylinositol 3' kinase-AKT-mTOR pathway.Keywords: pancreatic neuroendocrine tumors, everolimus, targeted therapies

Neuroendocrine tumors of the adrenal glands

International Nuclear Information System (INIS)

Antova, R.; Valcheva, V.; Genova, K.

2013-01-01

Full text: Introduction: Paraganglioma is neuroendocrine neoplasm derived from the sympathetic and parasympathetic paraganglia. They produce large amounts of catecholamine, usually noradrenaline and adrenaline. In 10% of cases are malignant, the criterion for which is not local tumor invasion, and the presence of distant metastases. What you will learn: We present a case of 17 years old boy with headache in the occipital region. Measured blood pressure is 200/100. Patient was consulted by children cardiologist and Holter examination was conducted and a high arterial hypertension (AH) with maximum values to 217/120 mmHg, was recognized with a pattern corresponding to secondary hypertension. An antihypertensive therapy with two drugs has started. Laboratory indicators showed enhanced levels of catecholamines in the urine, enhanced serum levels of noradrenaline, dopamine, renin, adosteron. Doppler ultrasound of the renal arteries showed evidence of stenosis of the left renal artery. Discussion: The performed CT abdomen with contrast enhancement demonstrated retroperitoneal heterogeneous, well- vascularized with lobular surface tumor formation, located between the left renal artery, as the latter ones are in varying degrees stenosed. It was considered that this was a paraganglioma. The diagnosis was confirmed postoperatively. Conclusion: CT is a diagnostic non-invasive imaging method serving for preoperative evaluation of tumors of the sympathetic and parasympathetic paraganglia

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

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Singh S

2014-08-01

Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

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...

Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate

NARCIS (Netherlands)

van Vliet, Esther I.; van Eijck, Casper H.; de Krijger, Ronald R.; Nieveen van Dijkum, Elisabeth J.; Teunissen, Jaap J.; Kam, Boen L.; de Herder, Wouter W.; Feelders, Richard A.; Bonsing, Bert A.; Brabander, Tessa; Krenning, Eric P.; Kwekkeboom, Dik J.

2015-01-01

Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. We

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...... disease and diarrhea with permanently low gastrin in plasma suggest that CCKomas may mimic gastrinoma-like symptoms, because CCK peptides are full agonists of the gastrin/CCK-B receptor....

Diagnosis and Management of Rectal Neuroendocrine Tumors

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Shreya Chablaney

2017-11-01

Full Text Available The incidence of rectal neuroendocrine tumors (NETs has increased by almost ten-fold over the past 30 years. There has been a heightened awareness of the malignant potential of rectal NETs. Fortunately, many rectal NETs are discovered at earlier stages due to colon cancer screening programs. Endoscopic ultrasound is useful in assessing both residual tumor burden after retrospective diagnosis and tumor characteristics to help guide subsequent management. Current guidelines suggest endoscopic resection of rectal NETs ≤10 mm as a safe therapeutic option given their low risk of metastasis. Although a number of endoscopic interventions exist, the best technique for resection has not been identified. Endoscopic submucosal dissection (ESD has high complete and en-bloc resection rates, but also an increased risk of complications including perforation. In addition, ESD is only performed at tertiary centers by experienced advanced endoscopists. Endoscopic mucosal resection has been shown to have variable complete resection rates, but modifications to the technique such as the addition of band ligation have improved outcomes. Prospective studies are needed to further compare the available endoscopic interventions, and to elucidate the most appropriate course of management of rectal NETs.

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 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.

[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.

Neuroendocrine Tumors: A Focus on Liver Metastatic Lesions

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Limouris, Georgios S., E-mail: nucleard@aretaieio.uoa.gr [Athens University Medical Faculty, Nuclear Medicine Division, Radiology Department, Aretaieion University Hospital, Athens (Greece)

2012-02-28

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

Neuroendocrine carcinoma of the breast - a pilot study of a Danish population of 240 breast cancer patients

DEFF Research Database (Denmark)

Brask, Julie Benedicte; Talman, Maj-Lis Møller; Wielenga, Vera Timmermans

2014-01-01

Neuroendocrine carcinoma of the breast - a very recent diagnosis, which was not recognized by WHO until 2003 - has lately been the subject of increasing attention. It is defined as a primary breast cancer with morphologic features similar to other types of neuroendocrine tumors of the lung......, apparent limitations of the WHO definition appear to influence diagnosis. Here, we present our own results obtained from 13 cases and furthermore review previous reports with particular reference to incidence, clinical, histological, and prognostic features....

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

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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.

Therapy of metastatic pancreatic neuroendocrine tumors (pNETs). Recent insights and advances

International Nuclear Information System (INIS)

Ito, Tetsuhide; Igarashi, Hisato; Jensen, R.T.

2012-01-01

Neuroendocrine tumors (NETs) [carcinoids, pancreatic neuroendocrine tumors (pNETs)] are becoming an increasing clinical problem because not only are they increasing in frequency, but they can frequently present with advanced disease that requires diagnostic and treatment approaches different from those used in the neoplasms that most physicians are used to seeing and treating. In the past few years there have been numerous advances in all aspects of NETs including: an understanding of their unique pathogenesis; specific classification systems developed which have prognostic value; novel methods of tumor localization developed; and novel treatment approaches described. In patients with advanced metastatic disease these include the use of newer chemotherapeutic approaches, an increased understanding of the role of surgery and cytoreductive methods, the development of methods for targeted delivery of cytotoxic agents, and the development of targeted medical therapies (everolimus, sunitinib) based on an increased understanding of the disease biology. Although pNETs and gastrointestinal NETs share many features, recent studies show they differ in pathogenesis and in many aspects of diagnosis and treatment, including their responsiveness to different therapies. Because of limited space, this review will be limited to the advances made in the management and treatment of patients with advanced metastatic pNETs over the past 5 years. (author)

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

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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.

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

International Nuclear Information System (INIS)

Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

2013-01-01

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

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

NARCIS (Netherlands)

Jilesen, Anneke P. J.; van Eijck, Casper H. J.; Busch, Olivier R. C.; van Gulik, Thomas M.; Gouma, Dirk J.; van Dijkum, Els J. M. Nieveen

2016-01-01

Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic

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

Combination of capecitabine and oxaliplatin is an effective treatment option for advanced neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Renata Ferrarotto

2013-09-01

Full Text Available The role of chemotherapy in well differentiated neuroendocrine tumors (NET has been questioned. It was recently demonstrated that everolimus and sunitinib have activity in low and intermediate grade pancreatic NET. The aim of this study was to evaluate the activity of capecitabine and oxaliplatin (CapOx combination in treating NET in an unselected population. In this regard, we retrospectively evaluated 24 patients diagnosed with metastatic NET treated with CapOx at two Brazilian institutes that are reference centers in cancer care. Tumor response was measured by RECIST criteria. Median age at diagnosis was 56 years, 71% had ECOG 0 or 1, the majority of tumors were primary from pancreas (67% followed by lung (17%, and 29% were functional. According to WHO classification criteria, 25% were grade 1, 37.5% grade 2 and 37.5% grade 3. Most patients received CapOx as second-line therapy, with a median of 6 cycles. Twenty-nine percent of patients had partial response by RECIST criteria. No association was observed between response rate and tumor grade, primary site or line of CapOx. The median time to progression was 9.8 months and median time to treatment failure was 12.1 months. Seventy-five percent of patients are alive at the time of this analysis; therefore, median overall survival was not reached. The CapOx combination was shown to be active in an unselected population with metastatic NET and may be a good platform for the incorporation of the newer molecular targeted agents being investigated for the treatment of this entity.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor

NARCIS (Netherlands)

A.P.J. Jilesen (Anneke P. J.); C.H.J. van Eijck (Casper); O.R.C. Busch (Olivier); T.M. van Gulik (Thomas); D.J. Gouma (Dirk); E.J.M.N. Van Dijkum (Els J. M. Nieveen)

2016-01-01

textabstractBackground: Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of

The 2015 World Health Organization Classification of Lung Tumors: Impact of Genetic, Clinical and Radiologic Advances Since the 2004 Classification.

Science.gov (United States)

Travis, William D; Brambilla, Elisabeth; Nicholson, Andrew G; Yatabe, Yasushi; Austin, John H M; Beasley, Mary Beth; Chirieac, Lucian R; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B; Geisinger, Kim; Hirsch, Fred R; Ishikawa, Yuichi; Kerr, Keith M; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A; Tsao, Ming Sound; Wistuba, Ignacio

2015-09-01

The 2015 World Health Organization (WHO) Classification of Tumors of the Lung, Pleura, Thymus and Heart has just been published with numerous important changes from the 2004 WHO classification. The most significant changes in this edition involve (1) use of immunohistochemistry throughout the classification, (2) a new emphasis on genetic studies, in particular, integration of molecular testing to help personalize treatment strategies for advanced lung cancer patients, (3) a new classification for small biopsies and cytology similar to that proposed in the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (4) a completely different approach to lung adenocarcinoma as proposed by the 2011 Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification, (5) restricting the diagnosis of large cell carcinoma only to resected tumors that lack any clear morphologic or immunohistochemical differentiation with reclassification of the remaining former large cell carcinoma subtypes into different categories, (6) reclassifying squamous cell carcinomas into keratinizing, nonkeratinizing, and basaloid subtypes with the nonkeratinizing tumors requiring immunohistochemistry proof of squamous differentiation, (7) grouping of neuroendocrine tumors together in one category, (8) adding NUT carcinoma, (9) changing the term sclerosing hemangioma to sclerosing pneumocytoma, (10) changing the name hamartoma to "pulmonary hamartoma," (11) creating a group of PEComatous tumors that include (a) lymphangioleiomyomatosis, (b) PEComa, benign (with clear cell tumor as a variant) and (c) PEComa, malignant, (12) introducing the entity pulmonary myxoid sarcoma with an EWSR1-CREB1 translocation, (13) adding the entities myoepithelioma and myoepithelial carcinomas, which can show EWSR1 gene rearrangements, (14) recognition of usefulness of WWTR1-CAMTA1 fusions in diagnosis of epithelioid

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

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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.)

Enhanced tumor growth in the remaining lung after major lung resection.

Science.gov (United States)

Sano, Fumiho; Ueda, Kazuhiro; Murakami, Junichi; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

2016-05-01

Pneumonectomy induces active growth of the remaining lung in order to compensate for lost lung tissue. We hypothesized that tumor progression is enhanced in the activated local environment. We examined the effects of mechanical strain on the activation of lung growth and tumor progression in mice. The mechanical strain imposed on the right lung after left pneumonectomy was neutralized by filling the empty space that remained after pneumonectomy with a polypropylene prosthesis. The neutralization of the strain prevented active lung growth. According to an angiogenesis array, stronger monocyte chemoattractant protein-1 (MCP-1) expression was found in the strain-induced growing lung. The neutralization of the strain attenuated the release of MCP-1 from the lung cells. The intravenous injection of Lewis lung cancer cells resulted in the enhanced development of metastatic foci in the strain-induced growing lung, but the enhanced development was canceled by the neutralization of the strain. An immunohistochemical analysis revealed the prominent accumulation of tumor-associated macrophages in tumors arising in the strain-induced growing lung, and that there was a relationship between the accumulation and the MCP-1 expression status. Our results suggested that mechanical lung strain, induced by pulmonary resection, triggers active lung growth, thereby creating a tumor-friendly environment. The modification of that environment, as well as the minimizing of surgical stress, may be a meaningful strategy to improve the therapeutic outcome after lung cancer surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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.

Transcription Factor NFIB Is a Driver of Small Cell Lung Cancer Progression in Mice and Marks Metastatic Disease in Patients

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Ekaterina A. Semenova

2016-07-01

Full Text Available Small cell lung cancer (SCLC is an aggressive neuroendocrine tumor, and no effective treatment is available to date. Mouse models of SCLC based on the inactivation of Rb1 and Trp53 show frequent amplifications of the Nfib and Mycl genes. Here, we report that, although overexpression of either transcription factor accelerates tumor growth, NFIB specifically promotes metastatic spread. High NFIB levels are associated with expansive growth of a poorly differentiated and almost exclusively E-cadherin (CDH1-negative invasive tumor cell population. Consistent with the mouse data, we find that NFIB is overexpressed in almost all tested human metastatic high-grade neuroendocrine lung tumors, warranting further assessment of NFIB as a tumor progression marker in a clinical setting.

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.

Neuroendocrine Carcinomas of the Gastroenteropancreatic System

DEFF Research Database (Denmark)

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

2015-01-01

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

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....

Treatment of neuroendocrine tumors (NETs) expressing SMT 90Y and 177Lu

International Nuclear Information System (INIS)

Oliva González, Juan P.; Baum, Richard

2016-01-01

Neuroendocrine tumors (NETs) are a relatively rare and extremely heterogeneous group, essentially characterized by a different metabolism and endocrine histologically pattern. NETs are a challenge for physicians not only for diagnosis but also for early treatment. In addition to this, QT or RT treatments that require a high rate of cell proliferation to be effective, they are not in these tumors as slow growth. The primary treatment of NETs is surgery, either with a curative intent or tumor shrinkage. Peptide Receptors Radiotherapy (RTPR) consists of the administration for therapeutic purposes of Radiolabeled Synthetic Peptides that bind specifically and with high affinity to receptors of tumor cells. The RTPR of TNE with SMT analogues is effective for handling or metastizados inoperable patients. The Conference gives an accurate picture of the treatment of these tumors both 90 Y as 177 Lu. (author)

Incidental Finding of a Neuroendocrine Tumor Arising from Meckel Diverticulum During Hernia Repair - A Case Report and Literature Review.

Science.gov (United States)

Bacalbasa, Nicolae; Costin, Radu; Orban, Carmen; Iliescu, Laura; Hurjui, Ioan; Hurjui, Marcela; Niculescu, Nicoleta; Cristea, Mirela; Balescu, Irina

2016-04-01

Meckel diverticulum is the most common abnormality of the gastrointestinal tract arising from an incomplete obliteration of the vitelline duct during the intrauterine life. Although tumor development in Meckel diverticulum is not a common situation, it can occur due to the persistence of cellular islets with gastric, pancreatic or intestinal origin. The presence of a neuroendocrine tumor arising from Meckel diverticulum is even scarcer. We present the case of a 59-year-old patient in whom a Meckel diverticulum was found during surgery for inguinal hernia; the histopathological and immunohistochemical studies revealed the presence of a well-differentiated neuroendocrine tumor with low mitotic index. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Hepatic Arterial Chemoembolization Using Drug-Eluting Beads in Gastrointestinal Neuroendocrine Tumor Metastatic to the Liver

International Nuclear Information System (INIS)

Gaur, Shantanu K.; Friese, Jeremy L.; Sadow, Cheryl A.; Ayyagari, Rajasekhara; Binkert, Christoph A.; Schenker, Matthew P.; Kulke, Matthew; Baum, Richard

2011-01-01

Purpose: This study was designed to evaluate short ( 3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. Methods: Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100–300 or 300–500 μm drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50–100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RECIST) or European Association for the Study of the Liver (EASL) criteria. Short-term ( 3 months) imaging response was determined and Kaplan–Meier survival curves were plotted. Results: Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163–1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. Conclusions: Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver.

Tumorous interstitial lung disease

International Nuclear Information System (INIS)

Dinkel, E.; Meyer, E.; Mundinger, A.; Helwig, A.; Blum, U.; Wuertemberger, G.

1990-01-01

The radiological findings in pulmonary lymphangitic carcinomatosis and in leukemic pulmonary infiltrates mirror the tumor-dependent monomorphic interstitial pathology of lung parenchyma. It is a proven fact that pulmonary lymphangitic carcinomatosis is caused by hematogenous tumor embolization to the lungs; pathogenesis by contiguous lymphangitic spread is the exception. High-resolution CT performed as a supplement to the radiological work-up improves the sensitivity for pulmonary infiltrates in general and thus makes the differential diagnosis decided easier. Radiological criteria cannot discriminate the different forms of leukemia. Plain chest X-ray allows the diagnosis of pulmonary involvement in leukemia due to tumorous infiltrates and of tumor- or therapy-induced complications. It is essential that the radiological findings be interpreted with reference to the stage of tumor disease and the clinical parameters to make the radiological differential diagnosis of opportunistic infections more reliable. (orig.) [de

Budget impact of somatostatin analogs as treatment for metastatic gastroenteropancreatic neuroendocrine tumors in US hospitals

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Ortendahl JD

2017-08-01

Full Text Available Jesse D Ortendahl,1 Sonia J Pulgar,2 Beloo Mirakhur,3 David Cox,3 Tanya GK Bentley,1 Alexandria T Phan4 1Health Economics, Partnership for Health, LLC, Beverly Hills, CA, USA; 2Health Economics and Outcomes Research, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 3Medical Affairs, Oncology, Ipsen Biopharmaceuticals, Basking Ridge, NJ, USA; 4GI Medical Oncology, University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA Objective: With the introduction of new therapies, hospitals have to plan spending limited resources in a cost-effective manner. To assist in identifying the optimal treatment for patients with locally advanced or metastatic gastroenteropancreatic neuroendocrine tumors, budget impact modeling was used to estimate the financial implications of adoption and diffusion of somatostatin analogs (SSAs. Patients and methods: A hypothetical cohort of 500 gastroenteropancreatic neuroendocrine tumor patients was assessed in an economic model, with the proportion with metastatic disease treated with an SSA estimated using published data. Drug acquisition, preparation, and administration costs were based on national pricing databases and published literature. Octreotide dosing was based on published estimates of real-world data, whereas for lanreotide, real-world dosing was unavailable and we therefore used the highest indicated dosing. Alternative scenarios reflecting the proportion of patients receiving lanreotide or octreotide were considered to estimate the incremental budget impact to the hospital. Results: In the base case, 313 of the initial 500 gastroenteropancreatic neuroendocrine tumor patients were treated with an SSA. The model-predicted per-patient cost was US$83,473 for lanreotide and US$89,673 for octreotide. With a hypothetical increase in lanreotide utilization from 5% to 30% of this population, the annual model-projected hospital costs decreased by US$488,615. When varying the inputs in one-way sensitivity

FOXM1: A novel drug target in gastroenteropancreatic neuroendocrine tumors

Science.gov (United States)

Briest, Franziska; Berg, Erika; Grass, Irina; Freitag, Helma; Kaemmerer, Daniel; Lewens, Florentine; Christen, Friederike; Arsenic, Ruza; Altendorf-Hofmann, Annelore; Kunze, Almut; Sänger, Jörg; Knösel, Thomas; Siegmund, Britta; Hummel, Michael; Grabowski, Patricia

2015-01-01

Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous tumors that need to be molecularly defined to obtain novel therapeutic options. Forkheadbox protein M1 (FOXM1) is a crucial transcription factor in neoplastic cells and has been associated with differentiation and proliferation. We found that FOXM1 is strongly associated with tumor differentiation and occurrence of metastases in gastrointestinal NENs. In vitro inhibition by the FOXM1 inhibitor siomycin A led to down-regulation of mitotic proteins and resulted in a strong inhibitory effect. Siomycin A decreased mitosis rate, induced apoptosis in GEP-NEN cell lines and exerts synergistic effects with chemotherapy. FOXM1 is associated with clinical outcome and FOXM1 inhibition impairs survival in vitro. We therefore propose FOXM1 as novel therapeutic target in GEP-NENs. PMID:25797272

Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

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Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Chapman, Christopher [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of Michigan School of Medicine, Ann Arbor, MI (United States); Rao, Aarti [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Davis, School of Medicine, Davis, CA (United States); Shen, John [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); University of California, Irvine, School of Medicine, Irvine, CA (United States); Quinlan-Davidson, Sean [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Department of Radiation Oncology, McMaster University, Juravinski Cancer Centre, Hamilton, Ontario (Canada); Filion, Edith J. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); Departement de Medecine, Service de Radio-Oncologie, Centre Hospitalier de l' Universite de Montreal, Montreal, Quebec (Canada); Wakelee, Heather A.; Colevas, A. Dimitrios [Department of Medicine, Division of Oncology, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); Whyte, Richard I. [Department of Cardiothoracic Surgery, Division of General Thoracic Surgery, Stanford University School of Medicine, Stanford, CA (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA (United States); and others

2012-09-01

Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18-25 Gy) (Group 1), and larger tumors (gross tumor volume {>=}12 mL) received multifraction regimens with BED {>=}100 Gy (total dose, 50-60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

Resolution of Hepatic Encephalopathy Following Hepatic Artery Embolization in a Patient with Well-Differentiated Neuroendocrine Tumor Metastatic to the Liver

International Nuclear Information System (INIS)

Erinjeri, Joseph P.; Deodhar, Ajita; Thornton, Raymond H.; Allen, Peter J.; Getrajdman, George I.; Brown, Karen T.; Sofocleous, Constantinos T.; Reidy, Diane L.

2010-01-01

Hepatic encephalopathy is considered a contraindication to hepatic artery embolization. We describe a patient with a well-differentiated neuroendocrine tumor metastatic to the liver with refractory hepatic encephalopathy and normal liver function tests. The encephalopathy was refractory to standard medical therapy with lactulose. The patient's mental status returned to baseline after three hepatic artery embolization procedures. Arteriography and ultrasound imaging before and after embolization suggest that the encephalopathy was due to arterioportal shunting causing hepatofugal portal venous flow and portosystemic shunting. In patients with a primary or metastatic well-differentiated neuroendocrine tumor whose refractory hepatic encephalopathy is due to portosystemic shunting (rather than global hepatic dysfunction secondary to tumor burden), hepatic artery embolization can be performed safely and effectively.

Surgery of resectable nonfunctioning neuroendocrine pancreatic tumors.

Science.gov (United States)

Dralle, Henning; Krohn, Sabine L; Karges, Wolfram; Boehm, Bernhard O; Brauckhoff, Michael; Gimm, Oliver

2004-12-01

Nonfunctioning neuroendocrine pancreatic tumors (NFNEPTs) comprise about one-third of pancreatic endocrine tumors. Based on immunohistochemistry, nonfunctioning tumors are difficult to distinguish from functioning ones; therefore the final diagnosis is basically the result of a synopsis of pathology and clinical data. Owing to their incapacity to produce hormone-dependent symptoms, NFNEPTs are detected incidentally or because of uncharacteristic symptoms resulting from local or distant growth. About two-thirds of NFNEPTs are located in the pancreatic head, so jaundice may be a late symptom of this tumor. Modern diagnostic procedures are best applied by a stepwise approach: first endoscopic ultrasonography and computed tomography/magnetic resonance imaging followed by somatostatin receptor scintigraphy or positron emission tomography (or both). Due to significant false-positive and false-negative findings, for decision-making the latter should be confirmed by a second imaging modality. Regarding indications for surgery and the surgical approach to the pancreas, three pancreatic manifestations of NFNEPTs can be distinguished: (1) solitary benign non-multiple endocrine neoplasia type 1 (non-MEN-1); (2) multiple benign MEN-1; and (3) malignant NFNEPTs. Reviewing the literature and including our experience with 18 NFNEPTs (8 benign, 10 malignant) reported here, the following conclusions can be drawn: (1) Solitary benign non-MEN-1 NFNEPTs can be removed by enucleation or by pancreas-, spleen-, and duodenum-preserving techniques in most cases. The choice of surgical technique depends on the location and site of the tumor and its anatomic relation to the pancreatic duct. (2) With multiple benign MEN-1 NFNEPTs, because of the characteristics of the underlying disease a preferred, more conservative concept (removal of only macrolesions) competes with a more radical procedure (left pancreatic resection with enucleation of head macrolesions). Further studies are necessary to

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, Sjoerd; van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Borel Rinkes, Inne H. M.; Vriens, Menno R.; Valk, Gerlof D.

2015-01-01

An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore, blood

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, S.; Leeuwaarde, R.S. van; Pieterman, C.R.; Laat, J.M. de; Hermus, A.R.M.M.; Dekkers, O.M.; Herder, W.W. de; Horst-Schrivers, A.N. van der; Drent, M.L.; Bisschop, P.H.; Havekes, B.; Rinkes, I.H.; Vriens, M.R.; Valk, G.D.

2015-01-01

CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

NARCIS (Netherlands)

Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

2015-01-01

Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

Pancreatic Neuroendocrine Neoplasms: Basic Biology, Current Treatment Strategies and Prospects for the Future

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Akihiro Ohmoto

2017-01-01

Full Text Available Pancreatic neuroendocrine neoplasms (pNENs are rare tumors accounting for only 1%–2% of all pancreatic tumors. pNENs are pathologically heterogeneous and are categorized into three groups (neuroendocrine tumor: NET G1, NET G2; and neuroendocrine carcinoma: NEC on the basis of the Ki-67 proliferation index and the mitotic count according to the 2010 World Health Organization (WHO classification of gastroenteropancreatic NENs. NEC in this classification includes both histologically well-differentiated and poorly differentiated subtypes, and modification of the WHO 2010 classification is under discussion based on genetic and clinical data. Genomic analysis has revealed NETs G1/G2 have genetic alterations in chromatin remodeling genes such as MEN1, DAXX and ATRX, whereas NECs have an inactivation of TP53 and RB1, and these data suggest that different treatment approaches would be required for NET G1/G2 and NEC. While there are promising molecular targeted drugs, such as everolimus or sunitinib, for advanced NET G1/G2, treatment stratification based on appropriate predictive and prognostic biomarkers is becoming an important issue. The clinical outcome of NEC is still dismal, and a more detailed understanding of the genetic background together with preclinical studies to develop new agents, including those already under investigation for small cell lung cancer (SCLC, will be needed to improve the prognosis.

Molecular characterization of radon-induced rat lung tumors

International Nuclear Information System (INIS)

Guillet Bastide, K.

2008-11-01

The radon gas is a well known lung carcinogenic factor in human at high doses but the cancer risk at low doses is not established. Indeed, epidemiological studies at low doses are difficult to conduct because of the human exposure to other lung carcinogenic factors. These data underlined the necessity to conduct experiments on lung tumors developed on animal model. The aim of this work was to characterize rat lung tumors by working on a series of radon-induced tumors that included adenocarcinomas (A.C.), squamous cell carcinomas (S.C.C.) and adeno-squamous carcinomas (A.S.C.), that are mixed tumors with both A.C. and S.C.C. cellular components. A C.G.H. analysis of the three types of tumors allowed us to define chromosomal recurrent unbalances and to target candidate genes potentially implicated in lung carcinogenesis, as p16Ink4a, p19Arf, Rb1, K-Ras or c-Myc. A more precise analysis of the p16Ink4a/Cdk4/Rb1 and p19Arf/Mdm2/Tp53 pathways was performed and indicated that the Rb1 pathway was frequently inactivated through an absence of p16 Ink4a protein expression, indicating that it has a major role in rat lung carcinogenesis. Finally, a comparative transcriptomic analysis of the three types of tumors allowed us to show for the first time that the complex tumors A.S.C. have a transcriptomic profile in accordance with their mixed nature but that they also display their own expression profiles specificities. This work allowed us to find molecular characteristics common to murine and human lung tumors, indicating that the model of lung tumors in rat is pertinent to search for radiation-induced lung tumors specificities and to help for a better molecular identification of this type of tumors in human. (author)

Tumor Volume-Adapted Dosing in Stereotactic Ablative Radiotherapy of Lung Tumors

International Nuclear Information System (INIS)

Trakul, Nicholas; Chang, Christine N.; Harris, Jeremy; Chapman, Christopher; Rao, Aarti; Shen, John; Quinlan-Davidson, Sean; Filion, Edith J.; Wakelee, Heather A.; Colevas, A. Dimitrios; Whyte, Richard I.

2012-01-01

Purpose: Current stereotactic ablative radiotherapy (SABR) protocols for lung tumors prescribe a uniform dose regimen irrespective of tumor size. We report the outcomes of a lung tumor volume-adapted SABR dosing strategy. Methods and Materials: We retrospectively reviewed the outcomes in 111 patients with a total of 138 primary or metastatic lung tumors treated by SABR, including local control, regional control, distant metastasis, overall survival, and treatment toxicity. We also performed subset analysis on 83 patients with 97 tumors treated with a volume-adapted dosing strategy in which small tumors (gross tumor volume <12 mL) received single-fraction regimens with biologically effective doses (BED) <100 Gy (total dose, 18–25 Gy) (Group 1), and larger tumors (gross tumor volume ≥12 mL) received multifraction regimens with BED ≥100 Gy (total dose, 50–60 Gy in three to four fractions) (Group 2). Results: The median follow-up time was 13.5 months. Local control for Groups 1 and 2 was 91.4% and 92.5%, respectively (p = 0.24) at 12 months. For primary lung tumors only (excluding metastases), local control was 92.6% and 91.7%, respectively (p = 0.58). Regional control, freedom from distant metastasis, and overall survival did not differ significantly between Groups 1 and 2. Rates of radiation pneumonitis, chest wall toxicity, and esophagitis were low in both groups, but all Grade 3 toxicities developed in Group 2 (p = 0.02). Conclusion: A volume-adapted dosing approach for SABR of lung tumors seems to provide excellent local control for both small- and large-volume tumors and may reduce toxicity.

Lung Shunt Fraction prior to Yttrium-90 Radioembolization Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis

International Nuclear Information System (INIS)

Ludwig, Johannes M.; Ambinder, Emily McIntosh; Ghodadra, Anish; Xing, Minzhi; Prajapati, Hasmukh J.; Kim, Hyun S.

2016-01-01

ObjectiveTo investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.MethodsA single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients’ baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low ( 1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.ConclusionsLSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

Grade Assignment by Ki-67 Proliferative Index, Mitotic Count, and Phosphohistone H3 Count in Surgically Resected Gastrointestinal and Pancreatic Neuroendocrine Tumors.

Science.gov (United States)

Murphy, Claire E; McCormick, Kinsey A; Shankaran, Veena; Reddi, Deepti M; Swanson, Paul E; Upton, Melissa P; Papanicolau-Sengos, Antonios; Khor, Sara; Westerhoff, Maria

The aim of this study was to evaluate the concordance in grade assignment for gastroenteropancreatic neuroendocrine tumors using mitotic count (MC), Ki-67 proliferative index (KPI), and phosphohistone H3 count (PHH3C). Resected gastroenteropancreatic neuroendocrine tumors were graded based on MC, KPI, and PHH3C. Concordance was determined using a weighted κ statistic. Median survival across each grade category was determined using Kaplan-Meier methods. Of the 110 patients, the majority had gastrointestinal primaries and grade 1 or 2 tumors. Rates of discordance in grade assignment were 29% of cases for KPI versus MC (κW = 0.26), 32% for PHH3C versus MC (κW = 0.34), and 32% for PHH3C versus KPI (κW = 0.37). There was fair agreement between grading by KPI and MC. Relative to grade by KPI and MC, PHH3C tended to upgrade tumors. The proportion alive at 3 and 5 years was not significantly different for patients with grade 1 versus grade 2 tumors. The concordance between KPI and MC was fair. Phosphohistone H3 count tended to upgrade tumors using the cutoffs established by MC. Grade 1 and grade 2 tumors were associated with similar survival regardless of grading method. The overall relevance of the current cutoff values used in grading neuroendocrine tumors may need to be revisited.

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

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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.

Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

Science.gov (United States)

Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

2017-01-01

Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

Metastatic neuroendocrine tumor with initial presentation of orbital apex syndrome

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Yen-Yu Huang

2017-03-01

Full Text Available The possible etiologies of orbital apex syndrome range from inflammatory, infectious, neoplastic, iatrogenic/traumatic, to vascular processes. In patients without obvious infection or systemic cancer history, judicious use of corticosteroids is a reasonable strategy. We describe a 64-year-old man who presented with orbital apex syndrome and had progressed to total visual loss in three days after admission. Radiological imaging and pathological studies were consistent with a neuroendocrine tumor with multiple metastases. We recommend that a biopsy-proven specimen is warranted in patient with orbital apex syndrome even without a cancer history.

Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

International Nuclear Information System (INIS)

Ivanova, D.; Balev, B.

2013-01-01

Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

A rare case with synchronous gastric gastrointestinal stromal tumor, pancreatic neuroendocrine tumor, and uterine leiomyoma.

Science.gov (United States)

Arabadzhieva, Elena; Yonkov, Atanas; Bonev, Sasho; Bulanov, Dimitar; Taneva, Ivanka; Vlahova, Alexandrina; Dikov, Tihomir; Dimitrova, Violeta

2016-11-15

Although gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, they comprise less than 1% of all gastrointestinal tumors. Neuroendocrine tumors (NET) of the gastro-enteropancreatic system are also rare, representing about 2% of all gastrointestinal neoplasms. Pancreatic localization of NET is extremely uncommon-these tumors are only 1-5% of all pancreatic cancers. We describe an unusual case with triple tumor localization-a gastric tumor, a formation in the pancreas, which involves the retroperitoneal space, and a uterine leiomyoma. The exact diagnosis was confirmed with immunohistochemical study after surgical treatment of the patient. Distal pancreatic resection, splenectomy, partial gastrectomy, omentectomy, and hysterectomy were performed. The histological examination proved an epithelioid type of gastric GIST. Immunostaining showed focal positive expression of c-kit and no mitotic figures per 50 HPF. Histology of the pancreatic and retroperitoneal formation proved a well-differentiated NET with origin from the islets of Langerhans. The immunohistochemical study demonstrated co-expression of chromogranin A and synaptophysin. This is the fourth case published so far of a patient with synchronous pancreatic NET and gastric GIST. The main objective of the study is to present a unique case because we have not found any reports for coexistence of the described three types of neoplasm, as in our patient, and we hope that it will be valuable in the future investigations about the genesis, diagnosis, and treatment of these types of tumors.

Perspectives of patients and physicians about neuroendocrine tumors. A qualitative study

Science.gov (United States)

Manolios, Emilie; Rebours, Vinciane; Revah-Levy, Anne; Ruszniewski, Philippe

2018-01-01

Purpose Gastrointestinal neuroendocrine tumors (NETs) are rare, complex to manage, and often have a chronic course. Qualitative methods are a tool of choice for focusing on patients' and physicians’ points of view especially when dealing with a complex and rare disease. Nonetheless, they remain undeveloped in research related to NETs. This study aimed to explore the experience of NETs among both patients and their physicians and to cross their perspectives for the purpose of finding pathways to improving care. Results Our analysis found two themes: (1) the questions raised by this disease, and (2) the complex experience of this singular disease. Our findings underlined the experience of confusion found among patients regarding the patient's unusual somatic experience and around the question of vocabulary, i.e. the naming of the disease and the semantic field of severity in the medical discourse. Conclusion Means for reducing the confusion that patients experience in this disease are needed. The explanations that the physician offers to the patient must clarify the issues related to NETs. We therefore propose a statement that all physicians can use to support patients diagnosed with neuroendocrine tumors to clear up potential confusion. Methods We conducted a qualitative study, based on 40 semi-structured interviews, in a specialized department of gastro-pancreatology. Participants, purposively selected until data saturation, came from two different sub-samples: (i) patients with a metastatic NETs (N = 20) and (ii) their referring physicians (N = 10). The data were examined by thematic analysis. PMID:29581833

Immune Checkpoint Inhibitors in the Treatment of Patients with Neuroendocrine Neoplasia.

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Weber, Matthias M; Fottner, Christian

2018-01-01

Well-differentiated neuroendocrine neoplasms (NENs) are usually controlled by antiproliferative, local ablative and/or radionuclide therapies, whereas poorly differentiated NENs generally require cytotoxic chemotherapy. However, treatment options for patients with advanced/metastatic high-grade NENs remain limited. Review of the literature and international congress abstracts on the efficacy and safety of immunotherapy by checkpoint inhibition in advanced/metastatic NENs. Evidence points to an important role of immune phenomena in the pathogenesis and treatment of neuroendocrine tumors (NETs). Programmed cell death 1 (PD-1) protein and its ligand are mainly expressed in poorly differentiated NENs. Microsatellite instability and high mutational load are more pronounced in high-grade NENs and may predict response to immunotherapy. Clinical experience of immune checkpoint blockade mainly exists for Merkel cell carcinoma, a high-grade cutaneous neuroendocrine carcinoma (NEC), which has led to approval of the anti-PD-1 antibody avelumab. In addition, there is anecdotal evidence for the efficacy of checkpoint inhibitors in large-cell lung NECs, ovarian NECs and others, including gastroenteropancreatic NENs. Currently, phase II studies investigate PDR001, pembrolizumab, combined durvalumab and tremelimumab, and avelumab treatment in patients with advanced/metastatic NENs. Immune checkpoint inhibitors are a promising therapeutic option, especially in progressive NECs or high-grade NETs with high tumor burden, microsatellite instability, and/or mutational load. © 2018 S. Karger GmbH, Freiburg.

Disentegrating lung tumor

International Nuclear Information System (INIS)

Mamedbekov, Eh.N.; Kyazimova, L.G.; Mamed''yarova, F.A.

1992-01-01

Clinical and roentgenological appearances of tuberculosis and tumoral lesions of bronchi and lungs are similar. It makes possible of wrong diagnosis of disease. Complications in diagnosis are connected with that fact that increase of frequency of pulmonary carcinoma both in patients with active tuberculosis and in persons with residual posttuberculous changes in respiratory organs is observed. Patients with specific processes in the lungs was presented. Additional X-ray examination was carried out on the base of clinical symptoms and results of X-ray examination. The diagnosis was established: disintegrating blastoma of the right lung with metastases to mediastinum lymph nodes

Molecular imaging of neuroendocrine tumors using 68Ga-labeled peptides (Somatostatin receptor PET/CT)

International Nuclear Information System (INIS)

Baum, R.P.; Prasad, V.; Hoersch, D.

2009-01-01

Receptor PET/CT using 68 Ga-labeled somatostatin analogues (DOTA-NOC, DOTA-TOC or DOTA-TATE) enables the highly sensitive molecular imaging of neuroendocrine tumors (NETs) based on the expression of somatostatin receptors and even the detection of receptor subtypes. Our experience after more than 3000 studies shows that receptor PET/CT has a significantly higher tumor detection rate than conventional scintigraphy (even in SPECT/CT technique), and that tumor lesions can be very accurately localized. By calculating standardized uptake values (SUV) - which are reproducible and investigator-independent - patients can be selected for peptide receptor radiotherapy and also the course after therapy can be controlled. Receptor-PET/CT is the most sensitive imaging modality for the detection of unknown primary tumors (CUP syndrome), which is especially true for the detection of neuroendocrine tumors of the pancreas and small bowel; whole-body staging (''one stop shop'') as well as restaging and selection of patients for peptide receptor radiotherapy can be performed using a patient-friendly procedure (examination finished within one hour) exposing the patient to less radiation than whole-body CT scanning. The 68 Ge/ 68 Ga generator has proved very reliable over the years - even in a hospital environment. The effective costs for 68 Ga labeled somatostatin analogues might be less than for scintigraphic agents, provided a certain number of studies per year are performed. The development of new tumor-specific peptides as well as of other DOTA- or NOTA-coupled radiopharmaceuticals opens a new avenue into the future: finally, the 68 Ga generator could play a similar important role for PET/CT as did the 99m Tc-Generator for conventional gamma camera imaging over the last decades. (orig.)

Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

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Daubenbüchel, Anna M. M.; Müller, Hermann L.

2015-01-01

Childhood-onset craniopharyngiomas are partly cystic embryonic malformations of the sellar/parasellar region. The therapy of choice in patients with favorable tumor localization is complete resection with a specific focus on maintaining optical and hypothalamic neuroendocrine functions. In patients with unfavorable tumor localization (i.e., hypothalamic involvement), a limited hypothalamus-sparing surgical strategy followed by local irradiation is recommended. Involvement and/or surgical lesions of posterior hypothalamic areas cause major neuroendocrine sequelae. The overall survival rates are high (92%) but neuroendocrine disorders such as obesity and metabolic syndrome due to involvement and/or treatment-related hypothalamic lesions have major negative impact on survival and quality of life. Recurrences and progressions are frequent post-surgical events. Because irradiation is efficient in preventing tumor progression, appropriate timing of post-surgical irradiation is currently under investigation in a randomized multinational trial (KRANIOPHARYNGEOM 2007). Childhood-onset craniopharyngioma should be recognized as a chronic disease requiring treatment and constant monitoring of the clinical and quality of life consequences, frequently impaired due to neuroendocrine disorders, by experienced multidisciplinary teams in order to provide optimal care of surviving patients. PMID:26239246

Neuroendocrine Disorders in Pediatric Craniopharyngioma Patients

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Anna M. M. Daubenbüchel

2015-03-01

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

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

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Rehfeld, Anders; Plass, Mireya; Døssing, Kristina; Knigge, Ulrich; Kjær, Andreas; Krogh, Anders; Friis-Hansen, Lennart

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 or 3' untranslated regions. Among these, 11 genes had been previously associated with cancer, with 4 genes being known tumor suppressors: DCC, PDZD2, MAGI1, and DACT2. We validated the APA in three out of three cases with quantitative real-time-PCR. Our findings suggest that changes of APA pattern in these 16 genes could be involved in the tumorigenesis of SI-NETs. Furthermore, they also point to APA as a new target for both diagnostic and treatment of SI-NETs. The identified genes with APA specific to the SI-NETs could be further tested as diagnostic markers and drug targets for disease prevention and treatment.

Argininosuccinate synthetase (ASS) deficiency in high-grade pulmonary neuroendocrine carcinoma: an opportunity for personalized targeted therapy.

Science.gov (United States)

Walts, Ann E; Bomalaski, John S; Ines, Delma; Orsulic, Sandra

2015-08-01

Cells deficient in argininosuccinate synthetase (ASS) must absorb the arginine they need for growth from circulating blood. Treatment with pegylated arginine deiminase (ADI-PEG 20) selectively eliminates arginine from the circulation and has shown some efficacy against ASS-deficient tumors including small cell lung cancer (SCLC). We sought to assess ASS expression in a cohort of high-grade pulmonary neuroendocrine carcinomas (PNEC) which include SCLC and large cell neuroendocrine carcinoma (LCNEC). Sixty-nine PNEC (49 SCLC and 20 LCNEC) were retrieved from our pathology archives. Formalin-fixed paraffin-embedded sections of the 54 primary tumors, 15 metastases and appropriate positive and negative controls were immunostained using an ASS-specific monoclonal antibody. Positive staining in ASS negative. 58 % of the PNEC including 61.2 % of the SCLC and 50 % of the LCNEC were ASS negative. These ASS-negative tumors included 63 % of the primary and 40 % of the metastatic lesions tested. More than 50 % of the high-grade PNEC tested lack immunohistochemically detectable ASS, suggesting that they are auxotrophic for arginine and potential candidates for arginine deprivation therapy. PNEC comprise about 25 % of primary lung cancers and have a 5-year overall survival of only 5-10 %, underscoring the need for new and more effective therapies. Immunostaining for ASS has potential to improve the selection of patients with PNEC for arginine deprivation therapy with ADI-PEG 20.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

International Nuclear Information System (INIS)

Min Yugang; Santhanam, Anand; Ruddy, Bari H; Neelakkantan, Harini; Meeks, Sanford L; Kupelian, Patrick A

2010-01-01

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion

Energy Technology Data Exchange (ETDEWEB)

Min Yugang; Santhanam, Anand; Ruddy, Bari H [University of Central Florida, FL (United States); Neelakkantan, Harini; Meeks, Sanford L [M D Anderson Cancer Center Orlando, FL (United States); Kupelian, Patrick A, E-mail: anand.santhanam@orlandohealth.co [Department of Radiation Oncology, University of California, Los Angeles, CA (United States)

2010-09-07

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

A GPU-based framework for modeling real-time 3D lung tumor conformal dosimetry with subject-specific lung tumor motion.

Science.gov (United States)

Min, Yugang; Santhanam, Anand; Neelakkantan, Harini; Ruddy, Bari H; Meeks, Sanford L; Kupelian, Patrick A

2010-09-07

In this paper, we present a graphics processing unit (GPU)-based simulation framework to calculate the delivered dose to a 3D moving lung tumor and its surrounding normal tissues, which are undergoing subject-specific lung deformations. The GPU-based simulation framework models the motion of the 3D volumetric lung tumor and its surrounding tissues, simulates the dose delivery using the dose extracted from a treatment plan using Pinnacle Treatment Planning System, Phillips, for one of the 3DCTs of the 4DCT and predicts the amount and location of radiation doses deposited inside the lung. The 4DCT lung datasets were registered with each other using a modified optical flow algorithm. The motion of the tumor and the motion of the surrounding tissues were simulated by measuring the changes in lung volume during the radiotherapy treatment using spirometry. The real-time dose delivered to the tumor for each beam is generated by summing the dose delivered to the target volume at each increase in lung volume during the beam delivery time period. The simulation results showed the real-time capability of the framework at 20 discrete tumor motion steps per breath, which is higher than the number of 4DCT steps (approximately 12) reconstructed during multiple breathing cycles.

Change from lung adenocarcinoma to small cell lung cancer as a mechanism of resistance to afatinib.

Science.gov (United States)

Manca, Paolo; Russano, Marco; Pantano, Francesco; Tonini, Giuseppe; Santini, Daniele

2017-08-29

We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib.

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

Neuroendocrine Carcinoma of the Stomach: A Case Study

Directory of Open Access Journals (Sweden)

Keisuke Kubota

2011-01-01

Full Text Available Gastric neuroendocrine carcinomas are rare and have a poor prognosis, and the diagnostic criteria for this disease have recently changed. We herein report a case of sporadic gastric neuroendocrine carcinoma. A 75-year-old man was referred to our hospital with epigastric pain. Endoscopic examination revealed a localized ulcerative lesion (diameter, 4 cm at the upper stomach. The diagnosis on biopsy was neuroendocrine carcinoma. Total gastrectomy with D2 lymphadenectomy, splenectomy, and cholecystectomy was performed. Pathologically, the tumor infiltrated the subserosal layer, and 6/49 lymph nodes were involved. The tumor was uniform in shape and arranged in a rosette-like structure to form solid nests, with medium-sized, round-to-cuboid-shaped tumor cells and intense mitosis 46/10 HPF. It was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 70–80%. The diagnosis of neuroendocrine carcinoma was made according to the WHO 2010 criteria. The patient was followed up for three years without recurrence.

Tumor Seeding Following Lung Radiofrequency Ablation: A Case Report

International Nuclear Information System (INIS)

Yamakado, Koichiro; Akeboshi, Masao; Nakatsuka, Atsuhiro; Takaki, Haruyuki; Takao, Motoshi; Kobayashi, Hiroyasu; Taguchi, Osamu; Takeda, Kan

2005-01-01

Lung radiofrequency (RF) ablation was performed for the treatment of a primary lung cancer measuring 2.5 cm in maximum diameter in a 78-year-old man. A contrast-enhanced computed tomography (CT) study performed 3 months after RF ablation showed incomplete ablation of the lung tumor and the appearance of a chest wall tumor 4.0 cm in maximum diameter that was considered to be the result of needle-tract seeding. RF ablation was performed for the treatment of both the lung and the chest wall tumors. Although tumor enhancement was eradicated in both of the treated tumors, follow-up CT studies revealed diffuse intra-pulmonary metastases in both lungs 2 months after the second RF session. He is currently receiving systemic chemotherapy

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

.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 ... with platinum-based chemotherapy has no impact on survival. High expression of ERCC1 in TC might represent a clue to the failure of platinum-based therapy in these patients. ERCC1 expression has prognostic impact in lung carcinoids. Ki 67 might be considered as a supplementary test to the histopatologic...... classification of NE tumors...

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells

Science.gov (United States)

Labrecque, Mark P.; Takhar, Mandeep K.; Nason, Rebecca; Santacruz, Stephanie; Tam, Kevin J.; Massah, Shabnam; Haegert, Anne; Bell, Robert H.; Altamirano-Dimas, Manuel; Collins, Colin C.; Lee, Frank J.S.; Prefontaine, Gratien G.; Cox, Michael E.; Beischlag, Timothy V.

2016-01-01

Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response. Previously, we demonstrated that Rb represses the transcriptional response to hypoxia by virtue of its association with HIF1. In this report, we further characterized the role Rb plays in mediating hypoxia-regulated genetic programs by stably ablating Rb expression with retrovirally-introduced short hairpin RNA in LNCaP and 22Rv1 human prostate cancer cells. DNA microarray analysis revealed that loss of Rb in conjunction with hypoxia leads to aberrant expression of hypoxia-regulated genetic programs that increase cell invasion and promote neuroendocrine differentiation. For the first time, we have established a direct link between hypoxic tumor environments, Rb inactivation and progression to late stage metastatic neuroendocrine prostate cancer. Understanding the molecular pathways responsible for progression of benign prostate tumors to metastasized and lethal forms will aid in the development of more effective prostate cancer therapies. PMID:27015368

Differential expression and prognostic value of the chemokine receptor CXCR4 in bronchopulmonary neuroendocrine neoplasms

Science.gov (United States)

Specht, Elisa; Wirtz, Ralph M.; Sayeg, Manal; Baum, Richard P.; Schulz, Stefan; Lupp, Amelie

2015-01-01

Introduction For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking. Methods CXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival. Results CXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival. Conclusions With increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy. PMID:25671300

[Malignant nonepithelial tumors of the lung].

Science.gov (United States)

Trakhtenberg, A Kh; Biriukov, Iu V; Frank, G A; Kunitsyn, A G; Grigor'eva, S P; Aĭtakov, Z N; Korenev, S V; Efimova, O Iu; Vial'tsev, N V

1990-01-01

The main peculiarities of the clinical course of lung sarcoma were determined from representative material of 134 patients. The main features differentiating malignant nonepithelial tumors from carcinoma of the lung are: younger age (average age 45.5 years), predominantly peripheral clinico-anatomical form (82.8%), and prevalent hematogenic metastasis. Five-year survival in the whole group of patients after surgical treatment was 54%. The size and histological form of the tumor are the main factors of prognosis. The degree of differentiation acquires prognostic significance in tumors measuring more than 3 cm in diameter.

Chromogranins - new sensitive markers for neuroendocrine tumors

International Nuclear Information System (INIS)

Eriksson, B.; Arnberg, H.; Oeberg, K.; Hellman, U.; Lundqvist, G.; Wernstedt, C.; Wilander, E.; Uppsala Hospital; Uppsala Hospital

1989-01-01

Chromogranins A, B and C, proteins that are costored and coreleased with peptides and amines, have been identified in a variety of endocrine and nervous tissues, both normal and neoplastic. We examined the secretion of chromogranin A and chromogranin A+B by hormone-producing tumors in patients with endocrine pancreatic tumors (EPT), carcinoid tumors, pheochromocytomas and small cell lung cancer (SCLC). Radioimmunoassay (RIA) of the plasma/serum concentrations of chromogranin A+B showed a greater sensitivity than RIA of chromogranin A alone. All patients with EPT, carcinoids and pheochromocytomas had increased levels of chromogranin A+B, whereas a small number of the patients (5/18 with EPT and 1/3 with pheochromocytomas) had normal levels of chromogranin A. Also in immunocytochemical stainings, our polyclonal antiserum detecting both chromogranin A and B showed a greater sensitivity than other available antisera against chromogranin A, B and C. (orig.)

Pancreatic non-functioning neuroendocrine tumor: a new entity genetically related to Lynch syndrome

OpenAIRE

Serracant Barrera, Anna; Serra Pla, Sheila; Blázquez Maña, Carmen María; Salas, Rubén Carrera; García Monforte, Neus; Bejarano González, Natalia; Romaguera Monzonis, Andreu; Andreu Navarro, Francisco Javier; Bella Cueto, Maria Rosa; Borobia, Francisco G.

2017-01-01

Some pancreatic neuroendocrine tumors (P-NETs) are associated with hereditary syndromes. An association between Lynch syndrome (LS) and P-NETs has been suggested, however it has not been confirmed to date. We describe the first case associating LS and P-NETs. Here we report a 65-year-old woman who in the past 20 years presented two colorectal carcinomas (CRC) endometrial carcinoma (EC), infiltrating ductal breast carcinoma, small intestine adenocarcinoma, two non-functioning P-NETs and seboma...

Primary Neuroendocrine Carcinoma of Breast: A Rare Case Report

African Journals Online (AJOL)

Introduction. Primary neuroendocrine carcinoma (PNEC) of breast ... than 50% neoplastic tumor cells expressing neuroendocrine. (NE) markers .... subtype also concluded that molecular classification helps ... decreased disease free survival.

[Neuroendocrine carcinoma of the digestive tract: a literature review].

Science.gov (United States)

Jacob, J; Chargari, C; Helissey, C; Ferrand, F-R; Ceccaldi, B; Le Moulec, S; Bauduceau, O; Fayolle, M; Védrine, L

2013-11-01

Neuroendocrine carcinoma is a rare and agressive malignant tumor, mainly developing at the expense of the respiratory and of the digestive tract. Among the digestive tract, appendix, small bowel, and pancreas are the preferential sites of involvement, other locations have been more rarely reported. Neuroendocrine digestive tumors may present with various symptoms in relationship with their localization and a complex pathophysiology. Diagnosis is often made at an advanced stage, explaining partly the bad prognosis of these tumors. The optimal management of digestive neuroendocrine tumors is rendered difficult by their rarity and by a low number of randomized trials. We review the literature regarding epidemiologic and prognostic features of these rare tumors, their diagnostic and therapeutic care. Potential complications are also discussed. Copyright © 2013 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

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.

Acromegaly in a patient with a pulmonary neuroendocrine tumor: case report and review of current literature.

Science.gov (United States)

Krug, Sebastian; Boch, Michael; Rexin, Peter; Pfestroff, Andreas; Gress, Thomas; Michl, Patrick; Rinke, Anja

2016-06-27

Pulmonary neuroendocrine tumors (NET) form a heterogeneous group of rare diseases. In these tumors, paraneoplastic syndromes have been described to drive the course of the disease, among them acromegaly induced by paraneoplastic secretion of growth hormone-releasing hormone (GHRH). We report the case of a 43 years old patient initially diagnosed with acromegaly accompanied by weight gain and acral enlargement. Subsequently, further diagnostic work-up identified a solitary pulmonary neuroendocrine tumor (NET). Laboratory tests revealed markedly increased growth hormone (GH) and insulin-like growth factor 1 (IGF-1) without GHRH elevation in the absence of pituitary pathologies confirming the paraneoplastic origin of clinical presentation with acromegaly. Curative surgery was performed leading to normalization of the elevated hormone levels and improvement of the clinical symptoms. Immunohistochemically, a typical carcinoid (TC) was seen with low proliferation index and abundant IGF-1 expression. The association of acromegaly and pulmonary NET has only rarely been reported. We present an individual case of paraneoplastic GH- and IGF-1 secretion in a patient with pulmonary NET. Based on their rarity, the knowledge of paraneoplastic syndromes occurring in patients with pulmonary NET such as acromegaly due to paraneoplastic GH- and IGF-1 secretion is mandatory to adequately diagnose and treat these patients.

Stereotactic Body Radiotherapy for Oligometastatic Lung Tumors

International Nuclear Information System (INIS)

Norihisa, Yoshiki; Nagata, Yasushi; Takayama, Kenji; Matsuo, Yukinori; Sakamoto, Takashi; Sakamoto, Masato; Mizowaki, Takashi; Yano, Shinsuke; Hiraoka, Masahiro

2008-01-01

Purpose: Since 1998, we have treated primary and oligometastatic lung tumors with stereotactic body radiotherapy (SBRT). The term 'oligometastasis' is used to indicate a small number of metastases limited to an organ. We evaluated our clinical experience of SBRT for oligometastatic lung tumors. Methods and Materials: A total of 34 patients with oligometastatic lung tumors were included in this study. The primary involved organs were the lung (n = 15), colorectum (n = 9), head and neck (n = 5), kidney (n = 3), breast (n = 1), and bone (n = 1). Five to seven, noncoplanar, static 6-MV photon beams were used to deliver 48 Gy (n = 18) or 60 Gy (n = 16) at the isocenter, with 12 Gy/fraction within 4-18 days (median, 12 days). Results: The overall survival rate, local relapse-free rate, and progression-free rate at 2 years was 84.3%, 90.0%, and 34.8%, respectively. No local progression was observed in tumors irradiated with 60 Gy. SBRT-related pulmonary toxicities were observed in 4 (12%) Grade 2 cases and 1 (3%) Grade 3 case. Patients with a longer disease-free interval had a greater overall survival rate. Conclusion: The clinical result of SBRT for oligometastatic lung tumors in our institute was comparable to that after surgical metastasectomy; thus, SBRT could be an effective treatment of pulmonary oligometastases

Video-Assisted Thoracoscopic Surgery in Patients With Clinically Resectable Lung Tumors

Directory of Open Access Journals (Sweden)

H. Sakai

1996-01-01

Full Text Available To investigate the feasibility of thoracoscopic resection, a pilot study was performed in patients with clinically resectable lung tumors. In 40 patients, Video-assisted thoracic surgery (VATS was performed because of suspicion of malignancy. There were 29 men and 11 women with a median age of 54.8 years (range 18 to 78. Preoperative indications were suspected lung cancer and tumor in 27 patients, assessment of tumor resectability in 7 patients, and probability of metastatic tumors in 6 patients. The final diagnoses in the 27 patients with suspected lung cancer were 12 primary lung cancers, 6 lung metastases, and 9 benign lesions. The success rates for VATS (no conversion to thoracotomy were 1 of 12 (8.3% for resectable stage I lung cancer, 8 of 12 (66.7% for metastatic tumors, and 9 of 9 (100% for benign tumors. With VATS, 6 of 7 patients (85.7%, possible stage III non-small cell lung cancer, an explorative thoracotomy with was avoided, significantly reducing morbidity. The reasons for conversion to thoracotomy were 1 oncological (N2 lymph node dissection and prevention of tumor spillage and 2 technical (inability to locate the nodule, central localization, no anatomical fissure, or poor lung function requiring full lung ventilation. The ultimate diagnoses were 19 lung cancers, 12 metastatic lung tumors, and 9 benign lung tumors. Our data show the limitations of VATS for malignant tumors in general use. These findings, together with the fact that experience in performing thoracoscopic procedures demonstrates a learning curve, may limit the use of thoracoscopic resection as a routine surgical procedure, especially when strict oncological rules are respected.

Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Aakhus Svend

2010-01-01

Full Text Available Abstract Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2 is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3. Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR. Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3. There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.

Primary Neuroendocrine Tumor of the Left Hepatic Duct: A Case Report with Review of the Literature

Directory of Open Access Journals (Sweden)

Ajay H. Bhandarwar

2012-01-01

Full Text Available Primary Biliary Tract Neuroendocrine tumors (NET are extremely rare tumors with only 77 cases been reported in the literature till now. We describe a case of a left hepatic duct NET and review the literature for this rare malignancy. To the best of our knowledge the present case is the first reported case of a left hepatic duct NET in the literature. In spite of availability of advanced diagnostic tools like Computerized Tomography (CT Scan and Endoscopic Retrograde Cholangio Pancreaticography (ERCP a definitive diagnosis of these tumors is possible only after an accurate histopathologic diagnosis of operative specimens with immunohistochemistry and electron microscopy. Though surgical excision remains the gold standard treatment for such tumors, patients with unresectable tumors have good survival with newer biologic agents like Octreotride.

Occupational doses in neuroendocrine tumors by using 177Lu DOTATATE

International Nuclear Information System (INIS)

Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de

2011-01-01

This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of 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 μSv to 450 μSv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 μSv/h

[Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto].

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Sampaio, Inês Lucena; Luiz, Henrique Vara; Violante, Liliana Sobral; Santos, Ana Paula; Antunes, Luís; Torres, Isabel; Sanches, Cristina; Azevedo, Isabel; Duarte, Hugo

2016-11-01

The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality. A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed. Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.

Manipulation of [C-11]-5-hydroxytryptophan and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine accumulation in neuroendocrine tumor cells

NARCIS (Netherlands)

Neels, Oliver C.; Koopmans, Klaas P.; Jager, Pieter L.; Vercauteren, Laya; van Waarde, Aren; Doorduin, Janine; Timmer-Bosscha, Hetty; Brouwers, Adrienne H.; de Vries, Elisabeth G. E.; Dierckx, Rudi A. J. O.; Kema, Ido P.; Elsinga, Philip H.

2008-01-01

[C-11]-5-Hydroxytryptophan ([C-11]HTP) and 6-[F-18]fluoro-3,4-dihydroxy-L-phenylalanine [F-18]FDOPA) are used to image neuroendocrine tumors with positron emission tomography. The precise mechanism by which these tracers accumulate in tumor cells is unknown. We aimed to study tracer uptake via large

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

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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

Tumor-Induced CD8+ T-Cell Dysfunction in Lung Cancer Patients

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Heriberto Prado-Garcia

2012-01-01

Full Text Available Lung cancer is the leading cause of cancer deaths worldwide and one of the most common types of cancers. The limited success of chemotherapy and radiotherapy regimes have highlighted the need to develop new therapies like antitumor immunotherapy. CD8+ T-cells represent a major arm of the cell-mediated anti-tumor response and a promising target for developing T-cell-based immunotherapies against lung cancer. Lung tumors, however, have been considered to possess poor immunogenicity; even so, lung tumor-specific CD8+ T-cell clones can be established that possess cytotoxicity against autologous tumor cells. This paper will focus on the alterations induced in CD8+ T-cells by lung cancer. Although memory CD8+ T-cells infiltrate lung tumors, in both tumor-infiltrating lymphocytes (TILs and malignant pleural effusions, these cells are dysfunctional and the effector subset is reduced. We propose that chronic presence of lung tumors induces dysfunctions in CD8+ T-cells and sensitizes them to activation-induced cell death, which may be associated with the poor clinical responses observed in immunotherapeutic trials. Getting a deeper knowledge of the evasion mechanisms lung cancer induce in CD8+ T-cells should lead to further understanding of lung cancer biology, overcome tumor evasion mechanisms, and design improved immunotherapeutic treatments for lung cancer.

The relationship between tumor markers and pulmonary embolism in lung cancer.

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Xiong, Wei; Zhao, Yunfeng; Xu, Mei; Guo, Jian; Pudasaini, Bigyan; Wu, Xueling; Liu, Jinming

2017-06-20

Tumor markers (TMs) and D-Dimer are both hallmarks of severity and prognosis of lung cancer. Tumor markers could be related to pulmonary embolism (PE) in lung cancer. The number of abnormal tumor markers of lung cancer patients with pulmonary embolism (3.9 ± 1.1vs1.6 ± 0.6,P 0.005) was more than that in patients without pulmonary embolism. TMs panel (P trend tumor markers, TMs panel (OR5.98, P Tumor markers were compared between lung cancer patients complicated with pulmonary embolism and those without pulmonary embolism Then the correlation between each tumor marker as well as panel of combined TMs and D-Dimer as well as pulmonary embolism were analyzed for patients with pulmonary embolism. There is a relationship between tumor markers and pulmonary embolism in patients with lung cancer. The panel of combined tumor markers is a valuable diagnostic marker for pulmonary embolism in lung cancer.

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

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Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

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Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

2017-01-01

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  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.

Additional value of hybrid SPECT/CT systems in neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas.

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Wong, K K; Chondrogiannis, S; Fuster, D; Ruiz, C; Marzola, M C; Giammarile, F; Colletti, P M; Rubello, D

The aim of this review was to evaluate the potential advantages of SPECT/CT hybrid imaging in the management of neuroendocrine tumors, adrenal tumors, pheochromocytomas and paragangliomas. From the collected data, the superiority of fused images was observed as providing both functional/molecular and morphological imaging compared to planar imaging. This provided an improvement in diagnostic imaging, with significant advantages as regards: (1) precise locating of the lesions; (2) an improvement in characterization of the findings, resulting higher specificity, improved sensitivity, and overall greater accuracy, (3) additional anatomical information derived from the CT component; (4) CT-based attenuation correction and potential for volumetric dosimetry calculations, and (5) improvement on the impact on patient management (e.g. in better defining treatment plans, in shortening surgical operating times). It can be concluded that SPECT/CT hybrid imaging provides the nuclear medicine physician with a powerful imaging modality in comparison to planar imaging, providing essential information about the location of lesions, and high quality homogeneous images. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

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Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Inflammatory myofibroblastic tumor of the lung in pregnancy mimicking carcinoid tumor

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Venkata Nagarjuna Maturu

2016-01-01

Full Text Available Inflammatory myofibroblastic tumors (IMT are uncommon neoplasms of the lung in adults. They constitute less than 1% of all lung neoplasms and usually present as parenchymal masses. Diagnosis requires a high index of suspicion. They are characterized by spindle-shaped tumor cells (fibroblasts/myofibroblasts in a background of lymphoplasmacytic infiltrate. About 50% of the tumors harbor an ALK gene rearrangement. They have to be differentiated from inflammatory pseudotumors (IPT, which show increased number of IgG4 plasma cells on immunostaining and are negative for anaplastic lymphoma kinase (ALK protein. Herein, we present a case of a 28-year old female who presented with hemoptysis and was diagnosed with an IMT of lung in the first trimester of pregnancy. We have not only reviewed the occurrence of IMT during pregnancy but also discuss the management options for IMT during pregnancy.

[Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

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Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

2017-10-20

Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

Nutritional status and nutritional risk in patients with neuroendocrine tumors

DEFF Research Database (Denmark)

Borre, Mette; Dam, Gitte Aarøe; Knudsen, Anne Wilkens

2018-01-01

BACKGROUND: Malnutrition is frequent among patients with malignancies and associated with impaired function, reduced quality of life and increased mortality. Few data are available in patients with neuroendocrine tumors (NET) on nutritional status, nutritional risk, and nutrition impact symptoms...... (NIS). We aimed to assess nutritional status (NS) and risk, level of function and associations with NIS in NET patients. METHODS: In a cross-sectional study of NET patients, we measured body mass index (BMI) and handgrip strength (HGS) as markers of NS and muscle function assessed by HGS....... The nutritional risk score (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). RESULTS: We included 186 patients (51% women), median age 66 years. We observed low BMI (

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.

Sinonasal malignancies with neuroendocrine differentiation: Case series and review of literature

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Menon Santosh

2010-01-01

Full Text Available Primary sinonasal tumors with neuroendocrine differentiation (SCND are uncommon tumors with considerable overlap of histological features. Based on their neuroendocrine differentiation they can be sub categorized into sinonasal undifferentiated carcinoma (SNUC, sinonasal neuroendocrine carcinoma (SNEC, esthesioneuroblastoma (ENB and small cell carcinoma (SmCC. The natural history and biological behavior varies in this group of tumors. Hence the histo-morphological diagnosis coupled with grading/staging is important for the prognostication of these tumors. Aim : To study the clinicopathological characteristics of sinonasal neuroendocrine malignancies at our institute. Material and Methods : We searched our institute′s pathology database for the period from 2002 to 2007, for the four subcategories of sinonasal tumors with neuroendocrine differentiation. Morphological and immunohistochemical features were studied and, grading, staging was done in accordance with standard criteria. The clinical treatment and follow- up data were retrieved from the case files in available cases. Results : A total of 37 cases were retrieved from our database which include 14 cases of SNUC, 14 cases of ENB and nine cases of SNEC. The cases of SNUC were immunopositive for cytokeratin, epithelial membrane antigen and weakly for neuron-specific enolase. SNEC showed strong reactivity with epithelial and neuroendocrine markers whereas ENB demonstrated immunoreactivity to synaptophysisn and chromogranin strongly, with weak to negative expression of epithelial markers. All cases of SNUC and SNEC were of high grade and stage whereas 50% of ENB cases were of grade II but high stage tumors. Most of the SNUC and SNEC patients had been treated with multimodality treatment regimens including upfront chemotherapy followed by surgery and loco- regional radiation. In contrast, ENB patients had undergone surgical extirpation followed by radiation therapy in majority of cases. With

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

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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.

Primary Neuroendocrine Tumor of Vulva: A Case Report

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Shaghayegh kamian

2018-02-01

Full Text Available Vulvar cancer is a rare malignancy representing less than 1% of the cancers, which is diagnosed in women with a high incidence of local recurrence and distant metastasis and carries a poor prognosis. We presented a 51-year-old woman with a lesion in the vulva appeared for three months. The lesion was large, ulcerative, hemorrhagic, tender, and mobile with no lymphadenopathy. Excisional biopsy demonstrated a high-grade malignant neoplasm with lymphovascular invasion. Based on the immunohistochemistry test, the patient was diagnosed with neuroendocrine carcinoma with poorly differentiated tumor. In the diagnostic workup, there were two small lymph nodes on the left inguinal area. The patient was subjected to radical vulvectomy and bilateral illioinguinal lymphadenectomy. In addition, she was prescribed to undergo adjuvant chemotherapy for three cycles. Subsequently, she was given hyperfractionated radiotherapy in the pelvis and bilateral inguinals  concurrently with chemotherapy. In the last follow-up visit in 32 months later, the patient was disease-free in the physical examination, and the laboratory tests and imaging findings were normal.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

International Nuclear Information System (INIS)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P.; Gelman, Andrew E.; Jarzembowski, Jason A.; Zhang, Hao; Pritchard, Kirkwood A. Jr.; Vikis, Haris G.

2014-01-01

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting

The role of neutrophil myeloperoxidase in models of lung tumor development.

Science.gov (United States)

Rymaszewski, Amy L; Tate, Everett; Yimbesalu, Joannes P; Gelman, Andrew E; Jarzembowski, Jason A; Zhang, Hao; Pritchard, Kirkwood A; Vikis, Haris G

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

Energy Technology Data Exchange (ETDEWEB)

Rymaszewski, Amy L.; Tate, Everett; Yimbesalu, Joannes P. [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Gelman, Andrew E. [Department of Surgery, Washington University in St. Louis, St. Louis, MO 63130 (United States); Jarzembowski, Jason A. [Department of Pathology, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Zhang, Hao; Pritchard, Kirkwood A. Jr. [Department of Surgery and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States); Vikis, Haris G., E-mail: hvikis@mcw.edu [Department of Pharmacology and Toxicology and MCW Cancer Center, Medical College of Wisconsin, Milwaukee, WI 53226 (United States)

2014-05-09

Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA)-initiated, butylated hydroxytoluene (BHT)-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO) activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC), a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC) tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

The Role of Neutrophil Myeloperoxidase in Models of Lung Tumor Development

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Amy L. Rymaszewski

2014-05-01

Full Text Available Chronic inflammation plays a key tumor-promoting role in lung cancer. Our previous studies in mice demonstrated that neutrophils are critical mediators of tumor promotion in methylcholanthrene (MCA-initiated, butylated hydroxytoluene (BHT-promoted lung carcinogenesis. In the present study we investigated the role of neutrophil myeloperoxidase (MPO activity in this inflammation promoted model. Increased levels of MPO protein and activity were present in the lungs of mice administered BHT. Treatment of mice with N-acetyl lysyltyrosylcysteine amide (KYC, a novel tripeptide inhibitor of MPO, during the inflammatory stage reduced tumor burden. In a separate tumor model, KYC treatment of a Lewis Lung Carcinoma (LLC tumor graft in mice had no effect on tumor growth, however, mice genetically deficient in MPO had significantly reduced LLC tumor growth. Our observations suggest that MPO catalytic activity is critical during the early stages of tumor development. However, during the later stages of tumor progression, MPO expression independent of catalytic activity appears to be required. Our studies advocate for the use of MPO inhibitors in a lung cancer prevention setting.

Lung cancer-associated tumor antigens and the present status of immunotherapy against non-small-cell lung cancer

International Nuclear Information System (INIS)

Yasumoto, Kosei; Hanagiri, Takeshi; Takenoyama, Mitsuhiro

2009-01-01

Despite recent advances in surgery, irradiation, and chemotherapy, the prognosis of patients with lung cancer is still poor. Therefore, the development and application of new therapeutic strategies are essential for improving the prognosis of this disease. Significant progress in our understanding of tumor immunology and molecular biology has allowed us to identify the tumor-associated antigens recognized by cytotoxic T lymphocytes. Immune responses and tumor-associated antigens against not only malignant melanoma but also lung cancer have been elucidated at the molecular level. In a theoretical sense, tumor eradication is considered possible through antigen-based immunotherapy against such diseases. However, many clinical trials of cancer vaccination with defined tumor antigens have resulted in objective clinical responses in only a small number of patients. Tumor escape mechanisms from host immune surveillance remain a major obstacle for cancer immunotherapy. A better understanding of the immune escape mechanisms employed by tumor cells is necessary before we can develop a more effective immunotherapeutic approach to lung cancer. We review recent studies regarding the identification of tumor antigens in lung cancer, tumor immune escape mechanisms, and clinical vaccine trials in lung cancer. (author)

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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Tao Cui

Full Text Available BACKGROUND: Small intestine neuroendocrine tumors (SI-NETs belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2 as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. METHODOLOGY/PRINCIPAL FINDINGS: A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC, to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. CONCLUSION: Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA for the risk of recurrence after radical operation of these tumors.

Paraneoplastic antigen Ma2 autoantibodies as specific blood biomarkers for detection of early recurrence of small intestine neuroendocrine tumors.

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Cui, Tao; Hurtig, Monica; Elgue, Graciela; Li, Su-Chen; Veronesi, Giulia; Essaghir, Ahmed; Demoulin, Jean-Baptiste; Pelosi, Giuseppe; Alimohammadi, Mohammad; Öberg, Kjell; Giandomenico, Valeria

2010-12-30

Small intestine neuroendocrine tumors (SI-NETs) belong to a rare group of cancers. Most patients have developed metastatic disease at the time of diagnosis, for which there is currently no cure. The delay in diagnosis is a major issue in the clinical management of the patients and new markers are urgently needed. We have previously identified paraneoplastic antigen Ma2 (PNMA2) as a novel SI-NET tissue biomarker. Therefore, we evaluated whether Ma2 autoantibodies detection in the blood stream is useful for the clinical diagnosis and recurrence of SI-NETs. A novel indirect ELISA was set up to detect Ma2 autoantibodies in blood samples of patients with SI-NET at different stages of disease. The analysis was extended to include typical and atypical lung carcinoids (TLC and ALC), to evaluate whether Ma2 autoantibodies in the blood stream become a general biomarker for NETs. In total, 124 blood samples of SI-NET patients at different stages of disease were included in the study. The novel Ma2 autoantibody ELISA showed high sensitivity, specificity and accuracy with ROC curve analysis underlying an area between 0.734 and 0.816. Ma2 autoantibodies in the blood from SI-NET patients were verified by western blot and sequential immunoprecipitation. Serum antibodies of patients stain Ma2 in the tumor tissue and neurons. We observed that SI-NET patients expressing Ma2 autoantibody levels below the cutoff had a longer progression and recurrence-free survival compared to those with higher titer. We also detected higher levels of Ma2 autoantibodies in blood samples from TLC and ALC patients than from healthy controls, as previously shown in small cell lung carcinoma samples. Here we show that high Ma2 autoantibody titer in the blood of SI-NET patients is a sensitive and specific biomarker, superior to chromogranin A (CgA) for the risk of recurrence after radical operation of these tumors.

Pasireotide in the treatment of neuroendocrine tumors: a review of the literature.

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Vitale, Giovanni; Dicitore, Alessandra; Sciammarella, Concetta; Di Molfetta, Sergio; Rubino, Manila; Faggiano, Antongiulio; Colao, Annamaria

2018-06-01

Somatostatin analogs have an important role in the medical therapy of neuroendocrine tumors (NETs). Octreotide and lanreotide, both somatostatin analogs binding with high affinity for the somatostatin receptor (SSTR)2, can control symptoms in functional NETs. In addition, these compounds, because of their antiproliferative effects, can stabilize growth of well-differentiated NETs. Pasireotide is a novel multireceptor-targeted somatostatin analog with high affinity for SSTR1, 2, 3, and 5. This review provides an overview of the state of the art of pasireotide in the treatment of NETs, with the aim of addressing clinical relevance and future perspectives for this molecule in the management of NETs. © 2018 Society for Endocrinology.

Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

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Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

2018-05-01

Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

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M. H. Sun

2004-01-01

Full Text Available Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.

Pulmonary emphysema and tumor microenvironment in primary lung cancer.

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Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

2016-02-01

To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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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

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

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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

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.

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Segelov, Eva; Chan, David; Lawrence, Ben; Pavlakis, Nick; Kennecke, Hagen F; Jackson, Christopher; Law, Calvin; Singh, Simron

2017-08-01

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. 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. 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. 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 reflect unmet needs and priorities in the field.

Sequence, 'subtle' alternative splicing and expression of the CYYR1 (cysteine/tyrosine-rich 1) mRNA in human neuroendocrine tumors

International Nuclear Information System (INIS)

Vitale, Lorenza; Coppola, Domenico; Strippoli, Pierluigi; Frabetti, Flavia; Huntsman, Shane A; Canaider, Silvia; Casadei, Raffaella; Lenzi, Luca; Facchin, Federica; Carinci, Paolo; Zannotti, Maria

2007-01-01

CYYR1 is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1 expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the CYYR1 mRNA in human NE tumors. The CYYR1 mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of CYYR1 mRNA differing in terms of the absence (CAG - isoform, the first described mRNA for CYYR1 locus) or the presence (CAG + isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two CYYR1 isoforms in other species. The CYYR1 CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either CYYR1 CAG - or CAG + isoform expression compared to control tissues. CYYR1 CAG - isoform was significantly more expressed than CAG + isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent with the possible existence of the two described mRNA isoforms. A new 'subtle' splicing isoform (CAG + ) of CYYR1 mRNA, the sequence and

Epidermal growth factor receptor expression in radiation-induced dog lung tumors by immunocytochemical localization

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Leung, F.L.; Park, J.F.; Dagle, G.E.

1993-06-01

In studies to determine the role of growth factors in radiation-induced lung cancer, epidermal growth factor (EGFR) expression was examined by immunocytochemistry in 51 lung tumors from beagle dogs exposed to inhaled plutonium; 21 of 51 (41%) tumors were positive for EGFR. The traction of tumors positive for EGFR and the histological type of EGFR-positive tumors in the plutonium-exposed dogs were not different from spontaneous dog lung tumors, In which 36% were positive for EGFR. EGFR involvement in Pu-induced lung tumors appeared to be similar to that in spontaneous lung tumors. However, EGFR-positive staining was observed in only 1 of 16 tumors at the three lowest Pu exposure levels, compared to 20 of 35 tumors staining positive at the two highest Pu exposure levels. The results in dogs were in good agreement with the expression of EGFR reported in human non-small cell carcinoma of the lung, suggesting that Pu-induced lung tumors in the dog may be a suitable animal model to investigate the role of EGFR expression in lung carcinogenesis. In humans, EGFR expression in lung tumors has been primarily related to histological tumor types. In individual dogs with multiple primary lung tumors, the tumors were either all EGFR positive or EGFR negative, suggesting that EGFR expression may be related to the response of the individual dog as well as to the histological type of tumor.

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.

Lung tumor segmentation in PET images using graph cuts.

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Ballangan, Cherry; Wang, Xiuying; Fulham, Michael; Eberl, Stefan; Feng, David Dagan

2013-03-01

The aim of segmentation of tumor regions in positron emission tomography (PET) is to provide more accurate measurements of tumor size and extension into adjacent structures, than is possible with visual assessment alone and hence improve patient management decisions. We propose a segmentation energy function for the graph cuts technique to improve lung tumor segmentation with PET. Our segmentation energy is based on an analysis of the tumor voxels in PET images combined with a standardized uptake value (SUV) cost function and a monotonic downhill SUV feature. The monotonic downhill feature avoids segmentation leakage into surrounding tissues with similar or higher PET tracer uptake than the tumor and the SUV cost function improves the boundary definition and also addresses situations where the lung tumor is heterogeneous. We evaluated the method in 42 clinical PET volumes from patients with non-small cell lung cancer (NSCLC). Our method improves segmentation and performs better than region growing approaches, the watershed technique, fuzzy-c-means, region-based active contour and tumor customized downhill. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

FNAB cytology of extra-cranial metastasis of glioblastoma multiforme may resemble a lung primary: A diagnostic pitfall

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Dincer HE

2005-01-01

Full Text Available Abstract Background As extra-cranial metastasis of glioblastoma multiforme (GBM is rare, it may create a diagnostic dilemma especially during interpretation of fine needle aspiration biopsy (FNAB cytology. Case presentation We present transbronchial FNAB findings in a 62-year-old smoker with lung mass clinically suspicious for a lung primary. The smears of transbronchial FNAB showed groups of cells with ill-defined cell margins and cytological features overlapping with poorly differentiated non-small cell carcinoma. The tumor cells demonstrated lack of immunoreactivity for cytokeratin, thyroid transcription factor-1, and usual neuroendocrine markers, synaptophysin and chromogranin in formalin-fixed cellblock sections. However, they were immunoreactive for the other neuroendocrine immunomarker, CD56, suggesting neural nature of the cells. Further scrutiny of clinical details revealed a history of GBM, 13 months status-post surgical excision with radiation therapy and systemic chemotherapy. The tumor recurred 7 months earlier and was debulked surgically and with intra-cranial chemotherapy. Additional evaluation of tumor cells for glial fibrillary acidic protein (GFAP immunoreactivity with clinical details resulted in final interpretation of metastatic GBM. Conclusion Lack of clinical history and immunophenotyping may lead to a diagnostic pitfall with possible misinterpretation of metastatic GBM as poorly differentiated non-small cell carcinoma of lung in a smoker.

Preliminary evaluation of the protocol scintigraphy of neuroendocrine tumor with metaiodobenzylguanidine (mIBG) labeled with {sup 123}I; Avaliacao preliminar do protocolo de cintilografia de tumores neuroendocrinos com meta-iodobenzilguanidina (mIBG) marcado com {sup 123}I

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Oliveira, Danillo M. [Hospital de Urgencia de Sergipe Gov. Joao Alves Filho, Aracaju, SE (Brazil); Mendes, Janaina Dutra Silvestre, E-mail: danillo_90@hotmail.com [Instituto Nacional de Cancer Jose Alencar Gomes da Silva, Rio de Janeiro, RJ (Brazil). Setor de Medicina Nuclear

2014-04-15

Neuroendocrine tumors have a property of capturing metaiodobenzylguanidine (mIBG) and because of this is possible to perform scintigraphy for diagnosis marking this molecule with {sup 123}I. However, {sup 123}I has some particularities, such as the release of X-ray low energy, which complicates the measurement of activity by activity meter, moreover emits a significant intensity of high energy gamma radiation, damaging the image quality. The acquisition protocol scintigraphy of neuroendocrine tumor was evaluated and the necessary recommendations for its optimization will be studied to ensure image quality with the least possible expense to the patient. (author)

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

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Kato, Akihisa; Hayashi, Kazuki; Naitoh, Itaru; Seno, Kyoji; Okada, Yukiko; Ban, Tesshin; Kondo, Hiromu; Nishi, Yuji; Umemura, Shuichiro; Hori, Yasuki; Natsume, Makoto; Joh, Takashi

2016-07-01

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

Percutaneous radiofrequency ablation of lung tumors in a large animal model.

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Ahrar, Kamran; Price, Roger E; Wallace, Michael J; Madoff, David C; Gupta, Sanjay; Morello, Frank A; Wright, Kenneth C

2003-08-01

Percutaneous radiofrequency ablation (RFA) is accepted therapy for liver tumors in the appropriate clinical setting, but its use in lung neoplasms remains investigational. We undertook this study to evaluate the feasibility and immediate effectiveness of RFA for treatment of both solitary pulmonary nodules and clusters of lung tumors in a large animal model. Percutaneous RFA of 14 lung tumors in five dogs was performed under CT guidance. Animals were euthanatized 8-48 hours after the procedure. The lungs and adjacent structures were harvested for gross and histopathologic evaluation. Five solitary pulmonary nodules (range, 17-26 mm) and three clusters of three nodules each (range, 7-17 mm per nodule) were treated with RFA. All ablations were technically successful. Perilesional ground-glass opacity and small asymptomatic pneumothoraces (n = 4) were visualized during the RFA sessions. One dog developed a large pneumothorax treated with tube thoracostomy but was euthanatized 8 hours post-RFA for persistent pneumothorax and continued breathing difficulty. Follow-up CT 48 hours post-RFA revealed opacification of the whole lung segment. Gross and histopathologic evaluation showed complete thermal coagulation necrosis of all treated lesions without evidence of any viable tumor. The region of thermal coagulation necrosis typically extended to the lung surface. Small regions of pulmonary hemorrhage and congestion often surrounded the areas of coagulation necrosis. RFA can be used to treat both solitary pulmonary nodules and clusters of tumor nodules in the canine lung tumor model. This model may be useful for development of specific RFA protocols for human lung tumors.

Advanced Research of mTOR and Lung Carcinoid Tumors

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Zixuan ZHANG

2013-01-01

Full Text Available Mammalian target of rapamycin (mTOR, a main protein kinase in the phosphoinositide 3-kinase (PI3K/AKT/mTOR signaling pathway, is an important intracellular mediator involved in multiple celluar functions including proliferation, differentiation, apoptosis, tumorigenesis, and angiogenesis. Recently, the high expression of mTOR and mTOR-related kinase have been found in neuroendocrin tumors. Therefore, mTOR pathway represents an attractive target for new anticancer therapies except surgery.

Lung Tumor Radiofrequency Ablation: Where Do We Stand?

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Baère, Thierry de

2011-01-01

Today, radiofrequency ablation (RFA) of primary and metastatic lung tumor is increasingly used. Because RFA is most often used with curative intent, preablation workup must be a preoperative workup. General anesthesia provides higher feasibility than conscious sedation. The electrode positioning must be performed under computed tomography for sake of accuracy. The delivery of RFA must be adapted to tumor location, with different impedances used when treating tumors with or without pleural contact. The estimated rate of incomplete local treatment at 18 months was 7% (95% confidence interval, 3–14) per tumor, with incomplete treatment depicted at 4 months (n = 1), 6 months (n = 2), 9 months (n = 2), and 12 months (n = 2). Overall survival and lung disease-free survival at 18 months were, respectively, 71 and 34%. Size is a key point for tumor selection because large size is predictive of incomplete local treatment and poor survival. The ratio of ablation volume relative to tumor volume is predictive of complete ablation. Follow-up computed tomography that relies on the size of the ablation zone demonstrates the presence of incomplete ablation. Positron emission tomography might be an interesting option. Chest tube placement for pneumothorax is reported in 8 to 12%. Alveolar hemorrhage and postprocedure hemoptysis occurred in approximately 10% of procedures and rarely required specific treatment. Death was mostly related to single-lung patients and hilar tumors. No modification of forced expiratory volume in the first second between pre- and post-RFA at 2 months was found. RFA in the lung provides a high local efficacy rate. The use of RFA as a palliative tool in combination with chemotherapy remains to be explored.

Vulnerability of cultured canine lung tumor cells to NK cell-mediated cytolysis

International Nuclear Information System (INIS)

Haley, P.J.; Kohr, J.M.; Kelly, G.; Muggenburg, B.A.; Guilmette, B.A.

1988-01-01

Five cell lines, designated as canine lung epithelial cell (CLEP), derived from radiation induced canine lung tumors and canine thyroid adeno-carcinoma (CTAC) cells were compared for their susceptibility to NK cell-mediated cytolysis using peripheral blood lymphocytes from normal, healthy Beagle dogs as effector cells. Effector cells and chromium 51 radiolabeled target cells were incubated for 16 h at ratios of 12.5:1, 25:1, 50:1, and 100:1. Increasing cytolysis was observed for all cell lines as the effector-to-target-cell ratios increased from 12.5:1 to 100:1. The percent cytotoxicity was significantly less for all lung tumor cell lines as compared to CTAC at the 100:1 ratio. One lung tumor cell line, CLEP-9, had 85% of the lytic vulnerability of the CTAC cell line and significantly greater susceptibility to NK cell-mediated lysis than all of the other lung tumor cell lines. Susceptibility to NK cell cytolysis did not correlate with in vivo malignant behavior of the original tumor. These data suggest that cultured canine lung tumor cells are susceptible to NK cell cytolytic activity in vitro and that at least one of these cell lines (CLEP-9) is a candidate for substitution of the standard canine NK cell target, CTAC, in NK cell assays. The use of lung tumor cells in NK cell assays may provide greater insight into the control of lung tumors by immune mechanisms. (author)

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

International Nuclear Information System (INIS)

Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-01-01

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

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

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Ambrosini, Valentina; Tomassetti, Paola; Castellucci, Paolo; Campana, Davide; Montini, Giancarlo; Rubello, Domenico; Nanni, Cristina; Rizzello, Anna; Franchi, Roberto; Fanti, Stefano

2008-08-01

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

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

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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.

meta-analysis of Serum Tumor Markers in Lung Cancer

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Xianfeng LU

2010-12-01

Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

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David Fecher

Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

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Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo

2013-01-01

A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

Uncommon of the uncommon: Malignant Perivascular epithelioid cell tumor of the lung

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Lim, Hyun Ju; Lee, Ho Yun; Han, Joung Ho; Choi, Yong Soo; Lee, Kyung Soo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2013-08-15

A perivascular epithelioid cell (PEC) tumor is a rare mesenchymal tumor characterized by abundant cytoplasmic Periodic acid-Schiff positive glycogen (also called sugar tumor or clear cell tumor of the lung for this characteristic) and is mostly benign. We report a case of a 63-year-old man who presented with an enlarging mass on chest radiograph. After a thorough workup, diagnosis of malignant pulmonary PEC tumor with lung to lung metastases was established. Herein, the difficulties of diagnosis and management we confronted are described.

SU-G-JeP1-06: Correlation of Lung Tumor Motion with Tumor Location Using Electromagnetic Tracking

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Muccigrosso, D; Maughan, N; Parikh, P [Washington University School of Medicine, Saint Louis, MO (United States); Schultejans, H; Bera, R [Lindbergh High School, St. Louis, MO (United States)

2016-06-15

Purpose: It is well known that lung tumors move with respiration. However, most measurements of lung tumor motion have studied long treatment times with intermittent imaging; those populations may not necessarily represent conventional LINAC patients. We summarized the correlation between tumor motion and location in a multi-institutional trial with electromagnetic tracking, and identified the patient cohort that would most benefit from respiratory gating. Methods: Continuous electromagnetic transponder data (Varian Medical, Seattle, WA) of lung tumor motion was collected from 14 patients (214 total fractions) across 3 institutions during external beam radiation therapy in a prospective clinical trial (NCT01396551). External intervention from the clinician, such as couch shifts, instructed breath-holds, and acquisition pauses, were manually removed from the 10 Hz tracking data according to recorded notes. The average three-dimensional displacement from the breathing cycle’s end-expiratory to end-inhalation phases (peak-to-peak distance) of the transponders’ isocenter was calculated for each patient’s treatment. A weighted average of each isocenter was used to assess the effects of location on motion. A total of 14 patients were included in this analysis, grouped by their transponders’ location in the lung: upper, medial, and lower. Results: 8 patients had transponders in the upper lung, and 3 patients each in the medial lobe and lower lung. The weighted average ± standard deviation of all peak-to-peak distances for each group was: 1.04 ± 0.39 cm in the lower lung, 0.56 ± 0.14 cm in the medial lung, and 0.30 ± 0.06 cm in the upper lung. Conclusion: Tumors in the lower lung are most susceptible to excessive motion and daily variation, and would benefit most from continuous motion tracking and gating. Those in the medial lobe might be at moderate risk. The upper lobes have limited motion. These results can guide different motion management strategies

Evaluation of somatostatin receptors in large cell pulmonary neuroendocrine carcinoma with 99mTc-EDDA/HYNIC-TOC scintigraphy.

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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.

Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience.

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Hatton, M Q; Reed, N S

1997-01-01

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

The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

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Graham, A R; Payne, C M; Nagle, R B; Angel, E

1987-02-01

We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

Therapeutic strategies and genetic profile comparisons in small cell carcinoma and large cell neuroendocrine carcinoma of the lung using next-generation sequencing.

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Ito, Masaoki; Miyata, Yoshihiro; Hirano, Shoko; Kimura, Shingo; Irisuna, Fumiko; Ikeda, Kyoko; Kushitani, Kei; Tsutani, Yasuhiro; Ueda, Daisuke; Tsubokawa, Norifumi; Takeshima, Yukio; Okada, Morihito

2017-12-12

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) of the lung are classified as variants of endocrine carcinoma and subdivided into pure or combined type. Clinical benefit of target therapy has not been established in these tumors. This study aimed to compare genetic and clinicopathological features between SCLC and LCNEC or pure and combined types, and explore the possibility of target therapy using next-generation sequencing. In 13 SCLC and 22 LCNEC cases, 72 point mutations, 19 deletions, and 3 insertions were detected. As therapeutically targetable variants, mutations in EGFR (L858R), KRAS (G12D, G12A, G12V), and PIK3CA (E545K) were detected in 5 cases. The case harboring EGFR mutation showed response to EGFR-tyrosine kinase inhibitor. However, there are no clinicopathological features associated with therapeutically targetable cases. And there was no significant genetic feature between SCLC and LCNEC or pure and combined types. In conclusion, although patients with SCLC and LCNEC may benefit from target therapy, they were not identifiable by clinicopathologic background. And there was not significant genetic difference between SCLC and LCNEC, including between pure and combined types. Classifying SCLC and LCNEC in same category is reasonable. However, distinguishing the pure type from combined type was not validated. Comprehensive genetic analysis should be performed to detect targetable variants in any type of SCLC and LCNEC.

Audiovisual Biofeedback Improves Cine–Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency

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Lee, Danny [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Greer, Peter B. [School of Mathematical and Physical Sciences, The University of Newcastle, Newcastle, NSW (Australia); Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Ludbrook, Joanna; Arm, Jameen; Hunter, Perry [Department of Radiation Oncology, Calvary Mater Newcastle, Newcastle, NSW (Australia); Pollock, Sean; Makhija, Kuldeep; O' brien, Ricky T. [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Kim, Taeho [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia); Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia (United States); Keall, Paul, E-mail: paul.keall@sydney.edu.au [Radiation Physics Laboratory, Sydney Medical School, The University of Sydney, Sidney, NSW (Australia)

2016-03-01

Purpose: To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients. Methods and Materials: Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio. Results: Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001). Conclusions: These results demonstrated that AV biofeedback significantly improved intra- and interfraction lung tumor motion consistency for lung cancer patients. These results demonstrate that AV biofeedback can facilitate consistent tumor motion, which is advantageous toward achieving more accurate medical imaging and radiation therapy procedures.

Audiovisual Biofeedback Improves Cine–Magnetic Resonance Imaging Measured Lung Tumor Motion Consistency

International Nuclear Information System (INIS)

Lee, Danny; Greer, Peter B.; Ludbrook, Joanna; Arm, Jameen; Hunter, Perry; Pollock, Sean; Makhija, Kuldeep; O'brien, Ricky T.; Kim, Taeho; Keall, Paul

2016-01-01

Purpose: To assess the impact of an audiovisual (AV) biofeedback on intra- and interfraction tumor motion for lung cancer patients. Methods and Materials: Lung tumor motion was investigated in 9 lung cancer patients who underwent a breathing training session with AV biofeedback before 2 3T magnetic resonance imaging (MRI) sessions. The breathing training session was performed to allow patients to become familiar with AV biofeedback, which uses a guiding wave customized for each patient according to a reference breathing pattern. In the first MRI session (pretreatment), 2-dimensional cine-MR images with (1) free breathing (FB) and (2) AV biofeedback were obtained, and the second MRI session was repeated within 3-6 weeks (mid-treatment). Lung tumors were directly measured from cine-MR images using an auto-segmentation technique; the centroid and outlier motions of the lung tumors were measured from the segmented tumors. Free breathing and AV biofeedback were compared using several metrics: intra- and interfraction tumor motion consistency in displacement and period, and the outlier motion ratio. Results: Compared with FB, AV biofeedback improved intrafraction tumor motion consistency by 34% in displacement (P=.019) and by 73% in period (P<.001). Compared with FB, AV biofeedback improved interfraction tumor motion consistency by 42% in displacement (P<.046) and by 74% in period (P=.005). Compared with FB, AV biofeedback reduced the outlier motion ratio by 21% (P<.001). Conclusions: These results demonstrated that AV biofeedback significantly improved intra- and interfraction lung tumor motion consistency for lung cancer patients. These results demonstrate that AV biofeedback can facilitate consistent tumor motion, which is advantageous toward achieving more accurate medical imaging and radiation therapy procedures.

The Role of Chemotherapy in Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors.

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Strosberg, Jonathan; Goldman, Jamie; Costa, Frederico; Pavel, Marianne

2015-01-01

Even though the neuroendocrine tumor (NET) field has entered the era of 'targeted therapy', the role of cytotoxic chemotherapy continues to be debated. High response rates, ranging from 30 to 70% depending on the line of therapy, are consistently observed in the treatment of pancreatic NETs, with lesser evidence of activity in other foregut tumors. Activity in midgut carcinoid tumors appears to be negligible. Unfortunately, placebo-controlled randomized controlled trials using modern response criteria are lacking: the bulk of the literature consists of small phase II trials and retrospective series. There are also no completed trials comparing modern chemotherapy regimens, and therefore little data exist to favor the use of streptozocin- versus temozolomide- versus oxaliplatin-based therapies. Due to the absence of high-level evidence, it is difficult to generate data-based guidelines on the appropriate sequencing of cytotoxic drugs versus targeted agents. Although conventional wisdom holds that targeted agents such as everolimus or sunitinib are more tolerable than cytotoxic drugs, there is no evidence to support this perception. As a general principle, chemotherapy may be more appropriate as early-line therapy in patients with bulky and/or symptomatic and/or rapidly progressive tumors, particularly of pancreatic origin. In patients with low-volume disease or slow-growing tumors, noncytotoxic drugs may be preferable in early lines of therapy, reserving chemotherapy for the salvage setting. Validation of predictive factors is imperative in order to appropriately match patients with optimal treatment. Methyl-guanine-methyl-transferase (MGMT) deficiency is likely to be a positive predictive factor for alkylating agents, but needs to be evaluated prospectively. It is also unclear whether immunostaining for MGMT expression, which can be somewhat subjective, is superior to PCR-based techniques, which assess MGMT methylation status. Other basic predictive factors, such

Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

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Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

2008-01-01

To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

Thoracoscopic lung lobectomy for treatment of lung tumors in dogs.

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Lansdowne, Jennifer L; Monnet, Eric; Twedt, David C; Dernell, William S

2005-01-01

To report use of thoracoscopic lung lobectomy (TLL) for treatment of lung tumors (LT) in dogs. Retrospective study. Nine dogs. Dogs that had TLL for tumor removal were included. Using general anesthesia and 1-lung ventilation, TLL was performed using a 30-60 mm endoscopic gastrointestinal anastomosis stapler. If the visual field was obscured, lobe resection was completed via thoracotomy. Metastatic and primary LT were resected by thoracoscopic lobectomy in 9 dogs (6 male, 3 female; mean (+/-SD) weight, 29+/-7 kg; mean age, 10.7+/-1.9 years). Six dogs had a solitary mass and 3 dogs had 2 masses within a single lobe. The left caudal lobe was removed in 3 dogs. In 5 dogs, TLL was used alone whereas conversion to thoracotomy was required in 4 dogs because of poor visibility. There were 7 metastatic LT and 2 primary LT. Mean duration of thoracoscopic surgery was 108.8+/-30.3 minutes compared with 150.75+/-55.4 minutes in dogs requiring conversion to thoracotomy. Mean hospitalization was 3.1+/-1.3 days. Provided the visual field is not obscured, TLL can be performed effectively in dogs. Dogs with metastatic or primary LTs should be considered for TLL, particularly for small masses positioned away from the hilus in the left caudal lung lobe.

A Rare Case of Primary Infiltrating Neuroendocrine Carcinoma of the Breast

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Nawawi, Ouzreiah; Ying Goh, Keat; Rahmat, Kartini

2012-01-01

Primary neuroendocrine carcinoma of the breast is a very rare malignant tumor. There are not many cases reported in the English literature since it was first documented in 1983. Reports on the imaging features, in particular the ultrasonographic features of this rare tumor are scarce. Herein, we report a case of aggressive primary infiltrating neuroendocrine carcinoma of the breast, masquerading as an inflammatory breast condition in a 22-year-old young lady, perhaps the youngest case ever reported in the English literature. We discuss the imaging features and highlight the Doppler ultrasonographic findings of this rare breast carcinoma. This is the first documentation on Doppler ultrasonographic findings of primary neuroendocrine carcinoma of the breast in the literature

Detection of lung tumor movement in real-time tumor-tracking radiotherapy

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Shimizu, Shinichi; Shirato, Hiroki; Ogura, Shigeaki; Akita-Dosaka, Hirotoshi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Nishimura, Masaji; Miyasaka, Kazuo

2001-01-01

Purpose: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. Methods and Materials: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined 'permitted dislocation'. The value was set at ±1 to ±3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. Results: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p=0.007), y (p=0.025), and z (p=0.002) coordinates, respectively. Conclusion: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the 'permitted dislocation' zone from the planned position

Effect of Audio Coaching on Correlation of Abdominal Displacement With Lung Tumor Motion

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Nakamura, Mitsuhiro; Narita, Yuichiro; Matsuo, Yukinori; Narabayashi, Masaru; Nakata, Manabu; Sawada, Akira; Mizowaki, Takashi; Nagata, Yasushi; Hiraoka, Masahiro

2009-01-01

Purpose: To assess the effect of audio coaching on the time-dependent behavior of the correlation between abdominal motion and lung tumor motion and the corresponding lung tumor position mismatches. Methods and Materials: Six patients who had a lung tumor with a motion range >8 mm were enrolled in the present study. Breathing-synchronized fluoroscopy was performed initially without audio coaching, followed by fluoroscopy with recorded audio coaching for multiple days. Two different measurements, anteroposterior abdominal displacement using the real-time positioning management system and superoinferior (SI) lung tumor motion by X-ray fluoroscopy, were performed simultaneously. Their sequential images were recorded using one display system. The lung tumor position was automatically detected with a template matching technique. The relationship between the abdominal and lung tumor motion was analyzed with and without audio coaching. Results: The mean SI tumor displacement was 10.4 mm without audio coaching and increased to 23.0 mm with audio coaching (p < .01). The correlation coefficients ranged from 0.89 to 0.97 with free breathing. Applying audio coaching, the correlation coefficients improved significantly (range, 0.93-0.99; p < .01), and the SI lung tumor position mismatches became larger in 75% of all sessions. Conclusion: Audio coaching served to increase the degree of correlation and make it more reproducible. In addition, the phase shifts between tumor motion and abdominal displacement were improved; however, all patients breathed more deeply, and the SI lung tumor position mismatches became slightly larger with audio coaching than without audio coaching.

A case report of metastatic neuroendocrine carcinoma of the right adrenal gland successfully treated with chemotherapy and surgery.

Science.gov (United States)

Ochiai, Toshiya; Komiyama, Sosuke; Ikoma, Hisashi; Kubota, Takeshi; Nakanishi, Masayoshi; Ichikawa, Daisuke; Kikuchi, Shojiro; Fujiwara, Hitoshi; Sakakura, Chohei; Kokuba, Yukihito; Sonoyama, Teruhisa; Otsuji, Eigo

2010-08-01

Poorly differentiated neuroendocrine carcinoma has a poor prognosis, especially when associated with distant metastasis. A 60-year-old man was admitted to a private hospital because of dyspnea at work in 2007. Computed tomography revealed lung infarction and a right adrenal tumor sized 12 cm in diameter that was tightly compressed against the inferior vena cava (IVC). Moreover, multiple lymph node metastases around the celiac axis and a solitary liver metastasis at the lateral segment were observed. Thus, we planned chemotherapy without surgery. We selected a combination therapy of irinotecan (CPT-11) and cisplatin (CDDP) (i.e., IP therapy): administration of CDDP [60 mg/m(2) body surface area (BSA)] on day 1 plus CPT-11 (80 mg/m(2)) BSA on days 1 and 8. Thereafter, this protocol was repeated at 3-week intervals. After 15 months of this chemotherapy strategy, the whole lesions showed a partial response by RECIST. The primary tumor had shrunk to 4.2 cm in diameter. In November 2008, we planned surgery to perform resection of the whole lesions. Histological diagnosis of the specimen was a poorly differentiated neuroendocrine carcinoma based on the immunostaining features, i.e., synaptophysin- and chromogranin positive. There were no viable tumor cells at the dissected lymph nodes or at the liver tumor. After surgery, CPT-11 administration was continued. The patient has remained well for 9 months without recurrence.

64Cu-DOTATATE PET for Neuroendocrine Tumors: a Prospective Head-to-Head Comparison with 111In-DTPA-octreotide in 112 Patients

DEFF Research Database (Denmark)

Pfeifer, Andreas Klaus; Knigge, Ulrich; Binderup, Tina

2015-01-01

Neuroendocrine tumors (NETs) can be visualized using radiolabeled somatostatin analogs. We have previously shown the clinical potential of (64)Cu-DOTATATE in a small first-in-human feasibility study. The aim of the present study was, in a larger prospective design, to compare on a head-to-head ba...

[Lung metastases: tumor reduction as an oncologic concept].

Science.gov (United States)

Dienemann, H; Hoffmann, H; Trainer, C; Muley, T

1998-01-01

The principle of surgery for lung metastases is the removal of all lesions in the lung that are either visible or detectable by palpation. This may be combined with complete dissection of all ipsilateral lymph nodes. Therefore, "tumor reduction" rather than "complete" or "radical resection" may be an adequate description of this surgical approach. Since the dissemination of--macroscopically not detectable--tumor cells represents the major mannerism of every metastatic disease, any local therapy appears to be a discrepancy. However, in most cases the rationale of surgery for lung metastases is the lack of effective systemic therapy and the low morbidity of surgery, along with up to 60% 5-year survival rates.

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...

Combination of cross-sectional and molecular imaging studies in the localization of gastroenteropancreatic neuroendocrine tumors.

Science.gov (United States)

Toumpanakis, Christos; Kim, Michelle K; Rinke, Anja; Bergestuen, Deidi S; Thirlwell, Christina; Khan, Mohid S; Salazar, Ramon; Oberg, Kjell

2014-01-01

Molecular imaging modalities exploit aspects of neuroendocrine tumors (NET) pathophysiology for both diagnostic imaging and therapeutic purposes. The characteristic metabolic pathways of NET determine which tracers are useful for their visualization. In this review, we summarize the diagnostic value of all available molecular imaging studies, present data about their use in daily practice in NET centers globally, and finally make recommendations about the appropriate use of those modalities in specific clinical scenarios. Somatostatin receptor scintigraphy (SRS) continues to have a central role in the diagnostic workup of patients with NET, as it is also widely available. However, and despite the lack of prospective randomized studies, many NET experts predict that Gallium-68 ((68)Ga)-DOTA positron emission tomography (PET) techniques may replace SRS in the future, not only because of their technical advantages, but also because they are superior in patients with small-volume disease, in patients with skeletal metastases, and in those with occult primary tumors. Carbon-11 ((11)C)-5-hydroxy-L-tryptophan (5-HTP) PET and (18)F-dihydroxyphenylalanine ((18)F-DOPA) PET are new molecular imaging techniques of limited availability, and based on retrospective data, their sensitivities seem to be inferior to that of (68)Ga-DOTA PET. Glucagon-like-peptide-1 (GLP-1) receptor imaging seems promising for localization of the primary in benign insulinomas, but is currently available only in a few centers. Fluorine-18 ((18)F)-fluorodeoxyglucose ((18)F-FDG) PET was initially thought to be of limited value in NET, due to their usually slow-growing nature. However, according to subsequent data, (18)F-FDG PET is particularly helpful for visualizing the more aggressive NET, such as poorly differentiated neuroendocrine carcinomas, and well-differentiated tumors with Ki67 values >10%. According to limited data, (18)F-FDG-avid tumor lesions, even in slow-growing NET, may indicate a more

Splenomegaly and tumor marker response following selective internal radiation therapy for non-resectable liver metastases from neuroendocrine tumor

International Nuclear Information System (INIS)

Shehata, M.; Yan, K.; Itoh, Seiji; King, J.; Glenn, D.; Quinn, R.; Morris, D.L.

2009-01-01

The aim of this study was to investigate changes in spleen size, the level of chromogranin A as a tumor marker, and the relationship between these two parameters before and 3 months after selective internal radiation therapy (SIRT) for non-resectable liver metastases from neuroendocrine tumor (NET). Our first serious adverse event with this relatively new treatment is also discussed. A retrospective review of a prospective database identified patients with non-resectable liver metastases from NET who underwent SIRT between 2003 and 2007. Patients who underwent CT scans before and 3 months after treatment were included. The patients were divided into two groups: those with and without a 20% or more increase in splenic volume on the CT scans. The percentages of patients showing a tumor marker response in the two groups were then compared. Fourteen patients were included in the present analysis. A tumor marker response was seen in 6 of 7 patients (85.7%) who showed an increase in splenic volume of >20%, and in 3 of 7 patients (42.9%) without an increase in splenic volume (p=0.266). There was one death as a result of oesophageal variceal bleeding due to portal hypertension at 9 months after treatment. Splenic enlargement after SIRT may be associated with tumor marker response, although this could not be confirmed statistically in this study due to the small number of patients. Long-term splenomegaly and portal hypertension may be important complications of SIRT. This issue needs to be investigated further using a larger number of patients and longer follow-up. (author)

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

International Nuclear Information System (INIS)

Bodei, Lisa; Kidd, Mark; Modlin, Irvin M.; Prasad, Vikas; Baum, Richard P.; Drozdov, Ignat

2014-01-01

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.

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.

Long-term exposure to hypoxia inhibits tumor progression of lung cancer in rats and mice

International Nuclear Information System (INIS)

Yu, Lunyin; Hales, Charles A

2011-01-01

Hypoxia has been identified as a major negative factor for tumor progression in clinical observations and in animal studies. However, the precise role of hypoxia in tumor progression has not been fully explained. In this study, we extensively investigated the effect of long-term exposure to hypoxia on tumor progression in vivo. Rats bearing transplanted tumors consisting of A549 human lung cancer cells (lung cancer tumor) were exposed to hypoxia for different durations and different levels of oxygen. The tumor growth and metastasis were evaluated. We also treated A549 lung cancer cells (A549 cells) with chronic hypoxia and then implanted the hypoxia-pretreated cancer cells into mice. The effect of exposure to hypoxia on metastasis of Lewis lung carcinoma in mice was also investigated. We found that long-term exposure to hypoxia a) significantly inhibited lung cancer tumor growth in xenograft and orthotopic models in rats, b) significantly reduced lymphatic metastasis of the lung cancer in rats and decreased lung metastasis of Lewis lung carcinoma in mice, c) reduced lung cancer cell proliferation and cell cycle progression in vitro, d) decreased growth of the tumors from hypoxia-pretreated A549 cells, e) decreased Na + -K + ATPase α1 expression in hypoxic lung cancer tumors, and f) increased expression of hypoxia inducible factors (HIF1α and HIF2α) but decreased microvessel density in the lung cancer tumors. In contrast to lung cancer, the growth of tumor from HCT116 human colon cancer cells (colon cancer tumor) was a) significantly enhanced in the same hypoxia conditions, accompanied by b) no significant change in expression of Na + -K + ATPase α1, c) increased HIF1α expression (no HIF2α was detected) and d) increased microvessel density in the tumor tissues. This study demonstrated that long-term exposure to hypoxia repressed tumor progression of the lung cancer from A549 cells and that decreased expression of Na + -K + ATPase was involved in hypoxic

Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

International Nuclear Information System (INIS)

Yang, Jie; Li, Jun-Wen; Wang, Lu; Chen, Zhaoli; Shen, Zhi-Qiang; Jin, Min; Wang, Xin-Wei; Zheng, Yufei; Qiu, Zhi-Gang; Wang, Jing-feng

2008-01-01

Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies. In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking. Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed. We conclude that VE might prevent lung tumor induced by smoking in Swiss mice

Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma

Directory of Open Access Journals (Sweden)

Lipika Lipi

2014-01-01

Full Text Available A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.

Science.gov (United States)

Jilesen, Anneke P J; van Eijck, Casper H J; Busch, Olivier R C; van Gulik, Thomas M; Gouma, Dirk J; van Dijkum, Els J M Nieveen

2016-03-01

Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease. Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and

Clinical application of 99mTc-HYNIC-TOC SPECT/CT in diagnosing and monitoring of pancreatic neuroendocrine neoplasms.

Science.gov (United States)

Xu, Junyan; Li, Yi; Xu, Xiaoping; Zhang, Jiangang; Zhang, Yingjian; Yu, Xianjun; Huang, Dan

2018-06-20

Our aim of this research was to determine the value of SPECT/CT with 99m Tc-HYNIC-TOC for evaluation of the pancreatic masses which were suspected as neuroendocrine neoplasms and follow-up of patients with pancreatic neuroendocrine neoplasms. We retrospectively analyzed 184 patients who performed 99m Tc-HYNIC-TOC SPECT/CT. All the patients were divided into two groups: one for assessment of diagnostic efficiency for pancreatic suspected masses (n = 140) and another for monitoring recurrence after surgery (n = 44). The image findings acquired at 2 h postinjection were compared to final diagnoses from pathological results and clinical follow-up. Then, the correlation between ratios of tumor-to-background (TBR) and tumor grade was analyzed. In group 1, 95/140 (67.9%) patients were confirmed as neuroendocrine neoplasms including 85 neuroendocrine tumors and 10 neuroendocrine carcinomas. Patient-based analysis showed that the sensitivity, specificity and accuracy of diagnosing neuroendocrine neoplasms with SPECT/CT were 81.1, 84.4 and 82.1%. There was significant difference of TBRs among G1, G2 and G3 (F = 3.175, P = 0.048). In group 2, 22/44 (50.0%) patients occurred metastasis mainly in liver. The sensitivity, specificity and accuracy of monitoring recurrence were 87.0, 100 and 93.2%. 99m Tc-HYNIC-TOC SPECT/CT is a reliable method of diagnosing and monitoring of pancreatic neuroendocrine neoplasms, especially neuroendocrine tumors.

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

DEFF Research Database (Denmark)

Knudsen, Mie Grunnet; Sorensen, J B

2012-01-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those...... relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA...

Impact of Therapy Sequence with Alkylating Agents and MGMT Status in Patients with Advanced Neuroendocrine Tumors.

Science.gov (United States)

Krug, Sebastian; Boch, Michael; Rexin, Peter; Gress, Thomas M; Michl, Patrick; Rinke, Anja

2017-05-01

Alkylating chemotherapeutics with either a streptozotocin-(STZ) or temozolomide-(TEM) backbone are routinely used in patients with progressive and unresectable pancreatic neuroendocrine tumors (PNET). In addition, dacarbazine (DTIC) was described as an alternative alkylating therapy option for PNETs. The optimal treatment sequence with alkylating compounds and a potential use of O6-methylguanine-DNA methyltransferase (MGMT) level as predictive biomarker have not yet been sufficiently elucidated. The aim of our study was the evaluation of therapy sequence with either STZ-based treatment followed by DTIC (group A) or the inverse schedule with upfront DTIC (group B) and to correlate MGMT status with clinicopathological characteristics and response to therapy. We retrospectively analyzed 28 patients with neuroendocrine tumors (NET) who were treated with STZ-based therapy and DTIC. Additionally, in a second group MGMT immunohistochemistry was performed from primary and metastatic tumor sites. For statistical evaluation Kaplan-Meier analysis, Cox regression methods and Fisher's exact test were used. There was no difference of objective response and disease control between either STZ-based therapy followed by DTIC treatment (group A) after progression or the reverse sequence (group B). Median time to progression (TTP) was estimated to be 21 months in both arms. First-line STZ-based chemotherapy was not superior to first-line DTIC treatment (16 vs. 13 months; p=0.8). MGMT status did not correlate with clinicopathological characteristics or response to therapy with these alkylating agents. Upfront chemotherapy with either STZ-based treatment or DTIC monotherapy showed similar efficacy and median TTP rates. In this study, MGMT protein expression assessed by immunohistochemistry did not play an important role as a predictive marker for alkylating agents. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

99mTc-EDDA/HYNIC-Tyr(3)-octreotide for staging and follow-up of patients with neuroendocrine gastro-entero-pancreatic tumors.

Science.gov (United States)

Gabriel, M; Muehllechner, P; Decristoforo, C; von Guggenberg, E; Kendler, D; Prommegger, R; Profanter, C; Moncayo, R; Virgolini, I

2005-09-01

To evaluate the use of 99mTc-EDDA-hydrazinonicotinyl-Tyr3-octreotide (Tc-TOC) for staging and follow-up of neuroendocrine gastro-entero-pancreatic (GEP) tumors with special focus on the acquisition protocol including single photon emission computed tomography (SPECT). Eighty-eight patients (37 female, 51 male; age range: 16 to 81 years; mean age: 56.3 years) were studied: 42 patients for staging after initial histological confirmation and 46 patients during post-therapy follow-up. An average activity of 400 MBq of the radiopharmaceutical was injected. All tumors originated from neuroendocrine tissue of the gastroenteropancreatic tract. Whole body scintigrams at 4 h postinjection and SPECT of the abdomen were obtained in all patients. Additional planar images of the abdomen were acquired at 2 h after injection in 68 patients. The Tc-TOC scan result was true-positive in 56 patients, true-negative in 17, false-negative in 14, and false-positive in 1 patient. The false-positive finding was caused by a colonic adenoma. Overall, a scan sensitivity of 80% (56/70 patients), specificity of 94.4% (17/18 patients) and accuracy of 82.9% (73/88 patients) were calculated on patient basis. In total, Tc-TOC detected 357 foci in 69 patients. In 7 patients equivocal findings were observed in the bowel at 4 h postinjection without corresponding tracer uptake in the scan 2 h earlier, meaning that these abnormal findings were correctly classified as non-malignant. In addition to planar views, SPECT revealed further 62 lesions. Tc-TOC with one-day, dual-time acquisition protocol is an accurate staging procedure in patients with neuroendocrine GEP tumors. SPECT shows high sensitivity for detection of abdominal lesions, while earlier images improve the reliability of abnormal abdominal findings.

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

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

International Nuclear Information System (INIS)

Santhanam, Prasanna; Chandramahanti, Sangeeta; Kroiss, Alexander; Yu, Run; Ruszniewski, Philippe; Kumar, Rakesh; Taieb, David

2015-01-01

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 68 Ga-labeled somatostatin analogs ( 68 Ga-DOTA-SSTa) and 18 F-DOPA have shown promise. In direct comparisons between 68 Ga-DOTA-SSTa PET/CT and 99m Tc-HYNIC-octreotide/ 111 In-pentetreotide SPECT(/CT), 68 Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. 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 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 68 Ga-DOTA-SSTa, alternatively 18 F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and 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 developed PET approaches (radiopharmaceuticals) and

Validation of a Cytotechnologist Manual Counting Service for the Ki67 Index in Neuroendocrine Tumors of the Pancreas and Gastrointestinal Tract.

Science.gov (United States)

Cottenden, Jennielee; Filter, Emily R; Cottreau, Jon; Moore, David; Bullock, Martin; Huang, Weei-Yuarn; Arnason, Thomas

2018-03-01

- Pathologists routinely assess Ki67 immunohistochemistry to grade gastrointestinal and pancreatic neuroendocrine tumors. Unfortunately, manual counts of the Ki67 index are very time consuming and eyeball estimation has been criticized as unreliable. Manual Ki67 counts performed by cytotechnologists could potentially save pathologist time and improve accuracy. - To assess the concordance between manual Ki67 index counts performed by cytotechnologists versus eyeball estimates and manual Ki67 counts by pathologists. - One Ki67 immunohistochemical stain was retrieved from each of 18 archived gastrointestinal or pancreatic neuroendocrine tumor resections. We compared pathologists' Ki67 eyeball estimates on glass slides and printed color images with manual counts performed by 3 cytotechnologists and gold standard manual Ki67 index counts by 3 pathologists. - Tumor grade agreement between pathologist image eyeball estimate and gold standard pathologist manual count was fair (κ = 0.31; 95% CI, 0.030-0.60). In 9 of 20 cases (45%), the mean pathologist eyeball estimate was 1 grade higher than the mean pathologist manual count. There was almost perfect agreement in classifying tumor grade between the mean cytotechnologist manual count and the mean pathologist manual count (κ = 0.910; 95% CI, 0.697-1.00). In 20 cases, there was only 1 grade disagreement between the 2 methods. Eyeball estimation by pathologists required less than 1 minute, whereas manual counts by pathologists required a mean of 17 minutes per case. - Eyeball estimation of the Ki67 index has a high rate of tumor grade misclassification compared with manual counting. Cytotechnologist manual counts are accurate and save pathologist time.

Primary Small Cell Neuroendocrine Carcinoma of Vagina: A Rare Case Report

Directory of Open Access Journals (Sweden)

Jignasa N. Bhalodia

2011-01-01

Full Text Available Primary small cell neuroendocrine carcinoma of vagina is an extremely rare disease. There have been only 26 previously reported cases in literature. Here, we report a case of primary small cell neuroendocrine carcinoma of vagina. Immunohistochemistry (IHC showed tumor cells positive for synaptophysin, chromogranin, and neuron-specific enolase (NSE.

[A case of lung abscess during chemotherapy for testicular tumor].

Science.gov (United States)

Hayashi, Yujiro; Miyago, Naoki; Takeda, Ken; Yamaguchi, Yuichiro; Nakayama, Masashi; Arai, Yasuyuki; Kakimoto, Ken-ichi; Nishimura, Kazuo

2014-05-01

32-year-old man was seen in a clinic because of prolonged cough and slight-fever. Chest X-ray showed multiple pulmonary nodules, and multiple lung and mediastinal lymph node metastases from right testicular tumor was suspected by positron emission tomography/CT (PET/CT) scan. He was diagnosed with right testicular germ cell tumor (embryonal carcinoma + seminoma, pT2N1M1b), and classified into the intermediate risk group according to International Germ Cell Cancer Collaborative Group. He underwent 4 cycles of chemotherapy with bleomycin, etoposide and cisplatin (BEP therapy). During BEP therapy, sputum with foul odor appeared and chest CT scan revealed lung abscess with a necrotic lesion of metastatic tumor. The lung abscess was treated successfully with antibiotics.

Synchronous Peripancreatic Lymph Node Gastrinoma and Gastric Neuroendocrine Tumor Type 2

Directory of Open Access Journals (Sweden)

Hee Woo Lee

2016-09-01

Full Text Available A 34-year-old man was referred to our hospital with gastric polypoid lesions and biopsy-confirmed neuroendocrine tumor (NET. Computed tomography (CT revealed a 3×3.5×8-cm retroperitoneal mass behind the pancreas, with multiple hepatic metastases. His serum gastrin level was elevated to 1,396 pg/mL. We performed a wedge resection of the stomach, a right hemi-hepatectomy, and a retroperitoneal mass excision. After careful review of the clinical, radiological, histopathological, and immunohistochemical findings, peripancreatic gastrinoma, and synchronous gastric NET were ultimately diagnosed. We reviewed a CT scan that had been performed 6 years previously after surgery for a duodenal perforation. There was no evidence of gastric or hepatic lesions, but the retroperitoneal mass was present at the same site. Had gastrinoma been detected earlier, our patient could have been cured using less invasive treatment. This case demonstrates how important it is to consider Zollinger-Ellison syndrome in patients with a recurrent or aggressive ulcer.

Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters.

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Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

2015-11-21

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney-Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney-Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney-Rivlin material model along left-right, anterior-posterior, and superior-inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation.

Lung inflammatory pseudo tumor

International Nuclear Information System (INIS)

Veliz, Elizabeth; Leone, Gaetano; Cano, Fernando; Sanchez, Jaime

2005-01-01

The inflammatory pseudo tumor is a non neoplastic process characterized by an irregular growth of inflammatory cells. We described the case of a 38 year-old patient, she went to our institute for a in situ cervix cancer and left lung nodule without breathing symptoms; valued by neumology who did bronchoscopy with biopsy whose result was negative for malignancy. She went to surgery in where we find intraparenquima nodule in felt lingula of approximately 4 cms, we remove it; the result was: Inflammatory pseudotumor. This pathology is a not very frequent, it can develop in diverse regions of the organism, it is frequent in lung. The image tests are not specific for the diagnose, which it is possible only with the biopsy. The treatment is the complete resection. (The author)

Comparison of neuroendocrine tumor detection and characterization using DOTATOC-PET in correlation with contrast enhanced CT and delayed contrast enhanced MRI

International Nuclear Information System (INIS)

Giesel, F.L.; Kratochwil, C.; Mehndiratta, A.; Wulfert, S.; Moltz, J.H.; Zechmann, C.M.; Kauczor, H.U.; Haberkorn, U.; Ley, S.

2012-01-01

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

Therapy of neuroendocrine carcinoma with Y-90 DOTA- preliminary results

International Nuclear Information System (INIS)

Artiko, V.; Obradovic, V.; Nadezda, N.; Djokic, D.; Jankovic, D.; Popovic, B.; Damjanovic, S.; Mikolajczak, R.; Pawlak, D.

2007-01-01

Full text: Aim: Cell membrane-specific somatostatin receptors are usually expressed by neuroendocrine tumors. Radiolabelled receptor-binding somatostatin analogues target tissues expressing these receptors and can be used for visualization and treatment. After the localization of tumors bearing somatostatin receptors with 111In or 99mTc labeled somatostatin analogues, in the case of high tumor uptake related to non target tissues, different radioisotopes have been used for their treatment. Thus, application of high doses of 111In- DTPA-octreotide had an impact on improvement of the clinical symptoms, without significant reduction of the tumor mass. However, 90Y somatostatin analogues (DOTA TOC, lanreotide) may be more effective for reduction of the tissue of the larger tumors while 177Lu labeled ones may be applied in smaller tumors. Combination of both of them seems to be the most effective therapy, particularly in tumors bearing both small and large lesions. The aim of this work is presentation of the preliminary results of the therapy of NETs with another octreotide analogue, 90Y DOTA TATE, which so far has been proved to have high therapeutic potential when labeled with 177Lu. Patients and methods: We investigated 7 patients with neuroendocrine tumors (two patients had neuroendocrine pancreatic carcinomas with liver metastases (one of them had metastases in peritoneal lymph nodes), one patient with operated (resected) bronchial carcinoid and liver metastases, three patients with neuroendocrine carcinomas of unknown origin and hepatic metastases (one with skeletal metastases) and one with pancreatic gastrinoma without metastases (surgery was impossible to perform). In all of them, together with other laboratory analyses and imaging methods, scintigraphy with somatostatin analogues was performed (in 3 with 111In Octreoscan and in the other 4 with 99mTc HYNIC TOC) and high tumor uptake was observed. The therapy was performed with 2- 4,5 GBq 90Y DOTA TATE per

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: Report of two cases.

Science.gov (United States)

García-Fontán, Eva; Blanco Ramos, Montserrat; García, Jose Soro; Carrasco, Rommel; Cañizares, Miguel Ángel; González Piñeiro, Ana

2018-05-19

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder characterized by a proliferation of neuroendocrine cells within the lung. It is classically described as a disease with persistent cough, dyspnea and wheezing in non-smoker middle aged females. CT of the chest reveals diffuse air trapping with mosaic pattern. We present two cases of DIPNECH that were sent to our department to perform a lung biopsy with the diagnostic suspicion of diffuse interstitial disease. Both cases were women with a history of chronic cough and moderate effort dyspnea. The aim of this paper is that physicians take into account this diagnostic entity before treating as an asthmatic a patient with these characteristics, not forgetting that they are prenoplastic lesions. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

Lymphovascular invasion in more than one-quarter of small rectal neuroendocrine tumors

Science.gov (United States)

Kwon, Mi Jung; Kang, Ho Suk; Soh, Jae Seung; Lim, Hyun; Kim, Jong Hyeok; Park, Choong Kee; Park, Hye-Rim; Nam, Eun Sook

2016-01-01

AIM To identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs). METHODS Between June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts. RESULTS We observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI. CONCLUSION LVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis. PMID:27895428

Dosimetric evaluation of lung tumor immobilization using breath hold at deep inspiration

International Nuclear Information System (INIS)

Barnes, Elizabeth A.; Murray, Brad R.; Robinson, Donald M.; Underwood, Lori J.; Hanson, John; Roa, Wilson H.Y.

2001-01-01

Purpose:To examine the dosimetric benefit of self-gated radiotherapy at deep-inspiration breath hold (DIBH) in the treatment of patients with non-small-cell lung cancer (NSCLC). The relative contributions of tumor immobilization at breath hold (BH) and increased lung volume at deep inspiration (DI) in sparing high-dose lung irradiation (≥20 Gy) were examined. Methods and Materials:Ten consecutive patients undergoing radiotherapy for Stage I-IIIB NSCLC who met the screening criteria were entered on this study. Patients were instructed to BH at DI without the use of external monitors or breath-holding devices (self-gating). Computed tomography (CT) scans of the thorax were performed during free breathing (FB) and DIBH. Fluoroscopy screened for reproducible tumor position throughout DIBH, and determined the maximum superior-inferior (SI) tumor motion during both FB and DIBH. Margins used to define the planning target volume (PTV) from the clinical target volume included 1 cm for setup error and organ motion, plus an additional SI margin for tumor motion, as determined from fluoroscopy. Three conformal treatment plans were then generated for each patient, one from the FB scan with FB PTV margins, a second from the DIBH scan with FB PTV margins, and a third from the DIBH scan with DIBH PTV margins. The percent of total lung volume receiving ≥20 Gy (using a prescription dose of 70.9 Gy to isocenter) was determined for each plan. Results:Self-gating at DIBH was possible for 8 of the 10 patients; 2 patients were excluded, because they were not able to perform a reproducible DIBH. For these 8 patients, the median BH time was 23 (range, 19-52) s. The mean percent of total lung volume receiving ≥20 Gy under FB conditions (FB scan with FB PTV margins) was 12.8%. With increased lung volume alone (DIBH scan with FB PTV margins), this was reduced to 11.0%, tending toward a significant decrease in lung irradiation over FB (p=0.086). With both increased lung volume and tumor

Quantitative CT analysis for the preoperative prediction of pathologic grade in pancreatic neuroendocrine tumors

Science.gov (United States)

Chakraborty, Jayasree; Pulvirenti, Alessandra; Yamashita, Rikiya; Midya, Abhishek; Gönen, Mithat; Klimstra, David S.; Reidy, Diane L.; Allen, Peter J.; Do, Richard K. G.; Simpson, Amber L.

2018-02-01

Pancreatic neuroendocrine tumors (PanNETs) account for approximately 5% of all pancreatic tumors, affecting one individual per million each year.1 PanNETs are difficult to treat due to biological variability from benign to highly malignant, indolent to very aggressive. The World Health Organization classifies PanNETs into three categories based on cell proliferative rate, usually detected using the Ki67 index and cell morphology: low-grade (G1), intermediate-grade (G2) and high-grade (G3) tumors. Knowledge of grade prior to treatment would select patients for optimal therapy: G1/G2 tumors respond well to somatostatin analogs and targeted or cytotoxic drugs whereas G3 tumors would be targeted with platinum or alkylating agents.2, 3 Grade assessment is based on the pathologic examination of the surgical specimen, biopsy or ne-needle aspiration; however, heterogeneity in the proliferative index can lead to sampling errors.4 Based on studies relating qualitatively assessed shape and enhancement characteristics on CT imaging to tumor grade in PanNET,5 we propose objective classification of PanNET grade with quantitative analysis of CT images. Fifty-five patients were included in our retrospective analysis. A pathologist graded the tumors. Texture and shape-based features were extracted from CT. Random forest and naive Bayes classifiers were compared for the classification of G1/G2 and G3 PanNETs. The best area under the receiver operating characteristic curve (AUC) of 0:74 and accuracy of 71:64% was achieved with texture features. The shape-based features achieved an AUC of 0:70 and accuracy of 78:73%.

Small cell neuroendocrine carcinoma of the endometrium, a rare aggressive tumor

International Nuclear Information System (INIS)

Rajab, Khalil E.; Sandhu, Amarjit K.; Rajeswari, Mangla S.; Malik, A.

2005-01-01

This is a report of a young infertile woman with a history of 8 years amenorrhea, who presented with history of vaginal bleeding of 2 months duration. Investigations revealed a small cell neuroendocrine carcinoma of the endometrium, which penetrated half of the thickness of uterine wall. We have described the clinical progress and management of this rare and highly malignant cancer. A review of the pathological types and behavior of clear cell neuroendocrine carcinoma is presented. (author)

Advances in the diagnosis and treatment of pancreatic neuroendocrine neoplasms in Japan.

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Ito, Tetsuhide; Hijioka, Susumu; Masui, Toshihiko; Kasajima, Atsuko; Nakamoto, Yuji; Kobayashi, Noritoshi; Komoto, Izumi; Hijioka, Masayuki; Lee, Lingaku; Igarashi, Hisato; Jensen, Robert Thomas; Imamura, Masayuki

2017-01-01

Several new developments have occurred in the field of pancreatic neuroendocrine neoplasm (PNEN) recently in Japan. First, the utility of chromogranin A (CgA), useful for the diagnosis and monitoring of the treatment response of neuroendocrine neoplasm (NEN), has been demonstrated in Japan. For PNEN diagnosis and treatment, grading and correct histological diagnosis according to the WHO 2010 classification is important. Regarding the histological diagnosis, the advent of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has enabled correct pathological diagnosis and suitable treatment for the affected tissue. Furthermore, EUS-FNA has also facilitates the assessment of the presence or absence of gene mutations. In addition, patients who have a well-differentiated neuroendocrine tumor (NET) showing a Ki-67 index of higher than 20 % according to the WHO 2010 classification, have also been identified, and their responses to treatment were found to be different from those of patients with poorly differentiated neuroendocrine carcinoma (NEC). Therefore, the concept of NET G3 was proposed. Additionally, somatostatin receptor type 2 is expressed in several cases of NET, and somatostatin receptor scintigraphy ( 111 In-octreoscan) has also been approved in Japan. This advancement will undoubtedly contribute to the localization diagnosis, the identification of remote metastasis, and assessments of the treatment responses of PNEN. Finally, regarding the treatment strategy for PNEN, the management of liver metastasis is important. The advent of novel molecular-targeted agents has dramatically improved the prognosis of advanced PNEN. Multimodality therapy that accounts for the tumor stage, degree of tumor differentiation, tumor volume, and speed of tumor growth is required.

Reciprocal modulation of mesenchymal stem cells and tumor cells promotes lung cancer metastasis

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Giulia Fregni

2018-03-01

Full Text Available Metastasis is a multi-step process in which direct crosstalk between cancer cells and their microenvironment plays a key role. Here, we assessed the effect of paired tumor-associated and normal lung tissue mesenchymal stem cells (MSCs on the growth and dissemination of primary human lung carcinoma cells isolated from the same patients. We show that the tumor microenvironment modulates MSC gene expression and identify a four-gene MSC signature that is functionally implicated in promoting metastasis. We also demonstrate that tumor-associated MSCs induce the expression of genes associated with an aggressive phenotype in primary lung cancer cells and selectively promote their dissemination rather than local growth. Our observations provide insight into mechanisms by which the stroma promotes lung cancer metastasis. Keywords: Tumor-associated MSCs, lung cancer, metastasis, GREM1, LOXL2, ADAMTS12, ITGA11

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

Evans Syndrome Presented with Marginal Zone Lymphoma and Duodenal Neuroendocrine Tumor in an Elderly Woman

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Daniele D'Ambrosio

2016-12-01

Full Text Available Evans syndrome (ES is an autoimmune disorder characterized by simultaneous or sequential development of autoimmune hemolytic anemia, immune thrombocytopenia, and/or neutropenia. ES can be classified as a primary (idiopathic or secondary (associated with an underlying disease syndrome. We report a case of ES in an elderly patient in the presence of multiple trigger factors such as recent influenza vaccine, marginal zone lymphoma, and neuroendocrine tumor G1. Whether this association is casual or causal remains a matter of speculation. It is however necessary to have a thorough work-up in a newly diagnosed ES and a more accurate search of miscellaneous factors especially in elderly patients.

Soluble tumor necrosis factor receptor-1 in preterm infants with chronic lung disease.

Science.gov (United States)

Sato, Miho; Mori, Masaaki; Nishimaki, Shigeru; An, Hiromi; Naruto, Takuya; Sugai, Toshiyuki; Shima, Yoshio; Seki, Kazuo; Yokota, Shumpei

2010-04-01

It is clear that inflammation plays an important role in developing chronic lung disease in preterm infants. The purpose of the present study is to investigate changes of serum soluble tumor necrosis factor receptor-1 levels over time in infants with chronic lung disease. The serum levels of soluble tumor necrosis factor receptor-1 were measured after delivery, and at 7, 14, 21 and 28 days of age in 10 infants with chronic lung disease and in 18 infants without chronic lung disease. The serum level of soluble tumor necrosis factor receptor-1 was significantly higher in infants with chronic lung disease than in infants without chronic lung disease after delivery. The differences between these two groups remained up to 28 days of age. Prenatal inflammation with persistence into postnatal inflammation may be involved in the onset of chronic lung disease.

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

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

2001-04-01

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

Sensitivity of tumor motion simulation accuracy to lung biomechanical modeling approaches and parameters

International Nuclear Information System (INIS)

Tehrani, Joubin Nasehi; Wang, Jing; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu

2015-01-01

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional computed tomography (4D-CT). A Quasi-Newton FEA was performed to simulate lung and related tumor displacements between end-expiration (phase 50%) and other respiration phases (0%, 10%, 20%, 30%, and 40%). Both linear isotropic and non-linear hyperelastic materials, including the neo-Hookean compressible and uncoupled Mooney–Rivlin models, were used to create a finite element model (FEM) of lung and tumors. Lung surface displacement vector fields (SDVFs) were obtained by registering the 50% phase CT to other respiration phases, using the non-rigid demons registration algorithm. The obtained SDVFs were used as lung surface displacement boundary conditions in FEM. The sensitivity of TCM displacement to lung and tumor biomechanical parameters was assessed in eight patients for all three models. Patient-specific optimal parameters were estimated by minimizing the TCM motion simulation errors between phase 50% and phase 0%. The uncoupled Mooney–Rivlin material model showed the highest TCM motion simulation accuracy. The average TCM motion simulation absolute errors for the Mooney–Rivlin material model along left-right, anterior–posterior, and superior–inferior directions were 0.80 mm, 0.86 mm, and 1.51 mm, respectively. The proposed strategy provides a reliable method to estimate patient-specific biomechanical parameters in FEM for lung tumor motion simulation. (paper)

Portal Vein Tumor Thrombus of Liver Metastasis from Lung Cancer

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Ryoko Ogawa

2009-01-01

Full Text Available We report a case of liver metastasis of lung carcinoma with portal vein tumor thrombus (PVTT. Although the primary lesion of lung tumor remained unchanged, the patient rapidly developed wide-spread metastases and formed PVTT of liver metastasis. The primary lesion showed features of mixed Clara and bronchial surface epithelial cell component type adenocarcinoma with small foci of micropapillary pattern. Micropapillary pattern was observed in the metastatic lesions in the liver and PVTT. Micropapillary pattern lung adenocarcinoma may develop rapid metastases and cause PVTT associated with liver metastasis. We should perform a detailed examination to establish correct diagnosis.

Toward in vivo lung's tissue incompressibility characterization for tumor motion modeling in radiation therapy

International Nuclear Information System (INIS)

Shirzadi, Zahra; Sadeghi-Naini, Ali; Samani, Abbas

2013-01-01

Purpose: A novel technique is proposed to characterize lung tissue incompressibility variation during respiration. Estimating lung tissue incompressibility parameter variations resulting from air content variation throughout respiration is critical for computer assisted tumor motion tracking. Continuous tumor motion is a major challenge in lung cancer radiotherapy, especially with external beam radiotherapy. If not accounted for, this motion may lead to areas of radiation overdosage for normal tissue. Given the unavailability of imaging modality that can be used effectively for real-time lung tumor tracking, computer assisted approach based on tissue deformation estimation can be a good alternative. This approach involves lung biomechanical model where its fidelity depends on input tissue properties. This investigation shows that considering variable tissue incompressibility parameter is very important for predicting tumor motion accurately, hence improving the lung radiotherapy outcome. Methods: First, an in silico lung phantom study was conducted to demonstrate the importance of employing variable Poisson's ratio for tumor motion predication. After it was established that modeling this variability is critical for accurate tumor motion prediction, an optimization based technique was developed to estimate lung tissue Poisson's ratio as a function of respiration cycle time. In this technique, the Poisson's ratio and lung pressure value were varied systematically until optimal values were obtained, leading to maximum similarity between acquired and simulated 4D CT lung images. This technique was applied in an ex vivo porcine lung study where simulated images were constructed using the end exhale CT image and deformation fields obtained from the lung's FE modeling of each respiration time increment. To model the tissue, linear elastic and Marlow hyperelastic material models in conjunction with variable Poisson's ratio were used. Results: The phantom study showed that

Neuroendocrine tumor of the pancreas causing biliary obstruction in a 12 year-old girl: A case report and literature review

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Kimberly A. Bertens

2014-09-01

Full Text Available Pancreatic tumors are uncommon in children and rarely result in biliary obstruction. A previously well 12-year old female presented with a one-week history of fatigue, pruritis, and painless jaundice. Abdominal ultrasound demonstrated a mass in the pancreatic head associated with dilation of the common bile duct. Further workup included abdominal MRI, CT and endoscopic retrograde pancreaticogram (ERCP with biliary stenting. Octreotide scan did not reveal uptake in the pancreatic tumor. Percutaneous biopsies were consistent with a grade 2 pancreatic neuroendocrine tumor (NET. Preoperative imaging demonstrated involvement of the portal vein. The patient was brought the operating room for a pancreaticoduodenectomy and portal vein resection. Final pathology revealed a T3N1M0 pancreatic NET. The patient recovered uneventfully.

Malignant Phyllodes Tumor Presenting in Bone, Brain, Lungs, and Lymph Nodes

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Eric D. Johnson

2016-12-01

Full Text Available Introduction: Phyllodes tumors (PTs are rare fibroepithelial tumors of the breast which are classified as benign, borderline, or malignant. Malignant PTs account for <1% of malignant breast tumors, and borderline tumors have potential to progress to malignant tumors. Metastatic recurrences are most commonly documented in bone and lungs. We report an extremely rare presentation of recurrent malignant PTs involving the brain, lung, lymph nodes, and bone. Case: A 66-year-old female presented with a large breast mass. Biopsy identified malignant PT, treated by mastectomy. One year later she presented with acute back pain; imaging showed pathological L4 spinal compression fracture. Core biopsy confirmed PT. Staging identified additional metastases in the lymph nodes, brain, and lung. Discussion: PTs are rare and fast-growing tumors that originate from periductal stromal tissues and are composed of both epithelial and stromal components. Histologically, they are classified as benign, borderline, or malignant. The prognosis of the malignant type is poorly defined, with local recurrence occurring in 10–40% and metastases in 10%. Chemotherapy and radiotherapy are generally ineffective in this tumor type. The most common metastatic sites for malignant cases are the lung and bones, but in rare instances, PTs may metastasize elsewhere. Conclusion: We report a rare presentation of recurrent malignant PT presenting as pathological fracture of the lumbar spine with impingement on the spinal column, along with cerebellar, nodal, and pulmonary metastases. Only 1 similar case has been previously reported.

Sensitivity of Tumor Motion Simulation Accuracy to Lung Biomechanical Modeling Approaches and Parameters

OpenAIRE

Tehrani, Joubin Nasehi; Yang, Yin; Werner, Rene; Lu, Wei; Low, Daniel; Guo, Xiaohu; Wang, Jing

2015-01-01

Finite element analysis (FEA)-based biomechanical modeling can be used to predict lung respiratory motion. In this technique, elastic models and biomechanical parameters are two important factors that determine modeling accuracy. We systematically evaluated the effects of lung and lung tumor biomechanical modeling approaches and related parameters to improve the accuracy of motion simulation of lung tumor center of mass (TCM) displacements. Experiments were conducted with four-dimensional com...

Time-dependent cell disintegration kinetics in lung tumors after irradiation

International Nuclear Information System (INIS)

Chvetsov, Alexei V; Palta, Jatinder J; Nagata, Yasushi

2008-01-01

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T 1/2 . The half-life T 1/2 is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T 1/2 of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations

Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue

International Nuclear Information System (INIS)

Waelti, Stephan L.; Garel, Laurent; Rypens, Francoise; Dubois, Josee; Dal Soglio, Dorothee; Messerli, Michael

2017-01-01

The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10 years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible. (orig.)

Neonatal congenital lung tumors - the importance of mid-second-trimester ultrasound as a diagnostic clue

Energy Technology Data Exchange (ETDEWEB)

Waelti, Stephan L.; Garel, Laurent; Rypens, Francoise; Dubois, Josee [University of Montreal, Department of Medical Imaging, Sainte-Justine Hospital, Quebec (Canada); Dal Soglio, Dorothee [University of Montreal, Department of Pathology, Sainte-Justine Hospital, Quebec (Canada); Messerli, Michael [University Hospital Zurich, University of Zurich, Department of Nuclear Medicine, Zurich (Switzerland)

2017-12-15

The differential diagnosis for primary lung masses in neonates includes a variety of developmental abnormalities; it also consists of the much rarer congenital primary lung tumors: cystic pleuropulmonary blastoma (cystic PPB), fetal lung interstitial tumor (FLIT), congenital peribronchial myofibroblastic tumor (CPMT), and congenital fibrosarcoma. Radiologic differentiation between malformations and tumors is often very challenging. The objective was to establish distinctive features between developmental pulmonary abnormalities and primary lung tumors. We conducted a retrospective study of 135 congenital lung lesions at a university mother and child center over a period of 10 years (2005-2015). During this time, we noted four tumors (two cystic PPBs and two FLITs) and 131 malformations. We recorded the following parameters: timing of conspicuity in utero (mid-second trimester, third trimester, or not seen prenatally), presence of symptoms at birth, prenatal and perinatal radiologic findings, and either histological diagnoses by pathology or follow-up imaging in non-operated cases. All lesions except the four tumors were detected during mid-second-trimester ultrasound. In none of the tumors was any pulmonary abnormality found on the mid-second-trimester sonogram, contrary to the developmental pulmonary abnormalities. The timing of conspicuity in utero appears to be a key feature for the differentiation between malformations and tumors. Lesions that were not visible at the mid-second-trimester ultrasound should be considered as tumor. A cystic lung lesion in the context of a normal mid-second-trimester ultrasound is highly suggestive of a cystic PPB. Differentiating the types of solid congenital lung tumors based upon imaging features is not yet feasible. (orig.)

Acute damage by naphthalene triggers expression of the neuroendocrine marker PGP9.5 in airway epithelial cells

DEFF Research Database (Denmark)

Poulsen, T.T.; Naizhen, X.; Linnoila, R.I.

2008-01-01

Protein Gene Product 9.5 (PGP9.5) is highly expressed in nervous tissue. Recently PGP9.5 expression has been found to be upregulated in the pulmonary epithelium of smokers and in non-small cell lung cancer, suggesting that it also plays a role in carcinogen-inflicted lung epithelial injury...... neuroendocrine markers was found in the non-neuroendocrine epithelial cells after naphthalene exposure. In contrast, immunostaining for the cell cycle regulator p27(Kip1), which has previously been associated with PGP9.5 in lung cancer cells, revealed transient downregulation of p27(Kip1) in naphthalene exposed...... and further strengthens the accumulating evidence of PGP9.5 as a central player in lung epithelial damage and early carcinogenesis Udgivelsesdato: 2008/9/26...

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

Directory of Open Access Journals (Sweden)

Petersenn Stephan

2006-04-01

Full Text Available Abstract Background ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. Case presentation A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. Conclusion This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide

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

2016-01-01

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. PMID:27259241

Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995-2012) in South China.

Science.gov (United States)

Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Wang, Jin-Hui; Chen, Min-Hu; Chen, Jie

2012-11-29

Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) is the most common type of neuroendocrine tumors accounting for 65-75% of neuroendocrine neoplasms (NENs). Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Pancreas was found the most common site of involvement (34.8%). 149 patients (83.7%) presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%); carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA) and synaptophysin (Syn) immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5%) had G1 tumors, 31(18.3%) G2 tumors and 51 (30.2%) G3 tumors. Neuroendocrine tumor (NET), neuroendocrine carcinoma (NEC) and mixed adenoendocrine carcinoma (MANEC) were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4%) patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

Adoptively transferred human lung tumor specific cytotoxic T cells can control autologous tumor growth and shape tumor phenotype in a SCID mouse xenograft model

Directory of Open Access Journals (Sweden)

Ferrone Soldano

2007-06-01

Full Text Available Abstract Background The anti-tumor efficacy of human immune effector cells, such as cytolytic T lymphocytes (CTLs, has been difficult to study in lung cancer patients in the clinical setting. Improved experimental models for the study of lung tumor-immune cell interaction as well as for evaluating the efficacy of adoptive transfer of immune effector cells are needed. Methods To address questions related to the in vivo interaction of human lung tumor cells and immune effector cells, we obtained an HLA class I + lung tumor cell line from a fresh surgical specimen, and using the infiltrating immune cells, isolated and characterized tumor antigen-specific, CD8+ CTLs. We then established a SCID mouse-human tumor xenograft model with the tumor cell line and used it to study the function of the autologous CTLs provided via adoptive transfer. Results The tumor antigen specific CTLs isolated from the tumor were found to have an activated memory phenotype and able to kill tumor cells in an antigen specific manner in vitro. Additionally, the tumor antigen-specific CTLs were fully capable of homing to and killing autologous tumors in vivo, and expressing IFN-γ, each in an antigen-dependent manner. A single injection of these CTLs was able to provide significant but temporary control of the growth of autologous tumors in vivo without the need for IL-2. The timing of injection of CTLs played an essential role in the outcome of tumor growth control. Moreover, immunohistochemical analysis of surviving tumor cells following CTL treatment indicated that the surviving tumor cells expressed reduced MHC class I antigens on their surface. Conclusion These studies confirm and extend previous studies and provide additional information regarding the characteristics of CTLs which can be found within a patient's tumor. Moreover, the in vivo model described here provides a unique window for observing events that may also occur in patients undergoing adoptive cellular

Two-stage resection of a bilateral pheochromocytoma and pancreatic neuroendocrine tumor in a patient with von Hippel-Lindau disease: A case report

Directory of Open Access Journals (Sweden)

Yutaka Endo

Full Text Available Introduction: von Hippel-Lindau disease (vHL disease is a hereditary disease in which tumors and cysts develop in many organs, in association with central nervous system hemangioblastomas, pheochromocytomas, and pancreatic tumors. We herein report a case of vHL disease (type 2A associated with bilateral pheochromocytomas, pancreatic neuroendocrine tumors (PNET, and cerebellar hemangioblastomas treated via pancreatectomy after adrenalectomy. Case presentation: A 51-year-old woman presented with a cerebellar tumor, bilateral hypernephroma, and pancreatic tumor detected during a medical checkup. 18F-fluorodeoxyglucose positron emission tomography–computed tomography revealed a bilateral adrenal gland tumor and a tumor in the head of the pancreas, while an abdominal computed tomography examination revealed a 30-mm tumor with strong enhancement in the head of the pancreas. Cranial magnetic resonance imaging showed a hemangioblastoma in the cerebellum. Therefore, a diagnosis of vHL disease (type 2A was made. Her family medical history included renal cell carcinoma in her father and bilateral adrenal pheochromocytoma and spinal hemangioblastoma in her brother. A detailed examination of endocrine function showed that the adrenal mass was capable of producing catecholamine. Treatment of the pheochromocytoma was prioritized, and therefore, laparoscopic left adrenalectomy and subtotal resection of the right adrenal gland were performed. Once the postoperative steroid levels were replenished, subtotal stomach-preserving pancreatoduodenectomy was performed for the PNET. After a good postoperative course, the patient was discharged in remission on the 11th day following surgery. Histopathological examination findings indicated NET G2 (MIB-1 index 10–15% pT3N0M0 Stage II A and microcystic serous cystadenoma throughout the resected specimen. The patient is scheduled to undergo treatment for the cerebellar hemangioblastoma. Conclusion: A two-staged resection

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.

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.

Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors

Directory of Open Access Journals (Sweden)

Chang Thomas

2007-10-01

Full Text Available Abstract Background Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. Methods Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3–5 were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45–60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. Results Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. Conclusion Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

Cyclin D expression in plutonium-induced lung tumors in F344 rats

Energy Technology Data Exchange (ETDEWEB)

Hahn, F.F.; Kelly, G. [SouthWest Scientific Resources, Inc., Albuquerque, NM (United States)

1995-12-01

The genetic mechanisms responsible for {alpha}-radiation-induced lung cancer in rats following inhalation of {sup 239}Pu is an ongoing area of research in our laboratory. Previous studies have examined the status of the p53 gene by immunohistochemistry. Only two tumors (2/26 squamous cell carcinomas) exhibited detectable levels of p53 products. Both were the result of mutations in codons 280 and 283. More recent studies of X-ray-induced lung tumors in rats showed a similar lack of involvement of p53. In conclusion, we found that {alpha}-radiation-induced rat lung tumors have a high incidence (31 of 39) of cyclin D{sub 1} overexpression.

Development of radioconjugate90Y-DOTATATE for therapy of neuroendocrine tumors positive to hSSTR2

International Nuclear Information System (INIS)

Gongora, M.; Alonso, L. M.; Rodriguez, A. M.; Leyva, R.; Solana, A.; Pino, M.; Alberti, A.

2015-01-01

Peptide receptor radionuclide therapy of patients with neuroendocrine tumors has expanded due to radiolabeling of DOTA-peptides, such as somatostatin analogue DOTA 0 -Tyr 3 -octreotate (DOTATATE) radiolabeled with Β-emitters radionuclides. The present work describes the labeling of DOTATATE with yttrium-90 from a novel electrochemical generator. All factors that could have influence in kinetic reaction of radiolabeled DOTA-peptide were also studied. The formulation with the highest radiochemical yield was assayed for serum stability, sera protein binding, stability in saline, in vitro stability in an excess of 50 mM EDTA and trans metallation studies in solutions of metal competitors (Fe 3+ , Ca 2+ , Mg 2+ and Za 2+ ). Our findings showed a formulation with high radiochemical purity and stability that allows further steps in the drug development process of this radiopharmaceutical. (Author) Peptide receptor radionuclide therapy of patients with neuroendocrine tumors has expanded due to radiolabeling of DOTA-peptides, such as somatostatin analogue DOTA 0 -Tyr 3 -octreotate (DOTATATE) radiolabeled with Β-emitters radionuclides. The present work describes the labeling of DOTATATE with yttrium-90 from a novel electrochemical generator. All factors that could have influence in kinetic reaction of radiolabeled DOTA-peptide were also studied. The formulation with the highest radiochemical yield was assayed for serum stability, sera protein binding, stability in saline, in vitro stability in an excess of 50 mM EDTA and trans metallation studies in solutions of metal competitors (Fe 3+ , Ca 2+ , Mg 2+ and Za 2+ ). Our findings showed a formulation with high radiochemical purity and stability that allows further steps in the drug development process of this radiopharmaceutical. (Author)

Time-dependent cell disintegration kinetics in lung tumors after irradiation

Energy Technology Data Exchange (ETDEWEB)

Chvetsov, Alexei V; Palta, Jatinder J [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Nagata, Yasushi [Department of Therapeutic Radiology and Oncology, Kyoto University, Kyoto (Japan)], E-mail: chvetsov@ufl.edu

2008-05-07

We study the time-dependent disintegration kinetics of tumor cells that did not survive radiotherapy treatment. To evaluate the cell disintegration rate after irradiation, we studied the volume changes of solitary lung tumors after stereotactic radiotherapy. The analysis is performed using two approximations: (1) tumor volume is a linear function of the total cell number in the tumor and (2) the cell disintegration rate is governed by the exponential decay with constant risk, which is defined by the initial cell number and a half-life T{sub 1/2}. The half-life T{sub 1/2} is determined using the least-squares fit to the clinical data on lung tumor size variation with time after stereotactic radiotherapy. We show that the tumor volume variation after stereotactic radiotherapy of solitary lung tumors can be approximated by an exponential function. A small constant component in the volume variation does not change with time; however, this component may be the residual irregular density due to radiation fibrosis and was, therefore, subtracted from the total volume variation in our computations. Using computerized fitting of the exponent function to the clinical data for selected patients, we have determined that the average half-life T{sub 1/2} of cell disintegration is 28.2 days for squamous cell carcinoma and 72.4 days for adenocarcinoma. This model is needed for simulating the tumor volume variation during radiotherapy, which may be important for time-dependent treatment planning of proton therapy that is sensitive to density variations.

Classification of primary lung tumors in dogs: 210 cases (1975-1985)

International Nuclear Information System (INIS)

Ogilvie, G.K.; Haschek, W.M.; Withrow, S.J.; Richardson, R.C.; Harvey, H.J.; Henderson, R.A.; Fowler, J.D.; Norris, A.M.; Tomlinson, J.; McCaw, D.

1989-01-01

Two hundred ten dogs that had primary lung tumors diagnosed between 1975 and 1985 were evaluated. The majority of the tumors were classified as adenocarcinoma (74.8%) and alveolar carcinoma (20%). The most common clinical signs of disease were cough (52%), dyspnea (23.8%), lethargy (18.1%), weight loss (12.4%), and tachypnea (4.8%). The clinical methods that were most successful in directly or indirectly leading to a diagnosis of primary lung tumor were thoracic radiography (77.1%) and cytologic examination of fine-needle aspirate specimens (24.8%)

Carcinoid crisis induced by receptor radionuclide therapy with 90Y-DOTATOC in a case of liver metastases from bronchial neuroendocrine tumor (atypical carcinoid).

Science.gov (United States)

Davì, M V; Bodei, L; Francia, G; Bartolomei, M; Oliani, C; Scilanga, L; Reghellin, D; Falconi, M; Paganelli, G; Lo Cascio, V; Ferdeghini, M

2006-06-01

SS receptors are overexpressed in many tumors, mainly of neuroendocrine origin, thus enabling the treatment with SS analogs. The clinical experience of receptor radionuclide therapy with the new analog [90Y-DOTA0-Tyr3 ]-octreotide [90Y-DOTATOC] has been developed over the last decade and is gaining a pivotal role in the therapeutic workout of these tumors. It is well known that some procedures performed in diagnostic and therapeutic management of endocrine tumors, such as agobiopsy and hepatic chemoembolization, can be associated with the occurrence of symptoms related to the release of vasoactive amines and/or hormonal peptides from tumor cell lysis. This is the first report of a severe carcinoid crisis developed after receptor radionuclide therapy with 90Y-DOTATOC administered in a patient affected by liver metastases from bronchial neuroendocrine tumor (atypical carcinoid). Despite protection with H1 receptor antagonists, octreotide and corticosteroids, few days after the therapy the patient complained of persistent flushing of the face and upper trunk, severe labial and periocular oedema, diarrhoea and loss of appetite. These symptoms increased and required new hospitalisation. The patient received iv infusion of octreotide associated with H1 and H2 receptor antagonists and corticosteroid therapy, which induced symptom remission within few days. The case here reported confirms that radionuclide therapy is highly effective in determining early rupture of metastatic tissue and also suggests that pre-medication should be implemented before the radiopeptide administration associated with a close monitoring of the patient in the following days.

A case of giant prolactinoma, initially misdiagnosed as sinonasal neuroendocrine carcinoma

Directory of Open Access Journals (Sweden)

Yasaman Mohtasebi, M.D.

2015-09-01

Full Text Available Giant prolactinomas are defined as pituitary tumors greater than 4 cm, often associated with very high prolactin level (>1000 ng/mL. They are relatively rare tumors and can present differently from typical prolactinomas. They can be highly invasive, resulting in acute neurological complication at the time of presentation. We present a case of a young woman with giant prolactinoma initially misdiagnosed as sinonasal neuroendocrine carcinoma. The acute presentation of headache, ptosis and impending brain herniation, requiring emergent ventriculostomy and intubation, led to the clinical suspicion of a more sinister diagnosis. Transnasal biopsy of the mass was consistent with sinonasal neuroendocrine carcinoma, and chemotherapy was planned. Laboratory testing, however, revealed an elevated prolactin (27,400 ng/mL, after 1:100 dilution. Re-review of pathology with additional immunohistochemical staining was requested and confirmed the diagnosis of prolactinoma. After 5 months of cabergoline treatment, prolactin level has decreased to 118 ng/mL. There has been a marked reduction in tumor size and an almost complete resolution of neurological symptoms. Given their atypical presentation and potential for sharing common immunohistochemical stains with other neuroendocrine neoplasms, giant prolactinomas extending into the nasal cavity can be misdiagnosed as other neuroendocrine neoplasms which may develop at this site. Accurate diagnosis is imperative to prevent unnecessary surgery and/or radiation and to ensure implementation of dopamine agonist therapy.

Gamma knife radiosurgery for metastatic brain tumors from lung cancer

Energy Technology Data Exchange (ETDEWEB)

Serizawa, Toru; Ono, Junichi; Iuchi, Toshihiko [Chiba Cardiovascular Center, Ichihara (Japan). Chiba Cancer Center] (and others)

2003-01-01

The purpose of this retrospective study is to evaluate the effectiveness of gamma knife radiosurgery (GKS) alone for metastatic brain tumors from lung cancer. Two hundred thirty-one consecutive patients with metastatic brain tumors from lung cancer filling the following 4 criteria were analyzed for this study; no prior brain tumor treatment, 25 or fewer lesions, a maximum 5 tumors with diameter of 2 cm or more, no surgically inaccessible tumor 3 cm or greater in diameter. According to the same treatment protocol, large tumors ({>=} 3 cm) were surgically removed and all the other small lesions (<3 cm) were treated with GKS. New lesions were treated with repeated GKS. The tumor-progression-free, overall, neurological, lowered-QOL (quality of life)-free and new-lesion-free survivals were calculated with the Kaplan-Meier method. The poor prognostic factors for each survival were also analyzed with the Cox's proportional hazard model. The tumor control rate at 1 year was 96.5%. The estimated median overall survival time was 7.7 months. The first-year survival rates were 83.0% in neurological survival and 76.0% in lowered-QOL-free survival. The new-lesion-free survival at 1 year was 27.9%. Multivariate analysis revealed significant poor prognostic factors for neurological and lowered-QOL-free survivals were carcinomatous meningitis and >10 brain lesions. This study suggests the results of GKS for metastatic brain tumors from lung cancer are quite satisfactory considering prevention of neurological death and maintenance of QOL. But cases with carcinomatous meningitis and/or >10 brain lesions are not good candidates for GKS alone. (author)

Pancreatic islet cell tumor

Science.gov (United States)

... cell tumors; Islet of Langerhans tumor; Neuroendocrine tumors; Peptic ulcer - islet cell tumor; Hypoglycemia - islet cell tumor ... stomach acid. Symptoms may include: Abdominal pain Diarrhea ... and small bowel Vomiting blood (occasionally) Glucagonomas make ...

Hypofractionated stereotactic radiotherapy for malignant tumors of the lung

Directory of Open Access Journals (Sweden)

О. Ю. Аникеева

2015-10-01

Full Text Available Hypofractionated stereotactic radiotherapy was used for 26 patients at medically inoperable stage I of non-small cell lung cancer with dose escalation of 48-54 Gy prescribed at 90 or 95% isodose level in 3-4 fractions. Nine-months local control and cancer-specific survival were 82.0 and 66.8% respectively, with minimal toxicity. For metastatic lung tumors local control was obtained in 92% cases. Hypofractionated stereotactic radiation therapy (SBRT is safe and feasible for the treatment of inoperable primary lung cancer and single lung metastasis.

A case of positive 68Ga-DOTATOC-PET/CT pancreatic heterotopia mimicking an intestinal neuroendocrine tumor.

Science.gov (United States)

Zilli, Alessandra; Fanetti, Ilaria; Conte, Dario; Massironi, Sara

Gallium-68 DOTA-peptide positron emission tomography/computed tomography ( 68 Ga-PET/CT) has emerged as a promising tool for the diagnosis and staging of gastro-entero-pancreatic neoplasms, thanks to its high sensitivity and specificity. Heterotopic pancreas, which is relatively rare, has never been reported as a possible cause of false positives of 68 Ga-PET/CT. We report on the first case of a heterotopic pancreas showing pathological uptake at 68 Ga-PET/CT, thus mimicking an intestinal neuroendocrine tumor. The present case suggests that heterotopic pancreas should be included among the possible causes of false positives at 68 Ga PET. Copyright © 2018 Elsevier Inc. All rights reserved.

Therapy monitoring using dynamic MRI: Analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Plathow, Christian [Eberhard-Karls University Tuebingen, Department of Diagnostic Radiology, Tuebingen (Germany); German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Hof, Holger; Kuhn, Sabine [University of Heidelberg, Department of Radiation Therapy, Clinic for Thoracic Diseases, Heidelberg (Germany); Puderbach, Michael; Ley, Sebastian; Biederer, Juergen; Kauczor, Hans-Ulrich [German Cancer Research Center, Department of Radiology, Heidelberg (Germany); Claussen, Claus D.; Schaefer, Juergen [Eberhard-Karls University Tuebingen, Department of Diagnostic Radiology, Tuebingen (Germany); Huber, Peter E. [University of Heidelberg, Department of Radiation Therapy, Clinic for Thoracic Diseases, Heidelberg (Germany); German Cancer Research Center, Department of Radiation Oncology, Heidelberg (Germany); Tuengerthal, Siegfried [University of Heidelberg, Department of Radiology, Heidelberg (Germany)

2006-09-15

A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2{+-}0.9 cm if the tumor was located in the lower LR (middle LR: 5.5{+-}0.8 cm; upper LR: 6.0{+-}0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P<0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5{+-}0.6 vs. 2.0{+-}0.3 cm (middle LR; P<0.05) vs. 0.7{+-}0.2 cm (upper LR; P<0.01). After RT, tumor mobility was significantly reduced in the lower LR (P<0.01) and in T2 tumor patients (P<0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter. (orig.)

Therapy monitoring using dynamic MRI: Analysis of lung motion and intrathoracic tumor mobility before and after radiotherapy

International Nuclear Information System (INIS)

Plathow, Christian; Hof, Holger; Kuhn, Sabine; Puderbach, Michael; Ley, Sebastian; Biederer, Juergen; Kauczor, Hans-Ulrich; Claussen, Claus D.; Schaefer, Juergen; Huber, Peter E.; Tuengerthal, Siegfried

2006-01-01

A frequent side effect after radiotherapy of lung tumors is a decrease of pulmonary function accompanied by dyspnea due to developing lung fibrosis. The aim of this study was to monitor lung motion as a correlate of pulmonary function and intrathoracic tumor mobility before and after radiotherapy (RT) using dynamic MRI (dMRI). Thirty-five patients with stage I non-small-cell lung carcinoma were examined using dMRI (trueFISP; three images/s). Tumors were divided into T1 and T2 tumors of the upper, middle and lower lung region (LR). Maximum craniocaudal (CC) lung dimensions and tumor mobility in three dimensions were monitored. Vital capacity (VC) was measured and correlated using spirometry. Before RT, the maximum CC motion of the tumor-bearing hemithorax was 5.2±0.9 cm if the tumor was located in the lower LR (middle LR: 5.5±0.8 cm; upper LR: 6.0±0.6 cm). After RT, lung motion was significantly reduced in the lower LR (P<0.05). Before RT, the maximum CC tumor mobility was significantly higher in tumors of the lower LR 2.5±0.6 vs. 2.0±0.3 cm (middle LR; P<0.05) vs. 0.7±0.2 cm (upper LR; P<0.01). After RT, tumor mobility was significantly reduced in the lower LR (P<0.01) and in T2 tumor patients (P<0.05). VC showed no significant changes. dMRI is capable of monitoring changes in lung motion that were not suspected from spirometry. This might make the treatment of side effects possible at a very early stage. Changes of lung motion and tumor mobility are highly dependent on the tumor localization and tumor diameter. (orig.)

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.

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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.

Metastatic Renal Cell Carcinoma versus Pancreatic Neuroendocrine Tumor in von Hippel-Lindau Disease: Treatment with Interleukin-2

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Christopher Williams

2005-01-01

Full Text Available Differentiating between clear cell neuroendocrine tumor (NET of the pancreas and renal cell carcinoma (RCC metastatic to the pancreas can be challenging in patients with von Hippel-Lindau disease (VHL. The clear cell features of both NET and RCC in VHL patients may lead to misdiagnosis, inaccurate staging, and alternative treatment. We present a patient in which this occurred. As clear cell NETs closely resembling metastatic RCC are distinctive neoplasms of VHL and metastatic RCC to the pancreas in the VHL population is rare, careful pathologic examination should be performed prior to subjecting patients to definitive surgical or medical therapies.

Involvement of growth factors and their receptors in radon-induced rat lung tumors

International Nuclear Information System (INIS)

Leung, F.C.; Dagle, G.E.; Cross, F.T.

1992-01-01

In this paper we examine the role of growth factors (GF) and their receptors (GFR) in radon-induced rat lung tumors. Inhalation exposure of radon and its daughters induced lung tumors in rats, but the molecule/cellular mechanisms are not known. Recent evidence suggests that GF/GFR play a critical role in the growth and development of lung cancer in humans and animals. We have developed immunocytochemical methods for identifying sites of production and action of GF/GFR at the cellular level; for example, the avidin-biotin horseradish peroxidase technique. In radon-induced rat epidermoid carcinomas, epidermal growth factor (EGF), EGF-receptors (EGF-R), transforming growth factor alpha (TGF-α), and bombesin were found to be abnormally expressed. These abnormal expressions, mainly associated with epidermoid carcinomas of the lung, were not found in any other lung tumor types. Our data suggest that EGF, EGF-R, TGF-α, and bombesin are involved in radon oncogenesis in rat lungs, especially in epidermoid carcinomas, possibly through the autocrine/paracrine pathway

Cutaneous squamous and neuroendocrine carcinoma: genetically and immunohistochemically different from Merkel cell carcinoma.

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Pulitzer, Melissa P; Brannon, A Rose; Berger, Michael F; Louis, Peter; Scott, Sasinya N; Jungbluth, Achim A; Coit, Daniel G; Brownell, Isaac; Busam, Klaus J

2015-08-01

Cutaneous neuroendocrine (Merkel cell) carcinoma most often arises de novo in the background of a clonally integrated virus, the Merkel cell polyomavirus, and is notable for positive expression of retinoblastoma 1 (RB1) protein and low expression of p53 compared with the rare Merkel cell polyomavirus-negative Merkel cell carcinomas. Combined squamous and Merkel cell tumors are consistently negative for Merkel cell polyomavirus. Little is known about their immunophenotypic or molecular profile. Herein, we studied 10 combined cutaneous squamous cell and neuroendocrine carcinomas for immunohistochemical expression of p53, retinoblastoma 1 protein, neurofilament, p63, and cytokeratin 20 (CK20). We compared mutation profiles of five combined Merkel cell carcinomas and seven 'pure' Merkel cell carcinomas using targeted next-generation sequencing. Combined tumors were from the head, trunk, and leg of Caucasian males and one female aged 52-89. All cases were highly p53- and p63-positive and neurofilament-negative in the squamous component, whereas RB1-negative in both components. Eight out of 10 were p53-positive, 3/10 p63-positive, and 3/10 focally neurofilament-positive in the neuroendocrine component. Six out of 10 were CK20-positive in any part. By next-generation sequencing, combined tumors were highly mutated, with an average of 48 mutations per megabase compared with pure tumors, which showed 1.25 mutations per megabase. RB1 and p53 mutations were identified in all five combined tumors. Combined tumors represent an immunophenotypically and genetically distinct variant of primary cutaneous neuroendocrine carcinomas, notable for a highly mutated genetic profile, significant p53 expression and/or mutation, absent RB1 expression in the context of increased RB1 mutation, and minimal neurofilament expression.

Air pollution and neuroendocrine stress-mediated systemic metabolic and inflammatory response

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New experimental evidence involving the role of neuroendocrine activation challenges an accepted mechanistic paradigm of how irritant air pollutants induce systemic metabolic impairment and lung injury/inflammation. We focus on recent air pollution studies highlighting how the re...

Ectopic Cushing' syndrome caused by a neuroendocrine carcinoma of the mesentery

International Nuclear Information System (INIS)

Fasshauer, Mathias; Paschke, Ralf; Koch, Christian A; Lincke, Thomas; Witzigmann, Helmut; Kluge, Regine; Tannapfel, Andrea; Moche, Michael; Buchfelder, Michael; Petersenn, Stephan; Kratzsch, Juergen

2006-01-01

ACTH overproduction within the pituitary gland or ectopically leads to hypercortisolism. Here, we report the first case of Cushing' syndrome caused by an ectopic ACTH-secreting neuroendocrine carcinoma of the mesentery. Moreover, diagnostic procedures and pitfalls associated with ectopic ACTH-secreting tumors are demonstrated and discussed. A 41 year-old man presented with clinical features and biochemical tests suggestive of ectopic Cushing's syndrome. First, subtotal thyroidectomy was performed without remission of hypercortisolism, because an octreotide scan showed increased activity in the left thyroid gland and an ultrasound revealed nodules in both thyroid lobes one of which was autonomous. In addition, the patient had a 3 mm hypoenhancing lesion of the neurohypophysis and a 1 cm large adrenal tumor. Surgical removal of the pituitary lesion within the posterior lobe did not improve hypercortisolism and we continued to treat the patient with metyrapone to block cortisol production. At 18-months follow-up from initial presentation, we detected an ACTH-producing neuroendocrine carcinoma of the mesentery by using a combination of octreotide scan, computed tomography scan, and positron emission tomography. Intraoperatively, use of a gamma probe after administration of radiolabeled 111 In-pentetreotide helped identify the mesenteric neuroendocrine tumor. After removal of this carcinoma, the patient improved clinically. Laboratory testing confirmed remission of hypercortisolism. An octreotide scan 7 months after surgery showed normal results. This case underscores the diagnostic challenge in identifying an ectopic ACTH-producing tumor and the pluripotency of cells, in this case of mesenteric cells that can start producing and secreting ACTH. It thereby helps elucidate the pathogenesis of neuroendocrine tumors. This case also suggests that patients with ectopic Cushing's syndrome and an octreotide scan positive in atypical locations may benefit from

Rare lung cancers

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Berzinec, P.

2013-01-01

The RARECARE Project (Rare Cancers in the Europe) supported by the European Union defined the rare cancers by the incidence rate of less than 6/100 000. There are several variants of lung cancer which are rare according to this definition. From the clinical point of view the most interesting are the rare adenocarcinomas and large cell neuroendocrine carcinoma. There are important differences in the diagnostic probability of EGFR and ALK mutations in the mutinous and non-mucin ous adenocarcinomas, in the signet ring cell adenocarcinomas, and large cell carcinomas. The optimal chemotherapy for neuroendocrine large cell carcinomas remains undefined. There is only very limited number of clinical trials aimed on the rare lung cancers and actually none phase III trial. Rare lung cancers continue to be a challenge both for the laboratory and the clinical research. (author)

Bioenergetics of lung tumors: alteration of mitochondrial biogenesis and respiratory capacity.

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Bellance, N; Benard, G; Furt, F; Begueret, H; Smolková, K; Passerieux, E; Delage, J P; Baste, J M; Moreau, P; Rossignol, R

2009-12-01

Little is known on the metabolic profile of lung tumors and the reminiscence of embryonic features. Herein, we determined the bioenergetic profiles of human fibroblasts taken from lung epidermoid carcinoma (HLF-a) and fetal lung (MRC5). We also analysed human lung tumors and their surrounding healthy tissue from four patients with adenocarcinoma. On these different models, we measured functional parameters (cell growth rates in oxidative and glycolytic media, respiration, ATP synthesis and PDH activity) as well as compositional features (expression level of various energy proteins and upstream transcription factors). The results demonstrate that both the lung fetal and cancer cell lines produced their ATP predominantly by glycolysis, while oxidative phosphorylation was only capable of poor ATP delivery. This was explained by a decreased mitochondrial biogenesis caused by a lowered expression of PGC1alpha (as shown by RT-PCR and Western blot) and mtTFA. Consequently, the relative expression of glycolytic versus OXPHOS markers was high in these cells. Moreover, the re-activation of mitochondrial biogenesis with resveratrol induced cell death specifically in cancer cells. A consistent reduction of mitochondrial biogenesis and the subsequent alteration of respiratory capacity was also observed in lung tumors, associated with a lower expression level of bcl2. Our data give a better characterization of lung cancer cells' metabolic alterations which are essential for growth and survival. They designate mitochondrial biogenesis as a possible target for anti-cancer therapy.

Gastric neuroendocrine carcinomas in bearded dragons (Pogona vitticeps).

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Ritter, J M; Garner, M M; Chilton, J A; Jacobson, E R; Kiupel, M

2009-11-01

This article describes a newly recognized highly malignant neoplastic entity in young bearded dragons (Pogona vitticeps), gastric neuroendocrine carcinomas, which readily metastasize. Ten bearded dragons with histories of anorexia (8), vomiting (3), hyperglycemia (2), and anemia (3) were included in this study. All animals had neoplastic masses in their stomach, with metastasis to the liver. Microscopically, 6 of these neuroendocrine carcinomas were well-differentiated and 4 were poorly differentiated. For further characterization, immunohistochemistry for protein gene product 9.5, neuron-specific enolase, endorphin, chromogranins A and B, synaptophysin, somatostatin, insulin, glucagon, gastrin, pancreatic polypeptide, and vasoactive intestinal peptide was performed on 5 animals. Because only immunolabeling for somatostatin was consistently observed in all neoplasms, a diagnosis of somatostatinoma was made for these 5 bearded dragons. Some neoplasms also exhibited multihormonal expression. Electron microscopy performed on 1 tumor confirmed the presence of neuroendocrine granules within neoplastic cells. Gastric neuroendocrine carcinomas, and specifically somatostatinomas, have not been previously reported in bearded dragons, or other reptiles, and may be underdiagnosed due to inconsistent, ambiguous clinical signs. In humans, pancreatic somatostatinomas are associated with a syndrome of hypersomatostatinemia, which includes hyperglycemia, weight loss, and anemia, as observed in some of these bearded dragons. Somatostatinomas in humans are commonly associated with neurofibromatosis type 1 (Von Recklinghausen's disease), caused by a mutation in the tumor suppressor gene NF1, which results in decreased expression of neurofibromin. In all 5 animals examined, neoplasms exhibited decreased neurofibromin expression compared with control tissues, suggesting that decreased functional neurofibromin may play a role in the pathogenesis of somatostatinomas in bearded dragons.

MR imaging-guided percutaneous cryotherapy for lung tumors: initial experience.

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Liu, Shangang; Ren, Ruimei; Liu, Ming; Lv, Yubo; Li, Bin; Li, Chengli

2014-09-01

To evaluate prospectively the initial clinical experience of magnetic resonance (MR) imaging-guided percutaneous cryotherapy of lung tumors. MR imaging-guided percutaneous cryotherapy was performed in 21 patients with biopsy-proven lung tumors (12 men, 9 women; age range, 39-79 y). Follow-up consisted of contrast-enhanced chest computed tomography (CT) scan performed at 3-month intervals to assess tumor control; CT scanning was carried out for 12 months or until death. Cryotherapy procedures were successfully completed in all 21 patients. Pneumothorax occurred in 7 (33.3%) of 21 patients. Chest tube placement was required in one (4.8%) case. Hemoptysis was exhibited by 11 (52.4%) patients, and pleural effusion occurred in 6 (28.6%) patients. Other complications were observed in 14 (66.7%) patients. The mean follow-up period was 10.5 months (range, 9-12 mo) in patients who died. At month 12 of follow-up, 7 (33.3%) patients had a complete response to therapy, and 10 (47.6%) patients showed a partial response. In addition, two patients had stable disease, and two patients developed progressive disease; one patient developed a tumor in the liver, and the other developed a tumor in the brain. The 1-year local control rate was 81%, and 1-year survival rate was 90.5%. MR imaging-guided percutaneous cryotherapy appears feasible, effective, and minimally invasive for lung tumors. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

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

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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.

Deep inspiration breath-hold technique for lung tumors: the potential value of target immobilization and reduced lung density in dose escalation

International Nuclear Information System (INIS)

Hanley, J.; Debois, M.M.; Raben, A.; Mageras, G.S.; Lutz, W.R.; Mychalczak, B.; Schwartz, L.H.; Gloeggler, P.J.; Leibel, S.A.; Fuks, Z.; Kutcher, G.J.

1996-01-01

Purpose/Objective: Lung tumors are subject to movement due to respiratory motion. Conventionally, a margin is applied to the clinical target volume (CTV) to account for this and other treatment uncertainties. The purpose of this study is to evaluate the dosimetric benefits of a deep inspiration breath-hold (DIBH) technique which has two distinct features - deep inspiration which reduces lung density and breath-hold which immobilizes lung tumors. Both properties can potentially reduce the mass of normal lung tissue in the high dose region, thus improving the possibility of dose escalation. Methods and Materials: To study the efficacy of the DIBH technique, CT scans are acquired for each patient under 4 respiration conditions: free-breathing; DIBH; shallow inspiration breath-hold; shallow expiration breath-hold. The free-breathing and DIBH scans are used to generate treatment plans for comparison of standard and DIBH techniques, while the shallow inspiration and expiration scans provide information on the maximum extent of tumor motion under free-breathing conditions. To acquire the breath-hold scans, the patients are brought to reproducible respiration levels using spirometry and slow vital capacity maneuvers. For the treatment plan comparison free-breathing and DIBH planning target volumes (PTVs) are constructed consisting of the CTV plus a margin for setup error and lung tumor motion. For both plans the margin for setup error is the same while the margin for lung tumor motion differs. The margin for organ motion in free-breathing is determined by the maximum tumor excursions in the shallow inspiration and expiration CT scans. For the DIBH, tumor motion is reduced to the extent to which DIBH can be maintained and the margin for any residual tumor motion is determined from repeat fluoroscopic movies, acquired with the patient monitored using spirometry. Three-dimensional treatment plans, generated using apertures based on the free-breathing and DIBH PTVs, are

MIB-1, AgNOR AND DNA DISTRIBUTION PARAMETERS AND THEIR PROGNOSTIC VALUE IN NEUROENDOCRINE TUMOURS OF THE LUNG

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Uta Jütting

2011-05-01

Full Text Available One of the most important questions in clinical routine is to find out patients with good or worse prognosis to apply an optimal therapy scheme for each patient. In this study 58 patients with different neuroendocrine tumours of the lung were investigated. Histological sections were prepared with different stainings (MIB-1, AgNOR, Feulgen. By means of high resolution image cytometry stereological parameters were derived which are indicators for proliferation, ploidy and kinetics of the tumours. Cox regression analysis was calculated to test the significance of the parameters with regard to prognosis. The best parameter was MIB-1 which can easily be applied as a clinical standard staining and measurement.

Establishment and characterization of murine small cell lung carcinoma cell lines derived from HPV-16 E6/E7 transgenic mice.

Science.gov (United States)

Carraresi, Laura; Martinelli, Rosanna; Vannoni, Alessandro; Riccio, Massimo; Dembic, Maja; Tripodi, Sergio; Cintorino, Marcella; Santi, Spartaco; Bigliardi, Elisa; Carmellini, Mario; Rossini, Mara

2006-01-08

We have established two murine cell lines derived from Small Cell Lung Carcinomas (SCLCs) developed by HPV-E6/E7 transgenic mice. These cells named PPAP-9 and PPAP-10 were isolated from mice bearing tumors, 9 and 10 months old, respectively. The cells, 5 microm in diameter, express HPV oncoproteins and sustain tumor formation after subcutaneous injection in syngenic mice. A detailed analysis indicated the epithelial origin and the neuroendocrine differentiation of these cells. We showed by confocal immunofluorescence the expression of the epithelial marker cytokeratin 5, whose gene promoter was used to direct the expression of HPV E6/E. Cells express several neuroendocrine markers such as CGRP, MAP-2, Ash1, CgrA, Scg2. The neuroendocrine differentiation of these cells was further confirmed by electron microscopy demonstrating neuropeptides secreting granules in their cytoplasm. Furthermore, in agreement with the altered expression observed in the majority of human SCLC we showed in these cells the absence of both p53 and pRB and a dramatic reduction in the expression of Caveolin-1.

Giant solitary fibrous tumor of the lung: A case report

OpenAIRE

Xiao, Ping; Sun, Linlin; Zhong, Diansheng; Lian, Linjuan; Xu, Dongbo

2014-01-01

A solitary fibrous tumor arising from the lung parenchyma is rarely described. Here, we present the clinical, imaging, and histological features of a case of a 54-year-old woman with an incidental lung mass of the right lower lobe on a chest radiograph.

Small cell and large cell neuroendocrine carcinomas of the pancreas are genetically similar and distinct from well-differentiated pancreatic neuroendocrine tumors.

Science.gov (United States)

Yachida, Shinichi; Vakiani, Efsevia; White, Catherine M; Zhong, Yi; Saunders, Tyler; Morgan, Richard; de Wilde, Roeland F; Maitra, Anirban; Hicks, Jessica; Demarzo, Angelo M; Shi, Chanjuan; Sharma, Rajni; Laheru, Daniel; Edil, Barish H; Wolfgang, Christopher L; Schulick, Richard D; Hruban, Ralph H; Tang, Laura H; Klimstra, David S; Iacobuzio-Donahue, Christine A

2012-02-01

Poorly differentiated neuroendocrine carcinomas (NECs) of the pancreas are rare malignant neoplasms with a poor prognosis. The aim of this study was to determine the clinicopathologic and genetic features of poorly differentiated NECs and compare them with other types of pancreatic neoplasms. We investigated alterations of KRAS, CDKN2A/p16, TP53, SMAD4/DPC4, DAXX, ATRX, PTEN, Bcl2, and RB1 by immunohistochemistry and/or targeted exomic sequencing in surgically resected specimens of 9 small cell NECs, 10 large cell NECs, and 11 well-differentiated neuroendocrine tumors (PanNETs) of the pancreas. Abnormal immunolabeling patterns of p53 and Rb were frequent (p53, 18 of 19, 95%; Rb, 14 of 19, 74%) in both small cell and large cell NECs, whereas Smad4/Dpc4, DAXX, and ATRX labeling was intact in virtually all of these same carcinomas. Abnormal immunolabeling of p53 and Rb proteins correlated with intragenic mutations in the TP53 and RB1 genes. In contrast, DAXX and ATRX labeling was lost in 45% of PanNETs, whereas p53 and Rb immunolabeling was intact in these same cases. Overexpression of Bcl-2 protein was observed in all 9 small cell NECs (100%) and in 5 of 10 (50%) large cell NECs compared with only 2 of 11 (18%) PanNETs. Bcl-2 overexpression was significantly correlated with higher mitotic rate and Ki67 labeling index in neoplasms in which it was present. Small cell NECs are genetically similar to large cell NECs, and these genetic changes are distinct from those reported in PanNETs. The finding of Bcl-2 overexpression in poorly differentiated NECs, particularly small cell NEC, suggests that Bcl-2 antagonists/inhibitors may be a viable treatment option for these patients.

[Computer aided diagnosis model for lung tumor based on ensemble convolutional neural network].

Science.gov (United States)

Wang, Yuanyuan; Zhou, Tao; Lu, Huiling; Wu, Cuiying; Yang, Pengfei

2017-08-01

The convolutional neural network (CNN) could be used on computer-aided diagnosis of lung tumor with positron emission tomography (PET)/computed tomography (CT), which can provide accurate quantitative analysis to compensate for visual inertia and defects in gray-scale sensitivity, and help doctors diagnose accurately. Firstly, parameter migration method is used to build three CNNs (CT-CNN, PET-CNN, and PET/CT-CNN) for lung tumor recognition in CT, PET, and PET/CT image, respectively. Then, we aimed at CT-CNN to obtain the appropriate model parameters for CNN training through analysis the influence of model parameters such as epochs, batchsize and image scale on recognition rate and training time. Finally, three single CNNs are used to construct ensemble CNN, and then lung tumor PET/CT recognition was completed through relative majority vote method and the performance between ensemble CNN and single CNN was compared. The experiment results show that the ensemble CNN is better than single CNN on computer-aided diagnosis of lung tumor.

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM...derive a prognostic classifier. 15. SUBJECT TERMS NSCLC; tumor evolution ; whole exome sequencing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Relationship between clinical characteristics and survival of gastroenteropancreatic neuroendocrine neoplasms: A single-institution analysis (1995–2012 in South China

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Wang Yu-hong

2012-11-01

Full Text Available Abstract Background Gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN is the most common type of neuroendocrine tumors accounting for 65–75% of neuroendocrine neoplasms (NENs. Given the fact that there are few studies on GEP-NENs among Chinese patients, we performed a retrospective study in South China. Methods Totally 178 patients with GEP-NENs treated at the First Affiliated Hospital of Sun Yat-sen University between January 1995 and May 2012 were analyzed retrospectively. Results Pancreas was found the most common site of involvement (34.8%. 149 patients (83.7% presented as non-functional tumors with non-specific symptoms such as abdominal pain (33.7%; carcinoid syndrome was not found in this study. Several methods are useful for localization of GEP-NENs, yielding varied detection rates from 77.8% to 98.7%. Positive rates of chromogranin A (CgA and synaptophysin (Syn immunhistochemically were 69.1% and 90.2%, respectively. 87 patients (51.5% had G1 tumors, 31(18.3% G2 tumors and 51 (30.2% G3 tumors. Neuroendocrine tumor (NET, neuroendocrine carcinoma (NEC and mixed adenoendocrine carcinoma (MANEC were 69.8%, 27.2% and 3.0%, respectively. 28.1% of patients presented with distant disease. Surgery was performed in 152 (85.4% patients, and overall 5-year survival rate was 54.5%. Functionality, G1 grading and NET classification were associated with favorable prognosis in univariate analysis. Distant metastasis contributed to unfavorable prognosis of these tumors. Conclusions Nonfunctional tumors with non-specific symptoms account for the majority of GEP-NENs. Diagnosis depends on pathological classification. Multidisciplinary treatments could help improve the outcome.

Lung Shunt Fraction prior to Yttrium-90 Radioembolization Predicts Survival in Patients with Neuroendocrine Liver Metastases: Single-Center Prospective Analysis

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Ludwig, Johannes M. [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Ambinder, Emily McIntosh [John Hopkins University School of Medicine, Department of Diagnostic Radiology (United States); Ghodadra, Anish [University of Pittsburgh School of Medicine, Interventional Radiology, Department of Radiology (United States); Xing, Minzhi [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States); Prajapati, Hasmukh J. [The University of Tennessee Health Science Center, Division of Interventional Radiology, Department of Radiology (United States); Kim, Hyun S., E-mail: kevin.kim@yale.edu [Yale University, Division of Interventional Radiology, Department of Radiology and Biomedical Imaging (United States)

2016-07-15

ObjectiveTo investigate survival outcomes following radioembolization with Yttrium-90 (Y90) for neuroendocrine tumor liver metastases (NETLMs). This study was designed to assess the efficacy of Y90 radioembolization and to evaluate lung shunt fraction (LSF) as a predictor for survival.MethodsA single-center, prospective study of 44 consecutive patients (median age: 58.5 years, 29.5 % male) diagnosed with pancreatic (52.3 %) or carcinoid (47.7 %) NETLMs from 2006 to 2012 who underwent Y90 radioembolization was performed. Patients’ baseline characteristics, including LSF and median overall survival (OS) from first Y90 radioembolization, were recorded and compared between patients with high (≥10 %) and low (<10 %) LSF. Baseline comparisons were performed using Fisher’s exact tests for categorical and Mann–Whitney U test for continuous variables. Survival was calculated using the Kaplan–Meier method. Univariate (Wilcoxon rank-sum test) and multivariate analyses (Cox Proportional Hazard Model) for risk factor analysis were performed.ResultsThere was no statistically significant difference in age, gender, race, tumor properties, or previous treatments between patients with high (n = 15) and low (n = 29) LSF. The median OS was 27.4 months (95 %CI 12.73–55.23), with 4.77 months (95 %CI 2.87–26.73) for high and 42.77 months (95 %CI 18.47–59.73) for low LSF (p = 0.003). Multivariate analysis identified high LSF (p = 0.001), total serum bilirubin >1.2 mg (p = 0.016), and lack of pretreatment with octreotide (p = 0.01) as independent prognostic factors for poorer survival. Tumor type and total radiation dose did not predict survival.ConclusionsLSF ≥10 %, elevated bilirubin levels, and lack of pretreatment with octreotide were found to be independent prognostic factors for poorer survival in patients with NETLMs.

Prognostic value of PET/CT in lung cancer. Study of survival and tumor metabolic characterization

International Nuclear Information System (INIS)

Ladron de Guevara, David; Fuentes Anibal; Farina, Ciro; Corral, Camilo; Pefaur, Raul

2013-01-01

PET/CT (Positron emission tomography/computed tomography) is a hybrid image modality widely used in oncology, for staging, therapy evaluation or follow up. Aim: To evaluate the prognostic value of PET/CT in lung cancer. Material and Methods: Retrospective review of PET/CT records, selecting 51 patients with a lung malignancy, mass or nodule referred for PET/CT between December 2008 and December 2010. All had pathological confirmation of malignancy and had not been treated previously. Age, gender, body mass index, radiological features of lung tumor and metastases, and lung tumor 18 F-fluoro-2-deoxy-d-glucose uptake using the SUV (Standardized uptake value) index were recorded. Survival was analyzed using Kaplan-Meier curves and a Cox proportional regression analysis. Results: Pathology confirmed the presence of lung cancer in 47 patients aged 30 to 88 years. Four patients (7.8%) had other type of tumors such as carcinoid or lymphoma. Fifty percent of lung cancer patients died during a mean observation lapse of 18 months (range: 2-34 months). Patients with metastases, local lymph node involvement, a lung tumor size ≥ 3 cm and high tumor uptake (SUVmax > 6) had significantly lower survival. Occurrence of metastases was the only independent prognostic factor in the Cox regression. A lung lesion with a SUVmax ≥ 12 was always associated to hilar/mediastinal lymph node involvement. Conclusions: PET/CT imaging gives important prognostic information in lung cancer patients

WE-AB-303-08: Direct Lung Tumor Tracking Using Short Imaging Arcs

International Nuclear Information System (INIS)

Shieh, C; Huang, C; Keall, P; Feain, I

2015-01-01

Purpose: Most current tumor tracking technologies rely on implanted markers, which suffer from potential toxicity of marker placement and mis-targeting due to marker migration. Several markerless tracking methods have been proposed: these are either indirect methods or have difficulties tracking lung tumors in most clinical cases due to overlapping anatomies in 2D projection images. We propose a direct lung tumor tracking algorithm robust to overlapping anatomies using short imaging arcs. Methods: The proposed algorithm tracks the tumor based on kV projections acquired within the latest six-degree imaging arc. To account for respiratory motion, an external motion surrogate is used to select projections of the same phase within the latest arc. For each arc, the pre-treatment 4D cone-beam CT (CBCT) with tumor contours are used to estimate and remove the contribution to the integral attenuation from surrounding anatomies. The position of the tumor model extracted from 4D CBCT of the same phase is then optimized to match the processed projections using the conjugate gradient method. The algorithm was retrospectively validated on two kV scans of a lung cancer patient with implanted fiducial markers. This patient was selected as the tumor is attached to the mediastinum, representing a challenging case for markerless tracking methods. The tracking results were converted to expected marker positions and compared with marker trajectories obtained via direct marker segmentation (ground truth). Results: The root-mean-squared-errors of tracking were 0.8 mm and 0.9 mm in the superior-inferior direction for the two scans. Tracking error was found to be below 2 and 3 mm for 90% and 98% of the time, respectively. Conclusions: A direct lung tumor tracking algorithm robust to overlapping anatomies was proposed and validated on two scans of a lung cancer patient. Sub-millimeter tracking accuracy was observed, indicating the potential of this algorithm for real-time guidance

Multiple fields may offer better esophagus sparing without increased probability of lung toxicity in optimized IMRT of lung tumors

International Nuclear Information System (INIS)

Chapet, Olivier; Fraass, Benedick A.; Haken, Randall K. ten

2006-01-01

Purpose: To evaluate whether increasing numbers of intensity-modulated radiation therapy (IMRT) fields enhance lung-tumor dose without additional predicted toxicity for difficult planning geometries. Methods and Materials: Data from 8 previous three dimensional conformal radiation therapy (3D-CRT) patients with tumors located in various regions of each lung, but with planning target volumes (PTVs) overlapping part of the esophagus, were used as input. Four optimized-beamlet IMRT plans (1 plan that used the 3D-CRT beam arrangement and 3 plans with 3, 5, or 7 axial, but predominantly one-sided, fields) were compared. For IMRT, the equivalent uniform dose (EUD) in the whole PTV was optimized simultaneously with that in a reduced PTV exclusive of the esophagus. Normal-tissue complication probability-based costlets were used for the esophagus, heart, and lung. Results: Overall, IMRT plans (optimized by use of EUD to judiciously allow relaxed PTV dose homogeneity) result in better minimum PTV isodose surface coverage and better average EUD values than does conformal planning; dose generally increases with the number of fields. Even 7-field plans do not significantly alter normal-lung mean-dose values or lung volumes that receive more than 13, 20, or 30 Gy. Conclusion: Optimized many-field IMRT plans can lead to escalated lung-tumor dose in the special case of esophagus overlapping PTV, without unacceptable alteration in the dose distribution to normal lung

Creation of a Tumor-Mimic Model Using a Muscle Paste for Radiofrequency Ablation of the Lung

International Nuclear Information System (INIS)

Kawai, T.; Kaminou, T.; Sugiura, K.; Hashimoto, M.; Ohuchi, Y.; Adachi, A.; Fujioka, S.; Ito, H.; Nakamura, K.; Ogawa, T.

2009-01-01

The purpose of this study was to develop an easily created tumor-mimic model and evaluate its efficacy for radiofrequency ablation (RFA) of the lung. The bilateral lungs of eight living adult swine were used. A tumor-mimic model was made by percutaneous injection of 1.0 ml muscle paste through the bone biopsy needle into the lung. An RFA probe was then inserted into the tumor mimics immediately after tumor creation. Ablation time, tissue impedance, and temperature were recorded. The tumor mimics and their coagulated regions were evaluated microscopically and macroscopically. The muscle paste was easily injected into the lung parenchyma through the bone biopsy needle and well visualized under fluoroscopy. In 10 of 12 sites the tumor mimics were oval shaped, localized, and homogeneous on gross specimens. Ten tumor mimics were successfully ablated, and four locations were ablated in the normal lung parenchyma as controls. In the tumor and normal lung parenchyma, ablation times were 8.9 ± 3.5 and 4.4 ± 1.6 min, respectively; tissue impedances at the start of ablation were 100.6 ± 16.6 and 145.8 ± 26.8 Ω, respectively; and temperatures at the end of ablation were 66.0 ± 7.9 and 57.5 ± 7.6 o C, respectively. The mean size of tumor mimics was 13.9 x 8.2 mm, and their coagulated area was 18.8 x 13.1 mm. In the lung parenchyma, the coagulated area was 15.3 x 12.0 mm. In conclusion, our tumor-mimic model using muscle paste can be easily and safely created and can be ablated using the ablation algorithm in the clinical setting.

Clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy for lung tumors.

Science.gov (United States)

Asai, Kaori; Nakamura, Katsumasa; Shioyama, Yoshiyuki; Sasaki, Tomonari; Matsuo, Yoshio; Ohga, Saiji; Yoshitake, Tadamasa; Terashima, Kotaro; Shinoto, Makoto; Matsumoto, Keiji; Hirata, Hidenari; Honda, Hiroshi

2015-12-01

We retrospectively investigated the clinical characteristics and outcome of pneumothorax after stereotactic body radiotherapy (SBRT) for lung tumors. Between April 2003 and July 2012, 473 patients with lung tumors were treated with SBRT. We identified 12 patients (2.5 %) with pneumothorax caused by SBRT, and evaluated the clinical features of pneumothorax. All of the tumors were primary lung cancers. The severity of radiation pneumonitis was grade 1 in 10 patients and grade 2 in two patients. Nine patients had emphysema. The planning target volume and pleura overlapped in 11 patients, and the tumors were attached to the pleura in 7 patients. Rib fractures were observed in three patients before or at the same time as the diagnosis of pneumothorax. The median time to onset of pneumothorax after SBRT was 18.5 months (4-84 months). The severity of pneumothorax was grade 1 in 11 patients and grade 3 in one patient. Although pneumothorax was a relatively rare late adverse effect after SBRT, some patients demonstrated pneumothorax after SBRT for peripheral lung tumors. Although most pneumothorax was generally tolerable and self-limiting, careful follow-up is needed.

The Potential Biomarkers and Immunological Effects of Tumor-Derived Exosomes in Lung Cancer

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Shamila D. Alipoor

2018-04-01

Full Text Available Lung cancer remains the leading cause of cancer-related deaths worldwide. Despite considerable achievements in lung cancer diagnosis and treatment, the global control of the disease remains problematic. In this respect, greater understanding of the disease pathology is crucially needed for earlier diagnosis and more successful treatment to be achieved. Exosomes are nano-sized particles secreted from most cells, which allow cross talk between cells and their surrounding environment via transferring their cargo. Tumor cells, just like normal cells, also secrete exosomes that are termed Tumor-Derived Exosome or tumor-derived exosome (TEX. TEXs have gained attention for their immuno-modulatory activities, which strongly affect the tumor microenvironment and antitumor immune responses. The immunological activity of TEX influences both the innate and adaptive immune systems including natural killer cell activity and regulatory T-cell maturation as well as numerous anti-inflammatory responses. In the context of lung cancer, TEXs have been studied in order to better understand the mechanisms underlying tumor metastasis and progression. As such, TEX has the potential to act both as a biomarker for lung cancer diagnosis as well as the response to therapy.

Movie prediction of lung tumor for precise chasing radiation therapy

International Nuclear Information System (INIS)

Chhatkuli, Ritu Bhusal; Demachi, Kazuyuki; Kawai, Masaki; Sakakibara, Hiroshi; Uesaka, Mitsuru

2012-01-01

In recent years, precision for radiation therapy is a major challenge in the field of cancer treatment. When it comes to a moving organ like lungs, limiting the radiation to the target and sparing the surrounding healthy tissue is always a concern. It can induce the limit in the accuracy of area irradiated during lung cancer radiation therapy. Many methods have been introduced to compensate the motion in order to reduce the effect of radiation to healthy tissue due to respiratory motion. The motion of lung along with the tumor makes it very difficult to spare the healthy tissue during radiation therapy. The fear of this unintended damage to the neighboring tissue often limits the dose that can be applied to the tumor. The purpose of this research is the prediction of future motion images for the improvement of tumor tracking method. We predict the motion images by using principal component analysis (PCA) and multi-channel singular spectral analysis (MSSA) method. Time series x-ray images are used as training images. The motion images were successfully predicted and verified using the developed algorithm. The real time implementation of this method in future is believed to be significant for higher level of real time tumor tracking during radiation therapy. (author)

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

International Nuclear Information System (INIS)

Treglia, Giorgio; Luca, Giovanella; Barbara, Muoio; Carmelo, Caldarella

2014-01-01

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

The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

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Linjie Liu

2017-01-01

Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

A hybrid approach for fusing 4D-MRI temporal information with 3D-CT for the study of lung and lung tumor motion.

Science.gov (United States)

Yang, Y X; Teo, S-K; Van Reeth, E; Tan, C H; Tham, I W K; Poh, C L

2015-08-01

Accurate visualization of lung motion is important in many clinical applications, such as radiotherapy of lung cancer. Advancement in imaging modalities [e.g., computed tomography (CT) and MRI] has allowed dynamic imaging of lung and lung tumor motion. However, each imaging modality has its advantages and disadvantages. The study presented in this paper aims at generating synthetic 4D-CT dataset for lung cancer patients by combining both continuous three-dimensional (3D) motion captured by 4D-MRI and the high spatial resolution captured by CT using the authors' proposed approach. A novel hybrid approach based on deformable image registration (DIR) and finite element method simulation was developed to fuse a static 3D-CT volume (acquired under breath-hold) and the 3D motion information extracted from 4D-MRI dataset, creating a synthetic 4D-CT dataset. The study focuses on imaging of lung and lung tumor. Comparing the synthetic 4D-CT dataset with the acquired 4D-CT dataset of six lung cancer patients based on 420 landmarks, accurate results (average error lung details, and is able to show movement of lung and lung tumor over multiple breathing cycles.

The multidisciplinary treatment of bronchobiliary fistula present in a patient with pancreatic neuroendocrine tumor

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Baris Ozcan

2017-09-01

Full Text Available Bronchobiliary Fistula (BBF is a rare condition that usually occurs after surgical treatments of pancreas, liver and biliary diseases. Clinical findings are bilioptysis, fever and dyspnea. In treating it, initially, drainage should be conducted using minimally invasive or endoscopic methods, such as endoscopic retrograde cholangiopancreatography (ERCP or percutaneous transhepatic cholangiography (PTK in cases where these methods failed. Next, treatment through performing surgical operations, like hepatectomy or pulmonary resection, should be carried out. In this work, the diagnostic and therapeutic phases of a female patient at the age of 40 who underwent a whipple procedure (pancreatoduodenectomy 10 years earlier because of pancreatic neuroendocrine tumor is presented. Their follow-ups exhibited multiple metastases in the liver, and for this reason, specific chemoembolization treatments were applied. After these treatments, bronchobiliary fistula was formed. [Arch Clin Exp Surg 2017; 6(3.000: 156-161

Neuroendocrine tumors of the abdomen; Neuroendokrine Tumoren des Abdomens

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Juchems, M. [Klinikum Konstanz, Diagnostische und Interventionelle Radiologie, Konstanz (Germany)

2018-01-15

Gastroenteropancreatic neuroendocrine neoplasia (GEP-NEN) are a heterogeneous group of complex tumors, which is often difficult to classify due to heterogeneity and varying locations. Ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron-emission tomography computed tomography (PET/CT) are available for the localization of NEN as well as for the staging. In particular, nuclear medical examination methods with somatostatin analogues are of great importance since radioactively labeled receptor ligands make tumors visible with high sensitivity. CT and MRT have high detection rates for GEP-NEN and have been further improved by developments such as diffusion weighted imaging. The nuclear medical methods, however, are superior in detection, especially in gastrointestinal NEN It is important for the radiologist to become acquainted with the NEN as they can occur ubiquitously in the abdomen and should be identified as such. Since GEP-NEN are predominantly hypervascularized, a biphasic examination technique is obligatory for contrast-enhanced cross-sectional imaging. PET/CT with somatostatin analogs should be used for further diagnosis. (orig.) [German] Gastroenteropankreatische neuroendokrine Neoplasien (GEP-NEN) sind eine heterogene Gruppe komplexer Tumoren, deren Einteilung aufgrund der Heterogenitaet und unterschiedlichen Lokalisation haeufig schwerfaellt. Fuer die Lokalisation der NEN sowie zur Ausbreitungsdiagnostik und Metastasensuche stehen Ultraschalldiagnostik, Computertomographie (CT), Magnetresonanztomographie (MRT) und die Positronenemissionstomographie-Computertomographie (PET-CT) zur Verfuegung. Insbesondere nuklearmedizinische Untersuchungsmethoden mit Somatostatinanaloga sind von hoher Wertigkeit, da sie ueber radioaktiv markierte Rezeptoliganden Tumoren mit hoher Sensitivitaet sichtbar machen. CT und MRT haben hohe Detektionsraten bei den GEP-NEN und konnten durch Weiterentwicklungen, wie Diffusionsbildgebung, weiter

Thymoma (World Health Organization type B3) with neuroendocrine differentiation in multiple endocrine neoplasia type 1

OpenAIRE

Tomita, Masaki; Ichiki, Nobuhiko; Ayabe, Takanori; Tanaka, Hiroyuki; Kataoka, Hiroaki; Nakamura, Kunihide

2017-01-01

Abstract Thymic epithelial tumors occur in 1?5% of patients with multiple endocrine neoplasia type 1 (MEN 1). Majority of these thymic epithelial tumors are thymic carcinoids and patients with thymoma in MEN 1 is rare. Furthermore, thymoma with neuroendocrine differentiation was also rarely reported. Herein, we report a 68-year-old man having type B3 thymoma with neuroendocrine differentiation in MEN 1 and to the best of our knowledge this is the first such case ever reported.

Immunohistochemical detection of epidermal growth factor receptor in radiation-induced lung tumors in Beagle dogs

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Gillett, N A; Haley, P J; Hahn, F F

1988-12-01

Increased levels of epidermal growth factor receptor have been reported in a variety of tumors, including pulmonary squamous cell carcinomas in man. The purpose of this study was to determine if increased levels of epidermal growth factor (EGFR) were present in lung tumors from Beagle dogs that had been exposed to {sup 239}PuO{sub 2}- Using immunohistochemical techniques, sections from 17 lung tumors were examined for the presence of EGFR. Seven of the tumors were strongly positive for EGFR; the remainder of the tumors and the normal lung sections were negative. The positive immunostaining could not be correlated with the histologic phenotype of the tumors. Work is in progress to determine the level of EGFR in preneoplastic, proliferative epithelial foci in the Iung. (author)

Expression of the p16{sup INK4a} tumor suppressor gene in rodent lung tumors

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Swafford, D.S.; Tesfaigzi, J.; Belinsky, S.A.

1995-12-01

Aberrations on the short arm of chromosome 9 are among the earliest genetic changes in human cancer. p16{sup INK4a} is a candidate tumor suppressor gene that lies within human 9p21, a chromosome region associated with frequent loss of heterozygosity in human lung tumors. The p16{sup INK4a} protein functions as an inhibitor of cyclin D{sub 1}-dependent kinases that phosphorylate the retinoblastoma (Rb) tumor suppressor gene product enabling cell-cycle progression. Thus, overexpression of cyclin D{sub 1}, mutation of cyclin-dependent kinase genes, or loss of p16{sup INK4a} function, can all result in functional inactivation of Rb. Inactivation of Rb by mutation or deletion can result in an increase in p16{sup INK4a} transcription, suggesting that an increased p16{sup INK4a} expression in a tumor cell signals dysfunction of the pathway. The p16{sup (INK4a)} gene, unlike some tumor suppressor genes, is rarely inactivated by mutation. Instead, the expression of this gene is suppressed in some human cancers by hypermethylation of the CpG island within the first exon or by homozygous deletion: 686. Chromosome losses have been observed at 9p21 syntenic loci in tumors of the mouse and rat, two species often used as animal models for pulmonary carcinogenesis. Expression of p16{sup INK4a} is lost in some mouse tumor cell lines, often due to homozygous deletion. These observations indicate that p16{sup INK4a} dysfunction may play a role in the development of neoplasia in rodents as well as humans. The purpose of the current investigation was to define the extent to which p16{sup INK4a} dysfunction contributes to the development of rodent lung tumors and to determine the mechanism of inactivation of the gene. There is no evidence to suggest a loss of function of the p16{sup INK4a} tumor suppressor gene in these primary murine lung tumors by mutation, deletion, or methylation.

Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

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Chii-Shuenn Yang

2009-08-01

Full Text Available We report a unique case of combined primary neuroendocrine carcinoma (NEC and hepatocellular carcinoma (HCC of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

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.

Association between Congenital Lung Malformations and Lung Tumors in Children and Adults: A Systematic Review.

Science.gov (United States)

Casagrande, Arianna; Pederiva, Federica

2016-11-01

The appropriate management of asymptomatic congenital pulmonary malformations (CPMs) remains controversial. Prophylactic surgery is recommended to avoid the risk for development of pulmonary infections and to prevent the highly debated development of malignancy. However, the true risk for development of malignancy remains unknown. A systematic review analyzed all cases in which lung tumors associated with CPMs in both the pediatric and adult populations were described. A comprehensive literature search was carried out; it included all the cases in which an association between CPMs and malignant pulmonary lesions was reported. In all, 134 publications were eligible for inclusion. In 168 patients CPM was found associated with lung tumor. The diagnosis was made in 76 children at a mean age of 3.68 ± 3.4, whereas in the adult population (n = 92) it was made at a mean age of 44.62 ± 16.09. Cough was the most frequent presenting symptom both in children and in adults. Most of the patients underwent lobectomy. The tumor most often associated with CPM was pleuropulmonary bastoma in children (n = 31) and adenocarcinoma (n = 20) or bronchioloalveolar carcinoma (n = 20) in adults. The CPM most frequenty associated with tumors in children was congenital cystic adenomatoid malformation (n = 37), especially type 1 (n = 21), whereas in adults it was bronchogenic cyst (n = 25), followed by congenital cystic adenomatoid malformation (n = 21). CPMs should be followed up and never underestimated because they may conceal a tumor. Apparently, there is no age limit for malignant progression of CPMs and no limit of the interval between first detection of the CPM and appearance of the associated tumor. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Imaging of tumor viability in lung cancer. Initial results using 23Na-MRI

International Nuclear Information System (INIS)

Henzler, T.; Apfaltrer, P.; Haneder, S.; Schoenberg, S.O.; Fink, C.; Konstandin, S.; Schad, L.; Schmid-Bindert, G.; Manegold, C.; Wenz, F.

2012-01-01

23 Na-MRI has been proposed as a potential imaging biomarker for the assessment of tumor viability and the evaluation of therapy response but has not yet been evaluated in patients with lung cancer. We aimed to assess the feasibility of 23 Na-MRI in patients with lung cancer. Three patients with stage IV adenocarcinoma of the lung were examined on a clinical 3 Tesla MRI system (Magnetom TimTrio, Siemens Healthcare, Erlangen, Germany). Feasibility of 23 Na-MRI images was proven by comparison and fusion of 23 Na-MRI with 1 H-MR, CT and FDG-PET-CT images. 23 Na signal intensities (SI) of tumor and cerebrospinal fluid (CSF) of the spinal canal were measured and the SI ratio in tumor and CSF was calculated. One chemonaive patient was examined before and after the initiation of combination therapy (Carboplatin, Gemcitabin, Cetuximab). All 23 Na-MRI examinations were successfully completed and were of diagnostic quality. Fusion of 23 Na-MRI images with 1 H-MRI, CT and FDG-PET-CT was feasible in all patients and showed differences in solid and necrotic tumor areas. The mean tumor SI and the tumor/CSF SI ratio were 13.3 ± 1.8 x 103 and 0.83 ± 0.14, respectively. In necrotic tumors, as suggested by central non-FDG-avid areas, the mean tumor SI and the tumor/CSF ratio were 19.4 x 103 and 1.10, respectively. 23 Na-MRI is feasible in patients with lung cancer and could provide valuable functional molecular information regarding tumor viability, and potentially treatment response. (orig.)

Detection of five tumor markers in lung cancer by trypsin digestion of sputum method

International Nuclear Information System (INIS)

Lin Min; Nong Tianlei; Liu Daying

2011-01-01

To explore the detection of five tumor markers by trypsin digestion of sputum in the diagnosis of lung cancer, the samples of sputum in patients with lung cancer and benign lung disease were digested by trypsin and used to measure five tumor markers. The results showed that the sputum were well digested by 6% trypsin at pH8 and no affect on the determination of tumor markers. The CEA, CA125, CA153, CA211 and NSE levels in lung cancer group were significantly higher than that of in benign group (P<0.05). The sputum CEA and CA125 levels were significantly higher than that of the serum levels (P<0.05). The detection of sputum CEA, CA125, CA153, CA211 and NSE levels have clinical value in the diagnosis of lung cancer. When combined with other diagnostic methods,it might be helpful for further diagnosis in non confirmed lung cancer patients. (authors)

Assessment of interpatient heterogeneity in tumor radiosensitivity for nonsmall cell lung cancer using tumor-volume variation data

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Chvetsov, Alexei V., E-mail: chvetsov2@gmail.com; Schwartz, Jeffrey L.; Mayr, Nina [Department of Radiation Oncology, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195-6043 (United States); Yartsev, Slav [London Regional Cancer Program, London Health Sciences Centre, 790 Commissioners Road East, London, Ontario 46A 4L6 (Canada)

2014-06-15

Purpose: In our previous work, the authors showed that a distribution of cell surviving fractionsS{sub 2} in a heterogeneous group of patients could be derived from tumor-volume variation curves during radiotherapy for head and neck cancer. In this research study, the authors show that this algorithm can be applied to other tumors, specifically in nonsmall cell lung cancer. This new application includes larger patient volumes and includes comparison of data sets obtained at independent institutions. Methods: Our analysis was based on two data sets of tumor-volume variation curves for heterogeneous groups of 17 patients treated for nonsmall cell lung cancer with conventional dose fractionation. The data sets were obtained previously at two independent institutions by using megavoltage computed tomography. Statistical distributions of cell surviving fractionsS{sub 2} and clearance half-lives of lethally damaged cells T{sub 1/2} have been reconstructed in each patient group by using a version of the two-level cell population model of tumor response and a simulated annealing algorithm. The reconstructed statistical distributions of the cell surviving fractions have been compared to the distributions measured using predictive assays in vitro. Results: Nonsmall cell lung cancer presents certain difficulties for modeling surviving fractions using tumor-volume variation curves because of relatively large fractional hypoxic volume, low gradient of tumor-volume response, and possible uncertainties due to breathing motion. Despite these difficulties, cell surviving fractionsS{sub 2} for nonsmall cell lung cancer derived from tumor-volume variation measured at different institutions have similar probability density functions (PDFs) with mean values of 0.30 and 0.43 and standard deviations of 0.13 and 0.18, respectively. The PDFs for cell surviving fractions S{sub 2} reconstructed from tumor volume variation agree with the PDF measured in vitro. Conclusions: The data obtained

Therapy of Pancreatic Neuroendocrine Tumors: Fine Needle Intervention including Ethanol and Radiofrequency Ablation

Directory of Open Access Journals (Sweden)

Sundeep Lakhtakia

2017-11-01

Full Text Available Pancreatic neuroendocrine tumors (PNETs are increasingly being detected, though usually as incidental findings. Majority of the PNETs are non-functional and surgical resection is the standard of care for most of them. However, in patients with small PNETs localized within the pancreas, who are unfit or unwilling for surgery, alternate methods of treatment are needed. Direct methods of ablation of PNETs, using either ethanol injection or radiofrequency ablation (RFA, are emerging as effective methods. The limited literature available as case reports or case series on endoscopic ultrasound (EUS-guided local ablation using either ethanol or RFA has demonstrated safety and efficacy along with short- to medium-term sustained relief. Long-term benefits with these local ablative therapies are awaited. Comparative studies are needed to show which of these two competing technologies is superior. Finally, comparative trials of EUS-guided ablation with surgical resection in terms of efficacy and safety will ensure their place in the management algorithm.

Evaluation of radiological prognostic factors of hepatic metastases in patients with non-functional pancreatic neuroendocrine tumors

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Denecke, Timm [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Baur, Alexander D.J., E-mail: alexander.baur@charite.de [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Ihm, Claudia; Steffen, Ingo G. [Klinik für Radiologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Tischer, Elisabeth [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Arsenic, Ruza [Institut für Pathologie, Campus Charité Mitte, Charité - Universitätsmedizin Berlin (Germany); Pascher, Andreas [Klinik für Allgemein-, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany); Wiedenmann, Bertram; Pavel, Marianne [Medizinische Klinik m.S. Hepatologie Gastroenterologie, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin (Germany)

2013-10-01

Purpose: There are different therapeutic options in non-functional well to moderately differentiated (G1 and G2) pancreatic neuroendocrine tumors (pNET) with unresectable hepatic metastases including systemic chemotherapy and novel molecular targeted therapies. Treatment with somatostatin analogs (SSA) as antiproliferative agents is optional. At initial diagnosis watchful waiting until tumor progression is a well-established approach. Goal of this study was to evaluate imaging features as potential prognostic factors predicting early tumor progression in order to select patients that might benefit from an earlier initiation of medical treatment. Patients and methods: In 44 patients we correlated tumor grade, chromogranin A (CgA) levels, treatment with SSA and imaging features of hepatic metastases on contrast-enhanced multiphase CT and MR imaging with time to tumor progression (TTP) according to RECIST 1.0. Results: In the total patient cohort none of the tested imaging features was found to be a statistically significant prognostic factor for TTP. Since treatment with SSA was associated with an increased TTP we also analyzed a subgroup of 30 patients not treated with SSA. In this subgroup of patients hypoenhancement of hepatic metastases during early contrast phases was found to be a negative prognostic factor for early tumor progression within 12 months (p = 0.039). The other evaluated parameters including hepatic tumor load, number of metastases, and presence of regressive morphological changes did not reveal significant results. Conclusion: Hypovascularization of liver metastases from G1 and G2 pNET reflected by hypoenhancement during the early contrast phases seems to be associated with early tumor progression. In patients with hypoenhancing metastases repeated biopsy for reassessment of grading of these metastases, and early initiation of therapy should be considered.

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.

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Rastogi, Vaibhav; Singh, Devina; Mazza, Joseph J; Yang, Dennis; Parajuli, Dipendra; Yale, Steven H

2018-04-12

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. The paper is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract. Part 1 covered is neuroendocrine tumors, (carcinoid, pheochromocytomas, vasoactive

Diagnostic value of combined detection of serum tumor markers for lung cancer

International Nuclear Information System (INIS)

Li Yanping; Wang Qun; Zhao Zihong; Zhou Shan

2013-01-01

Objective: To investigate the diagnostic value of combined detection of serum tumor markers, including CEA, CA125, neuron-specific enolase (NSE) and cytokeratin fragment antigen 21-1 (CYFRA21-1) for lung cancer patients. Methods: The subjects involved 138 diagnosed lung cancer patients (82 males, 56 females, average age 58.6 years, from October 2010 to March 2012), 96 patients with benign lung diseases (56 males, 40 females, average age 51.3 years) and 45 healthy adults (30 males, 15 females, average age 43.9 years). The pathological types of lung cancer consisted of 66 squamous cell carcinoma (SCC), 52 adenocarcinoma and 20 small cell lung cancer (SCLC). The serum levels of CEA, CA125, NSE and CYFRA21-1 were measured with electrochemiluminescence immunoassay. The diagnostic efficacy for different pathological types was compared among each single tumor marker and combination of tumor markers. One-way analysis of variance q test were used for statistical analysis. Results: The serum levels of CEA, CA125, NSE and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in healthy subjects (CEA: (19.99±30.99), (10.78±19.77), (3.25±3.42) μg/L; CA125: (79.70±95.98), (44.96±44.97), (20.66±7.13) μg/L; NSE: (35.23±40.22), (15.31±8.42), (13.30±5.65) μg/L; CYFRA21-1: (18.07±43.71), (8.30±8.83), (3.13±1.60) μg/L; F=4.481, 5.436, 4.776, 6.002, all P<0.05). The highest level of CEA, NSE or CYFRA21-1 were found in adenocarcinoma (F=4.932, P<0.05), SCLC (F=5.119, P<0.05) or SCC (F=5.378, P<0.05), respectively. The highest sensitivity tumor markers for SCC, SCLC and adenocarcinoma were CYFRA21-1 (78.8%, 52/66), NSE (75.0%, 15/20) and CEA (57.7%, 30/52), respectively. In combined detection, the highest sensitivity combinations for SCC, SCLC and adenocarcinoma were CEA + CYFRA21-1 + NSE (89.4%, 59/66), CEA + CYFRA21-1 + NSE (80.0%, 16/20) and CEA + CA125 + NSE (78.8%, 41/52), respectively. Conclusions: Combined detection

Long-term local control with radiofrequency ablation or radiotherapy for second, third, and fourth lung tumors after lobectomy for primary lung cancer

International Nuclear Information System (INIS)

Yokouchi, Hideoki; Murata, Kohei; Miyazaki, Masaki; Miyamoto, Takeaki; Minami, Takafumi; Tsuji, Fumio; Mikami, Koji

2016-01-01

A 78-year-old woman developed second, third, and fourth lung tumors at intervals of 1-3 years after left upper lobectomy for primary lung cancer. The tumors were controlled with radiofrequency ablation (RFA) or conventional conformal radiotherapy for 9 years postoperatively. For the treatment of second primary lung cancer or lung metastasis after surgical resection of the primary lung cancer, reoperation is not recommended because of the impaired respiratory reserve. Thus, local therapy such as radiotherapy or RFA is applied in some cases. Among these, stereotactic body radiotherapy (SBRT) is a feasible option because of its good local control and safety, which is comparable with surgery. On the other hand, for cases of multiple lesions that are not suitable for radiotherapy or combination therapy, RFA could be an option because of its short-term local control, easiness, safety, and repeatability. After surgery for primary lung cancer, a second lung tumor could be controlled with highly effective and minimally invasive local therapy if it is recognized as a local disease but is medically inoperable. Therefore, long-term postoperative follow-up for primary lung cancer is beneficial. (author)

Respiratory gating during stereotactic body radiotherapy for lung cancer reduces tumor position variability.

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Saito, Tetsuo; Matsuyama, Tomohiko; Toya, Ryo; Fukugawa, Yoshiyuki; Toyofuku, Takamasa; Semba, Akiko; Oya, Natsuo

2014-01-01

We evaluated the effects of respiratory gating on treatment accuracy in lung cancer patients undergoing lung stereotactic body radiotherapy by using electronic portal imaging device (EPID) images. Our study population consisted of 30 lung cancer patients treated with stereotactic body radiotherapy (48 Gy/4 fractions/4 to 9 days). Of these, 14 were treated with- (group A) and 16 without gating (group B); typically the patients whose tumors showed three-dimensional respiratory motion ≧5 mm were selected for gating. Tumor respiratory motion was estimated using four-dimensional computed tomography images acquired during treatment simulation. Tumor position variability during all treatment sessions was assessed by measuring the standard deviation (SD) and range of tumor displacement on EPID images. The two groups were compared for tumor respiratory motion and position variability using the Mann-Whitney U test. The median three-dimensional tumor motion during simulation was greater in group A than group B (9 mm, range 3-30 mm vs. 2 mm, range 0-4 mm; psimulation, tumor position variability in the EPID images was low and comparable to patients treated without gating. This demonstrates the benefit of respiratory gating.

Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

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Ono, Tomohiro; Nakamura, Mitsuhiro; Hirose, Yoshinori; Kitsuda, Kenji; Ono, Yuka; Ishigaki, Takashi; Hiraoka, Masahiro

2017-09-01

To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Incidentally diagnosed simultaneous second primary tumor of the sphenoid sinus in a patient with lung cancer

DEFF Research Database (Denmark)

Yigit, Ozgur; Taskin, Umit; Demir, Ahmet

2009-01-01

Synchronous tumors are described as multiple primary malignancies presenting within 6 months of diagnosis of index tumors. Synchronous tumors of the lung and the head and neck region is frequently seen. However, isolated sphenoid sinus and lung cancers are not reported yet. Here, we reported...... an incidentally diagnosed simultaneous second primary sphenoid sinus tumor in a patient with lung cancer. Radiological evaluation results demonstrated a significant contrast-enhanced mass in the sphenoid sinus extending through the nasopharynx because of the destruction of the sphenoid sinus. The decision...

Primary Neuroendocrine Carcinoma of the Breast: Histopathological Criteria, Prognostic Factors, and Review of the Literature

Science.gov (United States)

Marinova, Lena; Vicheva, Snezhinka

2016-01-01

We present here a case of a 42-year-old woman diagnosed with primary neuroendocrine carcinoma of the breast (NECB). We discuss the importance of histological criteria for primary neuroendocrine mammary carcinoma, established by WHO in 2003 and 2012. After an overview of different cases of primary neuroendocrine carcinoma of the breast published in the literature, we present information about differential diagnosis, prognostic factors, and surgical and adjuvant treatment. Prognosis of NECB is not different from that of other invasive breast carcinomas and the most important prognostic factor is tumor grade (G). There is no standard treatment and patients should be treated similarly to patients with invasive ductal carcinoma, NOS (not otherwise specified), whose choice of therapy depends on tumor's size, degree of differentiation, clinical stage, and hormonal status. PMID:27840759

O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

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Raj, Nitya; Klimstra, David S; Horvat, Natally; Zhang, Liying; Chou, Joanne F; Capanu, Marinela; Basturk, Olca; Do, Richard Kinh Gian; Allen, Peter J; Reidy-Lagunes, Diane

2017-07-01

Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

ErbB2 Pathway Activation upon Smad4 Loss Promotes Lung Tumor Growth and Metastasis

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Jian Liu

2015-03-01

Full Text Available Lung cancer remains the leading cause of cancer death. Genome sequencing of lung tumors from patients with squamous cell carcinoma has identified SMAD4 to be frequently mutated. Here, we use a mouse model to determine the molecular mechanisms by which Smad4 loss leads to lung cancer progression. Mice with ablation of Pten and Smad4 in airway epithelium develop metastatic adenosquamous tumors. Comparative transcriptomic and in vivo cistromic analyses determine that loss of PTEN and SMAD4 results in ELF3 and ErbB2 pathway activation due to decreased expression of ERRFI1, a negative regulator of ERBB2 in mouse and human cells. The combinatorial inhibition of ErbB2 and Akt signaling attenuate tumor progression and cell invasion, respectively. Expression profile analysis of human lung tumors substantiated the importance of the ErbB2/Akt/ELF3 signaling pathway as both a prognostic biomarker and a therapeutic drug target for treating lung cancer.

Treatment-related neuroendocrine prostate cancer resulting in Cushing's syndrome.

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Ramalingam, Sundhar; Eisenberg, Adva; Foo, Wen Chi; Freedman, Jennifer; Armstrong, Andrew J; Moss, Larry G; Harrison, Michael R

2016-12-01

Here we present, to the best of our knowledge, the first case of a paraneoplastic Cushing's syndrome (hypercortisolism) resulting from treatment-related neuroendocrine prostate cancer - a highly aggressive and difficult disease to treat. A 51-year-old man was started on androgen deprivation therapy after presenting with metastatic prostate cancer, characterized by diffuse osseous metastasis. Shortly thereafter, he developed progressive disease with biopsy proven neuroendocrine prostate cancer as well as symptoms of increased skin pigmentation, hypokalemia, hypertension, hyperglycemia and profound weakness, consistent with ectopic Cushing's syndrome. Molecular analysis of the patient's tumor through RNA sequencing showed high expression of several genes including CHGA, ASCL1, CALCA, HES6, PCSK1, CALCB and INSM1 confirming his neuroendocrine phenotype; elevated POMC expression was found, supporting the diagnosis of ectopic Cushing's syndrome. © 2016 The Japanese Urological Association.

A Genomics-Based Classification of Human Lung Tumors

NARCIS (Netherlands)

Seidel, Danila; Zander, Thomas; Heukamp, Lukas C.; Peifer, Martin; Bos, Marc; Fernandez-Cuesta, Lynnette; Leenders, Frauke; Lu, Xin; Ansen, Sascha; Gardizi, Masyar; Nguyen, Chau; Berg, Johannes; Russell, Prudence; Wainer, Zoe; Schildhaus, Hans-Ulrich; Rogers, Toni-Maree; Solomon, Benjamin; Pao, William; Carter, Scott L.; Getz, Gad; Hayes, D. Neil; Wilkerson, Matthew D.; Thunnissen, Erik; Travis, William D.; Perner, Sven; Wright, Gavin; Brambilla, Elisabeth; Buettner, Reinhard; Wolf, Juergen; Thomas, Roman; Gabler, Franziska; Wilkening, Ines; Mueller, Christian; Dahmen, Ilona; Menon, Roopika; Koenig, Katharina; Albus, Kerstin; Merkelbach-Bruse, Sabine; Fassunke, Jana; Schmitz, Katja; Kuenstlinger, Helen; Kleine, Michaela; Binot, Elke; Querings, Silvia; Altmueller, Janine; Boessmann, Ingelore; Nuemberg, Peter; Schneider, Peter; Groen, Harry; Timens, Wim

2013-01-01

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic

Automatic segmentation of tumor-laden lung volumes from the LIDC database

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O'Dell, Walter G.

2012-03-01

The segmentation of the lung parenchyma is often a critical pre-processing step prior to application of computer-aided detection of lung nodules. Segmentation of the lung volume can dramatically decrease computation time and reduce the number of false positive detections by excluding from consideration extra-pulmonary tissue. However, while many algorithms are capable of adequately segmenting the healthy lung, none have been demonstrated to work reliably well on tumor-laden lungs. Of particular challenge is to preserve tumorous masses attached to the chest wall, mediastinum or major vessels. In this role, lung volume segmentation comprises an important computational step that can adversely affect the performance of the overall CAD algorithm. An automated lung volume segmentation algorithm has been developed with the goals to maximally exclude extra-pulmonary tissue while retaining all true nodules. The algorithm comprises a series of tasks including intensity thresholding, 2-D and 3-D morphological operations, 2-D and 3-D floodfilling, and snake-based clipping of nodules attached to the chest wall. It features the ability to (1) exclude trachea and bowels, (2) snip large attached nodules using snakes, (3) snip small attached nodules using dilation, (4) preserve large masses fully internal to lung volume, (5) account for basal aspects of the lung where in a 2-D slice the lower sections appear to be disconnected from main lung, and (6) achieve separation of the right and left hemi-lungs. The algorithm was developed and trained to on the first 100 datasets of the LIDC image database.

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

727) were administered (64)Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin α(V), integrin β(3), and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data......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...... 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....

Prognostic factors of non-functioning pancreatic neuroendocrine tumor revisited: The value of WHO 2010 classification.

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Bu, Jiyoung; Youn, Sangmin; Kwon, Wooil; Jang, Kee Taek; Han, Sanghyup; Han, Sunjong; You, Younghun; Heo, Jin Seok; Choi, Seong Ho; Choi, Dong Wook

2018-02-01

Various factors have been reported as prognostic factors of non-functional pancreatic neuroendocrine tumors (NF-pNETs). There remains some controversy as to the factors which might actually serve to successfully prognosticate future manifestation and diagnosis of NF-pNETs. As well, consensus regarding management strategy has never been achieved. The aim of this study is to further investigate potential prognostic factors using a large single-center cohort to help determine the management strategy of NF-pNETs. During the time period 1995 through 2013, 166 patients with NF-pNETs who underwent surgery in Samsung Medical Center were entered in a prospective database, and those factors thought to represent predictors of prognosis were tested in uni- and multivariate models. The median follow-up time was 46.5 months; there was a maximum follow-up period of 217 months. The five-year overall survival and disease-free survival rates were 88.5% and 77.0%, respectively. The 2010 WHO classification was found to be the only prognostic factor which affects overall survival and disease-free survival in multivariate analysis. Also, pathologic tumor size and preoperative image tumor size correlated strongly with the WHO grades ( p <0.001, and p <0.001). Our study demonstrates that 2010 WHO classification represents a valuable prognostic factor of NF-pNETs and tumor size on preoperative image correlated with WHO grade. In view of the foregoing, the preoperative image size is thought to represent a reasonable reference with regard to determination and development of treatment strategy of NF-pNETs.

Central lung tumors with obstructive pneumonitis; ultrasonographic findings and usefulness of ultrasound-guided biopsy

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Kim, Jong An; Kim, Sun Su; Seon, Young Seok; Lee, Kyoung Rok; Kim, Byoung Geun; Park, Byung Ran; Kim, Se Jong [Kwangju Christian Hospital, Kwangju (Korea, Republic of)

2001-02-01

To determine the ultrasonographic findings and assess the usefulness of ultrasound (US)-guided biopsy of central lung tumors in patients with obstructive pneumonitis. Fourteen patients with central lung tumors causing obstructive pneumonitis, as seen on chest radiographs and chest CT scans, were examined between January 1997 and January 2000. In no patient conclusive histologic diagnosis obtained by means of bronchoscopic biopsy or sputum cytology. Eleven patients were men and three were women, and their ages ranged from 45 to 83 (mean, 64) years. For all examinations, real-time, linear-array, convex US units with a 3.75-and a 5.0-MHz transducer were used. The images obtained were analyzed for evidence of consolidation or atelectasis in the lung, demonstrable tumors, and tumor size and echogenicity. For US-guided percutaneous transthoracic biopsy, 19.5G automatic biopsy devices, were employed. Lung consolidation due to a wedge-shaped, homogeneous, hypoechoic lesion was revealed by sonographic fluid bronchograms, air bronchograms, air alvelograms, and visualization of intraparenchymal pulmonary vessels, which showed appropriate motion with respiration. The tumor presumed to be causing obstruction was seen as a hypoechoic nodule near the hilum or as a well-defined hyperechoic mass inside the partially consolidated lung. Pleural effusion was observed in one case. The cytologic findings indicated the presence of squamous cell carcinoma (n=4), adenocarcinoma (n=4), small cell carcinoma (n=3), non-small cell carcinoma (n=2) and large cell carcinoma (n=1). The success rate was 100%, and there were no complications. In patients with central lung tumors causing obstructive pneumonitis, chest ultrasonography and US-guided biopsy are useful adjunctive diagnostic modalities and techniques.

Analysis of Clinicopathological Features and Prognostic Factors in 39 Cases of Bladder Neuroendocrine Carcinoma.

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Zhou, Hui-Hui; Liu, Li-Yan; Yu, Guo-Hua; Qu, Gui-Mei; Gong, Pei-You; Yu, Xiao; Yang, Ping

2017-08-01

Through analysis and summarization of clinicopathological features, immunohistochemical expression, pathological diagnostic criteria, prognostic and other factors in patients suffering from bladder neuroendocrine carcinoma (BNEC), a better understanding of BNEC could be achieved to provide solid evidence for clinicopathology and prognosis. The clinicopathological data of 39 cases of BNEC with up to 5-year follow-up data (median follow-up=650 days) were analyzed retrospectively based on immunohistochemical staining. Survival analyses were carried out using the Kaplan-Meier method and tested with the log-rank method. Multivariate Cox regression analysis was adopted to screen independent risk factors affecting patients' survival. In these 39 cases of BNEC, there were 26 cases of male patients, 13 female, with the proportion of male to female being 2:1. The ages of onset ranged from 44 to 86, with the median age being 62 and the average age 61.97 years, respectively. Histologically, referring to the WHO standard of neuroendocrine lung tumor classification, there were 7 cases of typical carcinoid tumors, 8 atypical carcinoid, 12 small-cell carcinomas and 12 large-cell carcinomas. In these cases there were 11 cases of featured urothelium carcinomas and 9 cases of adenocarcinomas. Immunohistochemical staining showed that, in these 39 cases of BNEC, the positive expression for the neuroendocrinic markers, including neural cell adhesion molecule 56 (CD56), synaptophysin (Syn), chromogranin A (CgA), neuron-specific enolase (NSE), thyroid transcription factor-1 (TTF-1), cytokeratin (CK) and cytokeratin 7 (CK7), accounted for 39/39, 27/39, 18/39, 39/39, 19/39, 10/39 and 8/39, respectively. In contrast, cytokeratin 20 (CK20), protein 63 (P63), human melanoma black 45 (HMB45), S-lfln protein 100 (S-100) and leukocyte common antigen (LCA) were all negatively expressed. During the follow-up period, 12 patients died. The 1-, 3- and 5-year overall survival (OS) rates were 76.92%, 74