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Sample records for human gastrointestinal tumors

  1. C-kit gene mutation in human gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Ying-Yong Hou; Ai-Hua Zheng; Tai-Ming Zhang; Wen-Zhong Hou; Jian Wang; Xiang Du; Xiong-Zeng Zhu; Yun-Shan Tan; Meng-Hong Sun; Yong-Kun Wei; Jian-Fang Xu; Shao-Hua Lu; Su-Jie A-Ke-Su; Yan-Nan Zhou; Feng Gao

    2004-01-01

    AIM: To investigate the significance of c-kit gene mutation in gastrointestinal stromal tumors (GIST).METHODS: Fifty two cases of GIST and 28 cases of other tumors were examined. DNA samples were extracted from paraffin sections and fresh blocks. Exons 11, 9 and 13 of the c-kit gene were amplified by PCR and sequenced.RESULTS: Mutations of exon 11 were found in 14 of 25 malignant GISTs (56%), mutations of exon 11 of the c-kit gene were revealed in 2 of 19 borderline GISTs (10.5%),and no mutation was found in benign tumors. The mutation rate showed significant difference (X2=14.39, P<0.01)between malignant and benign GISTs. Most of mutations consisted of the in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, None of the mutations disrupted the downstream reading frame of the gene. Point mutations and frame deletions were most frequently observed at codons 550-560, but duplications were most concentrated at codons 570-585. No mutations of exons 9 and 13 were revealed in GISTs, Neither c-kit gene expression nor gene mutations were found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2malignant peripheral nerve sheath tumors, 2 intraabdominal fibromatoses, 2 malignant fibrous histiocytomas and 9 adenocarcinomas.CONCLUSION: C-kit gene mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs and can help to differentiate GISTs from other mesenchymal tumors of gastrointestinal tract, such as smooth muscle tumors,schwannomas, etc.

  2. What Are Gastrointestinal Stromal Tumors?

    Science.gov (United States)

    ... system, also known as the digestive system. The gastrointestinal system The gastrointestinal (GI) system (or digestive system) processes ... in “ How are gastrointestinal stromal tumors diagnosed? ” Other gastrointestinal tract cancers It is important to understand that GISTs ...

  3. PCR Expression Analysis Of the Estrogeninducible Gene Bcei in Gastrointestinal and Other Human Tumors

    Directory of Open Access Journals (Sweden)

    Iris Wundrack

    1994-01-01

    Full Text Available A polymerase chain reaction (PCR assay was developed to test for tumor cell specific expression of the BCEI gene. This new marker gene, reported at first for human breast cancer, was found specifically active in various gastrointestinal carcinomas by previously applying immunohistochemistry and RNA (Northern blot analysis. Presently, by using reverse transcription -PCR analysis, a series of primary tumor tissues and established tumor cell lines were testcd for BCEI transcription. This approach was compared to immunostaining achieved by an antibody directed against the BCEI gene’s product. The result demonstrate the superior sensitivity of PCR by indicating the gene’ s expression in cases where immunohistochemical testing remained negative.

  4. GASTROINTESTINAL STROMAL TUMOR (GIST

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    Luigi eTornillo

    2014-11-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors of the gastrointestinal tract. The discovery that these tumors, formerly thought of smooth muscle origin, are indeed better characterized by specific activating mutation in genes coding for the receptor tyrosine kinases CKIT and PDGFRA and that these mutations are strongly predictive for the response to targeted therapy with receptor tyrosine kinase inhibitors has made GISTs the typical example of the integration of basic molecular knowledge in the daily clinical activity. The information on the mutational status of these tumors is essential to predict (and subsequently to plan the therapy. As resistant cases are frequently wild-type, other possible oncogenic events, defining other entities, have been discovered (e.g. succinil dehydrogenase mutation/dysregulation, insuline growth factor expression, mutations in the RAS-RAF-MAPK pathway. The classification of disease must nowadays rely on the integration of the clinico-morphological characteristics with the molecular data.

  5. Tumor-initiating label-retaining cancer cells in human gastrointestinal cancers undergo asymmetric cell division.

    Science.gov (United States)

    Xin, Hong-Wu; Hari, Danielle M; Mullinax, John E; Ambe, Chenwi M; Koizumi, Tomotake; Ray, Satyajit; Anderson, Andrew J; Wiegand, Gordon W; Garfield, Susan H; Thorgeirsson, Snorri S; Avital, Itzhak

    2012-04-01

    Label-retaining cells (LRCs) have been proposed to represent adult tissue stem cells. LRCs are hypothesized to result from either slow cycling or asymmetric cell division (ACD). However, the stem cell nature and whether LRC undergo ACD remain controversial. Here, we demonstrate label-retaining cancer cells (LRCCs) in several gastrointestinal (GI) cancers including fresh surgical specimens. Using a novel method for isolation of live LRCC, we demonstrate that a subpopulation of LRCC is actively dividing and exhibits stem cells and pluripotency gene expression profiles. Using real-time confocal microscopic cinematography, we show live LRCC undergoing asymmetric nonrandom chromosomal cosegregation LRC division. Importantly, LRCCs have greater tumor-initiating capacity than non-LRCCs. Based on our data and that cancers develop in tissues that harbor normal-LRC, we propose that LRCC might represent a novel population of GI stem-like cancer cells. LRCC may provide novel mechanistic insights into the biology of cancer and regenerative medicine and present novel targets for cancer treatment. Copyright © 2012 AlphaMed Press.

  6. Ghrelin and gastrointestinal stromal tumors

    Science.gov (United States)

    Zhu, Chang-Zhen; Liu, Dong; Kang, Wei-Ming; Yu, Jian-Chun; Ma, Zhi-Qiang; Ye, Xin; Li, Kang

    2017-01-01

    Ghrelin, as a kind of multifunctional protein polypeptide, is mainly produced in the fundus of the stomach and can promote occurrence and development of many tumors, including gastrointestinal tumors, which has been proved by the relevant researches. Most gastrointestinal stromal tumors (GISTs, about 80%), as the most common mesenchymal tumor, also develop in the fundus. Scientific research has confirmed that ghrelin, its receptors and mRNA respectively can be found in GISTs, which demonstrated the existence of a ghrelin autocrine/paracrine loop in GIST tissues. However, no reports to date have specified the mechanism whether ghrelin can promote the occurrence and development of GISTs. Studies of pulmonary artery endothelial cells in a low-oxygen environment and cardiac muscle cells in an ischemic environment have shown that ghrelin can activate the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway. Moreover, some studies of GISTs have confirmed that activation of the PI3K/AKT/mTOR pathway can indeed promote the growth and progression of GISTs. Whether ghrelin is involved in the development or progression of GISTs through certain pathways remains unknown. Can we find a new target for the treatment of GISTs? This review explores and summaries the relationship among ghrelin, the PI3K/AKT/mTOR pathway and the development of GISTs.

  7. Gastrointestinal carcinoid tumors Tumores carcinoides digestivos

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    M. J. Varas Lorenzo

    2010-09-01

    Full Text Available Objective: carcinoid tumors (CTs represent the commonest neuroendocrine tumors. Those in the gastrointestinal tract are diagnosed in surgical specimens, clinically, and using imaging techniques (endoscopy, echoendoscopy, CT, Octreoscan, etc.. The goal of this retrospective study was to review a personal series of gastrointestinal carcinoid tumors, and to compare it to those in the literature. Patients and methods: the medical records of 40 Caucasian patients with over 50 gastrointestinal carcinoid tumors (including multiple cases who were seen for a period of 16 years (1994-2009 were reviewed. Results: mean age at presentation was 52 years, 50% were females, and mean tumor size was 9.9 mm. Most were gastroduodenal (42.5% or rectal (30%, and were treated endoscopically. Metastases and carcinoid syndrome (CS were seen in 5% of patients. Survival at study endpoint was 85%. Conclusions: age and gender were consistent with the literature. There was an increase in gastroduodenal (multifocal and rectal carcinoids, likely because the series was essentially endoscopical in nature (bias. There was a lower rate of CS and higher survival, likely due to earlier diagnosis and treatment.Objetivo: los tumores carcinoides (TC son los tumores neuroendocrinos más frecuentes. Los digestivos se diagnostican en las piezas quirúrgicas, en la clínica, y mediante los métodos de imagen (endoscopia, ecoendoscopia, TAC y Octreoscan, etc.. El objetivo de este trabajo retrospectivo fue revisar una serie personal de tumores carcinoides digestivos y compararla con la literatura. Pacientes y métodos: se revisaron las historias clínicas de 40 pacientes de raza blanca con más de 50 tumores carcinoides digestivos, algunos múltiples, observados durante 16 años (1994-2009. Resultados: la edad media de presentación fue 52 años, 50% mujeres, con un tamaño medio del tumor de 9,9 mm. La mayoría eran gastroduodenales (42,5% y rectales (30% y fueron tratados por vía endosc

  8. [Circulating "tumor markers" in gastrointestinal tumors].

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    Borlinghaus, P; Lamerz, R

    1991-09-01

    Tumor markers (TM) of the neoplastic cell can be divided into non-shedded substances and antigens shedded in blood, urine or other body fluids. For clinicians circulating TM are more important. All relevant circulating TM are not useful in screening of asymptomatic patients because of insufficient sensitivity and specificity. With caution they are useful in the observation of risk groups. Circulating TM have their main significance as additional parameters in monitoring symptomatic patients with malignancies. Several follow up determinations are more important than one single measurement. During follow up of tumor patients TM should not be checked automatically if there are no diagnostic or therapeutical consequences. The clinically most important circulating TM in non-hormone secreting tumors of the gastrointestinal tract are the oncofetal antigens CEA and AFP and antigens defined by monoclonal antibodies e. g. CA 19-9 and CA 72-4. AFP is the primary TM in hepatocellular carcinoma, often elevated in hepatoblastoma and always normal in cholangiocellular carcinoma. CEA is the TM of first choice in patients with colorectal carcinomas and liver metastasis. CA 19-9 is TM of first choice in pancreatic carcinoma and additionally of diagnostic value in cholangiocellular carcinoma and tumors of the bile ducts. In cancer of the stomach CA 19-9 and CEA are secondary TM in combination with CA 72-4 as primary TM. Care should be taken that slight and moderate elevations of TM can be observed in benign diseases of liver, pancreas and bowel.

  9. HER-2 status in gastrointestinal stromal tumor.

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    Lopes, Lisandro Ferreira; Bacchi, Carlos E

    2008-08-01

    Human epidermal growth factor receptor-2 (HER-2) encodes for the transmembrane glycoprotein HER-2 that is involved in activation of intracellular signal transduction pathways that control cell growth and differentiation. HER-2 is overexpressed in approximately 20% of patients with breast cancer and has been associated with poorer prognosis. Since 1998, the anti-HER-2 antibody trastuzumab has been used for the treatment of patients with HER-2-positive breast cancers. However, little information is available about the relationship between HER-2 and gastrointestinal stromal tumors. This study's purpose was to determine the HER-2 status in gastrointestinal stromal tumors. We found that all 477 cases included in this study were negative (score 0) by immunohistochemistry using HercepTest, and no HER-2 gene amplification was detected in 71 cases submitted to fluorescence in situ hybridization. These results show that HER-2 may not have any role in gastrointestinal stromal tumor pathogenesis and that the neoplasm may not be suitable for treatment with trastuzumab.

  10. Gastrointestinal stromal tumor (gist) of the duodenum.

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    Ghazanfar, Shahriyar; Sial, Khadim S; Quraishy, M S

    2007-06-01

    This is a report of a rare gastrointestinal stromal tumor of the duodenum in a 75 years old man who presented with recurrent episodes of intestinal obstruction and melena. The patient underwent successful Whipple's procedure.

  11. Androgen receptor expression in gastrointestinal stromal tumor.

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    Lopes, Lisandro F; Bacchi, Carlos E

    2009-03-01

    The aim of this study was to evaluate the expression of estrogen, progesterone, and androgen receptors in a large series of gastrointestinal stromal tumors. Clinical and pathologic data were reviewed in 427 cases of gastrointestinal stromal tumor and the expression of such hormone receptors was investigated by immunohistochemistry using tissue microarray technique. All tumors were negative for estrogen receptor expression. Progesterone and androgen receptors expression was observed in 5.4% and 17.6% of tumors, respectively. We found the higher average age at diagnosis, the lower frequency of tumors located in the small intestine, and the higher frequency of extragastrointestinal tumors to be statistically significant in the group of tumors with androgen receptor expression in contrast to the group showing no androgen receptor expression. There was no statistic difference between such groups regarding sex, tumor size, mitotic count, cell morphology, and risk of aggressive behavior. Considering that the expression of androgen receptors in gastrointestinal stromal tumors is not negligible, further studies are encouraged to establish the role of androgen deprivation therapy for gastrointestinal stromal tumors.

  12. Gastrointestinal stromal tumor and mitosis, pay attention

    Institute of Scientific and Technical Information of China (English)

    Federico Coccolini; Fausto Catena; Luca Ansaloni; Antonio Daniele Pinna

    2012-01-01

    The difference between stages I and III of gastric gastrointestinal stromal tumor depends principally on the number of mitosis. According with TNM classification, the presence in the tumor of high mitotic rate determines the upgrading. Many studies exposed different count techniques in evaluating the number of mitosis. An international standardized method to assess mitotic rate is needed.

  13. Down-regulation of human leukocyte antigens class I on peripheral T lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zhi-mian; LI Ying-jie; GUAN Xiao; YANG Xiao-yun; GAO Xi-mei; YANG Xiao-jing; WANG Li-shui; ZOU Xiong

    2011-01-01

    Background Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens (HLA) class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. The present study made an analysis of HLA class I expression on peripheral-blood T lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. Methods A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups: high-risk group (tumor markers positive group) and low-risk group (tumor markers negative group). The percentage of T lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry.Results Percentages of T lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. The expression level of HLA class I on peripheral T lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers (P<0.05), especially on the surface of NK cells (P<0.01). Compared with the low-risk group, there was a significant reduction of HLA class I on peripheral T lymphocytes (P <0.05) and NK cells (P <0.05) in the high-risk group.Conclusions HLA class I on peripheral T lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

  14. Gastrointestinal Neuroendocrine Tumors: Pancreatic Endocrine Tumors

    OpenAIRE

    2008-01-01

    Pancreatic endocrine tumors (PETs) have long fascinated clinicians and investigators despite their relative rarity. Their clinical presentation varies depending upon whether the tumor is functional or not and also according to the specific hormonal syndrome produced. Tumors may be sporadic or inherited but little is known about their molecular pathology, especially the sporadic forms. Chromogranin A appears to be the most useful serum marker for diagnosis, staging and monitoring. Initially, t...

  15. Maspin expression in gastrointestinal stromal tumors

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    Ozguc Halil

    2010-03-01

    Full Text Available Abstract Background To investigate the role of maspin expression in the progression of gastrointestinal stromal tumors, and its value as a prognostic indicator. Methods In the study 54 patients with GIST diagnosis were included in Uludag University of Faculty of Medicine, Department of Pathology between 1997-2007. The expression of maspin in 54 cases of gastrointestinal stromal tumor was detected by immunohistochemistry and compared with the clinicopathologic tumor parameters. Results The positive expression rates for maspin in the GISTs were 66,6% (36 of 54 cases. Maspin overexpression was detected in 9 of 29 high risk tumors (31% and was significantly higher in very low/low (78.6% and intermediate-risk tumors (63.6% than high-risk tumors. Conclusions Maspin expression might be an important factor in tumor progression and patient prognosis in GIST. In the future, larger series may be studied to examine the prognostic significance of maspin in GISTs and, of course, maspin expression may be studied in different mesenchymal tumors.

  16. [Subepithelial tumors of the gastrointestinal tract].

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    Stupnik, Silvio; Rafaelli, Claudio; González, Graciela Osorio; Pestalardo, María Luján; Quesada, Matías; Viúdez, Pedro

    2009-06-01

    The subepithelial lesions of the gastrointestinal tract are related to mesenchymal tumors and 80% of them are GIST (gastrointestinal stromal tumors). However, there are also other tumors, such as: leiomyomas, schwannomas, lipomas, glomus tumors, carcinoid tumors, aberrant pancreas and polyps or inflammatory tumors. Diagnosis of submucosal tumors is often performed during routine endoscopic examination, they are frequently located at the stomach and in most cases are clinically evidenced by their complications. Endoscopic ultrasonography (EUS) is the elected method for their staging; but other imaging diagnosis methods include computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography scan (PET). The differential diagnosis is made by inmunohistochemical techniques, revealing in the GIST the expression of the antigen CD117, and prognostic factors are determined by size and mitotic index. Surgery is the recommended therapeutic, although in small lesions not exceeding 2 cm it has also been suggested the endoscopic resection guided by EUS and a watchful behaviour based on periodical controls in lesions with benignity criteria. The series here exhibited (2 GIST 1 lyposarcoma, 1 schwannoma and 1 inflammatory fibroid polyp) shows that all these tumors were symptomatic; have been diagnosed using endoscopy and recognized by means of histopathology and immunohistochemical analysis after surgery.

  17. Endoscopic management of gastrointestinal smooth muscle tumor

    Institute of Scientific and Technical Information of China (English)

    Xiao-Dong Zhou; Nong-Hua Lv; Hong-Xia Chen; Chong-Wen Wang; Xuan Zhu; Ping Xu; You-Xiang Chen

    2007-01-01

    AIM: To systematically evaluate the efficacy and safety of endoscopic resection of gastrointestinal smooth muscle tumors (SMTs, including leiomyoma and leiomyosarcoma) and to review our preliminary experiences on endoscopic diagnosis of gastrointestinal SMTs.METHODS: A total of 69 patients with gastrointestinal SMT underwent routine endoscopy in our department.Endoscopic ultrasonography (EUS) was also performed in 9 cases of gastrointestinal SMT. The sessile submucosal gastrointestinal SMTs with the base smaller than 2 cm in diameter were resected by "pushing" technique or "grasping and pushing" technique while the pedunculated SMTs were resected by polypectomy. For those SMTs originating from muscularis propria or with the base size ≥ 2 cm, ordinary biopsy technique was performed in tumors with ulcers while the "Digging" technique was performed in those without ulcers.RESULTS: 54 cases of leiomyoma and 15 cases of leiomyosarcoma were identified. In them, 19 cases of submucosal leiomyoma were resected by "pushing"technique and 10 cases were removed by "grasping and pushing" technique. Three cases pedunculated submucosal leiomyoma were resected by polypectomy.No severe complications developed during or after the procedure. No recurrence was observed. The diagnostic accuracy of ordinary and the "Digging" biopsy technique was 90.0% and 94.1%, respectively.CONCLUSION: Endoscopic resection is a safe and effective treatment for leiomyomas with the base size ≤2 cm. The "digging" biopsy technique would be a good option for histologic diagnosis of SMTs.

  18. Chemokine receptor CXCR4-prognostic factor for gastrointestinal tumors

    Institute of Scientific and Technical Information of China (English)

    Carl C Schimanski; Peter R Galle; Markus Moehler

    2008-01-01

    To review the implication of CXCR4 for gastrointestinal cancer,a "Pubmed" analysis was performed in order to evaluate the relevance of CXCR4 and its ligands for gastrointestinal cancers.Search terms applied were "cancer,malignoma,esophageal,gastric,colon,colorectal,hepatic,pancreatic,CXCR4,SDF-1α,and SDF-1β"; CXCR4 expression correlated with dissemination of diverse gastrointestinal malignomas.The CXCR4 ligand SDF-1α might act as "chemorepellent"while SDF-1β might act as "chemorepellent" for CTLs,inducing tumor rejection.The paracrine expression of SDF-1α was furthermore closely associated with neoangiogenesis.CXCR4 and its ligands influence the dissemination,immune rejection,and neoangiogenesis of human gastrointestinal cancers.Inhibition of CXCR4 might be an interesting therapeutic option.

  19. Heme oxygenase-1 system and gastrointestinal tumors

    Institute of Scientific and Technical Information of China (English)

    Marie; CM; Lin; Hsiangfu; Kung

    2010-01-01

    Heme oxygenase-1(HO-1) system catabolizes heme into three products:carbon monoxide,biliverdin/bilirubin and free iron.It is involved in many physiological and pathophysiological processes.A great deal of data has demonstrated the roles of HO-1 in the formation,growth and metastasis of tumors.The interest in this system by investigators involved in gastrointestinal tumors is fairly recent,and few papers on HO-1 have touched upon this subject.This review focuses on the current understanding of the physiologic...

  20. Tumor del Estroma Gastrointestinal Gástrico.

    OpenAIRE

    Haydelisis Peraza González; Mirian Belkis Nápoles Valdés; Ofelia María Pompa Oliva

    2016-01-01

    Las neoplasias del estroma gastrointestinal (GIST) se producen en el estroma mesenquimático, en cualquier sitio del tubo digestivo, son tumores raros, y en muchas ocasiones su diagnóstico es incidental por lo que el objetivo de esta publicación es ofrecer una enseñanza clínica de la forma de presentación típica de un tumor de GIST gástrico no sospechado. Se refirió a consulta de Gastroenterología paciente masculino de 44 años de edad por presentar dolor en epigastrio, se le realizaron varios ...

  1. Tumor budding in upper gastrointestinal carcinomas

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    Viktor Hendrik Koelzer

    2014-08-01

    Full Text Available The basis of personalized medicine in oncology is the prediction of an individual’s risk of relapse and death from disease. The presence of tumor budding (TB at the tumor-host interface of gastrointestinal cancers has been recognized as a hallmark of unfavorable disease biology. TB is defined as the presence of dedifferentiated cells or small clusters of up to five cells at the tumor invasive front and can be observed in aggressive carcinomas of the esophagus, stomach, pancreas, ampulla, colon and rectum. Presence of TB reproducibly correlates with advanced tumor stage, frequent lymphovascular invasion, nodal and distant metastasis. The UICC has officially recognized TB as additional independent prognostic factor in cancers of the colon and rectum. Recent studies have also characterized TB as a promising prognostic indicator for clinical management of esophageal squamous cell carcinoma, adenocarcinoma of the gastro-esophageal junction and gastric adenocarcinoma. However, several important issues have to be addressed for application in daily diagnostic practice: 1 Validation of prognostic scoring systems for tumor budding in large, multi-center studies 2 Consensus on the optimal assessment method 3 Inter-observer reproducibility. This review provides a comprehensive analysis of TB in cancers of the upper gastrointestinal tract including critical appraisal of perspectives for further study.

  2. Tumor del Estroma Gastrointestinal Gástrico.

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    Haydelisis Peraza González

    2016-04-01

    Full Text Available Las neoplasias del estroma gastrointestinal (GIST se producen en el estroma mesenquimático, en cualquier sitio del tubo digestivo, son tumores raros, y en muchas ocasiones su diagnóstico es incidental por lo que el objetivo de esta publicación es ofrecer una enseñanza clínica de la forma de presentación típica de un tumor de GIST gástrico no sospechado. Se refirió a consulta de Gastroenterología paciente masculino de 44 años de edad por presentar dolor en epigastrio, se le realizaron varios exámenes, entre ellos TAC de doble contraste de abdomen donde constató masa intrabdominal, cuyo diagnostico definitivo fue Tumor de GIST gástrico. La conducta terapéutica fue la combinación de cirugía y terapia neoadyuvante con anticuerpo monoclonal. En las enfermedades que afectan el tracto gastrointestinal es necesario tener presente como diagnóstico nosológico este tipo de tumor maligno ya que un tratamiento oportuno puede asegurar una evolución satisfactoria para el paciente

  3. Giant gastrointestinal stromal tumor of the stomach.

    Science.gov (United States)

    Ionescu, Sever; Barbu, Emil; Ionescu, Călin; Costache, Adrian; Bălăşoiu, Maria

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the digestive tract. Gastric localization is the most frequent. The aim of this study is to evaluate the importance of immunohistochemical factors (CD117, CD34, α-SMA, vimentin, p53, Ki67) in diagnostic and size tumor and mitotic activity as prognostic factors for these tumors. We present the case of a 66-year-old male patient with a giant gastric GIST. Like in the vast majority, the symptomatology in this patient has long been faint, despite the large tumor size, and when it became manifest, it was nonspecific. Imagery wise, the computer tomography (CT) scan was the most efficient, showing the origin of the tumor from the greater curvature of the stomach, its dimensions, as well as the relations with the other abdominal viscera. Surgery in this patient was en-bloc, according to the principles of GIST. The histological aspect is characterized by a proliferation of spindle cells positive for CD117 and CD34. Despite complete microscopic resection, the size of the tumor (25×20×27 cm) and the mitotic activity (21÷5 mm2) remains important relapse factor.

  4. Updates in Tumor Profiling in Gastrointestinal Cancers.

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    Perez, Kimberly; Safran, Howard P

    2015-10-01

    In the last decade there has been a focus on biomarkers that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression of cancers. Characterization of genomes by next-generation sequencing (NGS) has permitted significant advances in gastrointestinal cancer care. These discoveries have fueled the development of novel therapeutics and have laid the groundwork for the development of new treatment strategies. Work in colorectal cancer (CRC) has been in the forefront of these advances. With the continued development of NGS technology and the positive clinical experience in CRC, genome work has begun in esophagogastric, pancreatic, and hepatocellular carcinomas as well.

  5. Gastrointestinal stromal tumor and its targeted therapeutics

    Institute of Scientific and Technical Information of China (English)

    Jheri Dupart; Wei Zhang; Jonathan C. Trent

    2011-01-01

    Over the past 60 years, investigators of basic science, pathology, and clinical medicine have studied gastrointestinal stromal tumor (GIST) and made minor advances in patient care. Recent discoveries have led to an understanding of the biological rote of KIT and platelet-derived growth factor receptor-α in GIST and the development of the tyrosine kinase inhibitor imatinib mesylate (Gleevec, formerly STI-571), one of the most exciting examples of targeted therapy to date. The success of targeted therapy in GIST has lead to new developments in our understanding of the medical and surgical management of the disease. Intense study of GIST may lead to new paradigms in the management of cancer.

  6. Upper gastrointestinal hemorrhage due to duodenal stromal tumor

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    Parreira José Gustavo

    2003-01-01

    Full Text Available BACKGROUND: Gastrointestinal stromal tumor represents a rare neoplasm that originates in the muscular wall of the hollow viscera. AIM: To report gastrointestinal stromal tumor as a source of upper gastrointestinal bleeding, which required urgent surgical control. PATIENT/METHOD: A man with 61 years old was admitted to the emergency service sustaining hematemesis and melena. Endoscopy showed active bleeding from a tumor in the second portion of the duodenum, which was controlled by heater probe cauterization. Surgery was performed through a median laparotomy. A local resection of a 4 cm tumor in the second portion of the duodenum was carried out, together with a primary end-to-end anastomosis and a duodenal diverticulization. No complications happened during the post-operative period. Morphologic examination showed gastrointestinal stromal tumor with no atypical mitosis and a preserved capsule. CONCLUSION: Albeit not being common, gastrointestinal stromal tumors can represent a source of substantial gastrointestinal hemorrhage.

  7. Gastrointestinal stromal tumor presenting with prominent calcification

    Institute of Scientific and Technical Information of China (English)

    Naoki Izawa; Takeshi Sawada; Ryuichi Abiko; Daisuke Kumon; Mami Hirakawa; Mika Kobayashi; Nobuyuki Obinata

    2012-01-01

    We present a rare case of a gastrointestinal stromal tumor (GIST) in the stomach with prominent calcification at presentation.A 61-year-old woman visited our hospital because of epigastric discomfort.A spherical calcified lesion with a diameter of about 30 mm was incidentally shown in the left upper quadrant on an abdominal X-ray.Computed tomography demonstrated that the tumor was growing from the upper gastric body,with calcification in the peripheral ring area.A laparoscopic partial gastrectomy was performed,and the resected specimen revealed a well-circumscribed tumor with exophytic growth from the gastric muscularis propria.Microscopic examination revealed spindleshaped tumor cells with calcification and hemorrhage.Additionally,positive immunoreactivity of the tumor to KIT and CD34 and a low mitotic index resulted in the diagnosis of very low risk GIST.There are a few case reports of heavily calcified GIST,although solitary or punctate calcification of primary GIST has been reported in several case series.Dystrophic calcification of necrotic or degenerative tissue is the supposed cause of primary calcified GISTs.In contrast,appearance of calcification after administration of imatinib mesylate,which may be one indicator of disease response,is possibly caused by a different mechanism.

  8. Update on gastrointestinal stromal tumors for radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Tirumani, Sree Harsha; O' Neill, Alibhe; Jagannathan, Jyothi P. [Dept. of Imaging, Dana-Farber Cancer Institute, Boston (United States); Baheti, Akahay D. [Dept. of Radiology, Tata Memorial Centre, Mumbai (India); Tirumani, Harika [Dept. of Radiology, University of Arkansas for Medical Sciences, Little Rock (United States)

    2017-01-15

    The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters. Surveillance of patients with GIST in the adjuvant setting is important for timely detection of recurrences.

  9. Radiologic findings of submucosal tumors of gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ja; Ahn, In Oak; You, Jin Jong [College of Medicine, Gyeongsang National University, Chinju (Korea, Republic of)

    2000-05-01

    Gastrointestinal submucosal tumors originate from submucosal histologic structures such as muscles, lymph nodes, nerves, fibers and vessels. Most patients are asymptomatic. Lesions that are large or ulcerated may cause abdominal pain or upper gastrointestinal bleeding, and those that grow intraluminally sometimes become pedunculated and occasionally prolapse to cause intussusception. Adenocarcinoma is the most common primary gastrointestinal tumor, accounting for approximately 90-95% of such lesions, while submucosal tumors account for approximately 2-6% of all gastrointestinal tumors. Because their overlying mucosa appears normal, submucosal tumors age after difficult to visualize endoscopically, and for this reason, barium studies or CT scans are helpful for diagnosis. In this paper, variable CT and barium study findings of the different types of gastrointestinal submucosal tumor are demonstrated, and a brief discussion of the respective disease entities is included. (author)

  10. Pediatric/"Wildtype" gastrointestinal stromal tumors.

    Science.gov (United States)

    Mullassery, Dhanya; Weldon, Christopher B

    2016-10-01

    Pediatric/"Wildtype" gastrointestinal stromal tumor (P/WT-GIST) is a rare cancer, distinct and markedly different from the phenotype found predominantly in older patients (adult, non-wildtype GIST). Having a different molecular signature, it is not responsive to standard adjuvant therapies utilized in adult GIST, and surgery remains the only effective cure. However, even with presumed complete resections in patients with localized disease at presentation, recurrence rates are high. Furthermore, it is an indolent cancer that can persist for decades, and treatment strategies must balance the possible morbid risks of intervention with the reality of preserving quality of life in the interim. Effective adjuvant therapies remain elusive, and research is critically needed to identify both targets and drugs for treatment consideration. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Tumor estromal gastrointestinal de intestino delgado

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    Francisco Marivaldo Benício da Silva

    Full Text Available Stromal tumors of the gastrointestinal tract (gists represent relatively rare lesions that arise from connective tissue elements located along the entire length of the gut. They were initially identified by immunohistochemical investigation, proving their origin from nondifferentiated mesenchymal cells. Only a minority of this lesions, mainly those confined to the esophagus and rectum, have been shown to correspond to mature, well-differentiated types of neoplasms such as leiomyoma or leiomyosarcoma. The majority of gists corresponds to a heterogeneous group of lesions that have as their common denominator an immature proliferation of epithelioid or spindle cells arising from its muscle layers, or between them, showing partial or incomplete myoide, neural, ganglionic, or mixed features of differentiation. This case report intends to show a gist of small bowel in a male, 46 years old, with a two-year of evolution.

  12. Obscure Gastrointestinal Bleeding Due to a Small Intestinal Gastrointestinal Stromal Tumor in a Young Adult

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    Mami Yamamoto

    2016-11-01

    Full Text Available The source of most cases of gastrointestinal bleeding is the upper gastrointestinal tract. Since bleeding from the small intestine is very rare and difficult to diagnose, time is required to identify the source. Among small intestine bleeds, vascular abnormalities account for 70–80%, followed by small intestine tumors that account for 5–10%. The reported peak age of the onset of small intestinal tumors is about 50 years. Furthermore, rare small bowel tumors account for only 1–2% of all gastrointestinal tumors. We describe a 29-year-old man who presented with obscure anemia due to gastrointestinal bleeding and underwent laparotomy. Surgical findings revealed a well-circumscribed lesion measuring 45 × 40 mm in the jejunum that initially appeared similar to diverticulosis with an abscess. However, the postoperative pathological diagnosis was a gastrointestinal stromal tumor with extramural growth.

  13. Gastrointestinal Stromal Tumors of the Pancreas

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    Muhammad Wasif Saif

    2010-07-01

    Full Text Available Dear Sir, We read with great interest the case report published by Padhi et al. in the 2010 May issue of JOP. J Pancreas (Online titled “Extragastrointestinal Stromal Tumor Arising in the Pancreas: A Case Report with a Review of the Literature” [1]. Extragastrointestinal stromal tumors arising in the pancreas are extremely rare. Only nine cases have been reported in the literature up to today including the one by Padhi et al. [1, 2, 3, 4, 5, 6, 7, 8, 9]. We here report another case, probably to be the 10th in medical literature of a pancreatic gastrointestinal stromal tumor (GIST patient with an aggressive outcome. Our patient is a 31-year-old male in his usual state of health until February 2009 when he began to experience abdominal pain and fatigue accompanied by a 4.5 kg weight loss. There was no history of pancreatitis or abdominal trauma. He had a small episode of hematemesis for which he had blood work performed including complete blood count that revealed hemoglobin of 4.6 g/dL (reference range: 14.0-18.0 g/dL. He was admitted to the hospital where received 5 units of packed red blood cells and he was subsequently evaluated with upper endoscopy. Upon the procedure a friable area of mucosa was identified on the duodenum of which no biopsy could be taken. After this finding he had a CT scan which showed a 5.1x4.2x5.6 cm hypervascular mass in the pancreatic head compressing the common bile duct with minimal dilatation. The mass was further characterized by MRI, in which a 5.0x4.3 soft tissue mass was invading the pancreatic head and duodenum, obstructing the common bile duct without pancreatic duct obstruction. On admission, his total bilirubin was 7.3 mg/dL (reference range: 0-1.20 mg/dL, alkaline phosphatase was 686 U/L (reference range: 30-130 U/L, CA 19-9 was 11 U/mL (reference range: 0-37 U/mL, and CEA was 0.9 ng/mL (reference range: 0-3.0 ng/mL. The patient underwent a pylorus-preserving pancreatoduodenectomy and the pathology

  14. Synchronous Acromegaly and Gastrointestinal Stromal Tumor: A Case Report

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    Hüsniye Başer

    2014-06-01

    Full Text Available Acromegaly is a rare endocrine disorder characterized by the manifestations of sustained hypersecretion of growth hormone and concomitant elevations in circulating concentrations of insulin-like growth factor-1. It has been reported that patients with acromegaly are at the increased risk of developing malignant tumors, particularly colorectal cancer. Gastrointestinal stromal tumors are mesenchymal tumors of the digestive tract. An association between gastrointestinal stromal tumors and insulin-like growth factor system has been reported. Here, we report a patient diagnosed with synchronous acromegaly and gastrointestinal stromal tumor. A 59-year-old man with iron deficiency anemia presented with enlarged hands, coarse facial feature and several skin tags. Thyroid function tests were within normal range. Growth hormone was 5.14 ng/mL, insulin-like growth factor-1 was 820 ng/mL, and no growth hormone suppression was observed on 75g oral glucose tolerance test. Pituitary magnetic resonance imaging revealed microadenoma, and the patient was diagnosed with acromegaly. Upper gastrointestinal tract endoscopy revealed an ulcerovegetan mass in the duodenum and the results of the histopathologcal analysis was consistent with gastrointestinal stromal tumor. The association of synchronous and asynchronous gastrointestinal stromal tumors with other malignancies have been reported. The most common accompanying neoplasms are colorectal and gastric adenocarcinomas, as well as pancreatic tumors. However, in the literature, the number of reported cases of synchronous acromegaly and gastrointestinal stromal tumor are limited, and there are no sufficient data on this association. Turk Jem 2014; 2: 52-55

  15. Primary omental Gastrointestinal stromal tumor (GIST

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    Hirahara Nobutsune

    2007-06-01

    Full Text Available Abstract Background We report herein a rare case of primary omental gastrointestinal stromal tumor (GIST. Case presentation A 65 year-old man was referred to our hospital with a huge abdominal mass occupying the entire left upper abdomen as shown by sonography. On computed tomography (CT, this appeared as a heterogeneous low-density mass with faint enhancement. Abdominal angiography revealed that the right gastroepiploic artery supplied the tumor. With such an indication of gastric GIST, liposarcoma, leiomyosarcoma or mesothelioma laparotomy was performed and revealed that this large mass measured 20 × 17 × 6 cm, arising from the greater omentum. It was completely resected. Histopathologically, it was composed of proliferating spindle and epithelioid cells with an interlacing bundle pattern. Immunohistochemically, the tumor was positive for myeloid stem cell antigen (CD34, weakly positive for c-KIT (CD117 and slightly positive for neuron-specific enolase (NSE, but negative for cytokeratin (CK, alpha-smooth muscle actin (SMA and S-100 protein. A mutation was identified in the platelet-derived growth factor alpha (PDGFRA juxtamembrane domain (exon 12, codon561 and the tumor was diagnosed as an omental GIST. The postoperative course was uneventful. The patient is treated by Glevec® and is alive well with no sign of relapse. Conclusion Our case demonstrated a weak immunohistochemical expression of c-kit (CD117 and a point mutation in PDGFRA exon 12 resulting in an Asp for Val561 substitution. Imatinib therapy as an adjuvant to complete resection has been carried out safely. Because of the rarity of primary omental GISTs, it is inevitable to analyze accumulating data from case reports for a better and more detailed understanding of primary omental GISTs.

  16. Synchronous occurrence of gastrointestinal stromal tumors and other primary gastrointestinal neoplasms

    Institute of Scientific and Technical Information of China (English)

    Marek Wronski; Bogna Ziarkiewicz-Wroblewska; Barbara Gornicka; Wlodzimierz Cebulski; Maciej Slodkowski; Aleksander Wasiutynski; Ireneusz W Krasnodebski

    2006-01-01

    AIM: To review clinical and pathologic features of Gastrointestinal stromal tumors (GISTs) occurring synchronously with other primary gastrointestinal neoplasms.METHODS: 28 patients with primary GIST were treated at our institution between 1989 and 2005. Clinical and pathologic records were reviewed.RESULTS: The gastrointestinal stromal tumor occurred simultaneously with other primary GI malignancies in 14% of all patients with GIST. The synchronous stromal tumors were located in the stomach and were incidentally found during the operation. The coexistent neoplasms were colon adenocarcinoma, gastric cancer (2 cases) and gastric lymphoma.CONCLUSION: The synchronous occurrence of GISTs and other gastrointestinal malignancies is more common than it has been considered. The development of gastrointestinal stromal tumors and other neoplasms may involvethe same carcinogenic agents.

  17. Classification of submucosal tumors in the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Laura Graves Ponsaing; Katalin Kiss; Mark Berner Hansen

    2007-01-01

    This review is part two of three, which will present an update on the classification of gastrointestinal submucosal tumors. Part one treats of the diagnosis and part three of the therapeutic methods regarding gastrointestinal submucosal tumors. In the past there has been some confusion as to the classification of gastrointestinal submucosal tumors. Changes in classifications have emerged due to recent advances in mainly immunohistochemistry and electron microscopy.The aim of this paper is to update the reader on the current classification. Literature searches were performed to find information related to classification of gastrointestinal submucosal tumors. Based on these searches the twelve most frequent submucosal tumor types were chosen for description of their classification.The factors that indicate whether tumors are benign or malignant are mainly size and number of mitotic counts.Gastrointestinal stromal tumors are defined mainly by their CD117 positivity. In the future, there should be no more confusion between gastrointestinal stromal tumors and other types of submucosal tumors.

  18. [Obscure gastrointestinal bleeding due to gastrointestinal stromal tumors].

    Science.gov (United States)

    Romero-Espinosa, Larry; Souza-Gallardo, Luis Manuel; Martínez-Ordaz, José Luis; Romero-Hernández, Teodoro; de la Fuente-Lira, Mauricio; Arellano-Sotelo, Jorge

    The gastrointestinal stromal tumours (GIST) are the most common soft tissue sarcomas of the digestive tract. They are usually found in the stomach (60-70%) and small intestine (25-30%) and, less commonly, in the oesophagus, mesentery, colon, or rectum. The symptoms present at diagnosis are, gastrointestinal bleeding, abdominal pain, abdominal mass, or intestinal obstruction. The type of symptomatology will depend on the location and size of the tumour. The definitive diagnosis is histopathological, with 95% of the tumours being positive for CD117. This is an observational and descriptive study of 5cases of small intestinal GIST that presented with gastrointestinal bleeding as the main symptom. The period from the initial symptom to the diagnosis varied from 1 to 84 months. The endoscopy was inconclusive in all of the patients, and the diagnosis was made using computed tomography and angiography. Treatment included resection in all patients. The histopathological results are also described. GIST can have multiple clinical pictures and unusual symptoms, such as obscure gastrointestinal bleeding. The use of computed tomography and angiography has shown to be an important tool in the diagnosis with patients with small intestine GISTs. Copyright © 2016. Publicado por Masson Doyma México S.A.

  19. Cancer stem cells in human gastrointestinal cancer.

    Science.gov (United States)

    Taniguchi, Hiroaki; Moriya, Chiharu; Igarashi, Hisayoshi; Saitoh, Anri; Yamamoto, Hiroyuki; Adachi, Yasushi; Imai, Kohzoh

    2016-11-01

    Cancer stem cells (CSCs) are thought to be responsible for tumor initiation, drug and radiation resistance, invasive growth, metastasis, and tumor relapse, which are the main causes of cancer-related deaths. Gastrointestinal cancers are the most common malignancies and still the most frequent cause of cancer-related mortality worldwide. Because gastrointestinal CSCs are also thought to be resistant to conventional therapies, an effective and novel cancer treatment is imperative. The first reported CSCs in a gastrointestinal tumor were found in colorectal cancer in 2007. Subsequently, CSCs were reported in other gastrointestinal cancers, such as esophagus, stomach, liver, and pancreas. Specific phenotypes could be used to distinguish CSCs from non-CSCs. For example, gastrointestinal CSCs express unique surface markers, exist in a side-population fraction, show high aldehyde dehydrogenase-1 activity, form tumorspheres when cultured in non-adherent conditions, and demonstrate high tumorigenic potential in immunocompromised mice. The signal transduction pathways in gastrointestinal CSCs are similar to those involved in normal embryonic development. Moreover, CSCs are modified by the aberrant expression of several microRNAs. Thus, it is very difficult to target gastrointestinal CSCs. This review focuses on the current research on gastrointestinal CSCs and future strategies to abolish the gastrointestinal CSC phenotype.

  20. Gastrointestinal autonomic nerve tumors:A surgical point of view

    Institute of Scientific and Technical Information of China (English)

    Anton Stift; Josef Friedl; Michael Gnant; Friedrich Herbst; Raimund Jakesz; Etienne Wenzl

    2004-01-01

    AIM: Gastrointestinal autonomic nerve tumors are uncommon stromal tumors of the intestinal tract. Their histological appearance is similar to that of other gastrointestinal stromal tumors. We report two cases and performed an analysis of the literature by comparing our findings with the available case reports in the medical literature.METHODS: Two patients were admitted with abdominal tumor masses. One occurred in the stomach with large multiple liver metastases and the second originated in Meckel's diverticulum. The latter site has never been reported previously. Both patients underwent surgery. In one patient gastrectomy, right liver resection and colon transversum resection were performed to achieve aggressive tumor debulking. In the other patient the tumor bearing diverticulum was removed.RESULTS: Postoperative recovery of both patients was uneventful. Histological examination, immunohistochemical analysis and electron microscopy revealed the diagnosis of a gastrointestinal autonomic nerve tumor. The patient with the tumor in Meckel's diverticulum died 6 mo after surgery because of pneumonia. The patient with liver metastases have been alive 13 years after initial tumor diagnosis and 7 years after surgery with no evidence of tumor progression. In light of our results, we performed a thorough comparison with available literature reports.CONCLUSION: Radical surgical resection of gastrointestinal autonomic nerve tumors seems to be the only available curative approach to date, and long term survival is possible even in large metastasized tumors.ACKNOWLEDGMENTWe thank Christine Brostjan, PhD for critical review of the manuscript.

  1. Staging and histologic grading of gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    何德明

    2013-01-01

    Objective To investigate the clinical stage and histological grade of gastrointestinal stromal tumors. Methods Twelve clinical and pathological parameters were assessed in 613 patients with follow-up information. These parameters were classified into two gross spread

  2. Esophageal Gastrointestinal Stromal Tumors Presenting as Mediastinal Mass

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    M. Kafeel

    2013-11-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the gastrointestinal tract and are predominant in the stomach and intestine but rare in the esophagus. Here, we report a case of esophageal GIST which presented as a mediastinal mass on chest X-ray and dyspnea. The case was initially diagnosed as leiomyosarcoma, which could create a diagnostic dilemma. Therefore, recognizing this uncommon presentation as a mediastinal mass with esophageal GIST is important in the differential diagnosis.

  3. Rare case of gastrointestinal stromal tumor of the anal canal

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    Madhu Kumar

    2013-01-01

    Full Text Available Gastrointestinal stromal tumor (GIST is a rare mesenchymal neoplasm of the gastrointestinal tract. GIST of anal canal is very rare representing only 3% of all anorectal mesenchymal tumors. We report an extremely rare case of GIST of the anal canal in 60-years-old man with history of irregular bowel habits with dark colored stool mixed with blood and constipation from 6 month. Diagnosis was made on the basis of histomorphological and immunohistochemical examination.

  4. Analysis of CD117-negative gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Chin-Yuan Tzen; Bey-Liing Mau

    2005-01-01

    AIM: To identify the gastrointestinal stromal tumors(GISTs) that are negative for CD117 expression by immunohistochemistry and to characterize their malignant potential.METHODS: A total of 108 primary mesenchymal tumors of the gastrointestinal tract were screened to select CD117-negative tumors, from which KIT(exons 9, 11, 13, and 17)and PDGFRA (exons 10, 12, 14, and 18) were sequenced to identify GISTs. Tumor recurrence and distant metastasis were used as the criteria of malignancy.RESULTS: The result showed that approximately 25%(29/108) of the gastrointestinal mesenchymal tumors were negative for CD117 and approximately 6% (7/108)of the tumors were CD117-negative GISTs. All these CD117-negative tumors had a mutated KITand a wildtype PDGFRA. All CD117-negative GISTs with mutations at codons 557/558 of KIThad mitotic counts >10/50 high power field, and 75% (3/4) of them showed multiple recurrence or distant metastasis.CONCLUSION: CD1 17-negative KITmutated GISTs account for approximately 6% of the gastrointestinal mesenchymal tumors. Tumor recurrence or distant metastasis correlates to both theKITmutations at codons 557/558 and the mitotic counts, but not to the tumor size.

  5. A large gastrointestinal stromal tumor of duodenum: a case report

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    Hadi Ahmadi Amoli

    2014-01-01

    Case presentation: The patient is a forty six years old man. He complained of frequent colic pain in left upper quadrant of abdomen for two months before admitting to the hospital. The pain resolved spontaneously after a few hours. This situation almost has been repeated every week. The patient had severe repeated melena and faint for two weeks. As soon as the patient was entered the Sina Hospital in 2012, supportive care was started. Then upper gastrointestinal endoscopy was performed for him and the bleeding point was detected. Also abdominal and pelvic computed tomography with oral and intravenous contrast was done. Finally the patient was operated on tumor diagnosis in duodenal area according to classic Whipple procedure. Conclusion: Gastrointestinal bleeding is the most common symptom of gastrointestinal stromal tumors. The bleeding is minimal and chronic. It will be progress to sudden and severe bleeding. Diagnosis is done by upper gastrointestinal endoscopy and biopsy. The large tumors with high mitotic

  6. Pancreatic Metastasis from Rectal Gastrointestinal Stromal Tumor: A Case Report

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    Saba Ebrahimian

    2016-07-01

    Full Text Available Gastrointestinal stromal tumors are mesenchymal neoplasms of the gastrointestinal tract that originate from all areas of the gastrointestinal tract. Metastases to the liver, peritoneum, bones, lungs and soft tissues have been reported. We present the case of a 47- year-old woman with rectal gastrointestinal stromal tumor that underwent wide local excision. She was treated with imatinib for a few months after surgery. After eight months, she was admitted to the emergency service with complaints of epigastric pain, nausea, vomiting, and anorexia. Imaging studies showed the presence of a pancreatic head tumor and three hepatic masses. The patient underwent exploratory laparatomy. Excisional biopsy of one hepatic mass and core needle biopsy of the pancreatic head mass revealed metastases to the liver and pancreas. During the hospital course the patient's condition deteriorated and she subsequently expired.

  7. Can Gastrointestinal Carcinoid Tumors Be Found Early?

    Science.gov (United States)

    ... may also be found when parts of the gastrointestinal system are removed to treat other diseases. For example, a person with stomach pain or bleeding may have a test called an upper endoscopy to look for an ulcer. In this ...

  8. Esophageal Gastrointestinal Stromal Tumor: Diagnostic Complexity and Management Pitfalls

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    Charalampos G. Markakis

    2013-01-01

    Full Text Available Introduction. Gastrointestinal stromal tumors of the esophagus are rare. Case Presentation. This is a case of a 50-year-old male patient who was referred to our department complaining of atypical chest pain. A chest computed tomographic scan and endoscopic ultrasound revealed a submucosal esophageal tumor measuring 5 cm in its largest diameter. Suspecting a leiomyoma, we performed enucleation via right thoracotomy. The pathology report yielded a diagnosis of an esophageal gastrointestinal stromal tumor. The patient has shown no evidence of recurrence one year postoperatively. Conclusions. This report illustrates the complexity and dilemmas inherent in diagnosing and treating esophageal GISTs.

  9. Tumor del estroma gastrointestinal del intestino delgado Gastrointestinal stromal tumor of small intestine

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    Magaly Marión Luna Gozá

    2011-12-01

    Full Text Available Los tumores del estroma gastrointestinal fueron catalogados originalmente como otros tumores (leiomioma, leiomioblastoma o leiomiosarcoma, debido a su apariencia histológica similar; sin embargo, los avances en la biología molecular y la inmunohistoquímica, han permitido diferenciarlos de otras neoplasias digestivas, y definirlos como una entidad clínica e histopatológica propia. Se presenta un paciente, de sexo femenino, de la raza negra, de 79 años de edad, con dolor abdominal de 3 días de evolución, que se había iniciado en fosa ilíaca derecha y luego se mantuvo en bajo vientre, acompañado de vómitos, fatiga y decaimiento. Se decide intervenir quirúrgicamente y se lleva al salón de operaciones con el diagnóstico de una apendicitis aguda, del muñón, tipo oclusiva en el anciano, sin descartar una oclusión por bridas. Al realizar laparotomía se encuentra sangre libre en cavidad que no coagula, y se observó tumor hemorrágico, pediculado, muy móvil, hacia íleon terminal. Se realiza exéresis de este, se resecan aproximadamente 5 cm de intestino delgado y se realiza sutura termino-terminal posteriormente. Se realizó amplia toillette de la cavidad peritoneal y el cierre habitual, con evolución satisfactoria, y con alta a los 7 días. Se mantiene asintomática al año y medio de operada, y la biopsia arrojó tumor de intestino delgado, de bajo grado de malignidad, de 5 cm de diámetro.The tumors of the gastrointestinal stroma were originally classified as other type of tumors (leiomyoma, leiomyobastoma or leiomyosarcoma due to it similar histological appearance; however, the advances in the molecular biology and the immunohistochemistry have allowed its differentiation of other digestive neoplasms and to define them as an own clinical and histopathological entity. This is the case of a black female patient aged 79 presenting with abdominal pain during 3 days of evolution started in the right iliac fossa and then it remains in

  10. Gastric carcinoid tumor in a patient with a past history of gastrointestinal stromal tumor of the stomach

    Institute of Scientific and Technical Information of China (English)

    Chien-Yuan Hung; Ming-Jen Chen; Shou-Chuan Shih; Tsang-Pai Liu; Yu-Jan Chan; Tsang-En Wang; Wen-Hsiung Chang

    2008-01-01

    Gastrointestinal stromal tumor is the most common mesenchymal tumor in the gastrointestinal tract. It may coexist with other type of cancers, and if so, the tumors usually involve the stomach. The most common associated cancers are gastrointestinal carcinomas. We report a 65-year-old woman with a history of gastric gastrointestinal stromal tumor who had undergone subtotal segmental gastrectomy. New polypoid lesions were detected on a follow-up gastroscopy one year later. The lesions were biopsied and found to be carcinoid tumors. There was serum hypergastrinemia, and type 1 gastric carcinoid tumor was diagnosed. A total gastrectomy was performed. Pathologic examination revealed both carcinoid tumors and a recurrent gastrointestinal stromal tumor.

  11. Anti-tumor effects of the Notch pathway in gastrointestinal stromal tumors.

    Science.gov (United States)

    Dumont, Amaury G; Yang, Yanwen; Reynoso, David; Katz, Daniela; Trent, Jonathan C; Hughes, Dennis P

    2012-09-01

    Gastrointestinal stromal tumors (GISTs) are driven by gain-of-function mutations of KIT or PDGFRa. The introduction of imatinib has significantly extended survival for patients. However, most patients develop resistances. Notch signaling is a conserved developmental pathway known to play a critical role in the development of several cancers, functioning as a tumor promoter or a tumor suppressor. Given that the normal progenitor cell for GIST, the interstitial cell of Cajal, has characteristics similar to those of cells of neuroendocrine origin, we hypothesized that Notch pathway impacts the biology of GIST cells. In this study, we retrovirally and pharmacologically manipulated the Notch pathway in human GIST cells. We also performed a retrospective analysis of a cohort on 15 primary tumors to determine the role of Hes1, a major target gene of Notch, as a prognostic marker for GIST. Constitutively, active intracellular domain of Notch1 (ICN1) expression potently induced growth arrest and downregulated KIT expression in vitro. Additionally, treatment with the histone deacetylase inhibitor suberoylanilide hydroxamic acid caused dose-dependent upregulation of Notch1 expression and a parallel decrease in viability in these cells. Retroviral silencing of downstream targets of Notch (dominant-negative Hes1) and pharmacological inhibition of Notch activation (γ-secretase inhibition) partially rescued GIST cells from suberoylanilide hydroxamic acid treatment. GIST patients with high Hes1 mRNA levels have a significantly longer relapse-free survival. These results identify a novel anti-tumor effect of Notch1 and cross talk between the Notch and KIT pathways. Thus, activation of this pathway by treatment with histone deacetylase inhibitors is an appealing potential therapeutic strategy for GISTs. Précis: This study is the first report of the tumor suppressor effects of Notch pathway in gastrointestinal stromal tumors via a negative feedback with the oncogene KIT and may

  12. [GASTROINTESTINAL INVOLVEMENT IN HUMAN BARTONELLOSIS

    Science.gov (United States)

    Maguiña, Ciro; Gotuzzo, Eduardo; Carcelén, Amador; Salinas, César; Cok, Jaime; Recavarren, Sixto; Bussalleu, Alejandro

    1997-01-01

    We present a prospective study of 68 patients with the acute phase of human bartonellosis, admitted to Cayetano Heredia National Hospital.Gastrointestinal symptoms were reported as follows: abdominal pain 46,3%, coluria 44,4%, vomiting 40,3%, jaundice 38,5%, diarrhea 29,9%, constipation 8,9%. The more common signs were pallor 97%, hepatomegaly 82%, fever 79,1%, malnutrition 75,2%, systolic heart murmur 77,9%, jaundice 71,6%, lymph node enlargement 70,1%.Signs observed during the hospital course were 29,4% lower extremities edema, 22,6% myalgia, 16,4% pericardial effusion, 16,4% generalized edema. The more common gastrointestinal signs were hepatomegaly 82%(52/68), jaundice 71,6% (48/68) and splenomegaly 29,4%(20/68).The -lower liver border was found between 1 to 4 below the lower rib border in 71,6%(48/67) and below 5 cm b. l. r. b. in 11,9%(8/67).60% had abnormal liver function tests, 54,6% had mainly direct bilirrubin elevationand 45,4% mainly indirect.SGOT was elevated in 28,5% and SGPT in 25%, 28,3% had elevated alkaline phosphatase. The bilirrubin media was 3,5 mg/dI (range 0,6-21), the indirect bilirrubin media was 1,6 mg/dI (range 0,5-11,5), the direct bilirrubin media was 1,9 mg/dI (range 0,3-18), The SGOT media 73,9 U/L (range 9-1250), SGPT media 65,5U/L (range 6-1596). Alkaline phosphatase 5,9 mui/ml (range 3-497). Albumin media 3,09 (range 2-4,2).Patients with bacterial coinfection (salmonella, staphilococcus, enterobacter, shigella) had a higher increase in bilirrubin and transaminases.Three patients had liver biopsies, two revealed Küpffer cells hyperplasia (moderate to severe), one revealed intracellular hyperplasia, one patient coinfected with diseminated hystoplasmosis had granulomas in the liver.Mortality(8,8%) was associated to hepatocellular involvement (SGOT media 330U/L, SGPT media 207 U/L, alkaline phosphatase media 183 mui/ml), hypoalbuminemia media = 2,4 gr/1) and generalized edema.

  13. A ruptured large extraluminal ileal gastrointestinal stromal tumor causing hemoperitoneum

    Institute of Scientific and Technical Information of China (English)

    Shoji Hirasaki; Kohei Fujita; Minoru Matsubara; Hiromitsu Kanzaki; Hiromichi Yamane; Masato Okuda; Seiyuu Suzuki; Atsuko Shirakawa; Hideyuki Saeki

    2008-01-01

    We describe an 87-year-old woman with a large ileal gastrointestinal stromal tumor (GIST) causing hernoperitoneum. A CT scan demonstrated a large heterogeneous mass measuring about 13 crn × 11 cmin the pelvis and hemoperitoneurn, with a non-uniform enhancement pattern. The mass was diagnosed as a GIST originating from the gastrointestinal tract. She underwent an urgent laparotomy and an ileal GIST with a rupture was found 130 cm from the anal to the Treitz's ligament. Hernoperitoneum caused by ileal GIST rupture is a rare condition. Bleeding in the large tumor leading to rupture of the capsule might cause hemoperitoneurn in the present case.

  14. Treatment of Gastrointestinal Carcinoid Tumors by Stage

    Science.gov (United States)

    ... of carcinoid syndrome worse. Recurrent carcinoid tumors When cancer come backs after treatment it is called a recurrence . Recurrence can be local (in or near the same place it started) or distant (spread to organs such as the lungs or bone). Patients with recurrent carcinoid tumors are ...

  15. Diagnostic procedures for submucosal tumors in the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Laura Graves Ponsaing; Katalin Kiss; Annika Loft; Lise Ingemann Jensen; Mark Berner Hansen

    2007-01-01

    This review is part one of three, which will present an update on diagnostic procedures for gastrointestinal (GI) submucosal tumors (SMTs). Part two identifies the classification and part three the therapeutic methods regarding GI SMTs. Submucosal tumors are typically asymptomatic and therefore encountered incidentally.Advances in diagnostic tools for gastrointestinal submucosal tumors have emerged over the past decade.The aim of this paper is to provide the readers with guidelines for the use of diagnostic procedures, when a submucosal tumor is suspected. Literature searches were performed to find information on diagnostics for gastrointestinal submucosal tumors. Based on the searches, the optimal diagnostic procedures and specific features of the submucosal tumors could be outlined.Standard endoscppy, capsule endoscopy and push-and-pull enteroscopy (PPE) together with barium contrast X-ray do not alone provide sufficient information, when examining submucosal tumors. Endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI) and fiuorodeoxyglucose-labeled positron emission tomography (FDG-PET) are recommended as supplementary tools.

  16. Gastrointestinal Stromal Tumor. A Case Presentation Tumor del estroma gastrointestinal. Presentación de un caso

    Directory of Open Access Journals (Sweden)

    Carlos Manuel Ramírez Pérez

    2012-06-01

    Full Text Available

    The terms gastrointestinal stromal tumor refers to tumors of the connective tissue that can be located from the mouth to the anus. The case of a male patient, 64 years old, who attended consultation because of upper gastrointestinal bleeding in the form of melena with a slight decrease in hemoglobin, good general condition and records of previous good health is presented. Gastrointestinal stromal tumor was suspected from the initial examination through video-assisted endoscopy, a diagnosis confirmed later through immunohistochemical examination. The patient underwent surgery with wedge resection of the tumor mass and conservation of gastric and esophageal sphincter. The biopsy results coincided before and after surgery.

    Los términos tumor del estroma gastrointestinal hacen referencia a tumores del tejido conectivo que pueden estar situados desde la boca hasta el ano. Se presenta el caso de un paciente masculino, de 64 años de edad, que acudió a consulta por presentar sangrado digestivo alto en forma de melena, con leve disminución de las cifras de hemoglobina, relativo buen estado general y antecedentes de buena salud. Se tuvo sospecha de tumor del estroma gastrointestinal desde el examen inicial mediante endoscopia asistida por video, diagnóstico confirmado después por el examen inmunohistoquímico. El paciente fue sometido a cirugía con resección en cuña de la masa tumoral y con conservación de los esfínteres gástrico y esofágico, el resultado de la biopsia pre y posoperatoria fue coincidente

  17. [Massive hemorrhage of upper gastrointestinal tract caused by gastrointestinal stromal tumor of the stomach--case report].

    Science.gov (United States)

    Lalović, Nenad; Dukić Vladicić, Nikolina; Marić, Radmil; Cuk, Mirjana; Simatović, Milan; Jokanović, Dragana

    2012-01-01

    Acute bleeding from the upper gastrointestinal system is a medical emergency which is followed by high mortality rate, ranging from 6 to 15% in spite of modern diagnostic methods and treatment. Bleeding from the upper gastrointestinal system may be caused by gastrointestinal stromal tumors of the stomach, which are mainly characterized by occult bleeding, while profuse bleeding rarely occurs accompanied by hemorrhagic shock. Gastrointestinal stromal tumors of stomach are the most common mesenchimal tumors of the gastrointestinal tract. In our study we showed a 60-year-old female patient with profuse bleeding from the stomach and the clinical picture of severe hemorrhagic shock, caused by gastrointestinal stromal tumor. An ovoid junction, raised towards the lumen, covered with ulcerated mucosa in several places and followed by massive arterial bleeding was found intraoperatively, after the performed gastrotomy. Histopathological examination with immunohistochemical analysis confirmed that this was a gastrointestinal stromal tumor of the stomach. Acute bleeding from the digestive system is a sudden and serious condition of the body. Urgent esophagogastroduodenoscopy is a sensitive and specific diagnostic and therapeutic method of choice. Massive bleeding from the upper gastrointestinal tract is very rarely caused by gastrointestinal stromal tumors, whose clinical picture is very heterogeneous and depends on tumor size and location. Abundant bleeding from the tumor is an indication for urgent surgical intervention. According to the literature massive hemorrhage of the upper digestive system can rarely be caused by gastrointestinal stromal tumor of the stomach. It is shown that abundant hemorrhage of the upper digestive tract can be caused with gastric gastrointestinal stromal tumor. Surgical resection is the main form of treatment of gastrointestinal stromal tumors of the digestive system and bleeding from these tumors caused by failure of endoscopic hemostasis.

  18. Multiple gastrointestinal stromal tumors and bilateral pheochromocytoma in neurofibromatosis

    Institute of Scientific and Technical Information of China (English)

    Klaus Kramer; Cornelia Hasel; Andrik J Aschoff; Doris Henne-Bruns; Peter Wuerl

    2007-01-01

    The coincidence of a gastrointestinal stromal tumor (GIST) and a neuroendocrine tumor (NET) in neurofibromatosis type 1 (NF1) is described only five times within the literature. We report on a 63 year old Caucasian female with the rare condition of neurofibromatosis type 1 coinciding with recurrent gastrointestinal stromal tumor plus bilateral pheochromocytoma (PCC). After a history of palpitations and dizziness that lasted for years, a left adrenal mass was detected by CT. Laparotomy revealed a pheochromocytoma of the left adrenal gland while an ileoterminal GIST was found incidentally intraoperatively.After six months contralateral PCC and multiple recurrent GIST were resected again. After four years the patient is doing well without any signs of further recurrent tumors.Discussion includes review of the literature.

  19. How Are Gastrointestinal Carcinoid Tumors Diagnosed?

    Science.gov (United States)

    ... don’t release enough serotonin for a positive test result. In other cases, the tumors do not make much serotonin, but they do make its precursor, 5-HTP, which can be converted to serotonin in the ...

  20. Ramucirumab Clinical Development: an Emerging Role in Gastrointestinal Tumors.

    Science.gov (United States)

    Sanchez-Gastaldo, Amparo; Gonzalez-Exposito, Reyes; Garcia-Carbonero, Rocío

    2016-08-01

    Ramucirumab (IMC-1121B, LY3009806) is a fully human G1 monoclonal antibody that specifically targets vascular endotelial growth factor receptor 2 (VEGFR-2) with a substantially greater binding affinity than that of its natural ligands. Early clinical trials in patients with advanced solid tumors demonstrated that biologically relevant blood target concentrations are achievable with tolerable doses, and also showed some preliminary evidence of clinical activity. Several pivotal phase III trials have now been concluded and have led regulatory agencies to grant marketing authorization to ramucirumab for use as second line therapy in patients with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma (as single agent or in combination with paclitaxel), in patients with advanced colorectal carcinoma (CRC) (in combination with infusional fluorouracil and irinotecan (FOLFIRI regimen)) and in patients with advanced non-small cell lung cancer (NSCLC) (in combination with docetaxel). In contrast, ramucirumab failed to significantly improve survival versus placebo as second line therapy in patients with advanced hepatocellular carcinoma (HCC). The aim of this review is to summarize the clinical development and emerging role of ramucirumab in gastrointestinal (GI) tumors, including relevant aspects of its mechanism of action, pharmacology, safety profile, and antitumor activity in gastric, HCC, and CRC carcinomas.

  1. Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas

    OpenAIRE

    Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing

    2013-01-01

    Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastr...

  2. The value of surgery for gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Boyko Koroukov

    2013-12-01

    Full Text Available 39 patients with GISTs were included in the study. Four of them have tumors with extra-gastrointestinal localization (retroperitoneal space – in 3 cases and one patient with tumor in the mesentery of the small intestine. The distribution of GISTs in the gastrointestinal tract was established as follows: stomach (21 cases, duodenum (4 cases, small intestine (7 cases and colon (3 cases. The most common clinical signs were abdominal pain and discomfort, weakness, dyspeptic complaints and gastrointestinal bleeding. 29 patients underwent radical operations with achieved R0 resection. Recurrence was observed in 5 patients. Achieved median, 1-, 3- and 5-year survival was respectively 52,91 months, 88%, 81% and 67%.

  3. Pheochromocytoma and gastrointestinal stromal tumors in patients with neurofibromatosis type I

    NARCIS (Netherlands)

    Vlenterie, M.; Flucke, U.E.; Hofbauer, L.C.; Timmers, H.J.L.M.; Gastmeier, J.; Aust, D.E.; Graaf, W.T. van der; Wesseling, P.; Eisenhofer, G.; Lenders, J.W.M.

    2013-01-01

    BACKGROUND: Neurofibromatosis I may rarely predispose to pheochromocytoma and gastrointestinal stromal tumors. METHODS: A 59-year-old woman with neurofibromatosis I presented with pheochromocytoma of the left adrenal gland. During surgery, 3 gastrointestinal stromal tumors adjacent to the stomach

  4. Endoscopic resection of superficial gastrointestinal tumors

    Institute of Scientific and Technical Information of China (English)

    Giovannini Marc; Cesar Vivian Lopes

    2008-01-01

    Therapeutic endoscopy plays a major role in the management of gastrointestinal (GI) neoplasia.Its indications can be generalized into four broad categories; to remove or obliterate neoplastic lesion,to palliate malignant obstruction, or to treat bleeding.Only endoscopic resection allows complete histologicalstaging of the cancer, which is critical as it allowss tratification and refinement for further treatment.Although other endoscopic techniques, such asablation therapy, may also cure early GI cancer, they can not provide a definitive pathological specimen.Early stage lesions reveal low frequency of lymph node metastasis which allows for less invasive treatments and thereby improving the quality of life when compared to surgery. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are now accepted worldwide as treatment modalities for early cancers of the GI tract.

  5. Current management and prognostic features for gastrointestinal stromal tumor (GIST

    Directory of Open Access Journals (Sweden)

    Lamba Gurpreet

    2012-06-01

    Full Text Available Abstract Stromal or mesenchymal neoplasms affecting the gastrointestinal (GI tract have undergone a remarkable evolution in how they are perceived, classified, approached, diagnosed and managed over the last 30 years. Gastrointestinal stromal tumors (GIST account for approximately 1% to 3% of all malignant GI tumors. The clinical features can vary depending on the anatomic location, size and aggressiveness of the tumor. Metastatic GIST represents a successful example of molecular targeted therapy. In this comprehensive review, we discuss the epidemiology, clinical features and diagnostic modalities for GIST. We also describe treatment options for early stage, locally advanced and metastatic GIST. Indications for neoadjuvant and adjuvant therapy along with duration of therapy are also explained. A brief discussion of latest biomarkers and updates from recent meetings is also provided.

  6. Therapeutic procedures for submucosal tumors in the gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Laura Graves Ponsaing; Mark Berner Hansen

    2007-01-01

    This review is part three of three and will present an update on the therapeutic options and procedures concerning gastrointestinal (GI) submucosal tumors (SMTs). The aim of this paper is to investigate the treatments of GI SMTs and to present a case of a gastrointestinal stromal tumor (GIST). Literature searches were performed to find information on therapy for GI SMTs. Based on these searches, the optimal therapeutic procedures could be outlined. The choice of treatment of localized tumors is endoscopic resection if possible or, alternatively, laparoscopic resection or surgical resection by an open procedure. However,benign SMTs should only be excised if symptoms are present, and GISTs should be treated with particular precautions. Irresectable or recurrent GISTs may be successfully treated with the tyrosine kinase inhibitor,imatinib.

  7. Gastric schwannoma: a benign tumor often misdiagnosed as gastrointestinal stromal tumor

    Directory of Open Access Journals (Sweden)

    Apurva S. Shah

    2015-10-01

    Full Text Available Gastric schwannomas are rare mesenchymal tumors that arise from the nerve plexus of gut wall. They present with nonspecific symptoms and are often detected incidentally. Preoperative investigation is not pathognomic and many are therefore misdiagnosed as gastrointestinal stromal tumors. We report a rare case of a 37-year old woman who underwent laparotomy for complex bilateral ovarian cyst with resection of gastric-gastrointestinal stromal tumor preoperatively, but confirmed to have a gastric schwannomas postoperatively. This case underscores the differential diagnosis of submucosal, exophytic gastric mass as schwannoma.

  8. A gastrointestinal stromal tumor of the duodenum masquerading as a pancreatic head tumor

    Institute of Scientific and Technical Information of China (English)

    Sung Ho Kwon; Jung Woo Shin; Neung Hwa Park; Do Ha Kim; Hee Jeong Cha; Seok Won Jung; Byung Chul Kim; Jae Serk Park; In Du Jeong; Jong Hwa Lee; Yang Won Nah; Sung Jo Bang

    2007-01-01

    Gastrointestinal stromal tumor (GIST) represents the most common kind of mesenchymal tumor that arises from the alimentary tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor showing CD117 (c-kit protein) positivity at immunohistochemistry.Throughout the whole length of the gastrointestinal tract, GIST arises most commonly from the stomach followed by the small intestine, the colorectum, and the esophagus. Only 3%-5% of GISTs occur in the duodenum, and especially, if GIST arises from the C loop of the duodenum, it can be difficult to differentiate from the pancreas head mass because of its anatomical proximity. Here, we report a case of duodenal GIST,which was assessed as a pancreatic head tumor preoperatively.

  9. Gastrointestinal Stromal Tumors, Somatic Mutations and Candidate Genetic Risk Variants

    OpenAIRE

    Katie M O'Brien; Irene Orlow; Antonescu, Cristina R.; Karla Ballman; Linda McCall; Ronald DeMatteo; Engel, Lawrence S.

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated w...

  10. Reliability of nutritional assessment in patients with gastrointestinal tumors.

    Science.gov (United States)

    Poziomyck, Aline Kirjner; Fruchtenicht, Ana Valeria Gonçalves; Kabke, Georgia Brum; Volkweis, Bernardo Silveira; Antoniazzi, Jorge Luiz; Moreira, Luis Fernando

    2016-01-01

    Patients with gastrointestinal cancer and malnutrition are less likely to tolerate major surgical procedures, radiotherapy or chemotherapy. In general, they display a higher incidence of complications such as infection, dehiscence and sepsis, which increases the length of stay and risk of death, and reduces quality of life. The aim of this review is to discuss the pros and cons of different points of view to assess nutritional risk in patients with gastrointestinal tract (GIT) tumors and their viability, considering the current understanding and screening approaches in the field. A better combination of anthropometric, laboratory and subjective evaluations is needed in patients with GIT cancer, since malnutrition in these patients is usually much more severe than in those patients with tumors at sites other than the GIT. RESUMO Pacientes com neoplasia gastrointestinal e desnutridos são menos propensos a tolerar procedimentos cirúrgicos de grande porte, radioterapia ou quimioterapia. Em geral, apresentam maior incidência de complicações, como infecção, deiscência e sepse, o que aumenta o tempo de internação e o risco de morte, e reduz a qualidade de vida. O objetivo desta revisão é abordar os prós e contras de diferentes pontos de vista que avaliam risco nutricional em pacientes com tumores do Trato Gastrointestinal (TGI) e sua viabilidade, considerando o atual entendimento e abordagens de triagem neste campo. Melhor combinação de avaliações antropométricas, laboratoriais e subjetivas se faz necessária em pacientes com câncer do TGI, uma vez que a desnutrição nestes pacientes costuma ser muito mais grave do que naqueles indivíduos com tumores em outros sítios que não o TGI.

  11. Management of gastrointestinal stromal tumor: The lmatinib era and beyond

    Directory of Open Access Journals (Sweden)

    P M Parikh

    2013-01-01

    Full Text Available The availability of imatinib followed by other tyrosine kinase inhibitors (TKIs has dramatically altered the outcome of gastrointestinal stromal tumor (GIST. Patients with advanced or poor risk disease can now expect survival measured in years instead of months. An experienced multi disciplinary team (MDT will be able to personalize therapy to ensure maximum benefit. This review will provide the updated information and finer points regarding state of the art management of GIST with the use of imatinib and other TKIs.

  12. A case of simultaneous triple primary gastrointestinal tumor

    Institute of Scientific and Technical Information of China (English)

    Xinglong Qu; Yu Han; Yi Zhang; Bing Wang

    2014-01-01

    Multiple primary carcinoma which is the same organ of the same patient or multiple organs, tissues has occurred two or more than two kinds of the primary malignant tumor. Al cancer at the same time or 6 months from diagnosis is caled simultaneous multiple primary carcinoma. In this case the patient sufering from cancer including rectal cancer, colon cancer and appendix gastrointestinal stromal tumor(GIST) three primary carcinoma, is simultaneous multiple primary carcinoma and it’s extremely rare on the clinical cases. This report address that the incidence of the patient with operation and pathological diagnosis.

  13. Gastrointestinal stromal tumor of rectum- a case report

    Directory of Open Access Journals (Sweden)

    Madhuri S.Kate

    2012-11-01

    Full Text Available Gastrointestinal stromal tumor (GIST is an uncommon neoplasm of GI tract with rectum being rare site. Biopsy of the lesion and immunohistochemistry (IHC confirms the diagnosis. Complete surgical resection is the principal curative procedure. Chemotherapy with Imatinib alone show cure in intermediate risk rectal GIST. We describe a case of a 45-year-old male with per rectal bleeding and generalized weakness. CT scan revealed rectal mass with metastasis in the right lobe of the liver. Rectal biopsy revealed intermediate grade tumor GIST which was confirmed on IHC (CD117 and CD34. Imatinib chemotherapy alone had good symptomatic improvement at 4 months of follow up.

  14. Gastric Glomus Tumor: A Rare Cause of Upper Gastrointestinal Bleeding

    Directory of Open Access Journals (Sweden)

    Yoshinori Handa

    2015-01-01

    Full Text Available A 24-year-old woman was referred to our department because of melena. These symptoms combined with severe anemia prompted us to perform an emergency upper endoscopy, which showed bleeding from an ulcerated 30 mm submucosal tumor in the gastric antrum. A computed tomography scan revealed a homogeneously enhanced mass, and endoscopic ultrasonography identified a well-demarcated mass in the third and fourth layers of the gastric wall. Because analysis of the possible medical causes remained inconclusive and the risk of rebleeding, laparoscopy-assisted gastric wedge resection was performed after administration of 10 units of red cell concentrate. Histological and immunohistological analysis revealed the tumor to be a gastric glomus tumor. Gastric submucosal tumors remain challenging to diagnose preoperatively as they show a variety of radiologic and clinicopathologic features and are associated with the risk of bleeding upon biopsy, as is indicated in the guidelines for gastric submucosal tumors. Gastric glomus tumors characteristically present with exsanguinating gastrointestinal hemorrhaging that often requires blood transfusion. Additionally, gastric submucosal tumors typically occur in elderly patients; however, this case involved a young patient who was 24 years old. Here, we describe this case in order to identify features that may aid in early differentiation of gastric submucosal tumors.

  15. Sensory testing of the human gastrointestinal tract.

    NARCIS (Netherlands)

    Brock, C.; Arendt-Nielsen, L.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and mo

  16. Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection

    Institute of Scientific and Technical Information of China (English)

    A Zoufaly; S Schmiedel; AW Lohse; J van Lunzen

    2007-01-01

    Diffuse intestinal Kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge.We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 (HHV8) and the diagnosis had to be changed to diffuse intestinal Kaposi's sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi's sarcoma should be determined, as distinct treatment is indicated.

  17. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    DEFF Research Database (Denmark)

    Paiva, Carlos Eduardo; Moraes Neto, Francisco Alves; Agaimy, Abbas

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms, either synchronously or metachronously. In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman...... with no evidence of tuberous sclerosis. A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature. Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small...... incidental hepatic PEComa and a high risky extramural gastric GIST, respectively. The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms. To our knowledge, this is the first report of PEComa in a patient with GIST. Hepatic lesions detected synchronously...

  18. Gastrointestinal stromal tumor in an XYY/XY male.

    Science.gov (United States)

    Limacher, Jean-Marc; Girard-Lemaire, Françoise; Jeandidier, Eric; Chenard-Neu, Marie-Pierre; Kassem, Maysoun; Flori, Elisabeth; Bergerat, Jean-Pierre

    2002-03-01

    A 32-year-old patient was diagnosed with a gastrointestinal stromal tumor of the small bowel. The pathologic diagnosis was confirmed by positive immunochemistry against CD34, and against CD117, the tyrosine-kinase c-kit. We performed a karyotypic analysis on the basis of the patient's tall stature and speech difficulties. One hundred thirty-two metaphases were obtained on PHA-stimulated peripheral blood; 123 of them presented an extra chromosome Y. Fluorescence in situ hybridization using a Y satellite III probe showed the presence of a sole copy of chromosome Y in the tumor cells precluding a direct relationship between the extra chromosome Y and the initiation of the tumor. This is, to our knowledge, the second occurrence of a nonhematologic malignancy reported in this genetic disorder. A review of the malignancies observed in men with the XYY constitution is presented.

  19. Tumores del estroma gastrointestinal: Estudio retrospectivo de 43 casos Gastrointestinal stromal tumors: a retrospective study of 43 cases

    Directory of Open Access Journals (Sweden)

    S. Alberto

    2008-11-01

    Full Text Available Introducción: los tumores del estroma gastrointestinal (GIST son poco frecuentes, con una incidencia de 10 a 20 casos por millón de habitantes y año. Aparecen en todo el tubo digestivo, mesenterio o epiplón adyacente; siendo más frecuentes en el estómago (60-70%; también pueden aparecer en el intestino delgado (20-25%, colon y recto (5% y esófago (Background: gastrointestinal stromal tumors (GISTs are rare (10 to 20/million. They exist in the whole digestive system and its surroundings, and are most common in the stomach (70%, followed by the small intestine (20-25%, colon and rectum (5%, and esophagus (< 5%. Their clinical presentation varies from small, incidentally found nodules to large and aggressive tumors. Nowadays GISTs are classified according to Fletcher's classification. Objective: to review the features of our GIST population. Methods: a retrospective study of GIST patients identified by immunohistochemical criteria, from 1997 to December 2007, and classified according to Fletcher's criteria. Results: 43 patients were included (24 men, 19 women with a mean age of 62.7 years. Gastric GISTs (20 cases, 46.5%, small intestine GISTs (18 cases, 41.9%; in 5 cases metastases of occult tumors were found. Eighteen cases had no symptoms. Tumors were classified according to Fletcher's criteria as high-risk (n = 19, intermediate-risk (n = 7, low-risk (n = 12, and indeterminate-risk (n = 5. Death occurred in 10 patients, and 13 patients had metastatic disease. Conclusions: our results are in accordance with the world literature, in which a majority of cases are men with gastric tumors. The 5-year survival rate was 42%. Fletcher's criteria were easily applicable criteria and could predict tumor behavior.

  20. Hemorragia digestiva provocada por tumor estromal gastrointestinal avançado de duodeno Gastrointestinal hemorrhage caused by advanced duodenal gastrointestinal stromal tumor

    Directory of Open Access Journals (Sweden)

    Ruy Jorge Cruz Jr

    2007-12-01

    Full Text Available INTRODUÇÃO: O tumor estromal gastrointestinal (GIST é neoplasia pouco freqüente, sendo rara a combinação de acometimento duodenal e hemorragia digestiva, por isso apresenta-se este relato. RELATO DO CASO: Homem de 64 anos admitido com quadro de dor abdominal, melena e tumoração palpável em epigástrio e hipocôndrio esquerdo, sendo notado um tumor de paredes espessadas e conteúdo cístico na tomografia computadorizada de abdome, em topografia de cauda pancreática. Encontrado na laparotomia de urgência tumor em quarta porção duodenal com invasão de cólon em ângulo esplênico, sendo realizada ressecção em bloco do duodeno acometido, segmento de cólon transverso e descendente, com boa evolução pós-operatória. Diagnosticado por imunoistoquímica GIST de duodeno com invasão de parede colônica, sendo o tratamento complementado com mesilato de imatinib. CONCLUSÃO: A hemorragia digestiva é uma das possíveis complicações do GIST. Apenas o tratamento cirúrgico precoce é capaz de prevenir as graves complicações do choque hemorrágico.BACKGROUND: Gastrointestinal stromal tumor (GIST represents an uncommon form of neoplasm. The combination of duodenal GIST and gastrointestinal bleeding consist of a rare presentation for such tumors. AIM: To report duodenal GIST case complicated by gastrointestinal bleeding. CASE REPORT: A 64-year-old male was admitted presenting abdominal pain, melena and a palpable mass in epigastrium and left upper abdomem regions. CT scan reveled a thick wall tumor containing cystic content in the pancreatic tail topography. At emergency laparotomy, a tumor in the fourth portion of the duodenum presenting colonic invasion in splenic flexure was found. En-bloc resection of the tumor was carried out, included the fourth portion of the duodenum and the transverse and descending colon, without postoperative complications. Immunohistochemical staining of the resected specimen confirmed the diagnosis of

  1. Coexistence of gastrointestinal stromal tumor, esophageal and gastric cardia carcinomas.

    Science.gov (United States)

    Zhou, Yong; Wu, Xu-Dong; Shi, Quan; Jia, Jing

    2013-03-28

    Gastric gastrointestinal stromal tumor (GIST), esophageal squamous cell carcinoma and gastric cardia adenocarcinoma are distinct neoplasms originating from different cell layers; therefore, simultaneous development of such carcinomas is relatively rare. Auxiliary examinations revealed coexistence of esophageal and gastric cardia carcinoma with lymph node metastasis in a 77-year-old man. Intraoperatively, an extraluminal tumor (about 6.0 cm × 5.0 cm × 6.0 cm) at the posterior wall of the gastric body, a tumor (about 2.5 cm × 2.0 cm) in the lower esophagus, and an infiltrative and stenosing tumor (about 1.0 cm × 2.0 cm) in the gastric cardia were detected. Wedge resection for extraluminal gastric tumor, radical esophagectomy for lower esophageal tumor, and cardiac resection with gastroesophageal (supra-aortic arch anastomoses) were performed. Postoperative histological examination showed synchronous occurrence of gastric GIST, esophageal squamous cell carcinoma, and gastric cardia adenocarcinoma. Furthermore, immunohistochemistry indicated strong staining for c-Kit/CD117, Dog-1, Ki-67 and smooth muscle, while expression of S-100 and CD34 was negative.

  2. Radiotherapy in the treament of gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Rebecca C. Heintzelman

    2011-10-01

    Full Text Available Gastrointestinal stromal tumors (GIST are uncommon mesenchymal tumors of the gastrointestinal tract. Up to one-third of GISTs are malignant with a high rate of metastasis. Surgical resection is the mainstay of care for patients with resectable disease. Imatinib mesylate, a selective tyrosine kinase inhibitor, is the current standard of care for GISTs that cannot be completely resected or in cases of metastatic GIST. Although often overlooked, radiation therapy is a viable option for select patients with GIST. We report the case of a patient with unresectable GIST who was treated with local radiotherapy and achieved longterm response. We also present a review of the literature regarding the use of radiotherapy in the treatment of GIST. GIST has been shown to be a radiosensitive tumor. Radiotherapy can offer long-term local control and should be considered in the adjuvant or palliative setting. The role of radiotherapy delivered concurrently with imatinib in the treatment of GIST may warrant further investigation.

  3. Giant Rectal Gastrointestinal Stromal Tumors: A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    C. Dickhoff

    2008-03-01

    Full Text Available Giant gastrointestinal stromal tumors (GISTs of the rectum are rare and often difficult to remove surgically. At the time metastases are found, GISTs are considered to be incurable and until recently no adequate therapy was of any value for these patients. Recently, imatinib was introduced: a signal transducing inhibitor acting specifically on the KIT-tyrosine kinase, which can be used to downsize giant GIST (neo-adjuvant before surgery or induce stable disease in case of metastases with few minor side-effects. Two patients with giant rectal GIST are presented, one of which was treated before the imatinib era, the other when imatinib was available.

  4. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Sarsenov, Dauren; Tırnaksız, Mehmet Bülent; Doğrul, Ahmet Bülent; Tanas, Özlem; Gedikoglu, Gökhan; Abbasoğlu, Osman

    2015-01-01

    Heterotopic pancreas is a relatively common variant of foregut embryologic dystopia that can be described as pancreatic tissue found outside the normal anatomic location, being independent from vascular supply of normal pancreas. Having all features of pancreatic tissue except for the major duct structures, this ectopic tissue may be clinically recognized when pathologic changes take place. Inflammation, hemorrhagic or obstructive states, and eventually malignancy-related problems may become a diagnostic challenge for clinician and finally lead to consequences of misdiagnosis. In this article we will discuss a case of heterotopic pancreatic tissue located in gastric cardia, which was diagnosed preoperatively as gastrointestinal stromal tumor. PMID:25785332

  5. Imatinib and gastrointestinal stromal tumor (GIST): a selective targeted therapy Imatinib y tumor del estroma gastrointestinal (GIST): un tratamiento selectivo frente a una diana molecular

    OpenAIRE

    A Fernández; Aparicio, J.

    2004-01-01

    Gastrointestinal stromal tumors are the most frequent mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by an anomalous receptor for a growth factor with tyrosine-kinase activity (c-kit). This anomaly causes a permanent activation of the receptor and uncontrolled cell growth. These tumors show a poor response to traditional chemotherapy drugs, and are thus associated with low survival in cases of advanced disease. Imati...

  6. [Gastrointestinal human myiasis caused by Eristalis tenax].

    Science.gov (United States)

    Kun, M; Kreiter, A; Semenas, L

    1998-08-01

    The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae) according to Hartley (1961) and Organización Panamericana de la Salud keys (1962). These 2 cases of human gastrointestinal myiasis were the first to be registered in Bariloche (Patagonia, Argentina) and their characteristics were similar to those described for this species in other parts of the world. The lack of specific control measures in the domestic water supply system was the most probable cause of the infestation. This event extends the distribution of E. tenax and human gastrointestinal myiasis in South America to 41 degrees 03' S.

  7. Anorectal Gastrointestinal Stromal Tumor: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Sanjeev Singhal

    2013-01-01

    Full Text Available Gastrointestinal stromal tumors or “GIST” are mesenchymal neoplasms expressing KIT(CD117 tyrosine kinase and showing the presence of activating mutations in KIT or PDGFRα (platelet-derived growth factor alpha. GIST of anal canal is an extremely rare tumor, accounting for only 3% of all anorectal mesenchymal tumors and 0.1–0.4% of all GIST. GIST with large tumor size and high mitotic activity are highly malignant, but the biological behavior of anorectal GIST is less clear. Abdominoperineal resection (APR or conservative surgery is the best treatment option. Imatinib mesylate, a tyrosine kinase inhibitor, has shown promising results in its management. We present a case of anorectal GIST diagnosed by computed tomography (CT scan, magnetic resonance imaging (MRI, and colonoscopy with biopsy. The patient underwent abdominoperineal resection (APR and was confirmed on histopathology to have anal canal GIST with tumor size more than 5 cm in maximum dimension and mitotic figures more than 5/50 high power field (HPF. The CD117—immunoreactive score—was 3+ in spindled cells. Therefore the patient was put on adjuvant imatinib mesylate 400 mg daily.

  8. Endogenous and exogenous fluorescence of gastrointestinal tumors: initial clinical observations

    Science.gov (United States)

    Borisova, Ekaterina; Plamenova, Lilia; Keremedchiev, Momchil; Vladimirov, Borislav; Avramov, Latchezar

    2013-03-01

    The limitations of standard endoscopy for detection and evaluation of cancerous changes in gastrointestinal tract (GIT) are significant challenge and initiate development of new diagnostic modalities. Therefore many spectral and optical techniques are applied recently into the clinical practice for obtaining qualitatively and quantitatively new data from gastrointestinal neoplasia with different level of clinical applicability and diagnostic success. One of the most promising approaches is fluorescence detection using naturally existing fluorescent molecules or added fluorescent markers. Deltaaminolevulinic acid / protoporphyrin IX is applied for exogenous fluorescent tumor detection in the upper part of gastrointestinal tract. The 5-ALA is administered per os six hours before measurements at dose 20mg/kg weight. Highpower light-emitting diode at 405 nm is used as a source and the excitation light is passed through the light-guide of standard video-endoscopic system to obtain 2-D visualization. Both kinds of spectra - autofluorescence signals and protoporphyrin IX signal are recorded and stored using a fiber-optic microspectrometer, as in endoscopy instrumental channel a fiber is applied to return information about fluorescence signals. In such way 1-D detection and 2-D visualization of the lesions' fluorescence are received. The results from in vivo detection show significant differentiation between normal and abnormal tissues in 1-D spectroscopic regime, but only moderate discrimination in 2-D imaging.

  9. Intra-cranial metastasis of gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    WONG Chun-sing; CHU Yiu-ching

    2011-01-01

    With the evolution of immunochemical staining techniques and better imaging modalities with better image resolution and whole body coverage,gastrointestinal stromal tumor (GIST),the most common mesenchymal tumor of the gastrointestinal tract,is often encountered in clinical practice.Metastasis is common with malignant GIST and can be found in up to 50% of patients at presentation.Liver and peritoneum are the two most common sites of metastasis and accounted for 95% of cases.Lymphatics,bone and lung metastasis are rare.Malignant GIST with intracranial metastasis is even rarer,with only a few cases reported in the literature,and most of these had earlier metastasis elsewhere.Radiological features for GISTs are not specific but it does contribute to confirming early and accurate diagnosis of malignant GISTs by judging the tumor size,enhancement pattern and the invasion of adjacent structures.We report a case of a 26-year-old male with metastatic GIST to the liver and subsequently to the brain and skull vault.This is the first case reported in our locality and he is the youngest patient reported with this disease entity.The clinical progress,radiological features and the role of imaging will be discussed further in this paper.The radiological and clinical features of the primary tumor will specifically be addressed.The purpose of this paper is to enrich the current database of this rare disease entity and to alert both radiologists and clinicians about the imaging features of GIST with intracranial metastasis.

  10. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Seshadri Ramakrishnan

    2009-01-01

    Full Text Available Aim : To study the role of neoadjuvant imatinib mesylate in downsizing tumors in patients with locally advanced nonmetastatic gastrointestinal stromal tumors (GISTs, thus improving the possibility of complete resection. Materials and Methods : We used neoadjuvant imatinib in six patients with locally advanced GISTs, at a dose of 400 mg daily, given orally in all patients for a median period of 3.5 months (range 1-20 months. All patients had a computerized tomography scan (CT scan once before starting the treatment and a repeat CT scan 1 month after starting imatinib. Some patients had another CT scan done at 3 months. The tumor volume was calculated using the formula V=4/3 πr 3 . Results : Following imatinib therapy, the median reduction in the tumor volume was 40% (range 20-50%. Four of the six patients underwent successful complete resection of the tumor following neoadjuvant imatinib for a median period of 2 months, and are disease free after a median follow-up of 10.5 months (range 3-20 months. Two patients in whom the tumors were deemed to be operable after downsizing refused surgery and are continuing imatinib. Imatinib did not produce serious toxicity in any patient. Conclusion : Neoadjuvant imatinib can be used successfully in patients with locally advanced nonmetastatic GISTs to improve the rates of complete resection and reduce the chance of tumor spill. The optimal duration of neoadjuvant treatment needs to be tailored based on response assessment at frequent intervals to identify the ideal window period for surgery.

  11. Diagnostic evaluatuin of gastrointestinal tumors; Diagnostik bei Tumoren im Gastrointestinaltrakt

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    Linke, R.; Tatsch, K. [Ludwig-Maximilians-Univ. Muenchen (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    1998-07-01

    Prior to surgery of gastrointestinal tumors exact information about tumor localization, extent and possible infiltration in adjacent structures are important. The task for radiological and scintigraphic methods is predominantly the preoperative tumor staging. The upper (esophagus, stomach, duodenum) and the lower (colon, rectum) gastrointestinal tract should be routinely investigated by endoscopy and endosonography. CT or MRI imaging may add information about tumor extent, infiltration in adjacent structures and pathologically enlarged lymph nodes. The latter may be detected with similar or higher sensitivity by PET as well. Furthermore, with PET it is possible to differentiate a tumor recurrence from postoperative scar tissue earlier than with conventional morphological imaging techniques, for example in colorectal cancer. Liver tumors should primarily be inspected sonographically followed by an MRI scan if dignity is uncertain. The receptor scintigraphy with radioactive ligands allows to further characterize a detected tumor. Benigne liver lesions can be distinguished from malignant tumors (metastasis, hepatocellular carcinoma [HCC]) by the neogalactoalbumin-(NGA-)scintigraphy, because NGA binds exclusively to the liver galactose receptors of normally functioning hepatocytes. For the differentiation between liver metastasis and HCC insulin scintigraphy can be used, since insulin binds significantly in HCC due to an overexpression of insulin receptors in these tumors. If a malignant process is suspected, additionally CT-arterioportography may be recommended, because this newer radiological technique is capable to visualize lesions smaller than 1 cm. In such cases PET is sensitive as well and due to increased glucose metabolism even small foci can be detected with comparably high sepcificity. The method of choice for the detection of a pancreatic tumor is endoscopic sonography. In most cases the dignity of the tumor can be verified by ERCP, but sometimes it is very

  12. A predominant pelvic gastrointestinal stromal tumor (GIST) mass observed on Tc-99m red blood cell gastrointestinal bleeding scintigraphy.

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    Sood, Ravi; Tee, Shang Ian

    2011-08-01

    A 51-year-old woman presented with recurrent bleeding per rectum. Her earlier endoscopies were negative. Tc-99m RBC GI bleeding scintigraphy was performed. It demonstrated an apparent hypervascular pelvic mass, and active small bowel bleeding. Based on scintigraphic finding of a predominant pelvic mass indicating tumor, CT of the abdomen and pelvis was performed for further gastrointestinal bleeding localization work up instead of an invasive angiography or endoscopy, which detected a small bowel tumor in the pelvis. A small bowel gastrointestinal stromal tumor was resected subsequently.

  13. P16 overexpression in BRAF-mutated gastrointestinal stromal tumors.

    Science.gov (United States)

    Shi, Shan-Shan; Wang, Xuan; Xia, Qiu-Yuan; Rao, Qiu; Shen, Qin; Ye, Sheng-Bin; Li, Rui; Shi, Qun-Li; Lu, Zhen-Feng; Ma, Heng-Hui; Zhou, Xiao-Jun

    2017-02-01

    The aims of this study were to analyze the histopathology, immunophenotype, molecular features, and prognosis in cases of BRAF-mutated gastrointestinal stromal tumors (GISTs) and to examine the p16 expression in these tumors, and further discuss its effects on tumor formation and progression. In all, 283 GIST cases (201 KIT mutants, 12 PDGFRA mutants and 70 wild-type) from the 2010 to 2014 surgical pathology files of the Department of Pathology at Nanjing Jinling Hospital were analyzed for mutations in BRAF exon 15. Patient follow-up and clinical data were collected if available in the medical records. To determine the clinicopathological features and potential molecular mechanism, the authors examined 10 BRAF-mutated GIST cases for KIT, DOG1, SMA, desmin, S-100, Ki-67 and p16 expression. The authors identified 10 cases (3.5%) of BRAF (V600E) mutations in a series of 283 primary GISTs, without KIT (exons 9, 11, 13, 17) or PDGFRA (exons 12, 18) gene mutations. All 10 cases exhibited spindle-cell features, and the morphology and immunophenotype of these cases were no different from those in cases of KIT-mutated GISTs. The clinical results indicated that BRAF-mutated GISTs tended to occur more frequently in females (7/10), older individuals (mean age, 54.9 years) and the stomach (7/10), and that these tumors were low risk and exhibited low recurrence and mortality rates. Two different forms of p16 were identified, which presented with simultaneously strong and diffuse nuclear and cytoplasmic expression patterns. GISTs with the BRAF V600E mutation are relatively benign tumors with a distinctive molecular mechanism. The expression of the nuclear and cytoplasmic forms of p16 represent two independent mechanisms, and both seemed to control proliferation in response to oncogenic stimuli, protecting the cell from malignant transformation in BRAF-mutated GISTs.

  14. Clinical and pathological studies of borderline gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    SHI Yuan; TAN Yun-shan; ZHU Xiong-zeng; HOU Ying-yong; LU Shao-hua; ZHOU Yang; XU Jian-fang; JI Yuan; HOU Jun; XU Chen; LIU Ya-lan

    2010-01-01

    Background Borderline gastrointestinal stromal tumors (GISTs) are intermediate tumors between benign and malignant variants; however, the clinical and pathological features of borderline GISTs remain poorly defined. This study aimed to characterize GISTs and to identify a set of borderline criteria for practical use.Methods Medical records and specimens of 840 patients from 12 hospitals were retrospectively examined. Totally 485 and 76 patients with any of the parameters predictive of either malignant or benign tumors were excluded. The Kaplan-Meier method was used to calculate disease-free survival and overall survival rates.Results Among the remaining 279 borderline GIST patients, 223 were followed up for 1 to 31.48 years. Two patients developed local recurrence, and both were cured by subsequent operations alone. The 5-year disease-free survival and overall survival rates were 99% and 100%, respectively. Morphologically, borderline GISTs typically exhibited moderate cellularity, and subsets of them also showed moderate atypia, low mitotic activities, or large tumor size. According to the National Institutes of Health (NIH) consensus criteria, the risk levels of the 279 GISTs were classified to be very low to high. However, the disease-free survival rates were not significantly different among these risk groups (P=0.681).Conclusions The proposed borderline GIST criteria in the current study may complement the existing NIH criteria,based primarily on tumor size and mitotic count, in the evaluation of the biological behaviors of GISTs. Since a subset of borderline GISTs with high risk level showed favorable outcome, the introduction of the borderline GIST system may avoid overdiagnosis and over therapy.

  15. Pheochromocytoma and gastrointestinal stromal tumors in patients with neurofibromatosis type I

    NARCIS (Netherlands)

    Vlenterie, M.; Flucke, U.E.; Hofbauer, L.C.; Timmers, H.J.L.M.; Gastmeier, J.; Aust, D.E.; Graaf, W.T. van der; Wesseling, P.; Eisenhofer, G.; Lenders, J.W.M.

    2013-01-01

    BACKGROUND: Neurofibromatosis I may rarely predispose to pheochromocytoma and gastrointestinal stromal tumors. METHODS: A 59-year-old woman with neurofibromatosis I presented with pheochromocytoma of the left adrenal gland. During surgery, 3 gastrointestinal stromal tumors adjacent to the stomach an

  16. Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy.

    Science.gov (United States)

    Hardt, Philip D; Ewald, Nils

    2008-09-01

    Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase. In the last few years, much attention has been paid to this novel tumor marker that can be determined in EDTA-plasma and in the feces. It has been used in diagnosis and surveillance of a variety of malignant diseases. As compared with the established tumor markers, Tumor M2-PK in EDTA-plasma proves to have at least equal sensitivity in pancreatic, gastric, esophageal, colorectal and cholangiocellular cancer. In combination with established tumor markers, EDTA-plasma M2-PK is a useful tool in diagnosis and surveillance of gastrointestinal tumors. In colorectal cancer, M2-PK in EDTA-plasma even proves superiority as compared with CEA. Fecal Tumor M2-PK testing resembles a good noninvasive screening parameter for colorectal cancer with a reported sensitivity of 68.8-91.0% and a specificity of 71.9-100%. It is superior to fecal occult blood testing in colorectal cancer screening. Since it is effective, easy to handle and bears rather low costs, fecal Tumor M2-PK testing is recommended for large-scale CRC screening.

  17. Multimodal treatment of gastrointestinal tract tumors: consequences for surgery.

    Science.gov (United States)

    Siewert, J Rüdiger; Stein, Hubert J; von Rahden, Burkhard H A

    2005-08-01

    Formerly an exclusive business of surgery, gastrointestinal (GI) tumors are nowadays increasingly approached with multimodal strategies. Neoadjuvant concepts have had a particularly far-reaching impact on surgery and have contributed to improved survival. Modern pre-treatment staging and risk assessment provide the basis for decision on one of three general treatment concepts (1) Early cancers, confined to the mucosal/submucosal layers, are approached with primary surgery, without prior antineoplastic therapy. (2) Systemically metastasized tumors receive merely palliative treatment. (3) Locally advanced cancers are increasingly approached with neoadjuvant strategies. The benefit from these preoperative protocols is proven for diverse entities, but is evidently confined to a specific subgroup patients, i.e., the responders to neoadjuvant treatment. These are the ones benefiting most from subsequent surgical resection, which is required to ensure complete removal of the residual tumor tissue, as complete tumor regression occurs very rarely and cannot be proven without a specimen. The fact that responders will benefit and non-responders will not benefit or will even deteriorate during the neoadjuvant treatment makes early response prediction most demanding. An amazing new approach is the use of position emission tomography with fluro-desoxyglucose (FDG-PET) to assess the "metabolic response," which is possible as early as 14 days after initiation of the neoadjuvant protocol. This strategy offers the chance for modulating the surgical approach in accord i.e., with such metrobolic response termination of the protocol and proceeding to resection in the case of nonresponse. The future of GI cancer surgery is multimodal therapy in a response-based fashion and requires reponse-based trials for further evaluation.

  18. Perivascular epithelioid cell tumor of the liver coexisting with a gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    Carlos Eduardo Paiva; Francisco Alves Moraes Neto; Abbas Agaimy; Maria Aparecida Custódio Domingues; Silvia Regina Rogatto

    2008-01-01

    Approximately 10% of patients with gastrointestinal stromal tumors (GIST) develop other neoplasms,either synchronously or metachronously.In this report we describe coexistence of a gastrointestinal stromal tumor and a hepatic perivascular epithelioid cell tumor (PEComa) in a 51-year-old woman with no evidence of tuberous sclerosis.A subcapsular hepatic nodule (0.8 cm in diameter) was found during surgery for symptomatic gastric neoplasm (15 cm in diameter) arising from the lesser curvature.Both tumors revealed histomorphological and immunohistochemical features confirming a diagnosis of a small incidental hepatic PEComa and a high risky extramural gastric GIST,respectively.The patient remained disease-free 25 mo after surgery with no evidence of tumor recurrence or new neoplasms.To our knowledge,this is the first report of PEComa in a patient with GIST.Hepatic lesions detected synchronously or metachronously in patients with GISTs may represent histogenetically distinct lesions and should be sampled to confirm or exclude metastatic GISTs.

  19. Glutathione Levels in Human Tumors

    Science.gov (United States)

    Gamcsik, Michael P.; Kasibhatla, Mohit S.; Teeter, Stephanie D.; Colvin, O. Michael

    2013-01-01

    This review summarizes clinical studies in which glutathione was measured in tumor tissue from patients with brain, breast, gastrointestinal, gynecological, head and neck and lung cancer. Glutathione tends to be elevated in breast, ovarian, head and neck and lung cancer and lower in brain and liver tumors compared to disease-free tissue. Cervical, colorectal, gastric and esophageal cancers show both higher and lower levels of tumor glutathione. Some studies show an inverse relationship between patient survival and tumor glutathione. Based on this survey, we recommend approaches that may improve the clinical value of glutathione as a biomarker. PMID:22900535

  20. Gastrointestinal Tumor Board: An Evolving Experience in Tehran Cancer Institute

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    Peiman Haddad

    2013-04-01

    Full Text Available Gastrointestinal (GI cancers are a significant source of morbidity and mortality in Iran, with stomach adenocarcinoma as the most common cancer in men and the second common cancer in women. Also, some parts of Northern Iran have one of the highest incidences of esophageal cancer in the world. Multi-disciplinary organ-based joint clinics and tumor boards are a well-recognized necessity for modern treatment of cancer and are routinely utilized in developed countries, especially in major academic centres. But this concept is relatively new in developing countries, where cancer treatment centres are burdened by huge loads of patients and have to cope with a suboptimum availability of resources and facilities. Cancer Institute of Tehran University of Medical Sciences is the oldest and the only comprehensive cancer treatment centre in Iran, with a long tradition of a general tumor board for all cancers. But with the requirements of modern oncology, there has been a very welcome attention to sub-specialized organ-based tumor boards and joint clinics here in the past few years. Considering this, we started a multi-disciplinary tumor board for GI cancers in our institute in early 2010 as the first such endeavor here. We hereby review this 2-year evolving experience. The process of establishment of a GI tumor board, participations from different oncology disciplines and related specialties, the cancers presented and discussed in the 2 years of this tumor board, the general intents of treatment for the decisions made and the development of interest in this tumor board among the Tehran oncology community will be reviewed. The GI tumor board of Tehran Cancer Institute started its work in January 2010, with routine weekly sessions. A core group of 2 physicians from each surgical, radiation and medical oncology departments plus one gastroenterologist, GI pathologist and radiologist was formed, but participation from all interested physicians was encouraged. An

  1. OUR EXPERIENCE WITH RARE PRESENTATION OF GASTROINTESTINAL STROMAL TUMORS IN A RURAL MEDICAL COLLEGE HOSPITAL

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    Jigar Vipul

    2013-10-01

    Full Text Available ABSTRACT : Gastrointestinal stromal tumors (GIST - are one of the most common mesenchymal tumors of the gastrointestinal tract [1 - 3% of all gastrointestinal malignancies]. Their behaviour is driven by mutations in the kit gene or PDGFRA gene and may or may not positively stain for kit. We report fo ur additional cases of a GIST presenting as an abdominal mass along with a pertinent review of the literature. All four patients received surgical resection. The mean tumor size was 10.5 with an average mitotic index of 6.25 per 50 high power fields. Three patients were disease free and one patient came with recurrence. In conclusion, symptomatic patents have an increased incidence of high - risk tumors and metastases at presentation. Adjuvant therapy with imatinib improves disease - free survival in patients w ith large abdominal GIST tumors, but no change in overall survival was noted. KEY WORD: Gastrointestinal stromal tumors; Imatinib; mitotic index;Meckel’s Diverticulum

  2. Human papillomavirus and gastrointestinal cancer: A review

    Science.gov (United States)

    Bucchi, Dania; Stracci, Fabrizio; Buonora, Nicola; Masanotti, Giuseppe

    2016-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Exposure to HPV is very common, and an estimated 65%-100% of sexually active adults are exposed to HPV in their lifetime. The majority of HPV infections are asymptomatic, but there is a 10% chance that individuals will develop a persistent infection and have an increased risk of developing a carcinoma. The International Agency for Research on Cancer has found that the following cancer sites have a strong causal relationship with HPV: cervix uteri, penis, vulva, vagina, anus and oropharynx, including the base of the tongue and the tonsils. However, studies of the aetiological role of HPV in colorectal and esophageal malignancies have conflicting results. The aim of this review was to organize recent evidence and issues about the association between HPV infection and gastrointestinal tumours with a focus on esophageal, colorectal and anal cancers. The ultimate goal was to highlight possible implications for prognosis and prevention. PMID:27672265

  3. Hubungan antara Imunoekspresi Ki-67 dan Risiko Agresivitas Tumor pada Gastrointestinal Stromal Tumor

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    Herry Yulianti

    2015-12-01

    Full Text Available Gastrointestinal stromal tumor (GIST is the most common mesenchymal tumor of the gastrointestinal tract, and arises from intestinal cells of Cajal localized in the muscular layer of the digestive tract, which functions as pacemaker cells in regulating intestinal motility. The incidence of GIST is about 3−5% of all soft tissue sarcomas. Gastrointestinal stromal tumor can occur along the gastrointestinal tract and predominantly in middle-aged and older persons, with a median age between 50 and 60 years. Histologically, there are three categories of GIST morphology such as spindle cells, epitheloid, and mixed type. A spesific marker of GIST is cluster of differentiation (CD117, which has good sensitivity and immunoreactive in 95% of GIST. The expression of Ki-67 correlates with proliferative activities and can be detected in G1, S, G2, and M phases of cell cycle but not in G0 phase. The aim of this study was to assessthe correlation between the risk of aggressive behaviors and proliferative activities as measured by Ki-67 in tumors confirmed as GIST by CD117. The method of this study was cross-sectional, performed on 29 cases of GIST from the Department of Pathology Anatomy Dr. Hasan Sadikin General Hospital/Faculty of Medicine Universitas Padjadjaran, Santo Borromeus Hospital, Immanuel Hospital, and Santosa Hospital between 2007−2012. A section from paraffin embedded tissue of 55 cases of GIST was stained with hematoxylin eosin for histological and immunohistochemical evaluations using monoclonal antibody CD117 to confirm the diagnosis of GIST. There were 29 positive cases for CD117. Further staining was performed using monoclonal antibody Ki-67. The categorized positive cells of immunoexpression of CD117 showed brown particles inside cytoplasma and the immunoexpression of Ki-67 was assessed by identification of nuclear brown staining of neoplastic cells. The result showed that there were significant correlations between the risk of tumor

  4. Gastrointestinal stromal tumor causing small bowel intussusception in a patient with Crohn's disease

    Institute of Scientific and Technical Information of China (English)

    George E Theodoropoulos; Dimitrios Linardoutsos; Dimitrios Tsamis; Paraskevas Stamopoulos; Dimitrios Giannopoulos; Flora Zagouri; Nikolaos V Michalopoulos

    2009-01-01

    We report a case of jejunoileal intussusception in a 42-year-old patient with Crohn's disease caused by a gastrointestinal stromal tumor. The patient complained of vague diffuse abdominal pain for a period of 4 mo. Intussusception was suspected at computer tomography and magnetic resonance imaging scans. Segmental resection of the small intestine was performed. Pathological examination of the surgical specimen revealed a gastrointestinal stromal tumor as well as aphthous ulcerations and areas of inflammation, which were characteristic of Crohn's disease. This is the first report of small bowel intussusception due to a gastrointestinal stromal tumor coexisting with Crohn's disease.

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

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    Bryan L. Balmadrid

    2012-01-01

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

  6. Optimizing Adherence to Adjuvant Imatinib in Gastrointestinal Stromal Tumor

    Science.gov (United States)

    Tetzlaff, Eric D.; Davey, Monica P.

    2013-01-01

    The increasing use of patient-administered oral anticancer drugs is paralleled by new challenges in maintaining treatment adherence. These challenges are particularly significant with adjuvant therapies for prevention of disease recurrence, where the benefits of ongoing treatment are not readily apparent to patients. Nurse practitioners and physician assistants (collectively referred to as advanced practitioners) play integral roles in providing education on disease and treatment to patients that can increase adherence to oral therapies and ideally improve outcomes. For patients with gastrointestinal stromal tumor (GIST), the oral targeted therapy imatinib has become the mainstay of treatment for advanced and recurrent disease and as adjuvant therapy following surgical resection. Recent data indicate significantly improved overall survival with 3 years vs. 1 year of adjuvant imatinib therapy. Continuous dosing with imatinib is needed for optimal efficacy and to limit additional health-care costs associated with management of disease progression in GIST. However, longer duration of therapy increases the risk of nonadherence. Imatinib adherence rates, as well as factors contributing to nonadherence to adjuvant therapy in routine clinical practice, are discussed in this review. Also explored are practical approaches for improving adherence to adjuvant imatinib therapy through greater patient education, in light of the increased duration of therapy in select patients. PMID:25032004

  7. Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

    Science.gov (United States)

    O'Brien, Katie M; Orlow, Irene; Antonescu, Cristina R; Ballman, Karla; McCall, Linda; DeMatteo, Ronald; Engel, Lawrence S

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs) in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT). Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836) and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836). CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively). Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic origins and

  8. Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

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    Katie M O'Brien

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs and 95% confidence intervals (CIs for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT. Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836 and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836. CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively. Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic

  9. Incidental detection of a bleeding gastrointestinal stromal tumor on Tc-99m red blood cell scintigraphy.

    Science.gov (United States)

    Santhosh, Sampath; Bhattacharya, Anish; Gupta, Vikas; Singh, Rajinder; Radotra, Bishan Dass; Mittal, Bhagwant Rai

    2012-10-01

    The role of 99m-technetium labeled red blood cell (RBC) scintigraphy in acute gastro-intestinal bleed is well-established. The authors report a case of a bleeding gastrointestinal stromal tumor (GIST) incidentally discovered on Tc-99m RBC scintigraphy.

  10. Small Submucosal Tumors of the Stomach: Differentiation of Gastric Schwannoma from Gastrointestinal Stromal Tumor with CT

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    Choi, Jin Wook; Choi, Dong Gil; Kim, Kyoung Mee; Sohn, Tae Sung; Lee, Jun Haeng; Kim, Hee Jung; Lee, Soon Jin [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-07-15

    To identify the CT features that help differentiate gastric schwannomas (GS) from small (5 cm or smaller) gastrointestinal stromal tumors (GIST) and to assess the growth rates of both tumors. We included 16 small GSs and 56 GISTs located in the stomach. We evaluated the CT features including size, contour, surface pattern, margins, growth pattern, pattern and degree of contrast enhancement, and the presence of intralesional low attenuation area, hemorrhage, calcification, surface dimpling, fistula, perilesional lymph nodes (LNs), invasion to other organs, metastasis, ascites, and peritoneal seeding. We also estimated the tumor volume doubling time. Compared with GISTs, GSs more frequently demonstrated a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs (each p < 0.05). The intralesional low attenuation area was more common in GISTs than GSs (p < 0.05). Multivariate analyses indicated that a homogeneous enhancement pattern, exophytic or mixed growth pattern, and the presence of perilesional LNs were statistically significant (p < 0.05). Tumor volume doubling times for GSs (mean, 1685.4 days) were significantly longer than that of GISTs (mean, 377.6 days) (p = 0.004). Although small GSs and GISTs show similar imaging findings, GSs more frequently show an exophytic or mixed growth pattern, homogeneous enhancement pattern, perilesional LNs and grow slower than GISTs.

  11. Imatinib and gastrointestinal stromal tumor (GIST: a selective targeted therapy Imatinib y tumor del estroma gastrointestinal (GIST: un tratamiento selectivo frente a una diana molecular

    Directory of Open Access Journals (Sweden)

    A. Fernández

    2004-10-01

    Full Text Available Gastrointestinal stromal tumors are the most frequent mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and are characterized by an anomalous receptor for a growth factor with tyrosine-kinase activity (c-kit. This anomaly causes a permanent activation of the receptor and uncontrolled cell growth. These tumors show a poor response to traditional chemotherapy drugs, and are thus associated with low survival in cases of advanced disease. Imatinib, a tyrosine kinase inhibitor, is an example of selective targeted oncologic therapy that induces improved survival in these patients. We discuss two cases of metastatic gastrointestinal stromal tumors with a good response to imatinib, and also review the pathophysiology and treatment-related outcome of this type of tumors. We include results from clinical phase-III studies.Los tumores del estroma gastrointestinal son los tumores mesenquimales más frecuentes del tracto digestivo y se originan de las células intersticiales de Cajal. Se caracterizan por presentar un receptor para el factor de crecimiento con actividad tirosin kinasa (c-kit anómalo que condiciona su activación permanente y un crecimiento celular incontrolado. Tienen una baja supervivencia en casos de enfermedad avanzada, con escasa respuesta a los agentes quimioterápicos tradicionales. El imatinib es un fármaco inhibidor de la tirosín kinasa y un ejemplo de terapia oncológica selectiva que condiciona un importante aumento en la supervivencia de estos pacientes. Se presentan 2 casos de enfermedad metastásica con buena respuesta a imatinib, así como una revisión sobre la fisiopatología y evolución en el tratamiento de este tipo de tumores, incluyendo resultados de estudios en fase III.

  12. SDHB immunohistochemistry: A useful tool in the diagnosis of Carney-Stratakis and Carney triad gastrointestinal stromal tumors

    NARCIS (Netherlands)

    J. Gaal (José); C.A. Stratakis (Constantine); M. Carney; E.R. Ball (Evan R.); E. Korpershoek (Esther); M.B. Lodish (Maya Beth); I. Levy (Isaac); P. Xekouki (Paraskevi); F.H. van Nederveen (Francien); M.A. den Bakker (Michael); M.J. O'Sullivan (Maureen); W.N.M. Dinjens (Winand); R.R. de Krijger (Ronald)

    2011-01-01

    textabstractMutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors

  13. EGFR and gastrointestinal stromal tumor: an immunohistochemical and FISH study of 82 cases.

    Science.gov (United States)

    Lopes, Lisandro F; Bacchi, Carlos E

    2007-09-01

    Gastrointestinal stromal tumor is the most common mesenchymal neoplasm of the gastrointestinal tract. Mutually exclusive KIT or platelet-derived growth factor receptor-alpha mutations are key events in gastrointestinal stromal tumor pathogenesis, and specific treatment targeting KIT/platelet-derived growth factor receptor-alpha activation is available. Epidermal growth factor receptor plays an important role in cancer biology and also constitutes a promising molecular target of therapy. Very few reports have been published in the literature about the relationship between gastrointestinal stromal tumor and epidermal growth factor receptor. The aim of this study was to investigate epidermal growth factor receptor immunohistochemical expression and epidermal growth factor receptor gene amplification in 82 consecutive gastrointestinal stromal tumor cases using tissue microarray technique. Hematoxylin- and eosin-stained sections and clinical information were reviewed, and expression of CD117 (KIT), CD34 and epidermal growth factor receptor was investigated by immunohistochemistry. Epidermal growth factor receptor gene copy number was determined using fluorescence in situ hybridization. Immunohistochemistry revealed that CD117 and CD34 were expressed in 96 and 57% of tumors, respectively. Variable epidermal growth factor receptor protein immunohistochemical overexpression was detected in 96% of gastrointestinal stromal tumor cases, but none of the 75 cases with represented tumor tissue cores and countable fluorescence signals exhibited epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. These results show that there is no correlation between epidermal growth factor receptor protein overexpression by immunohistochemistry and epidermal growth factor receptor gene amplification by fluorescence in situ hybridization. Considering that the mechanisms of epidermal growth factor receptor protein overexpression are not well understood and

  14. Effect of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors.

    Science.gov (United States)

    Hou, Lili; Xu, Lei; Shi, Yan; Gu, Fen

    2016-08-01

    To evaluate the effects of electric acupoint stimulation on gastrointestinal hormones and motility among geriatric postoperative patients with gastrointestinal tumors, and to explore an efficient and noninvasive method for postoperative recovery of bowel functions. Forty patients were randomly and evenly assigned into a regular nursing care group (RNC) and an acupoint electric stimulation group (AES). Patients in the RNC group received regular nursing care and patients in the AES group received regular nursing care plus electric stimulation of acupoints. The serum levels of gastrin (GAS), motilin (MOT), and cholecystokinin (CCK), and an electrogastrogram (EGG) of all the patients were evaluated on the first, third, and fifth day after surgery. The time to first flatus after surgery and the number of patients with side effects such as abdominal pain, abdominal distention, and diarrhea were recorded. There were significant differences between the two groups in GAS, MOT, EGG, time to first flatus, abdominal pain, abdominal distention, and diarrhea (P Electric stimulation on acupoints could increase levels of GAS and MOT, promote the recovery of gastrointestinal functions, and decrease complications among postoperative senile patients with gastrointestinal tumors.

  15. Optical imaging of breast tumors and of gastrointestinal cancer by laser-induced fluorescence.

    Science.gov (United States)

    Ebert, Bernd; Grosenick, Dirk

    2013-01-01

    Optical imaging offers a high potential for noninvasive detection of cancer in humans. Recent advances in instrumentation for diffuse optical imaging have led to new capabilities for the detection of cancer in highly scattering tissue such as the female breast. We review recent developments in the detection of breast cancer in humans by fluorescent contrast agents. So far, the unspecific contrast agents indocyanine green (ICG) and omocyanine have been applied, whereas molecular probes for direct targeted imaging of this disease are still in preclinical research. We discuss recent improvements in the differentiation of malignant and benign lesions with ICG based on its enhanced extravasation in breast cancer. Whereas fluorescence imaging in thick tissue layers is hampered by strong light scattering, tissue surfaces can be investigated with high spatial resolution. As an example for superficial tumors, lesions of the gastrointestinal tract (GI) are discussed. In these investigations, protoporphyrin IX is used as a tumor-specific (due to its strong enhancement in tumor cells) target for spectroscopic identification and imaging. We present a time-gated method for fluorescence imaging and spectroscopy with strong suppression of tissue autofluorescence and show results on patients with Barrett's esophagus and with colitis ulcerosa.

  16. Sensory testing of the human gastrointestinal tract

    Institute of Scientific and Technical Information of China (English)

    Christina Brock; Lars Arendt-Nielsen; Oliver Wilder-Smith; Asbjφrn Mohr Drewes

    2009-01-01

    The objective of this appraisal is to shed light on the various approaches to screen sensory information in the human gut. Understanding and characterization of sensory symptoms in gastrointestinal disorders is poor. Experimental methods allowing the investigator to control stimulus intensity and modality, as well as using validated methods for assessing sensory response have contributed to the understanding of pain mechanisms. Mechanical stimulation based on impedance planimetry allows direct recordings of luminal cross-sectional areas, and combined with ultrasound and magnetic resonance imaging, the contribution of different gut layers can be estimated. Electrical stimulation depolarizes free nerve endings non-selectively. Consequently, the stimulation paradigm (single, train, tetanic) influences the involved sensory nerves. Visual controlled electrical stimulation combines the probes with an endoscopic approach, which allows the investigator to inspect and obtain small biopsies from the stimulation site. Thermal stimulation (cold or warm) activates selectively mucosal receptors, and chemical substances such as acid and capsaicin (either alone or in combination) are used to evoke pain and sensitization. The possibility of multimodal (e.g. mechanical, electrical, thermal and chemical) stimulation in different gut segments has developed visceral pain research. The major advantage is involvement of distinctive receptors, various sensory nerves and different pain pathways mimicking clinical pain that favors investigation of central pain mechanisms involved in allodynia, hyperalgesia and referred pain. As impairment of descending control mechanisms partly underlies the pathogenesis in chronic pain, a cold pressor test that indirectly stimulates such control mechanisms can be added. Hence, the methods undoubtedly represent a major step forward in the future characterization and treatment of patients with various diseases of the gut, which provides knowledge to

  17. A large gastrointestinal stromal tumor of the duodenum: a case report

    Directory of Open Access Journals (Sweden)

    Al-Ahmad Firas

    2011-09-01

    Full Text Available Abstract Introduction Gastrointestinal stromal tumors of the duodenum are uncommon. They can reach a large size. Diagnosis can be elusive and managing them can be difficult. Our case report aims to increase awareness and highlight some issues related to the diagnosis and management of duodenal gastrointestinal stromal tumors. Case presentation We present the case of a 38-year-old Middle Eastern woman with a large, slowly-growing gastrointestinal stromal tumor of the duodenum. Her complaints were minor epigastric discomfort and swelling. A pancreaticoduodenectomy with complete tumor excision was performed. She was doing very well with no evidence of disease recurrence when she was last seen 34 months after her operation. Conclusion Gastrointestinal stromal tumors of the duodenum should be suspected in any patient with a duodenal wall mass. Extramural growth and central ulceration with or without bleeding should alert the endoscopist to the possibility of a duodenal gastrointestinal stromal tumor diagnosis. There is more than one surgical approach available; however, complete surgical excision, with negative margins, is the absolute requirement. Preoperative imatinib mesylate can be considered in unresectable or borderline resectable cases.

  18. Interstitial cells of Cajal in human gut and gastrointestinal disease

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J

    1999-01-01

    of their functional significance. Alterations of ICC reported in achalasia of cardia, infantile hypertrophic pyloric stenosis, chronic intestinal pseudoobstruction, Hirschsprung's disease, inflammatory bowel diseases, slow transit constipation, and some other disorders of GI motility as well as in gastrointestinal...... stromal tumors are reviewed, with emphasis on the place of ICC in the pathophysiology of disease....

  19. Perforation of metastatic melanoma to the small bowel with simultaneous gastrointestinal stromal tumor

    Institute of Scientific and Technical Information of China (English)

    Nathan Brummel; Ziad Awad; Shellaine Frazier; Jiafan Liu; Nitin Rangnekar

    2005-01-01

    The gastrointestinal tract (GIT) is a common site of metastases for malignant melanoma. These metastatic tumors are often asymptomatic. We describe a case of a 58-year-old male who presented with a sudden onset of generalized abdominal pain. The patient's past medical history was significant for lentigo melanoma of the right cheek. Laparotomy was performed and two segments ofsmall bowel, one with a perforated tumor, the other with a non-perforated tumor, were removed. Histology and immunohistochemical staining revealed the perforated tumor to be a metastatic malignant melanoma and the non-perforated tumor was found to be a gastrointestinal stromal tumor (GIST). The patient was discharged 7 d postoperatively. To the best of our knowledge, this is the first reported case in the literature of a simultaneous metastatic malignant melanoma and a GIST. Surgical intervention is warranted in patients with symptomatic GIT metastases to improve the quality of life or in those patients with surgical emergencies.

  20. [Endoscopic diagnostics and treatment of submucous tumors of the upper gastrointestinal tract].

    Science.gov (United States)

    Starkov, Iu G; Solodinina, E N; Shishin, K V; Novozhilova, A V; Kurushkina, N A

    2011-01-01

    The endoscopic ultrasonography (EUS) is considered to be the leading method of diagnostic of the submucous gastrointestinal tumors. Results of diagnostics and treatment of submucous tumors of the upper gastrointestinal tract in 38 patients were analyzed. EUS was performed in 37 (97,4%) of patients, which allowed to detect the origin, size and localization of the tumor. The differential diagnostic algorithm was suggested together with certain indications for various surgical treatment modalities. Thereby, endoscopic ablation is reasonable when the tumor invades not deeper than muscle plate of mucosa or the submucose layer. Laparoscopic full-layer resection of the organ wall is necessary when the tumor invades the muscle layer. Larger tumors or those of any size, but with preoperative signs of high malignancy must be eradicated through laparotomy, meeting all principles of oncology.

  1. Elective Surgery of Umbilical Hernia as a First Clinical Manifestation of a Gastrointestinal Stromal Tumor (Gist – Case Report

    Directory of Open Access Journals (Sweden)

    Cybułka Bartosz

    2016-09-01

    Full Text Available Gastrointestinal stromal tumor is a rare pathology. GISTs account for 0.3-1% of all tumors of the gastrointestinal tract. At the same time, this type of cancer is the most common, malignant, non-epithelial tumor of the gastrointestinal tube. Over 90% of GISTs are found in the stomach and small intestine. This cancer usually develops without characteristic clinical symptoms and is diagnosed incidentally.

  2. Synchronous Gastric Gastrointestinal Stromal Tumor and Colon Adenocarcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Thivi Vasilakaki

    2014-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs represent the majority of primary mesenchymal tumors of the gastrointestinal tract. They are generally considered to be solitary tumors and therefore the synchronous occurrence with other primary malignancies of gastrointestinal track is considered a rare event. Here we present the case of a 75-year-old man admitted to our hospital with a 10-day history of gastrointestinal bleeding. Colonoscopy revealed an ulcerative mass of 4 cm in diameter in the ascending colon. Gastroscopy revealed a bulge in the gastric body measuring 1 cm in diameter with normal overlying mucosa. Surgical intervention was suggested and ileohemicolectomy with regional lymph node resection along with gastric wedge resection was performed. Pathologic examination of the ascending colon mass showed an invasive moderately differentiated adenocarcinoma stage III B (T3N1M0. Grossly resected wedge of stomach showed a well circumscribed intramural tumor which microscopically was consistent with essentially benign gastrointestinal stromal tumor (according to Miettinen criteria. The patient did not receive additional treatment. Two years later the patient showed no evidence of recurrence or metastasis.

  3. DOG1 for the diagnosis of gastrointestinal stromal tumor (GIST): Comparison between 2 different antibodies.

    Science.gov (United States)

    Lopes, Lisandro F; West, Robert B; Bacchi, Livia M; van de Rijn, Matt; Bacchi, Carlos E

    2010-07-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Discovered on GIST-1 (DOG1) is a recently described protein expressed in GISTs irrespective of mutation status. The aim of this study was to investigate the immunohistochemical expression of DOG1 using 2 different monoclonal antibodies (DOG1.1 and the commercially available K9 antibody) in 668 GIST cases and to compare the results with the expression of KIT. DOG1 and KIT expression also were studied in most human normal tissues and several nonmesenchymal and mesenchymal tumors other than GIST. KIT was expressed in 643 (96.3%) GISTs. DOG1.1 and K9 were positive in 538 (80.5%) and 642 (96.1%) GIST cases, respectively. In 25 (3.7%) KIT-negative GIST cases, DOG1 was expressed in 5 (20.0%) and 19 (76.0%) using DOG1.1 and K9 antibodies, respectively. Only 0.9% of GISTs were negative for KIT, DOG1.1, and K9. Most normal human tissues did not reveal KIT and DOG1 expression. DOG1.1 was positive in only 2 of 57 synovial sarcomas and 1 of 61 soft tissue leiomyosarcomas. K9 was positive in 5 of 57 synovial sarcomas, 1 of 14 angiosarcomas, 1 of 61 soft tissue leiomyosarcomas, 3 of 4 adenoid cystic carcinomas of the head and neck, and in myoepithelial cells of 9 of 11 fibroadenomas of the breast. In conclusion, the commercially available K9 is of great utility for the diagnosis of most KIT-negative GISTs, and the combination of both KIT and K9 antibody in a panel of immunohistochemistry can define the diagnosis of GIST in more than 99% of cases.

  4. Control the invasive growth of gastrointestinal epithelial tumor

    Institute of Scientific and Technical Information of China (English)

    Wang Cunyu

    2014-01-01

    Invasive growth of epithelial tumor is a very complex process. Therefore,clarifying the molecular mechanisms of the invasive growth of tumor cells will help us find new targets for cancer therapy,and suppress tumor growth and development more effectively.

  5. An Intra-Abdominal Desmoid Tumor, Embedded in the Pancreas, Preoperatively Diagnosed as an Extragastric Growing Gastrointestinal Stromal Tumor

    Directory of Open Access Journals (Sweden)

    Mari Mizuno

    2017-04-01

    Full Text Available A 45-year-old woman was found to have a pancreatic tumor by abdominal ultrasound performed for a medical check-up. Abdominal contrast-enhanced computed tomography showed a hypovascular tumor measuring 30 mm in diameter in the pancreatic tail. Endoscopic ultrasound-guided fine needle aspiration was performed. An extragastric growing gastrointestinal stromal tumor was thereby diagnosed preoperatively, and surgical resection was planned. Laparoscopic surgery was attempted but conversion to open surgery was necessitated by extensive adhesions, and distal pancreatectomy, splenectomy, and partial gastrectomy were performed. The histological diagnosis was an intra-abdominal desmoid tumor. A desmoid tumor is a fibrous soft tissue tumor arising in the fascia and musculoaponeurotic tissues. It usually occurs in the extremities and abdominal wall, and only rarely in the abdominal cavity. We experienced a case with an intra-abdominal desmoid tumor that was histologically diagnosed after laparotomy, which had been preoperatively diagnosed as an extragastric growing gastrointestinal stromal tumor. Although rare, desmoid tumors should be considered in the differential diagnosis of intra-abdominal tumors. Herein, we report this case with a literature review.

  6. CD34 immunoreactivity and interstitial cells of Cajal in the human and mouse gastrointestinal tract

    DEFF Research Database (Denmark)

    Vanderwinden, J M; Rumessen, J J; De Laet, M H;

    2000-01-01

    Immunoreactivity for the tyrosine kinase receptor Kit (Kit-ir) is an established marker for the interstitial cells of Cajal (ICC) of the gut. Recently, the presence of CD34 immunoreactivity (CD34-ir) has been reported in Kit-ir ICC around the myenteric plexus in human small intestine. Conversely,......-localization. The ontogeny and function of CD34-ir cells in the gut, as well as the origin of gastrointestinal stromal tumors, remain unclear....

  7. Gastrointestinal-active oligosaccharides from human milk and functional foods

    NARCIS (Netherlands)

    Albrecht, S.A.

    2011-01-01

    Keywords: human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), konjac glucomannan (KGM), breast milk, baby feces, gastrointestinal metabolization, blood-group specific conjugates, CE-LIF-MSn   Oligosaccharides, as present in human milk or supplemented to food, are renowned for

  8. Molecular characterization of bacterial communities in the human gastrointestinal tract

    NARCIS (Netherlands)

    Zoetendal, E.G.

    2001-01-01

    The human gastrointestinal (GI) tract is a complex ecosystem in which host and microbial cells live in close contact with each other. The microbial community in the human GI tract has an important nutritional and protective function and mainly consists of anaerobic bacteria. After birth, the germ-fr

  9. Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Uchino, Keita, E-mail: uchino13@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirano, Gen [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Hirahashi, Minako [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Isobe, Taichi; Shirakawa, Tsuyoshi; Kusaba, Hitoshi; Baba, Eishi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tsuneyoshi, Masazumi [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka (Japan); Akashi, Koichi [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)

    2012-09-10

    There is emerging evidence that human solid tumor cells originate from cancer stem cells (CSCs). In cancer cell lines, tumor-initiating CSCs are mainly found in the side population (SP) that has the capacity to extrude dyes such as Hoechst 33342. We found that Nanog is expressed specifically in SP cells of human gastrointestinal (GI) cancer cells. Nucleotide sequencing revealed that NanogP8 but not Nanog was expressed in GI cancer cells. Transfection of NanogP8 into GI cancer cell lines promoted cell proliferation, while its inhibition by anti-Nanog siRNA suppressed the proliferation. Immunohistochemical staining of primary GI cancer tissues revealed NanogP8 protein to be strongly expressed in 3 out of 60 cases. In these cases, NanogP8 was found especially in an infiltrative part of the tumor, in proliferating cells with Ki67 expression. These data suggest that NanogP8 is involved in GI cancer development in a fraction of patients, in whom it presumably acts by supporting CSC proliferation. -- Highlights: Black-Right-Pointing-Pointer Nanog maintains pluripotency by regulating embryonic stem cells differentiation. Black-Right-Pointing-Pointer Nanog is expressed in cancer stem cells of human gastrointestinal cancer cells. Black-Right-Pointing-Pointer Nucleotide sequencing revealed that Nanog pseudogene8 but not Nanog was expressed. Black-Right-Pointing-Pointer Nanog pseudogene8 promotes cancer stem cells proliferation. Black-Right-Pointing-Pointer Nanog pseudogene8 is involved in gastrointestinal cancer development.

  10. Spontaneous Rupture of Recurrent Gastrointestinal Stromal Tumor Associated with Neurofibromatosis Type 1

    Directory of Open Access Journals (Sweden)

    Shin-Mae Wang

    2005-11-01

    Full Text Available The incidence of gastrointestinal stromal tumor (GIST among neurofibromatosis type 1 (NF-1 patients is approximately 3.9–25%, and this relationship is generally considered to be non-coincidental. We report a patient with NF-1 who underwent laparotomy 3 times due to recurrent intra-abdominal tumor rupture with internal bleeding in the space of 13 years. The pathologic diagnoses were schwannoma, malignant peripheral nerve sheath tumor and GIST. Because of the similar histologic features of these tumors, we considered them to be of the same nature. Immunohistochemical staining can help in the differential diagnosis. We suggest that NF-1 patients with gastrointestinal symptoms receive further survey to rule out GISTs.

  11. C-kit-targeted imaging of gastrointestinal stromal tumor using radiolabeled anti-c-kit monoclonal antibody in a mouse tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Sogawa, Chizuru [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Tsuji, Atsushi B. [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)], E-mail: a_tsuji@nirs.go.jp; Sudo, Hitomi [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Pathology and Oncology, Juntendo University School of Medicine, Tokyo 113-8421 (Japan); Sugyo, Aya [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Yoshida, Chisato [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Odaka, Kenichi [Molecular Probe Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan); Uehara, Tomoya; Arano, Yasushi [Department of Molecular Imaging and Radiotherapy, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675 (Japan); Koizumi, Mitsuru; Saga, Tsuneo [Diagnostic Imaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba 263-8555 (Japan)

    2010-02-15

    Introduction: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor arising from the gastrointestinal tract and highly expresses mutated c-kit. We aimed to develop a specific and sensitive method for detecting GISTs using radiolabeled anti-c-kit monoclonal antibody. Methods: A mutated c-kit-expressing cell clone was established by transfecting an expressing vector of mutated c-kit gene into HEK293 human embryonic kidney cells. The tumors were developed by inoculating c-kit-expressing cells into nude mice. {sup 125}I- and {sup 111}In-labeled anti-c-kit antibodies (12A8 and 41A11) were evaluated in vitro by cell binding, competitive inhibition and cellular internalization assays, and in vivo by biodistribution and imaging studies in tumor-bearing mice. Results: Both {sup 125}I- and {sup 111}In-labeled antibodies showed specific binding with c-kit-expressing cells with high affinity (dissociation constants = 2.2-7.1x10{sup 9} M{sup -1}). Internalization assay showed that {sup 125}I-labeled antibodies were rapidly internalized and dehalogenated, with the release of {sup 125}I from the cells, resulting in reduction of cell-associated radioactivity with time. In contrast, {sup 111}In-labeled antibody was internalized but did not result in the reduced radioactivity associated with tumor cells. Reflecting this phenomenon, the in vivo tumor uptake of {sup 125}I-labeled antibody was low on Day 1, further decreasing with time, while tumor uptake of {sup 111}In-labeled antibody was high on Day 1, further increasing with time. The xenografted tumor was clearly visualized by scintigraphy after injection of {sup 111}In-labeled antibody. Conclusion: The anti-c-kit monoclonal antibody labeled with a metal radionuclide would be promising for c-kit-targeted imaging of GISTs.

  12. Cytokeratin expression in gastrointestinal stromal tumor: a clinicopathologic and immunohistochemical study of 687 cases.

    Science.gov (United States)

    Lopes, Lisandro F; Bacchi, Carlos E

    2012-01-01

    Gastrointestinal stromal tumor is the most common clinically significant mesenchymal neoplasm of the gastrointestinal tract. The expression of the intermediate filament cytokeratin in gastrointestinal stromal tumor is not frequently reported in the literature. The aim of this study was to investigate the immunohistochemical expression of several types of cytokeratin in a large number of cases (n=687), including a pan-cytokeratin marker (AE1/AE3 cocktail antibodies), high-molecular weight cytokeratins (34ßE12 antibody), and individual cytokeratins 8 (35ßH11 and CAM5.2 antibodies), 7, 14, and 20. Ki-67 antigen was used for the determination of cell proliferation index, and the correlation between Ki-67 and cytokeratin expression was evaluated. Cytokeratin expression was also correlated with several clinicopathologic parameters. The expression of pan-cytokeratin was observed in 24 (3.5%) cases, with variable intensity. Only 1 of 687 (0.1%) cases showed cytokeratin 14 expression. All 687 cases revealed no expression of high-molecular weight cytokeratins, cytokeratins 7, 8, and 20. No significant statistical association was found between AE1/AE3 immunoreactivity and several clinicopathologic parameters, including sex, tumor location and size, cell morphology, mitotic count, risk of aggressive behavior, and Ki-67 antigen cell proliferation index. However, statistical correlation between AE1/AE3 immunoreactivity and a higher age at diagnosis was detected. These results show that cytokeratin expression is not frequent in gastrointestinal stromal tumor, but caution is necessary to avoid erroneous diagnoses.

  13. Gastrointestinal stromal tumor of the stomach with a giant abscess penetrating the gastric lumen

    Institute of Scientific and Technical Information of China (English)

    Taro Osada; Akihito Nagahara; Tomohiro Kodani; Akihiro Namihisa; Masato Kawabe; Takashi Yoshizawa; Toshifumi Ohkusa; Sumio Watanabe

    2007-01-01

    Gastrointestinal stromai tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. In large GISTs, cystic degeneration, necrosis and focal hemorrhage that occur inside the tumor can result in gastrointestinal bleeding. We describe a case of a 74-year old male with GIST of the stomach accompanied with a giant abscess that penetrated the gastric lumen. The patient experienced undiagnosed fever for two months prior to hospitalization. Gastrointestinal endoscopy, X-ray series and computed tomography of the patient's abdomen revealed a gastric submucosal tumor in the fornix, with a fistula to the gastric lumen that was inundated with a great deal of pus. The mass was diagnosed as a GIST from biopsy specimens. The patient was treated by endoscopic drainage of the abscess and intravenous administration of antibiotics. Eventually, a partial gastrectomy was performed. He was also administered Imanitib mesylate as adjuvant therapy. He was followed up for 2 years and no metastasis or recurrence was recognized at the followup examinations. This is the first report of a patient with clearly diagnosed GIST with endoscopic evidence of an abscess penetrating into the gastric lumen.

  14. Perivascular epithelioid cell tumor of gastrointestinal tract: case report and review of the literature

    NARCIS (Netherlands)

    Lu, B.; Wang, C.; Zhang, Junxiao; Kuiper, R.P.; Song, M.; Zhang, X.; Song, S.; Geurts van Kessel, A.; Iwamoto, A.; Wang, J; Liu, H.

    2015-01-01

    Perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas) are exceedingly rare, with only a limited number of published reports worldwide. Given the scarcity of GI PEComas and their relatively short follow-up periods, our current knowledge of their biologic behavior, molecular gene

  15. [Prevalence and trend of gastrointestinal malignant tumors in the elderly over 75 years old in China].

    Science.gov (United States)

    Zheng, Ying; Wu, Chunxiao

    2016-05-01

    Gastrointestinal malignant tumors are the most common malignant neoplasms among the elderly people over 75 years old in China. There are 122.1 thousand new gastric cases and 78.2 thousand new colorectal cancer cases diagnosed each year in China, which accounts for 42.73% and 18.08% respectively of the cases with same age in the world. The gastric cancer accounts for 25.13% and colorectal cancer accounts for 28.86%of all the malignancies in the elderly. The gastric cancer death accounts for 36.38% and colorectal cancer death accounts for 44.68% in those people over 75 years old in China. It was estimated that the risk of developing gastrointestinal malignant tumors of these elderly people was about 5-6 times and the risk of death of gastrointestinal malignant tumors was about 7-8 times of the general population. Compared with the general population and the people of 55-74 years old, the incidence of gastric cancer in the elderly decreased more slowly and the incidence of colorectal cancer increased more quickly over the past 40 years, which brought significant double burden. The survival rate of gastrointestinal malignant tumors in these elderly was lower than that of the general population. We summarized the incidence, mortality, survival and trend of gastrointestinal malignant tumors in the Chinese elderly, in order to provide data for predicting the age distribution and disease burden in the future, to improve the awareness for cancer prevention and control among these elderly, and to call attention to epidemiology, preclinical and clinical medicine for the elderly, especially in the field of study on the influence between comorbidity and cancer treatment, with the aim of improving survival and quality of life among the elderly.

  16. Gastrointestinal hormones stimulate growth of Foregut Neuroendocrine Tumors by transactivating the EGF receptor.

    Science.gov (United States)

    Di Florio, Alessia; Sancho, Veronica; Moreno, Paola; Delle Fave, Gianfranco; Jensen, Robert T

    2013-03-01

    Foregut neuroendocrine tumors [NETs] usually pursuit a benign course, but some show aggressive behavior. The treatment of patients with advanced NETs is marginally effective and new approaches are needed. In other tumors, transactivation of the EGF receptor (EGFR) by growth factors, gastrointestinal (GI) hormones and lipids can stimulate growth, which has led to new treatments. Recent studies show a direct correlation between NET malignancy and EGFR expression, EGFR inhibition decreases basal NET growth and an autocrine growth effect exerted by GI hormones, for some NETs. To determine if GI hormones can stimulate NET growth by inducing transactivation of EGFR, we examined the ability of EGF, TGFα and various GI hormones to stimulate growth of the human foregut carcinoid,BON, the somatostatinoma QGP-1 and the rat islet tumor,Rin-14B-cell lines. The EGFR tyrosine-kinase inhibitor, AG1478 strongly inhibited EGF and the GI hormones stimulated cell growth, both in BON and QGP-1 cells. In all the three neuroendocrine cell lines studied, we found EGF, TGFα and the other growth-stimulating GI hormones increased Tyr(1068) EGFR phosphorylation. In BON cells, both the GI hormones neurotensin and a bombesin analogue caused a time- and dose-dependent increase in EGFR phosphorylation, which was strongly inhibited by AG1478. Moreover, we found this stimulated phosphorylation was dependent on Src kinases, PKCs, matrix metalloproteinase activation and the generation of reactive oxygen species. These results raise the possibility that disruption of this signaling cascade by either EGFR inhibition alone or combined with receptor antagonists may be a novel therapeutic approach for treatment of foregut NETs/PETs.

  17. [A Case of Resected Giant Gastrointestinal Stromal Tumor Associated with Intraperitoneal Bleeding Following Imatinib Administration].

    Science.gov (United States)

    Ide, Ryuta; Suzuki, Takahisa; Takakura, Yuji; Oshita, Akihiko; Ikeda, Satoshi; Matsugu, Yasuhiro; Nakahara, Hideki; Urushihara, Takashi; Itamoto, Toshiyuki; Shinozaki, Katsunori

    2016-09-01

    A 76-year-old woman with tarry stool was referred to our hospital for further examination. Contrast-enhanced computed tomography(CT)revealed a heterogeneous 15 cm tumor located in the left upper abdominal cavity. The tumor had a rich vascularity and was associated with intra-abdominal bleeding. Gastroscopy showed a large submucosal tumor in the gastric body. A biopsy was performed, and the patient was diagnosed with a c-kit-positive gastrointestinal stromal tumor(GIST)of the stomach. Imatinib mesylate(400mg/day)was administered for 6 months. Vascularity in the tumor was diminished and no new lesion had emerged, although there was no remarkable reduction in tumor size. The patient underwent partial gastrectomy and splenectomy with curative intent. She is currently alive 1 year and 4 months after surgery with no evidence of recurrence.

  18. Incidental detection of gastrointestinal stromal tumor by Tc-99m MDP bone scan.

    Science.gov (United States)

    Shepherd, Timothy M; Idakoji, Ibrahim A; Pampaloni, Miguel H

    2012-02-01

    This case demonstrates extraosseous 99m-technetium methylene diphosphonate (Tc-99m MDP) accumulation from a gastrointestinal stromal tumor. A 75-year-old woman underwent a temporal bone CT for conductive hearing loss that showed sclerosis in the right occipital condyle. Follow-up Tc-99m MDP bone scan for osseous metastases instead showed a mass-like extraosseous accumulation of Tc-99m MDP in the anterior left upper quadrant. Differential diagnoses included gastric cancer, lymphoma, metastatic melanoma, systemic hypercalcemia, or heterotopic mesenteric ossification. Contrast CT showed a well-circumscribed mass arising from the stomach, and subsequent pathology confirmed gastrointestinal stromal tumor. These tumors rarely can contain osteoclast-like giant cells and should be considered for extraosseous Tc-99m MDP accumulation.

  19. 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.

  20. A massive bleeding from a gastrointestinal stromal tumor of a Meckel’s diverticulum

    Directory of Open Access Journals (Sweden)

    Chabowski Mariusz

    2016-01-01

    Full Text Available Introduction. Meckel’s diverticulum is the most common congenital anomaly of the gastro intestinal tract, present in about 2% of population. Case Outline. The article presents the case of a 44-year-old otherwise healthy man with anemia, who was diagnosed lower gastrointestinal bleeding. An abdominal CT scan revealed a clearly demarcated solid tumor in hypogastric region, measuring 65 Ч 45 mm. A laparotomy through lower midline incision was performed. A surgical resection of a lesion of a Meckel’s diverticulum was carried out and a final diagnosis of gastrointestinal stromal tumor was made. The patient made an uneventful recovery. Conclusion. The preoperative diagnosis of a complicated Meckel’s diverticulum may be challenging. CT is usually an adequate method to diagnose tumors arising from Meckel’s diverticulum.

  1. Endoscopic enucleation of gastrointestinal stromal tumors of the stomach: Report of five cases

    Institute of Scientific and Technical Information of China (English)

    Toshio Katoh; Yoshiyuki Itoh; Tomomi Mohri; Hiroshi Suzuki

    2008-01-01

    Gastrointestinal stromal tumor (GIST) of the stomach was treated by endoscopic enucleation in five patients.They were three men and two woman, aged 36-56 years.Tumors located in the cardia were completely enucleated endoscopically without any serious complication.The largest diameter of removed tumors ranged from 1.2 to 2.5 cm.Histopathological diagnosis was GIST with low risk of malignancy (mitotic index < 5/50 high power field) in all cases.The patients were disease-free for 10.5-42.2 mo after endoscopic enucleation.

  2. Gastrointestinal stromal tumor of stomach with inguinal lymph nodes metastasis: A case report

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the alimentary tract. To the best of our knowledge, few cases have been reported in the literature about the peripheral lymph node metastasis of GIST. Here we report an unusual case of gastric GIST with inguinal lymph nodes metastasis. After the metastatic lymph nodes were resected, the. patient started to take imatinib 400 mg/d for 12 mo. There were no signs of tumor recurrence at follow-up after 29 mo. This case suggests that th...

  3. Gastrointestinal stromal tumor masquerading as a lung neoplasm. A case presentation and literature review

    Directory of Open Access Journals (Sweden)

    Papagiannopoulos K

    2008-05-01

    Full Text Available Abstract Gastrointestinal stromal tumors (GISTs are rare neoplasms of the gastrointestinal tract. Their incidence in the esophagus is 1%–3%. Never has a GIST been documented to directly invade the lung. We report a primary esophageal GIST with direct invasion into the lung parenchyma, presenting predominantly with respiratory symptoms. We include a retrospective literature review. Although the principle 'common things are common' usually guides our everyday clinical practice, this case emphasizes that rare entities can mimic common pathologies and underlines the importance of having a clearly defined differential diagnostic list which should be meticulously scrutinized.

  4. Locoregional IL-2 low dose applications for gastrointestinal tumors

    Institute of Scientific and Technical Information of China (English)

    Zachary Krastev; Willem Den Otter; V Koltchakov; R Tomova; S Deredjian; A Alexiev; D Popov; B Tomov; Jan-Willem Koten; John Jacobs

    2005-01-01

    AIM: To explore the feasibility of local interleukin 2 (IL-2)in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application.METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with locoregionally applied IL-2 in low doses.RESULTS: No major problems applying locoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal, The therapeutic scheme was well tolerated, even in patients in a poor condition.CONCLUSION: This study demonstrates the feasibility of low dose locoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.

  5. A Pleural Solitary Fibrous Tumor, Multiple Gastrointestinal Stromal Tumors, Moyamoya Disease, and Hyperparathyroidism in a Patient Associated with NF1

    Directory of Open Access Journals (Sweden)

    Yoko Yamamoto

    2015-01-01

    Full Text Available Neurofibromatosis type 1 (NF1, also called von Recklinghausen’s disease, is a multisystemic disease caused by an alteration of the NF1 gene, a tumor suppressor located on the long arm of chromosome 17 (17q11.2. Loss of the gene function, due to a point mutation, leads to an increase in cell proliferation and the development of several tumors. We report a 60-year-old female patient manifesting hypercalcemia due to hyperparathyroidism, a solitary fibrous tumor (SFT of the pleura, multiple gastrointestinal stromal tumors (GISTs, and moyamoya disease associated with NF1. The SFT and GISTs were removed by staged operations. Then, hypercalcemia was successfully controlled after resection of the parathyroid adenoma. Based on a literature review, these combinations have never been reported, and the relevant literature is briefly discussed.

  6. [Papillomaviruses and human tumors].

    Science.gov (United States)

    Vonka, V; Hamsíková, E; Sobotková, E; Smahel, M; Kitasato, H; Sainerová, H; Ludvíková, V; Zák, R; Kanka, J; Kolár, Z; Kovarík, J

    2000-12-01

    The report summarizes the main results obtained in the course of our research project. The results of immunological and epidemiological studies provide further proofs that human papillomaviruses (HPV) are the etiological agents in cervical neoplasia. In addition, they raise hopes that immunological methods may be utilized in diagnostics of cervical cancer and for monitoring the clinical course of this disease in the near future. Since the etiological relationship between HPV and cervical carcinoma seems to be proven beyond reasonable doubt, the development of prophylactic and therapeutic vaccines has become the dominant of the contemporary HPV reseach. For studying immune reactions against HPV-induced tumours we developed a model of HPV16-transformed rodent cells.

  7. [Autopsy case of von Recklinghausen's disease associated with lung cancer, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor].

    Science.gov (United States)

    Satoh, Miki; Wakabayashi, Osamu; Araya, Yoshikazu; Jinushi, Eisei; Yoshida, Fumiaki

    2009-09-01

    A 58-year-old man with von Recklinghausen's disease was admitted for further investigation of right chest pain. Chest X-ray revealed multiple emphysematous bullae in both lungs and a tumor shadow in the right upper lobe. Bronchofiberscopy was performed, but an adequate specimen was not obtained. The tumor was diagnosed as a non-small-cell lung cancer with direct invasion to the adjacent rib. Although chemotherapy and radiotherapy resulted in decrease in tumor size, the tumor subsequently increased in size and the patient died 14 months after the first admission. Autopsy revealed multiple emphysematous bullae, poorly differentiated adenosquamous cell carcinoma of the lung, gastrointestinal stromal tumor of the stomach, and duodenal carcinoid tumor. This case suggests the possibility that von Recklinghausen's disease associated with emphysematous bullae is a risk factor for lung cancer. It has also been suggested that the genetic abnormality responsible for von Recklinghausen's disease increases the risk for various types of malignancy. Although von Recklinghausen's disease is reportedly associated with various malignant tumors, it is quite rare for von Recklinghausen's disease to be associated with triple non-neurogenic tumors. Careful observation is mandatory for patients with von Recklinghausen's disease.

  8. New concepts of staging in gastrointestinal tumors as a basis of diagnosis and multimodal therapy.

    Science.gov (United States)

    Gretschel, S; Moesta, K T; Hünerbein, M; Lange, T; Gebauer, B; Stroszczinski, C; Bembenek, A; Schlag, P M

    2004-02-01

    The therapy of gastrointestinal tumors is becoming more and more sophisticated and complex. This is due to an improved understanding of the pathogenesis of tumors, a more detailed classification and increasing therapeutic options. The basis of optimized therapeutic concepts is the exact evaluation of tumor spread and exact staging. The following review describes some of the most recent staging concepts in gastrointestinal tumors. Multislice computed tomography (CT), positron emission tomography (PET) and new supraparamagnetic iron oxide contrast agents for magnetic resonance imaging enable an increasing quality of the visualization of tumors and metastases. 3D imaging will be used for planning of surgical interventions in the future. Optical coherence tomography may contribute to an improved tumor staging and, thus, to the safety of limited interventions in early oesophageal- and gastric cancer patients. Laparoscopy and laparoscopic ultrasound become increasingly important for the identification of small metastases in the peritoneum, in lymph nodes and in the liver. The sentinel lymph node concept will contribute to an improved staging and individualized therapy as well.

  9. Gastrointestinal metabolization of human milk oligosaccharides

    NARCIS (Netherlands)

    Albrecht, S.A.; Heuvel, van den E.G.H.M.; Gruppen, H.; Schols, H.A.

    2013-01-01

    Breast feeding has a great impact on the growth of infants both physically and psychologically. Human breast milk is beneficial to infant health because it contains the necessary macro- and micro-nutrients for tissue accretion, repair and behavioural developments. The production of milk is a complex

  10. Therapeutic Efficacy Assessment of CK6, a Monoclonal KIT Antibody, in a Panel of Gastrointestinal Stromal Tumor Xenograft Models

    Directory of Open Access Journals (Sweden)

    Thomas Van Looy

    2015-04-01

    Full Text Available We evaluated the efficacy of CK6, a KIT monoclonal antibody, in a panel of human gastrointestinal stromal tumor (GIST xenograft models. Nude mice were bilaterally transplanted with human GIST xenografts (four patient derived and two cell line derived, treated for 3 weeks, and grouped as follows: control (untreated; CK6 (40 mg/kg, 3× weekly; imatinib (50 mg/kg, twice daily; sunitinib (40 mg/kg, once daily; imatinib + CK6; sunitinib + CK6 (same doses and schedules as in the single-agent treatments. Tumor volume assessment, Western blot analysis, and histopathology were used for evaluation of efficacy. Statistical analysis was performed using Mann-Whitney U (MWU and Wilcoxon matched-pairs tests. CK6 as a single agent only reduced tumor growth rate in the UZLX-GIST3 model (P = .053, MWU compared to control, while in none of the other GIST models an effect on tumor growth rate was observed. CK6 did not result in significant anti-proliferative or pro-apoptotic effects in any of the GIST models, and moreover, CK6 did not induce a remarkable inhibition of KIT activation. Furthermore, no synergistic effect of combining CK6 with tyrosine kinase inhibitors (TKIs was observed. Conversely, in certain GIST xenografts, anti-tumor effects seemed to be inferior under combination treatment compared to single-agent TKI treatment. In the GIST xenografts tested, the anti-tumor efficacy of CK6 was limited. No synergy was observed on combination of CK6 with TKIs in these GIST models. Our findings highlight the importance of using relevant in vivo human tumor xenograft models in the preclinical assessment of drug combination strategies.

  11. Gastrointestinal stromal tumor of colon: a case report and review of literature.

    Science.gov (United States)

    Niazi, Azfar Khan; Kaley, Kristin; Saif, Muhammad Wasif

    2014-05-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs originate from cells of Cajal and related stem cells. Surgery and imatinib therapy are the main lines of treatment. We report on a case with GIST in the colon treated with surgical resection followed by adjuvant imatinib therapy. This treatment showed no side-effects, and subsequent colonoscopy was unremarkable. The diagnosis was delayed for 12 months after initial presentation of vague abdominal pain, thus highlighting the need to improve clinical suspicion in order to detect GISTs in earlier stages when resection may be curative. Colonic GIST, in particular, may mimic presentation similar to ovarian cyst, as seen in the present case. This case report corroborates that patients with high-grade GISTs can be effectively treated with imatinib therapy. However, duration of treatment may vary depending on the grade of the tumor and side-effects.

  12. [Current status and progress of medical imaging in diagnosis of gastrointestinal stromal tumors].

    Science.gov (United States)

    Wang, Lingjie; Zhang, Ruiping; Li, Jianding

    2015-04-01

    Gastrointestinal stromal tumors (GISTs) are derived from non-directed differentiation of gastrointestinal mesenchymal tissue, which lack of typical clinical symptoms, and many asymptomatic GISTs are often found on physical examination. The tumor is primarily through implantation metastasis and blood metastasis. Currently, conventional medical imaging methods, such as X-ray barium meal, US, CT, MRI, PET/CT and ES, are still the main means of diagnosis of GISTs. Early diagnosis and early treatment are key factors of the prognosis in GISTs. Therefore, we need to be proficient in various medical imaging methods, then apply them to the diagnosis of GISTs, and to provide comprehensive and valuable information for clinical practice. Through retrieving and consulting literature of medical imaging associated with GISTs, this paper reviews the current status and progress of medical imaging in diagnosis of GISTs.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-15

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

  14. Lichenoid drug eruption caused by imatinib mesylate in a Chinese patient with gastrointestinal stromal tumor.

    Science.gov (United States)

    Luo, Jing-Ru; Xiang, Xiao-Jun; Xiong, Jian-Ping

    2016-09-01

    Imatinib mesylate, the first agent approved for the treatment of unresectable or metastatic gastrointestinal stromal tumor, is a tyrosine kinase inhibitor targeting (KIT) and the platelet-derived growth factor receptor-α and -β. However, imatinib administration can be accompanied by various adverse events. Here we report a case of Lichenoid drug eruption (LDE) that appeared 24 weeks after commencement of imatinib in a 73-year-old man with gastrointestinal stromal tumor (GIST). The skin lesions were distributed over his face, trunk and limbs, which improved only after discontinuation of imatinib therapy. To the best of our knowledge, this is the first report of imatinib-induced LDE in the Chinese population.

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

    NARCIS (Netherlands)

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

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

  16. Prognostic value of KTT mutation in gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hong Liu; Chen-Guang Bai; Qiang Xie; Fei Feng; Zhi-Yun Xu; Da-Lie Ma

    2005-01-01

    AIM: To examine the prevalence and prognostic significance of C-kit gene mutation and analysis the correlation of Ckit gene mutation and the clinicalpathologic parameters of GISTs.METHODS: Eighty-two GISTs were studied for the mutation of C-kit gene by PCR-SSCP, DNA sequence.Statistical comparison were used to analysis the correlation of C-kit gene mutation and clinicalpathology,clinical behavior, recurrence.RESULTS: (1) Mutation-positive and mutation-negative GISTs were 34 and 48,respectively; (2) Among these patients with C-kit mutation remained a significantly poor prognosis associated with 59% 3-year survival compared to those whose tumors did not; (3) Tunor size, PCNA index, mitotic cell number, presence of necrosis, microscopic invasion to adjacent tissues, recurrence and distant metastasis among mutation-positive and mutation-negative GISTs were significantly different.CONCLUSION: C-kit mutation is a undoubtedly pivotal event in GIST and may be associated with poor prognosis.Evaluation of C-kit gene mutation may have both prognosis and therapeutic significances.

  17. Gastrointestinal stromal tumor of large size, extragastrointestinal localization and different morphological features

    Directory of Open Access Journals (Sweden)

    Shpon’ka I.S.

    2015-09-01

    Full Text Available The problems of accurate verification of the gastro¬intestinal stromal tumor are relevant today for many reasons. Thus, the histological diagnosis is complicated by the morphological similarity of other gastrointestinal tract mesenchymal neoplasms and by histologicaly different zones within the same investigation. We present the situation with the above issues: the differential diagnosis includes an analysis of morphological criteria and received immunohisto-chemical reactions. Between immunophenotypes of histologicaly different zones principal difference is not revealed.

  18. Human breast milk and the gastrointestinal innate immune system.

    Science.gov (United States)

    Jakaitis, Brett M; Denning, Patricia W

    2014-06-01

    The gastrointestinal (GI) tract is a large potential portal for multiple infectious agents to enter the human body. The GI system performs multiple functions as part of the neonate's innate immune system, providing critical defense during a vulnerable period. Multiple mechanisms and actions are enhanced by the presence of human breast milk. Bioactive factors found in human milk work together to create and maintain an optimal and healthy environment, allowing the intestines to deliver ideal nutrition to the host and afford protection by a variety of mechanisms.

  19. Minimally invasive management of metastases from gastrointestinal stromal tumors; Minimalinvasive Therapieoptionen bei Metastasen gastrointestinaler Stromatumoren

    Energy Technology Data Exchange (ETDEWEB)

    Kamusella, P.C.; Bethke, A.; Platzek, I.; Wiggermann, P.; Wissgott, C.; Stroszczynski, C. [Universitaetsklinikum Dresden, Radiologisches Institut, Dresden (Germany)

    2009-12-15

    Minimally invasive radiological procedures can lead to an improvement in the prognosis and the clinical symptoms in cases of metastases of gastro-intestinal stromal tumors (GIST) in the context of multimodal therapy concepts. In the context of interdisciplinary therapy decision-making radiofrequency ablation (RFA) and transarterial tumor embolization should be considered. (orig.) [German] Minimalinvasive radiologische Verfahren koennen bei Metastasierung eines gastrointestinalen Stromatumors (GIST) im Rahmen multimodaler Therapiekonzepte zu einer Verbesserung der Prognose und klinischen Symptomatik fuehren. Im Rahmen des interdisziplinaeren Therapienentscheids sollten die Radiofrequenzablation (RFA) und die transarterielle Tumorembolisation in Betracht gezogen werden. (orig.)

  20. Current concepts in non-gastrointestinal stromal tumor soft tissue sarcomas: A primer for radiologists

    Energy Technology Data Exchange (ETDEWEB)

    Baheti, Akahay D. [Dept. of Radiology, Tata Memorial Centre, Mumbai (India); Tirumani, Harika [Dept. of Radiology, University of Arkansas for Medical Sciences, Little Rock (United States); O' Neill, Alibhe; Jagannathan, Jyothi P. [Dept. of Imaging, Dana-Farber Cancer Institute, Boston (United States)

    2017-01-15

    Non-gastrointestinal stromal tumor (GIST) soft tissue sarcomas (STSs) are a heterogeneous group of neoplasms whose classification and management continues to evolve with better understanding of their biologic behavior. The 2013 World Health Organization (WHO) has revised their classification based on new immunohistochemical and cytogenetic data. In this article, we will provide a brief overview of the revised WHO classification of soft tissue tumors, discuss in detail the radiology and management of the two most common adult non-GIST STS, namely liposarcoma and leiomyosarcoma, and review some of the emerging histology-driven targeted therapies in non-GIST STS, focusing on the role of the radiologist.

  1. Hypertensive crisis during wide excision of gastrointestinal stromal cell tumor (GIST): Undiagnosed paraganglioma -A case report-.

    Science.gov (United States)

    Shinn, Helen Ki; Jung, Jong Kwon; Park, Jay Kim; Kim, Jong Hoon; Jung, In Young; Lee, Hong Sik

    2012-03-01

    Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause severe hypertensive crisis during anesthesia or surgery if undiagnosed preoperatively. Extraluminal perigastric masses may be presumed to be gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when histologic confirmation is not possible. Therefore, without a histologic diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken for GIST. We report a case of preoperatively undiagnosed PGL which caused hypertensive crisis during anesthesia for retroperitoneal mass excision.

  2. Multiple non-metastatic gastrointestinal stromal tumors: Differential features Tumores del estroma gastrointestinal múltiples no metastásicos: Aspectos diferenciales

    Directory of Open Access Journals (Sweden)

    M. Díaz Delgado

    2010-08-01

    Full Text Available Introduction: gastrointestinal stromal tumors (GISTs are specific, generally KIT (CD117-positive, mesenchymal tumors of the digestive tract displaying KIT or PDGFRA gene mutations. Clinically, they tend to present as solitary tumors of the intestinal wall; more rarely, multiple tumors may occur in one or more organs. Objective: to review the morphological, immunohistochemical and molecular features of multiple, non-metastatic forms of GIST. Sources: review of the literature on Medline, and authors' own experience. Conclusions: multiples GISTs may occur in three different contexts: as spontaneous lesions (in both adults and children; due to familial GIST syndrome (autosomal dominant inheritance; or in association with specific syndromes (e.g. Carney's triad, Carney-Stratakis syndrome, type I neurofibromatosis. Outside these contexts, the existence of multiple GISTs is deemed to be the result of tumor metastasis, and therefore indicative of advanced-stage disease. Clinicians need to be aware of these variants, whose prognosis and treatment differ.Introducción: los tumores del estroma gastrointestinal (GIST son neoplasias mesenquimales del tubo digestivo que generalmente expresan el receptor KIT (CD117 y muestran mutaciones en los genes KIT o PDGFRA. Aunque la forma de presentación clínica habitual es como una neoplasia mural solitaria, excepcionalmente pueden presentarse formas múltiples en el mismo o diferente órgano. Objetivo: revisar las características morfológicas, inmunohistoquímicas y moleculares de las formas de GIST múltiples no metastásicos. Fuentes: revisión de la literatura en Medline y la propia experiencia. Conclusiones: los GIST múltiples pueden presentarse en tres contextos diferentes: lesiones espontáneas (del adulto o de la edad infantil; síndrome familiar propio (transmitido con herencia autosómica dominante; y lesiones asociadas a síndromes específicos (tríada de Carney, síndrome de Carney-Stratakis, y

  3. Nestin in gastrointestinal and other cancers: Effects on cells and tumor angiogenesis

    Institute of Scientific and Technical Information of China (English)

    Toshiyuki Ishiwata; Yoko Matsuda; Zenya Naito

    2011-01-01

    Nestin is a class Ⅵ intermediate filament protein that was originally described as a neuronal stem cell marker during central nervous system (CNS) development, and is currently widely used in that capacity. Nestin is also expressed in non-neuronal immature or progenitor cells in normal tissues. Under pathological conditions, nestin is expressed in repair processes in the CNS, muscle, liver, and infarcted myocardium. Furthermore, increased nestin expression has been reported in various tumor cells, including CNS tumors, gastrointestinal stromal tumors, pancreatic cancer, prostate cancer, breast cancer, malignant melanoma, dermatofibrosarcoma protuberances, and thyroid tumors. Nestin is reported to correlate with aggressive growth, metastasis, and poor prognosis in some tumors; however, the roles of nestin in cancer cells have not been well characterized. Furthermore, nestin is more specifically expressed in proliferating small-sized tumor vessels in glioblastoma and gastric, colorectal, and prostate cancers than are other tumor vessel markers. These findings indicate that nestin may be a marker for newly synthesized tumor vessels and a therapeutic target for tumor angiogenesis. It has received a lot of attention recently as a cancer stem cell marker in various cancer cells including brain tumors, malignant rhabdoid tumors, and uterine, cervical, prostate, bladder, head and neck, ovarian, testicular, and pancreatic cancers. The purpose of this review is to clarify the roles of nestin in cancer cells and in tumor angiogenesis, and to examine the association between nestin and cancer stem cells. Nestin has the potential to serve as a molecular target for cancers with nestin-positive cancer cells and nestin-positive tumor vasculature.

  4. Fluorescence spectroscopy of gastrointestinal tumors: in vitro studies and in vivo clinical applications

    Science.gov (United States)

    Angelova, L.; Borisova, E.; Zhelyazkova, Al.; Keremedchiev, M.; Vladimirov, B.; Avramov, L.

    2013-11-01

    The limitations of standard endoscopy for detection and evaluation of cancerous changes in the gastrointestinal tract (GIT) are significant challenges and initiate development of new diagnostic modalities. Therefore many spectral and optical techniques are applied recently into the clinical practice for obtaining qualitatively and quantitatively new data from gastrointestinal neoplasia with different levels of clinical applicability and diagnostic success. Fluorescence imaging has been one of the most promising technologies in this area. The technique is very topical with its practical application in intra-operative, image-guided resection of tumors, because it permits minimal surgery intervention and friendly therapeutic conditions. The investigations presented here are based on in vitro measurements of excitation-emission matrices (EEM) for GIT neoplasia and in vivo measurements in the frames of initial clinical trial for tumor fluorescence spectra detection, applied for introduction of spectroscopic diagnostic system for optical biopsy of GIT tumors in the daily clinical practice of the University Hospital "Queen Jiovanna - ISUL"- Sofia. Autofluorescence and exogenous fluorescence signals are detected from normal mucosa, inflammation, dysphasia and carcinoma and main spectral features are evaluated. The systems and methods developed for diagnosis and monitoring could open new dimensions in diagnostic and real-time tumor resection. This will make the entire procedure more personal, patient friendly and effective and will help for further understanding of the tumor nature.

  5. Gastrointestinal stromal tumor in Brazil: clinicopathology, immunohistochemistry, and molecular genetics of 513 cases.

    Science.gov (United States)

    Lopes, Lisandro Ferreira; Ojopi, Elida B; Bacchi, Carlos E

    2008-06-01

    The aim of the present study was to evaluate the clinicopathological, immunohistochemical, and molecular genetic features of gastrointestinal stromal tumors in Brazil and compare them with cases from other countries. Five hundred and thirteen cases were retrospectively analyzed. HE-stained sections and clinical information were reviewed and the immunohistochemical expression of CD117, CD34, smooth-muscle actin, S-100 protein, desmin, CD44v3 adhesion molecule, p53 protein, epidermal growth factor receptor, and Ki-67 antigen was studied using tissue microarrays. Mutation analysis of KIT and platelet-derived growth factor receptor-alpha genes was also performed. There was a slight female predominance (50.3%) and the median age at diagnosis was 59 years. The tumors were mainly located in the stomach (38.4%). Immunohistochemistry showed that CD117 was expressed in 95.7% of cases. Epidermal growth factor receptor expression was observed in 84.4% of tumors. p53 protein expression was found only in 2.6% of cases but all belonged to the high-risk group for aggressive behavior according to the National Institutes of Health consensus approach. No CD44v3 adhesion molecule expression was detected. KIT exon 11 mutations were the most frequent (62.2%). The present data confirm that gastrointestinal stromal tumors in Brazilian patients do not differ from tumors occurring in other countries.

  6. [Resection of a Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with Imatinib].

    Science.gov (United States)

    Sato, Yoshihiro; Karasawa, Hideaki; Aoki, Takeshi; Imoto, Hirofumi; Tanaka, Naoki; Watanabe, Kazuhiro; Abe, Tomoya; Nagao, Munenori; Ohnuma, Shinobu; Musha, Hiroaki; Takahashi, Masanobu; Motoi, Fuyuhiko; Naitoh, Takeshi; Ishioka, Chikashi; Unno, Michiaki

    2016-11-01

    We report a case of a huge gastric gastrointestinal stromal tumor(GIST)that was safely resected followingpreoperative imatinib therapy. A 72-year-old woman was hospitalized with severe abdominal distension. Computed tomography revealed a 27×17 cm tumor in the left upper abdominal cavity. The patient was diagnosed with high risk GIST by EUS-FNA. We initiated preoperative adjuvant chemotherapy with imatinib to achieve a reduction of operative risks and functional preservation. After 6 months of chemotherapy, CT showed a reduction in the tumor size and the patient underwent partial gastrectomy and partial resection of the diaphragm. Histologically, most of the tumor cells were replaced by hyalinized collagen and viable cells were scattered only around the blood vessels. Neoadjuvant chemotherapy with imatinib has the potential to become an important therapeutic option for the treatment of huge GISTs.

  7. Improved sensitivity in the diagnosis of gastro-intestinal tumors by fuzzy logic-based tumor marker profiles including the tumor M2-PK.

    Science.gov (United States)

    Schneider, Joachim; Bitterlich, Norman; Schulze, Guntram

    2005-01-01

    The aim of this study was to improve diagnostic efficiency in the detection of gastro-intestinal cancers by using fuzzy logic modeling in combination with a tumor marker panel (CEA, CA72-4, CA19-9) including Tumor M2-PK. In this prospective study histologically confirmed colorectal (n=247), esophageal (n=86) and gastric cancer (n=122) patients were investigated and compared to control (n=53) persons without any malignant diseases. Tumor M2-PK was measured in plasma with an ELISA (ScheBoBiotech, Germany); all other markers were measured in sera (Roche, Germany). At 95% specificity, tumor detection was possible by the best single marker in colorectal cancer patients in 48% (Tumor M2-PK), in gastric cancers in 61% (CA72-4) and in esophageal cancers in 56% (Tumor M2-PK). A fuzzy logic rule-based system employing a tumor marker panel increased sensitivity significantly in colorectal cancers (pTumor M2-PK and CEA), in gastric cancers (pTumor M2-PK and CA 72-4) and in esophageal cancers (pTumor M2-PK and CA72-4). Adding a third marker further improved the sensitivity only marginally. Fuzzy logic analysis has proven to be more powerful than measurement of single markers alone or combinations using multiple logistic regression analysis of the markers. Therefore, with the fuzzy logic method and a tumor marker panel (including Tumor M2-PK), a new diagnostic tool for the detection of gastro-intestinal cancers is available.

  8. Myiasis gastrointestinal humana por Eristalis tenax Gastrointestinal human myiasis for Eristalis tenax

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    Marcelo Kun

    1998-08-01

    Full Text Available Son caracterizadas las myiasis registradas en Bariloche y establecidas las condiciones probables bajo las cuales se produjeron las infestaciones. Las larvas obtenidas a partir de heces de 2 pacientes fueron identificadas como Eristalis tenax (Diptera: Syrphidae de acuerdo a las claves de Hartley (1961 y Organización Panamericana de la Salud (1962. Estos 2 casos de myiasis gastrointestinal humana constituyen los primeros registrados en Bariloche (Patagonia, Argentina y sus características responden a las registradas para esta especie de Díptera en otras partes del mundo. La falta de control específico en el sistema domiciliario de suministro de agua ha sido la causa más probable de la infestación. Este registro extiende la distribución de E. tenax y de las myiasis gastrointestinales humanas en América del Sur hasta los 41º 03' S.Foram caracterizadas as miasis registradas em Bariloche (Patagonia, Argentina e estabelecidas as prováveis condições sob as quais são produzidas as infestações. As larvas obtidas a partir das fezes de dois pacientes foram identificadas como Eristalis tenax (Diptera: Syrphdae. Esses dois casos de miasis gastrointestinal humana foram os primeiros registrados em Bariloche, Argentina, e suas características respondem às registradas para esta espécie de Diptera em outras partes do mundo. A falta de controle específico no sistema domiciliário de abastecimento de água tem sido a causa mais provável de infestação. Este registro amplia a distribuição de E. tenax e das miasis gastrointestinais humanas em América do Sul até os 41º 03's.The myiasis observed in Bariloche are characterized and the probable conditions under which the infestations took place established. The larvae obtained from faeces of 2 patients were identified as Eristalis tenax (Diptera: Syrphidae according to Hartley (1961 and Organización Panamericana de la Salud keys (1962. These 2 cases of human gastrointestinal myiasis were the

  9. Management of gastrointestinal smooth muscle tumors: Seven years experience of a teaching hospital in Saudi Arabia

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    Al Salamah Saleh

    2000-01-01

    Full Text Available Background: Gastrointestinal (GI smooth muscle tumors are a group of intramural GI tumors formerly known as leiomyoma and leiomyosarcoma. This retrospective study was made to review our experience in surgical management of GI smooth muscle tumors. Methods: The clinical records for patients with GI smooth muscle tumors during 1993-1999 were reviewed. Results: Ten tumors were located in stomach. Abdominal pain was the main presenting symptom followed by GI bleeding. The preoperative diagnosis was made by enhanced computerized tomography (CT on eleven patients out of thirteen, while upper GI endoscopy with biopsy identified six tumors out of thirteen patients had the test. Tumors were treated by conservative excision in four and radical excision in fourteen. Histology was leiomyoma in six patients (with mitotic figures < 4 per 10 high power field and leiomyosarcoma was found in twelve patients (with mitotic figures> 4 per 10 high power field. Median follow-up was 4 years. There was one recurrence for leiomyoma (size: 6cm. All patients with leiomyosarcoma presented later with metastasis and died. Conclusion: Size and mitotic activity of tumors are the main determinant factors. Enhanced CT remains the proper diagnostic tool.

  10. Diagnostic criteria, specific mutations, and genetic predisposition in gastrointestinal stromal tumors

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    Jean-Baptiste Bachet

    2010-10-01

    Full Text Available Jean-Baptiste Bachet1,2, Jean-François Emile1,31EA4340 “Epidémiologie et oncogènes des tumeurs digestives”, Faculté de médecine PIFO, UVSQ, Guyancourt, France; 2Service de Gastroentérologie et Oncologie Digestive, Hôpital Ambroise Paré, APHP, Boulogne, France; 3Service d’Anatomo-cyto-pathologie, Hôpital Ambroise Paré, APHP, Boulogne, FranceAbstract: In 1998, gastrointestinal stromal tumor (GIST emerged as a distinct oncogenetic entity and subsequently became a paradigm of targeted therapies in solid tumors. Diagnosis of GIST relies on both histology and immunohistochemistry. Ninety-five percent of GISTs express either KIT or DOG-1. Approximately 80%–90% of GISTs harbor gain-of-function mutations of either KIT or platelet-derived growth factor receptor alpha polypeptide (PDGFRA receptor tyrosine kinase (RTK. More than 100 different mutations have been described, some of which are associated with specific clinical and/or histological characteristics. Detection of KIT or PDGFRA mutations is recommended in advanced GISTs because they are highly predictive of tumor response to RTK inhibitors, as well as in KIT-negative cases to confirm diagnosis. In most cases, GISTs are sporadic, but in rare cases, they are related with genetic predisposition, such as neurofibromatosis type 1, Carney triad, Carney–Stratakis syndrome, and inherited KIT or PDGFRA germline mutations.Keywords: gastrointestinal stromal tumors, KIT, PDGFRA, genetic predispositions, imatinib

  11. Targeted therapies of gastrointestinal stromal tumors (GIST)--the next frontiers.

    Science.gov (United States)

    Duensing, Stefan; Duensing, Anette

    2010-09-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract and are caused by activating KIT or PDGFRA mutations. GISTs can be successfully treated with the small molecule kinase inhibitor imatinib mesylate (Gleevec, Novartis) with response rates of up to 85%. However, complete responses are rare, and most patients will develop imatinib resistance over time. Recent results have shown that although imatinib effectively stimulates apoptotic cell death in sensitive GIST cells, a considerable proportion of cells does not undergo apoptosis, but instead enters a state of quiescence. Quiescence is characterized by a reversible withdrawal from the cell division cycle, during which the cells remain alive and metabolically active. It is conceivable that quiescence not only plays a pivotal role in the emergence of residual disease but also in creating a pool of tumor cells that survive continuous small molecule therapy and may hence represent the "seeds" for the outgrowth of resistant clones. This review will summarize the current knowledge about GIST biology and treatment response to imatinib including the induction of cellular quiescence in GIST. In addition, we will highlight future strategies to design more effective treatment options to overcome these problems with an aim towards cure of this hitherto untreatable tumor entity. Copyright 2010 Elsevier Inc. All rights reserved.

  12. Comparative study of the different degrees of risk of gastrointestinal stromal tumor

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    Rodrigo Panno Basilio de Oliveira

    Full Text Available OBJECTIVE: To evaluate the applicability of the main categories of risk and morphological factors in the prognosis of gastrointestinal stromal tumors. METHODS: we retrospectively studied fifty-four cases of GIST, assessing the main prognostic factors of this neoplasis: risk levels, topography, size, mitotic index, necrosis, histological subtype and immunophenotype. We also verified their association and the reduction of overall survival. RESULTS: Univariate analysis showed that tumors with mitoses number greater than 5 per 50CGA (high-power fields, the presence of necrosis and a high risk for both the systems proposed by Fletcher and Miettinen had a significant association with reduced survival (p = 0.00001, 0.0056, 0.03 and 0.009, respectively. The remaining analyzed factors (size, histological subtype, topography and immunophenotype had no such association. Multivariate analysis (Jacard index showed that the Miettinen degree of risk was the one that best correlated with prognosis. CONCLUSION: the risk criteria of Fletcher and Miettinen are important in assessing the prognosis of patients with gastrointestinal stromal tumors, especially the latter, which adds to the mitotic index and the presence of tumor necrosis.

  13. Clinical manifestations and prognostic factors in patients with gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Shee-Chan Lin; Ming-Jer Huang; Chen-Yuan Zeng; Tzang-In Wang; Zen-Liang Liu; Ray-Kuan Shiay

    2003-01-01

    AIM: To investigate the incidence of CD117-positive immunohistochemical staining in previously diagnosed gastrointestinal (GI) tract stromal tumors (GTST) and to analyze the tumors' clinical manifestations and prognostic factors.METHODS: We retrospectively reviewed 91 cases with a previous diagnosis of GI stromal tumor, leiomyoma, or leiomyosarcoma. Tissue samples were assessed with CD117, CD34, SMA and S100 immunohistochemical staining. Clinical and pathological characteristics were analyzed for prognostic factors.RESULTS: CD117 was positive in 81 (89 %) of 91 tissue samples. There were 59 cases (72.8 %) positive for CD34,13 (16 %) positive for SMA, and 12 (14.8 %) positive for S100. There was no gender difference in patients with CD117-positive GIST. Their mean age was 65 years. There were 44 (54 %) tumors located in the stomach and 29 (36 %)in the small intestine. The most frequent presenting symptoms were abdominal pain and GI bleeding. The mean tumor size was 7.5±5.7 cm. There were 35 cases (43.2 %)with tumors >5 cm. The tumor size correlated significantly with tumor mitotic count and resectability. Tumor size, mitotic count, and resectability correlated significantly with tumor recurrence and survival. There was recurrent disease in 39 % of our patients, and their mean survival after recurrence was 16.6 months. Most recurrences were at the primary site or metastatic to the liver. Twenty-six percent of our patients died of their disease.CONCLUSION: Traditional histologic criteria are not specific enough to diagnose GIST. This diagnosis must be confirmed with CD117 immunohistochemical staining. Prognosis is dependent on tumor size, mitotic count, and resectability.

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

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

    2012-01-01

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

  15. Giant malignant gastrointestinal stromal tumors: Recurrence and effects of treatment with STI-571

    Institute of Scientific and Technical Information of China (English)

    Teng-Wei Chen; Hsiao-Dung Liu; Rong-Yaun Shyu; Jyh-Cherng Yu; Ming-Lang Shih; Tzu-Ming Chang; Chung-Bao Hsieh

    2005-01-01

    AIM: Malignant gastrointestinal stromal tumors (GISTs)are rare. Tumors larger than 10 cm tend to recur earlier:the larger the volume of the tumor, the worse the prognosis.We hypothesized that treatment with imatinib mesylate (Gleevec; STI-571), a c-kittyrosine kinase inhibitor, as palliative therapy would prolong the survival of patients with recurrent giant malignant GISTs after resection.METHODS: We performed a retrospective analysis of the effects of resection on patients with giant GISTs (>10 cm in diameter) to determine the overall survival and recurrence rates. Twenty-three patients diagnosed with giant GISTs were included from June 1996 to December 2003. STI571 was not available until January 2000. After that time,9 patients received this drug. The factors of age, sex, tumor location, histological surgical margin, and STI-571, tumor size changes and drug side effects were reviewed. We compared the survival rate to determine the prognostic factors and the effects of STI-571 on patients with recurrent malignant gastrointestinal stromal tumor.RESULTS: The positive surgical margin group had a significantly higher recurrence rate than the negative margin group (P = 0.012). A negative surgical margin and palliative treatment with STI-571 were significant prognostic variables (Log-rank test,P<0.05). Age, sex and tumor location were not significant prognostic variables. The 5-year survival rate of the surgical margin free patients was 80%and the 2-year survival rate of the surgical margin positive patients was 28%. The 5-year survival rate was 80% for the patients given STI-571 and 30% for the patients not given STI-571. The use of STI-571 gave a significant tumor shrinkage (6/9) rate in patients with giant GIST recurrence after resection.CONCLUSION: A negative surgical margin and the use of STI-571 after surgical resection were good prognostic indicators. Achieving a tumor-free surgical margin is still the best primary treatment for patients with such tumors

  16. [Gastrointestinal stromal tumors: definition, histological, immunohistochemical, and molecular features, and diagnostic strategy].

    Science.gov (United States)

    Coindre, Jean-Michel; Emile, Jean-François; Monges, Geneviève; Ranchère-Vince, Dominique; Scoazec, Jean-Yves

    2005-10-01

    Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have resulted in the delineation of a treatment that has become a model of targeted therapy in oncology. GISTs are defined as tumors of the gastrointestinal tract, but also of the mesentery and peritoneum, constituted by a proliferation of usually spindle-shaped, rarely epithelioid cells, usually, but not consistently expressing the KIT protein. Most GISTs are associated with molecular abnormalities in two target genes: KIT (which encodes the KIT protein) and PDGFRA (which encodes the A chain of the PDGF receptor). The diagnosis of GIST relies on histological arguments (proliferation of spindle-shaped cells in 70% of cases, of epithelioid cells in 20%; histological variants are rare and sometimes misleading) and on immunohistochemical arguments (expression of KIT in 95%, usually associated with CD34 expression in 60%-70% of cases). The demonstration of mutations in target genes is required only in cases that are histologically suggestive but KIT-negative; beyond this indication, this is only undertaken in research protocols. The differential diagnosis of GIST includes the other mesenchymal tumors of the gastrointestinal tract, such as leiomyomas and leiomyosarcomas, and the digestive locations of some sarcomas; it relies on both histological and immunohistochemical arguments. The evaluation of the prognosis is essential. According to the current concept, every GIST carries a risk of malignancy, which may vary from very low to very high. Prognosis is based on a simple algorithm using two histoprognostic parameters, i.e., tumor size and mitotic index. The treatment of localized GIST is surgical resection, which must be complete; that of advanced or unresectable GIST is based on the use of a targeted therapy

  17. Tumor abscess formation caused by Morganella morganii complicated with bacteremia in a patient with gastrointestinal stromal tumor.

    Science.gov (United States)

    Chen, Hsuan-Wei; Lin, Te-Yu

    2012-04-01

    We report the case of a 22-year-old man who presented with a 3-day history of watery diarrhea, abdominal pain, and fever. An image of the abdomen showed a heterogeneously echogenic mass lesion in the pelvis. The results of the blood cultures performed on admission showed the presence of Morganella morganii. Computed tomography-guided tube drainage was performed, and a culture of the drained abscess fluid yielded M. morganii growth. Exploratory laparotomy with segmental resection of the jejunum and excision of the tumor was performed. Pathological examination showed a gastrointestinal stromal tumor (GIST). A GIST abscess caused by M. morganii was diagnosed on the basis of radiological, microbiological, and histopathological findings. The possibility of an infected GIST should be considered during the differential diagnosis of patients with suspected abdominal neoplasm and bacteremia.

  18. New prognostic parameters for very-low-risk gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    WU Xian-hua; HOU Ying-yong; XU Chen; LIU Ya-lan; SHI Yuan; TAN Yun-shan; ZHU Xiong-zeng

    2011-01-01

    Background According to the National Institutes of Health consensus criteria, gastrointestinal stromal tumors (GISTs) smaller than 2 cm in diameter with less than 5 mitotic figures per 50 high-power fields are considered very-low-risk GISTs, but these two indices alone cannot reliably predict a benign outcome during long-term follow-ups. Therefore, identification of additional parameters for predicting the clinical behavior of GISTs is necessary.Methods Eighty-eight patients with tumors that meet the very-low-risk GIST criteria were retrospectively investigated and morphological parameters of tumors associated with the biological behavior of very-low-risk GISTs were evaluated in the present study. The Kaplan-Meier method was used to calculate disease-free survival rates.Results Eighty-one patients were followed up for one to 16.3 years. Five cases of relapses were identified in the patients. Distinctive infiltrative growth patterns such as muscularis propria, muscularis mucosa, or nerve infiltration were identified by microscopy in 4 patients with the relapse, including three patients who experienced multiple recurrences. The infiltrative growth features became more obvious in multiple recurrent tumors compared to the single recurrent tumor, while only one developed relapse in 76 patients without infiltration (P <0.0001).Conclusion Microscopic infiltrative growth patterns of the tumor may have clinical significance in predicting the prognosis of very-low-risk GISTs.

  19. Familial gastrointestinal stromal tumors associated with dysphagia and novel type germline mutation of KIT gene.

    Science.gov (United States)

    Hirota, Seiichi; Nishida, Toshirou; Isozaki, Koji; Taniguchi, Masahiko; Nishikawa, Kazuhiro; Ohashi, Akiko; Takabayashi, Arimichi; Obayashi, Tadashi; Okuno, Tomoko; Kinoshita, Kazuo; Chen, Hui; Shinomura, Yasuhisa; Kitamura, Yukihiko

    2002-05-01

    A family with multiple gastrointestinal stromal tumors (GISTs), a new type of germline mutation of KIT gene, and dysphagia is reported. The mutation was observed at Asp-820 in tyrosine kinase (TK) II domain. Mutations in TK II domain have been found in mast cell and germ cell tumors but not in GISTs, and the present family members are the first reported cases of GISTs with TK II domain mutations, including sporadic GISTs. Because interleukin 3-dependent Ba/F3 murine lymphoid cells transfected with the mutant KIT complementary DNA grew autonomously without any growth factors and formed tumors in nude mice, the mutation was considered to be gain-of-function type. Family members with the germline KIT mutation reported dysphagia, but those without the mutation did not. The mechanism of dysphagia was examined with gastrointestinal fiberscopy, endoscopic ultrasonography, and esophageal manometry. No mechanical obstruction was found, and the esophagus was not remarkably dilated. In the family members with dysphagia, endoscopic ultrasonography at the esophagocardiac junction showed a thickened hyperechoic layer between the circular and longitudinal muscle layers, suggesting hyperplasia of interstitial cells of Cajal at the myenteric plexus layer. Manometry showed low resting lower esophageal sphincter pressure and abnormal simultaneous contractions of the esophagus without normal peristalsis. These findings indicate that the dysphagia of the present family is different from typical achalasia. This is the first report of familial dysphagia caused by germline gain-of-function mutation of the KIT gene at the TK II domain.

  20. Differentiating gastrointestinal stromal tumors from gastric adenocarcinomas and normal mucosae using confocal Raman microspectroscopy

    Science.gov (United States)

    Hsu, Chih-Wei; Huang, Chia-Chi; Sheu, Jeng-Horng; Lin, Chia-Wen; Lin, Lien-Fu; Jin, Jong-Shiaw; Chen, Wenlung

    2016-07-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and gastric adenocarcinomas are a common cancer worldwide. To differentiate GISTs from adenocarcinomas is important because the surgical processes for both are different; the former excises the tumor with negative margins, while the latter requires radical gastrectomy with lymph node dissection. Endoscopy with biopsy is used to distinguish GISTs from adenocarcinomas; however, it may cause tumor bleeding in GISTs. We reported here the confocal Raman microspectroscopy as an effective tool to differentiate GISTs, adenocarcinomas, and normal mucosae. Of 119 patients enrolled in this study, 102 patients underwent gastrectomy (40 GISTs and 62 adenocarcinomas), and 17 patients with benign lesions were obtained as normal mucosae. Raman signals were integrated for 100 s for each spot on the specimen, and 5 to 10 spots, depending on the sample size, were chosen for each specimen. There were significant differences among those tissues as evidenced by different Raman signal responding to phospholipids and protein structures. The spectral data were further processed and analyzed by using principal component analysis. A two-dimensional plot demonstrated that GISTs, adenocarcinomas, and normal gastric mucosae could be effectively differentiated from each other.

  1. Heavily calcified gastrointestinal stromal tumors: Pathophysiology and implications of a rare clinicopathologic entity

    Science.gov (United States)

    Salati, Massimiliano; Orsi, Giulia; Reggiani Bonetti, Luca; Di Benedetto, Fabrizio; Longo, Giuseppe; Cascinu, Stefano

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, and are characterized by a broad spectrum of clinical, histological and molecular features at presentation. Although focal and scattered calcifications are not uncommon within the primary tumor mass, heavy calcification within a GIST is rarely described in the literature and the clinical-biological meaning of this feature remains unclear. Cases with such an atypical presentation are challenging and may be associated with diagnostic pitfalls. Herein, we report a gastric GIST with the unusual presentation of prominent calcifications that was identified incidentally on imaging during a post-trauma diagnostic work-up. The patient underwent laparoscopic surgery with a radical resection of the mass, which was subsequently characterized by histological analysis as spindle-shaped tumor cells, positive for CD117/c-KIT, CD34 and DOG1, and with calcified areas. Given the intermediate risk of recurrence, no adjuvant therapy was recommended and the patient underwent regular follow-up for 22 mo, with no evidence of relapse. Our case can be considered of interest because of the rarity of clinical presentation and the uniquely large size of the GIST at diagnosis (longest diameter exceeding 9 cm). In closing, we discuss the pathophysiology and clinical implications of calcifications in GISTs by reviewing the most up-to-date relevant literature. PMID:28344749

  2. Small gastrointestinal stromal tumor concomitant with early gastric cancer: A case report

    Institute of Scientific and Technical Information of China (English)

    Ying-Lung Lin; Jeh-En Tzeng; Chang-Kou Wei; Chih-Wen Lin

    2006-01-01

    The term gastrointestinal stromal tumors (GISTs)is defined diagnostically as the main group of mesenchymal tumors with spindle or epithelioid cells arising from the wall of the gastrointestinal tract with immunohistochemical reactivity for CD117 antibody.Previous studies revealed that cells in GISTs express a growth factor receptor with tyrosine kinase activity (termed c-kit), which is the product of the c-kit protooncogene. The most specific and practical diagnostic criteria for GISTs are: immunohistochemically determined c-kit (CD117) expression; mitotic score; and tumor size.A small GIST concomitant with early gastric cancer is rarely encountered clinically. Herein we have reported a case of a 1.1-cm GIST detected by esophagogastroduo denoscopy concomitant with a Ⅱc type of early gastric cancer (signet ring cell type). It was detected during a routine physical health examination. To our knowledge,this is the first report of a small GIST concomitant with a signet ring cell type of early gastric cancer.

  3. Gastrointestinal stromal tumor (GIST of the Treitz’s angle– a very rare cause of high bowel obstruction

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    Mădălina Elena Tobă

    2016-10-01

    Full Text Available Gastrointestinal stromal tumors (GIST are somewhat rare gastrointestinal tumors - approximately 1% to 3% incidence, but they are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs are usually found in the stomach or small intestine but can occur anywhere within the gastrointestinal tract, even in extremely uncommon locations like duodeno-jejunal flexure. Only 3% – 5% of GISTs are located in the duodenum and tumors occurring in the angle of Treitz are even rarer, most published studies being case reports. These tumors have a size ranging from small lesions to large masses and can cause digestive bleeding or high bowel obstruction. This paper is a case presentation illustrating an emergency situation involving a high bowel obstruction caused by a small tumor with an unusual location in the Treitz’s angle. A large percentage of duodenal GISTs are localized in the third and fourth part of the duodenum and may not be found through standard upper endoscopy; only the barium study of the upper gastrointestinal tract highlights the obstruction point. Preoperative diagnosis is difficult but non-invasive imaging techniques like ultrasonography and computed tomography of the abdomen can be helpful. Recently, targeted therapy with inhibitors of tyrosine kinase receptors (IMATINIB has been introduced for the management of advanced and metastatic tumors. In our opinion the surgical resection with curative intent is the treatment of choice.

  4. A malignant omental extra-gastrointestinal stromal tumor on a young man: a case report and review of the literature

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    Almaroof Babatunde

    2008-05-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST are uncommon intra-abdominal tumors. These tumors tend to present with higher frequency in the stomach and small bowel. In fewer than 5% of cases, they originate primarily from the mesentery, omentum, or peritoneum. Furthermore, these extra-gastrointestinal tumors (EGIST tend to be more common in patients greater than 50 years of age. Rarely do EGIST tumors present in those younger than 40 years of age. Case presentation We report a case of a large EGIST in a 27-year-old male. An abdominal pelvic computerized tomography imaging demonstrated an intra-abdominal mass of 22 cm, without invasion of adjacent viscera or liver lesions. This mass was resected en bloc with its fused omentum and an adherent portion of sigmoid colon. Pathology results demonstrated a malignant gastrointestinal stromal tumor with positive CD117 (c-kit staining, and negative margins of resection, and no continuity of tumor with the sigmoid colon. Due to the malignant and aggressive nature of this patient's tumor, he was started on STI-571 as adjuvant chemotherapy. Conclusion Stromal tumors of an extra-gastrointestinal origin are rare. Of the reported omental and mesenteric EGISTs in four published series, a total of 99 tumors were studied. Of the 99 patients in these series only 8 were under 40 years of age, none were younger than 30 years old; and only 5 were younger than 35 years old. Our patient's age is at the lower end of the age spectrum for the reported EGISTs. Young patients who present with an extra-gastrointestinal stromal tumor (EGIST, who have complete resection with negative margins, have a good prognosis. There is little data to support the role of STI-571 in adjuvant or neoadjuvant therapy after curative resection. Given the lack of data, the use of STI-571 must be individualized.

  5. 'Big'-insulin-like growth factor-II signaling is an autocrine survival pathway in gastrointestinal stromal tumors.

    NARCIS (Netherlands)

    Rikhof, B.; Graaf, W.T.A. van der; Suurmeijer, A.J.H.; Doorn, J. van; Meersma, G.J.; Groenen, P.J.T.A.; Schuuring, E.M.; Meijer, C.; Jong, S. de

    2012-01-01

    New treatment targets need to be identified in gastrointestinal stromal tumors (GISTs) to extend the treatment options for patients experiencing failure with small-molecule tyrosine kinase inhibitors, such as imatinib. Insulin-like growth factor (IGF)-II acts as an autocrine factor in several tumor

  6. Impact of Oat-Based Products on Human Gastrointestinal Tract

    Directory of Open Access Journals (Sweden)

    Staka Aiga

    2015-09-01

    Full Text Available Oat is rich in valuable nutrients. In comparison to other cereals, oat contains more total proteins, carbohydrate, fat, non-starch fibre, as well as unique antioxidants (one of them - avenanthramides, vitamins, and minerals. One of the most often studied components of oats is β-glucan - a type of soluble dietary fibre located throughout the starch endosperm, but with highest concentration in the bran. Many studies have shown the beneficial health effects of oat β-glucan as a soluble dietary fibre. Until now, most of the studies on this nutrient have been conducted in the cardiovascular and diabetology field. This article aimed to review the literature on studies that investigated the effects of oat-based products on human gastrointestinal tract - gastrointestinal microflora, irritable bowel syndrome, inflammatory bowel disease as well as prevention/treatment of colorectal cancer. A literature search was conducted using PubMed database. More than 80 potential articles were identified, which were selected afterwards according to aims of our study. Studies done on human were preferred. A long-term dietary intake of oat-based products improves human intestinal microflora, could have benefits in irritable bowel syndrome, and probable effects were seen in patients with ulcerative colitis, but this remains to be proven. There are few studies regarding prevention/treatment of colorectal cancer and they do not show clear benefit nor provide recommendations.

  7. Multifocal gastrointestinal stromal tumor (GIST) of the stomach in an 11-year-old girl

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin [University of North Carolina Hospitals, Department of Radiology, Chapel Hill, NC (United States); Rubinas, Tara C. [University of North Carolina Hospitals, Department of Pathology, Chapel Hill, NC (United States); Fordham, Lynn A. [University of North Carolina School of Medicine, Department of Radiology, Chapel Hill, NC (United States); Phillips, J.D. [University of North Carolina School of Medicine, Department of Surgery, Division of Pediatric Surgery, Chapel Hill, NC (United States)

    2006-11-15

    A previously healthy 11-year-old girl presented with an 8-month history of anemia and left upper quadrant abdominal pain. US examination demonstrated a 9-cm cystic mass with a fluid-fluid level in the left upper quadrant with unclear organ of origin. Abdominal MR imaging demonstrated a complex cystic mass, likely arising from the stomach. Additional T2 hyperintense submucosal lesions were identified in the gastric wall. Surgical excision confirmed the diagnosis of multifocal gastric gastrointestinal stromal tumor (GIST). MR imaging was helpful in suggesting a gastric origin of the primary mass and in demonstrating multifocal disease within the stomach. (orig.)

  8. Inflammatory pseudotumor of the liver in association with a gastrointestinal stromal tumor:A case report

    Institute of Scientific and Technical Information of China (English)

    Oswens S. Lo; Ronnie T. Poon; Chi Ming Lam; Sheung Tat Fan

    2004-01-01

    Inflammatory pseudotumor of the liver is a rare benign lesion that can mimic a malignant liver neoplasm. A case of inflammatory pseudotumor of the liver found in association with a malignant gastrointestinal stromal tumor (GIST) of the small bowel was reported. The inflammatory pseudotumor was misdiagnosed as a metastasis from the GIST by frozen section. A correct diagnosis was made only after histopathological examination of the paraffin section of the resected specimen. This case is particularly interesting because of the association of the two rare pathological entities and the diagnostic dilemma that arose from the similarity of their histological appearances. To our knowledge, this association has not been reported in the literature.

  9. Enucleation for gastrointestinal stromal tumors at the esophagogastric junction: Is this an adequate solution?

    Institute of Scientific and Technical Information of China (English)

    Nadia Peparini; Giovanni Carbotta; Piero Chirletti

    2011-01-01

    The authors discussed the proposal by Coccolini and colleagues to treat gastrointestinal stromal tumors (GISTs) at the esophagogastric junction with enucleation and, if indicated, adjuvant therapy, reducing the risks related to esophageal and gastroesophageal resection. They concluded that, because the prognostic impact of a T1 high-mitotic rate on esophageal GIST is worse than that of a T1 high-mitotic rate on gastric GIST, enucleation may not be an adequate surgery for esophagogastric GISTs with a high mitotic rate in which the guarantee of negative resection margins and adjuvant therapies can be the only chance of survival.

  10. Inhibition of KIT RNAi mediated with adenovirus in gastrointestinal stromal tumor xenograft

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate a therapeutic method for gastrointestinal stromal tumor (GIST) based on KIT RNA interference (RNAi) with AdMax adenovirus. METHODS: KIT short hairpin RNA (shRNA), whose lateral sides were decorated with restriction endonuclease sequences, was designed. T 4 DNA ligase catalyzed the joint of the KIT shRNA and the green fluorescent protein-containing PDC316-EGFP-U6 to form PDC316EGFP-U6-KIT. Homologous recombination of AdEGFPU6-KIT was performed with the AdMax system. Heterotopically transp...

  11. Is laparoscopic resection the appropriate management of a jejunal gastrointestinal stromal tumor (GIST)? Report of a case.

    Science.gov (United States)

    Pitiakoudis, Michail; Zezos, Petros; Courcoutsakis, Nikos; Papanas, Nikolaos; Giatromanolaki, Alexandra; Sivridis, Efthimios; Kouklakis, Georgios; Simopoulos, Constantinos

    2010-10-01

    A 51-year-old female patient presented with iron deficiency anemia. Upper and lower gastrointestinal endoscopy were unremarkable. Computed tomography enteroclysis showed an ovoid 3×4-cm jejunal tumor with intraluminal protrusion and exophytic growth pattern, without lymphadenopathy or metastatic disease. Laparoscopic resection of the tumor was successfully carried out. Histologically, a mesenchymal tumor composed of spindle cells with an interlacing bundle pattern and high-mitotic activity greater than 10 mitoses/50 high-power fields were observed. The immunohistochemistry showed that the tumor was KIT (CD117)-, vimentin-, smooth muscle actin-, and S-100-positive, whereas it was CD34-negative. These findings were consistent with the features of a gastrointestinal stromal tumor. The patient had an uneventful postoperative course, and after 10 months of follow-up, she is well without any evidence of tumor recurrence.

  12. UPPER GASTRO-INTESTINAL BLEEDING IN THE YOUNG - GASTRIC GIST TUMOR OR PEPTIC ULCER DISEASE?

    Directory of Open Access Journals (Sweden)

    Ayodele Atolagbe

    2015-09-01

    Full Text Available GIST tumors is very unusual in the young and middle aged and a high index of suspicion is needed for the diagnosis in young patients who present with upper gastrointestinal bleeding. Appropriate imaging such as a Computed tomographic scan (CT scan may identify this tumor which may easily be misdiagnosed as a bleeding Peptic Ulcer Disease in the young. We present a case of a healthy 38 year old man with no alcohol use who presented with epigastric pain and melena and subsequent torrential bleeding uncontrolled during endoscopy necessitating an emergency exploratory laparotomy by the general surgery team. The bleeding intraluminal component of the tumor with gross splenic and pancreatic involvement was identified and surgical management consisted of a wedge resection of the greater curvature of the stomach incorporating the tumor and the spleen with successful dissection of the tumor off the tail of the pancreas. Histology was positive for C-KIT and DOG-1 markers. Postoperative course was uneventful and he is presently on Imatinib Mesylate.

  13. Gastrointestinal stromal tumors: evolving role of the multidisciplinary team approach in management.

    Science.gov (United States)

    Reichardt, Peter; Morosi, Carlo; Wardelmann, Eva; Gronchi, Alessandro

    2012-08-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors of the GI tract arising from mesenchymal cells. Treatment options include surgical resection and medical therapy with imatinib. A summary of National Comprehensive Cancer Network and European Society of Medical Oncology clinical practice guidelines relating to GIST management are presented here. A multidisciplinary team of physicians is essential to the successful treatment of GIST. Evidence supports multidisciplinary team management with a gastroenterologist, surgeon, medical oncologist, pathologist and radiologist. Consultations between them are recommended to ensure optimal care of patients with GIST. The role for individual core team workers is highlighted. The benefits of multidisciplinary disease management of patients include reducing recurrent disease, optimizing timing of surgery and organ preservation, prolonging survival for the patient and enhancing response to targeted therapies.

  14. Malignant gastrointestinal stromal tumor of the ampulla of Vater presenting with obstructive jaundice

    Directory of Open Access Journals (Sweden)

    Filippou Dimitrios

    2006-01-01

    Full Text Available Malignant gastrointestinal stromal tumor (GIST consists a rare neoplasm, developing in small intestine and stomach. The presenting manifastations include weakness, weight loss, nausea, melena and anaemia. The present case refers to a 65 years old female patient with a GIST of the ampulla of Vater presenting with obstructive jaundice. Diagnosis was achieved pre-operatively by biopsies collected through diagnostic ERCP. The tumour was locally excised, with preservation of the ampulla. The histological analysis suggested low grade GIST positive for both CD 117 (c-kit and CD34. Two years after the surgery the patient remains free of disease. Malignant GIST of the ampulla of the Vater is extremely rare as only few similar cases have been described in the literature. This is the first time a GIST being presented as obstructive jaundice ever reported. Despite the unavailability of EUS-FNA, the diagnosis was set preoperatively and the tumor was resected.

  15. KIT-negative Gastrointestinal Stromal Tumor in a Child: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Se Woong; Lee, Young Hwan; Park, Sang Hyeon; Choi, Du young; Choi, Geum Ha [Wonkwang University School of Medicine and Hospital, Iksan (Korea, Republic of)

    2011-01-15

    We report here on the imaging findings of the case of KIT-negative gastrointestinal stromal tumor (GIST) in the stomach of a 12-year-old girl. Radiologic studies revealed the presence of a huge exophytic growing mass that originated from the gastric wall and this mass consisted of solid and cystic components on USG, CT and MR. The cystic regions were mainly located at the periphery of the mass and they were revealed to be myxoid degeneration and hemorrhage on histopathologic examination. The tumor consisted of epithelioid and typical spindle cells and they showed negative immunoreactivity for KIT. Although KIT-negative GISTs are rare, they can be considered in the differential diagnosis when a large heterogeneous extraluminal mass that contains solid portions and various degrees of peripheral cystic regions is observed

  16. Supraclavicular lymph node metastases from malignant gastrointestinal stromal tumor of the jejunum: A case report with review of the literature.

    Science.gov (United States)

    Ma, Chi; Hao, Shao-Long; Liu, Xin-Cheng; Nin, Jin-Yao; Wu, Guo-Chang; Jiang, Li-Xin; Fancellu, Alessandro; Porcu, Alberto; Zheng, Hai-Tao

    2017-03-14

    Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the alimentary tract. These tumors may have different clinical and biological behaviors. Malignant forms usually spread via a hematogenous route, and lymph node metastases rarely occur. Herein, we report a patient with a jejunal GIST who developed supraclavicular lymph node metastasis. We conclude that lymphatic diffusion via the mediastinal lymphatic station to the supraclavicular lymph nodes can be a potential metastatic route for GISTs.

  17. Deep biopsy via endoscopic submucosal dissection in upper gastrointestinal subepithelial tumors: a prospective study.

    Science.gov (United States)

    Tae, Hye Jin; Lee, Hang Lak; Lee, Kang Nyeong; Jun, Dae Won; Lee, Oh Young; Han, Dong Soo; Yoon, Byung Chul; Choi, Ho Soon; Hahm, Joon Soo

    2014-10-01

    Preoperative pathological diagnosis may improve clinical management decisions in patients with upper gastrointestinal subepithelial tumors (SETs). The aims of this study were to evaluate the diagnostic yield of deep biopsy via an endoscopic submucosal dissection (ESD) technique, the complications associated with the procedure, and the impact on management of patients with upper gastrointestinal SETs. A total of 68 patients with SETs in the stomach or esophagus were voluntarily assigned to two groups. One group underwent endoscopic ultrasound (EUS) and endoscopic deep biopsy using the ESD technique (40 patients), and the other group (28 patients) underwent surgical resection after EUS without obtaining preoperative pathological diagnosis, in accordance with accepted clinical management algorithms. The diagnostic yield of deep biopsy was 90 % (36/40). The results of deep biopsy changed the treatment plans in 14/40 patients (35 %). One patient with lymphoepithelial carcinoma was scheduled for surgical resection, and 13 patients with benign SETs of diameter ≥  2 cm avoided surgery. Of the 28 patients who underwent surgical resection without preoperative pathological diagnosis, 12 (42.9 %) were confirmed to have benign lesions. The mean procedure time for deep biopsy was 13.7 minutes. There were no procedure-related complications in the deep biopsy group.  Deep biopsy by the ESD technique is a safe, high-yield, diagnostic method in patients with upper gastrointestinal SETs. Pathologic confirmation could improve clinical decision making in the management of patients with upper gastrointestinal SETs. NCT 01993199. © Georg Thieme Verlag KG Stuttgart · New York.

  18. Three cases of bone metastases in patients with gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Maurizio Zompatori

    2011-04-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare, but represent the most common mesenchymal neoplasms of the gastrointestinal tract. Tumor resection is the treatment of choice for localized disease. Tyrosine kinase inhibitors (imatinib, sunitinib are the standard therapy for metastatic or unresectable GISTs. GISTs usually metastasize to the liver and peritoneum. Bone metastases are uncommon. We describe three cases of bone metastases in patients with advanced GISTs: two women (82 and 54 years of age, and one man (62 years of age. Bones metastases involved the spine, pelvis and ribs in one patient, multiple vertebral bodies and pelvis in one, and the spine and iliac wings in the third case. The lesions presented a lytic pattern in all cases. Two patients presented with multiple bone metastases at the time of initial diagnosis and one patient after seven years during the follow-up period. This report describes the diagnosis and treatment of the lesions and may help clinicians to manage bones metastases in GIST patients.

  19. Imatinib enchances the sensitivity of gastrointestinal stromal tumors to topoisomerase II inhibitors

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    S. V. Boichuk

    2015-01-01

    Full Text Available Objective: to study the sensitivity of gastrointestinal stromal tumors (GISTs to the topoisomerases type II inhibitors and ability of imatinib to enhance GISTs sensitivity to the chemotherapeutic drugs indicated above.Subjects and Methods. We studied the sensitivity of gastrointestinal stromal tumors (GISTs to the topoisomerases II inhibitors and ability of imatinib to enhance GISTs sensitivity to these chemotherapeutic agents. The expression of DNA damage and repair (DDR markers was examined by western-blotting. Cleaved forms of poly (ADP-rybose polymerase and caspase-3 were served as an apoptotic markers measured by western blotting. Amount of apoptotic cells was counted by flow cytometry analysis by using a propidium iodide DNA staining procedure and counting the numbers of hypodiploid cells.Results. We observed the sensitivity of GISTs to topoisomerase II inhibitors – doxorubicine and etoposide inducing DNA double-strand breaks and apoptotic cell death. Imatinib enhances GISTs sensitivity to topoisomerase II inhibitors. This might be due to reduced ability of GISTs to repair DNA damage by homologous recombination. Imatinib-induced reduction of Rad51 recombinase might be due to increased proteasome-dependent degradation.Conclusion. GIST cells are sensitive to topoisomerase II inhibitors (etoposide and doxorubicin in vitro. Imatinib enhances GISTs sensitivity to the chemotherapeutic agents indicated above.

  20. [Severe lower gastrointestinal bleeding due to GIST tumor. Radiological embolization and surgery].

    Science.gov (United States)

    Navas, Diana; Ríos, Antonio; Febrero, Beatriz; Rodríguez, José Manuel; Lloret, Francisco; Parrilla, Pascual

    2014-01-01

    Antecedentes: los tumores del estroma gastrointestinal (GIST) se identificaron hace muy poco tiempo. Son tumores que no suelen alertar con síntomas mientras permanecen en fase localizada, operable y curable. Aunque son poco frecuentes, cuando no se diagnostican y tratan oportunamente son muy agresivos. Su manifestación clínica más común es la hemorragia gastrointestinal por erosión de la mucosa, pero su presentación como hemorragia baja del tubo digestivo severa es excepcional. Caso clínico: se comunica un caso de hemorragia baja del tubo digestivo severa estabilizada por radiología intervencionista, que posteriormente requirió cirugía para su tratamiento definitivo. Conclusiones: la embolización radiológica está cada vez más difundida como tratamiento de hemorragias en distintos sitios porque permite la estabilización hemodinámica de los pacientes. No hay que olvidar, sin embargo, que en los casos de hemorragia baja del tubo digestivo, de origen desconocido, es necesario investigar las posibles causas.

  1. Assessment of TPS tumor marker with ELISA for early detection and monitoring of gastrointestinal cancers

    Directory of Open Access Journals (Sweden)

    Salehi Nodeh A.R

    2007-05-01

    Full Text Available Background: TPS is one of the tumor markers which has specially been considered due to its exclusive physiological characteristics like its easy measurement in serum of cancer patients. This study has been due to evaluate the efficiency of this tumor marker in the prognosis, treatment control and follow up of patients with gastrointestinal cancers including esophagus, stomach and colorectal. Methods: TPS has been measured in 109 persons including 28 healthy people and 81 patients with different gastrointestinal malignancies which were composed of 38 patients with esophageal cancer, 20 ones with stomach cancer and 23 ones with colorectal cancer. Sampling has been done in three times depending on treatment methods. TPS has been measured with ELISA in samples which contend of 2 to 3 ml of serum from patients and the health. Results: The obtained results, demonstrate the obvious changes in TPS serum level in patients underwent various treatment procedures. Conclusion: The results have revealed that the serum TPS is not only as a measure of prognosis but also would be helpful in follow up and treatment control of the disease. Moreover the results has shown that serological analysis can be settled in the diagnosis and follow up with production of polyclonal antibody against TPS gene family and planning appropriate pattern.

  2. KIT exon 11 deletion-inversions represent complex mutations in gastrointestinal stromal tumors.

    Science.gov (United States)

    Lasota, Jerzy; Miettinen, Markku

    2007-05-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. KIT expression and mutational KIT activation have been documented in a majority of GISTs. Most mutations have been found in KIT juxtamembrane domain encoded by exon 11. Recently, we have identified three, complex KIT exon 11 mutations previously unreported in GISTs. These mutations consisted of several nucleotide deletions accompanied by insertions of inverted complementary DNA strand sequences. All three mutations were found in the 5' part of KIT exon 11. At the protein level, these mutations lead to the same end result: in-frame loss and insertion of a number of amino acids and could be considered examples of deletion-insertion. Although proper description of these mutations at the genomic level is a complex task and requires an individual approach, the uniform name deletion-inversion is suggested for this type of mutation, based on the present study. The frequency of deletion-inversions among KIT exon 11 mutant GISTs was estimated to be <0.5%, based on evaluation of 700 KIT exon 11 mutants. Molecular events leading to formation of deletion-inversions remain elusive and should be studied further.

  3. NOTCH receptors in gastric and other gastrointestinal cancers: oncogenes or tumor suppressors?

    Science.gov (United States)

    Huang, Tingting; Zhou, Yuhang; Cheng, Alfred S L; Yu, Jun; To, Ka Fai; Kang, Wei

    2016-12-09

    Gastric cancer (GC) ranks the most common cancer types and is one of the leading causes of cancer-related death. Due to delayed diagnosis and high metastatic frequency, 5-year survival rate of GC is rather low. It is a complex disease resulting from the interaction between environmental factors and host genetic alterations that deregulate multiple signaling pathways. The Notch signaling pathway, a highly conserved system in the regulation of the fate in several cell types, plays a pivotal role in cell differentiation, survival and proliferation. Notch is also one of the most commonly activated signaling pathways in tumors and its aberrant activation plays a key role in cancer advancement. Whether Notch cascade exerts oncogenic or tumor suppressive function in different cancer types depends on the cellular context. Mammals have four NOTCH receptors that modulate Notch pathway activity. In this review, we provide a comprehensive summary on the functional role of NOTCH receptors in gastric and other gastrointestinal cancers. Increasing knowledge of NOTCH receptors in gastrointestinal cancers will help us recognize the underlying mechanisms of Notch signaling and develop novel therapeutic strategies for GC.

  4. Aspects of surgical treatment for gastro-intestinal stromal tumors; Chirurgische Therapieaspekte gastrointestinaler Stromatumoren

    Energy Technology Data Exchange (ETDEWEB)

    Hohenberger, P. [Medizinische Fakultaet Mannheim, Universitaet Heidelberg, Sektion Chirurgische Onkologie und Thoraxchirurgie, Chirurgische Universitaetsklinik, Mannheim (Germany)

    2009-12-15

    Gastro-intestinal stromal tumors (GIST) form the commonest subgroup of soft tissue sarcomas. They arise in the muscular layer of the esophagus, stomach, small intestines and rectum. Characteristic and important for the assessment of the extent of tumors is the peripheral rim vascularization of primary tumors and metastases. Indications for resection are given for tumors larger than 2 cm in size. Locally advanced GISTs can be advantageously treated with imatinib/sunitinib as neoadjuvant and it is often possible to select a low level of resection for this size of tumor and when the rim area is not hypervascularized. Even in the metastizing stage surgical treatment can be used for elimination of resistant metastases or for removal of residual tumor tissue in an attempt to counteract secondary tumor progression. The effect of this treatment is currently being tested in a randomized phase III study. (orig.) [German] Gastrointestinale Stromatumoren (GIST) stellen die haeufigste Subgruppe von Weichgewebesarkomen dar. Sie entstehen in der Muskularisschicht von Oesophagus, Magen, Duenndarm und Rektum. Charakteristisch und wichtig fuer die Einschaetzung des Tumorausmasses ist die Randvaskularisation von Primaertumoren und Metastasen. Die Indikation zur Resektion gilt fuer Tumoren ab 2 cm Groesse. Lokal fortgeschrittene GIST koennen sehr vorteilhaft mit Imatinib/Sunitinib neoadjuvant vorbehandelt werden, und es ist oft moeglich, bei der Tumorgroesse und wenn keine hypervaskularisierten Randbereiche vorliegen, ein geringeres Resektionsausmass zu waehlen. Auch im metastasierten Stadium hat die chirurgische Therapie einen Platz zur Eliminierung resistenter Metastasen bzw. zur Entfernung von Residualtumorgewebe als Versuch, einer sekundaeren Tumorprogression zu begegnen. Dieser Behandlungseffekt wird derzeit in einer randomisierten Phase-III-Studie ueberprueft. (orig.)

  5. Gastrointestinal stromal tumor (GIST coexisting with pancreatic cancer and hepatic hemangioma

    Directory of Open Access Journals (Sweden)

    M. A. Beltrán

    2014-11-01

    Full Text Available The occurrence of gastric gastrointestinal stromal tumors (GIST associated to pancreatic adenocarcinoma has been reported in 0.2% pancreatic cancers. There are no published reports on distal pancreatic adenocarcinoma associated to gastric antral GIST. Herein, we discuss a 75 years-old female patient who was admitted to our institution with upper digestive hemorrhage. The endoscopy showed large, superficial erosions over the cardias and, on the posterior wall of the antrum, a rounded sub-mucosal non-eroded lesion suspected of gastric GIST. An abdominal computed tomography scan found a hepatic hemangioma on the left hepatic lobe. In the pancreatic distal body and tail a solid exophytic lesion was identified. The surgical findings confirmed the radiologic diagnostic. The biopsy reported a hepatic hemangioma. The pancreatic tail and the proximal part of the body harbored a well-differentiated ductal adenocarcinoma measuring 3.4 cm x 3 cm x 2.5 cm with negative margins. The gastric tumor measured 4 cm x 2.5 cm x 1 cm, was positive for CD117, CD34, and DOG-1; it had a positive Ki67 in less than 2%, and 2 or less mitoses per 50 high-power fields. This uncommon case illustrates the occurrence of synchronous tumors of different cellular origins in the same patient, which were diagnosed during the study for another unrelated condition. The individual incidence of these tumors is low and if associated they probably will continue to be found incidentally.

  6. Coexistence of gastrointestinal stromal tumor (GIST and colorectal adenocarcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Evangelos Felekouras

    2007-08-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST represent the most common mesenchymal tumors of the digestive tract. Over the last ten years the management of GISTs has dramatically altered but their coexistence with other gasrointesinal tumors of different histogenesis presents a special interest. The coexistence of GISTs with other primaries is usually discovered incidentally during GI surgery for carcinomas. Case presentation We present here, a case of a 66-year-old patient with intestinal GIST and a synchronous colorectal adenocarcinoma discovered incidentally during surgical treatment of the recurrent GIST. Immunohistochemical examination revealed the concurrence of histologically proved GIST (strongly positive staining for c-kit, vimentin, SMA, and focal positive in S-100, while CD-34 was negative and Dukes Stage C, (T3, N3, M0 according the TNM staging classification of colorectal cancer. Conclusion The coexistence of GIST with either synchronous or metachronous colorectal cancer represents a phenomenon with increasing number of relative reports in the literature the last 5 years. In any case of GIST the surgeon should be alert to recognize a possible coexistent tumor with different histological origin and to perform a thorough preoperative and intraoperative control. The correct diagnosis before and at the time of the surgical procedure is the cornerstone that secures the patients' best prognosis.

  7. Survival of gastrointestinal stromal tumor patients in the imatinib era: life raft group observational registry

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    Call Jerry

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST, one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. Methods This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P Results Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group ( Conclusions Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant prognostic factors for each from a diverse real-world cohort. Additionally, these findings suggest that extra diligence be taken with "young adults" (aged 18-35 at diagnosis as pediatric-type GIST may present well beyond adolescence, particularly as these distinct sub-types have different causes, and consequently

  8. Incidence and clinicopathologic features of gastrointestinal stromal tumors. A population-based study

    Directory of Open Access Journals (Sweden)

    Marcheselli Luigi

    2007-12-01

    Full Text Available Abstract Background Although the diagnostic criteria and pathogenesis of gastrointestinal stromal tumors (GIST have recently been elucidated, knowledge of the epidemiology of this malignancy is still limited. This study examined the incidence of GIST in the province of Modena, including pathologic features and clinical outcome. Methods Gastrointestinal mesenchymal tumors identified by the Modena Cancer Registry between 1991 and 2004 were analyzed with an immunohistochemical panel that included staining for CD-117 and PDGFRα. Size, mitotic rate, and other pathologic parameters were recorded. Each tumor was categorized into National Institutes of Health risk categories (very low, low, intermediate, and high risk. Results One hundred twenty-four cases were classified as GIST. The age-adjusted incidence rate was 6.6 per million. Seventy-five percent of patients were symptomatic; 34% had a previous or concomitant history of cancer. High-risk features were present in 47% of cases. Seventy-eight percent were submitted to radical surgery. After complete resection, the 5-year disease-free survival rates were 94%, 92%, 100%, and 40% for patients at very low, low, intermediate, and high risk, respectively. In multivariate analysis, high risk was the main predictor of recurrence. Conclusion This population-based study shows that the incidence of GIST in Northern Italy is comparable to that reported in other European countries. Survival was favorable in lower risk categories and in most of the resected cases. In our study, resected patients at very low, low, and intermediate risk had a similar outcome. Our data support the need to consider high-risk patients after complete surgical resection for treatment with the best available approach.

  9. Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2001-01-01

    AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new

  10. Hepatic metabolism of toluene after gastrointestinal uptake in humans

    DEFF Research Database (Denmark)

    Bælum, Jesper; Mølhave, Lars; Honoré Hansen, S

    1993-01-01

    The metabolism of toluene and the influence of small doses of ethanol were measured in eight male volunteers after gastrointestinal uptake, the toluene concentration in alveolar air and the urinary excretion of hippuric acid and ortho-cresol being used as the measures of metabolism. During toluene...... exposure to 2 mg.min-1 for 3 h the alveolar toluene concentration was 0.07 (range 0-0.11) mg.m-3; exposure to 6 mg.min-1 for 30 min increased the alveolar concentration to 0.9 (range 0.03-2.6) mg.m-3. Ingestion of 0.08, 0.16, and 0.32 g of ethanol per kilogram of body weight during toluene exposure of 2 mg...... doses of ethanol inhibit toluene metabolism, and the procedure is sensitive enough to measure metabolic interactions between solvents and other xenobiotics in humans....

  11. Surgical management of gastric gastrointestinal stromal tumor: A single center experience

    Directory of Open Access Journals (Sweden)

    Ehab El-Hanafy

    2011-01-01

    Full Text Available Background/Aim: Gastrointestinal stromal tumors (GISTs are the most common mesenchymal tumors of the gastrointestinal tract. Surgery remains the mainstay of curative treatment. Our objective is to evaluate the outcome of surgical treatment of primary gastric GIST. Materials and Methods: Between January 1997 and April 2008, thirty seven consecutive patients underwent resection for GISTs (35 patients with primary gastric GISTs and two patients with intestinal GISTs who were excluded from the study. These patients underwent upper endoscopy ± biopsy, barium meal and abdominal CT scan. Patients′ demographics and clinical presentations were analyzed. Perioperative parameters measured included operative times, estimated blood loss, intraoperative finding, surgical techniques, morbidity and length of hospitalization. Recurrence and survival were also analyzed. Results: Of the 35 patients with gastric GISTs included in the study, 63% were female. The median age was 59 ± 14 years (range, 23 to 75 years. The primary presenting symptoms were bleeding and dyspepsia; 43% of these tumors were located mainly in the body of the stomach. Tumor size was < 10 cm in 80% of the patients. The average tumor size was 6.3 ±3.2 cm (range from 3 to 13 cm. Regarding the surgical management, 20 patients (57% underwent gastric wedge resection, eight patients (23% underwent partial gastrectomy and the remaining seven patients (20% underwent total gastrectomy. Radical resections were found in 32 patients (91.5% while palliative resections were found in three patients (8.5%. The resected lymph nodes were negative in 32 patients (91.5%. Recurrence was noted in three patients, with a median time to recurrence of 14.3 months (range, 7 to 28 months. The three- and five-years survival in patients who underwent wedge resection was 92% and 81%, respectively, where it was 95% and 87%, respectively, in patients who underwent gastrectomy (either partial or total. There were no major

  12. Correlation of Dynamic PET and Gene Array Data in Patients with Gastrointestinal Stromal Tumors

    Directory of Open Access Journals (Sweden)

    Ludwig G. Strauss

    2012-01-01

    Full Text Available Introduction. The results obtained with dynamic PET (dPET were compared to gene expression data obtained in patients with gastrointestinal stromal tumors (GIST. The primary aim was to assess the association of the dPET results and gene expression data. Material and Methods. dPET was performed following the injection of F-18-fluorodeoxyglucose (FDG in 22 patients with GIST. All patients were examined prior to surgery for staging purpose. Compartment and noncompartment models were used for the quantitative evaluation of the dPET examinations. Gene array data were based on tumor specimen obtained by surgery after the PET examinations. Results. The data analysis revealed significant correlations for the dPET parameters and the expression of zinc finger genes (znf43, znf85, znf91, znf189. Furthermore, the transport of FDG (k1 was associated with VEGF-A. The cell cycle gene cyclin-dependent kinase inhibitor 1C was correlated with the maximum tracer uptake (SUVmax in the tumors. Conclusions. The data demonstrate a dependency of the tracer kinetics on genes associated with prognosis in GIST. Furthermore, angiogenesis and cell proliferation have an impact on the tracer uptake.

  13. Gastrointestinal stromal tumors as an incidental finding in patients with a presumptive diagnosis of ovarian cancer.

    Science.gov (United States)

    Muñoz, Mario; Ramirez, Pedro T; Echeverri, Carolina; Alvarez, Luis Guillermo; Palomino, Maria Alejandra; Pareja, Luis René

    2012-01-01

    To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST). Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%. GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass.

  14. Comparison of Gene Expression Profile Between Tumor Tissue and Adjacent Non-tumor Tissue in Patients with Gastric Gastrointestinal Stromal Tumor (GIST).

    Science.gov (United States)

    Kou, Youwei; Zhao, Ying; Bao, Chenhui; Wang, Qiang

    2015-06-01

    Gastrointestinal stromal tumors (GISTs) are defined as spindle cell and/or epithelioid tumors originated from interstitial Cajal cells or precursors in the digestive tract. This study was conducted to identify genes differing in expression between the gastric tumors and the adjacent non-cancerous mucosas in patients with primary gastric GIST. The gene expression profile was determined by using oligonucleotide-based DNA microarrays and further validated by quantitative real-time PCR. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was performed to predict signaling pathways involved in gastric GIST. Our data showed that the expression levels of 957 genes (RAB39B, member RAS oncogene family; VCAN, versican; etc.) were higher and that of 526 genes (CXCL14, chemokine C-X-C motif ligand 14; MTUS1, microtubule-associated tumor suppressor 1; etc.) were lower in the gastric tumor tissues as compared with normal gastric tissues. Results from KEGG pathway analysis revealed that the differentially expressed genes were enriched into 16 signaling transduction pathways, including Hedeghog and Wnt signaling pathways. Our study may provide basis for identification of novel biomarkers associated with primary gastric GIST pathogenesis and for exploration of underlying mechanisms involved in this gastric sarcoma.

  15. Human neutrophils facilitate tumor cell transendothelial migration.

    LENUS (Irish Health Repository)

    Wu, Q D

    2012-02-03

    Tumor cell extravasation plays a key role in tumor metastasis. However, the precise mechanisms by which tumor cells migrate through normal vascular endothelium remain unclear. In this study, using an in vitro transendothelial migration model, we show that human polymorphonuclear neutrophils (PMN) assist the human breast tumor cell line MDA-MB-231 to cross the endothelial barrier. We found that tumor-conditioned medium (TCM) downregulated PMN cytocidal function, delayed PMN apoptosis, and concomitantly upregulated PMN adhesion molecule expression. These PMN treated with TCM attached to tumor cells and facilitated tumor cell migration through different endothelial monolayers. In contrast, MDA-MB-231 cells alone did not transmigrate. FACScan analysis revealed that these tumor cells expressed high levels of intercellular adhesion molecule-1 (ICAM-1) but did not express CD11a, CD11b, or CD18. Blockage of CD11b and CD18 on PMN and of ICAM-1 on MDA-MB-231 cells significantly attenuated TCM-treated, PMN-mediated tumor cell migration. These tumor cells still possessed the ability to proliferate after PMN-assisted transmigration. These results indicate that TCM-treated PMN may serve as a carrier to assist tumor cell transendothelial migration and suggest that tumor cells can exploit PMN and alter their function to facilitate their extravasation.

  16. Treatment of gastrointestinal stromal tumor with imatinib mesylate: a retrospective single-center experience in Heidelberg.

    Science.gov (United States)

    Kasper, Bernd; Kallinowski, Birgit; Herrmann, Thomas; Lehnert, Thomas; Mechtersheimer, Gunhild; Geer, Thomas; Ho, Anthony D; Egerer, Gerlinde

    2006-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Surgery has been the only effective therapy. However, many patients still eventually die of disease recurrence. Chemotherapy and radiation therapy have been of limited value. Imatinib mesylate (Glivec) is an orally administered competitive inhibitor of tyrosine kinases associated with the KIT, ABL protein, licensed for the treatment of metastatic GIST since 2002 in Germany. We summarized the data of 16 patients with advanced or metastatic GIST treated with imatinib mesylate in palliative and neoadjuvant settings. Overall response was 81%, with no evidence of disease (NED) in 3/16 (19%), partial response (PR) in 9/16 (56%) and stable disease (SD) in 1/16 (6%), whereas 3/16 patients (19%) suffered from progressive disease (PD). Mean follow-up was 18.6 months [range: 4-30]. Mean progression-free survival (PFS) was 17.6 months [range: 0-30], mean overall survival (OS) from initial diagnosis was 32.3 months [range: 5-122]. Most common side effects were periorbital edema and skin rash. Imatinib mesylate is well tolerated in a dose of up to 800 mg/day and has significant activity during long- term treatment of patients with advanced or metastatic GIST. Copyright 2006 S. Karger AG, Basel.

  17. Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model

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    In Hye Jung

    2016-08-01

    Full Text Available Severe combined immunodeficiency (SCID mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.

  18. Perforation of the colon by invading recurrent gastrointestinal stromal tumors during sunitinib treatment

    Institute of Scientific and Technical Information of China (English)

    Hoon Hur; Ae Ryoung Park; Sung Bae Jee; Seung Eun Jung; Week Kim; Hae Myung Jeon

    2008-01-01

    The molecular targets of sunitinib are receptor tyrosine kinases (RTKs), and this drug has also been known to exert blocking effects on the activation of KIT, which is similar to the mechanism of action of imatinib. Moreover, sunitinib has an additional anti-angiogenic effect through its inhibition of the vascular endothelial growth factor receptor activation. We report here a 70-year-old patient diagnosed with a recurrent gastrointestinal stromal tumor (GIST), which invaded the transverse colon and led to a perforation during sunitinib treatment. A computed tomography scan and 3-dimensional reconstruction showed necrosis of the recurrent hepatic mass and perforation of the invaded transverse colon. After percutaneous drainage of the intraperitoneal abscess, antibiotic treatment and restricted diet, the condition of the patient improved. The present case is the first to report that sunitinib, which is administered to treat GIST resistant to imatinib, can cause unexpected colon perforation and subsequent peritonitis.

  19. The progressive fragmentation of the KIT/PDGFRA wild-type (WT) gastrointestinal stromal tumors (GIST).

    Science.gov (United States)

    Nannini, Margherita; Urbini, Milena; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A

    2017-05-23

    Recent advances in molecular biology have revolutionized the concept of KIT/PDGFRA wild type (WT) gastrointestinal stromal tumors (GIST) than the past. Indeed, from being defined as GIST without KIT or PDGFRA mutations, we are now faced with the opposite scenario, where KIT/PDGFRA WT GIST are "positively" defined according to their specific molecular alterations. In particular, if until recently KIT/PDGFRA GIST without abnormalities of KIT, PDGFRA, SDH, and the RAS signaling pathway were referred as quadruple WT GIST, today also this small subset of GIST is emerging out as a group of heterogeneous distinct entities with multiple different molecular alterations. Therefore, given this still growing and rapidly evolving scenario, the progressive molecular fragmentation may inevitably lead over the time to the disappearance of KIT/PDGFRA WT GIST, destined to be singularly defined by their molecular fingerprint.

  20. Exophytic Colon Cancer: Resemblance to a Gastrointestinal Stromal Tumor of the Stomach: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Chul Hi; Kim, Ha Na; Byun, Sung Su; Ha, Seung Yeon [Gachon University of Medicine and Science, Incheon (Korea, Republic of)

    2009-04-15

    An exophytic adenocarcinoma of the colon is very rare with only a few reports to date. To the best of our knowledge, the CT appearance of colon cancer, which simulated the classic appearance of a GIST has only been reported once in the world's literature. We recently evaluated a patient with a large lobulated mass involving the stomach, pancreas and colon. The CT appearance of the case was consistent with the diagnosis of an exophytic gastric GIST. However, at surgery, the patient was found to have a large ulcerated carcinoma of the colon near the splenic flexure that had invaded the stomach and pancreas. We report a case of an exophytic adenocarcinoma of the colon that resembled the classic appearance of a gastrointestinal stromal tumor of the stomach.

  1. Laparoscopic resection of sporadic synchronous gastric and jejunal gastrointestinal stromal tumors: report of a case.

    Science.gov (United States)

    Dell'Avanzato, Roberto; Carboni, Fabio; Palmieri, Maria Beatrice; Palmirotta, Raffaele; Guadagni, Fiorella; Pippa, Giovanna; Santeusanio, Giuseppe; Antimi, Mauro; Lopez, Massimo; Carlini, Massimo

    2009-01-01

    Multicentricity of gastrointestinal stromal tumors (GISTs) has been described only in patients with neurofibromatosis type 1 (NF1) or within the small intestine, and different pathogenetic mechanisms are involved. We report a case of synchronous sporadic gastric and jejunal GISTs, which were resected laparoscopically in a 67-year-old man. Immunohistochemical analysis revealed that both lesions were KIT (CD117)-positive, but that the gastric lesion was CD34-positive, whereas the jejunal one was Vimentin-, S-100-, and SMA-positive. Molecular analysis of mutations in KIT exons 9, 11, 13, and 17, and in PDGFRA exons 12 and 18 revealed the presence of a gastric sporadic GIST with a KIT mutation of the exon 11 and a jejunal sporadic GIST without KIT or PDGFRA mutations. To our knowledge, this is the first report of laparoscopically resected synchronous sporadic gastric and jejunal GISTs.

  2. Tumor estromal gastrointestinal em cães: estudo clínico-anatomopatológico

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    R.M. Leandro

    2016-08-01

    Full Text Available RESUMO Os tumores estromais gastrointestinais (GIST são incomuns e apresentam elevada similaridade histológica com as neoplasias de músculo liso e de nervo periférico. Este trabalho relata e caracteriza GIST em cães do ponto de vista epidemiológico, clínico-laboratorial, anatomopatológico e imuno-histoquímico, com base na análise retrospectiva de três cães, machos, com média de idade de 10 anos, variando de porte médio a grande e peso médio de 18.5±6kg. As alterações clínicas foram progressivas e inespecíficas de quadro gastrointestinal crônico, tais como prostração, anorexia, perda de peso e melena. Anemia não regenerativa e leucocitose foram os principais achados laboratoriais. Macroscopicamente, os tumores apresentavam média de 19cm no eixo maior, localizados em jejuno e ceco, com a superfície ulcerada, e exibiam áreas de necrose. Na avaliação microscópica, os casos apresentaram proliferação de células fusiformes, arranjadas em feixes longos densamente celulares, que foram vimentina e CD117 positivas, com diferenciação neural (S100 positivo, muscular (actina e desmina positivas e anaplásica, cuja morfologia caracteriza neoplasias malignas com sobrevida de um dia a 12 meses. O GIST deve ser um dos diagnósticos diferenciais a serem considerados entre as neoplasias mesenquimais do trato gastrointestinal que acometem cães, e o diagnóstico final necessita de imuno-histoquímica.

  3. Study of orthotopic transplantation model of human gastrointestinal cancerand detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2000-01-01

    AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used forrepetitive investigations and may improve our understanding of carcinogenesis and cancer metastasis.METHODS Intact tissue of human colorectal and pancreatic cancers was transplanted in nude mice. Thebiological characteristics of the original and corresponding transplanted tumors were investigated by HEstaining, PAS staining and immunostaining. The metastases in livers and lungs of the nude mice wereinvestigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers.RESULTS Nine of 16 surgical specimens grew in the nude mice subcutaneously and/or orthotopically (4 of6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissuespecimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cell content, transplantation rate was 100% (3 cases of pancreatic cancerand 3 cases of colorectal cancer). The orthotopically transplanted tumors resembled the original tumormorphologically and biologically, including TAA expression such as CEA by immunohistochemistry, andCEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, were associated with the potential of tumor growth in nude mice. Micrometastases in the lungs andlivers of tumor bearing mice could be detected by immunostaining with biotinylated mab KL-1 and CK20-sepcific RT-PCR.CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude micehas been established. The sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCRwere also established to study xenotransplanted human cancer and its metastatic cancer cells in the liver andlung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and indeveloping new diagnostic methods and

  4. EFFECTS OF PERIOPERATIVE CIMETIDINE ADMINISTRATION ON TUMOR CELL NUCLEAR MORPHOMETRY AND DNA CONTENT IN PATIENTS WITH GASTROINTESTINAL CANCER

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To explore the effects of perioperative cimetidine administration on tumor cell nuclear morphometric parameters and DNA content in patients with gastrointestinal adenocarcinoma. Methods: 49 patients with pathologically confirmed gastrointestinal adenocarcinoma were randomized into test group (n=25) and control group (n=24). The test group started oral cimetidine intake 400 mg, tid, 7-10d before operation, followed by standard curative operation. The control group did not receive cimetidine. Tumor specimens were paraffin embedded for microsection and stained with hematoxylin and eosin (HE) and Feulgen stain. Morphometric studies and DNA content of tumor nuclei were performed on IBAS Image Analyzer. Results: The tumor cell nuclear area (m m2), nuclear perimeter (m m), maximal nuclear diameter (m m) for test group/control group were 23.54 ± 5.08/34.69± 10.08 (Pquintuple ploidy tumor cells for test group/control group were 16.64± 2.58/5.33± 2.14 (P0.50), 12.42± 5.00/14.48± 0.74 (P>0.20), 31.11± 6.86/ 45.97± 3.82 (P<0.005), respectively. Conclusion: Perioperative administration of cimetidine in gasgtrointestinal cancer patients could decrease the nuclear size and raise the percentage of diploid tumor cells, and convert high aneuploid tumor cells into low-aneuploid tumor cells, which might help reduce the invasiveness of tumor cells.

  5. Intraabdominal Intravascular Papillary Endothelial Hyperplasia (Masson’s Tumor: A Rare and Novel Cause of Gastrointestinal Bleeding

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    Michael C. Meadows

    2010-03-01

    Full Text Available Intravascular papillary endothelial hyperplasia (IPEH, or Masson’s tumor, a rare benign vascular lesion, occurs mainly in the head, neck, and hands in the human population. Aberrant tumor locations have been rarely reported. We present a case of a patient with chronic abdominal pain and melena of variable severity due to a Masson’s tumor, with no apparent Masson’s tumor-associated comorbidities, along with a comprehensive review of the literature. Using PubMed, a search engine provided by the U.S. National Library of Medicine and the National Institutes of Health, we searched for all reports of Masson’s tumor limited within the abdominal cavity. Furthermore, keywords such as ‘intravascular papillary endothelial hyperplasia’, ‘renal’, ‘gastrointestinal’, ‘hepatic’ and ‘intraabdominal’ were used to facilitate the search. We thus found fourteen cases of intraabdominal Masson’s tumors published. Six (42.9% of these were located in the renal vein, 4 (28.6% were reported in the gastrointestinal tract, 1 (7.1% in the adrenal gland, 1 (7.1% in the liver, and 1 (7.1% instance with multiple lesion sites including the renal hilum and retroperitoneum. Among these patients, 9 (64.3% were female and 5 (35.7% male, with a mean age of 38.9 years (7–69. IPEH is a reactive process, having three subtypes, all involving the proliferation of epithelial cells around a thrombus in the setting of venous stasis. In its pure form, the organized thrombus is solely localized within the vascular lumen. Mixed-form IPEH is formed in preexisting vascular lesions (such as arteriovenous malformation, hemangioma, pyogenic granuloma, etc.. The rarest form is the extravascular variety, which arises in hematomas often from recent trauma to the area. In its pure form, IPEH has a zero recurrence rate when an R0 resection is performed; all mixed and extravascular forms show the highest recurrence rates. The exact histogenesis of these epithelial cells

  6. Tumor Necrosis Factor-alpha Inhibitor Etanercept Does Not Alter Methotrexate-induced Gastrointestinal Mucositis in Rats

    NARCIS (Netherlands)

    Kuiken, Nicoline S S; Rings, Edmond H H M; Alffenaar, Jan-Willem C; Havinga, Rick; Jurdzinski, Angelika; Groen, Albert K; Tissing, Wim J E

    2016-01-01

    OBJECTIVES: Gastrointestinal (GI) mucositis is a severe side effect of chemotherapy and radiotherapy. Pro-inflammatory cytokines are thought to play an important role in the pathophysiology of GI mucositis. We aimed to determine the effect of the Tumor Necrosis Factor-alpha (TNF-α) inhibitor Etanerc

  7. Long-term survival of a patient after resection of a gastrointestinal stromal tumor arising from the pancreas

    Institute of Scientific and Technical Information of China (English)

    FilipČečka; BohumilJon; AlexanderFerko; ZdeněkŠubrt; DimitarHNikolov; VěraTyčová

    2011-01-01

    BACKGROUND: Gastrointestinal stromal tumors (GISTs) may arise in any part of the gastrointestinal tract; extra-gastrointestinal locations are extremely rare. Only a few cases of extragastrointestinal stromal tumor arising from the pancreas were reported. None of the reports described a long-term follow-up of the patients. METHOD: This report describes an interesting and unusual case of GIST arising from the pancreas. RESULTS:  A 74-year-old female presented with a palpable abdominal mass. CT scan showed a large mass 11×8×4 cm originating from the tail of the pancreas. Percutaneous biopsy revealed a GIST predominantly with spindle cells, but some parts also contained epitheloid cells. The patient was treated by distal pancreatic resection with splenectomy. Immunohistochemistry of the tumor showed a staining pattern characteristic of GIST. The patient has achieved a long-term survival of five years and six months without any sign of recurrence of the disease. CONCLUSION: This is the first reported case of an extra-gastrointestinal stromal tumor arising from the pancreas treated surgically, with a long-term survival.

  8. Malignant gastrointestinal stromal tumor presenting with hemoperitoneum in puerperium: report of a case with review of the literature

    Directory of Open Access Journals (Sweden)

    Vasilakaki Thivi

    2010-11-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs are mesenchymal tumors that develop in the wall of the gastrointestinal tract and their diagnosis during pregnancy or puerperium is extremely rare. Case A 28-year old patient presented with acute abdomen due to hemoperitoneum from a large mass arising of the small intestine with distended vessels on its top and a ruptured superficial vessel bleeding into the peritoneal cavity. The patient was at the tenth postpartum day of her first pregnancy. The preoperative diagnosis was a possible ovarian or uterine mass. After an emergency exploratory laparotomy a segmental bowel resection was performed, removing the tumor with a part of 3-cm of the small intestine. Histology revealed GIST with maximum diameter of 13 cm and mitotic rates more than 5 mitoses per 50 high power fields with some atypical forms, indicating a high risk malignancy. Immunohistochemical staining of the tumor tissue demonstrated strongly positive reactivity to CD 117 (c-kit and CD34 in almost all the tumor cells. The patient was treated with oral imatinib mesylate (Gleevec 400 mg daily for one year. Three years after surgery, the patient was alive without evidence of metastases or local recurrence. Conclusion Considering that only few patients with gastrointestinal stromal tumors have been reported in the obstetrical and gynecological literature, the awareness of such an entity by the obstetricians-gynecologists is necessary in order to facilitate coordinated approach with the general surgeons and oncologists for the optimal care of the patients.

  9. Pfetin as a Risk Factor of Recurrence in Gastrointestinal Stromal Tumors

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    Hajime Orita

    2014-01-01

    Full Text Available Background. Despite complete resection of gastrointestinal stromal tumors (GIST, recurrent and/or metastatic disease occurs, often depending on the grade of malignancy. As such, markers are needed that accurately predict patients at high risk for recurrence. Previously our group reported Pfetin as a prognostic biomarker for GIST. In order to create an approach for predicting risk of recurrence, we incorporated Pfetin expression with clinicopathological data to produce a predictive model. Object. Forty-five patients with localized primary GIST were treated with complete gross surgical resection surgically at our institution between 1995 and 2010 were included. The majority of tumors originated in the stomach (38 cases, as well as small intestine (6 cases and rectum (1 case. Method. (1 We performed retrospective analysis of the connection between Pfetin expression, clinicopathological data, and incidences of recurrence, using bivariate and multivariate analyses. (2 The reactivity of the monoclonal antibody against Pfetin was examined by immunohistochemistry. Pfetin. We have reported Pfetin, identified microarray technology, and compared between statistically different GISTs for good and poor prognoses and for prognostic marker. Results. There were 7 cases of recurrences. (1 By univariate analysis, tumor size, mitoses, exposure to abdominal cavity, and complete tumor removal predicted risk of recurrence. (2 Pfetin-negative cases were significantly related to recurrence (P = 0.002. Conclusions. This analysis demonstrates that lack of Pfetin expression is an additional predictor of recurrence in resected GIST. Further study may determine the role of this variable added to the current predictive model for selection of adjuvant therapy.

  10. GASTROINTESTINAL STROMAL TUMORS OF THE ANORECTUM--A SPECIAL ENTITY: GISTs OF THE ANORECTUM

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: Until recently gastrointestinal stromal tumor (GIST) has been separated from other mesenchymal neoplasms and categorized as a special entity. Morphology of tumor cells and immunohistochemical findings with CD117 are crucial in the pathological diagnosis of GISTs. Newly developed drug imatinib mesylate (formerly called STI571) has been proved effective for GISTs. The distinction of GISTs and other mesenchymal tumors has great clinical significance, especially for lesions located in the anorectum. Methods: The authors searched the database of Peking University, School of Oncology for patients with anorectal neoplasms treated from January 1995 to June 2002. Information of 12 patients with anorectal mesenchymal tumors was collected. The patients were reevaluated and discussed according to current criteria of GISTs with clinical data and immunohistochemical findings. Results: Six patients (including 3 males) were finally diagnosed as anorectal GISTs. The median age of those patients was 59.5 years (27(69). The symptoms were not specific. Three cases with original diagnosis of leiomyoma or leiomyosarcoma were actually GISTs. A total of six anorectal GISTs was found comprising about 1.06% of patients with anorectal neoplasmas in the same period. Besides CD117, CD34 and vimentin were also expressed in majority of these patients. Five of the six patients underwent surgical resection one of which received neoadjuvant chemotherapy before resection. Conclusion: Anorectal GISTs should be considered as a special entity using current diagnostic criteria. Surgical resection remains the primary therapeutic strategy. Neoadjuvant imatinib mesylate may be helpful in sphincter-sparing operations and improvement of the quality of life for these patients.

  11. Indian Council of Medical Research consensus document for the management of gastrointestinal stromal tumors

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    Shailesh V Shrikhande

    2014-01-01

    Full Text Available This consensus statement was produced along with the gastric cancer discussions as stomach is the most common site for gastrointestinal stromal tumor (GIST. The recommendations apply to treatment of GIST.Evaluation of a patient with newly diagnosed GIST should include essential tests: A standard white light endoscopy with 6-8 biopsies (c-KIT testing on immunohistochemistry from the tumor for confirmation of the diagnosis, a computed tomography (CT scan (multi-detector or helical of the abdomen and pelvis for staging with a CT chest or chest X-ray, and complete blood counts, renal function tests and liver function tests. Endoscopic ultrasonography (EUS/magnetic resonance imaging (MRI/positron emission tomography (PET-CT are not recommended for all patients.For localized and resectable disease, surgery is recommended. The need for adjuvant treatment with imatinib would be guided by the risk stratification on the histopathological analysis of the resected specimen.For localized but borderline resectable tumors, upfront surgery may be considered only if complications due to the tumor are present such as major bleeding or gastric outlet obstruction. In all other patients, neoadjuvant imatinib should be considered to downstage the disease followed by surgery (with a curative intent, if feasible in those with stable or partial response. This may be followed by adjuvant imatinib. In those patients with a poor response, further imatinib with dose escalation or sunitinib may be considered.Patients with metastatic disease must be assessed for treatment with imatinib as first-line therapy followed by sunitinib as second-line therapy versus best supportive care on an individual basis.

  12. Comparison of Endoscopic and Open Resection for Small Gastric Gastrointestinal Stromal Tumor

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    Fan Feng

    2015-12-01

    Full Text Available The National Comprehensive Cancer Network recommends conservative follow-up for gastric gastrointestinal stromal tumors (GISTs less than 2 cm. We have previously reported that the mitotic index of 22.22% of small gastric GISTs exceeded 5 per 50 high-power fields and recommended that all small gastric GISTs should be resected once diagnosed. The aim of the present study is to compare the safety and outcomes of endoscopic and open resection of small gastric GISTs. From May 2010 to March 2014, a total of 90 small gastric GIST patients were enrolled in the present study, including 40 patients who underwent surgical resection and 50 patients who underwent endoscopic resection. The clinicopathological characteristics, resection-related factors, and clinical outcomes were recorded and analyzed. The clinicopathological characteristics were comparable between the two groups except for tumor location and DOG-1 expression. Compared with the surgical resection group, the operation time was shorter (P = .000, blood loss was less (P = .000, pain intensity was lower (P < .05, duration of first flatus and defecation was shorter (P < .05, and medical cost of hospitalization was lower (P = .027 in the endoscopic resection group. The complications and postoperative hospital stay were comparable between the two groups. No in situ recurrence or liver metastasis was observed during follow-up. Endoscopic resection of small gastric GISTs is safe and feasible compared with surgical resection, although perforation could not be totally avoided during and after resection. The clinical outcome of endoscopic resection is also favorable.

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

    Science.gov (United States)

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

    2016-06-01

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

  14. Approval summary: imatinib mesylate in the adjuvant treatment of malignant gastrointestinal stromal tumors.

    Science.gov (United States)

    Cohen, Martin H; Cortazar, Patricia; Justice, Robert; Pazdur, Richard

    2010-01-01

    On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec(R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary endpoint. Eligible patients were > or =18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size > or =3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value or =3 adverse reactions. The most frequently reported adverse reactions (> or =20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively.

  15. Gastrointestinal stromal tumors (GISTs): SEAP-SEOM consensus on pathologic and molecular diagnosis.

    Science.gov (United States)

    Martin-Broto, J; Martinez-Marín, V; Serrano, C; Hindi, N; López-Guerrero, J A; Ramos-Asensio, R; Vallejo-Benítez, A; Marcilla-Plaza, D; González-Cámpora, R

    2016-12-09

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, with an incidence of 1.1 cases/100,000 inhabitants/year. A group of experts from the Spanish Society of Pathology and the Spanish Society of Oncology met to discuss a brief update on GISTs and agree on aspects relating to the pathological and molecular diagnosis of these tumors. GISTs are generally solitary, well-circumscribed lesions of variable size (<10 mm-35 cm) that may present with intra- or extra-luminal parietal growth or a mixed-type (hourglass) growth pattern. Histologically, they are unencapsulated neoplasms displaying expansive growth and spindle-shaped (70%), epithelioid (20%), or mixed cellularity (10%). Mitotic activity is generally moderate or low and should be evaluated only in areas with high cellularity or higher mitotic frequency. The great majority of GISTs harbour mutually exclusive activating mutations in genes coding for the type III receptor tyrosine kinases KIT and PDGFRA; less commonly, GISTs have also been reported to display mutations elsewhere, including BRAF and NF1 and SDH-complex genes. The method most widely used to detect KIT and PDGFRA mutations is amplification of the exons involved by polymerase chain reaction followed by direct sequencing (Sanger method) of these amplification products. Molecular analyses should always specify the type of analysis performed, the region or mutations evaluated, and the sensitivity of the detection method employed.

  16. The ING tumor suppressor genes: status in human tumors.

    Science.gov (United States)

    Guérillon, Claire; Bigot, Nicolas; Pedeux, Rémy

    2014-04-01

    ING genes (ING1-5) were identified has tumor suppressor genes. ING proteins are characterized as Type II TSGs since they are involved in the control of cell proliferation, apoptosis and senescence. They may also function as Type I TSGs since they are also involved in DNA replication and repair. Most studies have reported that they are frequently lost in human tumors and epigenetic mechanisms or misregulation of their transcription may be involved. Recently, studies have described that this loss may be caused by microRNA inhibition. Here, we summarize the current knowledge on ING functions, their involvement in tumor suppression and, in order to give a full assessment of the current knowledge, we review all the studies that have examined ING status in human cancers.

  17. SKP2 high expression, KIT exon 11 deletions, and gastrointestinal bleeding as predictors of poor prognosis in primary gastrointestinal stromal tumors.

    Directory of Open Access Journals (Sweden)

    Ang Lv

    Full Text Available BACKGROUND AND AIMS: Considering the indication of adjuvant therapy, the recurrence risk for primary gastrointestinal stromal tumor (GIST after surgery needs to be accurately estimated. However, current risk stratification schemes may still have room for improvement. This study seeks to analyze prognostic factors for primary GISTs from 3 aspects, including clinicopathological parameters, immunohistochemical biomarkers, and gene mutational status, and attempts to find novel valuable factors predicting the malignancy potential of GISTs. METHODS: Retrospective data from 114 primary GIST patients after R0 resection were collected. Clinicopathological data was obtained from medical records and re-evaluated. Immunohistochemical analysis was performed using the Tissue Microarray method for Ki67, p16, p27, p53, SKP2, CD133, and actin. KIT gene exons 9, 11, 13, and 17 and PDGFRα gene exons 12 and 18 were tested for mutations using PCR. RESULTS: Univariate analysis revealed the following factors as poor prognostic indicators for relapse-free survival with a median follow-up of 50 months: male gender, gastrointestinal bleeding, mitotic index >5/50HPFs, tumor size >5 cm, non-gastric site, necrosis, epithelioid or mixed cell type, surrounding tissue invasion, Ki67>5%, p16>20%, p53 index >10, SKP2>10%, and KIT exon 11 deletion. Besides mitotic index, tumor size and site, SKP2 high expression (RR = 2.91, 95% CI: 1.41-5.99, P = 0.004 and KIT exon 11 deletion (RR = 2.73, 95% CI: 1.04-7.16, P = 0.041 were also independent risk factors in multivariate analysis, with gastrointestinal bleeding also showing a trend towards significance (RR = 1.88, 95% CI: 0.98-3.64, P = 0.059. In addition, gastrointestinal bleeding and SKP2 high expression showed a good ability to stratify high-risk patients further. CONCLUSION: Our results show that gastrointestinal bleeding, SKP2 high expression, and KIT exon 11 deletions may be useful indicators of high recurrence risk for

  18. Emergency arterial embolization of upper gastrointestinal and jejunal tumors: An analysis of 12 patients with severe bleeding.

    Science.gov (United States)

    Zandrino, F; Tettoni, S M; Gallesio, I; Summa, M

    2017-01-01

    The goal of this study was to retrospectively assess the efficacy of emergency percutaneous transcatheter arterial embolization in patients with severe bleeding due to upper gastrointestinal or jejunal tumor. Twelve patients (7 men, 5 women; mean age, 74 years±14 (SD); range: 54-86 years) with severe bleeding from the upper gastrointestinal tract, with failed endoscopic treatment not eligible for emergency surgery were treated by emergency percutaneous transcatheter arterial embolization. The bleeding cause was gastric tumor in 7 patients, duodenal tumor in 4 patients and jejunal tumor in one patient. Procedure details and follow-up were reviewed. Twelve embolization procedures were performed using various embolic agents. Embolization was achieved and bleeding was stopped in all patients. Five patients underwent surgery within the 30 days following embolization. In the remaining 7 patients, no bleeding occurred at 1 month follow-up in 6 patients and bleeding recurred in one patient at 1 month. In this later patient, endoscopic treatment was successful. The results of our study suggest that transcatheter arterial embolization is safe and effective in patients with severe arterial bleeding due to upper gastrointestinal or jejunal tumor. In some patients, transcatheter arterial embolization can be used as a bridge to surgery. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

  19. Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor:A case report

    Institute of Scientific and Technical Information of China (English)

    Piergiuseppe Colombo; Daoud Rahal; Fabio Grizzi; Vittorio Quagliuolo; Massimo Roncalli

    2005-01-01

    Intra-abdominal fibromatosis (IAF) is a benign mesenchymal lesion that can occur throughout the gastrointestinal tract. Although rare, it is the most common primary tumor of the mesentery and can develop at any age. We describe a rare case of primary IAF involving the mesentery and small bowel which clinically, macroscopically and histologically mimicked malignant gastrointestinal stromal tumor (GIST). This report highlights the fact that benign IAF can be misdiagnosed as a malignant GIST localized in the mesentery or arising from the intestinal wall. Their diagnostic discrimination is essential because of their very different biological behaviors and the fact that the introduction of effective therapies involving tyrosine kinase inhibitor STI571 (imatinib mesylate) has greatly changed the clinical approach to intra-abdominal stromal spindle cell tumors.

  20. Development of multiple myeloma in a patient with gastrointestinal stromal tumor treated with imatinib mesylate: A case report

    Institute of Scientific and Technical Information of China (English)

    D Tzilves; A Gatopoulou; K Zervas; E Katodritou; F Patakiouta; A Tarpagos; I Katsos

    2007-01-01

    Gastrointestinal stromal tumors (GISTs) are rare tumors,which represent approximately 1% of the neoplasms of the gastrointestinal tract. These tumors rarely give extra-abdominal metastases. However, their clinical outcome is potentially adverse. In some rare cases, coexistance of GISTs with other malignancies has been reported. Here we present a case of a 74-year old male with GIST, which was managed by surgical resection.Fourteen months later, the patient presented with liver metastases and imatinib mesylated was administered.During treatment, the patient reported skeletal pain and plane X-rays revealed osteolytic bone lesions. Further investigation revealed the presence of multiple myeloma.To the best of our knowledge, this is the first report of the co-existence of multiple myeloma (MM) with GIST.

  1. Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Chun-Nan Yeh; Tsung-Wen Chen; Ting-Jung Wu; Swei Hsueh; Yi-Yin Jan

    2006-01-01

    AIM: To examine the impact of imatinib mesylate (Glivec)on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status.METHODS: Thirty-three of 74 (44.6%) small bowel gastrointestinal stromal tumor (GIST) patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients.Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients.Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha (PDGFRA). The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed.RESULTS: Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response (PR) (67.8%). Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate (PR) was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate (ORR) of 66.7% (not significant).CONCLUSION: Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients with advanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs.There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.

  2. Hypercalcemia secondary to gastrointestinal stromal tumors: parathyroid hormone-related protein independent mechanism?

    Science.gov (United States)

    Jasti, Prathima; Lakhani, Vipul Tulsi; Woodworth, Alison; Dahir, Kathryn McCrystal

    2013-01-01

    Hypercalcemia is a common paraneoplastic manifestation of many malignancies like breast, ovarian, and squamous-cell cancers of head and neck; however, there have been only a few case reports of hypercalcemia associated with gastrointestinal stromal tumors (GISTs). We report a case of GIST presenting with hypercalcemia without any osseous metastasis and provide a literature review regarding the mechanisms of hypercalcemia and therapeutic strategies. We present a report of case and a review of the relevant literature. A 52-year-old woman with history of localized breast cancer in remission and a pelvic 13 × 12 cm GIST with peritoneal, liver, and lung metastases presented with hypercalcemia of 14.3 mg/dL (8.5-10.5 mg/dL). Parathyroid hormone-related protein (PTHrP) was undetectable, intact parathyroid hormone (PTH) was appropriately low at 1 pg/mL (10-65 pg/mL), and 1,25 dihydroxy vitamin D (1,25 OH2 vit D) was elevated at 131 pg/mL (18-78 pg/mL) with normal renal function. Calcium responded transiently to tyrosine kinase inhibitor therapy and bisphosphonates but within a year, she expired due to tumor progression. GIST is a rare cause of hypercalcemia. In addition to PTHrP expression, direct tumor production of 1,25(OH)2 vit D or 1-α hydroxylase enzyme resulting in activation of 25-hydroxy vitamin D may be an alternative mechanism in GIST-related hypercalcemia. Therapy with tyrosine kinase inhibitors and bisphosphonates is recommended, though prognosis is poor. Further investigations are needed to characterize the etiology and management of hypercalcemia in these patients.

  3. Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Kun-Chun Chiang; Tsung-Wen Chen; Chun-Nan Yeh; Feng-Yuan Liu; Hsiang-Lin Lee; Yi-Yin Jan

    2006-01-01

    AIM: Most gastrointestinal stromal tumors (GISTs)express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha (PDGFRA), which are potential therapeutic targets for imatinib mesylate (Glivec). Partial response occurred in almost two thirds of GIST patients treated with Glivec.However, complete response (CR) after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment.METHODS: Between January 2001 and June 2005,42 advanced GIST patients were treated with Glivec.Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA.RESULTS: The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months (range, 1.0- 47.0 months). Overall, 3patients had complete response CR (7.1%), 26 partial response (67.8%), 5 stationary disease (11.9%), and 3 progressive disease (11.9%). The median duration of Glivec administration for the three patients was 36months (range, 23-36 months). The median time to CR after Glivec treatment was 20 months (range, 9-26months). Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively.CONCLUSION: Complete response (CR) can be achieyed in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.

  4. Gastrointestinal opportunistic infections in human immunodeficiency virus disease

    Directory of Open Access Journals (Sweden)

    Al Anazi Awadh

    2009-01-01

    Full Text Available Gastrointestinal (GI opportunistic infections (OIs are commonly encountered at various stages of human immunodeficiency virus (HIV disease. In view of the suppressive nature of the virus and the direct contact with the environment, the GI tract is readily accessible and is a common site for clinical expression of HIV. The subject is presented based on information obtained by electronic searches of peer-reviewed articles in medical journals, Cochrane reviews and PubMed sources. The spectrum of GI OIs ranges from oral lesions of Candidiasis, various lesions of viral infections, hepatobiliary lesions, pancreatitis and anorectal lesions. The manifestations of the disease depend on the level of immunosuppression, as determined by the CD4 counts. The advent of highly active antiretroviral therapy has altered the pattern of presentation, resorting mainly to features of antimicrobial-associated colitis and side effects of antiretroviral drugs. The diagnosis of GI OIs in HIV/ acquired immunodeficiency syndrome patients is usually straightforward. However, subtle presentations require that the physicians should have a high index of suspicion when given the setting of HIV infection.

  5. Endoscopic submucosal dissection for silent gastric Dieulafoy lesions mimicking gastrointestinal stromal tumors

    Science.gov (United States)

    Chen, Xue; Cao, Hailong; Wang, Sinan; Wang, Dan; Xu, Mengque; Piao, Meiyu; Wang, Bangmao

    2016-01-01

    Abstract Background: Dieulafoy lesion is a rare but serious cause of gastrointestinal hemorrhage. However, some cases can be occasionally found without bleeding during the endoscopic screening, and the management remains unclear. The aim of this article was to report the efficacy and safety of endoscopic submucosal dissection (ESD) for silent gastric Dieulafoy lesions, which presented as protrusion lesions mimicking gastrointestinal stromal tumors (GISTs). Methods: Data from the patients with gastric protrusion lesions who underwent ESD from September 2008 to April 2016 in General Hospital, Tianjin Medical University, China were recorded. Seven cases with pathological diagnosis of Dieulafoy lesion without bleeding were enrolled for further analysis. Results: A total of 7 patients (2 males and 5 females) with mean age of 57.7 ± 4.15 years were pathologically diagnosed as Dieulafoy lesion. Four of the lesions were located in gastric antrum, 2 in the fundus, and 1 in the body of stomach, respectively. The mean sizes of the Dieulafoy lesions under white light endoscopy and endoscopic ultrasonography (EUS) were 1.06 ± 0.28 and 0.84 ± 0.29 cm. The origins of these lesions were submucosa (6/7, 85.7%) and muscularis propria (1/7, 14.3%). Three of them appeared with mixed echo under EUS, 3 with hypoechogenicity, and 1 with hyperechogenicity. En bloc complete resection was achieved in all the lesions by ESD with average time of 76.00 ± 16.86 minutes, and no intraoperative bleeding happened. In addition, all patients were followed up for 1 to 53 months, and no recurrence or long-term complications was observed. Conclusion: Therefore, ESD can be an effective and safe treatment for silent gastric Dieulafoy lesions with clinical presentations of submucosal protrusion lesions mimicking GISTs. PMID:27603399

  6. Prognostic significance of clinicopathologic parameters in gastrointestinal stromal tumors: a study of 156 cases

    Institute of Scientific and Technical Information of China (English)

    Yumei LIANG; Xianghong LI; Youyong LU; Yali LV; Mei ZHONG; Xiaolu PU; Wenmei LI

    2008-01-01

    The biological behavior of gastrointestinal stromal tumors (GISTs) are highly variable. To invest-igate the biological behavior of GIST, we collected 83 cases of gastric and 62 cases of small intestinal GIST from the Department of Pathology of the Chinese PLA General Hospital. The parameters include age, primary tumor location, tumor diameter, mitotic index, tumor necrosis, risk assessment, clinical stage and the c-kit exon 11 muta-tion. All these were analyzed in 105 cases along with the follow-up data and tested by log rank and COX hazard proportional model. We find that the average age of gast-ric GIST was 55.4 years. Of the 62 cases that were fol-lowed up, 17 cases had metastasis or recurrence and the 5-year survival rate was (66.51±17.06)%. For the small intestinal GIST, the average age was 50.6 years and 43 cases were followed up. Of these, 22 cases had meta-stasis or recurrence and the 5-year survival rate was (61.76±18.30)%. Small intestinal GIST was more fre-quently associated with metastasis and tumor relapse than gastric GIST (χ2= 6.131, P=0.013). For gastric GIST, patients younger than 50 years (P = 0.046), the advanced clinical stage (P=0.0001), the large tumor diameter (P=0.0001), a high mitotic index (P=0.0001), necrosis (P=0.0001) and a high risk grade (P=0.004) were all correlated with a lower survival rate. The COX hazard proportional model revealed that advanced clinical stage (P=0.001), large tumor size (P=0.001), a high mitotic index (P = 0.002) and the high risk grade (P = 0.018) indi-cated a poorer prognosis in gastric GIST. For small intest-inal GIST, necrosis (P = 0.036) and advanced clinical stage (P = 0.010) were associated with lower survival rates and the clinical stage was shown to be an independent prognostic indicator. A total of 25 cases harbored muta-tions in c-kit exon 11. The frequency of c-kit mutation was 32% and 22.5% for gastric and small intestinal GIST, respectively. In gastric GIST, the mutated c-kit was pre-dominant in

  7. Effect of sunitinib on metastatic gastrointestinal stromal tumor in patients with neurofibromatosis type 1: A case report

    Institute of Scientific and Technical Information of China (English)

    M Emin Kalender; Alper Sevinc; Ediz Tutar; Akif Sirikci; Celalettin Camci

    2007-01-01

    Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal malignancy of the gastrointestinal (GI) tract. In neurofibromatosis (NF),the increased incidence of tumor needs to be considered even in non-symptomatic individuals. Patients with neurofibromatosis NF type 1 have an increased risk of developing GI tumors including rare types such as GIST.We report a case of GIST in a 53-year-old male patient with neurofibromatosis. The patient was diagnosed with NF four years ago and his medical history revealed that he was hospitalized 5 times with a provisional diagnosis of massive lower gastrointestinal bleeding. GIST was diagnosed at explorative laparotomy and the tumor was 21 cm × 13 cm × 7 cm in size. Immunohistochemical examination showed that vimentin, actin and CD117 were positive. Computerized tomography showed peritoneal implants three months later. Imatinib mesylate (600 mg/d) was initiated. However, control computerized tomography revealed liver and omental metastasis. The dosage was elevated to 800 mg/d. Despite high dosage,the progression of the metastatic lesions continued in the liver and omentum. The patient started oral sunitinib malate (Sutent)(R) Pfizer Inc, New York, NY, USA) 50 mg per day for 4 consecutive weeks, followed by 2 wk off per treatment cycle. The metastatic lesions in the liver and omentum were decreased in size after four courses,suggesting that sunitinib is also an effective treatment modality for metastatic GIST in NF patients.

  8. 消化道肿瘤与微生物感染%Gastrointestinal tract tumors and microbial infections

    Institute of Scientific and Technical Information of China (English)

    李健; 马军

    2013-01-01

    An increasing amount of data suggests the association of gastrointestinal tract tumor with microbial infections (bacterial colonization, virus and parasitic infection) . It is crucial importance to consider these inducers in cancer development, cell differentiation and transformation, cell cycle deregulation and the expression of tumor-associated genes. In this paper, the pathogen-induced tumorigenesis in gastrointestinal tract tumor were reviewed and to provide new insights into novel gastrointestinal tract tumor treatments.%越来越多的数据表明,胃肠道肿瘤与微生物感染(细菌定植、病毒和寄生虫感染)有关.这些诱导因素在消化道肿瘤的发生发展、细胞分化和转化、细胞周期失调和肿瘤相关基因表达中的作用值得重视.本文对细菌、病毒和寄生虫在消化道肿瘤(胃癌、结直肠癌和肝细胞癌)致癌机制的研究进展作一概述,旨在为消化道肿瘤的治疗提供新见解.

  9. Neuropilin-2 mediated β-catenin signaling and survival in human gastro-intestinal cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Shaija Samuel

    Full Text Available NRP-2 is a high-affinity kinase-deficient receptor for ligands belonging to the class 3 semaphorin and vascular endothelial growth factor families. NRP-2 has been detected on the surface of several types of human cancer cells, but its expression and function in gastrointestinal (GI cancer cells remains to be determined. We sought to determine the function of NRP-2 in mediating downstream signals regulating the growth and survival of human gastrointestinal cancer cells. In human gastric cancer specimens, NRP-2 expression was detected in tumor tissues but not in adjacent normal mucosa. In CNDT 2.5 cells, shRNA mediated knockdown NRP-2 expression led to decreased migration and invasion in vitro (p<0.01. Focused gene-array analysis demonstrated that loss of NRP-2 reduced the expression of a critical metastasis mediator gene, S100A4. Steady-state levels and function of β-catenin, a known regulator of S100A4, were also decreased in the shNRP-2 clones. Furthermore, knockdown of NRP-2 sensitized CNDT 2.5 cells in vitro to 5FU toxicity. This effect was associated with activation of caspases 3 and 7, cleavage of PARP, and downregulation of Bcl-2. In vivo growth of CNDT 2.5 cells in the livers of nude mice was significantly decreased in the shNRP-2 group (p<0.05. Intraperitoneal administration of NRP-2 siRNA-DOPC decreased the tumor burden in mice (p = 0.01. Collectively, our results demonstrate that tumor cell-derived NRP-2 mediates critical survival signaling in gastrointestinal cancer cells.

  10. First Case Report of a Sporadic Adrenocortical Carcinoma With Gastric Metastasis and a Synchronous Gastrointestinal Stromal Tumor of the Stomach.

    Science.gov (United States)

    Kovecsi, Attila; Jung, Ioan; Bara, Tivadar; Bara, Tivadar; Azamfirei, Leonard; Kovacs, Zsolt; Gurzu, Simona

    2015-09-01

    Adrenocortical carcinoma is a rare tumor with high aggresivity that can associate systemic metastases. A 71-year-old man was hospitalized for gastric cancer. The abdominal computed tomography also revealed a tumor above the right kidney. Total gastrectomy and right adrenalectomy were performed. The encapsulated tumor of the adrenal gland weighed 560 grams and presented diffuse tumor architecture under microscope, with capsular, sinusoidal, and vascular invasion. The large tumor cells had a polygonal shape, with slight basophilic, eosinophilic, or vacuolated cytoplasm, pleomorphic nuclei, and a high mitotic rate. In the stomach, the protruded tumor was covered by normal mucosa; under microscope, the tumor cells were observed only in the submucosal layer. In primary adrenal tumor and gastric metastasis the tumor cells were marked by vimentin, inhibin, synaptophysin, neuron-specific enolase, and calretinin. Based on these criteria, the diagnosis of adrenocortical carcinoma (ACC) with gastric metastasis and no lymph node metastases was established. A synchronous 10 × 10-mm-sized gastrointestinal stromal tumor (GIST) of the stomach, without mitoses, was also identified. So far, as we know, this is the 15th case of ever reported synchronous/metachronous sporadic ACCs; the ACC-related gastric metastases either synchronous ACC and GIST, has not been reported in the literature previously.

  11. Expression of COX-2, PCNA, Ki-67 and p53 in gastrointestinal stromal tumors and its relationship with histopathological parameters

    Institute of Scientific and Technical Information of China (English)

    Derya Gumurdulu; Seyda Erdogan; Fazilet Kayaselcuk; Gulsah Seydaoglu; Cem K Parsak; Orhan Demircan; Ilhan Tuncer

    2007-01-01

    AIM: To investigate the expression of Cyclooxygenase-2(COX-2), proliferating cell nuclear antigen (PCNA), Ki-67and p53 in gastrointestinal stromal tumors (GISTs) and its relationship with histopathological parameters.METHODS: Twenty-five GISTs were examined by light microscopy and immunohistochemistry. c-kit, CD34,SMA, S-100 protein, COX-2, PCNA, Ki-67 and p53 were detected immunohistochemically and the relationship was evaluated among histopathologic parameters such as mitotic index (MI), tumor grade, tumor size, COX-2,PCNA, Ki-67 and p53.RESULTS: COX-2 protein expression was found in 19 of 25 (76%) of the tumors, and expression was noted in the cytoplasm of the tumor cells. p53 was significantly related to MI and tumor grade but no relationship was found between COX-2, proliferation markers and MI,tumor grade and tumor size.CONCLUSION: COX-2 is expressed in most GISTs and it may play an important role in the proliferation and progression of these tumors or a useful marker to identify GIST. Although immunohistochemical assessment of p53 can be used for distinguishing the risk groups of GISTs, tumor size and mitotic rate should be considered at the same time.

  12. Tumor markers for diagnosis, monitoring of recurrence and prognosis in patients with upper gastrointestinal tract cancer.

    Science.gov (United States)

    Jing, Jie-Xian; Wang, Yan; Xu, Xiao-Qin; Sun, Ting; Tian, Bao-Guo; Du, Li-Li; Zhao, Xian-Wen; Han, Cun-Zhi

    2014-01-01

    To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of these tumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancer between January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA. The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%, 25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 had higher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCC was the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 and CA24-2, SCC and CA72-4 was significantly associated with pathological types (pdiagnosis of EC; CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA and CA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumor recurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis of patients with upper GIT cancer.

  13. Leiomyomas in the gastric cardia: CT findings and differentiation from gastrointestinal stromal tumors

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Hyun Kyung [Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707 (Korea, Republic of); Kim, Young Hoon, E-mail: yhkrad@gmail.com [Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707 (Korea, Republic of); Lee, Yoon Jin; Park, Ji Hoon; Kim, Ji Young; Lee, Kyoung Ho [Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707 (Korea, Republic of); Lee, Hye Seung [Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam-si, Gyeonggi-do 463-707 (Korea, Republic of)

    2015-09-15

    Highlights: • Gastric leiomyomas frequently involve the gastric cardia. • Gastric cardial leiomyomas and GISTs could be differentiated with CT. • Differentiation of cardial leiomyomas and GISTs can help choosing surgical procedure. - Abstract: Objective: To describe CT findings of leiomyomas and gastrointestinal stromal tumors (GISTs) in the gastric cardia and to identify their differentiating features. Materials and methods: CT images of pathologically proven leiomyomas (n = 26) and GISTs (n = 19) in the gastric cardia were retrospectively reviewed for esophagogastric junction (EGJ) involvement, contour, surface, growth pattern, enhancement pattern and degree of the tumor, and the presences of intralesional low attenuation, calcification and surface dimples or ulcers. The long (LD) and short diameters (SD), LD/SD ratio, and attenuation value of each lesion were measured. Results: EGJ involvement, homogeneous enhancement, intermediate or low enhancement, absences of intralesional low attenuation and surface dimples or ulcers, LD/SD ratio >1.2, and attenuation value ≤71.2 HU were significant findings for differentiating leiomyomas from GISTs (P < 0.05 for each finding). An LD/SD ratio of >1.2 and attenuation value of ≤71.2 HU yielded sensitivities of 84.6% and 61.5%, and specificities of 52.6% and 84.2%, respectively, on the receiver operating characteristic curve analysis. When at least five of these seven criteria were used in combination, the sensitivity and specificity for diagnosing leiomyomas were 100% (26 of 26) and 89.5% (17 of 19), respectively. When any six of these criteria were used, a specificity of 100% was achieved. Conclusions: CT features including EGJ involvement, enhancement pattern and degree, presences of intralesional low attenuation and surface dimples or ulcers, LD/SD ratio, and attenuation value could help differentiating leiomyomas from GISTs in the gastric cardia, particularly in the manner of combination.

  14. Sunitinib for Taiwanese patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

    Institute of Scientific and Technical Information of China (English)

    Yen-Yang Chen; Chun-Nan Yeh; Chi-Tung Cheng; Tsung-Wen Chen; Kun-Ming Rau; Yi-Yin Jan; Miin-Fu Chen

    2011-01-01

    AIM: To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwanese gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure. METHODS: Between 2001 and May 2010, 199 Taiwanese patients with metastatic GIST were treated at Chang Gung Memorial Hospital. Among them, 23 (11.6%) patients receiving sunitinib were investigated. RESULTS: Sixteen male and 7 female patients with a median age of 59 years (range: 24-83 years) received sunitinib. Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance. The median duration of sunitinib administration was 6.0 mo (range: 2-29 mo). The clinical benefit was 65.2% [2 complete response (CR), 4 partial response (PR), and 9 stationary disease (SD); 15/23]. In 12 patients harboring mutations of the kit gene at exon 11, the clinical benefit rate (CR, PR, and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant, P = 0.344). The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type, KIT exon 9, or KIT exon 11 mutations. Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%), followed by anemia (17.4%), and neutropenia (13.0%). During the median 7.5-mo follow-up after sunitinib use, the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo, respectively. CONCLUSION: Sunitinib appears to be an effective treatment for Taiwanese with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwanese advanced GIST patients.

  15. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors

    Directory of Open Access Journals (Sweden)

    K. Kramer

    2015-01-01

    Full Text Available Currently available data on prognostic implication of additional neoplasms in GIST miss comprehensive information on patient outcome with regard to overall or disease specific and disease free survival. Registry data of GIST patients with and without additional neoplasm were compared in retrospective case series. We investigated a total of 836 patients from the multi-center Ulmer GIST registry. Additionally, a second cohort encompassing 143 consecutively recruited patients of a single oncology center were analyzed. The frequency of additional malignant neoplasms in GIST patients was 31.9% and 42.0% in both cohorts with a mean follow-up time of 54 and 65 months (median 48 and 60 months, respectively. The spectrum of additional neoplasms in both cohorts encompasses gastrointestinal tumors (43.5%, uro-genital and breast cancers (34.1%, hematological malignancies (7.3%, skin cancer (7.3% and others. Additional neoplasms have had a significant impact on patient outcome. The five year overall survival in GIST with additional malignant neoplasms (n = 267 was 62.8% compared to 83.4% in patients without other tumors (n = 569 (P < .001, HR=0.397, 95% CI: 0.298-0.530. Five-year disease specific survival was not different between both groups (90.8% versus 90.9%. 34.2% of all deaths (n = 66 of n = 193 were GIST-related. The presented data suggest a close association between the duration of follow-up and the rate of additional malignancies in GIST patients. Moreover the data indicate a strong impact of additional malignant neoplasms in GIST on patient outcome. A comprehensive follow-up strategy of GIST patients appears to be warranted.

  16. HYPERMETHYLATION STATUS OF E-CADHERIN AND p16INK4a IN GASTROINTESTINAL STROMAL TUMOR

    Institute of Scientific and Technical Information of China (English)

    LIANG Jian-fang

    2006-01-01

    Objective: To investigate the methylation status of CpG island in E-cadherin(CDH1), P16INK4a(P16)promoter region ,and to analyze their role in gastrointestinal stromal tumor (GISTs). Methods: A total of 56 surgically resected GISTs were obtained from January 2003 to December 2005. The routine H&E-stained sections and CD117, CD34-immunoreactions were reviewed to verify the morphologic diagnosis. Methylation status of the CDH1, P16INK4a promoter region was analyzed by methylation specific polymerase chain reaction (MSP) from chemically modified DNA after Na-bisulfite treatment. Results: The frequency of CDH1gene methylation was 32% (18 of 56) in GISTs. The rate was 9% (1 of 11), 21% (4 of 19), 41.6% (5 of 12), and 57% (8 of 14) for very low risk, low risk, intermediate risk, and high risk GISTs; P16INK4a methylation was found in 19 of 56(34%) cases. The rate was 0% (0 of 11), 16% (3 of 19), 50% (6 of 12), and 71% (10 of 14) for very low risk, low risk, intermediate risk, and high risk GISTs. Statistical analysis indicated that of the 56 cases, there was significant association of CDH1 and/or P16INK4a methylation status with tumor malignant behavior (methylation rate 23/56, 41%, P<0.01) and site (P<0.05). Conclusion: E-cadherin (CDH1) and/or P16INK4a promoter hypermethylation is strongly associated with risk grade, may be a useful biomarker for GISTs risk assessment, and may shed light on new therapeutic options to treat GISTs

  17. Specific expression of human intelectin-1 in malignant pleural mesothelioma and gastrointestinal goblet cells.

    Directory of Open Access Journals (Sweden)

    Kota Washimi

    Full Text Available Malignant pleural mesothelioma (MPM is a fatal tumor. It is often hard to discriminate MPM from metastatic tumors of other types because currently, there are no reliable immunopathological markers for MPM. MPM is differentially diagnosed by some immunohistochemical tests on pathology specimens. In the present study, we investigated the expression of intelectin-1, a new mesothelioma marker, in normal tissues in the whole body and in many cancers, including MPM, by immunohistochemical analysis. We found that in normal tissues, human intelectin-1 was mainly secreted from gastrointestinal goblet cells along with mucus into the intestinal lumen, and it was also expressed, to a lesser extent, in mesothelial cells and urinary epithelial cells. Eighty-eight percent of epithelioid-type MPMs expressed intelectin-1, whereas sarcomatoid-type MPMs, biphasic MPMs, and poorly differentiated MPMs were rarely positive for intelectin-1. Intelectin-1 was not expressed in other cancers, except in mucus-producing adenocarcinoma. These results suggest that intelectin-1 is a better marker for epithelioid-type MPM than other mesothelioma markers because of its specificity and the simplicity of pathological assessment. Pleural intelectin-1 could be a useful diagnostic marker for MPM with applications in histopathological identification of MPM.

  18. Kinase genotype analysis of gastric gastrointestinal stromal tumor cytology samples using targeted next-generation sequencing.

    Science.gov (United States)

    Gleeson, Ferga C; Kipp, Benjamin R; Kerr, Sarah E; Voss, Jesse S; Graham, Rondell P; Campion, Michael B; Minot, Douglas M; Tu, Zheng J; Klee, Eric W; Lazaridis, Konstantinos N; Henry, Michael R; Levy, Michael J

    2015-01-01

    Gastric gastrointestinal stromal tumors (GISTs) usually contain the mast/stem cell growth factor receptor Kit gene (KIT) or platelet-derived growth factor receptor A (PDGFRA) mutations that can be targeted by, or mediate resistance to, imatinib. Diagnostic material often is obtained by endoscopic ultrasound-guided fine-needle aspiration, which often is unsuitable for molecular analysis. We investigated whether targeted next-generation sequencing (NGS) can be used in multiplex genotype analysis of cytology samples collected by endoscopic ultrasound-guided fine-needle aspiration. We used the Ion AmpliSeq V2 Cancer Hotspot NGS Panel (Life Technologies, Carlsbad, CA) to identify mutations in more than 2800 exons from 50 cancer-associated genes in GIST samples from 20 patients. We identified KIT mutations in 58% of samples (91% in exon 11 and 9% in exon 17) and PDGFRA mutations in 26% (60% in exon 18 and 40% in exon 12); 16% of samples had no mutations in KIT or PDGFRA. No pathogenic alterations were found in PIK3CA, BRAF, KRAS, NRAS, or FGFR3. We predicted that 32% of patients would have primary resistance to imatinib, based on mutations in exon 17 of KIT, exon 18 of PDGFRA (D842V), or no mutation in either gene. Targeted NGS of cytology samples from GISTs is feasible and provides clinically relevant data about kinase genotypes that can help guide individualized therapy.

  19. Efficacy of imatinib dose escalation in Chinese gastrointestinal stromal tumor patients

    Institute of Scientific and Technical Information of China (English)

    Jian Li; Ji-Fang Gong; Jie Li; Jing Gao; Nai-Ping Sun; Lin Shen

    2012-01-01

    AIM:To investigate the efficacy and safety of imatinib dose escalation in Chinese patients with advanced gastrointestinal stromal tumor (GIST).METHODS:Advanced GIST patients previously failing 400 mg imatinib treatment were enrolled in this study.Patients received imatinib with dose escalation to 600mg/d,and further dose escalation to 800 mg/d if imatinib 600 mg/d failed.Progression-free survival,overall survival,clinical efficacy,c-kit/PDGFRA genotype and safety were evaluated.RESULTS:52 patients were enrolled in this study.For the 47 evaluable patients receiving imatinib (600 mg/d),the disease control rate was 40.4%,and the median progression-free survival for all patients was 17 wk (95% CI:3.9-30.1).The median overall survival after dose escalation was 81 wk (95% CI:36.2-125.8).Adverse events,mainly edema,fatigue,granulocytopenia and skin rash were tolerable.However,further dose escalation (800 mg/d) in 14 cases was ineffective,with disease progression and severe adverse events.Among 30 cases examined for gene mutations,patients with exon 9 mutations experienced a better progression-free survival of 47 wk.CONCLUSION:Imatinib dose escalation to 600 mg/d is more appropriate for Chinese patients and may achieve further survival benefit.

  20. Expression and mutation of c-kit gene in gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Fei Feng; Xiao-Hong Liu; Qiang Xie; Wei-Qiang Liu; Cheng-Guang Bai; Da-Lie Ma

    2003-01-01

    AIM: To investigate the expression and mutation of c-kit gene and its correlation with the clinical pathology and prognosis of gastrointestinal stromal tumors (GISTs).METHODS: A total of 94 cases of GISTs, 10 leiomyomas and 2 schwannomas were studied for the expression of KIT by immunohistochemistry. The c-kit gene mutations in exon 11 of these specimens were detected by PCR-SSCP technique.RESULTS: Of the 94 cases of GISTs, 91 (96.8 %) expressed the KIT protein. Leiomyomas and schwannomas were negative for KIT. The c-kit gene mutations of exon 11 were found in 38 out of the 94 cases of GISTs (40.4 %). The mutations involved point mutations (Va1560-Asp, Ile563-Met),del 557-559 and 579ins12. No mutations were detectable in benign GISTs, leiomyomas or schwannomas. The patients with mutation-positive GISTs showed more frequent recurrences, invasion and metastasis in adjacent tissues than those with mutation-negative ones.CONCLUSION: KIT is a useful marker for diagnosis of GISTs.Mutation of the c-kit gene may play a significant role in the pathogenesis of GISTs and may be associated with poor prognosis in patients with GISTs.

  1. Adherence to imatinib therapy in gastrointestinal stromal tumors and chronic myeloid leukemia.

    Science.gov (United States)

    Al-Barrak, Jasem; Cheung, Winson Y

    2013-08-01

    The number of anticancer drugs available in oral formulation has risen sharply in the past few years and this is expected to continue to increase over the next several decades. For patients, the convenience of self-administration constitutes a major benefit associated with oral therapy. For clinicians, however, the transition from parenteral to oral therapy has resulted in concerns about adherence to therapy, its monitoring, and its effects on clinical outcomes. Several studies have demonstrated that imatinib is effective at improving overall survival and/or recurrence-free survival in patients with gastrointestinal stromal tumors and chronic myeloid leukemia (primary and metastatic disease). Despite the survival benefit and the favorable toxicity profile of imatinib, however, adherence to imatinib remains poor. Herein, we review the evidence showing the effects of nonadherence on patient outcomes as well as data indicating that adherence to imatinib (and oral anticancer therapy in general) is suboptimal. We also highlight factors that may contribute to nonadherence and suggest key steps that can be implemented by the multidisciplinary medical team to overcome the daily challenges of adherence. Improving adherence to imatinib depends on open communication and comprehensive patient education. All of this is essential to maximize benefits from therapy and improve clinical outcomes for our patients.

  2. Interactions of the p53 protein family in cellular stress response in gastrointestinal tumors.

    Science.gov (United States)

    Vilgelm, Anna E; Washington, Mary K; Wei, Jinxiong; Chen, Heidi; Prassolov, Vladimir S; Zaika, Alexander I

    2010-03-01

    p53, p63, and p73 are members of the p53 protein family involved in regulation of cell cycle, apoptosis, differentiation, and other critical cellular processes. Here, we investigated the contribution of the entire p53 family in chemotherapeutic drug response in gastrointestinal tumors. Real-time PCR and immunohistochemistry revealed complexity and variability of expression profiles of the p53 protein family. Using colon and esophageal cancer cells, we found that the integral transcription activity of the entire p53 family, as measured by the reporter analysis, associated with response to drug treatment in studied cells. We also found that p53 and p73, as well as p63 and p73, bind simultaneously to the promoters of p53 target genes. Taken together, our results support the view that the p53 protein family functions as an interacting network of proteins and show that cellular responses to chemotherapeutic drug treatment are determined by the total activity of the entire p53 family rather than p53 alone.

  3. Differentiation of large (≥5 cm) gastrointestinal stromal tumors from benign subepithelial tumors in the stomach: Radiologists’ performance using CT

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Ye Ra [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Kim, Se Hyung, E-mail: shkim7071@gmail.com [Department of Radiology, Seoul National University Hospital (Korea, Republic of); The Institute of Radiation Medicine, Seoul National University Hospital (Korea, Republic of); Kim, Sun-Ah [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Shin, Cheong-il [Department of Radiology, Seoul National University Hospital (Korea, Republic of); The Institute of Radiation Medicine, Seoul National University Hospital (Korea, Republic of); Kim, Hyung Jin; Kim, Seong Ho [Department of Radiology, Seoul National University Hospital (Korea, Republic of); Han, Joon Koo; Choi, Byung Ihn [Department of Radiology, Seoul National University Hospital (Korea, Republic of); The Institute of Radiation Medicine, Seoul National University Hospital (Korea, Republic of)

    2014-02-15

    Purpose: To identify significant CT findings for the differentiation of large (≥5 cm) gastric gastrointestinal stromal tumors (GIST) from benign subepithelial tumors and to assess whether radiologists’ performance in differentiation is improved with knowledge of significant CT criteria. Materials and methods: One-hundred twenty patients with pathologically proven large (≥5 cm) GISTs (n = 99), schwannomas (n = 16), and leiomyomas (n = 5) who underwent CT were enrolled. Two radiologists (A and B) retrospectively reviewed their CT images in consensus for the location, size, degree and pattern of enhancement, contour, growth pattern and the presence of calcification, necrosis, surface ulceration, or enlarged lymph nodes. CT findings considered significant for differentiation were determined using uni- and multivariate statistical analyses. Thereafter, two successive review sessions for the differentiation of GIST from non-GIST were independently performed by two other reviewers (C and D) with different expertise of 2 and 9 years using a 5-point confidence scale. At the first session, reviewers interpreted CT images without knowledge of significant CT findings. At the second session, the results of statistical analyses were provided to the reviewers. To assess improvement in radiologists’ performance, a pairwise comparison of receiver operating curves (ROC) was performed. Results: Heterogeneous enhancement, presence of necrosis, absence of lymph nodes, and mean size of ≥6 cm were found to be significant for differentiating GIST from schwannoma (P < 0.05). Non-cardial location, heterogeneous enhancement, and presence of necrosis were differential CT features of GIST from leiomyoma (P < 0.05). Multivariate analyses indicated that absence of enlarged LNs was the only statistically significant variable for GIST differentiating from schwannoma. The area under the curve of both reviewers obtained using ROC significantly increased from 0.682 and 0.613 to 0.903 and 0

  4. Strongyloidiasis in a diabetic patient accompanied by gastrointestinal stromal tumor: cause of eosinophilia unresponsive to steroid therapy.

    Science.gov (United States)

    Won, Eun Jeong; Jeon, Jin; Koh, Young-Il; Ryang, Dong Wook

    2015-04-01

    We report here a case of strongyloidiasis in a 72-year-old diabetic patient (woman) accompanied by gastrointestinal stromal tumor receiving imatinib therapy, first diagnosed as hypereosinophilic syndrome and treated with steroids for uncontrolled eosinophilia. She suffered from lower back pain and intermittent abdominal discomfort with nausea and diagnosed with gastrointestinal stromal tumor. After post-operative imatinib treatment eosinophilia persisted, so that steroid therapy was started under an impression of hypereosinophilic syndrome. In spite of 6 months steroid therapy, eosinophilia persisted. Stool examination was performed to rule out intestinal helminth infections. Rhabditoid larvae of Strongyloides stercoralis were detected and the patient was diagnosed as strongyloidiasis. This diagnosis was confirmed again by PCR. The patient was treated with albendazole for 14 days and her abdominal pain and diarrhea improved. This case highlights the need for thorough investigation, including molecular approaches, to test for strongyloidiasis before and during steroid therapies.

  5. Metabolic heterogeneity in human lung tumors

    Science.gov (United States)

    Hensley, Christopher T.; Faubert, Brandon; Yuan, Qing; Lev-Cohain, Naama; Jin, Eunsook; Kim, Jiyeon; Jiang, Lei; Ko, Bookyung; Skelton, Rachael; Loudat, Laurin; Wodzak, Michelle; Klimko, Claire; McMillan, Elizabeth; Butt, Yasmeen; Ni, Min; Oliver, Dwight; Torrealba, Jose; Malloy, Craig R.; Kernstine, Kemp; Lenkinski, Robert E.; DeBerardinis, Ralph J.

    2015-01-01

    SUMMARY Non-small cell lung cancer (NSCLC) is heterogeneous in the genetic and environmental parameters that influence cell metabolism in culture. Here, we assessed the impact of these factors on human NSCLC metabolism in vivo using intra-operative 13C-glucose infusions in nine NSCLC patients to compare metabolism between tumors and benign lung. While enhanced glycolysis and glucose oxidation were common among these tumors, we observed evidence for oxidation of multiple nutrients in each of them, including lactate as a potential carbon source. Moreover, metabolically heterogeneous regions were identified within and between tumors, and surprisingly, our data suggested potential contributions of non-glucose nutrients in well-perfused tumor areas. Our findings not only demonstrate the heterogeneity in tumor metabolism in vivo but also highlight the strong influence of the microenvironment on this feature. PMID:26853473

  6. Novel V600E BRAF Mutations in Imatinib-Naive and Imatinib-Resistant Gastrointestinal Stromal Tumors

    OpenAIRE

    Agaram, Narasimhan P; Wong, Grace C.; Guo, Tianhua; Maki, Robert G.; Singer, Samuel; DeMatteo, Ronald P; Besmer, Peter; Cristina R. Antonescu

    2008-01-01

    BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis....

  7. Endoscopic laser surgery of patients with pretumoral diseases and tumors of the organs of respiration and gastro-intestinal tract

    Science.gov (United States)

    Poddubny, Boris K.; Ungiadze, G. V.; Kuvshinov, Yury P.; Efimov, Oleg N.; Mazurov, S. T.

    1996-01-01

    The result of treatment of 566 patients with precancerous diseases, cancer and benign tumors of respiratory and gastro-intestinal tract are presented. The `Raduga-1' as a source of laser radiation has been used. The wavelength of radiation 1060 nm. The maximum of basic radiation at the end of lightguide is 50 W. It is shown that the method of endoscopic laser destruction is a highly effective one and may be recommended for radical treatment.

  8. Incidence and Survival Analysis of Gastrointestinal Stromal Tumors in Shanghai: A Population-Based Study from 2001 to 2010

    OpenAIRE

    Minzhi Lv; Chunxiao Wu; Ying Zheng; Naiqing Zhao

    2014-01-01

    Objectives. A population-based study was undertaken to investigate the epidemiological features of gastrointestinal stromal tumors (GISTs) in Shanghai, especially the incidence and the preliminary exploration of survival. Methods. A total of 1923 patients with GISTs diagnosed from 2001 to 2010 in Shanghai were reviewed. The annual incidence and overall survival of GISTs were calculated; Cox proportional hazards’ regression was used to analyze several prognostic factors. Results. The average...

  9. Tumores del estroma gastrointestinal (GIST: serie del Hospital Central de la Defensa Gómez Ulla

    Directory of Open Access Journals (Sweden)

    I. Bodega Quiroga

    2013-09-01

    Full Text Available Objetivo: Los tumores del estroma gastrointestinal (GIST se han diferenciado hace poco más de una década de los tumores de músculo liso y de origen neural gracias a métodos de identificación inmunohistoquímica (CD117. Al mismo tiempo, la introducción del Mesylato de Imatinib, fármaco empleado en el tratamiento de la leucemia mieloide crónica (LMC, ha mejorado la expectativa de vida, no sólo en GIST irresecables o metastáticos, sino también para aquéllos de intermedio o alto grado de malignidad como terapia adyuvante e incluso se plantea como tratamiento neoadyuvante. El objetivo de esta comunicación es estudiar los GIST diagnosticados e intervenidos quirúrgicamente en el Servicio de Cirugía General y del Aparato Digestivo del Hospital Central de la Defensa «Gómez Ulla» (Madrid en un periodo de 9 años y realizar una revisión de la literatura enfocada fundamentalmente a los avances en el tratamiento. Material y métodos: Estudio retrospectivo observacional de los pacientes diagnosticados de GIST e intervenidos quirúrgicamente en nuestro Servicio de 2003 a 2012. Se estudia el motivo de consulta inicial, la localización, el grado histológico y el tipo de intervención quirúrgica realizado. Resultados: Se encontraron 11 pacientes entre Noviembre de 2003 y Abril de 2012, todos hombres. La edad media fue de 65´17 años (rango, 53-84. Hay que destacar que en 8 casos (72´7 % el hallazgo fue incidental, sin ninguna sintomatología previa. La localización más frecuente fue el estómago en 6 casos (54´5%, y en el intestino delgado en 5 (45´5%. En cuanto al riesgo de malignidad, 5 casos (45´5% fueron de bajo grado, 4 (36´4% de grado intermedio, 1 (9% de muy bajo grado y 1 (9´1% de alto grado de malignidad. La técnica quirúrgica empleada fue la gastrectomía parcial en 6 casos (54´5% seguida de la resección intestinal segmentaria en 5 casos (45´5%. Conclusiones: La incidencia anual de tumores GIST intervenidos en nuestro

  10. Gastrointestinal osmoreceptors and renal sodium excretion in humans

    DEFF Research Database (Denmark)

    Andersen, L J; Skram, Thomas Ulrik; Bestle, M H;

    2000-01-01

    The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered by a nasogas......The hypothesis that natriuresis can be induced by stimulation of gastrointestinal osmoreceptors was tested in eight supine subjects on constant sodium intake (150 mmol NaCl/day). A sodium load equivalent to the amount contained in 10% of measured extracellular volume was administered......-angiotensin system....

  11. The inside mystery of jejunal gastrointestinal stromal tumor: a rare case report and review of the literature.

    Science.gov (United States)

    Dhull, A K; Kaushal, V; Dhankhar, R; Atri, R; Singh, H; Marwah, N

    2011-01-01

    Gastrointestinal stromal tumors (GISTs) are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA) has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.

  12. The Inside Mystery of Jejunal Gastrointestinal Stromal Tumor: A Rare Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    A. K. Dhull

    2011-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are malignant and rare form of soft tissue sarcoma of the digestive tract. The incidence of gastrointestinal stromal tumors is very low Kramer et al. 2005 Jejunal GISTs are extremely rare. Here we present a rare case of jejunal GIST with unusually large size at presentation. The patient presented with severe abdomen pain, exophytic growth, and dimorphic anemia. Surgical resection of the tumor was carried out, and operative findings revealed a 15 × 10 cm growth, arising from serosal surface of jejunum, at the antimesenteric surface. Diagnosis in this case was made by subjecting the resected specimen to immunohistochemical analysis. In view of large size of the resected tumor, and high-risk histopathological features, imatinib mesylate 400 mg once daily was given as adjuvant chemotherapy. Patient is asymptomatic without any evidence of tumor recurrence after six months of postoperative followup. Imatinib as such is recommended in metastatic, residual or recurrent cases of GISTs or which are surgically not removable; however, recent recommendations suggests the use of imatinib mesylate after radical surgery in high-risk cases, because it has shown a significant decrease in the recurrence rate, and the Food and Drug Administration (FDA has also approved the use of imatinib as adjuvant therapy after complete resection of localized, primary GIST.

  13. The human gastrointestinal microbiota - An unexplored frontier for pharmaceutical discovery

    NARCIS (Netherlands)

    Roeselers, G.; Bouwman, J.; Venema, K.; Montijn, R.

    2012-01-01

    The mammalian gastrointestinal tract (GIT) harbors microorganisms (the microbiota) of vast phylogentic, genomic, and metabolic diversity, and recent years have seen a rapid development in the techniques for studying these complex microbial ecosystems. It is increasingly apparent that the GIT microbi

  14. The role of KCNQ1 in mouse and human gastrointestinal cancers.

    Science.gov (United States)

    Than, B L N; Goos, J A C M; Sarver, A L; O'Sullivan, M G; Rod, A; Starr, T K; Fijneman, R J A; Meijer, G A; Zhao, L; Zhang, Y; Largaespada, D A; Scott, P M; Cormier, R T

    2014-07-17

    Kcnq1, which encodes for the pore-forming α-subunit of a voltage-gated potassium channel, was identified as a gastrointestinal (GI) tract cancer susceptibility gene in multiple Sleeping Beauty DNA transposon-based forward genetic screens in mice. To confirm that Kcnq1 has a functional role in GI tract cancer, we created Apc(Min) mice that carried a targeted deletion mutation in Kcnq1. Results demonstrated that Kcnq1 is a tumor suppressor gene as Kcnq1 mutant mice developed significantly more intestinal tumors, especially in the proximal small intestine and colon, and some of these tumors progressed to become aggressive adenocarcinomas. Gross tissue abnormalities were also observed in the rectum, pancreas and stomach. Colon organoid formation was significantly increased in organoids created from Kcnq1 mutant mice compared with wild-type littermate controls, suggesting a role for Kcnq1 in the regulation of the intestinal crypt stem cell compartment. To identify gene expression changes due to loss of Kcnq1, we carried out microarray studies in the colon and proximal small intestine. We identified altered genes involved in innate immune responses, goblet and Paneth cell function, ion channels, intestinal stem cells, epidermal growth factor receptor and other growth regulatory signaling pathways. We also found genes implicated in inflammation and in cellular detoxification. Pathway analysis using Ingenuity Pathway Analysis and Gene Set Enrichment Analysis confirmed the importance of these gene clusters and further identified significant overlap with genes regulated by MUC2 and CFTR, two important regulators of intestinal homeostasis. To investigate the role of KCNQ1 in human colorectal cancer (CRC), we measured protein levels of KCNQ1 by immunohistochemistry in tissue microarrays containing samples from CRC patients with liver metastases who had undergone hepatic resection. Results showed that low expression of KCNQ1 expression was significantly associated with poor

  15. Atypical presentation of myoepithelial hamartoma in the antrum of the stomach, mimicking a gastrointestinal stromal tumor: a case report

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    Nabi Junaid

    2012-11-01

    Full Text Available Abstract Introduction A myoepithelial hamartoma is a very uncommon submucosal tumor of the stomach. In an atypical presentation in our case, it mimicked the clinical presentation of a gastrointestinal stromal tumor. To the best of our knowledge, it is the first case of a hamartoma of the stomach reported from Bangladesh and one of few cases described in the literature. Case presentation We describe the case of a 35-year-old Bengali man with recurrent epigastric pain and occasional vomiting with radiographic findings of a gut mass. An upper gastrointestinal endoscopy revealed a healed duodenal ulcer, deformed ‘D’ bulb and a submucosal swelling in his antrum. Ultrasonography and a contrast-enhanced computed tomography scan confirmed the presence of a well-defined, oval gut mass in his upper abdomen, compressing his duodenum. The mass had a mixed density and was considered to probably be a gastrointestinal stromal tumor. Ultrasonography-guided fine needle aspiration cytology was inconclusive. After resection at laparotomy, a histopathological examination revealed a myoepithelial hamartoma. These tumors are characterized by hypertrophic smooth muscle bands surrounding varied epithelial elements, which may be arranged in diverse patterns such as simple glandular structure, Brunner’s gland, pancreatic ducts and sometimes pancreatic acini. This case report is complemented by a literature review relating to the atypical presentation. Conclusion Gut masses need to be investigated thoroughly and the possibility of rare tumors should not be excluded. Although the recommended treatment for such lesions is limited resection, radical procedures such as a pancreaticoduodenectomy are often performed when the lesion occurs in the periampullary area because of preoperative misdiagnosis as a carcinoma. Therefore, it is essential for clinicians to maintain current knowledge of the lesion to avoid inaccurate diagnosis and prevent unnecessary surgery.

  16. Oncogenic signaling by Kit tyrosine kinase occurs selectively on the Golgi apparatus in gastrointestinal stromal tumors.

    Science.gov (United States)

    Obata, Y; Horikawa, K; Takahashi, T; Akieda, Y; Tsujimoto, M; Fletcher, J A; Esumi, H; Nishida, T; Abe, R

    2017-02-13

    Gastrointestinal stromal tumors (GISTs) are caused by gain-of-function mutations in the Kit receptor tyrosine kinase. Most primary GIST patients respond to the Kit inhibitor imatinib, but this drug often becomes ineffective because of secondary mutations in the Kit kinase domain. The characteristic intracellular accumulation of imatinib-sensitive and -resistant Kit protein is well documented, but its relationship to oncogenic signaling remains unknown. Here, we show that in cancer tissue from primary GIST patients as well as in cell lines, mutant Kit accumulates on the Golgi apparatus, whereas normal Kit localizes to the plasma membrane (PM). In imatinib-resistant GIST with a secondary Kit mutation, Kit localizes predominantly on the Golgi apparatus. Both imatinib-sensitive and imatinib-resistant Kit (Kit(mut)) become fully auto-phosphorylated only on the Golgi and only if in a complex-glycosylated form. Kit(mut) accumulates on the Golgi during the early secretory pathway, but not after endocytosis. The aberrant kinase activity of Kit(mut) prevents its export from the Golgi to the PM. Furthermore, Kit(mut) on the Golgi signals and activates the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) pathway, signal transducer and activator of transcription 5 (STAT5), and the Mek-Erk pathway. Blocking the biosynthetic transport of Kit(mut) to the Golgi from the endoplasmic reticulum inhibits oncogenic signaling. PM localization of Kit(mut) is not required for its signaling. Activation of Src-family tyrosine kinases on the Golgi is essential for oncogenic Kit signaling. These results suggest that the Golgi apparatus serves as a platform for oncogenic Kit signaling. Our study demonstrates that Kit(mut)'s pathogenicity is related to its mis-localization, and may offer a new strategy for treating imatinib-resistant GISTs.Oncogene advance online publication, 13 February 2017; doi:10.1038/onc.2016.519.

  17. Cerebral relapse of metastatic gastrointestinal stromal tumor during treatment with imatinib mesylate: Case report

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    Waring Paul

    2004-10-01

    Full Text Available Abstract Background The management of unresectable or metastatic gastrointestinal stromal tumors (GISTs has previously been difficult as they are resistant to conventional chemotherapy and radiation. The development of imatinib mesylate has made a major impact on the management of advanced GISTs. It is apparent that there are sanctuary sites such as the central nervous system where imatinib does not achieve adequate concentrations. We describe the case of a man with metastatic GIST who experienced multiple cerebral relapses of disease while systemic disease progression appeared to be controlled by imatinib. Case presentation A 47-year-old man presented in July 1999 with a jejunal GIST with multiple hepatic metastases. The jejunal primary was resected and after unsuccessful cytoreductive chemotherapy, the liver metastases were also resected in December 1999. The patient subsequently relapsed in August 2001 with symptomatic hepatic, subcutaneous gluteal, left choroidal and right ocular metastases all confirmed on CT and PET scanning. Biopsy confirmed recurrent GIST. MRI and lumbar puncture excluded central nervous system involvement. The patient was commenced on imatinib 400 mg bd in September 2001 through a clinical trial. The symptoms improved with objective PET and CT scan response until December 2002 when the patient developed a right-sided foot drop. MRI scan showed a left parasagittal tumor which was resected and confirmed histologically to be metastatic GIST. Imatinib was ceased pre-operatively due to the trial protocol but recommenced in February 2003 on a compassionate use program. The left parasagittal metastasis recurred and required subsequent re-excision in September 2003 and January 2004. Control of the systemic GIST was temporarily lost on reduction of the dose of imatinib (due to limited drug supply but on increasing the dose back to 800 mg per day, systemic disease was stabilized for a period of time before generalised progression

  18. Pancreatic Extra-Gastrointestinal Stromal Tumor: An Unusual Presentation of a Rare Diagnosis

    Science.gov (United States)

    Joshi, Jitesh; Rustagi, Tarun

    2010-01-01

    Background: Gastrointestinal stromal tumors (GISTs) rarely develop outside the digestive tract and such tumors are designated extra-GISTs (EGISTs). The majority of EGISTs are located in the mesentery, omentum, and retroperitoneum, and the primary localization in the pancreas has been reported in only about six cases. We describe a patient with a large metastatic pancreatic EGIST that had metastasized to the liver at time of presentation. Case: An 84-year-old male presented with worsening confusion and agitation for the past few days. He also reported progressively increasing abdominal distension for the past 3 years, more so in the past few months. He denied any abdominal pain, nausea, or vomiting. He mentioned one episode of melena 2 months ago. There was a history of unintentional weight loss of 30 pounds over the past few months. Review of systems was otherwise negative. Past medical history was significant for diabetes mellitus and lactose intolerance. Pertinent examination findings included a cachectic appearance, altered mentation without any focal neurologic deficit, and marked abdominal distension with dullness on percussion. Investigations were significant for elevated ammonia level (168 ug/dL), AST/ALT/Alk. phosphatase (424/153/102 U/L), and total bilirubin of 1.7 mg/dL. CEA and CA19-9 were within normal limits. Computed tomography (CT) scan of the abdomen showed an extremely large central heterogeneous mass of 34 × 24 × 27 cm replacing the entire pancreatic tissue and multiple hepatic metastases. Subsequently, a CT-guided liver biopsy demonstrated a spindle cell neoplasm with CD117 (c-kit), CD34, and vimentin-positive cells, consistent with liver metastasis from an EGIST. On day 3, he had massive hematemesis, for which he was transferred to the intensive care unit. His condition rapidly deteriorated with hemodynamic instability and further worsening of mental status. After a thorough discussion about treatment options and prognosis, his family

  19. MRI and MRS of human brain tumors.

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    Hou, Bob L; Hu, Jiani

    2009-01-01

    The purpose of this chapter is to provide an introduction to magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of human brain tumors, including the primary applications and basic terminology involved. Readers who wish to know more about this broad subject should seek out the referenced books (1. Tofts (2003) Quantitative MRI of the brain. Measuring changes caused by disease. Wiley; Bradley and Stark (1999) 2. Magnetic resonance imaging, 3rd Edition. Mosby Inc; Brown and Semelka (2003) 3. MRI basic principles and applications, 3rd Edition. Wiley-Liss) or reviews (4. Top Magn Reson Imaging 17:127-36, 2006; 5. JMRI 24:709-724, 2006; 6. Am J Neuroradiol 27:1404-1411, 2006).MRI is the most popular means of diagnosing human brain tumors. The inherent difference in the magnetic resonance (MR) properties of water between normal tissues and tumors results in contrast differences on the image that provide the basis for distinguishing tumors from normal tissues. In contrast to MRI, which provides spatial maps or images using water signals of the tissues, proton MRS detects signals of tissue metabolites. MRS can complement MRI because the observed MRS peaks can be linked to inherent differences in biochemical profiles between normal tissues and tumors.The goal of MRI and MRS is to characterize brain tumors, including tumor core, edge, edema, volume, types, and grade. The commonly used brain tumor MRI protocol includes T2-weighted images and T1-weighted images taken both before and after the injection of a contrast agent (typically gadolinium: Gd). The commonly used MRS technique is either point-resolved spectroscopy (PRESS) or stimulated echo acquisition mode (STEAM).

  20. A Case of Gastrointestinal Stromal Tumor That Underwent Endoscopic Ultrasound-Guided Aspiration with a 25-Gauge Biopsy Needle

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    Minoru Tomizawa

    2016-05-01

    Full Text Available Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA is performed to obtain specimens for pathological analysis. For this procedure, 19-gauge (19G, 22-guage (22G, and 25-guage (25G needles are available. The needles are classified into aspiration type and biopsy type. A 56-year-old woman underwent upper gastrointestinal endoscopy that showed a 38-mm-diameter submucosal tumor. The elevated lesion was diagnosed as a submucosal tumor of the stomach. Contrast-enhanced computed tomography showed a low-density area on the luminal surface of the gastric wall, which was covered with a thin layer of gastric mucosa. EUS showed a hypoechoic lesion in the submucosal layer. Color Doppler image showed a pulsating vascular signal extending into the center of the hypoechoic lesion from the periphery. EUS-FNA was performed with a 25G biopsy needle. The specimen tissue consisted of spindle-shaped cells. The cells were positive for CD117 and CD34. The submucosal tumor was diagnosed as a gastrointestinal stromal tumor.

  1. A Case of Gastrointestinal Stromal Tumor That Underwent Endoscopic Ultrasound-Guided Aspiration with a 25-Gauge Biopsy Needle.

    Science.gov (United States)

    Tomizawa, Minoru; Shinozaki, Fuminobu; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is performed to obtain specimens for pathological analysis. For this procedure, 19-gauge (19G), 22-guage (22G), and 25-guage (25G) needles are available. The needles are classified into aspiration type and biopsy type. A 56-year-old woman underwent upper gastrointestinal endoscopy that showed a 38-mm-diameter submucosal tumor. The elevated lesion was diagnosed as a submucosal tumor of the stomach. Contrast-enhanced computed tomography showed a low-density area on the luminal surface of the gastric wall, which was covered with a thin layer of gastric mucosa. EUS showed a hypoechoic lesion in the submucosal layer. Color Doppler image showed a pulsating vascular signal extending into the center of the hypoechoic lesion from the periphery. EUS-FNA was performed with a 25G biopsy needle. The specimen tissue consisted of spindle-shaped cells. The cells were positive for CD117 and CD34. The submucosal tumor was diagnosed as a gastrointestinal stromal tumor.

  2. Tumores del estroma gastrointestinal (GIST: factores pronósticos de supervivencia tras citorreducción R0 Gastrointestinal stromal tumors (GIST: factors predictive of survival after R0-cytoreduction

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    J. M. Sánchez Hidalgo

    2007-12-01

    Full Text Available Objetivo: analizar los posibles factores pronósticos de supervivencia en tumores estromales gastrointestinales c-kit positivo (GIST, tras citorreducción óptima R0. Pacientes y método: estudio de 35 pacientes intervenidos en nuestra Unidad desde enero 2002 a febrero 2007, con tumores del estroma gastrointestinal CD117/c-kit positivo en los que se alcanzó citorreducción quirúrgica sin residuo tumoral macroscópico. Una base de datos prospectiva nos proporcionó las distintas variables analizadas, de carácter demográfico, anatómico, clínico, histopatológico e inmunohistoquímico, entre otras. El análisis de la supervivencia actuarial se realizó según el método de Kaplan-Meier y el análisis multivariante mediante el método de regresión múltiple de Cox. Resultados: la supervivencia global a 5 años fue del 77%, con una supervivencia media de 52 meses. El riesgo de malignidad según la clasificación de Fletcher y el tamaño tumoral mayor de 10 cm, influyeron significativamente de forma negativa sobre la supervivencia de los pacientes, tras el análisis univariante realizado (p 50% y vivos en la actualidad. Conclusiones: el índice proliferativo Ki-67 podría representar un excelente marcador pronóstico de supervivencia en aquellos pacientes con tumores del estroma gastrointestinal c-kit positivo. Su confirmación y el punto de corte adecuado deberían ser objeto de futuros estudios prospectivos, así como su posible utilidad para seleccionar pacientes candidatos al tratamiento con mesilato de imatinib.Objective: to analyze the different factors predictive of survival associated with optimal R0-cytoreduction in c-kit-positive gastrointestinal stromal tumors. Methods: thirty-five patients were operated on in our Oncological Surgery Department from January 2002 to February 2007 because of CD117/c-kit-positive gastrointestinal stromal tumors, and an optimal surgical cytoreduction was obtained without macroscopical residual disease

  3. High adhesion of tumor cells to mesothelial monolayers derived from peritoneal wash of disseminated gastrointestinal cancers.

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    Danilo Ranieri

    Full Text Available The role of the mesothelial layer in the peritoneal spreading of cancer cells is only partially clarified. Here we attempted to better define the mesothelial contribution to the tumor cell adhesion using a direct adhesion test applied to human primary cultures of mesothelial cells (HPMCs derived from the peritoneal washes of patients with gastric and colorectal cancers. Gastric and colon carcinoma cells were seeded on different mesothelial monolayers and quantitative fluorescence analysis was performed to analyze their growth and adhesive properties. The adhesion of the cancer cells was not affected by the origin of the HPMCs when derived from patients with different cancers or with benign disease. In contrast, the high levels of ICAM1 expression and ROS production, which characterize these senescent mesothelial cells, enhanced the tumor cell adhesion. These results suggest that the mesothelial adhesive properties are dependent on the cell senescence, while are not affected by the tumor environment. The use of peritoneal washes as a source to isolate HPMCs provides a practical and reliable tool for the in vitro analysis of the mesothelial conditions affecting the peritoneal carcinomatosis.

  4. Surgical treatment and prognostic analysis for gastrointestinal stromal tumors (GISTs of the small intestine: before the era of imatinib mesylate

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    Jan Yi-Yin

    2006-10-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GISTs, the most common type of mesenchymal tumors of the gastrointestinal (GI tract, demonstrate positive kit staining. We report our surgical experience with 100 small intestine GIST patients and identify predictors for long-term disease-free survival (DFS and overall survival (OS to clarify the difference between high- and low-risk patients. Methods The clinicopathologic and follow-up records of 100 small intestine GIST patients who were treated at Chung Gung Memorial Hospital between 1983 and 2002 were retrospectively reviewed. Clinical and pathological factors were assessed for long-term DFS and OS by using a univariate log-rank test and a multivariate Cox proportional hazard model. Results The patients included 52 men and 48 women. Their ages ranged from 27 to 82 years. Among the 85 patients who underwent curative resection, 44 (51.8% developed disease recurrence (liver metastasis was the most common form of recurrence. The follow-up period ranged from 5 to 202 months (median: 33.2 months. The 1-, 3-, and 5-year DFS and OS rates were 85.2%, 53.8%, and 43.7%, and 91.5%, 66.6%, and 50.5%, respectively. Using multivariate analysis, it was found that high tumor cellularity, mitotic count >5/50 high-power field, and a Ki-67 index ≧10% were three independent factors that were inversely associated with DFS. However, absence of tumor perforation, mitotic count Conclusion Tumors with low cellularity, low mitotic count, and low Ki-67 index, which indicate low risk, predict a more favorable DFS for small intestine GIST patients undergoing curative resection. Absence of tumor perforation with low mitotic count and low cellularity, which indicates low risk, can predict long-term OS for small intestine GIST patients who have undergone curative resection.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

  6. Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to ¹⁸F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors.

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    Min-Hee Cho

    Full Text Available Fluorine-18 fluorodeoxyglucose (18F-FDG positron emission tomography-computed tomography (PET/CT is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs; however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated 18F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that 18F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1, hexokinase 1 (HK1, and lactate dehydrogenase A (LDHA. Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2 and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.

  7. Robot-Assisted Excision of a Pararectal Gastrointestinal Stromal Tumor in a Patient with Previous Ileal Neobladder

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    A. Ploumidis

    2014-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the most frequent mesenchymal tumors of the gastrointestinal tract with surgical resection remaining the cornerstone of therapy. Pararectal lesions are considered to be technically difficult and pose in some cases a challenge. We report, to the best of our knowledge, the first robotic-assisted pararectal GIST excision. A 43-year-old man was referred to our center with pararectal GIST recurrence, despite treatment with targeted therapy. Eleven years ago, he underwent extensive abdominal surgery including cystoprostatectomy with ileal neobladder diversion due to GIST resection in the rectoprostatic space. Robot-assisted surgical resection was successfully performed without the need for temporary colostomy. The postoperative course of the patient was uneventful, and the pathology report confirmed a GIST recurrence with negative surgical margins and pelvic lymph nodes free of any tumor. Robotic-assisted pelvic surgery can be extended to incorporate excision of pararectal GISTs, as a safe, less invasive surgical alternative with promising oncological results and minimal injury to adjacent structures.

  8. Respiration rate in human pituitary tumor explants.

    Science.gov (United States)

    Anniko, M; Bagger-Sjöbäck, D; Hultborn, R

    1982-01-01

    Studies on the respiration rate of human pituitary tumor tissue have so far been lacking in the literature. This study presents the results from four adenomas causing acromegaly, all with different clinical degrees of the disease. Determination of oxygen uptake was performed in vitro with a spectrophotorespirometric system. Pieces of the tumors were explanted to an organ culture system with a high degree of stability. The secretion rate of growth hormone (GH) and prolactin (PRL) was determined. After 4-8 days in vitro, specimens were analyzed for respiration rate. This was approximately 1-1.5 microliters O2/h/micrograms dry weight. The activity of the pituitary tumor tissue was characterized by both the hormone secretion rate and the respiration rate. Particularly active foci were found to occur in the adenoma tissue. Depending on the individual tumor, the GH secretion rate was approximately 0.1-100 pmol/micrograms dry weight/h and PRL secretion rate approximately 0.4-18 micrograms/micrograms dry weight/h. The respiration rate--as is also the hormone secretion rate--is dependent on the time in vitro prior to analysis. The respiration rate in individual tumors is a parameter which does not reflect GH or PRL serum levels or clinical activity of the disease.

  9. Helical CT findings and clinicopathologic featuresin malignant gastrointestinal stromal tumors: the correlation between radiologic appearance and malignant potential

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Xu; Aizhen Pan; Fang Yong; Yingyu Chen; Bin Li; Qiang Gao; Renhua Wu

    2011-01-01

    Objective: In this pictorial essay, we described the clinical, pathologic, and computed tomographic (CT) findings of malignant gastrointestinal stromal tumors (MGISTs) and attempt to establish the correlation between radiologic appearance and malignant potential. Methods: This retrospective analysis included 20 patients receiving treatment for MGIST between 2008 and 2010. The diagnosis was established by pathology and immunohistochemistry. All these patients underwent pre-operative CT. Clinical presentation, pathology and CT images were analyzed. Helical CT images were reviewed for morpho-logic features such as tumor size, number and location, tumor margins, necrosis, degree of enhancement and metastasis. Results: Gastrointestinal bleeding, abdominal pain and discomfort, and without clinical symptom were common findings and were observed in 9 (45%), 6 (30%), and 5 (25%) of the 20 patients. 8 (40%) tumors were located in stomach, and 10 (50%), 1 (5%) and 1 (5%) were located in small intestine, mesentery and peritoneum, respectively. Male to female ratio was about 1:2. The size of MGIST ranged from 2.6 cm to 17.5 cm with a mean of 8.7 cm. All tumors density was inhomogeneous and heterogeneous enhancement. MGISTs with highly malignant located in small intestine were about 30% higher than stomach. The "satellite" tumours were found in 6 cases with high malignant risk. 7 cases were suffered from liver metastasis, and 4 cases went with seeding into the abdominal cavity, 1 cases went with lymph node metastasis. Histologically, 19 cases (95%) were of spindle cell type. Immunohistochemical stains demonstrated a strong positivity for both c-kit (CD117) and CD34s enhancement in 19 (95%). Conclusion: Clinical expression is varied in MGIST patients. Female might be predominance in MGIST. The GISTs located in small intestine would tend to be more aggressive. The satellite tumours, necrosis and cystic degeneration were strongly benefit for MGIST diagnosis. Furthermore, intestinal

  10. Metachronous Gastrointestinal Stromal Tumor and Acute Leukemia after Liver Transplantation for Cholangiocellular Carcinoma: Is There a Link?

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    Mrzljak, Anna; Košuta, Iva; Škrtićl, Anita; Kardum-Skelin, Ika; Vrhovac, Radovan

    2013-01-01

    The synchronous or metachronous coexistence of gastrointestinal stromal tumors (GISTs) with solid and hematologic neoplasms has been addressed in a non-transplant population. However, the association with primary hepatic neoplasms and leukemias is uncommon. Scarce data exist considering association of GISTs and other neoplasms in a transplant population where long-term immunosuppression carries the additional burden of de novo malignancy. We present a case of posttransplant metachronous GIST and acute biphenotypic leukemia in a patient transplanted for intrahepatic cholangiocellular carcinoma, emphasizing the possible link between mechanisms of carcinogenesis and influence of other factors upon their development. PMID:23626555

  11. Endo-laparoscopic reduction and resection of gastroduodenal intussuception of gastrointestinal stromal tumor (GIST): a synchronous endoscopic and laparoscopic treatment.

    Science.gov (United States)

    Chan, Christina Tin Yan; Wong, Simon Kin Hung; Ping Tai, Yuk; Li, Michael Ka Wah

    2009-06-01

    Gastrointestinal stromal tumor (GIST) commonly occurs in the stomach. We would like to report an uncommon presentation of gastric GIST with gastroduodenal intussuception. A patient with known history of gastric GIST at fundus for 10 years presented to the casualty department with recurrent epigastric pain, deranged liver function, and hyperamylasemia. Computed tomography of the abdomen showed intussuception of the gastric GIST into duodenum. Emergency operation with synchronous endoscopic reduction and laparoscopic wedge resection was performed and patient had uneventful recovery. This simultaneous endoscopic and laparoscopic treatment should be considered for this rare complication of GIST.

  12. Human epididymis protein 4 immunostaining of malignant ascites differentiates cancer of Müllerian origin from gastrointestinal cancer.

    Science.gov (United States)

    Stiekema, Anna; Van de Vijver, Koen K; Boot, Henk; Broeks, Annegien; Korse, Catharina M; van Driel, Willemien J; Kenter, Gemma G; Lok, Christianne A R

    2017-03-01

    An accurate diagnosis of cancer of Müllerian origin is required before the initiation of treatment. An overlap in clinical presentation and cytological, histological, or imaging studies with other nongynecological tumors does occur. Therefore, immunocytochemistry markers are used to determine tumor origin. Human epididymis protein 4 (HE4) is overexpressed in tissue of epithelial ovarian cancer (EOC). It has shown to be a sensitive and specific serum marker for EOC and to be of value for the differentiation between EOC and ovarian metastases of gastrointestinal origin. The objective of the current study was to evaluate HE4 immunocytochemistry in malignant ascites for differentiation between cancer of Müllerian origin, including EOC, and adenocarcinomas of the gastrointestinal tract. Cytological specimens of 115 different adenocarcinomas (45 EOCs, 46 cases of gastric cancer, and 24 cases of colorectal cancer) were stained for HE4, paired box 8 (PAX8), and other specific markers. 91% of the ascites samples from patients with EOC stained for both HE4 and PAX8. The 4 samples without HE4 staining were a clear cell carcinoma, a low-grade serous adenocarcinoma, an undifferentiated adenocarcinoma, and a neuroendocrine carcinoma. All high-grade serous adenocarcinomas (n = 37, 100%) stained with HE4, compared with 94% that stained positively for PAX8. In cases of gastric or colorectal cancer, 25% and 21% of cases, respectively, stained positive for HE4. No PAX8 staining was observed in colorectal or gastric adenocarcinomas. HE4 staining in ascites is feasible and appears to have a high sensitivity for high-grade serous ovarian cancer. HE4 is a useful addition to the current panel of immunocytochemistry markers for the diagnosis of EOC and for differentiation with gastrointestinal adenocarcinomas. Cancer Cytopathol 2017;125:197-204. © 2016 American Cancer Society. © 2017 American Cancer Society.

  13. [Ultrasound imaging of mesenchymal small intestine tumors in diagnosis of unexplained gastrointestinal hemorrhage].

    Science.gov (United States)

    Bozkurt, T; Butsch, B; Schmiegelow, P; Lux, G

    1993-12-01

    The presented case reports highlight the value of transabdominal ultrasound as a complementary and non-invasive diagnostic tool in unexplained gastrointestinal bleeding. Seven patients with intermittent melaena and/or chronic anaemia were examined. In all patients, diagnostic procedures like abdominal ultrasound, EGD, colonoscopy and enteroclysis were performed primarily and did not point to a bleeding source. Transabdominal bowel wall ultrasound discovered in all cases a round and smoothly delineated tumour of homogeneous and hypoechoic structure. The diagnosis was confirmed using selective angiography in three cases revealing a roundish hypervascular lesion. Fine-needle aspiration biopsy and re-endoscopy were used in two cases, respectively, to verify the diagnosis. Postoperative histology revealed a benign leiomyoma (n = 3), schwannoma (n = 2), lipoma (n = 1) and angiofibroma (n = 1) with vascular erosions. Transabdominal ultrasound can operate as a complementary imaging technique in case of gastrointestinal haemorrhage, if endoscopic procedures fail to identify the bleeding source in the upper gastrointestinal tract and large bowel.

  14. When is a GIST not a GIST? A case report of synchronous metastatic gastrointestinal stromal tumor and fibromatosis

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    Desilva Keshani

    2009-01-01

    Full Text Available Abstract Background A number of non-malignant diseases that share similar morphological features as gastrointestinal stromal tumor (GIST have been reported. Co-existence of GIST with these other diseases is rarely recognized or reported. Case presentation We report a case of a 62 year-old man with long-term stable control of metastatic GIST with systemic therapy, presented with an apparent intra-abdominal progression but not supported by imaging with positron emission tomography. Subsequent resection of the intra-abdominal tumor identified a non-malignant fibroid. Conclusion Differentiating localized progression of GIST from other diseases has important prognostic and therapeutic implications. The potential for co-existence of non-malignant soft tissue neoplasm should always be considered.

  15. One-stage laparoscopic resection for a large gastric gastrointestinal stromal tumor and synchronous liver metastases following preoperative imatinib therapy: A case report

    OpenAIRE

    2013-01-01

    Laparoscopic partial gastrectomy without lymph node dissection has been accepted worldwide for the treatment of small gastric gastrointestinal stromal tumors (GISTs). However, the role of laparoscopic surgery in the treatment of large gastric GISTs remains under debate due to the risk of tumor spillage or rupture of the tumor capsule leading to peritoneal seeding. To the best of our knowledge, one-stage laparoscopic resection for a large gastric GIST and synchronous liver metastases following...

  16. Gastrointestinal stromal tumor and other primary metachronous or synchronous neoplasms as a suspicion criterion for syndromic setting.

    Science.gov (United States)

    Ponti, Giovanni; Luppi, Gabriele; Martorana, Davide; Rossi, Giulio; Losi, Lorena; Bertolini, Federica; Sartori, Giuliana; Pellacani, Giovanni; Seidenari, Stefania; Boni, Elisa; Neri, Tauro Maria; Silini, Enrico; Tamburini, Elisa; Maiorana, Antonio; Conte, Pier Franco

    2010-02-01

    Gastrointestinal stromal tumors (GISTs) may be sporadic or inherited. Although KIT and PDGFRA activating mutations are the oncogenic mechanisms in most sporadic and inherited GISTs, a small subset of GISTs are negative for both. Besides the classical Familial GIST Syndrome, GIST can occur as part of multi-neoplastic disease. The present study was designed to analyze the synchronous and metachronous tumors developed among GIST patients assessed by our institution for GIST Syndrome setting recognition. Patients (n=141) with primary GIST (77 men and 64 women) were recruited between 1988 and 2007 and their clinical and pathological records were reviewed. Mutation analysis of KIT, PDGFRA, NF1 and MMR genes was performed on somatic and peripheral blood DNA. GISTs occurred associated with other primary malignancies in 46 of 141 (32.6%) patients. The most common neoplasms were gastrointestinal and genitourinary. A novel exon 6 germline large deletion of NF1 was identified in the NF1/GIST kindred. The development of GIST associated with other neoplasms is common and diagnosis of peculiar benign associated-neoplasms warrants the search for familial cancer susceptibility. In particular, syndromic or familial settings have to be suspected in the presence of neurofibroma or lung chordoma in C-KIT and PDGFRA negative GIST patients.

  17. Does imatinib turn recurrent and/or metastasized gastrointestinal stromal tumors into a chronic disease? - single center experience.

    Science.gov (United States)

    Armbrust, Thomas; Sobotta, Michael; Gunawan, Bastian; Füzesi, Laszlo; Langer, Claus; Cameron, Silke; Ramadori, Giuliano

    2009-07-01

    Gastrointestinal stromal tumors (GIST) are mesenchymal tumors of the gastrointestinal tract supposed to arise from the cells of Cajal because of gain-of-function mutations of the tyrosine receptor kinases c-kit or platelet-derived growth factor receptor A. Imatinib selectively inhibits the kinase activity of both receptors. Despite this breakthrough in the treatment of GIST, resistance against imatinib has been reported to be as high as 50% after the first 2 years of treatment. Outcome of 13 consecutive patients with relapsed or metastasized GIST who were treated with imatinib was analyzed. Mean duration of treatment was 53.5 months. Four patients developed progressive disease and died after a mean treatment time of 31 months in spite of increase of imatinib dosages to 800 mg daily. Two patients (23%) developed a progressive disease after 46 months or 52 months of treatment. Two patients had a stable disease and five had a partial response. The overall progression rate was 46%, the mean survival time since primary diagnosis was 85.8 months. From our experience, frequency of resistance development to imatinib may be below that given in the literature (50% after 2 years). Individual treatment in specialized centers may improve compliance.

  18. Viability of Lactobacillus delbrueckii Under Human Gastrointestinal Conditions Simulated In Vitro

    Directory of Open Access Journals (Sweden)

    Karina C. Pacheco

    2010-01-01

    Full Text Available Problem statement: Lactobacillus delbrueckii subsp. bulgaricus is a lactic bacteria mostly used in the production of yoghurt and it has an important probiotic activity that brings benefits to the human body. However, the gastrointestinal tract has aggressive conditions, such as the acid pH in the stomach and the bile in the duodenum, that reduce the viability of this bacteria. Approach: In order to evaluate the effect of the human gastrointestinal conditions on Lactobacillus delbrueckiis viability, a simulated in vitro gastrointestinal system was designed, which consisted of two reactors where stomach and human small intestine conditions were simulated. Results: Lactobacillus delbrueckii cells were treated in human gastric conditions simulated in vitro (gastric juice adjusted to pH 2, 37°C, 90 min and 50 rpm and in intestinal conditions simulated in vitro (pancreatic juice adjusted to pH 6.8, 37°C, 150 min and 50 rpm and in presence of a sample of food or beverages. A sample of typical Mexican food was added and at the end of the treatment 73% of the cells remained viable. This means 36.5 times more viability with respect to the cells treated under the same conditions in presence of a sample of milk with 8% starch. At the end of the treatment, the viability of cells treated in simulated in vitro gastrointestinal juices without sample of food or beverage (blank was 1%. Conclusion: The results indicated that the in vitro simulated human gastrointestinal conditions were aggressive to the Lactobacillus delbrueckiis viability. To minimize this negative effect it is suggested that probiotics be consumed with some food because this could increase the probability that the bacteria reach the human colon in a large number and carry out their probiotic effect.

  19. Analyzing global gene expression of Lactobacillus plantarum in the human gastrointestinal tract

    NARCIS (Netherlands)

    Vries, de M.C.

    2006-01-01

    The human gastrointestinal (GI)-tract represents a dynamic ecosystem comprising various habitats each with niche-specific microbial communites, collectively called microbiota. Lactic acid bacteria (LAB) are considered to be a large group of the microbiota in the upper GI-tract that is involved in he

  20. Behaviour of silver nanoparticles and silver ions in an in vitro human gastrointestinal digestion model

    NARCIS (Netherlands)

    Walczak, A.P.; Fokkink, R.G.; Peters, R.J.B.; Tromp, P.; Herrera Rivera, Z.E.; Rietjens, I.M.C.M.; Hendriksen, P.J.M.; Bouwmeester, H.

    2013-01-01

    Oral ingestion is an important exposure route for silver nanoparticles (AgNPs), but their fate during gastrointestinal digestion is unknown. This was studied for 60 nm AgNPs and silver ions (AgNO3) using in vitro human digestion model. Samples after saliva, gastric and intestinal digestion were

  1. Measurement of Gastrointestinal and Colonic Motor Functions in Humans and Animals

    OpenAIRE

    Camilleri, Michael; Linden, David R

    2016-01-01

    Accurately measuring the complex motor behaviors of the gastrointestinal tract has tremendous value for the understanding, diagnosis and treatment of digestive diseases. This review synthesizes the literature regarding current tests that are used in both humans and animals. There remains further opportunity to enhance such tests, especially when such tests are able to provide value in both the preclinical and the clinical settings.

  2. Isolation of DNA from bacterial samples of the human gastrointestinal tract

    NARCIS (Netherlands)

    Zoetendal, E.G.; Heilig, G.H.J.; Klaassens, E.S.; Booijink, C.C.G.M.; Kleerebezem, M.; Smidt, H.; Vos, de W.M.

    2006-01-01

    The human gastrointestinal (GI) tract contains a complex microbial community that develops in time and space. The most widely used approaches to study microbial diversity and activity are all based on the analysis of nucleic acids, DNA, rRNA and mRNA. Here, we present a DNA isolation protocol that i

  3. Analyzing global gene expression of Lactobacillus plantarum in the human gastrointestinal tract

    NARCIS (Netherlands)

    Vries, de M.C.

    2006-01-01

    The human gastrointestinal (GI)-tract represents a dynamic ecosystem comprising various habitats each with niche-specific microbial communites, collectively called microbiota. Lactic acid bacteria (LAB) are considered to be a large group of the microbiota in the upper GI-tract that is involved in he

  4. Gastrointestinal Physiology During Head Down Tilt Bedrest in Human Subjects

    Science.gov (United States)

    Vaksman, Z.; Guthienz, J.; Putcha, L.

    2008-01-01

    Introduction: Gastrointestinal (GI) motility plays a key role in the physiology and function of the GI tract. It directly affects absorption of medications and nutrients taken by mouth, in addition to indirectly altering GI physiology by way of changes in the microfloral composition and biochemistry of the GI tract. Astronauts have reported nausea, loss of appetite and constipation during space flight all of which indicate a reduction in GI motility and function similar to the one seen in chronic bed rest patients. The purpose of this study is to determine GI motility and bacterial proliferation during -6 degree head down tilt bed rest (HTD). Methods: Healthy male and female subjects between the ages of 25-40 participated in a 60 day HTD study protocol. GI transit time (GITT) was determined using lactulose breath hydrogen test and bacterial overgrowth was measured using glucose breath hydrogen test. H. Pylori colonization was determined using C13-urea breath test (UBIT#). All three tests were conducted on 9 days before HDT, and repeated on HDT days 2, 28, 58, and again on day 7 after HDT. Results: GITT increased during HTD compared to the respective ambulatory control values; GITT was significantly lower on day 7 after HTD. A concomitant increase in bacterial colonization was also noticed during HDT starting after approximately 28 days of HDT. However, H. Pylori proliferation was not recorded during HDT as indicated by UBIT#. Conclusion: GITT significantly decreased during HDT with a concomitant increase in the proliferation of GI bacterial flora but not H. pylori.

  5. Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

    Directory of Open Access Journals (Sweden)

    Schachner Melitta

    2011-05-01

    Full Text Available Abstract Background L1 cell adhesion molecule (CD171 is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Methods Using a sensitive enzyme-linked immunosorbent assay (ELISA, soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Results Median levels of soluble L1 were significantly higher (p p Conclusion These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy.

  6. Malignant Peripheral Nerve Sheath Tumor in the Lesser Sac Masquerading as a Gastrointestinal Stromal Tumor of the Stomach: A Case Report

    Directory of Open Access Journals (Sweden)

    Yeo

    2016-09-01

    Full Text Available A malignant peripheral nerve sheath tumor (MPNST is very rare, representing 3 - 10% of all soft tissue sarcomas. Approximately half of all such tumors are diagnosed in patients with neurofibromatosis type 1 (NF1. The extremities are involved most commonly, and the patient’s age is usually 20 - 50 years. Herein, we present a case of an MPNST that developed sporadically in an unusual location and in an unusually younger patient. A 16-year-old girl presented with dyspepsia and abdominal distension. Computed tomography (CT demonstrated a well-defined mass approximately 12 cm in diameter in the lesser sac. The mass was composed principally of a heterogeneously enhancing solid portion and exhibited some cystic changes. Clinically and radiologically, the mass appeared to be a gastrointestinal stromal tumor of the stomach. The patient underwent exploratory laparotomy and mass excision. The surgical specimen revealed a solid firm mass measuring 13 × 13 × 6 cm. Histopathological and immunohistochemical analyses identified an MPNST. The patient underwent adjuvant chemotherapy but developed local recurrence with peritoneal seeding 8 months after surgery. Despite treatment with a different chemotherapeutic regimen, the disease progressed systemically and the patient died 3 years and 5 months after surgery. The uncommon tumor location and CT findings of our present MPNST case provide valuable information in terms of future clinical diagnoses of this rare but highly malignant disease.

  7. Extra-Gastrointestinal Stromal Tumor of Retroperitoneal Origin: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Hyung Sik; Park, Yul Ri; Choi, Hye Young [Dept. of Radiology, Gachon Medical Center, Gachon University of Medicine and Science, Incheon (Korea, Republic of)

    2012-03-15

    Extragastrointestinal stromal tumors (EGIST) are relatively rare, and cases originating in the retroperitoneum even rarer. We report a 60-year-old woman who presented with an EGIST originating in the retroperitoneum. Computed tomography results demonstrated a soft tissue mass on the right side of the retroperitoneum. The tumor abutted the duodenum, head of the pancreas, and right kidney. The mass was surgically proven to be a retroperitoneal tumor and histopathologically proven to be a retroperitoneal EGIST.

  8. Human milk glycobiome and its impact on the infant gastrointestinal microbiota

    OpenAIRE

    Zivkovic, Angela M.; German, J. Bruce; Lebrilla, Carlito B.; David A. Mills

    2010-01-01

    Human milk contains an unexpected abundance and diversity of complex oligosaccharides apparently indigestible by the developing infant and instead targeted to its cognate gastrointestinal microbiota. Recent advances in mass spectrometry-based tools have provided a view of the oligosaccharide structures produced in milk across stages of lactation and among human mothers. One postulated function for these oligosaccharides is to enrich a specific “healthy” microbiota containing bifidobacteria, a...

  9. Reversible sarcopenia in patients with gastrointestinal stromal tumor treated with imatinib

    OpenAIRE

    Moryoussef, Frédérick; Dhooge, Marion; Volet, Julien; Barbe, Coralie; Brezault, Catherine; Hoeffel, Christine; Coriat, Romain; Bouché, Olivier

    2015-01-01

    Background Imatinib is a long-term, oral, targeted therapy for high-risk resected and advanced gastrointestinal stromal tumours (GIST). It is known that sarcopenia affects prognosis and treatment tolerance in patients with various solid cancers. We analysed lumbar skeletal muscle index changes in imatinib-treated GIST patients. Imatinib tolerance was also assessed to evaluate the influence of pre-treatment sarcopenia. Methods Thirty-one patients with advanced (n = 16) or high-risk resected (n...

  10. Relevance of Bifidobacterium animalis subsp. lactis Plasminogen Binding Activity in the Human Gastrointestinal Microenvironment ▿

    Science.gov (United States)

    Candela, Marco; Turroni, Silvia; Centanni, Manuela; Fiori, Jessica; Bergmann, Simone; Hammerschmidt, Sven; Brigidi, Patrizia

    2011-01-01

    Human plasmin(ogen) is regarded as a component of the molecular cross talk between the probiotic species Bifidobacterium animalis subsp. lactis and the human host. However, up to now, only in vitro studies have been reported. Here, we demonstrate that the probiotic strain B. animalis subsp. lactis BI07 is capable of recruiting plasmin(ogen) present at physiological concentrations in crude extracts from human feces. Our results provide evidence that supports the significance of the B. lactis-plasmin(ogen) interaction in the human gastrointestinal tract. PMID:21821753

  11. Relevance of Bifidobacterium animalis subsp. lactis plasminogen binding activity in the human gastrointestinal microenvironment.

    Science.gov (United States)

    Candela, Marco; Turroni, Silvia; Centanni, Manuela; Fiori, Jessica; Bergmann, Simone; Hammerschmidt, Sven; Brigidi, Patrizia

    2011-10-01

    Human plasmin(ogen) is regarded as a component of the molecular cross talk between the probiotic species Bifidobacterium animalis subsp. lactis and the human host. However, up to now, only in vitro studies have been reported. Here, we demonstrate that the probiotic strain B. animalis subsp. lactis BI07 is capable of recruiting plasmin(ogen) present at physiological concentrations in crude extracts from human feces. Our results provide evidence that supports the significance of the B. lactis-plasmin(ogen) interaction in the human gastrointestinal tract.

  12. Notch receptors in human choroid plexus tumors.

    Science.gov (United States)

    Beschorner, R; Waidelich, J; Trautmann, K; Psaras, T; Schittenhelm, J

    2013-08-01

    Notch signaling plays a role in development and formation of the normal choroid plexus (nCP), and in formation of various tumors in humans. Activation of Notch3 has been reported to promote tumor growth in invasive gliomas and to initiate formation of choroid plexus tumors (CPT) in mice. We investigated the expression of all currently known Notch receptors (Notch 1-4) in 55 samples of nCP and 88 CPT, including 61 choroid plexus papillomas (CPP), 22 atypical CPP and 5 choroid plexus carcinomas by immunohistochemistry. Notch expression was semiquantitatively evaluated separately for membranous/cytoplasmic and for nuclear staining. In addition, we examined Her2 expression (EGFR2, Her2/neu, ErbB2, CD340) because of its functional link to Notch signaling. All samples were negative for Notch3. Membranous/cytoplasmic expression of Notch1 (pnCP compared to CPT. Nuclear expression of Notch1, -2 and -4 was significantly higher in CPT compared to nCP (pnCP to a predominant nuclear expression in CPT. Her2 was weakly expressed in 42/84 CPT but only in 2/53 nCP (p=0.0001) and positively correlated with nuclear expression of Notch1, -2 and 4 in CPT. In summary, a shift between membranous/cytoplasmic (non-canonical signaling pathway) and nuclear expression (canonical signaling pathway) of Notch1, -2 and -4 and upregulation of Her2 indicate neoplastic transformation in human CP and may reveal new therapeutic approaches.

  13. Integrated and Quantitative Proteomics of Human Tumors.

    Science.gov (United States)

    Yakkioui, Y; Temel, Y; Chevet, E; Negroni, L

    2017-01-01

    Quantitative proteomics represents a powerful approach for the comprehensive analysis of proteins expressed under defined conditions. These properties have been used to investigate the proteome of disease states, including cancer. It has become a major subject of studies to apply proteomics for biomarker and therapeutic target identification. In the last decades, technical advances in mass spectrometry have increased the capacity of protein identification and quantification. Moreover, the analysis of posttranslational modification (PTM), especially phosphorylation, has allowed large-scale identification of biological mechanisms. Even so, increasing evidence indicates that global protein quantification is often insufficient for the explanation of biology and has shown to pose challenges in identifying new and robust biomarkers. As a consequence, to improve the accuracy of the discoveries made using proteomics in human tumors, it is necessary to combine (i) robust and reproducible methods for sample preparation allowing statistical comparison, (ii) PTM analyses in addition to global proteomics for additional levels of knowledge, and (iii) use of bioinformatics for decrypting protein list. Herein, we present technical specificities for samples preparation involving isobaric tag labeling, TiO2-based phosphopeptides enrichment and hydrazyde-based glycopeptides purification as well as the key points for the quantitative analysis and interpretation of the protein lists. The method is based on our experience with tumors analysis derived from hepatocellular carcinoma, chondrosarcoma, human embryonic intervertebral disk, and chordoma experiments.

  14. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors.

    Science.gov (United States)

    Agaram, Narasimhan P; Wong, Grace C; Guo, Tianhua; Maki, Robert G; Singer, Samuel; Dematteo, Ronald P; Besmer, Peter; Antonescu, Cristina R

    2008-10-01

    BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis. Alterations in RAS/MEK/ERK pathway may also be involved in development of imatinib resistance in GIST, particularly in tumors lacking secondary KIT or PDGFRA mutations. Imatinib-naive wild-type GISTs from 61 patients, including 15 children and 28 imatinib-resistant tumors without secondary KIT mutations were analyzed. Screening for hot spots mutations in BRAF (exons 11 and 15) and NRAS (exons 2 and 3) was performed. A BRAF exon 15 V600E was identified in 3 of 61 GIST patients, who shared similar clinical features, being 49- to 55-years-old females and having their tumors located in the small bowel. The tumors were strongly KIT immunoreactive and had a high risk of malignancy. An identical V600E BRAF mutation was also identified in one of 28 imatinib resistant GIST lacking a defined mechanism of drug resistance. In conclusion, we identified a primary BRAF V600E mutations in 7% of adult GIST patients, lacking KIT/PDGFRA mutations. The BRAF-mutated GISTs show predilection for small bowel location and high risk of malignancy. A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.

  15. Comparison of Different Risk Classification Systems in 558 Patients with Gastrointestinal Stromal Tumors after R0-Resection

    Science.gov (United States)

    Schmieder, Michael; Henne-Bruns, Doris; Mayer, Benjamin; Knippschild, Uwe; Rolke, Claudia; Schwab, Matthias; Kramer, Klaus

    2016-01-01

    Background: Due to adjuvant treatment concepts for patients with R0-resected gastrointestinal stromal tumors (GIST), a reproducible and reliable risk classification system proved of utmost importance for optimal treatment of patients and prediction of prognosis. The aim of this study was to reevaluate the impact of five widely-applied and well-established GIST risk classification systems (i.e., scores by Fletcher, Miettinen, Huang, Joensuu, and TNM classification) on a series of 558 GIST patients with long-term follow-up after R0 resection. Methods: Tumor size, mitotic count and site were used in variable combination to predict high- and low risk patients by the use of the five risk classification models. For survival analyses disease-specific survival, disease-free survival and overall-survival were investigated. Patients with initial metastatic disease or incompletely resectable tumors were excluded. Results: All GIST classification models distinguished well between patients with high-risk and low-risk tumors and none of the five risk systems was superior to predict patient outcome. The models showed significant heterogeneity. There was no significant difference between the different risk-groups regarding overall-survival. Subdivision of GIST patients with very low- and low-risk appeared to be negligible. Conclusions: Currently applied GIST risk classification systems are comparable to predict high- or low-risk patients with initial non-metastatic and completely resected GIST. However, the heterogeneity of the high-risk group and the absence of differences in overall survival indicate the need for more precise tumor- and patient-related criteria for better stratification of GIST and identification of patients who would benefit best from adjuvant tyrosine kinase inhibitor therapy. PMID:28082898

  16. Imatinib mesylate induces responses in patients with liver metastases from gastrointestinal stromal tumor failing intra-arterial hepatic chemotherapy

    Directory of Open Access Journals (Sweden)

    Fiorentini Giammaria

    2006-01-01

    Full Text Available Background: Imatinib mesylate represents a real major paradigm shift in cancer therapy, targeting the specific molecular abnormalities, crucial in the etiology of tumor. Intra-arterial hepatic chemotherapy (IAHC followed by embolization, has been considered an interesting palliative option for patients with liver metastases from gastrointestinal stromal tumor (GIST, due to the typically hypervascular pattern of the tumor. Aims: We report our experience with IAHC followed by Imatinib mesylate, in order to show the superiority of the specific molecular approach in liver metastases from GIST. Materials and Methods: Three patients (pts with pretreated massive liver metastases from GIST, received IAHC with Epirubicin 50 mg/mq, every 3 weeks for 6 cycles. At the evidence of progression, they received Imatinib mesylate. Results: We observed progressive diseases in all cases. In 1998, one patient underwent Thalidomide at 150 mg orally, every day for 4 months, with evidence of stable disease and clinical improvement. In 2001, two patients received Imatinib mesylate at 400 mg orally, every day, with evidence of partial response lasting 18+ months and 16 months. One of them had grade 3 neutropenia, with suspension of therapy for 3 weeks. Conclusion: No patient treated with IAHC, reported objective responses, but two of them obtained partial response after the assumption of Imatinib mesylate and one showed temporary stabilization with thalidomide. Imatinib mesylate represents a new opportunity in GIST therapy, targeting the specific molecular alteration. It seems to be superior to conventional intra arterial hepatic chemotherapy.

  17. Development of nano radiopharmaceutical based on Bevacizumab labelled with Technetium-99m for early diagnosis of gastrointestinal stromal tumor; Desenvolvimento de nanorradiofarmaco a base de Bevacizumabe marcado com tecnecio-99m para diagnostico precoce do tumor estromal gastrointestinal

    Energy Technology Data Exchange (ETDEWEB)

    Braga, Thais Ligiero

    2015-06-01

    The development of new radiopharmaceuticals is an essential activity to improve nuclear medicine, and essential for the early and effective diagnosis of oncological diseases. Among the various possibilities current research in the world, the radiopharmaceuticals to chemotherapeutic base may be the most effective in detecting tumors, particularly Gastrointestinal Stromal Tumor (GIST), the Metastatic Renal Cell Carcinoma and neuroendocrine pancreatic tumors. However, difficulties in directing, as well as adhesion of the radiopharmaceutical in the desired location, are currently the main problems in the early detection and treatment of some of these tumors. Advances in the field of nanotechnology, particularly in recent years, indicate significant contribution to overcoming these obstacles, particularly in the implementation of molecular barriers as well as the functionalization of the nanoparticles, thereby improving targeting by the use of surface nucleotides, and the increased adhesion, which facilitates the release of the drug and therefore increases the chances of early diagnosis and more effective treatment. This study aimed to the production, characterization and evaluation of cytotoxicity, as well as in vivo biodistribution test Bevacizumab nanoparticles labeled with Technetium-99m radionuclide for detection of type GIST tumors. Bevacizumab was encapsulated in the form of nanoparticles by the emulsification method using double poly-acetic acid and polyvinyl alcohol polymers (PLA / PVA) at a concentration of 2% of the monoclonal antibody. The characterization of the nanoparticles was performed by the technique of scanning electron microscopy (SEM). The cytotoxicity assessment was performed by XTT assay with various cell lines of solid tumor cells. The labeling with technetium-99m was done by the direct method, and its yield determined by paper chromatography using paper Whatmam 1 as the stationary phase and acetone as mobile phase. In the biodistribution study

  18. Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors

    Directory of Open Access Journals (Sweden)

    Gennadiy Bondarenko

    2015-09-01

    Full Text Available Patient-derived xenograft (PDX tumor models have emerged as a new approach to evaluate the effects of cancer drugs on patients’ personalized tumor grafts enabling to select the best treatment for the cancer patient and providing a new tool for oncology drug developers. Here, we report that human tumors engrafted in immunodeficient mice are susceptible to formation of B-and T-cell PDX tumors. We xenografted human primary and metastatic tumor samples into immunodeficient mice and found that a fraction of PDX tumors generated from patients’ samples of breast, colon, pancreatic, bladder and renal cancer were histologically similar to lymphocytic neoplasms. Moreover, we found that the first passage of breast and pancreatic cancer PDX tumors after initial transplantation of the tumor pieces from the same human tumor graft could grow as a lymphocytic tumor in one mouse and as an adenocarcinoma in another mouse. Whereas subcutaneous PDX tumors resembling human adenocarcinoma histology were slow growing and non-metastatic, we found that subcutaneous PDX lymphocytic tumors were fast growing and formed large metastatic lesions in mouse lymph nodes, liver, lungs, and spleen. PDX lymphocytic tumors were comprised of B-cells which were Epstein-Barr virus positive and expressed CD45 and CD20. Because B-cells are typically present in malignant solid tumors, formation of B-cell tumor may evolve in a wide range of PDX tumor models. Although PDX tumor models show great promise in the development of personalized therapy for cancer patients, our results suggest that confidence in any given PDX tumor model requires careful screening of lymphocytic markers.

  19. Partial response to imatinib treatment in a patient with unresectable gastrointestinal stromal tumor: A case report and mini literature review

    Science.gov (United States)

    Wu, Xiaolong; Feng, Libo; Liu, Qing; Xia, Dong; Xu, Liang

    2016-01-01

    The aim of the present study was to evaluate the efficacy and safety of imatinib mesylate in unresectable gastrointestinal stromal tumor (GIST) and to discuss its therapeutic regimen. A patient with unresectable GIST is described, and several key clinical studies are reviewed, including the clinical trials B2222 and S0033, which contain recently reported results of the long-term clinical outcome of imatinib in patients with unresectable or metastatic GIST. The recent results of the two studies demonstrate the long-term efficacy and safety of imatinib for unresectable or metastatic GIST. A positive response to imatinib treatment was observed in the present patient, which is consistent with the data of the B2222 and S0033 trials. However, further long-term, large-scale, multicenter and controlled trials are required to determine the relative efficacy of combining imatinib agents with surgical procedures or administering imatinib alone. PMID:27698727

  20. Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate

    Institute of Scientific and Technical Information of China (English)

    Seiji Suzuki; Shotaro Maeda; Takashi Tajiri; Koji Sasajima; Masayuki Miyamoto; Hidehiro Watanabe; Tadashi Yokoyama; Hiroshi Maruyama; Takeshi Matsutani; Aimin Liu; Masaru Hosone

    2008-01-01

    A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor (GIST). Computed tomography (CT) and magnetic resonance imaging (MRI) 107 mo after the operation, revealed a cystic mass (14 cm in diameter) and a solid mass (9 cm in diameter) in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate (IM) treatment, 400mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy (S4+S5). The effect of IM on the metastatic lesions was interpreted as pathologic complete response (CR). Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

  1. Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors.

    Science.gov (United States)

    Pusceddu, Sara; Prinzi, Natalie; Lo Russo, Giuseppe; Femia, Daniela; Milione, Massimo; Perrone, Federica; Tamborini, Elena; Concas, Laura; Pulice, Iolanda; Vernieri, Claudio; Corti, Francesca; Buzzoni, Roberto; de Braud, Filippo

    2017-08-01

    Metformin (MET) has recently emerged as a potentially active agent in cancer prevention and treatment. MET is thought to exert its antitumor effects either via modification of systemic metabolism or through cell-autonomous effects (e.g., activation of AMPK and inhibition of the mTOR pathway). Preliminary findings of the PRIME-NET study suggest that the addition of MET to treatment with everolimus (EVE) and/or somatostatin analogs (SSAs) can provide clinical benefit in diabetic neuroendocrine tumor (NET) patients. In light of this and other retrospective evidence of MET's anticancer activity in NETs, prospective studies are needed. A pilot, single-arm, open-label, prospective study (MetNET-2 trial, NCT02823691) was designed to evaluate the safety of MET in combination with lanreotide in well-differentiated gastrointestinal (WD GI) and lung NETs.

  2. Reduced Expression of PTEN Protein and Its Prognostic Significance in the Gastrointestinal Stromal Tumor

    Institute of Scientific and Technical Information of China (English)

    张永红; 于冬冬; 李小兰; 胡俊波; 龚建平

    2010-01-01

    Little is reported about the role of PTEN gene in the progression and prognosis of GISTs.This study examined the clinical implications of the tumor suppressor gene PTEN as a prognostic factor in the GISTs.Immunohistological staining and immunoblotting were employed to examine the PTEN protein expression,and its association with clinical measures.Clinicopathological features were reviewed by a retrospective examination of medical records.Reduced PTEN expression was significantly associated with tumor diamete...

  3. Small bowel Gastrointestinal Stromal Tumors can physiologically alter gut motility before causing mechanical obstruction

    OpenAIRE

    Kothari, Manish S; Kosmoliaptsis, Vasilis; Meyrick-Thomas, John

    2005-01-01

    Background Gastro Intestinal Stromal Tumors (GISTs) are rare stromal neoplasms that represent the most common mesenchymal tumor of the G.I. tract, accounting for 5% of all sarcomas [1,2]. Originating from interstitial cells of Cajal, which are regulators of gut peristalsis, they are preferentially located in the stomach and the small intestine [3] and clinical presentation is variable, ranging from vague complaints to major G.I. bleeding. Surgical resection is the mainstay of treatment for pa...

  4. The effect of selected factors on the survival of Bacillus cereus in the human gastrointestinal tract.

    Science.gov (United States)

    Berthold-Pluta, Anna; Pluta, Antoni; Garbowska, Monika

    2015-05-01

    Bacillus cereus is a Gram-positive bacterium widely distributed in soil and vegetation. This bacterial species can also contaminate raw or processed foods. Pathogenic B. cereus strains can cause a range of infections in humans, as well as food poisoning of an emetic (intoxication) or diarrheal type (toxico-infection). Toxico-infections are due to the action of the Hbl toxin, Nhe toxin, and cytotoxin K produced by the microorganism in the gastrointestinal tract. This occurs once the spores or vegetative B. cereus cells survive the pH barrier of the stomach and reach the small intestine where they produce toxins in sufficient amounts. This article discusses the effect of various factors on the survival of B. cereus in the gastrointestinal tract, including low pH and the presence of digestive enzymes in the stomach, bile salts in the small intestine, and indigenous microflora in the lower parts of the gastrointestinal tract. Additional aspects also reported to affect B. cereus survival and virulence in the gastrointestinal tract include the interaction of the spores and vegetative cells with enterocytes. In vitro studies revealed that both vegetative B. cereus and spores can survive in the gastrointestinal tract suggesting that the biological form of the microorganism may have less influence on the occurrence of the symptoms of infection than was once believed. It is most likely the interaction between the pathogen and enterocytes that is necessary for the diarrheal form of B. cereus food poisoning to develop. The adhesion of B. cereus to the intestinal epithelium allows the bacterium to grow and produce enterotoxins in the proximity of the epithelium. Recent studies suggest that the human intestinal microbiota inhibits the growth of vegetative B. cereus cells considerably.

  5. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    Science.gov (United States)

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Gastrointestinal stem cells in health and disease: from flies to humans

    Directory of Open Access Journals (Sweden)

    Hongjie Li

    2016-05-01

    Full Text Available The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions.

  7. Gastrointestinal stem cells in health and disease: from flies to humans

    Science.gov (United States)

    Li, Hongjie; Jasper, Heinrich

    2016-01-01

    ABSTRACT The gastrointestinal tract of complex metazoans is highly compartmentalized. It is lined by a series of specialized epithelia that are regenerated by specific populations of stem cells. To maintain tissue homeostasis, the proliferative activity of stem and/or progenitor cells has to be carefully controlled and coordinated with regionally distinct programs of differentiation. Metaplasias and dysplasias, precancerous lesions that commonly occur in the human gastrointestinal tract, are often associated with the aberrant proliferation and differentiation of stem and/or progenitor cells. The increasingly sophisticated characterization of stem cells in the gastrointestinal tract of mammals and of the fruit fly Drosophila has provided important new insights into these processes and into the mechanisms that drive epithelial dysfunction. In this Review, we discuss recent advances in our understanding of the establishment, maintenance and regulation of diverse intestinal stem cell lineages in the gastrointestinal tract of Drosophila and mice. We also discuss the field's current understanding of the pathogenesis of epithelial dysfunctions. PMID:27112333

  8. Identification and localization of soluble sulfotransferases in the human gastrointestinal tract

    OpenAIRE

    Teubner, Wera; Meinl, Walter; Florian, Simone; Kretzschmar, Michael; Glatt, Hansruedi

    2007-01-01

    Abstract Soluble sulfotransferases (SULTs) are important in the regulation of messenger molecules and the elimination of xenobiotics. However, sulfo-conjugation of various substrates can also lead to the formation of reactive metabolites that may induce cancer and cause other damage. Our aim was to identify the SULT forms expressed in the human gastrointestinal tract, especially colon and rectum (common sites for cancer) and to determine their cellular localization. Normal colonic ...

  9. Clinical Analysis of 31 Gastrointestinal Stromal Tumors Cases%31例胃肠间质瘤临床分析

    Institute of Scientific and Technical Information of China (English)

    王巨義; 辛芝; 孔棣

    2014-01-01

    目的:探讨胃肠间质瘤的诊断及治疗特点。方法:回顾性分析31例胃肠间质瘤患者的临床病理结果及治疗方法。31例患者全部行手术治疗,术后行病理及免疫组织化学诊断,中高危险度患者予以伊马替尼治疗。结果:31例中24例为胃间质瘤,7例为小肠间质瘤,其中CD117阳性28例,CD34阳性26例,S-100阳性表达6例,SMA阳性表达7例。根据Fletcher分级,极低度危险组7例,低度危险组14例,中度危险组4例,高度危险组6例。2例中高危险度患者未规律服药出现复发及转移。结论:胃肠间质瘤确诊需行临床病理及免疫组化检查,主要病理学依据为CD117,外科手术是首选治疗。CD34 was positive in twenty six cases,S-100 was positive in six cases,SMA was positive in seven cases. Accord-ing to Fletcher risk classification,the patients of extremely-low risk,low risk,intermediate risk,and high risk were seven cases,fourteen cases,four cases,and six cases respectively. Ten cases(four cases in intermediate risk, and six cases in high risk )were treated with imatinib after surgical resection. Two cases in intermediate risk and high risk were found to present local recurrences and metastasis because of irregular imatinib treatment. Conclusion The final diagnosis of gastrointestinal stromal tumors can be based on postoperative pathology and immunohistochemistry detection, mainly depended on CD117. Surgical resection is the preferred treatment.%Objective To explore the clinical characteristics of diagnosis and therapeutic strategies of gas-trointestinal stromal tumors (GIST). Methods Thirty one patients with GIST were retrospectively analyzed, in-cluding the clinical manifestations ,diagnosis and treatment. All patients undertook surgery and the final diagno-sis was based on postoperative pathology and immunohistochemistry. The patinets in intermediate risk and high risk were treated with imatinib

  10. Campylobacter hominis sp nov., from the human gastrointestinal tract

    DEFF Research Database (Denmark)

    Lawson, A.J.; On, Stephen L.W.; Logan, J.M.J.

    2001-01-01

    Sequences of 16S rDNA of a novel campylobacter from faeces of healthy humans were previously shown to originate from a new taxon, 'Candidatus Campylobacter hominis', which could not be cultured. Since phylogenetic analysis suggested that anaerobic conditions might be required for growth......, an isolation strategy was developed employing initial non-selective membrane filtration onto fastidious anaerobe agar. Campylobacters were then isolated from the resulting mixed microbial flora by a dilution strategy and/or by immunomagnetic separation with genus-specific polyclonal antibody. Isolates were...... identified by a genus and taxon-specific PCR assay, and 16S rDNA nucleotide sequence analysis was carried out. All isolates exhibited the typical Campylobacter characteristics of being non-fermentative, oxidase-positive, catalase-negative and Gram-negative. Unusually, however, they were straight rods lacking...

  11. Anticancer drug sensitivity by human tumor clonogenic assay.

    Directory of Open Access Journals (Sweden)

    Hiraki,Shunkichi

    1986-10-01

    Full Text Available The anticancer drug sensitivity of human cancers was tested by the human tumor clonogenic assay (HTCA. Of 152 human cancer specimens tested, 63 (41% formed more than 30 tumor cell colonies in control plates and could be used to evaluate the drug sensitivity of tumor cells. In 42 (93% of 45 clinical trials in 24 patients, a parallel correlation was observed between the in vitro anticancer drug sensitivity measured by the HTCA and the clinical response of tumors to anticancer drugs. These results suggest that the HTCA is a good technique for the in vitro test of the anticancer drug sensitivity of human cancers.

  12. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

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    Ilaria Turin

    2014-03-01

    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  13. Laparoscopic Versus Open Resection of Small Bowel Gastrointestinal Stromal Tumors: Systematic Review and Meta-Analysis

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    Ke Chen

    2017-01-01

    Conclusions: LAP for small bowel GISTs is a safe and feasible procedure with shorter operation time, less blood loss, less overall complications, and quicker recovery. Besides, tumor recurrence and the long-term survival rate are similar to open approach. Because of the limitations of this study, methodologically high-quality studies are needed for certain appraisal.

  14. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST after imatinib failure - one institution study

    Directory of Open Access Journals (Sweden)

    Rutkowski Piotr

    2012-03-01

    Full Text Available Abstract Background Gastrointestinal stromal tumors (GIST mutational status is recognized factor related to the results of tyrosine kinase inhibitors therapy such as imatinib (IM or sunitinib (SU. Arterial hypertension (AH is common adverse event related to SU, reported as predictive factor in renal cell carcinoma. The aim of the study was to analyze the outcomes and factors predicting results of SU therapy in inoperable/metastatic CD117(+ GIST patients after IM failure. Methods We identified 137 consecutive patients with advanced inoperable/metastatic GIST treated in one center with SU (2nd line treatment. Median follow-up time was 23 months. Additionally, in 39 patients there were analyzed selected constitutive single nucleotide polymorphisms (SNPs of VEGFA and VEGFR2 genes. Results One year progression-free survival (PFS; calculated from the start of SU rate was 42% and median PFS was 43 weeks. The estimated overall survival (OS, calculated both from start of SU or IM was 74 weeks and 51 months, respectively. One-year PFS was 65% (median 74 weeks in 55 patients with AH vs. 22% (median 17 weeks in patients without AH. Patients with primary tumors carrying mutations in KIT exon 9 or wild-type had substantially better 1-year PFS (68% and 57%; median 65.5 and 50.5 weeks, respectively than patients having tumors with KIT exon 11 or PDGFRA mutations (34% and 15%; median 36.8 and 9 weeks, respectively. We identified two independent factors with significant impact on PFS and OS in univariate and multivariate analysis: primary tumor genotype and presence of AH. The most common adverse events during therapy were: fatigue, AH, hypothyroidism, hand and foot syndrome, mucositis, skin reactions, dyspepsia, and diarrhea. Two deaths were assessed as related to tumor rupture caused by reaction to SU therapy. The presence of C-allele in rs833061 and the T-allele in rs3025039 polymorphism of VEGFA were associated with significantly higher risk of hypothyroidism

  15. The importance of molecular biology in development, prognosis, treatment and resistance to targeted therapy in gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    Alessandro Comandone

    2011-12-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the commonest mesenchymal tumors of the gastroenteric tract, and are generally believed to originate from the neoplastic transformation of the interstitial cells of Cajal, the pacemaker structures of the stomach and intestine. Exon and genetic mutations (point/deletions are fundamental for the development of GISTs: the constitutional characteristic of this neoplasm is the presence of the cell surface Kit receptor. Kit is the product of the proto-oncogene cKit, situated in chromosome 4. Ninety-eight percent of GISTs express mutated isoforms of Kit or of PDGFRA (Platelet growth factor receptor a. Kit mutation is the basic condition for autophosphorylation of tyrosine kinase residues in proteins. Autophosphorylation initiates pathogenetic processes in Cajal cells, toward a neoplastic transformation. Imatinib mesilate and, more recently, sunitinib are tyrosine kinase inhibitors, specific antagonists for Kit and PDGFRA, with good activity against GISTs. Most molecular and clinical data currently available concern imatinib. Exon mutations are strategic as prognostic and as predictive factors. In recent years, much evidence suggests that survival, response to therapy and resistance to imatinib are related to different mutations. In the near future, GIST patients will receive treatment differentiated by expressed Kit and PDGFRA mutations, thus truly individualized therapy.

  16. Predicting malignant potential of gastrointestinal stromal tumors: Role of p16 and E2F1 expression.

    Science.gov (United States)

    Tetikkurt, Umit Seza; Ozaydin, Ipek Yildiz; Ceylan, Sule; Gurbuz, Yesim; Erdogan, Nusret; Oz, Feriha

    2010-07-01

    Altered expression of cell cycle regulatory proteins in GISTs (gastrointestinal stromal tumors) may be the mechanism for their diversity in clinical behavior. The use of these tumorigenetic and cell proliferative proteins may provide an alternative route for follow-up and treatment. The aim of this study was to determine the prognostic relevance of the E2F1 and p16 expression in GISTs. Tissues from 21 cases with GIST were collected retrospectively. Tumor grade was designated according to the consensus system. Immunohistochemistry was done with antibodies against Ki-67, p16, E2F1. For statistical analysis, Ki-67 proliferation index was evaluated in 2 categories: 10%, whereas p16 expression was scored as negative or positive. E2F1 expression cutoff values were tested for risk group variables as >5% and >10%. Correlation between the presence of necrosis, Ki-67 proliferation index, p16, E2F1 expression and the risk grade was determined by Spearman correlation test. Sensitivity and specificity were determined by Fisher exact test with P p16 expression. Our results suggest that in addition to high Ki-67 proliferation index, high E2F1 expression may also be a useful predictive marker for malignant potential of GISTs.

  17. Spontaneous rupture of pedunculate gastric gastrointestinal stromal tumor into the gastrocelic ligament presenting as a stalked mass surrounded by loculated hematoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun Soo; Ahn, Sung Eun; Park, Seong Jin; Moon, Sung Kyoung; Lim, Joo Won; Lee, Dong Ho; Kim, Yong Ho [Kyung Hee University Medical Center, Kyung Hee University School of Medicine, Seoul (Korea, Republic of)

    2015-04-15

    Gastric gastrointestinal stromal tumor (GIST) is one of the most common mesenchymal tumors of the stomach, which may be asymptomatic or cause symptoms such as pain, gastrointestinal bleeding, and obstruction. Hemoperitoneum due to spontaneous rupture of the tumor is an extremely rare complication. We described a case of a 52-year-old man with a large pedunculated GIST causing loculated hematoma within the gastrocolic ligament. The patient visited our hospital due to a 3 week history of epigastric pain. A computed tomography scan revealed a 10.3 x 7.5 x 9.4 cm sized mass that was growing exophytically from the greater curvature of the stomach and was surrounded by loculated hematoma within the gastrocolic ligament. Laparotomy revealed a large stalked gastric mass surrounded by loculated hematoma within the gastrocolic ligament and blood fluid in the peritoneal cavity. Pathologic examination confirmed a GIST, of the high risk group.

  18. Early detection of response to imatinib therapy for gastrointestinal stromal tumor by using 18F-FDG-positron emission tomography and computed tomography imaging

    Institute of Scientific and Technical Information of China (English)

    Sabri Zincirkeser; Alper Sevinc; M Emin Kalender; Celalettin Camci

    2007-01-01

    A 41-year old female with metastatic gastrointestinal stromal tumor was referred to 18F-FDG-positron emission tomography and computed tomography (PET/CT) scan before and after one-month treatment with imatinib(Glivec(R), Gleevec(R), Novartis, Basel, Switzerland), a tyrosine kinase inhibitor (400 mg/d). Metabolic response was evaluated before and after one month of therapy. The decrease of the maximum standardised uptake value (SUV)was 79% (from 9.8 to 2.1). Positron emission tomography demonstrated complete metabolic response after one-month of imatinib treatment. Additionally, the previous lesion was compared with the coronal computerized tomographic image. There was no difference in the size of the tumor before and after therapy according to CT images. However, metabolic activity was inhibited.18F-FDG-PET is a valuable method for the detection of response to one-month imatinib treatment in patients with gastrointestinal stromal tumors.

  19. Technical success and short-term results of surgical treatment of gastrointestinal stromal tumors: an experience of three centers.

    Science.gov (United States)

    Gluzman, Mark Igorevich; Kashchenko, Victor Anatolevich; Karachun, Aleksei Mikhailovich; Orlova, Rashida Vakhidovna; Nakatis, Iakov Aleksandrovich; Pelipas, Iurii Vasilevich; Vasiukova, Evgenia Leonidovna; Rykov, Ivan Vladimirovich; Petrova, Veronika Vladimirovna; Nepomniashchaia, Svetlana Leonidovna; Klimov, Anton Sergeevich

    2017-01-01

    Gastrointestinal stromal tumors (GIST) comprise about 80% of gastrointestinal sarcomas. In patients with localized disease, surgery is considered as "Gold Standard" treatment. Organ-sparing radical en-block resection is widely accepted practice. Since lymph node dissection is not routinely indicated, minimally invasive approach is of particular interest. The aim of this study is to investigate the short-term outcomes of different surgical treatment of GISTs. We analyzed data of 116 patients who received surgical treatment for localized forms of GIST. Tumors were located in the stomach in 87 (75%) cases, in the small intestine in 26 (22.4%) cases, and extragastrointestinal GISTs were found in 3 (2.6%) patients. Four different approaches were used-open surgery (OpS, n=48), laparoscopic surgery (LS, n=40), endoscopic procedures (EP, n=22) and hybrid rendezvous (HR, n=6). Patient demographics, clinical presentation of tumors, characteristics of operation procedures (duration, intraoperative blood loss, frequency of R0-resection and fragmentation of tumor), postoperative complications and length of hospital stay were examined in all these groups. Radical treatment (R0-resection) was performed in all patients. There were no cases of tumor ruptures during surgical procedure. Mean size of GIST in OpS was 9.1±2.0 [2-35] cm; in LS: 4.9±0.8 (1.5-15) cm; in HR: 3.5±0.8 (2-4.5) cm and in EP: 2.3±0.3 (0.4-3.5) cm. Intraoperative blood loss in OpS was 369.7±209.5 [0-4,000] mL; LS: 63.9±16.0 [0-150] mL; in HR: 96.7±44.3 [50-200] mL; in EP: 33.3±11.0 [0-150] mL. Duration of operation in OpS was 160±20.4 [50-310] min; in LS: 104.7±12.7 [50-185]; in HR: 176.7±44.0 [110-260] min and in EP: 89.8±15.5 [25-190] min. Complication rate in OpS was 5 (10.4%); in LS: 3 (7.5%); in HR: 0% and in EP: 3 (13.6%). Length of hospital stay in OpS was 13.8±2.2 [7-52] days; in LS: 11, 4±2.2 [4-21] days; in HR: 11±3.2 [7-15] days and in EP: 11, 9±2.1 [5-22] days. There were no

  20. Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts.

    Directory of Open Access Journals (Sweden)

    Youichi Higuchi

    Full Text Available Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body.Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs and the subperitoneal layer (subperitoneal fibroblasts: SPFs. Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup.In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling.GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract.

  1. One-stage laparoscopic resection for a large gastric gastrointestinal stromal tumor and synchronous liver metastases following preoperative imatinib therapy: A case report.

    Science.gov (United States)

    Cao, Feng; Li, Jia; Li, Ang; Fang, Yu; Li, Fei

    2013-04-01

    Laparoscopic partial gastrectomy without lymph node dissection has been accepted worldwide for the treatment of small gastric gastrointestinal stromal tumors (GISTs). However, the role of laparoscopic surgery in the treatment of large gastric GISTs remains under debate due to the risk of tumor spillage or rupture of the tumor capsule leading to peritoneal seeding. To the best of our knowledge, one-stage laparoscopic resection for a large gastric GIST and synchronous liver metastases following preoperative imatinib therapy has not been previously reported. Here, we present our initial experience of this method of treatment.

  2. Extra-gastrointestinal Stromal Tumor :Clinical Characteristics,Diagnosis, Treatment, and Prognosis

    Institute of Scientific and Technical Information of China (English)

    赵善峰; 闫丙健; 周岩冰

    2015-01-01

    Objective:To explore the clinicopathological characteristics,treatment and prognosis of extrogastrointestinal stromal tumor(EGIST).Methods:In our study,Clinicopathological data of EGISTs from January 2010 to October 2014were systematically investigated.Pathology results were rechecked.Patients also were followed Up.Prognostic factors were evaluated using Cox proportional hazard models and univariate and multivariate with Log-rank test.Results:An amount of EGISTs cases were selected due to inclusion criteria,including 28males and 26Females,with age from 18 To78 years(median,58).Patients were follwed up.12cases were dead.The 1-,3-,5-year survival rates were 91%,75%,66%.Patients undergoing R0 resection had a better 5-year overall survival rate than those undergoing R1 resection(75%vs46%,P<0.05).For patients with high risk of recurrence after surgery,the 5-year overall survival rate was 62%and 40%respectively(P<0.05).Conclusions:Tumor size,mitotic count and tumor rupture affect the prognosis of patients after resection of primary EGISTs independently.Adjuvant imatinib can effectively improve the prognosis of the patients with high risk of recurrence,and the survival rate of patients after surgery.Surgical resection is the main treatment of EGIST,and R0 resection helps to prolong the survival time.

  3. Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors.

    Science.gov (United States)

    Cohen, Martin H; Farrell, Ann; Justice, Robert; Pazdur, Richard

    2009-02-01

    The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate (Gleevec; Novartis Pharmaceuticals, East Hanover, NJ) in patients with CD117(+) unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs). In addition, this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose. Two open-label, controlled, multicenter, intergroup, international, randomized phase III studies were submitted -- one conducted by the European Organization for Research and Treatment of Cancer (n = 946) and the other by the Southwest Oncology Group (n = 746). These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib. A combined analysis of the two studies was prospectively defined and agreed to by both groups. Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression. Objective responses were achieved in >50% of patients receiving either imatinib dose. The median progression-free survival time was approximately 20 months and the median overall survival (OS) time was approximately 49 months. In the combined analysis, 347 patients crossed over to 800 mg/day imatinib at the time of progression. The median OS time after crossover was 14.3 months. The most common adverse events (AEs) were fluid retention, nausea, fatigue, skin rash, gastrointestinal complaints, and myalgia. The most common laboratory abnormality was anemia. Most often the AEs were of mild-to-moderate severity. Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients.

  4. Molecular alterations and expression of succinate dehydrogenase complex in wild-type KIT/PDGFRA/BRAF gastrointestinal stromal tumors.

    Science.gov (United States)

    Celestino, Ricardo; Lima, Jorge; Faustino, Alexandra; Vinagre, João; Máximo, Valdemar; Gouveia, António; Soares, Paula; Lopes, José Manuel

    2013-05-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract, disclosing somatic KIT, PDGFRA and BRAF mutations. Loss of function of succinate dehydrogenase (SDH) complex is an alternative molecular mechanism in GISTs, namely in carriers of germline mutations of the SDH complex that develop Carney-Stratakis dyad characterized by multifocal GISTs and multicentric paragangliomas (PGLs). We studied a series of 25 apparently sporadic primary wild-type (WT) KIT/PDGFRA/BRAF GISTs occurring in patients without personal or familial history of PGLs, re-evaluated clinicopathological features and analyzed molecular alterations and immunohistochemistry expression of SDH complex. As control, we used a series of well characterized 49 KIT/PDGFRA/BRAF-mutated GISTs. SDHB expression was absent in 20% and SDHB germline mutations were detected in 12% of WT GISTs. Germline SDHB mutations were significantly associated to younger age at diagnosis. A significant reduction in SDHB expression in WT GISTs was found when compared with KIT/PDGFRA/BRAF-mutated GISTs. No significant differences were found when comparing DOG-1 and c-KIT expression in WT, SDHB-mutated and KIT/PDGFRA/BRAF-mutated GISTs. Our results confirm the occurrence of germline SDH genes mutations in isolated, apparently sporadic WT GISTs. WT KIT/PDGFRA/BRAF GISTs without SDHB or SDHA/SDHB expression may correspond to Carney-Stratakis dyad or Carney triad. Most importantly, the possibility of PGLs (Carney-Stratakis dyad) and/or pulmonary chondroma (Carney triad) should be addressed in these patients and their kindred.

  5. Human development index is associated with mortality-to-incidence ratios of gastrointestinal cancers.

    Science.gov (United States)

    Hu, Qi-Da; Zhang, Qi; Chen, Wei; Bai, Xue-Li; Liang, Ting-Bo

    2013-08-28

    To identify the role of human development in the incidence and mortality rates of gastrointestinal cancers worldwide. The age-standardized incidence and mortality rates for gastrointestinal cancers, including cancers of the esophagus, stomach, pancreas, liver, gallbladder, and colorectum, were obtained from the GLOBOCAN 2008 database and United States Cancer Statistics (USCS) report. The human development index (HDI) data were calculated according to the 2011 Human Development Report. We estimated the mortality-to-incidence ratios (MIRs) at the regional and national levels, and explored the association of the MIR with development levels as measured by the HDI using a modified "drug dose to inhibition response" model. Furthermore, countries were divided into four groups according to the HDI distribution, and the MIRs of the four HDI groups were compared by one-way ANOVA followed by the Tukey-Kramer post-hoc test. State-specific MIRs in the United States were predicted from the estimated HDI using the fitted non-linear model, and were compared with the actual MIRs calculated from data in the USCS report. The worldwide incidence and mortality rates of gastrointestinal cancers were as high as 39.4 and 54.9 cases per 100000 individuals, respectively. Linear and non-linear regression analyses revealed an inverse correlation between the MIR of gastrointestinal cancers and the HDI at the regional and national levels (β < 0; P = 0.0028 for regional level and < 0.0001 for national level, ANOVA). The MIR differed significantly among the four HDI areas (very high HDI, 0.620 ± 0.033; high HDI, 0.807 ± 0.018; medium HDI, 0.857 ± 0.021; low HDI, 0.953 ± 0.011; P < 0.001, one-way ANOVA). Prediction of the MIRs for individual United States states using best-fitted non-linear models showed little deviation from the actual MIRs in the United States. Except for 28 data points (9.93% of 282), the actual MIRs of all gastrointestinal cancers were mostly located in the prediction

  6. From reverse transcription to human brain tumors

    Directory of Open Access Journals (Sweden)

    Dmitrenko V. V.

    2013-05-01

    Full Text Available Reverse transcriptase from avian myeloblastosis virus (AMV was the subject of the study, from which the investi- gations of the Department of biosynthesis of nucleic acids were started. Production of AMV in grams quantities and isolation of AMV reverse transcriptase were established in the laboratory during the seventies of the past cen- tury and this initiated research on the cDNA synthesis, cloning and investigation of the structure and functions of the eukaryotic genes. Structures of salmon insulin and insulin-like growth factor (IGF family genes and their transcripts were determined during long-term investigations. Results of two modern techniques, microarray-ba- sed hybridization and SAGE, were used for the identification of the genes differentially expressed in astrocytic gliomas and human normal brain. Comparison of SAGE results on the genes overexpressed in glioblastoma with the results of microarray analysis revealed a limited number of common genes. 105 differentially expressed genes, common to both methods, can be included in the list of candidates for the molecular typing of glioblastoma. The first experiments on the classification of glioblastomas based on the data of the 20 genes expression were conducted by using of artificial neural network analysis. The results of these experiments showed that the expression profiles of these genes in 224 glioblastoma samples and 74 normal brain samples could be according to the Koho- nen’s maps. The CHI3L1 and CHI3L2 genes of chitinase-like cartilage protein were revealed among the most overexpressed genes in glioblastoma, which could have prognostic and diagnostic potential. Results of in vitro experiments demonstrated that both proteins, CHI3L1 and CHI3L2, may initiate the phosphorylation of ERK1/ ERK2 and AKT kinases leading to the activation of MAPK/ERK1/2 and PI3K/AKT signaling cascades in human embryonic kidney 293 cells, human glioblastoma U87MG, and U373 cells. The new human cell line

  7. DNA ploidy and c-Kit mutation in gastrointestinal stromal tumors

    Institute of Scientific and Technical Information of China (English)

    Ju Han Lee; Xianglan Zhang; Woon Yong Jung; Yang Seok Chae; Jong-Jae Park; Insun Kim

    2004-01-01

    AIM: To investigate the prognostic significance of c-Kit gene mutation and DNA ploidy in gastointestinal stromal tumors (GISTs).METHODS: A total of 55 cases of GISTs were studied for the expression of c-Kit by immunohistochemistry, and the c-Kit gene mutations in exons 9, 11, 13, and 17 were detected by polymerase chain reaction-single strand confirmation polymarphism (PCR-SSCP) and denaturing high performance liquid chromatography (D-HPLC)techniques. DNA ploidy was determined by flow cytometry.RESULTS: Of the 55 cases of GISTs, 53 cases (96.4%)expressed c-Kit protein. The c-Kit gene mutations of exons 11 and 9 were found in 30 (54.5%) and 7 cases (12.7%),respectively. No mutations were found in exons 13 and 17.DNA aneuploidy was seen in 10 cases (18.2%). The c-Kit mutation positive GISTs were larger in size than the negative GISTs. The aneuploidy tumors were statistically associated with large size, high mitotic counts, high risk groups, high cellularity and severe nuclear atypia, and epithelioid type.There was a tendency that c-Kit mutations were more frequently found in aneuploidy GISTs.CONCLUSION: DNA aneuploidy and c-Kit mutations can be considered as prognostic factors in GISTs.

  8. Synchronous Occurrence of Diffuse Large B-cell Lymphoma of the Duodenum and Gastrointestinal Stromal Tumor of the Ileum in a Patient with Immune Thrombocytopenic Purpura

    Science.gov (United States)

    Takahashi, Tohru; Maruyama, Yumiko; Saitoh, Mayuko; Itoh, Hideto; Yoshimoto, Mitsuru; Tsujisaki, Masayuki; Nakayama, Masato

    2016-01-01

    A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. 18F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor. Subsequently, the patient was treated with 2 more cycles of the chemotherapy. Eventually, thrombocytopenia completely resolved. PMID:27746431

  9. The immune landscape of human tumors

    Science.gov (United States)

    Bindea, Gabriela; Mlecnik, Bernhard; Angell, Helen K; Galon, Jérôme

    2014-01-01

    Understanding the spontaneous immune response of cancer patients is critical for the design of efficient anticancer immunotherapies. The power of integrative tumor immunology approaches allowed for a comprehensive view of the immune system evolution in the course of tumor progression and recurrence. We have demonstrated that tumor-infiltrating immune cells are spatiotemporally regulated, a finding that has profound implications for the development of efficient anticancer immunotherapies. PMID:24800163

  10. In Vitro Culture Conditions for Maintaining a Complex Population of Human Gastrointestinal Tract Microbiota

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    Bong-Soo Kim

    2011-01-01

    Full Text Available A stable intestinal microbiota is important in maintaining human physiology and health. Although there have been a number of studies using in vitro and in vivo approaches to determine the impact of diet and xenobiotics on intestinal microbiota, there is no consensus for the best in vitro culture conditions for growth of the human gastrointestinal microbiota. To investigate the dynamics and activities of intestinal microbiota, it is important for the culture conditions to support the growth of a wide range of intestinal bacteria and maintain a complex microbial community representative of the human gastrointestinal tract. Here, we compared the bacterial community in three culture media: brain heart infusion broth and high- and low-carbohydrate medium with different growth supplements. The bacterial community was analyzed using denaturing gradient gel electrophoresis (DGGE, pyrosequencing and real-time PCR. Based on the molecular analysis, this study indicated that the 3% fecal inoculum in low-concentration carbohydrate medium with 1% autoclaved fecal supernatant provided enhanced growth conditions to conduct in vitro studies representative of the human intestinal microbiota.

  11. Prevalence of upper gastrointestinal symptoms and their influence on nutritional state and performance status in patients with different primary tumors receiving palliative care.

    Science.gov (United States)

    Bovio, Giacomo; Fonte, Maria Luisa; Baiardi, Paola

    2014-02-01

    The aim of this study was to investigate the relationship between gastrointestinal symptoms, nutritional balance, and performance status in patients receiving palliative care for advanced cancers originating in different sites. We studied a total of 105 patients. Upper gastrointestinal symptoms, Eastern Cooperative Oncology Group Performance Status score (ECOG-PS), dietary intakes, anthropometric measures, and some serum proteins were determined. Unintentional weight loss, alterations in anthropometric measures, and highest number of symptoms were greater in patients with lung and stomach cancer. No differences were found in ECOG-PS according to cancer site. Patients with gastric or lung cancer have most evidence of protein-calorie malnutrition and a higher prevalence of upper gastrointestinal symptoms. The performance status is not affected by tumor site. Early nutritional support should be planned for all patients with cancer, especially for patients with gastric or lung cancer.

  12. Tissue-engineered models of human tumors for cancer research

    Science.gov (United States)

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  13. Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

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    Yingjen Jeffrey Wu

    2009-02-01

    Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

  14. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-10-15

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

  15. Stem cell factor-mediated wild-type KIT receptor activation is critical for gastrointestinal stromal tumor cell growth

    Institute of Scientific and Technical Information of China (English)

    Chen-Guang Bai; Xiao-Wei Hou; Feng Wang; Cen Qiu; Yan Zhu; Ling Huang; Jing Zhao

    2012-01-01

    AIM:To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth.METHODS:The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry,and the results were correlated with clinicopathological parameters,including the mitotic count,proliferative index (Ki-67 immunohistochemical staining),mitotic index (phospho-histone H3 immunohistochemical staining)and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling).Using primary cultured GIST cells,the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting,methyl thiazolyl tetrazolium (MTT),and apoptosis assays.RESULTS:We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples,respectively,and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis,including larger tumor size (P =0.0118),higher mitotic count (P =0.0058),higher proliferative index (P =0.0012),higher mitotic index (P =0.0282),lower apoptosis index (P =0.0484),and increased National Institutes of Health risk level (P =0.0012).We also found that the introduction of exogenous SCF potently increased KIT kinase activity,stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation,while a KIT immunoblocking antibody suppressed proliferation (P =0.01) and promoted apoptosis (P < 0.01)in cultured GIST cells.CONCLUSION:SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth.The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.

  16. Human papillomavirus and gastrointestinal cancer in Iranian population: A systematic review and meta-analysis.

    Science.gov (United States)

    Omrani-Navai, Versa; Alizadeh-Navaei, Reza; Yahyapour, Yousef; Hedayatizadeh-Omran, Akbar; Abediankenari, Saeid; Janbabaei, Ghasem; Toghani, Fatima

    2017-01-01

    Gastrointestinal (GI) malignancies are the most common cancers and account for nearly half of all cancer-related deaths in Iran. There was a strong association between human papillomavirus (HPV) infection and urogenital cancers, in particular the cervix. However, there is no clear causal relationship in all types of cancers, including gastrointestinal cancers. Therefore, the present study as a systematic review and meta-analysis was designed to evaluate the prevalence and relation of HPV in GI cancers. This systematic review and meta-analysis study assess the prevalence of human papillomavirus in GI cancers in Iran. Data were collected by searching electronic databases, including PubMed, Google Scholar, Scopus, SID and Iranmedex by English and Persian key words up to August 2016. Key words included: Human Papillomavirus, HPV, Cancer, Neoplasm, Carcinoma, Esophageal, colorectal, Gastrointestinal and Iran articles were entered in the EndNote software and duplicate papers were excluded. Data were extracted and analyzed by comprehensive meta-analysis software, Version 2 (CMA.V2) and random effects model. Finally, we included 17 studies in this meta-analysis. The prevalence of HPV in Iranian patients with GI cancers was 16.4% (CI95%: 10.4-24.9). Considering all HPV types, the odds ratio of GI cancers in positive patients was 3.03 (CI95%: 1.42-6.45) while in patients with HPV-16 was 3.62 (CI: 1.43-4.82). The results show a strong relationship between HPV infection especially high-risk HPV type 16 and GI cancers in Iranian population.

  17. Massive Intra-Abdominal Imatinib-Resistant Gastrointestinal Stromal Tumor in a 21-Year-Old Male

    Directory of Open Access Journals (Sweden)

    Ann Falor

    2013-01-01

    Full Text Available Gastrointestinal stromal tumors (GISTs in adolescence are far less common than adult GISTs and have varied GIST genotypes that present diagnostic and therapeutic challenges. Here, we discuss a 21-year-old male with diagnosis of unresectable, imatinib-resistant GIST. At initial evaluation, a neoadjuvant treatment approach was recommended. As such, the patient received imatinib over the course of one year. Unfortunately, the GIST increased in size, and a subsequent attempt at surgical resection was aborted fearing infiltration of major vascular structures. The patient was then referred to our institution, at which time imatinib therapy was discontinued. Surgical intervention was again considered and the patient underwent successful resection of massive intra-abdominal GIST with total gastrectomy and Roux-en-Y esophagojejunostomy. Since pediatric GISTs are typically resistant to imatinib, we performed genotype analysis of the operative specimen that revealed KIT mutations associated with imatinib sensitivity and resistance. Given the sequencing data and operative findings, the patient was started postoperatively on sunitinib. This case illustrates the importance of understanding both adult and pediatric GISTs when implementing appropriate treatment regimens. Since the genotype of GISTs dictates phenotypic behavior, mutational analysis is an important component of care especially for adolescents whose disease may mirror the pediatric or adult population.

  18. Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial

    Directory of Open Access Journals (Sweden)

    Mueller Joachim M

    2009-03-01

    Full Text Available Abstract Background The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe. Methods In the settings of a multicentre (three University Hospitals prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD or 0.25% povidone-iodine (control intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall level of IL-1beta in peritoneal fluid. Results Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36, the cancer-related death rate (17 vs. 19, p = .2, the local recurrence rate (7 vs. 12, p = .16, the distant metastasis rate (13 vs. 18, p = 0.2 as well as the time to relapse were not statistically significant different. Conclusion Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection. Trial registration ISRCTN66478538

  19. Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial

    Science.gov (United States)

    Braumann, Chris; Gutt, Carsten N; Scheele, Johannes; Menenakos, Charalambos; Willems, Wilhelm; Mueller, Joachim M; Jacobi, Christoph A

    2009-01-01

    Background The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe. Methods In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid. Results Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different. Conclusion Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection. Trial registration ISRCTN66478538 PMID:19309495

  20. Tuberculous and Non-Tuberculous Granulomatous Lymphadenitis in Patients Receiving ImatinibMesylate (Glivec for Metastatic Gastrointestinal Stromal Tumor

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    Abbas Agaimy

    2013-03-01

    Full Text Available Background: Imatinib mesylate (IM is the standard treatment for BCR-ABL-positive chronic myelogenous leukemia (CML and is the first-line adjuvant and palliative treatment for metastatic and inoperable gastrointestinal stromal tumor (GIST. IM is not known to be associated with an increased risk for development of granulomatous diseases. Methods: We describe our experience with 2 patients (42 and 62 years of age who developed granulomatous disease during IM treatment for metastatic GIST. Results: Mean duration of IM treatment was 12 (range 8-16 months. Enlarged lymph nodes with increased metabolism on FDG-PET-CT examination were detected and resected. Affected sites were supraclavicular (1 and subcarinal/mediastinal (1 lymph nodes. Histological examination revealed caseating and non-caseating granulomas suggestive of tuberculosis and sarcoidosis, respectively. Mycobacterium tuberculosis was detected by PCR in lymph nodes of 1 patient who was then successfully treated by anti-tuberculous agents. The other patient had negative sputum test for acid-fast bacilli and PCR-DNA-analysis was negative for M. tuberculosis and other mycobacteria. He received no anti-tuberculous therapy and had no evidence of progressive lymphadenopathy or new lung lesions during follow-up. Conclusion: Our observations underline the necessity to obtain biopsy material from enlarged or metabolically active lymph nodes developing during IM treatment for timely diagnosis and appropriate treatment of these rare complications. Follow-up without treatment is safe for patients without detectable microorganisms by sputum examination and PCR.

  1. Genes Expressed in Human Tumor Endothelium

    Science.gov (United States)

    St. Croix, Brad; Rago, Carlo; Velculescu, Victor; Traverso, Giovanni; Romans, Katharine E.; Montgomery, Elizabeth; Lal, Anita; Riggins, Gregory J.; Lengauer, Christoph; Vogelstein, Bert; Kinzler, Kenneth W.

    2000-08-01

    To gain a molecular understanding of tumor angiogenesis, we compared gene expression patterns of endothelial cells derived from blood vessels of normal and malignant colorectal tissues. Of over 170 transcripts predominantly expressed in the endothelium, 79 were differentially expressed, including 46 that were specifically elevated in tumor-associated endothelium. Several of these genes encode extracellular matrix proteins, but most are of unknown function. Most of these tumor endothelial markers were expressed in a wide range of tumor types, as well as in normal vessels associated with wound healing and corpus luteum formation. These studies demonstrate that tumor and normal endothelium are distinct at the molecular level, a finding that may have significant implications for the development of anti-angiogenic therapies.

  2. Horizontal gene transfer in the human gastrointestinal tract: potential spread of antibiotic resistance genes

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    Huddleston JR

    2014-06-01

    Full Text Available Jennifer R HuddlestonBiology Department, Abilene Christian University, Abilene, TX, USAAbstract: Bacterial infections are becoming increasingly difficult to treat due to widespread antibiotic resistance among pathogens. This review aims to give an overview of the major horizontal transfer mechanisms and their evolution and then demonstrate the human lower gastrointestinal tract as an environment in which horizontal gene transfer of resistance determinants occurs. Finally, implications for antibiotic usage and the development of resistant infections and persistence of antibiotic resistance genes in populations as a result of horizontal gene transfer in the large intestine will be discussed.Keywords: gut microbiome, conjugation, natural transformation, transduction

  3. Recombinant human erythropoietin alpha improves the efficacy of radiotherapy of a human tumor xenograft, affecting tumor cells and microvessels

    Energy Technology Data Exchange (ETDEWEB)

    Loevey, J. [Dept. of Radiotherapy, National Inst. of Oncology, Budapest (Hungary); Bereczky, B.; Gilly, R.; Kenessey, I.; Raso, E.; Simon, E.; Timar, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); Dobos, J. [Dept. of Tumor Progression, National Inst. of Oncology, Budapest (Hungary); National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Vago, A. [Central Lab., National Inst. of Oncology, Budapest (Hungary); Kasler, M. [Head and Neck Surgery, National Inst. of Oncology, Budapest (Hungary); Doeme, B. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); Tovari, J. [National Koranyi Inst. of TBC and Pulmonology, Budapest (Hungary); 1. Inst. of Pathology and Experimental Cancer Research, Semmelweis Univ., Budapest (Hungary)

    2008-01-15

    Background and purpose: tumor-induced anemia often occurs in cancer patients, and is corrected by recombinant human erythropoietins (rHuEPOs). Recent studies indicated that, besides erythroid progenitor cells, tumor and endothelial cells express erythropoietin receptor (EPOR) as well; therefore, rHuEPO may affect their functions. Here, the effect of rHuEPO{alpha} on irradiation in EPOR-positive human squamous cell carcinoma xenograft was tested. Material and methods: A431 tumor-bearing SCID mice were treated from the tumor implantation with rHuEPO{alpha} at human-equivalent dose. Xenografts were irradiated (5 Gy) on day 14, and the final tumor mass was measured on day 22. The systemic effects of rHuEPO{alpha} on the hemoglobin level, on tumor-associated blood vessels and on hypoxia-inducible factor-(HIF-)1{alpha} expression of the tumor xenografts were monitored. The proliferation, apoptosis and clonogenic capacity of A431 cancer cells treated with rHuEPO{alpha} and irradiation were also tested in vitro. Results: in vitro, rHuEPO{alpha} treatment alone did not modify the proliferation of EPOR-positive A431 tumor cells but enhanced the effect of irradiation on proliferation, apoptosis and clonogenic capacity. In vivo, rHuEPO{alpha} administration compensated the tumor-induced anemia in SCID mice and decreased tumoral HIF-1{alpha} expression but had no effect on tumor growth. At the same time rHuEPO{alpha} treatment significantly increased the efficacy of radiotherapy in vivo (tumor weight of 23.9 {+-} 4.7 mg and 34.9 {+-} 4.6 mg, respectively), mediated by increased tumoral blood vessel destruction. Conclusion: rHuEPO{alpha} treatment may modulate the efficacy of cancer radiotherapy not only by reducing systemic hypoxia and tumoral HIF-1{alpha} expression, but also by destroying tumoral vessels. (orig.)

  4. Human milk glycobiome and its impact on the infant gastrointestinal microbiota.

    Science.gov (United States)

    Zivkovic, Angela M; German, J Bruce; Lebrilla, Carlito B; Mills, David A

    2011-03-15

    Human milk contains an unexpected abundance and diversity of complex oligosaccharides apparently indigestible by the developing infant and instead targeted to its cognate gastrointestinal microbiota. Recent advances in mass spectrometry-based tools have provided a view of the oligosaccharide structures produced in milk across stages of lactation and among human mothers. One postulated function for these oligosaccharides is to enrich a specific "healthy" microbiota containing bifidobacteria, a genus commonly observed in the feces of breast-fed infants. Isolated culture studies indeed show selective growth of infant-borne bifidobacteria on milk oligosaccharides or core components therein. Parallel glycoprofiling documented that numerous Bifidobacterium longum subsp. infantis strains preferentially consume small mass oligosaccharides that are abundant early in the lactation cycle. Genome sequencing of numerous B. longum subsp. infantis strains shows a bias toward genes required to use mammalian-derived carbohydrates by comparison with adult-borne bifidobacteria. This intriguing strategy of mammalian lactation to selectively nourish genetically compatible bacteria in infants with a complex array of free oligosaccharides serves as a model of how to influence the human supraorganismal system, which includes the gastrointestinal microbiota.

  5. The fingerprint of the human gastrointestinal tract microbiota: a hypothesis of molecular mapping.

    Science.gov (United States)

    Tomasello, G; Mazzola, M; Jurjus, A; Cappello, F; Carini, F; Damiani, P; Gerges Geagea, A; Zeenny, M N; Leone, A

    2017-01-01

    The precise etiology of Inflammatory Bowel Disease (IDB) remains unclear and several factors are believed to play a role in its development and progression, including the composition of microbial communities resident in the gastrointestinal tract. Human intestinal microbiota are extensive with at least 15,000-36,000 bacterial species. However, thanks to the new development in sequencing and molecular taxonomic methodologies, our understanding of the microbiota population composition, dynamics, and ecology has greatly increased. Intestinal microbiota play a critical role in the maintenance of the host intestinal barrier homeostasis, while dysbiosis, which involves reduction in the microbiome diversity, can lead to progression of inflammatory disorders, such as IBD and colorectal cancer. It is hypothesized that fingerprinting characterization of the microbiota community composition is the first step in the study of this complex bacterial ecosystem and a crucial step in the targeted therapy. Molecular fingerprinting of human gastrointestinal tract microbiota could be performed by different techniques including the semi quantitation, 16SrRNA, the DNA- microarray as well as other relatively new methods which were developed to study many complex bacterial ecosystems. These techniques provide individual data and profiles, using fast and sensitive tools for the high taxonomic level fingerprint of the human intestinal microbiota and provide estimation of the relative presence of the microbial target groups within each individual. Such personalized information serves as a remarkable and unprecedented opportunity to improve targeted medical treatment and probably develop strategies to prevent disease.

  6. The use of BLT humanized mice to investigate the immune reconstitution of the gastrointestinal tract.

    Science.gov (United States)

    Wahl, Angela; Victor Garcia, J

    2014-08-01

    The gastrointestinal (GI) track represents an important battlefield where pathogens first try to gain entry into a host. It is also a universe where highly diverse and ever changing inhabitants co-exist in an exceptional equilibrium without parallel in any other organ system of the body. The gut as an organ has its own well-developed and fully functional immune organization that is similar and yet different in many important ways to the rest of the immune system. Both a compromised and an overactive immune system in the gut can have dire and severe consequences to human health. It has therefore been of great interest to develop animal models that recapitulate key aspects of the human condition to better understand the interplay of the host immune system with its friends and its foes. However, reconstitution of the GI tract in humanized mice has been difficult and highly variable in different systems. A better molecular understanding of the development of the gut immune system in mice has provided critical cues that have been recently used to develop novel humanized mouse models that fully recapitulate the genesis and key functions of the gut immune system of humans. Of particular interest is the presence of human gut-associated lymphoid tissue (GALT) aggregates in the gut of NOD/SCID BLT humanized mice that demonstrate the faithful development of bona fide human plasma cells capable of migrating to the lamina propria and producing human IgA1 and IgA2.

  7. Zoonotic gastrointestinal parasite burden of local dogs in Zaria, Northern Nigeria: Implications for human health

    Directory of Open Access Journals (Sweden)

    Christopher I. Ogbaje

    2015-10-01

    Full Text Available Background: Zoonotic gastrointestinal parasites of dogs are of the global problem particularly in the developing countries. Dogs are the most common pet animals worldwide and have been reported to be hosts of many intestinal parasites of zoonotic importance globally. In Nigeria, gastrointestinal helminthes of dogs is currently endemic in 20 of the 36 states. Aim: In general, dogs are the closest animals to humans and for that reason we decided to carry out a survey study to check the incidence of these parasites in dogs and to ascertain the level of environmental contamination in the study area. Materials and Methods: Fecal samples were collected from dog patients presented to small animal clinic of Veterinary Teaching Hospital of Faculty of Veterinary Medicine, Ahmadu Bello University Zaria, dog’s fecal droppings from the streets, and residential Quarters of the University and gastrointestinal tracts (GIT of dogs from dogs slaughtering house at Basawa Barrack, Zaria. Three methods were used in the analysis of the samples; simple flotation, sedimentation, and GIT processing methods within 48 h of collection. Results: Out of 224 samples analyzed 76(33.9% were positive of at least one of the parasites. Of the 101 samples from streets and residential quarters of ABU, Zaria, Isospora spp. 12(11.9% recorded the highest prevalence rate followed by Taenia spp. 6(5.9%, then Toxocara canis, Ancylostoma caninum, and Dipylidium caninum were 5.0%, 4.0%, and 1.0%, respectively. Isospora spp. (19.0% recorded the highest prevalence rate for the 100 samples collected from small animal clinic. Other parasites encountered were T. canis (8.0%, A. caninum (8.0% and Taenia spp. (5.0%. Parasites observed from the 23 gastrointestinal contents from “dog slaughtered houses” were T. canis (17.3%, Isospora spp.(13.1% and A. caninum (4.3. Conclusion: The study revealed that zoonotic gastrointestinal parasites of dogs are endemic in Zaria and the general public in the

  8. Surgical Management of Adolescents and Young Adults With Gastrointestinal Stromal Tumors: A US Population-Based Analysis.

    Science.gov (United States)

    Fero, Katherine E; Coe, Taylor M; Fanta, Paul T; Tang, Chih-Min; Murphy, James D; Sicklick, Jason K

    2017-05-01

    There is a dearth of population-based evidence regarding outcomes of the adolescent and young adult (AYA) population with gastrointestinal stromal tumors (GISTs). To describe a large cohort of AYA patients with GISTs and investigate the effect of surgery on GIST-specific survival (GSS) and overall survival (OS). This retrospective cohort study of 392 AYA patients and 5373 older adult (OA) patients in the Surveillance, Epidemiology, and End Results (SEER) database with GISTs histologically diagnosed from January 1, 2001, through December 31, 2013, with follow-up through December 31, 2015, compared the baseline characteristics of AYA (13-39 years old) and OA (≥40 years old) patients and among AYA patients stratified by operative management. Kaplan-Meier estimates were used for OS analyses. Cumulative incidence functions were used for GSS analysis. The effect of surgery on survival was evaluated with a multivariable Fine-Gray regression model. Tumor resection. GIST-specific survival and OS. This study included 392 AYA and 5373 OA patients diagnosed with GISTs (207 [52.8%] male AYA patients, 2767 [51.5%] male OA patients, 277 [70.7%] white AYA patients, and 3661 [68.1%] white OA patients). Compared with the OA patients, more AYA patients had small-intestine GISTs (139 [35.5%] vs 1465 [27.3%], P = .008) and were managed operatively (332 [84.7%] vs 4212 [78.4%], P = .003). Multivariable analysis of AYA patients found that nonoperative management was associated with a more than 2-fold increased risk of death from GISTs (subdistribution hazard ratio, 2.27; 95% CI, 1.21-2.25; P = .01). On subset analysis of 349 AYA patients with tumors of the stomach and small intestine, small-intestine location was associated with improved survival (OS: 91.1% vs 77.2%, P = .01; GSS: 91.8% vs 78.0%, P = .008). On subset analysis of 91 AYA patients with metastatic disease, operative management was associated with improved survival (OS: 69.5% vs 53.7%, P = .04; GSS

  9. Newcastle disease virus selectively kills human tumor cells.

    Science.gov (United States)

    Reichard, K W; Lorence, R M; Cascino, C J; Peeples, M E; Walter, R J; Fernando, M B; Reyes, H M; Greager, J A

    1992-05-01

    Newcastle disease virus (NDV), strain 73-T, has previously been shown to be cytolytic to mouse tumor cells. In this study, we have evaluated the ability of NDV to replicate in and kill human tumor cells in culture and in athymic mice. Plaque assays were used to determine the cytolytic activity of NDV on six human tumor cell lines, fibrosarcoma (HT1080), osteosarcoma (KHOS), cervical carcinoma (KB8-5-11), bladder carcinoma (HCV29T), neuroblastoma (IMR32), and Wilm's tumor (G104), and on nine different normal human fibroblast lines. NDV formed plaques on all tumor cells tested as well as on chick embryo cells (CEC), the native host for NDV. Plaques did not form on any of the normal fibroblast lines. To detect NDV replication, virus yield assays were performed which measured virus particles in infected cell culture supernatants. Virus yield increased 10,000-fold within 24 hr in tumor and CEC supernatants. Titers remained near zero in normal fibroblast supernatants. In vivo tumoricidal activity was evaluated in athymic nude Balb-c mice by subcutaneous injection of 9 x 10(6) tumor cells followed by intralesional injection of either live or heat-killed NDV (1.0 x 10(6) plaque forming units [PFU]), or medium. After live NDV treatment, tumor regression occurred in 10 out of 11 mice bearing KB8-5-11 tumors, 8 out of 8 with HT-1080 tumors, and 6 out of 7 with IMR-32 tumors. After treatment with heat-killed NDV no regression occurred (P less than 0.01, Fisher's exact test). Nontumor-bearing mice injected with 1.0 x 10(8) PFU of NDV remained healthy. These results indicate that NDV efficiently and selectively replicates in and kills tumor cells, but not normal cells, and that intralesional NDV causes complete tumor regression in athymic mice with a high therapeutic index.

  10. Metallothioneins in human tumors and potential roles in carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Cherian, M. George; Jayasurya, A.; Bay, Boon-Huat

    2003-12-10

    Metallothioneins (MT) are a group of low-molecular weight, cysteine rich intracellular proteins, which are encoded by a family of genes containing at least 10 functional isoforms in human. The expression and induction of these proteins have been associated with protection against DNA damage, oxidative stress and apoptosis. Moreover, MT may potentially activate certain transcriptional factors by donating zinc. Although MT is a cytosolic protein in resting cells, it can be translocated transiently to the cell nucleus during cell proliferation and differentiation. A number of studies have shown an increased expression of MT in various human tumors of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, salivary gland, testes, thyroid and urinary bladder. However, MT is down-regulated in certain tumors such as hepatocellular carcinoma and liver adenocarcinoma. Hence, the expression of MT is not universal to all human tumors, but may depend on the differentiation status and proliferative index of tumors, along with other tissue factors and gene mutations. In certain tumors such as germ cell carcinoma, the expression of MT is closely related to the tumor grade and proliferative activity. Increased expression of MT has also been observed in less differentiated tumors. Thus, expression of MT may be a potential prognostic marker for certain tumors. There are few reports on the expression of the different isoforms of MT which have been analyzed by specific gene probes. They reveal that certain isoforms are expressed in specific cell types. The factors which can influence MT induction in human tumors are not yet understood. Down-regulation of MT synthesis in hepatic tumors may be related to hypermethylation of the MT-promoter or mutation of other genes such as the p53 tumor suppressor gene. In vitro studies using human cancer cells suggest a possible role for p53 and the estrogen-receptor on the expression and induction of MT in epithelial neoplastic cells

  11. Successful Removal of a Metastatic Gastrointestinal Stromal Tumor in the Craniovertebral Junction using an Occipital Artery to Posterior Inferior Cerebellar Artery Bypass

    Directory of Open Access Journals (Sweden)

    Yukitomo Ishi

    2014-05-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are rare mesenchymal neoplasms arising from the gastrointestinal tract. The authors present a case of the successful removal of a metastatic GIST in the craniovertebral junction, using an occipital artery to posterior inferior cerebellar artery (OA-PICA bypass. The patient is a 54-year-old male who underwent his first surgery for a small-bowel tumor at the age of 45 and was diagnosed with GIST. Nine years after his primary diagnosis, the patient suffered from severe neck pain. MRI demonstrated a large demarcated mass adjacent to the right atlas. The right vertebral artery (VA, completely engulfed by the tumor, showed a narrowing and ended in the PICA. Poor collateral blood supply in the right PICA territory was presumed. To prevent ischemic complications, an OA-PICA bypass was performed prior to the tumor resection. After the OA-PICA bypass, the tumor associated with the right VA was successfully removed, and the patient was discharged without any neurological deficits.

  12. Human in vivo and in vitro studies on gastrointestinal absorption of titanium dioxide nanoparticles.

    Science.gov (United States)

    Jones, Kate; Morton, Jackie; Smith, Ian; Jurkschat, Kerstin; Harding, Anne-Helen; Evans, Gareth

    2015-03-04

    The study was designed to conduct human in vivo and in vitro studies on the gastrointestinal absorption of nanoparticles, using titanium dioxide as a model compound, and to compare nanoparticle behaviour with that of larger particles. A supplier's characterisation data may not fully describe a particle formulation. Most particles tested agreed with their supplied characterisation when assessed by particle number but significant proportions of 'nanoparticle formulations' were particles >100nm when assessed by particle weight. Oral doses are measured by weight and it is therefore important that the weight characterisation is taken into consideration. The human volunteer studies demonstrated that very little titanium dioxide is absorbed gastrointestinally after an oral challenge. There was no demonstrable difference in absorption for any of the three particle sizes tested. All tested formulations were shown to agglomerate in simulated gastric fluid, particularly in the smaller particle formulations. Further agglomeration was observed when dispersing formulations in polymeric or elemental foods. Virtually no translocation of titanium dioxide particles across the cell layer was demonstrated. This study found no evidence that nanoparticulate titanium dioxide is more likely to be absorbed in the gut than micron-sized particles.

  13. The Value of CT in Localizing Extra Gastrointestinal Stromal Tumors%CT定位诊断胃肠道外间质瘤的价值

    Institute of Scientific and Technical Information of China (English)

    罗小华; 宋彬; 董鹏; 庄雄杰; 吴秀蓉

    2012-01-01

    Objective To evaluate the value of CT in the localization diagnosis of extra gastrointestinal stromal tumors (EGIST). Methods The CT appearances of 13 patients with EGIST and 23 with exogenous GIST proved by surgery and pathology were analyzed retrospectively. Emphasis of image observation was focused on the following findings: the tumor location, size, shape,the presence of gas,ulcers,calcification and necrosis in masses,the state of neighboring gastrointestinal rmieosa,and the relation between the mass and the gastrointestinal vascular arch and its branches. Results Among the 13 cases with EGIST,the gas and intestinal mucosal damage was revealed in 1 case respectively. Vascular arch were showed between the masses and the gastrointestinal tract in 10 cases,and no stretching of vascular arch tributaries adjacent to the masses could be seen. Among the 23 cases with exogenous GIST, the gas, ulcers and gastrointestinal mucosal damage were found in 10,12 and 20 cases respectively. 17 cases showed the stretching of vascular arch tributaries adjacent to the masses, and no vascular arch and its tributaries could be visualized between the masses and the gastrointestinal tract. Their difference was significance(P<0. 05). Conclusion Based on the presence of gas, ulcers, gastrointestinal mucosal damage and the relation between the mass and the gastrointestinal vascular arch and its branches, it is possible to differentiate EGIST from exogenous GIST accurately.%目的 探讨CT定位诊断胃肠道外间质瘤(extra-gastrointestinal stromal tumors,EGIST)的价值.方法 回顾性分析13例经手术病理证实的EGIST患者的CT资料,重点观察病变的部位、大小、形态,病灶内有无气体、溃疡、钙化及坏死,邻近胃肠道黏膜有无破坏,以及病变与胃肠道血管弓及其属支血管的关系,并与23例经手术病理证实的外生性胃肠道间质瘤(gastrointestinal stromal tumors,GIST)对比.结果 13例EGIST患者中,发现

  14. Comparison of five in vitro digestion models to in vivo experimental results: Lead bioaccessibility in the human gastrointestinal tract

    NARCIS (Netherlands)

    Wiele, T.R. van de; Oomen, A.G.; Wragg, J.; Cave, M.; Minekus, M.; Hack, A.; Cornelis, C.; Rompelberg, C.J.M.; Zwart, L.L. de; Klinck, B.; Wijnen, J. van; Verstraete, W.; Sips, A.J.A.M.

    2007-01-01

    This paper presents a multi-laboratory comparison study of in vitro models assessing bioaccessibility of soil-bound lead in the human gastrointestinal tract under simulated fasted and fed conditions. Oral bioavailability data from a previous human in vivo study on the same soil served as a reference

  15. Comprehensive models of human primary and metastatic colorectal tumors in immunodeficient and immunocompetent mice by chemokine targeting.

    Science.gov (United States)

    Chen, Huanhuan Joyce; Sun, Jian; Huang, Zhiliang; Hou, Harry; Arcilla, Myra; Rakhilin, Nikolai; Joe, Daniel J; Choi, Jiahn; Gadamsetty, Poornima; Milsom, Jeff; Nandakumar, Govind; Longman, Randy; Zhou, Xi Kathy; Edwards, Robert; Chen, Jonlin; Chen, Kai Yuan; Bu, Pengcheng; Wang, Lihua; Xu, Yitian; Munroe, Robert; Abratte, Christian; Miller, Andrew D; Gümüş, Zeynep H; Shuler, Michael; Nishimura, Nozomi; Edelmann, Winfried; Shen, Xiling; Lipkin, Steven M

    2015-06-01

    Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired subcutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening.

  16. 4-Hydroxylation of estrogens as marker of human mammary tumors.

    OpenAIRE

    Liehr, J G; Ricci, M J

    1996-01-01

    Estrogen is a known risk factor in human breast cancer. In rodent models, estradiol has been shown to induce tumors in those tissues in which this hormone is predominantly converted to the catechol metabolite 4-hydroxyestradiol by a specific 4-hydroxylase enzyme, whereas tumors fail to develop in organs in which 2-hydroxylation predominates. We have now found that microsomes prepared from human mammary adenocarcinoma and fibroadenoma predominantly catalyze the metabolic 4-hydroxylation of est...

  17. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    Science.gov (United States)

    Shinagare, Atul B.; Krajewski, Katherine M.; Pyo, Junhee; Tirumani, Sree Harsha; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.

    2015-01-01

    Objective We aimed to describe radiologic signs and time-course of imatinib-associated fluid retention (FR) in patients with gastrointestinal stromal tumor (GIST), and its implications for management. Materials and Methods In this Institutional Review Board-approved, retrospective study of 403 patients with GIST treated with imatinib, 15 patients with imaging findings of FR were identified by screening radiology reports, followed by manual confirmation. Subcutaneous edema, ascites, pleural effusion, and pericardial effusion were graded on a four-point scale on CT scans; total score was the sum of these four scores. Results The most common radiologic sign of FR was subcutaneous edema (15/15, 100%), followed by ascites (12/15, 80%), pleural effusion (11/15, 73%), and pericardial effusion (6/15, 40%) at the time of maximum FR. Two distinct types of FR were observed: 1) acute/progressive FR, characterized by acute aggravation of FR and rapid improvement after management, 2) intermittent/steady FR, characterized by occasional or persistent mild FR. Acute/progressive FR always occurred early after drug initiation/dose escalation (median 1.9 month, range 0.3-4.0 months), while intermittent/steady FR occurred at any time. Compared to intermittent/steady FR, acute/progressive FR was severe (median score, 5 vs. 2.5, p = 0.002), and often required drug-cessation/dose-reduction. Conclusion Two distinct types (acute/progressive and intermittent/steady FR) of imatinib-associated FR are observed and each type requires different management. PMID:25741192

  18. Effect of Glutamine Enriched Nutrition Support on Surgical Patients with Gastrointestinal Tumor: A Meta-Analysis of Randomized Controlled Trials

    Institute of Scientific and Technical Information of China (English)

    Kai Kang; Xiao-Liang Shu; Yong-Sheng Zhang; Xian-Li Liu; Jian Zhao

    2015-01-01

    Background:Associations between glutamine (Gln) enriched nutrition support and surgical patients with gastrointestinal (GI) tumor remain controversy.The purpose of this meta-analysis was to assess the effect of Gln enriched nutrition support on surgical patients with GI tumor in term of relevant biochemical indices,immune indices,and clinical outcomes.Methods:Six databases were systematically searched to find eligible randomized controlled trials (RCTs) from 1966 to May 2014.When estimated the analysis indexes,the relative risk (RR) was used as the effect size of the categorical variable,while the weighted mean difference (MD) was used as the effect size of a continuous variable.Meta-analysis was conducted with Rev Man 5.2.Results:Thirteen RCTs,involving 1034 patients,were included in the meta-analysis.The analysis showed that Gln enriched nutrition support was more effective in increasing serum albumin (MD:0.10; 95% confidence interval [CI]:0.02-0.18; P < 0.05),serum prealbumin (MD:1.98; 95% CI:1.40-2.55; P < 0.05) and serum transferring (MD:0.35; 95% CI:0.12-0.57; P < 0.05),concentration of IgG (MD:1.26; 95% CI:0.90-1.63; P < 0.05),IgM (MD:0.18; 95% CI:0.11-0.25; P < 0.05),IgA (MD:0.22; 95% CI:0.10-0.33; P < 0.05),CD3+ (MD:3.71; 95% CI:2.57-4.85; P < 0.05) and CD4/CD8 ratio (MD:0.27; 95% CI:0.12-0.42; P < 0.05).Meanwhile,it was more significant in decreasing the incidence of infectious complications (RR:0.67; 95% CI:0.50-0.90; P < 0.05) and shortening the length of hospital stay (MD:-1.72; 95% CI:-3.31--0.13; P < 0.05).Conclusions:Glutamine enriched nutrition support was superior in improving immune function,reducing the incidence of infectious complications and shortening the length of hospital stay,playing an important role in the rehabilitation of surgical GI cancer patients.

  19. miR-200 family and gastrointestinal tumors%miR-200家族在消化系肿瘤中的研究进展

    Institute of Scientific and Technical Information of China (English)

    杜平; 张庆瑜

    2011-01-01

    The miR-200 family (including miR-200a, miR-200b, miR-200c, miR-141, and miR-429) play important roles in proliferation, invasion and metastasis of tumors of epithelial origin. Gastrointestinal tumors belong to a group of tumors of epithelial origin. This article reviews the latest advances in understanding the relationship between the miR-200 family and gastrointestinal tumors.%miR-200家族(miR-200a、miR-200b、miR-200c、miR-141、miR-429)是众多已被发现的mieroRNA中的一员,其在上皮来源肿瘤的增殖、侵袭、转移中的作用成为近年来的研究热点之一,本文对miR-200家族在同为上皮来源的消化系肿瘤中的研究进展进行了综述.

  20. Multidisciplinary comprehensive treatment of gastrointestinal stromal tumor%胃肠间质瘤多学科综合治疗的价值及评价

    Institute of Scientific and Technical Information of China (English)

    何裕隆; 张信华; 侯洵

    2015-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. A combination of surgery and targeted therapy is the rational treatment modality for GIST. Establishing a multidisciplinary collaboration medical system, organizing multidisciplinary case discussion regularly and formatting a stable treatment team can improve the level of diagnosis and treatment quickly, reduce misdiagnosis and improve the therapeutic effect significantly. A scientific and effective individualized treatment plan should be made according to the specific circumstances of the patient.%胃肠间质瘤(gastrointestinal stromal tumor,GIST)是胃肠道最常见的间叶来源肿瘤。外科手术联合靶向药物综合治疗是GIST的合理治疗模式。建立多学科协作的诊疗制度,定期组织多学科病例讨论,形成稳定的治疗团队,能够快速提高疾病的诊疗水平,减少误诊,显著提高治疗效果。根据病人的具体情况制定科学、有效的个体化治疗方案。

  1. Is photodynamic therapy a selective treatment? Analysis of local complications after endoscopic photodynamic therapy of early stage tumors of gastrointestinal, tracheobronchial, and urinary tracts

    Science.gov (United States)

    Spinelli, Pasquale; Dal Fante, Marco; Mancini, Andrea

    1995-03-01

    Selectivity is the most emphasized advantage of photodynamic therapy (PDT). However, at drug and light doses used for clinical applications, response from normal tissue surrounding the tumor reduces the real selectivity of the drug-light system and increases the surface of the area responding to the treatment. It is now evident that light irradiation of a sensitized patient produces damage at a various degree not only in the tumor but also in non-neoplastic tissues included in the field of irradiation. We report our experience in endoscopic PDT of early stage tumors in tracheobronchial, gastrointestinal and urinary tracts, describing early and late local complications caused by the damage of normal tissues adjacent to the tumors and included in the field of light irradiation. Among 44 patients treated, local complications, attributable to a poor selectivity of the modality, occurred in 6 patients (14%). In particular, the rate of local complications was 9% in patients treated for esophageal tumors, 14% in patients with gastric tumors, 9% in patients with tracheobronchial tumors, and 67% in bladder cancer patients. Clinical pictures as well as endoscopic findings at various intervals from treatment showed that mucositis is a common event following endoscopic PDT. It causes exudation and significant tissue inflammatory response, whose consequences are different in the various organs treated. Photoradiation must be, as much as possible, limited to the malignant area.

  2. Animal Farm: Considerations in Animal Gastrointestinal Physiology and Relevance to Drug Delivery in Humans.

    Science.gov (United States)

    Hatton, Grace B; Yadav, Vipul; Basit, Abdul W; Merchant, Hamid A

    2015-09-01

    "All animals are equal, but some are more equal than others" was the illustrious quote derived from British writer George Orwell's famed work, Animal Farm. Extending beyond the remit of political allegory, however, this statement would appear to hold true for the selection of appropriate animal models to simulate human physiology in preclinical studies. There remain definite gaps in our current knowledge with respect to animal physiology, notably those of intra- and inter-species differences in gastrointestinal (GI) function, which may affect oral drug delivery and absorption. Factors such as cost and availability have often influenced the choice of animal species without clear justification for their similarity to humans, and lack of standardization in techniques employed in past studies using various animals may also have contributed to the generation of contradictory results. As it stands, attempts to identify a single animal species as appropriately representative of human physiology and which may able to adequately simulate human in vivo conditions are limited. In this review, we have compiled and critically reviewed data from numerous studies of GI anatomy and physiology of various animal species commonly used in drug delivery modeling, commenting on the appropriateness of these animals for in vivo comparison and extrapolation to humans.

  3. Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions.

    Science.gov (United States)

    Baltz, Katrin M; Krusch, Matthias; Bringmann, Anita; Brossart, Peter; Mayer, Frank; Kloss, Mercedes; Baessler, Tina; Kumbier, Ingrid; Peterfi, Andrea; Kupka, Susan; Kroeber, Stefan; Menzel, Dagmar; Radsak, Markus P; Rammensee, Hans-Georg; Salih, Helmut R

    2007-08-01

    Glucocorticoid-induced TNF-related protein (GITR) has been shown to stimulate T cell-mediated antitumor immunity in mice. However, the functional relevance of GITR and its ligand (GITRL) for non-T cells has yet to be fully explored. In addition, recent evidence suggests that GITR plays different roles in mice and humans. We studied the role of GITR-GITRL interaction in human tumor immunology and report for the first time that primary gastrointestinal cancers and tumor cell lines of different histological origin express substantial levels of GITRL. Signaling through GITRL down-regulated the expression of the immunostimulatory molecules CD40 and CD54 and the adhesion molecule EpCAM, and induced production of the immunosuppressive cytokine TGF-beta by tumor cells. On NK cells, GITR is constitutively expressed and up-regulated following activation. Blocking GITR-GITRL interaction in cocultures of tumor cells and NK cells substantially increased cytotoxicity and IFN-gamma production of NK cells demonstrating that constitutive expression of GITRL by tumor cells diminishes NK cell antitumor immunity. GITRL-Ig fusion protein or cell surface-expressed GITRL did not induce apoptosis in NK cells, but diminished nuclear localized c-Rel and RelB, indicating that GITR might negatively modulate NK cell NF-kappaB activity. Taken together, our data indicate that tumor-expressed GITRL mediates immunosubversion in humans.

  4. Stathmin与胃肠道肿瘤关系的研究进展%The Study of Relationship between Stathmin and Gastrointestinal Tumor

    Institute of Scientific and Technical Information of China (English)

    刘海荣; 李岩

    2014-01-01

    Stathmin expresses high in many malignant tumor cells,The proliferation,differentiation,and other biological behavior changes of cells can be activated by stathmin protein. Overexpression of Stathmin may affect the efficacy of anti-microtubule chemotherapeutic agents. The level of stathmin expression in gastrointestinal tumors is also high,The study of stathmin has important significance for the treatment of tumors.%Stathmin在多种恶性肿瘤细胞中都高水平表达,Stathmin蛋白可以改变细胞的增殖、分化、活性等生物学行为。Stathmin的过表达可影响抗微管化学治疗药物的疗效。Stathmin在胃肠道肿瘤中也有高水平表达,针对Stathmin的研究对肿瘤的治疗有重要的意义。

  5. Targeted Radionuclide Therapy of Human Tumors

    Directory of Open Access Journals (Sweden)

    Sergey V. Gudkov

    2015-12-01

    Full Text Available Targeted radionuclide therapy is one of the most intensively developing directions of nuclear medicine. Unlike conventional external beam therapy, the targeted radionuclide therapy causes less collateral damage to normal tissues and allows targeted drug delivery to a clinically diagnosed neoplastic malformations, as well as metastasized cells and cellular clusters, thus providing systemic therapy of cancer. The methods of targeted radionuclide therapy are based on the use of molecular carriers of radionuclides with high affinity to antigens on the surface of tumor cells. The potential of targeted radionuclide therapy has markedly grown nowadays due to the expanded knowledge base in cancer biology, bioengineering, and radiochemistry. In this review, progress in the radionuclide therapy of hematological malignancies and approaches for treatment of solid tumors is addressed.

  6. Tumor Associated Neutrophils in Human Lung Cancer

    Science.gov (United States)

    2016-10-01

    Internet site(s) Penn Medicine News Site: ▪ http://www.uphs.upenn.edu/news/News_Releases/2016/07/eruslanov/ Technologies or techniques Nothing to...determine whether the tumor microenvironment stimu- lates trafficking of neutrophils, resting PBNs were assayed for tran- swell migration in the presence of...Ray, Neutrophilic inflammatory response and oxidative stress in premenopausal women chronically exposed to indoor air pollution from biomass burning

  7. Absence of Y chromosome in human placental site trophoblastic tumor.

    Science.gov (United States)

    Hui, Pei; Wang, Hanlin L; Chu, Peiguo; Yang, Bin; Huang, Jiaoti; Baergen, Rebecca N; Sklar, Jeffrey; Yang, Ximing J; Soslow, Robert A

    2007-10-01

    Placental site trophoblastic tumor is a neoplasm of extravillous intermediate trophoblast at the implantation site, preceded in the majority of cases by a female gestational event. Our pilot investigation suggested that the development of this tumor might require a paternally derived X chromosome and the absence of a Y chromosome. Twenty cases of placental site trophoblastic tumor were included in this study. Genotyping at 15 polymorphic loci and one sex determination locus was performed by multiplex PCR followed by capillary electrophoresis. X chromosome polymorphisms were determined by PCR amplification of exon 1 of the human androgen receptor gene using primers flanking the polymorphic CAG repeats within this region. Genotyping at 15 polymorphic loci was informative and paternal alleles were present in all tumors, confirming the trophoblastic origin of the tumors. The presence of an X chromosome and the absence of a Y chromosome were observed in all tumors. Among 13 cases in which analysis of the X chromosome polymorphism was informative, all but one demonstrated at least two X alleles and seven cases showed one identifiable paternal X allele. These results confirm a unique pathogenetic mechanism in placental site trophoblastic tumor, involving an exclusion of the Y chromosome from the genome and, therefore, a tumor arising from the trophectoderm of a female conceptus. As epigenetic regulations of imprinting during X chromosome inactivation are of significant biological implications, placental site trophoblastic tumor may provide an important model for studying the sex chromosome biology and the proliferative advantage conferred by the paternal X chromosome.

  8. A Big Bang model of human colorectal tumor growth.

    Science.gov (United States)

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  9. CFTR is a tumor suppressor gene in murine and human intestinal cancer.

    Science.gov (United States)

    Than, B L N; Linnekamp, J F; Starr, T K; Largaespada, D A; Rod, A; Zhang, Y; Bruner, V; Abrahante, J; Schumann, A; Luczak, T; Niemczyk, A; O'Sullivan, M G; Medema, J P; Fijneman, R J A; Meijer, G A; Van den Broek, E; Hodges, C A; Scott, P M; Vermeulen, L; Cormier, R T

    2016-08-11

    CFTR, the cystic fibrosis (CF) gene, encodes for the CFTR protein that plays an essential role in anion regulation and tissue homeostasis of various epithelia. In the gastrointestinal (GI) tract CFTR promotes chloride and bicarbonate secretion, playing an essential role in ion and acid-base homeostasis. Cftr has been identified as a candidate driver gene for colorectal cancer (CRC) in several Sleeping Beauty DNA transposon-based forward genetic screens in mice. Further, recent epidemiological and clinical studies indicate that CF patients are at high risk for developing tumors in the colon. To investigate the effects of CFTR dysregulation on GI cancer, we generated Apc(Min) mice that carried an intestinal-specific knockout of Cftr. Our results indicate that Cftr is a tumor suppressor gene in the intestinal tract as Cftr mutant mice developed significantly more tumors in the colon and the entire small intestine. In Apc(+/+) mice aged to ~1 year, Cftr deficiency alone caused the development of intestinal tumors in >60% of mice. Colon organoid formation was significantly increased in organoids created from Cftr mutant mice compared with wild-type controls, suggesting a potential role of Cftr in regulating the intestinal stem cell compartment. Microarray data from the Cftr-deficient colon and the small intestine identified dysregulated genes that belong to groups of immune response, ion channel, intestinal stem cell and other growth signaling regulators. These associated clusters of genes were confirmed by pathway analysis using Ingenuity Pathway Analysis and gene set enrichment analysis (GSEA). We also conducted RNA Seq analysis of tumors from Apc(+/+) Cftr knockout mice and identified sets of genes dysregulated in tumors including altered Wnt β-catenin target genes. Finally we analyzed expression of CFTR in early stage human CRC patients stratified by risk of recurrence and found that loss of expression of CFTR was significantly associated with poor disease

  10. Functional Development of the Human Gastrointestinal Tract: Hormone- and Growth Factor-Mediated Regulatory Mechanisms

    Directory of Open Access Journals (Sweden)

    Daniel Ménard

    2004-01-01

    Full Text Available The present review focuses on the control of gastrointestinal (GI tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial

  11. Prognositic factors and clinicopathologic characteristics of small gastrointestinal stromal tumor of the stomach:a retrospective analysis of 31 cases in one center

    Institute of Scientific and Technical Information of China (English)

    Zhen Huang; Yuan Li; Hong Zhao; Jian-Jun Zhao; Jian-Qiang Cai

    2013-01-01

    Objective:To analyze the clinicopathologic characteristics and prognostic factors of small gastrointestinal stromal tumor (GIST) of the stomach. Methods:A total of 31 small gastric GIST patients, including 10 males and 21 females, with a median age of 58 years (37-81 years), who underwent surgery at any time from 1999 to 2012 were included in this study. The clinical records of the patients were analyzed retrospectively. Results:Abdominal discomfort and pain (10 cases, 32.3%, respectively) were the two most common complaints among the patients. All patients received surgery, 11 received gastric wedge resection, 11 received subtotal gastrectomy, 5 received laparoscopic gastric wedge resection, and 4 received endoscopic submucosal dissection. No severe adverse complication was observed. A total of 29 patients (93.5%) were followed up. During the follow-up, 2 patients were found to exhibit tumor recurrence, and 1 patient had liver metastases. One patient died of tumor progression, while another died of another malignant tumor. Median progression free survival (PFS) time was 120.3 months, and median overall survival (OS) time was 130.4 months. Conclusion:Small gastric GIST has better prognosis. Surgery is the best choice for therapy. Micro-invasive procedures are safe and effective for elective patients. Tumor necrosis, tumor bleeding, and muscle invasion are potential prognostic factors of small gastric GIST.

  12. A Double-Blind, Placebo-Controlled Trial of Oral Human Immunoglobulin for Gastrointestinal Dysfunction in Children with Autistic Disorder

    Science.gov (United States)

    Handen, Benjamin L.; Melmed, Raun D.; Hansen, Robin L.; Aman, Michael G.; Burnham, David L.; Bruss, Jon B.; McDougle, Christopher J.

    2009-01-01

    Controversy exists regarding the extent and possible causal relationship between gastrointestinal symptoms and autism. A randomized, double-blind, placebo-controlled, parallel groups, dose-ranging study of oral, human immunoglobulin (IGOH 140, 420, or 840 mg/day) was utilized with 125 children (ages 2-17 years) with autism and persistent GI…

  13. [Multiple gastro-intestinal stromal tumors (GIST) in a patient with type I neurofibromatosis revealed by chronic bleeding: pre-operative radiological diagnosis].

    Science.gov (United States)

    Guillaud, Olivier; Dumortier, Jérôme; Bringuier, Pierre-Paul; Saurin, Jean-Christophe; Poncet, Gilles; Boulez, Jean; Henry, Luc; Chayvialle, Jean-Alain; Scoazec, Jean-Yves

    2006-02-01

    Recent studies have pointed out a high incidence of GIST, usually multiple and of small intestinal location, in patients with type I neurofibromatosis. We here report an additional case, revealed by chronic gastro-intestinal bleeding and diagnosed at pre-operative imaging studies. A 56-year-old patient, with known type I neurofibromatosis, was referred to our department for the exploration of chronic gastro-intestinal bleeding during anti-aggregant therapy. Endoscopical examination was negative. Enteroscanner showed the presence of four tumor lesions, 3 in the jejunum and 1 in the ileum. Segmental surgical resections were performed. At histological examination, 2 of among the 3 jejunal lesions were diagnosed as typical GIST, of low risk of malignancy, CD117+, CD34+, whereas the last jejunal and ileal lesions were identified as fibroid tumors. Mutations of c-kit gene and of the gene coding for PDGF-Ralpha were not detected. Post-operative recovery was uneventful; no recurrent bleeding was observed. Our case report underlines the potential role of enteroscanner in the management of patients with type I neurofibromatosis with possible digestive complications. It also emphasizes the importance of an accurate diagnosis of the digestive tumors associated with type I neurofibromatosis: GISTs are frequent in this setting and must not be misdiagnosed as neurofibromas.

  14. Expressional patterns of chaperones in ten human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Slavc Irene

    2004-12-01

    Full Text Available Abstract Background Chaperones (CH play an important role in tumor biology but no systematic work on expressional patterns has been reported so far. The aim of the study was therefore to present an analytical method for the concomitant determination of several CH in human tumor cell lines, to generate expressional patterns in the individual cell lines and to search for tumor and non-tumor cell line specific CH expression. Human tumor cell lines of neuroblastoma, colorectal and adenocarcinoma of the ovary, osteosarcoma, rhabdomyosarcoma, malignant melanoma, lung, cervical and breast cancer, promyelocytic leukaemia were homogenised, proteins were separated on two-dimensional gel electrophoresis with in-gel digestion of proteins and MALDI-TOF/TOF analysis was carried out for the identification of CH. Results A series of CH was identified including the main CH groups as HSP90/HATPas_C, HSP70, Cpn60_TCP1, DnaJ, Thioredoxin, TPR, Pro_isomerase, HSP20, ERP29_C, KE2, Prefoldin, DUF704, BAG, GrpE and DcpS. Conclusions The ten individual tumor cell lines showed different expression patterns, which are important for the design of CH studies in tumor cell lines. The results can serve as a reference map and form the basis of a concomitant determination of CH by a protein chemical rather than an immunochemical method, independent of antibody availability or specificity.

  15. Brain tumors induced in rats by human adenovirus type 12

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    Murao,Tsuyoshi

    1974-02-01

    Full Text Available Oncogenesis of human adenovirus type 12 in the brain of rats was examined. Newborn rats of Sprague-Dawley and Donryu strains were injected intracranially with human adenovirus type 12. The incidence of intracranial tumors was 91% (30/33 in SpragueDawley and 56% (14/25 in Donryu rats. Except for one tumor nodule located in the parietal cortex of a Sprague.Dawley rat, all tumors developed in the paraventricular areas or in the meninges. Tumors were quite similar histologically to those induced in hamsters and mice resembling the undifferentiated human brain tumors such as medulloblastoma, ependymoblastoma and embryonic gliomas. From the histological features and primary sites of tumor development, it is suggested that the tumors in the brain of rats induced by adenovirus type 12 originate from the embryonic cells in the paraventricular area and also from the undifferentiated supporting cells of the peripheral nerves in the leptomeninges.

  16. Expression of epidermal growth factor receptors in human brain tumors.

    Science.gov (United States)

    Libermann, T A; Razon, N; Bartal, A D; Yarden, Y; Schlessinger, J; Soreq, H

    1984-02-01

    The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

  17. Bioengineered models of solid human tumors for cancer research

    Science.gov (United States)

    Marturano-Kruik, Alessandro; Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2016-01-01

    Summary The lack of controllable in vitro models that can recapitulate the features of solid tumors such as Ewing’s sarcoma limits our understanding of the tumor initiation and progression and impedes the development of new therapies. Cancer research still relies of the use of simple cell culture, tumor spheroids, and small animals. Tissue-engineered tumor models are now being grown in vitro to mimic the actual tumors in patients. Recently, we have established a new protocol for bioengineering the Ewing’s sarcoma, by infusing tumor cell aggregates into the human bone engineered from the patient’s mesenchymal stem cells. The bone niche allows crosstalk between the tumor cells, osteoblasts and supporting cells of the bone, extracellular matrix and the tissue microenvironment. The bioreactor platform used in these experiments also allows the implementation of physiologically relevant mechanical signals. Here, we describe a method to build an in vitro model of Ewing’s sarcoma that mimics the key properties of the native tumor and provides the tissue context and physical regulatory signals. PMID:27115504

  18. Induction of tumor necrosis factor expression and resistance in a human breast tumor cell line.

    OpenAIRE

    Spriggs, D; Imamura, K; Rodriguez, C; Horiguchi, J; Kufe, D W

    1987-01-01

    Tumor necrosis factor (TNF) is a polypeptide cytokine that is cytotoxic to some but not all tumor cells. The basis for resistance to the cytotoxic effects of this agent remains unclear. We have studied the development of TNF resistance in human ZR-75-1 breast carcinoma cells. ZR-75-1 cells have undetectable levels of TNF RNA and protein. However, TNF transcripts are transiently induced in these cells by exposure to recombinant human TNF. This induction of TNF RNA is associated with production...

  19. Role of CCK/gastrin receptors in gastrointestinal/metabolic diseases and results of human studies using gastrin/CCK receptor agonists/antagonists in these diseases

    Science.gov (United States)

    Berna, Marc J.; Jensen, Robert T.

    2009-01-01

    In this paper, the estabished and possible roles of CCK1 and CCK2 receptors in gastrointestinal (GI) and metabolic diseases are reviewed and available results from human agonist/antagonist studies are discussed. While there is evidence for the involvement of CCK1R in numerous diseases including pancreatic disorders, motility disorders, tumor growth, regulation of satiety and a number of CCK-deficient states, the role of CCK1R in these conditions is not clearly defined. There are encouraging data from several clinical studies of CCK1R antagonists in some of these conditions, but their role as therapeutic agents remains unclear. The role of CCK2R in physiological (atrophic gastritis, pernicious anemia) and pathological (Zollinger-Ellison syndrome) hypergastrinemic states, its effects on the gastric mucosa (ECL cell hyperplasia, carcinoids, parietal cell mass) and its role in acid-peptic disorders are clearly defined. Furthermore, recent studies point to a possible role for CCK2R in a number of GI malignancies. Current data from human studies of CCK2R antagonists are presented and their potential role in the treatment of these conditions reviewed. Furthermore, the role of CCK2 receptors as targets for medical imaging is discussed. Even though cholecystokinin (CCK) and gastrin were among the first gastrointestinal hormones discovered [1,2], both their physiological roles as well as their roles in clinically relevant gastrointestinal diseases remain unclear and even controversial in many cases [3–6]. The structural characterization of CCK and gastrin [7,8], pharmacological identification [9–13] and cloning [14,15] of CCK and gastrin receptors (CCK1R, CCK2R), characterization of receptor location, peptide and receptor genes, development of receptor antagonists and receptor/agonist knockout animals [16–21] have led to important advancements in our understanding of the physiological and pathophysiological role of CCK and gastrin signaling [3]. Most of these topics

  20. Significado clínico-patológico de las mutaciones de los genes c-Kit y PDGFRa en tumores del estroma del tracto gastrointestinal

    OpenAIRE

    Calabuig Fariñas, Silvia

    2009-01-01

    Los tumores del estroma gastrointestinal (GIST) se caracterizan por la hiperexpresión del receptor de membrana c-KIT (CD117) que se detecta en un 95% de los GIST. Recientemente, se ha descrito que entre el 5-7% de GIST expresan PDGFRα. En nuestro estudio se quiere observar la relación directa entre las mutaciones y tipo de mutaciones obtenidas en los dos genes a estudiar (c-KIT y PDGFRα) con la evolución clínico-histopatológica de los pacientes. Para ello se han recogido un total de 1...

  1. The study of new methods in gastrointestinal stromal tumor therapy%胃肠道间质瘤治疗新方法的探讨

    Institute of Scientific and Technical Information of China (English)

    郭花; 余东亮; 谢惠; 盛剑秋; 余长忠; 金鹏; 李娜; 赵晓军; 王海红; 王昕; 李爱琴

    2012-01-01

    Objective To explore the efficacy and safety of laparoscopy combined with endoscopy and endoscopio submucosal excavation (ESE) in gastrointestinal stromal tumor therapy. Methods 37 patients were identified gastrointestinal stromal tumor by endoscopy, endoscopic ultrasonography, pathology and immunohistochemical methods. 28 patients underwent endoscopic submucosal excavation ( ESE) , 9 patients underwent laparoscopy combined with endoscopy. Results The turner was resected completely in all. All patients underwent endoscopic therapy resected the tumor completely. No bleeding and abodminal pain happened during and after the operation. Patient with gastric cardia tumor remained good function after the tumor resection. Conclusion Laparoscopy combined with endoscopy and ESE are minimal invasive, safe and effective new methods in gastrointestinal stromal tumor therapy.%目的 探讨胃镜与腹腔镜双镜联合及内镜黏膜下挖除术(endoscopic submucosal excavation,ESE)治疗胃肠道间质瘤的效果和安全性.方法 经胃(肠)镜、超声内镜及病理学、免疫组化证实的胃肠道间质瘤患者37例,对其中28例患者采用ESE、9例采用胃镜与腹腔镜双镜联合进行瘤体切除.结果 ESE及双镜联合治疗的所有患者均完整切除瘤体,两种方法均无术中及术后迟发性出血、剧烈腹痛等并发症,瘤体位于贲门者,切除后患者贲门功能保持良好,术后随访无复发.结论 胃镜与腹腔镜双镜联合技术及ESE是治疗胃肠道间质瘤的微创、安全、有效的新方法.

  2. The use of formulation technology to assess regional gastrointestinal drug absorption in humans.

    Science.gov (United States)

    Basit, Abdul W; Podczeck, Fridrun; Newton, J Michael; Waddington, Wendy A; Ell, Peter J; Lacey, Larry F

    2004-02-01

    The aim of this study was to assess the feasibility of using oral modified-release formulations for the purposes of site-specific targeting and regional drug absorption assessment in man. An immediate release pellet formulation containing ranitidine as the model drug of choice for the study was fabricated by extrusion-spheronisation, and then film coated with either the enteric polymer polyvinyl acetate phthalate or the bacteria-degradable polymer amylose, in combination with ethylcellulose, to effect drug release within the small intestine and colon, respectively. Optimised formulations were evaluated in vivo in ten healthy volunteers, who each received, on four separate occasions, the immediate release, small intestinal release and colonic release formulations (each equivalent to 150mg ranitidine), and an intravenous injection of ranitidine (equivalent to 50mg ranitidine). Blood samples were collected and assessed for ranitidine concentration, and radiolabelled placebo pellets were co-administered with the coated ranitidine pellets to monitor their gastrointestinal transit using a gamma camera. Ranitidine was rapidly released and absorbed from the immediate release formulation, whereas the enteric formulation (10% coat weight gain) delayed drug release until some or all of the pellets had emptied into the small intestine. The amylose-ethylcellulose coated formulation (coat ratio 1:3, coat weight gain 25%) retarded ranitidine release until the pellets had reached the colon. The mean absolute bioavailability of ranitidine from the immediate release, small intestinal release and colonic release formulations were 50.6, 46.1 and 5.5%, respectively. These data are in general agreement to those obtained from a previous regional intubation study. The present study therefore demonstrates the practical potential of utilising a non-invasive, formulation-based approach to assess drug absorption from different regions of the human gastrointestinal tract.

  3. Sensitive detection of viral transcripts in human tumor transcriptomes.

    Directory of Open Access Journals (Sweden)

    Sven-Eric Schelhorn

    Full Text Available In excess of 12% of human cancer incidents have a viral cofactor. Epidemiological studies of idiopathic human cancers indicate that additional tumor viruses remain to be discovered. Recent advances in sequencing technology have enabled systematic screenings of human tumor transcriptomes for viral transcripts. However, technical problems such as low abundances of viral transcripts in large volumes of sequencing data, viral sequence divergence, and homology between viral and human factors significantly confound identification of tumor viruses. We have developed a novel computational approach for detecting viral transcripts in human cancers that takes the aforementioned confounding factors into account and is applicable to a wide variety of viruses and tumors. We apply the approach to conducting the first systematic search for viruses in neuroblastoma, the most common cancer in infancy. The diverse clinical progression of this disease as well as related epidemiological and virological findings are highly suggestive of a pathogenic cofactor. However, a viral etiology of neuroblastoma is currently contested. We mapped 14 transcriptomes of neuroblastoma as well as positive and negative controls to the human and all known viral genomes in order to detect both known and unknown viruses. Analysis of controls, comparisons with related methods, and statistical estimates demonstrate the high sensitivity of our approach. Detailed investigation of putative viral transcripts within neuroblastoma samples did not provide evidence for the existence of any known human viruses. Likewise, de-novo assembly and analysis of chimeric transcripts did not result in expression signatures associated with novel human pathogens. While confounding factors such as sample dilution or viral clearance in progressed tumors may mask viral cofactors in the data, in principle, this is rendered less likely by the high sensitivity of our approach and the number of biological replicates

  4. Succinate Dehydrogenase Subunit B (SDHB Is Expressed in Neurofibromatosis 1-Associated Gastrointestinal Stromal Tumors (Gists: Implications for the SDHB Expression Based Classification of Gists

    Directory of Open Access Journals (Sweden)

    Jeanny H. Wang, Jerzy Lasota, Markku Miettinen

    2011-01-01

    Full Text Available Gastrointestinal Stromal Tumor (GIST is the most common mesenchymal tumor of the digestive tract. GISTs develop with relatively high incidence in patients with Neurofibromatosis-1 syndrome (NF1. Mutational activation of KIT or PDGFRA is believed to be a driving force in the pathogenesis of familial and sporadic GISTs. Unlike those tumors, NF1-associated GISTs do not have KIT or PGDFRA mutations. Similarly, no mutational activation of KIT or PDGFRA has been identified in pediatric GISTs and in GISTs associated with Carney Triad and Carney-Stratakis Syndrome. KIT and PDGFRA-wild type tumors are expected to have lesser response to imatinib treatment. Recently, Carney Triad and Carney-Stratakis Syndrome -associated GISTs and pediatric GISTs have been shown to have a loss of expression of succinate dehydrogenase subunit B (SDHB, a Krebs cycle/electron transport chain interface protein. It was proposed that GISTs can be divided into SDHB- positive (type 1, and SDHB-negative (type 2 tumors because of similarities in clinical features and response to imatinib treatment. In this study, SDHB expression was examined immunohistochemically in 22 well-characterized NF1-associated GISTs. All analyzed tumors expressed SDHB. Based on SDHB-expression status, NF1-associated GISTs belong to type 1 category; however, similarly to SDHB type 2 tumors, they do not respond well to imatinib treatment. Therefore, a simple categorization of GISTs into SDHB-positive and-negative seems to be incomplete. A classification based on both SDHB expression status and KIT and PDGFRA mutation status characterize GISTs more accurately and allow subdivision of SDHB-positive tumors into different clinico-genetic categories.

  5. Gastrointestinal stromal tumors (GIST) from risk stratification systems to the new TNM proposal: more questions than answers? A review emphasizing the need for a standardized GIST reporting

    Science.gov (United States)

    Agaimy, Abbas

    2010-01-01

    Following the successful introduction of the receptor tyrosine kinase inhibitors (TKI) as the mainstay for the treatment of advanced and metastatic gastrointestinal stromal tumor (GIST), GIST has received a special attention in the recent literature. This resulted in major achievements on the surgical pathology diagnosis and improved our understanding of the molecular biology of the disease. Availability of the effective TKI therapy has emphasized the need for a more reliable and reproducible system for assessment of the malignant potential in GIST to allow for an optimal individualized patient treatment. All of the risk stratification systems proposed so far have emphasized the value of tumor size, mitotic count and anatomic site for risk estimation, at the same time appreciating the difficulty of classifying individual tumors as either benign or malignant. The newly proposed UICC TNM classification for GISTs represents the most recent hallmark on this topic; yet its usefulness remains to be tested in future clinical studies. This review briefly summarizes and discusses the most pertinent risk systems proposed for assessment of the malignant potential of GIST stressing their advantages and limitations and including some critical remarks on the newly proposed UICC TNM system for classifying GIST. Most importantly, an emphasis is made on the urgent need for a standardized approach for histopathological evaluation and reporting of GIST specimens to allow for a reproducible tumor size, mitotic count and tumor growth pattern, and hence for a better risk classification. PMID:20606727

  6. HMGA1-pseudogene expression is induced in human pituitary tumors

    Science.gov (United States)

    Esposito, Francesco; De Martino, Marco; D'Angelo, Daniela; Mussnich, Paula; Raverot, Gerald; Jaffrain-Rea, Marie-Lise; Fraggetta, Filippo; Trouillas, Jacqueline; Fusco, Alfredo

    2015-01-01

    Numerous studies have established that High Mobility Group A (HMGA) proteins play a pivotal role on the onset of human pituitary tumors. They are overexpressed in pituitary tumors, and, consistently, transgenic mice overexpressing either the Hmga1 or the Hmga2 gene develop pituitary tumors. In contrast with HMGA2, HMGA1 overexpression is not related to any rearrangement or amplification of the HMGA1 locus in these tumors. We have recently identified 2 HMGA1 pseudogenes, HMGA1P6 and HMGA1P7, acting as competitive endogenous RNA decoys for HMGA1 and other cancer related genes. Here, we show that HMGA1 pseudogene expression significantly correlates with HMGA1 mRNA levels in growth hormone and nonfunctioning pituitary adenomas likely inhibiting the repression of HMGA1 through microRNAs action. According to our functional studies, these HMGA1 pseudogenes enhance the proliferation and migration of the mouse pituitary tumor cell line, at least in part, through their upregulation. Our results point out that the overexpression of HMGA1P6 and HMGA1P7 could contribute to increase HMGA1 levels in human pituitary tumors, and then to pituitary tumorigenesis. PMID:25894544

  7. Results on prognostic value of mutations in localized gastrointestinal stromal tumors (GIST: in one single center Valor pronóstico de las mutaciones en tumores estromales gastrointestinales localizados (GIST: resultados de un solo centro

    Directory of Open Access Journals (Sweden)

    Marina Garcés-Albir

    2012-08-01

    Full Text Available Introduction: to study the prognostic value of mutations in KIT or PDGFRA in gastrointestinal stromal tumors (GIST managed in our department. Materials and methods: forty five patients with localized GIST underwent surgery between 1998 and 2010. Thirty six patients were enrolled in a retrospective study. DNA was isolated from 3 to 5 µm sections of fixed and paraffin-embedded tissue. Exon 9, 11, 13 and 17 of c-kit gene and exon 12 and 18 of PDGFRA were amplified by PCR and sequenced. Results: tumors with mutations were larger at the surgery and showed higher mitotic count (p 50 mitosis/HPF (42 vs. 88%, p < 0.03. Multivariate analyses indicated that the mutations, mitotic counts, and tumor size were independent prognostic factors for survival in patients with localized GIST. Conclusions: in this series, having a detected mutation is a poor prognostic factor with significantly increased recurrence rate and shortens survival.

  8. [Carbon monoxide in human physiology--its role in the gastrointestinal tract].

    Science.gov (United States)

    Jasnos, Katarzyna; Magierowski, Marcin; Kwiecień, Sławomir; Brzozowski, Tomasz

    2014-01-30

    Carbon monoxide (CO) is produced endogenously in the body as a byproduct of heme degradation catalyzed by the action of heme oxygenase (HO) enzymes. An inducible form, HO-1, responds to many factors such as oxidative stress, hypoxia, heme, bacterial endotoxins, proinflammatory cytokines and heavy metals. HO-2 is constitutively expressed under basal conditions in most human tissues including brain and gonads. Recent data show that CO is a gaseous mediator with multidirectional biological activity. It is involved in maintaining cellular homeostasis and many physiological and pathophysiological processes. CO shares many properties with another established vasodilatator and neurotransmitter - nitric oxide (NO). Both CO and NO are involved in neural transmission, modulation of blood vessel function and inhibition of platelet aggregation. The binding to guanylate cyclase, stimulation of the production of cGMP, activation of Ca2+-dependent potassium channels and stimulation of mitogen-activated protein kinases are well known cellular targets of CO action. Since CO is nowadays a subject of extensive investigation in many centers worldwide, the aim of the present study was to present the role of CO in various aspects of human physiology with special focus on its activity in the gastrointestinal tract.

  9. A wireless capsule system with ASIC for monitoring the physiological signals of the human gastrointestinal tract.

    Science.gov (United States)

    Xu, Fei; Yan, Guozheng; Zhao, Kai; Lu, Li; Gao, Jinyang; Liu, Gang

    2014-12-01

    This paper presents the design of a wireless capsule system for monitoring the physiological signals of the human gastrointestinal (GI) tract. The primary components of the system include a wireless capsule, a portable data recorder, and a workstation. Temperature, pH, and pressure sensors; an RF transceiver; a controlling and processing application specific integrated circuit (ASIC); and batteries were applied in a wireless capsule. Decreasing capsule size, improving sensor precision, and reducing power needs were the primary challenges; these were resolved by employing micro sensors, optimized architecture, and an ASIC design that include power management, clock management, a programmable gain amplifier (PGA), an A/D converter (ADC), and a serial peripheral interface (SPI) communication unit. The ASIC has been fabricated in 0.18- μm CMOS technology with a die area of 5.0 mm × 5.0 mm. The wireless capsule integrating the ASIC controller measures Φ 11 mm × 26 mm. A data recorder and a workstation were developed, and 20 cases of human experiments were conducted in hospitals. Preprocessing in the workstation can significantly improve the quality of the data, and 76 original features were determined by mathematical statistics. Based on the 13 optimal features achieved in the evaluation of the features, the clustering algorithm can identify the patients who lack GI motility with a recognition rate reaching 83.3%.

  10. A piglet model for studying Candida albicans colonization of the human oro-gastrointestinal tract.

    Science.gov (United States)

    Hoeflinger, Jennifer L; Coleman, David A; Oh, Soon-Hwan; Miller, Michael J; Hoyer, Lois L

    2014-08-01

    Pigs from a variety of sources were surveyed for oro-gastrointestinal (oro-GIT) carriage of Candida albicans. Candida albicans-positive animals were readily located, but we also identified C. albicans-free pigs. We hypothesized that pigs could be stably colonized with a C. albicans strain of choice, simply by feeding yeast cells. Piglets were farrowed routinely and remained with the sow for 4 days to acquire a normal microbiota. Piglets were then placed in an artificial rearing environment and fed sow milk replacer. Piglets were inoculated orally with one of three different C. albicans strains. Piglets were weighed daily, and culture swabs were collected to detect C. albicans orally, rectally and in the piglet's environment. Stable C. albicans colonization over the course of the study did not affect piglet growth. Necropsy revealed mucosally associated C. albicans throughout the oro-GIT with the highest abundance in the esophagus. Uninoculated control piglets remained C. albicans-negative. These data establish the piglet as a model to study C. albicans colonization of the human oro-GIT. Similarities between oro-GIT colonization in humans and pigs, as well as the ease of working with the piglet model, suggest its adaptability for use among investigators interested in understanding C. albicans-host commensal interactions.

  11. Comparative expression pathway analysis of human and canine mammary tumors

    Directory of Open Access Journals (Sweden)

    Marconato Laura

    2009-03-01

    Full Text Available Abstract Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies.

  12. Targeting a single mismatched minor histocompatibility antigen with tumor-restricted expression eradicates human solid tumors

    NARCIS (Netherlands)

    L. Hambaeh (Lothar); M. Vermeij (Marcel); A. Buser (Andreas); Z. Aghai (Zohara); Th.H. van der Kwast (Theo); E. Goulmy (Els)

    2008-01-01

    textabstractRegressions of metastatic solid tumors after allogeneic human leukocyte antigen (HLA)-matched stem cell transplantation (SCT) are often associated with detrimental graft-versus-host disease (GVHD). The graft-versus-host reaction of the HLA-matched donor is directed mainly against the mul

  13. Regorafenib: A novel tyrosine kinase inhibitor: A brief review of its therapeutic potential in the treatment of metastatic colorectal carcinoma and advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    P Thangaraju

    2015-01-01

    Full Text Available Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti-angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side-effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing.

  14. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation.

    Science.gov (United States)

    Kajimoto, Noriko; Nakai, Norihiro; Ohkouchi, Mizuka; Hashikura, Yuka; Liu-Kimura, Ning-Ning; Isozaki, Koji; Hirota, Seiichi

    2015-01-01

    Sporadic mast cell neoplasms and gastrointestinal stromal tumors (GISTs) often have various types of somatic gain-of-function mutations of the c-kit gene which encodes a receptor tyrosine kinase, KIT. Several types of germline gain-of-function mutations of the c-kit gene have been detected in families with multiple GISTs. All three types of model mice for the familial GISTs with germline c-kit gene mutations at exon 11, 13 or 17 show development of GIST, while they are different from each other in skin mast cell number. Skin mast cell number in the model mice with exon 17 mutation was unchanged compared to the corresponding wild-type mice. In the present study, we characterized various types of mast cells derived from the model mice with exon 17 mutation (KIT-Asp818Tyr) corresponding to human familial GIST case with human KIT-Asp820Tyr to clarify the role of the c-kit gene mutation in mast cells. Bone marrow-derived cultured mast cells (BMMCs) derived from wild-type mice, heterozygotes and homozygotes were used for the experiments. Immortalized BMMCs, designated as IMC-G4 cells, derived from BMMCs of a homozygote during long-term culture were also used. Ultrastructure, histamine contents, proliferation profiles and phosphorylation of various signaling molecules in those cells were examined. In IMC-G4 cells, presence of additional mutation(s) of the c-kit gene and effect of KIT inhibitors on both KIT autophosphorylation and cell proliferation were also analyzed. We demonstrated that KIT-Asp818Tyr did not affect ultrastructure and proliferation profiles but did histamine contents in BMMCs. IMC-G4 cells had an additional novel c-kit gene mutation of KIT-Tyr421Cys which is considered to induce neoplastic transformation of mouse mast cells and the mutation appeared to be resistant to a KIT inhibitor of imatinib but sensitive to another KIT inhibitor of nilotinib. IMC-G4 cells might be a useful mast cell line to investigate mast cell biology.

  15. Heme oxygenase-1 accelerates tumor angiogenesis of human pancreatic cancer.

    Science.gov (United States)

    Sunamura, Makoto; Duda, Dan G; Ghattas, Maivel H; Lozonschi, Lucian; Motoi, Fuyuhiko; Yamauchi, Jun-Ichiro; Matsuno, Seiki; Shibahara, Shigeki; Abraham, Nader G

    2003-01-01

    Angiogenesis is necessary for the continued growth of solid tumors, invasion and metastasis. Several studies clearly showed that heme oxygenase-1 (HO-1) plays an important role in angiogenesis. In this study, we used the vital microscope system, transparent skinfold model, lung colonization model and transduced pancreatic cancer cell line (Panc-1)/human heme oxygenase-1 (hHO-1) cells, to precisely analyze, for the first time, the effect of hHO-1 gene on tumor growth, angiogenesis and metastasis. Our results revealed that HO-1 stimulates angiogenesis of pancreatic carcinoma in severe combined immune deficient mice. Overexpression of human hHO-1 after its retroviral transfer into Panc-1 cells did not interfere with tumor growth in vitro. While in vivo the development of tumors was accelerated upon transfection with hHO-1. On the other hand, inhibition of heme oxygenase (HO) activity by stannous mesoporphyrin was able transiently to delay tumor growth in a dose dependent manner. Tumor angiogenesis was markedly increased in Panc-1/hHO-1 compared to mock transfected and wild type. Lectin staining and Ki-67 proliferation index confirmed these results. In addition hHO-1 stimulated in vitro tumor angiogenesis and increased endothelial cell survival. In a lung colonization model, overexpression of hHO-1 increased the occurrence of metastasis, while inhibition of HO activity by stannous mesoporphyrin completely inhibited the occurrence of metastasis. In conclusion, overexpression of HO-1 genes potentiates pancreatic cancer aggressiveness, by increasing tumor growth, angiogenesis and metastasis and that the inhibition of the HO system may be of useful benefit for the future treatment of the disease.

  16. Expression of muscarinic binding sites in primary human brain tumors.

    Science.gov (United States)

    Gurwitz, D; Razon, N; Sokolovsky, M; Soreq, H

    1984-05-01

    The expression of muscarinic binding sites was examined in a collection of primary brain tumors of different cellular origins and various degrees of dedifferentiation, as compared to control specimens. Eleven gliogenous tumors were examined, all of which contained substantial amounts of muscarinic binding sites. Most of the other tumor types examined did not display detectable binding of [3H]N-methyl-4-piperidyl benzilate ([3H]4NMPB). Scatchard analysis indicated the existence of homogeneous antagonist sites in both normal forebrain and glioblastoma multiforme, with Kd values of 1.2 nM and 0.9 nM, respectively. The density of muscarinic binding sites varied between tumors from different patients, and also between specimens prelevated from different areas of the same tumor. This variability, as well as the average density of binding sites, appeared to be larger in highly malignant tumors than in less malignant ones. In contrast, the density of muscarinic receptors from control specimens was invariably high, but within the same order of magnitude. To test whether the muscarinic binding activity in the brain tumors is correlated to other cholinoceptive properties, cholinesterase activity was also examined. Individual data for density of [3H]4NMPB binding sites were then plotted against corresponding values of cholinesterase activity. The pattern of distribution of these values was clearly different in tumor specimens, when compared to that observed in samples derived from non-malignant brain. Our observations indicate that human brain cells of gliogenous origin are capable of expressing muscarinic binding sites, and that, if a correlation exists between muscarinic receptors and cholinesterase levels in gliogenous tumors, it differs from that of non-malignant brain tissue.

  17. A novel germline SDHB mutation in a gastrointestinal stromal tumor patient without bona fide features of the Carney-Stratakis dyad.

    Science.gov (United States)

    Celestino, Ricardo; Lima, Jorge; Faustino, Alexandra; Máximo, Valdemar; Gouveia, António; Vinagre, João; Soares, Paula; Lopes, José Manuel

    2012-06-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchyme neoplasms of the gastrointestinal tract. Gain-of-function somatic mutations of the KIT or PDGFRA genes represent the most prevalent molecular alterations in GISTs. In Carney-Stratakis dyad, patients portray germline mutations of the succinate dehydrogenase subunits B (SDHB), C (SDHC) and D (SDHD) and develop multifocal GISTs and multicentric paragangliomas (PGLs). We herein report a novel germline SDHB mutation (c.T282A--Ile44Asn) occurring in a 26 years-old patient diagnosed with a spindle cell intermediate risk GIST that did not present KIT/PDGFRA/BRAF gene mutations. Further analyses revealed loss of the wild-type SDHB allele and complete loss of SDHB expression in the tumor tissue. After genetic screening of other family members, we detected in the patient's mother a SDHB mutation without any clinical/laboratorial evidence of GIST or PGL. Altogether, our findings (germline SDHB mutation with absence of PGL in the index case and of GIST and/or PGL in his mother) raise the possibility that this familiar setting corresponds to an incomplete phenotype of the Carney-Stratakis dyad.

  18. [Clinical and pathological features of gastrointestinal stromal tumors (GIST) in a single institution: A descriptive study and review of the literature].

    Science.gov (United States)

    Flores-Funes, Diego; Lirón-Ruiz, Ramón José; Pérez-Guarinos, Carmen Victoria; Martín-Lorenzo, Juan Gervasio; Torralba-Martínez, José Antonio; Giménez-Bascuñana, Alberto; Chaves-Benito, María Asunción; Aguayo-Albasini, José Luis

    2017-07-25

    This study was aimed to assess the main clinical, pathological and therapeutic characteristics of a cohort of gastrointestinal stromal tumors (GIST). Observational study including 66 patients diagnosed with GIST admitted to our hospital between 2002 and 2015. Parameters related to medical history, clinical manifestations, medical and surgical treatment, histopathology, and morbi-mortality were studied. A review of the literature was included to correlate with the results. The most frequent location of GIST in our patients was the stomach (65.2%), in which the gastric fondo was the predominant region. The most common clinical manifestation was gastrointestinal hemorrhage (45.5%), followed by incidental finding after imaging or invasive procedures (33.3%). 58 patients underwent surgery (90.6%), 15.5% were urgent. A total of 69% of the GISTs had a size between 2 and 10cm. The one-year mortality was 7.9%, all cases related to local or remote extension, or surgical complications. There is a large clinical variability among GIST cases. The first choice of treatment is surgery, which is feasible in most cases and should be as conservative as possible. The prognosis varies depending on the size and proliferation index, thus close follow-up should be performed. No tumor marker is clearly associated with a poor prognosis. New molecular biology studies are needed in order to find therapeutic targets. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. A Successfully Treated Case of Gastrointestinal Stromal Tumor Causing Severe Anemia and Localized Peritonitis Showing Angina Pectoris Resulting in Watershed Cerebral Infarction

    Directory of Open Access Journals (Sweden)

    Yoshihide Sehara

    2017-01-01

    Full Text Available Ischemic stroke following acute myocardial infarction is a rare but a serious complication. Because the pathophysiology of stroke is dynamic, it is often hard to identify the cause of stroke. Here, we present the case of a 75-year-old man with ischemic stroke following angina pectoris caused by severe anemia and localized peritonitis due to gastrointestinal stromal tumor of small intestine. On admission, he showed consciousness disturbance, fever, and left hemiplegia. The electrocardiogram on admission showed ST-segment depression in V2 to V6 which was normalized 4 hours later. The ultrasound cardiogram showed the mild hypokinesis in the apical portion of left ventricle which was also normalized later. The magnetic resonance imaging and angiography showed ischemic stroke in watershed area between right anterior and middle cerebral arteries area and stenosis of distal portion of right middle cerebral artery. The computed tomography of abdomen showed a mass of small intestine. We decided to perform curative surgery after transfusion and successfully resected the mass of the small intestine, which was revealed to be a gastrointestinal stromal tumor (GIST. This is a successfully treated case of GIST in which the complicated pathophysiology of watershed cerebral infarction following angina pectoris might be clearly revealed.

  20. CTHRC1 Acts as a Prognostic Factor and Promotes Invasiveness of Gastrointestinal Stromal Tumors by Activating Wnt/PCP-Rho Signaling

    Directory of Open Access Journals (Sweden)

    Ming-Ze Ma

    2014-03-01

    Full Text Available Gastrointestinal stromal tumors (GISTs are the major gastrointestinal mesenchymal tumors with a variable malignancy ranging from a curable disorder to highly malignant sarcomas. Metastasis and recurrence are the main causes of death in GIST patients. To further explore the mechanism of metastasis and to more accurately estimate the recurrence risk of GISTs after surgery, the clinical significance and functional role of collagen triple helix repeat containing-1 (CTHRC1 in GIST were investigated. We found that CTHRC1 expression was gradually elevated as the risk grade of NIH classification increased, and was closely correlated with disease-free survival and overall survival in 412 GIST patients. In vitro experiments showed that recombinant CTHRC1 protein promoted the migration and invasion capacities of primary GIST cells. A luciferase reporter assay and pull down assay demonstrated that recombinant CTHRC1 protein activated noncanonical Wnt/PCP-Rho signaling but inhibited canonical Wnt signaling. The pro-motility effect of CTHRC1 on GIST cells was reversed by using a Wnt5a neutralizing antibody and inhibitors of Rac1 or ROCK. Taken together, these data indicate that CTHRC1 may serve as a new predictor of recurrence risk and prognosis in post-operative GIST patients and may play an important role in facilitating GIST progression. Furthermore, CTHRC1 promotes GIST cell migration and invasion by activating Wnt/PCP-Rho signaling, suggesting that the CTHRC1-Wnt/PCP-Rho axis may be a new therapeutic target for interventions against GIST invasion and metastasis.

  1. Tumorer

    DEFF Research Database (Denmark)

    Prause, J.U.; Heegaard, S.

    2005-01-01

    oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer......oftalmologi, øjenlågstumorer, conjunctivale tumorer, malignt melanom, retinoblastom, orbitale tumorer...

  2. Ki-67 Expression in Human Tumors Measured by Flow Cytometry

    Science.gov (United States)

    1990-01-01

    proliferation. One of the first proliferation antigens to be studied was the transferrin receptor (TfR). Proliferating normal and tumor cells require iron and...obtained by incubation in NP-40. When the antibody was used to stain frozen sections of human tonsil , the chromosomes were stained. The antibody was...proliferation. When applied to frozen sections of human tonsil , the antibody appeared to be reactive with a mitotic spindle-associated protein. It bound

  3. Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

    Science.gov (United States)

    Kocheril, S V; Grignon, D J; Wang, C Y; Maughan, R L; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J e; Hillman, G G

    1999-01-01

    We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

  4. 15例胃肠道类癌的诊治分析%Analysis of clinical diagnosis and treatment of 15 cases of gastrointestinal carcinoid tumors

    Institute of Scientific and Technical Information of China (English)

    王辉; 宋军; 徐为

    2012-01-01

    Objective To summarize the experience of diagnosis and treatment of gastrointestinal carcinoid tumors . Methods The clinical data of 15 cases of gastrointestinal carcinoid tumors were analyzed retrospectively . Results Of the 15 cases of gastrointestinal carcinoid tumors , 10 cases were male and 5 cases were female, with the median age of 57 years. 9 cases (60.0% ) were gastric carcinoids, 5 cases (33.3% ) were rectal carcinoids , 1 case (6.7% ) was ileal carcinoid. Clinical symptoms were as follows : 9 cases (60%) with abdominal pain, 4 cases (26.7%) with abdominal distention, 4 cases (26.7%) with increased frequency of defecation. CT scan was performed in 6 cases, primary lesion or metastasis were detected in 5 cases, and no obvious abnormality was found in 1 case. Endoscopy and biopsy were performed in all cases,ll cases were definitely diagnosed , the other 4 cases were misdiagnosed as adenocarcinoma , mesenchymoma, or polypus respectively at the very beginning. 9 cases were treated with surgical resection , among whom 2 cases received local resection, 6 cases received radical operation , 1 case with liver metastasis received palliative surgery , liver medicine injection and microwave ablation of liver metastases . The other 5 cases were treated by endoscopic submucosal dissection , and only 1 case gave up treatment. Conclusion The clinical manifestations of gastrointestinal carcinoid tumors are non-specific. These neoplasms pose a diagnostic challenge. Endoscopic biopsy is an important technique for diagnosis . Surgical resection and endoscopic treatment are the most effective approach to treatment of gastrointestinal carcinoid tumors .%目的 总结胃肠道类癌的诊断和治疗经验.方法收集15例胃肠道类癌患者的临床资料,对其临床特征、诊疗过程进行总结分析.结果 本组15例胃肠道类癌患者,中位年龄57岁;男性10例,女性5例;其中胃类癌9例(60.0%),直肠类癌5例(33.3%),小肠类癌1例(6.7%).

  5. [Gastrointestinal bezoars].

    Science.gov (United States)

    Espinoza González, Ricardo

    2016-08-01

    Gastrointestinal bezoars are a concretion of indigested material that can be found in the gastrointestinal tract of humans and some animals. This material forms an intraluminal mass, more commonly located in the stomach. During a large period of history animal bezoars were considered antidotes to poisons and diseases. We report a historical overview since bezoars stones were thought to have medicinal properties. This magic conception was introduced in South America by Spanish conquerors. In Chile, bezoars are commonly found in a camelid named guanaco (Lama guanicoe). People at Central Chile and the Patagonia believed that bezoar stones had magical properties and they were traded at very high prices. In Santiago, during the eighteenth century the Jesuit apothecary sold preparations of bezoar stones. The human bezoars may be formed by non-digestible material like cellulose (phytobezoar), hair (trichobezoar), conglomerations of medications or his vehicles (pharmacobezoar or medication bezoar), milk and mucus component (lactobezoar) or other varieties of substances. This condition may be asymptomatic or can produce abdominal pain, ulceration, gastrointestinal bleeding, gastric outlet obstruction, perforation and mechanical intestinal obstruction. We report their classification, diagnostic modalities and treatment.

  6. [A case report of two-term surgery for focal progression of a huge liver metastasis and peritoneal dissemination from gastrointestinal stromal tumor during imatinib mesylate treatment].

    Science.gov (United States)

    Toyokawa, Takahiro; Teraoka, Hitoshi; Kitayama, Kisyu; Nomura, Shinya; Kanehara, Isao; Nishino, Hiroji

    2014-03-01

    We report a patient who underwent 2-term surgery to treat focal progression of a huge liver metastasis and peritoneal dissemination from a gastric gastrointestinal stromal tumor(GIST)during imatinib mesylate treatment. A 59-year-old man underwent an emergency surgery for perforative peritonitis caused by gastric GIST in June 2006 and a partial resection of the stomach in September 2006. Four years later, abdominal computed tomography(CT)detected a huge liver tumor that occupied the entire right lobe. We initiated imatinib mesylate treatment(400mg/day), and the patient maintained stable disease for several months. However, focal progression of the huge liver tumor and a peritoneal tumor at the splenic hilum were revealed by CT; therefore, an extended right hepatic resection was performed in August 2011 and a distal pancreatectomy, splenectomy, and partial resection of the stomach were performed in February 2012. The patient died of the primary disease at 16 months after the hepatic resection for focal progression.

  7. RASAL1 expression and ras activity with gastrointestinal tumors: a review%RASAL1表达及ras活性与胃肠道肿瘤临床关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    吕成余; 谢洪虎; 樊红

    2011-01-01

    Approximately 20% of human tumors are associated with mutations of ras genes. Ras proteins control cellular signaling pathways responsible for cell proliferation, differentiation, survival and apoptosis. Ras proteins belong to the large family of small GTPases, which are activated in response-to various extracellular stimuli. RASAL1, as a ras GTPase activating protein, inhibits ras activation. Regulation of ras and RASAL1 activities may lead the direction of target treatment of tumors. Detection of ras and RASAL1 activities can provide more relevant information about diagnosis and prognosis of gastrointestinal tumors. In this paper, we reviewed the structure, the biochemical properties of ras proteins, and the role of its mutations in tumors. We further discussed the inhibitive effects of RASAL1 on ras activities. Finally, we commented the correlation of ras and RASAL1 with gastrointestinal tumors.%大约有20%的人类肿瘤与ras的突变有关.ras蛋白调控细胞的一系列生物学行为,包括细胞增殖、分化、生存及凋亡等.ras蛋白属于小GTP结合蛋白,通过响应细胞外信号产生活性.RASAL1是一种ras GTP酶激活蛋白,可以抑制ras的活性.调节ras以及RASAL1的活性,可能是肿瘤靶向治疗的方向之一.检测ras以及RASAL1的活性有助于胃肠道肿瘤的早期诊断以及预后的判断.本文从ras的结构、功能及突变与肿瘤的关系,RASALl作为ras的效应分子抑制ras的活性,ras、RASAL1与胃肠道肿瘤的关系三方面来综述了RASAL1表达及ras活性与胃肠道肿瘤临床关系的研究进展.

  8. Sangre de grado Croton palanostigma induces apoptosis in human gastrointestinal cancer cells.

    Science.gov (United States)

    Sandoval, Manuel; Okuhama, Nataly N; Clark, Melinda; Angeles, Fausto M; Lao, Juan; Bustamante, Sergio; Miller, Mark J S

    2002-05-01

    Sangre de grado is an ethnomedicinal red tree sap obtained from Croton spp. that is used to treat gastrointestinal ulcers, cancer and to promote wound healing. To evaluate the potential role of sangre de grado (SdG) in cancer we examined its effects on human cancer cells, AGS (stomach), HT29 and T84 (colon). Viability of cells treated with SdG (10-200 microg/ml) decreased (P100 microg/ml). When cells in suspension were treated with SdG (100 microg/ml) cell adherence was severely compromised (>85%). Cells treated with SdG (100 microg/ml) underwent apoptosis as detected by nucleus condensation and DNA fragmentation determined by ELISA, and flow cytometry. Morphological changes as assessed by acridine orange. These effects were similar to that observed with Taxol (30 microM). A significant alteration of microtubular architecture was equally observed in both stomach and colon cancer cells exposed to SdG (100 microg/ml). The induction of apoptosis and microtubule damage in AGS, HT29 and T84 cells suggest that sangre de grado should be evaluated further as a potential source of anti-cancer agents.

  9. Effects of Genetically Modified Milk Containing Human Beta-Defensin-3 on Gastrointestinal Health of Mice.

    Directory of Open Access Journals (Sweden)

    Xin Chen

    Full Text Available This study was performed to investigate the effects of genetically modified (GM milk containing human beta-defensin-3 (HBD3 on mice by a 90-day feeding study. The examined parameters included the digestibility of GM milk, general physical examination, gastric emptying function, intestinal permeability, intestinal microflora composition of mice, and the possibility of horizontal gene transfer (HGT. The emphasis was placed on the effects on gastrointestinal (GI tract due to the fact that GI tract was the first site contacting with food and played crucial roles in metabolic reactions, nutrition absorption and immunity regulation in the host. However, the traditional methods for analyzing the potential toxicological risk of GM product pay little attention on GI health. In this study, the results showed GM milk was easy to be digested in simulated gastric fluid, and it did not have adverse effects on general and GI health compared to conventional milk. And there is little possibility of HGT. This study may enrich the safety assessment of GM product on GI health.

  10. Behaviour of silver nanoparticles and silver ions in an in vitro human gastrointestinal digestion model.

    Science.gov (United States)

    Walczak, Agata P; Fokkink, Remco; Peters, Ruud; Tromp, Peter; Herrera Rivera, Zahira E; Rietjens, Ivonne M C M; Hendriksen, Peter J M; Bouwmeester, Hans

    2013-11-01

    Oral ingestion is an important exposure route for silver nanoparticles (AgNPs), but their fate during gastrointestinal digestion is unknown. This was studied for 60 nm AgNPs and silver ions (AgNO₃) using in vitro human digestion model. Samples after saliva, gastric and intestinal digestion were analysed with SP-ICPMS, DLS and SEM-EDX. In presence of proteins, after gastric digestion the number of particles dropped significantly, to rise back to original values after the intestinal digestion. SEM-EDX revealed that reduction in number of particles was caused by their clustering. These clusters were composed of AgNPs and chlorine. During intestinal digestion, these clusters disintegrated back into single 60 nm AgNPs. The authors conclude that these AgNPs under physiological conditions can reach the intestinal wall in their initial size and composition. Importantly, intestinal digestion of AgNO₃ in presence of proteins resulted in particle formation. These nanoparticles (of 20-30 nm) were composed of silver, sulphur and chlorine.

  11. A New High-Throughput Approach to Genotype Ancient Human Gastrointestinal Parasites.

    Science.gov (United States)

    Côté, Nathalie M L; Daligault, Julien; Pruvost, Mélanie; Bennett, E Andrew; Gorgé, Olivier; Guimaraes, Silvia; Capelli, Nicolas; Le Bailly, Matthieu; Geigl, Eva-Maria; Grange, Thierry

    2016-01-01

    Human gastrointestinal parasites are good indicators for hygienic conditions and health status of past and present individuals and communities. While microscopic analysis of eggs in sediments of archeological sites often allows their taxonomic identification, this method is rarely effective at the species level, and requires both the survival of intact eggs and their proper identification. Genotyping via PCR-based approaches has the potential to achieve a precise species-level taxonomic determination. However, so far it has mostly been applied to individual eggs isolated from archeological samples. To increase the throughput and taxonomic accuracy, as well as reduce costs of genotyping methods, we adapted a PCR-based approach coupled with next-generation sequencing to perform precise taxonomic identification of parasitic helminths directly from archeological sediments. Our study of twenty-five 100 to 7,200 year-old archeological samples proved this to be a powerful, reliable and efficient approach for species determination even in the absence of preserved eggs, either as a stand-alone method or as a complement to microscopic studies.

  12. Human STEAP3 maintains tumor growth under hypoferric condition

    Energy Technology Data Exchange (ETDEWEB)

    Isobe, Taichi, E-mail: tisobe@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Baba, Eishi, E-mail: e-baba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Arita, Shuji, E-mail: arita.s@nk-cc.go.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Komoda, Masato, E-mail: komoda@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Tamura, Shingo, E-mail: tamshin@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Shirakawa, Tsuyoshi, E-mail: t-w-r@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Ariyama, Hiroshi, E-mail: hariyama@kyumed.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Takaishi, Shigeo, E-mail: takaishi@med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); Kusaba, Hitoshi, E-mail: hkusaba@intmed1.med.kyushu-u.ac.jp [Department of Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan); and others

    2011-11-01

    Iron is essential in cellular proliferation and survival based on its crucial roles in DNA and ATP synthesis. Tumor cells proliferate rapidly even in patients with low serum iron, although their actual mechanisms are not well known. To elucidate molecular mechanisms of efficient tumor progression under the hypoferric condition, we studied the roles of six-transmembrane epithelial antigen of the prostate family member 3 (STEAP3), which was reported to facilitate iron uptake. Using Raji cells with low STEAP3 mRNA expression, human STEAP3-overexpressing cells were established. The impact of STEAP3 expression was analyzed about the amount of iron storage, the survival under hypoferric conditions in vitro and the growth of tumor in vivo. STEAP3 overexpression increased ferritin, an indicator of iron storage, in STEAP3-overexpressing Raji cells. STEAP3 gave Raji cells the resistance to iron deprivation-induced apoptosis. These STEAP3-overexpressing Raji cells preserved efficient growth even in hypoferric mice, while parental Raji cells grew less rapidly. In addition, iron deficiency enhanced STEAP3 mRNA expression in tumor cells. Furthermore, human colorectal cancer tissues exhibited more STEAP3 mRNA expression and iron storage compared with normal colon mucosa. These findings indicate that STEAP3 maintains iron storage in human malignant cells and tumor proliferation under the hypoferric condition. -- Highlights: {yields} STEAP3 expression results in increment of stored intracellular iron. {yields} Iron deprivation induces expression of STEAP3. {yields} Colorectal cancer expresses STEAP3 highly and stores iron much. {yields} STEAP3 expressing tumors preserves growth even in mice being hypoferremia.

  13. Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma

    Science.gov (United States)

    Yeung, Bonnie H. Y.; Shek, Felix H.; Lee, Nikki P.; Wong, Chris K. C.

    2015-01-01

    Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1) in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC) an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL)-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal ≥ 2) were significantly smaller than the lower level (tumor/normal<2) samples (p = 0.008). A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 overexpression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients. PMID:26469082

  14. Stanniocalcin-1 Reduces Tumor Size in Human Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Bonnie H Y Yeung

    Full Text Available Growing evidence has revealed high expression levels of stanniocalcin-1 (STC1 in different types of human cancers. Numerous experimental studies using cancer cell lines demonstrated the involvement of STC1 in inflammatory and apoptotic processes; however the role of STC1 in carcinogenesis remains elusive. Hepatocellular carcinoma (HCC an exemplified model of inflammation-related cancer, represents a paradigm of studying the association between STC1 and tumor development. Therefore, we conducted a statistical analysis on the expression levels of STC1 using clinicopathological data from 216 HCC patients. We found that STC1 was upregulated in the tumor tissues and its expression levels was positively correlated with the levels of interleukin (IL-6 and IL-8. Intriguingly tumors with greater expression levels of STC1 (tumor/normal ≥ 2 were significantly smaller than the lower level (tumor/normal<2 samples (p = 0.008. A pharmacological approach was implemented to reveal the functional correlation between STC1 and the ILs in the HCC cell-lines. IL-6 and IL-8 treatment of Hep3B cells induced STC1 expression. Lentiviral-based STC1 overexpression in Hep3B and MHCC-97L cells however showed inhibitory action on the pro-migratory effects of IL-6 and IL-8 and reduced size of tumor spheroids. The inhibitory effect of STC1 on tumor growth was confirmed in vivo using the stable STC1-overexpressing 97L cells on a mouse xenograft model. Genetic analysis of the xenografts derived from the STC1-overexpressing 97L cells, showed upregulation of the pro-apoptotic genes interleukin-12 and NOD-like receptor family, pyrin domain-containing 3. Collectively, the anti-inflammatory and pro-apoptotic functions of STC1 were suggested to relate its inhibitory effect on the growth of HCC cells. This study supports the notion that STC1 may be a potential therapeutic target for inflammatory tumors in HCC patients.

  15. Intracellular insulin in human tumors: examples and implications

    Directory of Open Access Journals (Sweden)

    Radulescu Razvan T

    2011-04-01

    Full Text Available Abstract Insulin is one of the major metabolic hormones regulating glucose homeostasis in the organism and a key growth factor for normal and neoplastic cells. Work conducted primarily over the past 3 decades has unravelled the presence of insulin in human breast cancer tissues and, more recently, in human non-small cell lung carcinomas (NSCLC. These findings have suggested that intracellular insulin is involved in the development of these highly prevalent human tumors. A potential mechanism for such involvement is insulin's binding and inactivation of the retinoblastoma tumor suppressor protein (RB which in turn is likely controlled by insulin-degrading enzyme (IDE. This model and its supporting data are collectively covered in this survey in order to provide further insight into insulin-driven oncogenesis and its reversal through future anticancer therapeutics.

  16. Age and gender affect the composition of fungal population of the human gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Francesco Strati

    2016-08-01

    Full Text Available The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C, to acidic and oxidative stress and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals’ life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics

  17. Significance of rat mammary tumors for human risk assessment.

    Science.gov (United States)

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. © 2014 by The Author(s).

  18. Tumor necrosis factor alpha modulates the dynamics of the plasminogen-mediated early interaction between Bifidobacterium animalis subsp. lactis and human enterocytes.

    Science.gov (United States)

    Centanni, Manuela; Bergmann, Simone; Turroni, Silvia; Hammerschmidt, Sven; Chhatwal, Gursharan Singh; Brigidi, Patrizia; Candela, Marco

    2012-04-01

    The capacity to intervene with the host plasminogen system has recently been considered an important component in the interaction process between Bifidobacterium animalis subsp. lactis and the human host. However, its significance in the bifidobacterial microecology within the human gastrointestinal tract is still an open question. Here we demonstrate that human plasminogen favors the B. animalis subsp. lactis BI07 adhesion to HT29 cells. Prompting the HT29 cell capacity to activate plasminogen, tumor necrosis factor alpha (TNF-α) modulated the plasminogen-mediated bacterium-enterocyte interaction, reducing the bacterial adhesion to the enterocytes and enhancing migration to the luminal compartment.

  19. Ex Vivo Behaviour of Human Bone Tumor Endothelial Cells

    Energy Technology Data Exchange (ETDEWEB)

    Infante, Teresa [SDN-Foundation, Institute of Diagnostic and Nuclear Development, IRCCS, 80143 Naples (Italy); Cesario, Elena [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy); Gallo, Michele; Fazioli, Flavio [Division of Skeletal Muscles Oncology Surgery, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); De Chiara, Annarosaria [Anatomic Pathology Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Tutucci, Cristina; Apice, Gaetano [Medical Oncology of Bone and Soft Sarcoma tissues Unit, National Cancer Institute, Pascale Foundation, 80131 Naples (Italy); Nigris, Filomena de, E-mail: filomena.denigris@unina2.it [Department of Biochemistry and Biophysics, Second University of Naples, 80138 Naples (Italy)

    2013-04-11

    Cooperation between endothelial cells and bone in bone remodelling is well established. In contrast, bone microvasculature supporting the growth of primary tumors and metastasis is poorly understood. Several antiangiogenic agents have recently been undergoing trials, although an extensive body of clinical data and experimental research have proved that angiogenic pathways differ in each tumor type and stage. Here, for the first time, we characterize at the molecular and functional level tumor endothelial cells from human bone sarcomas at different stages of disease and with different histotypes. We selected a CD31{sup +} subpopulation from biopsies that displayed the capability to grow as adherent cell lines without vascular endothelial growth factor (VEGF). Our findings show the existence in human primary bone sarcomas of highly proliferative endothelial cells expressing CD31, CD44, CD105, CD146 and CD90 markers. These cells are committed to develop capillary-like structures and colony formation units, and to produce nitric oxide. We believe that a better understanding of tumor vasculature could be a valid tool for the design of an efficacious antiangiogenic therapy as adjuvant treatment of sarcomas.

  20. Synchronous poorly-differentiated neuroendocrine carcinoma and gastrointestinal stromal tumor of the stomach: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA.

    Science.gov (United States)

    Ding, Jun; Sun, Ping; Cai, Xiao-Yan; Fei, Shao-Hua; Wu, Jian; Qi, Yu-Kai; Liu, Ze-Bin; Yuan, Lin; He, Yu-Jie; Song, Hui; Chen, Wei-Xiang

    2014-01-01

    Although the stomach is the most common location for gastrointestinal stromal tumor (GIST) with co-primary tumors, the synchronous appearance of a poorly differentiated neuroendocrine carcinoma (NEC) and GIST in the stomach is extremely rare. To the best of our knowledge, this is the first case of gastric GIST coexisting with gastric NEC to be reported in the literature. The current study reports the case of a 71-year-old male with gastric poorly differentiated NEC and GIST discovered incidentally during surgical treatment of the NEC. Immunohistochemistry analysis showed that the NEC tumor cells were positive for CK (cytokeratin), CD57, synaptophysin, chromogranin, CD117 (KIT protein), Dog-1 (discovered on GIST-1 protein) and CD34. The synchronous GIST immunophenotype showed positivity for CD117, Dog-1 and CD34 (100%), whereas staining for CK, SMA, desmin and S100 was negative. Ki-67 labeling of proliferating cells was 90% in NEC and 1% in GIST. An accurate diagnosis was confirmed by immunohistochemical findings. Furthermore, genetic analysis using PCR direct sequencing identified no mutations in the KIT (exons 9, 11, 13 and 17) and PDGFRA (exons 12 and 18) genes. The patient developed lymph node metastases and underwent cisplatin-based chemotherapy after the operation. This is the first documented case of synchronous gastric GIST and NEC with the examination of protein expression and gene mutations in KIT and PDGFRA, which will help to further understand the etiology and pathogenesis of NEC coexisting with GIST in a gastric location.

  1. KIT exon 11 codon 557/558 deletion/insertion mutations define a subset of gastrointestinal stromal tumors with malignant potential

    Institute of Scientific and Technical Information of China (English)

    Katerina Kontogianni-Katsarou; Euthimios Dimitriadis; Constantina Lariou; Evi Kairi-Vassilatou; Nikolaos Pandis; Agatha Kondi-Paphiti

    2008-01-01

    AIM: To study the association of the frequency and pattern of KIT and PDGFRA mutations and dinicopathological factors in a group of patients with gastrointestinal stromal tumors (GIST).METHODS: Thirty patients with GIST were examined. Exons 9, 11,13, and 17 of the KIT and exons 12 and 18 of the PDGFRA gene were analyzed for the presence of mutations by PCR amplification and direct sequencing.RESULTS: KIT or PDGFRA mutations were detected in 21 of the 30 patients (70%). Sixteen patients had mutations within KIT exon 11, three within KIT exon 9, and two within PDGFRA exon 18. GISTs with KIT exon 9 mutations were predominantly located in the small intestine, showed a spindle cell phenotype, and were assessed as potentially malignant. GISTs with KIT exon 11 mutations were located in the stomach and intestine, showed mainly a spindle cell phenotype, and were scored as potentially malignant (P < 0.05). Tumors with KIT exon 11 codon 557/558 deletion/insertion mutations were found to be associated with a potentially malignant clinical behaviour (P < 0.003). GISTs with PDGFRA mutations located in stomach showed a mixed cell phenotype and were classified as of very low or low moderate malignant potential.CONCLUSION: Determination of KIT and PDGFRA mutations should be additional parameters for the better prediction of GISTs clinical behaviour. Tumors with deletion/insertion mutations affecting codons 557/558 of the KIT gene seem to represent a distinct subset of malignant GISTs.

  2. Robotic Versus Laparoscopic Gastric Resection for Primary Gastrointestinal Stromal Tumors >5 cm: A Size-Matched and Location-Matched Comparison.

    Science.gov (United States)

    de'Angelis, Nicola; Genova, Pietro; Amiot, Aurelien; Charpy, Cecile; Disabato, Mara; Belgaumkar, Ajay P; Chahrour, Ali; Legou, Francois; Azoulay, Daniel; Brunetti, Francesco

    2017-02-01

    This study compared robotic (RR) and laparoscopic resection (LR) for primary gastrointestinal stromal tumors (GISTs) of the stomach >5 cm. Twelve consecutive patients who underwent RR from 2012 to 2015 were matched for tumor size and location with 24 patients who underwent LR from 2000 to 2012. The median tumor size was 7.1 cm (range, 5.5 to 11.5). GISTs were resected by wedge resection (91.7%) or distal gastrectomy. The median RR operative time was longer than that of LR (162.5 vs. 130 min, respectively; P=0.004). Only 1 LR patient required conversion. The time to flatus and hospital stay were similar between groups. Overall, 3 patients developed minor postoperative complications that were medically treated. Mortality was nil. All resections were R0. No difference was observed in the incidence of recurrence. RR was significantly more expensive (+21.6%) than LR. RR appears to be safe and feasible for GISTs>5 cm, but is associated with longer operative times and greater costs.

  3. Photon emission from normal and tumor human tissues.

    Science.gov (United States)

    Grasso, F; Grillo, C; Musumeci, F; Triglia, A; Rodolico, G; Cammisuli, F; Rinzivillo, C; Fragati, G; Santuccio, A; Rodolico, M

    1992-01-15

    Photon emission in the visible and near ultraviolet range by samples of human tissue removed during surgery has been measured by means of a low noise photomultiplier coupled to a data acquisition system. The results show that among the 25 analyzed samples the 9 from normal tissues had an emission rate of the order of some tens of photons/cm2 min, while most of the 16 tumor tissue samples had a very much higher rate.

  4. Functional Study of the Human BRCA2 Tumor Suppressor

    Science.gov (United States)

    2005-08-01

    Wang, Y., Lee, M. & Venkitaraman, A. R. Abnormal cytokinesis in cells deficient in the breast cancer susceptibility protein BRCA2. Science 306, 876...tumor suppressor genes in mitotic and meiotic cells. Mol Cell 2, 317-28 (1998). 28. Fuks, F., Milner, J. & Kouzarides, T. BRCA2 associates with...Scully, R. et al. Association of BRCA1 with Rad5l in mitotic and meiotic cells. Cell 88, 265-75 (1997). 49. Nakanishi, K. et al. Human Fanconi anemia

  5. 机器人外科手术系统在胃肠肿瘤外科中的应用%Robotic surgery in gastrointestinal tumor

    Institute of Scientific and Technical Information of China (English)

    陈伟平; 鞠海星

    2012-01-01

    The application of robotic surgery can provide solutions to the many drawbacks of traditional laparoscopic surgery.Robotic surgery is a feasible and safe procedure for patients with gastrointestinal tumor.It can harvest adequate lymph node with low postoperative morbidity.Longer follow-up and further raudomized clinical trials are needed to validate the utility and efficacy of this technology in the field of gastrointestinal surgery.%近年来机器人外科手术系统逐渐被应用于胃肠肿瘤根治术中.机器人手术具有安全性与可行性,能克服传统腹腔镜手术的许多缺点,在胃肠肿瘤根治术中能清扫足够数目的淋巴结,术后并发症发病率较低.但还需长期随访及更多临床随机对照研究来证实机器人外科手术系统在肿瘤近、远期方面的疗效.

  6. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To study the expression of human insulin gene in gastrointestinal tracts of diabetic rats. METHODS: pCHV.Ins, an expression plasmid of the human insulin gene, wrapped with chitosan nanoparticles, was transfected to the diabetic rats through lavage and coloclysis, respectively. Fasting blood glucose and plasma insulin levels were measured for 7 d. Reverse transcription polymerase chain reaction (RT-PCR) analysis and Western blot analysis were performed to confirm the expression of human insulin gene. RESULTS: Compared with the control group, the fasting blood glucose levels in the lavage and coloclysis groups were decreased significantly in 4 d (5.63 ± 0.48 mmol/L and 5.07 ± 0.37 mmol/L vs 22.12± 1.31 mmol/L, respectively, P < 0.01), while the plasma insulin levels were much higher (32.26±1.81 μIU/mL and 32.79 ± 1.84 μIU/mL vs 14.23 ± 1.38 μIU/mL, respectively, P<0.01). The human insulin gene mRNA and human insulin were only detected in the lavage and coloclysis groups. CONCLUSION: Human insulin gene wrapped with chitosan nanoparticles can be successfully transfected to rats through gastrointestinal tract, indicating that chitosan is a promising non-viral vector.

  7. Multiple primary malignant tumors of upper gastrointestinal tract:A novel role of ~(18)F-FDG PET/CT

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To evaluate the capacity of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for detecting multiple primary cancer of upper gastrointestinal (UGI) tract. METHODS: Fifteen patients (12 without cancer histories and 3 with histories of upper GI tract cancer) were investigated due to the suspicion of primary cancer of UGI tract on X-ray barium meal and CT scan. Subsequent whole body 18F-FDG PET/CT scan was carried out for initial staging or restaging. All the patient...

  8. Fibromatosis of the Sigmoid Colon With CTNNB1 (β-Catenin) Gene Mutation, Arising at the Site of Ileocolic Anastomosis for Resection of Gastrointestinal Stromal Tumor.

    Science.gov (United States)

    Thway, Khin; Abou Sherif, Sara; Riddell, Angela M; Mudan, Satvinder

    2016-05-01

    We describe a case of intra-abdominal fibromatosis, which occurred in a 44-year-old woman who had a previous history of gastrointestinal stromal tumor (GIST) of the sigmoid mesocolon, which was treated with imatinib and resection. A mass was detected at the site of ileocolic anastomosis of the previous small bowel resection and sigmoid colectomy, nearly 3 years later. Clinically, this was suspected to represent recurrent GIST and was excised, but histology and mutational analysis showed desmoid-type fibromatosis with a mutation in codon 41 of exon 3 of the CTNNB1 (β-catenin) gene. The occurrence of fibromatosis at the site of excision of GIST is very rare, but its recognition is important as the treatment of the two neoplasms differs significantly. As imaging cannot reliably distinguish between these 2 entities, histological diagnosis is crucial for correct clinical management. © The Author(s) 2015.

  9. GASTROINTESTINAL EOSINOPHILIA

    Science.gov (United States)

    Zuo, Li; Rothenberg, Marc E.

    2007-01-01

    SYNOPSIS Gastrointestinal eosinophilia, as a broad term for abnormal eosinophil accumulation in the GI tract, involves many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in HES and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them. All three groups of GI eosinophila are described in this chapter although the focus is on primary gastrointestinal eosinophilia, i.e. EGID. PMID:17868858

  10. Implementing Tumor Detection and Area Calculation in Mri Image of Human Brain Using Image Processing Techniques

    OpenAIRE

    Sunil L. Bangare; Madhura Patil

    2015-01-01

    This paper is based on the research on Human Brain Tumor which uses the MRI imaging technique to capture the image. In this proposed work Brain Tumor area is calculated to define the Stage or level of seriousness of the tumor. Image Processing techniques are used for the brain tumor area calculation and Neural Network algorithms for the tumor position calculation. Also in the further advancement the classification of the tumor based on few parameters is also expected. Proposed wor...

  11. 多排螺旋CT在胃肠道肿瘤及并发症的诊断价值%Multi-slice Spiral CT in the Diagnosis of Gastrointestinal Tumor and Complications

    Institute of Scientific and Technical Information of China (English)

    高云; 郑晓林; 尹昌媛

    2013-01-01

    目的 探讨多排螺旋CT在胃肠道肿瘤及并发症的诊断价值. 材料和方法 回顾性分析43例胃肠道肿瘤的多排螺旋CT表现,观察分析胃肠道肿瘤的直接CT征象及并发症征象.结果 CT可以直接发现胃肠道肿块的32例,肠管壁增厚11例,肠梗阻18例,肠套叠3例,肠扭转5例,消化道出血1例,肠系膜血管增粗26,肠系膜淋巴结肿大15例,肝脏转移7例,大网膜转移3例.结论 多排螺旋CT在消化道肿瘤的诊断方面有较高的临床实用价值,值得推广应用.%Objective To investigate diagnostic value of multi-slice spiral CT on the gastrointestinal tumor and complications.Materials and methods Multi-slice spiral CT performance of 43 patients with gastrointestinal tumors were retrospectively analyzed,to observe and analyze direct CT findings and complications CT findings of gastrointestinal tumors.Results 32 cases of the gastrointestinal masses could be directly found by multislice spiral CT; 11 cases of bowel wall thickening; 27 cases of intestinal obstruction; 3 cases of intussusception; 5 cases of volvulus; 1 case of gastrointestinal bleeding; 26 cases of mesenteric vascular thickening; 15 cases of mesenteric lymph nodes; 7 cases of liver metastases; 3 cases of omentum metastasis.Conclusion Multi-slice spiral CT in the diagnosis of gastrointestinal tumors had higher clinical value,should be widely applied.

  12. 胃肠道肿瘤影像诊断技术进展和评价%Progress and Evaluation in Gastrointestinal Tumor for Diagnosis- Imaging Technique

    Institute of Scientific and Technical Information of China (English)

    卢延

    2001-01-01

    In the present study, patients with gastrointestinal tumor were examined by using GI barium examination, CT(computed tomography), MRI(magnetic resonnance imaging). Recently, the rapid devel opment of imaging diagnosis techniques provide a variety of modalities, such as spiral CT(SCT): SCT oral small bowel examination, gastrointestinal tract SCT - 3D reformation, SCT gastro - colon air cast imag ing. MR hydrography of intestinal tract, MR colonography and CT or MRI virtual endoscopy. Various new techniques are accepted as the diagnostic imaging tool for the gastrointestinal neoplasm and may be helpful for staging tumor befor operation. This article introduces the clinical applications and evaluates the various examination methods in GI tract. Especially, various imaging modalities in modern imageolo gy have made full use of the advantage of imaging characterization and also limitation as well as being avoided the deficit of them. Combined evaluation of new options have considerable potential for diagnosis GI neoplasms.%用于胃肠道检查的影像学诊断技术有多种,最常用的方法有胃肠钡剂检查,CT和MRI。近年发展的新的 技术有:螺旋CT口服法小肠造影,胃肠道螺旋CT三维重建,螺旋CT胃,结肠空气铸型成像;肠道MR水成 象,MR结肠造影;以及CT,MRI仿真内窥镜技术。各种新技术在胃肠道肿瘤诊断领域中发挥了作用,有助于胃 肠道肿瘤的诊断和肿瘤侵犯范围的术前评估。本文概述了胃肠道各种影象检查方法的应用价值,并予以评价;特 别要注意的是;每一种影象检查手段都以其独特的成象原理显示各自的优越性,但也有其相对的局限性,因此, 联合应用,互相补充,综合诊断是极为重要的。

  13. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  14. Cat Mammary Tumors: Genetic Models for the Human Counterpart

    Directory of Open Access Journals (Sweden)

    Filomena Adega

    2016-08-01

    Full Text Available The records are not clear, but Man has been sheltering the cat inside his home for over 12,000 years. The close proximity of this companion animal, however, goes beyond sharing the same roof; it extends to the great similarity found at the cellular and molecular levels. Researchers have found a striking resemblance between subtypes of feline mammary tumors and their human counterparts that goes from the genes to the pathways involved in cancer initiation and progression. Spontaneous cat mammary pre-invasive intraepithelial lesions (hyperplasias and neoplasias and malignant lesions seem to share a wide repertoire of molecular features with their human counterparts. In the present review, we tried to compile all the genetics aspects published (i.e., chromosomal alterations, critical cancer genes and their expression regarding cat mammary tumors, which support the cat as a valuable alternative in vitro cell and animal model (i.e., cat mammary cell lines and the spontaneous tumors, respectively, but also to present a critical point of view of some of the issues that really need to be investigated in future research.

  15. Epigenetic regulation of putative tumor suppressor TGFBI in human leukemias

    Institute of Scientific and Technical Information of China (English)

    Fang Hongbo; Liu Jing; Guo Dan; Liu Peixiang; Zhao Yongliang

    2014-01-01

    Background Both in vitro and in vivo data have demonstrated the TGFBI gene functions as a putative tumor suppressor and is frequently downregulated in human tumors of different histological types.The hypermethylation of the TGFBI promoter,as one of the main regulatory mechanisms,is associated with TGFBI silencing.In this study,we used a methylation-specific PCR (MSP) method to evaluate the methylation status of the TGFBI promoter in human leukemias.Methods Real-time RT-PCR and methylation-specific PCR approaches were performed to define the TGFBI expression and promoter methylation in human leukemia call lines and clinical samples.Genomic DNA was isolated from peripheral blood mononuclear cells from leukemia patients,bisulfite-converted,and analyzed by the MSP method.Results Hypermethylation of the TGFBI promoter occurred in leukemia cell lines and demethylation treatment reexpressed TGFBI at a substantially increased level in most of leukemia cell lines tested.Furthermore,a much higher level of CpG island methylation and a significantly lower TGFBI expression were also identified in clinical leukemia samples.Conclusion The results suggest an important role of promoter methylation in regulating TGFBI expression in leukemia,which provides a useful diagnostic marker for clinical management of human leukemias.

  16. Triparanol suppresses human tumor growth in vitro and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Bi, Xinyu [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China); Han, Xingpeng [Department of Pathology, Tianjin Chest Hospital, Tianjin 300051 (China); Zhang, Fang [Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang (China); He, Miao [Life Sciences School, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhi, Xiu-Yi, E-mail: xiuyizhi@yahoo.com.cn [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

  17. Transcriptional silencing of Dickkopf gene family by CpG island hypermethylation in human gastrointestinal cancer

    Institute of Scientific and Technical Information of China (English)

    Tadateru Maehata; Fumio Itoh; Hiroaki Taniguchi; Hiroyuki Yamamoto; Katsuhiko Nosho; Yasushi Adachi; Nobuki Miyamoto; Chic Miyamoto; Noriyuki Akutsu; Satoshi Yamaoka

    2008-01-01

    AIM:To clarify alterations of Dickkopfs (Dkks) and Kremen2 (Krm2) in gastrointestinal cancer.METHODS:We investigated the expression profiles and epigenetic alterations of Dkks and Krm2 genes in gastrointestinal cancer using RT-PCR,tissue microarray analysis,and methylation specific PCR (MSP).Cancer cells were treated with the demethylating agent and/or histone deacetylase inhibitor.WST-8 assays and in vitro invasion assays after treatment with specific siRNA for those genes were performed.RESULTS:Dkks and Krm2 expression levels were reduced in a certain subset of the gastrointestinal cancer cell lines and cancer tissues.This was correlated with promoter hypermethylation.There were significant correlations between Dkks over-expression levels and beta-catenin over-expression in colorectal cancer.In colorectal cancers with beta-catenin over-expression,Dkk-1 expression levels were significantly lower in those with lymph node metastases than in those without.Down-regulation of Dkks expression by siRNA resulted in a significant increase in cancer cell growth and invasiveness in vitro.CONCLUSION:Down-regulation of the Dkks associated to promoter hypermethylation appears to be frequently involved in gastrointestinal tumorigenesis.

  18. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

    NARCIS (Netherlands)

    Hernandez, E.; Bargiela, R.; Suarez Diez, M.; Friedrichs, A.; Pérez-Cobas, A.E.; Gosalbes, M.J.; Knecht, H.; Martinez-Martinez, M.; Seifert, J.; Bergen, von M.; Martins Dos Santos, V.A.P.

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to ca

  19. Oral Human Immunoglobulin for Children with Autism and Gastrointestinal Dysfunction: A Prospective, Open-Label Study

    Science.gov (United States)

    Schneider, Cindy K.; Melmed, Raun D.; Barstow, Leon E.; Enriquez, F. Javier; Ranger-Moore, James; Ostrem, James A.

    2006-01-01

    Immunoglobulin secretion onto mucosal surfaces is a major component of the mucosal immune system. We hypothesized that chronic gastrointestinal (GI) disturbances associated with autistic disorder (AD) may be due to an underlying deficiency in mucosal immunity, and that orally administered immunoglobulin would be effective in alleviating chronic GI…

  20. Functional consequences of microbial shifts in the human gastrointestinal tract linked to antibiotic treatment and obesity

    NARCIS (Netherlands)

    Hernandez, E.; Bargiela, R.; Suarez Diez, M.; Friedrichs, A.; Pérez-Cobas, A.E.; Gosalbes, M.J.; Knecht, H.; Martinez-Martinez, M.; Seifert, J.; Bergen, von M.; Martins Dos Santos, V.A.P.

    2013-01-01

    The microbiomes in the gastrointestinal tract (GIT) of individuals receiving antibiotics and those in obese subjects undergo compositional shifts, the metabolic effects and linkages of which are not clearly understood. Herein, we set to gain insight into these effects, particularly with regard to

  1. Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

    DEFF Research Database (Denmark)

    Falkén, Y; Hellström, P M; Sanger, G J

    2010-01-01

    Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis...

  2. Thyroxine 5'-deiodinase in human anterior pituitary tumors.

    Science.gov (United States)

    Itagaki, Y; Yoshida, K; Ikeda, H; Kaise, K; Kaise, N; Yamamoto, M; Sakurada, T; Yoshinaga, K

    1990-08-01

    The activity of T4 5'-monodeiodinase (5'D) in the pituitary was measured in 12 patients with pituitary adenoma (3 patients with acromegaly, 2 with prolactinoma, 1 with Cushing's disease, 1 with TSH-producing tumor, and 5 with nonfunctioning tumor) and, as a control, in a patient who died of parotid cancer. The pituitaries, obtained at operation or autopsy, were homogenized in 0.1 mol/L potassium phosphate buffer, pH 7.0, and centrifuged at 800 x g. Supernatants were incubated with [125I]T4 and 20 mmol/L dithiothreitol (DTT) at 37C for 90 min. T4 5'-D was measured by the release of 125I- with the ion exchange method. The activity of T4 5'-D in the pituitaries from patients with prolactinoma and parotid cancer was dependent on protein concentration, incubation time, incubation temperature, and T4 concentration, and was labile to prior heating at 70 C for 30 min. T4 5'-D was not inhibited by 1 mmol/L propylthiouracil, but was inhibited 95% by 0.1 mmol/L iopanoic acid. The apparent Km and maximum velocity for T4 5'-D in homogenates of prolactinoma at 20 mmol/L DTT were 11 nmol/L and 1.54 pmol/mg protein.h, respectively. This reaction followed sequential-type reaction kinetics when the DTT concentration was varied. All other homogenates of pituitary tumors, except two nonfunctioning tumors, also demonstrated T4 5'-D activity. These results indicate that 1) the human pituitary express a low Km and PTU-insensitive T4 5'-D activity which is very similar to the type II enzyme activity in the rat pituitary; and 2) various types of pituitary tumor cells contain T4 5'-D activity.

  3. Large gastrointestinal stromal tumor and advanced adenocarcinoma in the rectum coexistent with an incidental prostate carcinoma: A case report

    Directory of Open Access Journals (Sweden)

    Toshiaki Suzuki

    2014-01-01

    CONCLUSION: Radical surgery with perioperative adjuvant chemotherapy using tyrosine kinase inhibitors is the choice for treatment of large GISTs with a malignant potential. Our report suggests that aggressive surgical approach would be feasible, when a secondary tumor is present near the GIST.

  4. Estudio del anticuerpo DOG1 en el diagnóstico de tumores del estroma gastrointestinal - GIST The role of the DOG1 antibody in the diagnosis of gastrointestinal stromal tumours - GIST

    Directory of Open Access Journals (Sweden)

    M.R. Mercado

    2011-08-01

    Full Text Available Los tumores del estroma gastrointestinal (GIST poseen mutaciones en los genes del receptor de la tirosín quinasa (RTKs KIT y PDGFRA. La posibilidad de bloquear esta actividad ha significado una nueva esperanza terapéutica. El diagnóstico de GIST recae en la expresión inmunohistoquímica del c-KIT, pero un 4-15% son c-KIT negativos (aún en presencia de mutación, y sin embargo estos pacientes podrían beneficiarse del tratamiento con inhibidores tirosín quinasa (TKIs. El DOG1 es un nuevo anticuerpo cuya sensibilidad y especificidad parece ser superior o igual a la del c-KIT. El objetivo de este trabajo es evaluar la sensibilidad (Se y especificidad (Sp de DOG1 en GIST de tipo usual (c-KIT positivos, de tipo inusual (c-KIT negativos y frente a otros tumores fusocelulares mesenquimales, y comparar la validez diagnóstica del DOG1 frente al c-KIT. Estudiamos 40 GIST, 39 c-KIT positivos y un c-KIT negativo. Se realizó un panel inmunohistoquímico con los anticuerpos: c-KIT, CD34, actina músculo liso, DOG1 y S100, en los GIST como en siete tumores fusocelulares. La Se y Sp de GIST para DOG1 fue del 100 y 97,5% para c-KIT. La inmunoreactividad para DOG1 en todos los tumores fusocelulares fue negativa. La validez diagnóstica de DOG1 y C-KIT fue similar a la hora de detectar GIST y no GIST. DOG1 es un marcador específico y sensible para el diagnóstico y diagnóstico diferencial de GISTs (es capaz de detectar algunos GIST sin mutación en RTK. El DOG1 debería de formar parte del panel inmunohistoquímico para el diagnóstico de GIST.Gatrointestinal stromal tumours (GIST harbour oncogenic mutations in tyrosin kynases receptors (RTKs including KIT and PDGFRA. The inhibition of this activity has been regarded as the primary target for the treatment of these patients. Diagnosis of GIST relies on c-KIT inmunoreactivity; however there is a 4-15% of GISTs that are C-KIT negative which may lead to underdiagnosis of GISTs and possible withholding of

  5. Delta-ALA-mediated fluorescence spectroscopy of gastrointestinal tumors: comparison of in vivo and in vitro results

    Science.gov (United States)

    Vladimirov, B.; Borisova, E.; Avramov, L.

    2007-06-01

    The limitations of standard endoscopy for detection of dysplastic changes of mucosa are significant challenge and initiate development of new photodiagnostic techniques, additional to diagnostic possibilities of standard endoscopic equipment. One of the most widely examined optical modalities is the laser- or light-induced fluorescence spectroscopy (LIFS), because of its rapid and highly sensitive response to early biochemical and morphological changes in biological tissues. In the recent study delta-aminolevulinic acid/protoporphyrin IX is used as fluorescent marker for dysplasia and tumor detection in esophagus and stomach. The δ -ALA is administered per os six hours before measurements at dose 20mg/kg weight. High-power light-emitting diode at 405 nm is used as an excitation source. Special opto-mechanical device is built to use the light guide of standard video-endoscopic system. Through endoscopic instrumental channel a fiber is applied to return information about fluorescence to microspectrometer. The fluorescence detected from in vivo tumor sites has very complex spectral origins. It consists of autofluorescence, fluorescence from exogenous fluorophores and re-absorption from the chromophores accumulated in the tissue investigated. Mucosa autofluorescence lies at 450-600 nm region. The fluorescence of PpIX is clearly pronounced at the 630-710 nm region. Deep minima in the tumor fluorescence signals are observed in the region 540-575 nm, related to hemoglobin re-absorption. Such high hemoglobin content is an indication of the tumors vascularization and it is clearly pronounced in all dysplastic and tumor sites investigated. After formalin conservation for in vitro samples hemoglobin absorption is strongly reduced that increases mucous fluorescence signal in green-yellow spectral region. Simultaneously the maxima at 635 nm and 720 nm are reduced.

  6. Gastrointestinal fistula

    Science.gov (United States)

    Entero-enteral fistula; Enterocutaneous fistula; Fistula - gastrointestinal ... Most gastrointestinal fistulas occur after surgery. Other causes include: Blockage in the intestine Infection Crohn disease Radiation to the abdomen (most ...

  7. SYNCHROTRON RADIATION XRF MICROPROBE STUDY OF HUMAN BONE TUMOR SLICE

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The experimental apparatus of X-ray fluorescence (XRF) microprobe analysis at Beijing Synchrotron Radiation Facility (BSRF) is described Using the bovine liver as the standard reference.the minimum detection limit(MDL) of trace element was measured to determine the capability of biological sample analysis by synchrotron radiation XRF microprobe.The relative change of the content of the major or trace element in the normal and tumor part of human bone tissue slice was investigated The experimental result relation to the clinical medicine was also discussed.

  8. Shh基因与消化道肿瘤的关系%Shh Gene and Gastrointestinal Tumors

    Institute of Scientific and Technical Information of China (English)

    赵华

    2013-01-01

    Hedgehog( Hh ) signaling pathway is a very important pathway, the abnormal expression of which has far-reaching impact on cell growth, development, proliferation and differentiation. It can cause a variety of malignancies. Sonic hedgehog( Shh )gene is core of Shh signaling pathway, which can be used as diagnostic and prognostic evaluation index of some tumors. Studies have shown that Hh pathway were expressed in multiple tumors such as esophageal cancer,gastric cancer,medulloblastoma,and prostate cancer etc. ,closely related to the occurrence,development and metastasis of the tumors.%Hedgehog(Hh)信号通路是一条非常重要的转导途径,其异常表达将对细胞的生长、发育、增殖及分化产生深远的影响,可导致多种恶性肿瘤的发生.Sonic Hedgehog(Shh)基因是Shh信号通路的核心,该基因可作为某些肿瘤的诊断及预后评价的指标.研究显示Hh信号通路在食管癌、胃癌、髓母细胞瘤、前列腺癌等多种肿瘤中表达,且与肿瘤的发生、发展及转移密切相关.

  9. A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.

    Science.gov (United States)

    Burgos-Ojeda, Daniela; McLean, Karen; Bai, Shoumei; Pulaski, Heather; Gong, Yusong; Silva, Ines; Skorecki, Karl; Tzukerman, Maty; Buckanovich, Ronald J

    2013-06-15

    Human tumor vessels express tumor vascular markers (TVM), proteins that are not expressed in normal blood vessels. Antibodies targeting TVMs could act as potent therapeutics. Unfortunately, preclinical in vivo studies testing anti-human TVM therapies have been difficult to do due to a lack of in vivo models with confirmed expression of human TVMs. We therefore evaluated TVM expression in a human embryonic stem cell-derived teratoma (hESCT) tumor model previously shown to have human vessels. We now report that in the presence of tumor cells, hESCT tumor vessels express human TVMs. The addition of mouse embryonic fibroblasts and human tumor endothelial cells significantly increases the number of human tumor vessels. TVM induction is mostly tumor-type-specific with ovarian cancer cells inducing primarily ovarian TVMs, whereas breast cancer cells induce breast cancer specific TVMs. We show the use of this model to test an anti-human specific TVM immunotherapeutics; anti-human Thy1 TVM immunotherapy results in central tumor necrosis and a three-fold reduction in human tumor vascular density. Finally, we tested the ability of the hESCT model, with human tumor vascular niche, to enhance the engraftment rate of primary human ovarian cancer stem-like cells (CSC). ALDH(+) CSC from patients (n = 6) engrafted in hESCT within 4 to 12 weeks whereas none engrafted in the flank. ALDH(-) ovarian cancer cells showed no engraftment in the hESCT or flank (n = 3). Thus, this model represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.

  10. Endoscopic submucosal dissection for silent gastric Dieulafoy lesions mimicking gastrointestinal stromal tumors: Report of 7 cases-a case report series.

    Science.gov (United States)

    Chen, Xue; Cao, Hailong; Wang, Sinan; Wang, Dan; Xu, Mengque; Piao, Meiyu; Wang, Bangmao

    2016-09-01

    Dieulafoy lesion is a rare but serious cause of gastrointestinal hemorrhage. However, some cases can be occasionally found without bleeding during the endoscopic screening, and the management remains unclear. The aim of this article was to report the efficacy and safety of endoscopic submucosal dissection (ESD) for silent gastric Dieulafoy lesions, which presented as protrusion lesions mimicking gastrointestinal stromal tumors (GISTs). Data from the patients with gastric protrusion lesions who underwent ESD from September 2008 to April 2016 in General Hospital, Tianjin Medical University, China were recorded. Seven cases with pathological diagnosis of Dieulafoy lesion without bleeding were enrolled for further analysis. A total of 7 patients (2 males and 5 females) with mean age of 57.7 ± 4.15 years were pathologically diagnosed as Dieulafoy lesion. Four of the lesions were located in gastric antrum, 2 in the fundus, and 1 in the body of stomach, respectively. The mean sizes of the Dieulafoy lesions under white light endoscopy and endoscopic ultrasonography (EUS) were 1.06 ± 0.28 and 0.84 ± 0.29 cm. The origins of these lesions were submucosa (6/7, 85.7%) and muscularis propria (1/7, 14.3%). Three of them appeared with mixed echo under EUS, 3 with hypoechogenicity, and 1 with hyperechogenicity. En bloc complete resection was achieved in all the lesions by ESD with average time of 76.00 ± 16.86 minutes, and no intraoperative bleeding happened. In addition, all patients were followed up for 1 to 53 months, and no recurrence or long-term complications was observed. Therefore, ESD can be an effective and safe treatment for silent gastric Dieulafoy lesions with clinical presentations of submucosal protrusion lesions mimicking GISTs.

  11. Phase transitions in tumor growth: IV relationship between metabolic rate and fractal dimension of human tumor cells

    Science.gov (United States)

    Betancourt-Mar, J. A.; Llanos-Pérez, J. A.; Cocho, G.; Mansilla, R.; Martin, R. R.; Montero, S.; Nieto-Villar, J. M.

    2017-05-01

    By the use of thermodynamics formalism of irreversible processes, complex systems theory and systems biology, it is derived a relationship between the production of entropy per unit time, the fractal dimension and the tumor growth rate for human tumors cells. The thermodynamics framework developed demonstrates that, the dissipation function is a Landau potential and also the Lyapunov function of the dynamical behavior of tumor growth, which indicate the directional character, stability and robustness of the phenomenon. The entropy production rate may be used as a quantitative index of the metastatic potential of tumors. The current theoretical framework will hopefully provide a better understanding of cancer and contribute to improvements in cancer treatment.

  12. Modulation of Ingestive Behavior and Gastrointestinal Motility by Ghrelin in Diabetic Animals and Humans

    Directory of Open Access Journals (Sweden)

    Chih-Yen Chen

    2010-05-01

    Full Text Available Acyl ghrelin, a 28-amino acid peptide hormone, is the endogenous cognate ligand for the growth hormone secretagogue receptor. Ghrelin is involved in stimulating growth hormone release, eliciting feeding behavior, inducing adiposity and stimulating gastrointestinal motility. Ghrelin is unique for its post-translational modification of O-n-octanoylation at serine 3 through ghrelin O-acyltransferase, and is the only peripheral signal to enhance food intake. Plasma ghrelin levels manifest “biphasic changes” in diabetes mellitus (DM. In the early stage of DM, the stomach significantly increases the secretion of ghrelin into the plasma, and elevated plasma ghrelin levels are correlated with diabetic hyperphagic feeding and accelerated gastrointestinal motility. In the late stage of DM, plasma ghrelin levels may be lower, which might be linked with anorexia/muscle wasting, delayed gastrointestinal transit, and even gastroparesis. Therefore, the unique ghrelin system may be the most important player compared to the other hindgut hormones participating in the “entero-insular axis”. Further studies using either knockdown or knockout of ghrelin gene products and ghrelin O-acyltransferase may unravel the pathogenesis of DM, and show benefits in combating this disease and metabolic syndrome.

  13. Terpinen-4-ol: A Novel and Promising Therapeutic Agent for Human Gastrointestinal Cancers.

    Directory of Open Access Journals (Sweden)

    Shiran Shapira

    Full Text Available Terpinen-4-ol, a naturally occurring monoterpene is the main bioactive component of tea-tree oil and has been shown to have many biological activities.To study the antitumor effects of terpinen-4-ol and its mechanism of action in prostate and GI malignancies, alone and in combination with chemotherapeutic and biological agents.Terpinen-4-ol was administrated alone or combined with standard chemotherapy (Oxaliplatin, Fluorouracil, Gemcitabine, Tarceva and biological agent (Cetuximab. It was also combined with humanized anti-CD24 mAbs (was developed by us. Killing effects were measured qualitatively by light microscopy and quantitatively using the MTT and FACS analysis, following treatment of colorectal, pancreatic, gastric and prostate cancer cells. Terpinen-4-ol effect on tumor development was evaluated in xenograft model.Terpinen-4-ol induces a significant growth inhibition of colorectal, pancreatic, prostate and gastric cancer cells in a dose-dependent manner (10-90% in 0.005-0.1%. Terpinen-4-ol and various anti-cancer agents (0.2μM oxaliplatin and 0.5μM fluorouracil demonstrated a synergistic inhibitory effect (83% and 91%, respectively on cancer cell proliferation. In KRAS mutated colorectal cancer cells, which are resistant to anti-EGFR therapy, combining of terpinen-4-ol with cetuximab (1 μM resulted in impressive efficacy of 80-90% growth inhibition. Sub-toxic concentrations of terpinen-4-ol potentiate anti-CD24 mAb (150μg/ml-induced growth inhibition (90%. Considerable reduction in tumor volume was seen following terpinen-4-ol (0.2% treatment alone and with cetuximab (10mg/kg (40% and 63%, respectively as compare to the control group.Terpinen-4-ol significantly enhances the effect of several chemotherapeutic and biological agents. The possible molecular mechanism for its activity involves induction of cell-death rendering this compound as a potential anti-cancer drug alone and in combination in the treatment of numerous malignancies