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Sample records for incidental gastrointestinal stromal

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

    PubMed

    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.

  2. Gastric gastrointestinal stromal tumor (GIST) incidentally found and resected during laparoscopic sleeve gastrectomy.

    PubMed

    Beltran, Marcelo A; Pujado, Blazenko; Méndez, Pedro E; Gonzáles, Francisco J; Margulis, David I; Contreras, Mario A; Cruces, Karina S

    2010-03-01

    The incidence of incidental pathology found during laparoscopic bariatric surgery has been estimated to be around 2%, and gastric gastrointestinal stromal tumors (GISTs) have been found in 0.8% of patients, constituting a rather uncommon finding. Safe laparoscopic resection of gastric GISTs is an established procedure and has been described associated to gastric Roux-en-Y bypass for morbid obesity. We discuss one case of a gastric GIST incidentally discovered during laparoscopic sleeve gastrectomy for morbid obesity. The procedure was performed via laparoscopy, and the patient recovered without any complication. Currently, the patient has lost weight according to what was expected, is asymptomatic, and free of disease.

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

    PubMed

    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.

  4. What's New in Gastrointestinal Stromal Tumor Research and Treatment?

    MedlinePlus

    ... Stromal Tumor (GIST) About Gastrointestinal Stromal Tumor What’s New in Gastrointestinal Stromal Tumor Research and Treatment? There ... the Key Statistics About Gastrointestinal Stromal Tumors? What’s New in Gastrointestinal Stromal Tumor Research and Treatment? More ...

  5. What Are the Risk Factors for Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... Gastrointestinal Stromal Tumors Be Prevented? Gastrointestinal Stromal Tumor (GIST) Causes, Risk Factors, and Prevention What Are the ... few known risk factors for gastrointestinal stromal tumors (GISTs). Being older These tumors can occur in people ...

  6. What Are the Key Statistics about Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... About Gastrointestinal Stromal Tumor What Are the Key Statistics About Gastrointestinal Stromal Tumors? Gastrointestinal stromal tumors (GISTs) ... They are slightly more common in men. Survival statistics for GIST are discussed in “ Survival rates for ...

  7. Ghrelin and gastrointestinal stromal tumors

    PubMed Central

    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. PMID:28348480

  8. Ghrelin and gastrointestinal stromal tumors.

    PubMed

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

    2017-03-14

    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.

  9. What Happens After Treatment for Gastrointestinal Stromal Tumor?

    MedlinePlus

    ... Tumor Is No Longer Working Gastrointestinal Stromal Tumor (GIST) After Treatment What Happens After Treatment for Gastrointestinal ... For some people with a gastrointestinal stromal tumor (GIST), treatment may remove or destroy the cancer. Completing ...

  10. Gastrointestinal Stromal Tumours: An Update

    PubMed Central

    Somerhausen, Nicolas De Saint Aubain

    1998-01-01

    Purpose. To study the evolution of concepts concerning gastrointestinal stromal tumours (GISTs) over 30 years. Discussion. GISTs have been, for more than 30 years, the subject of considerable controversy regarding their line of differentiation as well as the prediction of their behaviour. Furthermore, once they spread within the peritoneal cavity, they are extremely hard to control. The recent findings of c-Kit mutations and the immunohistochemical detection of the product of this gene, KIT or CD117, in the mainly non-myogenic subset of this family of tumours, has led to a reappraisal of this group of lesions, which, with some exceptions, is now thought to be derived from the interstitial cells of Cajal, and this has facilitated a clearer definition of their pathological spectrum. In this article, we review chronologically the evolution of the concept of GIST with the gradual application of electron microscopy, immunohistochemistry, DNA ploidy analysis. We discuss the impact of these techniques on the pathological assessment and clinical management of GISTs. PMID:18521245

  11. Skull metastasis from rectal gastrointestinal stromal tumours.

    PubMed

    Gil-Arnaiz, Irene; Martínez-Trufero, Javier; Pazo-Cid, Roberto Antonio; Felipo, Francesc; Lecumberri, María José; Calderero, Verónica

    2009-09-01

    Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasm of the gastrointestinal tract. Rectum localisation is infrequent for these neoplasms, accounting for about 5% of all cases. Distant metastases of GIST are also rare. We present a patient with special features: the tumour is localised in rectum and it has an uncommon metastatic site, the skull, implying a complex differential diagnosis approach.

  12. Management of early asymptomatic gastrointestinal stromal tumors of the stomach

    PubMed Central

    Scherübl, Hans; Faiss, Siegbert; Knoefel, Wolfram-Trudo; Wardelmann, Eva

    2014-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the digestive tract. Approximately two thirds of clinically manifest tumors occur in the stomach, nearly one third in the small bowel, and the rest in the colorectal region with a few cases in the esophagus. GIST originate within the smooth muscle layer in the wall of the tubular gastrointestinal tract and grow mostly toward the serosa, far less often toward the mucosa. In the latter case, ulceration may develop and can cause gastrointestinal bleeding as the cardinal symptom. However, most GIST of the stomach are asymptomatic. They are increasingly detected incidentally as small intramural or submucosal tumors during endoscopy and particularly during endoscopic ultrasound. Epidemiological and molecular genetic findings suggest that early asymptomatic GIST of the stomach (< 1 cm) show self-limiting tumorigenesis. Thus, early (< 1 cm) asymptomatic gastric GIST (synonym: micro-GIST) are found in 20%-30% of the elderly. The mostly elderly people with early gastric GIST have an excellent GIST-specific prognosis. Patients with early GIST of the stomach can therefore be managed by endoscopic surveillance. PMID:25031785

  13. Ectopic Pancreas Imitating Gastrointestinal Stromal Tumor (GIST) In The Stomach.

    PubMed

    Zińczuk, Justyna; Bandurski, Roman; Pryczynicz, Anna; Konarzewska-Duchnowska, Emilia; Kemona, Andrzej; Kędra, Bogusław

    2015-05-01

    Ectopic pancreas is a rare congenital disorder defined as pancreatic tissue lacking vascular or anatomic communication with the normal body of the pancreas. Most cases of ectopic pancreas are asymptomatic, but it may become clinically evident depending on the size, location and the pathological changes similar to those observed in case of the normal pancreas. It is often an incidental finding and can be located at different sites in the gastrointestinal tract. The most common locations are: the stomach, duodenum or the proximal part of small intestine. The risk of malignancy, bleeding and occlusion are the most serious complications. Despite the development in diagnostics, it still remains a challenge for the clinician to differentiate it from neoplasm. In this report, we described a case of 28-years old woman who presented recurrent epigastric pain. The upper gastrointestinal endoscopy revealed gastrointestinal stromal tumor on the border of the body and antrum of the back wall of great curvature of the stomach. The histopathological examination after surgery showed heterotopic pancreatic tissue. Ectopic pancreas should be considered in the differential diagnosis of gastric mass lesions.

  14. Gastrointestinal stromal tumors: the histology report.

    PubMed

    Dei Tos, Angelo P; Laurino, Licia; Bearzi, Italo; Messerini, Luca; Farinati, Fabio

    2011-03-01

    Gastrointestinal stromal tumors (GISTs) represent a mesenchymal neoplasm occurring primarily in the gastrointestinal tract, and showing differentiation toward the interstitial cell of Cajal. Its incidence is approximately 15 case/100,000/year. Stomach and small bowel are the most frequently affected anatomic sites. GIST represents a morphological, immunophenotypical and molecular distinct entity, the recognition of which has profound therapeutic implications. In fact, they have shown an exquisite sensitivity to treatment with the tyrosine kinase inhibitor imatinib. Diagnosis relies upon morphology along with immunodetection of KIT and/or DOG1. When dealing with KIT negative cases, molecular analysis of KIT/PDGFRA genes may help in confirming diagnosis. Molecular evaluation of both genes are in any case recommended as mutational status provides key predictive information. Pathologists also play a key role in providing an estimation of the risk of biological aggressiveness, which is currently based on anatomic location of the tumor, size, and mitotic activity.

  15. Laparoscopic resection of duodenal gastrointestinal stromal tumour

    PubMed Central

    Zioni, Tammy; Dizengof, Vitaliy; Kirshtein, Boris

    2017-01-01

    Only a few studies have revealed using laparoscopic technique with limited resection of gastrointestinal stromal tumour (GIST) of the duodenum. A 68-year-old man was admitted to the hospital due to upper gastrointestinal (GI) bleeding. Evaluation revealed an ulcerated, bleeding GI tumour in the second part of the duodenum. After control of bleeding during gastroduodenoscopy, he underwent a laparoscopic wedge resection of the area. During 1.5 years of follow-up, the patient is disease free, eats drinks well, and has regained weight. Surgical resection of duodenal GIST with free margins is the main treatment of this tumour. Various surgical treatment options have been reported. Laparoscopic resection of duodenal GIST is an advanced and challenging procedure requiring experience and good surgical technique. The laparoscopic limited resection of duodenal GIST is feasible and safe, reducing postoperative morbidity without compromising oncologic results. PMID:28281485

  16. Imatinib treatment for gastrointestinal stromal tumour (GIST).

    PubMed

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins.

  17. Imatinib treatment for gastrointestinal stromal tumour (GIST)

    PubMed Central

    Lopes, Lisandro F; Bacchi, Carlos E

    2010-01-01

    Abstract Gastrointestinal stromal tumour (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. GISTs are believed to originate from intersticial cells of Cajal (the pacemaker cells of the gastrointestinal tract) or related stem cells, and are characterized by KIT or platelet-derived growth factor receptor alpha (PDGFRA) activating mutations. The use of imatinib has revolutionized the management of GIST and altered its natural history, substantially improving survival time and delaying disease progression in many patients. The success of imatinib in controlling advanced GIST led to interest in the neoadjuvant and adjuvant use of the drug. The neoadjuvant (preoperative) use of imatinib is recommended to facilitate resection and avoid mutilating surgery by decreasing tumour size, and adjuvant therapy is indicated for patients at high risk of recurrence. The molecular characterization (genotyping) of GISTs has become an essential part of the routine management of the disease as KIT and PDGFRA mutation status predicts the likelihood of achieving response to imatinib. However, the vast majority of patients who initially responded to imatinib will develop tumour progression (secondary resistance). Secondary resistance is often related to secondary KIT or PDGFRA mutations that interfere with drug binding. Multiple novel tyrosine kinase inhibitors may be potentially useful for the treatment of imatinib-resistant GISTs as they interfere with KIT and PDGFRA receptors or with the downstream-signalling proteins. PMID:19968734

  18. Update on Gastrointestinal Stromal Tumors for Radiologists

    PubMed Central

    Baheti, Akshay D.; Tirumani, Harika; O'Neill, Ailbhe; Jagannathan, Jyothi P.

    2017-01-01

    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. PMID:28096720

  19. Targeted therapy of gastrointestinal stromal tumours

    PubMed Central

    Jakhetiya, Ashish; Garg, Pankaj Kumar; Prakash, Gaurav; Sharma, Jyoti; Pandey, Rambha; Pandey, Durgatosh

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are mesenchymal neoplasms originating in the gastrointestinal tract, usually in the stomach or the small intestine, and rarely elsewhere in the abdomen. The malignant potential of GISTs is variable ranging from small lesions with a benign behaviour to fatal sarcomas. The majority of the tumours stain positively for the CD-117 (KIT) and discovered on GIST-1 (DOG-1 or anoctamin 1) expression, and they are characterized by the presence of a driver kinase-activating mutation in either KIT or platelet-derived growth factor receptor α. Although surgery is the primary modality of treatment, almost half of the patients have disease recurrence following surgery, which highlights the need for an effective adjuvant therapy. Traditionally, GISTs are considered chemotherapy and radiotherapy resistant. With the advent of targeted therapy (tyrosine kinase inhibitors), there has been a paradigm shift in the management of GISTs in the last decade. We present a comprehensive review of targeted therapy in the management of GISTs. PMID:27231512

  20. Gastrointestinal stromal tumors (GISTs) and second malignancies

    PubMed Central

    Rodriquenz, Maria Grazia; Rossi, Sabrina; Ricci, Riccardo; Martini, Maurizio; Larocca, Mario; Dipasquale, Angelo; Quirino, Michela; Schinzari, Giovanni; Basso, Michele; D’Argento, Ettore; Strippoli, Antonia; Barone, Carlo; Cassano, Alessandra

    2016-01-01

    Abstract Several evidences showed that patients with gastrointestinal stromal tumors (GISTs) develop additional malignancies. However, thorough incidence of second tumors remains uncertain as the possibility of a common molecular pathogenesis. A retrospective series of 128 patients with histologically proven GIST treated at our institution was evaluated. Molecular analysis of KIT and PDGFR-α genes was performed in all patients. Following the involvement of KRAS mutation in many tumors’ pathogenesis, analysis of KRAS was performed in patients with also second neoplasms. Forty-six out of 128 GIST patients (35.9%) had a second neoplasm. Most second tumors (52%) raised from gastrointestinal tract and 19.6% from genitourinary tract. Benign neoplasms were also included (21.7%). Molecular analysis was available for 29/46 patients with a second tumor: wild-type GISTs (n. 5), exon 11 (n. 16), exon 13 (n. 1), exon 9 (n. 1) KIT mutations, exon 14 PDGFR-α mutation (n. 2) and exon 18 PDGFR-α mutation (n. 4). KIT exon 11 mutations were more frequent between patients who developed a second tumor (P = 0.0003). Mutational analysis of KRAS showed a wild-type sequence in all cases. In metachronous cases, the median time interval between GIST and second tumor was 21.5 months. The high frequency of second tumors suggests that an unknown common molecular mechanism might play a role, but it is not likely that KRAS is involved in this common pathogenesis. The short interval between GIST diagnosis and the onset of second neoplasms asks for a careful follow-up, particularly in the first 3 years after diagnosis. PMID:27661019

  1. LAPAROSCOPIC RESECTION OF GASTROINTESTINAL STROMAL TUMORS (GIST)

    PubMed Central

    LOUREIRO, Marcelo de Paula; de ALMEIDA, Rômulo Augusto Andrade; CLAUS, Christiano Marlo Paggi; BONIN, Eduardo Aimoré; CURY-FILHO,, Antônio Moris; DIMBARRE, Daniellson; da COSTA, Marco Aurélio Raeder; VITAL, Marcílio Lisboa

    2016-01-01

    Background Gastrointestinal mesenchymal or stromal tumors (GIST) are lesions originated on digestive tract walls, which are treated by surgical resection. Several laparoscopic techniques, from gastrectomies to segmental resections, have been used successfully. Aim Describe a single center experience on laparoscopic GIST resection. Method Charts of 15 operated patients were retrospectively reviewed. Thirteen had gastric lesions, of which ten were sub epithelial, ranging from 2-8 cm; and three were pure exofitic growing lesions. The remaining two patients had small bowel lesions. Surgical laparoscopic treatment consisted of two distal gastrectomies, 11 wedge gastric resections and two segmental enterectomies. Mechanical suture was used in the majority of patients except on six, which underwent resection and closure using manual absorbable sutures. There were no conversions to open technique. Results Mean operative time was 1h 29 min±92 (40-420 min). Average lenght of hospital stay was three days (2-6 days). There were no leaks, postoperative bleeding or need for reintervention. Mean postoperative follow-up was 38±17 months (6-60 months). Three patients underwent adjuvant Imatinib treatment, one for recurrence five months postoperatively and two for tumors with moderate risk for recurrence . Conclusion Laparoscopic GIST resection, not only for small lesions but also for tumors above 5 cm, is safe and acceptable technique. PMID:27120729

  2. Giant gastrointestinal stromal tumor of the stomach.

    PubMed

    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.

  3. Intestinal gastrointestinal stromal tumor in a cat

    PubMed Central

    SUWA, Akihisa; SHIMODA, Tetsuya

    2017-01-01

    A 12-year-old, 3.6-kg, spayed female domestic shorthaired cat had a 2-month history of anorexia and weight loss. Abdominal ultrasonography and computed tomography revealed an exophytic mass originating from the jejunum with very poor central and poor peripheral contrast enhancement. On day 14, surgical resection of the jejunum and mass with 5-cm margins and an end-to-end anastomosis were performed. Histopathological examination revealed the mass was a transmural, invasive cancer showing exophytic growth and originating from the small intestinal muscle layer. Immunohistochemical analysis of tumor cells revealed diffuse positivity for KIT protein and negativity for desmin and S-100. The mass was diagnosed as a gastrointestinal stromal tumor (GIST). Ultrasonographic findings indicated the tumor probably metastasized to the liver and omentum, as seen in humans and dogs. The owner rejected further treatment at the last visit on day 192. To our knowledge, this is the first report of intestinal tumor and metastasis in feline GIST and its imaging features. PMID:28163271

  4. Gastrointestinal and Extragastrointestinal Stromal Tumors: Report of Two Cases and Review of the Literature

    PubMed Central

    Antonopoulos, Petros; Leonardou, Polytimi; Barbagiannis, Nikolaos; Alexiou, Konstantinos; Demonakou, Maria; Economou, Nikolaos

    2014-01-01

    We present two cases, one of a gastrointestinal stromal tumor (GIST) in the stomach and one of an extragastrointestinal stromal tumor (EGIST) in the hepatogastric ligament, which were discovered as incidental findings during computed tomography (CT) scans performed for other reasons. In both cases the diagnosis of the tumor was confirmed histologically and immunohistochemically. During the follow-up CT examinations these tumors proved to have a completely different natural course. The first case refers to an 82-year-old male patient with GIST of the stomach who refused to be operated and was followed by CT scans for a 4-year period. This patient did not show any significant changes in the morphology, size and density of the lesion. The second case refers to a 58-year-old female patient with EGIST of the hepatogastric ligament who presented with simultaneous liver metastases and remained healthy for 2 years after surgical resection, but developed local recurrence later. As a conclusion, both GISTs/EGISTs can be revealed as incidental findings in a CT scan performed for other purposes. Moreover, an untreated GIST located in the stomach can remain unchanged and without metastatic lesions for a long period of time, as in our case for a 4-year period. To our knowledge, this is the first report in the literature in whom a GIST was proved to remain almost unchanged for many years without any treatment, and we therefore attempt a further review of the current literature on stromal tumors. PMID:24707244

  5. Atypical presentation of gastrointestinal stromal tumours-a case report.

    PubMed

    Raja, Kalpana; Dev, Bhawna; Santosham, Roy; Santhosh, Joseph

    2013-06-01

    Gastrointestinal stromal tumors (GISTs) are benign mesenchymal tumors of the gastrointestinal tract (GIT). Their clinical presentations are variable. We report a case of a 31-year-old man who presented with pain in the abdomen and vomiting. CT abdomen revealed a large exophytic mass in the epigastrium with enhancement pattern similar to hemangioma. No relationship of the mass could be made out with the adjacent structures on CT, histopathology proved it to be a GIST.

  6. Spontaneous Perforation as a First Presentation of Ileal Gastrointestinal Stromal Tumour (GIST) with Synchronous Breast Sarcoma.

    PubMed

    Sharma M, Bir Kumar; Barad, Arun Kumar; Padu, Kemba; Singh K, Sridartha; Singh Th, Sudhir Chandra

    2014-05-01

    Gastrointestinal Stromal Tumours (GIST's) are the most common mesenchymal neoplasms of the gastrointestinal tract. Majority of the GISTs are asymptomatic and often diagnosis is incidental. Synchronous second malignancies have been reported in patients with GIST. We report a case of 50-year-old female presenting with features of hollow viscous perforation, found to have ileal GIST with perforations along with a synchronous breast sarcoma. GIST with spontaneous perforation as its first clinical manifestation is rare. Synchronous occurrence of an ileal GIST with a breast sarcoma is unique and deserves reporting. This case report highlights the varied nature of clinical presentation of the GIST and also stresses on the importance of extensive search for the synchronous second malignancies in the extra abdominal sites as well.

  7. Synchronous gastric gastrointestinal stromal tumor (GIST) and other primary neoplasms of gastrointestinal tract: report of two cases.

    PubMed

    Kaur, Ramneet; Bhalla, Sunita; Nundy, Samiran; Jain, Sunila

    2013-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasms of the gastrointestinal tract with a malignant potential. However, uncommonly they can be associated with synchronous tumors of different histogenesis. We herein report two cases of gastric GIST with synchronous tumors. The first case is of a 50-year-old male patient who was suspected with GIST of stomach and was incidentally found to have an associated duodenal neuroendo-crine neoplasm. The second case is of a 62-year-old male who, while undergoing surgery for a primary colon adenocarcinoma, was incidentally detected to have a coexistent gastric GIST initially suspected to be a metastatic nodule. Coexistence of gastric GIST with neuroendocrine tumor is extremely rare. To the best of our knowledge this is the second case of gastric GIST coexisting with duodenal neuroendocrine tumor to be reported in the literature. Similarly, association of GIST with adenocarcinoma is uncommon. We herein analyze the pathological findings of two such cases, and we review the malignant potential of these synchronous tumors.

  8. Molecular diagnostics in soft tissue sarcomas and gastrointestinal stromal tumors.

    PubMed

    Smith, Stephen M; Coleman, Joshua; Bridge, Julia A; Iwenofu, O Hans

    2015-04-01

    Soft tissue sarcomas are rare malignant heterogenous tumors of mesenchymal origin with over fifty subtypes. The use of hematoxylin and eosin stained sections (and immunohistochemistry) in the morphologic assessment of these tumors has been the bane of clinical diagnosis until recently. The last decade has witnessed considerable progress in the understanding and application of molecular techniques in refining the current understanding of soft tissue sarcomas and gastrointestinal stromal tumors beyond the limits of traditional approaches. Indeed, the identification of reciprocal chromosomal translocations and fusion genes in some subsets of sarcomas with potential implications in the pathogenesis, diagnosis and treatment has been revolutionary. The era of molecular targeted therapy presents a platform that continues to drive biomarker discovery and personalized medicine in soft tissue sarcomas and gastrointestinal stromal tumors. In this review, we highlight how the different molecular techniques have enhanced the diagnosis of these tumors with prognostic and therapeutic implications.

  9. Meckel Diverticulum Harboring a Rare Gastrointestinal Stromal Tumor

    PubMed Central

    Berry, Andrew C.; Nakshabendi, Rahman; Kanar, Ozdemir; Hamer, Sean

    2017-01-01

    Background: Tumors within a Meckel diverticulum are a rare complication observed in only 0.5%-3.2% of symptomatic cases. The majority of tumors are benign, but some malignant tumors, such as gastrointestinal stromal tumors (GISTs) can occur. Case Report: We report the case of a 48-year-old female who presented with severe abdominal pain and nausea and was found to have a GIST arising from a Meckel diverticulum. Conclusion: The differential diagnosis of a pelvic mass in a middle-aged female presenting with gastrointestinal symptoms must remain broad. With an atypical presentation site, distinguishing benign tumors from malignant tumors such as GISTs is of paramount importance. PMID:28331460

  10. [Gastrointestinal stromal tumors: case reports and review of the literature].

    PubMed

    Bronzino, P; Colombini, M; Ferro, A; Gambetta, G; Gennaro, M; Ivaldi, L; Revetria, P

    2008-01-01

    The Authors describe four cases of gastrointestinal stromal tumours (GIST) two of them were localized in the stomach, the others in the ileum. GIST are neoplasms of mesenchymal origin which develop inside the wall of the digestive tract. The most frequent site is the stomach, followed by the small bowel; less commonly these tumors can affect the oesophagus, the colon and the rectum. GIST originate from precursors of the interstitial cells of Cajal, which are localized in the gastro-intestinal wall and are involved in the regulation of the peristalsis. The treatment is surgical resection. For advanced disease there is a new interesting treatment based on the imatinib, a tyrosine kinase inhibitor.

  11. Diagnosis and treatment of gastrointestinal stromal tumor extending to prostate

    PubMed Central

    Xu, Huan; Liu, Chong; Chen, Yanbo; Gu, Meng; Cai, Zhikang; Chen, Qi; Wang, Zhong

    2016-01-01

    Abstract Rationale: Gastrointestinal stromal tumor (GIST) is the neoplasm of gastrointestinal tract. Patient concerns: The patient complained about the retention of urinary. Diagnoses: GIST. Interventions: radical prostatectomy and the imatinib therapy. Outcomes: No recurrence and metastasis have been found during a 14-month follow-up. Lessons: comprehensive treatment is necessary for the GIST treatment. Furthermore, we summarize a review of the literature of GIST occurring in the prostate gland treated by different methods and 4 kinds of rare diseases in prostate. PMID:27861390

  12. Giant rectal gastrointestinal stromal tumours: a diagnostic and therapeutic challenge

    PubMed Central

    Alder, L.S.; Elver, G.; Foo, F.J.; Dobson, M.

    2013-01-01

    Gastrointestinal stromal tumour (GIST are the most common mesenchymal tumours; however, rectal GISTs account for <5%. In the pelvis they represent a diagnostic challenge with giant GISTs likely to be malignant. They may present with urological, gynaecological or rectal symptoms. Sphincter-preserving surgery can be aided by neoadjuvant therapy. We present an uncommon case of giant rectal GIST masquerading as acute urinary retention. PMID:24968434

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

    PubMed Central

    Yamamoto, Mami; Yamamoto, Kentaroh; Taketomi, Hirotaka; Yamamoto, Fumio; Yamamoto, Hiroshi

    2016-01-01

    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. PMID:27920659

  14. Gastrointestinal Stromal Tumor Arising From a Gastric Duplication Cyst

    PubMed Central

    Machicado, Jorge; Davogustto, Giovanni

    2016-01-01

    Gastric duplication cysts (GDC) are rarely diagnosed in adults, but previous cases have been associated with malignancy. We present a case of gastrointestinal stromal tumor (GIST) arising from a GDC in a 71-year-old woman who presented with 3 years of early satiety, anorexia, abdominal distention, and weight loss. Abdominal CT showed a 9.3 x 5.2 x 9.5-cm well-circumscribed cystic mass arising 3 cm above the gastroduodenal junction. The cyst was resected, and histopathology was consistent with GDC. Future studies are needed to clarify the malignant potential of GDC and the molecular pathways for its development. PMID:27144196

  15. Primary gastrointestinal stromal tumor of the liver: A case report

    PubMed Central

    Luo, Xiao-Li; Liu, Dan; Yang, Jian-Jun; Zheng, Min-Wen; Zhang, Jing; Zhou, Xiao-Dong

    2009-01-01

    We report a case of primary gastrointestinal stromal tumor (GIST) of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound (CEUS) revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography (CT) showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CD117. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT. PMID:19653356

  16. Heterotopic Pancreatic Pseudocyst Radiologically Mimicking Gastrointestinal Stromal Tumor

    PubMed Central

    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

  17. Mesenteric gastrointestinal stromal tumour presenting as intracranial space occupying lesion

    PubMed Central

    Puri, Tarun; Gunabushanam, Gowthaman; Malik, Monica; Goyal, Shikha; Das, Anup K; Julka, Pramod K; Rath, Goura K

    2006-01-01

    Background Gastrointestinal stromal tumours (GIST) usually present with non-specific gastrointestinal symptoms such as abdominal mass, pain, anorexia and bowel obstruction. Methods We report a case of a 42 year old male who presented with a solitary intracranial space occupying lesion which was established as a metastasis from a mesenteric tumour. Results The patient was initially treated as a metastatic sarcoma, but a lack of response to chemotherapy prompted testing for CD117 which returned positive. A diagnosis of mesenteric GIST presenting as solitary brain metastasis was made, and the patient was treated with imatinib. Conclusion We recommend that all sarcomas with either an intraabdominal or unknown origin be routinely tested for CD117 to rule out GIST. PMID:17105654

  18. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

    PubMed Central

    Kindblom, L. G.; Remotti, H. E.; Aldenborg, F.; Meis-Kindblom, J. M.

    1998-01-01

    The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 PMID:9588894

  19. A gist of gastrointestinal stromal tumors: A review

    PubMed Central

    Rammohan, Ashwin; Sathyanesan, Jeswanth; Rajendran, Kamalakannan; Pitchaimuthu, Anbalagan; Perumal, Senthil-Kumar; Srinivasan, UP; Ramasamy, Ravi; Palaniappan, Ravichandran; Govindan, Manoharan

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive tumor type, different from smooth muscle and neural tumors of the gastrointestinal tract (GIT). They constitute the majority of gastrointestinal mesenchymal tumors of the GIT and are known to be refractory to conventional chemotherapy or radiation. They are defined and diagnosed by the expression of a proto-oncogene protein detected by immunohistochemistry which serves as a crucial diagnostic and therapeutic target. The identification of these mutations has resulted in a better understanding of their oncogenic mechanisms. The remarkable antitumor effects of the molecular inhibitor imatinib have necessitated accurate diagnosis of GIST and their distinction from other gastrointestinal mesenchymal tumors. Both traditional and minimally invasive surgery are used to remove these tumors with minimal morbidity and excellent perioperative outcomes. The revolutionary use of specific, molecularly-targeted therapies, such as imatinib mesylate, reduces the frequency of disease recurrence when used as an adjuvant following complete resection. Neoadjuvant treatment with these agents appears to stabilize disease in the majority of patients and may reduce the extent of surgical resection required for subsequent complete tumor removal. The important interplay between the molecular genetics of GIST and responses to targeted therapeutics serves as a model for the study of targeted therapies in other solid tumors. This review summarizes our current knowledge and recent advances regarding the histogenesis, pathology, molecular biology, the basis for the novel targeted cancer therapy and current evidence based management of these unique tumors. PMID:23847717

  20. Characteristics of gastrointestinal stromal tumours, diagnostic procedure and therapeutic management and main directions of nursing practice in gastrointestinal stromal tumours

    PubMed Central

    Głuszek, Stanisław; Kozieł, Dorota

    2014-01-01

    Gastrointestinal stromal tumours (GIST) constitute a separate group of mesenchymal neoplasms of the gastrointestinal tract. They have been commonly recognized for a few years, they have created a new problem in medical practice. GIST are more often centred in the stomach. They equally affect female and male patients and occur mainly in patients older than 50 years of age. The clinical picture of the tumour is non-specific. Radical surgical treatment and molecularly targeted therapy with tyrosine kinase inhibitors are used in GIST treatment. Nursing practice with reference to GIST danger is connected with biopsychosocial interventions of perioperative, oncological and palliative procedures and involves the area of health education mainly oriented towards shaping preventive procedures which favour early disease detection and support therapy and recovery. PMID:25784835

  1. [A rare case of bone metastasis from gastro-intestinal stromal tumour: place of radiotherapy].

    PubMed

    Heymann, S; Imperiale, A; Schlund-Schoettel, E; Sauer, B; Dourthe, L-M

    2014-01-01

    Gastro-intestinal stromal tumours are the most common mesenchymal neoplasms of the gastrointestinal tract. Their usual metastatic sites are the liver and the peritoneum, but gastro-intestinal stromal tumours rarely metastasize to the bones. We report the case of a 56-year-old male presenting with bone lesions six years after initial surgical resection. We discuss through this paper the possibilities of management of these lesions and the place of radiotherapy.

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

    PubMed Central

    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

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

    PubMed

    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.

  4. Paraneoplastic Hypoglycaemia: A Rare Manifestation of Pelvic Gastrointestinal Stromal Tumour

    PubMed Central

    Hadi, Rahat; Mehrotra, Kiranpreet; Rastogi, Shivani; Masood, Shakeel

    2017-01-01

    Non-Islet Cell Tumour Induced Hypoglycaemia (NICTH), presenting with recurrent fasting hypoglycaemia is a very rare paraneoplastic syndrome. It usually presents with large metastatic mesenchymal tumours. NICTH secondary to Gastrointestinal Stromal Tumour (GIST) is even rarer. Diagnosis of NICTH is based on the low serum insulin level, low serum concentrations of Insulin Like Growth Factor (IGF-I) and IGF binding protein- III (IGFBP-III) in combination with elevated concentrations of pro-IGF-II. Various Immunohistochemical (IHC) markers are integral to diagnosis of GIST namely 2-deoxyglucose-6-phosphate phosphatase -1(DOG-1), Cluster Differentiation 34 (CD 34), Cluster Differentiation 117 (CD117). The management requires prompt intravenous hydration and glucose infusions followed by surgical resection. We hereby, report a rare case of a 65-year-old female with intractable fasting hypoglycaemia due to overproduction of "big" insulin-like growth factor II diagnosed to have pelvic GIST and managed by Steroids and Imatinib.

  5. CCI-779 in Treating Patients With Soft Tissue Sarcoma or Gastrointestinal Stromal Tumor

    ClinicalTrials.gov

    2013-06-03

    Gastrointestinal Stromal Tumor; Recurrent Adult Soft Tissue Sarcoma; Stage I Adult Soft Tissue Sarcoma; Stage II Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

  6. CT Features of Colorectal Schwannomas: Differentiation from Gastrointestinal Stromal Tumors

    PubMed Central

    Kang, Ji Hee; Kim, Se Hyung; Kim, Young Hoon; Rha, Sung Eun; Hur, Bo Yun; Han, Joon Koo

    2016-01-01

    Purpose To find differential CT features of colorectal schwannomas from gastrointestinal stromal tumors (GISTs). Materials and Methods CT features of 13 pathologically proven colorectal schwannomas and 21 GISTs were retrospectively reviewed. The following CT items were analyzed: size, longitudinal and transverse location, shape, margin, homogeneity, necrosis, surface ulceration, calcification, degree of attenuation, the presence of enlarged lymph node (LN), and metastasis. Among the features, significant variables were evaluated using univariate statistical tests. The optimal cut-off point of tumor size was obtained by ROC analysis. Binary logistic regression analysis was used to find the most independent CT variables. Results Small size, non-rectum location, smooth margin, homogeneous high attenuation without necrosis, and the presence of enlarged LNs were found to be significant variables to differentiate schwannomas from GISTs (P<0.05). The optimized cut-off point for tumor size in distinguishing GISTs from schwannomas was 3.9 cm (AUC = 0.808, sensitivity = 66.7%, specificity = 92.3%, P<0.0001). Binary regression analysis revealed that only non-rectum location remained independent predictor for schwannomas differentiated from GISTs (odds ratio = 31.667, P = 0.001). Conclusion Colorectal schwannomas usually located in non-rectum and appear as small subepithelial nodules showing homogeneous high attenuation and smooth margin. Schwannomas exclusively accompany with enlarged LNs. PMID:28005903

  7. [Gastrointestinal stromal tumors (GIST): at the forefront of targeted therapies].

    PubMed

    Emile, Jean-François

    2013-01-01

    Although gastrointestinal stromal tumors (GIST) are the most frequent sarcomas, they were usually not diagnosed before 1998. GIST derive from interstitial cells of Cajal, and may develop along the digestive tract, mainly from stomach and small intestine. GIST are characterized by the expression of KIT (CD117), and mutations KIT or PDGFRA are present in 85 % of cases. More than 150 different types of mutations have been reported. They are responsible for a constitutive activation of these tyrosine kinase receptors, in absence of their specific ligand. Detection of these mutations may help to confirm the diagnosis or to evaluate the prognosis. The mutations also have a predictive value. Indeed patients with metastatic GIST and duplication within exon 9 of KIT deserve to receive twice the dose of imatinib, while GIST with PDGFRA p.D842 V mutation are resistant to this drug. This review presents the main characteristics of GIST, and focus on the important insights of studies on GIST and their cell models in the field of oncology.

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

    PubMed

    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.

  9. Liquid biopsy in gastrointestinal stromal tumors: a novel approach.

    PubMed

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

    2014-08-14

    The role of molecular analysis in the management of gastrointestinal stromal tumors (GIST) remains indisputable. To date, tumor tissue extracted from specimens obtained by surgical or biopsy procedures has been the only source of the tumor DNA required for the molecular and genomic assessment of cancer. However, tumor tissue sampling has several clinical limitations: for example, the invasiveness of these procedures precludes repeated sampling. Thus, it is possible to obtain only a static molecular picture of the disease, a picture that lacks the inter- and intra-metastatic molecular heterogeneity that characterizes most GIST. In contrast, circulating tumor DNA obtained from a patient's bloodstream, known as liquid biopsy, can theoretically overcome the limitations of tissue biopsies and provide the same molecular and genomic information. GIST are recognized as a paradigm of molecular biology among solid tumors. Although few but promising data on liquid biopsy in GIST have been accumulated to date, these tumors may provide the optimal field for application of this challenging approach.

  10. Proapoptotic activity of bortezomib in gastrointestinal stromal tumor cells.

    PubMed

    Bauer, Sebastian; Parry, Joshua A; Mühlenberg, Thomas; Brown, Matthew F; Seneviratne, Danushka; Chatterjee, Payel; Chin, Anna; Rubin, Brian P; Kuan, Shih-Fan; Fletcher, Jonathan A; Duensing, Stefan; Duensing, Anette

    2010-01-01

    Gastrointestinal stromal tumors (GIST) are caused by activating mutations in the KIT or PDGFRA receptor tyrosine kinase genes. Although >85% of GIST patients treated with the small-molecule inhibitor imatinib mesylate (Gleevec) achieve disease stabilization, complete remissions are rare and a substantial proportion of patients develop resistance to imatinib over time. Upregulation of soluble, non-chromatin-bound histone H2AX has an important role in imatinib-induced apoptosis of GIST cells. Additionally, H2AX levels in untreated GIST are maintained at low levels by a pathway that involves KIT, phosphoinositide 3-kinase, and the ubiquitin-proteasome system. In this study, we asked whether bortezomib-mediated inhibition of the ubiquitin-proteasome machinery could lead to upregulation of histone H2AX and GIST cell death. We show that bortezomib rapidly triggers apoptosis in GIST cells through a combination of mechanisms involving H2AX upregulation and loss of KIT protein expression. Downregulation of KIT transcription was an underlying mechanism for bortezomib-mediated inhibition of KIT expression. In contrast, the nuclear factor-kappaB signaling pathway did not seem to play a major role in bortezomib-induced GIST cell death. Significantly, we found that bortezomib would induce apoptosis in two imatinib-resistant GIST cell lines as well as a short-term culture established from a primary imatinib-resistant GIST. Collectively, our results provide a rationale to test the efficacy of bortezomib in GIST patients with imatinib-sensitive or -resistant tumors.

  11. Diagnostic and treatment strategy for small gastrointestinal stromal tumors

    PubMed Central

    Goto, Osamu; Raut, Chandrajit Premanand; Yahagi, Naohisa

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are considered to be potentially malignant mesenchymal tumors of the gastrointestinal tract. Clinically relevant GISTs are rare; however, subclinical GISTs (mini‐GISTs) (1‐2 cm) and pathologic GISTs (micro‐GISTs) (<1 cm) are frequently reported. Most mini‐GISTs and almost all micro‐GISTs of the stomach may exhibit benign clinical behavior, and only mini‐GISTs with high‐risk features may progress. For this review, a provisional algorithm was used to propose diagnostic and treatment strategies for patients with small GISTs. Because surgery is the only potentially curative treatment, in its application for small GISTs, the principles of sarcoma surgery should be maintained, and cost effectiveness should be considered. Indications for surgery include GISTs measuring ≥2 cm, symptomatic GISTs, and mini‐GISTs with high‐risk features (irregular borders, cystic spaces, ulceration, echogenic foci, internal heterogeneity, and tumor progression during follow‐up); however, a preoperative pathologic diagnosis is infrequently obtained. For small intestinal and colorectal GISTs, surgery is indicated irrespective of size because of their greater malignant potential. Otherwise, mini‐GISTs without high‐risk features, micro‐GISTs, and small submucosal tumors measuring <5 cm without high‐risk features may be followed by periodical endoscopic ultrasonography. Although surgical approaches and operative methods are selected according to tumor size, location, growth pattern, and surgical teams, laparoscopic surgery has produced similar oncologic outcomes and is less invasiveness compared with open surgery. After resection, pathologic examination for diagnosis and risk assessment is mandatory, and genotyping is also recommended for high‐risk GISTs. Endoscopic resection techniques, although feasible, are not routinely indicated for most mini‐GISTs or micro‐GISTs. Cancer 2016;122:3110–8. © 2016 The Authors

  12. Recurrent epimutation of SDHC in gastrointestinal stromal tumors.

    PubMed

    Killian, J Keith; Miettinen, Markku; Walker, Robert L; Wang, Yonghong; Zhu, Yuelin Jack; Waterfall, Joshua J; Noyes, Natalia; Retnakumar, Parvathy; Yang, Zhiming; Smith, William I; Killian, M Scott; Lau, C Christopher; Pineda, Marbin; Walling, Jennifer; Stevenson, Holly; Smith, Carly; Wang, Zengfeng; Lasota, Jerzy; Kim, Su Young; Boikos, Sosipatros A; Helman, Lee J; Meltzer, Paul S

    2014-12-24

    Succinate dehydrogenase (SDH) is a conserved effector of cellular metabolism and energy production, and loss of SDH function is a driver mechanism in several cancers. SDH-deficient gastrointestinal stromal tumors (dSDH GISTs) collectively manifest similar phenotypes, including hypermethylated epigenomic signatures, tendency to occur in pediatric patients, and lack of KIT/PDGFRA mutations. dSDH GISTs often harbor deleterious mutations in SDH subunit genes (SDHA, SDHB, SDHC, and SDHD, termed SDHx), but some are SDHx wild type (WT). To further elucidate mechanisms of SDH deactivation in SDHx-WT GIST, we performed targeted exome sequencing on 59 dSDH GISTs to identify 43 SDHx-mutant and 16 SDHx-WT cases. Genome-wide DNA methylation and expression profiling exposed SDHC promoter-specific CpG island hypermethylation and gene silencing in SDHx-WT dSDH GISTs [15 of 16 cases (94%)]. Six of 15 SDHC-epimutant GISTs occurred in the setting of the multitumor syndrome Carney triad. We observed neither SDHB promoter hypermethylation nor large deletions on chromosome 1q in any SDHx-WT cases. Deep genome sequencing of a 130-kbp (kilo-base pair) window around SDHC revealed no recognizable sequence anomalies in SDHC-epimutant tumors. More than 2000 benign and tumor reference tissues, including stem cells and malignancies with a hypermethylator epigenotype, exhibit solely a non-epimutant SDHC promoter. Mosaic constitutional SDHC promoter hypermethylation in blood and saliva from patients with SDHC-epimutant GIST implicates a postzygotic mechanism in the establishment and maintenance of SDHC epimutation. The discovery of SDHC epimutation provides a unifying explanation for the pathogenesis of dSDH GIST, whereby loss of SDH function stems from either SDHx mutation or SDHC epimutation.

  13. Clinicopathologic Features and Clinical Outcomes of Esophageal Gastrointestinal Stromal Tumor

    PubMed Central

    Feng, Fan; Tian, Yangzi; Liu, Zhen; Xu, Guanghui; Liu, Shushang; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-01-01

    Abstract Clinicopathologic features and clinical outcomes of gastrointestinal stromal tumors (GISTs) in esophagus are limited, because of the relatively rare incidence of esophageal GISTs. Therefore, the aim of the current study was to investigate the clinicopathologic features and clinical outcomes of esophageal GISTs, and to investigate the potential factors that may predict prognosis. Esophageal GIST cases were obtained from our center and from case reports and clinical studies extracted from MEDLINE. Clinicopathologic features and survivals were analyzed and compared with gastric GISTs from our center. The most common location was lower esophagus (86.84%), followed by middle and upper esophagus (11.40% and 1.76%). The majority of esophageal GISTs were classified as high-risk category (70.83%). Mitotic index was correlated with histologic type, mutational status, and tumor size. The 5-year disease-free survival and disease-specific survival were 65.1% and 65.9%, respectively. Tumor size, mitotic index, and National Institutes of Health risk classification were associated with prognosis of esophageal GISTs. Only tumor size, however, was the independent risk factor for the prognosis of esophageal GISTs. In comparison to gastric GISTs, the distribution of tumor size, histologic type, and National Institutes of Health risk classification were significantly different between esophageal GISTs and gastric GISTs. The disease-free survival and disease-specific survival of esophageal GISTs were significantly lower than that of gastric GISTs. The most common location for esophageal GISTs was lower esophagus, and most of the esophageal GISTs are high-risk category. Tumor size was the independent risk factor for the prognosis of esophageal GISTs. Esophageal GISTs differ significantly from gastric GISTs in respect to clinicopathologic features. The prognosis of esophageal GISTs was worse than that of gastric GISTs. PMID:26765432

  14. Large gastrointestinal stromal tumours of the stomach: Is laparoscopy reasonable?

    PubMed Central

    Severino, Beatrice Ulloa; Fuks, David; Lainas, Panagiotis; Blain, Antoine; Validire, Pierre; Ferraz, Jean-Marc; Perniceni, Thierry; Gayet, Brice

    2016-01-01

    BACKGROUND: Laparoscopic resection (LR) offers significant advantages compared to open resections for gastric gastrointestinal stromal tumours (GISTs). We aimed to evaluate whether LR outcomes jeopardised short and long-term outcomes of patients with large GISTs. PATIENTS AND METHODS: Among 50 patients undergoing surgery for gastric GISTs, 12 underwent LR for large GISTs (>5 cm). Their characteristics, perioperative results and survival were retrospectively compared to those of 22 patients who underwent LR for ‘small GIST’. RESULTS: The two groups were similar regarding demographics, rate of wedge resection and mean blood loss. No patient required transfusion or conversion. Operative time was significantly increased in the ‘large GIST’ group (160 min vs 112 min, P = 0.001). Mean tumour size was significantly lower in the ‘small GIST’ group (8.4 cm vs 2.4 cm, P = 0.0001). Resection margins were negative. The mortality rate was nil and the overall morbidity rates was similar in both groups. Median length of hospital stay was significantly increased in the ‘large GIST’ group (7 days vs 5 days, P = 0.004). Median follow-up was 47 months and one patient in the ‘small GIST’ group developed recurrence and died during follow-up 11 years after surgery. No patient died during follow-up. CONCLUSIONS: LR for large GISTs is safe and technically feasible and does not negatively influence the oncologic course. Prospective randomised trials should be performed before using this approach in routine surgical care. PMID:27073308

  15. Endometrial Stromal Sarcoma Presented as an Incidental Lung Mass with Multiple Pulmonary Nodules

    PubMed Central

    Kang, Dong Oh; Choi, Sue In; Oh, Jee Youn; Sim, Jae Kyeom; Choi, Jong Hyun; Choo, Ji Yung; Hwang, Jin Wook; Lee, Seung Heon; Lee, Ju-Han; Lee, Ki Yeol; Shin, Chol

    2014-01-01

    Low-grade endometrial stromal sarcoma (ESS) is an uncommon gynecologic malignancy of mesodermal origin. Pulmonary metastasis of low-grade ESS can occur years and decades after the treatment of the primary disease. Low-grade ESS is frequently mistaken as benign uterine neoplasm like uterine leiomyoma, which can potentially lead to a misdiagnosis. We present a case of a 42-year-old woman with low-grade ESS, that initially presented as an incidental lung mass with multiple pulmonary nodules, seven years after an uterine myomectomy. A 6.9×5.8 cm-sized intrapelvic mass suspected of uterine origin was discovered while searching for potential extrathoracic primary origin. A pelviscopy and simultaneous thoracoscopic lung biopsy were conducted for pathologic diagnosis. Finally, the diagnosis was confirmed as low-grade ESS with lung metastasis based on the histopathologic examination with immunohistochemical stain, which was showed positive for CD10 and hormone receptor markers (estrogen and progesterone receptors) in both pelvic and lung specimens. PMID:24734101

  16. Concurrent gastrointestinal stromal tumor and digestive tract carcinoma: a single institution experience in China

    PubMed Central

    Zhang, Peng; Deng, Rui; Xia, Zefeng; Shuai, Xiaoming; Chang, Weilong; Gao, Jinbo; Wang, Guobin; Tao, Kaixiong

    2015-01-01

    The aim of this study was to review the clinicopathological characteristics and survival outcomes of patients with concurrent gastrointestinal stromal tumor (GIST) and digestive tract carcinoma. Among 585 patients diagnosed with GIST from January 2005 to July 2014, 32 (5.5%) had synchronous digestive tract carcinoma, including 19 (59.4%) men and 13 (40.6%) women. The median age was 64 years (range, 43-84). GIST was located in the stomach (n=24), small intestine (n=6), duodenum (n=1) and retroperitoneum (n=1). GISTs were intra- or postoperatively discovered (n=28) or preoperatively identified (n=4). The tumor size was less than 10 mm (microGIST) in 23 (71.9%) GIST patients. The preoperatively identified GIST subgroup showed a significantly larger tumor size, more mitotic figures and a higher risk grade than the intra- or postoperatively identified GIST subgroup. Concurrent digestive tract carcinomas were most frequently located in the stomach (24 cases, 75%). The other involved sites were the esophagus (n=5), duodenum (n=2) and colon (n=1). With a median follow-up of 32 months (range, 9-80), 24 patients were alive without evidence of disease, 6 patients had died of carcinoma progression, 1 patient had died from an accident, and 1 patient experienced GIST metastasis to the liver. In summary, we discovered that 5.5% of GIST patients also developed a concurrent digestive tract carcinoma in a series of 585 GIST cases. The majority of GISTs are incidentally identified microGISTs. The concurrent carcinoma seems to have a greater unfavorable effect on prognosis than the GIST. However, for a GIST that is identified preoperatively with a high risk of progression, adjuvant therapy is warranted. PMID:26885079

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

    PubMed

    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

  18. Immune cells in primary and metastatic gastrointestinal stromal tumors (GIST).

    PubMed

    Cameron, Silke; Gieselmann, Marieke; Blaschke, Martina; Ramadori, Giuliano; Füzesi, Laszlo

    2014-01-01

    We have previously described immune cells in untreated primary gastrointestinal stromal tumors (GIST). Here we compare immune cells in metastatic and primary GIST, and describe their chemoattractants. For this purpose, tissue microarrays from 196 patients, 188 primary and 51 metastasized GIST were constructed for paraffin staining. Quantitative analysis was performed for cells of macrophage lineage (Ki-M1P, CD68), T-cells (CD3, CD56) and B-cells (CD20). Chemokine gene-expression was evaluated by real-time RT-PCR. Immuno-localisation was verified by immunofluorescence. Ki-M1P+ cells were the predominant immune cells in both primary and metastatic GIST (2 8.8% ± 7.1, vs. 26.7% ± 6.3). CD68+ macrophages were significantly fewer, with no significant difference between primary GIST (3.6% ± 2.1) and metastases (4.6% ± 1.5). CD3+ T-cells were the most dominant lymphocytes with a significant increase in metastases (7.3% ± 2.3 vs. 2.2% ± 1.8 in primary GIST, P < 0.01). The percentage of CD56+ NK-cells was 1.1% ± 0.9 in the primary, and 2.4 ± 0.7 (P < 0.05) in the metastases. The number of CD20+ B-cells was generally low with 0.6% ± 0.7 in the primary and 1.8% ± 0.3 (P < 0.05) in the metastases. Analysis of the metastases showed significantly more Ki-M1P+ cells in peritoneal metastases (31.8% ± 7.4 vs. 18.2% ± 3.7, P < 0.01), whilst CD3+ T-cells were more common in liver metastases (11.7% ± 1.8 vs. 4.4% ± 2.6, P < 0.01). The highest transcript expression was seen for monocyte chemotactic protein 1 (MCP1/CCL2), macrophage inflammatory protein 1α (MIP-1α/CCL3) and the pro-angiogenic growth-related oncoprotein 1 (Gro-α/CXCL-1). Whilst the ligands were predominantly expressed in tumor cells, their receptors were mostly present in immune cells. This locally specific microenvironment might influence neoplastic progression of GIST at the different metastatic sites.

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

    PubMed Central

    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

  20. A Foregut Duplication Cyst of the Stomach in Association with a Gastrointestinal Stromal Tumor and a Leiomyoma: A Case Report

    PubMed Central

    Gagné, Andréanne; Sazonova, Olga; Marceau, Simon; Périgny, Martine

    2016-01-01

    Objectives. Duplication cysts are rare benign lesions usually arising in the gastrointestinal tract. We report a case of a 52-year-old woman with an incidental gastric mass found on computed tomography during a pregraft workup for a familial cardiomyopathy. Methods. The mass was completely excised by partial gastrectomy and gross examination revealed a cystic lesion containing two small solid nodules in its wall. Microscopic evaluation and immunohistochemistry study were performed to further characterize the cyst and the nodules. A comprehensive literature review of the NCBI database PubMed was also carried out. Results. While the cyst was diagnosed as a foregut duplication cyst, the solid nodules proved to be concomitant gastrointestinal stromal tumor (GIST) and leiomyoma. Both morphologic features and immunohistochemistry stains, including CD117, smooth muscle actin, and CD34 supported the diagnosis. Clinical course was benign and the patient had no clinical evidence of relapse ten months following the surgical procedure. The literature search did not reveal any other published case of a foregut duplication cyst presenting in combination with a GIST and a leiomyoma. Conclusions. To our knowledge, this is the first case of a composite lesion comprising a foregut duplication cyst of the stomach along with a leiomyoma and a GIST. PMID:28097030

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

    PubMed

    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.

  2. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report

    PubMed Central

    Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-01-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols. PMID:27042477

  3. Synchronous Appearance of Adenocarcinoma and Gastrointestinal Stromal Tumour (GIST) of the Stomach: A Case Report.

    PubMed

    Telugu, Ramesh Babu; Pushparaj, Magesh; Masih, Dipti; Pulimood, Anna

    2016-02-01

    Adenocarcinoma is the most common histological type of gastric tumour, accounting for approximately 95% of all gastric carcinomas. Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms of the digestive tract. Synchronous adenocarcinoma and gastrointestinal stromal tumour (GIST) occurring in the stomach is rare and very few cases have been reported in literature. Synchronous tumours in the stomach are rarely diagnosed preoperatively. A 63-year-old gentleman was diagnosed with a gastric adenocarcinoma on endoscopic biopsy and underwent surgery. Postoperative histopathologic examination revealed 2 synchronous tumours with both adenocarcinoma and GIST. The adenocarcinoma was determined to be the aggressive tumour based on histologic features. GIST was categorized as a very low risk of malignancy, based on its size and mitosis. The patient underwent chemotherapy for adenocarcinoma. He is under follow up and is currently disease free. Careful histopathologic evaluation is required to detect co-existing rare synchronous tumours. Presence of the second tumour may require additional procedures or protocols.

  4. [Gastrointestinal stromal tumors: report of a clinical case and review of the literature].

    PubMed

    Bronzino, P; Cassinelli, G; Arena, E; Rassu, P C; Partipilo, F; Rusca, I; Cuneo, A E; Casaccia, M

    2002-01-01

    In this case report, the Authors describe a case of stromal gastric tumour, in a male 65 years old, who presented gastrointestinal bleeding. Gastro-Intestinal Stromal Tumors (GISTs) are neoplasm with an incidence of 1-3 per cent of the digestive tract malignant neoplasms. The rarity of this disease, its visceral wall localization, the histopathological characteristics make the diagnosis difficult. Moreover there is no correlation between the behaviour of these neoplasms and the histologic features. Surgery represents the main treatment for GISTs based on complete resection, followed by a long-term follow-up. Chemotherapy and radiotherapy don't seem to play a crucial role in the treatment of these neoplasms. A new treatment with inhibitors of the tyrosinekinase is under discussion. Follow-up represents the only way to evaluate the effective behaviour of the disease, due to the lack of classic prognostic factors impact.

  5. Small gastrointestinal stromal tumor in the stomach: identification of precursor for clinical gastrointestinal stromal tumor using c-kit and α-smooth muscle actin expression.

    PubMed

    Mikami, Tetuo; Nemoto, Yuta; Numata, Yoshiko; Hana, Kiyomi; Nakada, Norihiro; Ichinoe, Masaaki; Murakumo, Yoshiki; Okayasu, Isao

    2013-12-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. To find precursors for clinical GISTs of the stomach, small gastric stromal tumors of less than 3 cm were collected and examined immunohistochemically with analysis of the KIT mutation. Sixty-eight of 74 lesions were classified into 4 representative groups according to the expression of c-kit and α-smooth muscle actin (αSMA): group A, c-kit diffusely positive and αSMA negative (18 cases); group B, c-kit diffusely positive and αSMA focally positive (13); group C, c-kit focally positive and αSMA diffusely positive (27); and group D, c-kit negative and αSMA diffusely positive (10). Of the 4 groups, groups A and B of c-kit diffuse expression showed higher cellularity and labeling indices of p27(Kip1) and Ki-67 than did groups C and D of diffuse αSMA expression. Incidence of KIT exon 11 mutation in groups A and B was 86% (25/29), whereas that in groups C and D was 0% (0/20). Small gastric stromal tumors with c-kit diffuse expression were considered precursors for clinical GIST because they were significantly different from c-kit focally positive or negative tumors. The mutation of KIT is considered as an early event in tumorigenesis of GIST.

  6. Pancreatic extra-gastrointestinal stromal tumour masquerading as a bleeding duodenal mass

    PubMed Central

    Wegge, Jacqueline; Bartholomew, David M; Burke, Leandra H; Miller, Lisa A

    2012-01-01

    We describe a 55-year-old man presenting to our institution with a gastrointestinal bleed. He was found to have a 5 cm pancreatic extra-gastrointestinal stromal tumours (EGISTs) eroding into the duodenum and ampulla of Vater. Pancreaticoduodenectomy was performed and the tumour was noted to be positive for CD117 and CD34 with six mitotic figures per 50/high-powered field. At 5 months postoperatively he is receiving treatment with imatinib and doing well. To the best of our knowledge, our patient is only the 18th case reported in the literature to date. PMID:23087281

  7. Clinical activity of regorafenib in PDGFRA-mutated gastrointestinal stromal tumor.

    PubMed

    Grellety, Thomas; Kind, Michèle; Coindre, Jean-Michel; Italiano, Antoine

    2015-11-01

    Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal tumor of the gastrointestinal tract and one of the most frequent sarcoma. Mutually exclusive KIT and PDGFRA mutations are central events in GIST pathogenesis, and their understanding is crucial because specific treatment targeting oncogenic KIT and PDGFRA activation (especially imatinib) has become available. The most frequent PDGFRA mutation (D842V) is associated with primary resistance to imatinib. Data related to regorafenib efficacy in PDGFRA-mutated GIST are lacking. We report here a case report of a prolonged response with regorafenib in a patient with a PDGFRA-mutated GIST.

  8. Skull Metastasis of Gastric Gastrointestinal Stromal Tumor Successfully Managed by Surgery

    PubMed Central

    Park, Inkeun; Chung, Dong Hae; Yoo, Chan Jong; Shin, Dong Bok

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are rare, but are the most common mesenchymal neoplasm of the gastrointestinal tract. The most common sites of metastasis are liver and peritoneum, while bone metastasis is rare. We report on a patient with skull metastasis after seven years of treatment with imatinib for metastatic GIST. She underwent metastasectomy consisting of craniectomy with excision of the mass, and cranioplasty and continued treatment with imatinib and sunitinib, without evidence of cranial recurrence. She died of pneumonia sepsis one year after metastasectomy. Skull metastasis of GIST is a very rare presentation, and an aggressive multidisciplinary approach should be considered whenever possible. PMID:28061498

  9. Gastrointestinal Stromal Tumor Showing Intense Tracer Uptake on PSMA PET/CT.

    PubMed

    Noto, Benjamin; Weckesser, Matthias; Buerke, Boris; Pixberg, Michaela; Avramovic, Nemanja

    2017-03-01

    A 70-year-old man with suspected prostate cancer was referred for Ga-PSMA-HBED-CC PET/CT (short PSMA PET/CT) for staging of tumor extent. Apart from vivid tracer uptake in the prostate gland and osseous metastasis, PSMA PET/CT revealed a large soft tissue mass with calcifications in the left upper abdomen showing intense tracer uptake. Histologic examination revealed the mass to be a gastrointestinal stromal tumor.

  10. Primary gastrointestinal stromal tumor of the liver: A case report and review of the literature

    PubMed Central

    Cheng, Xiaobin; Chen, Dong; Chen, Wenbin; Sheng, Qinsong

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors located in the alimentary tract. A small portion of GISTs are observed in extra-gastrointestinal regions, primarily in the omentum, mesentery and retroperioneum, and these types of GISTs are referred to as extra-gastrointestinal stromal tumors. The present study reports of a patient with unique primary liver GIST. The patient underwent en bloc resection and post-operative administration of imatinib, and subsequently experienced a good prognosis. The present case is followed by a brief review of reported cases of liver GISTs identified in the literature. The literature revealed that primary liver GISTs are usually large in size and possess a high mitotic index, which contributes to malignant characterization, thus classifying these tumors as high-risk. En bloc resection remains the mainstay of treatment for resectable primary liver GISTs. However, the prognosis of these patients is not favorable. Perioperative administration of imatinib may be useful to a certain extent, and interventional therapy, including radiofrequency ablation, should be considered. PMID:27698856

  11. Management of gastrointestinal stromal tumours of limited size: proposals from a French panel of physicians.

    PubMed

    Landi, Bruno; Bouché, Olivier; Guimbaud, Rosine; Aparicio, Thomas; Berger, Anne; Bonvalot, Sylvie; Buecher, Bruno; Blay, Jean-Yves; Boustière, Christian; Coindre, Jean-Marie; Emile, Jean-François; Giovannini, Marc; Lecomte, Thierry; Le Cesne, Axel; Monges, Geneviève; Napoléon, Bertrand; Palazzo, Laurent; Chayvialle, Jean-Alain

    2011-12-01

    A number of guidelines on the management of gastro-intestinal stromal tumours (GISTs) have been published, mostly based on expert consensus. However, these guidelines have generally failed to address the specific problem of GISTs of limited size (i.e. those measuring a few centimetres in diameter) with which gastroenterologists are increasingly confronted. The aim of the present work was to draw up proposals for the diagnosis and treatment of GISTs measuring less than 5 cm in diameter. For this purpose, a number of practical questions were put to a panel of French experts.

  12. Current Concepts in Non-Gastrointestinal Stromal Tumor Soft Tissue Sarcomas: A Primer for Radiologists

    PubMed Central

    Jagannathan, Jyothi P.; O'Neill, Ailbhe; Tirumani, Harika; Tirumani, Sree Harsha

    2017-01-01

    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. PMID:28096721

  13. Gastrointestinal stromal tumors of the stomach with extensive calcification: report of two cases.

    PubMed

    Kim, Hyun-Soo; Sung, Ji-Youn; Park, Won Seo; Kim, Youn Wha

    2012-01-01

    Gastrointestinal stromal tumors (GISTs) can present with focal calcification. However, the presence of extensive calcification that constitutes the major portion of a GIST is extremely rare and can be associated with diagnostic pitfalls. We herein present the first two cases of rare gastric GIST with predominantly calcified components that mimicked pancreatic solid and pseudopapillary neoplasms with extensive calcification. In patients presenting with hyper-dense, heavily calcified masses in the abdominal cavity, the possibility of GIST should be considered in the differential diagnosis. A careful search for cellular areas and the judicious application of immunostaining will thus make it possible to make a correct diagnosis.

  14. Imatinib-induced Ototoxicity in a Patient with Gastrointestinal Stromal Tumor (GIST)

    PubMed Central

    Wasif, Komal; Wasif, Nawal

    2016-01-01

    Imatinib (Gleevec) is a biological agent that is approved for the treatment of chronic myeloid leukemia (CML) as well as gastrointestinal stromal tumor (GIST). The most frequently seen adverse effects in patients treated with imatinib include superficial edema, muscle cramps, musculoskeletal pain, rash, fatigue, headache, abdominal pain, and joint pain. Ototoxicity has rarely been reported except in two cases. We report a case of bilateral irreversible sensorineural hearing loss (SNHL) caused by imatinib in a patient receiving this agent in the adjuvant setting. This case underlines the importance of early recognition of this potential toxicity that can impact the quality of life. PMID:27909636

  15. Gastrointestinal Stromal Tumour with Synchronous Bone Metastases: A Case Report and Literature Review

    PubMed Central

    Rochigneux, Philippe; Mescam-Mancini, Lénaig; Perrot, Delphine; Bories, Erwan; Moureau-Zabotto, Laurence; Sarran, Anthony; Guiramand, Jérôme; Bertucci, François

    2017-01-01

    Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the digestive tract, derived from Cajal interstitial cells. Bone metastases are very rare, and there is no consensus regarding their treatment. Here, we present the unusual case of a 66-year-old man with a gastric GIST with synchronous bone and liver metastases, fully documented at the pathological and molecular levels with a KIT exon 11 mutation. After 9 months of imatinib, the scanner showed a 33% partial response of target lesions. We also review the literature and describe the characteristics, treatment, and outcome of all cases previously reported. PMID:28203166

  16. Epigenetics in gastrointestinal stromal tumors: clinical implications and potential therapeutic perspectives.

    PubMed

    Sioulas, Athanasios D; Vasilatou, Diamantina; Pappa, Vasiliki; Dimitriadis, George; Triantafyllou, Konstantinos

    2013-11-01

    Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal neoplasms affecting the gastrointestinal tract. Activating mutations in either the KIT or PDGFRa gene are the principal oncogenic triggers with the former accounting for more than 80 % of cases. In the small subset of GIST that are wild type for both the aforementioned changes, other germline or somatic mutations have been identified. GIST exhibit a highly variable clinical behavior and the main prognostic determinants are tumor size, mitotic rate, and location. It is, however, strongly believed that, beyond classic genetics, additional epigenetic phenomena such as DNA hypomethylation and hypermethylation, microRNA alterations, and chromatin modifications underlie GIST tumorigenesis and influence the clinical course and response to standard treatment. This review aims to illuminate current advances in terms of epigenetics in GIST, as well as possible implications in prognosis and therapeutics.

  17. Case report of pneumatosis intestinalis secondary to sunitinib treatment for refractory gastrointestinal stromal tumor.

    PubMed

    Jarkowski, Anthony; Hare, Ryan; Francescutti, Valerie; Wilkinson, Neal; Khushalani, Nikhil

    2011-10-01

    Pneumatosis intestinalis (PI) occurs when inter-luminal air enters the bowel wall of the gastrointestinal tract via a mucosal defect. The condition is caused by numerous disease states, direct trauma, and various drugs. When PI is secondary to drug therapy, discontinuation of the offending agent results in the resolution of PI. We report on the case of a 73-year-old male with a history of refractory gastrointestinal stromal tumor experiencing PI while on sunitinib treatment. PI was noted via computed tomography (CT) scans 68 days after starting sunitinib therapy and showed near complete resolution on a follow up CT performed one month after discontinuing sunitinib. Given that a CT scan performed five months prior to the initiation of sunitinib did not show PI, lack of abdominal symptoms in our patient, and resolution of PI after discontinuing sunitinib, the cause of PI in our patient was likely due to sunitinib treatment.

  18. Familial and multiple gastrointestinal stromal tumors with fair response to a half-dose of imatinib.

    PubMed

    Bamba, Shigeki; Hirota, Seiichi; Inatomi, Osamu; Ban, Hiromitsu; Nishimura, Takashi; Shioya, Makoto; Imaeda, Hirotsugu; Nishida, Atsushi; Sasaki, Masaya; Murata, Satoshi; Andoh, Akira

    2015-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Since our first report in 1998, approximately 30 families with multiple GISTs due to a germline gain-of-function mutation of c-kit have been reported. We herein present a case of a family with multiple GISTs that have a germline c-kit mutation in exon 11 (Del-Val560) in two siblings. One of the patients showed a fair response to treatment with a half-dose of imatinib (200 mg/day). There are few reports describing the response to imatinib in familial GISTs and this drug appears to be a promising therapeutic option.

  19. Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach

    PubMed Central

    Jiang, Meng-jie; Weng, Shan-Shan; Cao, Ying; Li, Xiao-Fen; Wang, Liu-Hong; Xu, Jing-Hong; Yuan, Ying

    2015-01-01

    Abstract Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in gastrointestinal tracts; however, the synchronous or metachronous coexistence of GIST with additional primary malignancy is not common. Here, we present an unusual case of gastric GIST with metachronous primary lung adenocarcinoma diagnosed during his adjuvant treatment with oral receptor tyrosine kinase inhibitor imatinib mesylate (400 mg daily). After 6-month use of imatinib, the patient suffered from dry cough and dyspnea. Subsequent lung biopsy demonstrated adenocarcinoma with diffuse interstitial changes. Our research emphasizes the possibility of an additional primary tumor with GIST, and reminds the clinicians to strengthen the surveillance of the additional cancer during the follow-up of GIST patients. PMID:26356712

  20. Insulin-like Growth Factor (IGF) system and gastrointestinal stromal tumours (GIST): present and future.

    PubMed

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

    2014-02-01

    In the last decades, the concept that Insulin-like Growth Factor (IGF) axis plays a key role in several steps of tumorigenesis, cancer growth and metastasis has been widely documented. The aberration of the IGF system has been described in many kinds of tumours, providing several lines of evidence in support of IGF receptor type 1 (IGF1R) as molecular target in cancer treatment. Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumor of the gastrointestinal tract, commonly characterized in most cases by KIT and PDGFRA gain mutations. Beyond to the well recognized KIT and PDGFRA gain mutations, in the last years other molecular aberrations have been investigated. Recently, several lines of evidence about the involvement of the IGF system in GIST have been accumulated. The aim of this review is to report all current data about the IGF system involvement in GIST, focusing on the current clinical implication and future perspectives.

  1. Development of enterohepatic fistula after embolization in ileal gastrointestinal stromal tumor: a case report.

    PubMed

    Lee, Yun Ho; Koo, Ja Seol; Jung, Chang Ho; Chung, Sang Yoon; Lee, Jae Joong; Kim, Seung Young; Hyun, Jong Jin; Jung, Sung Woo; Choung, Rok Seon; Lee, Sang Woo; Choi, Jai Hyun

    2013-11-21

    Gastrointestinal stromal tumor (GIST) is a rare mesenchymal tumor of the gastrointestinal tract that has been associated with the formation of fistulas to adjacent organs in few case reports. However, GIST with enterohepatic fistula has not been reported. Here we report the case of an enterohepatic fistula that occurred after embolization of a liver mass originating in the distal ileum. An 87-year-old woman was hospitalized for melena. On initial conventional endoscopy, a bleeding focus in the gastrointestinal tract was not found. Because of massive hematochezia, enteroscopy was performed through the anus. A protruding, ulcerative mass was found in the distal ileum that was suspected to be the source of the bleeding; a biopsy sample was taken. Electrocoagulation was not successful in controlling the bleeding; therefore, embolization was performed. After embolization, the patient developed a high fever and severe abdominal tenderness with rebound tenderness. Follow-up abdominopelvic computed tomography revealed an enterohepatic fistula between the liver and distal ileum. The fistula was treated surgically by segmental resection of the distal ileum and unlooping of the liver mass.

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

    PubMed

    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.

  3. Ménétrier disease and gastrointestinal stromal tumors: hyperproliferative disorders of the stomach

    PubMed Central

    Coffey, Robert J.; Washington, Mary Kay; Corless, Christopher L.; Heinrich, Michael C.

    2007-01-01

    Ménétrier disease and gastrointestinal stromal tumors (GISTs) are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases (RTKs). In Ménétrier disease, overexpression of TGF-α, a ligand for the RTK EGFR, results in selective expansion of surface mucous cells in the body and fundus of the stomach. In GISTs, somatic mutations of the genes encoding the RTK KIT (or PDGFRA in a minority of cases) result in constitutive kinase activity and neoplastic transformation of gut pacemaker cells (interstitial cells of Cajal). On the basis of the involvement of these RTKs in the pathogenesis of these disorders, Ménétrier disease patients have been effectively treated with a blocking monoclonal antibody specific for EGFR and GIST patients with KIT and PDGFRA tyrosine kinase inhibitors. PMID:17200708

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

    PubMed

    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

  5. Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report

    PubMed Central

    Kubo, Naoki; Takeuchi, Nobumichi

    2017-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment (sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis. PMID:28321172

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

    NASA Astrophysics Data System (ADS)

    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.

  7. Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): Clinical Implications of the Somatic and Germline DNA Analysis

    PubMed Central

    Ravegnini, Gloria; Nannini, Margherita; Sammarini, Giulia; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A.; Hrelia, Patrizia; Angelini, Sabrina

    2015-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA tyrosine kinase receptors, with their consequent constitutive activation. The gold standard therapy is imatinib that offers a good and stable response for approximately 18–36 months. However, resistance is very common and it is vital to identify new biomarkers. Up until now, there have been two main approaches with focus to characterize novel targets. On the one hand, the focus is on the tumor genome, as the final clinical outcome depends mainly from the cancer specific mutations/alterations patterns. However, the germline DNA is important as well, and it is inconceivable to think the patients response to the drug is not related to it. Therefore the aim of this review is to outline the state of the art of the personalized medicine in GIST taking into account both the tumor DNA (somatic) and the patient DNA (germline). PMID:26184165

  8. Gastrointestinal stromal tumors in kidney transplant recipients: Report of two cases and literature review.

    PubMed

    Cheung, Chi Yuen; Lo, Stanley Hok King; Chan, Ching Kit; Li, Fu Keung; Cheng, Ignatius Kum Po; Chau, Ka Foon

    2017-02-01

    Gastrointestinal stromal tumors (GISTs) are the most common primary mesenchymal gastrointestinal neoplasms. However, GISTs occurring in kidney transplant recipients, including their treatment and outcome, are rarely described in literature. We hereby report two kidney transplant recipients with GISTs. Our first patient was diagnosed with high-risk epithelioid gastric GIST 2 years after kidney transplant. He received everolimus after resection and remained disease-free for 2 years before liver metastasis was confirmed. Imatinib therapy was planned but he died of fulminant pneumonia shortly. Our second patient was diagnosed with spindle cell GISTs in the mesentery 1 year after kidney transplant. Only partial response was obtained with imatinib as new lesions continued to develop. Withdrawal of cyclosporine and introduction of sirolimus resulted in complete shrinkage of existing tumors and no new lesions. He remained disease-free for more than 10 years. Combination therapy consisting of imatinib and inhibitors of mammalian target of rapamycin (mTORi) seems to be safe and effective in kidney transplant recipients. However, therapeutic drug monitoring of mTORi is essential to avoid nephrotoxicity. Further trials addressing the optimal dosage of imatinib and mTORi in kidney transplant recipients are recommended.

  9. Antitumor effects in gastrointestinal stromal tumors using photodynamic therapy with a novel glucose-conjugated chlorin.

    PubMed

    Tanaka, Mamoru; Kataoka, Hiromi; Yano, Shigenobu; Ohi, Hiromi; Moriwaki, Kazuhiro; Akashi, Haruo; Taguchi, Takahiro; Hayashi, Noriyuki; Hamano, Shingo; Mori, Yoshinori; Kubota, Eiji; Tanida, Satoshi; Joh, Takashi

    2014-04-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Except for surgical resection, no effective treatment strategies have been established. Photodynamic therapy (PDT) consists of intravenous administration of a photosensitizer, activated by a specific wavelength of light, which produces reactive oxygen species that directly kill tumor cells. We analyzed the efficacy of PDT using a newly developed photosensitizer, 5,10,15,20-tetrakis [4-[β-d-glucopyranosylthio-2,3,5,6-tetrafluorophenyl]-2,3,[methano[N-methyl] iminomethano] chlorin (H(2)TFPC-SGlc), for the GIST treatment. Various photosensitizers were administered in vitro to GIST (GIST-T1) and fibroblast (WI-38) cells, followed by irradiation, after which cell death was compared. We additionally established xenograft mouse models with GIST-T1 tumors and examined the accumulation and antitumor effects of these photosensitizers in vivo. In vitro, the expression of the glucose transporters GLUT1, GLUT3, and GLUT4, the cellular uptake of H(2)TFPC-SGlc, and apoptosis mediated by PDT with H(2)TFPC-SGlc were significantly higher in GIST-T1 than in WI-38 cells. In vivo, H(2)TFPC-SGlc accumulation was higher in xenograft tumors of GIST-T1 cells than in the adjacent normal tissue, and tumor growth was significantly suppressed following PDT. PDT with novel H(2)TFPC-SGlc is potentially useful for clinical applications about the treatment of GIST.

  10. Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor

    PubMed Central

    Koo, Dong-Hoe; Ryu, Min-Hee; Kim, Kyoung-Mee; Yang, Han-Kwang; Sawaki, Akira; Hirota, Seiichi; Zheng, Jie; Zhang, Bo; Tzen, Chin-Yuan; Yeh, Chun-Nan; Nishida, Toshirou; Shen, Lin; Chen, Li-Tzong; Kang, Yoon-Koo

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries. PMID:27384163

  11. Endoscopic en bloc resection of an exophytic gastrointestinal stromal tumor with suction excavation technique.

    PubMed

    Choi, Hyuk Soon; Chun, Hoon Jai; Kim, Kyoung-Oh; Kim, Eun Sun; Keum, Bora; Jeen, Yoon-Tae; Lee, Hong Sik; Kim, Chang Duck

    2016-06-21

    Here, we report the first successful endoscopic resection of an exophytic gastrointestinal stromal tumor (GIST) using a novel perforation-free suction excavation technique. A 49-year-old woman presented for further management of a gastric subepithelial tumor on the lesser curvature of the lower body, originally detected via routine upper gastrointestinal endoscopy. Abdominal computed tomography and endoscopic ultrasound showed a 4-cm extraluminally protruding mass originating from the muscularis propria layer. The patient firmly refused surgical resection owing to potential cardiac problems, and informed consent was obtained for endoscopic removal. Careful dissection and suction of the tumor was repeated until successful extraction was achieved without serosal injury. We named this procedure the suction excavation technique. The tumor's dimensions were 3.5 cm × 2.8 cm × 2.5 cm. The tumor was positive for C-KIT and CD34 by immunohistochemical staining. The mitotic count was 6/50 high-power fields. The patient was followed for 5 years without tumor recurrence. This case demonstrated the use of endoscopic resection of an exophytic GIST using the suction excavation technique as a potential therapy without surgical resection.

  12. Personalized Medicine in Gastrointestinal Stromal Tumor (GIST): Clinical Implications of the Somatic and Germline DNA Analysis.

    PubMed

    Ravegnini, Gloria; Nannini, Margherita; Sammarini, Giulia; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A; Hrelia, Patrizia; Angelini, Sabrina

    2015-07-09

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. They are characterized by gain of function mutations in KIT or PDGFRA tyrosine kinase receptors, with their consequent constitutive activation. The gold standard therapy is imatinib that offers a good and stable response for approximately 18-36 months. However, resistance is very common and it is vital to identify new biomarkers. Up until now, there have been two main approaches with focus to characterize novel targets. On the one hand, the focus is on the tumor genome, as the final clinical outcome depends mainly from the cancer specific mutations/alterations patterns. However, the germline DNA is important as well, and it is inconceivable to think the patients response to the drug is not related to it. Therefore the aim of this review is to outline the state of the art of the personalized medicine in GIST taking into account both the tumor DNA (somatic) and the patient DNA (germline).

  13. Gastrointestinal stromal tumour masquerading as a cyst in the lesser sac

    PubMed Central

    Hamza, Ahmed Mahmoud; Ayyash, Emad Helmi; Alzafiri, Raed; Francis, Issam; Asfar, Sami

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are solid tumours of the gastrointestinal tract, mostly found in the stomach and intestine. They rarely present as cystic lesions. A 74-year-old woman referred to the hepatopancreaticobiliary unit, with 3 months history of upper abdominal discomfort. Abdominal ultrasound scan showed a large cystic lesion in the epigastric region suggestive of a pancreatic pseudocyst. The CT-scan showed a 6.6×6×6.3 cm size cyst related to the pancreas and extending to the hepatogastric omentum. Endoscopic ultrasound (EUS) scan was suggestive of a pancreatic pseudocyst. Aspirated Cyst fluid via EUS showed benign cytology with normal amylase, lipase and tumour markers (CEA, CA-19.9 and CA-125). She was referred as a case of pancreatic pseudocyst. After surgical excision, the histopathology confirmed the presence GIST in the wall of the cystic lesion. The possibility of GIST should be kept in mind in the presence of unusual features of a cyst on abdominal imaging. PMID:27469382

  14. Integrated genomic analyses identify frequent gene fusion events and VHL inactivation in gastrointestinal stromal tumors

    PubMed Central

    Sun, Choong-Hyun; Park, Inho; Lee, Seungmook; Kwon, Jekeun; Do, Ingu; Hong, Min Eui; Van Vrancken, Michael; Lee, Jeeyun; Park, Joon Oh; Cho, Jeonghee; Kim, Kyoung-Mee; Sohn, Tae Sung

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two genomes of GISTs for integrated analyses. We detected 306 somatic variants in nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome sequencing revealed 328 gene fusions, and the most frequently involved fusion events were associated with IGF2 fused to several partner genes including CCND1, FUS, and LASP1. We additionally identified three recurrent read-through fusion transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found intragenic deletions in one of three exons of the VHL gene and increased mRNAs of VEGF, PDGF-β, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link between VHL inactivation and overexpression of hypoxia-inducible factor target genes in the absence of hypoxia. We also identified copy number gain and increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy number and gene expression results to the KEGG pathways revealed activation of the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type GISTs. These observations will allow us to determine the genetic basis of GISTs and will facilitate further investigation to develop new therapeutic options. PMID:25987131

  15. Integrated genomic analyses identify frequent gene fusion events and VHL inactivation in gastrointestinal stromal tumors.

    PubMed

    Kang, Guhyun; Yun, Hongseok; Sun, Choong-Hyun; Park, Inho; Lee, Seungmook; Kwon, Jekeun; Do, Ingu; Hong, Min Eui; Van Vrancken, Michael; Lee, Jeeyun; Park, Joon Oh; Cho, Jeonghee; Kim, Kyoung-Mee; Sohn, Tae Sung

    2016-02-09

    Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. We sequenced nine exomes and transcriptomes, and two genomes of GISTs for integrated analyses. We detected 306 somatic variants in nine GISTs and recurrent protein-altering mutations in 29 genes. Transcriptome sequencing revealed 328 gene fusions, and the most frequently involved fusion events were associated with IGF2 fused to several partner genes including CCND1, FUS, and LASP1. We additionally identified three recurrent read-through fusion transcripts: POLA2-CDC42EP2, C8orf42-FBXO25, and STX16-NPEPL1. Notably, we found intragenic deletions in one of three exons of the VHL gene and increased mRNAs of VEGF, PDGF-β, and IGF-1/2 in 56% of GISTs, suggesting a mechanistic link between VHL inactivation and overexpression of hypoxia-inducible factor target genes in the absence of hypoxia. We also identified copy number gain and increased mRNA expression of AMACR, CRIM1, SKP2, and CACNA1E. Mapping of copy number and gene expression results to the KEGG pathways revealed activation of the JAK-STAT pathway in small intestinal GISTs and the MAPK pathway in wild-type GISTs. These observations will allow us to determine the genetic basis of GISTs and will facilitate further investigation to develop new therapeutic options.

  16. Sunitinib in the treatment of gastrointestinal stromal tumor: patient selection and perspectives

    PubMed Central

    Mulet-Margalef, Nuria; Garcia-del-Muro, Xavier

    2016-01-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. In advanced setting and after progression to imatinib, the multi-targeted receptor tyrosine kinase inhibitor sunitinib has clearly demonstrated a clinical benefit in terms of response rate and progression-free survival with an acceptable toxicity profile. The recommended schedule for sunitinib administration is 50 mg per day 4 weeks ON and 2 weeks OFF; however, potential alternative schedules are also reviewed in the present article. Several biomarkers have been explored to better select candidates for sunitinib therapy, such as the value of early changes in standardized uptake value assessed by positron emission tomography with 18F-fluorodeoxyglucose, circulating biomarkers, clinical biomarkers such as the appearance of arterial hypertension during treatment that correlates with better outcomes, and the GIST genotype. GISTs with KIT mutations at exon 9 and the so-called wild-type GISTs seem to better respond to sunitinib. Nonetheless, further investigation is required to confirm these findings as well as to understand the mechanisms of sunitinib resistance such as the development of new KIT mutations or conformational changes in KIT receptor. PMID:28008275

  17. Gastrointestinal stromal tumors and KIT-positive mesenchymal cells in the omentum.

    PubMed

    Sakurai, S; Hishima, T; Takazawa, Y; Sano, T; Nakajima, T; Saito, K; Morinaga, S; Fukayama, M

    2001-07-01

    Gastrointestinal stromal tumor (GIST) is currently considered to be derived from the interstitial cells of Cajal (ICC). To test the hypothesis that omental mesenchymal tumor is also a type of GIST, we evaluated the expression of specific molecules in GIST, and c-kit gene mutation in omental mesenchymal tumors, and we identified a possible counterpart of ICC in the omentum. Immunohistochemically, all of the omental mesenchymal tumors (n = 5) were positive for both KIT and CD34, and three of the five tumors were also positive for an embryonic form of smooth-muscle myosin heavy chain (SMemb). Polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP) and direct sequencing revealed mutations in c-kit gene exon 11 in all five tumors. As for the ICC counterparts in the omentum, there were some KIT-positive mesenchymal cells resembling ICC at the surface of the omentum. Double fluorescence immunostaining, using anti-KIT polyclonal antibodies and monoclonal antibodies against other molecules, demonstrated that KIT-, CD34- and SMemb-positive cells were present just beneath the mesothelial cells of the omentum. These results show that omental mesenchymal tumor corresponds to GIST of the omentum, and that KIT-positive bipolar mesenchymal cells may be a counterpart of ICC in the gastrointestinal tract. Identification of a new type of KIT-positive mesenchymal cell in the omentum may lead to the discovery of a new physiological role for this organ.

  18. Evidence for Ca2+-Regulated ATP Release in Gastrointestinal Stromal Tumors

    PubMed Central

    Berglund, Erik; Berglund, David; Akcakaya, Pinar; Ghaderi, Mehran; Daré, Elisabetta; Berggren, Per-Olof; Köhler, Martin; Aspinwall, Craig A.; Lui, Weng-Onn; Zedenius, Jan; Larsson, Catharina; Bränström, Robert

    2013-01-01

    Gastrointestinal stromal tumors (GISTs) are thought to originate from the electrically active pacemaker cells of the gastrointestinal tract. Despite the presence of synaptic-like vesicles and proteins involved in cell secretion it remains unclear whether GIST cells possess regulated release mechanisms. The GIST tumor cell line GIST882 was used as a model cell system, and stimulus-release coupling was investigated by confocal microscopy of cytoplasmic free Ca2+ concentration ([Ca2+]i), flow cytometry, and luminometric measurements of extracellular ATP. We demonstrate that GIST cells have an intact intracellular Ca2+-signaling pathway that regulates ATP release. Cell viability and cell membrane integrity was preserved, excluding ATP leakage due to cell death and suggesting active ATP release. The stimulus-secretion signal transduction is at least partly dependent on Ca2+ influx since exclusion of extracellular Ca2+ diminishes the ATP release. We conclude that measurements of ATP release in GISTs may be a useful tool for dissecting the signal transduction pathway, mapping exocytotic components, and possibly for the development and evaluation of drugs. Additionally, release of ATP from GISTs may have importance for tumor tissue homeostasis and immune surveillance escape. PMID:23499741

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

    PubMed

    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.

  20. Endosonographic features predictive of benign and malignant gastrointestinal stromal cell tumours

    PubMed Central

    Palazzo, L; Landi, B; Cellier, C; Cuillerier, E; Roseau, G; Barbier, J

    2000-01-01

    BACKGROUND/AIM—Some endoscopic ultrasonographic (EUS) features have been reported to be suggestive of malignancy in gastrointestinal stromal cell tumours (SCTs). The aim of this study was to assess the predictive value of these features for malignancy.
METHODS—A total of 56 histologically proven cases of SCT studied by EUS between 1989 and 1996 were reviewed. There were 42 gastric tumours, 12 oesophageal tumours, and two rectal tumours. The tumours were divided into two groups: (a) benign SCT, comprising benign leiomyoma (n = 34); (b) malignant or borderline SCT (n = 22), comprising leiomyosarcoma (n = 9), leiomyoblastoma (n = 9), and leiomyoma of uncertain malignant potential (n = 4). The main EUS features recorded were tumour size, ulceration, echo pattern, cystic spaces, extraluminal margins, and lymph nodes with a malignant pattern. The two groups were compared by univariate and multivariate analysis.
RESULTS—Irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern were most predictive of malignant or borderline SCT. Pairwise combinations of the three features had a specificity and positive predictive value of 100% for malignant or borderline SCT, but a sensitivity of only 23%. The presence of at least one of these three criteria had 91% sensitivity, 88% specificity, and 83% predictive positive value. In multivariate analysis, cystic spaces and irregular margins were the only two features independently predictive of malignant potential. The features most predictive of benign SCTs were regular margins, tumour size ⩽30 mm, and a homogeneous echo pattern. When the three features were combined, histology confirmed a benign SCT in all cases.
CONCLUSIONS—The combined presence of two out of three EUS features (irregular extraluminal margins, cystic spaces, and lymph nodes with a malignant pattern) had a positive predictive value of 100% for malignant or borderline gastrointestinal SCT. Tumours less than 30

  1. Fine needle aspiration biopsy of gastrointestinal stromal tumor presenting as an umbilical mass (Sister Mary Joseph's Nodule).

    PubMed

    Scudeler, Donizete; Wakely, Paul E

    2006-04-01

    The Sister Mary Joseph (SMJ) nodule is a clinical sign of metastatic cancer involving the umbilicus. The vast majority of these instances represent adenocarcinomas arising from ovarian or colorectal primaries. We present a patient who presented with ascites and the SMJ lesion that turned out to be a metastatic gastrointestinal stromal tumor after fine needle aspiration biopsy was performed. The lesion was subsequently histologically confirmed. Gastrointestinal stroma tumor involving the umbilicus is exceedingly uncommon and only rarely presents in this fashion. The cytomorphological features, differential diagnosis, and comparison with the tissue specimen are made.

  2. State of the Art in the Treatment of Gastrointestinal Stromal Tumors

    PubMed Central

    Garlipp, Benjamin; Bruns, Christiane J.

    2014-01-01

    Background Gastrointestinal stromal tumors (GISTs) are the most frequently diagnosed mesenchymal neoplasms of the gastrointestinal tract. Despite their biological and clinical heterogeneity, the majority of these tumors are positive for the receptor tyrosine kinase KIT and are driven by KIT- or platelet-derived growth factor receptor alpha (PDGFRA)-activating mutations. There are still uncertainties regarding their clinical and molecular characterization and the optimal treatment regimens, making it difficult to establish a universal treatment algorithm for these tumors. Summary From a clinical perspective, the main difference between GISTs and other gastrointestinal neoplasms is that the benign or malignant behavior of GISTs cannot be predicted from histopathology, but instead relies on empirically established scoring systems. Clinical data suggest that malignant potential may be an inherent quality of some GISTs rather than a feature acquired by the tumor during disease progression. Thus, some patients may require prolonged anti-tumor treatment even after complete surgical removal of the tumor. Key Message Although GISTs are the most frequently occurring mesenchymal neoplasms in the gastrointestinal tract, no universal treatment algorithms exist. This paper reviews the current evidence that guides the management of GISTs. Practical Implications The management of localized GISTs involves the use of surgical resection, with the inclusion of preoperative tyrosine kinase inhibitor treatment for locally advanced, primarily unresectable tumors and for resectable cases requiring extensive surgery. Imatinib is also indicated as adjuvant therapy after complete surgical removal of GISTs with a high estimated risk of recurrence unless specific mutations conferring imatinib resistance are present. The optimal duration of adjuvant treatment is still controversial. For patients with metastatic imatinib-sensitive GISTs, imatinib constitutes the first-line standard treatment

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

    PubMed Central

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

    2017-01-01

    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. PMID:28348499

  4. Gastric gastrointestinal stromal tumor with incomplete duplication cyst - a case with possibility of neoplasia in fetal-period malformed tissues.

    PubMed

    Lewitowicz, Piotr; Matykiewicz, Jaroslaw; Koziel, Dorota; Gluszek, Stanislaw Z; Sosnowski, Zbigniew; Horecka-Lewitowicz, Agata; Nasierowska-Guttmejer, Anna

    2015-03-01

    The coincidence of GIST and other gastric malignancies are documented well but arising GIST from congenital anomalies is still rarity in literature. To date, only a few papers have been concerned on the possibility of arising neoplasms from duplication cyst of gastrointestinal tract. There, are dominating usual cancers, neuroendocrine cancers or lymphomas but GIST has been noted only once. Here, we report a case of 73 years old female-patient with typical gastric stromal tumor comprised centrally locked an incomplete duplication cyst.

  5. Severe paraneoplastic hypoglycemia in a patient with a gastrointestinal stromal tumor with an exon 9 mutation: a case report

    PubMed Central

    Escobar, Guillermo A; Robinson, William A; Nydam, Trevor L; Heiple, Drew C; Weiss, Glen J; Buckley, Linda; Gonzalez, Rene; McCarter, Martin D

    2007-01-01

    Background Non-islet cell tumor induced hypoglycemia (NICTH) is a very rare phenomenon, but even more so in gastrointestinal stromal tumors. It tends to present in large or metastatic tumors, and can appear at any time in the progression of the disease. We present herein a case of NICTH in a GIST tumor and report an exon 9 mutation associated to it. Case presentation A thirty nine year-old man with a recurrent, metastatic gastrointestinal stromal tumor presented to the hospital with nausea, dizziness, loss of consciousness, and profound hypoglycemia (20 mg/dL). There was no evidence of factitious hypoglycemia. He was stabilized with a continuous glucose infusion and following selective vascular embolization, the patient underwent debulking of a multicentric 40 cm × 25 cm × 10 cm gastrointestinal stromal tumor. After resection, the patient became euglycemic and returned to his normal activities. Tumor analysis confirmed excessive production of insulin-like growth factor II m-RNA and the precursor protein, "big" insulin-like growth factor II. Mutational analysis also identified a rare, 6 bp tandem repeat insert (gcctat) at position 1530 in exon 9 of KIT. Conclusion Optimal management of gastrointestinal stromal tumor-induced hypoglycemia requires a multidisciplinary approach, and surgical debulking is the treatment of choice to obtain immediate symptom relief. Imatinib or combinations of glucocorticoids and growth hormone are alternative palliative strategies for symptomatic hypoglycemia. In addition, mutations in exon 9 of the tyrosine kinase receptor KIT occur in 11–20% of GIST and are often associated with poor patient outcomes. The association of this KIT mutation with non-islet cell tumor induced hypoglycemia has yet to be established. PMID:17229322

  6. Comparison between air and carbon dioxide insufflation in the endoscopic submucosal excavation of gastrointestinal stromal tumors

    PubMed Central

    Shi, Wei-Bin; Wang, Zi-Hao; Qu, Chun-Ying; Zhang, Yi; Jiang, Han; Zhou, Min; Chen, Ying; Xu, Lei-Ming

    2012-01-01

    AIM: To evaluate the safety and efficacy of CO2 insufflation compared with air insufflation in the endoscopic submucosal excavation (ESE) of gastrointestinal stromal tumors. METHODS: Sixty patients were randomized to undergo endoscopic submucosal excavation, with the CO2 group (n = 30) and the air group (n = 30) undergoing CO2 insufflation and air insufflation in the ESE, respectively. The end-tidal CO2 level (pETCO2) was observed at 4 time points: at the beginning of ESE, at total removal of the tumors, at completed wound management, and 10 min after ESE. Additionally, the patients’ experience of pain at 1, 3, 6 and 24 h after the examination was registered using a visual analog scale (VAS). RESULTS: Both the CO2 group and air group were similar in mean age, sex, body mass index (all P > 0.05). There were no significant differences in PetCO2 values before and after the procedure (P > 0.05). However, the pain scores after the ESE at different time points in the CO2 group decreased significantly compared with the air group (1 h: 21.2 ± 3.4 vs 61.5 ± 1.7; 3 h: 8.5 ± 0.7 vs 42.9 ± 1.3; 6 h: 4.4 ± 1.6 vs 27.6 ± 1.2; 24 h: 2.3 ± 0.4 vs 21.4 ± 0.7, P < 0.05). Meanwhile, the percentage of VAS scores of 0 in the CO2 group after 1, 3, 6 and 24 h was significantly higher than that in the air group (60.7 ± 1.4 vs 18.9 ± 1.5, 81.5 ± 2.3 vs 20.6 ± 1.2, 89.2 ± 0.7 vs 36.8 ± 0.9, 91.3 ± 0.8 vs 63.8 ± 1.3, respectively, P < 0.05). Moreover, the condition of the CO2 group was better than that of the air group with respect to anal exsufflation. CONCLUSION: Insufflation of CO2 in the ESE of gastrointestinal stromal tumors will not cause CO2 retention and it may significantly reduce the level of pain, thus it is safe and effective. PMID:23326136

  7. Contrast-enhanced (endoscopic) ultrasound and endoscopic ultrasound elastography in gastrointestinal stromal tumors

    PubMed Central

    Ignee, Andre; Jenssen, Christian; Hocke, Michael; Dong, Yi; Wang, Wen-Ping; Cui, Xin-Wu; Woenckhaus, Matthias; Iordache, Sevastita; Saftoiu, Adrian; Schuessler, Gudrun; Dietrich, Christoph F.

    2017-01-01

    Background and Objectives: Gastrointestinal stromal tumors (GISTs) represent the largest group of subepithelial tumors (SET) of the upper gastrointestinal (GI) tract. They may show malignant behavior, in contrast to other SET. Endoscopic ultrasound (EUS) is frequently used to characterize SET. With the introduction of contrast-enhanced ultrasound (CEUS) into EUS (CE-EUS), distinct enhancement patterns can be detected. In the presented study, the characteristic features of CE-EUS in GIST are analyzed and compared with those of other SET. Materials and Methods: Consecutive patients from four centers with SET of the upper and middle GI tract were included and received endoscopic or transcutaneous CEUS. The results were compared with EUS-guided tissue acquisition, forceps biopsy, or surgical resection. Results: Forty-two out of 62 (68%) patients had SET of the stomach, 17/62 (27%) of the small intestine, 2/62 (3%) of the esophagus, and 1/62 (2%) extraintestinal. Eighty-one percent underwent surgery. Leiomyoma was found in 5/62 (8%) and GIST in 57/62 patients (92%). Thirty-nine out of 57 (68%) patients had GIST lesions in the stomach, 17/57 (30%) had GIST of the small intestine, and 1/57 (2%) patients had extraintestinal GISTs. GIST size was 62.6 ± 42.1 (16–200) mm. Hyperenhancement had a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 98%, 100%, 100%, 93%, and 98% for the diagnosis of GIST. Fifty out of 57 patients with GIST (88%) showed avascular areas in the center of the lesions. Conclusion: CE-EUS and CEUS show hyperenhancement and avascular areas in a high percentage of GIST but not in leiomyoma. Thus, GIST and leiomyoma can be discriminated accurately. PMID:28218202

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

    PubMed

    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.

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

    PubMed Central

    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

  10. GLP-2 receptors in human disease: high expression in gastrointestinal stromal tumors and Crohn's disease.

    PubMed

    Körner, Meike; Rehmann, Ruth; Reubi, Jean Claude

    2012-11-25

    Peptide hormones of the glucagon-like peptide (GLP) family play an increasing clinical role, as reported for GLP-1 in diabetes therapy and insulinoma diagnostics. GLP-2, despite its known trophic and anti-inflammatory intestinal actions translated into preliminary clinical studies using the GLP-2 analogue teduglutide for treatment of short bowel syndrome and Crohn's disease, remains poorly characterized in terms of expression of its receptor in tissues of interest. Therefore, the GLP-2 receptor expression was assessed in 237 tumor and 148 non-neoplastic tissue samples with in vitro receptor autoradiography. A GLP-2 receptor expression was present in 68% of gastrointestinal stromal tumors (GIST). Furthermore, GLP-2 receptors were identified in the intestinal myenteric plexus, with significant up-regulation in active Crohn's disease. The GLP-2 receptors in GIST may be used for clinical applications like in vivo targeting with radiolabelled GLP-2 analogues for imaging and therapy. Moreover, the over-expressed GLP-2 receptor in the myenteric plexus may represent the morphological correlate of the clinical target of teduglutide in Crohn's disease.

  11. The DREAM complex in anti-tumor activity of imatinib mesylate in gastrointestinal stromal tumors (GISTs)

    PubMed Central

    DeCaprio, James A.; Duensing, Anette

    2014-01-01

    Purpose of review Although most gastrointestinal stromal tumors (GISTs) respond well to treatment with the small molecule kinase inhibitor imatinib mesylate (Gleevec), the majority of patients achieve disease stabilization and complete remissions are rare. Furthermore, discontinuation of treatment in the presence of residual tumor mass almost inevitably leads to tumor progression. These observations suggest that a subset of tumor cells not only persists under imatinib treatment, but remains viable. The current article reviews the molecular basis for these findings and explores strategies to exploit them therapeutically. Recent findings Although imatinib can induce apoptosis in a subset of GIST cells, it can induce a reversible exit from the cell division cycle and entry into G0, a cell cycle state called quiescence, in the remaining cells. Mechanistically, this process involves the DREAM complex, a newly identified key regulator of quiescence. Interfering with DREAM complex formation either by siRNA-mediated knockdown or by pharmacological inhibition of the regulatory kinase DYRK1A was shown to enhance imatinib-induced GIST cell death. Summary Targeting the DREAM complex and imatinib-induced quiescence could provide opportunities for future therapeutic interventions toward more efficient imatinib responses. PMID:24840522

  12. A Case of a Gastrointestinal Stromal Tumor Diagnosed at the Postpartum Period

    PubMed Central

    Canda, Aras Emre; Karadeniz, Emre; Yavuzsen, Tugba; Sagol, Ozgul; Obuz, Funda; Canda, Mehmet Serefettin

    2016-01-01

    Introduction. We discuss a rare gastrointestinal stromal tumor (GIST) case detected at the 10th postpartum week and we want to pay attention to the challenges and improvements in the diagnosis, surgery, chemotherapy, and follow-up of this rare tumor accompanied with the review of the current literature. Case Presentation. A 32-year-old multiparous woman presented with abdominal swelling 10 weeks after her second vaginal birth. Abdominal examination revealed a mass starting from the pelvic level and extending to the right upper quadrant. Radiological examinations showed a solid, multiloculated, and hypervascular mass starting from the pelvis and extending to the transverse colon. En bloc mass with a 20 cm jejunal segment resection and a left pelvic side wall peritonectomy with omentectomy was performed. The pathologic examination revealed a high-risk GIST which originated from the jejunum and disseminated to the peritoneum. The patient has been given imatinib 400 mg/day since then. She did not reveal any progression during the 15-month follow-up postoperatively. Conclusion. GIST tumors are rare and there is not sufficient information in the literature regarding its management. In this patient having high risk GIST and GIST sarcomatosis we successfully treated the patient by surgery and adjuvant imatinib chemotherapy. PMID:27957364

  13. The roles of serum CXCL16 in circulating Tregs and gastrointestinal stromal tumor cells

    PubMed Central

    Xing, Ya-Nan; Zhang, Jun-Yan; Xu, Hui-Mian

    2016-01-01

    Gastrointestinal stromal tumors (GIST) are the most common sarcomas of the digestive system. Abnormal expression of CXCL16 and its sole receptor, CXCR6, has been demonstrated in many cancers. However, no studies have shown the relationship between CXCL16 or CXCR6 expression and GIST. In this study, we detected CXCL16 and CXCR6 expression in GIST patient samples by using immunohistochemistry analysis and Western blot analysis. Serum CXCL16 level was determined by using enzyme-linked immunosorbent assay. Circulating Tregs were isolated by using flow cytometry. MTT assay, cell cycle assay, and transwell assay were used to test the effects of recombinant CXCL16 on Tregs and GIST cells in vitro. The levels of CXCL16 and CXCR6 protein were higher in cancer tissues than in normal tissues. Serum CXCL16 level and circulating Tregs were higher in GIST patients than that in the healthy volunteers. CXCL16, CXCR6, serum CXCL16, and circulating Tregs were significantly associated with a decreased survival time of patients. Relative to control cells, high concentration recombinant CXCL16 treated Tregs and GIST cells exhibited lower proliferation and mobility rates as assessed by MTT assay and transwell assay, respectively. Taken together, CXCL16 was observed to mediate the inhibitory effects in Tregs and GIST cells, and these involved suppression of the MEK/ERK signaling pathway. PMID:27418838

  14. Primary gastrointestinal stromal tumour of the ileum pre-operatively diagnosed as an abdominal abscess

    PubMed Central

    Rubini, Patrizia; Tartamella, Francesco

    2016-01-01

    The present case report described the acute presentation, diagnosis and management of a primary gastrointestinal stromal tumour (GIST) of the ileum. A male patient (age, 51 years) was admitted to Maggiore Hospital (Parma, Italy) due to presenting with fever, dysuria and lower abdominal pain. Ultrasonography and computed tomography showed a 7,5×5,5-cm pelvic mass containing air and purulent fluid indicative of an intraperitoneal abscess. The patient was subjected to diagnostic laparoscopy, which revealed a huge, soft cystic mass arising from the small bowel. The procedure was then converted to an open exploration through a midline incision. Ileal resection including a Meckel's diverticulum was performed. Macroscopic examination revealed that the cystic mass was filled with a large amount of pus, probably due to communication between the tumour mass and the small bowel lumen. In fact, the surgical specimen showed enteric leakage from the ileal mucosal ulcer into the tumour mass. Histopathology and immunohistochemistry of the abscess wall identified a spindle-cell mesenchymal-type, c-KIT-positive neoplasm. The post-operative course was uneventful and adjuvant imatinib mesylate was administered for 1 year. Follow-up by computed tomography demonstrated no tumour recurrence at 72 months after surgery. PMID:27900093

  15. Integrative Genomic Characterization and a Genomic Staging System for Gastrointestinal Stromal Tumors

    PubMed Central

    Ylipää, Antti; Hunt, Kelly K.; Yang, Jilong; Lazar, Alexander J. F.; Torres, Keila E.; Lev, Dina Chelouche; Nykter, Matti; Pollock, Raphael E.; Trent, Jonathan; Zhang, Wei

    2010-01-01

    Gastrointestinal stromal tumors (GISTs) were historically grouped with leiomyosarcomas (LMSs) based on their morphological similarities, but recently they have been unequivocally established as a distinct type of sarcoma based on the molecular features and response to imatinib treatment. To gain further insight into the genomic differences between GISTs and LMSs, we mapped gene copy number aberrations (CNAs) in 42 GISTs and 30 LMSs and integrated them with gene expression profiles. Our studies revealed distinct patterns of CNAs between GISTs and LMSs. Losses in chromosomes 1p, 14q, 15q, and 22q were significantly more frequent in GISTs than in LMSs (P < 0.001), whereas losses in chromosomes 10 and 16 as well as gains in 1q, 14q, and 15q (P < 0.001) were more common in LMSs. By integrating CNAs with gene expression data and clinical information, we found several clinically relevant CNAs that were prognostic of survival in patients with GIST. Furthermore, GISTs were categorized into four groups according to an accumulating pattern of genetic alterations. Many key cellular pathways were differently expressed in the four groups and the patients had increasingly worse prognosis as the extent of genomic alterations increased. These findings lead us to propose a new tumor-progression genetic staging system termed Genomic Instability Stage (GIS) to complement the current prognostic predictive system based on tumor size, mitotic index (MI), and KIT mutation. PMID:20818650

  16. ZNF-Mediated Resistance to Imatinib Mesylate in Gastrointestinal Stromal Tumor

    PubMed Central

    Zhou, Yan; von Mehren, Margaret; Godwin, Andrew K.

    2013-01-01

    Although imatinib mesylate (IM) has transformed the treatment of gastrointestinal stromal tumors (GIST), many patients experience primary/secondary drug resistance. In a previous study, we identified a gene signature, consisting mainly of Kruppel-associated box (KRAB) domain containing zinc finger (ZNF) transcriptional repressors that predict short-term response to IM. To determine if these genes have functional significance, a siRNA library targeting these genes was constructed and applied to GIST cells in vitro. These screens identified seventeen “IM sensitizing genes” in GIST cells (sensitization index (SI) <0.85 ratio of drug/vehicle) with a false discovery rate (FDR) <15%, including twelve ZNF genes, the majority of which are located within the HSA19p12–13.1 locus. These genes were shown to be highly specific to IM and another tyrosine kinase inhibitor (TKI), sunitinib, in GIST cells. In order to determine mechanistically how these ZNFs might be modulating response to IM, RNAi approaches were used to individually silence genes within the predictive signature in GIST cells and expression profiling was performed. Knockdown of the 14 IM-sensitizing genes (10 ZNFs) universally led to downregulation of six genes, including TGFb3, periostin, and NEDD9. These studies implicate a role of KRAB-ZNFs in modulating response to TKIs in GIST. PMID:23372733

  17. KIT and PDGFRA mutations and PDGFRA immunostaining in gastrointestinal stromal tumors.

    PubMed

    Barreca, Antonella; Fornari, Alessandro; Bonello, Lisa; Tondat, Fabrizio; Chiusa, Luigi; Lista, Patrizia; Pich, Achille

    2011-01-01

    In the present study, we investigated the association of PDGFRA and KIT mutations as well as PDGFRA immunohistochemical expression with clinicopathologic features and prognosis in a series of gastrointestinal stromal tumors (GISTs). Tumor DNA from 40 GISTs was sequenced for the presence of mutations in KIT exons 9, 11, 13 and 17, and in PDGFRA exons 12 and 18. Tissue sections were stained with polyclonal anti-PDGFRA antibody. KIT mutations occurred in 26 cases. There were 13 deletions, 6 substitutions, 3 deletion-substitutions, 3 duplications and 1 insertion. Tumors with KIT deletions/insertion were large with a high mitotic index (MI), and were associated with a high rate of symptoms at diagnosis, invasion into adjacent organs, distant metastasis, relapse and a short disease-free survival (DFS). PDGFRA mutations occurred in 6 gastric GISTs. There were 4 deletions and 2 substitutions. Tumors with PDGFRA mutations were small, with a low MI and Ki67 score, and were associated with a very low rate of symptoms at diagnosis, invasion into adjacent organs and distant metastasis. PDGFRA immunopositivity was found in 23 cases: a peculiar 'dotlike' staining was found in 5 out of 6 PDGFRA mutated cases. Patients with positive PDGFRA immunostaining had a longer DFS than those with negative staining. Our data confirm that the type of KIT mutation is associated with various clinicopathologic features of GISTs, and indicate that PDGFRA mutations are associated with rather indolent tumors. PDGFRA immunopositivity reflects PDGFRA mutational status and is associated with a favorable outcome.

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

    PubMed

    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. Pharmacological inhibition of KIT activates MET signaling in gastrointestinal stromal tumors

    PubMed Central

    Cohen, Noah A.; Zeng, Shan; Seifert, Adrian M.; Kim, Teresa S.; Sorenson, Eric C.; Greer, Jonathan B.; Beckman, Michael J.; Santamaria-Barria, Juan A.; Crawley, Megan H.; Green, Benjamin L.; Rossi, Ferdinand; Besmer, Peter; Antonescu, Cristina R.; DeMatteo, Ronald P.

    2015-01-01

    Gastrointestinal stromal tumors (GIST) are the most common adult sarcomas and the oncogenic driver is usually a KIT or PDGFRA mutation. While GIST are often initially sensitive to imatinib or other tyrosine kinase inhibitors, resistance generally develops necessitating backup strategies for therapy. In this study, we determined that a subset of human GIST specimens that acquired imatinib resistance acquired expression of activated forms of the MET oncogene. MET activation also developed after imatinib therapy in a mouse model of GIST (KitV558del/+ mice), where it was associated with increased tumor hypoxia. MET activation also occurred in imatinib-sensitive human GIST cell lines after imatinib treatment in vitro. MET inhibition by crizotinib or RNA interference was cytotoxic to an imatinib-resistant human GIST cell population. Moreover, combining crizotinib and imatinib was more effective than imatinib alone in imatinib-sensitive GIST models. Lastly, cabozantinib, a dual MET and KIT small molecule inhibitor, was markedly more effective than imatinib in multiple preclinical models of imatinib-sensitive and imatinib-resistant GIST. Collectively, our findings showed that activation of compensatory MET signaling by KIT inhibition may contribute to tumor resistance. Furthermore, our work offered a preclinical proof of concept for MET inhibition by cabozantinib as an effective strategy for GIST treatment. PMID:25836719

  20. Primary omental gastrointestinal stromal tumour (GIST) presenting with a large abdominal mass and spontaneous haemoperitoneum.

    PubMed

    Seow-En, Isaac; Seow-Choen, Francis; Lim, Tony Kiat Hon; Leow, Wei Qiang

    2014-11-03

    A 60-year-old Indonesian woman presented with a 9-day history of increasing abdominal distension, pain and tiredness. Physical examination revealed significant pallor with a palpable mass in the abdomen. CT of the abdomen reported a 22 cm complex mass in the peritoneal cavity with free intra-abdominal fluid. Laboratory results showed anaemia with a raised serum CA 125 level. At laparotomy a large haemorrhagic tumour with blood filled cystic cavities was found attached to both greater omentum and the transverse mesocolon with 2.2 L of blood in the peritoneal cavity. There was no invasion of any part of the stomach or intestines and there were no metastases seen. Histopathology of the resected specimen was consistent with that of a gastrointestinal stromal tumour arising from the omentum. Immunohistochemical studies revealed the tumour to be strongly positive for discovered on GIST-1 (DOG1) but negative for both CD117 and CD34. Platelet-derived growth factor receptor α (PDGFRA) exon 18 mutation D842V was detected.

  1. Drug Repurposing Identifies a Synergistic Combination Therapy with Imatinib Mesylate for Gastrointestinal Stromal Tumor

    PubMed Central

    Pessetto, Ziyan Y.; Ma, Yan; Hirst, Jeff J.; von Mehren, Margaret; Weir, Scott J.; Godwin, Andrew K.

    2014-01-01

    Gastrointestinal Stromal Tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor, imatinib mesylate (IM) radically improved the clinical response of patients with GIST; however, its effects are often short-lived, with GISTs demonstrating a median time to progression of approximately two years. Although many investigational drugs, approved first for other cancers, have been subsequently evaluated for the management of GIST, few have greatly impacted the overall survival of patients with advanced disease. We employed a novel, focused, drug repurposing effort for GIST including IM-resistant GIST evaluating a large library of FDA-approved drugs regardless of current indication. As a result of the drug repurposing screen, we identified eight FDA-approved drugs including fludarabine phosphate (F-AMP) that showed synergy with and/or overcame resistance to IM. F-AMP induces DNA damage, annexin V and caspase 3/7 activities as the cytotoxic effects on GIST cells, including IM-resistant GIST cells. F-AMP and IM combination treatment showed greater inhibition of GIST cell proliferation when compared to IM alone and F-AMP alone. Successful in vivo experiments confirmed the combination of IM with F-AMP enhanced the antitumor effects compared to IM alone. Our results identified F-AMP as a promising, repurposed drug therapy for the treatment of GISTs, with potential to be administered in combination with IM or for treatment of IM-refractory tumors. PMID:25122069

  2. Succinate dehydrogenase mutation underlies global epigenomic divergence in gastrointestinal stromal tumor.

    PubMed

    Killian, J Keith; Kim, Su Young; Miettinen, Markku; Smith, Carly; Merino, Maria; Tsokos, Maria; Quezado, Martha; Smith, William I; Jahromi, Mona S; Xekouki, Paraskevi; Szarek, Eva; Walker, Robert L; Lasota, Jerzy; Raffeld, Mark; Klotzle, Brandy; Wang, Zengfeng; Jones, Laura; Zhu, Yuelin; Wang, Yonghong; Waterfall, Joshua J; O'Sullivan, Maureen J; Bibikova, Marina; Pacak, Karel; Stratakis, Constantine; Janeway, Katherine A; Schiffman, Joshua D; Fan, Jian-Bing; Helman, Lee; Meltzer, Paul S

    2013-06-01

    Gastrointestinal stromal tumors (GIST) harbor driver mutations of signal transduction kinases such as KIT, or, alternatively, manifest loss-of-function defects in the mitochondrial succinate dehydrogenase (SDH) complex, a component of the Krebs cycle and electron transport chain. We have uncovered a striking divergence between the DNA methylation profiles of SDH-deficient GIST (n = 24) versus KIT tyrosine kinase pathway-mutated GIST (n = 39). Infinium 450K methylation array analysis of formalin-fixed paraffin-embedded tissues disclosed an order of magnitude greater genomic hypermethylation relative to SDH-deficient GIST versus the KIT-mutant group (84.9 K vs. 8.4 K targets). Epigenomic divergence was further found among SDH-mutant paraganglioma/pheochromocytoma (n = 29), a developmentally distinct SDH-deficient tumor system. Comparison of SDH-mutant GIST with isocitrate dehydrogenase-mutant glioma, another Krebs cycle-defective tumor type, revealed comparable measures of global hypo- and hypermethylation. These data expose a vital connection between succinate metabolism and genomic DNA methylation during tumorigenesis, and generally implicate the mitochondrial Krebs cycle in nuclear epigenomic maintenance.

  3. Beyond Standard Therapy: Drugs Under Investigation for The Treatment of Gastrointestinal Stromal Tumor

    PubMed Central

    Alturkmani, Hani J; Pessetto, Ziyan Y; Godwin, Andrew K

    2015-01-01

    Introduction Gastrointestinal stromal tumor (GIST) is the most common non-epithelial malignancy of the GI tract. With the discovery of KIT and later PDGFRA gain-of-function mutations as factors in the pathogenesis of the disease, GIST was the quintessential model for targeted therapy. Despite the successful clinical use of imatinib mesylate, a selective receptor tyrosine kinase (RTK) inhibitor that targets KIT, PDGFRA and BCR-ABL, we still do not have treatment for the long-term control of advanced GIST. Areas covered This review summarizes the drugs that are under investigation or have been assessed in trials for GIST treatment. The article focuses on their mechanisms of actions, the preclinical evidence of efficacy, and the clinical trials concerning safety and efficacy in humans. Expert opinion It is known that KIT and PDGFRA mutations in GIST patients influence the response to treatment. This observation should be taken into consideration when investigating new drugs. RECIST was developed to help uniformly report efficacy trials in oncology. Despite the usefulness of this system, many questions are being addressed about its validity in evaluating the true efficacy of drugs knowing that new targeted therapies do not affect the tumor size as much as they halt progression and prolong survival. PMID:26098203

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

    PubMed

    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.

  5. Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor

    PubMed Central

    Rossi, Ferdinand; Ehlers, Imke; Agosti, Valter; Socci, Nicholas D.; Viale, Agnes; Sommer, Gunhild; Yozgat, Yasemin; Manova, Katia; Antonescu, Cristina R.; Besmer, Peter

    2006-01-01

    Kit receptor-activating mutations are critical in the pathogenesis of gastrointestinal stromal tumors (GIST). We investigated mechanisms of oncogenic Kit signaling and the consequences of therapeutic intervention in a mouse model of human GIST. Treatment of GIST mice with imatinib decreased cell proliferation and increased apoptosis in the tumor. Analysis of tumor tissue from imatinib-treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit signaling critically contributes to the translational response in GIST. Treatment with RAD001 (everolimus), an mTOR inhibitor, diminished the translational response and cell proliferation in tumor lesions, pointing to mTOR inhibition as a therapeutic approach for imatinib-resistant GIST. Analysis of RNA expression profiles in GIST lesions with and without imatinib treatment showed changes in expression of IFN-inducible genes and cell cycle regulators. These results convincingly show that KitV558Δ/+ mice represent a unique faithful mouse model of human familial GIST, and they demonstrate the utility of these mice for preclinical investigations and to elucidate oncogenic signaling mechanisms by using genetic approaches and targeted pharmacological intervention. PMID:16908864

  6. Neoadjuvant imatinib in locally advanced gastrointestinal stromal tumors of the stomach: report of three cases.

    PubMed

    Oh, Ji Seon; Lee, Jae-Lyun; Kim, Mi-Jung; Ryu, Min-Hee; Chang, Heung Moon; Kim, Tae Won; Jang, Se Jin; Yook, Jeong Hwan; Oh, Sung Tae; Kim, Byung Sik; Kang, Yoon-Koo

    2006-01-01

    Neoadjuvant imatinib therapy used to treat locally advanced or metastatic gastrointestinal stromal tumors (GI ST) remains under active investigation. We studied three cases of locally advanced gastric GISTs treated with imatinib on a neoadjuvant basis, followed by a complete surgical resection. Three patients were diagnosed with locally advanced unresectable GIST of the stomach and were started on imatinib 400 mg/day. After the imatinib treatment, partial responses were achieved in all patients and the tumors were considered resectable. Surgical resection was done after 7, 11, and 8 months of imatinib therapy, respectively. In one case, a metastatic liver lesion was detected during the imatinib treatment using computed tomography scans, so the imatinib therapy was maintained for 11 months postoperatively. In the other two patients without distant metastasis, imatinib treatment was not restarted after surgery. Mutational analysis revealed a mutation in exon 11 of the c-kit gene in two patients, and wild-type c-kit and PDGFRA in one patient. During pathology review of all three cases, we noted several features common to imatinib treatment. There was no evidence of tumor recurrence in all three patients at respective follow-up visits of 22, 15, and 7 months. These results suggest that the neoadjuvant imatinib therapy is a potentially curative approach for selected patients with locally advanced GIST.

  7. Genomic and transcriptomic analysis of imatinib resistance in gastrointestinal stromal tumors

    PubMed Central

    Takahashi, Tsuyoshi; Elzawahry, Asmaa; Mimaki, Sachiyo; Furukawa, Eisaku; Nakatsuka, Rie; Nakamura, Hiromi; Nishigaki, Takahiko; Serada, Satoshi; Naka, Tetsuji; Hirota, Seiichi; Shibata, Tatsuhiro; Tsuchihara, Katsuya

    2017-01-01

    Gastrointestinal stromal tumors represent the most common mesenchymal tumor of the digestive tract, driven by gain‐of‐function mutations in KIT. Despite its proven benefits, half of the patients treated with imatinib show disease progression within 2 years due to secondary resistance mutations in KIT. It remains unclear how the genomic and transcriptomic features change during the acquisition of imatinib resistance. Here, we performed exome sequencing and microarray transcription analysis for four imatinib‐resistant cell lines and one cell line briefly exposed to imatinib. We also performed exome sequencing of clinical tumor samples. The cell line briefly exposed to imatinib exhibited few single‐nucleotide variants and copy‐number alterations, but showed marked upregulation of genes related to detoxification and downregulation of genes involved in cell cycle progression. Meanwhile, resistant cell lines harbored numerous genomic changes: amplified genes related to detoxification and deleted genes with cyclin‐dependent kinase activity. Some variants in the resistant samples were traced back to the drug‐sensitive samples, indicating the presence of ancestral subpopulations. The subpopulations carried variants associated with cell death. Pre‐existing cancer cells with genetic alterations promoting apoptosis resistance may serve as a basis whereby cancer cells with critical mutations, such as secondary KIT mutations, can establish full imatinib resistance. © 2017 The Authors Genes, Chromosomes and Cancer Published by Wiley Periodicals, Inc. PMID:27997714

  8. Duration of adjuvant treatment following radical resection of metastases from gastrointestinal stromal tumours

    PubMed Central

    NANNINI, MARGHERITA; PANTALEO, MARIA ABBONDANZA; MALEDDU, ALESSANDRA; SAPONARA, MARISTELLA; MANDRIOLI, ANNA; LOLLI, CRISTIAN; PALLOTTI, MARIA CATERINA; GATTO, LIDIA; SANTINI, DONATELLA; PATERINI, PAOLA; DI SCIOSCIO, VALERIO; CATENA, FAUSTO; FUSAROLI, PIETRO; PINNA, ANTONIO DANIELE; DEI TOS, ANGELO PAOLO; BIASCO, GUIDO

    2011-01-01

    Large-scale studies have demonstrated that continuative treatment in advanced and adjuvant settings results in a gain-of-survival. However, the discontinuation, and the duration of treatment in disease-free patients who have undergone radical surgical resection of metastases from gastrointestinal stromal tumours (GISTs) have yet to be evaluated. We retrospectively reviewed 40 patients with advanced and recurrent GIST, included in our GIST database, focusing on patients (5 males and 2 females; median age 56 years) who continued medical treatment following radical surgical resection of metastatic lesions. Seven out of 40 patients underwent surgery and continued medical treatment following radical surgical resection of metastatic lesions. The duration of adjuvant therapy was 3, 12, 16, 24, 35, 37 and 52 months, respectively, with a median of 26 months. No patients discontinued therapy and all were disease-free at the final CT-scan evaluation. Considering that the discontinuation of imatinib in responding patients with advanced GIST (even in complete remission) results in a rapid high risk of progression, and a short adjuvant therapy results in a shorter disease-free and overall survival in high-risk GIST patients, it is also likely that treatment should not be discontinued in this setting. However, large-scale studies are required to better assess the optimal duration of treatment, particularly after 5 years, by focusing on the identification of predictive factors for the selection of patients who may benefit from a prolonged or lifelong imatinib treatment. PMID:22740975

  9. Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour.

    PubMed

    Wachter, Nicolas; Wörns, Marcus-Alexander; Dos Santos, Daniel Pinto; Lang, Hauke; Huber, Tobias; Kneist, Werner

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology-controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve-sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs.

  10. Transanal minimally invasive surgery (TAMIS) approach for large juxta-anal gastrointestinal stromal tumour

    PubMed Central

    Wachter, Nicolas; Wörns, Marcus-Alexander; dos Santos, Daniel Pinto; Lang, Hauke; Huber, Tobias; Kneist, Werner

    2016-01-01

    Gastrointestinal stromal tumours (GISTs) are rarely found in the rectum. Large rectal GISTs in the narrow pelvis sometimes require extended abdominal surgery to obtain free resection margins, and it is a challenge to preserve sufficient anal sphincter and urogenital function. Here we present a 56-year-old male with a locally advanced juxta-anal non-metastatic GIST of approximately 10 cm in diameter. Therapy with imatinib reduced the tumour size and allowed partial intersphincteric resection (pISR). The patient underwent an electrophysiology-controlled nerve-sparing hybrid of laparoscopic and transanal minimally invasive surgery (TAMIS) in a multimodal setting. The down-to-up approach provided sufficient dissection plane visualisation and allowed the confirmed nerve-sparing. Lateroterminal coloanal anastomosis was performed. Follow-up showed preserved urogenital function and good anorectal function, and the patient remains disease-free under adjuvant chemotherapy as of 12 months after surgery. This report suggests that the TAMIS approach enables extraluminal high-quality oncological and function-preserving excision of high-risk GISTs. PMID:27279406

  11. Promoter methylation of PCDH10 by HOTAIR regulates the progression of gastrointestinal stromal tumors

    PubMed Central

    Lee, Na Keum; Lee, Jung Hwa; Kim, Won Kyu; Yun, Seongju; Youn, Young Hoon; Park, Chan Hyuk; Choi, Yun Young; Kim, Hogeun; Lee, Sang Kil

    2016-01-01

    HOTAIR, a long non-coding RNA (lncRNA), plays a crucial role in tumor initiation and metastasis by interacting with the PRC2 complex and the modulation of its target genes. The role of HOTAIR in gastrointestinal stromal tumors (GISTs) is remains unclear. Herein we investigate the mechanism of HOTAIR in the genesis and promotion of GISTs. The expression of HOTAIR was found to be higher in surgically resected high-risk GISTs than that in low- and intermediate-risk GISTs. Using GIST-T1 and GIST882 cells, we demonstrated that HOTAIR repressed apoptosis, was associated with cell cycle progression, and controlled the invasion and migration of GIST cells. Using a gene expression microarray and lists of HOTAIR-associated candidate genes, we suggested that protocadherin 10 (PCDH10) is a key molecule. PCDH10 expression was significantly decreased in GIST-T1 and GIST882 cells, possibly as a consequence of hypermethylation. We observed that HOTAIR induced PCDH10 methylation in a SUZ12-dependent manner. In this study, we found that the malignant character of GISTs was initiated and amplified by PCDH10 in a process regulated by HOTAIR. In summary, our findings imply that PCDH10 and HOTAIR may be useful markers of disease progression and therapeutic targets. PMID:27659532

  12. Safety of Regular-Dose Imatinib Therapy in Patients with Gastrointestinal Stromal Tumors Undergoing Dialysis.

    PubMed

    Niikura, Ryota; Serizawa, Takako; Yamada, Atsuo; Yoshida, Shuntaro; Tanaka, Mariko; Hirata, Yoshihiro; Koike, Kazuhiko

    2016-01-01

    The number of cancer patients undergoing dialysis has been increasing, and the number of these patients on chemotherapy is also increasing. Imatinib is an effective and safe therapy for KIT-positive gastrointestinal stromal tumors (GIST), but the efficacy and safety of imatinib in dialysis patients remain unclear. Because clinical trials have not been conducted in this population, more investigations are required. We report on a 75-year-old Japanese man undergoing dialysis who presented with massive tarry stool from a duodenal GIST. The duodenal GIST was 14 cm in diameter with multiple liver and bone metastases. The patient underwent an urgent pancreaticoduodenectomy to achieve hemostasis. After surgery, he was administered imatinib 400 mg/day. No severe adverse event including myelosuppression, congestive heart failure, liver functional impairment, intestinal pneumonia, or Steven-Johnson syndrome occurred, and the liver metastasis remained stable for 4 months. During chemotherapy, hemodialysis continued three times per week without adverse events. We suggest that regular-dose imatinib is an effective and safe treatment in patients with GIST undergoing dialysis. In addition, we present a literature review of the effectiveness and safety of imatinib treatment in dialysis patients.

  13. NCCN Task Force Report: Update on the Management of Patients with Gastrointestinal Stromal Tumors

    PubMed Central

    Demetri, George D.; von Mehren, Margaret; Antonescu, Cristina R.; DeMatteo, Ronald P.; Ganjoo, Kristen N.; Maki, Robert G.; Pisters, Peter W.T.; Raut, Chandrajit P.; Riedel, Richard F.; Schuetze, Scott; Sundar, Hema M.; Trent, Jonathan C.; Wayne, Jeffrey D.

    2014-01-01

    The standard of care for managing patients with gastrointestinal stromal tumors (GISTs) rapidly changed after the introduction of effective molecularly targeted therapies involving tyrosine kinase inhibitors (TKIs), such as imatinib mesylate and sunitinib malate. A better understanding of the molecular characteristics of GISTs have improved the diagnostic accuracy and led to the discovery of novel immunomarkers and new mechanisms of resistance to TKI therapy, which in turn have resulted in the development of novel treatment strategies. To address these issues, the NCCN organized a task force consisting of a multidisciplinary panel of experts in the fields of medical oncology, surgical oncology, molecular diagnostics, and pathology to discuss the recent advances, identify areas of future research, and recommend an optimal approach to care for patients with GIST at all stages of disease. The task force met for the first time in October 2003 and again in December 2006 and October 2009. This supplement describes the recent developments in the field of GIST as discussed at the October 2009 meeting. PMID:20457867

  14. Canine and human gastrointestinal stromal tumors display similar mutations in c-KIT exon 11

    PubMed Central

    2010-01-01

    Background Gastrointestinal stromal tumors (GISTs) are common mesenchymal neoplasms in the gastrointestinal tract of humans and dogs. Little is known about the pathogenesis of these tumors. This study evaluated the role of c-KIT in canine GISTs; specifically, we investigated activating mutations in exons 8, 9, 11, 13, and 17 of c-KIT and exons 12, 14, and 18 of platelet-derived growth factor receptor, alpha polypeptide (PDGFRA), all of which have been implicated in human GISTs. Methods Seventeen canine GISTs all confirmed to be positive for KIT immunostaining were studied. Exons 8, 9, 11, 13 and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA, were amplified from DNA isolated from formalin-fixed paraffin-embedded samples. Results Of these seventeen cases, six amplicons of exon 11 of c-KIT showed aberrant bands on gel electrophoresis. Sequencing of these amplicons revealed heterozygous in-frame deletions in six cases. The mutations include two different but overlapping six base pair deletions. Exons 8, 9, 13, and 17 of c-KIT and exons 12, 14, and 18 of PDGFRA had no abnormalities detected by electrophoresis and sequencing did not reveal any mutations, other than synonymous single nucleotide polymorphisms (SNPs) found in exon 11 of c-KIT and exons 12 and 14 of PDGFRA. Conclusions The deletion mutations detected in canine GISTs are similar to those previously found in the juxtamembrane domain of c-KIT in canine cutaneous mast cell tumors in our laboratory as well as to those reported in human GISTs. Interestingly, none of the other c-KIT or PDGFRA exons showed any abnormalities in our cases. This finding underlines the critical importance of c-KIT in the pathophysiology of canine GISTs. The expression of KIT and the identification of these activating mutations in c-KIT implicate KIT in the pathogenesis of these tumors. Our results indicate that mutations in c-KIT may be of prognostic significance and that targeting KIT may be a rational approach to treatment of these

  15. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer

    PubMed Central

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-01-01

    Abstract The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer. From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed. Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474). The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer. PMID:27828865

  16. A Screen for Epigenetically Silenced microRNA Genes in Gastrointestinal Stromal Tumors

    PubMed Central

    Nojima, Masanori; Kai, Masahiro; Yamamoto, Eiichiro; Maruyama, Reo; Nobuoka, Takayuki; Nishida, Toshirou; Kanda, Tatsuo; Taguchi, Takahiro; Hasegawa, Tadashi; Tokino, Takashi; Hirata, Koichi; Suzuki, Hiromu; Shinomura, Yasuhisa

    2015-01-01

    Background Dysregulation of microRNA (miRNA) has been implicated in gastrointestinal stromal tumors (GISTs) but the mechanism is not fully understood. In this study, we aimed to explore the involvement of epigenetic alteration of miRNA genes in GISTs. Methods GIST-T1 cells were treated with 5-aza-2’-deoxycytidine (5-aza-dC) and 4-phenylbutyric acid (PBA), after which miRNA expression profiles were analyzed using TaqMan miRNA arrays. DNA methylation was then analyzed using bisulfite pyrosequencing. The functions of miRNAs were examined using MTT assays, wound-healing assays, Boyden chamber assays and Matrigel invasion assays. Gene expression microarrays were analyzed to assess effect of ectopic miRNA expression in GIST-T1 cells. Results Of the 754 miRNAs analyzed, 61 were significantly upregulated in GIST-T1 cells treated with 5-aza-dC plus PBA. Among those, 21 miRNA genes were associated with an upstream CpG island (CGI), and the CGIs of miR-34a and miR-335 were frequently methylated in GIST-T1 cells and primary GIST specimens. Transfection of miR-34a or miR-335 mimic molecules into GIST-T1 cells suppressed cell proliferation, and miR-34a also inhibited migration and invasion by GIST-T1 cells. Moreover, miR-34a downregulated a number of predicted target genes, including PDGFRA. RNA interference-mediated knockdown of PDGFRA in GIST-T1 cells suppressed cell proliferation, suggesting the tumor suppressive effect of miR-34a is mediated, at least in part, through targeting PDGFRA. Conclusions Our results suggest that miR-34a and miR-335 are candidate tumor suppressive miRNAs in GISTs, and that they are frequent targets of epigenetic silencing in GISTs. PMID:26214687

  17. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors

    PubMed Central

    Tarn, Chi; Rink, Lori; Merkel, Erin; Flieder, Douglas; Pathak, Harsh; Koumbi, Daphne; Testa, Joseph R.; Eisenberg, Burton; von Mehren, Margaret; Godwin, Andrew K.

    2008-01-01

    A subset of gastrointestinal stromal tumors (GISTs) lack gain-of-function mutations in c-KIT and PDGFRα. These so-called wild-type (WT) GISTs tend to be less responsive to imatinib-based therapies and have a poor prognosis. We identified amplification of IGF1R in a SNP analysis of GIST and thus studied its potential as a therapeutic target in WT and mutant GIST. Expression of IGF1R and downstream effectors in clinical GIST samples was examined by using immunoblots and immunohistochemistry. The roles of IGF1R signaling in GIST and viability were analyzed by using NVP-AEW541, an inhibitor of IGF1R, alone and in combination with imatinib, or via siRNA silencing of IGF1R. IGF1R was strongly overexpressed, and IGF1R amplification was detected at a significantly higher frequency in WT GISTs, including a pediatric WT GIST, compared with mutant GISTs (P = 0.0173 and P = 0.0163, respectively). Inhibition of IGF1R activity in vitro with NVP-AEW541 or down-regulation of expression with siIGF1R led to cytotoxicity and induced apoptosis in GIST cell lines via AKT and MAPK signaling. Combination of NVP-AEW541 and imatinib in GIST cell lines induced a strong cytotoxicity response. Our results reveal that IGF1R is amplified and the protein is overexpressed in WT and pediatric GISTs. We also demonstrate that the aberrant expression of IGF1R may be associated with oncogenesis in WT GISTs and suggest an alternative and/or complementary therapeutic regimen in the clinical management of all GISTs, especially in a subset of tumors that respond less favorably to imatinib-based therapy. PMID:18550829

  18. Chronic therapy in gastrointestinal stromal tumours (GISTs): the big gap between theory and practice.

    PubMed

    Saponara, Maristella; Pantaleo, Maria Abbondanza; Nannini, Margherita; Biasco, Guido

    2012-12-01

    The advent of imatinib mesilate, an oral target therapy, has dramatically changed the natural history of gastrointestinal stromal tumours (GISTs). This rare neoplasm has become the paradigm of targeted therapies in solid tumours, also introducing a home-based cure concept in oncology. However, it should be retained that oral drug administration entails new and relevant management problems. Multiple studies have demonstrated the efficacy of imatinib in GISTs associated with a good toxicity profile. However, the efficacy of imatinib, according to its mechanism of action and pharmacokinetics, is closely related to daily assumption. No interruption or "jerky" assumption is permitted in order to avoid efficacy loss. Thus, the issue of treatment adherence is crucial for a successful strategy and should not be overlooked. We think that dealing with the problem means assessing a wide spectrum of not only clinical and general but also psychological and individual aspects. Furthermore, both patient and family should play an active role in the "cure process" and physicians should reduce the distance separating them from their patients due to home-based target therapy, promoting communication and consolidation of a trust-based physician-patient relationship. Several advantages have been introduced by oral target therapies in oncology. However, chronic drug administration, even if generally well tolerated, when prolonged for an undetermined time could heavily impact on patients' quality of life. This could induce non-prescribed drug suspension, with negative impact on disease control. More studies would be necessary in order to detect real patients' adherence, to correlate drug assumption with clinical outcome and to optimize imatinib treatment strategy.

  19. Clinicopathological features and prognosis of coexistence of gastric gastrointestinal stromal tumor and gastric cancer.

    PubMed

    Liu, Zhen; Liu, Shushang; Zheng, Gaozan; Yang, Jianjun; Hong, Liu; Sun, Li; Fan, Daiming; Zhang, Hongwei; Feng, Fan

    2016-11-01

    The coexistence of gastric gastrointestinal stromal tumor (GIST) and gastric cancer is relatively high, and its prognosis is controversial due to the complex and variant kinds of presentation. Thus, the present study aimed to explore the clinicopathological features and prognostic factors of gastric GIST with synchronous gastric cancer.From May 2010 to November 2015, a total of 241 gastric GIST patients were retrospectively enrolled in the present study. The patients with coexistence of gastric GIST and gastric cancer were recorded. The clinicopathological features and prognoses of patients were analyzed.Among 241 patients, 24 patients had synchronous gastric cancer (synchronous group) and 217 patients did not (no-synchronous group). The synchronous group presented a higher percentage of elders (66.7% vs 39.6%, P = 0.001) and males (87.5% vs 48.4%, P < 0.001) than the no-synchronous group. The tumor diameter, mitotic index, and National Institutes of Health degree were also significantly different between the 2 groups (all P < 0.05). The 5-year disease-free survival and disease-specific survival rates of synchronous group were significantly lower than those of no-synchronous group (54.9% vs 93.5%, P < 0.001; 37.9% vs 89.9%, P < 0.001, respectively). However, the 5-year overall survival rates between synchronous and gastric cancer groups were comparable (37.9% vs 57.6%, P = 0.474).The coexistence of gastric GIST and gastric cancer was common in elder male patients. The synchronous GIST was common in low-risk category. The prognosis of gastric GIST with synchronous gastric cancer was worse than that of primary-single gastric GIST, but was comparable with primary-single gastric cancer.

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

    PubMed Central

    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 = 15) GIST treated with imatinib (400 mg/day) were analysed retrospectively. Lumbar skeletal muscle indexes were evaluated on computed tomography images obtained before starting imatinib for all patients and at 6 months for those initially sarcopenic. Sarcopenia was defined using consensual cutoffs. Imatinib-induced toxicities were assessed after 3 months of administration. Results Twelve (38.7%) of the 31 patients were sarcopenic, including one unassessable at 6 months. Seven (63.6%) of the 11 assessable sarcopenic patients became non-sarcopenic after 6 months of imatinib. Pre-treatment sarcopenia was not associated with grades 3–4 toxicities, but the mean number of all-grade toxicities per sarcopenic patient was significantly higher for those non-sarcopenic (4.1 vs. 1.7, respectively, p < 0.01) after 3 months of treatment. Grades 1–2 anaemia and grades 1–2 fatigue were more frequent for sarcopenic than non-sarcopenic patients (83% vs. 26%, P < 0.01 and 42% vs. 5%, P = 0.02, respectively). Conclusions Sarcopenia is reversible in some GIST patients treated with imatinib. Pre-imatinib sarcopenia is predictive of non-severe toxicities, particularly anaemia and fatigue. PMID:26673372

  1. Severe Imatinib-Associated Skin Rash in Gastrointestinal Stromal Tumor Patients: Management and Clinical Implications

    PubMed Central

    Park, Sook Ryun; Ryu, Min-Hee; Ryoo, Baek-Yeol; Beck, Mo Youl; Lee, In Soon; Choi, Mi Jung; Lee, Mi Woo; Kang, Yoon-Koo

    2016-01-01

    Purpose This study evaluated the incidence of imatinib-associated skin rash, the interventional outcomes of severe rash, and impact of severe rash on the outcomes of imatinib treatment in gastrointestinal stromal tumor (GIST) patients. Materials and Methods A total of 620 patients were administered adjuvant or palliative imatinib for GIST at Asan Medical Center between January 2000 and July 2012. This analysis focused on a group of 42 patients who developed a severe rash requiring major interventions, defined as dose interruption or reduction of imatinib or systemic steroid use. Results Of the 620 patients treated with imatinib, 148 patients (23.9%) developed an imatinib-associated skin rash; 42 patients (6.8%) developed a severe rash requiring major intervention. Of these, 28 patients (66.8%) successfully continued imatinib with interventions. Serial blood eosinophil levels during imatinib treatment were associated with skin rash and severity. A significant association was observed between successful intervention and blood eosinophil level at the time of intervention initiation. In metastatic settings, patients with severe rash requiring major interventions tended to show poorer progression-free survival than patients who did not require major intervention and patients with no rash, although this finding was not statistically significant (p=0.326). Conclusion By aggressive treatment of severe rash through modification of imatinib dose or use of systemic steroid, the majority of patients can continue on imatinib. In particular, imatinib dose intensity can be maintained with use of systemic steroid. Measuring the blood eosinophil levels may be helpful in guiding the management plan for skin rash regarding the intensity and duration of interventions. PMID:26323636

  2. Transcriptomic reappraisal identifies MGLL overexpression as an unfavorable prognosticator in primary gastrointestinal stromal tumors

    PubMed Central

    Liu, Ting-Ting; Chen, Ko-Chin; Chen, Yen-Yang; Fang, Fu-Min; Li, Shau-Hsuan; Chen, Tzu-Ju; Yu, Shih-Chen; Lan, Jui; Huang, Hsuan-Ying

    2016-01-01

    The role of deregulated cellular metabolism, particularly lipid metabolism, in gastrointestinal stromal tumors (GISTs) remains unclear. Through data mining of published transcriptomes, we examined lipid metabolism-regulating drivers differentially upregulated in high-risk cases and identified monoglyceride lipase (MGLL) as the top-ranking candidate involved in GIST progression. MGLL expression status was examined in three GIST cell lines and two independent sets of primary localized GISTs. MGLL mRNA abundance and immunoexpression was determined in 70 cases through the QuantiGene assay and H-scoring on whole sections, respectively. H-scoring was extended to another cohort for evaluating MGLL immunoexpression on tissue microarrays, yielding 350 informative cases, with KIT/PDGFRA mutation genotypes noted in 213 of them. Both imatinib-sensitive (GIST882) and -resistant (GIST48 and GIST430) cell lines exhibited increased MGLL expression. MGLL mRNA levels significantly increased from adjacent normal tissue to the non-high-risk group (p = 0.030) and from the non-high-risk group to high-risk GISTs (p = 0.012), and were associated with immunoexpression levels (p < 0.001, r = 0.536). MGLL overexpression was associated with the nongastric location (p = 0.022) and increased size (p = 0.017), and was strongly related to mitosis and risk levels defined by NIH and NCCN criteria (all p ≤ 0.001). Univariately, MGLL overexpression was strongly predictive of poorer disease-free and overall survival (both p < 0.001), which remained prognostically independent for both endpoints, along with higher risk levels. Conclusively, MGLL is a lipid metabolic enzyme causatively implicated in GIST progression given its association with unfavorable clincopathological factors and independent negative prognostic effects. PMID:27366945

  3. Detection of Treatment-Induced Changes in Signaling Pathways in Gastrointestinal Stromal Tumors using Transcriptomic Data

    PubMed Central

    Ochs, Michael F.; Rink, Lori; Tarn, Chi; Mburu, Sarah; Taguchi, Takahiro; Eisenberg, Burton; Godwin, Andrew K.

    2009-01-01

    Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins, however off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally feasible during treatment, there is a need for more powerful methods to determine if therapeutics inhibit their targets and when off-target effects occur. We have used the Bayesian Decomposition algorithm and data on transcriptional regulation to create a novel methodology, DESIDE (Differential Expression for SIgnaling DEtermination), for inferring signaling activity from microarray measurements. We applied DESIDE to deduce signaling activity in gastrointestinal stromal tumor cell lines treated with the targeted therapeutic imatinib mesylate (Gleevec). We detected the expected reduced activity in the KIT pathway, as well as unexpected changes in the P53 pathway. Pursuing these findings, we have determined that imatinib-induced DNA damage is responsible for the increased activity of P53, identifying a novel off-target activity for this drug. We then used DESIDE on data from resected, post-imatinib treatment tumor samples and identified a pattern in these tumors similar to that at late time points in the cell lines, and this pattern correlated with initial clinical response. The pattern showed increased activity of ELK1 and STAT3 transcription factors, which are associated with the growth of side population cells. DESIDE infers the global reprogramming of signaling networks during treatment, permitting treatment modification that leverages ongoing drug development efforts, which is crucial for personalized medicine. PMID:19903850

  4. Histopathological Features of Gastrointestinal Stromal Tumors and the Contribution of DOG1 Expression to the Diagnosis

    PubMed Central

    Güler, Beril; Özyılmaz, Filiz; Tokuç, Burcu; Can, Nuray; Taştekin, Ebru

    2015-01-01

    Background: Gastrointestinal stromal tumors (GIST) have KIT or platelet-derived growth factor receptor α (PDGFRα) mutations affecting receptor tyrosine kinase activity and do not benefit from classic treatment regimens. Aims: The aim of this study was to review the algorithm that may be followed for the diagnosis and differential diagnosis in GISTs by investigating the histomorphological parameters and expression characteristics of classical immunohistochemical antibodies used in routine tests in addition to DOG1 expression. Study Design: Diagnostic accuracy study. Methods: We reevaluated the histological and immunohistochemical parameters of 37 GISTs. The standard immunohistochemical diagnosis and differential diagnosis panel antibodies (CD117, PDGFRα, CD34, vimentin, desmin, SMA, S-100, and Ki67) were studied on the tumor sections. We also used the popular marker DOG1 antibody with accepted sensitivity for GISTs in recent years and the PDGFRα immune marker for which the benefit in routine practice is discussed. Results: Classification according to progressive disease risk groups of the 37 cases revealed that 54% were in the high risk, 19% in the moderate risk, 16% in the low risk, 8% in the very low risk and 8% in the no risk group. Cytological atypia, necrosis, mucosal invasion and the Ki67 index were found to be related to the progressive disease risk groups of the tumors (p<0.05). Positive immunoreaction was observed with CD117 and PDGFRα in all GISTs in the study (100%). Positivity with the DOG1 antibody was found in 33 (89%) cases. CD34 was positive in 62% (23) of the cases. Conclusion: The CD117 antibody still plays a key role in GIST diagnosis. However, the use of DOG1 and PDGFRα antibodies combined with CD117 as sensitive markers can be beneficial. PMID:26740899

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

    PubMed

    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.

  6. Dysregulated expression of Snail and E-cadherin correlates with gastrointestinal stromal tumor metastasis.

    PubMed

    Liu, Sheng; Liao, Guoqing; Ding, Jie; Ye, Ke; Zhang, Yi; Zeng, Liang; Chen, Senlin

    2014-09-01

    Snail, a zinc finger structure transcription inhibitory factor, has been reported to play an important role in the metastatic progression of several types of cancer. The aim of the study was to identify potential biomarkers for metastasis in gastrointestinal stromal tumors (GISTs) by examining the expression levels of Snail, E-cadherin, and Vimentin in GISTs and investigate their clinical significance. The protein expression of Snail, E-cadherin, and Vimentin in 74 GIST specimens was detected by immunohistochemical analysis, and the correlation between expression levels and clinicopathological data was analyzed. Snail, E-cadherin, and Vimentin were positively expressed in 51.4% (38/74), 32.4% (24/74), and 68.9% (51/74) of GIST tissue samples, respectively. Snail protein expression was significantly higher in GISTs with distant metastasis compared with GISTs without distant metastasis (P<0.05). E-cadherin expression level was significantly lower in cases of GIST with distant metastasis compared with those without distant metastasis (P<0.05), whereas the expression level of Vimentin did not significantly change according to clinical and pathological characteristics (all P>0.05). Snail expression was significantly negatively correlated with E-cadherin expression (r's=-0.276, P=0.017) but not with Vimentin expression (r's=0.041, P=0.728) in GISTs. High Snail expression and low E-cadherin expression were significantly correlated with metastasis in GISTs, and Snail, because of positive correlation, is potentially a biomarker of GIST with distant metastasis.

  7. Laparoscopic management of gastrointestinal stromal tumours: review at a Canadian centre

    PubMed Central

    Daigle, Carl; Meneghetti, Adam T.; Lam, Jasmine; Panton, Ormond N.M.

    2012-01-01

    Background Laparoscopic wedge resection has been widely accepted for small benign gastric tumours. Large gastrointestinal stromal tumours (GISTs), however, can be difficult to manipulate laparoscopically and are at risk for capsule disruption, which can then result in peritoneal seeding. Some authors have suggested that large GISTs (> 8 cm) are best approached using an open technique. However, there has been no consensus as to what the cut-off size should be. We conducted one of the largest Canadian series to date to assess outcomes and follow-up of the laparoscopic management of GISTs. Methods All patients with gastric GISTs presenting to Vancouver General Hospital and University of British Columbia Hospital between 2000 and 2008 were reviewed. Most lesions were resected using a wedge technique with closure of the stomach facilitated by an endoscopic linear stapling device. Results In all, 23 patients presented with GISTs; 19 patients underwent laparoscopic resection and, of these, 15 had a purely laparoscopic operation and 4 had a hand-assisted laparoscopic resection. Mean tumour size was 3.2 cm, with the largest tumour measuring 6.8 cm. There were no episodes of tumour rupture or spillage and no major intraoperative complications. All margins were negative. Mean follow-up was 13.3 (range 1–78) months. There was no evidence of recurrence or metastasis. Conclusion The laparoscopic management of gastric GISTs is safe and effective with short hospital stays and good results over a mean follow-up of 13.3 months. We believe that it should be the preferred technique offered to patients. PMID:22269221

  8. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations

    PubMed Central

    Janeway, Katherine A.; Kim, Su Young; Lodish, Maya; Nosé, Vânia; Rustin, Pierre; Gaal, José; Dahia, Patricia L. M.; Liegl, Bernadette; Ball, Evan R.; Raygada, Margarita; Lai, Angela H.; Kelly, Lorna; Hornick, Jason L.; O'Sullivan, Maureen; de Krijger, Ronald R.; Dinjens, Winand N. M.; Demetri, George D.; Antonescu, Cristina R.; Fletcher, Jonathan A.; Helman, Lee; Stratakis, Constantine A.

    2011-01-01

    Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1–associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis. PMID:21173220

  9. Life-threatening bleeding of a duodenal gastrointestinal stromal tumor in a teenager: a rare case report

    PubMed Central

    Valli, Piero V.; Valli, Carlo; Pfammatter, Thomas; Bauerfeind, Peter

    2016-01-01

    Duodenal gastrointestinal stromal tumors (GIST) are per se infrequent and are exceptional in children or young adults. So far, only 2 cases of pediatric duodenal GISTs have been published. Here we report on the case of a 19-year-old female patient who was admitted in hemorrhagic shock due to arterial bleeding of a duodenal GIST located in immediate proximity to the major duodenal papilla. After several attempts of endoscopic hemostasis failed, the tumor bleeding was controlled with a second coil embolization of the pancreaticoduodenal arcades. PMID:27995183

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

    PubMed

    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.

  11. A case of multiple gastrointestinal stromal tumors caused by a germline KIT gene mutation (p.Leu576Pro).

    PubMed

    Vale Rodrigues, Rita; Santos, Filipa; Pereira da Silva, João; Francisco, Inês; Claro, Isabel; Albuquerque, Cristina; Lemos, Maria Manuel; Limbert, Manuel; Dias Pereira, António

    2017-04-01

    Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls. Somatic mutational analysis of the KIT gene revealed a substitution at codon 576 in exon 11 (p.Leu576Pro) in all tumors and normal ileal mucosa. The germline nature of this mutation was confirmed by mutation analysis in peripheral blood leukocytes. However, she had no familial history of GISTs and her parents did not carry the respective germline mutation.

  12. Generation of orthotopic patient-derived xenografts from gastrointestinal stromal tumor

    PubMed Central

    2014-01-01

    Background Gastrointestinal stromal tumor (GIST) is the most common sarcoma and its treatment with imatinib has served as the paradigm for developing targeted anti-cancer therapies. Despite this success, imatinib-resistance has emerged as a major problem and therefore, the clinical efficacy of other drugs has been investigated. Unfortunately, most clinical trials have failed to identify efficacious drugs despite promising in vitro data and pathological responses in subcutaneous xenografts. We hypothesized that it was feasible to develop orthotopic patient-derived xenografts (PDXs) from resected GIST that could recapitulate the genetic heterogeneity and biology of the human disease. Methods Fresh tumor tissue from three patients with pathologically confirmed GISTs was obtained immediately following tumor resection. Tumor fragments (4.2-mm3) were surgically xenografted into the liver, gastric wall, renal capsule, and pancreas of immunodeficient mice. Tumor growth was serially assessed with ultrasonography (US) every 3-4 weeks. Tumors were also evaluated with positron emission tomography (PET). Animals were sacrificed when they became moribund or their tumors reached a threshold size of 2500-mm3. Tumors were subsequently passaged, as well as immunohistochemically and histologically analyzed. Results Herein, we describe the first model for generating orthotopic GIST PDXs. We have successfully xenografted three unique KIT-mutated tumors into a total of 25 mice with an overall success rate of 84% (21/25). We serially followed tumor growth with US to describe the natural history of PDX growth. Successful PDXs resulted in 12 primary xenografts in NOD-scid gamma or NOD-scid mice while subsequent successful passages resulted in 9 tumors. At a median of 7.9 weeks (range 2.9-33.1 weeks), tumor size averaged 473±695-mm3 (median 199-mm3, range 12.6-2682.5-mm3) by US. Furthermore, tumor size on US within 14 days of death correlated with gross tumor size on necropsy. We also

  13. Gastrointestinal stromal tumor as entry port for S. intermedius causing bacteremia and multiple liver abscesses. Case report and review of literature.

    PubMed

    Benou, C; Walter, B M; Schlitter, M A; Wilhelm, D; Neu, B; Schmid, R M

    2016-03-01

    We report a case of a previously healthy 52-year-old man who presented with fever and liver lesions suspicious for metastatic disease, which proved subsequently to be abscesses. Further workup revealed a gastrointestinal stromal tumor (GIST) in the gastric corpus as entry port to Streptococcus intermedius-associated bacteremia and liver abscesses. After antibiotic treatment and surgical resection of the tumor, the patient recovered well. This unusual case indicates that gastrointestinal stromal tumors can remain undetected until they cause a life threatening infection. A review of recent literature pertaining to GIST and liver abscesses follows.

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

    PubMed

    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.

  15. Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: European group on tumor markers 2014 guidelines update.

    PubMed

    Duffy, M J; Lamerz, R; Haglund, C; Nicolini, A; Kalousová, M; Holubec, L; Sturgeon, C

    2014-06-01

    Biomarkers currently play an important role in the detection and management of patients with several different types of gastrointestinal cancer, especially colorectal, gastric, gastro-oesophageal junction (GOJ) adenocarcinomas and gastrointestinal stromal tumors (GISTs). The aim of this article is to provide updated and evidence-based guidelines for the use of biomarkers in the different gastrointestinal malignancies. Recommended biomarkers for colorectal cancer include an immunochemical-based fecal occult blood test in screening asymptomatic subjects ≥50 years of age for neoplasia, serial CEA levels in postoperative surveillance of stage II and III patients who may be candidates for surgical resection or systemic therapy in the event of distant metastasis occurring, K-RAS mutation status for identifying patients with advanced disease likely to benefit from anti-EGFR therapeutic antibodies and microsatellite instability testing as a first-line screen for subjects with Lynch syndrome. In advanced gastric or GOJ cancers, measurement of HER2 is recommended in selecting patients for treatment with trastuzumab. For patients with suspected GIST, determination of KIT protein should be used as a diagnostic aid, while KIT mutational analysis may be used for treatment planning in patients with diagnosed GISTs.

  16. Splenosis in gastric fundus mimicking gastrointestinal stromal tumor: a report of two cases and review of the literature.

    PubMed

    Li, Bin; Huang, Ya; Chao, Baoting; Zhao, Qi; Hao, Jinghua; Qin, Chengyong; Xu, Hongwei

    2015-01-01

    Splenosis refers to heterotopic autotransplantation and implantation of splenic tissue following splenic trauma or surgery. Splenosis in gastric fundus is rare and difficult to diagnose, since splenosis has similar manifestation with gastrointestinal stromal tumor (GIST) under routine endoscopy examination. In this report, we present two quite rare case of splenosis. Both of their pre-operative diagnose under endoscopic ultrasonography was considered as GIST. Finally, one in the abdominal cavity, adhering closely to the gastric fundus, measuring 20 mm × 15 mm, was resected by surgical operation, and one in the gastric fundus, measuring 20 mm × 20 mm, was resected by endoscopic surgery. The precise diagnosis of splenosis was distinct by post-operative histopathologic examination. In addition, we also made a mini review of previously published articles, in order to provide indication to solve future doubts in diagnosing and treating splenosis.

  17. Gastrointestinal stromal tumor with a PDGFRA mutation masquerading as gastric plexiform fibromyxoma: A comparative clinicopathological study of two cases

    PubMed Central

    Zhou, Jun; Xu, Jingjing; Jiang, Guozhong; Ma, Yihui; Qi, Jingwen; Li, Wencai; Zhang, Dandan

    2017-01-01

    Gastric plexiform fibromyxoma (PF) is a rare mesenchymal tumor with a histologically distinctive multinodular pattern, dissimilar to conventional gastrointestinal stromal tumor (GIST). The current study presents one case of gastric PF, and one case of GIST with a platelet-derived growth factor receptor α (PDGFRA) mutation mimicking PF, and discusses their differential diagnoses. The two patients were a 51-year-old male with PF and a 47-year-old female with GIST, each of whom presented with an occupying lesion in the gastric antrum. Histologically, the two cases shared a rare and approximately unanimous morphological pattern of a prominent multinodular and plexiform figuration in the gastric wall, including mucoid matrix, short spindle cells and small caliber vascular elements, and areas of stromal tumor cells exhibited an epithelioid appearance. Immunohistochemistry revealed that the PF tumor cells were positive for smooth muscle actin (SMA), but negative for mast/stem cell growth factor receptor (KIT), GIST-1 (DOG1), cluster of differentiation (CD) 34, S-100, desmin and cytokeratin AE1/AE3. The case of GIST expressed KIT and DOG1, but was negative for SMA, CD34, S-100, desmin and AE1/AE3. In addition, the GIST case, which was observed to harbor a D842V mutation in exon 18 of PDGFRA, was demonstrated to be genetically distinct from PF. The cases presented in the current study were uncommon in that GIST exhibited a plexiform appearance that mimicked the histology of the rare PF tumor; therefore, GIST must be considered and discounted first when determining a differential diagnosis for a gastrointestinal mesenchymal neoplasm. PMID:28356974

  18. Clinicopathologic study of 275 cases of gastrointestinal stromal tumors: the experience at 3 large medical centers in Mexico.

    PubMed

    Alvarado-Cabrero, Isabel; Vázquez, Gonzálo; Sierra Santiesteban, Francisca I; Hernández-Hernández, Dulce Ma; Pompa, Angel Zavala

    2007-02-01

    It is important to distinguish gastrointestinal (GI) stromal tumors (GISTs) from other GI mesenchymal tumors (GIMTs) because of the availability of molecular-targeted therapy for GISTs. The aim of the study was to reclassify GIMTs and to determine the clinicopathologic features of GISTs in Mexico. Cases of GIMT identified from the database of 3 large diagnostic centers in Mexico between 1995 and 2004 were reclassified according to current criteria. Hematoxylin and eosin-stained sections and clinical histories were reviewed, and immunohistochemistry was performed using anti-CD117, CD34, smooth muscle actin, and S-100 protein. A total of 275 GISTs were identified. The tumors were located in the stomach (40%), small intestine (35%), colorectum (12%), abdominal cavity (11%), and esophagus (2%). There were equal numbers of men and women with a mean age at diagnosis of 61 years. The tumors ranged in size from 3.5 to 34 cm (mean, 9.1 cm); 95 tumors (34%) were larger than 10 cm. Colorectal and omental tumors were the largest. The cell types included pure spindle (68%), pure epithelioid (16%), and mixed epithelioid/spindle (14%). Whereas 17.8% of tumors were regarded as low risk, 43% of tumors were in the high-risk category. CD117 positivity was detected in most of the tumors (96%). In addition to CD117, 255 cases (92%) were positive for CD34, 82 cases (32%) were positive for smooth muscle actin, and 13 cases (4.7%) were positive for desmin. Gastrointestinal stromal tumors in Mexico have the same clinicopathologic and immunohistochemical features as those reported in other countries. It is not always easy to distinguish GISTs from other soft tissue lesions. The diagnosis can be difficult even for experienced pathologists.

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

    PubMed

    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.

  20. Hedgehog pathway dysregulation contributes to the pathogenesis of human gastrointestinal stromal tumors via GLI-mediated activation of KIT expression

    PubMed Central

    Burgoyne, Adam M.; Leonard, Stephanie Y.; Gao, Fei; Chan, Jonathan C.; Shi, Eileen; Chmielecki, Juliann; Morosini, Deborah; Wang, Kai; Ross, Jeffrey S.; Kendrick, Michael L.; Bardsley, Michael R.; De Siena, Martina; Mao, Junhao; Harismendy, Olivier

    2016-01-01

    Gastrointestinal stromal tumors (GIST) arise within the interstitial cell of Cajal (ICC) lineage due to activating KIT/PDGFRA mutations. Both ICC and GIST possess primary cilia (PC), which coordinate PDGFRA and Hedgehog signaling, regulators of gastrointestinal mesenchymal development. Therefore, we hypothesized that Hedgehog signaling may be altered in human GIST and controls KIT expression. Quantitative RT-PCR, microarrays, and next generation sequencing were used to describe Hedgehog/PC-related genes in purified human ICC and GIST. Genetic and pharmacologic approaches were employed to investigate the effects of GLI manipulation on KIT expression and GIST cell viability. We report that Hedgehog pathway and PC components are expressed in ICC and GIST and subject to dysregulation during GIST oncogenesis, irrespective of KIT/PDGFRA mutation status. Using genomic profiling, 10.2% of 186 GIST studied had potentially deleterious genomic alterations in 5 Hedgehog-related genes analyzed, including in the PTCH1 tumor suppressor (1.6%). Expression of the predominantly repressive GLI isoform, GLI3, was inversely correlated with KIT mRNA levels in GIST cells and non-KIT/non-PDGFRA mutant GIST. Overexpression of the 83-kDa repressive form of GLI3 or small interfering RNA-mediated knockdown of the activating isoforms GLI1/2 reduced KIT mRNA. Treatment with GLI1/2 inhibitors, including arsenic trioxide, significantly increased GLI3 binding to the KIT promoter, decreased KIT expression, and reduced viability in imatinib-sensitive and imatinib-resistant GIST cells. These data offer new evidence that genes necessary for Hedgehog signaling and PC function in ICC are dysregulated in GIST. Hedgehog signaling activates KIT expression irrespective of mutation status, offering a novel approach to treat imatinib-resistant GIST. PMID:27793025

  1. High-risk gastrointestinal stromal tumour (GIST) and synovial sarcoma display similar angiogenic profiles: a nude mice xenograft study

    PubMed Central

    Giner, Francisco; Machado, Isidro; Lopez-Guerrero, Jose Antonio; Mayordomo-Aranda, Empar; Llombart-Bosch, Antonio

    2017-01-01

    Background Gastrointestinal stromal tumour (GIST) is the most common primary mesenchymal tumour of the gastrointestinal tract. Spindle cell monophasic synovial sarcoma (SS) can be morphologically similar. Angiogenesis is a major factor for tumour growth and metastasis. Our aim was to compare the angiogenic expression profiles of high-risk GIST and spindle cell monophasic SS by histological, immunohistochemical and molecular characterisation of the neovascularisation established between xenotransplanted tumours and the host during the initial phases of growth in nude mice. Methods The angiogenic profile of two xenotransplanted human soft-tissue tumours were evaluated in 15 passages in nude mice using tissue microarrays (TMA). Tumour pieces were also implanted subcutaneously on the backs of 14 athymic Balb-c nude mice. The animals were sacrificed at 24, 48, and 96 h; and 7, 14, 21, and 28 days after implantation to perform histological, immunohistochemical, and molecular studies (neovascularisation experiments). Results Morphological similarities were apparent in the early stages of neoplastic growth of these two soft-tissue tumours throughout the passages in nude mice and in the two neovascularisation experiments. Immunohistochemistry demonstrated overexpression of pro-angiogenic factors between 24 h and 96 h after xenotransplantation in both tumours. Additionally, neoplastic cells coexpressed chemokines (CXCL9, CXCL10, GRO, and CXCL12) and their receptors in both tumours. Molecular studies showed two expression profiles, revealing an early and a late phase in the angiogenic process. Conclusion This model could provide information on the early stages of the angiogenic process in monophasic spindle cell SS and high-risk GIST and offers an excellent way to study possible tumour response to antiangiogenic drugs. PMID:28386296

  2. Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model.

    PubMed

    Pantaleo, M A; Landuzzi, L; Nicoletti, G; Nanni, C; Boschi, S; Piazzi, G; Santini, D; Di Battista, M; Castellucci, P; Lodi, F; Fanti, S; Lollini, P-L; Biasco, G

    2009-09-01

    The large use of target therapies in the treatment of gastrointestinal stromal tumors (GISTs) highlighted the urgency to integrate new molecular imaging technologies, to develop new criteria for tumor response evaluation and to reach a more comprehensive definition of the molecular target. These aspects, which come from clinical experiences, are not considered enough in preclinical research studies which aim to evaluate the efficacy of new drugs or new combination of drugs with molecular target. We developed a xenograft animal model GIST882 using nude mice. We evaluated both the molecular and functional characterization of the tumor mass. The mutational analysis of KIT receptor of the GIST882 cell lines and tumor mass showed a mutation on exon 13 that was still present after in vivo cell growth. The glucose metabolism and cell proliferation was evaluated with a small animal PET using both FDG and FLT. The experimental development of new therapies for GIST treatment requires sophisticated animal models in order to represent the tumor molecular heterogeneity already demonstrated in the clinical setting and in order to evaluate the efficacy of the treatment also considering the inhibition of tumor metabolism, and not only considering the change in size of tumors. This approach of cancer research on GISTs is crucial and essential for innovative perspectives that could cross over to other types of cancer.

  3. Microfluidic Deletion/Insertion Analysis for Rapid Screening of KIT and PDGFRA Mutations in CD117-Positive Gastrointestinal Stromal Tumors

    PubMed Central

    Zamò, Alberto; Bertolaso, Anna; Franceschetti, Ilaria; Weirich, Gregor; Capelli, Paola; Pecori, Sara; Chilosi, Marco; Hoefler, Heinz; Menestrina, Fabio; Scarpa, Aldo

    2007-01-01

    Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions ≥3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We propose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases. PMID:17384206

  4. Sporadic diffuse segmental interstitial cell of Cajal hyperplasia harbouring two gastric gastrointestinal stromal tumours (GIST) mimicking hereditary GIST syndromes

    PubMed Central

    Neves, Mafalda Costa; Stamp, Gordon; Mudan, Satvinder

    2015-01-01

    Introduction Gastrointestinal stromal tumours (GISTs) are thought to derive from or differentiate towards the interstitial cells of Cajal (ICC) as most demonstrate a similar immunoprofile: CD117+, CD34+ and DOG1+. ICC hyperplasia refers to KIT-expressing microscopic spindle cell proliferations involving the myenteric plexus. Case report 74 year-old male presented with a 5-year history of heartburn and dysphagia. Imaging revealed a 4 cm GIST in the gastric fundus. Pathology of the resected specimen revealed diffuse segmental ICC hyperplasia harbouring two macroscopic GISTs and a ‘tumorlet’. A mutation in c-KIT exon 11 was detected in both the solid and the diffuse components. Discussion ICC hyperplasia can occur either as a sporadic focal lesion or in a syndromic setting, known to predispose to multiple GIST tumours at different sites. The majority of cases of sporadic ICC hyperplasia previously reported were of localised type. The hereditary form is mostly caused by germline mutations in c-KIT and PDGFRA or in patients with NF-1 andpresents as a diffuse hyperplasia, usually with a confluent, nodular or multifocal growth pattern. Conclusion We describe a diffuse form of sporadic ICC hyperplasia harbouring multifocal GISTs, mimicking diffuse ICC hyperplasia in hereditary GIST syndromes. Detection of somatic c-KIT exon 11 mutation ruled out a hereditary disorder. PMID:26521201

  5. Opposing roles of KIT and ABL1 in the therapeutic response of gastrointestinal stromal tumor (GIST) cells to imatinib mesylate.

    PubMed

    Rausch, Jessica L; Boichuk, Sergei; Ali, Areej A; Patil, Sneha S; Liu, Lijun; Lee, Donna M; Brown, Matthew F; Makielski, Kathleen R; Liu, Ying; Taguchi, Takahiro; Kuan, Shih-Fan; Duensing, Anette

    2017-01-17

    Most gastrointestinal stromal tumors (GISTs) are caused by activating mutations of the KIT receptor tyrosine kinase. The small molecule inhibitor imatinib mesylate was initially developed to target the ABL1 kinase, which is constitutively activated through chromosomal translocation in BCR-ABL1-positive chronic myeloid leukemia. Because of cross-reactivity of imatinib against the KIT kinase, the drug is also successfully used for the treatment of GIST. Although inhibition of KIT clearly has a major role in the therapeutic response of GIST to imatinib, the contribution of concomitant inhibition of ABL in this context has never been explored. We show here that ABL1 is expressed in the majority of GISTs, including human GIST cell lines. Using siRNA-mediated knockdown, we demonstrate that depletion of KIT in conjunction with ABL1 - hence mimicking imatinib treatment - leads to reduced apoptosis induction and attenuated inhibition of cellular proliferation when compared to depletion of KIT alone. These results are explained by an increased activity of the AKT survival kinase, which is mediated by the cyclin-dependent kinase CDK2, likely through direct phosphorylation. Our results highlight that distinct inhibitory properties of targeted agents can impede antitumor effects and hence provide insights for rational drug development. Novel KIT-targeted agents to treat GIST should therefore comprise an increased specificity for KIT while at the same time displaying a reduced ability to inhibit ABL1.

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

    PubMed

    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.

  7. The diagnostic value of endoscopic ultrasonography and contrast-enhanced harmonic endoscopic ultrasonography in gastrointestinal stromal tumors

    PubMed Central

    Zhao, Yanchao; Qian, Linxue; Li, Peng; Zhang, Shutian

    2016-01-01

    Objective: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) and contrast-enhanced harmonic (CEH) EUS in patients with gastrointestinal stromal tumors (GISTs). Patients and Methods: About 19 patients with suspected GISTs underwent EUS and CEH-EUS before tumor resection. The malignant potential was assessed according to the modified Fletcher classification system. Patients were divided into lower (Group I) and higher (Group II) malignant potential group. The clinical characteristics and EUS/CEH-EUS features were compared between two groups. Results: The tumor size in Group II was significantly larger than that in Group I (14.6 ± 5.8 mm vs. 32.1 ± 8.4 mm, P < 0.05). Heterogeneous echogenicity was observed in 4 (4/8) cases in Group II and none in Group I (P < 0.05). Irregular intratumoral vessels were detected in 6 cases in Group II and none in Group I (P < 0.05). The sensitivity and specificity of irregular vessel detection for discriminating higher from lower malignant potential GISTs were 75% and 100%, respectively. The positive predictive value and negative predictive value of detection of irregular vessels to high malignant potential GISTs were 33% and 100%, respectively. Conclusion: Detection of irregular intratumoral vessels can predict higher malignant potential before tumor resection. The tumor size and echogenicity are assistant factors for malignant potential assessment. Endoscopic resection is an efficacious treatment with good security for appropriate patients. PMID:27080610

  8. Is surgery mandatory in locally advanced gastrointestinal stromal tumors after imatinib? A case report and literature review

    PubMed Central

    Congedo, Teresa; Ricci, Riccardo; Martini, Maurizio; Di Noia, Vincenzo; Di Dio, Carmela; Quirino, Michela; Barone, Carlo; Cassano, Alessandra

    2017-01-01

    Oesophageal gastrointestinal stromal tumors (GISTs) are rare neoplasms (about 2% of all GISTs); radical surgery is the standard treatment of all GISTs but in case of locally advanced and unresectable disease no clear treatment guide lines are available. Studies including neoadjuvant imatinib mesylate (IM) are relatively recent, includes small sample size of heterogeneous patients and do not report a standardized duration of neoadjuvant treatment. The main question still remains whether surgery after neoadjuvant IM gives a survival benefit in locally advanced disease. A 46-year-old man with locally advanced unresectable oesophageal GIST harboring KIT exon 11 mutation was treated in our institution for 12 months with neoadjuvant IM; a reduction of 83% of tumor volume was obtained in 9-month of neoadjuvant IM, but in the last 3 months no further response was seen. After neoadjuvant therapy, patient underwent radical surgery and adjuvant IM, which is still ongoing. Since no definitive data are available about survival benefit of surgery after neoadjuvant IM in locally advanced GISTs, a careful balance between morbidity and mortality derived from surgery should be considered and more studies are needed to better define the utility and the optimal duration of neoadjuvant treatment. PMID:28280629

  9. The HSP90 Inhibitor, AT13387, Is Effective against Imatinib-Sensitive and -Resistant Gastrointestinal Stromal Tumor Models

    PubMed Central

    Smyth, Tomoko; Van Looy, Thomas; Curry, Jayne E.; Rodriguez-Lopez, Ana M.; Wozniak, Agnieszka; Zhu, Meijun; Donsky, Rachel; Morgan, Jennifer G.; Mayeda, Mark; Fletcher, Jonathan A.; Schöffski, Patrick; Lyons, John; Thompson, Neil T.; Wallis, Nicola G.

    2013-01-01

    The majority of gastrointestinal stromal tumors (GIST) are characterized by activating mutations of KIT, an HSP90 client protein. Further secondary resistance mutations within KIT limit clinical responses to tyrosine kinase inhibitors, such as imatinib. The dependence of KIT and its mutated forms on HSP90 suggests that HSP90 inhibition might be a valuable treatment option for GIST, which would be equally effective on imatinib-sensitive and -resistant clones. We investigated the activity of AT13387, a potent HSP90 inhibitor currently being evaluated in clinical trials, in both in vitro and in vivo GIST models. AT13387 inhibited the proliferation of imatinib-sensitive (GIST882, GIST-T1) and -resistant (GIST430, GIST48) cell lines, including those resistant to the geldanamycin analogue HSP90 inhibitor, 17-AAG. Treatment with AT13387 resulted in depletion of HSP90 client proteins, KIT and AKT, along with their phospho-forms in imatinib-sensitive and -resistant cell lines, irrespective of KIT mutation. KIT signaling was ablated, whereas HSP70, a marker of HSP90 inhibition, was induced. In vivo, antitumor activity of AT13387 was showed in both the imatinib-sensitive, GIST-PSW, xenograft model and a newly characterized imatinib-resistant, GIST430, xenograft model. Induction of HSP70, depletion of phospho-KIT and inhibition of KIT signaling were seen in tumors from both models after treatment with AT13387. A combination of imatinib and AT13387 treatment in the imatinib-resistant GIST430 model significantly enhanced tumor growth inhibition over either of the monotherapies. Importantly, the combination of AT13387 and imatinib was well tolerated. These results suggest AT13387 is an excellent candidate for clinical testing in GIST in combination with imatinib. PMID:22714264

  10. Gastrointestinal stromal tumors (GIST): a rare entity, a tumor model for personalized therapy, and yet ten different molecular subtypes.

    PubMed

    Blay, Jean-Yves; Le Cesne, Axel; Cassier, Philippe A; Ray-Coquard, Isabelle L

    2012-05-01

    Gastrointestinal stromal tumors (GIST) are the most frequent sarcoma and were recognized as distinct molecular entities in 1998. Following the identification of driving molecular alterations in KIT, imatinib was rapidly introduced for the treatment of GIST, and became the paradigm of molecularly targeted therapies for solid tumors. While surgery was the only known effective treatment in 1998, two drugs are approved by the FDA and EMA in 2012 for the treatment of localized and advanced forms of this disease. Imatinib has been shown to provide a high level of clinical efficacy in patients with advanced GIST, a median progression-free survival (PFS) of 2 years and median overall survival close to 5 years, with 20% patients progression-free after 10 years of treatment. Imatinib has also been proven to improve overall survival and reduce the risk of relapse in localized GIST at high risk for relapse after resection. Sunitinib is indicated in advanced GIST after failure of imatinib, and provided a median PFS close to 6 months after imatinib failure. However, there is an important variability in the molecular and genetic characteristics that drive the pathogenesis of GIST, allowing thus for the identification of distinct molecular subtypes of GIST with different prognosis and sensitivity to the targeted treatments. Different strategies are now recommended in these different molecular subtypes of GIST which must be recognized as different entities regarding sensitivity to tyrosine kinase inhibitors and treatment decisions. This fragmentation of a yet recently recognized disease entity illustrates to strong trend of fragmentation in nosology of cancers, even in rare tumors such as GIST. For this aspect also, GIST is again a paradigmatic model for oncology, as many tumors with a higher prevalence will be fragmented in different molecular subsets and are going to become rare disease in the years to come.

  11. Antitumor effect of the tyrosine kinase inhibitor nilotinib on gastrointestinal stromal tumor (GIST) and imatinib-resistant GIST cells.

    PubMed

    Sako, Hiroyuki; Fukuda, Kazumasa; Saikawa, Yoshiro; Nakamura, Rieko; Takahashi, Tsunehiro; Wada, Norihito; Kawakubo, Hirohumi; Takeuchi, Hiroya; Ohmori, Tai; Kitagawa, Yuko

    2014-01-01

    Despite the benefits of imatinib for treating gastrointestinal stromal tumors (GIST), the prognosis for high risk GIST and imatinib-resistant (IR) GIST remains poor. The mechanisms of imatinib resistance have not yet been fully clarified. The aim of the study was to establish imatinib-resistant cell lines and investigate nilotinib, a second generation tyrosine kinase inhibitor (TKI), in preclinical models of GIST and imatinib-resistant GIST. For a model of imatinib-resistant GIST, we generated resistant cells from GK1C and GK3C cell lines by exposing them to imatinib for 6 months. The parent cell lines GK1C and GK3C showed imatinib sensitivity with IC50 of 4.59±0.97 µM and 11.15±1.48 µM, respectively. The imatinib-resistant cell lines GK1C-IR and GK3C-IR showed imatinib resistance with IC50 values of 11.74±0.17 µM (P<0.001) and 41.37±1.07 µM (P<0.001), respectively. The phosphorylation status of key cell signaling pathways, receptor tyrosine kinase KIT (CD117), platelet-derived growth factor receptor alpha (PDGFRA) and downstream signaling kinases: serine-threonine kinase Akt (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) or the non-receptor tyrosine kinase: proto-oncogene tyrosine-protein kinase Src (SRC), was analyzed in established cell lines and ERK1/2 phosphorylation was found to be increased compared to the parental cells. Nilotinib demonstrated significant antitumor efficacy against GIST xenograft lines and imatinib-resistant GIST cell lines. Thus, nilotinib may have clinical potential for patients with GIST or imatinib-resistant GIST.

  12. Folate-related polymorphisms in gastrointestinal stromal tumours: susceptibility and correlation with tumour characteristics and clinical outcome

    PubMed Central

    Angelini, Sabrina; Ravegnini, Gloria; Nannini, Margherita; Bermejo, Justo Lorenzo; Musti, Muriel; Pantaleo, Maria A; Fumagalli, Elena; Venturoli, Nicola; Palassini, Elena; Consolini, Nicola; Casali, Paolo G; Biasco, Guido; Hrelia, Patrizia

    2015-01-01

    The folate metabolism pathway has a crucial role in tumorigenesis as it supports numerous critical intracellular reactions, including DNA synthesis, repair, and methylation. Despite its importance, little is known about the influence of the folate pathway on gastrointestinal stromal tumour (GIST), a rare tumour with an incidence ranging between 6 and 19.6 cases per million worldwide. The importance of folate metabolism led us to investigate the influence of polymorphisms in the genes coding folate-metabolising enzymes on GIST susceptibility, tumour characteristics and clinical outcome. We investigated a panel of 13 polymorphisms in 8 genes in 60 cases and 153 controls. The TS 6-bp deletion allele (formerly rs34489327, delTInsTTAAAG) was associated with reduced risk of GIST (OR=0.20, 95% CI 0.05–0.67, P=0.0032). Selected polymorphisms in patients stratified by age, gender, and other main molecular and clinical characteristics showed that few genotypes may show a likely correlation. We also observed a significant association between the RFC AA/AG genotype and time to progression (HR=0.107, 95% CI 0.014–0.82; P=0.032). Furthermore, we observed a tendency towards an association between the SHMT1 variant allele (TT, rs1979277) and early death (HR=4.53, 95% CI 0.77–26.58, P=0.087). Aware of the strengths and limitations of the study, these results suggest that polymorphisms may modify the risk of GIST and clinical outcome, pointing to the necessity for further investigations with information on folate plasma levels and a larger study population. PMID:25227144

  13. Successful establishment of patient-derived tumor xenografts from gastrointestinal stromal tumor-a single center experience

    PubMed Central

    Jiang, Quan; Tong, Han-Xing; Zhang, Yong; Hou, Ying-Yong; Li, Jing-Lei; Wang, Jiong-Yuan; Zhou, Yu-Hong; Lu, Wei-Qi

    2016-01-01

    Patient-derived tumor xenografts (PDTX) generally represent a kind of more reliable model of human disease, by which a potential drugs’ preclinical efficacy could be evaluated. To date, no stable gastrointestinal stromal tumor (GIST) PDTX models have been reported. In this study, we aimed to establish stable GIST PDTX models and to evaluate whether these models accurately reflected the histological feature of the corresponding patient tumors and create a reliable GIST PDTX models for our future experiment. By engrafting fresh patient GIST tissues into immune-compromised mice (BALB/c athymic mice), 4 PDTX models were established. Histological features were assessed by a qualified pathologist based on H&E staining, CD117 and DOG-1. We also conduct whole exome sequencing(WES) for the 4 established GIST PDTX models to test if the model still harbored the same mutation detected in corresponding patient tumors and get a more intensive vision for the genetic profile of the models we have established, which will help a lot for our future experiment. To explore the tumorigenesis mechanism for GIST, we also have a statistical analysis for the genes detected as nonsynchronous-mutated simultaneously in 4 samples. All 4 GIST PDTX models retained the histological features of the corresponding human tumors, with original morphology type and positive stains for CD117 and DOG-1. Between the GIST PDTX models and their parental tumors, a same mutation site was detected, which confirmed the genetic consistency. The stability of molecular profiles observed within the GIST PDTX models provides confidence in the utility and translational significance of these models for in vivo testing of personalized therapies. To date, we conducted the first study to successfully establish a GIST PDTX model whose genetic profiles were revealed by whole exome sequencing. Our experience could be of great use. PMID:27186422

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

    PubMed Central

    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

  15. Autophagy is involved in endogenous and NVP-AUY922-induced KIT degradation in gastrointestinal stromal tumors

    PubMed Central

    Hsueh, Yuan-Shuo; Yen, Chueh-Chuan; Shih, Neng-Yao; Chiang, Nai-Jung; Li, Chien-Feng; Chen, Li-Tzong

    2013-01-01

    Gastrointestinal stromal tumor (GIST) is a prototype of mutant KIT oncogene-driven tumor. Prolonged tyrosine kinase inhibitor (TKI) treatment may result in a resistant phenotype through acquired secondary KIT mutation. Heat shock protein 90 (HSP90AA1) is a chaperone protein responsible for protein maturation and stability, and KIT is a known client protein of HSP90AA1. Inhibition of HSP90AA1 has been shown to destabilize KIT protein by enhancing its degradation via the proteasome-dependent pathway. In this study, we demonstrated that NVP-AUY922 (AUY922), a new class of HSP90AA1 inhibitor, is effective in inhibiting the growth of GIST cells expressing mutant KIT protein, the imatinib-sensitive GIST882 and imatinib-resistant GIST48 cells. The growth inhibition was accompanied with a sustained reduction of both total and phosphorylated KIT proteins and the induction of apoptosis in both cell lines. Surprisingly, AUY922-induced KIT reduction could be partially reversed by pharmacological inhibition of either autophagy or proteasome degradation pathway. The blockade of autophagy alone led to the accumulation of the KIT protein, highlighting the role of autophagy in endogenous KIT turnover. The involvement of autophagy in endogenous and AUY922-induced KIT protein turnover was further confirmed by the colocalization of KIT with MAP1LC3B-, acridine orange- or SQSTM1-labeled autophagosome, and by the accumulation of KIT in GIST cells by silencing either BECN1 or ATG5 to disrupt autophagosome activity. Therefore, the results not only highlight the potential application of AUY922 for the treatment of KIT-expressing GISTs, but also provide the first evidence for the involvement of autophagy in endogenous and HSP90AA1 inhibitor-induced KIT degradation. PMID:23196876

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

    PubMed

    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.

  17. Fluid Retention Associated with Imatinib Treatment in Patients with Gastrointestinal Stromal Tumor: Quantitative Radiologic Assessment and Implications for Management

    PubMed Central

    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. Analysis of the amount of tissue sample necessary for mitotic count and Ki-67 index in gastrointestinal stromal tumor sampling.

    PubMed

    Kobara, Hideki; Mori, Hirohito; Rafiq, Kazi; Fujihara, Shintaro; Nishiyama, Noriko; Chiyo, Taiga; Matsunaga, Tae; Ayaki, Maki; Yachida, Tatsuo; Kato, Kiyohito; Kamada, Hideki; Fujita, Koji; Morishita, Asahiro; Oryu, Makoto; Tsutsui, Kunihiko; Iwama, Hisakazu; Kushida, Yoshio; Haba, Reiji; Masaki, Tsutomu

    2015-01-01

    There are no established opinions concerning whether the amount of tissue affects the accuracy of histological analyses in gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the appropriate amount of tissue sample needed for mitotic count based on the risk classification of GISTs and the Ki-67 index using the following three methods: endoscopic ultrasound-guided fine-needle aspiration (FNA), a novel sampling method called tunneling bloc biopsy (TBB), and biopsy forceps followed by TBB (Bf). Forty-three samples (12 FNA, 17 TBB and 14 Bf) diagnosed as GISTs by immunohistological analysis were utilized. The major and minor axes and overlay area of one piece of specimen (OPS) from the three sampling methods were measured using digital imaging software and were analyzed comparatively regarding the acquisition of histological data. The mean major and minor axes (mm) and overlay areas (mm2) were in the order of TBB > Bf > FNA. The evaluable rates by mitotic count and Ki-67 were, respectively, 75% (9/12) and 83.3% (10/12) for FNA samples, 100% (17/17) and 100% (17/17) for TBB samples, and 100% (14/14) and 100% (14/14) for Bf samples (P>0.05). Three FNA samples were judged unevaluable due to too small specimens in overall diagnosis including mitotic count and Ki-67, calculating the cut-off value for the overlay area of OPS as 0.17 mm2. Comparing the concordance rates between the pre- and post-operative samples, TBB samples was significantly better than FNA (P<0.05). Conclusively, while the amounts of tissues obtained by TBB and Bf are unnecessary for the histological assessment of mitotic count and Ki-67 index, developments of the FNA method are needed to minimize sample error. Considering the technical aspects, as well as the size of the specimens, could help to guide therapeutic planning and improve diagnostic yield for GI subepithelial tumors.

  19. Frequence, Spectrum and Prognostic Impact of Additional Malignancies in Patients With Gastrointestinal Stromal Tumors1234

    PubMed Central

    Kramer, K.; Wolf, S.; Mayer, B.; Schmidt, S.A.; Agaimy, A.; Henne-Bruns, D.; Knippschild, U.; Schwab, M.; Schmieder, M.

    2015-01-01

    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. PMID:25622906

  20. Feasibility and Timing of Cytoreduction Surgery in Advanced (Metastatic or Recurrent) Gastrointestinal Stromal Tumors During the Era of Imatinib

    PubMed Central

    Chang, Shih-Chun; Liao, Chien-Hung; Wang, Shang-Yu; Tsai, Chun-Yi; Chiang, Kun-Chun; Cheng, Chi-Tung; Yeh, Ta-Sen; Chen, Yen-Yang; MA, Ming-Chun; Liu, Chien-Ting; Yeh, Chun-Nan

    2015-01-01

    Abstract The prognosis of advanced gastrointestinal stromal tumors (GISTs) was dramatically improved in the era of imatinib. Cytoreduction surgery was advocated as an additional treatment for advanced GISTs, especially when patients having poor response to imatinib or developing resistance to it. However, the efficacy and benefit of cytoreduction were still controversial. Likewise, the sequence between cytoreduction surgery and imatinib still need evaluation. In this study, we tried to assess the feasibility and efficiency of cytoreduction in advanced GISTs. Furthermore, we analyzed the impact of timing of the cytoreduction surgery on the prognosis of advanced GISTs. We conducted a prospective collecting retrospective review of patients with advanced GISTs (metastatic, unresectable, and recurrent GISTs) treated in Chang Gung memorial hospital (CGMH) since 2001 to 2013. We analyzed the impact of cytoreduction surgery to response to imatinib, progression-free survival (PFS), and overall survival (OS) in patients with advanced GISTs. Moreover, by the timing of cytoreduction to imatinib, we divided the surgical patients who had surgery before imatinib use into early group and those who had surgery after imatinib into late. We compared the clinical response to imatinib, PFS and OS between early and late cytoreduction surgical groups. Totally, 182 patients were enrolled into this study. Seventy-six patients underwent cytoreduction surgery. The demographic characteristics and tumor presentation were similar between surgical and non-surgical groups. The surgical group showed better complete response rate (P < 0.001) and partial response rate (P = 0.008) than non-surgical group. The 1-year, 3-year, and 5-year PFS were significantly superior in surgical group (P = 0.003). The 1-year, 3-year, and 5-year OS were superior in surgical group, but without statistical significance (P = 0.088). Dividing by cytoreduction surgical timing, the demographic

  1. Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation.

    PubMed

    Miettinen, Markku; Killian, Jonathan Keith; Wang, Zeng-Feng; Lasota, Jerzy; Lau, Christopher; Jones, Laura; Walker, Robert; Pineda, Marbin; Zhu, Yuelin Jack; Kim, Su Y; Helman, Lee; Meltzer, Paul

    2013-02-01

    A subset (7% to 10%) of gastric gastrointestinal stromal tumors (GISTs) is notable for the immunohistochemical loss of succinate dehydrogenase (SDH) subunit B (SDHB), which signals the loss of function of the SDH complex consisting of mitochondrial inner membrane proteins. These SDH-deficient GISTs are known to be KIT/PDGFRA wild type, and most patients affected by this subset of GISTs are young. Some of these patients have germline mutations of SDH subunit genes SDHB, SDHC, or SDHD, known as Carney-Stratakis syndrome when combined with paraganglioma. More recently, germline mutations in SDH subunit A gene (SDHA) have also been reported in few patients with KIT/PDGFRA wild-type GISTs. In this study we immunohistochemically examined 127 SDHB-negative and 556 SDHB-positive gastric GISTs and 261 SDHB-positive intestinal GISTs for SDHA expression using a mouse monoclonal antibody 2E3 (Abcam). Cases with available DNA were tested for SDHA, SDHB, SDHC, and SDHD gene mutations using a hybridization-based custom capture next-generation sequencing assay. A total of 36 SDHA-negative GISTs (28%) were found among 127 SDHB-negative gastric GISTs. No SDHB-positive GIST was SDHA negative. Among 7 SDHA-negative tumors analyzed, there were 7 SDHA mutants, most germline. A second hit indicating biallelic inactivation of SDHA was present in 6 of those cases. These patients had no other SDH subunit gene mutations. Among the 25 SDHA-positive, SDHB-negative GISTs analyzed, we identified 3 SDHA mutations (1 germline), and 11 SDHB, SDHC, or SDHD mutations (mostly germline), and 11 patients with no SDH mutations. Compared with patients with SDHA-positive GISTs, those with SDHA-negative GISTs had an older median age (34 vs. 21 y), lower female to male ratio (1.8 vs. 3.1) but similar mitotic counts and median tumor sizes, with a slow course of disease in most cases, despite a slightly higher rate of liver metastases. SDHA-negative GISTs comprise approximately 30% of SDHB

  2. Incidental Finding and Management of Mesenteric Fibromatosis

    PubMed Central

    Nicolas, Gregory; Kfoury, Tony; Shimlati, Rasha; Tohme, Maroon; Wakim, Raja

    2016-01-01

    Patient: Male, 45 Final Diagnosis: Mesenteric fibromatosis Symptoms: — Medication: — Clinical Procedure: Surgical removal of the mesenteric fibromatosis Specialty: Surgery Objective: Rare disease Background: Mesenteric fibromatosis, also known as mesenteric desmoids, is part of the clinical-pathologic spectrum of deep fibromatosis, which encompasses a group of benign fibro-proliferative processes that are locally aggressive and have the capacity to infiltrate or recur without metastasis. Case Report: Case of a 45-year-old man, with a history of hypertension and lung fibrosis, presenting for a left abdominal mass, which was found incidentally during his lung fibrosis imaging. He complained of constipation due to pressure upon his bowel leading to difficulty in defecation. Conclusions: Although there are many overlapping criteria between gastrointestinal stromal tumors and mesenteric fibromatosis, making it difficult to discriminate between the two, there are differences that are unique to mesenteric fibromatosis that should be noticed during the diagnosis. In this case, mesenteric fibromatosis was unusual as it is not associated with Gardner’s syndrome, desmoid tumors, nor familial adenomatous polyposis, but was an incidental finding. PMID:27279600

  3. [Gastrointestinal stromal tumours (GIST)--development in pathology, surgery and medical therapy. Developed during the 10th German GIST-meeting, Göttingen].

    PubMed

    Agaimy, A; Bauer, S; Beham, A; Bertolini, J; Haller, F; Koschny, R; Maier, J; Montemurro, M; Perez, D; Schaefer, I-M; Schildhaus, H-U; Wurst, C; Cameron, S

    2015-03-01

    The first description of ligand-independent activating mutations in the KIT gene, which encodes the tyrosine-kinase KIT, greatly improved our understanding of gastrointestinal stromal tumour (GIST) biology. The therapeutic success in GIST has made tyrosine kinase inhibitors a "paradigm of targeted therapy". Deciphering resistance mechanisms in GIST has had implications for many other kinase-driven cancers. To exchange current knowledge within the field of GIST, the German GIST Meeting has taken place for now 10 years, traditionally in Göttingen. Subjects discussed include clinical diagnostics, pathology, surgery, and medical therapy. The following presentation gives an overview of the last meeting held in December 2013, including distinctive features in GIST and current data on the different topics.

  4. 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

    PubMed Central

    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

  5. Successful treatment of bleeding large duodenal gastrointestinal stromal tumour in a patient under dual antiplatelet therapy after recent drug-eluting coronary stent implantation

    PubMed Central

    Fukuyama, Keita; Fujikawa, Takahisa; Kuramitsu, Shoichi; Tanaka, Akira

    2014-01-01

    We report a case of a 69-year-old man who started dual antiplatelet therapy (APT) with aspirin and clopidogrel after recent implantation of drug-eluting coronary stent and developed massive bleeding due to large duodenal gastrointestinal stromal tumour (GIST). Following endoscopic haemostasis and discontinuation of dual APT, neoadjuvant chemotherapy with imatinib was started under continuation of ‘single’ APT with aspirin. A good chemotherapeutic response was achieved without recurrence of bleeding, and subsequent less invasive surgical resection of the tumour was performed, while preoperative single APT was continued for prevention of stent thrombosis. The patient recovered well without any thromboembolic or bleeding events. Neoadjuvant imatinib therapy and subsequent less invasive surgery under continuation of APT is one of the preferred approaches for patients with duodenal GIST with severe thromboembolic comorbidities, as in the current case. PMID:24777088

  6. Incidental GIST after appendectomy in a pediatric patient: a first instance and review of pediatric patients with CD117 confirmed GISTs.

    PubMed

    Tran, Sifrance; Dingeldein, Michael; Mengshol, Sarah C; Kay, Saundra; Chin, Anthony C

    2014-04-01

    A 7-year-old boy underwent uncomplicated laparoscopic appendectomy for acute appendicitis. Incidentally, he was found to have a spindle cell tumor with CD117 immunopositivity, consistent with gastrointestinal stromal tumor (GIST) in the appendix. Although commonly reported in adults, pediatric GISTs are rare gastrointestinal malignancies that occur in only 1.4-2.7% of children and adolescents. Due to the paucity of reports, data are insufficient to adequately characterize tumor behavior, recurrence, and survival. We present the first case of pediatric GIST in the appendix. In addition, a review of the literature for CD117 confirmed pediatric GISTs was conducted to summarize its clinical features and current treatment options.

  7. Genetic alteration and mutation profiling of circulating cell-free tumor DNA (cfDNA) for diagnosis and targeted therapy of gastrointestinal stromal tumors.

    PubMed

    Yan, Weixin; Zhang, Aiguo; Powell, Michael J

    2016-07-21

    Gastrointestinal stromal tumors (GISTs) have been recognized as a biologically distinctive type of tumor, different from smooth muscle and neural tumors of the gastrointestinal tract. The identification of genetic aberrations in proto-oncogenes that drive the growth of GISTs is critical for improving the efficacy of cancer therapy by matching targeted drugs to specific mutations. Research into the oncogenic mechanisms of GISTs has found that these tumors frequently contain activating gene mutations in either platelet-derived growth factor receptor A (PDGFRA) or a receptor tyrosine protein associated with a mast cell growth factor receptor encoded by the KIT gene. Mutant cancer subpopulations have the potential to disrupt durable patient responses to molecularly targeted therapy for GISTs, yet the prevalence and size of subpopulations remain largely unexplored. Detection of the cancer subpopulations that harbor low-frequency mutant alleles of target proto-oncogenes through the use of molecular genetic methods, such as polymerase chain reaction (PCR) target amplification technology, is hampered by the high abundance of wild-type alleles, which limit the sensitivity of detection of these minor mutant alleles. This is especially true in the case of mutant tumor DNA derived "driver" and "drug-resistant" alleles that are present in the circulating cell-free tumor DNA (cfDNA) in the peripheral blood circulation of GIST patients. So-called "liquid biopsy" allows for the dynamic monitoring of the patients' tumor status during treatment using minimally invasive sampling. New methodologies, such as a technology that employs a xenonucleic acid (XNA) clamping probe to block the PCR amplification of wild-type templates, have allowed improved molecular detection of these low-frequency alleles both in tissue biopsy samples and in cfDNA. These new methodologies could be widely applied for minimally invasive molecular testing in the therapeutic management of GISTs.

  8. Kit K641E oncogene up-regulates Sprouty homolog 4 and Trophoblast glycoprotein in interstitial cells of Cajal in a murine model of gastrointestinal stromal tumours

    PubMed Central

    Gromova, Petra; Ralea, Sebastian; Lefort, Anne; Libert, Frédérick; Rubin, Brian P; Erneux, Christophe; Vanderwinden, Jean-Marie

    2009-01-01

    Gastrointestinal stromal tumours (GIST) are thought to derive from the interstitial cells of Cajal (ICC) or an ICC precursor. Oncogenic mutations of the receptor tyrosine kinase KIT are present in most GIST. KIT K642E was originally identified in sporadic GIST and later found in the germ line of a familial GIST cohort. A mouse model harbouring a germline Kit K641E mutant was created to model familial GIST. The expression profile was investigated in the gastric antrum of the KitK641E murine GIST model by microarray, quantitative PCR and immunofluorescence. Gja1/Cx43, Gpc6, Gpr133, Pacrg, Pde3a, Prkar2b, Prkcq/Pkce, Rasd2, Spry4 and Tpbg/5T4 were found to be up-regulated. The proteins encoded by Gja1/Cx43, Pde3a, Prkcq/Pkce were localized in Kit-ir ICC in wild-type and KitK641E animals while Spry4 and Tpbg/5T4 were detected in Kit-ir cells only in KitK641E, but not in KitWT/WT animals. Most up-regulated genes in this mouse model belong to the gene expression profile of human GIST but also to the profile of normal Kit+ ICC in the mouse small intestine. Spry4 and Tpbg/5T4 may represent candidates for targeted therapeutic approaches in GIST with oncogenic KIT mutations. PMID:19453770

  9. Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy

    PubMed Central

    Costa Neves, Mafalda; Giakoustidis, Alexandros; Benson, Charlotte

    2015-01-01

    Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free. PMID:26075122

  10. Consensus report on the radiological management of patients with gastrointestinal stromal tumours (GIST): recommendations of the German GIST Imaging Working Group.

    PubMed

    Kalkmann, Janine; Zeile, Martin; Antoch, Gerald; Berger, Frank; Diederich, Stefan; Dinter, Dietmar; Fink, Christian; Janka, Rolf; Stattaus, Jörg

    2012-05-07

    The aim was to reach consensus in imaging for staging and follow-up as well as for therapy response assessment in patients with gastrointestinal stromal tumours (GIST). The German GIST Imaging Working Group was formed by 9 radiologists engaged in assessing patients with GIST treated with targeted therapy. The following topics were discussed: indication and optimal acquisition techniques of computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT; tumour response assessment considering response criteria and measurement techniques on CT, MRI and PET/CT; result interpretation; staging interval and pitfalls. Contrast-enhanced CT is the standard method for GIST imaging. MRI is the method of choice in case of liver-specific questions or contraindications to CT. PET/CT should be used for early response assessment or inconclusive results on morphologic imaging. All imaging techniques should be standardized allowing a reliable response assessment. Response has to be assessed with respect to lesion size, lesion density and appearance of new lesions. A critical issue is pseudoprogression due to myxoid degeneration or intratumoural haemorrhage. The management of patients with GIST receiving a targeted therapy requires a standardized algorithm for imaging and an appropriate response assessment with respect to changes in lesion size and density.

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

    PubMed

    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.

  12. Imatinib-induced hyperbilirubinemia with UGT1A1 (*28) promoter polymorphism: first case series in patients with gastrointestinal stromal tumor

    PubMed Central

    Saif, Muhammad Wasif; Smith, Melissa Hennessey; Maloney, Antonia; Diasio, Robert B.

    2016-01-01

    Imatinib, an orally administered protein-tyrosine kinase inhibitor (TKI) is indicated for the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumor (GIST). Severe hepatotoxicity associated with imatinib is rare, and relationship to polymorphism of uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) expression and related frequency of hyperbilirubinemia or toxicity are not well known. We present a case series patients who developed hyperbilirubinemia while on oral administration imatinib for treatment of GIST. Genetic testing for polymorphism of UGT1A1 showed the first patient to be homozygous for the UGT1A1 TA7 (*28) polymorphism and the second patient heterozygous for the UGT1A1 TA1 (*28) polymorphism. The first patient had to stop imatinib due to severe and persistent hyperbilirubenemia peaking >3 despite reducing imatininb to only 100 mg every other day while the second patient improved at this dose. Our case series represent the first data associating UGT1A1 polymorphism and imatinib in patients being treated for GIST. Given the prevalence of Gilbert’s syndrome and the increasing use of imatinib, we encourage physicians to be aware of this possible toxicity as hepatotoxicity can be fatal if not managed in a timely fashion. This association is also timely due to recent FDA requirement for testing UGT1A1 polymorphism for nilotinib, another TKI. PMID:27708529

  13. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing.

    PubMed

    Pantaleo, Maria A; Astolfi, Annalisa; Indio, Valentina; Moore, Richard; Thiessen, Nina; Heinrich, Michael C; Gnocchi, Chiara; Santini, Donatella; Catena, Fausto; Formica, Serena; Martelli, Pier Luigi; Casadio, Rita; Pession, Andrea; Biasco, Guido

    2011-06-22

    Approximately 10%-15% of gastrointestinal stromal tumors (GISTs) in adults do not harbor any mutation in the KIT or PDGFRA genes (ie, KIT/PDGFRA wild-type GISTs). Recently, mutations in SDHB and SDHC (which encode succinate dehydrogenase subunits B and C, respectively) but not in SDHA and SDHD (which encode subunits A and D, respectively) were identified in KIT/PDGFRA wild-type GISTs. To search for novel pathogenic mutations, we sequenced the tumor transcriptome of two young adult patients who developed sporadic KIT/PDGFRA wild-type GISTs by using a massively parallel sequencing approach. The only variants identified as disease related by computational analysis were in SDHA. One patient carried the homozygous nonsense mutation p.Ser384X, the other patient was a compound heterozygote harboring a p.Arg31X nonsense mutation and a p.Arg589Trp missense mutation. The heterozygous nonsense mutations in both patients were present in germline DNA isolated from peripheral blood. Protein structure analysis indicates that all three mutations lead to functional inactivation of the protein. This is the first report, to our knowle dge, that identifies SDHA inactivation as a common oncogenic event in GISTs that lack a mutation in KIT and PDGFRA.

  14. Robotic Versus Laparoscopic Gastric Resection for Primary Gastrointestinal Stromal Tumors >5 cm: A Size-Matched and Location-Matched Comparison.

    PubMed

    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.

  15. Effective Downsizing of a Large Oesophageal Gastrointestinal Stromal Tumour with Neoadjuvant Imatinib Enabling an Uncomplicated and without Tumour Rupture Laparoscopic-Assisted Ivor-Lewis Oesophagectomy.

    PubMed

    Neofytou, Kyriakos; Costa Neves, Mafalda; Giakoustidis, Alexandros; Benson, Charlotte; Mudan, Satvinder

    2015-01-01

    Neoadjuvant imatinib for gastrointestinal stromal tumours (GISTs) is increasingly used nowadays. As oesophagectomy is associated with high morbidity and mortality, a preoperative downsizing of an oesophageal GIST to limit the extent of resection would be ideal. Because these tumours are rare and neoadjuvant treatment with imatinib is recent, there is limited literature available regarding neoadjuvant administration of imatinib in patients with oesophageal GISTs. A 50-year-old woman presented with total dysphagia. An upper endoscopy and biopsy revealed a large submucosal KIT-positive GIST obstructing the mid oesophagus. CT confirmed a lesion measuring 99 mm × 50 mm × 104 mm. Because the size and location of the tumour increased the risk of intraoperative rupture, it was decided to administer preoperative imatinib. The patient had an excellent clinical and radiological response. Her dysphagia gradually resolved and the follow-up CT scans of the first 10 months showed a gradually reducing tumour size to 54 mm × 33 mm × 42 mm. The patient underwent an uneventful laparoscopic-assisted Ivor-Lewis oesophagectomy. Postoperatively, the patient continued with adjuvant imatinib. At the last follow-up, 1 year from operation and 38 months from the diagnosis, the patient is disease free.

  16. Chemical modifications in the seed region of miRNAs 221/222 increase the silencing performances in gastrointestinal stromal tumor cells.

    PubMed

    Durso, Montano; Gaglione, Maria; Piras, Linda; Mercurio, Maria Emilia; Terreri, Sara; Olivieri, Michele; Marinelli, Luciana; Novellino, Ettore; Incoronato, Mariarosaria; Grieco, Paolo; Orsini, Gaetano; Tonon, Giancarlo; Messere, Anna; Cimmino, Amelia

    2016-03-23

    Most GastroIntestinal Stromal Tumors (GISTs) are characterized by KIT gene overexpression, which in turn is regulated by levels of microRNA 221 and microRNA 222. GISTs can also be distinguished by their miRNAs expression profile in which miRNAs 221/222 result reduced in comparison with GI normal tissues. In this paper, to restore normal miRNAs levels and to improve the silencing performances of miRNAs 221/222, new miRNA mimics in which guide strands are modified by Phosphorothioate (PS) and/or 2'-O-methyl RNA (2'-OMe) inside and outside the seed region, were synthesized and tested in GIST48 cells. We evaluated the positional effect of the chemical modifications on the miRNAs silencing activity, compared to natural and several commercial miRNA mimics. Our results show that chemically modified miRNAs 221/222 with alternating 2'-OMe-PS and natural nucleotides in the seed region are effective inhibitors of KIT gene expression and exhibit increased stability in rat plasma. Besides, their transfection in GIST 48 cells showed significant effects on different cellular processes in which KIT plays a functional role for tumor development (such as migration, cell proliferation, and apoptosis). Therefore, modified miRNAs 221/222 may provide an alternative therapeutic option for GIST treatment also aimed to overcome drug resistance concerns.

  17. Treatment of non-resectable and metastatic gastrointestinal stromal tumors: experience with the use of tyrosine kinase inhibitors in a third level hospital in Mexico

    PubMed Central

    Pimentel Renteria, Alberto; Pluma Jiménez, Miguel; Pérez Martínez, Mario; Martínez Martínez, Gloria; Rivera Rivera, Samuel; Grajales Álvarez, Rocío; Bautista Aragón, Yolanda; Quintana Quintana, Miguel; Alejandro Silva, Juan

    2016-01-01

    Background Stromal tumors of the digestive tract are uncommon malignant diseases, are subclassified as leiomyosarcomas and Gastrointestinal Stromal Tumors (GIST) depending on the molecular expression of tyrosine kinase receptor KIT (CD117). GISTs represent 1% of malignant tumors affecting this anatomical site. Localized tumours diseases are reasonably well controlled by surgical resection and several criteria define the need for adjuvant therapy. In the case of metastatic disease a poor prognosis has been reported with systemic treatment based on chemotherapy. Recently, significant advances have been shown since tyrosine kinase inhibitors (TKIs) were introduced, with median overall survival close to 5 years. Unfortunately in Mexico, even though the therapy has been long used there are no published data of the experience in the treatment of these tumors. Methods We used an electronic data base to obtain clinical, radiological and histological data of patients diagnosed with GIST and treated in the oncological center of the Mexican Institute of Social Security, patients were subclassified by stage, symptoms at diagnosis as well as the initial and subsequent systemic treatment. Finally we made an analysis for progression free survival and overall survival identifying prognostic factors. Results We obtained information of 71 patients with metastatic, non-resectable or recurrent GIST, treated with a TKI, we observed a predominant relation for women (60.4%) with median age of 58 years. Stage at diagnosis was predominantly metastatic (46.5%), most frequently affected sites were lung, liver and retroperitoneum. Median progression free survival was 30.6 months and overall survival was 81.3 months. All patients were initially treated with imatinib at a dose of 400 mg per day. Treatment was well-tolerated in most cases. Conclusions Metastatic GIST evaluated in our center shows a different affection in gender and age, and our population shows a different response to TKIs

  18. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

    PubMed Central

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-01-01

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of $17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients. PMID:18506179

  19. Functional role of the Ca{sup 2+}-activated Cl{sup −} channel DOG1/TMEM16A in gastrointestinal stromal tumor cells

    SciTech Connect

    Berglund, Erik; Akcakaya, Pinar; Berglund, David; Karlsson, Fredrik; Vukojević, Vladana; Lee, Linkiat; Bogdanović, Darko; Lui, Weng-Onn; Larsson, Catharina; Zedenius, Jan; Fröbom, Robin; Bränström, Robert

    2014-08-15

    DOG1, a Ca{sup 2+}-activated Cl{sup −} channel (CaCC), was identified in 2004 to be robustly expressed in gastrointestinal stromal tumors (GIST). It was rapidly included as a tumor marker in routine diagnostics, but the functional role remained unknown. CaCCs are important regulators of normal physiological functions, but also implicated in tumorigenesis, cancer progression, metastasis, cell migration, apoptosis, proliferation and viability in several malignancies. We therefore investigated whether DOG1 plays a role in the three latter in GIST by utilizing in vitro cell model systems. Confocal microscopy identified different subcellular localizations of DOG1 in imatinib-sensitive and imatinib-resistant cells. Electrophysiological studies confirmed that DOG1-specific pharmacological agents possess potent activating and inhibiting properties. Proliferation assays showed small effects up to 72 h, and flow cytometric analysis of adherent cells with 7-AAD/Annexin V detected no pharmacological effects on viable GIST cells. However, inhibition of DOG1 conveyed pro-apoptotic effects among early apoptotic imatinib-resistant cells. In conclusion, DOG1 generates Cl{sup −} currents in GIST that can be regulated pharmacologically, with small effects on cell viability and proliferation in vitro. Inhibition of DOG1 might act pro-apoptotic on some early apoptotic GIST cell populations. Further studies are warranted to fully illuminate the function of DOG1 and its potential as therapeutic target. - Highlights: • Subcellular DOG1 localization varies between GIST cells. • DOG1 in GIST is voltage- and Ca{sup 2+}-activated. • Known TMEM16A modulators, like A01 and Eact, modulate DOG1. • DOG1 has small effects on cell viability and proliferation in vitro. • DOG1 impact early apoptotic GIST cells to undergo late apoptosis.

  20. A Role for Adjuvant RFA in Managing Hepatic Metastases from Gastrointestinal Stromal Tumors (GIST) After Treatment with Targeted Systemic Therapy Using Kinase Inhibitors

    SciTech Connect

    Hakimé, Antoine Cesne, Axel Le Deschamps, Frederic Farouil, Geoffroy Boudabous, Sana Aupérin, Anne Domont, Julien Debaere, Thierry

    2013-04-16

    PurposeThis study was designed to assess the role of radiofrequency ablation (RFA) in the multimodality management of gastrointestinal stromal tumors (GIST) in patients undergoing targeted tyrosine kinase inhibitor therapy (TKI) for liver metastases.MethodsOutcomes of 17 patients who underwent liver RFA for 27 metastatic GIST after TKI therapy, from January 2004 to March 2012, were retrospectively analyzed. Mean maximum tumor diameter was 2.5 ± 1 cm (range 0.9–4.5 cm). In seven patients (group A), RFA of all residual tumors was performed, with curative intent, and TKI therapy was discontinued. In five patients (group B), RFA of all residual tumors was performed upon achieving the best morphological response with TKI therapy, which was maintained after RFA. In another five patients (group C), RFA was performed on individual liver metastases which were progressive under TKI therapy.ResultsAll 27 targeted tumors were completely ablated, without local recurrence during the mean follow-up period of 49 months. No major complications occurred. Two minor complications were reported (11 %). Only two patients (both in group C) died at 20 and 48 months. Two-year progression-free survival (PFS) after RFA was 29 % in group A, 75 % in group B, and 20 % in group C.ConclusionsRFA in patients, previously treated with TKI, is feasible and safe. Our data suggest that RFA is a useful therapeutic option in patients with metastatic GIST and should be performed at the time of best clinical response with patient maintained under TKI after the procedure.

  1. The Therapeutic Response of Gastrointestinal Stromal Tumors to Imatinib Treatment Assessed by Intravoxel Incoherent Motion Diffusion-Weighted Magnetic Resonance Imaging with Histopathological Correlation

    PubMed Central

    Zhang, Chunfang; Wang, He; Cheng, Jin; Wu, Weizhen; Hong, Nan; Wang, Yi

    2016-01-01

    Purpose To exploit the intravoxel incoherent motion (IVIM) diffusion-weighted (DW) MRI when evaluating the therapeutic response of gastrointestinal stromal tumors (GIST) to Imatinib in a mouse model. Materials and Methods Mice with xenografts bearing cells from the GIST-T1 cell line were randomly divided into a treated group receiving Imatinib and a control group. DWMRI scans with 14 b-values (0–1500 s/mm2) were performed before and after treatment (days 1, 3 and 7). IVIM related parameters perfusion fractions (fp) and perfusion-related diffusion coefficients (D*) and the conventional apparent diffusion coefficients (ADC) were calculated by fitting the DWMRI signal decay. The mean changes from baseline to each post-treatment time point for each measurement (ΔADC, Δfp and ΔD*) were calculated. The differences of mean changes between the two groups were tested for statistical significance. Histopathological analyses including Ki-67, CD31, TUNEL and H&E were conducted in conjunction with the MRI scans. Results Increases in ADC of the treated group were higher than those of the control group after treatment, whereas statistical significances were not observed. Compared to the control group, D* in the treated group decreased significantly (ΔD*treated = -41%, -49%, and -49% with P = 0.0001, 0.0001 and 0.0001), and fp increased significantly (Δfptreated = 79%, 82% and 110%, with P = 0.001, 0.0001 and P = 0.0007) on days 1, 3 and 7 after treatment. Histopathological analyses demonstrated different tumor tissue characteristics between the treated and control groups. Conclusion IVIM measurements may serve as more sensitive imaging biomarkers than ADC when assessing GIST response to Imatinib as early as one day after treatment. PMID:27911930

  2. Safety, efficacy and prognostic analyses of sunitinib in the post-marketing surveillance study of Japanese patients with gastrointestinal stromal tumor

    PubMed Central

    Komatsu, Yoshito; Ohki, Emiko; Ueno, Naomi; Yoshida, Ai; Toyoshima, Yasuharu; Ueda, Eiji; Houzawa, Hiroyuki; Togo, Kanae; Nishida, Toshirou

    2015-01-01

    Objective This study was conducted to expand the sunitinib safety database in Japanese imatinib-resistant/-intolerant gastrointestinal stromal tumor patients. Retrospective analyses investigated common adverse events as potential prognostic markers. Methods Four hundred and seventy patients who received sunitinib between June 2008 and November 2009 were analyzed for safety, progression-free survival and overall survival; 386 for objective response rate; 88% received sunitinib on Schedule 4/2 starting at 50 mg/day. Results No unexpected safety issues occurred. Grade ≥ 3 adverse events occurred in 70%, most commonly thrombocytopenia (33%), neutropenia (22%) and leukopenia (15%). Objective response rate was 20% (95% confidence interval 16–24). Median progression-free survival was 22.4 weeks (95% confidence interval, 21.7–24.0). The overall survival rate at 24 weeks was 91% (95% confidence interval, 88–94). Higher relative dose intensity (≥70 vs. <70%) during the first 6 weeks and better Eastern Cooperative Oncology Group performance status (0 vs. ≥1) were associated with longer progression-free survival (24.0 vs. 20.1 weeks; P = 0.011; and 24.1 vs. 16.9 weeks; P < 0.001) and higher 24-week overall survival rate (94 vs. 83%; P < 0.001; and 96 vs. 83%; P < 0.001). Increased progression-free survival and overall survival rates were associated with specific adverse events. Cox proportional hazard modeling adjusted for relative dose intensity and performance status established hand–foot syndrome (hazard ratio = 0.636; 95% confidence interval, 0.456–0.888) and leukopenia (hazard ratio = 0.683; 95% confidence interval, 0.492–0.948) occurring within 12 weeks were significantly correlated with increased progression-free survival. Conclusion Sunitinib showed good efficacy and tolerable safety. Factors associated with greater efficacy were relative dose intensity, performance status and specific early adverse events. PMID:26373318

  3. A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours.

    PubMed

    Contreras-Hernández, I; Mould-Quevedo, J F; Silva, A; Salinas-Escudero, G; Villasís-Keever, M A; Granados-García, V; Dávila-Loaiza, G; Petersen, J A; Garduño-Espinosa, J

    2008-06-03

    Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day(-1) of imatinib mesylate, 50 mg day(-1) of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day(-1) of imatinib had the highest MC (+/-s.d.) of treatment at $35,225.61 USD (+/-1253.65 USD); while sunitinib incurred a median MC of $17,805.87 USD (+/-694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (+/-472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients.

  4. Gastrointestinal stromal tumors with KIT exon 9 mutations: Update on genotype-phenotype correlation and validation of a high-resolution melting assay for mutational testing.

    PubMed

    Künstlinger, Helen; Huss, Sebastian; Merkelbach-Bruse, Sabine; Binot, Elke; Kleine, Michaela Angelika; Loeser, Heike; Mittler, Jens; Hartmann, Wolfgang; Hohenberger, Peter; Reichardt, Peter; Büttner, Reinhard; Wardelmann, Eva; Schildhaus, Hans-Ulrich

    2013-11-01

    KIT exon 9 mutations in gastrointestinal stromal tumors (GISTs) are highly relevant and have direct therapeutic implications. In this context, we established and validated a fast and sensitive high-resolution melting assay. Analyzing 126 primary and 18 metastatic KIT exon 9-mutated cases from our registry, we demonstrate that the mutational spectrum of exon 9 is broader than previously thought and describe 3 novel mutations. Including these cases and the common p.A502_Y503dup mutation, we provide a comprehensive list of all known KIT exon 9 mutations according to the Human Genome Variation Society nomenclature. Two of the newly described mutations were associated with an aggressive phenotype and tumor progression while being treated with 400 mg imatinib, indicating that also GIST with rare exon 9 mutations could be treated with increased imatinib dosage. On the basis of >1500 GISTs from our registry, we have determined the frequency of KIT exon 9 mutations to be 9.2% among all GISTs and 22.5% among small-bowel cases. We describe for the first time that nearly 20% of exon 9-mutated GIST occur in the stomach or rectum. Furthermore, we provide first evidence that exon 9-mutated GISTs metastasize significantly more often to the peritoneum than to the liver. Performing extensive statistical analyses on data from our registry and from the literature, we demonstrate that KIT exon 9 mutations are neither associated with intermediate-risk/high-risk status nor overrepresented among metastatic lesions. Thus, we conclude that exon 9 mutations per se do not have prognostic relevance.

  5. miRNA-221 and miRNA-222 induce apoptosis via the KIT/AKT signalling pathway in gastrointestinal stromal tumours.

    PubMed

    Ihle, Michaela Angelika; Trautmann, Marcel; Kuenstlinger, Helen; Huss, Sebastian; Heydt, Carina; Fassunke, Jana; Wardelmann, Eva; Bauer, Sebastian; Schildhaus, Hans-Ulrich; Buettner, Reinhard; Merkelbach-Bruse, Sabine

    2015-08-01

    Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. In gastrointestinal stromal tumours (GISTs) expression of miR-221 and miR-222 is reduced compared to control tissue and other sarcomas but the functional effects of this downregulation are not fully understood. This study aimed at evaluating the miR-221 and miR-222 expression profiles in different GIST subtypes and the functional role of these miRNAs. Expression of miR-221 and miR-222 was analysed in six KIT exon 9 and three KIT exon 11 mutated and nine wildtype GISTs by qPCR. Viability and apoptosis were examined in three different, KIT positive GIST cell lines (GIST882, GIST-T1 and GIST48) after overexpression of these miRNAs. The modulation of KIT and the PI3K/AKT pathways was determined by Western blot. Wildtype and KIT mutated GISTs revealed reduced miRNA expression compared to adequate control tissue. miRNA expression was lower for wildtype compared to mutated GISTs. Transient transfection of miR-221 and miR-222 reduced viability and induced apoptosis by inhibition of KIT expression and its phosphorylation and activation of caspases 3 and 7 in all three GIST cell lines. p-AKT, AKT and BCL2 expression was reduced after miRNA transfection whereas only slight influence on p-MTOR, MTOR and BCL2L11 (BIM) was detected. Our results demonstrate that miR-221 and miR-222 which are downregulated in wildtype and mutated GISTs, induce apoptosis in vitro by a signalling cascade involving KIT, AKT and BCL2. Therefore, overexpression of these miRNAs seems to functionally counteract oncogenic signalling pathways in GIST.

  6. Surgical Management of Wild-Type Gastrointestinal Stromal Tumors: A Report From the National Institutes of Health Pediatric and Wildtype GIST Clinic.

    PubMed

    Weldon, Christopher B; Madenci, Arin L; Boikos, Sosipatros A; Janeway, Katherine A; George, Suzanne; von Mehren, Margaret; Pappo, Alberto S; Schiffman, Joshua D; Wright, Jennifer; Trent, Jonathan C; Pacak, Karel; Stratakis, Constantine A; Helman, Lee J; La Quaglia, Michael P

    2016-12-28

    Purpose Wild-type gastrointestinal stromal tumors (WT-GISTs) that lack KIT or PDGFRA mutations represent a unique subtype of GIST that predominantly affects children. We sought to determine the effect on event-free survival (EFS) of staging variables, extent of resection, and repeat resection of tumors. Methods In 2008, a WT-GIST clinic was established at the National Cancer Institute, allowing the development of a large clinical database. We included participants who underwent resection of WT-GIST. Associations with EFS (ie, freedom from disease progression or recurrence) were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. Results Among 76 participants with WT-GISTs, the median follow-up was 4.1 years. Overall EFS (± SE) was 72.6 ± 5.4% at 1 year, 57.6 ± 6.2% at 2 years, 23.7 ± 6.0% at 5 years, and 16.3 ± 5.5% at 10 years postoperatively. Hazard of disease progression or recurrence was significantly increased for patients with metastatic disease (adjusted hazard ratio [AHR], 2.3; 95% CI, 1.0 to 5.1; P = .04) and > 5 mitoses per 50 high-power fields (AHR, 2.5; 95% CI, 1.1 to 6.0; P = .03), whereas there was no significant effect of negative microscopic resection margins (AHR, 0.9; 95% CI, 0.4 to 2.2; P = 0.86). There was no association between type of gastric resection (ie, anatomic v partial/wedge) and EFS ( P = .67). Repeated resection after the initial resection was significantly associated with decreasing postoperative EFS ( P < .01). Five patients (6%) died after initial enrollment in 2008. Conclusion WT-GIST is an indolent disease, and most patients survive with disease progression. We found no improvement in EFS with more extensive or serial resections. Disease progression or recurrence may be more closely related to tumor biology than surgical management. These data suggest that resections for WT-GISTs be restricted to the initial procedure and that subsequent resections be performed only to address symptoms such as

  7. Short- and Long-Term Outcomes of Laparoscopic Versus Open Resection for Gastric Gastrointestinal Stromal Tumors: A Propensity Score-Matching Analysis.

    PubMed

    Chen, Qing-Feng; Huang, Chang-Ming; Lin, Mi; Lin, Jian-Xian; Lu, Jun; Zheng, Chao-Hui; Li, Ping; Xie, Jian-Wei; Wang, Jia-Bin; Chen, Qi-Yue; Cao, Long-Long; Tu, Ru-Hong

    2016-04-01

    Published reports on laparoscopic resection of gastric gastrointestinal stromal tumor (GIST) were limited to small experiences and selection bias. Two hundred fourteen patients who underwent primary gastric GIST resection at our institution (January 2006-December 2012) were identified from a prospectively collected database. Laparoscopic resections (LAP) were performed in 133 patients, and open resections (OPEN) were performed in 81 patients. The short- and long-term outcomes were analyzed using propensity-score matching (PSM) by comparing the clinicopathological factors between these groups. The tumor resection method and tumor size were significantly different between the LAP and OPEN groups. After PSM, there were no differences (P > 0.05) in these clinicopathological factors. The LAP group had less blood loss and shorter operation time, time to first flatus, time to first fluid diet, time to gastric tube removal, and postoperative stay before PSM. In addition, there were no differences regarding the time of drainage tube removal or hospitalization expense. Other than the time of gastric tube removal, which was similar in these 2 groups, the short-term outcomes were similar before and after PSM. The rates of postoperative complications in the LAP and OPEN groups were 6.8% and 22.8%, respectively, before PSM (P = 0.001) and 5.6% and 22.5%, respectively, after PSM (P = 0.004). The multivariate analyses for complications showed that tumors were located in the middle of the stomach, and the operation method and proximal gastrectomy were independent risk factors before and after PSM. The 5-year cumulative survival rates in the LAP and OPEN groups were 95.4% and 85.9%, respectively, (P = 0.07) before PSM and 93.1% and 91.9%, respectively, (P = 0.69) after PSM (not significantly different). Laparoscopic resection for gastric GISTs had better short-term outcomes and similar long-term outcomes compared with open surgery. Localized gastric GISTs can be

  8. Characterization of various types of mast cells derived from model mice of familial gastrointestinal stromal tumors with KIT-Asp818Tyr mutation.

    PubMed

    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.

  9. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients

    PubMed Central

    2012-01-01

    Abstract Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib : an active agent only in non progressive patients. Background Imatinib is a standard treatment for advanced/metastatic GIST and in adjuvant setting. Anaemia is frequently observed in patients with advanced GIST, and is one of the most frequent side effects of imatinib with grade 3–4 anaemia in 10% of patients. Whether EPO treatment is useful in the management of GIST patients receiving imatinib treatment is unknown. Methods A retrospective study of EPO treatment in GIST patients receiving imatinib was undertaken in 4 centres. Thirty four patients received EPO treatment among the 319 GIST patients treated with imatinib in clinical trials or with compassionate use between 2001 and 2003. The efficacy of EPO on the anaemia of patients with GIST treated with imatinib was analyzed. Results There were 18 males and 16 females with a median age of 59 years. Median WHO-PS was 1. Primary tumour sites were mainly gastric (32%) and small bowel (29%). Sites of metastases were mainly liver (82%) and peritoneum (79%). The median delay between the initiation of imatinib treatment and EPO was 58 days (range 0–553). Median haemoglobin (Hb) level prior to EPO was 9 g/dL (range 6,9-11,8) and 11,7 g/dL (range 6,8-14,4) after 2 months. An increase of more than 2 g/dL was observed in 18 (53%) of patients. None of the 7 patients who progressed (PD) under imatinib treatment (400 mg/day) experienced HB response, as compared to 66% (18/27) of the remaining patients (PR + SD) (p = 0,002). Primary tumour site, liver metastases, peritoneal metastases, age, gender did not correlate with HB response to EPO. Response to EPO was observed in 2/11 patients receiving high-dose imatinib (800 mg/day) vs 16/23 of others. Using logistic regression, only PD before EPO treatment was retained as a predictive factor for EPO response. Conclusion EPO enables to

  10. What Are Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... the GI tract, called the interstitial cells of Cajal (ICCs). ICCs are cells of the autonomic nervous system, the part of the nervous system that regulates body processes such as digesting food. ICCs are sometimes ...

  11. Expression of neural cell adhesion molecule L1 (CD171) in neuroectodermal and other tumors. An immunohistochemical study of 5155 tumors and critical evaluation of CD171 prognostic value in gastrointestinal stromal tumors

    PubMed Central

    Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy P.; Miettinen, Markku M.

    2016-01-01

    The neural cell adhesion molecule L1 (CD171) is a multidomain type 1 membrane glycoprotein of the immunoglobulin superfamily important in the nervous system development, kidney morphogenesis, and maintenance of the immune system. Recent studies reported CD171 expression being associated with adverse clinical outcome in different types of cancer and there has been a growing interest in targeting this cell membrane molecule on neoplastic cells by chimeric antigen receptor redirected T lymphocytes or specific antibodies. Nevertheless, conflicting results regarding the prognostic value of CD171 expression in renal cell carcinomas and gastrointestinal stromal tumors were published. In this study, CD171 expression was immunohistochemically analyzed in 5155 epithelial, mesenchymal, melanocytic, and lymphohematopoietic tumors to assess its utility in diagnostic pathology and to pinpoint potential targets for CD171-targeting therapy. A newly developed anti-CD171 rabbit monoclonal antibody, clone 014, was selected from the panel of commercially available CD171 antibodies. Immunohistochemistry was performed using Leica Bond Max automation and multitumor blocks containing up to 60 tumor samples. CD171 was constitutively and strongly expressed in neuroectodermal tumors such as schwannoma, neuroblastoma, and paraganglioma, whereas other mesenchymal tumors including schwannoma mimics showed only rarely CD171 positivity. Frequent CD171-expression was also detected in ovarian serous carcinoma, malignant mesothelioma, and testicular embryonal carcinoma. CD171 immunohistochemistry may have some role in immunophenotypic differential diagnosis of neurogenic tumors and pinpointing potential candidates for anti-CD171 therapy. Though, because of its rare expression and lack of predictive value, CD171 is neither a diagnostic nor prognostic marker for gastrointestinal stromal tumors. PMID:27419370

  12. Targeted ultra-deep sequencing unveils a lack of driver-gene mutations linking non-hereditary gastrointestinal stromal tumors and highly prevalent second primary malignancies: random or nonrandom, that is the question

    PubMed Central

    Kuo, Yung-Chia; Hsu, Hung-Chih; Chen, Jen-Shi; Chen, Tse-Ching; Wu, Ren-Chin; Chiu, Cheng-Tang; Yeh, Chun-Nan; Yeh, Ta-Sen

    2016-01-01

    The association of non-hereditary (sporadic) gastrointestinal stromal tumors (GISTs) and second primary malignancies is known to be nonrandom, although the underlying molecular mechanisms remain unknown. In this study, 136 of 749 (18.1%) patients with sporadic GISTs were found to have additional associated cancers, with gastrointestinal and genitourinary/gynecologic/breast cancers being the most prevalent. Gene mutations in GISTs and their associated colorectal cancers (CRCs) (n=9) were analyzed using a panel of 409 cancer-related genes, while a separate group of 40 sporadic CRCs not associated with GISTs served as controls. All 9 of the GISTs had either KIT (8 of 9) or PDGFRA (1 of 9) mutations that were not present in their associated CRCs. Conversely, all but one of the 9 GIST-associated CRCs exhibited an APC mutation, a TP53 mutation or both, while none of their corresponding GISTs harbored either APC or TP53 mutations. The genetic profile of CRCs with and without associated GISTs did not differ. Although population-based studies and case series worldwide, including ours, have unanimously indicated that the GIST-CRC association is nonrandom, our targeted ultra-deep sequencing unveiled a lack of driver-gene mutations linking sporadic GISTs to highly prevalent second primaries. Further studies are needed to elucidate other genetic alterations that may be responsible for this puzzling contradiction. PMID:27806309

  13. Ovarian mucinous epithelial neoplasm showing immunohistochemical pattern of lower gastrointestinal origin with stromal minor sex-cord elements: A case report.

    PubMed

    Ueda, Taeko; Nakagawa, Hitomi; Hachisuga, Toru

    2014-12-01

    •We report a case of an ovarian mucinous cystadenoma that exhibited extensive sex-cord differentiation.•The ovarian tumor coincided with a uterine endometrial carcinoma.•The immunohistochemical pattern of mucinous epithelium of the ovarian tumor was suggestive of lower gastrointestinal origin.

  14. Incidental finding of esophageal pneumatosis

    PubMed Central

    Chelimilla, Haritha; Makker, Jasbir S; Dev, Anil

    2013-01-01

    Pneumatosis of the gastrointestinal tract is a rare condition characterized by the presence of air filled cavities in the gastrointestinal tract wall. Its occurrence has been described throughout the gastrointestinal tract from the esophagus to the rectum, however it is most commonly reported in the small intestine. Despite multiple case reports in literature, its pathogenesis still remains unclear. Pneumatosis may be idiopathic or associated with a variety of disorders namely peptic ulcer disease, jejunoileal bypass, intestinal obstruction and non-gastrointestinal disorders like asthma, chronic obstructive pulmonary disease, systemic lupus erythematosus, infectious enteritis, etc. We here present a rare case of pneumatosis of the esophagus diagnosed incidentally at an esophagogastroduodenoscopy (EGD). A 78-year-old asymptomatic woman underwent EGD and colonoscopy at our hospital for evaluation of anemia. Few months prior to EGD, she had undergone excision of laryngocele at our hospital. EGD revealed extensive submucosal blebs distributed throughout the esophagus, otherwise unremarkable stomach and duodenum. Colonoscopy showed a tubular adenomatous polyp. Since our patient was asymptomatic she did not require any surgical intervention. Management of pneumatosis depends on the underlying cause. PMID:23422740

  15. Incidental finding of esophageal pneumatosis.

    PubMed

    Chelimilla, Haritha; Makker, Jasbir S; Dev, Anil

    2013-02-16

    Pneumatosis of the gastrointestinal tract is a rare condition characterized by the presence of air filled cavities in the gastrointestinal tract wall. Its occurrence has been described throughout the gastrointestinal tract from the esophagus to the rectum, however it is most commonly reported in the small intestine. Despite multiple case reports in literature, its pathogenesis still remains unclear. Pneumatosis may be idiopathic or associated with a variety of disorders namely peptic ulcer disease, jejunoileal bypass, intestinal obstruction and non-gastrointestinal disorders like asthma, chronic obstructive pulmonary disease, systemic lupus erythematosus, infectious enteritis, etc. We here present a rare case of pneumatosis of the esophagus diagnosed incidentally at an esophagogastroduodenoscopy (EGD). A 78-year-old asymptomatic woman underwent EGD and colonoscopy at our hospital for evaluation of anemia. Few months prior to EGD, she had undergone excision of laryngocele at our hospital. EGD revealed extensive submucosal blebs distributed throughout the esophagus, otherwise unremarkable stomach and duodenum. Colonoscopy showed a tubular adenomatous polyp. Since our patient was asymptomatic she did not require any surgical intervention. Management of pneumatosis depends on the underlying cause.

  16. Microfluidic deletion/insertion analysis for rapid screening of KIT and PDGFRA mutations in CD117-positive gastrointestinal stromal tumors: diagnostic applications and report of a new KIT mutation.

    PubMed

    Zamò, Alberto; Bertolaso, Anna; Franceschetti, Ilaria; Weirich, Gregor; Capelli, Paola; Pecori, Sara; Chilosi, Marco; Hoefler, Heinz; Menestrina, Fabio; Scarpa, Aldo

    2007-04-01

    Gastrointestinal stromal tumors (GISTs) frequently harbor mutations in the KIT and PDGFRA genes, the presence and type of which correlate with the response to the kinase inhibitor imatinib mesylate. Because most GIST mutations are deletions/insertions, we used a microfluidic apparatus to detect these size variations in polymerase chain reaction-amplified DNA. This approach, termed microfluidic deletion/insertion analysis (MIDIA), identified mutations in 30 of 50 DNA samples from paraffin-embedded CD117-positive GISTs (60%), comprising 25 deletions and five insertions. Sequencing of 14 MIDIA-positive samples confirmed the deletions/insertions, including two 3-bp alterations. Sequencing of all 20 MIDIA-negative samples also showed highly consistent results with MIDIA because 10 cases were wild type and eight displayed a single base substitution in which detection by MIDIA was not expected. Sequencing also revealed a 3-bp deletion undetected by MIDIA, thus establishing the resolution limit of MIDIA at deletions/insertions >or=3 bp. Denaturing high-pressure liquid chromatography analysis confirmed all mutations detected by MIDIA and sequencing. We pro-pose MIDIA as the first step in mutational screening of GIST because it allowed the detection of 75% of mutated cases (94% of deletions/insertions) in less than 30 minutes after polymerase chain reaction amplification and at a lower cost compared with denaturing high-pressure liquid chromatography and sequencing, which might then be used only for MIDIA-negative cases.

  17. Gastrointestinal stromal tumors - quantitative detection of the Ki-67, TPX2, TOP2A, and hTERT telomerase subunit mRNA levels to determine proliferation activity and a potential for aggressive biological behavior.

    PubMed

    Kalfusova, A; Hilska, I; Krskova, L; Kalinova, M; Linke, Z; Kodet, R

    2016-01-01

    Gastrointestinal stromal tumors (GISTs) have an unpredictable biological potential ranging from benign to malignant. Molecular markers involved in the mechanisms of proliferation and cellular senescence may provide additional information about biological behavior of the tumor. The aim of the present study was to investigate Ki-67, TPX2, TOP2A and hTERT mRNA expression levels in specimens from patients with GISTs to define relationships between proliferation activity and biological potential and progression of the disease. We measured Ki-67, TPX2, TOP2A and hTERT mRNA levels using quantitative real-time reverse transcription PCR (RQ RT PCR). The highest Ki-67, TPX2, TOP2A and hTERT mRNA expression levels were found in the highly proliferative BLs (18 specimens), in comparison with GISTs (137 specimens) and LMSs (9 specimens). Patients with GISTs and adequate information about mitotic activity, tumor size and anatomical site (84 specimens) were divided into two groups - GISTs with benign (29 patients) and with malignant (55 patients) potential. We observed association between higher Ki-67, TPX2 and hTERT mRNA levels and the GISTs with malignant potential. Univariate analysis (57 patients with available follow-up information) of survival (Kaplan Meier curves method) revealed a correlation between higher levels of TPX2, Ki-67 and hTERT markers and shorter event-free survival (EFS) or poorer overall survival (OS). The results demonstrate the importance of quantitative assessment of the proliferation activity in GISTs. Proliferation markers of Ki-67, TPX2, TOP2A and hTERT are suitable markers for detection the proliferation activity and telomerase activity of these tumors. Furthermore, the assessment of TPX2, Ki-67 and hTERT expression levels is appropriate for determination of malignant potential of GISTs.

  18. Gastrointestinal complications of von Recklinghausen's disease: two case reports and a review of the literature.

    PubMed

    Pinsk, I; Dukhno, O; Ovnat, A; Levy, I

    2003-12-01

    There are few reports of the association between neurofibromatosis (von Recklinghausen's disease) and large, solid stromal tumours of the gastrointestinal tract. The prevalence of gastrointestinal involvement in von Recklinghausen's disease has been estimated at 11%-25%. Some associated gastrointestinal stromal tumours present clinically as bowel obstruction, perforation or gastrointestinal bleeding. We recently treated two patients with this condition who presented with gastrointestinal bleeding and were diagnosed with gastrointestinal stromal tumours. We report the unique aspects of these cases and discuss the diagnostic and management problems that are posed by this unusual association.

  19. Incidental vertebral lesions.

    PubMed

    Coumans, Jean-Valery C E; Walcott, Brian P

    2011-12-01

    Incidental vertebral lesions on imaging of the spine are commonly encountered in clinical practice. Contributing factors include the aging population, the increasing prevalence of back pain, and increased usage of MR imaging. Additionally, refinements in CT and MR imaging have increased the number of demonstrable lesions. The management of incidental findings varies among practitioners and commonly depends more on practice style than on data or guidelines. In this article we review incidental findings within the vertebral column and review management of these lesions, based on available Class III data.

  20. Irinotecan, Fluorouracil, and Leucovorin in Treating Patients With Advanced Gastrointestinal Cancer

    ClinicalTrials.gov

    2016-04-19

    Anal Cancer; Carcinoma of the Appendix; Colorectal Cancer; Esophageal Cancer; Extrahepatic Bile Duct Cancer; Gallbladder Cancer; Gastric Cancer; Gastrointestinal Carcinoid Tumor; Gastrointestinal Stromal Tumor; Liver Cancer; Pancreatic Cancer; Small Intestine Cancer

  1. Incidental Auditory Category Learning

    PubMed Central

    Gabay, Yafit; Dick, Frederic K.; Zevin, Jason D.; Holt, Lori L.

    2015-01-01

    Very little is known about how auditory categories are learned incidentally, without instructions to search for category-diagnostic dimensions, overt category decisions, or experimenter-provided feedback. This is an important gap because learning in the natural environment does not arise from explicit feedback and there is evidence that the learning systems engaged by traditional tasks are distinct from those recruited by incidental category learning. We examined incidental auditory category learning with a novel paradigm, the Systematic Multimodal Associations Reaction Time (SMART) task, in which participants rapidly detect and report the appearance of a visual target in one of four possible screen locations. Although the overt task is rapid visual detection, a brief sequence of sounds precedes each visual target. These sounds are drawn from one of four distinct sound categories that predict the location of the upcoming visual target. These many-to-one auditory-to-visuomotor correspondences support incidental auditory category learning. Participants incidentally learn categories of complex acoustic exemplars and generalize this learning to novel exemplars and tasks. Further, learning is facilitated when category exemplar variability is more tightly coupled to the visuomotor associations than when the same stimulus variability is experienced across trials. We relate these findings to phonetic category learning. PMID:26010588

  2. Genetics Home Reference: gastrointestinal stromal tumor

    MedlinePlus

    ... membrane of certain cell types and stimulate signaling pathways inside the cell. Receptor proteins have specific sites ... of a series of proteins in multiple signaling pathways. These signaling pathways control many important cellular processes, ...

  3. How Are Gastrointestinal Stromal Tumors Diagnosed?

    MedlinePlus

    ... is injected into the blood. The amount of radioactivity used is very low. Because cancer cells in ... special camera creates a picture of areas of radioactivity in your body. PET scan images are not ...

  4. How Are Gastrointestinal Stromal Tumors Staged?

    MedlinePlus

    ... The cancer has spread to nearby lymph nodes. M categories for GIST M0: The cancer has not ... lungs). Stage grouping Once the T, N, and M categories have been determined, this information is combined, ...

  5. Crane. Incidental Classroom Instruction 20295

    SciTech Connect

    Reynolds, Richard Jennings

    2016-04-01

    The purpose of this course is to introduce safe hoisting and rigging practices to personnel who are attempting to become LANL incidental crane operators and to review and refresh safe hoisting and rigging practices with existing incidental crane operators.

  6. Gastric stromal tumor.

    PubMed

    Ovali, Gülgün Yilmaz; Tarhan, Serdar; Serter, Selim; Pabuşçu, Yüksel

    2005-06-01

    Gastric stromal tumors are rare neoplasms of the stomach. In this report we present a gastric stromal tumor with an exophytic growth pattern, and describe magnetic resonance imaging and endoscopic ultrasonography findings.

  7. Incidental and non-incidental thyroid microcarcinoma

    PubMed Central

    KALISZEWSKI, KRZYSZTOF; WOJTCZAK, BEATA; STRUTYŃSKA-KARPIŃSKA, MARTA; ŁUKIEŃCZUK, TADEUSZ; FORKASIEWICZ, ZDZISŁAW; DOMOSŁAWSKI, PAWEŁ

    2016-01-01

    There is no clear therapeutic approach for thyroid microcarcinoma (TMC). This may be as a consequence of recent observations that have reported biologically different types of TMC, which should be treated differently. The objective of the present study was to compare incidental TMC (ITMC) and non-incidental TMC (NITMC) in order to assess the differences in the incidence, diagnostic results, clinicopathological characteristics and surgical treatment. The study consisted of a retrospective chart review of 3,218 patients consecutively admitted and surgically treated in a single institution due to thyroid pathology. A total of 246 (7.64%) patients presented with a thyroid malignancy, and 97 (39.43%) of these individuals were diagnosed with TMC; 37 (38.14%) patients exhibited ITMC and 60 (61.86%) exhibited NITMC. All 37 (100.00%) patients with ITMC exhibited a papillary type of cancer. In the NITMC group, 1 (1.67%) patient presented with follicular microcarcinoma, 1 (1.67%) individual with papillary- and follicular-type microcarcinoma, 1 (1.67%) individual with medullary microcarcinoma, and the remaining 57 (95.00%) patients presented with papillary microcarcinoma. The number of younger patients (<45 years old) was higher in the NITMC group, but this difference was not significant (P=0.205). In all patients with ITMC, ultrasound-guided fine-needle aspiration biopsy did not reveal malignant processes. In the NITMC group, the number of larger tumors (>5 mm) was significantly higher compared with that in the ITMC group (P<0.001). ITMC was significantly associated with multinodular goiter (MNG) (P<0.001). Amongst the NITMC group, 18.33% of patients presented with cervical lymph node involvement (P<0.001). Overall, the incidence of TMC is high, and consists of ITMC and NITMC, although the prevalence of NITMC is higher than that of ITMC. The majority of ITMCs and NITMCs are composed of a papillary type of cancer. The majority of ITMCs have dimensions ≤5 mm in diameter and

  8. Colon in the Chest: An Incidental Dextrocardia

    PubMed Central

    Abd Elrazek, Abd Elrazek; Shehab, Abdullah; Elnour, Asim A.; Al Nuaimi, Saif K.; Baghdady, Shazly

    2015-01-01

    Abstract Diaphragmatic injury is an uncommon traumatic injury (<1%). Although most diaphragmatic injuries can be obvious (eg, herniation of abdominal contents on chest radiograph), some injuries may be subtle and imaging studies can be nondiagnostic in many situations. Patients with diaphragmatic hernia either traumatic or nontraumatic may initially have no symptoms or signs to suggest an injury to the diaphragm. Here, we report a case of a 75-year-old woman diagnosed with irritable bowel syndrome –associated dominant constipation, presented with shortness of breath, cough, expectoration, tachycardia, and chest pain. Dextrocardia was an incidental finding, diagnosed by electrocardiography, chest radiograph, and CT chest. Parts of the colon, small intestine, and stomach were within the thorax in the left side due to left diaphragmatic hernia of a nontraumatic cause. Acquired incidental dextrocardia was the main problem due to displacement of the heart to contralateral side by the GI (gastrointestinal) viscera (left diaphragmatic hernia). The patient was prepared for the laparoscopic surgical repair, using a polyethylene mesh 20 cm to close the defect, and the patient recovered with accepted general condition. However, 5 days postoperative, the patient passed away suddenly due to unexplained cardiac arrest. Intrathoracic herniation of abdominal viscera should be considered in patients presented with sudden chest pain concomitant with a history of increased intra-abdominal pressure. PMID:25674744

  9. [Managing focal incidental renal lesions].

    PubMed

    Nicolau, C; Paño, B; Sebastià, C

    2016-01-01

    Incidental renal lesions are relatively common in daily radiological practice. It is important to know the different diagnostic possibilities for incidentally detected lesions, depending on whether they are cystic or solid. The management of cystic lesions is guided by the Bosniak classification. In solid lesions, the goal is to differentiate between renal cancer and benign tumors such as fat-poor angiomyolipoma and oncocytoma. Radiologists need to know the recommendations for the management of these lesions and the usefulness of the different imaging techniques and interventional procedures in function of the characteristics of the incidental lesion and the patient's life expectancy.

  10. [Extragastrointestinal stromal tumor (EGIST)--a case review].

    PubMed

    Kolarík, J; Drápela, J

    2012-04-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Due to the presence of thyrosine kinase receptors within the tumor tissue, GIST is thought to originate from gastrointestinal pacemaker cells, the intersticial cells of Cajal. Tumors with the same morphological and imunohistochemical characteristics detected outside the gastrointestinal tract, are called extragastrointestinal stromal tumors (EGIST). Biological characteristics of these tumors is uncertain and the malignancy rates are difficult to predict. Surgical R0 resection in resecable tumors is the only option with the potential for complete cure. Nevertheless, the recurrence rates are high. Adjuvant biological treatment with imatinib, a thyrosine kinase inhibitor, reduces the risk of relapses. Imatinib administration is also the principal treatment method in metastatic GIST disorders. The article offers a short and complex overview of gastrointestinal stromal tumor (GIST) problematics and presents a case report of a patient suffering from EGIST of mesocolon transversum treated by R0 resection which was performed under multidisciplinary cooperation, with a specialist follow up.

  11. Pancreatic extragastrointestinal stromal tumor: A case report and comprehensive literature review

    PubMed Central

    Akbulut, Sami; Yavuz, Rıdvan; Otan, Emrah; Hatipoglu, Sinan

    2014-01-01

    AIM: To provide an overview of the literature on pancreatic extragastrointestinal stromal tumors (EGISTs). METHODS: We report a case of pancreatic EGIST and review published studies on pancreatic EGIST accessed via the PubMed, MEDLINE, Google Scholar, and Google databases. The keywords used were “pancreas and GIST”, “pancreas and extra GIST”, “pancreas and gastrointestinal stromal tumor”, and “pancreas and extragastrointestinal stromal tumor”. Literature reviews and/or duplicate studies were excluded. The search included articles published in the English language between January 1, 2000 and May 15, 2014. RESULTS: From our literature survey, 30 manuscripts on pancreatic EGISTs were considered, of which 27 met the search criteria and three were excluded. The studies involved 30 patients (15 men, 15 women) with a mean age of 55.3 ± 14.3 years (range 30-84 years). The mean age of the male patients was 50.8 ± 13.7 years (range 30-84 years); that of the female patients was 59.9 ± 13.3 years (range 38-81 years). Tumor dimensions were obtained for 28 cases (mean 114.4 ± 78.6 mm; range 20-350 mm). Tumors were diagnosed incidentally in 23.3% of patients; abdominal discomfort and weight loss were the major complaints in symptomatic patients. Risk of aggressive behavior according to Fletcher criteria was determined in 25 of 30 patients (68%: high risk, 28%: intermediate risk, 4%: low risk). Histopathological examination revealed the presence of spindle cells in 96.1% of cases; CD117 and CD34 were present immunohistochemically in 96.6% and 84% of patients, respectively. The most common surgical procedures were distal pancreatectomy with splenectomy (n = 9) and pancreaticoduodenectomy (n = 7). The total follow-up period for the 28 patients ranged from 3-66 mo, during which locoregional or distant metastases were diagnosed in six patients and two patients died. CONCLUSION: Studies on EGISTs have only been published in the last decade. The lack of studies with

  12. Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.

    PubMed

    Bourke, Anita Geraldine; Tiang, Stephen; Harvey, Nathan; McClure, Robert

    2015-10-16

    Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.

  13. Incidental discovery of acoustic neuromas.

    PubMed

    Selesnick, S H; Deora, M; Drotman, M B; Heier, L A

    1999-06-01

    Our objective is to report 4 cases of incidentally discovered acoustic neuromas (ANs) and to determine the incidence of asymptomatic ANs. A prospective study of 161 consecutive patients undergoing gadolinium-enhanced MRI (Gd-MRI) at a tertiary-care university-affiliated medical center was carried out from September 1994 to April 1995. The Gd-MRI scans were performed for tentative diagnoses other than AN or sensorineural hearing loss. In 161 consecutive patients examined, no ANs were found incidentally on Gd-MRI scans. Previous studies have suggested that the incidence of occult ANs is as high as 1%. On the basis of our results, we suggest that the actual incidence may be lower. However, our study is limited by its small size and the low incidence of ANs in the general population. Also reported are the clinical and MRI characteristics of 4 patients with incidentally diagnosed ANs.

  14. Incidental carcinoma of the thyroid.

    PubMed

    Pezzolla, Angela; Marzaioli, Rinaldo; Lattarulo, Serafina; Docimo, Giovanni; Conzo, Giovanni; Ciampolillo, Anna; Barile, Graziana; Anelli, Ferdinando Massimiliano; Madaro, Andrea

    2014-01-01

    The diagnosis of incidental thyroid carcinoma in patients submitted to thyroidectomy for a benign disease is quite frequent. A retrospective analysis was performed on 455 patients submitted to surgical intervention in order to establish the incidence of this kind of carcinoma. Two hundred fifty-six patients (56%) were affected by benign disease (176 multinodular goiter, 12 uninodular goiter, 1 Plummer disease and 67 Basedow disease) and 202 (44%) by carcinoma. In 28 of 256 patients (11%), affected by benign disease, occurred a histological diagnosis of thyroid carcinoma, (10 papillary carcinoma, 1 follicular carcinoma, 29 papillary carcinoma follicular variant). In this study it's considered incidental thyroid carcinoma the one occurred in patients who never underwent Fine Needle Aspiration (FNA) and there were no suspicious features in all exams that may suggest the presence of carcinoma. Twenty-three of the 40 incidental carcinoma (57.5%) were microcarcinomas. Ten patients had a sincronous carcinoma. Actually, these patients are still in a follow up program and no recurrency of disease is occasionally observed. This study shows that the only way to put doubts on the real benignity of the disease is the fine needle aspiration; there are no other instruments that could identify the occurrence of the carcinoma. Moreover in the majority of cases the incidental carcinoma is a microcarcinoma, it doesn't reach significant volume, may be not centered by a FNA, but in most cases it's not really biologically aggressive.

  15. Gastrointestinal manifestations.

    PubMed

    Tanowitz, H B; Simon, D; Weiss, L M; Noyer, C; Coyle, C; Wittner, M

    1996-11-01

    Gastrointestinal disease is a common problem in the setting of HIV-1 infection. As patients live longer and other opportunistic pathogens are suppressed, these problems are becoming even more important in the quality of life.

  16. Hereditary gastrointestinal cancer syndromes.

    PubMed

    Lynch, Henry T; Lynch, Jane F; Shaw, Trudy G

    2011-07-01

    The rapid growth of molecular genetics and its attendant germline mutation discoveries has enabled identification of persons who are at an inordinately high cancer risk and, therefore, ideal candidates for prevention. However, one must fully appreciate the extensive genotypic and phenotypic heterogeneity that exists in hereditary cancer. Once the causative germline mutation has been identified in a patient, high-risk members of the family can be similarly tested and identified and provided highly targeted surveillance and management opportunities. DNA testing can change the individual's presumed risk status and affect decision making by patients and their physicians regarding surveillance and management. Our purpose is to describe familial/hereditary cancers of the gastrointestinal tract, including familial Barrett's esophagus, hereditary diffuse gastric cancer, gastrointestinal stromal tumors, familial adenomatous polyposis and desmoid tumors, Lynch syndrome, small bowel cancer, and familial pancreatic cancer. We use our discussion of Lynch syndrome as a model for diagnostic and clinical translation strategies for all hereditary gastrointestinal tract cancers, which clearly can then be extended to cancer of all anatomic sites. Highly pertinent questions from the patient's perspective include the following: What kind of counseling will be provided to a patient with a Lynch syndrome mutation, and should that counseling be mandatory? Does the proband have the responsibility to inform relatives about the familial mutation, even if the relatives do not want to know whether they carry it? Is the patient is responsible for notifying family members that a parent or sibling has Lynch syndrome? Can notification be forced and, if so, under what circumstances? These questions point out the need for criteria regarding which family members to inform and how to inform them.

  17. Extragastrointestinal Stromal Tumour of The Abdominal Wall - A Case Report

    PubMed Central

    Kumar, A. Sathish Selva; Padmini, R; Veena, G; Murugesan, N

    2013-01-01

    Stromal tumours occurring in areas other than the GastroIntestinal Tract (GIT) are known as Extra GastroIntestinal Stromal Tumours (EGISTs). They usually arise in the mesentery, omentum or retroperitoneum, while EGISTs which occur in the abdominal wall are very rare. Both gastrointestinal stromal tumours (GISTs) and EGISTs are histologically and immunophenotypically similar. We are reporting a case of EGIST, which occurred in the anterior abdominal wall in a twenty five-year-old female patient. The tumour was present in the right loin and imaging studies suggested that it was a desmoid tumour. It was surgically excised by doing an abdominal wall mesh repair. The histological examinations revealed a tumour with spindle cell morphology, with <2 mitoses per 50 High Power Field (HPF) and no necrosis, with tumour free margins. Immunohistochemistry was strongly positive for CD117 and Smooth Muscle Actin (SMA), while it was negative for β-catenin and S100. The patient is well post operatively and is on close follow up. EGISTs should be considered in the differential diagnosis of mesenchymal tumours which occur in the abdominal wall, inspite of their rarity, as the high risk patients may need Imatinib chemotherapy. PMID:24551695

  18. [Gastrointestinal bleeding].

    PubMed

    Lanas, Ángel

    2015-09-01

    In the Digestive Disease Week in 2015 there have been some new contributions in the field of gastrointestinal bleeding that deserve to be highlighted. Treatment of celecoxib with a proton pump inhibitor is safer than treatment with nonselective NSAID and a proton pump inhibitor in high risk gastrointestinal and cardiovascular patients who mostly also take acetylsalicylic acid. Several studies confirm the need to restart the antiplatelet or anticoagulant therapy at an early stage after a gastrointestinal hemorrhage. The need for urgent endoscopy before 6-12 h after the onset of upper gastrointestinal bleeding episode may be beneficial in patients with hemodynamic instability and high risk for comorbidity. It is confirmed that in Western but not in Japanese populations, gastrointestinal bleeding episodes admitted to hospital during weekend days are associated with a worse prognosis associated with delays in the clinical management of the events. The strategy of a restrictive policy on blood transfusions during an upper GI bleeding event has been challenged. Several studies have shown the benefit of identifying the bleeding vessel in non varicose underlying gastric lesions by Doppler ultrasound which allows direct endoscopic therapy in the patient with upper GI bleeding. Finally, it has been reported that lower gastrointestinal bleeding diverticula band ligation or hemoclipping are both safe and have the same long-term outcomes.

  19. Collection of Biospecimen & Clinical Information in Patients w/ Gastrointestinal Cancers

    ClinicalTrials.gov

    2012-05-24

    Gastrointestinal Neoplasms; Gynecologic Cancers; Gynecologic Cancers Cervical Cancer; Gastric (Stomach) Cancer; Gastro-Esophageal(GE) Junction Cancer; Gastrointenstinal Stromal Tumor (GIST); Colon/Rectal Cancer; Colon/Rectal Cancer Colon Cancer; Colon/Rectal Cancer Rectal Cancer; Colon/Rectal Cancer Anal Cancer; Anal Cancer; Hepatobiliary Cancers; Hepatobiliary Cancers Liver; Pancreatic Cancer

  20. Incidental findings: a common law approach.

    PubMed

    Tovino, Stacey A

    2008-01-01

    Federal regulations governing human subjects research do not address key questions raised by incidental neuroimaging findings, including the scope of a researcher's disclosure with respect to the possibility of incidental findings and the question whether a researcher has an affirmative legal cuty to seek, detect, and report incidental findings. The scope of researcher duties may, however, be mapped with reference to common law doctrine, including fiduciary, tort, contract, and bailment theories of liability.

  1. 78 FR 18965 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-28

    ... Specified Activities; Taking Marine Mammals Incidental to an Exploration Drilling Program in the Chukchi Sea... harassment, incidental to conducting offshore exploration drilling on Outer Continental Shelf (OCS) leases in... small numbers of marine mammals, by harassment, incidental to conducting offshore exploration...

  2. 76 FR 13130 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-10

    ... Specified Activities; Taking Marine Mammals Incidental to Polar Bear Captures AGENCY: National Marine..., incidental to a capture-recapture program of polar bears in the U.S. Chukchi Sea. DATES: Effective March 14... taking, by harassment, of marine mammals incidental to a capture-recapture program of polar bears in...

  3. Incidental context information increases recollection

    PubMed Central

    Norman, Liam J.; Eacott, Madeline J.; Easton, Alexander

    2017-01-01

    The current study describes a receiver-operating characteristic (ROC) task for human participants based on the spontaneous recognition memory paradigms typically used with rodents. Recollection was significantly higher when an object was in the same location and background as at encoding, a combination used to assess episodic-like memory in animals, but not when only one of these task-irrelevant cues was present. The results show that incidentally encoded cue information can determine the degree of recollection, and opens up the possibility of assessing recollection across species in a single experimental paradigm, allowing better understanding of the cognitive and biological mechanisms at play. PMID:28202718

  4. Incidental context information increases recollection.

    PubMed

    Ameen-Ali, Kamar E; Norman, Liam J; Eacott, Madeline J; Easton, Alexander

    2017-03-01

    The current study describes a receiver-operating characteristic (ROC) task for human participants based on the spontaneous recognition memory paradigms typically used with rodents. Recollection was significantly higher when an object was in the same location and background as at encoding, a combination used to assess episodic-like memory in animals, but not when only one of these task-irrelevant cues was present. The results show that incidentally encoded cue information can determine the degree of recollection, and opens up the possibility of assessing recollection across species in a single experimental paradigm, allowing better understanding of the cognitive and biological mechanisms at play.

  5. Incidental isolated pancreatic hydatid cyst.

    PubMed

    Kısaoğlu, Abdullah; Özoğul, Bünyami; Atamanalp, Sabri Selçuk; Pirimoğlu, Berhan; Aydınlı, Bülent; Korkut, Ercan

    2015-03-01

    Isolated pancreatic hydatid cysts are a rare parasitic disease even in endemic areas. It is difficult to discriminate primary pancreatic hydatid cysts from other cystic and solid lesions of the pancreas. This is a case report of an incidental isolated pancreatic hydatid cyst. A heterogeneous cystic lesion in the body of the pancreas was identified on magnetic resonance imaging of a patient previously diagnosed patient with cholelithiasis, and because of the malignant possibility of the lesion, splenectomy with distal pancreatectomy and cholecystectomy was performed. The histopathologic diagnosis was reported as a hydatid cyst. Pancreatic hydatid cysts should be kept in mind in the differential diagnosis of pancreatic pseudocysts and cystic malignancies.

  6. 12 CFR 975.4 - Incidental powers.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Incidental powers. 975.4 Section 975.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD MISCELLANEOUS FEDERAL HOME LOAN BANK OPERATIONS AND AUTHORITIES COLLECTION, SETTLEMENT, AND PROCESSING OF PAYMENT INSTRUMENTS § 975.4 Incidental powers....

  7. 12 CFR 975.4 - Incidental powers.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 8 2012-01-01 2012-01-01 false Incidental powers. 975.4 Section 975.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD MISCELLANEOUS FEDERAL HOME LOAN BANK OPERATIONS AND AUTHORITIES COLLECTION, SETTLEMENT, AND PROCESSING OF PAYMENT INSTRUMENTS § 975.4 Incidental powers....

  8. 12 CFR 975.4 - Incidental powers.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 8 2013-01-01 2013-01-01 false Incidental powers. 975.4 Section 975.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD MISCELLANEOUS FEDERAL HOME LOAN BANK OPERATIONS AND AUTHORITIES COLLECTION, SETTLEMENT, AND PROCESSING OF PAYMENT INSTRUMENTS § 975.4 Incidental powers....

  9. 12 CFR 975.4 - Incidental powers.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 7 2011-01-01 2011-01-01 false Incidental powers. 975.4 Section 975.4 Banks and Banking FEDERAL HOUSING FINANCE BOARD MISCELLANEOUS FEDERAL HOME LOAN BANK OPERATIONS AND AUTHORITIES COLLECTION, SETTLEMENT, AND PROCESSING OF PAYMENT INSTRUMENTS § 975.4 Incidental powers....

  10. 12 CFR 1271.4 - Incidental powers.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 10 2014-01-01 2014-01-01 false Incidental powers. 1271.4 Section 1271.4 Banks and Banking FEDERAL HOUSING FINANCE AGENCY FEDERAL HOME LOAN BANKS MISCELLANEOUS FEDERAL HOME LOAN... Incidental powers. In connection with the collection, processing, and settlement of items and...

  11. Incidental fleurodeoxyglucose uptake in the prostate.

    PubMed

    Wong, W L; Moule, R N; Nunan, T

    2010-11-01

    This commentary confirms the rarity of prostatic cancer associated with incidental prostatic fleurodeoxyglucose (FDG) uptake. The study adds to the literature by showing that even if a prostate lesion is FDG avid it is unlikely to be due to cancer. The commentary considers the management of incidental prostate FDG uptake on the basis of the available evidence.

  12. Incidental fleurodeoxyglucose uptake in the prostate

    PubMed Central

    Wong, W L; Moule, R N; Nunan, T

    2010-01-01

    This commentary confirms the rarity of prostatic cancer associated with incidental prostatic fleurodeoxyglucose (FDG) uptake. The study adds to the literature by showing that even if a prostate lesion is FDG avid it is unlikely to be due to cancer. The commentary considers the management of incidental prostate FDG uptake on the basis of the available evidence. PMID:20965899

  13. 47 CFR 15.13 - Incidental radiators.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Incidental radiators. 15.13 Section 15.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.13 Incidental radiators. Manufacturers of these devices shall employ good engineering practices to minimize the risk...

  14. 47 CFR 15.13 - Incidental radiators.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Incidental radiators. 15.13 Section 15.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.13 Incidental radiators. Manufacturers of these devices shall employ good engineering practices to minimize the risk...

  15. 47 CFR 15.13 - Incidental radiators.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Incidental radiators. 15.13 Section 15.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.13 Incidental radiators. Manufacturers of these devices shall employ good engineering practices to minimize the risk...

  16. 47 CFR 15.13 - Incidental radiators.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Incidental radiators. 15.13 Section 15.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.13 Incidental radiators. Manufacturers of these devices shall employ good engineering practices to minimize the risk...

  17. 47 CFR 15.13 - Incidental radiators.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Incidental radiators. 15.13 Section 15.13 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL RADIO FREQUENCY DEVICES General § 15.13 Incidental radiators. Manufacturers of these devices shall employ good engineering practices to minimize the risk...

  18. Incidental Learning and Recall in Children.

    ERIC Educational Resources Information Center

    Fox, Robert A.; And Others

    Incidental learning research with mentally retarded children has produced findings inconsistent with those reported for the intellectually normal population. This study was designed to further investigate the efficacy of incidental semantic classification instructions relative to taxonomic classification instructions or superficial color…

  19. [Gastrointestinal bezoars].

    PubMed

    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.

  20. Focal liver lesions found incidentally

    PubMed Central

    Algarni, Abdullah A; Alshuhri, Abdullah H; Alonazi, Majed M; Mourad, Moustafa Mabrouk; Bramhall, Simon R

    2016-01-01

    Incidentally found focal liver lesions are a common finding and a reason for referral to hepatobiliary service. They are often discovered in patients with history of liver cirrhosis, colorectal cancer, incidentally during work up for abdominal pain or in a trauma setting. Specific points should considered during history taking such as risk factors of liver cirrhosis; hepatitis, alcohol consumption, substance exposure or use of oral contraceptive pills and metabolic syndromes. Full blood count, liver function test and tumor markers can act as a guide to minimize the differential diagnosis and to categorize the degree of liver disease. Imaging should start with B-mode ultrasound. If available, contrast enhanced ultrasound is a feasible, safe, cost effective option and increases the ability to reach a diagnosis. Contrast enhanced computed tomography should be considered next. It is more accurate in diagnosis and better to study anatomy for possible operation. Contrast enhanced magnetic resonance is the gold standard with the highest sensitivity. If doubt still remains, the options are biopsy or surgical excision. PMID:27028805

  1. Do We Know What Causes Gastrointestinal Stromal Tumors?

    MedlinePlus

    ... gene is found in all cells of the body. It directs the cell to make a protein called KIT, which causes the cell to grow and divide. Usually the c-kit gene in interstitial cells of Cajal (ICCs) is inactive. It is only active if ...

  2. Treatment for Gastrointestinal Stromal Tumors (GISTs) Based on Tumor Spread

    MedlinePlus

    ... These treatments may include radiofrequency ablation (RFA; using electric currents to heat the tumor), or ethanol ablation ( ... Life Events College Relay For Life Donate a Car Ways to Give Memorial Giving Planned Giving Leadership ...

  3. [Medical treatment for gastrointestinal stromal tumor (GIST) in Japan].

    PubMed

    Sato, Atsushi; Hamada, Kazuyuki; Imataka, Hiromi

    2012-05-01

    To facilitate an optimal diagnosis and treatment of GIST in Japan, the Japanese Clinical Practice Guideline for GIST was proposed by the GIST Guideline Subcommittee. Multidisciplinary treatment planning is needed(involving pathologists, radiologists, surgeons and medical oncologists)for patients with GIST. Medical treatment is usually selected for unresectable GIST, metastatic GIST at the initial examination, and recurrent GIST. Imatinib is strongly recommended for patients with KIT-positive GIST; the standard dose of imatinib mesylate(Glivec)is 400 mg/day. For patients with imatinib-resistant GIST, Sunitinib (Sutent)is now approved in Japan and is covered by medical insurance. However, high-dose imatinib(>400mg/day)has not yet been approved in Japan.

  4. Rare cases reports of gastrointestinal stromal tumour (GIST)

    PubMed Central

    AMENDOLARA, M.; RAMUSCELLO, S.; BROGGIATO, A.; ANDREOTTI, A.; STEVANATO, G.; BONFIGLIO, M.; BERNARDI, M.; PARINI, D.; GALEOTTI, F.; RIZZO, M.

    2014-01-01

    The GISTs are rare tumours but even rarer is the localization in some districts. We reported two GISTs of the duodenum, two of the omentum and peritoneum, one of the rectum and one of a Meckel’s diverticulum. These exceptional locations are confirmed by the relative difficult diagnosis, obtained in some cases only by the surgical treatment despite the CT and MR. The endoscopy is useful in hemorrhagic and duodenum forms, only for the diagnosis and for the control of blood loss. Surgical treatment in all cases was decisive without the need to make use of adjuvant therapy, with positive long-term results, which excluded the disappearance of relapses or secondary lesions. PMID:24979104

  5. Accomplishments in 2008 in the Management of Gastrointestinal Stromal Tumors

    PubMed Central

    Renouf, Daniel; Blay, Jean-Yves; Blanke, Charles

    2009-01-01

    SUMMARY Overview of the Disease ProcessIncidencePrognosisPredictive MarkersCurrent General Therapy Standards in North America and EuropeLocalized or Potentially Resectable DiseaseUnresectable or Metastatic DiseaseAccomplishments During the YearTherapySurgical Issues and Perioperative TherapyImatinibSunitinibNew DrugsBiomarkersBasic and Other Translational ScienceWhat Needs to Be DoneFuture DirectionsComments on ResearchObstacles to Progress PMID:20011569

  6. [Incidental appendectomy: standard or unjustified risk?].

    PubMed

    Kaderli, Reto

    2014-12-01

    Incidental appendectomy is the surgical removal of a macroscopically non-diseased appendix during another primary surgical procedure. The benefits and risks of this surgery give rise to controversy. Incidental appendectomy is contraindicated in patients whose conditions are unstable, with previous diagnosis of Crohn's disease, inaccessible appendix, planned radiation treatment, immunosuppression, vascular grafts or other intraabdominal foreign material. It should be conditional on primary disease, surgical technique (open vs. laparoscopic) and age of the patient. Independently from the surgical technique used, incidental appendectomy should be evaluated in healthy patients younger than 25 years old. In any case, preoperative informed consent is necessary.

  7. The Role of Thymic Stromal Lymphopoietin (TSLP) in Allergic Disorders

    PubMed Central

    Ziegler, Steven F.

    2010-01-01

    Summary The importance of the epithelium in initiating and controlling immune responses is becoming more appreciated. For example, allergens contact first occurs at mucosal sites in exposed to the external environment such as the skin, airways and gastrointestinal tract. This exposure leads to the production of a variety of cytokines and chemokines that are involved in driving allergic inflammatory responses. One such product is thymic stromal lymphopoietin (TSLP). Recent studies, in both humans and mouse models, have implicated TSLP in the development and progression of atopy and atopic diseases. This review will discuss this work and place TSLP in the inflammatory cascade that leads to allergic disease. PMID:21109412

  8. Level 1: Incidental crane operator`s and incidental rigger`s manual. Revision

    SciTech Connect

    Neubauer, P.

    1992-11-01

    This document is a safety manual for incidental crane operators and incidental riggers. The information contained in this manual includes: Terminology and definitions, safety orientation, general operating procedures, high-consequence/high value lifts, sling safety, basic rules of hitching and rigging, and common errors in hitching.

  9. 78 FR 37209 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE National Oceanic and Atmospheric Administration RIN 0648-XC564 Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to Marine Seismic Survey in the Beaufort Sea,...

  10. 75 FR 49709 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to Shell Offshore Inc. (Shell) to take, by harassment, small numbers of 8 species of marine mammals incidental to a marine survey program, which includes site clearance and shallow hazards, ice gouge, and strudel scour surveys,......

  11. 75 FR 49759 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to Statoil USA E&P Inc. (Statoil) to take, by harassment, small numbers of 12 species of marine mammals incidental to a marine seismic survey program in the Chukchi Sea, Alaska, during the 2010 Arctic open water...

  12. 76 FR 4093 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-24

    ... Specified Activities; Taking Marine Mammals Incidental to Exploration Drilling Programs in the Chukchi and.... (Shell) incidental to offshore exploration drilling on Outer Continental Shelf (OCS) leases in the... IHAs were not issued, and Shell did not conduct the proposed exploration drilling programs in...

  13. 76 FR 330 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-04

    ... Specified Activities; Taking Marine Mammals Incidental to Polar Bear Captures AGENCY: National Marine...) to take marine mammals, by harassment, incidental to a capture- recapture program of polar bears in...-recapture program of polar bears in the U.S. Chukchi Sea. NMFS reviewed the USFWS' application...

  14. 76 FR 68974 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ...NMFS received an application from Shell Offshore Inc. (Shell) for an Incidental Harassment Authorization (IHA) to take marine mammals, by harassment, incidental to offshore exploration drilling on Outer Continental Shelf (OCS) leases in the Beaufort Sea, Alaska. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS is requesting comments on its proposal to issue an IHA to Shell to take, by......

  15. 78 FR 12541 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ...NMFS received an application from ConocoPhillips Company (COP) for an Incidental Harassment Authorization (IHA) to take marine mammals, by harassment, incidental to offshore exploration drilling on Outer Continental Shelf (OCS) leases in the Chukchi Sea, Alaska. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS is requesting comments on its proposal to issue an IHA to COP to take, by......

  16. 77 FR 40007 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to BP Exploration (Alaska), Inc. (BP) to take, by harassment, small numbers of 10 species of marine mammals incidental to ocean bottom cable (OBC) seismic surveys in the Simpson Lagoon area of the Beaufort Sea, Alaska, during the......

  17. 76 FR 46729 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to Statoil USA E&P Inc. (Statoil) to take, by harassment, small numbers of 13 species of marine mammals incidental to shallow hazards and geotechnical surveys in the Chukchi Sea, Alaska, during the 2011 Arctic open-water...

  18. 77 FR 65059 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-24

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to ION Geophysical (ION) to take, by harassment, small numbers of nine species of marine mammals incidental to in-ice marine seismic surveys in the Beaufort and Chukchi Seas, Alaska, during the fall and winter of...

  19. 77 FR 27321 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to Shell Gulf of Mexico Inc. (Shell) to take marine mammals, by harassment, incidental to offshore exploration drilling on Outer Continental Shelf (OCS) leases in the Chukchi Sea,...

  20. 77 FR 27283 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-09

    ...In accordance with the Marine Mammal Protection Act (MMPA) regulations, notification is hereby given that NMFS has issued an Incidental Harassment Authorization (IHA) to Shell Offshore Inc. (Shell) to take marine mammals, by harassment, incidental to offshore exploration drilling on Outer Continental Shelf (OCS) leases in the Beaufort Sea,...

  1. Rare recurrence of a rare ovarian stromal tumor with luteinized cells: a case report

    PubMed Central

    2011-01-01

    Introduction Sex cord-stromal tumors of the ovary are uncommon. They behave unpredictably and often have a late recurrence, making counseling, management, and prediction of prognosis challenging. Case presentation A 52-year-old Moroccan woman with an sex cord-stromal tumors underwent a bilateral oophorectomy. The histology was unusual but was likely to be a luteinized thecoma with suspicious features for invasion. Seven years later, after a gastrointestinal bleed, a metastasis within the small bowel mucosa was detected. This represents probable isolated hematogenous or lymphatic spread, which is highly unusual, especially in the absence of concurrent peritoneal disease. Conclusions To the best of our knowledge, this is the second reported case of an sex cord-stromal tumors recurring in small bowel mucosa and mimicking a primary colorectal tumor. This highlights the diverse nature and behavior of these tumors. PMID:21816048

  2. Mesenchymal stromal cell cryopreservation.

    PubMed

    Renzi, Sabrina; Lombardo, Tina; Dotti, Silvia; Dessì, Sara S; De Blasio, Pasquale; Ferrari, Maura

    2012-06-01

    The advent of stem cells and stem cell-based therapies for specific diseases requires particular knowledge of laboratory procedures, which not only guarantee the continuous production of cells, but also provide them an identity and integrity as close as possible to their origin. Their cryopreservation at temperatures below -80°C and typically below -140°C is of paramount importance. This target can be achieved by incorporating high molar concentrations of cryoprotectant mixtures that preserve cells from deleterious ice crystal formation. Usually, dimethyl sulfoxide (DMSO) and animal proteins are used as protectant reagents, but unexpected changes in stem cell fate and downstream toxicity effects have been reported, limiting their wide use in clinical settings. In scientific reviews, there are not much data regarding viability of mesenchymal stromal cells (MSCs) after the freezing/thawing process. During our routine analysis, a poor resistance to cryopreservation of these cells was observed, as well as their weak ability to replicate. This is an important point in the study of MSCs; moreover, it represents a limit for preservation and long-term storage. For this reason, MSCs isolated from equine, ovine, and rodent bone marrow and equine adipose tissue were compared using different cryopreservation solutions for this study of vitality. Our findings showed the best results regarding cell viability using a solution of fetal bovine serum with addition of 10% DMSO. In particular, we noted an increase in survival of equine bone marrow MSCs. This parameter has been evaluated by Trypan blue staining at fixed times (0, 24, and 48 hours post-thaw). This result highlights the fact that equine bone marrow MSCs are the frailest we analyzed. Therefore, it could be useful to delve further into this topic in order to improve the storage possibility for these cells and their potential use in cell-based therapies.

  3. Negative incidental emotions augment fairness sensitivity.

    PubMed

    Liu, Cuizhen; Chai, Jing Wen; Yu, Rongjun

    2016-04-22

    Previous studies have shown that task-unrelated emotions induced incidentally exert carryover effects on individuals' subsequent decisions in financial negotiations. However, the specificity of these emotion effects are not clear. In three experiments, we systematically investigated the role of seven transiently induced basic emotions (disgust, sadness, anger, fear, happiness, surprise and neutral) on rejection of unfair offers using the ultimatum game. We found that all negative emotions (disgust, sadness, anger and fear), but not happiness or surprise, significantly increased rejection rates, suggesting that the effect of incidental negative emotions on fairness is not specific to the type of negative emotion. Our findings highlight the role of fleeting emotions in biasing decision-making processes and suggest that all incidental negative emotions exert similar effects on fairness sensitivity, possibly by potentiating attention towards negative aspects of the situation.

  4. Negative incidental emotions augment fairness sensitivity

    PubMed Central

    Liu, Cuizhen; Chai, Jing Wen; Yu, Rongjun

    2016-01-01

    Previous studies have shown that task-unrelated emotions induced incidentally exert carryover effects on individuals’ subsequent decisions in financial negotiations. However, the specificity of these emotion effects are not clear. In three experiments, we systematically investigated the role of seven transiently induced basic emotions (disgust, sadness, anger, fear, happiness, surprise and neutral) on rejection of unfair offers using the ultimatum game. We found that all negative emotions (disgust, sadness, anger and fear), but not happiness or surprise, significantly increased rejection rates, suggesting that the effect of incidental negative emotions on fairness is not specific to the type of negative emotion. Our findings highlight the role of fleeting emotions in biasing decision-making processes and suggest that all incidental negative emotions exert similar effects on fairness sensitivity, possibly by potentiating attention towards negative aspects of the situation. PMID:27101931

  5. Incidental Learning in a Paired-Associate Task.

    ERIC Educational Resources Information Center

    Shelton, Dennis; Newhouse, Robert C.

    1981-01-01

    Differences in recall and number of trials to criterion between incidental learning groups and control groups of undergraduate students when memorizing CVC trigrams of high or low intralist similarity were investigated in this study. Results indicate that incidental learning did occur and suggest that incidental learning facilitates intentional…

  6. Stages of Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  7. Necrotizing cellulitis of the abdominal wall, caused by Pediococcus sp., due to rupture of a retroperitoneal stromal cell tumor

    PubMed Central

    Michalopoulos, Nick; Arampatzi, Stergiani; Papavramidis, Theodossis S.; Kotidis, Efstathios; Laskou, Styliani; Papavramidis, Spiros T.

    2013-01-01

    INTRODUCTION Soft tissue necrotizing infections are a significant cause of morbidity and mortality. The aim of this study is to present a patient with necrotizing infection of abdominal wall resulting from the rupture of a retroperitoneal stromal tumor. PRESENTATION OF CASE We present a 60-year-old Caucasian male patient with necrotizing infection of abdominal wall secondary to the rupture of a retroperitoneal stromal tumor. The patient was initially treated with debridement and fasciotomy of the anterior abdominal wall. Laparotomy revealed purulent peritonitis caused by infiltration and rupture of the splenic flexure by the tumor. Despite prompt intervention the patient died 19 days later. The isolated microorganism causing the infection was the rarely identified as cause of infections in humans Pediococcus sp., a gram-positive, catalase-negative coccus. DISCUSSION Necrotizing infections of abdominal wall are usually secondary either to perineal or to intra-abdominal infections. Gastrointestinal stromal cell tumors could be rarely complicated with perforation and abscess formation. In our case, the infiltrated by the extra-gastrointestinal stromal cell tumor ruptured colon was the source of the infection. The pediococci are rarely isolated as the cause of severe septicemia. CONCLUSION Ruptured retroperitoneal stromal cell tumors are extremely rare cause of necrotizing fasciitis, and before this case, Pediococcus sp. has never been isolated as the responsible agent. PMID:23357010

  8. Zinc and gastrointestinal disease

    PubMed Central

    Skrovanek, Sonja; DiGuilio, Katherine; Bailey, Robert; Huntington, William; Urbas, Ryan; Mayilvaganan, Barani; Mercogliano, Giancarlo; Mullin, James M

    2014-01-01

    This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases. PMID:25400994

  9. Incidental Learning in a Complex Clinical Workplace

    ERIC Educational Resources Information Center

    Harner, Michael Dean

    2013-01-01

    Workplace learning is complex as employees engage in activities to meet organizational objectives. This study investigates incidental learning in a complex clinical environment. The systems created to collect information and perform patient-visit functions involve several people who have distinct roles that can impact how subsequent people in the…

  10. Incidental Foreign Language Acquisition from Media Exposure

    ERIC Educational Resources Information Center

    Kuppens, An H.

    2010-01-01

    A number of experimental studies have demonstrated the incidental acquisition of a foreign language by children and adolescents when watching foreign language television. While such experiments can only establish short-term effects, this article investigates the extent to which children's foreign language skills benefit from their long-term…

  11. Incidental Education (for Women) in Rural Communities.

    ERIC Educational Resources Information Center

    Crosby, Valmai

    The Country Women's Association (CWA) is a nationwide Australian group that started in the 1920s in response to isolated women's need to socialize. The group's activities have expanded greatly over time. It distributes essential food and clothing to needy rural families, and its extensive involvement in incidental education for women includes…

  12. Incidental Learning, Intelligence, and Verbal Ability.

    ERIC Educational Resources Information Center

    Necka, Edward; And Others

    1992-01-01

    The effects of incidental learning were assessed in 2 experiments involving 201 seventh graders in Poland through an experimental paradigm based on the levels of processing theory. Data suggest that an important aspect of intelligence is "opportunistic" learning (learning in advance). Intelligent people take cognitive advantage of…

  13. Incidental finding of carcinoid tumor on Meckel's diverticulum: case report and literature review, should prophylactic resection be recommended?

    PubMed

    Caracappa, Daniela; Gullà, Nino; Lombardo, Francesco; Burini, Gloria; Castellani, Elisa; Boselli, Carlo; Gemini, Alessandro; Burattini, Maria Federica; Covarelli, Piero; Noya, Giuseppe

    2014-05-08

    Meckel's diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is caused by incomplete obliteration of the vitelline duct during intrauterine life. MD affects less than 2% of the population. In most cases, MD is asymptomatic and the estimated average complication risk of MD carriers, which is inversely proportional to age, ranges between 2% and 4%. The most common MD-related complications are gastrointestinal bleeding, intestinal obstruction and acute phlogosis. Excision is mandatory in the case of symptomatic diverticula regardless of age, while surgical treatment for asymptomatic diverticula remains controversial. According to the majority of studies, the incidental finding of MD in children is an indication for surgical resection, while the management of adults is not yet unanimous. In this case report, we describe the prophylactic resection of an incidentally detected MD, which led to the removal of an occult mucosal carcinoid tumor. In literature, the association of MD and carcinoid tumor is reported as a rare finding. Even though the strategy for adult patients of an incidental finding of MD during surgery performed for other reasons divides the experts, we recommend prophylactic excision in order to avoid any further risk.

  14. Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment.

    PubMed

    Giordani, Erika; Zoratto, Federica; Strudel, Martina; Papa, Anselmo; Rossi, Luigi; Minozzi, Marina; Caruso, Davide; Zaccarelli, Eleonora; Verrico, Monica; Tomao, Silverio

    2016-01-01

    Gastrointestinal cancer treatment is based more on molecular biology that has provided increasing knowledge about cancer pathogenesis on which targeted therapy is being developed. Precisely, targeted therapy is defined as a "type of treatment that uses drugs, such as monoclonal antibodies or tyrosine kinase inhibitors, to identify and attack specific cancer cells". Nowadays, the United States Food and Drug Administration has approved many targeted therapies for gastrointestinal cancer treatment, as many are in various phases of development as well. In a previous review we discussed the main monoclonal antibodies used and studied in gastrointestinal cancer. In addition to monoclonal antibodies, tyrosine kinase inhibitors represent another class of targeted therapy and following the approval of imatinib for gastrointestinal stromal tumours, other tyrosine kinase inhibitors have been approved for gastrointestinal cancers treatment such as sunitinib, regoragenib, sorafenib and erlotinib. Moving forward, the purpose of this review is to focus on the efficacy data of main tyrosine kinase inhibitors commonly used in the personalized treatment of each gastrointestinal tumour and to provide a comprehensive overview about experimental targeted therapies ongoing in this setting.

  15. Incidental renocolic fistula with xanthogranulomatous pyelonephritis

    PubMed Central

    McDermott, R.L.; Dowling, C.M.; Alsinnawi, M.; Grainger, R.

    2012-01-01

    INTRODUCTION We report the case of a 66-year-old female undergoing elective nephrectomy for a non-functioning kidney in whom an incidental renocolic fistula was detected. PRESENTATION OF CASE She presented with recurrent urinary tract infections and left flank pain. Investigations revealed a nonfunctioning left kidney with a large staghorn calculus and features suggestive of xanthogranulomatous pyelonephritis (XPG). At nephrectomy, an incidental renocolic fistula was found and excised. DISCUSSION XGP is a rare, chronic inflammatory disorder of the kidney characterized by a destructive mass invading the renal parenchyma. Renocolic fistulae complicating XGP are uncommon and not widely reported in the literature. CONCLUSION Herein, we describe a case of XGP with renocolic fistula formation, its management and a review of the literature. PMID:23291328

  16. Incidental pleural-based pulmonary lymphangioma.

    PubMed

    Benninghoff, Michael G; Todd, William U; Bascom, Rebecca

    2008-09-01

    Adult benign thoracic lymphangiomas typically present as incidental mediastinal lesions, or, more rarely, as solitary pulmonary nodules. Symptomatic compression of vital structures may require lesion resection or sclerotherapy. In the present report, we describe the incidental finding of a solitary pleural-based pulmonary lymphangioma in a 38-year-old woman with chronic arm and shoulder pain. Positron emission tomography revealed that the lesion was highly fluorodeoxyglucose-avid. Biopsy exposed benign tissue consistent with lymphangioma. After continued radiographic tests, the lesion was determined to be an unlikely source of the patient's chronic pain. The present report is, to our knowledge, the first published case of solitary pleural-based pulmonary lymphangioma in the medical literature.

  17. The persistent impact of incidental experience.

    PubMed

    Wilder, Matthew H; Jones, Matt; Ahmed, Alaa A; Curran, Tim; Mozer, Michael C

    2013-12-01

    As we perform daily activities--driving to work, unlocking the office door, or grabbing a coffee cup--our actions seem automatic and preprogrammed. Nonetheless, routine, well-practiced behavior is continually modulated by incidental experience: In repetitive experimental tasks, recent (~4) trials reliably influence performance and action choice. Psychological theories downplay the significance of sequential effects, explaining them as rapidly decaying perturbations of behavior, with no long-term consequences. We challenged this traditional perspective in two experiments designed to probe the impact of more distant experience, finding evidence for effects spanning up to a thousand intermediate trials. We present a normative theory in which these persistent effects reflect optimal adaptation to a dynamic environment exhibiting varying rates of change. The theory predicts a heavy-tailed decaying influence of past experience, consistent with our data, and suggests that individual incidental experiences are catalogued in a temporally extended memory utilized in order to optimize subsequent behavior.

  18. Incidental Anterior Cruciate Ligament Calcification: Case Report

    PubMed Central

    Hayashi, Hisami; Fischer, Hans

    2016-01-01

    The calcification of knee ligaments is a finding noted only in a handful of case reports. The finding of an anterior cruciate ligament calcification has been reported once in the literature. Comparable studies involving the posterior cruciate ligament, medial collateral ligament and an ossicle within the anterior cruciate ligament are likewise discussed in reports of symptomatic patients. We report a case of incidentally discovered anterior cruciate ligament calcification. We discuss the likely etiology and clinical implications of this finding. PMID:27200163

  19. Incidental finding of lymphoma after septoplasty

    PubMed Central

    Tajudeen, Bobby A.; Bhuta, Sunita M.; Palma Diaz, Miguel Fernando; Kedeshian, Paul A.; Suh, Jeffrey D.

    2016-01-01

    Introduction: Septoplasty, or surgical correction of the deviated septum, is an elective, routinely performed rhinologic procedure to address nasal airway obstruction. In many cases, resected septal cartilage and bone fragments are sent for pathologic review, although there is no consensus on this practice. We reported two cases of incidentally diagnosed lymphoma after elective septoplasty and discussed clinical presentation, diagnosis, and management. Methods: Retrospective chart review of two patients who underwent septoplasty at a tertiary academic medical center and found to have incidental lymphoma based on histopathology. Results: Two patients who underwent septoplasty had an incidental diagnosis of lymphoma on pathologic analysis. One patient was noted to have an S-shaped septal deviation that produced bilateral nasal obstruction. She underwent a difficult septoplasty, in which the mucoperichondrial flap was firmly adherent to the underlying septum and bone. Final pathology demonstrated diffuse large B-cell lymphoma. She was treated with chemoradiation and remained free of disease at 59 months. The other patient had a history of nasal trauma, which produced left septal deviation. He underwent an uncomplicated septoplasty, with pathology that demonstrated low-grade B-cell lymphoma. Because there was no evidence of active disease, the decision was made to not treat and to observe the patient clinically. Conclusions: This is the first reported series of septal lymphoma incidentally diagnosed on routine septoplasty. Although histopathologic review of specimens from routine nasal and sinus surgery is not routinely performed, this report highlighted the importance of this process, on a case-by-case basis, in detecting unexpected malignancies that otherwise were clinically silent. PMID:27470206

  20. 257 Incidental Appendectomies During Total Laparoscopic Hysterectomy

    PubMed Central

    Fisher, Deidre T.; O'Holleran, Michael S.

    2007-01-01

    Objective: This retrospective observational report analyzes the demographics, blood loss, length of surgical duration, number of days in the hospital, and complications for 821 consecutive patients undergoing total laparoscopic hysterectomy over a 11-year period stratified by incidental appendectomy. Methods: A retrospective chart abstraction was performed. ANOVA and chi-square tests were performed with significance preset at P<0.05. Results: Of 821 consecutive patients undergoing total laparoscopic hysterectomy, 257 underwent elective appendectomy with the ultrasonic scalpel, either as part of their staging, treatment for pelvic pain, or prophylaxis against appendicitis. Comparing the 2 groups, no difference existed in mean age of 50±10 years or mean BMI of 27.6±6.7. Both groups had a similar mean blood loss of 130 mL. Surgery took less time (137 vs 118 minutes, P<0.0012) and the hospital stay was shorter in the appendectomy group (1.5 vs 1.2, P<0.0001) possibly because it was performed incidentally in most cases. No complications were attributable to the appendectomy, and complication types and rates in both groups were similar. Though all appendicies appeared normal, pathology was documented in 9%, including 3 carcinoid tumors. Conclusions: Incidental appendectomy during total laparoscopic hysterectomy is not associated with significant risk and can be routinely offered to patients planning elective gynecologic laparoscopic procedures, as is standard for open procedures. PMID:18237505

  1. Stromal genes discriminate preinvasive from invasive disease, predict outcome, and highlight inflammatory pathways in digestive cancers

    PubMed Central

    Saadi, Amel; Shannon, Nicholas B.; Lao-Sirieix, Pierre; O’Donovan, Maria; Walker, Elaine; Clemons, Nicholas J.; Hardwick, James S.; Zhang, Chunsheng; Das, Madhumita; Save, Vicki; Novelli, Marco; Balkwill, Frances; Fitzgerald, Rebecca C.

    2010-01-01

    The stromal compartment is increasingly recognized to play a role in cancer. However, its role in the transition from preinvasive to invasive disease is unknown. Most gastrointestinal tumors have clearly defined premalignant stages, and Barrett’s esophagus (BE) is an ideal research model. Supervised clustering of gene expression profiles from microdissected stroma identified a gene signature that could distinguish between BE metaplasia, dysplasia, and esophageal adenocarcinoma (EAC). EAC patients overexpressing any of the five genes (TMEPAI, JMY, TSP1, FAPα, and BCL6) identified from this stromal signature had a significantly poorer outcome. Gene ontology analysis identified a strong inflammatory component in BE disease progression, and key pathways included cytokine–cytokine receptor interactions and TGF-β. Increased protein levels of inflammatory-related genes significantly up-regulated in EAC compared with preinvasive stages were confirmed in the stroma of independent samples, and in vitro assays confirmed functional relevance of these genes. Gene set enrichment analysis of external datasets demonstrated that the stromal signature was also relevant in the preinvasive to invasive transition of the stomach, colon, and pancreas. These data implicate inflammatory pathways in the genesis of gastrointestinal tract cancers, which can affect prognosis. PMID:20080664

  2. Mycobacterium Xenopi Found Incidentally on MRI of the Cervical Spine

    DTIC Science & Technology

    2010-01-01

    Mycobacterium Xenopi Found Incidentally on MRI of the Cervical Spine Military Medicine Radiology Corner, Vol. 175. January, 2010 Radiology Corner...Mycobacterium Xenopi Found Incidentally on MRI of the Cervical Spine Guarantor: Chris Walker1 Contributors: Chris Walker; 1 Col Les Folio...Mycobacterium xenopi in her lung. A mass was incidentally noted in the right upper apex on an MRI ordered to evaluate a subluxation seen in her cervical

  3. Nerve regeneration by human corneal stromal keratocytes and stromal fibroblasts

    PubMed Central

    Yam, Gary Hin-Fai; Williams, Geraint P.; Setiawan, Melina; Yusoff, Nur Zahirah Binte M.; Lee, Xiao-wen; Htoon, Hla Myint; Zhou, Lei; Fuest, Matthias; Mehta, Jodhbir S.

    2017-01-01

    Laser refractive surgeries reshape corneal stroma to correct refractive errors, but unavoidably affect corneal nerves. Slow nerve regeneration and atypical neurite morphology cause desensitization and neuro-epitheliopathy. Following injury, surviving corneal stromal keratocytes (CSKs) are activated to stromal fibroblasts (SFs). How these two different cell types influence nerve regeneration is elusive. Our study evaluated the neuro-regulatory effects of human SFs versus CSKs derived from the same corneal stroma using an in vitro chick dorsal root ganglion model. The neurite growth was assessed by a validated concentric circle intersection count method. Serum-free conditioned media (CM) from SFs promoted neurite growth dose-dependently, compared to that from CSKs. We detected neurotrophic and pro-inflammatory factors (interleukin-8, interleukin-15, monocyte chemoattractant protein-1, eotaxin, RANTES) in SFCM by Bio-Plex Human Cytokine assay. More than 130 proteins in SFCM and 49 in CSKCM were identified by nanoLC-MS/MS. Proteins uniquely present in SFCM had reported neuro-regulatory activities and were predicted to regulate neurogenesis, focal adhesion and wound healing. Conclusively, this was the first study showing a physiological relationship between nerve growth and the metabolically active SFs versus quiescent CSKs from the same cornea source. The dose-dependent effect on neurite growth indicated that nerve regeneration could be influenced by SF density. PMID:28349952

  4. Stromal Cell Subsets Directing Neonatal Spleen Regeneration

    PubMed Central

    Tan, Jonathan K. H.; Watanabe, Takeshi

    2017-01-01

    Development of lymphoid tissue is determined by interactions between stromal lymphoid tissue organiser (LTo) and hematopoietic lymphoid tissue inducer (LTi) cells. A failure for LTo to receive appropriate activating signals during embryogenesis through lymphotoxin engagement leads to a complete cessation of lymph node (LN) and Peyer’s patch development, identifying LTo as a key stromal population for lymphoid tissue organogenesis. However, little is known about the equivalent stromal cells that induce spleen development. Here, by dissociating neonatal murine spleen stromal tissue for re-aggregation and transplant into adult mouse recipients, we have identified a MAdCAM-1+CD31+CD201+ spleen stromal organizer cell-type critical for new tissue formation. This finding provides an insight into the regulation of post-natal spleen tissue organogenesis, and could be exploited in the development of spleen regenerative therapies. PMID:28067323

  5. Pathological analysis of collision (double primary) cancer in the upper digestive tract concomitant with gastric stromal tumor: a case report

    PubMed Central

    Sun, Xun; Zou, Yabin; Hao, Yueming; Cheng, Hongjing; Zhou, Changli; Meng, Xiangwei

    2015-01-01

    Carcinoma of the esophagus and cardiac cancer are common malignancies, while multiple primary cancers in the esophagus and cardia is rarely encountered and easily misdiagnosed. Multiple primary cancers mean the same organs (tissues) or different organs (tissues) have two or more than two primary malignant tumors at the same time or in sequence in the same individual. The case below of two independent primary lesions is double primary carcinoma which meets the diagnosis standard of multiple primary cancers. Gastrointestinal stromal tumor is the most common stromal tumor, which is usually considered as originating from Cajal cells in the gastrointestinal tract or mesenchymal stem cells with the mutation of KIT or PDGFRA gene. Study on stromal tumor with digestive tract cancer is less both at home and abroad, while double primary carcinoma with stromal tumor is rare, which has not been reported at present. Although scholars have different viewpoints on the prognosis, but the full understanding of this disease can be as a warning for the future work and to avoid misdiagnosis. PMID:26722567

  6. Primary gastrointestinal lymphoma

    PubMed Central

    Ghimire, Prasanna; Wu, Guang-Yao; Zhu, Ling

    2011-01-01

    Gastrointestinal tract is the most common extranodal site involved by lymphoma with the majority being non-Hodgkin type. Although lymphoma can involve any part of the gastrointestinal tract, the most frequent sites in order of its occurrence are the stomach followed by small intestine and ileocecal region. Gastrointestinal tract lymphoma is usually secondary to the widespread nodal diseases and primary gastrointestinal tract lymphoma is relatively rare. Gastrointestinal lymphomas are usually not clinically specific and indistinguishable from other benign and malignant conditions. Diffuse large B-cell lymphoma is the most common pathological type of gastrointestinal lymphoma in essentially all sites of the gastrointestinal tract, although recently the frequency of other forms has also increased in certain regions of the world. Although some radiological features such as bulky lymph nodes and maintenance of fat plane are more suggestive of lymphoma, they are not specific, thus mandating histopathological analysis for its definitive diagnosis. There has been a tremendous leap in the diagnosis, staging and management of gastrointestinal lymphoma in the last two decades attributed to a better insight into its etiology and molecular aspect as well as the knowledge about its critical signaling pathways. PMID:21390139

  7. Advances in gastrointestinal bleeding.

    PubMed

    Lanas, Ángel

    2016-09-01

    The main innovations of the latest meeting of the Gastroenterological Association (2016) concerning upper gastrointestinal bleeding from the clinician's perspective can be summarised as follows: a) The Glasgow-Blatchford scale has the best accuracy in predicting the need for surgical intervention and hospital mortality; b) Prognostic scales for non-variceal upper gastrointestinal bleeding are also useful for lower gastrointestinal bleeding; c) Preliminary data suggest that treatment with hemospray does not seem to be superior to current standard treatment in controlling active peptic ulcer bleeding; d) Either famotidine or a proton pump inhibitor may be effective in preventing haemorrhagic recurrence in patients taking aspirin, but this finding needs to be confirmed in further studies; e) There was confirmation of the need to re-introduce antiplatelet therapy as early as possible in patients with antiplatelet-associated gastrointestinal bleeding in order to prevent cardiovascular mortality; f) Routine clinical practice suggests that gastrointestinal or cardiovascular complications with celecoxib or traditional NSAIDs are very low; g) Dabigatran is associated with an increased incidence of gastrointestinal bleeding compared with apixaban or warfarin. At least half of the episodes are located in the lower gastrointestinal tract; h) Implant devices for external ventricular circulatory support are associated with early gastrointestinal bleeding in up to one third of patients; the bleeding is often secondary to arteriovenous malformations.

  8. Radiologic diagnosis of gastrointestinal perforation.

    PubMed

    Rubesin, Stephen E; Levine, Marc S

    2003-11-01

    Perforations of the gastrointestinal tract have many causes. Holes in the wall of gastrointestinal organs can be created by blunt or penetrating trauma, iatrogenic injury, inflammatory conditions that penetrate the serosa or adventitia, extrinsic neoplasms that invade the gastrointestinal tract, or primary neoplasms that penetrate outside the wall of gastrointestinal organs. This article provides a radiologic approach for investigating the wide variety of gastrointestinal perforations. General principles about contrast agents and studies are reviewed, and then perforations in specific gastrointestinal organs are discussed.

  9. 76 FR 74805 - Draft Environmental Assessment, Incidental Take Plan, and Application for an Incidental Take...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-01

    ... Program; Correction AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of availability; announcement of public meeting. SUMMARY: On November 9, 2011, we, the U.S. Fish and Wildlife Service (Service... Fish and Wildlife Service Draft Environmental Assessment, Incidental Take Plan, and Application for...

  10. 78 FR 24731 - Taking Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to an...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-26

    ... Specified Activities; Taking Marine Mammals Incidental to an Exploration Drilling Program in the Chukchi Sea... drilling on Outer Continental Shelf (OCS) leases in the Chukchi Sea, Alaska, during the 2014 open-water... exploration drilling in the Chukchi Sea during the 2014 open- ] water season. NMFS published a Notice...

  11. 75 FR 53672 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-01

    ... liquefied natural gas (LNG) facility in the Massachusetts Bay for a period of 1 year. DATES: This... Incidental to Operations of a Liquified Natural Gas Port Facility in Massachusetts Bay AGENCY: National...-cm) outside diameter natural gas pipeline lateral (Pipeline Lateral) owned and operated by...

  12. 76 FR 43639 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-21

    ... Liquefied Natural Gas Port Facility in Massachusetts Bay AGENCY: National Marine Fisheries Service (NMFS... take marine mammals, by harassment, incidental to operating a liquefied natural gas (LNG) port facility... diameter natural gas pipeline which interconnects the Port to an offshore natural gas pipeline known as...

  13. 77 FR 51773 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... retinal injury. Biosonics Up to three Bird-Guard broadcasting units (bird distress calls) could be used to... distress and predator calls could be used. The bird calls are naturally occurring sounds and are not... Specified Activities; Taking Marine Mammals Incidental to Bird Mitigation Research in the Farallon...

  14. 75 FR 34700 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Coastal Commercial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-18

    ... Sanctuary (MBNMS) to incidentally take, by Level B harassment only, California sea lions (Zalophus californianus) and Pacific harbor seals (Phoca vitulina) incidental to professional fireworks displays...

  15. 77 FR 43270 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Coastal Commercial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ... Sanctuary (MBNMS) to incidentally take, by Level B harassment only, California sea lions (Zalophus californianus) and harbor seals (Phoca vitulina) incidental to professional fireworks displays within the...

  16. Inflammatory stromal keratopathies: medical management of stromal keratomalacia, stromal abscesses, eosinophilic keratitis, and band keratopathy in the horse.

    PubMed

    Brooks, Dennis E

    2004-08-01

    This article discusses the diagnosis and medical treatment of stromal keratomalacia or "melting ulcers," stromal abscesses, eosinophilic keratitis (EK), and calcific band keratopathy. These are common and important inflammatory keratopathies of the equine corneal stroma. Keratomalacia and stromal abscesses are associated with infection, leukocytic invasion of the stroma, and loss of tissue and tear film proteinase homeostasis. Eosinophils infiltrate the stroma in response to unknown stimuli in EK. Calcium is deposited in the stroma and epithelium secondary to chronic equine recurrent uveitis in calcific band keratopathy. They are all associated with varying degrees of iridocyclitis.

  17. Incidental Focus on Form in University Spanish Literature Courses

    ERIC Educational Resources Information Center

    Zyzik, Eve; Polio, Charlene

    2008-01-01

    Incidental focus on form is one of several ways to direct language learners' attention to formal aspects of language within meaningful communicative contexts. Learners can benefit from focus on form, but the extent to which incidental focus on form, or any other type, is available to learners in advanced foreign language literature classes has not…

  18. 20 CFR 202.14 - Service incidental to railroad transportation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 20 Employees' Benefits 1 2014-04-01 2012-04-01 true Service incidental to railroad transportation. 202.14 Section 202.14 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT § 202.14 Service incidental to railroad transportation....

  19. 20 CFR 202.14 - Service incidental to railroad transportation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 1 2012-04-01 2012-04-01 false Service incidental to railroad transportation. 202.14 Section 202.14 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT § 202.14 Service incidental to railroad transportation....

  20. 20 CFR 202.14 - Service incidental to railroad transportation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 20 Employees' Benefits 1 2013-04-01 2012-04-01 true Service incidental to railroad transportation. 202.14 Section 202.14 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT § 202.14 Service incidental to railroad transportation....

  1. 20 CFR 202.14 - Service incidental to railroad transportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Service incidental to railroad transportation. 202.14 Section 202.14 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT § 202.14 Service incidental to railroad transportation....

  2. 20 CFR 202.14 - Service incidental to railroad transportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Service incidental to railroad transportation. 202.14 Section 202.14 Employees' Benefits RAILROAD RETIREMENT BOARD REGULATIONS UNDER THE RAILROAD RETIREMENT ACT EMPLOYERS UNDER THE ACT § 202.14 Service incidental to railroad transportation....

  3. Incidental Exposure and L3 Learning of Morphosyntax

    ERIC Educational Resources Information Center

    Grey, Sarah; Williams, John N.; Rebuschat, Patrick

    2014-01-01

    Evidence of learning following incidental exposure has been found for aspects of nonnative syntax in adults (Rebuschat & Williams, 2006, 2012; Williams & Kuribara, 2008). However, little research has tested delayed effects of learning under an incidental condition or moved beyond word order. This study investigated learning of third…

  4. The Effectiveness of Incidental Teaching of Grammar to Iranian Students

    ERIC Educational Resources Information Center

    Ghabanchi, Z.

    2010-01-01

    This article reports the results of a study and a pilot study. The "study" considers the effectiveness of incidental teaching of grammar in a learning class of English As A Second Language by Persian speaking students. The "pilot study" examines the students' attitudes toward the incidental learning of grammar from the…

  5. The Effects of Training on Caregiver Implementation of Incidental Teaching

    ERIC Educational Resources Information Center

    Hsieh, Hsing-Hsiu; Wilder, David A.; Abellon, O. Elizabeth

    2011-01-01

    A brief training package consisting of modeling, rehearsal, and feedback was evaluated to train caregivers to use incidental teaching to teach 3 children with autism to request an item or activity. The training package improved correct implementation of the incidental teaching procedure by caregivers. In addition, probes indicated that caregivers…

  6. [Subepithelial tumors of the gastrointestinal tract].

    PubMed

    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.

  7. Laparoscopic Repair of Incidentally Found Spigelian Hernia

    PubMed Central

    Nickloes, Todd; Mancini, Greg; Solla, Julio A.

    2011-01-01

    Background and Objectives: A Spigelian hernia is a rare type of hernia that occurs through a defect in the anterior abdominal wall adjacent to the linea semilunaris. Estimation of its incidence has been reported as 0.12% of all abdominal wall hernias. Traditionally, the method of repair has been an open approach. Herein, we discuss a series of laparoscopic repairs. Methods: Case series and review of the literature. Cases: Three patients are presented. All were evaluated and taken to surgery initially for a different disease process, and all were incidentally found to have a spigelian hernia. These patients underwent laparoscopic repair of their hernias; 2 were repaired intraperitoneally and one was repaired totally extraperitoneally. Two patients initially underwent a mesh repair, while the third had an attempted primary repair. Conclusions: There is evidence that supports the use of laparoscopy for both diagnosis and repair of spigelian hernias. There are also reports of successful repairs both primarily and with mesh. In our experience with the preceding 3 patients, we found that laparoscopic repair of incidentally discovered spigelian hernias is a viable option, and we also found that implantation of mesh, when possible, resulted in satisfactory results and no recurrence. PMID:21902949

  8. 78 FR 56659 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-13

    ...NMFS has received a request from the U.S. Navy (Navy) for authorization to take marine mammals incidental to construction activities as part of a pier maintenance project. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS is requesting public comment on its proposal to issue an incidental harassment authorization (IHA) to the Navy to take, by harassment only, two species of marine......

  9. Gastrointestinal leiomyosarcoma in a pygmy sperm whale (Kogia breviceps).

    PubMed

    Leone, Angelique; Dark, Michael; Kondo, Hirotaka; Rotstein, David S; Kiupel, Matti; Walsh, Michael T; Erlacher-Reid, Claire; Gordon, Nadia; Conway, Julia A

    2013-09-01

    An adult male pygmy sperm whale (Kogia breviceps) was stranded within a tidal pool on Fernandina Beach on the north Florida Atlantic coast (USA) and expired soon after discovery. Necropsy findings included a small intestinal mass markedly expanding the intestinal wall and partially obstructing the lumen. This finding likely led to the malnutrition and ultimately the stranding of this whale. The differential diagnoses for the mass based on gross evaluation included a duodenal adenocarcinoma, leiomyoma/sarcoma, gastrointestinal stroma tumor, and benign/malignant peripheral nerve sheath tumor, previously referred to as neurofibromas or schwannomas. The mass was presumptively diagnosed as a leiomyosarcoma via routine histopathology and confirmed by immunoreactivity for desmin and smooth actin (SMA). KIT, a gene name for CD 117, was negative, excluding a gastrointestinal stromal tumor (GIST). Leiomyosarcomas have been reported within numerous wild and domestic species, although this is the first reported case of any neoplasm in a pygmy sperm whale (K. breviceps).

  10. Osteoporosis and Gastrointestinal Disease

    PubMed Central

    Weinerman, Stuart

    2010-01-01

    Gastrointestinal disease is often overlooked or simply forgotten as a cause of osteoporosis. Yet, the consequences of osteoporotic fractures can be devastating. Although the bulk of the published experience regarding osteoporosis is derived from the postmenopausal population, this review will focus on gastrointestinal disorders implicated in osteoporosis, with an emphasis on inflammatory bowel disease and celiac disease. The unique aspects of gastrointestinal diseases associated with osteoporosis include early onset of disease (and, therefore, prolonged exposure to risk factors for developing osteoporosis, particularly with inflammatory bowel disease and celiac disease), malabsorption, and maldigestion of nutrients necessary for bone health and maintenance (eg, calcium, vitamin D), as well as the impact of glucocorticoids. These factors, when added to smoking, a sedentary lifestyle, hypogonadism, and a family history of osteoporosis, accumulate into an imposing package of predictors for osteoporotic fracture. This paper will review the identification and treatment strategies for patients with gastrointestinal disorders and osteoporosis. PMID:20978554

  11. Vasculitis and gastrointestinal involvement.

    PubMed

    Casella, G; Bronzino, B; Cutrino, L; Montani, N; Somma, A; Baldini, V

    2006-06-01

    The incidence of gastrointestinal involvement is relatively observed in patients with vasculitis processes. Vasculitis can be primary (necrotising or hypersensitivity) or secondary to another primary disease. Gastrointestinal involvement is present in up to 50% of the various forms of systemic vasculitis. Primary or secondary vasculitic process, according to the classification in necrotizing and hypersensitivity vasculitis, are described in this paper. A review of the literature on the the subject is also presented.

  12. Asbestos and Gastrointestinal Cancer

    PubMed Central

    Morgan, Robert W.; Foliart, Donna E.; Wong, Otto

    1985-01-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, we listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, we calculated summary SMRs for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMRs remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. Based on the results after reanalysis, the elevations in summary SMRs for stomach and total gastrointestinal tract cancer are of a magnitude that could result from diagnostic and investigator error. We conclude that more studies are required before stomach and colorectal cancers are documented as asbestos-related diseases. PMID:4036114

  13. Angiography and the gastrointestinal bleeder

    SciTech Connect

    Baum, S.

    1982-05-01

    The role of angiography in the diagnosis and treatment of gastrointestinal hemorrhage is discussed. Three categories of gastrointestinal bleeding are considered: upper gastrointestinal bleeding due to gastroesophageal varices, upper gastrointestinal bleeding of arterial or capillary origin, and lower gastrointestinal bleeding. The advantages and disadvantages of angiography are compared with those of radionuclide scanning and endoscopy or colonoscopy. It is anticipated that, as radionuclide scans are more widely employed, angiography will eventually be performed only in those patients with positive scans.

  14. Incidental Reflector Comparison of Containerized Dry Fire Extinguishing Agents

    SciTech Connect

    Chapman, Bryan Scott; Wysong, Andrew Russell

    2016-12-14

    This document addresses the incidental reflector reactivity worth of containerized fire extinguishing agents authorized for use in PF-4 at Los Alamos National Laboratory (LANL). The intent of the document is to analyze dry fire extinguishing agent that remains in a container and is not actively being used in a fire emergency. The incidental reflector reactivity worth is determined by comparison to various thicknesses of close fitting water reflection which is commonly used to bound incidental reflectors in criticality safety evaluations. The conclusion is that even in unlimited quantities, when containerized the authorized dry fire extinguishing agents are bound by 0.4 inches of close fitting water.

  15. Nodule-Forming Pseudoangiomatous Stromal Hyperplasia of the Breast: Report of Three Cases

    PubMed Central

    Kelten, Canan; Boyaci, Ceren; Leblebici, Cem; Nazli, Mehmet Ali; Aksoy, Şefika; Trabulus, Didem Can; Bozkurt, Erol Rüştü

    2015-01-01

    Pseudoangiomatous stromal hyperplasia (PASH) is a benign proliferative entity of mammary stroma. It is generally found as an incidental finding. It may rarely present as a palpable nodule. Three patients, who were 29, 45, and 58 years of age, were referred to our clinic with nodule and pain in the breast. The physical examinations and ultrasound findings of all three patients were consistent with fibroadenoma. Core biopsies were performed and reported as “benign breast parenchyma including stromal fibrosis.” PASH areas were noted in one case. The excision specimens were observed as solid nodular masses with smooth external surfaces and white in colour. Microscopically, well-demarcated hyalinized stroma, including slit-like pseudovascular spaces lined by bland spindle cells, was observed. Immunohistochemically, these cells showed positive staining for CD34 and negative staining for CD31. Nodule-forming PASH mostly confuses with fibroadenoma with respect to clinical examination and radiological findings. Definite diagnosis requires histopathological verification. Differential diagnosis should be made with low grade angiosarcoma, fibroepithelial tumors, and myofibroblastoma.

  16. Asbestos and gastrointestinal cancer

    SciTech Connect

    Morgan, R.W.; Foliart, D.E.; Wong, O.

    1985-07-01

    Exposure to asbestos is among several factors cited as possible causes of esophageal, gastric and colorectal cancer. More than 45 published studies have presented mortality data on asbestos-exposed workers. For each cohort, the authors listed the observed and expected rates of deaths from types of gastrointestinal cancer based on the latest published follow-up. Summary standardized mortality ratios (SMRs) were then derived. Finally, summary SMRs were calculated for total gastrointestinal tract cancer for three occupational groups: asbestos factory workers, insulators/shipyard workers and asbestos miners. Statistically significant elevations in summary SMRs were found for esophageal, stomach and total gastrointestinal tract cancer in all asbestos-exposed workers. Esophageal cancer summary SMR remained significantly elevated when data were reanalyzed to include only those cohorts with death certificate diagnoses for cause of observed deaths. However, summary SMRs were not statistically significant for stomach and total gastrointestinal tract cancer after reanalysis. Summary SMRs by occupational group showed a significant elevation for total gastrointestinal cancer in insulators/shipyard workers. The elevation was not significant after reanalysis. 59 references, 5 tables.

  17. The Radiological Prevalence of Incidental Kienböck Disease

    PubMed Central

    Golay, Saroj K.; Rust, Philippa; Ring, David

    2016-01-01

    Background: To determine the prevalence of incidental Kienböck disease. Methods: A retrospective analysis of 150,912 radiological reports or images obtained over a five year period was performed of 76,174 patients who underwent a radiograph or computed tomography scan which included the wrist, in Edinburgh and Lothian, UK. Results: There were 5 cases of incidental Kienböck disease and 13 cases of symptomatic Kienböck disease. There were no significant differences in age, sex, ethnicity, comorbidities, smoking status, excess alcohol use or Lichtman stage between the incidental and symptomatic Kienböck groups. Conclusion: The radiological prevalence of incidental Kienböck disease was 0.0066% or 7 in 100,000 patients. PMID:27517065

  18. Gastrointestinal Stent Update

    PubMed Central

    2010-01-01

    The use of self-expanding metallic stents in the upper gastrointestinal tract, placed under radiologic imaging or endoscopic guidance, is the current treatment of choice for the palliation of malignant gastrointestinal outlet obstructions. Advances in metallic stent design and delivery systems have progressed to the stage where this treatment is now considered a minimally invasive therapy. Metallic stent placement will broaden further into the field of nonsurgical therapy for the gastrointestinal tract. To date, metallic stents placed in the esophagus, gastric outlet, colorectum, and bile ducts are not intended to be curative, but rather to provide a palliative treatment for obstructions. The evolution of metallic stent technology will render such procedures not only palliative but also therapeutic, by enabling local drug delivery, and the use of biodegradable materials will reduce procedure-related complications. PMID:21103290

  19. Brunner's Gland Adenoma – A Rare Cause of Gastrointestinal Bleeding: Case Report and Systematic Review

    PubMed Central

    Sorleto, Michele; Timmer-Stranghöner, Annette; Wuttig, Helge; Engelhard, Oliver; Gartung, Carsten

    2017-01-01

    Brunner's gland adenoma is an extremely rare benign small bowel neoplasm, often discovered incidentally during upper gastrointestinal endoscopy or radiological diagnostics. In few cases, it tends to cause gastrointestinal hemorrhage or intestinal obstruction. We report here our experience with a 47-year-old woman with a Brunner's gland adenoma of more than 6 cm in size, located in the first part of the duodenum and causing gastrointestinal bleeding. Initially, we performed a partial endoscopic resection using endoloop and snare alternatively to prevent severe bleeding. A rest endoscopic polypectomy with the submucosal dissection technique was planned. However, on request of the patient, an elective surgical duodenotomy with submucosal resection of the remaining small duodenal tumor was performed. To better define the patient's characteristics and treatment options of such lesions, we performed a systematic review of the available literature in PubMed. Recently, an endoscopic removal is being increasingly practiced and is considered as a safe treatment modality of such lesions. PMID:28203131

  20. Is incidental gestational thrombocytopaenia really always safe for the neonate?

    PubMed

    Pourrat, O; Valère, G; Pierre, F

    2014-08-01

    It is widely admitted that neonates' platelet counts (PCs) are always normal in babies born to mothers with incidental gestational thrombocytopaenia. However, results of PC determinations at delivery have led us to wonder whether incidental gestational thrombocytopaenia is actually safe for the neonate under all circumstances, and to recommend that for every baby born to a mother with a pregnancy-associated thrombocytopaenia, even in the case of confirmed IGT, platelet counts on umbilical cord blood be closely monitored.

  1. Critical social theory approach to disclosure of genomic incidental findings.

    PubMed

    Bevan, Jeffrey L; Senn-Reeves, Julia N; Inventor, Ben R; Greiner, Shawna M; Mayer, Karen M; Rivard, Mary T; Hamilton, Rebekah J

    2012-11-01

    Technology has expanded genomic research and the complexity of extracted gene-related information. Health-related genomic incidental findings pose new dilemmas for nurse researchers regarding the ethical application of disclosure to participants. Consequently, informed consent specific to incidental findings is recommended. Critical Social Theory is used as a guide in recognition of the changing meaning of informed consent and to serve as a framework to inform nursing of the ethical application of disclosure consent in genomic nursing research practices.

  2. 77 FR 39485 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-03

    .... Under the MMPA, the term ``take'' means to harass, hunt, capture, or kill or to attempt to harass, hunt, capture, or kill any marine mammal. Authorization for incidental taking, in the form of annual LOAs,...

  3. 77 FR 45341 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-31

    ... issued. Under the MMPA, the term ``take'' means to harass, hunt, capture, or kill or to attempt to harass, hunt, capture, or kill any marine mammal. Authorization for incidental taking, in the form of...

  4. 78 FR 13865 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-01

    ... issued. Under the MMPA, the term ``take'' means to harass, hunt, capture, or kill or to attempt to harass, hunt, capture, or kill any marine mammal. Authorization for incidental taking, in the form of...

  5. 77 FR 10481 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-22

    ... regulations are issued. Under the MMPA, the term ``take'' means to harass, hunt, capture, or kill or to attempt to harass, hunt, capture, or kill any marine mammal. Authorization for incidental taking, in...

  6. 78 FR 22517 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-16

    ... the MMPA, the term ``take'' means to harass, hunt, capture, or kill or to attempt to harass, hunt, capture, or kill any marine mammal. Authorization for incidental taking, in the form of annual LOAs,...

  7. 78 FR 30273 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ...NMFS has received an application from the U.S. Navy (Navy) for an Incidental Harassment Authorization (IHA) to take marine mammals, by harassment, incidental to construction activities as part of a barge mooring project. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS is requesting comments on its proposal to issue an IHA to the Navy to take, by Level B Harassment only, four species......

  8. Treatment Option Overview (Gastrointestinal Carcinoid Tumors)

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  9. Treatment Options for Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  10. General Information about Gastrointestinal Carcinoid Tumors

    MedlinePlus

    ... carcinoid tumor is cancer that forms in the lining of the gastrointestinal tract. The gastrointestinal (GI) tract ... Rectum . Enlarge Gastrointestinal carcinoid tumors form in the lining of the gastrointestinal tract, most often in the ...

  11. Diagnostic procedures for submucosal tumors in the gastrointestinal tract

    PubMed Central

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

    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 fluorodeoxyglucose-labeled positron emission tomography (FDG-PET) are recommended as supplementary tools. PMID:17659668

  12. Apollo gastrointestinal analysis

    NASA Technical Reports Server (NTRS)

    Nichols, B. L.; Huang, C. T. L.

    1975-01-01

    Fecal bile acid patterns for the Apollo 17 flight were studied to determine the cause of diarrhea on the mission. The fecal sterol analysis gave no indication of an infectious diarrhea, or specific, or nonspecific etiology occurring during the entire flight. It is assumed that the gastrointestinal problems encountered are the consequences of altered physiology, perhaps secondary to physical or emotional stress of flight.

  13. Pediatric functional gastrointestinal disorders

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Functional gastrointestinal disorders continue to be a prevalent set of conditions faced by the healthcare team and have a significant emotional and economic impact. In this review, the authors highlight some of the common functional disorders seen in pediatric patients (functional dyspepsia, irrita...

  14. Gastrointestinal endoscopy in pregnancy.

    PubMed

    Savas, Nurten

    2014-11-07

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure.

  15. Gastrointestinal endoscopy in pregnancy

    PubMed Central

    Savas, Nurten

    2014-01-01

    Gastrointestinal endoscopy has a major diagnostic and therapeutic role in most gastrointestinal disorders; however, limited information is available about clinical efficacy and safety in pregnant patients. The major risks of endoscopy during pregnancy include potential harm to the fetus because of hypoxia, premature labor, trauma and teratogenesis. In some cases, endoscopic procedures may be postponed until after delivery. When emergency or urgent indications are present, endoscopic procedures may be considered with some precautions. United States Food and Drug Administration category B drugs may be used in low doses. Endoscopic procedures during pregnancy may include upper gastrointestinal endoscopy, percutaneous endoscopic gastrostomy, sigmoidoscopy, colonoscopy, enteroscopy of the small bowel or video capsule endoscopy, endoscopic retrograde cholangiopancreatography and endoscopic ultrasonography. All gastrointestinal endoscopic procedures in pregnant patients should be performed in hospitals by expert endoscopists and an obstetrician should be informed about all endoscopic procedures. The endoscopy and flexible sigmoidoscopy may be safe for the fetus and pregnant patient, and may be performed during pregnancy when strong indications are present. Colonoscopy for pregnant patients may be considered for strong indications during the second trimester. Although therapeutic endoscopic retrograde cholangiopancreatography may be considered during pregnancy, this procedure should be performed only for strong indications and attempts should be made to minimize radiation exposure. PMID:25386072

  16. Gastrointestinal Bleeding in Athletes.

    ERIC Educational Resources Information Center

    Eichner, Edward R.

    1989-01-01

    Describes the scope and importance of gastrointestinal bleeding in runners and other athletes, discussing causes, sites, and implications of exercise-related bleeding. Practical tips to mitigate the problem, potentially more troublesome in women because of lower iron stores, are presented (e.g., gradual conditioning and avoidance of prerace…

  17. Hepatic immune regulation by stromal cells.

    PubMed

    Schildberg, Frank A; Sharpe, Arlene H; Turley, Shannon J

    2015-02-01

    A metabolic organ, the liver also has a central role in tolerance induction. Stromal cells lining the hepatic sinusoids, such as liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs), are the first liver cells to encounter gut-derived and systemic antigens, thereby shaping local and systemic tolerance. Recent studies have demonstrated that stromal cells can modulate immune responses by antigen-dependent and independent mechanisms. Stromal cells interfere with the function of other antigen-presenting cells (APCs) and induce non-responsive T cells as well as regulatory T cells and myeloid-derived suppressor cells (MDSCs). The immunosuppressive microenvironment thus created provides a means to protect the liver from tissue damage. Such tolerized surroundings, however, can be exploited by certain pathogens, promoting persistent liver infections.

  18. Incidental sounds of locomotion in animal cognition.

    PubMed

    Larsson, Matz

    2012-01-01

    The highly synchronized formations that characterize schooling in fish and the flight of certain bird groups have frequently been explained as reducing energy expenditure. I present an alternative, or complimentary, hypothesis that synchronization of group movements may improve hearing perception. Although incidental sounds produced as a by-product of locomotion (ISOL) will be an almost constant presence to most animals, the impact on perception and cognition has been little discussed. A consequence of ISOL may be masking of critical sound signals in the surroundings. Birds in flight may generate significant noise; some produce wing beats that are readily heard on the ground at some distance from the source. Synchronization of group movements might reduce auditory masking through periods of relative silence and facilitate auditory grouping processes. Respiratory locomotor coupling and intermittent flight may be other means of reducing masking and improving hearing perception. A distinct border between ISOL and communicative signals is difficult to delineate. ISOL seems to be used by schooling fish as an aid to staying in formation and avoiding collisions. Bird and bat flocks may use ISOL in an analogous way. ISOL and interaction with animal perception, cognition, and synchronized behavior provide an interesting area for future study.

  19. Clinical approach to incidental pancreatic cysts

    PubMed Central

    Chiang, Austin L; Lee, Linda S

    2016-01-01

    The approach to incidentally noted pancreatic cysts is constantly evolving. While surgical resection is indicated for malignant or higher risk cysts, correctly identifying these highest risk pancreatic cystic lesions remains difficult. Using parameters including cyst size, presence of solid components, and pancreatic duct involvement, the 2012 International Association of Pancreatology (IAP) and the 2015 American Gastroenterological Association (AGA) guidelines have sought to identify the higher risk patients who would benefit from further evaluation using endoscopic ultrasound (EUS). Not only can EUS help further assess the presence of solid component and nodules, but also fine needle aspiration of cyst fluid aids in diagnosis by obtaining cellular, molecular, and genetic data. The impact of new endoscopic innovations with novel methods of direct visualization including confocal endomicroscopy require further validation. This review also highlights the differences between the 2012 IAP and 2015 AGA guidelines, which include the thresholds for sending patients for EUS and surgery and methods, interval, and duration of surveillance for unresected cysts. PMID:26811661

  20. Incidental Findings on Knee Radiographs in Children and Adolescents

    PubMed Central

    Seo, Sang Gyo; Chung, Chin Youb; Lee, Kyoung Min; Lee, Seung Yeol; Choi, Young; Kim, Tae Gyun; Baek, Jeong Kook; Kwon, Soon-Sun; Kwon, Dae Gyu; Choi, In Ho; Cho, Tae-Joon; Yoo, Won Joon; Park, Moon Seok

    2014-01-01

    Background Despite the wide use of knee radiography in children and adolescent patients visiting the outpatient clinic, there has been no analysis about the prevalence and type of incidental findings yet. This study was performed to investigate the incidental findings on knee radiographs in children and adolescents according to age. Methods A total of 1,562 consecutive patients younger than 18 years of age were included. They who visited Seoul National University Bundang Hospital's outpatient clinic with a chief complaint of knee pain or malalignment between 2010 and 2011. We reviewed the knee radiographs and analyzed the prevalence and type of incidental findings, such as metaphyseal lucent area, epiphyseal cortical irregularity, osteochondroma and Harris growth arrest line. Results The mean age of the patients was 10.2 years (range, 1 month to 18 years). We identified 355 incidental findings in 335 patients (21.4%) and 98 abnormal findings (6.3%). The most common incidental finding was metaphyseal lucent area (131, 8.4%), followed by epiphyseal cortical irregularity (105, 6.7%), Harris growth arrest line (75, 4.8%), and osteochondroma (44, 2.8%). An epiphyseal cortical irregularity tended to have a higher prevalence at younger age (p < 0.001) and the prevalences of metaphyseal lucent area and Harris growth arrest line were also higher at a younger age (p = 0.001 and p < 0.001, respectively). However, the osteochondroma tended to have a higher prevalence at an older age (p = 0.004). Conclusions This study describes the incidental findings on knee radiographs in children and adolescents and provides effective information from a viewpoint of an orthopedic doctor. The authors recommend considering those incidental findings if unfamiliar findings appear on a knee radiograph in the pediatric outpatient clinic. PMID:25177456

  1. Parkinson disease and incidental Lewy body disease

    PubMed Central

    Geraci-Erck, Maria; Rabin, Marcie L.; Adler, Charles H.; Serrano, Geidy; Beach, Thomas G.; Kurlan, Roger

    2015-01-01

    Objective: To quantify the loss of pigmented neurons in the substantia nigra (SN) of autopsy-confirmed Parkinson disease (PD) and incidental Lewy body disease (ILBD) vs age-matched controls (C). Methods: Unbiased stereology methods were used to rigorously count number and measure volumes of nigral pigmented neurons in PD, ILBD, and C brains. The obtained stereologic results were correlated with Lewy body (LB), amyloid plaque (AP), neurofibrillary tangle (NFT), and vascular pathology loads assessed in nigral and extranigral regions of each PD, ILBD, and C brain. The stereologic measurements were also correlated to predeath motor and cognitive scores as available for each participant. Results: A marked nigral neuronal loss (NNL) in PD (−82%) and ILBD (−40%) compared to C (p < 0.0001) was found. While there was significant correlation between NNL and LB in some cortical areas of PD (i.e., olfactory bulb), there were no correlations between NNL and LB, AP, or NFT loads or cerebral infarct volumes in any other examined regions for PD and ILBD brains. Conclusions: Using unbiased stereology methods, we show that there is a significant loss and absence of hypertrophic changes in nigral pigmented neurons of ILBD in comparison to C brains. Intriguingly, no significant correlations were found between NNL and LB loads in the SN of both PD and ILBD brains. These autopsy-verified stereologically based findings are novel and support ILBD as a pathologic condition. These results suggest possible new and alternative pathophysiologic hypotheses on the actual relationship between NNL and LB pathology. PMID:26468408

  2. A Structured approach to incidental take decision making

    USGS Publications Warehouse

    McGowan, Conor P.

    2013-01-01

    Decision making related to incidental take of endangered species under U.S. law lends itself well to a structured decision making approach. Incidental take is the permitted killing, harming, or harassing of a protected species under the law as long as that harm is incidental to an otherwise lawful activity and does not “reduce appreciably the probability of survival and recovery in the wild.” There has been inconsistency in the process used for determining incidental take allowances across species and across time for the same species, and structured decision making has been proposed to improve decision making. I use an example decision analysis to demonstrate the process and its applicability to incidental take decisions, even under significant demographic uncertainty and multiple, competing objectives. I define the example problem, present an objectives statement and a value function, use a simulation model to assess the consequences of a set of management actions, and evaluate the tradeoffs among the different actions. The approach results in transparent and repeatable decisions.

  3. Gastrointestinal parasite infestation.

    PubMed

    Abd El Bagi, Mohamed E; Sammak, Bassam M; Mohamed, Abdulrahman E; Al Karawi, Mohamed A; Al Shahed, Mona; Al Thagafi, Mohamed A

    2004-03-01

    Twenty-five percent of the world's population could be suffering parasitic infestation. Highest prevalence is in underdeveloped agricultural and rural areas in the tropical and subtropical regions. In some areas incidence may reach 90% of the population. In contrast, some major economic projects intended to promote local development have, paradoxically, caused parasitic proliferation, e.g. bilharziasis in Egypt and Sudan and Chagas disease in Brazil. The commonest cosmopolitan gastrointestinal parasite is Entamoeba histolytica. Some intestinal parasite are endemic in temperate climates, e.g. Entrobius vermicularis. The AIDS epidemic has increased the prevalence and severity of parasitic disease, particularly Strongyloides stercolaris. Tropical parasites are seen in Western people who travel to tropical countries. Radiology has acquired a major role in diagnosis and management of gastrointestinal parasite infestations and their complications.

  4. [Microbiota and gastrointestinal diseases].

    PubMed

    Polanco Allué, I

    2015-12-01

    The bacterial colonisation is established immediately after birth, through direct contact with maternal microbiota, and may be influenced during lactation. There is emerging evidence indicating that quantitative and qualitative changes on gut microbiota contribute to alterations in the mucosal activation of the immune system, leading to intra- or extra-intestinal diseases. A balance between pathogenic and beneficial microbiota throughout childhood and adolescence is important to gastrointestinal health, including protection against pathogens, inhibition of pathogens, nutrient processing (synthesis of vitamin K), stimulation of angiogenesis, and regulation of host fat storage. Probiotics can promote an intentional modulation of intestinal microbiota favouring the health of the host. A review is presented on the modulation of intestinal microbiota on prevention, and adjuvant treatment of some paediatric gastrointestinal diseases.

  5. Origin of hemopoietic stromal progenitor cells in chimeras

    SciTech Connect

    Chertkov, J.L.; Drize, N.J.; Gurevitch, O.A.; Samoylova, R.S.

    1985-12-01

    Intravenously injected bone marrow cells do not participate in the regeneration of hemopoietic stromal progenitors in irradiated mice, nor in the curetted parts of the recipient's marrow. The hemopoietic stromal progenitors in allogeneic chimeras are of recipient origin. The adherent cell layer (ACL) of long-term cultures of allogeneic chimera bone marrow contains only recipient hemopoietic stromal progenitors. However, in ectopic hemopoietic foci produced by marrow implantation under the renal capsule and repopulated by the recipient hemopoietic cells after irradiation and reconstitution by syngeneic hemopoietic cells, the stromal progenitors were of implant donor origin, as were stromal progenitors of the ACL in long-term cultures of hemopoietic cells from ectopic foci. Our results confirm that the stromal and hemopoietic progenitors differ in origin and that hemopoietic stromal progenitors are not transplantable by the intravenous route in mice.

  6. Sonic hedgehog signals to multiple prostate stromal stem cells that replenish distinct stromal subtypes during regeneration

    PubMed Central

    Peng, Yu-Ching; Levine, Charles M.; Zahid, Sarwar; Wilson, E. Lynette; Joyner, Alexandra L.

    2013-01-01

    The adult mouse prostate has a seemingly endless capacity for regeneration, and sonic hedgehog (SHH) signaling has been implicated in this stem cell-driven process. However, it is not clear whether SHH acts on the epithelium or stromal cells that secrete factors required for epithelial expansion. Because little is known about stromal stem cells compared with their epithelial counterparts, we used in vivo mouse genetics tools to characterize four prostate stromal subtypes and their stem cells. Using knockin reporter alleles, we uncovered that SHH signals from prostate basal epithelial cells to adjacent stromal cells. Furthermore, the SHH target gene Gli1 is preferentially expressed in subepithelial fibroblast-like cells, one of four prostate stromal subtypes and the subtype closest to the epithelial source of SHH. Using Genetic Inducible Fate Mapping to mark adult Gli1- or Smooth muscle actin-expressing cells and follow their fate during regeneration, we uncovered that Gli1-expressing cells exhibit long-term self-renewal capacity during multiple rounds of androgen-mediated regeneration after castration-induced involution, and depleted smooth muscle cells are mainly replenished by preexisting smooth muscle cells. Based on our Genetic Inducible Fate Mapping studies, we propose a model where SHH signals to multiple stromal stem cells, which are largely unipotent in vivo. PMID:24218555

  7. Gastrointestinal food allergies.

    PubMed

    Heine, Ralf G

    2015-01-01

    Gastrointestinal food allergies present during early childhood with a diverse range of symptoms. Cow's milk, soy and wheat are the three most common gastrointestinal food allergens. Several clinical syndromes have been described, including food protein-induced enteropathy, proctocolitis and enterocolitis. In contrast with immediate, IgE-mediated food allergies, the onset of gastrointestinal symptoms is delayed for at least 1-2 hours after ingestion in non-IgE-mediated allergic disorders. The pathophysiology of these non-IgE-mediated allergic disorders is poorly understood, and useful in vitro markers are lacking. The results of the skin prick test or measurement of the food-specific serum IgE level is generally negative, although low-positive results may occur. Diagnosis therefore relies on the recognition of a particular clinical phenotype as well as the demonstration of clear clinical improvement after food allergen elimination and the re-emergence of symptoms upon challenge. There is a significant clinical overlap between non-IgE-mediated food allergy and several common paediatric gastroenterological conditions, which may lead to diagnostic confusion. The treatment of gastrointestinal food allergies requires the strict elimination of offending food allergens until tolerance has developed. In breast-fed infants, a maternal elimination diet is often sufficient to control symptoms. In formula-fed infants, treatment usually involves the use an extensively hydrolysed or amino acid-based formula. Apart from the use of hypoallergenic formulae, the solid diets of these children also need to be kept free of specific food allergens, as clinically indicated. The nutritional progress of infants and young children should be carefully monitored, and they should undergo ongoing, regular food protein elimination reassessments by cautious food challenges to monitor for possible tolerance development.

  8. Management of gastrointestinal hemorrhage.

    PubMed Central

    Hilsden, R. J.; Shaffer, E. A.

    1995-01-01

    Acute gastrointestinal hemorrhage is a common problem that requires prompt recognition and management to prevent serious morbidity and mortality. Management goals are stabilization of the patient with vigorous fluid resuscitation followed by investigation and definitive treatment of the bleeding source. Endoscopy is often the initial diagnostic test and allows therapeutic measures to be performed at the same time. Images Figure 1 Figure 2 PMID:8563510

  9. Smad4 signalling in T cells is required for suppression of gastrointestinal cancer.

    PubMed

    Kim, Byung-Gyu; Li, Cuiling; Qiao, Wenhui; Mamura, Mizuko; Kasprzak, Barbara; Kasperczak, Barbara; Anver, Miriam; Wolfraim, Lawrence; Hong, Suntaek; Mushinski, Elizabeth; Potter, Michael; Kim, Seong-Jin; Fu, Xin-Yuan; Deng, Chuxia; Letterio, John J

    2006-06-22

    SMAD4 (MAD homologue 4 (Drosophila)), also known as DPC4 (deleted in pancreatic cancer), is a tumour suppressor gene that encodes a central mediator of transforming growth factor-beta signalling. Germline mutations in SMAD4 are found in over 50% of patients with familial juvenile polyposis, an autosomal dominant disorder characterized by predisposition to hamartomatous polyps and gastrointestinal cancer. Dense inflammatory cell infiltrates underlay grossly normal appearing, non-polypoid colonic and gastric mucosa of patients with familial juvenile polyposis. This prominent stromal component suggests that loss of SMAD4-dependent signalling in cells within the epithelial microenvironment has an important role in the evolution of intestinal tumorigenesis in this syndrome. Here we show that selective loss of Smad4-dependent signalling in T cells leads to spontaneous epithelial cancers throughout the gastrointestinal tract in mice, whereas epithelial-specific deletion of the Smad4 gene does not. Tumours arising within the colon, rectum, duodenum, stomach and oral cavity are stroma-rich with dense plasma cell infiltrates. Smad4(-/-) T cells produce abundant T(H)2-type cytokines including interleukin (IL)-5, IL-6 and IL-13, known mediators of plasma cell and stromal expansion. The results support the concept that cancer, as an outcome, reflects the loss of the normal communication between the cellular constituents of a given organ, and indicate that Smad4-deficient T cells ultimately send the wrong message to their stromal and epithelial neighbours.

  10. 76 FR 11205 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Construction and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-01

    ... Marine Mammals Incidental to Construction and Operation of a Liquefied Natural Gas Deepwater Port in the... marine mammal species incidental to construction and operation of a liquefied natural gas (LNG)...

  11. 77 FR 23547 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Columbia River Crossing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ... Part 217 Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Columbia River... Incidental to Columbia River Crossing Project, Washington and Oregon AGENCY: National Marine Fisheries... Transit Authority (FTA) and Federal Highway Administration (FHWA), on behalf of the Columbia...

  12. Incidental findings on brain and spine imaging in children.

    PubMed

    Maher, Cormac O; Piatt, Joseph H

    2015-04-01

    In recent years, the utilization of diagnostic imaging of the brain and spine in children has increased dramatically, leading to a corresponding increase in the detection of incidental findings of the central nervous system. Patients with unexpected findings on imaging are often referred for subspecialty evaluation. Even with rational use of diagnostic imaging and subspecialty consultation, the diagnostic process will always generate unexpected findings that must be explained and managed. Familiarity with the most common findings that are discovered incidentally on diagnostic imaging of the brain and spine will assist the pediatrician in providing counseling to families and in making recommendations in conjunction with a neurosurgeon, when needed, regarding additional treatments and prognosis.

  13. A Review of Effect of Different Tasks on Incidental Vocabulary Acquisition

    ERIC Educational Resources Information Center

    Liu, Chen L.

    2015-01-01

    Studies of incidental vocabulary acquisition in second language learning have got more and more attention both at home and abroad. By first introducing the definition and theoretical foundations of incidental vocabulary acquisition, this paper reviews empirical studies of effect of different tasks on incidental vocabulary acquisition and points…

  14. 78 FR 54437 - Interagency Cooperation-Endangered Species Act of 1973, as Amended; Incidental Take Statements

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-04

    ... address the use of surrogates to express the amount or extent of anticipated incidental take, and... Services to consider clarifying two aspects of incidental take statements: (1) The use of surrogates such... anticipated incidental take, including circumstances where project impacts to the surrogate are...

  15. 50 CFR 18.24 - Taking incidental to commercial fishing operations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MARINE MAMMALS General Exceptions § 18.24 Taking incidental to commercial fishing operations. Persons may take marine mammals incidental to commercial fishing operations... regulations issued by the Secretary of Commerce. However, any marine mammal taken as an incidental catch...

  16. 77 FR 23463 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Space Vehicle and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-19

    ... Marine Mammals Incidental to Space Vehicle and Missile Launch Operations at Kodiak Launch Complex, Alaska... two species of pinnipeds incidental to space vehicle and missile launch operations at the Kodiak... vitulina) (adults by harassment and pups by injury or mortality), incidental to space vehicle and...

  17. Plague Masquerading as Gastrointestinal Illness

    PubMed Central

    Hull, Harry F.; Montes, Jean M.; Mann, Jonathan M.

    1986-01-01

    In clinical descriptions of human plague, fever and tender lymphadenitis are emphasized and gastrointestinal manifestations are rarely mentioned. A review of 71 human plague cases showed that gastrointestinal symptoms occurred commonly (57%). Vomiting (39%) was the most frequent symptom, with nausea (34%), diarrhea (28%) and abdominal pain (17%) occurring less often. Physicians treating patients who reside in or have recently visited plague-endemic areas should include plague in the differential diagnosis in the presence of gastrointestinal symptoms and fever. PMID:3788132

  18. Gastrointestinal Manifestations of Cystic Fibrosis

    PubMed Central

    2016-01-01

    Cystic fibrosis has historically been considered a pulmonary disease, but with the increasing life expectancy of these patients, gastrointestinal manifestations are becoming more important. Furthermore, nutritional status is closely linked to pulmonary function and, thus, overall mortality. This article discusses gastrointestinal manifestations (which involve nutritional, pancreatic, hepatobiliary, and, in particular, gastrointestinal tract issues) of cystic fibrosis as well as management of the disease. In addition, the article discusses studies that have been critical to our understanding of gastrointestinal manifestations of cystic fibrosis. PMID:27330503

  19. Management of gastrointestinal haemorrhage

    PubMed Central

    Ghosh, S; Watts, D; Kinnear, M

    2002-01-01

    A variety of endoscopic haemostatic techniques have enabled major advances in the management of not only bleeding peptic ulcers and bleeding varices, but also in a variety of bleeding lesions in the small intestine and in the colon. Indeed, the development and widespread implementation of endoscopic haemostasis has been one of the most important developments in clinical gastroenterology in the past two decades. An increasingly ageing cohort of patients with multiple co-morbidity are being treated and therefore improving the outcome of gastrointestinal bleeding continues to pose major challenges. PMID:11796865

  20. Mixed epithelial and stromal tumor of the kidney.

    PubMed

    Adsay, N V; Eble, J N; Srigley, J R; Jones, E C; Grignon, D J

    2000-07-01

    We describe the clinicopathologic features of 12 patients with a distinctive tumor of the kidney characterized by a mixture of epithelial and stromal elements that form solid and cystic growth patterns. Similar tumors were reported previously in the literature under various names, including adult mesoblastic nephroma. All but one of the patients were women. The only man had a long history of treatment with lupron and diethylstilbesterol. Seven of the women had histories of long-term oral estrogen use of whom six had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy several years prior, and the seventh patient had been using oral contraceptives for many years. Another woman had this operation but did not receive any hormone therapy. Ages ranged from 31 to 71 years (mean, 56 yrs). Six patients presented with symptoms, including pain and infections attributable to mass effect, and in six the tumor was detected incidentally. Grossly, the tumors were well-circumscribed (mean size, 6 cm; range, 3-12 cm) and consisted of solid and cystic components, most often in equal proportions but in variable distribution. Microscopically, the spindle cell component ranged in appearance from scar-like fibrous tissue to leiomyoma-like interlacing fascicles; usually there was a mixture of both. More cellular foci reminiscent of ovarian stroma or solitary fibrous tumor were also present. No blastema was present. Epithelial elements (composed of clusters of tubules with variable lining) were scattered amidst the spindle cells, and focally transformed into large cysts lined by cells with abundant pink cytoplasm and a hobnail appearance. Immature epithelial elements typical of Wilms' tumor were not present. Muscle markers (desmin and smooth muscle actin) were positive diffusely and strongly in the spindle cells of all tumors, whereas HMB-45 and CD34 were absent. Estrogen receptors were detected in the nuclei of spindle cells in seven tumors and progesterone

  1. Crosstalk between stromal cells and cancer cells in pancreatic cancer: New insights into stromal biology.

    PubMed

    Zhan, Han-Xiang; Zhou, Bin; Cheng, Yu-Gang; Xu, Jian-Wei; Wang, Lei; Zhang, Guang-Yong; Hu, San-Yuan

    2017-04-28

    Pancreatic cancer (PC) remains one of the most lethal malignancies worldwide. Increasing evidence has confirmed the pivotal role of stromal components in the regulation of carcinogenesis, invasion, metastasis, and therapeutic resistance in PC. Interaction between neoplastic cells and stromal cells builds a specific microenvironment, which further modulates the malignant properties of cancer cells. Instead of being a "passive bystander", stroma may play a role as a "partner in crime" in PC. However, the role of stromal components in PC is complex and requires further investigation. In this article, we review recent advances regarding the regulatory roles and mechanisms of stroma biology, especially the cellular components such as pancreatic stellate cells, macrophages, neutrophils, adipocytes, epithelial cells, pericytes, mast cells, and lymphocytes, in PC. Crosstalk between stromal cells and cancer cells is thoroughly investigated. We also review the prognostic value and molecular therapeutic targets of stroma in PC. This review may help us further understand the molecular mechanisms of stromal biology and its role in PC development and therapeutic resistance. Moreover, targeting stroma components may provide new therapeutic strategies for this stubborn disease.

  2. BRAF exon 15 mutations in pediatric renal stromal tumors: prevalence in metanephric stromal tumors.

    PubMed

    Marsden, Lily; Jennings, Lawrence J; Gadd, Samantha; Yu, Min; Perlman, Elizabeth J; Cajaiba, Mariana M

    2017-02-01

    Metanephric stromal tumors (MSTs) are rare renal stromal tumors that predominantly affect children. They belong to the metanephric family of tumors, along with metanephric adenofibroma and metanephric adenoma. The previous documentation of BRAF exon 15 mutations in 88% of metanephric adenomas and in isolated cases of metanephric adenofibroma prompted us to investigate the prevalence of these mutations in MSTs and in other pediatric renal stromal tumors. In this study, 17 MSTs, 22 congenital mesoblastic nephromas, and 6 ossifying renal tumors of infancy were selected for BRAF exon 15 testing. Tumor genomic DNA was extracted from formalin-fixed paraffin-embedded tissue, followed by polymerase chain reaction amplification and Sanger dideoxy sequencing with primers flanking the BRAF exon 15 gene. BRAF exon 15 mutations were found in 11 (65%) of the 17 cases of MST, all corresponding to a thymidine-to-adenine substitution at codon 600 (BRAF V600E). All other renal stromal tumors tested were negative for BRAF exon 15 mutations. In conclusion, BRAF V600E mutations are encountered in most MSTs, supporting a link with other metanephric tumors and suggesting a clonal event possibly affecting primordial renal cells. In addition, BRAF V600E mutations have been associated with oncogene-induced senescence in other benign tumors, providing clues to the pathogenesis of metanephric neoplasms in keeping with their overall benign behavior. Our results also suggest a potential diagnostic use for BRAF exon 15 mutations in differentiating MSTs from other pediatric renal stromal tumors, particularly in limited samples.

  3. Mesenchymal stromal cells for treatment of arthritis.

    PubMed

    Swart, J F; Wulffraat, N M

    2014-08-01

    Patients with refractory inflammatory arthritis can still respond favourable to autologous haematopoietic stem cell transplantation. However, this treatment has a high morbidity and even 5% mortality. Mesenchymal stromal cells (MSC), a subset of the non-haematopoietic stromal cells obtained from bone marrow, were found to have a strong immunosuppressive effect. MSC treatment is explored in many diseases like diabetes, SLE, MS and RA. This review covers all relevant literature regarding MSC treatment of inflammatory arthritis (RA and JIA). This review contains data of in vitro studies, animal studies and clinical studies. The following subjects will be discussed in detail: properties of MSC, presence of MSC in the joint, intra-articular versus intravenous route, autologous versus allogeneic, ideal source of MSC, distribution, transdifferentiation, engraftment, rejection, efficacy and toxicology. After reading this review the reader will be totally updated in this quickly evolving field of MSC therapy.

  4. 78 FR 35363 - Marine Mammals; Incidental Take During Specified Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-12

    ...In accordance with the Marine Mammal Protection Act of 1972, as amended (MMPA), and its implementing regulations, we, the U.S. Fish and Wildlife Service (Service or we), are finalizing regulations that authorize the nonlethal, incidental, unintentional take of small numbers of Pacific walruses (Odobenus rosmarus divergens) and polar bears (Ursus maritimus) during oil and gas Industry......

  5. Representations of an Incidental Learning Framework to Support Mobile Learning

    ERIC Educational Resources Information Center

    Scanlon, Eileen; Gaved, Mark; Jones, Ann; Kukulska-Hulme, Agnes; Paletta, Lucas; Dunwell, Ian

    2014-01-01

    This paper discusses how the particular features of mobile learning can be harnessed to provide new informal learning opportunities in relation to context aware and location based learning. The MASELTOV project is developing representations of an incidental learning framework to enable software developers and researchers to both design and analyse…

  6. 21 CFR 178.3570 - Lubricants with incidental food contact.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Lubricants with incidental food contact. 178.3570 Section 178.3570 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) INDIRECT FOOD ADDITIVES: ADJUVANTS, PRODUCTION AIDS, AND SANITIZERS Certain Adjuvants...

  7. Playground Exploration: An Opportunity for Incidental Learning of Mechanical Principles

    ERIC Educational Resources Information Center

    Lyons, Brian

    2005-01-01

    Play involves unstructured activity that is freely entered into and intrinsically rewarding. When children engage in play there is little intentional learning. There are no lesson plans. There are no daily objectives or specific learning outcomes. Incidental learning can cause relatively permanent changes in the way one thinks; accidental learning…

  8. Incidental Vocabulary Acquisition from Reading an Authentic Text

    ERIC Educational Resources Information Center

    Daskalovska, Nina

    2014-01-01

    A number of studies have demonstrated that second/foreign language learners can acquire vocabulary from reading. This study was designed to examine whether advanced EFL learners can acquire vocabulary incidentally from reading an authentic text. Eighteen first year English major students read and listened to the first eight chapters of Pride and…

  9. An Analysis of Adult Interaction Styles and Children's Incidental Imitation.

    ERIC Educational Resources Information Center

    Sharkey, Robert W.; Morris, Edward K.

    This paper describes two experiments designed to determine whether traditional effects of adult nurturance on children's incidental imitation could be obtained using a within-subject design and a functional (rather than operational) definition of nurturance. Four preschool children served as subjects, with four others serving as cross-sex…

  10. Gallium accumulation in the stomach. A frequent incidental finding

    SciTech Connect

    MacMahon, H.; Vyborny, C.; Sephardari, S.; Kirchner, P.; Ryan, J.

    1985-10-01

    Accumulation of tracer by the stomach is a frequent incidental occurrence on gallium scans. Gastric concentration of Ga-67 equal to or greater than that seen in the liver was observed in approximately 10% of patients in a large series. Although a few of these patients had known or subsequently demonstrated gastric pathologic conditions, most had no clinically or radiographically identifiable gastric disease.

  11. 75 FR 42121 - Marine Mammals; Incidental Take During Specified Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-20

    ... applicant to incidentally take, by harassment, small numbers of southern sea otters for a period of 6 months... does not apply to southern sea otters. Section 101(a)(5)(D) of the MMPA established an expedited... Region (Applicant) for MMPA authorization to take by harassment southern sea otters (Enhydra...

  12. 76 FR 18232 - Marine Mammals; Incidental Take During Specified Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... harassment, small numbers of northern sea otters for a period of 1 year, beginning July 1, 2011. We... by harassment of northern sea otters (Enhydralutriskenyoni) incidental to the Akutan Airport, Alaska... authorizing Level B harassment of northern sea otters for a period of 1 year. The term of the IHAs...

  13. Effects of Captioning on Video Comprehension and Incidental Vocabulary Learning

    ERIC Educational Resources Information Center

    Perez, Maribel Montero; Peters, Elke; Clarebout, Geraldine; Desmet, Piet

    2014-01-01

    This study examines how three captioning types (i.e., on-screen text in the same language as the video) can assist L2 learners in the incidental acquisition of target vocabulary words and in the comprehension of L2 video. A sample of 133 Flemish undergraduate students watched three French clips twice. The control group (n = 32) watched the clips…

  14. Incidental Language Learning in Foreign Language Content Courses

    ERIC Educational Resources Information Center

    Rodgers, Daryl M.

    2015-01-01

    This study examined the extent to which 40 students enrolled in upper level foreign language literary/cultural studies content courses showed evidence of incidental language learning over the course of a semester. Students completed a cloze passage and provided both writing and speaking samples at the beginning and end of the semester. In…

  15. Word Frequency Effects on Memory and Incidental/Intentional Learning.

    ERIC Educational Resources Information Center

    Meinke, Dean L.; And Others

    Four separate experiments were completed using the same stimulus materials but different groups of subjects to determine if orienting tasks created problems of control in incidental/intentional learning studies. Subjects were all Caucasians and heterogeneous in age (from 24 to 64 years), educational experiences, and career choices. Those in the…

  16. Guidance of Spatial Attention by Incidental Learning and Endogenous Cuing

    ERIC Educational Resources Information Center

    Jiang, Yuhong V.; Swallow, Khena M.; Rosenbaum, Gail M.

    2013-01-01

    Our visual system is highly sensitive to regularities in the environment. Locations that were important in one's previous experience are often prioritized during search, even though observers may not be aware of the learning. In this study we characterized the guidance of spatial attention by incidental learning of a target's spatial probability,…

  17. 76 FR 13453 - Marine Mammals; Incidental Take During Specified Activities

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-11

    ...The Fish and Wildlife Service (Service) proposes regulations that would authorize the nonlethal, incidental, unintentional take of small numbers of polar bears and Pacific walruses during year-round oil and gas industry (Industry) exploration, development, and production operations in the Beaufort Sea and adjacent northern coast of Alaska. Industry operations for the covered period are similar......

  18. Concurrent Movement Impairs Incidental but Not Intentional Statistical Learning

    ERIC Educational Resources Information Center

    Stevens, David J.; Arciuli, Joanne; Anderson, David I.

    2015-01-01

    The effect of concurrent movement on incidental versus intentional statistical learning was examined in two experiments. In Experiment 1, participants learned the statistical regularities embedded within familiarization stimuli implicitly, whereas in Experiment 2 they were made aware of the embedded regularities and were instructed explicitly to…

  19. Implicit and Explicit Cognitive Processes in Incidental Vocabulary Acquisition

    ERIC Educational Resources Information Center

    Ender, Andrea

    2016-01-01

    Studies on vocabulary acquisition in second language learning have revealed that a large amount of vocabulary is learned without an overt intention, in other words, incidentally. This article investigates the relevance of different lexical processing strategies for vocabulary acquisition when reading a text for comprehension among 24 advanced…

  20. Endometriosis-associated serous borderline tumor and endometrial stromal sarcoma of the ovary: a report of a rare lesion in an infant.

    PubMed

    Ho, Ronnie S L; Chan, Godfrey C F; Ha, Shau Yin; Ip, Philip P C

    2012-01-01

    Endometriosis in infancy is most unusual, and associated tumors in this age group are exceptionally rare. We report a case of a serous borderline tumor and endometrial stromal sarcoma arising in an ovarian endometriotic cyst. The patient was an infant of 18 months of age who presented with an incidental abdominal mass. The serum sex hormones were at prepubertal levels. There was no evidence of precocious puberty or any obvious genital anomaly. Intraoperative findings included a solitary solid and multicystic right ovarian mass without evidence of any extraovarian disease. On microscopic examination, the tumor was composed of an intimate mixture of florid papillary and stromal cell proliferation in the wall of an endometriotic cyst. The papillae showed hierarchical branching and had hyalinized and edematous cores with scattered psammoma bodies. The epithelial cells were mildly atypical and mitotically inactive. The underlying endometrial stromal cells were arranged in irregular tongues that permeated the thickened fibrous cyst wall. They were mitotically active and immunoreactive for CD10. There was no evidence of any primitive germ cell tumor. The patient received no adjuvant treatment and had an uneventful postoperative follow-up period of 30 months. To the best of our knowledge, endometriosis associated with this most unusual combination of ovarian tumors has never been reported in an infant.

  1. Epiglottic Cyst Incidentally Discovered During Screening Endoscopy: A Case Report and Review of Literature

    PubMed Central

    Lee, Seung-Hwa; Kim, Kwang-Min; Kim, Kyu-Nam; Seo, Sang-Wook; Park, Young-Kyu; Cho, Sung-Min; Choi, Young-Ah; Lee, Jung-Un; Lee, Dong-Ryul

    2014-01-01

    From the endoscopists' point of view, although the main focus of upper gastrointestinal endoscopic examination is the esophagus, stomach, and duodenum (usually bulb and 2nd portion including ampulla of Vater), the portions of the upper airway may also be observed during insertion and withdrawal of the endoscope, such as pharynx and larynx. Thus, a variety of pathologic lesions of the upper airway can be encountered during upper endoscopy. Among these lesions, an epiglottic cyst is relatively uncommon. The cyst has no malignant potential and mostly remains asymptomatic in adults. However, if large enough, epiglottic cysts can compromise the airway and can be potentially life-threatening when an emergency endotracheal intubation is needed. Thus, patients may benefit from early detection and treatment of these relatively asymptomatic lesions. In this report, we present a case of epiglottic cyst in an asymptomatic adult incidentally found by family physician during screening endoscopy, which was successfully removed without complication, using a laryngoscopic carbon dioxide laser. PMID:24921035

  2. Gastrointestinal Headache; a Narrative Review

    PubMed Central

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-01-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder. PMID:27800536

  3. Gastrointestinal Headache; a Narrative Review.

    PubMed

    T Noghani, Majid; Rezaeizadeh, Hossein; Fazljoo, Sayed Mohammad Baqer; Keshavarz, Mansoor

    2016-11-01

    There are studies reporting primary headaches to be associated with gastrointestinal disorders, and some report resolution of headache following the treatment of the associated gastrointestinal disorder. Headache disorders are classified by The International Headache Society as primary or secondary; however, among the secondary headaches, those attributed to gastrointestinal disorders are not appreciated. Therefore, we aimed to review the literature to provide evidence for headaches, which originate from the gastrointestinal system. Gastrointestinal disorders that are reported to be associated with primary headaches include dyspepsia, gastro esophageal reflux disease (GERD), constipation, functional abdominal pain, inflammatory bowel syndrome (IBS), inflammatory bowel disorders (IBD), celiac disease, and helicobacter pylori (H. Pylori) infection. Some studies have demonstrated remission or improvement of headache following the treatment of the accompanying gastrointestinal disorders. Hypotheses explaining this association are considered to be central sensitization and parasympathetic referred pain, serotonin pathways, autonomic nervous system dysfunction, systemic vasculopathy, and food allergy. Traditional Persian physicians, namely Ebn-e-Sina (Avicenna) and Râzi (Rhazes) believed in a type of headache originating from disorders of the stomach and named it as an individual entity, the "Participatory Headache of Gastric Origin". We suggest providing a unique diagnostic entity for headaches coexisting with any gastrointestinal abnormality that are improved or cured along with the treatment of the gastrointestinal disorder.

  4. Sclerosing stromal tumor of the ovary in a premenarchal female.

    PubMed

    Fefferman, Nancy R; Pinkney, Lynne P; Rivera, Rafael; Popiolek, Dorota; Hummel-Levine, Pascale; Cosme, Jaqueline

    2003-01-01

    Sclerosing stromal tumor (SST) is a rare benign ovarian neoplasm of stromal origin with less than 100 cases reported in the literature. Unlike the other stromal tumors, thecomas and fibromas, which tend to occur in the fifth and sixth decades, sclerosing stromal tumors predominantly affect females in the second and third decades. Computed tomography (CT), magnetic resonance imaging (MRI), and ultrasound findings have been described, but have not been reported previously in the pediatric literature. We present a case of SST of the ovary in a 10-year-old premenarchal female, the youngest patient to our knowledge reported in the literature, and describe the ultrasound and CT findings with pathologic correlation.

  5. Stromal Effects on Mammary Gland Development and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  6. 76 FR 35856 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-20

    ... the explosive removal of offshore oil and gas structures (EROS) in the Gulf of Mexico. DATES: The... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  7. 75 FR 31423 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-03

    ... removal of offshore oil and gas structures (EROS) in the Gulf of Mexico. DATES: These authorizations are... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  8. 77 FR 16539 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-21

    ... and gas structures (EROS) in the Gulf of Mexico. DATES: These authorizations are effective from March... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  9. 75 FR 28566 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-21

    ... of offshore oil and gas structures (EROS) in the Gulf of Mexico. DATES: These authorizations are... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  10. 75 FR 38078 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-01

    ... removal of offshore oil and gas structures (EROS) in the Gulf of Mexico. DATES: These authorizations are... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  11. 75 FR 54851 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-09

    ... removal of offshore oil and gas structures (EROS) in the Gulf of Mexico. DATES: These authorizations are... taking. Regulations governing the taking of marine mammals incidental to EROS were published on June 19... during EROS activities are bottlenose dolphins (Tursiops truncatus), Atlantic spotted dolphins...

  12. 76 FR 41463 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-14

    .... Instructions: All comments received are a part of the public record and will generally be posted to http://www....noaa.gov/pr/permits/incidental.htm . The National Science Foundation (NSF), which is providing funding... on- board processing system. In addition, at least 72 sonobuoys will be deployed in order to...

  13. MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing.

    PubMed

    Gyvyte, Ugne; Juzenas, Simonas; Salteniene, Violeta; Kupcinskas, Juozas; Poskiene, Lina; Kucinskas, Laimutis; Jarmalaite, Sonata; Stuopelyte, Kristina; Steponaitiene, Ruta; Hemmrich-Stanisak, Georg; Hübenthal, Matthias; Link, Alexander; Franke, Sabine; Franke, Andre; Pangonyte, Dalia; Lesauskaite, Vaiva; Kupcinskas, Limas; Skieceviciene, Jurgita

    2017-03-29

    Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways. Further, we used an integrated analysis of miRNA-mRNA correlations for KIT and PDGFRA target genes and found a significant correlation between all of the enriched miRNAs and their target gene KIT. Results of the phenotype analysis showed miR-509-3p to be up-regulated in epithelioid and mixed cell types compared to spindle type, whereas miR-215-5p showed negative correlation with risk grade of GIST. These data reveal a detailed miRNA profile of GIST and highlight new candidates that may be important in the development of malignant disease.

  14. Study on the Evolution of Genes Mutation Related With Gastrointestinal Stromal Tumors

    ClinicalTrials.gov

    2012-01-05

    Full Gene Sequences of c-KIT、PDGFRA and DOG1 Are Analyzed With the Screening-sequencing Approach; Investigate the Characteristics and Variations Associated With the Different Gene Mutations of c-KIT、PDGFRA and DOG1 in GIST Patients

  15. Prognostic values of DLK1 for surgery and imatinib mesylate adjuvant therapy in gastrointestinal stromal tumors

    PubMed Central

    Xu, Jia; Wang, Ming; Zhang, Zizhen; Zhao, Wenyi; Wang, Chaojie; Tu, Lin; Zhang, Yeqian; Cao, Hui

    2016-01-01

    The Delta-like 1 homolog (DLK1) gene is a paternal imprinting gene located on human chromosome 14q32, a site associated with frequent chromosomal mutations in GIST. The expression level of DLK1 is closely associated with the outcome of tumours. However, no study has reported the DLK1 expression in GIST. Here, we demonstrated that DLK1 showed low expression in GIST patients with low risk according to the modified National Institute of Health (NIH) criteria. With increasing tumour risk level, DLK1 gene and protein expression levels gradually increased. In the test cohort, tissue microarray data showed that DLK1 protein expression was significantly associated with tumour size, mitotic figure count, NIH risk level, and Ki67 expression. In terms of either disease-free survival (DFS) or overall survival (OS), the long-term outcome was significantly better in DLK1-negative patients than in DLK1-positive patients. Univariate and multivariate analyses suggested that DLK1 expression was an independent risk factor influencing tumour DFS. Additionally, for intermediate/high-risk GIST patients received postoperative IM adjuvant therapy, Kaplan-Meier analysis showed that IM adjuvant therapy was associated with a better outcome in DLK1-negative patients than in DLK1-positive patients. All of the above results were verified in the validation cohort. Taken together, DLK1 is a promising prognostic biomarker for GISTs that may help to predict surgical outcomes and guide adjuvant IM therapy. PMID:27904782

  16. Extragastrointestinal Stromal Tumor (EGIST) in the abdominal wall: Case report and literature review

    PubMed Central

    Alkhatib, Loiy; Albtoush, Omar; Bataineh, Nesreen; Gharaibeh, Kamal; Matalka, Ismail; Tokuda, Yasuharu

    2011-01-01

    INTRODUCTION Gastro Intestinal Stromal Tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract (GI). GIST that arises primarily outside the GI tract is termed Extragastrointestinal Stromal Tumor (EGIST). To the best of our knowledge, few cases of EGIST in the abdominal wall were reported. PRESENTATION OF CASE We present a rare case of EGIST in the abdominal wall of a 57 year-old female patient. The asymptomatic tumor was located in the superior aspect of the left rectus abdominis muscle, measured 5.4 × cm 5.3 × cm 6.9 cm and was well circumscribed. Histological examination showed an epithelioid cell morphology. The mitotic count was 7/50 HPFs. Immunohistochemistry showed diffuse strong CD117 positivity, focal positivity for S100. The tumor was excised and the margins were free of malignancy. The patient was doing well postoperatively and was discharged on STI-571 regimen. DISCUSSION Although GIST is the most common mesenchymal tumor of the gastrointestinal tract, a case with EGIST in the abdominal wall is rare. Positive immunohistochemical staining for CD117 is a defining feature of GISTs. A great percentage of EGISTs represent a metastasis from a primary GIST. In our case, the clinical and diagnostic work-up have been proved it to be an EGIST. CONCLUSION The existing data on EGIST is insufficient to make a final conclusion regarding the malignant potential and clinicopathological factors of EGISTs that determine patient prognosis. Thus a follow-up for a long period is required. EGISTs should be kept in mind in the differential diagnosis for patients presenting with solid mass of the abdominal wall. PMID:22096744

  17. Hereditary gastrointestinal cancer.

    PubMed

    Hata, Keisuke; Yamamoto, Yoko; Kiyomatsu, Tomomichi; Tanaka, Toshiaki; Kazama, Shinsuke; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Junichiro; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kishikawa, Junko; Nagai, Yuzo; Anzai, Hiroyuki; Shinagawa, Takahide; Arakawa, Keiichi; Yamaguchi, Hironori; Ishihara, Soichiro; Sunami, Eiji; Kitayama, Joji; Watanabe, Toshiaki

    2016-10-01

    Gastrointestinal (GI) cancer, including gastric and colorectal cancer, is a major cause of death worldwide. A substantial proportion of patients with GI cancer have a familial history, and several causative genes have been identified. Gene carriers with these hereditary GI syndromes often harbor several kinds of cancer at an early age, and genetic testing and specific surveillance may save their lives through early detection. Gastroenterologists and GI surgeons should be familiar with these syndromes, even though they are not always associated with a high penetrance of GI cancer. In this review, we provide an overview and discuss the diagnosis, genetic testing, and management of four major hereditary GI cancers: familial adenomatous polyposis, Lynch syndrome, hereditary diffuse gastric cancer, and Li-Fraumeni syndrome.

  18. Dysbiosis in gastrointestinal disorders.

    PubMed

    Chang, Christopher; Lin, Henry

    2016-02-01

    The recent development of advanced sequencing techniques has revealed the complexity and diverse functions of the gut microbiota. Furthermore, alterations in the composition or balance of the intestinal microbiota, or dysbiosis, are associated with many gastrointestinal diseases. The looming question is whether dysbiosis is a cause or effect of these diseases. In this review, we will evaluate the contribution of intestinal microbiota in obesity, fatty liver, inflammatory bowel disease, and irritable bowel syndrome. Promising results from microbiota or metabolite transfer experiments in animals suggest the microbiota may be sufficient to reproduce disease features in the appropriate host in certain disorders. Less compelling causal associations may reflect complex, multi-factorial disease pathogenesis, in which dysbiosis is a necessary condition. Understanding the contributions of the microbiota in GI diseases should offer novel insight into disease pathophysiology and deliver new treatment strategies such as therapeutic manipulation of the microbiota.

  19. [Gastrointestinal dysmotility in children].

    PubMed

    Fluge, G; Olafsdottir, E

    2001-03-20

    Motility disorders were previously impossible to penetrate, but new technics have made it possible to investigate these disorders. An overview of neurophysiological functions of the gastrointestinal tract is given, and various conditions representing primary and secondary motility disorders are discussed. Diagnostic procedures and treatment options are presented. The clinical picture of such disorders is demonstrated by two cases. A girl born in 1995, having megacystis microcolon hypoperistalsis syndrome was the first Norwegian individual to have an intestinal transplantation, which was performed in London, UK. A girl with hypoganglionosis is also reported. Since May 1998, manometry of the oesophagus was performed in 44 children, and pathological findings were demonstrated in 18 of these patients. The motoric activity of the stomach was investigated in 17 patients using two-dimensional ultrasound and electrogastrography pre- and post-prandially. Disturbed function was found in nine of these children. Anorectal manometry was performed in 147 individuals, and Hirschsprung's disease was diagnosed in four.

  20. Gastrointestinal infections in children.

    PubMed

    Mönkemüller, K E; Wilcox, C M

    2001-01-01

    Gastrointestinal infections in children are a major cause of morbidity and mortality worldwide. Children living in developing countries are particularly susceptible to infectious diarrhea because of poor standards of hygiene and sanitation. Although the magnitude of diarrheal illnesses in developed countries is less, costly hospital admissions are still frequent. The causal agent of infectious diarrhea is most frequently related to age, geographical location, lifestyle habits, use of antibiotics, associated medical conditions, social circumstances, and degree of immune competence. In this article we present some of the most important articles published in the field during the last year. The role of Helicobacter pylori in the pathogenesis of gastritis and peptic ulcer disease has been shown in adults and children. Information about the natural history of H. pylori, symptomatology, and diagnostic therapeutic approaches for children are being generated constantly; we discuss some of the most relevant information in this review.

  1. Disorders of gastrointestinal hypomotility

    PubMed Central

    Bielefeldt, Klaus; Tuteja, Ashok; Nusrat, Salman

    2016-01-01

    Ingestion and digestion of food as well as expulsion of residual material from our gastrointestinal tract requires normal propulsive, i.e. motor, function. Hypomotility refers to inherited or acquired changes that come with decreased contractile forces or slower transit. It not only often causes symptoms but also may compromise nutritional status or lead to other complications. While severe forms, such as pseudo-obstruction or ileus, may have a tremendous functional impact, the less severe forms of hypomotility may well be more relevant, as they contribute to common disorders, such as functional dyspepsia, gastroparesis, chronic constipation, and irritable bowel syndrome (IBS). Clinical testing can identify changes in contractile activity, defined by lower amplitudes or abnormal patterns, and the related effects on transit. However, such biomarkers show a limited correlation with overall symptom severity as experienced by patients. Similarly, targeting hypomotility with pharmacological interventions often alters gut motor function but does not consistently improve symptoms. Novel diagnostic approaches may change this apparent paradox and enable us to obtain more comprehensive information by integrating data on electrical activity, mechanical forces, patterns, wall stiffness, and motions with information of the flow of luminal contents. New drugs with more selective effects or more specific delivery may improve benefits and limit adverse effects. Lastly, the complex regulation of gastrointestinal motility involves the brain-gut axis as a reciprocal pathway for afferent and efferent signaling. Considering the role of visceral input in emotion and the effects of emotion on visceral activity, understanding and managing hypomotility disorders requires an integrative approach based on the mind-body continuum or biopsychosocial model of diseases. PMID:27583135

  2. Low-Grade Endometrial Stromal Sarcoma with Intravenous and Intracardiac Extension: A Multidisciplinary Approach

    PubMed Central

    Inafuku, Hitoshi; Nakamoto, Tomoko; Taira, Yusuke; Taira, Rie; Tsubakimoto, Maho; Totsuka, Yuichi; Kuniyoshi, Yukio; Tamaki, Tomoko; Aoyama, Hajime

    2016-01-01

    Background. A rare case of low-grade endometrial stromal sarcoma (LG-ESS) extending to inferior vena cava (IVC) and cardiac chambers. Case Report. A 40-year-old woman had IVC tumor, which was incidentally detected by abdominal ultrasonography during a routine medical checkup. CT scan revealed a tumor in IVC, right iliac and ovarian veins, which was derived from the uterus and extended into the right atrium and ventricle. The operation was performed, the heart and IVC were exposed, and cardiopulmonary bypass was initiated. A right atriotomy was performed, and the intracardiac mass was removed. Then the tumor in IVC and the right internal iliac vein were removed after longitudinal venotomies in the suprarenal and infrarenal vena cava, the right common iliac vein. Next the pelvis was explored. Tumors were found originating from the posterior wall of the uterus and continuing into both the right uterine and ovarian vein. The patient underwent total hysterectomy with bilateral salpingooophorectomy. Complete tumor resection was achieved. Histopathological analysis confirmed a diagnosis of LG-ESS. She showed no evidence of disease for 2 years and 3 months. Conclusions. Our case highlights the importance of a multidisciplinary approach in treating this rare cardiovascular pathological condition through preoperative assessment to final operation. PMID:27239357

  3. An Air-Liquid Interface Culture System for 3D Organoid Culture of Diverse Primary Gastrointestinal Tissues.

    PubMed

    Li, Xingnan; Ootani, Akifumi; Kuo, Calvin

    2016-01-01

    Conventional in vitro analysis of gastrointestinal epithelium usually relies on two-dimensional (2D) culture of epithelial cell lines as monolayer on impermeable surfaces. However, the lack of context of differentiation and tissue architecture in 2D culture can hinder the faithful recapitulation of the phenotypic and morphological characteristics of native epithelium. Here, we describe a robust long-term three-dimensional (3D) culture methodology for gastrointestinal culture, which incorporates both epithelial and mesenchymal/stromal components into a collagen-based air-liquid interface 3D culture system. This system allows vigorously expansion of primary gastrointestinal epithelium for over 60 days as organoids with both proliferation and multilineage differentiation, indicating successful long-term intestinal culture within a microenvironment accurately recapitulating the stem cell niche.

  4. What Are the Key Statistics about Gastrointestinal Carcinoid Tumors?

    MedlinePlus

    ... About Gastrointestinal Carcinoid Tumors What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? Although the exact number ... a Gastrointestinal Carcinoid Tumor? What Are the Key Statistics About Gastrointestinal Carcinoid Tumors? What’s New in Gastrointestinal ...

  5. Autistic disorder and gastrointestinal disease.

    PubMed

    Horvath, Karoly; Perman, Jay A

    2002-10-01

    Autistic disorder is a pervasive developmental disorder manifested in the first 3 years of life by dysfunction in social interaction and communication. Many efforts have been made to explore the biologic basis of this disorder, but the etiology remains unknown. Recent publications describing upper gastrointestinal abnormalities and ileocolitis have focused attention on gastrointestinal function and morphology in these children. High prevalence of histologic abnormalities in the esophagus, stomach, small intestine and colon, and dysfunction of liver conjugation capacity and intestinal permeability were reported. Three surveys conducted in the United States described high prevalence of gastrointestinal symptoms in children with autistic disorder. Treatment of the digestive problems may have positive effects on their behavior.

  6. Epithelial and Stromal Spectral Imaging for Rapid Surgical Margin Analysis

    DTIC Science & Technology

    2012-03-01

    for key diagnostic classes. The optical system samples mesoscopic tissue volumes; therefore, microscopic segmentation of glandular , stromal and...heterogeneous, but imaging-pathology correlates revealed that this variation had a spatial pattern that reflected the organization of glandular structures...characterized by marked expansion of glandular units by neo-plastic cells, compressing (but not invading) the surrounding stromal environment

  7. Concurrent movement impairs incidental but not intentional statistical learning.

    PubMed

    Stevens, David J; Arciuli, Joanne; Anderson, David I

    2015-07-01

    The effect of concurrent movement on incidental versus intentional statistical learning was examined in two experiments. In Experiment 1, participants learned the statistical regularities embedded within familiarization stimuli implicitly, whereas in Experiment 2 they were made aware of the embedded regularities and were instructed explicitly to learn these regularities. Experiment 1 demonstrated that while the control group were able to learn the statistical regularities, the resistance-free cycling group and the exercise group did not demonstrate learning. This is in contrast with the findings of Experiment 2, where all three groups demonstrated significant levels of learning. The results suggest that the movement demands, rather than the physiological stress, interfered with statistical learning. We suggest movement activates the striatum, which is not only responsible for motor control but also plays a role in incidental learning.

  8. Gastrointestinal tract spindle cell lesions--just like real estate, it's all about location.

    PubMed

    Voltaggio, Lysandra; Montgomery, Elizabeth A

    2015-01-01

    Interpretation of gastrointestinal tract mesenchymal lesions is simplified merely by knowing in which anatomic layer they are usually found. For example, Kaposi sarcoma is detected on mucosal biopsies, whereas inflammatory fibroid polyp is nearly always in the submucosa. Gastrointestinal stromal tumors (GISTs) are generally centered in the muscularis propria. Schwannomas are essentially always in the muscularis propria. Mesenteric lesions are usually found in the small bowel mesentery. Knowledge of the favored layer is even most important in interpreting colon biopsies, as many mesenschymal polyps are encountered in the colon. Although GISTs are among the most common mesenchymal lesions, we will concentrate our discussion on other mesenchymal lesions, some of which are in the differential diagnosis of GIST, and point out some diagnostic pitfalls, particularly in immunolabeling.

  9. Stromal cells can contribute oncogenic signals

    NASA Technical Reports Server (NTRS)

    Tlsty, T. D.

    2001-01-01

    The majority of studies of neoplastic transformation have focused attention on events that occur within transformed cells. These cell autonomous events result in the disruption of molecular pathways that regulate basic activities of the cells such as proliferation, death, movement and genomic integrity. Other studies have addressed the microenvironment of tumor cells and documented its importance in supporting tumor progression. Recent work has begun to expand on these initial studies of tumor microenvironment and now provide novel insights into the possible initiation and progression of malignant cells. This review will address the transforming effect of stromal cells on epithelial components. Copyright 2001 Academic Press.

  10. Schwann cells induce neuronal differentiation of bone marrow stromal cells.

    PubMed

    Zurita, Mercedes; Vaquero, Jesús; Oya, Santiago; Miguel, Miriam

    2005-04-04

    Bone marrow stromal cells are multipotent stem cells that have the potential to differentiate into bone, cartilage, fat and muscle. Recently, bone marrow stromal cells have been shown to have the capacity to differentiate into neurons under specific experimental conditions, using chemical factors. We now describe how bone marrow stromal cells can be induced to differentiate into neuron-like cells when they are co-cultured with Schwann cells. When compared with chemical differentiation, expression of neuronal differentiation markers begins later, but one week after beginning co-culture, most bone marrow stromal cells showed a typical neuronal morphology. Our present findings support the transdifferentiation of bone marrow stromal cells, and the potential utility of these cells for the treatment of degenerative and acquired disorders of the nervous system.

  11. Stromal networking: cellular connections in the germinal centre.

    PubMed

    Denton, Alice E; Linterman, Michelle A

    2017-03-17

    Secondary lymphoid organs are organized into distinct zones, governed by different types of mesenchymal stromal cells. These stromal cell subsets are critical for the generation of protective humoral immunity because they direct the migration of, and interaction between, multiple immune cell types to form the germinal centre. The germinal centre response generates long-lived antibody-secreting plasma cells and memory B cells which can provide long-term protection against re-infection. Stromal cell subsets mediate this response through control of immune cell trafficking, activation, localization and antigen access within the secondary lymphoid organ. Further, distinct populations of stromal cells underpin the delicate spatial organization of immune cells within the germinal centre. Because of this, the interactions between immune cells and stromal cells in secondary lymphoid organs are fundamental to the germinal centre response. Herein we review how this unique relationship leads to effective germinal centre responses.

  12. The Interaction Between Human Papillomaviruses and the Stromal Microenvironment.

    PubMed

    Woodby, B; Scott, M; Bodily, J

    2016-01-01

    Human papillomaviruses (HPVs) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs, or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology, focusing on stromal fibroblasts, immune cells, and endothelial cells. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

  13. Giant fibroepithelial stromal polyp of the vulva: largest case reported

    PubMed Central

    2013-01-01

    Background Fibroepithelial stromal polyps are site-specific mesenchymal lesions that are commonly found in the vulvovaginal region in premenopausal females. These polyps usually are less than 5 cm in diameter and are most commonly identified during routine gynecological examination. Although the stromal polyp is benign, its differential diagnosis includes some malignant vulva lesions making it critical to ensure that an accurate pathologic diagnosis is made. Case We present a case of a 21 year old female with a giant fibroepithelial stromal polyp of the vulva. Upon review of the literature this is the largest reported fibroepithelial stromal polyp to date. Conclusion Fibroepithelial stromal polyps can grow as large as 390 grams and can be 18.5-cm in diameter. Microscopic evaluation of the polyp is critical in the exclusion of malignancy with this diagnosis. PMID:23842282

  14. Incidental finding of a microsporidian parasite from an AIDS patient.

    PubMed Central

    McDougall, R J; Tandy, M W; Boreham, R E; Stenzel, D J; O'Donoghue, P J

    1993-01-01

    Light microscopic examination of feces from a human immunodeficiency virus-positive patient with chronic diarrhea, anorexia, and lethargy revealed the presence of numerous refractile bodies resembling microsporidian spores. They were subsequently identified as belonging to the genus Nosema on the basis of their ultrastructural characteristics. However, the microsporidia were enclosed within striated muscle cells, suggesting that they were probably ingested in food; thus, this represented an incidental finding rather than a true infection. Images PMID:8432833

  15. Incidental gallbladder cancer diagnosed during and after laparoscopic cholecystectomy.

    PubMed

    Shimizu, Tetsuya; Arima, Yasuo; Yokomuro, Shigeki; Yoshida, Hiroshi; Mamada, Yasuhiro; Nomura, Tsutomu; Taniai, Nobuhiko; Aimoto, Takayuki; Nakamura, Yoshiharu; Mizuguchi, Yoshiaki; Kawahigashi, Yutaka; Uchida, Eiji; Akimaru, Koho; Tajiri, Takashi

    2006-06-01

    With the increasingly widespread acceptance of laparoscopic cholecystectomy (LC), the number of cases of incidental gallbladder carcinoma (GBC) has increased; however, management of incidental GBC is a difficult issue in the absence of established guidelines. The present study aims to evaluate the treatment of patients with incidental GBC diagnosed with LC. We performed a 14-year review of 10 patients with GBC discovered with LC. From April 1991 through March 2004, we performed LC for 1,195 patients at Nippon Medical School Main Hospital. Of these patients, 10 (0.83%) were found to have GBC. Seven patients were women and 3 were men, with a mean age of 61.4 years. Four patients had mucosal tumors (pT1a), 5 had subserosal tumors (pT2), and 1 had a serosal lesion (pT3). Eight of the 10 patients underwent radical surgery. Two patients with pT1a tumors underwent no additional surgery. All 4 patients with pT1a tumors are alive without recurrence. One patient with a pT2 tumor with metastases to the liver and pericholedochal lymph nodes found with additional resection died of recurrence of metastasis to the liver and lung 70 months after LC. One patient with a pT2 tumor died of primary lung cancer 35 months after LC. The remaining 3 patients with pT2 tumors are alive without recurrence 51 to 128 months after surgery. One patient with a pT3 tumor is alive with no recurrence for 9 months. For stage Tis or T1a tumors, LC is sufficient. Patients with T1b tumors should undergo liver-bed resection and lymphadenectomy, and patients with >pT2 tumors should undergo systematic liver resection with lymphadenectomy. Even when incidental GBC diagnosed with LC is advanced, adequate additional surgery may improve the prognosis.

  16. Primary Sarcoid of the Breast with Incidental Malignancy

    PubMed Central

    Isley, Laura M.; Cluver, Abbie R.; Leddy, Rebecca J.; Baker, Megan K.

    2012-01-01

    Breast sarcoidosis is rare and usually presents in patients with known sarcoid involving other organ systems. In the breast, sarcoidosis may mimic malignancy which must be excluded by core biopsy. We report a very unusual case of primary breast sarcoidosis with incidentally discovered breast carcinoma. The roles of mammography, ultrasound, and MRI in the diagnosis as well as other potential differential diagnosis are discussed. PMID:22919560

  17. Incidentally Detected Blue Nevus of Endocervix: a Case Report

    PubMed Central

    Bhat, Shaila Talengala; Shivamurthy, Archana; Kini Rao, Anuradha Calicut

    2015-01-01

    Blue nevi are uncommon, asymptomatic lesions of the uterine cervix. These lesions are not often detected clinically or on colposcopy. Careful histopathological examination is required. The nevus cells are said to originate from the immature melanoblasts of the neural crest. These lesions need to be differentiated from malignant melanoma and melanosis of the cervix. We present here a case report of incidentally detected cervical blue nevus in a 52 year old lady. PMID:26351493

  18. Contributory and incidental blood concentrations in deaths involving citalopram.

    PubMed

    Darke, Shane; Torok, Michelle; Duflou, Johan

    2013-03-01

    All cases presenting to the New South Wales Department of Forensic Medicine between January 1, 2001 and December 31, 2010 in which citalopram was detected were retrieved. A total of 348 cases were identified. Citalopram contributed to death in 21.0%, and was incidental in 79.0%. Cases in which citalopram was contributory to death had significantly higher blood citalopram concentrations than incidental cases (0.50 mg/L vs. 0.30 mg/L). Citalopram concentrations varied significantly by contributory status: sole citalopram toxicity (median = 1.30 mg/L), citalopram/other drug toxicity (0.50 mg/L), and incidental cases (0.30 mg/L). Citalopram concentrations also varied by suicide status, with the highest concentration found in suicides where citalopram contributed to death (0.70 mg/L) compared with 0.50 mg/L for nonsuicide cases where citalopram contributed to death. In almost all contributory cases (69/73), other psychoactive substances were also detected, most commonly benzodiazepines (47.9%), alcohol (45.2%), and opioids (40.1%).

  19. Incidental pheochromocytoma in a patient with nasopharyngeal carcinoma.

    PubMed

    Baldane, S; Ipekci, S H; Celik, E; Gedik, G K; Ozaslan, E; Guler, I; Kebapcilar, L

    2015-10-01

    Because the adrenal glands are common locations for metastases, pheochromocytoma is frequently misdiagnosed as adrenal metastasis in patients with a history of cancer. An incidental adrenal mass was detected during an abdominal computed tomography (CT) scan performed to stage the nasopharyngeal carcinoma in a 35-year-old male patient. The features of an adrenal mass on the CT, magnetic resonance imaging (MRI), and fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) were thought to show adrenal metastasis. However, the patient did not complain about flushing, palpitation, headache or excessive sweating. His blood pressure was 132/74 mmHg, and his pulse rate was 82 bpm. A pheochromocytoma was found during a biochemical diagnosis that evaluated the catecholamine in urine collected over a 24-hour period. The urine had elevated urinary adrenaline, metanephrine, and vanillylmandelic. An I123 MIBG scan showed avid tracer uptake in the right adrenal mass with no evidence of abnormal uptake elsewhere. A right adrenalectomy operation was performed and a diagnosis of pheochromocytoma was confirmed histopathologically. Incidental adrenal masses detected in the presence history of cancer should always be subjected to hormonal evaluation. Although patients may be asymptomatic, the probability of incidental pheochromocytoma should not be ignored.

  20. Incidental Learning of Melodic Structure of North Indian Music.

    PubMed

    Rohrmeier, Martin; Widdess, Richard

    2016-11-17

    Musical knowledge is largely implicit. It is acquired without awareness of its complex rules, through interaction with a large number of samples during musical enculturation. Whereas several studies explored implicit learning of mostly abstract and less ecologically valid features of Western music, very little work has been done with respect to ecologically valid stimuli as well as non-Western music. The present study investigated implicit learning of modal melodic features in North Indian classical music in a realistic and ecologically valid way. It employed a cross-grammar design, using melodic materials from two modes (rāgas) that use the same scale. Findings indicated that Western participants unfamiliar with Indian music incidentally learned to identify distinctive features of each mode. Confidence ratings suggest that participants' performance was consistently correlated with confidence, indicating that they became aware of whether they were right in their responses; that is, they possessed explicit judgment knowledge. Altogether our findings show incidental learning in a realistic ecologically valid context during only a very short exposure, they provide evidence that incidental learning constitutes a powerful mechanism that plays a fundamental role in musical acquisition.

  1. The effects of ordinal load on incidental temporal learning.

    PubMed

    Silva, Susana; Petersson, Karl Magnus; Castro, São Luís

    2017-04-01

    How can we grasp the temporal structure of events? A few studies have indicated that representations of temporal structure are acquired when there is an intention to learn, but not when learning is incidental. Response-to-stimulus intervals, uncorrelated temporal structures, unpredictable ordinal information, and lack of metrical organization have been pointed out as key obstacles to incidental temporal learning, but the literature includes piecemeal demonstrations of learning under all these circumstances. We suggest that the unacknowledged effects of ordinal load may help reconcile these conflicting findings, ordinal load referring to the cost of identifying the sequence of events (e.g., tones, locations) where a temporal pattern is embedded. In a first experiment, we manipulated ordinal load into simple and complex levels. Participants learned ordinal-simple sequences, despite their uncorrelated temporal structure and lack of metrical organization. They did not learn ordinal-complex sequences, even though there were no response-to-stimulus intervals nor unpredictable ordinal information. In a second experiment, we probed learning of ordinal-complex sequences with strong metrical organization, and again there was no learning. We conclude that ordinal load is a key obstacle to incidental temporal learning. Further analyses showed that the effect of ordinal load is to mask the expression of temporal knowledge, rather than to prevent learning.

  2. Incidental Breast Lesions Detected on Computed Thorax Tomography

    PubMed Central

    Poyraz, Necdet; Emlik, Ganime Dilek; Keskin, Suat; Kalkan, Havva

    2015-01-01

    Objective Although mammography is the primary imaging method of the breast, incidental benign and malignant breast lesions are increasingly being detected on computed tomographies (CTs) performed to detect different pathologies. Therefore, the detection and accurate identification of these lesions is important. In this study, we aimed to evaluate the frequency, morphological features, and results of incidental breast lesions on CTs performed for the detection of extramammarian pathologies. Materials and Methods Incidental breast lesions on CTs performed in our department between 2011 and 2013 were evaluated. Patients who had previously diagnosed breast lesions were excluded from the study. The inclusion criteria were histopathologic diagnose and being followed-up for at least 2 years. Results The study population consisted of 33 women whose mean age was 55±1.38 (37–78) years. Of the 33 women, 12 (36%) had malignant and 21 (64%) had benign or normal findings. The most common malignant lesion was invasive ductal carcinoma, and the most common benign lesion was fibroadenoma. Ill-defined contour and lymphadenopathy in malignant lesions and well-defined contour in benign lesions were the most important CT findings. Conclusion Breast must be carefully evaluated if it is included in the scans. An accurate report of breast lesions gives an opportunity for early diagnosis and treatment.

  3. Incidental Parathyroidectomy during Total Thyroidectomy: Risk Factors and Consequences

    PubMed Central

    Balalis, Dimitrios; Soulou, Vasiliki N.; Korkolis, Dimitrios P.; Plataniotis, Georgios; Gontikakis, Emmanouil

    2016-01-01

    Objective. To evaluate the incidence of accidental parathyroidectomy in our series of total thyroidectomies, to investigate its clinical and biochemical consequences, and to identify potential risk factors. Methods. Patients who underwent total thyroidectomy between January 2006 and December 2015 were retrospectively analyzed. Pathology reports were reviewed to identify those cases who had an incidental parathyroidectomy and these were compared to patients with no parathyroidectomy, in terms of clinical (age, sex, and symptoms of hypocalcemia), pathological (thyroid specimen weight, Hashimoto thyroiditis, and malignancy), and biochemical (serum calcium and phosphate levels) factors. Results. 281 patients underwent total thyroidectomy during the study period. Incidental parathyroidectomy was noticed in 24.9% of cases, with 44.3% of parathyroid glands found in an intrathyroidal location. Evidence of postoperative biochemical hypocalcemia was noticed in 28.6% of patients with parathyroidectomy, compared with 13.3% in the no-parathyroidectomy group (p = 0.003). Symptomatic hypocalcemia was observed in 5.7% and 3.8%, respectively (p = 0.49). Age, sex, thyroid specimen weight, Hashimoto thyroiditis, and malignancy did not differ significantly between the two groups. Conclusions. Our study found an association of incidental parathyroidectomy with transient postoperative biochemical hypocalcemia, but not with clinically symptomatic disease. Age, sex, thyroid gland weight, Hashimoto thyroiditis, and malignancy were not identified as risk factors. PMID:27635137

  4. Hedgehog signaling and gastrointestinal cancer

    PubMed Central

    Saqui-Salces, Milena; Merchant, Juanita L.

    2017-01-01

    Hedgehog (Hh) signaling is critical for embryonic development and in differentiation, proliferation, and maintenance of multiple adult tissues. De-regulation of the Hh pathway is associated with birth defects and cancer. In the gastrointestinal tract, Hh ligands Sonic (Shh) and Indian (Ihh), as well as the receptor Patched (Ptch1), and transcription factors of Glioblastoma family (Gli) are all expressed during development. In the adult, Shh expression is restricted to the stomach and colon, while Ihh expression occurs throughout the luminal gastrointestinal tract, its expression being highest in the proximal duodenum. Several studies have demonstrated a requirement for Hh signaling during gastrointestinal tract development. However to date, the specific role of the Hh pathway in the adult stomach and intestine is not completely understood. The current review will place into context the implications of recent published data related to the biochemistry and cell biology of Hh signaling on the luminal gastrointestinal tract during development, normal physiology and subsequently carcinogenesis. PMID:20307590

  5. Epigenetic mechanisms and gastrointestinal development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review considers the hypothesis that nutrition during infancy affects developmental epigenetics in the gut, causing metabolic imprinting of gastrointestinal (GI) structure and function. Fundamentals of epigenetic gene regulation are reviewed, with an emphasis on the epigenetic mechanism of DNA ...

  6. The Gastrointestinal Microbiome

    PubMed Central

    Engen, Phillip A.; Green, Stefan J.; Voigt, Robin M.; Forsyth, Christopher B.; Keshavarzian, Ali

    2015-01-01

    The excessive use of alcohol is a global problem causing many adverse pathological health effects and a significant financial health care burden. This review addresses the effect of alcohol consumption on the microbiota in the gastrointestinal tract (GIT). Although data are limited in humans, studies highlight the importance of changes in the intestinal microbiota in alcohol-related disorders. Alcohol-induced changes in the GIT microbiota composition and metabolic function may contribute to the well-established link between alcohol-induced oxidative stress, intestinal hyperpermeability to luminal bacterial products, and the subsequent development of alcoholic liver disease (ALD), as well as other diseases. In addition, clinical and preclinical data suggest that alcohol-related disorders are associated with quantitative and qualitative dysbiotic changes in the intestinal microbiota and may be associated with increased GIT inflammation, intestinal hyperpermeability resulting in endotoxemia, systemic inflammation, and tissue damage/organ pathologies including ALD. Thus, gut-directed interventions, such as probiotic and synbiotic modulation of the intestinal microbiota, should be considered and evaluated for prevention and treatment of alcohol-associated pathologies. PMID:26695747

  7. Gastrointestinal mucormycosis in immunocompromised hosts.

    PubMed

    Dioverti, M Veronica; Cawcutt, Kelly A; Abidi, Maheen; Sohail, M Rizwan; Walker, Randall C; Osmon, Douglas R

    2015-12-01

    Invasive mucormycosis is a rare fungal infection in immunocompromised hosts, but it carries a high mortality rate. Primary gastrointestinal disease is the least frequent form of presentation. Early diagnosis and treatment are critical in the management; however, symptoms are typically non-specific in gastrointestinal disease, leading to delayed therapy. To describe the clinical presentation, diagnosis, treatment and outcomes of gastrointestinal mucormycosis in immunocompromised hosts, we reviewed all cases of primary gastrointestinal mucormycosis in immunocompromised hosts reported in English literature as well as in our Institution from January 1st 1991 to December 31st 2013 for a total of 31 patients. About 52% of patients underwent solid organ transplant (SOT), while the rest had an underlying haematologic malignancy. Abdominal pain was the most common presenting symptom, followed by gastrointestinal bleeding and fever. Gastric disease was more common in SOT, whereas those with haematologic malignancy presented with intestinal disease (P = 0.002). Although gastrointestinal mucormycosis remains an uncommon condition in immunocompromised hosts, it carries significant morbidity and mortality, particularly in cases with intestinal involvement. A high index of suspicion is of utmost importance to institute early and appropriate therapy and improve outcomes.

  8. Lipomas of the gastrointestinal system.

    PubMed

    Dolai, Matilda; Andrejić, Bojana; Ivanov, Dejan

    2012-01-01

    Lipomas are rare benign tumors in the gastrointestinal system. Within the gastrointestinal system, 65% of the lipomas are located in the colon (sigmoid part of the colon or rectum) and rarely in the stomach and esophagus. The paper presents two gastrointestinal lipomas. First is the case of lipoma of the sigmoid colon and the other one is gastric lipoma. In both cases the material was sent for histopathological analysis due to suspicion of malignancy of the lesions. In both cases, the histopathologic analysis showed tumor made of mature adipocytes, localized in the submucosa both of the stomach and intestine. Hypercellularity and/or atypia of the cell was found in neither case. Lipomas are shown because of its atypical localization and clinically suspicious malignancy in the stomach and sigmoid colon. These cases show that the applied methods of preoperative diagnosis of tumors in the gastrointestinal system are not sufficient to determine the origin and biological behavior of tumors. Histopathological diagnosis provides a correct insight into the nature of tumors and determine the course of treatment. This paper presents a rare localization of lipomas in the gastrointestinal system. The preoperative diagnosis of lesions in the gastrointestinal system may not be sufficient to determine the origin and biological behavior of the lesions, hence the histopathological diagnosis gives an accurate insight into the nature of the change, preventing the possibility of further aggressive therapy.

  9. COX2 (PTGS2) gene methylation in epithelial, subepithelial lymphocyte and stromal tissue compartments in a spectrum of esophageal squamous neoplasia

    PubMed Central

    Dawsey, Sonja P.; Roth, Mark J.; Adams, Lisa; Hu, Nan; Wang, Quan-Hong; Taylor, Philip R.; Woodson, Karen

    2008-01-01

    Background Previous studies have shown important effects of stromal elements in carcinogenesis. To explore the tumor-stromal relationship in esophageal neoplasia, we examined methylation of COX-2 (PTGS2), a gene etiologically associated with the development of gastrointestinal cancers, in adjacent foci of epithelium, subepithelial lymphocytes and non-lymphocytic stromal cells found in sections of normal squamous epithelium, squamous dysplasia and invasive esophageal squamous cell carcinoma. Methods Adjacent foci of epithelium, subepithelial lymphocytic aggregates and non-lymphocytic stromal tissues were laser microdissected from six fully embedded, ethanol fixed, esophagectomy samples from Shanxi, China, a high-risk region for esophageal cancer. Promoter CpG site-specific hypermethylation status of COX-2 was determined using real-time methylation specific PCR (qMS-PCR) based on Taqman Chemistry. The methylation status of a subset of samples was confirmed by pyrosequencing. Results Forty-nine microdissected foci were analyzed. COX-2 gene methylation was significantly more common in subepithelial lymphocytes (12/16 (75% of all foci)) than in epithelial foci (3/16 (19%)) or foci of non-lymphocytic stromal tissues (3/17 (18%)) (Fisher’s Exact p=0.05). Two of three epithelial samples and all three stromal samples that showed COX-2 methylation were adjacent to foci of methylated subepithelial lymphocytes. Pyrosequencing confirmed the methylation status in a subset of samples. Conclusions In these esopohageal cancer patients, COX-2 gene methylation was more common in subepithelial lymphocytes than in adjacent epithelial or stromal cells in both grades of dysplasia and in foci of invasive cancer. These findings raise the possibility that methylation of subepithelial lymphocytes may be important for tumorigenesis. Future studies of gene methylation should consider separate evaluation of epithelial and non-epithelial cell populations. Condensed abstract COX2 (PTGS2) gene

  10. Primary gastrointestinal lymphoma

    PubMed Central

    Aledavood, Amir; Nasiri, Mohammad Reza Ghavam; Memar, Bahram; Shahidsales, Soodabeh; Raziee, Hamid Reza; Ghafarzadegan, Kamran; Mohtashami, Samira

    2012-01-01

    Background: Extranodal lymphoma may arise anywhere outside lymph nodes mostly in the gastrointestinal (GI) tract as non-Hodgkin's disease. We reviewed the clinicopathological features and treatment results of patients with primary GI lymphoma. Materials and Methods: A total number of 30 cases with primary GI lymphoma were included in this study. Patients referred to the Radiation Oncology Department of Omid Hospital (Mashhad, Iran) during a 5-year period (2006-11). Clinical, paraclinical, and radiological data was collected from medical records of the patients. Results: Out of the 30 patients with primary GI lymphoma in the study, 12 were female (40%) and 18 were male (60%) (male to female ratio: 3/2). B symptoms were present in 27 patients (90%). Antidiuretic hormone (LDH) levels were elevated in 9 patients (32.1%). The most common primary site was stomach in 14 cases (46.7%). Other common sites included small intestine and colon each in 8 patients (26.7%). All patients had histopathologically proven non-Hodgkin's lymphoma. The most common histologic subtype was diffuse large B-cell lymphoma (DLBL) in 16 patients (53.3%). In addition, 28 patients (93.3%) received chemotherapy with cyclophosphamide, vincristine, doxorubicin, prednisolone (CHOP regimen). The median course of chemotherapy was 6 cources. Moreover, 8 patients (26.7%) received radiotherapy with cobalt 60. The median follow-up time was 26 months. The overall 5-year survival rate was 53% and the median survival time was 60 months. Conclusion: Primary GI lymphoma is commonly seen in stomach and small intestine and mostly is DLBCL or mucosa-associated lymphoid tissue (MALT) lymphoma. PMID:23626617

  11. Gastrointestinal Physiology and Function.

    PubMed

    Greenwood-Van Meerveld, Beverley; Johnson, Anthony C; Grundy, David

    2017-02-08

    The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.

  12. Childhood functional gastrointestinal disorders

    PubMed Central

    Rasquin-Weber, A; Hyman, P; Cucchiara, S; Fleisher, D; Hyams, J; Milla, P; Staiano, A

    1999-01-01

    This is the first attempt at defining criteria for functional gastrointestinal disorders (FGIDs) in infancy, childhood, and adolescence. The decision-making process was as for adults and consisted of arriving at consensus, based on clinical experience. This paper is intended to be a quick reference. The classification system selected differs from the one used in the adult population in that it is organized according to main complaints instead of being organ-targeted. Because the child is still developing, some disorders such as toddler's diarrhea (or functional diarrhea) are linked to certain physiologic stages; others may result from behavioral responses to sphincter function acquisition such as fecal retention; others will only be recognizable after the child is cognitively mature enough to report the symptoms (e.g., dyspepsia). Infant regurgitation, rumination, and cyclic vomiting constitute the vomiting disorders. Abdominal pain disorders are classified as: functional dyspepsia, irritable bowel syndrome (IBS), functional abdominal pain, abdominal migraine, and aerophagia. Disorders of defecation include: infant dyschezia, functional constipation, functional fecal retention, and functional non-retentive fecal soiling. Some disorders, such as IBS and dyspepsia and functional abdominal pain, are exact replications of the adult criteria because there are enough data to confirm that they represent specific and similar disorders in pediatrics. Other disorders not included in the pediatric classification, such as functional biliary disorders, do occur in children; however, existing data are insufficient to warrant including them at the present time. For these disorders, it is suggested that, for the time being, clinicians refer to the criteria established for the adult population.


Keywords: infant vomiting; cyclic vomiting syndrome; functional dyspepsia in children; irritable bowel syndrome in children; functional abdominal pain in children; functional

  13. Acquisition of incidental information during instruction for a response-chain skill.

    PubMed

    Wall, M E; Gast, D L

    1999-01-01

    We examined the acquisition of incidental information and observational learning of incidental information by adolescents with moderate intellectual disabilities during school-directed systematic instruction. Effectiveness of constant time-delay instruction for vocational-skill acquisition was evaluated within a multiple-probe design across six dyads. Dyadic instructional arrangements allowed the assessment of incidental information acquired through observation. The constant time-delay procedure was effective in teaching the target vocational skill. In addition, participants acquired and retained approximately 50% of the incidental information to which they were exposed during the consequent events of constant time-delay instruction either through direct verbal presentation or through observation of their peers' instruction.

  14. 76 FR 35995 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Operation and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-21

    ... Mammals; Taking Marine Mammals Incidental to Operation and Maintenance of the Neptune Liquefied Natural Gas Facility of Massachusetts; Correction AGENCY: National Marine Fisheries Service (NMFS),...

  15. Decellularization of human stromal refractive lenticules for corneal tissue engineering

    PubMed Central

    Yam, Gary Hin-Fai; Yusoff, Nur Zahirah Binte M.; Goh, Tze-Wei; Setiawan, Melina; Lee, Xiao-Wen; Liu, Yu-Chi; Mehta, Jodhbir S.

    2016-01-01

    Small incision lenticule extraction (SMILE) becomes a procedure to correct myopia. The extracted lenticule can be used for other clinical scenarios. To prepare for allogeneic implantation, lenticule decellularization with preserved optical property, stromal architecture and chemistry would be necessary. We evaluated different methods to decellularize thin human corneal stromal lenticules created by femtosecond laser. Treatment with 0.1% sodium dodecylsulfate (SDS) followed by extensive washes was the most efficient protocol to remove cellular and nuclear materials. Empty cell space was found inside the stroma, which displayed aligned collagen fibril architecture similar to native stroma. The SDS-based method was superior to other treatments with hyperosmotic 1.5 M sodium chloride, 0.1% Triton X-100 and nucleases (from 2 to 10 U/ml DNase and RNase) in preserving extracellular matrix content (collagens, glycoproteins and glycosaminoglycans). The stromal transparency and light transmittance was indifferent to untreated lenticules. In vitro recellularization showed that the SDS-treated lenticules supported corneal stromal fibroblast growth. In vivo re-implantation into a rabbit stromal pocket further revealed the safety and biocompatibility of SDS-decellularized lenticules without short- and long-term rejection risk. Our results concluded that femtosecond laser-derived human stromal lenticules decellularized by 0.1% SDS could generate a transplantable bioscaffold with native-like stromal architecture and chemistry. PMID:27210519

  16. A typical presentation of a rare cause of obscure gastrointestinal bleeding

    PubMed Central

    Reuter, Stefan; Bettenworth, Dominik; Mees, Sören Torge; Neumann, Jörg; Beyna, Torsten; Domschke, Wolfram; Wessling, Johannes; Ullerich, Hansjörg

    2011-01-01

    A 52-year-old white woman had suffered from intermittent gastrointestinal (GI) bleeding for one year. Upper GI endoscopy, colonoscopy and peroral double-balloon enteroscopy (DBE) did not detect any bleeding source, suggesting obscure GI bleeding. However, in videocapsule endoscopy a jejunal ulceration without bleeding signs was suspected and this was endoscopically confirmed by another peroral DBE. After transfusion of packed red blood cells, the patient was discharged from our hospital in good general condition. Two weeks later she was readmitted because of another episode of acute bleeding. Multi-detector row computed tomography with 3D reconstruction was performed revealing a jejunal tumor causing lower gastrointestinal bleeding. The patient underwent exploratory laparotomy with partial jejunal resection and end-to-end jejunostomy for reconstruction. Histological examination of the specimen confirmed the diagnosis of a low risk gastrointestinal stromal tumor (GIST). Nine days after surgery the patient was discharged in good health. No signs of gastrointestinal rebleeding occurred in a follow-up of eight months. We herein describe the complex presentation and course of this patient with GIST and also review the current approach to treatment. PMID:21403816

  17. Superficial leiomyomas of the gastrointestinal tract with interstitial cells of Cajal

    PubMed Central

    Janevska, Vesna; Qerimi, Adelina; Basheska, Neli; Stojkova, Elena; Janevski, Vlado; Jovanovic, Rubens; Zhivadinovik, Julija; Spasevska, Liljana

    2015-01-01

    Objective: Some authors suggest common origin of gastrointestinal stromal tumors from stem cells, which may show diverse differentiation. There are reports in which cells morphologically identical to the interstitial cells of Cajal are found in deep leiomyomas. The aim of this study was to demonstrate CD117 positive cells in superficial gastrointestinal (GI) leiomyomas and to find other cells that would suggest diverse differentiation in histologically typical leiomyoma. Materials and methods: We analyzed 8 cases of superficial leiomyomas and one deep leiomyoma, received in our institutions as endoscopically or surgically obtained material. The tumor sections were immunohistochemicaly stained with CD117, CD34, NF, S100, αSMA, desmin, caldesmon and mast cell antigen. Results: All leiomyomas showed diffuse positivity for αSMA, caldesmon and desmin. All of them had CD117 and CD34 positive cells morphologically identical to the interstitial cells of Cajal between smooth muscle fibers, 5 had S-100 and NF positive cells and 2 showed positivity for GFAP. The cells were found in different quantity; they were usually diffusely scattered through the tumors without predilection site, forming small groups in some areas. Conclusion: CD177, CD34, S-100 and NF positive cells are present in superficial leiomyomas and they may suggest common origin of GI stromal tumors. PMID:26884872

  18. Staphylococcus aureus Blepharitis Associated with Multiple Corneal Stromal Microabscess, Stromal Edema, and Uveitis.

    PubMed

    Boto-de-los-Bueis, Ana; del Hierro Zarzuelo, Almudena; García Perea, Adela; de Pablos, Manuela; Pastora, Natalia; Noval, Susana

    2015-04-01

    We report a case of an immunocompetent woman with atypical marginal keratitis. She presented with recurrent episodes of multiples microabscess distributed in a triangular pattern associated with stromal oedema and anterior chamber uveitis, affecting both eyes, but not simultaneously. The episodes responded to steroid drops, corneal inflammation was coincidental with a worsening of her blepharitis in the affected eye and S. aureus was isolated from the lids.

  19. Immunological hallmarks of stromal cells in the tumour microenvironment.

    PubMed

    Turley, Shannon J; Cremasco, Viviana; Astarita, Jillian L

    2015-11-01

    A dynamic and mutualistic interaction between tumour cells and the surrounding stroma promotes the initiation, progression, metastasis and chemoresistance of solid tumours. Far less understood is the relationship between the stroma and tumour-infiltrating leukocytes; however, emerging evidence suggests that the stromal compartment can shape antitumour immunity and responsiveness to immunotherapy. Thus, there is growing interest in elucidating the immunomodulatory roles of the stroma that evolve within the tumour microenvironment. In this Review, we discuss the evidence that stromal determinants interact with leukocytes and influence antitumour immunity, with emphasis on the immunological attributes of stromal cells that may foster their protumorigenic function.

  20. Sex cord-gonadal stromal tumor of the rete testis.

    PubMed

    Sajadi, Kamran P; Dalton, Rory R; Brown, James A

    2009-01-01

    A 34-year-old tetraplegic patient with suppurative epididymitis was found on follow-up examination and ultrasonography to have a testicular mass. The radical orchiectomy specimen contained an undifferentiated spindled sex cord-stromal tumor arising in the rete testis. Testicular sex cord-stromal tumors are far less common than germ cell neoplasms and are usually benign. The close relationship between sex cords and ductules of the rete testis during development provides the opportunity for these uncommon tumors to arise anatomically within the rete tesis. This undifferentiated sex cord-stromal tumor, occurring in a previously unreported location, is an example of an unusual lesion mimicking an intratesticular malignant neoplasm.

  1. Bilateral Sclerosing Stromal Ovarian Tumor in an Adolescent

    PubMed Central

    Naidu, Anjani; Chung, Betty; Simon, Mitchell; Marshall, Ian

    2015-01-01

    Sclerosing stromal tumor of the ovary is a rare, benign, sex cord stromal tumor occurring predominantly in younger women in the 2nd and 3rd decades of life. It typically presents unilaterally with only 2 previously reported cases of bilateral presentation. Common clinical presentations include pelvic or abdominal pain, a mass, or menstrual changes. Although occasionally presenting with hormonal manifestations, virilization as a result of androgen production by the tumor is rare. Here we present an extremely rare case of a sclerosing stromal ovarian tumor in a 14-year-old patient with bilateral presentation and with clinical and biochemical evidence of hyperandrogenemia. PMID:26064755

  2. Gastrointestinal Amyloidosis Presenting with Multiple Episodes of Gastrointestinal Bleeding

    SciTech Connect

    Kim, Sang Hyeon Kang, Eun Ju; Park, Jee Won; Jo, Jung Hyun; Kim, Soo Jin; Cho, Jin Han; Kang, Myong Jin; Park, Byeong Ho

    2009-05-15

    Amyloidosis is characterized by the extracellular deposition of amyloid protein in various organs. Gastrointestinal involvement in amyloidosis is common, but a diagnosis of amyloidosis is often delayed. Severe gastrointestinal hemorrhage in amyloidosis is rare but can be fatal in some cases. We experienced a case of a 49-year-old man who presented with recurrent massive hematochezia. Although embolization was performed eight times for bleeding from different sites of the small intestine, hematochezia did not cease. We report the case, with a review of the literature.

  3. Incidental adenocarcinoma in patients undergoing surgery for stricturing Crohn's disease

    PubMed Central

    Kristo, Ivan; Riss, Stefan; Argeny, Stanislaus; Maschke, Svenja; Chitsabesan, Praminthra; Stift, Anton

    2017-01-01

    AIM To evaluate frequency and clinical course of incidental adenocarcinoma in patients with stricturing Crohn's disease (CD). METHODS In this study, consecutive patients, who were operated on for stricturing CD between 1997-2012, were included at an academic tertiary referral center. Demographic data and clinical course were obtained by an institutional database and individual chart review. Besides baseline characteristics, intraoperative findings and CD related history were also recorded. Colorectal cancer was classified and staged according to the Union for International Cancer Control (UICC). RESULTS During the study period 484 patients underwent resections due to stricturing CD. Incidental adenocarcinoma was histologically confirmed in 6 (1.2%) patients (4 males, 2 females). Patients diagnosed with colorectal cancer had a median age of 43 (27-66) years and a median history of CD of 16 (7-36) years. Malignant lesions were found in the rectum (n = 4, 66.7%), descending colon (n = 1, 16.7%) and ileocolon (n = 1, 16.7%). According to the UICC classification two patients were stages as I (33.3%), whereas the other patients were classified as stage IIA (16.7%), stage IIIB (16.7%), stage IIIC (16.7%) and stage IV (16.7%), respectively. After a median follow-up of 2 (0.03-8) years only 1 patient is still alive. CONCLUSION The frequency of incidental colorectal cancer in patients, who undergo surgery for stenotic CD, is low but associated with poor prognosis. However, surgeons need to be aware about the possibility of malignancy in stricturing CD, especially if localized in the rectum. PMID:28210083

  4. Gastrointestinal Symptoms of Marathon Runners

    PubMed Central

    Keeffe, Emmet B.; Lowe, Daniel K.; Goss, J. Richard; Wayne, Robert

    1984-01-01

    A survey of 707 participants in the 13th Annual Trail's End Marathon in Seaside, Oregon, showed a high incidence of gastrointestinal disturbances, predominantly of the lower tract, associated with long-distance running. The urge to defecate, both during and immediately after running, occurred in over a third of runners. Bowel movements (35%) and diarrhea (19%) were relatively common after running, and runners occasionally interrupted hard runs or races for bowel movements (18%) or diarrhea (10%). Lower gastrointestinal disturbances were more frequent in women than in men and in younger than in older runners. Awareness of the frequency and nature of gastrointestinal symptoms documented by this survey will assist physicians in evaluating abdominal complaints in runners. PMID:6506684

  5. Gastrointestinal symptoms of marathon runners.

    PubMed

    Keeffe, E B; Lowe, D K; Goss, J R; Wayne, R

    1984-10-01

    A survey of 707 participants in the 13th Annual Trail's End Marathon in Seaside, Oregon, showed a high incidence of gastrointestinal disturbances, predominantly of the lower tract, associated with long-distance running. The urge to defecate, both during and immediately after running, occurred in over a third of runners. Bowel movements (35%) and diarrhea (19%) were relatively common after running, and runners occasionally interrupted hard runs or races for bowel movements (18%) or diarrhea (10%). Lower gastrointestinal disturbances were more frequent in women than in men and in younger than in older runners. Awareness of the frequency and nature of gastrointestinal symptoms documented by this survey will assist physicians in evaluating abdominal complaints in runners.

  6. Incidental Intravascular Lipoleiomyomatosis in A Hysterectomy Specimen: How To Manage?

    PubMed Central

    Aslanova, Rakhshanda; Can, Nuray; Okten, Sabri Berkem; Aslan, Mehmet Musa

    2015-01-01

    Leiomyomas are common benign tumors in female gynaecologic surgery. They are originated from smooth muscle cells of the uterus and/or sometimes of the uterine vessels. Intravascular lipoleiomyomatosis is a very rare form of leiomyomas which grow within veins and can extend up to vena cava inferior and right heart chamber with cardiac symptoms and is diagnosed by cardiovascular surgeons. We report a case of incidental intravascular lipoleiomyomatosis which was confined to the uterus being diagnosed after a total abdominal hysterectomy by pathology and its management strategy. PMID:25738043

  7. Incidentally detected clear cell renal cell carcinoma with rhabdoid differentiation.

    PubMed

    Krishnamoorthy, Venkatesh; Gowda, Kiran Krishne; Rao, Raman Narayana

    2016-01-01

    Renal cell carcinoma with rhabdoid differentiation (RCC-R) has an aggressive biologic behavior and poor prognosis. A recent consensus statement of the International Society of Urological Pathology (ISUP) proposed a nucleolar grading system (ISUP grade) for RCC to replace Fuhrman system and recommended reporting the presence of rhabdoid differentiation and considering tumors with rhabdoid differentiation to be ISUP Grade 4. We report a case of incidentally detected clear cell RCC-R in a 52-year-old man. This is one of the earliest cases of RCC-R (pT1b) detected and first such case from Indian subcontinent.

  8. Incidental finding of meningioma on C11-PIB PET.

    PubMed

    Kim, Hee-Young; Kim, Jaeseung; Lee, Jae-Hong

    2012-02-01

    As a healthy volunteer for amyloid imaging study, a 83-year-old woman with no history of neurologic or psychiatric illness underwent carbon 11-labeled Pittsburgh compound-B (PIB) PET, which showed focal increased PIB binding in the right anterior temporal region. This focal PIB uptake turned out to be a mass lesion on MRI, which was consistent with a benign meningioma. This is the first case report on the incidentally found intracranial meningioma by PIB PET scan, highlighting the excellent sensitivity of PIB radiotracer in detecting brain amyloid deposition.

  9. Incidental finding of a giant asymptomatic right atrial tumor

    PubMed Central

    Strecker, Thomas; Agaimy, Abbas; Zelzer, Peter; Weyand, Michael; Wachter, David Lukas

    2014-01-01

    Primary cardiac tumors are very rare, atrial myxoma being the most common benign tumor of the heart. They may present with a great variety of incidental asymptomatic masses to severe life-threatening cardiovascular complications necessitating emergency surgery. Here we report the diagnostic evaluation and successful surgical resection of such a giant cardiac tumor which was found on a routine medical check-up in a 62-year-old patient. Histology confirmed diagnosis of unusually huge myxoma. This article demonstrates it’s necessary to include cardiac tumors in the differential diagnosis of subtle and non-specific cardiothoracic symptoms. PMID:25120848

  10. Incidental Findings in Neuroimaging: Ethical and Medicolegal Considerations.

    PubMed

    Leung, Lawrence

    2013-01-01

    With the rapid advances in neurosciences in the last three decades, there has been an exponential increase in the use of neuroimaging both in basic sciences and clinical research involving human subjects. During routine neuroimaging, incidental findings that are not part of the protocol or scope of research agenda can occur and they often pose a challenge as to how they should be handled to abide by the medicolegal principles of research ethics. This paper reviews the issue from various ethical (do no harm, general duty to rescue, and mutual benefits and owing) and medicolegal perspectives (legal liability, fiduciary duties, Law of Tort, and Law of Contract) with a suggested protocol of approach.

  11. 77 FR 61017 - Draft Habitat Conservation Plan and Application for an Incidental Take Permit, Yamhill County, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-05

    ...'' of the endangered Fender's blue butterfly incidental to otherwise lawful activities associated with... and mitigate the impacts of incidental take of the Fender's blue butterfly caused by covered... regulatory assurances for potential impacts on the Fender's blue butterfly (Icaricia icarioides...

  12. Tissue Digestion for Stromal Cell and Leukocyte Isolation.

    PubMed

    Nayar, Saba; Campos, Joana; Steinthal, Nathalie; Barone, Francesca

    2017-01-01

    Tissue mechanical disruption is often not sufficient to disrupt cell-to-cell interactions; this is particularly relevant for stromal cells that are embedded within the extracellular matrix. For this reason, different enzyme combinations have been described to enable the isolation of single-cell populations, particularly stromal cells. This chapter aims to describe different methods used for enzymatic digestion of stromal cell and leukocyte populations from secondary and tertiary lymphoid organs. Collagenase D and P and collagenase D and dispase protocols provide a good yield of stromal cells, while a collagenase dispase-only protocol should be used if the main aim of the technique is to retrieve leukocyte populations. However, for isolation of both stroma and leukocyte populations the collagenase D and P protocol would provide the best results. Protocols for these techniques and illustrative results from flow cytometry analysis can be found in this chapter.

  13. Effect of hydrocortisone on multipotent human mesenchymal stromal cells.

    PubMed

    Shipunova, N N; Petinati, N A; Drize, N I

    2013-05-01

    We studied the effect of natural glucocorticosteroid hydrocortisone on total cell production, cloning efficiency, and expression of genes important for the function of mesenchymal stromal cells. Addition of hydrocortisone to the culture medium reduces the total cell yield by 2 times and significantly increased cloning efficiency by 2-3 times; this effect was more pronounced in multipotent mesenchymal stromal cells obtained from female donors. Hydrocortisone had no effect on the expression of immunomodulatory factors produced by multipotent mesenchymal stromal cells. Hydrocortisone inhibits the expression of bone differentiation markers, increases the expression of the early adipocyte differentiation marker at the beginning of culturing, and dramatically stimulates the expression of the late adipocyte differentiation marker throughout the culturing period. The findings suggest that hydrocortisone activates multipotent mesenchymal stromal cells.

  14. Stromal infrastructure of the lymph node and coordination of immunity.

    PubMed

    Chang, Jonathan E; Turley, Shannon J

    2015-01-01

    The initiation of adaptive immune responses depends upon the careful maneuvering of lymphocytes and antigen into and within strategically placed lymph nodes (LNs). Non-hematopoietic stromal cells form the cellular infrastructure that directs this process. Once regarded as merely structural features of lymphoid tissues, these cells are now appreciated as essential regulators of immune cell trafficking, fluid flow, and LN homeostasis. Recent advances in the identification and in vivo targeting of specific stromal populations have resulted in striking new insights to the function of stromal cells and reveal a level of complexity previously unrealized. We discuss here recent discoveries that highlight the pivotal role that stromal cells play in orchestrating immune cell homeostasis and adaptive immunity.

  15. Blood thinners and gastrointestinal endoscopy

    PubMed Central

    Ahmed, Monjur

    2016-01-01

    As the number of diagnostic and therapeutic gastrointestinal endoscopies is increasing, and there is an increase in number of patients taking blood thinners, we are seeing more and more patients on blood thinners prior to endoscopic procedures. Gastrointestinal bleeding or thromboembolism can occur in this category of patients in the periendoscopic period. To better manage these patients, endoscopists should have a clear concept about the various blood thinners in the market. Patients’ risk of thromboembolism off anticoagulation, and the risk of bleeding from endoscopic procedures should be assessed prior to endoscopy. The endoscopic procedure should be done when it is safe to do it. PMID:27668068

  16. Incidental Vocabulary Learning in Second Language Acquisition: A Literature Review (Aprendizaje incidental de vocabulario en la adquisición de una segunda lengua: una revisión de literatura)

    ERIC Educational Resources Information Center

    Restrepo Ramos, Falcon Dario

    2015-01-01

    This literature review aims to analyze previous studies that address the incidental learning of vocabulary in second language acquisition. The articles included in this literature review look into the understanding of vocabulary learning through incidental means, the relationship of reading and incidental vocabulary learning, and the strategies…

  17. The Relationship between Experience, Education and Teachers' Use of Incidental Focus-on-Form Techniques

    ERIC Educational Resources Information Center

    Mackey, Alison; Polio, Charlene; McDonough, Kim

    2004-01-01

    This paper reports the findings of an empirical study that explored whether ESL teachers' use of incidental focus-on-form techniques was influenced by their level of experience. The results showed that experienced ESL teachers used more incidental focus-on-form techniques than inexperienced teachers. A follow-up study investigated whether…

  18. 30 CFR 921.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 921.702 Section 921.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE MASSACHUSETTS § 921.702 Exemption for coal extraction incidental to the extraction...

  19. 30 CFR 903.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 903.702 Section 903.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE ARIZONA § 903.702 Exemption for coal extraction incidental to the extraction of...

  20. 30 CFR 933.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 933.702 Section 933.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE NORTH CAROLINA § 933.702 Exemption for coal extraction incidental to the extraction...

  1. 30 CFR 941.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 941.702 Section 941.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE SOUTH DAKOTA § 941.702 Exemption for coal extraction incidental to the extraction...

  2. 30 CFR 947.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 947.702 Section 947.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE WASHINGTON § 947.702 Exemption for coal extraction incidental to the extraction...

  3. 30 CFR 912.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 912.702 Section 912.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE IDAHO § 912.702 Exemption for coal extraction incidental to the extraction of...

  4. 30 CFR 922.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 922.702 Section 922.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE MICHIGAN § 922.702 Exemption for coal extraction incidental to the extraction of...

  5. 30 CFR 937.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 937.702 Section 937.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE OREGON § 937.702 Exemption for coal extraction incidental to the extraction of...

  6. 30 CFR 942.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 942.702 Section 942.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE TENNESSEE § 942.702 Exemption for coal extraction incidental to the extraction of...

  7. 30 CFR 939.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 939.702 Section 939.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE RHODE ISLAND § 939.702 Exemption for coal extraction incidental to the extraction...

  8. 30 CFR 905.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 905.702 Section 905.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE CALIFORNIA § 905.702 Exemption for coal extraction incidental to the extraction...

  9. 30 CFR 910.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 910.702 Section 910.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... WITHIN EACH STATE GEORGIA § 910.702 Exemption for coal extraction incidental to the extraction of...

  10. The Effects of Distance Education and Student Involvement on Incidental Learning

    ERIC Educational Resources Information Center

    Konetes, George D.

    2011-01-01

    Incidental learning is an occurrence that is not generally accounted for using the traditional methods of instructional objectives and outcomes assessment. This type of learning occurs in part as a product of social interaction and active involvement in both online and onsite courses. This study examines various incidental learning outcomes and…

  11. 77 FR 31062 - Programs To Reduce Incidental Capture of Sea Turtles in Shrimp Fisheries; Certifications Pursuant...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ... of Sea Turtles in Shrimp Fisheries; Certifications Pursuant to Public Law 101-162 SUMMARY: On April... nations have adopted programs to reduce the incidental capture of sea turtles in their shrimp fisheries... environments in 26 other countries and one economy do not pose a threat of the incidental taking of sea...

  12. 19 CFR 148.17 - Declaration on arrival incidental to further foreign travel.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... foreign travel. 148.17 Section 148.17 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF... § 148.17 Declaration on arrival incidental to further foreign travel. (a) Declaration on incidental arrival. A resident who enters the United States merely as an incident of foreign travel and who...

  13. 50 CFR 18.24 - Taking incidental to commercial fishing operations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Taking incidental to commercial fishing operations. 18.24 Section 18.24 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF... IMPORTATION OF WILDLIFE AND PLANTS (CONTINUED) MARINE MAMMALS General Exceptions § 18.24 Taking incidental...

  14. 78 FR 15374 - Notice of Availability of Draft Habitat Conservation Plan; Receipt of Application for Incidental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-11

    ... would authorize incidental take of the federally endangered Hine's Emerald Dragonfly (hereafter ``HED... the Hine's Emerald Dragonfly (hereafter ``HED''; Somatochlora hineana). Under the ESA, we announce... conducted for Hine's Emerald Dragonfly at the project site. An Incidental Take Permit is being...

  15. Spectrum of intracranial incidental findings on pediatric brain magnetic resonance imaging: What clinician should know?

    PubMed Central

    Gupta, Surya N; Gupta, Vikash S; White, Andrew C

    2016-01-01

    Intracranial incidental findings on magnetic resonance imaging (MRI) of the brain continue to generate interest in healthy control, research, and clinical subjects. However, in clinical practice, the discovery of incidental findings acts as a “distractor”. This review is based on existing heterogeneous reports, their clinical implications, and how the results of incidental findings influence clinical management. This draws attention to the followings: (1) the prevalence of clinically significant incidental findings is low; (2) there is a lack of a systematic approach to classification; and discusses (3) how to deal with the detected incidental findings based a proposed common clinical profile. Individualized neurological care requires an active discussion regarding the need for neuroimaging. Clinical significance of incidental findings should be decided based on lesion’s neuroradiologic characteristics in the given clinical context. Available evidence suggests that the outcome of an incidentally found “serious lesion in children” is excellent. Future studies of intracranial incidental findings on pediatric brain MRI should be focused on a homogeneous population. The study should address this clinical knowledge based review powered by the statistical analyses. PMID:27610341

  16. 75 FR 39335 - Incidental Takes of Marine Mammals During Specified Activities; Marine Seismic Survey in the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-08

    ...NMFS has received an application from the U.S. Geological Survey (USGS) for an Incidental Harassment Authorization (IHA) to take small numbers of marine mammals, by harassment, incidental to conducting a marine seismic survey in the Arctic Ocean during August to September, 2010. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS requests comments on its proposal to authorize USGS to......

  17. 30 CFR 905.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 905.702 Section 905.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction...

  18. 30 CFR 903.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 903.702 Section 903.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

  19. 30 CFR 922.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 922.702 Section 922.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

  20. 30 CFR 921.702 - Exemption for coal extraction incidental to the extraction of other minerals.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Exemption for coal extraction incidental to the extraction of other minerals. 921.702 Section 921.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of the chapter, Exemption for Coal Extraction Incidental to the Extraction...