[Treatment progress of gastrointestinal stromal tumor].

PubMed

Ji, Xin; Ji, Jia-fu

2013-03-01

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Its pathogenesis is defined by mutations within the KIT and PDGFRα gene. Surgical resection is the only radical treatment at present, but recurrence is common. In recent years, targeted therapy with imatinib mesylate, which inhibits KIT kinase activity, represents the other cornerstone for the treatment of GIST. For resectable GIST, operation combined with neoadjuvant and adjuvant therapy with imatinib mesylate or other tyrosine kinase inhibitors can improve the prognosis of high-risk patients before or after complete resection. For unresectable GIST, targeted therapy with imatinib mesylate can effectively inhibit and ameliorate the progression of GIST.

[Obscure gastrointestinal bleeding due to gastrointestinal stromal tumors].

PubMed

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

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

Management of hemorrhage in gastrointestinal stromal tumors: a review

PubMed Central

Liu, Qi; Kong, Fanmin; Zhou, Jianping; Dong, Ming; Dong, Qi

2018-01-01

Gastrointestinal stromal tumors (GISTs) are relatively common mesenchymal tumors. They originate from the wall of hollow viscera and may be found in any part of the digestive tract. The prognosis of patients with stromal tumors depends on various risk factors, including size, location, presence of mitotic figures, and tumor rupture. Emergency surgery is often required for stromal tumors with hemorrhage. The current literature suggests that stromal tumor hemorrhage indicates poor prognosis. Although the optimal treatment options for hemorrhagic GISTs are based on surgical experience, there remains controversy with regard to optimum postoperative management as well as the classification of malignant potential. This article reviews the biological characteristics, diagnostic features, prognostic factors, treatment, and postoperative management of GISTs with hemorrhage. PMID:29695930

Management of resectable gastrointestinal stromal tumor.

PubMed

Chaudhry, Umer I; DeMatteo, Ronald P

2009-02-01

Gastrointestinal stromal tumor (GIST) is a rare neoplasm that recently has become an intense focus of scientific investigation, as it serves as a model for the molecular therapy for cancer. Although surgery remains the principle treatment of primary localized GIST, imatinib mesylate, a selective inhibitor of KIT protein, achieves dramatic responses in metastatic GIST. Multimodality therapy integrating surgery and molecular therapy has shown promise. This article summarizes the epidemiology, clinicopathologic features, natural history, and clinical management of GIST.

Gastrointestinal Stromal Tumors Treatment (PDQ®)—Health Professional Version

Cancer.gov

Gastrointestinal stromal tumor (GIST) treatment depends on the extent of disease and may involve surgery and/or tyrosine kinase inhibitors. Get detailed information about the diagnosis, prognosis, and treatment of newly diagnosed and recurrent GIST in this summary for clinicians.

Gastrointestinal stromal tumor of Meckel's diverticulum: a rare cause of intestinal volvulus.

PubMed

Cengız, Fevzi; Sun, Mehmet Ali; Esen, Özgür Sipahi; Erkan, Nazif

2012-08-01

Meckel's diverticulum is the most common congenital abnormality of the gastrointestinal tract. Most cases are asymptomatic; however, when symptomatic, it is often misdiagnosed at presentation. Common complications presenting in adults include bleeding, obstruction, diverticulitis, and perforation. Tumors within a Meckel's diverticulum are rare. Herein, we present a gastrointestinal stromal tumor arising from the Meckel's diverticulum that led to intestinal obstruction by volvulus.

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. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd.. All rights reserved.

Aggressive gastrointestinal stromal tumor with spinal metastases: a case report.

PubMed

Waterman, Brian R; Kusnezov, Nicholas; Dunn, John C; Hakim, M Nawar

2015-05-01

We report a case of a 56-year-old male who presented with several month history of severe low back pain. Physical examination revealed generalized tenderness at his thoracolumbar spine without notable neuromuscular findings. Radiographs revealed a chronic compression fracture of T10 and T11 with anterior height loss. Subsequent magnetic resonance imaging demonstrated multiple lytic lesions in the thoracolumbar spine without canal compromise. During his hospital stay, he developed acute cord compression with loss of motor and sensory levels below T12 and an absence of sphincter tone. The patient was taken for emergent multilevel, posterior decompression and fusion with biopsy of the lesion. Microscopic examination of the tissue in addition to immunohistochemical analysis utilizing CD117-antibody/c-kit revealed gastrointestinal stromal tumor. Further workup revealed the primary tumor to be intra-abdominal and the patient was subsequently begun on adjuvant chemotherapy. Gastrointestinal stromal tumors should be considered in the workup of patients with bone metastasis with an unknown primary malignancy. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Characteristics of Emergency Gastrointestinal Stromal Tumor (GIST).

PubMed

Uçar, Ahmet Deniz; Oymaci, Erkan; Carti, Erdem Bariş; Yakan, Savaş; Vardar, Enver; Erkan, Nazif; Mehmet, Yildirim

2015-05-01

Gastrointestinal Stromal Tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT). Importance of GISTs is increasing while surgeons are facing with more frequent either in emergency setting of elective cases. Delineating the presentation and management of emergency GIST is important. From 2005 to 2014, emergency cases with final diagnosis of GIST were examined retrospectively. Total of 13 operated cases were evaluated by patients characteristics, clinical presentation, operational findings and postoperative prognosis. There were 9 male and 4 female with the mean age of 48.15 years. The most frequent presentations are ileus and GIT hemorrhage both covering the 84% of patients. Small bowel was the dominating site with ileus. Stomach was the second frequent site of the disease with the finding of hemorrhage. Emergency patients are more likely to come with small bowel GIST and obstruction symptoms. Hemorrhage is the most frequent symptom for emergency GIST of stomach and duodenum.

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review

PubMed Central

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-01-01

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature. PMID:20805952

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review.

PubMed

Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-07-26

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature.

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

PubMed Central

Muñoz, Mario; Ramirez, Pedro T.; Echeverri, Carolina; Álvarez, Luis Guillermo; Palomino, Maria Alejandra

2012-01-01

Objective To report the clinical presentation and oncologic outcomes of a series of patients who presented with an abdominal or pelvic mass and were diagnosed with a gastrointestinal stromal tumor (GIST). Methods Data were obtained on all patients who presented with an abdominal or pelvic mass between September 2007 and June 2010 and who were ultimately diagnosed with a GIST. The patients' medical records were reviewed. A literature review was also conducted. Results Six patients were identified who met the inclusion criteria. All six patients had a tumor in the intestinal tract arising from the small bowel. The mean tumor size was 12 cm (range, 6 to 22 cm). A complete resection was achieved in five of the six patients. There were no intraoperative complications; one patient had a postoperative complication. Two patients were treated with imatinib after surgery. The mean follow-up time was 32 months (range, 0.3 to 40 months). At the last follow-up, five of the six patients were without any evidence of disease. One patient died of an unrelated hepatic encephalopathy. The incidence in our institution is 3%. Conclusion GISTs are uncommon; however, they should be considered in the differential diagnosis of patients presenting with an abdominal or pelvic mass. PMID:22355467

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

PubMed

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

2012-01-01

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

Mesenteric fibromatosis with intestinal involvement mimicking a gastrointestinal stromal tumour

PubMed Central

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

2011-01-01

Introduction Mesenteric fibromatosis or intra-abdominal desmoid tumour is a rare proliferative disease affecting the mesentery. It is a locally aggressive tumour that lacks metastatic potential, but the local recurrence is common. Mesenteric fibromatosis with the intestinal involvement can be easily confused with other primary gastrointestinal tumours, especially with that of the mesenchymal origin. Case report We report a case of a 44-year-old female who presented with an abdominal mass that radiologically and pathologically mimicked a gastrointestinal stromal tumour. Conclusions The diagnosis of mesenteric fibromatosis should always be considered in the case of mesenchymal tumours apparently originating from the bowel wall that diffusely infiltrate the mesentery. PMID:22933936

Coexistence of gastrointestinal stromal tumors and gastric adenocarcinomas.

PubMed

Yan, Yan; Li, Ziyu; Liu, Yiqiang; Zhang, Lianhai; Li, Jiyou; Ji, Jiafu

2013-04-01

The purpose of this study is to detect the clinicopathology of gastrointestinal stromal tumors (GISTs) occurring synchronously with gastric adenocarcinomas and to unveil the potential underlying relationship between the synchronous GIST and gastric adenocarcinoma. This study included 15 patients with incidental GISTs found during operations for gastric adenocarcinoma and 30 patients who underwent gastrectomy for gastric cancer without discovering GIST between January 2005 and December 2010 at the Beijing Cancer Institute. We collected the clinicopathological data and analyzed the KIT/PDGFRA mutational status of GISTs, corresponding gastric adenocarcinoma specimens, and the normal tissue around the cancer lesions. Additionally, as a control group, the mutational status of the patients with gastric adenocarcinoma and no other tumors was assayed. Overall, 18 GISTs were found in 15 gastric adenocarcinoma patients. Multiple GIST lesions were found in three cases (20 %). The patients' age ranged from 46 to 85 years, with an average of 67.6 years. The average size of the GISTs was 0.85 cm. All mesenchymal lesions showed low proliferative activity, were of low or very low risk, and were identified as CD117-positive by immunostaining. In GIST lesions, mutations in KIT were detected in 7 out of 13 cases, and of these mutations, 6 were found in exon 11 (46.2 %), and 1 was found in exon 9 (7.7 %). A total of five deletions and one point mutation were in exon 11, and one insertion was in exon 9. Mutations were not detected in exon 17 or 13 of KIT. There was no remarkable mutation analyzed in the gastric adenocarcinoma lesions or normal tissues from either the test or control groups. Clinicopathological profiles and molecular analysis of KIT/PDGFRA showed no obvious relationship between gastric cancer and GISTs in tumor genesis, such as similar oncogene mutations.

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.

[Intestinal intussusception due to ileal gastrointestinal stromal tumor--a case report].

PubMed

Andrei, S; Andrei, A; Tonea, A; Andronesi, D; Preda, C; Herlea, V; Popescu, I

2011-01-01

Intestinal occlusion due to intussusception produced by intestinal tumors is a very rare condition. Gastrointestinal stromal tumors are also rare digestive neopasias, with an impredictable malignant behavior, which are usually growing outside the intestinal wall, being rarely the initiators of an intestinal intussusception. We present the case of a 59 years old female, admitted in our hospital to elucidate the etiology of her iron deficient anaemia, which developed an intestinal occlusion at the intestinal preparation for colonoscopy. The abdominal CT scan performed in emergency conditions highlighted occlusive intestinal tumor complicated with intestinal intussusception. We performed an emergency laparotomy that revealed intestinal occlusion due to ileo-ileal intussusception produced by an ileal tumor. The surgical intervention consisted in segmental ileal enterectomy including the tumor with latero-lateral entero-enteral anastomosis. The patient recovered without complications. The histopathological and immunohisto-chemical examinations established the diagnose of gastro-intestinal stromal tumor with high risk malignant behavior, therefore the patient was guided in the oncological department for specific treatment and oncological surveillance.

A gastrointestinal stromal tumour with pulmonary metastases mimicking unilateral gynaecomastia

PubMed Central

Guler Cimen, Sanem; MacDonald, Frank; Cimen, Sertac; Molinari, Michele

2013-01-01

Gastrointestinal stromal tumours (GISTs) represent 1% of primary gastrointestinal cancers. These neoplasms most frequently metastasise to the liver and peritoneum and rarely to the lungs and bones. Treatment of unresectable GISTs involves systemic chemotherapy with tyrosine kinase inhibitors, imatinib and sunitinib being first-line and second-line drugs. We report the case of a 52-year-old man with GIST who developed a right-sided subareolar breast swelling and subsequently discovered to be an invasive metastatic pulmonary GIST. Given that gynaecomastia is a known adverse effect of imatinib and sunitinib, this case report illustrates the importance of including metastatic disease in the differential diagnosis of patients with GIST and with the new onset of soft tissue masses. PMID:24343802

A gastrointestinal stromal tumour with pulmonary metastases mimicking unilateral gynaecomastia.

PubMed

Cimen, Sanem Guler; MacDonald, Frank; Cimen, Sertac; Molinari, Michele

2013-12-16

Gastrointestinal stromal tumours (GISTs) represent 1% of primary gastrointestinal cancers. These neoplasms most frequently metastasise to the liver and peritoneum and rarely to the lungs and bones. Treatment of unresectable GISTs involves systemic chemotherapy with tyrosine kinase inhibitors, imatinib and sunitinib being first-line and second-line drugs. We report the case of a 52-year-old man with GIST who developed a right-sided subareolar breast swelling and subsequently discovered to be an invasive metastatic pulmonary GIST. Given that gynaecomastia is a known adverse effect of imatinib and sunitinib, this case report illustrates the importance of including metastatic disease in the differential diagnosis of patients with GIST and with the new onset of soft tissue masses.

Pancreas-preserving segmental duodenectomy for gastrointestinal stromal tumor of the duodenum and splenectomy for splenic angiosarcoma.

PubMed

Muroni, Mirko; Ravaioli, Matteo; Del Gaudio, Massimo; Nigri, Giuseppe; D'Angelo, Francesco; Uccini, Stefania; Ramacciato, Giovanni

2012-06-01

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract and occur rarely in the duodenum. Splenic angiosarcoma is an aggressive neoplasm with an extremely poor prognosis. We report a case of a 70-year-old man hospitalized for abdominal pain in the upper quadrants, dyspepsia and nausea, previously treated for Hodgkin lymphoma 30 years ago. Abdominal CT showed a solid nodular lesion in the third portion of the duodenum, the presence of retropancreatic, aortic and caval lymph nodes, and four nodular splenic masses. (111)In-octreotide scintigraphy revealed pathological tissue accumulation in the duodenal region, and in the retropancreatic, retroduodenal, aortic and caval lymph nodes, suggesting a nonfunctioning neuroendocrine peripancreatic tumor. At exploratory laparotomy, an exophytic soft tumor was found originating from the third portion of the duodenum. Pancreas-preserving duodenectomy with duodenojejunostomy, splenectomy and lymphnodectomy of retropancreatic aortic and caval lymph nodes were performed. Pathological evaluation and immunohistochemical studies showed the presence of a duodenal gastrointestinal stromal tumor with low mitotic activity and a well-differentiated angiosarcoma localized to the spleen and invading lymph nodes. We speculated that the angiosarcoma and duodenal gastrointestinal stromal tumors of this patient were due to the treatment of Hodgkin lymphoma with radiotherapy 30 years ago. Pancreas-preserving segmental duodenectomy can be used to treat non-malignant neoplasms of the duodenum and avoid extensive surgery. Splenectomy is the treatment of choice for localized angiosarcomas but a strict follow-up is mandatory because of the possibility of recurrence.

Gastrointestinal Stromal Tumors - Diagnosis and Surgical Treatment.

PubMed

Alecu, L; Tulin, A; Enciu, O; Bărbulescu, M; Ursuţ, B; Obrocea, F

2015-01-01

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, previously classified as leiomyomas, leiomyosarcomas, leiomyoblastomas or schwannomas. They are now recognized as a distinct entity with origin in the mesodermal interstitial cell of Cajal, cells that express the c-KIT protein (tirozine kinase receptor). The definitive diagnosis is established by immunohistochemistry, more than 95% of GISTs being positive for CD117. Despite the major progress of chemotherapy, the treatment of choice is surgery, and it implies the complete resection of the tumor. The evolution of these tumors is unpredictable and the prognosis depends on localization, tumor size and mitotic index. Benign tumors have an excellent prognosis after surgery, with a 5 year survival of 90%, while malignant tumors resistant to radiotherapy and chemotherapy have a dismal prognosis even after surgical resection, with a median survival of 1 year. We studied a group of 15 patients diagnosed with TSGI in the Surgery Clinic of the œProf. Dr. Agrippa Ionescu Clinical Emergency Hospital, between 2003 and 2013, following the particularities of presentation, diagnosis and treatment, with focus on the prognostic factors according to available literature data. Celsius.

The diagnostic importance of matrix metalloproteinase-7 and nestin in gastrointestinal stromal tumors

PubMed Central

Peker, Kemal; Sayar, Ilyas; Gelincik, İbrahim; Bulut, Gülay; Ünal, Tuba Dilay Kökenek; Şenol, Serkan; Gökçe, Aysun; Isik, Arda

2014-01-01

Background The importance of the matrix metalloproteinase-7 (MMP-7) and nestin immunomarkers, C-kit proto-oncogene (CD117), and the efficiency of the Ki-67 proliferation index for gastrointestinal stromal tumors were evaluated. Material/Methods This study was conducted by examining the microscope slides of 72 patients with gastrointestinal stromal tumors that were sent to the pathology laboratory between 2007 and 2012. Immunohistochemical staining for CD117, MMP-7, nestin, and marker of proliferation Ki-67 was performed. The correlations between the positive results for Ki-67, CD117, MMP-7, and nestin were evaluated relative to the tumor characteristics of size, localization, grade, cellular type, cellularity, cytology type, growth pattern, ulceration, necrosis, hemorrhage, invasion depth, and lymph node metastasis. Results The tumor was localized in the stomach in 42 of the patients, the intestines in 19, the colon in 7, and the rectum in 4. Comparisons among the groups showed that MMP-7 was correlated with the tumor grade (p<0.001), cellularity (p<0.009), cytologic atypia (p<0.001), ulceration (p=0.002), necrosis (p<0.001), and tumor size (p=0.001). Nestin was correlated with the tumor grade (p=0.013), and tumor size (p=0.024). Correlations among CD117, MMP-7, nestin, and Ki-67 were examined. Nestin and Ki-67 were both significantly correlated with CD117 and MMP-7 [(r=0.279, p=0.018), (r=0.322, p=0.006), (r=0.386, p=0.001), (r=0.386, p=0.002)], respectively. Conclusions MMP-7 and nestin may be beneficial as markers, given their sensitivity to gastrointestinal stromal tumors. PMID:24755685

A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis to the cervix uteri

PubMed Central

Gupta, Nupur; Mittal, Suneeta; Lal, Neena; Misra, Renu; Kumar, Lalit; Bhalla, Sunita

2007-01-01

Background Gastrointestinal stromal tumors are CD117 (C Kit) positive mesenchymal neoplasms, that may arise anywhere in the gastrointestinal tract. Their current therapy is imatinib mesylate before or after surgery. Case presentation We describe a case of 17-year-old female with metastasis to the cervix uteri of a primary mesenteric gastrointestinal tumor. Conclusion Surgery remains the mainstay of known curative treatment. The manifestations of GIST are not restricted to the typical locations within the bowel; may have very unusual metastatic sites or infiltrations per continuitatem. PMID:18045506

Pancreatic Gastrointestinal Stromal Tumor after Upper Gastrointestinal Hemorrhage and Performance of Whipple Procedure: A Case Report and Literature Review.

PubMed

Aziret, Mehmet; Çetinkünar, Süleyman; Aktaş, Elife; İrkörücü, Oktay; Bali, İlhan; Erdem, Hasan

2015-08-03

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal system. These types of tumors originate from any part of the tract as well as from the intestine, colon, omentum, mesentery or retroperitoneum. GIST is a rare tumor compared to other types of tumors, accounting for less than 1% of all gastrointestinal tumors. A 56-year-old male patient was hospitalized due to an upper gastrointestinal hemorrhage and the start of abdominal pain on the same day. In the upper gastrointestinal endoscopy that was performed, a solitary mass was found in the second section of the duodenum and a blood vessel (Forrest type 2a) was seen. The extent and location of the mass was detected by abdominal tomography. After hemodynamic recovery, a Whipple procedure was performed without any complications. A subsequent histopathological examination detected a c-kit-positive (CD117) pancreatic GIST with high mitotic index. The most effective treatment method for GISTs is surgical resection. In patients with a head of pancreatic GIST, the Whipple procedure can be used more safely and effectively.

Gastrointestinal Stromal Tumors: Management of metastatic disease and emerging therapies

PubMed Central

Vadakara, Joseph

2013-01-01

Synopsis Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Prior to the advent of tyrosine kinase inhibitors like imatinib, there were few treatment options available to patients with metastatic GIST. Surgery was the mainstay of treatment and the prognosis for patients with metastatic GIST was dismal. With the advent of imatinib the prognosis of metastatic GIST has improved dramatically. Second line tyrosine kinase inhibitors (TKI) such as sunitinib and regorafenib have further bettered prognosis, however there is still a need for therapies for patients with disease refractory to TKI therapy. Newer agents such as the Hsp90 inhibitors, PI3K-AKT-mTOR inhibitors and IGF1-R inhibitors are currently under investigation and may have promise. This review discusses the current standard of care in terms of pharmacotherapy, both standard and investigational (summarized in Box 1), in the management of metastatic GIST. PMID:24093167

Ocular side effects associated with imatinib mesylate and perifosine for gastrointestinal stromal tumor.

PubMed

Dogan, S Serdar; Esmaeli, Bita

2009-02-01

Imatinib mesylate and perifosine are two relatively new drugs that have improved outcomes for patients with gastrointestinal stromal tumors in recent years. The ocular side effects of these two drugs are discussed in this chapter. The most common ocular side effect associated with imatinib mesylate is periorbital edema. Perifosine has been associated with a ring-shaped perilimbal corneal ulceration that can be treated with topical steroids and topical antibiotics.

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

C-kit mutations in gastrointestinal stromal tumours.

PubMed

Morey, Adrienne L; Wanigesekera, G David; Hawkins, Nicholas J; Ward, Robyn L

2002-08-01

Gastrointestinal stromal tumours (GISTs), once assumed to be of smooth muscle origin, generally express CD117 and CD34, similar to the interstitial cells of Cajal. Assessment of malignant potential in GISTs is problematic, especially on small biopsies. Some recent data indicate that mutations in the juxtamembrane domain (exon 11) of the c-kit (CD117) proto-oncogene may be associated with a worse prognosis. In this study, the frequency of c-kit exon 11 mutations has been determined in a series of 18 gut stromal tumours. Immunophenotype was assessed by immunoperoxidase stains for smooth muscle actin, desmin, S100, CD34 and CD117, and each tumour classified as being of low, uncertain (intermediate) or high malignant potential based on standard histological criteria. DNA from each tumour was extracted from fresh (n = 5) or formalin-fixed, paraffin-embedded (n= 13) tissues using the direct lysis method. Exon 11 was amplified by PCR and sequencing of both sense and antisense strands was performed on two occasions using an ABI 377 sequencer. Mutations in exon 11 were detected in three of 14 confirmed GISTs, two being point mutations at codon 560 and one a 3-bp deletion resulting in the in-frame deletion of glutamine at codon 561. All three tumours were of high or intermediate malignant potential histologically. Three other 'high risk' primary GISTs and a metastatic GIST deposit were negative for exon 11 mutations. Data on this relatively small cohort of Australian patients indicate that c-kit exon 11 mutation analysis does not correlate well with histological assessment of malignant potential, and cannot be regarded as a reliable objective marker for poor prognosis in GISTs.

C-kit-positive gastric metastasis of lobular carcinoma of the breast masquerading as gastrointestinal stromal tumor.

PubMed

Vennapusa, Bharathi; Oman, Sarah A; Parasher, Gulshan; Cerilli, Lisa A

2010-10-01

A 61-year-old woman with no significant past history underwent gastric biopsies demonstrating a strongly c-kit-positive epithelioid malignancy, initially thought to represent gastrointestinal stromal tumor (GIST). Subsequent clinical and immunohistochemical evaluation proved the neoplasm to represent metastatic lobular carcinoma. This case illustrates that although c-kit is highly specific and sensitive for GIST, its expression may occur in a variety of other neoplasms, some of which morphologically resemble GIST and may present in the gastrointestinal tract as metastases. Therefore, a review of other c-kit-positive lesions is also highlighted.

Robotic pancreaticoduodenectomy in a case of duodenal gastrointestinal stromal tumor.

PubMed

Parisi, Amilcare; Desiderio, Jacopo; Trastulli, Stefano; Grassi, Veronica; Ricci, Francesco; Farinacci, Federico; Cacurri, Alban; Castellani, Elisa; Corsi, Alessia; Renzi, Claudio; Barberini, Francesco; D'Andrea, Vito; Santoro, Alberto; Cirocchi, Roberto

2014-12-04

Laparoscopic pancreaticoduodenectomy is rarely performed, and it has not been particularly successful due to its technical complexity. The objective of this study is to highlight how robotic surgery could improve a minimally invasive approach and to expose the usefulness of robotic surgery even in complex surgical procedures. The surgical technique employed in our center to perform a pancreaticoduodenectomy, which was by means of the da Vinci™ robotic system in order to remove a duodenal gastrointestinal stromal tumor, is reported. Robotic technology has improved significantly over the traditional laparoscopic approach, representing an evolution of minimally invasive techniques, allowing procedures to be safely performed that are still considered to be scarcely feasible or reproducible.

Gastrointestinal Stromal Tumors: Clinical Symptoms, Location, Metastasis Formation, and Associated Malignancies in a Single Center Retrospective Study.

PubMed

Aghdassi, Ali; Christoph, Agnes; Dombrowski, Frank; Döring, Paula; Barth, Christoph; Christoph, Jan; Lerch, Markus M; Simon, Peter

2018-06-05

Gastrointestinal stromal tumors (GISTs) are rare malignancies but the most common mesenchymal tumors of the digestive tract. Recent advances in diagnostic imaging and an increasing incidence will confront us more frequently with stromal tumors. This single center study aimed to characterize GIST patients in terms of tumor location, clinical presentation, metastasis formation, as well as associated secondary malignancies. In a retrospective study, 104 patients with a histologically confirmed diagnosis of GIST, collected between 1993 and 2011, were characterized for several clinical features. The most common GIST location was the stomach (67.6%) followed by the small intestine (16.2%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most frequently reported symptoms whereas about one-third of patients remained clinically asymptomatic (31.6%); 14.4% of patients had either synchronous or metachronous metastases and there was a significant prevalence also in the low risk group. The proportion of secondary malignant associated neoplasms was 31% in our GIST cohort, among which gastrointestinal, genitourinary tumors, and breast cancer were the most prevalent. There was a considerable risk for metastasis formation and the development of secondary neoplasias that should encourage discussion about the appropriate surveillance strategy after surgery for GIST. © 2018 S. Karger AG, Basel.

Germline mutations of KIT in gastrointestinal stromal tumor (GIST) and mastocytosis.

PubMed

Ke, Hengning; Kazi, Julhash U; Zhao, Hui; Sun, Jianmin

2016-01-01

Somatic mutations of KIT are frequently found in mastocytosis and gastrointestinal stromal tumor (GIST), while germline mutations of KIT are rare, and only found in few cases of familial GIST and mastocytosis. Although ligand-independent activation is the common feature of KIT mutations, the phenotypes mediated by various germline KIT mutations are different. Germline KIT mutations affect different tissues such as interstitial cells of Cajal (ICC), mast cells or melanocytes, and thereby lead to GIST, mastocytosis, or abnormal pigmentation. In this review, we summarize germline KIT mutations in familial mastocytosis and GIST and discuss the possible cellular context dependent transforming activity of KIT mutations.

[Gastrointestinal stromal tumor with primary hepatic unique location--clinical case].

PubMed

Alecu, L; Tulin, A; Ursut, Beatrice; Ursut, B; Oproiu, Al; Obrocea, F; Ionescu, M

2011-01-01

The gastrointestinal stromal tumors are mesenchymal tumors whose primary extradigestive location is very rare (less than 10% primary liver localization). We present a clinical case of primary hepatic location of GIST in a 28 year-old patient. The discovery of this tumor is a chance, the patient presenting for non-specific dyspeptic syndrome and epigastralgia. During the presentation an abdominal ultrasound is performed which identifies an whell-delineated hepatic mass - 5/4 cm. Clinical and paraclinical investigations (CT, EDS, EDI, examination of the intestinal lumen with the videocapsula), confirm the diagnosis of unique hepatic mass of segments III-IV. The diagnosis is confirmed intraoperatory and we perform an atypical liver resection of segments III-IV (with 1 cm safety-margin). The histopatologic exam: GIST.

Extragastrointestinal Stromal Tumor during Pregnacy.

PubMed

Gözükara, Ilay; Dilek, T U Kutlu; Durukan, Hüseyin; Düsmez Apa, Duygu; Kabil Kucur, Suna; Dilek, Saffet

2012-01-01

Extragastrointestinal stromal tumors (EGISTs) are mesenchymal neoplasms without connection to the gastrointestinal tract. Gastrointestinal stromal tumors (GISTs) and EGIST are similar according to their clinicopathologic and histomorphologic features. Both of them most often express immunoreactivity for CD-117, a c-kit proto-oncogene protein. The coexistence of GIST and pregnancy is very rare, with only two cases reported in the literature. In this paper, we presented the first EGIST case during pregnancy in the literature.

Imatinib mesylate: in the treatment of gastrointestinal stromal tumours.

PubMed

Croom, Katherine F; Perry, Caroline M

2003-01-01

Imatinib mesylate (imatinib) is an orally administered competitive inhibitor of the tyrosine kinases associated with the KIT protein (stem cell factor receptor), ABL protein and platelet-derived growth factor receptors. The KIT tyrosine kinase is abnormally expressed in gastrointestinal stromal tumour (GIST), a rare neoplasm for which there has been no effective systemic therapy. In a randomised, nonblind, multicentre study that evaluated imatinib 400 or 600mg once daily in 147 patients with advanced GIST, confirmed partial responses were achieved in 54% of patients overall (median duration of follow-up was 288 days). Stable disease was experienced by 28% of patients and the estimated 1-year survival rate was 88%. Similar response rates were reported in a smaller, dose-escalation study, in which objective tumour response was a secondary endpoint. Although nearly all patients with GIST treated with imatinib experienced adverse events, most events were mild or moderate in nature. Severe or serious adverse events occurred in 21% of patients in the larger study, and included gastrointestinal or tumour haemorrhage. The control of cellular processes, such as cell growth, division and death, involves signal transduction, which commonly involves the transfer of phosphate from adenosine triphosphate (ATP) to tyrosine residues on substrate proteins, by tyrosine kinase enzymes. Activation of oncogenes coding for kinase proteins can lead to the production of kinases that are continually active in the absence of a normal stimulus,leading to increased cell proliferation and/or decreased apoptosis. A major focus of cancer research in recent years has been to identify oncogenic molecules and the signal transduction pathways in which they are involved, in order to develop specifically targeted drugs. One such drug is imatinib mesylate (imatinib, Glivic/Gleevec), an orally administered 2-phenylaminopyrimidine derivative that is a competitive inhibitor of the tyrosine kinases

Extragastrointestinal Stromal Tumor during Pregnacy

PubMed Central

Gözükara, Ilay; Dilek, T. U. Kutlu; Durukan, Hüseyin; Düsmez Apa, Duygu; Kabil Kucur, Suna; Dilek, Saffet

2012-01-01

Extragastrointestinal stromal tumors (EGISTs) are mesenchymal neoplasms without connection to the gastrointestinal tract. Gastrointestinal stromal tumors (GISTs) and EGIST are similar according to their clinicopathologic and histomorphologic features. Both of them most often express immunoreactivity for CD-117, a c-kit proto-oncogene protein. The coexistence of GIST and pregnancy is very rare, with only two cases reported in the literature. In this paper, we presented the first EGIST case during pregnancy in the literature. PMID:23119199

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

PubMed

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.

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

Diagnosis of gastrointestinal stromal tumors from minute specimens: cytomorphology, immunohistochemistry, and molecular diagnostic findings.

PubMed

Layfield, Lester J; Wallander, Michelle L

2012-06-01

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal neoplasm arising from the gastrointestinal tract. Workup of these lesions includes morphologic study and immunohistochemical and often molecular diagnostic analysis. Historically, these neoplasms had been included under a number of diagnostic categories including leiomyoma, leiomyosarcoma, schwannoma, and leiomyoblastoma. The lesions that were clearly sarcomatous were difficult to treat and therapeutically refractory to chemotherapeutic agents. Significant progress in our understanding of these neoplasms and our ability to successfully treat them occurred following the discovery that they were immunoreactive for KIT protein and harbored activating mutations in the KIT gene. Many are initially diagnosed by fine-needle aspiration (FNA) but workup may include mutational analysis to help direct therapy. This review outlines a practical approach to the cytologic diagnosis of GISTs and their molecular workup on small specimens obtained by FNA or core biopsy. Copyright © 2012 Wiley Periodicals, Inc.

Efficacy and Clinical Outcomes of Transcatheter Arterial Embolization for Gastrointestinal Bleeding from Gastrointestinal Stromal Tumor.

PubMed

Koo, Hyun Jung; Shin, Ji Hoon; Shin, Sooyoung; Yoon, Hyun-Ki; Ko, Gi-Young; Gwon, Dong Il

2015-09-01

To evaluate the efficacy and clinical outcomes of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding from gastrointestinal stromal tumor (GIST). TAE was performed in 20 referred patients (male:female = 13:7; median age, 56.3 y) for GI bleeding from GISTs. The locations of GISTs were assessed using contrast-enhanced computed tomography (CT) and catheter angiography. The technical and clinical success of TAE and clinical outcomes including procedure-related complications, recurrent bleeding, 30-day and overall mortality, and cumulative survival were evaluated. The sites of GIST-related bleeding or tumor staining were the jejunum (n = 9), stomach (n = 5), ileum (n = 3), duodenum (n = 2), and jejunum and colon (n = 1). Angiography showed bleeding from GIST in 5 patients, and tumor staining was noted in only 15 patients. TAE was performed for patients with and without contrast medium extravasation on angiography. Technical and clinical success rates of TAE were 95% (19 of 20 patients) and 90% (18 of 20 patients), respectively. Recurrent bleeding was noted in 1 patient. There were no procedure-related complications. In 15 patients, surgical resection of the tumors was performed after TAE. The 30-day and overall mortality rates were 10% (2 of 20 patients) and 30% (6 of 20 patients), respectively. TAE is a safe and effective method for controlling GI bleeding from the GIST. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Primary cilia in gastric Gastrointestinal Stromal Tumours (GISTs): an ultrastructural study

PubMed Central

Castiella, Tomás; Muñoz, Guillermo; Luesma, María José; Santander, Sonia; Soriano, Mario; Junquera, Concepción

2013-01-01

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal (non-epithelial) neoplasms of the human gastrointestinal (GI) tract. They are thought to derive from interstitial cells of Cajal (ICCs) or an ICC progenitor based on immunophenotypical and ultrastructural similarities. Because ICCs show primary cilium, our hypothesis is based on the possibility that some of these neoplastic cells could also present it. To determine this, an exhaustive ultrastructural study has been developed on four gastric GISTs. Previous studies had demonstrated considerable variability in tumour cells with two dominating phenotypes, spindly and epithelioid. In addition to these two types, we have found another cell type reminiscent of adult ICCs with a voluminous nucleus surrounded by narrow perinuclear cytoplasm with long slender cytoplasmic processes. We have also noted the presence of small undifferentiated cells. In this study, we report for the first time the presence of primary cilia (PCs) in spindle and epithelioid tumour cells, an ultrastructural feature we consider of special interest that has hitherto been ignored in the literature dealing with the ultrastructure of GISTs. We also point out the frequent occurrence of multivesicular bodies (MVBs). The ultrastructural findings described in gastric GISTs in this study appear to be relevant considering the critical roles played by PCs and MVBs recently demonstrated in tumourigenic processes. PMID:23672577

Gastrointestinal stromal tumors (GIST): Facing cell death between autophagy and apoptosis.

PubMed

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

2017-03-04

Autophagy and apoptosis are 2 fundamental biological mechanisms that may cooperate or be antagonistic, although both are involved in deciding the fate of cells in physiological or pathological conditions. These 2 mechanisms coexist simultaneously in cells and share common upstream signals and stimuli. Autophagy and apoptosis play pivotal roles in cancer development. Autophagy plays a key function in maintaining tumor cell survival by providing energy during unfavorable metabolic conditions through its recycling mechanism, and supporting the high energy requirement for metabolism and growth. This review focuses on gastrointestinal stromal tumors and cell death through autophagy and apoptosis, taking into account the involvement of both of these processes in tumor development and growth and as mechanisms of drug resistance. We also focus on the crosstalk between autophagy and apoptosis as an emerging field with major implications for the development of novel therapeutic options.

Gastrointestinal stromal tumors: retrospective analysis of the computer-tomographic aspects.

PubMed

Lupescu, Ioana G; Grasu, Mugur; Boros, Mirela; Gheorghe, Cristian; Ionescu, Mihnea; Popescu, Irinel; Herlea, Vlad; Georgescu, Serban A

2007-06-01

To describe the computer-tomographic (CT) aspects of gastrointestinal stromal tumors (GISTs) in correlation to their histology. The medical records of all patients at our hospital with a histologic diagnosis of GIST between January 2002 and June 2006, and investigated before surgery by CT, were reviewed. Two radiologists with knowledge of the diagnosis reviewed the CT findings. Amongst 15 cases of GISTs, 9 cases involved the stomach and 4 cases the small intestine. Location of the primary tumor could not be determined for 2 of 15 tumors, because of the presence of extensive peritoneal metastases. Most primary tumors were predominantly extraluminal (13 cases) while two were clearly endoluminal. The mean diameter of the primary tumor was 8 cm. The tumor margin was well defined in 12 patients and irregular in 3 cases. Central fluid attenuation was present in 11 tumors, while central gas was seen in two cases. Metastases were seen in 2 cases at presentation and in another 2 patients during follow-up. Spread was exclusive to the liver or peritoneum. Visceral obstruction was absent even in extensive peritoneal metastatic disease. Ascites was an unusual finding. CT plays an important role not only in the detection and the localization but also in the evaluation of the extension and follow-up of theses tumors. Using only CT aspects, we can only suspect the diagnosis to GISTs. Often other soft-tissue tumors with gastrointestinal involvement can mimic GISTs. In all cases histological diagnosis is essential.

miRNA profiling in gastrointestinal stromal tumors: implication as diagnostic and prognostic markers.

PubMed

Nannini, Margherita; Ravegnini, Gloria; Angelini, Sabrina; Astolfi, Annalisa; Biasco, Guido; Pantaleo, Maria A

2015-01-01

MicroRNAs are a class of short noncoding RNAs, that play a relevant role in multiple biological processes, such as differentiation, proliferation and apoptosis. Gastrointestinal stromal tumors (GIST) are considered as a paradigm of molecular biology in solid tumors worldwide, and after the discovery of specific alterations in the KIT and PDGFRA genes, they have emerged from anonymity to become a model for targeted therapy. Epigenetics have an emerging and relevant role in different steps of GIST biology such as tumorigenesis, disease progression, prognosis and drug resistance. The aim of the present review was to summarize the current evidence about the role of microRNAs in GIST, including their potential application as well as their limits.

Giant gastrointestinal stromal tumour of rare sarcomatoid epithelioid subtype: Case study and literature review

PubMed Central

Lech, Gustaw; Korcz, Wojciech; Kowalczyk, Emilia; Guzel, Tomasz; Radoch, Marcin; Krasnodębski, Ireneusz Wojciech

2015-01-01

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract, but they represent less than 3% of all gastrointestinal tract malignancies. This is a detailed case study of a 52-year-old male patient treated for very uncommon histological subtype of gastric GIST with atypical clinical presentation, asymptomatic progress and late diagnosis. The resected tumour, giant in diameters, was confirmed to represent the most rare histopathologic subtype of GISTs - sarcomatoid epithelioid GIST. We report this case and review the literature with a special focus on pathomorphological evaluation, biological aggressiveness and prognostic factors. To our knowledge this is the first report of giant GIST of very uncommon sarcomatoid epithelioid subtype. It is concluded that clinicians should pay attention to the fact that initial diagnosis may be delayed due to mildly asymptomatic and non-specific clinical presentation. Asymptomatic tumours diagnosed at a late stage, which is often the case, can be large on presentation. Prognosis for patients diagnosed with GIST depend on tumour size, mitotic rate, histopathologic subtype and tumour location. That is why early diagnosis and R0 resection, which is usually feasible and safe even in giant gastric sarcomatoid epithelioid subtype of GISTs, are the key factors for further treatment and good prognosis. PMID:25805949

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

PubMed

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

2012-03-01

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

New targets and therapies for gastrointestinal stromal tumors.

PubMed

Wozniak, Agnieszka; Gebreyohannes, Yemarshet K; Debiec-Rychter, Maria; Schöffski, Patrick

2017-12-01

The majority of gastrointestinal stromal tumors (GIST) are driven by an abnormal receptor tyrosine kinase (RTK) signaling, occurring mainly due to somatic mutations in KIT or platelet derived growth factor receptor alpha (PDGFRA). Although the introduction of tyrosine kinase inhibitors (TKIs) has revolutionized therapy for GIST patients, with time the vast majority of them develop TKI resistance. Advances in understanding the molecular background of GIST resistance allows for the identification of new targets and the development of novel strategies to overcome or delay its occurrence. Areas covered: The focus of this review is on novel, promising therapeutic approaches to overcome heterogeneous resistance to registered TKIs. These approaches involve new TKIs, including drugs specific for a mutated form of KIT/PDGFRA, drugs with inhibitory effect against multiple RTKs, compounds targeting dysregulated downstream signaling pathways, drugs affecting KIT expression and degradation, inhibitors of cell cycle, and immunotherapeutics. Expert commentary: As the resistance to standard TKI treatment can be heterogeneous, a combinational approach for refractory GIST could be beneficial. Moreover, the understanding of the molecular background of resistant disease would allow development of a more personalized approach for these patients and their response to targeted therapy could be monitored closely using 'liquid biopsy'.

Assessment of early response to imatinib 800 mg after 400 mg progression by ¹⁸F-fluorodeoxyglucose PET in patients with metastatic gastrointestinal stromal tumors.

PubMed

Chacón, Matías; Eleta, Martín; Espindola, Adriel Rodríguez; Roca, Enrique; Méndez, Guillermo; Rojo, Sandra; Pupareli, Carmen

2015-01-01

Imatinib is the standard first-line therapy for advanced gastrointestinal stromal tumor. (18)F-fluorodeoxyglucose PET computed tomography (FDG PET/CT) shows a faster response than computed tomography in nonpretreated patients. After disease progression on imatinib 400 mg, 16 patients were exposed to 800 mg. Tumor response was evaluated by FDG PET/CT on days 7 and 37. Primary objective was to correlate early metabolic response (EMR) with progression-free survival (PFS). EMR by FDG PET/CT scan was not predictive of PFS. Median PFS in these patients was 3 months. Overall survival was influenced by gastric primary site (p = 0.05). The assessment of EMR by FDG PET/CT in patients with advanced gastrointestinal stromal tumor exposed to imatinib 800 mg was not predictive of PFS or overall survival.

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

PubMed Central

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

2012-01-01

Although paraganglioma (PGL), an extra-adrenal retroperitoneal pheochromocytoma (PHEO), is a rare catecholamine-secreting neuroendocrine tumor, it can cause severe hypertensive crisis during anesthesia or surgery if undiagnosed preoperatively. Extraluminal perigastric masses may be presumed to be gastrointestinal stromal tumors (GISTs) or soft tissue sarcomas even when histologic confirmation is not possible. Therefore, without a histologic diagnosis or symptoms of excessive catecholamine secretion, PGL may be mistaken for GIST. We report a case of preoperatively undiagnosed PGL which caused hypertensive crisis during anesthesia for retroperitoneal mass excision. PMID:22474560

Imaging, morphologic, and immunohistochemical correlation in gastrointestinal stromal tumors.

PubMed

Logrono, Roberto; Bhanot, Punam; Chaya, Charles; Cao, Li; Waxman, Irving; Bhutani, Manoop S

2006-08-25

Gastrointestinal stromal tumors (GISTs) recently have been distinguished morphologically, immunohistochemically, and genetically from other gastrointestinal-tract spindle cell neoplasms. The objective of this study was to correlate clinical and imaging findings with morphology and immunohistochemistry to diagnose GISTs and to differentiate them from other spindle cell lesions in the gastrointestinal tract. The authors reviewed 9 patients who had tumors that were diagnosed as GIST by image-guided and endosonographic-guided fine-needle aspiration (FNA) with or without core biopsy (7 stomach tumors and 2 intraabdominal tumors). The male:female ratio was 3:6, and the patients ranged in age from 38 years to 80 years. Onsite evaluation, preliminary cytologic evaluation, and immunohistochemistry were provided for 6 patients. Immunostains were performed, depending on sample size, on aspirates and/or core biopsies. On imaging studies, most tumors were smooth and homogenous, consistent with GIST. Tumors ranged in size from 1.8 cm to 22 cm. The largest neoplasm showed solid/cystic and necrotic components. Aspirates consisted of spindle cell, neoplastic proliferation arranged in fascicles that exhibited focal, nuclear palisading; indistinct, cytoplasmic borders; and no significant atypia or mitosis. Focal epithelioid changes or cytologic atypia and mitoses were observed in 2 tumors. Immunostains revealed tumor expression of CD117 and/or CD34 in 5 of 6 tumors, expression of actin in 3 of 6 tumors, and expression of desmin in 1 of 6 tumors. All tumors were diagnosed as GIST (or consistent with GIST for tumors that lacked immunochemical analysis). Five patients underwent surgical excision, and the GIST diagnosis was confirmed in 3 patients, whereas 1 tumor proved to be neurofibroma, and another tumor was leiomyoma. No surgical follow-up was available for the remaining 4 patients, who had imaging and morphologic findings consistent with GIST. In the setting of consistent clinical

Perspectives on the evolving state of the art management of gastrointestinal stromal tumours

PubMed Central

Szucs, Zoltan

2018-01-01

Gastrointestinal stromal tumours (GISTs) represent a very exciting tumour entity for the medical oncologist. There has been extensive clinical and preclinical research dissecting the natural behaviour, molecular landscape and therapeutic responsiveness of this rare mesenchymal tumour. Various molecular subtypes of GIST have a differing prognostic and predictive relevance in the state of the art management of the disease. Emerging mature clinical trial data gathered over the last one and half decade provided substantial molecular profiling information in understanding the success and eventual failure of treatment. In our review of the most relevant literature we aim to guide the clinician in tailoring neoadjuvant, adjuvant and palliative treatment of GIST alongside the different, now well established molecular subgroups of GISTs. PMID:29780899

Metachronous Primary Adenocarcinoma of Lung During Adjuvant Imatinib Mesylate Therapy for Gastrointestinal Stromal Tumor of Stomach: A Case Report.

PubMed

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

2015-09-01

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.

Non-exposed endoscopic wall-inversion surgery for gastrointestinal stromal tumor

PubMed Central

Mitsui, Takashi; Aikou, Susumu; Niimi, Keiko; Fujishiro, Mitsuhiro; Seto, Yasuyuki

2018-01-01

Laparoscopic and endoscopic cooperative surgery (LECS) is an accepted method of laparoscopic wedge resection, which is minimally invasive, for gastrointestinal stromal tumors (GISTs). We established a type of LECS achieving a full-thickness resection, non-exposed endoscopic wall-inversion surgery (NEWS), in an effort to prevent exposure of the peritoneal cavity to gastric intraluminal contents. We employed this surgical technique in 28 gastric GIST patients. We failed to complete NEWS in the initial two patients and in one patient with a large tumor (40 mm × 35 mm), but otherwise carried out the procedure successfully. Although a learning effect is speculated to occur, based on a decreasing trend in the operation time, the median operation time was 184 minutes showing that NEWS is still a time-consuming method. No significant differences were recognized in tumor size or location, except near the esophagogastric junction (EGJ), nor in the cross-sectional circumference. NEWS is feasible and appears to be a good option, especially for small GISTs with mucosal ulceration rendering full-thickness enucleation by opening of the gastric wall unfeasible. PMID:29682624

Lymphoid stromal reaction in gastrointestinal lymphomas: immunohistochemical study of 14 cases.

PubMed Central

Jarry, A; Brousse, N; Souque, A; Barge, J; Molas, G; Potet, F

1987-01-01

The lymphoid stromal reaction, particularly the T lymphoid reaction, was studied immunohistochemically on cryostat sections in 14 cases of primary gastrointestinal B lymphomas, and compared with the type and distribution of lymphoid cells in three cases of gastric lymphoid hyperplasia. A pronounced T lymphoid reaction, mainly of the T helper phenotype, occurred in both lesions. Most of these T cells bore HLA-DR antigens, but only a few of them had the receptor for interleukin 2. The T lymphoid reaction was observed inside the lymphomas in seven of a total of 14 cases, and around the lymphomas in four of the six cases clinically classified as stage I. Perivascular mucosal and submucosal nodules, entirely composed of T cells, seemed characteristic of gastric lymphoid hyperplasias. A T lymphoid reaction in lymphoid hyperplasias suggests an amplification of the cell mediated immune response; in lymphomas it could represent a host reaction against the lymphomatous infiltrate, therefore favouring a better prognosis. Images Fig 1 Fig 2 Fig 3 PMID:3305585

Surgical management of acutely presenting gastrointestinal stromal tumors of the stomach among elderly: experience of an emergency surgery department.

PubMed

Marano, Luigi; Arru, Giovanni Maria Antonio; Piras, Mario; Fiume, Stefania; Gemini, Sergio

2014-01-01

The incidence of gastrointestinal stromal tumors (GISTs), requiring often an emergency surgical management, is extremely rare among elderly. We aimed to present the experience of the Emergency Surgery Department, Brotzu Hospital, in the management of elderly patients with GIST related emergencies. This study was carried out on 12 patients with gastrointestinal stromal tumors who presented to in an emergency situation during the period from January 2010 to December 2013. All patients' data, clinical presentations, surgical procedures, complications, and survival data were collected and analyzed. Between 2010 and 2013, 12 patients (8 males and 4 females), with a mean age of 70 years (range: 65-79 years) were admitted with different emergency presentations of clinically and radiologically suspected GISTs. The incidence of proximal obstruction was 41.7% of all gastric GIST cases, resulting acute gastrointestinal bleeding and perforation in 41.7% and 16.6% respectively. The mean length of hospitalization was 9.1 ± 2.3 days and there were no posterative complications or mortalities. At a mean follow-up of 21 months, 11 patients (91.6%) were alive and disease free. Although GISTs are uncommon among elderly, their incidence is increasing especially in their emergency presentation and surgeon should be prepared to treat this condition following the principles of GIST surgery as stated by the GIST consensus conference. In conclusion our data demonstrate that age itself does not affect the outcome of surgical treatment of GISTs in emergency situation. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

Abdominal Hernias, Giant Colon Diverticulum, GIST, Intestinal Pneumatosis, Colon Ischemia, Cold Intussusception, Gallstone Ileus, and Foreign Bodies: Our Experience and Literature Review of Incidental Gastrointestinal MDCT Findings

PubMed Central

Gatta, G.; Rella, R.; Donatello, D.; Falco, G.; Grassi, R.

2017-01-01

Incidental gastrointestinal findings are commonly detected on MDCT exams performed for various medical indications. This review describes the radiological MDCT spectrum of appearances already present in the past literature and in today's experience of several gastrointestinal acute conditions such as abdominal hernia, giant colon diverticulum, GIST, intestinal pneumatosis, colon ischemia, cold intussusception, gallstone ileus, and foreign bodies which can require medical and surgical intervention or clinical follow-up. The clinical presentation of this illness is frequently nonspecific: abdominal pain, distension, nausea, fever, rectal bleeding, vomiting, constipation, or a palpable mass, depending on the disease. A proper differential diagnosis is essential in the assessment of treatment and in this case MDCT exam plays a central rule. We wish that this article will familiarize the radiologist in the diagnosis of this kind of incidental MDCT findings for better orientation of the therapy. PMID:28638830

Abdominal Hernias, Giant Colon Diverticulum, GIST, Intestinal Pneumatosis, Colon Ischemia, Cold Intussusception, Gallstone Ileus, and Foreign Bodies: Our Experience and Literature Review of Incidental Gastrointestinal MDCT Findings.

PubMed

Di Grezia, G; Gatta, G; Rella, R; Donatello, D; Falco, G; Grassi, R; Grassi, R

2017-01-01

Incidental gastrointestinal findings are commonly detected on MDCT exams performed for various medical indications. This review describes the radiological MDCT spectrum of appearances already present in the past literature and in today's experience of several gastrointestinal acute conditions such as abdominal hernia, giant colon diverticulum, GIST, intestinal pneumatosis, colon ischemia, cold intussusception, gallstone ileus, and foreign bodies which can require medical and surgical intervention or clinical follow-up. The clinical presentation of this illness is frequently nonspecific: abdominal pain, distension, nausea, fever, rectal bleeding, vomiting, constipation, or a palpable mass, depending on the disease. A proper differential diagnosis is essential in the assessment of treatment and in this case MDCT exam plays a central rule. We wish that this article will familiarize the radiologist in the diagnosis of this kind of incidental MDCT findings for better orientation of the therapy.

Expression of the Intermediate Filament Nestin in Gastrointestinal Stromal Tumors and Interstitial Cells of Cajal

PubMed Central

Tsujimura, Tohru; Makiishi-Shimobayashi, Chiaki; Lundkvist, Johan; Lendahl, Urban; Nakasho, Keiji; Sugihara, Ayako; Iwasaki, Teruo; Mano, Masayuki; Yamada, Naoko; Yamashita, Kunihiro; Toyosaka, Akihiro; Terada, Nobuyuki

2001-01-01

It has recently been proposed that gastrointestinal stromal tumors (GISTs) originate from stem cells that differentiate toward a phenotype of interstitial cells of Cajal (ICCs). Nestin is a newly identified intermediate filament protein, and is predominantly expressed in immature cells, such as neuroectodermal stem cells and skeletal muscle progenitor cells, and tumors originating from these cells. In this study, we examined, using immunohistochemistry, the nestin expression in GISTs and ICCs to clarify the origin of GISTs. Strong immunoreactivity for nestin was observed in all 18 GISTs, and its expression was confirmed by Western blot and Northern blot analyses. In contrast, three leiomyomas and a schwannoma that developed in the gastrointestinal tract showed no apparent immunoreactivity for nestin. Among 17 mesenchymal tumors (seven leiomyosarcomas, five malignant peripheral nerve sheath tumors, and five fibrosarcomas) that occurred in sites other than the gastrointestinal tract, only two malignant peripheral nerve sheath tumors were moderately immunoreactive for nestin. Furthermore, with fluorescence double immunostaining of the normal small intestine, nestin expression was demonstrated in ICCs. These results show that nestin may be a useful marker for diagnosis of GISTs, and support the current hypothesis that GISTs are tumors of stem cells that differentiate toward an ICC phenotype. PMID:11238030

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

PubMed

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

2016-11-15

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

Perivascular epithelioid cell tumor of the descending colon mimicking a gastrointestinal stromal tumor: a case report.

PubMed

Iwamoto, Ryuta; Kataoka, Tatsuki R; Furuhata, Ayako; Ono, Kazuo; Hirota, Seiichi; Kawada, Kenji; Sakai, Yoshiharu; Haga, Hironori

2016-11-14

We present a case of perivascular epithelioid cell tumor (PEComa), which clinically and histologically mimics a gastrointestinal stromal tumor (GIST). A 42-year-old woman was found to have a mass in the left flank during her annual medical checkup. Computed tomography examination revealed a submucosal tumor of the descending colon. Surgeons and radiologists suspected that the lesion was a GIST, and left hemicolectomy was performed without biopsy. Microscopic examination showed that the lesion was composed of spindle and epithelioid cells, which were immunohistochemically negative for c-kit and positive for platelet-derived growth factor receptor (PDGFR) α. Initial diagnosis of PDGFRα-positive GIST was made. However, gene analysis did not reveal mutations in PDGFRα. Additional immunohistochemistry showed that tumor cells were positive for human melanin black 45 (HMB45), melanA, and the myogenic marker calponin. A final diagnosis of PEComa was made. PEComa should be included in the differential diagnosis of PDGFRα-positive spindle cell tumors in the wall of the gastrointestinal tract.

Gastrointestinal stromal tumors: Thirty years experience of an Institution

PubMed Central

Arolfo, Simone; Teggia, Paolo Mello; Nano, Mario

2011-01-01

AIM: To report our experience of gastrointestinal stromal tumors (GISTs) during the last 29 years. METHODS: Thirty two cases of GIST referred to our Institution from the 1st January 1981 to the 10th June 2010 were reviewed. Metastases, recurrence and survival data were collected in relation to age, history, clinical presentation, location, size, resection margins and cellular features. RESULTS: Mean age was 63.7 years (range, 40-90) and incidence was slightly higher in males (56%). R0 resection was performed in 90.7% of cases, R1 in 6.2% (2 cases) and R2 in 3.1% (one case). Using Fletcher’s classification 8/32 (25%) had high risk, 9/32 (28%) intermediate and 15/32 (47%) low risk tumors. Follow-up varied from 1 mo to 29 years, with a median of 8 years; overall survival was 75% (24/32), disease-free survival was 72% and tumor-related mortality was 9.3%. Three patients with high risk GIST were treated with imatinib mesylate: one developed a recurrence after 36 mo, and 2 are free from disease at 41 mo. CONCLUSION: Surgical treatment remains the gold standard therapy for resectable GISTs. Pathological and biological features of the neoplasm represent the most important factors predicting the prognosis. PMID:21528056

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

PubMed Central

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

2016-01-01

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. PMID:27340363

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.

Prognostic impact of gastrointestinal bleeding and expression of PTEN and Ki-67 on primary gastrointestinal stromal tumors

PubMed Central

2014-01-01

Background Prognostic indicators for gastrointestinal stromal tumors (GISTs) are under investigation. The latest risk classification criteria may still have room for improvement. This study aims to investigate prognostic factors for primary GISTs from three aspects, including clinicopathological parameters, immunohistochemical (IHC) expression of PTEN, and Ki-67 labeling index (LI), and attempts to find valuable predictors for the malignancy potential of primary GISTs. Methods Tumor samples and clinicopathological data from 84 patients with primary GISTs after R0 resection were obtained. Immunohistochemical analysis was performed based on tissue microarray (TMA) to estimate expression of PTEN and Ki-67 in tumor cells. Results The cut-off point of Ki-67 LI was determined as 1%, using a receiver operator characteristic test with a sensitivity of 71.7% and a specificity of 64.5%. Univariate analysis demonstrated the following factors as poor prognostic indicators for relapse-free survival (RFS) against a median follow-up of 40.25 months: gastrointestinal (GI) bleeding (P = 0.009), non-gastric tumor location (P = 0.001), large tumor size (P = 0.022), high mitotic index (P < 0.001), high cellularity (P = 0.012), tumor rupture (P = 0.013), absent or low expression of PTEN (P = 0.036), and Ki-67 LI >1% (P = 0.043). Gastrointestinal bleeding (hazard ratio, 3.85; 95% confidence interval, 1.63 to 9.10; P = 0.002) was a negative independent risk predictor in multivariate analysis, in addition to tumor size (P = 0.023), and mitotic index (P = 0.002). In addition, GI bleeding showed a good ability to predict recurrence potential, when included in our re-modified risk stratification criteria. Conclusions This study suggests that GI bleeding is an independent predictor of poor prognosis for RFS in primary GISTs. Expression of PTEN and Ki-67 are correlated with high risk potential and may predict early recurrence in univariate analysis

Surgical Pathology of Gastrointestinal Stromal Tumors: Practical Implications of Morphologic and Molecular Heterogeneity for Precision Medicine.

PubMed

Charville, Gregory W; Longacre, Teri A

2017-11-01

Gastrointestinal stromal tumor (GIST), the most common mesenchymal neoplasm of the gastrointestinal tract, exhibits diverse histologic and clinical manifestations. With its putative origin in the gastrointestinal pacemaker cell of Cajal, GIST can arise in association with any portion of the tubular gastrointestinal tract. Morphologically, GISTs are classified as spindled or epithelioid, though each of these subtypes encompasses a broad spectrum of microscopic appearances, many of which mimic other histologic entities. Despite this morphologic ambiguity, the diagnosis of GIST is aided in many cases by immunohistochemical detection of KIT (CD117) or DOG1 expression. The natural history of GIST ranges from that of a tumor cured by surgical resection to that of a locally advanced or even widely metastatic, and ultimately fatal, disease. This clinicopathologic heterogeneity is paralleled by an underlying molecular diversity: the majority of GISTs are associated with spontaneous activating mutations in KIT, PDGFRA, or BRAF, while additional subsets are driven by genetic lesions-often inherited-of NF1 or components of the succinate dehydrogenase enzymatic complex. Specific gene mutations correlate with particular anatomic or morphologic characteristics and, in turn, with distinct clinical behaviors. Therefore, prognostication and treatment are increasingly dictated not only by morphologic clues, but also by accompanying molecular genetic features. In this review, we provide a comprehensive description of the heterogenous molecular underpinnings of GIST, including implications for the practicing pathologist with regard to morphologic identification, immunohistochemical diagnosis, and clinical management.

Clinical significance of duodenal lymphangiectasia incidentally found during routine upper gastrointestinal endoscopy.

PubMed

Kim, J H; Bak, Y T; Kim, J S; Seol, S Y; Shin, B K; Kim, H K

2009-06-01

Although duodenal lymphangiectasia in individuals without clinical evidence of malabsorption has been reported, the prevalence and clinical significance in this situation are not yet known. The aim of this study was to evaluate the prevalence and clinical significance of incidentally found duodenal lymphangiectasia. A retrospective review of medical records was undertaken for consecutive patients who had undergone diagnostic upper endoscopy between January 2005 and June 2006. A prospective study was then performed in consecutive individuals undergoing routine upper endoscopy for health examination between July 2006 to October 2006. Endoscopic features of duodenal lymphangiectasia were classified into three types: (1) multiple scattered pinpoint white spots; (2) diffuse prominent villi with whitish-discolored tips; and (3) focal small whitish macule or nodule. The histologic grade of duodenal lymphangiectasia was classified according to the depth and severity of lymphatic duct dilatations. Prevalence and clinical data of incidentally found duodenal lymphangiectasia were evaluated in the retrospective and prospective studies. Among 1866 retrospective cases, duodenal lymphangiectasia was endoscopically suspected in 59 cases (3.2%), and histologically confirmed in 35 cases (1.9%). No clinical evidence of malabsorption was noted in the duodenal lymphangiectasia cases. The "scattered pinpoint white spots" type was the most frequently found endoscopic feature (40.0%). Duodenal lymphangiectasia was persistent in seven of 10 individuals who underwent repeat endoscopy after a median of 12 months. Among 134 prospective cases, duodenal lymphangiectasia was histologically confirmed in 12 cases (8.9%). There was no significant clinical difference between groups with and without duodenal lymphangiectasia. Lymphatic duct dilatation was histologically more severe in the "focal small whitish macule or nodule" type than in the other types. Duodenal lymphangiectasia without clinical

[Gastric stromal tumor treated by laparoscopic surgery].

PubMed

Alecu, L; Costan, I; Vitalariu, A; Obrocea, F; Păcuraru, Elena; Gulinescu, L

2002-01-01

The authors describe a 59 years old female patient, with a gastrointestinal stromal tumor located on the posterior wall of the gastric funds, who was treated successfully by laparoscopic wedge resection (with clear resection margins), through an anteriorly placed gastrotomy, thus allowing an endoscopic linear cutter Endo GIA, to excise the tumor with a cuff of normal gastric tissue. The anterior gastrotomy was performed with Ultra-Shears. Delivery of the tumor through the gastrotomy is essential for success. The operative time was 110 minutes. The tumor was diagnosed as a gastrointestinal stromal submucosal tumor (of low-grade malignancy) and immunohistochemicaly, this tumor was positive for CD 34. Posterior gastric tumor can be removed using laparoscopic surgery.

Preoperative diagnosis of obscure gastrointestinal bleeding due to a GIST of the jejunum: a case report.

PubMed

Gourgiotis, Stavros; Kotoulas, Dimitrios; Aloizos, Stavros; Kolovou, Aikaterini; Salemis, Nikolaos S; Kantounakis, Ioannis

2009-09-10

Gastrointestinal stromal tumours are rare mesenchymal neoplasms affecting the digestive tract or nearby structures within the abdomen. We present a case of a 66-year-old female patient who presented with obscure anemia due to gastrointestinal bleeding and underwent exploratory laparotomy during which a large gastrointestinal stromal tumour of the small intestine was discovered. Examining the preoperative results of video capsule endoscopy, computed tomography, and angiography and comparing them with the operative findings we discuss which of these investigations plays the most important role in the detection and localization of gastrointestinal stromal tumours. A sort review of the literature is also conducted on these rare mesenchymal tumours.

Extragastrointestinal stromal tumor of the mesoappendix: CT findings and a review of the literature

PubMed Central

2012-01-01

Background Gastrointestinal stromal tumors (GISTs) are nonepithelial, mesenchymal neoplasms that rarely occur in children. Case presentation We present a unique case of a GIST that developed outside the gastrointestinal tract within the mesoappendix of a 6-year old boy. Computed tomography (CT) revealed a slightly lobulated, homogeneous soft-tissue mass, with marked contrast enhancement. Conclusion This case study provides new insight into the CT appearance of extragastrointestinal stromal tumors. PMID:23039908

Clinical outcomes of gastrointestinal stromal tumor in southern Thailand

PubMed Central

Pornsuksiri, Kittima; Chewatanakornkul, Siripong; Kanngurn, Samornmas; Maneechay, Wanwisa; Chaiyapan, Walawee; Sangkhathat, Surasak

2012-01-01

AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients. PMID:23444235

[Umbilical Hernia Complicated by Gastrointestinal Stromal Tumor of the Small Intestine - A Case Report].

PubMed

Tsukada, Manabu; Ozaki, Akihiko; Ohira, Hiromichi; Sawano, Toyoaki; Nemoto, Tsuyoshi; Kanazawa, Yukio

2016-11-01

Intraabdominal tumors can cause umbilical hernia and may lead to serious consequences, such as incarcerated or necrotized intestine. However, little information is available concerning how the location and characteristics of tumors may affect the process of umbilical hernia development. A 46-year-old Japanese man presented at the department of surgery with abdominal pain and abdominal retention, which appeared on the day of presentation and 4 years before the presentation, respectively. Abdominal computed tomography revealed a suspected gastrointestinal stromal tumor(GIST)and an umbilical hernia close to the tumor, both of which were clinically diagnosed. Surgical tumor resection and hernia repair were conducted successfully. The patient was pathologically diagnosed with high-risk GIST. Adjuvant therapy with imatinib was administered with no recurrence as of 1 year post-surgery. This is a case of GIST complicated by umbilical hernia. Small solid tumors may cause umbilical hernia if they are in close proximity to vulnerable parts of the abdominal wall.

Pharmacogenetics of tyrosine kinase inhibitors in gastrointestinal stromal tumor and chronic myeloid leukemia.

PubMed

Ravegnini, Gloria; Sammarini, Giulia; Angelini, Sabrina; Hrelia, Patrizia

2016-07-01

Gastrointestinal stromal tumors (GIST) and chronic myeloid leukemia (CML) are two tumor types deeply different from each other. Despite the differences, these disorders share treatment with tyrosine kinase inhibitor imatinib. Despite the success of imatinib, the response rates vary among different individuals and pharmacogenetics may play an important role in the final clinical outcome. In this review, the authors provide an overview of the pharmacogenetic literature analyzing the role of polymorphisms in both GIST and CML treatment efficacy and toxicity. So far, several polymorphisms influencing the pharmacokinetic determinants of imatinib have been identified. However, the data are not yet conclusive enough to translate pharmacogenetic tests in clinical practice. In this context, the major obstacles to pharmacogenetic test validation are represented by the small sample size of most studies, ethnicity and population admixture as confounding source, and uncertainty related to genetic variants analyzed. In conclusion, a combination of different theoretical approaches, experimental model systems and statistical methods is clearly needed, in order to appreciate pharmacogenetics applied to clinical practice in the near future.

[Clinical analysis of 31 patients with gastric stromal tumors].

PubMed

Li, Junxia; Liu, Ping; Wang, Huahong; Yu, Jing; Xie, Pengyan; Liu, Xinguang

2002-11-01

To investigate the clinical manifestations, diagnosis and treatment of gastric stromal tumors. 31 patients with gastric stromal tumors treated from 1993, 1 - 2001, 9 were analyzed retrospectively. All cases were diagnosed by pathological and immunohistochemistry examinations. According to Levin's standard combining with Hurliman's and Goldbum's methods, the patients were classified. There are no significant difference between male and female patients. 50 - 60 years old patients have high incidence. The distribution of gastric tromal tumors is fundus > body > antrum. Diagnosis of this condition is sometimes difficult and treatment is often delayed because patients usually present with nonspecific abdominal symptoms. The main manifestations of gastric stromal tumors are upper gastrointestinal hemorrhage 61.3% (19/31), 7 patients with acute hemorrhage and 12 with chronic hemorrhage. Most of them were malignant. Abdominal malaises and/or distention 32.3% (10/31) and abdominal pain 22.6% (7/31). Gastroscopy, ultrasound gastroscopy, computed tomography, B type ultrasound and upper gastrointestinal X-ray series are helpful to diagnosis. But the final diagnosis is decided by pathological and immunohistochemistry examinations. Gastric stromal tumors exhibit consistent immunohistochemical expressions of CD(117) and/or CD(34). The operative treatment is thought of the first choice. Effect of the chemotherapy isn't satisfied. There is no standard chemotherapy for gastric stromal tumors. Gastric stromal tumor is a kind of separated submucosal tumor which is different from leiomyoma, leiomyosarcoma and neurogenic tumors. Pathological and immunohistochemistry inspectations are very important to make clear diagnosis. Early diagnosis and rational treatment are the keys to improve the prognosis.

Establishment and characterization of a human gastrointestinal stromal tumour (GIST) xenograft in athymic nude mice.

PubMed

Revheim, Mona-Elisabeth; Seierstad, Therese; Berner, Jeanne-Marie; Bruland, Oyvind Sverre; Røe, Kathrine; Ohnstad, Hege Oma; Bjerkehagen, Bodil; Bach-Gansmo, Tore

2009-11-01

The majority of gastrointestinal stromal tumours (GISTs) contain oncogenic KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor-alpha (PDGFRA) receptor tyrosine kinase (TK) mutations and are initially, but only temporarily sensitive to TK inhibitors. The aim of this study was to establish and characterize a human GIST xenograft that could be used for evaluating various molecularly targeted therapies. GIST tissue from four patients was implanted under the skin of athymic nude mice. In one case a tumour line was established. The xenograft showed characteristic GIST morphology and exhibited the same mutation profile as that of the patient. A human GIST xenograft with mutation in KIT exons 11 and 17 has been established and maintained in nude mice for 3 years (13 passages). This model will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.

Conditional Disease-Free Survival After Surgical Resection of Gastrointestinal Stromal Tumors

PubMed Central

Bischof, Danielle A.; Kim, Yuhree; Dodson, Rebecca; Jimenez, M. Carolina; Behman, Ramy; Cocieru, Andrei; Fisher, Sarah B.; Groeschl, Ryan T.; Squires, Malcolm H.; Maithel, Shishir K.; Blazer, Dan G.; Kooby, David A.; Gamblin, T. Clark; Bauer, Todd W.; Quereshy, Fayez A.; Karanicolas, Paul J.; Law, Calvin H. L.; Pawlik, Timothy M.

2015-01-01

IMPORTANCE Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed mesenchymal tumors of the gastrointestinal tract. The risk of recurrence following surgical resection of GISTs is typically reported from the date of surgery. However, disease-free survival (DFS) over time is dynamic and changes based on disease-free time already accumulated following surgery. OBJECTIVES To assess the comparative performance of established GIST recurrence risk prognostic scoring systems and to characterize conditional DFS following surgical resection of GISTs. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort study of 502 patients who underwent surgery for a primary, nonmetastatic GIST between January 1, 1998, and December 31, 2012, at 7 major academic cancer centers in the United States and Canada. MAIN OUTCOMES AND MEASURES Disease-free survival of the patients was classified according to 5 prognostic scoring systems, including the National Institutes of Health criteria, modified National Institutes of Health criteria, Memorial Sloan Kettering Cancer Center GIST nomogram, and American Joint Committee on Cancer gastric and nongastric categories. The concordance index (also known as the C statistic or the area under the receiver operating curve) of established GIST recurrence risk prognostic scoring systems. Conditional DFS estimates were calculated. RESULTS Overall 1-year, 3-year, and 5-year DFS following resection of GISTs was 95%, 83%, and 74%, respectively. All the prognostic scoring systems had fair prognostic ability. For all tumor sites, the American Joint Committee on Cancer gastric category demonstrated the best discrimination (C = 0.79). Using conditional DFS, the probability of remaining disease free for an additional 3 years given that a patient was disease free at 1 year, 3 years, and 5 years was 82%, 89%, and 92%, respectively. Patients with the highest initial recurrence risk demonstrated the greatest increase in conditional survival as time

Gossypiboma Mimicking Gastrointestinal Stromal Tumor Causing Intestinal Obstruction: A Case Report

PubMed Central

Kawamura, Yurika; Ogasawara, Naotaka; Yamamoto, Sayuri; Sasaki, Makoto; Kawamura, Naohiko; Izawa, Shinya; Kobayashi, Yuji; Kamei, Seiji; Miyachi, Masahiko; Kasugai, Kunio

2012-01-01

A 41-year-old woman was admitted to our hospital with abdominal pain that developed about 1 year after a Cesarean section. Pelvic computed tomography (CT) revealed diffuse dilation of the small intestine with fluid shadows and a pelvic tumor 55 mm in diameter. The density of the tumor, which was not enhanced by intravenous contrast medium, was diffuse and similar to that of muscular tissue, whereas the density of a capsule surrounding the mass was relatively high. T1- and T2-weighted pelvic magnetic resonance imaging (MRI) of the tumor revealed the same diffuse low-intensity signals as muscular tissue, and diffuse high-intensity signals, respectively. The CT and MRI findings were consistent with those of a gastrointestinal stromal tumor (GIST) causing ileus of the small intestine. As inserting an ileus tube did not improve her symptoms, the patient was scheduled for tumor resection. The operative findings revealed a hard, solid tumor adhering to the surrounding small intestine. The macroscopic findings revealed that the tumor consisted of layers of stratified gauze surrounded by a thick granulomatous wall. The gossypiboma was considered to have originated from gauze that had been left behind after the Cesarean section. If a patient has a history of surgery, the possibility of gossypiboma should be considered when CT or MRI findings indicate features of GIST. PMID:22679410

Gastrointestinal stromal tumours of the oesophagus: a clinicopathological and molecular analysis of 27 cases.

PubMed

Kang, Guhyun; Kang, Yuna; Kim, Kyung-Hee; Ha, Sang Yun; Kim, Jung Yeon; Shim, Young Mog; Heinrich, Michael C; Kim, Kyoung-Mee; Corless, Christopher L

2017-11-01

Gastrointestinal stromal tumours (GISTs) may arise anywhere in the gastrointestinal tract, but are rare in the oesophagus. We describe the clinical, pathological and molecular characteristics of 27 primary oesophageal GISTs, the largest series to date. DNA was extracted and exons 9, 11, 13 and 17 of KIT, exons 12, 14 and 18 of PDGFRA and exon 15 of BRAF were amplified and sequenced. Oesophageal GISTs occurred in 14 men and 13 women aged between 22 and 80 years (mean: 56 years). All 27 cases were immunohistochemically positive for KIT, and 92 and 47% co-expressed CD34 or smooth muscle actin, respectively. Fifteen (71% of analysed cases) harboured KIT exon 11 mutations and one case each had a mutation in KIT exon 13 (K642E) or BRAF exon 15 (V600E). Long-term follow-up data (median, 96.5 months) were obtained for 20 cases; two patients had metastases at presentation and seven had developed local recurrence and/or metastasis after surgery. A large tumour size (≥ 10 cm), high mitotic rate (> 5/5 mm 2 ), presence of a deletion mutation in KIT exon 11 involving codons 557-558 and a positive microscopic margin were associated with recurrence and metastasis. The KIT mutations identified in oesophageal GISTs are similar to those observed in gastric GISTs. Complete surgical resection with clear margins is recommended, if technically feasible, and genotyping can help to improve diagnosis and further patient management in oesophageal GIST. © 2017 John Wiley & Sons Ltd.

Using molecular diagnostic testing to personalize the treatment of patients with gastrointestinal stromal tumors.

PubMed

Bannon, Amber E; Klug, Lillian R; Corless, Christopher L; Heinrich, Michael C

2017-05-01

The diagnosis and treatment of gastrointestinal stromal tumor (GIST) has emerged as a paradigm for modern cancer treatment ('precision medicine'), as it highlights the importance of matching molecular defects with specific therapies. Over the past two decades, the molecular classification and diagnostic work up of GIST has been radically transformed, accompanied by the development of molecular therapies for specific subgroups of GIST. This review summarizes the developments in the field of molecular diagnosis of GIST, particularly as they relate to optimizing medical therapy. Areas covered: Based on an extensive literature search of the molecular and clinical aspects of GIST, the authors review the most important developments in this field with an emphasis on the differential diagnosis of GIST including mutation testing, therapeutic implications of each molecular subtype, and emerging technologies relevant to the field. Expert commentary: The use of molecular diagnostics to classify GIST has been shown to be successful in optimizing patient treatment, but these methods remain under-utilized. In order to facilitate efficient and comprehensive molecular testing, the authors have developed a decision tree to aid clinicians.

[Lancet in the era of targeted drug therapy: the role of surgery in the management of advanced gastrointestinal stromal tumor].

PubMed

Cao, Hui; Wang, Ming

2016-11-25

Gastrointestinal stromal tumor(GIST) is the most common mesenchymal tumor in the gastrointestinal tract. Due to the occult onset, GIST may present as local advanced or with metastatic disease at diagnosis. Imatinib mesylate (IM) has effectively improved the prognosis of GIST patients and has been established as principle therapy in metastatic GIST. The role of IM as an adjunction to surgery in the management of high-risk and local advanced GIST is also highly regarded. The role of surgery in metastatic or recurrent GIST is still a controversial clinic problem. For local advanced GIST or GIST in the unfavorable anatomic site(e.g. esophagogastric junction, duodenum, and rectum), based on the limited evidence, surgery may have potential benefits as conversion therapy. Surgery may have a limited favorable impact on progression-free survival and overall survival for those patients whose disease is responding to imatinib or those with limited focal progression. Patients with extensive advanced relapse metastatic GIST or imatinib-resistant disease should not undergo surgery unless emergency situation or complication occurs, where palliative intervention may be justified.

Succinate Dehydrogenase Mutation Underlies Global Epigenomic Divergence in Gastrointestinal Stromal Tumor

PubMed Central

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.

2014-01-01

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. SIGNIFICANCE This study shows that SDH deficiency underlies pervasive DNA hypermethylation in multiple tumor lineages, generally defining the Krebs cycle as mitochondrial custodian of the methylome. We propose that this phenomenon may result from a failure of maintenance CpG demethylation, secondary to inhibition of the TET 5-methylcytosine dioxgenase demethylation pathway, by inhibitory metabolites that accumulate in tumors with Krebs cycle dysfunction. PMID:23550148

The effect of surgery and grade on outcome of gastrointestinal stromal tumors.

PubMed

Pierie, J P; Choudry, U; Muzikansky, A; Yeap, B Y; Souba, W W; Ott, M J

2001-04-01

Gastrointestinal stromal tumors (GIST) are aggressive, rare, and difficult-to-cure gastrointestinal tumors. We believe that the clinical behavior of these tumors can be predicted by reproducible prognostic factors. A retrospective review of all patients (N = 70) with GIST treated at a tertiary care center from 1973 to 1998. Adequate data for evaluation were available for 69 patients. Male-female distribution was 40:29. Median age was 60 years. Median follow-up duration was 38 months. Tumor grade, stage, and histologic subtype at presentation; effect of grade, surgery and adjuvant therapy on recurrence, salvage, and survival. Tumor distribution included 61% in the upper, 23% in the middle, and 16% in the lower digestive tract, with a median tumor size of 7.9 cm (range, 1.8-25 cm). Tumors with more than 1 mitosis per 10 high-power fields constituted 57% of neoplasia in the series. Distant disease at initial visit occurred in 49% of patients. Complete gross resection occurred in 59% of patients. After complete resection, the 5-year survival rate was 42%, compared with 9% after incomplete resection (hazard ratio = 0.27, P<.001). Neither radiation nor chemotherapy demonstrated any significant benefit. Among 39 patients who were disease free after complete resection, 2% developed lymph node recurrence, 25% developed local recurrence, and 33% developed distant recurrences (54% liver, 20% peritoneum). By multivariate analysis the risk of local and/or distant metastases was significantly increased for tumors with more than 1 mitosis and size larger than 5 cm (P<.05). Multivariate analysis in all 69 patients revealed that incomplete resection, age greater than 50 years, non-smooth muscle histological feature, tumor with more than 1 mitosis, and tumor size larger than 5 cm significantly decreased survival. Complete gross surgical resection is presently the only means of cure for GIST. Tumors with more than 1 mitosis and a size larger than 5 cm have an especially poor

Clinicopathological feature and prognosis of primary hepatic gastrointestinal stromal tumor.

PubMed

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

2016-09-01

Compared to gastric gastrointestinal stromal tumor (GIST), hepatic GIST is very rare in clinic. Reports on clinicopathological feature and prognosis of this rare disease are limited in literature. The purpose of this study was, therefore, to summarize clinical and pathological features as well as prognosis of the primary hepatic GIST. One case of primary hepatic GIST from our center and 22 cases reported in MEDLINE or China National Knowledge Infrastructure (CNKI) were enrolled into this study. Clinicopathological features as well as survival data of hepatic GIST were analyzed and compared with 297 gastric GISTs and 59 small intestinal GISTs from our center. Majority of the 22 cases (95.7%) of hepatic GIST was larger than 5 cm in size, and 75.0% of the tumors were over 5/50 HPF in mitotic index. Most of the hepatic GISTs (85.7%) displayed spindle cell shape in morphology. All of the hepatic GIST (100%) enrolled in this study were classified as high-risk category by the National Institute of Health (NIH) risk classification. The 5-year median disease-free survival (DFS) time was 24.0 months and 5-year disease-specific survival (DSS) rate was 33.3%, respectively. Distribution of clinicopathological features was significantly different among hepatic, gastric, and small intestinal GIST. The DFS and DSS of hepatic GIST were significantly lower than those of the other two groups. Majority of the hepatic GIST is large in size and highly malignant. Prognosis of the primary hepatic GIST is worse than that of gastric GIST and small intestinal GIST. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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. 2014 BMJ Publishing Group Ltd.

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

Neoadjuvant imatinib treatment and laparoscopic anus-preserving surgery for a large gastrointestinal stromal tumor of the rectum.

PubMed

Kyo, Kennoki; Azuma, Masaki; Okamoto, Kazuya; Nishiyama, Motohiro; Shimamura, Takahiro; Maema, Atsushi; Kanamaru, Hitoshi; Shirakawa, Motoaki; Nakamura, Toshio; Shinmura, Kazuya; Koda, Kenji; Yokoyama, Hidetaro

2016-03-08

Resection of a gastrointestinal stromal tumor (GIST) of the rectum can be difficult because of the particular location in the pelvis, and a large rectal GIST often requires abdominoperineal resection. Recent reports demonstrate that neoadjuvant imatinib treatment improves surgical outcomes in patients with a rectal GIST, and there are only a few reports of the effectiveness of laparoscopic surgery for a rectal GIST. A 46-year-old man was found to have a rectal GIST that measured 80 mm and was located on the anterior wall of the lower rectum. After 6 months treatment with imatinib, the tumor decreased in size to 37 mm, and laparoscopic low anterior resection was performed. The patient is currently alive without any evidence of recurrence 37 months after surgery. Neoadjuvant imatinib should be a treatment of choice for a large rectal GIST. When marked tumor shrinkage is achieved, laparoscopic surgery may be the preferred procedure.

Imaging and Clinicopathologic Features of Esophageal Gastrointestinal Stromal Tumors

PubMed Central

Winant, Abbey J.; Gollub, Marc J.; Shia, Jinru; Antonescu, Christina; Bains, Manjit S.; Levine, Marc S.

2016-01-01

OBJECTIVE The purpose of this article is to describe the imaging and clinicopathologic characteristics of esophageal gastrointestinal stromal tumors (GISTs) and to emphasize the features that differentiate esophageal GISTs from esophageal leiomyomas. MATERIALS AND METHODS A pathology database search identified all surgically resected or biopsied esophageal GISTs, esophageal leiomyomas, and esophageal leiomyosarcomas from 1994 to 2012. Esophageal GISTs were included only if imaging studies (including CT, fluoroscopic, or 18F-FDG PET/CT scans) and clinical data were available. RESULTS Nineteen esophageal mesenchymal tumors were identified, including eight esophageal GISTs (42%), 10 esophageal leiomyomas (53%), and one esophageal leiomyosarcoma (5%). Four patients (50%) with esophageal GIST had symptoms, including dysphagia in three (38%), cough in one (13%), and chest pain in one (13%). One esophageal GIST appeared on barium study as a smooth submucosal mass. All esophageal GISTs appeared on CT as well-marginated predominantly distal lesions, isoattenuating to muscle, that moderately enhanced after IV contrast agent administration. Compared with esophageal leiomyomas, esophageal GISTs tended to be more distal, larger, and more heterogeneous and showed greater IV enhancement on CT. All esophageal GISTs showed marked avidity (mean maximum standardized uptake value, 16) on PET scans. All esophageal GISTs were positive for c-KIT (a cell-surface transmembrane tyrosine kinase also known as CD117) and CD34. On histopathology, six esophageal GISTs (75%) were of the spindle pattern and two (25%) were of a mixed spindle and epithelioid pattern. Five esophageal GISTs had exon 11 mutations (with imatinib sensitivity). Clinical outcome correlated with treatment strategy (resection plus adjuvant therapy or resection alone) rather than risk stratification. CONCLUSION Esophageal GISTs are unusual but clinically important mesenchymal neoplasms. Although esophageal GISTs and

A gastrointestinal stromal tumor of the jejunum presenting with an intratumoral abscess: A case report and a literature review.

PubMed

Ito, Soichi; Tsuchitani, Yuma; Kim, Yuro; Hashimoto, Souhei; Miura, Yuichi; Uemura, Takuji; Katsura, Kazunori; Abe, Takayuki; Sato, Koichiro; Kato, Hirotaka

2018-05-29

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. The small intestine is the second-most frequent location where GISTs occur after the stomach. Attention should be paid to small intestinal GISTs because they infrequently present with acute abdomen, which necessitates emergency surgery. This report describes a patient with a small intestinal GIST developing a giant intratumoral abscess, in whom emergency surgery was performed. A 56-year-old woman presented with worsening abdominal pain. Computed tomography scan showed an approximately 9.5 cm × 9 cm tumor bearing a thick and hypervascularized wall with an internal air-fluid level. Emergency laparotomy revealed the tumor originated from the jejunum, and partial resection of the jejunum was performed. A large amount of pus was contained inside the tumor. Immunohistochemically, the tumor was diagnosed as a high risk GIST of the Cjejunum, and imatinib mesylate was initiated. When an intratumoral abscess in the abdomen is confirmed, GISTs should be listed as differential diagnosis. Complete surgical resetcion with careful handling and adjuvant chemotherapy with imatinib mesylate are considered to be important for this state. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Concurrent Male Gynecomastia and Testicular Hydrocele after Imatinib Mesylate Treatment of a Gastrointestinal Stromal Tumor

PubMed Central

Kim, Hawk; Chang, Heung-Moon; Ryu, Min-Hee; Kim, Tae-Won; Sohn, Hee-Jung; Kim, So-Eun; Kang, Hye-Jin; Park, Sarah; Lee, Jung-Shin

2005-01-01

We report a gastrointestinal stromal tumor (GIST) patient with male gynecomastia and testicular hydrocele after treatment with imatinib mesylate. A 42 yr-old male patient presented for management of hepatic masses. Two years earlier, he had undergone a small bowel resection to remove an intraabdominal mass later shown to be a GIST, followed by adjuvant radiation therapy. At presentation, CT scan revealed multiple hepatic masses, which were compatible with metastatic GIST, and he was prescribed imatinib 400 mg/day. During treatment, he experienced painful enlargement of the left breast and scrotal swelling. Three months after cessation of imatinib treatment, the tumors recurred, and, upon recommencing imatinib, he experienced painful enlargement of the right breast and scrotal swelling. He was diagnosed with male gynecomastia caused by decreased testosterone and non-communicative testicular hydrocele. He was given androgen support and a hydrocelectomy, which improved his gynecomastia. The mechanism by which imatinib induces gynecomastia and hydrocele is thought to be associated with an inhibition of c-KIT and platelet-derive growth factor. This is the first report, to our knowledge, describing concurrent male gynecomastia and testicular hydrocele after imatinib treatment of a patient with GIST. PMID:15953881

A meta-analysis of prognostic value of KIT mutation status in gastrointestinal stromal tumors

PubMed Central

Jiang, Zhiqiang; Zhang, Jian; Li, Zhi; Liu, Yingjun; Wang, Daohai; Han, Guangsen

2016-01-01

Numerous types of KIT mutations have been reported in gastrointestinal stromal tumors (GISTs); however, controversy still exists regarding their clinicopathological significance. In this study, we reviewed the publicly available literature to assess the data by a meta-analysis to characterize KIT mutations and different types of KIT mutations in prognostic prediction in patients with GISTs. Twenty-eight studies that included 4,449 patients were identified and analyzed. We found that KIT mutation status was closely correlated with size of tumors and different mitosis indexes, but not with tumor location. KIT mutation was also observed to be significantly correlated with tumor recurrence, metastasis, as well as the overall survival of patients. Interestingly, there was higher risk of progression in KIT exon 9-mutated patients than in exon 11-mutated patients. Five-year relapse-free survival (RFS) rate was significantly higher in KIT exon 11-deleted patients than in those with other types of KIT exon 11 mutations. In addition, RFS for 5 years was significantly worse in patients bearing KIT codon 557–558 deletions than in those bearing other KIT exon 11 deletions. Our results strongly support the hypothesis that KIT mutation status is another evaluable factor for prognosis prediction in GISTs. PMID:27350754

Gastrointestinal Bleeding Is an Independent Risk Factor for Poor Prognosis in GIST Patients

PubMed Central

Liu, Qi; Li, Yuji; Dong, Ming; Kong, Fanmin

2017-01-01

A retrospective analysis of prognosis of GIST was used to assess the prognostic effects of hemorrhage of digestive tract induced by mucosal invasion of primary gastrointestinal stromal tumors and related mechanisms. The conclusion is that GISTs with gastrointestinal hemorrhage are more likely to recur, which indicates poor prognosis. Therefore, gastrointestinal hemorrhage may be used as a significant indicator to assess the prognosis of patients. PMID:28589146

Estimated Costs of Sporadic Gastrointestinal Illness ...

EPA Pesticide Factsheets

BACKGROUND: The ·burden of illness can be described by addressing both incidence and illness severity attributable to water recreation. Monetized as cost. attributable disease burden estimates can be useful for environmental management decisions. OBJECTIVES: We characterize the disease burden attributable to water recreation using data from two cohort studies using a cost of illness (COI) approach and estimate the largest drivers of the disease burden of water recreation. METHODS: Data from the NEEAR study, which evaluated swimming and wading in marine and freshwater beaches in six U.S. states, and CHEERS, which evaluated illness after incidental-contact recreation (boating, canoeing, fishing, kayaking, and rowing) on waterways in the Chicago area, were used to estimate the cost per case of gastrointestinal illness and costs attributable to water recreation. Data on health care and medication utilization and missed days of work or leisure were collected and combined with cost data to construct measures of COI. RESULTS: Depending on different assumptions, the cost of gastrointestinal symptoms attributable to water recreation are estimated to be $1,220 for incidental-contact recreation (range $338-$1,681) and $1,676 for swimming/wading (range $425-2,743) per 1,000 recreators. Lost productivity is a major driver of the estimated COI, accounting for up to 90% of total costs. CONCLUSIONS: Our estimates suggest gastrointestinal illness attributed to surface water rec

Limited resection for duodenal gastrointestinal stromal tumors: Surgical management and clinical outcome

PubMed Central

Hoeppner, Jens; Kulemann, Birte; Marjanovic, Goran; Bronsert, Peter; Hopt, Ulrich Theodor

2013-01-01

AIM: To analyze our experience in patients with duodenal gastrointestinal stromal tumors (GIST) and review the appropriate surgical approach. METHODS: We retrospectively reviewed the medical records of all patients with duodenal GIST surgically treated at our medical institution between 2002 and 2011. Patient files, operative reports, radiological charts and pathology were analyzed. For surgical therapy open and laparoscopic wedge resections and segmental resections were performed for limited resection (LR). For extended resection pancreatoduodenectomy was performed. Age, gender, clinical symptoms of the tumor, anatomical localization, tumor size, mitotic count, type of resection resectional status, neoadjuvant therapy, adjuvant therapy, risk classification and follow-up details were investigated in this retrospective study. RESULTS: Nine patients (5 males/4 females) with a median age of 58 years were surgically treated. The median follow-up period was 45 mo (range 6-111 mo). The initial symptom in 6 of 9 patients was gastrointestinal bleeding (67%). Tumors were found in all four parts of the duodenum, but were predominantly located in the first and second part of the duodenum with each 3 of 9 patients (33%). Two patients received neoadjuvant medical treatment with 400 mg imatinib per day for 12 wk before resection. In one patient, the GIST resection was done by pancreatoduodenectomy. The 8 LRs included a segmental resection of pars 4 of the duodenum, 5 wedge resections with primary closure and a wedge resection with luminal closure by Roux-Y duodeno-jejunostomy. One of these LRs was done minimally invasive; seven were done in open fashion. The median diameter of the tumors was 54 mm (14-110 mm). Using the Fletcher classification scheme, 3/9 (33%) tumors had high risk, 1/9 (11%) had intermediate risk, 4/9 (44%) had low risk, and 1/9 (11%) had very low risk for aggressive behaviour. Seven resections showed microscopically negative transsection margins (R0), two

Identification of key genes related to high-risk gastrointestinal stromal tumors using bioinformatics analysis.

PubMed

Jin, Shuan; Zhu, Wenhua; Li, Jun

2018-01-01

The purpose of this study was to identify predictive biomarkers used for clinical therapy and prognostic evaluation of high-risk gastrointestinal stromal tumors (GISTs). In this study, microarray data GSE31802 were used to identify differentially expressed genes (DEGs) between high-risk GISTs and low-risk GISTs. Then, enrichment analysis of DEGs was conducted based on the gene ontology and kyoto encyclopedia of genes and genomes pathway database. In addition, the transcription factors and cancer-related genes in DEGs were screened according to the TRANSFAC, TSGene, and TAG database. Finally, protein-protein interaction (PPI) network was constructed and analyzed to look for critical genes involved in high-risk GISTs. A total of forty DEGs were obtained and these genes were mainly involved in four pathways, including melanogenesis, neuroactive ligand-receptor interaction, malaria, and hematopoietic cell lineage. The enriched biological processes were related to the regulation of insulin secretion, integrin activation, and neuropeptide signaling pathway. Transcription factor analysis of DEGs indicated that POU domain, class 2, associating factor 1 (POU2AF1) was significantly downregulated in high-risk GISTs. By constructing the PPI network of DEGs, ten genes with high degrees formed local networks, such as PNOC, P2RY14, and SELP. Four genes as POU2AF1, PNOC, P2RY14, and SELP might be used as biomarkers for prognosis of high-risk GISTs.

Laparoscopic resection of locally advanced gastrointestinal stromal tumour (GIST) of the stomach following neoadjuvant imatinib chemoreduction.

PubMed

Berney, Christophe R

2015-01-01

Laparoscopic resection of locally advanced gastrointestinal stromal tumours (GISTs) is rarely offered to patients as a first line of treatment. We present two cases of locally advanced gastric GISTs successfully treated with neoadjuvant imatinib and followed up by complete laparoscopic excision of the residual tumour mass. There was no evidence of local recurrence or distant metastases after a mean follow up of more than 40 months. Over the last decade, the development of imatinib has totally revolutionized management of metastatic GISTs and it is now possible to achieve primary tumour downstaging of more than 80%. Unfortunately, current literature on laparoscopic excision of locally advanced gastric GISTs following neoadjuvant treatment of imatinib remains scarce. The present cases strongly suggest that this new therapeutic approach might become the preferred medical option in such clinical situation. Patients with locally advanced non-metastatic gastric GISTs should be offered first-line neoadjuvant. Imatinib-based cytoreductive chemotherapy as an alternative to radical debulking surgery, as a substantial proportion of them will experience significant tumour shrinkage and therefore benefit from a much less invasive laparoscopic approach. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Distinctive features of gastrointestinal stromal tumors arising from the colon and rectum

PubMed Central

Zhu, Rebecca; Liu, Fangfang; Grisotti, Gabriella; Pérez-Irizarry, Javier; Cha, Charles H.; Johnson, Caroline H.; Boffa, Daniel J.; Han, Dale; Johung, Kimberly L.; Zhang, Yawei

2018-01-01

Background Colon and rectal gastrointestinal stromal tumors (GISTs) are rare and poorly characterized. Because the majority of treatment guidelines for GISTs are extrapolated from tumors of gastric and small bowel origin, our aim was to better characterize the unique clinicopathologic features and prognostic factors of colon and rectal GISTs to guide clinical care. Methods The National Cancer Data Base (NCDB) was queried from 2006 to 2013 for cases of GISTs in the stomach, colon, and rectum. Patient demographics, clinical characteristics, and survival were compared. Results A total of 11,302 gastric GISTs were compared to 398 colon and 393 rectal GISTs. After propensity matching, compared to gastric GISTs, rectal GISTs had improved overall survival (HR =0.695, P=0.0264), while colon GISTs had worse overall survival (HR =1.6, P=0.0005). Surgical treatment for rectal GISTs was more likely to be local excision compared to colonic GISTs (51.1% vs. 8.4%, P<0.0001). Colon and gastric GISTs were less likely to receive systemic therapy compared to rectal GISTs (34.2% vs. 34.0% vs. 55.2%, P<0.0001). Adjuvant systemic therapy conveyed a survival advantage to rectal GISTs (HR =0.47, P=0.042) but not colon GISTs. There was a negative impact of adjuvant therapy on survival for colon GISTs <5 cm (HR =3.41, P=0.032). Conclusions Patients with rectal GISTs live longer than those with colon and gastric GISTs, and adjuvant therapy prolongs their survival. Many patients with colon GISTs are treated with adjuvant therapy despite a detrimental effect on survival. Tumor biology of colon and rectal GISTs needs to be better studied to tailor treatment.

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

PubMed

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

2017-01-01

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. 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). 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. 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.

A Case of Retained Graphite Anterior Chamber Foreign Body Masquerading as Stromal Keratitis

PubMed Central

Han, Eun Ryung; Wee, Won Ryang; Lee, Jin Hak

2011-01-01

We report a case of a retained graphite anterior chamber foreign body that was masquerading as stromal keratitis. A 28-year-old male visited with complaints of visual disturbance and hyperemia in his right eye for four weeks. On initial examination, he presented with a stromal edema involving the inferior half of the cornea, epithelial microcysts, and moderate chamber inflammation. Suspecting herpetic stromal keratitis, he was treated with anti-viral and anti-inflammatory agents. One month after the initial visit, anterior chamber inflammation was improved and his visual acuity recovered to 20/20, but subtle corneal edema still remained. On tapering the medication, after three months, a foreign body was incidentally identified in the inferior chamber angle and was surgically removed resulting in complete resolution of corneal edema. The removed foreign body was a fragment of graphite and he subsequently disclosed a trauma with mechanical pencil 12 years earlier. This case showed that the presence of an anterior chamber foreign body should always be considered in the differential diagnosis of idiopathic localized corneal edema. PMID:21461226

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

PubMed

Call, Jerry; Walentas, Christopher D; Eickhoff, Jens C; Scherzer, Norman

2012-03-19

Gastrointestinal stromal tumors (GIST), one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations) and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies) types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P < 0.05 used to identify independent factors. Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group (< age 18 at diagnosis) was also as previously reported with predominantly stomach tumors, females, wild-type GIST or SDH mutations, and extended survival. "Young adults" however formed a third group aged 18-35 at diagnosis, and were a clear mix of these two previously reported distinct sub-types. Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant prognostic factors for each from a diverse

Prevalence of incidental pancreatic cyst on upper endoscopic ultrasound

PubMed Central

Martínez, Belén; Martínez, Juan F.; Aparicio, José R.

2018-01-01

Background: This study aimed to determine the prevalence of incidental pancreatic cysts in patients undergoing upper endoscopic ultrasound without a known pancreatic abnormality. Methods: This prospective study was conducted in two hospitals in Spain and enrolled consecutive patients referred for upper endoscopic ultrasound for a condition unrelated to the pancreas. Patients with a previous pancreatic anomaly, history of acute or chronic pancreatitis, evidence of acute pancreatitis, previous upper gastrointestinal surgery, or chronic abdominal pain suggestive of pancreatic origin were excluded. Univariate logistic regression was performed to evaluate individual covariates and the incidental pancreatic cyst risk. Results: A total of 298 patients were included, of whom 64 had pancreatic cysts (21.5%; 16.9-26.6%). The mean size of the cysts was 6.3±3.7 (range 3-25) mm. Six cysts (2%) were >10 mm and 16 (5.4%) were compatible with branch duct intraductal papillary mucinous neoplasm. The pancreatic cyst prevalence was similar in the two hospitals and increased significantly with age. Conclusion: The prevalence of incidental pancreatic cysts during endoscopic ultrasound was very high in our study population. PMID:29333072

Drug repurposing identifies a synergistic combination therapy with imatinib mesylate for gastrointestinal stromal tumor.

PubMed

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

2014-10-01

Gastrointestinal stromal tumor (GIST) is a rare and therefore often neglected disease. Introduction of the kinase inhibitor imatinib mesylate 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 affected the overall survival of patients with advanced disease. We employed a novel, focused, drug-repurposing effort for GIST, including imatinib mesylate-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 imatinib mesylate. F-AMP induces DNA damage, Annexin V, and caspase-3/7 activities as the cytotoxic effects on GIST cells, including imatinib mesylate-resistant GIST cells. F-AMP and imatinib mesylate combination treatment showed greater inhibition of GIST cell proliferation when compared with imatinib mesylate and F-AMP alone. Successful in vivo experiments confirmed the combination of imatinib mesylate with F-AMP enhanced the antitumor effects compared with imatinib mesylate 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 imatinib mesylate or for treatment of imatinib mesylate-refractory tumors. ©2014 American Association for Cancer Research.

Evidence mapping based on systematic reviews of therapeutic interventions for gastrointestinal stromal tumors (GIST).

PubMed

Ballesteros, Mónica; Montero, Nadia; López-Pousa, Antonio; Urrútia, Gerard; Solà, Ivan; Rada, Gabriel; Pardo-Hernandez, Hector; Bonfill, Xavier

2017-09-07

Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach. We followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot. A total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm. The most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.

[Possibilities of laparoscopic gastric resection for gastrointestinal stromal tumors].

PubMed

Grubnik, V V; Kovahichuk, A L; Malinovskiy, A V; Barannikov, K V

2016-08-01

Possibilities of laparoscopic technologies application while surgical excision of gas- trointestinal stromal tumors (GIST) were analyzed. In 2000 - 2015 yrs in the clinic 28 patients were operated on for gastric GIST. In 10 of them laparoscopic gastric resec- tion with tumor (in 3 - the tumor excision in borders of nonaffected tissues, in 4 - gas- tric fundus resection or stapler resection of a great curvature together with tumor, in 3 - transgastric excision of the tumor, using staplers) surgery was done. The disease recurrence in 2-5 yrs follow-up was absent. Laparoscopic operations has advantage over open interventions while preserving oncological radicalism.

Rare cause of fever of unknown origin: gastrointestinal stromal tumour.

PubMed

Dodamani, Manjunath Havalappa; Kumar, Rajiv Ranjan; Parkhi, Mayur; Basher, Rajendar

2018-03-28

A 44-year-old man presented with fever (low to high grade) for 2-month duration despite treatment with oral antibiotics and antipyretics. Further, enquiry did not yield any potentially explanatory clues to a diagnosis. Physical examination revealed only left axillary lymphadenopathy, but was otherwise unremarkable. A number of diagnosis included tuberculosis, malignancy, lymphoma, connective disease disorder and infective endocarditis. Further evaluation revealed severe anaemia due to iron deficiency which was supported with blood transfusion and oral iron supplementation. Septic work-up including blood cultures and urine culture sterile and procalcitonin, but all these proved negative. Transthoracic echocardiography followed by transoesophageal echocardiography did not reveal any vegetations suggestive of infective endocarditis. Contrast-enhanced CT of chest and abdomen showed a polypoidal mass in the caecum. Lymph node biopsy from left axillary lymph node showed changes consistent with reactive hyperplasia. A bone marrow biopsy was inconclusive. Mantoux test was negative. A colonoscopy revealed a polypoidal growth arising from caecum with dull-looking mucosa. Biopsy of the mass suggested a leiomyoma. Positron emission tomography CT showed fluorodeoxyglucose (FDG)-avid caecal mass with FDG-avid mesenteric lymph nodes (figure 1). Inspite of extensive work-up, we could not find a source of the fever except for caecal mass. Thus, in the absence of other explanatory findings, a decision for resection of the mass was taken. A laparoscopic right hemicolectomy done with primary anastomosis. Histology confirmed a gastrointestinal stromal tumour (figure 2, which was smooth muscle actin positive (figure 3), S-100 positive, vimentin positive, but c-KIT negative (figure 4), CD34 positive and desmin negative. Additional immunohistochemistry and gene mutational analysis could not be done due to resource limitations. The postoperative course was good, and the patient was

Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases.

PubMed

Cao, Guang; Li, Jian; Shen, Lin; Zhu, Xu

2012-11-14

To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs). Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety. Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable. TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may

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

PubMed

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

2014-01-01

Gastrointestinal stromal tumors (GIST) were identified only recently. These tumors usually have no symptoms, although they are localized, operable and curable. Although rare, if they are not diagnosed and treated early, they become very aggressive. The most common manifestation is gastrointestinal bleeding from mucosal erosion. Their presentation as severe lower gastrointestinal bleeding is exceptional. We report a patient with severe lower gastrointestinal bleeding stabilized by interventional radiology that subsequently required surgery for definitive care. Therapeutic use of radiological embolization is increasingly widespread in bleeding at various levels, achieving hemodynamic stabilization of patients. However, it must be kept in mind that, in cases of unknown etiology of lower gastrointestinal bleeding, possible causes must be investigated.

Dual Targeting of Insulin Receptor and KIT in Imatinib-Resistant Gastrointestinal Stromal Tumors.

PubMed

Chen, Weicai; Kuang, Ye; Qiu, Hai-Bo; Cao, Zhifa; Tu, Yuqing; Sheng, Qing; Eilers, Grant; He, Quan; Li, Hai-Long; Zhu, Meijun; Wang, Yuexiang; Zhang, Rongqing; Wu, Yeqing; Meng, Fanguo; Fletcher, Jonathan A; Ou, Wen-Bin

2017-09-15

Oncogenic KIT or PDGFRA receptor tyrosine kinase (RTK) mutations are compelling therapeutic targets in gastrointestinal stromal tumors (GIST), and treatment with the KIT/PDGFRA inhibitor imatinib is the standard of care for patients with metastatic GIST. Most GISTs eventually acquire imatinib resistance due to secondary mutations in the KIT kinase domain, but it is unclear whether these genomic resistance mechanisms require other cellular adaptations to create a clinically meaningful imatinib-resistant state. Using phospho-RTK and immunoblot assays, we demonstrate activation of KIT and insulin receptor (IR) in imatinib-resistant GIST cell lines (GIST430 and GIST48) and biopsies with acquisition of KIT secondary mutations, but not in imatinib-sensitive GIST cells (GIST882 and GIST-T1). Treatment with linsitinib, a specific IR inhibitor, inhibited IR and downstream intermediates AKT, MAPK, and S6 in GIST430 and GIST48, but not in GIST882, exerting minimal effect on KIT phosphorylation in these cell lines. Additive effects showing increased apoptosis, antiproliferative effects, cell-cycle arrest, and decreased pAKT and pS6 expression, tumor growth, migration, and invasiveness were observed in imatinib-resistant GIST cells with IR activation after coordinated inhibition of IR and KIT by linsitinib (or IR shRNA) and imatinib, respectively, compared with either intervention alone. IGF2 overexpression was responsible for IR activation in imatinib-resistant GIST cells, whereas IR activation did not result from IR amplification, IR mutation, or KIT phosphorylation. Our findings suggest that combinatorial inhibition of IR and KIT warrants clinical evaluation as a novel therapeutic strategy in imatinib-resistant GISTs. Cancer Res; 77(18); 5107-17. ©2017 AACR . ©2017 American Association for Cancer Research.

Percutaneous microwave ablation liver partition and portal vein embolization for planned hepatectomy due to large gastrointestinal stromal tumor metastases

PubMed Central

Liu, Jie; Zhang, Chengwu; Hong, Defei; Shang, Minjie; Yao, Weifeng; Chen, Yuan

2017-01-01

Abstract Rationale: The liver is the most frequent site of relapse of gastrointestinal stromal tumors (GISTs). Surgery is always considered to be unsuitable because of the multiple metastases. Patient concerns: In this report, we describe a case of large, multiple GIST liver metastases that were treated with percutaneous microwave ablation liver partition and portal vein embolization for planned hepatectomy (PALPP). A 44-year-old woman had undergone pancreaticoduodenectomy 4 years previously because of the diagnosis of a large duodenal GIST. Large, multiple liver metastases were observed 2 years later. Diagnoses: GIST liver metastasis was diagnosed using percutaneous ultrasound-guided biopsy. Interventions: After 6 months of treatment with imatinib, the liver metastasis was stable. PALPP was performed because of insufficient future liver remnant (FLR) and right trisegmentectomy was successfully completed 10 days later. Outcomes: The patient has had no signs of local or systemic disease during 17 months of postsurgical follow-up. Lessons: PALPP provides a new methodology for treatment of GIST liver metastasis in patients with insufficient FLR, and may have benefit in prolonging a durable remission. PMID:29049221

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.

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

PubMed

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

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. 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. 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). 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.

Prognostic significance of KIT exon 11 deletion mutation in intermediate-risk gastrointestinal stromal tumor.

PubMed

Quek, Richard; Farid, Mohamad; Kanjanapan, Yada; Lim, Cindy; Tan, Iain Beehuat; Kesavan, Sittampalam; Lim, Tony Kiat Hon; Oon, Lynette Lin-Ean; Goh, Brian Kp; Chan, Weng Hoong; Teo, Melissa; Chung, Alexander Yf; Ong, Hock Soo; Wong, Wai Keong; Tan, Patrick; Yip, Desmond

2017-06-01

Benefit of adjuvant imatinib therapy following curative resection in patients with intermediate-risk gastrointestinal stromal tumor (GIST) is unclear. GIST-specific exon mutations, in particular exon 11 deletions, have been shown to be prognostic. We hypothesize that specific KIT mutations may improve risk stratification in patients with intermediate-risk GIST, identifying a subgroup of patients who may benefit from adjuvant therapy. In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included. Risk classification was based on the modified National Institute of Health (NIH) criteria. In this cohort, 74% (n = 105) of patients harbored a KIT mutation; 61% (n = 86) were found in exon 11 of which nearly 70% were KIT exon 11 deletions (n = 60). A total of 18% (n = 25) of cases were classified as having intermediate-risk disease. Univariate analysis confirmed tumor size, mitotic index, nongastric origin, presence of tumor rupture and modified NIH criteria were adversely prognostic for relapse-free survival (RFS). Among KIT/PDGFRA mutants, KIT exon 11 deletions had a significantly worse prognosis (hazard ratio 2.31; 95% confidence interval, 1.30-4.10; P = 0.003). Multivariate analysis confirmed KIT exon 11 deletion (P = 0.003) and clinical risk classification (P < 0.001) as independent adverse prognostic factors for RFS. Intermediate-risk patients harboring KIT exon 11 deletions had RFS outcomes similar to high-risk patients. The presence of KIT exon 11 deletion mutation in patients with intermediate-risk GIST is associated with an inferior clinical outcome with RFS similar to high-risk patients. © 2016 John Wiley & Sons Australia, Ltd.

Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs).

PubMed

Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

2017-12-19

KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC 50 : 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC 50 : 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan ™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs.

Discovery of a highly selective KIT kinase primary V559D mutant inhibitor for gastrointestinal stromal tumors (GISTs)

PubMed Central

Yu, Kailin; Liu, Xuesong; Jiang, Zongru; Hu, Chen; Zou, Fengming; Chen, Cheng; Ge, Juan; Wu, Jiaxin; Liu, Xiaochuan; Wang, Aoli; Wang, Wenliang; Wang, Wenchao; Qi, Ziping; Wang, Beilei; Wang, Li; Yan, Hezhong; Wang, Jiaoxue; Ren, Tao; Tang, Jun; Liu, Qingsong; Liu, Jing

2017-01-01

KIT kinase V559D mutation is the most prevalent primary gain-of-function mutation in Gastrointestinal Stromal Tumors (GISTs). Here we reported a highly selective KIT V559D inhibitor CHMFL-KIT-031, which displayed about 10-20 fold selectivity over KIT wt in the biochemical assay (IC50: 28 nM over 168 nM; Kd: 266 nM versus 6640 nM) and in cell (EC50: 176 nM versus 2000 nM for pY703) examination. It also displayed 15∼400-fold selectivity over other primary mutants such as L576P and secondary mutants including T670I, V654A (ATP binding pocket) as well as N822K and D816V (activation loop). In addition, it exhibited a selectivity S score (1) of 0.01 among 468 kinases/mutants in the KINOMEScan™ assay. CHMFL-KIT-031 showed potent inhibitory efficacy for KIT V559D mediated signaling pathways in cell and anti-tumor activity in vivo (Tumor Growth Inhibition: 68.5%). Its superior selectivity would make it a good pharmacological tool for further dissection of KIT V559D mediated pathology in the GISTs. PMID:29340041

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

PubMed Central

2014-01-01

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. PMID:24884768

Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors: Current Status and Future Directions.

PubMed

Bauer, Sebastian; Joensuu, Heikki

2015-08-01

Imatinib is strongly positioned as the recommended first-line agent for most patients with advanced gastrointestinal stromal tumor (GIST) due to its good efficacy and tolerability. Imatinib-resistant advanced GIST continues to pose a therapeutic challenge, likely due to the frequent presence of multiple mutations that confer drug resistance. Sunitinib and regorafenib are approved as second- and third-line agents, respectively, for patients whose GIST does not respond to imatinib or who do not tolerate imatinib, and their use is supported by large randomized trials. ATP-mimetic tyrosine kinase inhibitors provide clinical benefit even in heavily pretreated GIST suggesting that oncogenic dependency on KIT frequently persists. Several potentially useful tyrosine kinase inhibitors with distinct inhibitory profiles against both KIT ATP-binding domain and activation loop mutations have not yet been fully evaluated. Agents that have been found promising in preclinical models and early clinical trials include small molecule KIT and PDGFRA mutation-specific inhibitors, heat shock protein inhibitors, histone deacetylase inhibitors, allosteric KIT inhibitors, KIT and PDGFRA signaling pathway inhibitors, and immunological approaches including antibody-drug conjugates. Concomitant or sequential administration of tyrosine kinase inhibitors with KIT signaling pathway inhibitors require further evaluation, as well as rotation of tyrosine kinase inhibitors as a means to suppress drug-resistant cell clones.

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

PubMed

El Mehdi, Tazi; Essadi, Ismail; M'rabti, Hind; Errihani, Hassan

2011-08-04

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. 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. 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.

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

PubMed Central

2012-01-01

Background Gastrointestinal stromal tumors (GIST), one of the most common mesenchymal tumors of the gastrointestinal tract, prior to routine immunohistochemical staining and the introduction of tyrosine kinase inhibitors, were often mistaken for neoplasms of smooth muscle origin such as leiomyomas, leiomyosarcomas or leiomyoblastomas. Since the advent of imatinib, GIST has been further delineated into adult- (KIT or PDGFRα mutations) and pediatric- (typified by wild-type GIST/succinate dehydrogenase deficiencies) types. Using varying gender ratios at age of diagnosis we sought to elucidate prognostic factors for each sub-type and their impact on overall survival. Methods This is a long-term retrospective analysis of a large observational study of an international open cohort of patients from a GIST research and patient advocacy's lifetime registry. Demographic and disease-specific data were voluntarily supplied by its members from May 2000-October 2010; the primary outcome was overall survival. Associations between survival and prognostic factors were evaluated by univariate Cox proportional hazard analyses, with backward selection at P < 0.05 used to identify independent factors. Results Inflections in gender ratios by age at diagnosis in years delineated two distinct groups: above and below age 35 at diagnosis. Closer analysis confirmed the above 35 age group as previously reported for adult-type GIST, typified by mixed primary tumor sites and gender, KIT or PDGFRα mutations, and shorter survival times. The pediatric group (< age 18 at diagnosis) was also as previously reported with predominantly stomach tumors, females, wild-type GIST or SDH mutations, and extended survival. "Young adults" however formed a third group aged 18-35 at diagnosis, and were a clear mix of these two previously reported distinct sub-types. Conclusions Pediatric- and adult-type GIST have been previously characterized in clinical settings and these observations confirm significant

Familial gastrointestinal stromal tumors, lentigines, and café-au-lait macules associated with germline c-kit mutation treated with imatinib.

PubMed

Gupta, Divya; Chandrashekar, Laxmisha; Larizza, Lidia; Colombo, Elisa A; Fontana, Laura; Gervasini, Cristina; Thappa, Devinder M; Rajappa, Medha; Rajendiran, Kalai Selvi; Sreenath, Gubbi Shamanna; Kate, Vikram

2017-02-01

Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes. We report on molecular characterization and tumor histopathology of two siblings in whom lentigines and café-au-lait macules were present along with multifocal GIST. Immuhistochemical analysis of CD34 and CD117 was performed on GIST biopsy samples from both siblings, while c-kit mutational analysis was done by PCR and direct sequencing on DNA from peripheral blood leukocytes of all family members and from paraffin-embedded gastric biopsy specimens of affected siblings. Histopathology revealed positive expression of CD117 and CD34. Mutational analysis showed the germline c.1676T>C mutation in c-kit exon 11, (p.(Val559Ala)), in the peripheral blood of both siblings and a second exon 11 mutation, c.1669T>A (p.(Trp557Arg)) in the tumor biopsy of one of them. Initiation of imatinib treatment resulted in striking resolution of their hyperpigmentation and a stable gastrointestinal disease in one of them. A c-kit mutational test in familial GISTs is indicated before initiation of imatinib therapy, as it can help predict tumor response to treatment. © 2017 The International Society of Dermatology.

Cabozantinib Is Active against Human Gastrointestinal Stromal Tumor Xenografts Carrying Different KIT Mutations.

PubMed

Gebreyohannes, Yemarshet K; Schöffski, Patrick; Van Looy, Thomas; Wellens, Jasmien; Vreys, Lise; Cornillie, Jasmien; Vanleeuw, Ulla; Aftab, Dana T; Debiec-Rychter, Maria; Sciot, Raf; Wozniak, Agnieszka

2016-12-01

In the majority of gastrointestinal stromal tumors (GIST), oncogenic signaling is driven by KIT mutations. Advanced GIST is treated with tyrosine kinase inhibitors (TKI) such as imatinib. Acquired resistance to TKI is mainly caused by secondary KIT mutations, but can also be attributed to a switch of KIT dependency to another receptor tyrosine kinase (RTK). We tested the efficacy of cabozantinib, a novel TKI targeting KIT, MET, AXL, and vascular endothelial growth factor receptors (VEGFR), in patient-derived xenograft (PDX) models of GIST, carrying different KIT mutations. NMRI nu/nu mice (n = 52) were bilaterally transplanted with human GIST: UZLX-GIST4 (KIT exon 11 mutation, imatinib sensitive), UZLX-GIST2 (KIT exon 9, imatinib dose-dependent resistance), or UZLX-GIST9 (KIT exon 11 and 17 mutations, imatinib resistant). Mice were grouped as control (untreated), imatinib (50 mg/kg/bid), and cabozantinib (30 mg/kg/qd) and treated orally for 15 days. Cabozantinib resulted in significant tumor regression in UZLX-GIST4 and -GIST2 and delayed tumor growth in -GIST9. In all three models, cabozantinib inhibited the proliferative activity, which was completely absent in UZLX-GIST4 and significantly reduced in -GIST2 and -GIST9. Increased apoptotic activity was observed only in UZLX-GIST4. Cabozantinib inhibited the KIT signaling pathway in UZLX-GIST4 and -GIST2. In addition, compared with both control and imatinib, cabozantinib significantly reduced microvessel density in all models. In conclusion, cabozantinib showed antitumor activity in GIST PDX models through inhibition of tumor growth, proliferation, and angiogenesis, in both imatinib-sensitive and imatinib-resistant models. Mol Cancer Ther; 15(12); 2845-52. ©2016 AACR. ©2016 American Association for Cancer Research.

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event

PubMed Central

2011-01-01

Background Imatinib mesylate has been the standard therapeutic treatment for chronic myeloid leukemia, advanced and metastatic gastrointestinal stromal tumor (GIST). It is well tolerated with mild adverse effects. Gynecomastia development during the course of treatment has been rarely reported. Methods Ninety-eight patients with advanced or recurrent GIST were treated with imatinib mesylate. Among the fifty-seven male patients six developed gynecomastia during the treatment. The lesions were confirmed by sonography. Sex hormone levels were determined in six patients with and without the presence of gynecomastia respectively. The patients with gynecomatia were treated with tamoxifene and the sex hormones were assayed before and after tamoxifene treatment. Results In patients with gynecomastia the lump underneath the bilateral nipples was 2.5 to 5 centimeters in diameter. Their serum free testosterone levels ranged between 356.61 and 574.60 ng/dl with a mean ± SD of 408.64 ± 82.06 ng/dl (95% CI 343.03~474.25 ng/dl), which is within the normal range. The level of serum estradiol was 42.89 ± 16.54 pg/ml (95% CI 29.66~56.12 pg/ml). Three patients had higher levels (43.79~71.21 pg/ml) and the others' were within normal range of 27.00~34.91 pg/ml. Six patients without the development of gynecomastia had normal free testosterone. One patient died because of large tumor burden. The sex hormones had no significant changes before and after tamoxifene treatment.(P > 0.05) Conclusions Testosterone levels were not decreased in the six GIST patients with gynecomastia. Three patients had increased serum estradiol level which suggests that imbalance of sex hormones may be the cause of gynecomastia during treatment with imatinib mesylate. PMID:22047550

Lower gastrointestinal bleeding secondary to a rectal leiomyoma

PubMed Central

Palma, Giovanni D De; Rega, Maria; Masone, Stefania; Siciliano, Saverio; Persico, Marcello; Salvatori, Francesca; Maione, Francesco; Esposito, Dario; Bellino, Antonio; Persico, Giovanni

2009-01-01

The occurrence of leiomyoma of the rectum is uncommon. Most of these lesions are clinically silent and are found incidentally during laparotomy or endoscopic procedures for unrelated conditions. Symptomatic leiomyomas of the rectum are encountered less frequently, with only sporadic reports in the literature. We describe a case of a leiomyoma of the rectum presenting as recurrent lower gastrointestinal hemorrhage and secondary anemia. PMID:19360922

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

Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor

PubMed Central

Pandurengan, R. K.; Dumont, A. G.; Araujo, D. M.; Ludwig, J. A.; Ravi, V.; Patel, S.; Garber, J.; Benjamin, R. S.; Strom, S. S.; Trent, J. C.

2010-01-01

Background: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies. Patients and methods: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected. Results: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002). Conclusions: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated. PMID:20348145

Pseudoangiomatous stromal hyperplasia causing massive breast enlargement

PubMed Central

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

2015-01-01

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. PMID:26475873

[Radical Resection of Huge Gastrointestinal Stromal Tumor of the Stomach Following Neoadjuvant Chemotherapy with lmatinib - ACase Report].

PubMed

Hiraki, Yoko; Kato, Hiroaki; Shiraishi, Osamu; Tanaka, Yumiko; Iwama, Mitsuru; Yasuda, Atsushi; Shinkai, Masayuki; Kimura, Yutaka; Imano, Motohiro; Imamoto, Haruhiko; Yasuda, Takushi

2017-11-01

The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.

The expression of hematopoietic progenitor cell antigen CD34 is regulated by DNA methylation in a site-dependent manner in gastrointestinal stromal tumours.

PubMed

Bure, Irina; Braun, Alexander; Kayser, Claudia; Geddert, Helene; Schaefer, Inga-Marie; Cameron, Silke; Ghadimi, Michael B; Ströbel, Philipp; Werner, Martin; Hartmann, Arndt; Wiemann, Stefan; Agaimy, Abbas; Haller, Florian; Moskalev, Evgeny A

2017-12-01

The anatomic site-dependent expression of hematopoietic progenitor cell antigen CD34 is a feature of gastrointestinal stromal tumours (GISTs). The basis for the differential CD34 expression is only incompletely understood. This study aimed at understanding the regulation of CD34 in GISTs and clarification of its site-dependent expression. Two sample sets of primary GISTs were interrogated including 52 fresh-frozen and 134 paraffin-embedded and formalin-fixed specimens. DNA methylation analysis was performed by HumanMethylation450 BeadChip array in three cell lines derived from gastric and intestinal GISTs, and differentially methylated CpG sites were established upstream of CD34. The methylation degree was further quantified by pyrosequencing, and inverse correlation with CD34 mRNA and protein abundance was revealed. The gene's expression could be activated upon induction of DNA hypomethylation with 5-aza-2'-deoxycytidine in GIST-T1 cells. In patient samples, a strong inverse correlation of DNA methylation degree with immunohistochemically evaluated CD34 expression was documented. Both CD34 expression and DNA methylation levels were specific to the tumours' anatomic location and mutation status. A constant decrease in methylation levels was observed ranging from almost 100% hypermethylation in intestinal GISTs from duodenum to hypomethylation in rectum. CD34 was heavily methylated in gastric PDGFRA-mutant GISTs in comparison to hypomethylated KIT-mutant counterparts. Next to CD34 hypermethylation, miR-665 was predicted and experimentally confirmed to target CD34 mRNA in GIST-T1 cells. Our results suggest that CD34 expression in GISTs may undergo a complex control by DNA methylation and miR-665. Differential methylation and expression of CD34 in GISTs along the gastrointestinal tract axis and in tumours that harbour different gain-of-function mutations suggest the origin from different cell populations in the gastrointestinal tract. © 2017 UICC.

Stromal Progenitor Cells in Mitigation of Non-Hematopoietic Radiation Injuries

PubMed Central

Kulkarni, Shilpa; Wang, Timothy C.; Guha, Chandan

2016-01-01

Purpose of review Therapeutic exposure to high doses of radiation can severely impair organ function due to ablation of stem cells. Normal tissue injury is a dose-limiting toxicity for radiation therapy (RT). Although advances in the delivery of high precision conformal RT has increased normal tissue sparing, mitigating and therapeutic strategies that could alleviate early and chronic radiation effects are urgently needed in order to deliver curative doses of RT, especially in abdominal, pelvic and thoracic malignancies. Radiation-induced gastrointestinal injury is also a major cause of lethality from accidental or intentional exposure to whole body irradiation in the case of nuclear accidents or terrorism. This review examines the therapeutic options for mitigation of non-hematopoietic radiation injuries. Recent findings We have developed stem cell based therapies for the mitigation of acute radiation syndrome (ARS) and radiation-induced gastrointestinal syndrome (RIGS). This is a promising option because of the robustness of standardized isolation and transplantation of stromal cells protocols, and their ability to support and replace radiation-damaged stem cells and stem cell niche. Stromal progenitor cells (SPC) represent a unique multipotent and heterogeneous cell population with regenerative, immunosuppressive, anti-inflammatory, and wound healing properties. SPC are also known to secrete various key cytokines and growth factors such as platelet derived growth factors (PDGF), keratinocyte growth factor (KGF), R-spondins (Rspo), and may consequently exert their regenerative effects via paracrine function. Additionally, secretory vesicles such as exosomes or microparticles can potentially be a cell-free alternative replacing the cell transplant in some cases. Summary This review highlights the beneficial effects of SPC on tissue regeneration with their ability to (a) target the irradiated tissues, (b) recruit host stromal cells, (c) regenerate endothelium and

Small Bowel Gastrointestinal Stromal Tumors: Multidetector Computed Tomography Enhancement Pattern and Risk of Progression.

PubMed

Verde, Franco; Hruban, Ralph H; Fishman, Elliot K

Small bowel gastrointestinal stromal tumors (SB-GISTs) are rare lesions with a variable appearance on computed tomography (CT). This case series analyzes the CT enhancement pattern with the histologic risk assessment of tumor progression. Local institutional pathology database was searched for SB-GISTs from 2000 to 2015. Pathology reports and clinical notes were reviewed. Imaging was qualitatively reviewed for pattern of enhancement categorized into homogeneous or heterogeneous groups. Nonparametric statistical analysis was performed comparing enhancement to segment of bowel involved, presence of necrosis, tumor size, histologic grade (ie, G1 or G2), and histologic risk of progression (ie low, moderate, high). For simplicity, risk of progression was binned into low-risk or non-low-risk groups. Twenty-six pathology-proven, first presentation, nonmetastatic SB-GISTs were included into study. Seventeen were located in duodenum, 7 in jejunum, and 2 within the ileum. Dual phase (arterial and venous) CT imaging was available for 22 cases. Four cases did not have dual phase (three venous phase and one arterial phase only). Seventeen cases demonstrated heterogeneous enhancement and 9 cases homogeneous enhancement. Statistically significant difference was found between size versus enhancement groups (3.1 cm for homogeneous versus 6.8 cm for heterogeneous) (Mann-Whitney U test, n = 26, P = 0.002). Presence of necrosis versus enhancement group was statistically significant (Pearson χ, P = 0.001). Low-risk and non-low-risk groups versus enhancement groups was very significant (P = 0.001). Bowel segment involvement and histologic grading versus enhancement group did not reach statistical significance (P = 0.174 and P = 0.07, respectively). This case series reveals an important significant association between heterogeneous enhancement and non-low risk (ie, moderate/high) SB-GISTs. Beyond just describing the tumor, using enhancing pattern, the interpreting radiologist can

Cost-Effectiveness Analysis of Tyrosine Kinase Inhibitors for Patients with Advanced Gastrointestinal Stromal Tumors.

PubMed

Nerich, Virginie; Fleck, Camille; Chaigneau, Loïc; Isambert, Nicolas; Borg, Christophe; Kalbacher, Elsa; Jary, Marine; Simon, Pauline; Pivot, Xavier; Blay, Jean-Yves; Limat, Samuel

2017-01-01

The management of advanced gastrointestinal stromal tumors (GISTs) has been modified considerably by the availability of costly tyrosine kinase inhibitors (TKIs); however, the best therapeutic sequence in terms of cost and effectiveness remains unknown. The aim of this study was to compare four potential strategies (reflecting the potential daily practice), each including imatinib 400 mg/day, as first-line treatment: S1 (imatinib 400 /best supportive care [BSC]); S2 (imatinib 400 /imatinib 800 /BSC); S3 (imatinib 400 /sunitinib/BSC); and S4 (imatinib 400 /imatinib 800 /sunitinib/BSC). A Markov model was developed with a hypothetical cohort of patients and a lifetime horizon. Transition probabilities were estimated from the results of clinical trials. The analysis was performed from the French payer perspective, and only direct medical costs were included. Clinical and economic parameters were discounted, and the robustness of results was assessed. The least costly and effective strategy was S1, at a cost of €65,744 for 32.9 life months (reference). S3 was the most cost-effective strategy, with an incremental cost-effectiveness ratio (ICER) of €48,277/life-year saved (LYS). S2 was dominated, and S4 yielded an ICER of €363,320/LYS compared with S3. Sensitivity analyses confirmed the robustness of these results; however, when taking into account a price reduction of 80 % for imatinib, S2 and S4 become the most cost-effective strategies. Our approach is innovative to the extent that our analysis takes into account the sequential application of TKIs. The results suggest that the S1 strategy is the best cost-effective strategy, but a price reduction of imatinib impacts on the results. This approach must continue, including new drugs and their impact on the quality of life of patients with advanced GISTs.

Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site.

PubMed

Antonescu, Cristina R; Viale, Agnes; Sarran, Lisa; Tschernyavsky, Sylvia J; Gonen, Mithat; Segal, Neil H; Maki, Robert G; Socci, Nicholas D; DeMatteo, Ronald P; Besmer, Peter

2004-05-15

Gastrointestinal stromal tumors (GISTs) are specific KIT expressing and KIT-signaling driven mesenchymal tumors of the human digestive tract, many of which have KIT-activating mutations. Previous studies have found a relatively homogeneous gene expression profile in GIST, as compared with other histological types of sarcomas. Transcriptional heterogeneity within clinically or molecularly defined subsets of GISTs has not been previously reported. We tested the hypothesis that the gene expression profile in GISTs might be related to KIT genotype and possibly to other clinicopathological factors. An HG-U133A Affymetrix chip (22,000 genes) platform was used to determine the variability of gene expression in 28 KIT-expressing GIST samples from 24 patients. A control group of six intra-abdominal leiomyosarcomas was also included for comparison. Statistical analyses (t tests) were performed to identify discriminatory gene lists among various GIST subgroups. The levels of expression of various GIST subsets were also linked to a modified version of the growth factor/KIT signaling pathway to analyze differences at various steps in signal transduction. Genes involved in KIT signaling were differentially expressed among wild-type and mutant GISTs. High gene expression of potential drug targets, such as VEGF, MCSF, and BCL2 in the wild-type group, and Mesothelin in exon 9 GISTs were found. There was a striking difference in gene expression between stomach and small bowel GISTs. This finding was validated in four separate tumors, two gastric and two intestinal, from a patient with familial GIST with a germ-line KIT W557R substitution. GISTs have heterogeneous gene expression depending on KIT genotype and tumor location, which is seen at both the genomic level and the KIT signaling pathway in particular. These findings may explain their variable clinical behavior and response to therapy.

qPCR in gastrointestinal stromal tumors: Evaluation of reference genes and expression analysis of KIT and the alternative receptor tyrosine kinases FLT3, CSF1-R, PDGFRB, MET and AXL

PubMed Central

2010-01-01

Background Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the gastrointestinal tract. About 85% carry an activating mutation in the KIT or PDGFRA gene. Approximately 10% of GIST are so-called wild type GIST (wt-GIST) without mutations in the hot spots. In the present study we evaluated appropriate reference genes for the expression analysis of formalin-fixed, paraffin-embedded and fresh frozen samples from gastrointestinal stromal tumors. We evaluated the gene expression of KIT as well as of the alternative receptor tyrosine kinase genes FLT3, CSF1-R, PDGFRB, AXL and MET by qPCR. wt-GIST were compared to samples with mutations in KIT exon 9 and 11 and PDGFRA exon 18 in order to evaluate whether overexpression of these alternative RTK might contribute to the pathogenesis of wt-GIST. Results Gene expression variability of the pooled cDNA samples is much lower than the single reverse transcription cDNA synthesis. By combining the lowest variability values of fixed and fresh tissue, the genes POLR2A, PPIA, RPLPO and TFRC were chosen for further analysis of the GIST samples. Overexpression of KIT compared to the corresponding normal tissue was detected in each GIST subgroup except in GIST with PDGFRA exon 18 mutation. Comparing our sample groups, no significant differences in the gene expression levels of FLT3, CSF1R and AXL were determined. An exception was the sample group with KIT exon 9 mutation. A significantly reduced expression of CSF1R, FLT3 and PDGFRB compared to the normal tissue was detected. GIST with mutations in KIT exon 9 and 11 and in PDGFRA exon 18 showed a significant PDGFRB downregulation. Conclusions As the variability of expression levels for the reference genes is very high comparing fresh frozen and formalin-fixed tissue there is a strong need for validation in each tissue type. None of the alternative receptor tyrosine kinases analyzed is associated with the pathogenesis of wild-type or mutated GIST. It

Downsizing Treatment with Tyrosine Kinase Inhibitors in Patients with Advanced Gastrointestinal Stromal Tumors Improved Resectability

PubMed Central

Sjölund, Katarina; Andersson, Anna; Nilsson, Erik; Nilsson, Ola; Ahlman, Håkan

2010-01-01

Background Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first-line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high-risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ-preserving surgery was facilitated. Methods Ten high-risk GIST-patients had downsizing/adjuvant TKI treatment: nine with imatinib and one with sunitinib. The patients were matched with historical controls (n = 89) treated with surgery alone, from our population-based series (n = 259). Mutational analysis of KIT and PDGFRA was performed in all cases. The progression-free survival was calculated. Results The primary tumors decreased in mean diameter from 20.4 cm to 10.5 cm on downsizing imatinib. Four patients with R0 resection and a period of adjuvant imatinib had no recurrences versus 67% in the historical control group. Four patients with residual liver metastases have stable disease on continuous imatinib treatment after surgery. One patient has undergone reoperation with liver resection. The downsizing treatment led to organ-preserving surgery in nine patients and improved preoperative nutritional status in one patient. Conclusions Downsizing TKI is recommended for patients with bulky tumors with invasion of adjacent organs. Sunitinib can be used for patients in case of imatinib resistance (e.g., wild-type GISTs), underlining the importance of mutational analysis for optimal surgical planning. PMID:20512492

Imatinib as the first and only treatment in Europe for adult patients at significant risk of relapse following gastrointestinal stromal tumor removal

PubMed Central

Duffaud, F; Salas, S; Huyn, T; Deville, JL

2010-01-01

Mutations of the KIT gene are the molecular hallmark of most gastrointestinal stromal tumors (GISTs). GIST has become a model for targeted treatment of solid tumors, imatinib becoming the standard first-line treatment of these tumors in the advanced/metastatic phase. Because of the efficacy of imatinib treatment in the advanced setting, its role following resection of a primary non-metastatic GIST was investigated. The recently published phase III, double-blind, placebo-controlled, multicenter ACOSOG Z9001 study showed that adjuvant therapy is safe, and significantly improves recurrence-free survival compared to placebo when given after resection. To what extent imatinib will improve overall survival has yet to be answered. What is clear is that high-risk GIST patients definitely need adjuvant therapy, and that 1 year of imatinib is not enough for the patients who do need it. The questions of optimal duration of imatinib treatment in the adjuvant setting, adequate selection of risk patients and effect of imatinib on overall survival are currently being studied. PMID:21694845

Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor.

PubMed

Bosbach, Benedikt; Rossi, Ferdinand; Yozgat, Yasemin; Loo, Jennifer; Zhang, Jennifer Q; Berrozpe, Georgina; Warpinski, Katherine; Ehlers, Imke; Veach, Darren; Kwok, Andrew; Manova, Katia; Antonescu, Cristina R; DeMatteo, Ronald P; Besmer, Peter

2017-10-03

Gastrointestinal stromal tumors (GISTs) predominantly harbor activating mutations in the receptor tyrosine kinase KIT. To genetically dissect in vivo the requirement of different signal transduction pathways emanating from KIT for tumorigenesis, the oncogenic Kit V558Δ mutation was combined with point mutations abrogating specific phosphorylation sites on KIT. Compared with single-mutant Kit V558Δ/+ mice, double-mutant Kit V558Δ;Y567F/Y567F knock-in mice lacking the SRC family kinase-binding site on KIT (pY567) exhibited attenuated MAPK signaling and tumor growth. Surprisingly, abrogation of the PI3K-binding site (pY719) in Kit V558Δ;Y719F/Y719F mice prevented GIST development, although the interstitial cells of Cajal (ICC), the cells of origin of GIST, were normal. Pharmacologic inhibition of the PI3K pathway in tumor-bearing Kit V558Δ/+ mice with the dual PI3K/mTOR inhibitor voxtalisib, the pan-PI3K inhibitor pilaralisib, and the PI3K-alpha-restricted inhibitor alpelisib each diminished tumor proliferation. The addition of the MEK inhibitor PD-325901 or binimetinib further decreased downstream KIT signaling. Moreover, combining PI3K and MEK inhibition was effective against imatinib-resistant Kit V558Δ;T669I/+ tumors.

Direct engagement of the PI3K pathway by mutant KIT dominates oncogenic signaling in gastrointestinal stromal tumor

PubMed Central

Bosbach, Benedikt; Rossi, Ferdinand; Yozgat, Yasemin; Loo, Jennifer; Zhang, Jennifer Q.; Berrozpe, Georgina; Warpinski, Katherine; Ehlers, Imke; Kwok, Andrew; Manova, Katia; Antonescu, Cristina R.; DeMatteo, Ronald P.; Besmer, Peter

2017-01-01

Gastrointestinal stromal tumors (GISTs) predominantly harbor activating mutations in the receptor tyrosine kinase KIT. To genetically dissect in vivo the requirement of different signal transduction pathways emanating from KIT for tumorigenesis, the oncogenic KitV558Δ mutation was combined with point mutations abrogating specific phosphorylation sites on KIT. Compared with single-mutant KitV558Δ/+ mice, double-mutant KitV558Δ;Y567F/Y567F knock-in mice lacking the SRC family kinase-binding site on KIT (pY567) exhibited attenuated MAPK signaling and tumor growth. Surprisingly, abrogation of the PI3K-binding site (pY719) in KitV558Δ;Y719F/Y719F mice prevented GIST development, although the interstitial cells of Cajal (ICC), the cells of origin of GIST, were normal. Pharmacologic inhibition of the PI3K pathway in tumor-bearing KitV558Δ/+ mice with the dual PI3K/mTOR inhibitor voxtalisib, the pan-PI3K inhibitor pilaralisib, and the PI3K-alpha–restricted inhibitor alpelisib each diminished tumor proliferation. The addition of the MEK inhibitor PD-325901 or binimetinib further decreased downstream KIT signaling. Moreover, combining PI3K and MEK inhibition was effective against imatinib-resistant KitV558Δ;T669I/+ tumors. PMID:28923937

Blue nevus of the prostate: incidental finding in radical prostatectomy specimen with a pre-operative echographic image of peripheral hypoechogenic nodule.

PubMed

Raspollini, Maria Rosaria; Masieri, Lorenzo; Tosi, Nicola; Santucci, Marco

2011-12-01

Blue nevus is a stromal melanin deposition, which is microscopically characterized by deeply pigmented melanin-filled spindle cells within the fibromuscular stroma. Cases with prominent melanosis such as those with grossly visible pigment are uncommon. Melanocytic lesions of the prostate are incidental findings with no evidence of malignant transformation. There have only been very few reports of a malignant melanoma of primary prostatic origin. We report an incidental finding of a blue nevus of the prostate, in a radical prostatectomy specimen, in a 64-years-old man with a pre-operative ecographic image of peripheral hypoechogenic nodule. The are very few reports of blue nevi associated to prostatic adenocarcinoma, but none has been evidentiated before surgery as a distinct ultrasound lesion interpreted as adenocarcinoma, therefore inducing the clinician to perform biopsies and consequently a radical prostatectomy.

Numerous eosinophilic globules (skeinoid fibers) in a duodenal stromal tumor: an exceptional case showing smooth muscle differentiation.

PubMed

Matsukuma, S; Doi, M; Suzuki, M; Ikegawa, K; Sato, K; Kuwabara, N

1997-11-01

A unique case of duodenal stromal tumor in a 51-year-old man is reported. The tumor histologically showed spindle cell proliferation and numerous eosinophilic globules. Most globules were composed of tangled 45 nm thick fibrils, which were ultrastructurally identical to 'skeinoid fibers'. The presence of glycogen granules in the tumor cells and the immunoreactivity for alpha-smooth muscle actin suggested smooth muscle differentiation. Focal ultrastructural findings also supported the smooth muscle nature of this tumor. There were no immunohistochemical and ultrastructural features indicating neural differentiation. In previous studies, the presence of such 'skeinoid fibers' was suggested to be a histological marker for neural differentiation in gastrointestinal stromal tumor. However, the findings in the present case suggest that numerous 'skeinoid fibers' can be identified in duodenal stromal tumor with smooth muscle differentiation, although this condition may be rare.

Overcoming Cost Implications of Mutational Analysis in Patients with Gastrointestinal Stromal Tumors: A Pragmatic Approach.

PubMed

Schöffski, Patrick; Wozniak, Agnieszka; Schöffski, Oliver; van Eycken, Liesbet; Debiec-Rychter, Maria

2016-01-01

Genetic analysis of tissue derived from patients with advanced gastrointestinal stromal tumors (GISTs) is not uniformly applied on a national and international level, even though mutational data can provide clinically relevant prognostic and predictive information, especially in patients qualifying for treatment with expensive targeted agents. The current article describes the rationale for genetic testing of GIST tissue, looks at financial implications associated with such analysis and speculates on potential cost savings introduced by routine mutational testing and tailored use of tyrosine kinase inhibitors based on genotyping. This work is based on a hypothetical analysis of epidemiological data, drug costs, reimbursement criteria and market research figures. The cost burden for routine genotyping of important genes in GISTs, especially in patients at high risk for relapse after primary surgery and in advanced, inoperable metastatic disease, is relatively low. The early identification of GISTs with primary resistance mutations should be the basis for personalized GIST treatment and reimbursement of drugs. As illustrated by Belgian figures, the exclusive use of a drug such as imatinib in patients who are likely to benefit from the agent based on genetic information can lead to significant cost savings, which outweigh the costs for testing. Mutational analysis of GIST should be considered early in all patients at risk for relapse after curative surgery and in the case of advanced, inoperable, metastatic disease. The costs for the actual genotyping should not be used as an argument against profiling of the tumor. The adjuvant and palliative systemic treatment of GISTs should be personalized based on the genotype and other known prognostic and predictive factors. Reimbursement criteria for essential agents such as imatinib should be adapted accordingly. © 2016 S. Karger GmbH, Freiburg.

Plastic bread-bag clips in the gastrointestinal tract: report of 5 cases and review of the literature

PubMed Central

Newell, K J; Taylor, B; Walton, J C; Tweedie, E J

2000-01-01

Plastic bread-bag clips have been identified as a cause of local perforation or obstruction at many sites in the gastrointestinal tract. This study is the largest case series yet reported, consisting of 3 cases presenting as small-bowel perforation, 1 case in which the clip was found incidentally in the small bowel at laparotomy during vascular surgery and 1 case in which the clip was found incidentally in the small bowel at autopsy. In all cases there was no radiographic evidence to suggest a foreign body in the gastrointestinal tract. People older than 60 years of age who have either partial or full dentures seem to be particularly at risk for the accidental ingestion of these devices. If accidentally ingested, plastic bread-bag clips represent a significant health hazard. As the population ages, small-bowel perforation secondary to ingestion of such clips may occur with increasing frequency. The authors recommend elimination or redesign of the clips, to prevent their being swallowed and becoming impacted in the small bowel or to allow them to be identified in the gastrointestinal tract by conventional radiography. PMID:10701390

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.

Oncogenic Kit signalling on the Golgi is suppressed by blocking secretory trafficking with M-COPA in gastrointestinal stromal tumours.

PubMed

Obata, Yuuki; Horikawa, Keita; Shiina, Isamu; Takahashi, Tsuyoshi; Murata, Takatsugu; Tasaki, Yasutaka; Suzuki, Kyohei; Yonekura, Keita; Esumi, Hiroyasu; Nishida, Toshirou; Abe, Ryo

2018-02-28

Most gastrointestinal stromal tumours (GISTs) are caused by constitutively active mutations in Kit tyrosine kinase. The drug imatinib, a specific Kit inhibitor, improves the prognosis of metastatic GIST patients, but these patients become resistant to the drug by acquiring secondary mutations in the Kit kinase domain. We recently reported that a Kit mutant causes oncogenic signals only on the Golgi apparatus in GISTs. In this study, we show that in GIST, 2-methylcoprophilinamide (M-COPA, also known as "AMF-26"), an inhibitor of biosynthetic protein trafficking from the endoplasmic reticulum (ER) to the Golgi, suppresses Kit autophosphorylation at Y703/Y721/Y730/Y936, resulting in blockade of oncogenic signalling. Results of our M-COPA treatment assay show that Kit Y703/Y730/Y936 in the ER are dephosphorylated by protein tyrosine phosphatases (PTPs), thus the ER-retained Kit is unable to activate downstream molecules. ER-localized Kit Y721 is not phosphorylated, but not due to PTPs. Importantly, M-COPA can inhibit the activation of the Kit kinase domain mutant, resulting in suppression of imatinib-resistant GIST proliferation. Our study demonstrates that Kit autophosphorylation is spatio-temporally regulated and may offer a new strategy for treating imatinib-resistant GISTs. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Integrated Molecular Characterization of Gastrointestinal Stromal Tumors (GIST) Harboring the Rare D842V Mutation in PDGFRA Gene

PubMed Central

Astolfi, Annalisa; Patterson, Janice; Nannini, Margherita; Saponara, Maristella; Gatto, Lidia; Santini, Donatella; do Valle, Italo F.; Castellani, Gastone; Fiorentino, Michelangelo; von Mehren, Margaret; Brandi, Giovanni; Biasco, Guido; Heinrich, Michael C.; Pantaleo, Maria Abbondanza

2018-01-01

Gastrointestinal stromal tumors (GIST) carrying the D842V activating mutation in the platelet-derived growth factor receptor alpha (PDGFRA) gene are a very rare subgroup of GIST (about 10%) known to be resistant to conventional tyrosine kinase inhibitors (TKIs) and to show an indolent behavior. In this study, we performed an integrated molecular characterization of D842V mutant GIST by whole-transcriptome and whole-exome sequencing coupled with protein–ligand interaction modelling to identify the molecular signature and any additional recurrent genomic event related to their clinical course. We found a very specific gene expression profile of D842V mutant tumors showing the activation of G-protein-coupled receptor (GPCR) signaling and a relative downregulation of cell cycle processes. Beyond D842V, no recurrently mutated genes were found in our cohort. Nevertheless, many private, clinically relevant alterations were found in each tumor (TP53, IDH1, FBXW7, SDH-complex). Molecular modeling of PDGFRA D842V suggests that the mutant protein binds imatinib with lower affinity with respect to wild-type structure, showing higher stability during the interaction with other type I TKIs (like crenolanib). D842V mutant GIST do not show any actionable recurrent molecular events of therapeutic significance, therefore this study supports the rationale of novel TKIs development that are currently being evaluated in clinical studies for the treatment of D842V mutant GIST. PMID:29510530

The timing and probability of treatment switch under cost uncertainty: an application to patients with gastrointestinal stromal tumor.

PubMed

de Mello-Sampayo, Felipa

2014-03-01

Cost fluctuations render the outcome of any treatment switch uncertain, so that decision makers might have to wait for more information before optimally switching treatments, especially when the incremental cost per quality-adjusted life year (QALY) gained cannot be fully recovered later on. To analyze the timing of treatment switch under cost uncertainty. A dynamic stochastic model for the optimal timing of a treatment switch is developed and applied to a problem in medical decision taking, i.e. to patients with unresectable gastrointestinal stromal tumour (GIST). The theoretical model suggests that cost uncertainty reduces expected net benefit. In addition, cost volatility discourages switching treatments. The stochastic model also illustrates that as technologies become less cost competitive, the cost uncertainty becomes more dominant. With limited substitutability, higher quality of technologies will increase the demand for those technologies disregarding the cost uncertainty. The results of the empirical application suggest that the first-line treatment may be the better choice when considering lifetime welfare. Under uncertainty and irreversibility, low-risk patients must begin the second-line treatment as soon as possible, which is precisely when the second-line treatment is least valuable. As the costs of reversing current treatment impacts fall, it becomes more feasible to provide the option-preserving treatment to these low-risk individuals later on. Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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.

Combined DNA methylation and gene expression profiling in gastrointestinal stromal tumors reveals hypomethylation of SPP1 as an independent prognostic factor.

PubMed

Haller, Florian; Zhang, Jitao David; Moskalev, Evgeny A; Braun, Alexander; Otto, Claudia; Geddert, Helene; Riazalhosseini, Yasser; Ward, Aoife; Balwierz, Aleksandra; Schaefer, Inga-Marie; Cameron, Silke; Ghadimi, B Michael; Agaimy, Abbas; Fletcher, Jonathan A; Hoheisel, Jörg; Hartmann, Arndt; Werner, Martin; Wiemann, Stefan; Sahin, Ozgür

2015-03-01

Gastrointestinal stromal tumors (GISTs) have distinct gene expression patterns according to localization, genotype and aggressiveness. DNA methylation at CpG dinucleotides is an important mechanism for regulation of gene expression. We performed targeted DNA methylation analysis of 1.505 CpG loci in 807 cancer-related genes in a cohort of 76 GISTs, combined with genome-wide mRNA expression analysis in 22 GISTs, to identify signatures associated with clinicopathological parameters and prognosis. Principal component analysis revealed distinct DNA methylation patterns associated with anatomical localization, genotype, mitotic counts and clinical follow-up. Methylation of a single CpG dinucleotide in the non-CpG island promoter of SPP1 was significantly correlated with shorter disease-free survival. Hypomethylation of this CpG was an independent prognostic parameter in a multivariate analysis compared to anatomical localization, genotype, tumor size and mitotic counts in a cohort of 141 GISTs with clinical follow-up. The epigenetic regulation of SPP1 was confirmed in vitro, and the functional impact of SPP1 protein on tumorigenesis-related signaling pathways was demonstrated. In summary, SPP1 promoter methylation is a novel and independent prognostic parameter in GISTs, and might be helpful in estimating the aggressiveness of GISTs from the intermediate-risk category. © 2014 UICC.

Incidental gall bladder carcinoma in laparoscopic cholecystectomy: a report of 6 cases and a review of the literature.

PubMed

Sujata, Jetley; S, Rana; Sabina, Khan; Mj, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases.

Tumeur stromale du mésentère: une cause inhabituelle d'une masse abdominale

PubMed Central

Tarchouli, Mohamed; Bounaim, Ahmed; Boudhas, Adil; Ratbi, Moulay Brahim; Ndjota, Bobby Nguele; Ali, Abdelmounaim Ait; Sair, Khalid

2015-01-01

Les tumeurs stromales gastro-intestinales (GIST) sont les tumeurs mésenchymateuses les plus fréquentes du tractus digestif. Elles représentent une entité nosologique individualisée depuis la découverte de l'expression quasi-constante de la protéine c-Kit détectée par la coloration immunohistochimique de l'antigène CD117. Des tumeurs avec les mêmes caractéristiques morphologiques et immuno-phénotypiques peuvent rarement apparaître en dehors du tractus gastro-intestinal. Nous rapportons le cas d'une jeune patiente de 34 ans présentant une masse tumorale mésentérique se révélant être de nature stromale sans aucun contact avec la paroi intestinale. Il s'agit d'une localisation très rare des tumeurs stromales à laquelle il faut penser en préopératoire afin d'avoir une conduite thérapeutique adaptée et efficace. PMID:26327998

Prognostic value of mutational characteristics in gastrointestinal stromal tumors: a single-center experience in 275 cases.

PubMed

Wang, Ming; Xu, Jia; Zhao, Wenyi; Tu, Lin; Qiu, Weiqing; Wang, Chaojie; Shen, Yangyin; Liu, Qiang; Cao, Hui

2014-01-01

The objective of this study was to investigate the impact of KIT/PDGFRA mutations on the prognosis of gastrointestinal stromal tumors (GISTs). In the present study, genotype analyses were performed based on GIST samples from 275 patients. The relationship between mutation and clinicopathological characteristics were explored. All factors were evaluated for their impacts on relapse-free survival (RFS). Briefly, the results of genotype analyses showed that mutations were identified in 258 (93.8 %) patients, and deletion was the most frequent type of mutation accounting for 47.3 % (122/258) of all mutation cases, followed by substitution (87/258, 33.7 %) and duplication (49/258, 19.0 %). Moreover, for KIT exon 11 mutation, the most frequently involved area was from codon 557 to 560. Deep analyses showed that the mutation types were correlated with tumor location (P = 0.005), tumor size (P = 0.022), mitosis rate (P < 0.001), risk grade (P < 0.001), and relapse (P = 0.004). Furthermore, delW557-K558 correlated with mitosis rate (P = 0.042) and relapse (P = 0.036), and delTyr568/570 correlated with tumor origin (P = 0.018). Most importantly, mitotic rate [HR = 2.901 (95 % CI 1.094-7.695), P = 0.032] and risk grade [HR = 9.629 (95 % CI 1.997-46.416), P = 0.005] would be the representative traditional prognostic factors, and deletion with >3 codons would be an novel independent predictor of poor outcome for RFS in GIST patients with deletion mutation of KIT exon 11 [HR = 7.970 (95 % CI 1.774-35.803), P = 0.007]. All results indicated that mutation determined clinicopathological features and prognosis of GISTs, and more than three codons involvement may be a novel adverse indicator.

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST

PubMed Central

Kelly, Lorna; Bryan, Kenneth; Kim, Su Young; Janeway, Katherine A.; Killian, J. Keith; Schildhaus, Hans-Ulrich; Miettinen, Markku; Helman, Lee; Meltzer, Paul S.; van de Rijn, Matt; Debiec-Rychter, Maria; O’Sullivan, Maureen

2013-01-01

In contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate post-transcriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wild-type gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster

Post-transcriptional dysregulation by miRNAs is implicated in the pathogenesis of gastrointestinal stromal tumor [GIST].

PubMed

Kelly, Lorna; Bryan, Kenneth; Kim, Su Young; Janeway, Katherine A; Killian, J Keith; Schildhaus, Hans-Ulrich; Miettinen, Markku; Helman, Lee; Meltzer, Paul S; van de Rijn, Matt; Debiec-Rychter, Maria; O'Sullivan, Maureen

2013-01-01

In contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate post-transcriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wild-type gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster

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

PubMed Central

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

2017-01-01

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. PMID:28192400

Unraveling the spectrum of KIT mutations in gastrointestinal stromal tumors: An Indian Tertiary Cancer Center Experience.

PubMed

Pai, Trupti; Bal, Munita; Shetty, Omshree; Gurav, Mamta; Ostwal, Vikas; Ramaswamy, Anant; Ramadwar, Mukta; Desai, Sangeeta

2017-01-01

Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. Morphological and immunohistochemically confirmed GIST cases ( n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape ® and Chromas Lite. KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502-503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series.

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.

Prognostic factors of primary gastrointestinal stromal tumors: a cohort study based on high-volume centers.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2018-02-01

We aimed to evaluate the clinicopathologic characteristics, immunohistochemical expression and prognostic factors of patients with primary gastrointestinal stromal tumors (GISTs). Data from 2,570 consecutive GIST patients from four medical centers in China (January 2001-December 2015) were reviewed. Survival curves were constructed by the Kaplan-Meier method, and Cox regression models were used to identify independent prognostic factors. Of the included patients, 1,375 (53.5%) were male, and the patient age range was 18 to 95 (median, 58) years. The tumors were mostly found in the stomach (64.5%), small intestine (25.1%) and colorectal region (5.1%). At the time of diagnosis, the median tumor size was 4.0 (range: 0.1-55.0) cm, and the median mitotic index per 50 high power fields (HPFs) was 3 (range: 0-254). Of the 2,168 resected patients, 2,009 (92.7%) received curative resection. According to the modified National Institutes of Health (NIH) classification, 21.9%, 28.9%, 14.1% and 35.1% were very low-, low-, intermediate- and high-risk tumors, respectively. The rate of positivity was 96.4% for c-Kit, 87.1% for CD34, 96.9% for delay of germination 1 (DOG-1), 8.0% for S-100, 31.0% for smooth muscle actin (SMA) and 5.1% for desmin. However, the prognostic value of each was limited. Multivariate analysis showed that age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors. Furthermore, we found that high-risk patients benefited significantly from postoperative imatinib (P<0.001), whereas intermediate-risk patients did not (P=0.954). Age, tumor size, mitotic index, tumor site, occurrence of curative resection and postoperative imatinib were independent prognostic factors in patients with GISTs. Moreover, determining whether intermediate-risk patients can benefit from adjuvant imatinib would be of considerable interest in future studies.

Clinicopathologic study of succinate-dehydrogenase-deficient gastrointestinal stromal tumors: A single-institutional experience in China.

PubMed

Liu, Weizhen; Zeng, Xiangyu; Wu, Xiuli; He, Jun; Gao, Jinbo; Shuai, Xiaoming; Wang, Guobin; Zhang, Peng; Tao, Kaixiong

2017-08-01

Gastrointestinal stromal tumors (GISTs) that are not driven by kinase mutations, as are most GISTs, often show loss of function of the succinate dehydrogenase (SDH) complex and are considered SDH-deficient GISTs. SDH-deficient GISTs share many distinct characteristics compared with conventional GISTs. However, data regarding these characteristics, particularly among Asian people, are relatively limited. The objective of this study was to characterize the clinicopathologic characteristics, treatment, and prognosis of these uncommon GISTs.This retrospective observational study enrolled 12 patients with SDH-deficient GISTs, who were selected from 335 patients with GIST diagnosed at our institution between October 31, 2013 and October 31, 2016 by succinate dehydrogenase subunit B staining.There were 8 male and 4 female patients, with a median age of 57 years (range, 21-73 years). Ten patients (83.3%) were diagnosed at or after the age of 40 years and represented 7.2% (10/138) of the entire population of elderly patients with gastric GISTs. The tumor size ranged from 3 to 19 cm (median, 7 cm); the primary tumor was multifocal in 6 cases (50%), and tumors had a multinodular or plexiform architecture in 10 cases (83.3%). Ten cases (83.3%) showed pure epithelioid morphology, with the remaining 2 cases (16.7%) showing mixed histologic subtype. Lymph node metastasis was found at the time of primary resection in 50% (3/6) of patients. Four cases (33.3%) had distant metastasis at presentation. Four patients (33.3%) developed disease progression during imatinib treatment after initial resection, but all of these patients regained disease control when the treatment was altered to sunitinib targeted therapy.SDH-deficient GISTs arise exclusively in the stomach and account for approximately 7.4% (12/162) of gastric GISTs. Moreover, those affecting people older than 40 years are not uncommon and sunitinib may work well for cases showing treatment failure with imatinib.

Should we excise? Are there any clinical or histologic features that predict upgrade in papillomas, incidental or non-incidental?

PubMed

Zaleski, Michael; Chen, Yun An; Chetlen, Alison L; Mack, Julie; Xu, Liyan; Dodge, Daleela G; Karamchandani, Dipti M

2018-05-11

The clinical decision to excise intraductal papilloma (IDP) without atypia diagnosed on biopsy remains controversial. We sought to establish clinical and histologic predictors (if any) which may predict upgrade in IDP. 296 biopsies (in 278 women) with histologic diagnosis of IDP without atypia were retrospectively identified and placed into Incidental (no corresponding imaging correlate), or Non-incidental (positive imaging correlate) groups. 253/296 (85.5%) cases were non-incidental, and 43/296 (14.5%) were incidental. 73.1% (185/253) non-incidental and 48.8% (21/43) incidental cases underwent excision. 12.4% (23/185) non-incidental cases underwent an upgrade to cancer or high-risk lesion; namely 8-Ductal carcinoma in situ (DCIS), 8-atypical ductal hyperplasia (ADH), 6-lobular neoplasia, and 1-flat epithelial atypia. There was no histopathologic feature on the biopsy in the non-incidental group which predicted upgrade; however a past history of atypia was significantly associated with upgrade. 2 of the 21 incidental cases upgraded (1 to ADH and 1 to lobular neoplasia); the former had a past history of ADH. Both incidental upgrades were >1 mm in size, and were not completely excised on the biopsy. None of the incidental cases which appeared completely excised on biopsy upgraded, irrespective of the size on biopsy. These findings suggest that all non-incidental IDPs should be considered candidates for surgical excision, given the 12.4% upgrade rate and no definitive histologic predictors of upgrade. Patients with incidental IDPs (if <1 mm, completely excised on biopsy and with no history of high risk breast lesion) can be spared excision. Copyright © 2018 Elsevier Inc. All rights reserved.

Stromal and epithelial cells react differentially to c-kit in fibroepithelial tumors of the breast.

PubMed

Logullo, Angela F; Nonogaki, Suely; Do Socorro Maciel, Maria; Mourão-Neto, Mário; Soares, Fernando Augusto

2008-01-01

The CD117 protein is a tyrosine-kinase receptor encoded by the c-kit gene that frequently bears activating mutations in gastrointestinal tumors. Conflicting findings regarding CD117 expression in other stromal tumors, including phyllodes tumors (PTs), have been reported in the literature. The purpose of this study was to evaluate c-kit expression in the stroma and epithelia of fibroepithelial breast tumors and its correlation with clinical pathological variables. Ninety-six fibroepithelial tumors of the breast, including 14 fibroadenomas (FAs), 12 juvenile FAs and 70 PTs, were classified according to stromal cellularity, atypia, epithelial hyperplasia, mitosis and borders into 45 benign (PTB), 17 borderline (PTBL) and 8 malignant (PTM) tumors. CD117 expression was identified in the stromal component in only two cases of PTBL. Overall, 38 cases (39.6%) showed positive CD117 in the epithelial component, including 20 FAs (10 regular, 10 juvenile) and 18 PTs (11 PTBs and 8 PTBLs). Other cases, including all PTMs, 6 FAs (4 regular, 2 juvenile), 34 PTBs and 10 PTBLs, showed no positivity in the epithelial component. Expression of c-kit did not correlate with diagnosis or malignancy (p>0.05). In conclusion, c-kit is expressed more often in the epithelial than in the stromal component in fibroepithelial tumors of the breast, and is associated with benign lesions.

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.

Incidental Gall Bladder Carcinoma in Laparoscopic Cholecystectomy: A Report of 6 Cases and a Review of the Literature

PubMed Central

Sujata, Jetley; S, Rana; Sabina, Khan; MJ, Hassan; Jairajpuri, Zeeba Shamim

2013-01-01

Background: Gall bladder carcinoma accounts for 98% of all the gall bladder malignancies and it is the sixth most common malignancy of the gastrointestinal tract worldwide. The incidence of incidental gall bladder carcinoma which is diagnosed during or after a laparoscopic cholecystectomy is reported to be around 0.19-3.3% in the literature. Aim: This study was aimed at detecting the incidence of gall bladder carcinomas which were diagnosed incidentally during or after laparoscopic cholecystectomies which were done for gall stone disease and cholecystitis. Materials and Methods: We analyzed the medical records of patients with symptomatic gallstone disease and acute or chronic cholecystitis, who underwent laparoscopic cholecystectomies at the Hakeem Abdul Hameed Centenary Hospital during the period from January 2007 to June 2012. Results: A total of 622 laparoscopic cholecystectomies were performed at our institute during the study period of five and a half years. In 6 (0.96%) cases, incidental carcinomas of the gallbladder were discovered. Conclusion: A laparoscopic cholecystectomy which is performed for benign gall bladder disease rarely results in a diagnosis of unexpected gallbladder cancer. The microscopic examination of the specimens, with special attention to the depth of invasion, range of the mucosal spread and the lymphovascular involvement, is critical in diagnosing the incidental malignancies as well as for the subsequent management of the cases. PMID:23449518

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

Managing incidental findings on abdominal CT: white paper of the ACR incidental findings committee.

PubMed

Berland, Lincoln L; Silverman, Stuart G; Gore, Richard M; Mayo-Smith, William W; Megibow, Alec J; Yee, Judy; Brink, James A; Baker, Mark E; Federle, Michael P; Foley, W Dennis; Francis, Isaac R; Herts, Brian R; Israel, Gary M; Krinsky, Glenn; Platt, Joel F; Shuman, William P; Taylor, Andrew J

2010-10-01

As multidetector CT has come to play a more central role in medical care and as CT image quality has improved, there has been an increase in the frequency of detecting "incidental findings," defined as findings that are unrelated to the clinical indication for the imaging examination performed. These "incidentalomas," as they are also called, often confound physicians and patients with how to manage them. Although it is known that most incidental findings are likely benign and often have little or no clinical significance, the inclination to evaluate them is often driven by physician and patient unwillingness to accept uncertainty, even given the rare possibility of an important diagnosis. The evaluation and surveillance of incidental findings have also been cited as among the causes for the increased utilization of cross-sectional imaging. Indeed, incidental findings may be serious, and hence, when and how to evaluate them are unclear. The workup of incidentalomas has varied widely by physician and region, and some standardization is desirable in light of the current need to limit costs and reduce risk to patients. Subjecting a patient with an incidentaloma to unnecessary testing and treatment can result in a potentially injurious and expensive cascade of tests and procedures. With the participation of other radiologic organizations listed herein, the ACR formed the Incidental Findings Committee to derive a practical and medically appropriate approach to managing incidental findings on CT scans of the abdomen and pelvis. The committee has used a consensus method based on repeated reviews and revisions of this document and a collective review and interpretation of relevant literature. This white paper provides guidance developed by this committee for addressing incidental findings in the kidneys, liver, adrenal glands, and pancreas. Copyright © 2010 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Incidental findings in pediatric research.

PubMed

Wilfond, Benjamin S; Carpenter, Katherine J

2008-01-01

The approach to incidental research findings in children emerges by considering the child-parent relationship and balancing divergent interests and preferences. Incidental findings with clear and proximate clinical importance should be disclosed to both. We recommend that particularly sensitive or private information (e.g., pregnancy or drug use) should be disclosed to the adolescent first, while particularly serious information (e.g., cancer) should first be disclosed to the parent. These approaches allow the researcher to form an alliance with one party prior to engaging the other. However, unlike clinical settings, where there may be presumptive expectations of confidentiality about sharing information within the family, in most research settings it is reasonable to plan to disclose such information to both parties. It is important to communicate this plan during the informed consent process separately to adolescents to avoid enrolling adolescents when sensitive incidental findings such as pregnancy and drug use may be detected. The approach to incidental findings without clear and proximate benefit is challenging. Researchers should plan more limited disclosure of such incidental findings for pediatric participants than for adult participants.

Endometrial stromal sarcoma mimicking submucosal myoma protruding to the vagina: MRI findings.

PubMed

Chien, J C W; Hsieh, S C; Lee, R C; Chen, C Y; Cheng, C J; Chan, W P

2005-01-01

A 46-year-old woman complained of persistent abnormal vaginal bleeding over ten days. Her intrauterine device had been removed two years before. Soon after, she suffered from menorrhagia and metrorrhagia. An incidental finding of severe anemia was also noted. In this admission, our initial T2-weighted magnetic resonance imaging (MRI) revealed a well-demarcated mass predominantly in the uterine cavity. The mass was depicted by an isointense signal relative to the myometrium on T1-weighted images, high signal intensity on T2-weighted images, and slightly heterogeneous enhancement on post-contrast images. The patient refused surgery. After two years, follow-up MRI showed a pedunculated mass protruding into the upper third of the vagina with a stalk connecting to the posterior wall of the uterine cavity, simulating submucosal myoma. Histological diagnosis was compatible with low-grade endometrial stromal sarcoma.

Contribution of galectin-1, a glycan-binding protein, to gastrointestinal tumor progression.

PubMed

Bacigalupo, María L; Carabias, Pablo; Troncoso, María F

2017-08-07

Gastrointestinal cancer is a group of tumors that affect multiple sites of the digestive system, including the stomach, liver, colon and pancreas. These cancers are very aggressive and rapidly metastasize, thus identifying effective targets is crucial for treatment. Galectin-1 (Gal-1) belongs to a family of glycan-binding proteins, or lectins, with the ability to cross-link specific glycoconjugates. A variety of biological activities have been attributed to Gal-1 at different steps of tumor progression. Herein, we summarize the current literature regarding the roles of Gal-1 in gastrointestinal malignancies. Accumulating evidence shows that Gal-1 is drastically up-regulated in human gastric cancer, hepatocellular carcinoma, colorectal cancer and pancreatic ductal adenocarcinoma tissues, both in tumor epithelial and tumor-associated stromal cells. Moreover, Gal-1 makes a crucial contribution to the pathogenesis of gastrointestinal malignancies, favoring tumor development, aggressiveness, metastasis, immunosuppression and angiogenesis. We also highlight that alterations in Gal-1-specific glycoepitopes may be relevant for gastrointestinal cancer progression. Despite the findings obtained so far, further functional studies are still required. Elucidating the precise molecular mechanisms modulated by Gal-1 underlying gastrointestinal tumor progression, might lead to the development of novel Gal-1-based diagnostic methods and/or therapies.

Incidental health information use on the Internet.

PubMed

Tian, Yan; Robinson, James D

2009-01-01

This study investigates the correlates of incidental or nonpurposive health information use on the Internet. Through a secondary analysis of the Health Information National Trends Survey II data, this study reveals that incidental health information use on the Internet is positively associated with overall Internet use, active health information seeking on the Internet, and incidental health information use from traditional media. Thus, this study extends the notion of media complementarity to incidental media usage in a health communication context. This study also reveals that adults who have been diagnosed with cancer are more likely to have incidental health information use from traditional media but not the Internet. More important, this study suggests that incidental health information use on the Internet is positively associated with health knowledge. The findings have important implications for health information campaigns on the Internet.

Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs).

PubMed

de Oliveira, Antônio Talvane Torres; Pinheiro, Céline; Longatto-Filho, Adhemar; Brito, Maria Jose; Martinho, Olga; Matos, Delcio; Carvalho, André Lopes; Vazquez, Vinícius Lima; Silva, Thiago Buosi; Scapulatempo, Cristovam; Saad, Sarhan Sydney; Reis, Rui Manuel; Baltazar, Fátima

2012-02-01

Monocarboxylate transporters (MCTs) have been described to play an important role in cancer, but to date there are no reports on the significance of MCT expression in gastrointestinal stromal tumors (GISTs). The aim of the present work was to assess the value of MCT expression, as well as co-expression with the MCT chaperone CD147 in GISTs and evaluate their clinical-pathological significance. We analyzed the immunohistochemical expression of MCT1, MCT2, MCT4 and CD147 in a series of 64 GISTs molecularly characterized for KIT, PDGFRA and BRAF mutations. MCT1, MCT2 and MCT4 were highly expressed in GISTs. CD147 expression was associated with mutated KIT (p = 0.039), as well as a progressive increase in Fletcher's Risk of Malignancy (p = 0.020). Importantly, co-expression of MCT1 with CD147 was associated with low patient's overall survival (p = 0.037). These findings suggest that co-expression of MCT1 with its chaperone CD147 is involved in GISTs aggressiveness, pointing to a contribution of cancer cell metabolic adaptations in GIST development and/or progression.

Amyloidoma of Stomach: A Case Report.

PubMed

Savant, Deepika; Adler, Michael; Kahn, Leonard; Cocker, Rubina

2018-04-25

Amyloidomas are tumor-like deposits of amyloid. Amyloidoma of the gastrointestinal tract is rare. To the best of our knowledge, this is the first instance of diagnosis of an amyloidoma in the gastrointestinal tract by fine needle aspiration (FNA). We report a case of a 64-year-old male with a history of ulcerative colitis and primary sclerosing cholangitis who was incidentally found to have a mass in the stomach wall. Initially thought to be gastrointestinal stromal tumor, FNA demonstrated the lesion to be amyloidoma with a prominent giant cell reaction. This was further confirmed by mass spectrometry. This is the only case report of diagnosis of a gastric amyloidoma by FNA. The presence of a florid giant cell reaction in the absence of ulceration or an inflammatory or neoplastic lesion should alert the pathologist to the possibility of an amyloidoma. This is the only case report of diagnosis of a gastric amyloidoma by FNA. © 2018 S. Karger AG, Basel.

F-18 FDG PET, CT, and MRI for detecting the malignant potential in patients with gastrointestinal stromal tumors: A protocol for a network meta-analysis of diagnostic test accuracy.

PubMed

Wei, Kongyuan; Pan, Bei; Yang, Huan; Lu, Cuncun; Ge, Long; Cao, Nong

2018-04-01

Gastrointestinal stromal tumor (GIST) is a rare cancer in gastrointestinal carcinomas and has been widely known as a curable disease among all the digestive tumors. However, early detection of malignant potential in patients with GIST has still been a huge challenge all around the world. CT, MRI, and F-18 FDG PET are all considered as good tests for diagnosing malignant GIST efficiently, but no recommended suggestions presents which test among the 3 is the prior one in detecting the malignant potential of GIST. We perform this study to assess the accuracy between CT, MRI, and F-18 FDG PET through network meta-analysis method, and to rank these tests. PubMed, EMBASE.com, CNKI, and CBM databases will be searched without search date and language restrictions. We will include diagnostic tests which assessed the accuracy of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST. The risk of bias in each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. This study is ongoing, and will be submitted to a peer-reviewed journal for publication. This study will provide a comprehensive evidence summary of CT, MRI, and F-18 FDG PET in detecting the malignant potential of GIST.

Hereditary Gastrointestinal Cancer Syndromes

PubMed Central

Lynch, Jane F.; Shaw, Trudy G.

2011-01-01

ABSTRACT 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. PMID:22368732

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.

[Unusually large stromal tumor of the rectum causing obstruction].

PubMed

Hornok, L; Lestár, B; Nagy, P; Ritter, L; László, S; Kiss, J

2000-06-01

A male, 74 years old patient with perineal, sacral pain and with defecation disorders attended the outpatient clinic of HIETE. The origine of the complains was a retrorectal, fist like, rectum narrowing tumor. The tumor was covered by normal mucosa from rectal side. Preoperative examinations--endoscopy, CT, MRI transrectal US--detected a tumor with size 7 x 6 x 5 cm, growing from the muscular wall of the rectum, with no connection with the surrounding tissues. Deep biopsy revealed malignant mesenchymal tumor. After preoperative irradiation abdominoperineal rectum amputation was performed. The recovery was uneventful. The definitive hystological examination proved a gastrointestinal stromal tumor (GIST). This type of tumor rarely occurs in the large intestine or in the rectum, that why the publishing can be interesting.

Preoperative diagnosis of obscure gastrointestinal bleeding due to a GIST of the jejunum: a case report.

PubMed

Gourgiotis, Stavros; Kotoulas, Dimitrios; Aloizos, Stavros; Kolovou, Aikaterini; Salemis, Nikolaos S; Kantounakis, Ioannis

2009-11-25

Gastrointestinal stromal tumours (GISTs) are rare mesenchymal neoplasms affecting the digestive tract or nearby structures within the abdomen. We present a case of a 66-year-old female patient who presented with obscure anemia due to gastrointestinal bleeding and underwent exploratory laparotomy during which a large GIST of the small intestine was discovered. Examining the preoperative results of video capsule endoscopy, computed tomography, and angiography and comparing them with the operative findings we discuss which of these investigations plays the most important role in the detection and localization of GIST. A sort review of the literature is also conducted on these rare mesenchymal tumours.

Gastrointestinal stromal tumours of stomach: Robot-assisted excision with the da Vinci Surgical System regardless of size and location site.

PubMed

Furbetta, Niccolo; Palmeri, Matteo; Guadagni, Simone; Di Franco, Gregorio; Gianardi, Desirée; Latteri, Saverio; Marciano, Emanuele; Moglia, Andrea; Cuschieri, Alfred; Di Candio, Giulio; Mosca, Franco; Morelli, Luca

2018-03-23

The role of minimally invasive surgery of gastrointestinal stromal tumours (GISTs) of the stomach remains uncertain especially for large and/or difficult located tumours. We are hereby presenting a single-centre series of robot-assisted resections using the da Vinci Surgical System (Si or Xi). Data of patients undergoing robot-assisted treatment of gastric GIST were retrieved from the prospectively collected institutional database and a retrospective analysis was performed. Patients were stratified according to size and location of the tumour. Difficult cases (DCs) were considered for size if tumour was> 50 mm and/or for location if the tumour was Type II, III or IV sec. Privette/Al-Thani classification. Between May 2010 and February 2017, 12 consecutive patients underwent robot-assisted treatment of GIST at our institution. DCs were 10/12 cases (83.3%), of which 6/10 (50%) for location, 2/10 (25%) for size and 2/10 (25%) for both. The da Vinci Si was used in 8 patients, of which 6 (75%) were DC, and the da Vinci Xi in 4, all of which (100%) were DC. In all patients, excision was by wedge resection. All lesions had microscopically negative resection margins. There was no conversion to open surgery, no tumour ruptures or spillage and no intraoperative complications. Our experience suggests a positive role of the robot da Vinci in getting gastric GIST removal with a conservative approach, regardless of size and location site. Comparative studies with a greater number of patients are necessary for a more robust assessment.

Survivin is a novel transcription regulator of KIT and is downregulated by miRNA‐494 in gastrointestinal stromal tumors

PubMed Central

Yun, SeongJu; Kim, Won Kyu; Kwon, Yujin; Jang, Mi; Bauer, Sebastian

2018-01-01

Gain‐of‐function mutations of KIT are pathognomonic in sporadic gastrointestinal stromal tumors (GISTs). Several microRNAs have been shown to be dysregulated in GISTs and impact KIT expression. Little is known though on KIT‐independent targets of KIT‐regulating mRNAs. We sought to investigate how miR‐494 inhibits GIST proliferation and to identify novel target gene. We used microarray‐based gene expression analyses to identify pathways and target genes affected by miR‐494. The expressional relationship between survivin and miR‐494 was determined in 35 GIST tissues. Cell proliferation assay, FACS analysis, colony formation assay, promoter assays and chromatin immunoprecipitation (ChiP) were performed to clarify the roles of survivin in GIST progression. Gene expression microarray analysis revealed that miR‐494 inhibited GISTs by affecting multiple genes in the cell cycle pathway. Survivin (BIRC5) was a key target of miR‐494, and its expression showed an inverse correlation with miR‐494 expression in 35 GIST tissues (Pearson's correlation coefficient, r = −0.418, p = 0.012). Downregulation of survivin inhibited proliferation and colony formation, and resulted in cell cycle alteration. Induced survivin overexpression relieved miR‐494‐mediated inhibition of GIST progression. Targeting PI3K effectively suppressed proliferation of GISTs with downregulation of survivin. Survivin also regulated KIT expression at the transcription level. Immunohistochemical analysis using 113 GISTs revealed that survivin expression was significantly correlated with overall survival of GIST patients (p = 0.004). Our findings indicated that miR‐494 synergistically suppressed GISTs by concomitantly targeting survivin and KIT. PMID:29277888

Gastrointestinal stromal tumor (GIST) with liver metastases: An 18-year experience from the GIST cooperation group in North China.

PubMed

Shi, Yi-Nan; Li, Yong; Wang, Li-Ping; Wang, Zhen-Hua; Liang, Xiao-Bo; Liang, Han; Zhang, Li; Li, Bin; Fan, Li-Qiao; Zhao, Qun; Ma, Zhi-Xue; Zhao, Xue-Feng; Zhang, Zhi-Dong; Liu, Yu; Tan, Bi-Bo; Wang, Dong; Wang, Li-Li; Hao, Ying-Jie; Jia, Nan

2017-11-01

Approximately 40% to 50% of gastrointestinal stromal tumor (GIST) patients will have recurrence or metastases after resection of the primary lesion, and the most common affected sites will be liver and peritoneum. Imatinib has been considered as the first-line therapy of metastatic GIST. Surgery for metastases is proposed when possible. Furthermore, there are controversies concerning hepatic resection and systemic tyrosin kinase inhibitors (TKIs). The therapeutic conditions and long-term outcome of GIST patients with liver metastases in northern China remain unknown.The clinical, pathological, and follow-up data of 144 GIST patients, who had liver metastases between June 1996 and June 2014 from 3 tertiary cancer centers in northern China, were reviewed.Thirty-two cases (22.2%) had hepatectomy with 23 (23/32, 71.9%) R0 resections and 9 (9/32, 28.1%) R1/R2 resections, respectively. Twenty-three patients were given imatinib postoperatively. Furthermore, 98 (68.1%) patients were given TKIs only to control disease progression, and sunitinib was considered after imatinib failure in 12 patients. The 1-, 3- and 5-year survival rate was 82%, 51%, and 24%, with a median overall survival of 48 months for all patients. Patients who had hepatic resection combined with TKIs had a tendency of improved outcome, and the median survival time was 89 months. This was in contrast to patients who received TKIs only, in which median survival time was 53 months. Patients who received imatinib plus sunitinib had a tendency of longer survival time, compared with patients who received imatinib only (not reached vs 50 months).TKIs combined with hepatic resection had a role in improving the outcome of GIST patients with liver metastases.

Remarkable effects of imatinib in a family with young onset gastrointestinal stromal tumors and cutaneous hyperpigmentation associated with a germline KIT-Trp557Arg mutation: case report and literature overview.

PubMed

Farag, S; van der Kolk, L E; van Boven, H H; van Akkooi, A C J; Beets, G L; Wilmink, J W; Steeghs, N

2018-04-01

Gastrointestinal stromal tumors (GISTs) occur mostly sporadically. GISTs associated with a familial syndrome are very rare and are mostly wild type for KIT and platelet-derived growth factor alpha (PDGFRA). To date 35 kindreds and 8 individuals have been described with GISTs associated with germline KIT mutations. This is the third family described with a germline p.Trp557Arg mutation in exon 11 of the KIT gene. The effect of imatinib in patients harboring a germline KIT mutation has been rarely described. Moreover, in some studies imatinib treatment was withheld considering the lack of evidence for efficacy of this treatment in GIST patients harboring a germline KIT mutation. This paper describes a 52-year old patient with a de novo germline p.Trp557Arg mutation with multiple GISTs throughout the gastrointestinal tract and cutaneous hyperpigmentation. Imatinib treatment showed long-term regression of the GISTs and evident pathological response was seen after resection. Remarkably, the hyperpigmentation of the skin also diminished during imatinib treatment. Genetic screening of the family revealed the same mutation in two daughters, both with similar cutaneous hyperpigmentation. One daughter, aged 23, was diagnosed with multiple small intestine GISTs, which were resected. She was treated with adjuvant imatinib which prompted rapid regression of the cutaneous hyperpigmentation. Imatinib treatment in GIST patients harboring a germline KIT mutation shows favorable and long-term responses in both the tumor and the phenotypical hyperpigmentation.

Laparoscopic resection of gastric and small bowel gastrointestinal stromal tumors: 10-year experience at a single center.

PubMed

Tabrizian, Parissa; Sweeney, Robert E; Uhr, Joshua H; Nguyen, Scott Q; Divino, Celia M

2014-03-01

Complete curative resection remains the treatment of choice for nonmetastatic gastrointestinal stromal tumors (GISTs). The safety and feasibility of laparoscopy in the treatment of this disease has been shown, however, the long-term oncologic outcomes of this technique remain unclear. An ongoing prospectively maintained database including all laparoscopically resected gastric and small bowel GISTs (n = 116) at Mount Sinai Medical Center from July 1999 to December 2011 was retrospectively analyzed. Recurrence and survival outcomes were calculated using the Kaplan-Meier method and compared with log-rank test. Tumors were of gastric (77.6%) and small bowel (22.4%) origins. Overall mean tumor size was 4.0 cm (±2.7 cm) and R0 resection was achieved in 113 (97.4%) cases. Overall perioperative complication rate was 14.7%, with a reoperative rate of 4.3% at 90 days. When comparing gastric with small bowel GISTs, a more acute presentation requiring emergent resections was noted in patients with small bowel GISTs (p = 008). However tumor size, operative data, and perioperative outcomes were comparable in both groups (p = NS). At a median follow-up of 56.4 months (range 0.1 to 162.4 months), recurrence rate was 7.8% and comparable in both gastric and small bowel GISTs (p = NS). Risk factors for recurrence on univariate analysis were presence of ulceration/necrosis (p < 0.001) and tumor size >5 cm (p = 0.05). Overall 10-year survival rate was 90.8%. Gastric and small bowel overall survival rates were similar (90.7% vs 91.3%, respectively). Overall 10-year disease-free survival was 80.0% (84.3% gastric vs 71.6% small bowel; p = NS). Our series demonstrates the safety and feasibility of laparoscopy in patients undergoing resection of small bowel and gastric GISTs. Comparable long-term oncologic outcomes with a 10-year survival of 90.8% were achieved. Copyright © 2014. Published by Elsevier Inc.

Renal cell carcinoma: incidental detection and pathological staging.

PubMed

Siow, W Y; Yip, S K; Ng, L G; Tan, P H; Cheng, W S; Foo, K T

2000-10-01

In developed countries, there has been increased incidental detection of renal cell carcinoma (RCC). The incidence, pathological stage and survival of incidentally detected carcinoma in a developing country in Asia where, from 1990 to 1998, 165 renal cell carcinomas were identified. The clinical presentation, diagnostic-imaging modality employed, pathological staging and patient survival was reviewed. Incidental renal cancers included those that were diagnosed through health screening or detected incidentally through imaging studies for other conditions. The survival between these incidentally detected lesions and their symptomatic counterparts (suspected group) was compared. Sixty-four patients (39%) had their tumours detected incidentally, including 39 who were entirely asymptomatic and 25 who presented with non-specific symptoms, not initially suggestive of RCC. For the entire group, computed tomography provided the definitive diagnosis in 81% of cases. The incidental detection group had significantly smaller size of tumour (5.9 cm c.f. 7.6 cm), lower stage and lower histological grading. In particular, 78% of patients with incidental RCC had stage I or II diseases (TNM stage classification), compared with 57% of patients with suspected tumour (p < 0.05; Chi-square test). The disease free survival was significantly better for those with incidental detection (86% c.f. 66% at last follow up; p < 0.05; log-rank test) over a mean follow up period of 33 months (range 1-91). Regression analysis showed that stage of disease was the only independent variable predictive of clinical outcome. In conclusion, that significant numbers of RCC were detected incidentally. These tumours were of a lower clinical pathological stage and had a better prognosis.

Dose-escalation study of a second-generation non-ansamycin HSP90 inhibitor, onalespib (AT13387), in combination with imatinib in patients with metastatic gastrointestinal stromal tumour.

PubMed

Wagner, Andrew J; Agulnik, Mark; Heinrich, Michael C; Mahadevan, Daruka; Riedel, Richard F; von Mehren, Margaret; Trent, Jonathan; Demetri, George D; Corless, Christopher L; Yule, Murray; Lyons, John F; Oganesian, Aram; Keer, Harold

2016-07-01

Gastrointestinal stromal tumours (GIST) treated with the tyrosine kinase inhibitor (TKI) imatinib can become resistant when additional mutations in the receptor tyrosine kinases KIT or PDGFRA block imatinib activity. Mutated KIT requires the molecular chaperone heat-shock protein 90 (HSP90) to maintain stability and activity. Onalespib (AT13387) is a potent non-ansamycin HSP90 inhibitor. We hypothesised that the combination of onalespib and imatinib may be safe and effective in managing TKI-resistant GIST. In this dose-escalation study, we evaluated the safety and efficacy of combination once-weekly intravenous onalespib for 3 weeks and daily oral imatinib in 28-d cycles. Twenty-six patients with TKI-resistant GIST were enrolled into four sequential dose cohorts of onalespib (dose range, 150-220 mg/m(2)) and imatinib 400 mg. The relationship between tumour mutational status (KIT/PDGFRA) and efficacy of treatment was explored. Common onalespib-related adverse events were diarrhoea (58%), nausea (50%), injection site events (46%), vomiting (39%), fatigue (27%), and muscle spasms (23%). Overall, 81% of patients reported more than one onalespib-related gastrointestinal disorder. Nine patients (35%) had a best response of stable disease, including two patients who had KIT mutations known to be associated with resistance to imatinib and sunitinib. Disease control at 4 months was achieved in five patients (19%), and median progression-free survival was 112 d (95% confidence interval 43-165). One patient with PDGFRA-mutant GIST had a partial response for more than 376 d. The combination of onalespib plus imatinib was well tolerated but exhibited limited antitumour activity as dosed in this TKI-resistant GIST patient population. Trial registration ID: clinicaltrials.gov: NCT01294202. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

[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. Copyright © 2015 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

77 FR 61575 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-10

... surveys (1979-80), quantitative survey effort started in 1981, when nine permanent research sites in rocky..., several species of marine mammal incidental to abalone research surveys on San Nicolas Island (SNI). DATES... only, of marine mammals incidental to research surveys investigating the black abalone (Haliotis...

Accuracy and Feasibility of Estimated Tumour Volumetry in Primary Gastric Gastrointestinal Stromal Tumours: Validation Using Semi-automated Technique in 127 Patients

PubMed Central

Tirumani, Sree Harsha; Shinagare, Atul B.; O’Neill, Ailbhe C.; Nishino, Mizuki; Rosenthal, Michael H.; Ramaiya, Nikhil H.

2015-01-01

Objective To validate estimated tumour volumetry in primary gastric gastrointestinal stromal tumours (GISTs) using semi-automated volumetry. Materials and Methods In this IRB-approved retrospective study, we measured the three longest diameters in x, y, z axes on CTs of primary gastric GISTs in 127 consecutive patients (52 women, 75 men, mean age: 61 years) at our institute between 2000 and 2013. Segmented volumes (Vsegmented) were obtained using commercial software by two radiologists. Estimate volumes (V1–V6) were obtained using formulae for spheres and ellipsoids. Intra- and inter-observer agreement of Vsegmented and agreement of V1–6 with Vsegmented were analysed with concordance correlation coefficients (CCC) and Bland-Altman plots. Results Median Vsegmented and V1–V6 were 75.9 cm3, 124.9 cm3, 111.6 cm3, 94.0 cm3, 94.4cm3, 61.7 cm3 and 80.3 cm3 respectively. There was strong intra- and inter-observer agreement for Vsegmented. Agreement with Vsegmented was highest for V6 (scalene ellipsoid, x≠y≠z), with CCC of 0.96 [95%CI: 0.95–0.97]. Mean relative difference was smallest for V6 (0.6%), while it was −19.1% for V5, +14.5% for V4, +17.9% for V3, +32.6 % for V2 and +47% for V1. Conclusion Ellipsoidal approximations of volume using three measured axes may be used to closely estimate Vsegmented when semi-automated techniques are unavailable. PMID:25991487

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.

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

Survivin is a novel transcription regulator of KIT and is downregulated by miRNA-494 in gastrointestinal stromal tumors.

PubMed

Yun, SeongJu; Kim, Won Kyu; Kwon, Yujin; Jang, Mi; Bauer, Sebastian; Kim, Hoguen

2018-05-15

Gain-of-function mutations of KIT are pathognomonic in sporadic gastrointestinal stromal tumors (GISTs). Several microRNAs have been shown to be dysregulated in GISTs and impact KIT expression. Little is known though on KIT-independent targets of KIT-regulating mRNAs. We sought to investigate how miR-494 inhibits GIST proliferation and to identify novel target gene. We used microarray-based gene expression analyses to identify pathways and target genes affected by miR-494. The expressional relationship between survivin and miR-494 was determined in 35 GIST tissues. Cell proliferation assay, FACS analysis, colony formation assay, promoter assays and chromatin immunoprecipitation (ChiP) were performed to clarify the roles of survivin in GIST progression. Gene expression microarray analysis revealed that miR-494 inhibited GISTs by affecting multiple genes in the cell cycle pathway. Survivin (BIRC5) was a key target of miR-494, and its expression showed an inverse correlation with miR-494 expression in 35 GIST tissues (Pearson's correlation coefficient, r = -0.418, p = 0.012). Downregulation of survivin inhibited proliferation and colony formation, and resulted in cell cycle alteration. Induced survivin overexpression relieved miR-494-mediated inhibition of GIST progression. Targeting PI3K effectively suppressed proliferation of GISTs with downregulation of survivin. Survivin also regulated KIT expression at the transcription level. Immunohistochemical analysis using 113 GISTs revealed that survivin expression was significantly correlated with overall survival of GIST patients (p = 0.004). Our findings indicated that miR-494 synergistically suppressed GISTs by concomitantly targeting survivin and KIT. © 2017 The Authors International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

Accuracy and feasibility of estimated tumour volumetry in primary gastric gastrointestinal stromal tumours: validation using semiautomated technique in 127 patients.

PubMed

Tirumani, Sree Harsha; Shinagare, Atul B; O'Neill, Ailbhe C; Nishino, Mizuki; Rosenthal, Michael H; Ramaiya, Nikhil H

2016-01-01

To validate estimated tumour volumetry in primary gastric gastrointestinal stromal tumours (GISTs) using semiautomated volumetry. In this IRB-approved retrospective study, we measured the three longest diameters in x, y, z axes on CTs of primary gastric GISTs in 127 consecutive patients (52 women, 75 men, mean age 61 years) at our institute between 2000 and 2013. Segmented volumes (Vsegmented) were obtained using commercial software by two radiologists. Estimate volumes (V1-V6) were obtained using formulae for spheres and ellipsoids. Intra- and interobserver agreement of Vsegmented and agreement of V1-6 with Vsegmented were analysed with concordance correlation coefficients (CCC) and Bland-Altman plots. Median Vsegmented and V1-V6 were 75.9, 124.9, 111.6, 94.0, 94.4, 61.7 and 80.3 cm(3), respectively. There was strong intra- and interobserver agreement for Vsegmented. Agreement with Vsegmented was highest for V6 (scalene ellipsoid, x ≠ y ≠ z), with CCC of 0.96 [95 % CI 0.95-0.97]. Mean relative difference was smallest for V6 (0.6 %), while it was -19.1 % for V5, +14.5 % for V4, +17.9 % for V3, +32.6 % for V2 and +47 % for V1. Ellipsoidal approximations of volume using three measured axes may be used to closely estimate Vsegmented when semiautomated techniques are unavailable. Estimation of tumour volume in primary GIST using mathematical formulae is feasible. Gastric GISTs are rarely spherical. Segmented volumes are highly concordant with three axis-based scalene ellipsoid volumes. Ellipsoid volume can be used as an alternative for automated tumour volumetry.

Cooperative laparoscopic endoscopic and hybrid laparoscopic surgery for upper gastrointestinal tumors: Current status

PubMed Central

Ntourakis, Dimitrios; Mavrogenis, Georgios

2015-01-01

AIM: To investigate the cooperative laparoscopic and endoscopic techniques used for the resection of upper gastrointestinal tumors. METHODS: A systematic research of the literature was performed in PubMed for English and French language articles about laparoscopic and endoscopic cooperative, combined, hybrid and rendezvous techniques. Only original studies using these techniques for the resection of early gastric cancer, benign tumors and gastrointestinal stromal tumors of the stomach and the duodenum were included. By excluding case series of less than 10 patients, 25 studies were identified. The study design, number of cases, tumor pathology size and location, the operative technique name, the endoscopy team and surgical team role, operative time, type of closure of visceral wall defect, blood loss, complications and length of hospital stay of these studies were evaluated. Additionally all cooperative techniques found were classified and are presented in a systematic approach. RESULTS: The studies identified were case series and retrospective cohort studies. A total of 706 patients were operated on with a cooperative technique. The tumors resected were only gastrointestinal stromal tumors (GIST) in 4 studies, GIST and various benign submucosal tumors in 22 studies, early gastric cancer (pT1a and pT1b) in 6 studies and early duodenal cancer in 1 study. There was important heterogeneity between the studies. The operative techniques identified were: laparoscopic assisted endoscopic resection, endoscopic assisted wedge resection, endoscopic assisted transgastric and intragastric surgery, laparoscopic endoscopic cooperative surgery (LECS), laparoscopic assisted endoscopic full thickness resection (LAEFR), clean non exposure technique and non-exposed endoscopic wall-inversion surgery (NEWS). Each technique is illustrated with the roles of the endoscopic and laparoscopic teams; the indications, characteristics and short term results are described. CONCLUSION: Along with

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…

Animation, Incidental Learning, and Continuing Motivation.

ERIC Educational Resources Information Center

Rieber, Lloyd P.

1991-01-01

Effects of animated graphics presentations on incidental learning and the degree to which various computer practice activities contain intrinsically motivating characteristics were studied with 70 fourth graders learning about Newton's laws of motion. Incidental learning occurred without sacrifice of intentional learning. Students were highly…

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 of...

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. In...

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. In...

22 CFR 228.25 - Incidental services.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Incidental services. 228.25 Section 228.25 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT RULES ON SOURCE, ORIGIN AND NATIONALITY FOR... for USAID Financing § 228.25 Incidental services. Source and nationality rules do not apply to...

Incidental findings in youths volunteering for brain MRI research.

PubMed

Gur, R E; Kaltman, D; Melhem, E R; Ruparel, K; Prabhakaran, K; Riley, M; Yodh, E; Hakonarson, H; Satterthwaite, T; Gur, R C

2013-10-01

MRIs are obtained in research in healthy and clinical populations, and incidental findings have been reported. Most studies have examined adults with variability in parameters of image acquisition and clinical measures available. We conducted a prospective study of youths and documented the frequency and concomitants of incidental findings. Youths (n = 1400) with an age range from 8-23 years were imaged on the same 3T scanner, with a standard acquisition protocol providing 1.0 mm(3) isotropic resolution of anatomic scans. All scans were reviewed by an experienced board-certified neuroradiologist and were categorized into 3 groups: 1) normal: no incidental findings; 2) coincidental: incidental finding(s) were noted, further reviewed with an experienced pediatric neuroradiologist, but were of no clinical significance; 3) incidental findings that on further review were considered to have potential clinical significance and participants were referred for appropriate clinical follow-up. Overall, 148 incidental findings (10.6% of sample) were noted, and of these, 12 required clinical follow-up. Incidental findings were not related to age. However, whites had a higher incidence of pineal cysts, and males had a higher incidence of cavum septum pellucidum, which was associated with psychosis-related symptoms. Incidental findings, moderated by race and sex, occur in approximately one-tenth of participants volunteering for pediatric research, with few requiring follow-up. The incidence supports a 2-tiered approach of neuroradiologic reading and clinical input to determine the potential significance of incidental findings detected on research MR imaging scans.

Peritonitis secondary to spontaneous perforation of a primary gastrointestinal stromal tumour of the small intestine: A case report and a literature review.

PubMed

Alessiani, Mario; Gianola, Marco; Rossi, Sabina; Perfetti, Vittorio; Serra, Piero; Zelaschi, Daniela; Magnani, Enzo; Cobianchi, Lorenzo

2015-01-01

A few cases of acute abdomen caused by perforation of small-intestinal gastrointestinal stromal tumours (GISTs) have been reported in the literature. Together with a review of the published cases, here we report a case of an elderly patient with peritonitis due to spontaneous perforation of a GIST of the jejunum. An 82-year-old man was admitted to the emergency unit of our hospital with fever and severe abdominal pain. An abdominal enhanced computed tomography scan detected a 6cm solid mass in the left upper quadrant adherent to a jejunal loop and surrounded by free fluid and free air. Due to the radiological features of the mass, the diagnosis of a perforation of a GIST arising from the jejunum wall was suspected. The patient underwent emergency laparotomy. Intraoperative findings confirmed diffuse peritonitis secondary to jejunal tumour perforation. A segmental resection of the jejunum containing the mass was performed followed by a mechanical end-to-side anastomosis. The histopathologic examination of the mass confirmed the diagnosis of a perforated GIST of the small intestine (high-risk category). The post-operative course was uneventful and the patient was treated with adjuvant imatinib therapy. Twenty-one other cases of spontaneous perforation of small intestine GISTs are reported in the literature and are summarized in the present review. The described case is the tip of the iceberg and spontaneous rupture or perforation of GISTs are a far more frequent first presentation of this rare tumour. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

12 CFR 721.2 - What is an incidental powers activity?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 12 Banks and Banking 6 2011-01-01 2011-01-01 false What is an incidental powers activity? 721.2 Section 721.2 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS INCIDENTAL POWERS § 721.2 What is an incidental powers activity? An incidental powers activity is one that is...

21 CFR 1307.13 - Incidental manufacture of controlled substances.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Incidental manufacture of controlled substances... MISCELLANEOUS Special Exceptions for Manufacture and Distribution of Controlled Substances § 1307.13 Incidental manufacture of controlled substances. Any registered manufacturer who, incidentally but necessarily...

Clinical Outcomes of Patients with Advanced Gastrointestinal Stromal Tumors: Safety and Efficacy in a Worldwide Treatment-use Trial of Sunitinib

PubMed Central

Reichardt, Peter; Kang, Yoon-Koo; Rutkowski, Piotr; Schuette, Jochen; Rosen, Lee S; Seddon, Beatrice; Yalcin, Suayib; Gelderblom, Hans; Williams, Charles C; Fumagalli, Elena; Biasco, Guido; Hurwitz, Herbert I; Kaiser, Pamela E; Fly, Kolette; Matczak, Ewa; Chen, Liang; Lechuga, Maria José; Demetri, George D

2015-01-01

BACKGROUND To provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain sunitinib; to obtain broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. METHODS Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule (IDS) of 50 mg/day in 6-week cycles (4 weeks on treatment, 2 weeks off). Tumor assessment frequency was per local practice, with response assessed by investigators per Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post-hoc analyses evaluated different patterns of treatment management. RESULTS At final data cutoff, 1124 patients comprised the intent-to-treat population; 15% had a baseline Eastern Cooperative Oncology Group performance status ≥2. Median treatment duration was 7.0 months. Median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0–9.4), and median OS was 16.6 months (95% CI, 14.9–18.0) with 36% of patients alive at the time of analysis. Patients in whom the IDS was modified exhibited longer median OS (23.5 months) than those treated strictly per the IDS (11.1 months). The most common treatment-related grade 3/4 adverse events (AEs) were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related AEs associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each. CONCLUSIONS This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure. PMID:25641662

Chemical Burn-Induced Stromal Demarcation Line.

PubMed

Brosh, Koby; Rozenman, Yaacov

2016-02-01

A stromal demarcation line is a well-known sign after collagen cross-linking. It has been proposed that this line is the transition zone between cellular and acellular stroma, and thus it might reveal the depth of photochemical changes in the corneal stroma. We report 2 cases of a similar demarcation line after chemical alkali burns. To the best of our knowledge, this is the first report of a stromal demarcation line after a chemical burn. Two patients presented to the emergency department after an ocular alkali burn. At presentation, both had total corneal erosion, corneal edema, and limbal ischemia. After 12 to 15 days, a stromal line was apparent by both slit-lamp examination and anterior segment optical coherence tomography. The stromal demarcation lines disappeared approximately 3 months after the injury. A stromal demarcation line may appear not only after collagen cross-linking but also after a chemical burn. The line depth may be associated with the severity of the injury, and therefore, may have prognostic significance. Patients with chemical burns should be examined for evidence of a stromal line in the cornea.

Stromal signatures in endometrioid endometrial carcinomas.

PubMed

Espinosa, Iñigo; Catasus, Lluis; D' Angelo, Emanuela; Mozos, Ana; Pedrola, Nuria; Bértolo, Cristina; Ferrer, Irene; Zannoni, Gian Franco; West, Robert B; van de Rijn, Matt; Matias-Guiu, Xavier; Prat, Jaime

2014-04-01

The pattern of myometrial invasion in endometrioid endometrial carcinomas varies considerably; ie, from widely scattered glands and cell nests, often associated with a fibromyxoid stromal reaction (desmoplasia) and/or a lymphocytic infiltrate, to invasive glands with little or no stromal response. Recently, two distinct stromal signatures derived from a macrophage response (colony-stimulating factor 1, CSF1) and a fibroblastic response (desmoid-type fibromatosis, DTF) were identified in breast carcinomas and correlated with clinicopathologic features including outcome. In this study, we explored whether these stromal signatures also apply to endometrioid carcinomas and how their expression patterns correlated with morphologic changes. We studied the stromal signatures both by immunohistochemistry and in situ hybridization in 98 primary endometrioid carcinomas with (87 cases) and without (11 cases) myometrial invasion as well as in the corresponding regional lymph nodes metatases of 9 myoinvasive tumors. Desmoplasia correlated positively with the DTF expression signature. Likewise, mononuclear infiltrates were found in the stroma of tumors expressing CSF1. Twenty-four out of eighty-seven (27%) myoinvasive endometrioid carcinomas were positive for the macrophage signature and thirteen out of eighty-seven (15%) expressed the fibroblast signature. Eleven additional cases were positive for both DTF and CSF1 signatures (11/87; 13%). However, over half of the cases (39/87; 45%) and the majority of the non-myoinvasive tumors (8/11; 73%) failed to express any of the two stromal signatures. The macrophage response (CSF1) was associated with higher tumor grade, lymphovascular invasion, and PIK3CA mutations (P<0.05). There was a concordance in the expression of the CSF1 signature in the primary tumors and their corresponding lymph node metastases. This study is the first characterization of stromal signatures in endometrioid carcinomas. Our findings shed new light on the

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 season.

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. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence of Incidental Clinoid Segment Saccular Aneurysms.

PubMed

Revilla-Pacheco, Francisco; Escalante-Seyffert, María Cecilia; Herrada-Pineda, Tenoch; Manrique-Guzman, Salvador; Perez-Zuniga, Irma; Rangel-Suarez, Sergio; Rubalcava-Ortega, Johnatan; Loyo-Varela, Mauro

2018-04-12

Clinoid segment aneurysms are cerebral vascular lesions recently described in the neurosurgical literature. They arise from the clinoid segment of the internal carotid artery, which is the segment limited rostrally by the dural carotid ring and caudally, by the carotid-oculomotor membrane. Even although clinoid segment aneurysms represent a common incidental finding in magnetic resonance studies, its prevalence has not been yet reported. To determine the prevalence of incidental clinoid segment saccular aneurysms diagnosed by magnetic resonance imaging as well as their anatomic architecture and their association with smoking, arterial hypertension, age, and sex of patients. A total of 500 patients were prospectively studied with magnetic resonance imaging time-of-flight sequence and angioresonance with contrast material, to search for incidental saccular intracranial aneurysms. The site of primary interest was the clinoid segment, but the presence of aneurysms in any other location was determined for comparison. The relation among the presence of clinoid segment aneurysms, demographic factors, and secondary diagnosis of arterial hypertension, smoking, and other vascular/neoplastic cerebral lesions was analyzed. We found a global prevalence of incidental aneurysms of 7% (95% confidence interval, 5-9), with a prevalence of clinoid segment aneurysms of 3% (95% confidence interval, 2-4). Univariate logistic regression analysis showed a statistically significant relationship among incidental aneurysms, systemic arterial hypertension (P = 0.000), and smoking (P = 0.004). In the studied population, incidental clinoid segment aneurysms constitute the variety with highest prevalence. Copyright © 2018 Elsevier Inc. All rights reserved.

Incidental emotions influence risk preference and outcome evaluation.

PubMed

Zhao, Ding; Gu, Ruolei; Tang, Ping; Yang, Qiwei; Luo, Yue-Jia

2016-10-01

Incidental emotions, which are irrelevant to the current decision, play a significant role in the decision-making process. In this study, to investigate the influence of incidental emotions on behavioral, psychological, and electrophysiological responses in the process of decision making, participants were required to perform a monetary gambling task. During the selection stage, an emotional picture, which was chosen from the Chinese Affective Picture System and fell into one of three categories: negative, neutral, and positive, was presented between two alternatives (small/large amount of bet). The pictures were provided to induce incidental emotions. ERPs and self-rating emotional experiences to outcome feedback were recorded during the task. Behavioral results showed that positive incidental emotions elicited risk preference, but emotional experiences to outcome feedback were not influenced by incidental emotions. The feedback-related negativity amplitudes were larger in the positive emotion condition than in the negative and neutral emotion conditions for small outcomes (including wins and losses), whereas there was no difference between the three conditions for large outcomes. In addition, the amplitudes of P3 were reduced overall in the negative emotion condition. We suggest that incidental emotions have modulated both the option assessment stage (manifested in behavioral choices) and the outcome evaluation stage (manifested in ERP amplitudes) of decision making unconsciously (indicated by unchanged subjective emotional experiences). The current findings have expanded our understanding of the role of incidental emotion in decision making. © 2016 Society for Psychophysiological Research.

Management and follow-up of gallbladder polyps : Joint guidelines between the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE).

PubMed

Wiles, Rebecca; Thoeni, Ruedi F; Barbu, Sorin Traian; Vashist, Yogesh K; Rafaelsen, Søren Rafael; Dewhurst, Catherine; Arvanitakis, Marianna; Lahaye, Max; Soltes, Marek; Perinel, Julie; Roberts, Stuart Ashley

2017-09-01

The management of incidentally detected gallbladder polyps on radiological examinations is contentious. The incidental radiological finding of a gallbladder polyp can therefore be problematic for the radiologist and the clinician who referred the patient for the radiological examination. To address this a joint guideline was created by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), European Association for Endoscopic Surgery and other Interventional Techniques (EAES), International Society of Digestive Surgery - European Federation (EFISDS) and European Society of Gastrointestinal Endoscopy (ESGE). A targeted literature search was performed and consensus guidelines were created using a series of Delphi questionnaires and a seven-point Likert scale. A total of three Delphi rounds were performed. Consensus regarding which patients should have cholecystectomy, which patients should have ultrasound follow-up and the nature and duration of that follow-up was established. The full recommendations as well as a summary algorithm are provided. These expert consensus recommendations can be used as guidance when a gallbladder polyp is encountered in clinical practice. • Management of gallbladder polyps is contentious • Cholecystectomy is recommended for gallbladder polyps >10 mm • Management of polyps <10 mm depends on patient and polyp characteristics • Further research is required to determine optimal management of gallbladder polyps.

Co-incidental Plasmodium Knowlesi and Mucormycosis infections presenting with acute kidney injury and lower gastrointestinal bleeding.

PubMed

Ramaswami, Arunachalam; Pisharam, Jayakrishnan K; Aung, Hla; Ghazala, Kafeel; Maboud, Khalil; Chong, Vui Heng; Tan, Jackson

2013-01-01

Plasmodium knowlesi is frequently reported in Southeast Asian countries and is now widely regarded as the fifth malarial parasite. Mucormycosis is a rare fungal infection that can occur in patients with a weakened immune system. We report a case of acute kidney injury secondary to Plasmodium knowlesi malaria infection and mucormycosis fungal infection. In addition, the patient also had lower gastrointestinal bleeding from invasive gastrointestinal mucormycosis. P. knowlesi infection was diagnosed by blood film and mucormycosis was diagnosed by histopathological examination of biopsy specimen of the colon. The patient recovered with antimalarial treatment (Quinine), antifungal treatment (Lipophilic Amphotericin), and supportive hemodialysis treatment. We hypothesize that P. knowlesi malarial infection can lower the immunologic threshold and predisposes vulnerable individuals to rare disseminated fungal infections. To the best of our knowledge, this is the first P. Knowlesi malaria-associated invasive fungal infection reported in the literature.

Question of bone marrow stromal fibroblast traffic

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maloney, M.A.; Lamela, R.A.; Patt, H.M.

Bone marrow stromal fibroblasts (CFU-F) normally do not exchange bone marrow sites in vivo. Restitution of the CFU-F after radiation damage is primarily recovery by the local fibroblasts from potentially lethal damage. Migration of stromal fibroblasts from shielded sites to an irradiated site makes a minimal contribution, if any, to CFU-F recovery. Determination of the relative contribution of donor stromal cells in bone marrow transplants by karyotyping the proliferating bone marrow stromal cells in vitro may not reflect the relative distribution of fibroblasts in the marrow. If there is residual damage to the host stromal fibroblasts from treatment before transplantation,more » these cells may not be able to proliferate in vitro. Therefore, an occasional transplanted fibroblast may contribute most of the metaphase figures scored for karyotype.« less

Endometrial stromal tumors: the new WHO classification.

PubMed

Conklin, Christopher M J; Longacre, Teri A

2014-11-01

Endometrial stromal tumors are rare uterine mesenchymal neoplasms that have intrigued pathologists for years, not only because they commonly pose diagnostic dilemmas, but also because the classification and pathogenesis of these tumors has been widely debated. The current World Health Organization recognizes 4 categories of endometrial stromal tumor: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). uterine sarcoma. These categories are defined by the presence of distinct translocations as well as tumor morphology and prognosis. Specifically, the JAZF1-SUZ12 (formerly JAZF1-JJAZ1) fusion identifies a large proportion of ESN and LG-ESSs, whereas the YWHAE-FAM22 translocation identifies HG-ESSs. The latter tumors appear to have a prognosis intermediate between LG-ESS and UUS, which exhibits no specific translocation pattern. This review (1) presents the clinicopathologic features of endometrial stromal tumors; (2) discusses their immunophenotype; and (3) highlights the recent advances in molecular genetics which explain their pathogenesis and lend support for a new classification system.

A single digital droplet PCR assay to detect multiple KIT exon 11 mutations in tumor and plasma from patients with gastrointestinal stromal tumors.

PubMed

Boonstra, Pieter A; Ter Elst, Arja; Tibbesma, Marco; Bosman, Lisette J; Mathijssen, Ron; Atrafi, Florence; van Coevorden, Frits; Steeghs, Neeltje; Farag, Sheima; Gelderblom, Hans; van der Graaf, Winette T A; Desar, Ingrid M E; Maier, Jacqueline; Overbosch, Jelle; Suurmeijer, Albert J H; Gietema, Jourik; Schuuring, Ed; Reyners, Anna K L

2018-03-02

Gastrointestinal stromal tumors (GISTs) are characterized by oncogenic KIT mutations that cluster in two exon 11 hotspots. The aim of this study was to develop a single, sensitive, quantitative digital droplet PCR (ddPCR) assay for the detection of common exon 11 mutations in both GIST tumor tissue and in circulating tumor DNA (ctDNA) isolated from GIST patients' plasma. A ddPCR assay was designed using two probes that cover both hotspots. Available archival FFPE tumor tissue from 27 consecutive patients with known KIT exon 11 mutations and 9 randomly selected patients without exon 11 mutations were tested. Plasma samples were prospectively collected in a multicenter bio-databank from December 2014. ctDNA was analyzed of 22 patients with an exon 11 mutation and a baseline plasma sample. The ddPCR assay detected the exon 11 mutation in 21 of 22 tumors with exon 11 mutations covered by the assay. Mutations in ctDNA were detected at baseline in 13 of 14 metastasized patients, but in only 1 of 8 patients with localized disease. In serial plasma samples from 11 patients with metastasized GIST, a decrease in mutant droplets was detected during treatment. According to RECIST 1.1, 10 patients had radiological treatment response and one patient stable disease. A single ddPCR assay for the detection of multiple exon 11 mutations in ctDNA is a feasible, promising tool for monitoring treatment response in patients with metastasized GIST and should be further evaluated in a larger cohort.

Incidental Learning of Gender Agreement in L2.

PubMed

Denhovska, Nadiia; Serratrice, Ludovica

2017-10-01

Incidental learning of grammar has been an area of interest for many decades; nevertheless, existing research has primarily focused on artificial or semi-artificial languages. The present study examines the incidental acquisition of the grammar of a natural language by exposing adult speakers of an ungendered L1 (English) to the gender agreement patterns in Russian (a language that was novel to the learners). Both receptive and productive knowledge and the mediating role of working memory (WM) in learning were measured. Speakers of the ungendered language were able to successfully acquire receptive but not productive grammatical knowledge in a new language under incidental exposure. WM was engaged in production but not in a grammaticality judgment task in the incidental learning condition, indicating cognitive effort during knowledge retrieval.

Stromal cell-based immunotherapy in transplantation.

PubMed

Charles, Ronald; Lu, Lina; Qian, Shiguang; Fung, John J

2011-12-01

Organs are composed of parenchymal cells that characterize organ function and nonparenchymal cells that are composed of cells in transit, as well as tissue connective tissue, also referred to as tissue stromal cells. It was originally thought that these tissue stromal cells provided only structural and functional support for parenchymal cells and were relatively inert. However, we have come to realize that tissue stromal cells, not restricted to in the thymus and lymphoid organs, also play an active role in modulating the immune system and its response to antigens. The recognition of these elements and the elucidation of their mechanisms of action have provided valuable insight into peripheral immune regulation. Extrapolation of these principles may allow us to utilize their potential for clinical application. In this article, we will summarize a number of tissue stromal elements/cell types that have been shown to induce hyporesponsiveness to transplants. We will also discuss the mechanisms by which these stromal cells create a tolerogenic environment, which in turn results in long-term allograft survival.

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.

[Neuroendocrine tumors of the gastrointestinal tract. Prospective analysis of 29 patients and review of the literature].

PubMed

Wenisch, H J

2001-01-01

Neuroendocrine tumors are rare and can be observed in different gastrointestinal organs. The diagnosis often is made by incidence like in carcinoids of the appendix vermiformis, or special clinical symptoms may develop due to tumor growth. 29 consecutive patients were evaluated prospectively during 30 months. In 21 of them, the first diagnosis was obtained after an operative procedure. In 3 cases, the tumor was found incidentally during another oncological procedure. In 4 patients, the histological examination of biopsy specimens had shown an undifferentiated adenocarcinoma. In 8 of the patients, recurrent surgery was necessary because of recurrency of the disease. The mean observation time of all patients was 10.6 months. 6 of 29 patients died on disease-related symptoms. The results are discussed based on the literature with special regard to organ-related characteristics of different gastrointestinal neuroendocrine tumors.

Assessing tumor vascularization as a potential biomarker of imatinib resistance in gastrointestinal stromal tumors by dynamic contrast-enhanced magnetic resonance imaging.

PubMed

Consolino, Lorena; Longo, Dario Livio; Sciortino, Marianna; Dastrù, Walter; Cabodi, Sara; Giovenzana, Giovanni Battista; Aime, Silvio

2017-07-01

Most metastatic gastrointestinal stromal tumors (GISTs) develop resistance to the first-line imatinib treatment. Recently, increased vessel density and angiogenic markers were reported in GISTs with a poor prognosis, suggesting that angiogenesis is implicated in GIST tumor progression and resistance. The purpose of this study was to investigate the relationship between tumor vasculature and imatinib resistance in different GIST mouse models using a noninvasive magnetic resonance imaging (MRI) functional approach. Immunodeficient mice (n = 8 for each cell line) were grafted with imatinib-sensitive (GIST882 and GIST-T1) and imatinib-resistant (GIST430) human cell lines. Dynamic contrast-enhanced MRI (DCE-MRI) was performed on GIST xenografts to quantify tumor vessel permeability (K trans ) and vascular volume fraction (v p ). Microvessel density (MVD), permeability (mean dextran density, MDD), and angiogenic markers were evaluated by immunofluorescence and western blot assays. Dynamic contrast-enhanced magnetic resonance imaging showed significantly increased vessel density (P < 0.0001) and permeability (P = 0.0002) in imatinib-resistant tumors compared to imatinib-sensitive ones. Strong positive correlations were observed between MRI estimates, K trans and v p , and their related ex vivo values, MVD (r = 0.78 for K trans and r = 0.82 for v p ) and MDD (r = 0.77 for K trans and r = 0.94 for v p ). In addition, higher expression of vascular endothelial growth factor receptors (VEGFR2 and VEFGR3) was seen in GIST430. Dynamic contrast-enhanced magnetic resonance imaging highlighted marked differences in tumor vasculature and microenvironment properties between imatinib-resistant and imatinib-sensitive GISTs, as also confirmed by ex vivo assays. These results provide new insights into the role that DCE-MRI could play in GIST characterization and response to GIST treatment. Validation studies are needed to confirm these findings.

50 CFR 216.107 - Incidental harassment authorization for Arctic waters.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Incidental harassment authorization for Arctic waters. 216.107 Section 216.107 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL... Incidental to Specified Activities § 216.107 Incidental harassment authorization for Arctic waters. (a...

50 CFR 216.107 - Incidental harassment authorization for Arctic waters.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Incidental harassment authorization for Arctic waters. 216.107 Section 216.107 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL... Incidental to Specified Activities § 216.107 Incidental harassment authorization for Arctic waters. (a...

Incidental mood state before dissonance induction affects attitude change

PubMed Central

Martinie, Marie-Amélie; Almecija, Yves; Ros, Christine; Gil, Sandrine

2017-01-01

The way that incidental affect impacts attitude change brought about by controlled processes has so far been examined when the incidental affective state is generated after dissonance state induction. We therefore investigated attitude change when the incidental mood occurs prior to dissonance state induction. We expected a negative mood to induce systematic processing, and a positive mood to induce heuristic processing. Given that both systematic processing and attitude change are cognitively costly, we expected participants who experienced the dissonance state in a negative mood to have insufficient resources to allocate to attitude change. In our experiment, after mood induction (negative, neutral or positive), participants were divided into low-dissonance and high-dissonance groups. They then wrote a counterattitudinal essay. Analysis of their attitudes towards the essay topic indicated that attitude change did not occur in the negative incidental mood condition. Moreover, written productivity–one indicator of cognitive resource allocation–varied according to the type of incidental mood, and only predicted attitude change in the high-dissonance group. Our results suggest that incidental mood before dissonance induction influences the style of information processing and, by so doing, affects the extent of attitude change. PMID:28708861

Incidental mood state before dissonance induction affects attitude change.

PubMed

Martinie, Marie-Amélie; Almecija, Yves; Ros, Christine; Gil, Sandrine

2017-01-01

The way that incidental affect impacts attitude change brought about by controlled processes has so far been examined when the incidental affective state is generated after dissonance state induction. We therefore investigated attitude change when the incidental mood occurs prior to dissonance state induction. We expected a negative mood to induce systematic processing, and a positive mood to induce heuristic processing. Given that both systematic processing and attitude change are cognitively costly, we expected participants who experienced the dissonance state in a negative mood to have insufficient resources to allocate to attitude change. In our experiment, after mood induction (negative, neutral or positive), participants were divided into low-dissonance and high-dissonance groups. They then wrote a counterattitudinal essay. Analysis of their attitudes towards the essay topic indicated that attitude change did not occur in the negative incidental mood condition. Moreover, written productivity-one indicator of cognitive resource allocation-varied according to the type of incidental mood, and only predicted attitude change in the high-dissonance group. Our results suggest that incidental mood before dissonance induction influences the style of information processing and, by so doing, affects the extent of attitude change.

Comparison of stromal hydration techniques for clear corneal cataract incisions: conventional hydration versus anterior stromal pocket hydration.

PubMed

Mifflin, Mark D; Kinard, Krista; Neuffer, Marcus C

2012-06-01

Anterior stromal pocket hydration was compared with conventional hydration for preventing wound leak after 2.8 mm uniplanar clear corneal incisions (CCIs) in patients having routine cataract surgery. Conventional hydration involves hydration of the lateral walls of the main incision with visible whitening of the stroma. The anterior stromal pocket hydration technique involves creation of an additional supraincisional stromal pocket overlying the main incision, which is then hydrated instead of the main incision. Sixty-six eyes of 48 patients were included in the data analysis with 33 assigned to each study group. The anterior stromal pocket hydration technique was significantly better than conventional hydration in preventing wound leak due to direct pressure on the posterior lip of the incision. Copyright © 2012 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

78 FR 80385 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-31

...NMFS received an application from Apache Alaska Corporation (Apache) for an Incidental Harassment Authorization (IHA) to take marine mammals, by harassment, incidental to a proposed 3D seismic survey in Cook Inlet, Alaska, between March 1, 2014, and December 31, 2014. Pursuant to the Marine Mammal Protection Act (MMPA), NMFS requests comments on its proposal to issue an IHA to Apache to take, by Level B harassment only, five species of marine mammals during the specified activity.

Cost analysis of incidental durotomy in spine surgery.

PubMed

Nandyala, Sreeharsha V; Elboghdady, Islam M; Marquez-Lara, Alejandro; Noureldin, Mohamed N B; Sankaranarayanan, Sriram; Singh, Kern

2014-08-01

Retrospective database analysis. To characterize the consequences of an incidental durotomy with regard to perioperative complications and total hospital costs. There is a paucity of data regarding how an incidental durotomy and its associated complications may relate to total hospital costs. The Nationwide Inpatient Sample database was queried from 2008 to 2011. Patients who underwent cervical or lumbar decompression and/or fusion procedures were identified, stratified by approach, and separated into cohorts based on a documented intraoperative incidental durotomy. Patient demographics, comorbidities (Charlson Comorbidity Index), length of hospital stay, perioperative outcomes, and costs were assessed. Analysis of covariance and multivariate linear regression were used to assess the adjusted mean costs of hospitalization as a function of durotomy. The incidental durotomy rate in cervical and lumbar spine surgery is 0.4% and 2.9%, respectively. Patients with an incidental durotomy incurred a longer hospitalization and a greater incidence of perioperative complications including hematoma and neurological injury (P < 0.001). Regression analysis demonstrated that a cervical durotomy and its postoperative sequelae contributed an additional adjusted $7638 (95% confidence interval, 6489-8787; P < 0.001) to the total hospital costs. Similarly, lumbar durotomy contributed an additional adjusted $2412 (95% confidence interval, 1920-2902; P < 0.001) to the total hospital costs. The approach-specific procedural groups demonstrated similar discrepancies in the mean total hospital costs as a function of durotomy. This analysis of the Nationwide Inpatient Sample database demonstrates that incidental durotomies increase hospital resource utilization and costs. In addition, it seems that a cervical durotomy and its associated complications carry a greater financial burden than a lumbar durotomy. Further studies are warranted to investigate the long-term financial implications of

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.

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

Natural history of incidental World Health Organization grade II gliomas.

PubMed

Pallud, Johan; Fontaine, Denys; Duffau, Hugues; Mandonnet, Emmanuel; Sanai, Nader; Taillandier, Luc; Peruzzi, Philippe; Guillevin, Rémy; Bauchet, Luc; Bernier, Valérie; Baron, Marie-Hélène; Guyotat, Jacques; Capelle, Laurent

2010-11-01

Seizure is the presenting symptom in most of World Health Organization grade II gliomas (GIIGs). Rarely, a GIIG is discovered incidentally on imaging. Little is known about the natural course and prognosis of incidental GIIGs. The aim of the present study is to characterize their natural history and to investigate whether their clinical and radiological behaviors differ from those of symptomatic GIIGs. The clinical and radiological findings, treatments, and outcomes of 47 histologically-proven incidental GIIGs were compared with those of 1249 symptomatic GIIGs. Incidental GIIGs differ significantly from symptomatic GIIGs: they have a female predominance (p = 0.05), smaller initial tumor volumes (p < 0.001), lower incidence of contrast enhancement (p = 0.009), and are more likely to undergo gross total surgical removal (p < 0.001). Proliferation rates were similar to that observed among symptomatic GIIGs. Younger age at the time of discovery, frontal lobes, and noneloquent brain regions were associated with incidental GIIGs, as compared to their symptomatic counterparts. When not treated, incidental GIIGs demonstrated radiological growth (median velocity of diametric expansion at 3.5 mm/year), and became symptomatic at a median interval of 48 months after radiological discovery. Overall, incidental discovery was associated with a significant survival benefit (p = 0.04). Incidental GIIGs are progressive tumors leading to clinical transformation toward symptomatic GIIGs. They may represent an earlier step in the natural history of a glioma than the symptomatic GIIGs.

Association of Dasatinib With Progression-Free Survival Among Patients With Advanced Gastrointestinal Stromal Tumors Resistant to Imatinib.

PubMed

Schuetze, Scott M; Bolejack, Vanessa; Thomas, Dafydd G; von Mehren, Margaret; Patel, Shreyaskumar; Samuels, Brian; Choy, Edwin; D'Amato, Gina; Staddon, Arthur P; Ganjoo, Kristen N; Chow, Warren A; Rushing, Daniel A; Forscher, Charles A; Priebat, Dennis A; Loeb, David M; Chugh, Rashmi; Okuno, Scott; Reinke, Denise K; Baker, Laurence H

2018-04-26

Gastrointestinal stromal tumors (GISTs) are life-threatening when metastatic or not amenable to surgical removal. In a few patients with advanced GISTs refractory to imatinib mesylate, treatment with sunitinib malate followed by regorafenib provides tumor control; however, additional active treatments are needed for most patients. To evaluate the 6-month progression-free survival (PFS), tumor objective response, and overall survival rates in patients with GISTs treated with dasatinib. This single-arm clinical trial used a Bayesian design to enroll patients 13 years or older with measurable imatinib-refractory metastatic GISTs treated at 14 sarcoma referral centers from June 1, 2008, through December 31, 2009. A control group was not included. Patients were followed up for survival for a minimum of 5 years from date of enrollment. Tumor imaging using computed tomography or magnetic resonance imaging was performed every 8 weeks for the first 24 weeks and every 12 weeks thereafter. Tumor response was assessed by local site using the Choi criteria. Treatment was continued until tumor progression, unacceptable toxic effects after reduction in drug dose, or patient or physician decision. Archival tumor tissue was evaluated for expression of the proto-oncogene tyrosine-protein kinase Src (SRC), phosphorylated SRC (pSRC), and succinate dehydrogenase complex iron sulfur subunit B (SDHB) proteins and for mutation in the V-Kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) and platelet-derived growth factor receptor α (PDGFRA) genes. Data analysis was performed from May 19, 2017, through December 20, 2017. Dasatinib, 70 mg orally twice daily. The primary end point was the 6-month PFS estimate using greater than 30% as evidence of an active drug and less than 10% as evidence of inactive treatment. In this study, 50 patients were enrolled (median age, 60 years; age range, 19-78 years; 31 [62%] male and 19 [38%] female; 41 [82%] white), and 48 were evaluable for

Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: A randomized controlled open-label trial

PubMed Central

Adenis, A.; Blay, J.-Y.; Bui-Nguyen, B.; Bouché, O.; Bertucci, F.; Isambert, N.; Bompas, E.; Chaigneau, L.; Domont, J.; Ray-Coquard, I.; Blésius, A.; Van Tine, B. A.; Bulusu, V. R.; Dubreuil, P.; Mansfield, C. D.; Acin, Y.; Moussy, A.; Hermine, O.; Le Cesne, A.

2014-01-01

Background Masitinib is a highly selective tyrosine kinase inhibitor with activity against the main oncogenic drivers of gastrointestinal stromal tumor (GIST). Masitinib was evaluated in patients with advanced GIST after imatinib failure or intolerance. Patients and methods Prospective, multicenter, randomized, open-label trial. Patients with inoperable, advanced imatinib-resistant GIST were randomized (1 : 1) to receive masitinib (12 mg/kg/day) or sunitinib (50 mg/day 4-weeks-on/2-weeks-off) until progression, intolerance, or refusal. Primary efficacy analysis was noncomparative, testing whether masitinib attained a median progression-free survival (PFS) (blind centrally reviewed RECIST) threshold of >3 months according to the lower bound of the 90% unilateral confidence interval (CI). Secondary analyses on overall survival (OS) and PFS were comparative with results presented according to a two-sided 95% CI. Results Forty-four patients were randomized to receive masitinib (n = 23) or sunitinib (n = 21). Median follow-up was 14 months. Patients receiving masitinib experienced less toxicity than those receiving sunitinib, with significantly lower occurrence of severe adverse events (52% versus 91%, respectively, P = 0.008). Median PFS (central RECIST) for the noncomparative primary analysis in the masitinib treatment arm was 3.71 months (90% CI 3.65). Secondary analyses showed that median OS was significantly longer for patients receiving masitinib followed by post-progression addition of sunitinib when compared against patients treated directly with sunitinib in second-line [hazard ratio (HR) = 0.27, 95% CI 0.09–0.85, P = 0.016]. This improvement was sustainable as evidenced by 26-month follow-up OS data (HR = 0.40, 95% CI 0.16–0.96, P = 0.033); an additional 12.4 months survival advantage being reported for the masitinib treatment arm. Risk of progression while under treatment with masitinib was in the same range as for sunitinib (HR = 1.1, 95% CI 0.6–2.2, P

Needle biopsy through the abdominal wall for the diagnosis of gastrointestinal stromal tumour - Does it increase the risk for tumour cell seeding and recurrence?

PubMed

Eriksson, Mikael; Reichardt, Peter; Sundby Hall, Kirsten; Schütte, Jochen; Cameron, Silke; Hohenberger, Peter; Bauer, Sebastian; Leinonen, Mika; Reichardt, Annette; Rejmyr Davis, Maria; Alvegård, Thor; Joensuu, Heikki

2016-05-01

Preoperative percutaneous transabdominal wall biopsy may be considered to diagnose gastrointestinal stromal tumour (GIST) and plan preoperative treatment with tyrosine kinase inhibitors when an endoscopic biopsy is not possible. Hypothetically, a transabdominal wall biopsy might lead to cell seeding and conversion of a local GIST to a disseminated one. We investigated the influence of preoperative needle biopsy on survival outcomes. We collected the clinical data from hospital case records of the 397 patients who participated in the Scandinavian Sarcoma Group (SSG) XVIII/Arbeitsgemeinschaft Internistische Onkologie (AIO) randomised trial and who had a transabdominal fine needle and/or core needle biopsy carried out prior to study entry. The SSG XVIII/AIO trial compared 1 and 3 years of adjuvant imatinib in a patient population with a high risk of GIST recurrence after macroscopically radical surgery. The primary end-point was recurrence-free survival (RFS), and the secondary end-points included overall survival (OS). A total of 47 (12.0%) out of the 393 patients with data available underwent a percutaneous biopsy. No significant difference in RFS or OS was found between the patients who underwent or did not undergo a percutaneous biopsy either in the entire series or in subpopulation analyses, except for a statistically significant RFS advantage for patients who had a percutaneous biopsy and a tumour ≥10 cm in diameter. A preoperative diagnostic percutaneous biopsy of a suspected GIST may not increase the risk for GIST recurrence in a patient population who receive adjuvant imatinib after the biopsy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incidental and Intentional Memory: Their Relation with Attention and Executive Functions.

PubMed

Kontaxopoulou, Dionysia; Beratis, Ion N; Fragkiadaki, Stella; Pavlou, Dimosthenis; Yannis, George; Economou, Alexandra; Papanicolaou, Andrew C; Papageorgiou, Sokratis G

2017-08-01

The aim of the current study was to investigate the impact of gender and age on incidental and intentional memory in healthy participants and to explore the strength of the association of incidental and intentional memory with attentional and executive functioning. A total number of 47 participants underwent a driving simulation experiment and went through detailed neuropsychological testing. Incidental memory was assessed with a questionnaire that evaluated the memorization of information related to the driving simulator task while intentional memory was assessed using the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. The analysis revealed a greater impact of age on incidental as compared to intentional memory. Gender did not appear to have such an effect on either incidental or intentional memory. Finally, attentional and executive functioning were more strongly associated with incidental memory than the intentional memory measures that were utilized in the current study. Ageing appears to affect incidental rather than intentional memory to a greater extent. In addition, attentional and executive functioning seem to play a more important role in incidental than intentional encoding and consolidation processes. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma.

PubMed

Farrell, Eric; Heffron, Cynthia; Murphy, Matthew; O'Leary, Gerard; Sheahan, Patrick

2017-01-01

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers. We conducted a retrospective review of 713 consecutive patients who underwent thyroidectomies. Incidental thyroid cancer was defined as an unexpected cancer discovered on pathological examination outside the index nodule undergoing preoperative cytology. We excluded 65 cases because of preoperative diagnosis of thyroid cancer, and 68 because of nonincidental cancer within the index nodule. Among the remaining 580 cases, there were 43 cases (7.4%) of incidental thyroid cancers. Incidental thyroid cancers were significantly associated with moderate/severe lymphocytic thyroiditis (relative risk = 2.5; p = .03). Sixteen of 56 patients with moderate/severe lymphocytic thyroiditis had Graves' disease, none of whom had incidental thyroid cancer. The risk of incidental thyroid cancer associated with moderate/severe lymphocytic thyroiditis was significantly higher in non-Graves' than patients with Graves' disease (p = .05). The risk of incidental thyroid cancer is significantly increased in patients with moderate/severe lymphocytic thyroiditis. Moderate/severe lymphocytic thyroiditis associated with Graves' disease seems to have a lower risk of incidental thyroid cancer. © 2016 Wiley Periodicals, Inc. Head Neck 39: 122-127, 2017. © 2016 Wiley Periodicals, Inc.

IL-33 promotes gastrointestinal allergy in a TSLP-independent manner

PubMed Central

Han, Hongwei; Roan, Florence; Johnston, Laura K.; Smith, Dirk E.; Bryce, Paul J.; Ziegler, Steven F.

2017-01-01

Atopic dermatitis (AD) often precedes asthma and food allergy, indicating that epicutaneous sensitization to allergens may be important in the induction of allergic responses at other barrier surfaces. Thymic stromal lymphopoietin (TSLP) and IL-33 are two cytokines that may drive type 2 responses in the skin; both are potential targets in the treatment of allergic diseases. We tested the functional role of IL-33 and the interplay between IL-33 and TSLP in mouse models of atopic march and gastrointestinal allergy. IL-33-driven allergic disease occurred in a TSLP-independent manner. In contrast, mice lacking IL-33 signaling were protected from onset of allergic diarrhea in TSLP-driven disease. Epithelial-derived IL-33 was important in this model, since specific loss of IL-33 expression in the epithelium attenuated cutaneous inflammation. Notably, the development of diarrhea following sensitization with TLSP plus antigen was ameliorated even when IL-33 was blocked after sensitization. Thus, IL-33 plays an important role during early cutaneous inflammation and during challenge. These data reveal critical roles for IL-33 in the “atopic march” that leads from atopic dermatitis to gastrointestinal allergy. PMID:28656964

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hakimé, Antoine, E-mail: thakime@yahoo.com; Cesne, Axel Le, E-mail: Axel.LECESNE@igr.fr; Deschamps, Frederic, E-mail: frederic.deschamps@igr.fr

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 bestmore » 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.« less

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berglund, Erik, E-mail: erik.berglund@ki.se; Department of Breast and Endocrine Surgery, Karolinska University Hospital, Stockholm; Akcakaya, Pinar

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 confirmedmore » 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.« less

Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature.

PubMed

Prakash, Sonam; Sarran, Lisa; Socci, Nicholas; DeMatteo, Ronald P; Eisenstat, Jonathan; Greco, Alba M; Maki, Robert G; Wexler, Leonard H; LaQuaglia, Michael P; Besmer, Peter; Antonescu, Cristina R

2005-04-01

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.

Fostering incidental experiences of nature through green infrastructure planning.

PubMed

Beery, Thomas H; Raymond, Christopher M; Kyttä, Marketta; Olafsson, Anton Stahl; Plieninger, Tobias; Sandberg, Mattias; Stenseke, Marie; Tengö, Maria; Jönsson, K Ingemar

2017-11-01

Concern for a diminished human experience of nature and subsequent decreased human well-being is addressed via a consideration of green infrastructure's potential to facilitate unplanned or incidental nature experience. Incidental nature experience is conceptualized and illustrated in order to consider this seldom addressed aspect of human interaction with nature in green infrastructure planning. Special attention has been paid to the ability of incidental nature experience to redirect attention from a primary activity toward an unplanned focus (in this case, nature phenomena). The value of such experience for human well-being is considered. The role of green infrastructure to provide the opportunity for incidental nature experience may serve as a nudge or guide toward meaningful interaction. These ideas are explored using examples of green infrastructure design in two Nordic municipalities: Kristianstad, Sweden, and Copenhagen, Denmark. The outcome of the case study analysis coupled with the review of literature is a set of sample recommendations for how green infrastructure can be designed to support a range of incidental nature experiences with the potential to support human well-being.

Rectal GIST presenting as a submucosal calculus.

PubMed

Testroote, Mark; Hoornweg, Marije; Rhemrev, Steven

2007-04-01

This case report presents an incidental finding of a rectal GIST (gastrointestinal stromal tumor) presenting as a submucosal calculus, not previously reported. A 53-year-old man without a significant medical history presented with abdominal pain in the left lower quadrant, and with constipation. Upon rectal examination, a hard submucosal swelling was palpated 4 cm from the anus, at 3 o'clock, in the left rectum wall. X-ray photos, computerized tomography (CT)-scan and a magnetic resonance imaging (MRI) scan clearly showed a calculus. Excision revealed a turnip-like lesion, 3.1 x 2.3 x 1.8 cm. Analysis showed it was a rectal GIST, a rare mesenchymal tumor of the gastrointestinal tract, which expressed CD117 (or c-kit, a marker of kit-receptor tyrosine kinase) and CD34. Calcification is not a usual clinicopathological feature of GISTs [1-3], and although a number of rectal GISTs have been reported [4-9], we have found no cases so far of rectal GIST presenting as a submucosal calculus. In general, GISTs are rare mesenchymal tumors of the gastrointestinal tract (nerve tissue, smooth muscle). Histology and immunohistochemistry discriminate gastrointestinal stromal tumors from leiomyomas and neurinomas. The most important location is the stomach; the rectal location is rare. Usually, the classic signs of malignancy such as cellular invasion and metastasis are missing. A set of histologic criteria stratifies GIST for risk of malignant behavior such as mitotic activity and tumor size, cellular pleomorphism, developmental stage of the cell and quantity of cytoplasma [7,13]. Tumors with a high mitotic activity and size above 5 cm are considered malignant. Recent pharmacological advances such as tyrosine kinase inhibitors have determined c-kit (i.e., CD117) as the most important marker, amongst others. C-kit positive tumors respond extremely well to chemotherapy with Imatinib (Glivec, Gleevec) [10-12].

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…

Incidental fear cues increase monetary loss aversion.

PubMed

Schulreich, Stefan; Gerhardt, Holger; Heekeren, Hauke R

2016-04-01

In many everyday decisions, people exhibit loss aversion-a greater sensitivity to losses relative to gains of equal size. Loss aversion is thought to be (at least partly) mediated by emotional--in particular, fear-related--processes. Decision research has shown that even incidental emotions, which are unrelated to the decision at hand, can influence decision making. The effect of incidental fear on loss aversion, however, is thus far unclear. In two studies, we experimentally investigated how incidental fear cues, presented during (Study 1) or before (Study 2) choices to accept or reject mixed gambles over real monetary stakes, influence monetary loss aversion. We find that the presentation of fearful faces, relative to the presentation of neutral faces, increased risk aversion-an effect that could be attributed to increased loss aversion. The size of this effect was moderated by psychopathic personality: Fearless dominance, in particular its interpersonal facet, but not self-centered impulsivity, attenuated the effect of incidental fear cues on loss aversion, consistent with reduced fear reactivity. Together, these results highlight the sensitivity of loss aversion to the affective context. (c) 2016 APA, all rights reserved).

PHD-2 Suppression in Mesenchymal Stromal Cells Enhances Wound Healing.

PubMed

Ko, Sae Hee; Nauta, Allison C; Morrison, Shane D; Hu, Michael S; Zimmermann, Andrew S; Chung, Michael T; Glotzbach, Jason P; Wong, Victor W; Walmsley, Graham G; Peter Lorenz, H; Chan, Denise A; Gurtner, Geoffrey C; Giaccia, Amato J; Longaker, Michael T

2018-01-01

Cell therapy with mesenchymal stromal cells is a promising strategy for tissue repair. Restoration of blood flow to ischemic tissues is a key step in wound repair, and mesenchymal stromal cells have been shown to be proangiogenic. Angiogenesis is critically regulated by the hypoxia-inducible factor (HIF) superfamily, consisting of transcription factors targeted for degradation by prolyl hydroxylase domain (PHD)-2. The aim of this study was to enhance the proangiogenic capability of mesenchymal stromal cells and to use these modified cells to promote wound healing. Mesenchymal stromal cells harvested from mouse bone marrow were transduced with short hairpin RNA (shRNA) against PHD-2; control cells were transduced with scrambled shRNA (shScramble) construct. Gene expression quantification, human umbilical vein endothelial cell tube formation assays, and wound healing assays were used to assess the effect of PHD knockdown mesenchymal stromal cells on wound healing dynamics. PHD-2 knockdown mesenchymal stromal cells overexpressed HIF-1α and multiple angiogenic factors compared to control (p < 0.05). Human umbilical vein endothelial cells treated with conditioned medium from PHD-2 knockdown mesenchymal stromal cells exhibited increased formation of capillary-like structures and enhanced migration compared with human umbilical vein endothelial cells treated with conditioned medium from shScramble-transduced mesenchymal stromal cells (p < 0.05). Wounds treated with PHD-2 knockdown mesenchymal stromal cells healed at a significantly accelerated rate compared with wounds treated with shScramble mesenchymal stromal cells (p < 0.05). Histologic studies revealed increased blood vessel density and increased cellularity in the wounds treated with PHD-2 knockdown mesenchymal stromal cells (p < 0.05). Silencing PHD-2 in mesenchymal stromal cells augments their proangiogenic potential in wound healing therapy. This effect appears to be mediated by overexpression of HIF family

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…

Incidental Focus on Form and Second Language Learning

ERIC Educational Resources Information Center

Loewen, Shawn

2005-01-01

Incidental focus on form overtly draws learners' attention to linguistic items as they arise spontaneously--without prior planning--in meaning-focused interaction. This study examined the effectiveness of incidental focus on form in promoting second language (L2) learning. Seventeen hours of naturally occurring, meaning-focused L2 lessons were…

Sevelamer crystals in the mucosa of the gastrointestinal tract in a teenager with end-stage renal disease.

PubMed

Kim, Joseph; Olson, Kristin; Butani, Lavjay

2016-02-01

Non-calcium-containing phosphate binders, such as sevelamer preparations, are being increasingly used in patients on dialysis due to their lower association with hypercalcemia and cardiovascular morbidity and mortality. While minor gastrointestinal side effects are quite common with the use of sevelamer, more serious gastrointestinal toxicities have only rarely been reported. We report a pediatric patient on maintenance dialysis receiving sevelamer hydrochloride who developed severe abdominal pain and a high-grade stricture of the sigmoid colon. The patient underwent exploratory laparotomy, resulting in a partial colectomy and colostomy. Histopathologic examination showed colonic mucosal injury and characteristic "fish-scale"-like sevelamer hydrochloride crystals within the mucosa. Whether the sevelamer crystals were causal, contributory or purely incidental remains to be clearly elucidated. However, our case raises sufficient concern to warrant additional investigation into whether there is a causal relationship between sevelamer use and intestinal mucosal injury.

A potent combination of the novel PI3K Inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal.

PubMed

Floris, Giuseppe; Wozniak, Agnieszka; Sciot, Raf; Li, Haifu; Friedman, Lori; Van Looy, Thomas; Wellens, Jasmien; Vermaelen, Peter; Deroose, Christophe M; Fletcher, Jonathan A; Debiec-Rychter, Maria; Schöffski, Patrick

2013-02-01

Oncogenic signaling in gastrointestinal stromal tumors (GIST) is sustained via PI3K/AKT pathway. We used a panel of six GIST xenograft models to assess efficacy of GDC-0941 as single agent or in combination with imatinib (IMA). Nude mice (n = 136) were grafted bilaterally with human GIST carrying diverse KIT mutations. Mice were orally dosed over four weeks, grouped as follows: (A) control; (B) GDC-0941; (C) imatinib, and (D) GDC+IMA treatments. Xenografts regrowth after treatment discontinuation was assessed in groups C and D for an additional four weeks. Tumor response was assessed by volume measurements, micro-PET imaging, histopathology, and immunoblotting. Moreover, genomic alterations in PTEN/PI3K/AKT pathway were evaluated. In all models, GDC-0941 caused tumor growth stabilization, inhibiting tumor cell proliferation, but did not induce apoptosis. Under GDC+IMA, profound tumor regression, superior to either treatment alone, was observed. This effect was associated with the best histologic response, a nearly complete proliferation arrest and increased apoptosis. Tumor regrowth assays confirmed superior activity of GDC+IMA over imatinib; in three of six models, tumor volume remained reduced and stable even after treatment discontinuation. A positive correlation between response to GDC+IMA and PTEN loss, both on gene and protein levels, was found. GDC+IMA has significant antitumor efficacy in GIST xenografts, inducing more substantial tumor regression, apoptosis, and durable effects than imatinib. Notably, after treatment withdrawal, tumor regression was sustained in tumors exposed to GDC+IMA, which was not observed under imatinib. Assessment of PTEN status may represent a useful predictive biomarker for patient selection.

Incidental Learning of Gender Agreement in L2

ERIC Educational Resources Information Center

Denhovska, Nadiia; Serratrice, Ludovica

2017-01-01

Incidental learning of grammar has been an area of interest for many decades; nevertheless, existing research has primarily focused on artificial or semi-artificial languages. The present study examines the incidental acquisition of the grammar of a natural language by exposing adult speakers of an ungendered L1 (English) to the gender agreement…

29 CFR 793.12 - Related and incidental work.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false Related and incidental work. 793.12 Section 793.12 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR STATEMENTS OF GENERAL... Requirements for Exemption § 793.12 Related and incidental work. An employee who is employed primarily in one...

Estimated Costs of Sporadic Gastrointestinal Illness Associated with Surface Water Recreation: A Combined Analysis of Data from NEEAR and CHEERS Studies.

PubMed

DeFlorio-Barker, Stephanie; Wade, Timothy J; Jones, Rachael M; Friedman, Lee S; Wing, Coady; Dorevitch, Samuel

2017-02-01

The burden of illness can be described by addressing both incidence and illness severity attributable to water recreation. Monetized as cost, attributable disease burden estimates can be useful for environmental management decisions. We characterize the disease burden attributable to water recreation using data from two cohort studies using a cost of illness (COI) approach and estimate the largest drivers of the disease burden of water recreation. Data from the NEEAR study, which evaluated swimming and wading in marine and freshwater beaches in six U.S. states, and CHEERS, which evaluated illness after incidental-contact recreation (boating, canoeing, fishing, kayaking, and rowing) on waterways in the Chicago area, were used to estimate the cost per case of gastrointestinal illness and costs attributable to water recreation. Data on health care and medication utilization and missed days of work or leisure were collected and combined with cost data to construct measures of COI. Depending on different assumptions, the cost of gastrointestinal symptoms attributable to water recreation are estimated to be $1,220 for incidental-contact recreation (range $338-$1,681) and $1,676 for swimming/wading (range $425-2,743) per 1,000 recreators. Lost productivity is a major driver of the estimated COI, accounting for up to 90% of total costs. Our estimates suggest gastrointestinal illness attributed to surface water recreation at urban waterways, lakes, and coastal marine beaches is responsible for costs that should be accounted for when considering the monetary impact of efforts to improve water quality. The COI provides more information than the frequency of illness, as it takes into account disease incidence, health care utilization, and lost productivity. Use of monetized disease severity information should be included in future studies of water quality and health. Citation: DeFlorio-Barker S, Wade TJ, Jones RM, Friedman LS, Wing C, Dorevitch S. 2017. Estimated costs of

Comparison of clinical outcomes of incidental and non- incidental gallbladder cancers: a single-center cross- sectional study.

PubMed

Cha, Byung Hyo; Bae, Jong-Myun

2014-01-01

Gallbladder cancer (GBC) is a rare malignancy characterized by high invasiveness and poor survival. In a nation-wide cancer survey, the age-standardized incidence rate of GBC was the highest in Jeju Island compared to 15 other provinces in Korea. The purpose of this study was to compare the clinical outcomes of GBC according to the nature of diagnosis, that is, incidental versus non-incidental. Consecutive patients who were newly diagnosed with GBC at the Digestive Disease Center and Department of Internal Medicine, Cheju Halla General Hospital, between November 2008 and November 2011, were enrolled and divided into 2 groups: incidental gallbladder cancer (IGBC) and non-incidental gallbladder cancer (NIGBC). Clinical outcomes were retrospectively compared between the two groups. Seventy-nine patients were enrolled and analyzed in our study. Thirty-three (41.8%) and 46 (58.2%) were identified as IGBC and NIGBC, respectively. The proportions of patients with gallstone disease, gallbladder polyp, and cholecystectomy were significantly different between the two groups. Additionally, the median survival rate was significantly higher for patients with IGBC than for those with NIGBC (11.4, 95% confidence interval, 5.6-13.7 vs 4.0, 95% confidence interval 3.03-5.96 months; p=0.01) during a median follow-up period of 5.7 months. Patients with IGBC showed better clinical prognosis than those with NIGBC. Therefore, patients with gallstone disease or gallbladder polyps, major predictive risk factors for IGBC, should undergo advanced work-up for chelecystectomy.

Anorectal gastrointestinal stromal tumors: a retrospective multicenter analysis of 15 cases emphasizing their high local recurrence rate and the need for standardized therapeutic approach.

PubMed

Agaimy, Abbas; Vassos, Nikolaos; Märkl, Bruno; Meidenbauer, Norbert; Köhler, Jens; Spatz, Johann; Hohenberger, Werner; Haller, Florian; Croner, Roland S; Schneider-Stock, Regine; Matzel, Klaus

2013-08-01

This study aims to report our multicenter experience with diagnosis, management, and prognosis of anorectal gastrointestinal stromal tumors (GIST). We retrospectively reviewed cases treated and/or followed up at our institutions in the period 2000-2011. Fifteen patients were identified (eight men and seven women; mean age, 55 years). Presenting symptoms were rectal/perirectal (eight), rectovaginal space (four), or retrovesical/prostatic (three) mass. Primary surgical treatment was local excision (six), deep anterior resection (eight), and palliative diagnostic excision (one). Tumor mean size was 4.8 cm. All but two cases were high risk (Miettinen and Lasota, Semin Diagn Pathol 23:70-83, 2006). R0 resection was achieved in 46% of cases: one of six local excisions vs. five of seven deep anterior resection (16 vs. 71%, respectively). All three cases who received total mesorectal excision had R0. Non-R0 status was mainly due to opening of tumor capsule at surgery (Rx). Seven of 14 patients (50%) developed ≥1 pelvic local recurrences at a mean period of 48.4 months (mean follow-up, 61.6 months). Only two patients developed distant metastasis (adrenal, liver, and peritoneal). Recurrences developed after Rx (three), R1 (two), and unknown R-status (two). Successful mutational analysis in 13 patients revealed KIT mutations in all (10 exon 11, 2 exon 9, and 1 exon 13). Our results confirm the high local recurrence rate of anorectal GISTs (50%) which correlates with the common practice of suboptimal oncological primary tumor resection (Rx or R1 = 7/13). This uncommon subset of GISTs needs more standardized oncological surgical approach to minimize the propensity for local disease recurrence.

29 CFR 793.12 - Related and incidental work.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Requirements for Exemption § 793.12 Related and incidental work. An employee who is employed primarily in one... to their principal occupation”, (S. Rept. 145, 87th Cong., 1st sess., p. 37). Time spent in such... 29 Labor 3 2010-07-01 2010-07-01 false Related and incidental work. 793.12 Section 793.12 Labor...

Targeting Stromal Androgen Receptor Suppresses Prolactin-Driven Benign Prostatic Hyperplasia (BPH)

PubMed Central

Lai, Kuo-Pao; Huang, Chiung-Kuei; Fang, Lei-Ya; Izumi, Kouji; Lo, Chi-Wen; Wood, Ronald; Kindblom, Jon; Yeh, Shuyuan

2013-01-01

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9®, led to the reduction of prostate size, which could be used in future therapy. PMID:23893956

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. An...

46 CFR 276.1 - Partial repayment-incidental domestic trading.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 8 2011-10-01 2011-10-01 false Partial repayment-incidental domestic trading. 276.1 Section 276.1 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING...—incidental domestic trading. In every instance where a vessel, with respect to which a construction...

21 CFR 1307.13 - Incidental manufacture of controlled substances.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Incidental manufacture of controlled substances. 1307.13 Section 1307.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE MISCELLANEOUS Special Exceptions for Manufacture and Distribution of Controlled Substances § 1307.13 Incidental...

21 CFR 1307.13 - Incidental manufacture of controlled substances.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Incidental manufacture of controlled substances. 1307.13 Section 1307.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE MISCELLANEOUS Special Exceptions for Manufacture and Distribution of Controlled Substances § 1307.13 Incidental...

21 CFR 1307.13 - Incidental manufacture of controlled substances.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Incidental manufacture of controlled substances. 1307.13 Section 1307.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE MISCELLANEOUS Special Exceptions for Manufacture and Distribution of Controlled Substances § 1307.13 Incidental...

21 CFR 1307.13 - Incidental manufacture of controlled substances.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Incidental manufacture of controlled substances. 1307.13 Section 1307.13 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE MISCELLANEOUS Special Exceptions for Manufacture and Distribution of Controlled Substances § 1307.13 Incidental...

46 CFR 276.1 - Partial repayment-incidental domestic trading.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 8 2010-10-01 2010-10-01 false Partial repayment-incidental domestic trading. 276.1 Section 276.1 Shipping MARITIME ADMINISTRATION, DEPARTMENT OF TRANSPORTATION REGULATIONS AFFECTING...—incidental domestic trading. In every instance where a vessel, with respect to which a construction...

Hemangioblastomas: histogenesis of the stromal cell studied by immunocytochemistry.

PubMed

Jurco, S; Nadji, M; Harvey, D G; Parker, J C; Font, R L; Morales, A R

1982-01-01

Twenty-one cases of hemangioblastoma from the cerebellum, spinal cord and retina were studied using the unlabeled antibody peroxidase-antiperoxidase technique with antibodies directed against glial fibrillary acidic protein (GFAP) and factor VIII related antigen (VIIIR:Ag). In 19 of 21 cases studied with anti-GFAP, astrocytes were identified peripherally, and in 13 cases they were found centrally within the tumor. In no instance did stromal cells react positively for GFAP. Sixteen cases with anti-VIIIR:Ag antibody were examined, and in all cases many stromal cells showed positive staining. It is concluded that the stromal cells were of endothelial origin. The occasional stromal cells that other investigators have identified as reacting positively for GFAP may represent stromal cells capable of ingesting extracellular GFAP derived from reactive astrocytes within the tumor, or they may be lipidized astrocytes.

Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.

PubMed

Ma, C; Tsai, H; Su, W; Sun, L; Shih, Y; Wang, J

2018-05-31

Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.

Toxocariasis masquerading as liver and lung metastatic nodules in patents with gastrointestinal cancer: clinicopathologic study of five cases.

PubMed

Park, Sanghui; Kim, Yun Soo; Kim, Yu Jin; Kyung, Sun Young; Park, Jeong-Woong; Jeong, Sung Hwan; Lee, Sang Pyo

2012-01-01

There are sporadic reports in the literature in which radiologic liver and lung lesions found incidentally during follow-up metastatic surveillance were shown to be caused by toxocariasis. The objective of the work discussed in this report was to identify common clinical and histopathological features of toxocariasis resembling metastatic nodules in five patients with gastrointestinal cancer. We retrospectively analyzed clinical features of five gastrointestinal cancer patients with liver or lung nodules mimicking metastasis. Serologic tests for parasitic infestations and pathologic examinations were performed. All five patients were males and three patients had gastric cancer and two had colorectal cancer. All the cases of toxocariasis were confirmed serologically. On follow-up imaging, the lesions improved or resolved, suggestive of the phenomenon of visceral larva migrans. In two patients, liver biopsy was performed and showed eosinophilic abscess. Serologic tests and liver or lung biopsy should be performed aggressively to exclude toxocariasis when patients with underlying gastrointestinal cancer present with hepatic or pulmonary nodules associated with eosinophilia, particularly if the patients have a clinical history of raw animal liver ingestion. Curative surgical intervention should not be excluded just because of multiple nodules in the liver or the lungs.

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…

Gastric GIST with synchronous neuroendocrine tumour of the pancreas in a patient without neurofibromatosis type 1

PubMed Central

Tavares, Amelia Brandao; Viveiros, Fernando Arruda; Cidade, Cassilda Neves; Maciel, Jorge

2012-01-01

The gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract. These are rare tumours with an incidence of 15 new cases per million per year. The occurrence of neuroendocrine tumours of the pancreas is rare, representing 1–5% of pancreatic cancers, and it is estimated that its incidence does not exceed five to one million. GISTs are common in patients with neurofibromatosis type 1 (NF1); there are few reported cases of synchronous neuroendocrine tumours in these patients and most are pheochromocytomas. The case reports a 64-year-old woman referred to the General Surgery Outpatient for incidental finding of gastric and pancreatic tumours. She underwent a radical subtotal pancreatectomy + partial gastrectomy with jejunal transposition. The pathological examination revealed: gastric GISTs and a well-differentiated neuroendocrine carcinoma of the pancreas. This is the second case published so far of a patient with both tumours  and without NF1. Posterior studies must be performed to evaluate if some other genetic disorder is involved in these patients without NF1. PMID:22675144

CASTIN: a system for comprehensive analysis of cancer-stromal interactome.

PubMed

Komura, Daisuke; Isagawa, Takayuki; Kishi, Kazuki; Suzuki, Ryohei; Sato, Reiko; Tanaka, Mariko; Katoh, Hiroto; Yamamoto, Shogo; Tatsuno, Kenji; Fukayama, Masashi; Aburatani, Hiroyuki; Ishikawa, Shumpei

2016-11-09

Cancer microenvironment plays a vital role in cancer development and progression, and cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome. We present CASTIN (CAncer-STromal INteractome analysis), a novel framework for the evaluation of cancer-stromal interactome from RNA-Seq data using cancer xenograft models. For each ligand-receptor interaction which is derived from curated protein-protein interaction database, CASTIN summarizes gene expression profiles of cancer and stroma into three evaluation indices. These indices provide quantitative evaluation and comprehensive visualization of interactome, and thus enable to identify critical cancer-microenvironment interactions, which would be potential drug targets. We applied CASTIN to the dataset of pancreas ductal adenocarcinoma, and successfully characterized the individual cancer in terms of cancer-stromal relationships, and identified both well-known and less-characterized druggable interactions. CASTIN provides comprehensive view of cancer-stromal interactome and is useful to identify critical interactions which may serve as potential drug targets in cancer-microenvironment. CASTIN is available at: http://github.com/tmd-gpat/CASTIN .

Conventional Risk Stratification Fails to Predict Progression of Succinate Dehydrogenase-deficient Gastrointestinal Stromal Tumors: A Clinicopathologic Study of 76 Cases.

PubMed

Mason, Emily F; Hornick, Jason L

2016-12-01

Gastrointestinal stromal tumors (GISTs) that lack kinase mutations often show loss of function of the succinate dehydrogenase (SDH) complex, due to germline mutation or promoter hypermethylation. SDH-deficient GISTs are exclusive to the stomach and have a multinodular architecture. It has been suggested that conventional risk stratification criteria may not predict outcome for this group of tumors, although data are limited. Here, we report the clinical, histologic, and genetic findings from a large cohort of 76 SDH-deficient GISTs diagnosed from 2005 to 2015, identified on the basis of histologic features or family history (45 female/31 male; mean age at diagnosis 32 y; range 11 to 71 y; 10 patients 50 y of age or above). Immunohistochemistry for SDHB and SDHA showed loss of SDHB in all cases and loss of SDHA in 28 (37%) tumors. Tumor size ranged from 1.9 to 22.5 cm; the primary tumor was multifocal in 29%. Mitotic rate ranged from 1 to 80 per 5 mm (median 5.5). Lymph node metastases were found at primary resection in 14 (18%) patients. Twenty-four patients (32%) had distant metastases at presentation, and 52 of 70 patients (74%) with follow-up developed distant metastases, most often to the liver, but also bone, lungs, breast, and brain. Applying conventional criteria (size and mitotic rate), 60% to 82% of patients with tumors ranging from very low risk to high risk for progressive disease developed distant metastases, regardless of the category. Carney-Stratakis syndrome and Carney triad were diagnosed in 6 and 8 patients, respectively. Of 35 patients tested, 26 harbored SDH mutations (11 SDHA, 8 SDHB, 6 SDHC, 1 SDHD). Follow-up data available for 70 patients ranged from 1 month to 39.3 years: 20 patients had no evidence of disease (mean 6.1 y), 32 were alive with metastases (mean 10.9 y), and 18 died of disease (mean 7.0 y after diagnosis). In summary, SDH-deficient GISTs account for approximately 8% of gastric GISTs and are associated with a high rate of

Multifocal small bowel stromal tumours presenting with peritonitis in an HIV positive patient.

PubMed

Mansoor, Ebrahim

2014-01-01

The most common mesenchymal tumour of the gastrointestinal tract is stromal tumours (GISTs). Symptomatic GISTs can present with complications such as haemorrhage, obstruction and perforation. Complete surgical resection with negative margins is the mainstay of treatment but may be imprudent on emergent occasion. Tyrosine-kinase inhibitors (TKIs) have been revolutionary in the treatment of GISTs and have resulted in improved outcomes. A 41 year old HIV positive male presented with an acute history of abdominal pain and obstructive symptoms. Clinical examination revealed sepsis and peritonitis. One of the several small bowel tumours discovered at exploratory laparotomy was necrotic and perforated. The perforated tumour alone was resected and a small bowel internal hernia reduced. The patient made an uneventful recovery and will be considered for TKI therapy with a view to later re-operation. GISTs very rarely perforate. The pathophysiology of stromal tumour necrosis is poorly understood. Multifocality and small bowel location are poor prognosticators and may occur in the setting of familial GISTs, specific syndromes and sporadic cases. There is no established association between HIV and GISTs. Perforation occurs infrequently in ≤8% of symptomatic cases and poses increased risk of local recurrence. The surgical management of perforation takes precedence in an emergency. The surgeon must however take cognisance of the adherence to ideal oncologic principles where feasible. TKI therapy is invaluable if a re-exploration is to be later considered. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

A potent combination of the novel PI3K inhibitor, GDC-0941, with imatinib in gastrointestinal stromal tumor xenografts: long-lasting responses after treatment withdrawal

PubMed Central

Floris, Giuseppe; Wozniak, Agnieszka; Sciot, Raf; Li, Haifu; Friedman, Lori; Van Looy, Thomas; Wellens, Jasmien; Vermaelen, Peter; Deroose, Christophe M.; Fletcher, Jonathan A.; Debiec-Rychter, Maria; Schöffski, Patrick

2015-01-01

Introduction Oncogenic signaling in gastrointestinal stromal tumors (GIST) is sustained via PI3K/AKT pathway. We used a panel of six GIST xenograft models to assess efficacy of GDC-0941 as single agent or in combination with imatinib (IMA). Experimental design Nude mice (n=136) were grafted bilaterally with human GIST carrying divers KIT mutations. Mice were orally dosed over four weeks, grouped as follows: A) control; B) GDC-0941; C) IMA and D) GDC+IMA treatments. Xenografts re-growth after treatment discontinuation was assessed in group C and D for additional four weeks. Tumor response was assessed by volume measurements, micro-PET imaging, histopathology and immunoblotting. Moreover genomic alterations in PTEN/PI3K/AKT pathway were evaluated. Results In all models, GDC-0941 caused tumor growth stabilization, inhibiting tumor cells proliferation but did not induce apoptosis. Under GDC+IMA, profound tumor regression, superior to either treatment alone, was observed. This effect was associated with the best histologic response, a nearly complete proliferation arrest and increased apoptosis. Tumor re-growth assays confirmed superior activity of GDC+IMA over IMA; in three out of six models tumor volume remained reduced and stable even after treatment discontinuation. A positive correlation between response to GDC+IMA and PTEN loss, both on gene and protein levels, was found. Conclusion GDC+IMA has significant antitumor efficacy in GIST xenografts, inducing more substantial tumor regression, apoptosis and durable effects than IMA. Notably, after treatment withdrawal, tumor regression was sustained in tumors exposed to GDC+IMA, which was not observed under IMA. Assessment of PTEN status may represent a useful predictive biomarker for patient selection. PMID:23231951

Involvement of stromal p53 in tumor-stroma interactions

PubMed Central

Bar, Jair; Moskovits, Neta; Oren, Moshe

2009-01-01

p53 is a major tumor-suppressor gene, inactivated by mutations in about half of all human cancer cases, and probably incapacitated by other means in most other cases. Most research regarding the role of p53 in cancer has focused on its ability to elicit apoptosis or growth arrest of cells that are prone to become malignant owing to DNA damage or oncogene activation, i.e. cell-autonomous activities of p53. However, p53 activation within a cell can also exert a variety of effects upon neighboring cells, through secreted factors and paracrine and endocrine mechanisms. Of note, p53 within cancer stromal cells can inhibit tumor growth and malignant progression. Cancer cells that evolve under this inhibitory influence acquire mechanisms to silence stromal p53, either by direct inhibition of p53 within stromal cells, or through pressure for selection of stromal cells with compromised p53 function. Hence, activation of stromal p53 by chemotherapy or radiotherapy might be part of the mechanisms by which these treatments cause cancer regression. However, in certain circumstances, activation of stromal p53 by cytotoxic anti-cancer agents might actually promote treatment resistance, probably through stromal p53-mediated growth arrest of the cancer cells or through protection of the tumor vasculature. Better understanding of the underlying molecular mechanisms is thus required. Hopefully, this will allow their manipulation towards better inhibition of cancer initiation, progression and metastasis. PMID:19914385

S0502: A SWOG Phase III Randomized Study of Imatinib, With or Without Bevacizumab, in Patients With Untreated Metastatic or Unresectable Gastrointestinal Stromal Tumors.

PubMed

Blanke, Charles D; Rankin, Cathy; Corless, Christopher; Eary, Janet F; Mulder, Karen; Okuno, Scott H; George, Suzanne; Heinrich, Michael

2015-12-01

Despite having significant rationale, S0502 failed to accrue for a number of reasons.Vetting a trial first, with scientific experts and funding agencies, does not guarantee success, especially when dealing with a rare tumor and/or one with an existing highly effective therapy.In the present case, adding an intravenous drug to an oral medication as part of a regimen expected to be continued for many years likely decreased patient (and physician) convenience and, thus, interest in the study. Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). However, most imatinib-treated tumors eventually become resistant, accounting for a median progression-free survival of 19-23 months. Expression of vascular endothelial growth factor (VEGF) correlates with poor prognosis in GIST; bevacizumab, a monoclonal antibody against VEGF, is effective in a variety of solid tumors. We postulated combination therapy with imatinib plus bevacizumab would benefit patients with advanced GIST, particularly those reliant on VEGFA-dependent angiogenesis. Patients with metastatic or surgically unresectable GIST were eligible for this phase III open-label clinical trial, S0502. At registration, patients were randomly assigned to either imatinib 400 mg (standard) or 800 mg (patients with exon 9 KIT mutations), or imatinib plus bevacizumab, 7.5 mg/kg i.v. every 3 weeks. Patients were treated to progression, symptomatic deterioration, unacceptable toxicity, treatment delay greater than 4 weeks, or patient choice to withdraw from the study. The primary objective was to determine whether the addition of bevacizumab to imatinib would improve progression-free survival (PFS) in first-line treatment of incurable GIST. S0502 opened on April 15, 2008. As of fall 2009, only 12 patients from at least 178 eligible SWOG centers plus those participating through Cancer Trials Support Unit had been

The value of (18) F-fluorodeoxyglucose positron emission tomography for prediction of treatment response in gastrointestinal stromal tumors: a systematic review and meta-analysis.

PubMed

Hassanzadeh-Rad, Arman; Yousefifard, Mahmoud; Katal, Sanaz; Asady, Hadi; Fard-Esfahani, Armaghan; Moghadas Jafari, Ali; Hosseini, Mostafa

2016-05-01

Early detection of response to treatment is critically important in gastrointestinal stromal tumors (GIST). Therefore, the present systematic review and meta-analysis assessed the value of (18) f-fluorodeoxyglucose positron emission tomography ((18) FDG-PET) on prediction of therapeutic response of GIST patients to systemic treatments. The literature search was conducted using PubMed, SCOPUS, Cochrane, and Google Scholar databases, and review article references. Eligible articles were defined as studies included confirmed GIST patients who underwent (18) FDG-PET as well as assessing the screening role of it. Finally, 21 relevant articles were included. The analysis showed the pooled sensitivity and specificity of 18FDG-PET in evaluation of response to treatment of GIST patient were 0.90 (95% CI: 0.85-0.94; I(2)  = 52.59, P = 0.001) and 0.62 (95% CI: 0.49-0.75; I(2)  = 69.7, P = 0.001), respectively. In addition, the pooled prognostic odds ratio of (18) FDG-PET for was 14.99 (95% CI, 6.42-34.99; I(2)  = 100.0, P < 0.001). The Meta regression showed that sensitivity of (18) FDG-PET was higher if the sample size of study was equal or more than 30 cases (sensitivity = 0.93; 95% CI: 0.89-0.97), when using PET/CT (sensitivity = 0.92; 95% CI: 0.89-0.97), and self-design criteria (sensitivity = 0.93; 95% CI: 0.87-1.0). The present meta-analysis showed (18) FDG-PET has a significant value in predicting treatment response in GIST patients. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Comparison of performance of various tumour response criteria in assessment of regorafenib activity in advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib.

PubMed

Shinagare, Atul B; Jagannathan, Jyothi P; Kurra, Vikram; Urban, Trinity; Manola, Judith; Choy, Edwin; Demetri, George D; George, Suzanne; Ramaiya, Nikhil H

2014-03-01

To compare performance of various tumour response criteria (TRCs) in assessment of regorafenib activity in patients with advanced gastrointestinal stromal tumour (GIST) with prior failure of imatinib and sunitinib. Twenty participants in a phase II trial received oral regorafenib (median duration 47 weeks; interquartile range (IQR) 24-88) with computed tomography (CT) imaging at baseline and every two months thereafter. Tumour response was prospectively determined on using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1, and retrospectively reassessed for comparison per RECIST 1.0, World Health Organization (WHO) and Choi criteria, using the same target lesions. Clinical benefit rate [CBR; complete or partial response (CR or PR) or stable disease (SD)≥16 weeks] and progression-free survival (PFS) were compared between various TRCs using kappa statistics. Performance of TRCs in predicting overall survival (OS) was compared by comparing OS in groups with progression-free intervals less than or greater than 20 weeks by each TRC using c-statistics. PR was more frequent by Choi (90%) than RECIST 1.1, RECIST 1.0 and WHO (20% each), however, CBR was similar between various TRCs (overall CBR 85-90%, 95-100% agreement between all TRC pairs). PFS per RECIST 1.0 was similar to RECIST 1.1 (median 44 weeks versus 58 weeks), and shorter for WHO (median 34 weeks) and Choi (median 24 weeks). With RECIST 1.1, RECIST 1.0 and WHO, there was moderate concordance between PFS and OS (c-statistics 0.596-0.679). Choi criteria had less favourable concordance (c-statistic 0.506). RECIST 1.1 and WHO performed somewhat better than Choi criteria as TRC for response evaluation in patients with advanced GIST after prior failure on imatinib and sunitinib. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

PubMed Central

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. PMID:26722383

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…

Incidental finding of upper lip Warthin tumor.

PubMed

Petrocelli, Marzia; Sbordone, Carolina; Salzano, Giovanni; Orabona, Giovanni Dell'Aversana; Cassandro, Francesco Maria; Fusetti, Stefano; Califano, Luigi; Cassandro, Ettore

2017-11-14

This report shows an incidental finding of Warthin tumor in upper lip mucosa during hospitalization for a biting lesion of cheek mucosa MATERIALS AND METHODS: A 32-year-old male affected by a biting lesion of cheek mucosa was presented at Maxillo- Facial Unit of Federico II University. Clinical examination showed as an incidental finding a solid mass in the superficial layer of upper lip mucosa. We performed mini-invasive surgical treatment to obtain a radical excision of the cheek lesion at the same time as excision of Warthin tumor. a follow up of 12 months was performed. The complete healing of the two wounds was achieved, with no recurrence of any of the pathologies. The location of this Warthin tumor of minor salivary glands is very unusual. The role of imaging in diagnosis of Warthin tumor of minor salivary glands is to define localization, shape and dimension, contour, malignant features, nodal involvement. The role of fine needle aspiration cytology (FNAC) is critical in the diagnosis and therapy of minor salivary gland tumors. The surgical treatment in patients affected by Warthin tumour of minor salivary glands is local excision with a wide tumor free margin to prevent potential recurrence. Warthin tumor of minor salivary glands is a rare disease. We report a singular case of Warthin tumor localized in the upper lip mucosa, found as an incidental finding during a recovery for a biting lesion of cheek mucosa. Incidental finding, Minor salivary glands, Warthin tumor.

The facilitative effects of incidental teaching on preposition use by autistic children.

PubMed Central

McGee, G G; Krantz, P J; McClannahan, L E

1985-01-01

In a comparison of incidental teaching and traditional training procedures, three language-delayed autistic children were taught expressive use of prepositions to describe the location of preferred edibles and toys. Traditional highly structured training and incidental teaching procedures were used in a classroom setting, and generalization was assessed during free-play sessions. Results clearly indicate that incidental teaching promoted greater generalization and more spontaneous use of prepositions. These findings have important implications for language programming and teacher training, suggesting that incidental teaching should be included as a standard component of language development curricula for autistic and other developmentally delayed children. PMID:3997695

Incidental Reflector Comparison of Containerized Dry Fire Extinguishing Agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, Bryan Scott; Wysong, Andrew Russell

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 0.4more » inches of close fitting water.« less

50 CFR 18.24 - Taking incidental to commercial fishing operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Taking incidental to commercial fishing... commercial fishing operations. Persons may take marine mammals incidental to commercial fishing operations... of marine mammals permitted in the course of commercial fishing operations be reduced to...

50 CFR 18.24 - Taking incidental to commercial fishing operations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Taking incidental to commercial fishing... commercial fishing operations. Persons may take marine mammals incidental to commercial fishing operations... of marine mammals permitted in the course of commercial fishing operations be reduced to...

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... commercial fishing operations. Persons may take marine mammals incidental to commercial fishing operations... of marine mammals permitted in the course of commercial fishing operations be reduced to...

50 CFR 18.24 - Taking incidental to commercial fishing operations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Taking incidental to commercial fishing... commercial fishing operations. Persons may take marine mammals incidental to commercial fishing operations... of marine mammals permitted in the course of commercial fishing operations be reduced to...

Diagnosis of incidental gallbladder cancer after laparoscopic cholecystectomy: our experience

PubMed Central

2013-01-01

Background Gallbladder carcinoma is a rare high malignancy neoplasm. The incidence of intra or post-operative incidental gallbladder carcinoma diagnosis is estimated between 0,2 and 2,8%. Primary aim of our study is to evaluate incidental gallbladder carcinoma's incidence in our experience. Methods We retrospectively reviewed our Surgery Division's experience about the totality of laparoscopic cholecystectomies with post-operative histological evidence of incidental gallbladder cancer. We evaluated patients' characteristics, surgical related variables, histological response, surgivcal radicalization characteristics and surgical outcome. Results In the considered sample we observed 7 accidental gallbladder adenocarcinomas in post-operative histological examination. Pathological results were:1 pT1b N0 (G1), 2 pT2 N0 (G2), 2 pT2 N1 (G3b), 2 pT3 N1 (G3b) (Table 1). In 5 cases we performed neoplasm radicalization surgery with standard procedure revision. Two patients died before radicalization. Median global survival was 34 months. Conclusion With the increase of laparoscopic cholecystectomies both elective and urgent performed in our centre we observed also an increase of incidentally diagnosed gallbladder neoplasms. Early diagnosis, meticulous peri-operative study and accurate surgical strategy are essential factors to obtain good results in incidental gallbladder cancer. PMID:24268097

Estimated Costs of Sporadic Gastrointestinal Illness Associated with Surface Water Recreation: A Combined Analysis of Data from NEEAR and CHEERS Studies

PubMed Central

DeFlorio-Barker, Stephanie; Wade, Timothy J.; Jones, Rachael M.; Friedman, Lee S.; Wing, Coady; Dorevitch, Samuel

2016-01-01

Background: The burden of illness can be described by addressing both incidence and illness severity attributable to water recreation. Monetized as cost, attributable disease burden estimates can be useful for environmental management decisions. Objectives: We characterize the disease burden attributable to water recreation using data from two cohort studies using a cost of illness (COI) approach and estimate the largest drivers of the disease burden of water recreation. Methods: Data from the NEEAR study, which evaluated swimming and wading in marine and freshwater beaches in six U.S. states, and CHEERS, which evaluated illness after incidental-contact recreation (boating, canoeing, fishing, kayaking, and rowing) on waterways in the Chicago area, were used to estimate the cost per case of gastrointestinal illness and costs attributable to water recreation. Data on health care and medication utilization and missed days of work or leisure were collected and combined with cost data to construct measures of COI. Results: Depending on different assumptions, the cost of gastrointestinal symptoms attributable to water recreation are estimated to be $1,220 for incidental-contact recreation (range $338–$1,681) and $1,676 for swimming/wading (range $425–2,743) per 1,000 recreators. Lost productivity is a major driver of the estimated COI, accounting for up to 90% of total costs. Conclusions: Our estimates suggest gastrointestinal illness attributed to surface water recreation at urban waterways, lakes, and coastal marine beaches is responsible for costs that should be accounted for when considering the monetary impact of efforts to improve water quality. The COI provides more information than the frequency of illness, as it takes into account disease incidence, health care utilization, and lost productivity. Use of monetized disease severity information should be included in future studies of water quality and health. Citation: DeFlorio-Barker S, Wade TJ, Jones RM

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

Incidental findings on computed tomography scans in children with mild head trauma.

PubMed

Ortega, Henry W; Vander Velden, Heidi; Reid, Samuel

2012-09-01

Computed tomography (CT) scans are frequently used in managing traumatic brain injuries in children. To assess incidental findings in children with head trauma undergoing CT scan and to describe any associated clinical ramifications. Retrospective review of 524 children treated in 2 emergency departments for closed head injury who received a CT scan. Overall, 137 (26.2%) patients had an incidental finding on CT scan. The most common incidental finding was sinus opacification with an air fluid level (115/137, 83.9%). Thirty-five interventions were reported in children with incidental findings. Children 2 years old or younger were more likely to receive a prescription for antibiotics (relative risk [RR] = 2.66, 95% confidence interval [CI] = 1.08-6.51) and be referred to a specialist (RR = 10.26, 95% CI = 3.56-29.56) than older children. Incidental findings in minor head trauma are common. Clinicians should be prepared to address these findings if clinically indicated.

Defining incidental perineural invasion: the need for a national registry.

PubMed

Buchanan, Lauren; De'Ambrosis, Brian; DeAmbrosis, Kathryn; Warren, Timothy; Huilgol, Shyamala; Soyer, H Peter; Panizza, Benedict

2014-05-01

This article by the Perineural Invasion (PNI) Registry Group aims to clarify clinical and histopathological ambiguities surrounding PNI in non-melanoma skin cancer (NMSC). PNI is reportedly present in approximately 2-6% of cases of NMSC and is associated with greater rates of morbidity and mortality. The distinction between clinical PNI and incidental PNI is somewhat unclear, especially in regard to management and prognosis. One important objective of the PNI Registry is to develop a standardised method of classifying perineural invasion. Hence, in this article we propose a definition for PNI and for its sub-classification. This article also provides a critical analysis of the current literature on the treatment of incidental PNI by evaluating the key cohort studies that have investigated the use of surgery or radiotherapy in the management of incidental PNI. At present, there are no universal clinical guidelines that specify the acceptable treatment of NMSC exhibiting incidental PNI. Consequently, patients often receive surgery with varying wider margins, or radiotherapy despite the limited evidence substantiating such management options. It is evident from the existing literature that current opinion is divided over the benefit of adjuvant radiotherapy. Certain prognostic factors have been proposed, such as the size and depth of tumour invasion, nerve diameter, the presence of multifocal PNI and the type of tumour. The PNI Registry is a web-based registry that has been developed to assist in attaining further data pertaining to incidental PNI in NMSC. It is envisaged that this information will provide the foundation for identifying and defining best practice in managing incidental PNI. © 2013 The Australasian College of Dermatologists.

To search or to like: Mapping fixations to differentiate two forms of incidental scene memory.

PubMed

Choe, Kyoung Whan; Kardan, Omid; Kotabe, Hiroki P; Henderson, John M; Berman, Marc G

2017-10-01

We employed eye-tracking to investigate how performing different tasks on scenes (e.g., intentionally memorizing them, searching for an object, evaluating aesthetic preference) can affect eye movements during encoding and subsequent scene memory. We found that scene memorability decreased after visual search (one incidental encoding task) compared to intentional memorization, and that preference evaluation (another incidental encoding task) produced better memory, similar to the incidental memory boost previously observed for words and faces. By analyzing fixation maps, we found that although fixation map similarity could explain how eye movements during visual search impairs incidental scene memory, it could not explain the incidental memory boost from aesthetic preference evaluation, implying that implicit mechanisms were at play. We conclude that not all incidental encoding tasks should be taken to be similar, as different mechanisms (e.g., explicit or implicit) lead to memory enhancements or decrements for different incidental encoding tasks.

Stromal p16 Overexpression in Adult Granulosa Cell Tumors of the Ovary.

PubMed

Na, Kiyong; Sung, Ji-Youn; Kim, Hyun-Soo

2017-05-01

Adult granulosa cell tumor of the ovary is usually diagnosed at an early stage. However, most patients with advanced or recurrent disease will die of the disease due to limited treatment options. Data on the stromal p16 expression of ovarian adult granulosa cell tumors are limited. The aim of this study was to analyze the immunohistochemical p16 expression in the peritumoral stroma of primary and recurrent adult granulosa cell tumors and investigate whether there were significant differences in stromal p16 expression among nonpathological ovaries, benign sex cord-stromal tumors, and adult granulosa cell tumors. This study included 13 and 11 cases of primary and recurrent adult granulosa cell tumors, respectively. Non-pathological ovaries and benign sex cord-stromal tumors showed negative or weak positive expression, whereas most of the adult granulosa cell tumors showed diffuse and moderate-to-strong immunostaining. Primary adult granulosa cell tumors had significantly higher stromal p16 expression levels than nonpathological ovaries and benign sex cord-stromal tumors (p<0.001). Moreover, recurrent adult granulosa cell tumors showed significantly elevated levels of stromal p16 expression compared to primary adult granulosa cell tumors (p=0.032). In contrast, the difference in stromal p16 expression between non-pathological ovaries and benign sex cord-stromal tumors was not statistically significant (p=0.522). Our observations suggest that stromal p16 expression may be involved in the development and progression of ovarian adult granulosa cell tumors. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Radiology reports for incidental thyroid nodules on CT and MRI: high variability across subspecialties.

PubMed

Grady, A T; Sosa, J A; Tanpitukpongse, T P; Choudhury, K R; Gupta, R T; Hoang, J K

2015-02-01

Variability in radiologists' reporting styles and recommendations for incidental thyroid nodules can lead to confusion among clinicians and may contribute to inconsistent patient care. Our aim was to describe reporting practices of radiologists for incidental thyroid nodules seen on CT and MR imaging and to determine factors that influence reporting styles. This is a retrospective study of patients with incidental thyroid nodules reported on CT and MR imaging between January and December 2011, identified by text search for "thyroid nodule" in all CT and MR imaging reports. The studies included CT and MR imaging scans of the neck, spine, and chest. Radiology reports were divided into those that mentioned the incidental thyroid nodules only in the "Findings" section versus those that reported the incidental thyroid nodules in the "Impression" section as well, because this latter reporting style gives more emphasis to the finding. Univariate and multivariate analyses were performed to identify radiologist, patient, and nodule characteristics that influenced reporting styles. Three hundred seventy-five patients met the criterion of having incidental thyroid nodules. One hundred thirty-eight (37%) patients had incidental thyroid nodules reported in the "Impression" section. On multivariate analysis, only radiologists' divisions and nodule size were associated with reporting in "Impression." Chest radiologists and neuroradiologists were more likely to report incidental thyroid nodules in the "Impression" section than their abdominal imaging colleagues, and larger incidental thyroid nodules were more likely to be reported in "Impression" (P ≤ .03). Seventy-three percent of patients with incidental thyroid nodules of ≥20 mm were reported in the "Impression" section, but higher variability in reporting was seen for incidental thyroid nodules measuring 10-14 mm and 15-19 mm, which were reported in "Impression" for 61% and 50% of patients, respectively. Reporting

Underestimation of malignancy in biopsy-proven cases of stromal fibrosis

PubMed Central

Lad, S; Seely, J M; Schweitzer, M E

2014-01-01

Objective: To determine the rate of underestimation of malignancy in patients with biopsy-proven stromal fibrosis. Methods: Following institutional review board approval, we retrospectively reviewed the charts of patients with biopsy-proven stromal fibrosis who underwent percutaneous breast biopsy in the 5-year period between 1 January 2005 and 31 December 2009. The medical records and the histopathology in patients who underwent repeat biopsy and/or surgical excision at the site of stromal fibrosis within 2 years were reviewed. Interval stability for up to 2 years was documented in patients who did not undergo additional biopsy or surgical excision. An upgrade was defined as any patient with biopsy-proven stromal fibrosis or fibroadenoma with evidence of malignancy at the site of biopsy within 2 years. Results: 365 cases of stromal fibrosis were identified, of which 25 (7%) were upgraded to in situ or invasive malignancy on repeat biopsy or surgical excision. 7 were upgraded to ductal carcinoma in situ and 18 were upgraded to invasive cancer. Of the upgraded cases, 8 out of 24 (32%) were considered concordant with a benign diagnosis. The false-negative rate, that is, cases of stromal fibrosis concordant with benignity, but with subsequent upgrade, comprised 2% of all cases. Conclusion: In biopsy-proven cases of stromal fibrosis, there is a 7% upgrade to malignancy. We recommend that all instances of stromal fibrosis with radiology–pathology discordance undergo repeat biopsy or surgical excision. Cases that demonstrate radiology–pathology concordance can be safely categorized as a Breast Imaging Reporting and Data System 3 (BI-RADS® 3) lesion with a 6-month follow-up, owing to a false-negative rate for missed cancer of 2%. Advances in knowledge: We now recommend that concordant cases of stromal fibrosis be categorized as BI-RADS 3 with a short-term follow-up, as this results in a missed cancer rate of 2%. PMID:24846442

A phase 1 study of the heat shock protein 90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft tissue sarcomas

PubMed Central

Wagner, Andrew J.; Chugh, Rashmi; Rosen, Lee S.; Morgan, Jeffrey A.; George, Suzanne; Gordon, Michael; Dunbar, Joi; Normant, Emmanuel; Grayzel, David; Demetri, George D.

2015-01-01

Purpose Heat shock protein 90 (Hsp90) is required for the proper folding, function, and stability of various client proteins, two of which (KIT and PDGFRα) are critical in the pathogenesis and progression of gastrointestinal stromal tumors (GIST). This phase 1 study investigated the safety and maximum tolerated dose (MTD) of retaspimycin hydrochloride (IPI-504), a novel potent and selective Hsp90 inhibitor, in patients with metastatic and/or unresectable GIST or other soft-tissue sarcomas (STS). Experimental Design IPI-504 was administered intravenously at doses ranging from 90 to 500 mg/m2 twice weekly for 2 weeks on/1 week off. Safety, pharmacokinetic, and pharmacodynamic profiles were determined. Response was assessed by Response Evaluation Criteria for Solid Tumors (RECIST) 1.0 and optionally via 18-fluorodeoxyglucose positron emission tomography (18-FDG-PET) imaging. Results Fifty-four patients received IPI-504; 37 with GIST and 17 with other STS. The MTD was 400 mg/m2 twice weekly for 2 weeks on/1 week off. Common related adverse events were fatigue (59%), headache (44%), and nausea (43%). Exposure to IPI-504, 17-AAG, and 17-AG increased with IPI-504 dose. Stable disease (SD) was observed in 70% (26/37) of patients with GIST and 59% (10/17) of patients with STS. There was one confirmed partial response (PR) in a patient with GIST and one PR in a patient with liposarcoma. Metabolic partial responses occurred in 11/29 (38%) of GIST patients. Conclusions In this study of advanced GIST or other STS, IPI-504 was generally well-tolerated with some evidence of anti-tumor activity, serving as a clinical proof-of-concept that HSP90 inhibition remains a promising strategy. PMID:24045182

Prognostic role of tumor necrosis in patients undergoing curative resection for gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in China.

PubMed

Liu, Xuechao; Qiu, Haibo; Zhang, Peng; Feng, Xingyu; Chen, Tao; Li, Yong; Tao, Kaixiong; Li, Guoxin; Sun, Xiaowei; Zhou, Zhiwei

2017-12-01

Tumor necrosis is associated with poor clinical outcomes in many malignancies. We aimed to determine whether tumor necrosis was an independent predictor of outcomes in gastric gastrointestinal stromal tumors (GISTs). We retrospectively analyzed data from 740 patients undergoing curative resection for gastric GIST at four centers between 2001 and 2015. Disease-free survival (DFS) was estimated with the Kaplan-Meier method, and associations with prognosis were assessed with Cox regression models. Tumor necrosis was present in 122 cases (16.5%). The prevalence of tumor necrosis increased with higher risk-stratification, including 0.7%, 7.4%, 17.3%, and 39.3% for very low-, low-, intermediate- and high-risk tumors, respectively (P < 0.001). Tumor necrosis was associated with aggressive tumor biology, such as larger tumor size, higher mitotic index, tumor rupture, and presence of nuclear atypia (all P < 0.05). Multivariate analysis revealed that tumor necrosis was an independent predictor of unfavorable DFS (HR: 2.641; 95% CI: 1.359-5.131; P = 0.004). When stratified by the modified National Institutes of Health (NIH) classification, tumor necrosis still independently predicted DFS in high-risk patients (P = 0.001) but not in non-high-risk patients (P = 0.349). The 5-year DFS rate in high-risk patients with and without tumor necrosis was 56.5% and 82.9%, respectively (P = 0.004). Notably, the prognostic significance of tumor necrosis was maintained when the patients were stratified by age, sex, tumor location, tumor size, and mitotic index (All P < 0.05). Tumor necrosis is a useful predictor of outcomes in gastric GIST, especially in high-risk patients. Based on these results, we recommend that the current NIH classification should be further improved and expanded to include tumor necrosis as a valuable prognostic indicator. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

A phase II trial of regorafenib in patients with metastatic and/or a unresectable gastrointestinal stromal tumor harboring secondary mutations of exon 17.

PubMed

Yeh, Chun-Nan; Chen, Ming-Huang; Chen, Yen-Yang; Yang, Ching-Yao; Yen, Chueh-Chuan; Tzen, Chin-Yuan; Chen, Li-Tzong; Chen, Jen-Shi

2017-07-04

Gastrointestinal stromal tumors (GISTs) are caused by the constitutive activation of KIT or platelet-derived growth factor receptor alpha (PDGFRA) mutations. Imatinib selectively inhibits KIT and PDGFR, leading to disease control for 80%-90% of patients with metastatic GIST. Imatinib resistance can occur within a median of 2-3 years due to secondary mutations in KIT. According to preclinical studies, both imatinib and sunitinib are ineffective against exon 17 mutations. However, the treatment efficacy of regorafenib for patients with GIST with exon 17 mutations is still unknown. Documented patients with GIST with exon 17 mutations were enrolled in this study. Patients received 160 mg of oral regorafenib daily on days 1-21 of a 28-day cycle. The primary end point of this trial was the clinical benefit rate (CBR; i.e., complete or partial response [PR], as well as stable disease [SD]) at 16 weeks. The secondary end points of this study included progression free survival (PFS), overall survival, and safety. Between June 2014 to May 2016, 18 patients were enrolled (15 of which were eligible for response evaluation). The CBR at 16 weeks was 93.3% (14 of 15; 6 PR and 8 SD). The median PFS was 22.1 months. The most common grade 3 toxicities were hand-and-foot skin reactions (10 of 18; 55.6%), followed by hypertension (5 of 18; 27.8%). Regorafenib significantly prolonged PFS in patients with advanced GIST harboring secondary mutations of exon 17. A phase III trial of regorafenib versus placebo is warranted. This trial is registered at ClinicalTrials.gov in November 2015, number NCT02606097.Key message: This phase II trial was conducted to assess the efficacy and safety of regorafenib in patients with GIST with exon 17 mutations. The results provide strong evidence that regorafenib significantly prolonged PFS in patients with advanced GIST harboring secondary mutations of exon 17.

Stromal-Based Signatures for the Classification of Gastric Cancer.

PubMed

Uhlik, Mark T; Liu, Jiangang; Falcon, Beverly L; Iyer, Seema; Stewart, Julie; Celikkaya, Hilal; O'Mahony, Marguerita; Sevinsky, Christopher; Lowes, Christina; Douglass, Larry; Jeffries, Cynthia; Bodenmiller, Diane; Chintharlapalli, Sudhakar; Fischl, Anthony; Gerald, Damien; Xue, Qi; Lee, Jee-Yun; Santamaria-Pang, Alberto; Al-Kofahi, Yousef; Sui, Yunxia; Desai, Keyur; Doman, Thompson; Aggarwal, Amit; Carter, Julia H; Pytowski, Bronislaw; Jaminet, Shou-Ching; Ginty, Fiona; Nasir, Aejaz; Nagy, Janice A; Dvorak, Harold F; Benjamin, Laura E

2016-05-01

Treatment of metastatic gastric cancer typically involves chemotherapy and monoclonal antibodies targeting HER2 (ERBB2) and VEGFR2 (KDR). However, reliable methods to identify patients who would benefit most from a combination of treatment modalities targeting the tumor stroma, including new immunotherapy approaches, are still lacking. Therefore, we integrated a mouse model of stromal activation and gastric cancer genomic information to identify gene expression signatures that may inform treatment strategies. We generated a mouse model in which VEGF-A is expressed via adenovirus, enabling a stromal response marked by immune infiltration and angiogenesis at the injection site, and identified distinct stromal gene expression signatures. With these data, we designed multiplexed IHC assays that were applied to human primary gastric tumors and classified each tumor to a dominant stromal phenotype representative of the vascular and immune diversity found in gastric cancer. We also refined the stromal gene signatures and explored their relation to the dominant patient phenotypes identified by recent large-scale studies of gastric cancer genomics (The Cancer Genome Atlas and Asian Cancer Research Group), revealing four distinct stromal phenotypes. Collectively, these findings suggest that a genomics-based systems approach focused on the tumor stroma can be used to discover putative predictive biomarkers of treatment response, especially to antiangiogenesis agents and immunotherapy, thus offering an opportunity to improve patient stratification. Cancer Res; 76(9); 2573-86. ©2016 AACR. ©2016 American Association for Cancer Research.

Postirradiation Leiomyosarcoma of Rectum Presenting as a Polyp: Case Report and Review of the Literature.

PubMed

Jayakumar, Rajeswari; Basu, Prithwijit Patrick; Huang, Tao; Axiotis, Constantine A

2016-04-01

Radiation-induced leiomyosarcomas of the gastrointestinal tract are rare. Very few cases have been documented to date. The histological similarity to gastrointestinal stromal tumor has raised doubts if many of the cases originally reported to be leiomyosarcoma before the widespread use of CD117 were indeed gastrointestinal stromal tumors. We present a case of post-irradiation leiomyosarcoma presenting as a rectal polyp and review the literature. © The Author(s) 2015.

Comparison of stromal corneal nerves between normal and keratoconus patients using confocal microscopy.

PubMed

Ramírez Fernández, M; Hernández Quintela, E; Naranjo Tackman, R

2014-08-01

To evaluate the differences in stromal corneal nerves between normal patients and keratoconus patients. A total of 140 eyes of 70 normal patients (group A) and 122 eyes of 87 keratoconus patients (group B) were examined with the confocal microscope, with a central scan of the total corneal thickness being taken. The morphology and thickness of the corneal stromal nerves were evaluated by using the Navis v. 3.5.0. software. Nerve thickness was obtained from the mean between the widest and the narrowest portions of each stromal nerve. Corneal stromal nerves were observed as irregular linear hyper-reflective structures with wide and narrow portions in all cases. Mean corneal stromal nerves thickness in group A was 5.7±1.7 (range from 3.3 to 10.4 μ), mean corneal stromal nerves thickness in group B was 7.2±1.9 (range from 3.5 to 12.0 μ). There was a statistical significant difference (P<.05) in stromal corneal nerves thickness between group A and group B. Stromal corneal nerves morphology was similar in both groups, but stromal nerves were thicker in keratoconus patients. Copyright © 2013 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

Effects of Enhancement Techniques on L2 Incidental Vocabulary Learning

ERIC Educational Resources Information Center

Duan, Shiping

2018-01-01

Enhancement Techniques are conducive to incidental vocabulary learning. This study investigated the effects of two types of enhancement techniques-multiple-choice glosses (MC) and L1 single-gloss (SG) on L2 incidental learning of new words and retention of them. A total of 89 university learners of English as a Foreign Language (EFL) were asked to…

Reciprocal within-day associations between incidental affect and exercise: An EMA study.

PubMed

Emerson, Jessica A; Dunsiger, Shira; Williams, David M

2018-01-01

Previous research suggests that how people feel throughout the course of a day (i.e. incidental affect) is predictive of exercise behaviour. A mostly separate literature suggests that exercise can lead to more positive incidental affect. This study examines the potential reciprocal effects of incidental affect and exercise behaviour within the same day. Fifty-nine low-active (exercise <60 min/week), overweight (BMI: 25.0-39.9) adults (ages 18-65) participated in a six-month print-based exercise promotion programme. Ecological momentary assessment was used to record self-reported exercise sessions in real time and incidental affective valence (feeling good/bad) as assessed by the 11-point Feeling Scale at random times throughout the day. Use of a within-subjects cross-lagged, autoregressive model showed that participants were more likely to exercise on days when they experienced more positive incidental affect earlier in the day (b = .58, SE = .10, p < .01), and participants were more likely to experience more positive incidental affect on days when they had exercised (b = .26, SE = .03, p < .01), with the former association significantly stronger than the latter (t = 23.54, p < .01). The findings suggest a positive feedback loop whereby feeling good and exercising are reciprocally influential within the course of a day.

50 CFR 229.7 - Monitoring of incidental mortalities and serious injuries.

Code of Federal Regulations, 2010 CFR

2010-10-01

... OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS AUTHORIZATION FOR COMMERCIAL FISHERIES UNDER THE MARINE MAMMAL PROTECTION ACT OF 1972 General Provisions § 229.7 Monitoring of incidental... incidental mortality and serious injury of marine mammals during the course of commercial fishing operations...

Altered prostate epithelial development in mice lacking the androgen receptor in stromal fibroblasts.

PubMed

Yu, Shengqiang; Yeh, Chiuan-Ren; Niu, Yuanjie; Chang, Hong-Chiang; Tsai, Yu-Chieh; Moses, Harold L; Shyr, Chih-Rong; Chang, Chawnshang; Yeh, Shuyuan

2012-03-01

Androgens and the androgen receptor (AR) play important roles in the development of male urogenital organs. We previously found that mice with total AR knockout (ARKO) and epithelial ARKO failed to develop normal prostate with loss of differentiation. We have recently knocked out AR gene in smooth muscle cells and found the reduced luminal infolding and IGF-1 production in the mouse prostate. However, AR roles of stromal fibroblasts in prostate development remain unclear. To further probe the stromal fibroblast AR roles in prostate development, we generated tissue-selective knockout mice with the AR gene deleted in stromal fibroblasts (FSP-ARKO). We also used primary culture stromal cells to confirm the in vivo data and investigate mechanisms related to prostate development. The results showed cellular alterations in the FSP-ARKO mouse prostate with decreased epithelial proliferation, increased apoptosis, and decreased collagen composition. Further mechanistic studies demonstrated that FSP-ARKO mice have defects in the expression of prostate stromal growth factors. To further confirm these in vivo findings, we prepared primary cultured mouse prostate stromal cells and found knocking down the stromal AR could result in growth retardation of prostate stromal cells and co-cultured prostate epithelial cells, as well as decrease of some stromal growth factors. Our FSP-ARKO mice not only provide the first in vivo evidence in Cre-loxP knockout system for the requirement of stromal fibroblast AR to maintain the normal development of the prostate, but may also suggest the selective knockdown of stromal AR might become a potential therapeutic approach to battle prostate hyperplasia and cancer. Copyright © 2011 Wiley Periodicals, Inc.

Co-Culturing of Multipotent Mesenchymal Stromal Cells with Autological and Allogenic Lymphocytes.

PubMed

Kapranov, N M; Davydova, Yu O; Gal'tseva, I V; Petinati, N A; Bakshinskaitė, M V; Drize, N I; Kuz'mina, L A; Parovichnikova, E N; Savchenko, V G

2018-03-01

We studied the effect of autologous and allogeneic lymphocytes on multipotent mesenchymal stromal cells in co-culture. It is shown that changes in multipotent mesenchymal stromal cells and in lymphocytes did not depend on the source of lymphocytes. Contact with lymphocytes triggers expression of HLA-DR molecules on multipotent mesenchymal stromal cells and these cells lose their immune privilege. In multipotent mesenchymal stromal cells, the relative level of expression of factors involved in immunomodulation (IDO1, PTGES, and IL-6) and expression of adhesion molecule ICAM1 increased, while expression of genes involved in the differentiation of multipotent mesenchymal stromal cells remained unchanged. Priming of multipotent mesenchymal stromal cells with IFN did not affect these changes. In turn, lymphocytes underwent activation, expression of HLA-DR increased, subpopulation composition of lymphocytes changed towards the increase in the content of naïve T cells. These findings are important for cell therapy.

Targeting Stromal Recruitment by Prostate Cancer Cells

DTIC Science & Technology

2006-03-01

Ensinger, C., Tumer , Z., Tommerup, N. et al.: Hedgehog signaling in small-cell lung cancer : frequent in vivo but a rare event in vitro. Lung Cancer , 52...W81XWH-04-1-0157 TITLE: Targeting Stromal Recruitment by Prostate Cancer Cells PRINCIPAL INVESTIGATOR: Jingxian Zhang, Ph.D...DATES COVERED (From - To) 15 Feb 2004 – 14 Feb 2006 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Stromal Recruitment by Prostate Cancer

The Interaction between Human Papillomaviruses and the Stromal Microenvironment

PubMed Central

Woodby, Brittany; Scott, Matthew; Bodily, Jason

2017-01-01

Human papillomaviruses (HPV) 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. 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. PMID:27865458

Do researchers have an obligation to actively look for genetic incidental findings?

PubMed

Gliwa, Catherine; Berkman, Benjamin E

2013-01-01

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise.

Do Researchers Have an Obligation to Actively Look for Genetic Incidental Findings?

PubMed Central

Gliwa, Catherine; Berkman, Benjamin E.

2014-01-01

The rapid growth of next-generation genetic sequencing has prompted debate about the responsibilities of researchers toward genetic incidental findings. Assuming there is a duty to disclose significant incidental findings, might there be an obligation for researchers to actively look for these findings? We present an ethical framework for analyzing whether there is a positive duty to look for genetic incidental findings. Using the ancillary care framework as a guide, we identify three main criteria that must be present to give rise to an obligation to look: high benefit to participants, lack of alternative access for participants, and reasonable burden on researchers. Our analysis indicates that there is no obligation to look for incidental findings today, but during the ongoing translation of genomic analysis from research to clinical care, this obligation may arise. PMID:23391059

Managing Incidental Pancreatic Cysts.

PubMed

Phan, Jennifer; Raman Muthusamy, V

2018-06-09

The goal of this review is to critically analyze the current literature regarding the management of incidental pancreatic cysts. Given their increased rates of detection due to the frequent use of cross-sectional imaging, correctly identifying the subset of high risk lesions that are appropriate for surgical resection is critical. However, the existing consensus and societal guidelines discussed in this review lack high quality data to create evidence-based recommendations, making achieving this important aim challenging. Several recent studies have focused on the natural history of pancreatic cysts and defining the role of endoscopic ultrasound, which remains unclear. EUS-guided diagnostic tools include molecular analysis of obtained fluid; EUS-guided FNA, FNB, and intracystic forceps biopsy of the cyst wall; and confocal endomicroscopy. While their precise role in diagnosing pancreatic cystic neoplasms remains to be defined, they represent promising innovations that may play a future role in cyst assessment and management. Large, long-term, prospective studies of incidentally identified pancreatic cysts are essential to fully understand their natural history and potential for neoplastic progression. Given the absence of such data at present, an individualized patient approach is recommended.

50 CFR 229.7 - Monitoring of incidental mortalities and serious injuries.

Code of Federal Regulations, 2011 CFR

2011-10-01

... incidental mortality and serious injury of marine mammals during the course of commercial fishing operations...) Identify changes in fishing methods or technology that may increase or decrease incidental mortality and... fishing trips. (2) After being notified by NMFS, or by a designated contractor providing observer services...

50 CFR 229.7 - Monitoring of incidental mortalities and serious injuries.

Code of Federal Regulations, 2013 CFR

2013-10-01

... incidental mortality and serious injury of marine mammals during the course of commercial fishing operations...) Identify changes in fishing methods or technology that may increase or decrease incidental mortality and... fishing trips. (2) After being notified by NMFS, or by a designated contractor providing observer services...

50 CFR 229.7 - Monitoring of incidental mortalities and serious injuries.

Code of Federal Regulations, 2014 CFR

2014-10-01

... incidental mortality and serious injury of marine mammals during the course of commercial fishing operations...) Identify changes in fishing methods or technology that may increase or decrease incidental mortality and... fishing trips. (2) After being notified by NMFS, or by a designated contractor providing observer services...

50 CFR 229.7 - Monitoring of incidental mortalities and serious injuries.

Code of Federal Regulations, 2012 CFR

2012-10-01

... incidental mortality and serious injury of marine mammals during the course of commercial fishing operations...) Identify changes in fishing methods or technology that may increase or decrease incidental mortality and... fishing trips. (2) After being notified by NMFS, or by a designated contractor providing observer services...

50 CFR 216.108 - Requirements for monitoring and reporting under incidental harassment authorizations for Arctic...

Code of Federal Regulations, 2010 CFR

2010-10-01

... under incidental harassment authorizations for Arctic waters. 216.108 Section 216.108 Wildlife and... for monitoring and reporting under incidental harassment authorizations for Arctic waters. (a) Holders of an incidental harassment authorization in Arctic waters and their employees, agents, and designees...

Incidental acquisition of foreign language vocabulary through brief multi-modal exposure.

PubMed

Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

2013-01-01

First language acquisition requires relatively little effort compared to foreign language acquisition and happens more naturally through informal learning. Informal exposure can also benefit foreign language learning, although evidence for this has been limited to speech perception and production. An important question is whether informal exposure to spoken foreign language also leads to vocabulary learning through the creation of form-meaning links. Here we tested the impact of exposure to foreign language words presented with pictures in an incidental learning phase on subsequent explicit foreign language learning. In the explicit learning phase, we asked adults to learn translation equivalents of foreign language words, some of which had appeared in the incidental learning phase. Results revealed rapid learning of the foreign language words in the incidental learning phase showing that informal exposure to multi-modal foreign language leads to foreign language vocabulary acquisition. The creation of form-meaning links during the incidental learning phase is discussed.

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

... 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 marine mammal. Authorization for incidental taking, in the form...

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

... 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 the...

Mesenchymal Stromal Cells for Antineoplastic Drug Loading and Delivery.

PubMed

Petrella, Francesco; Rimoldi, Isabella; Rizzo, Stefania; Spaggiari, Lorenzo

2017-11-23

Mesenchymal stromal cells are a population of undifferentiated multipotent adult cells possessing extensive self-renewal properties and the potential to differentiate into a variety of mesenchymal lineage cells. They express broad anti-inflammatory and immunomodulatory activity on the immune system and after transplantation can interact with the surrounding microenvironment, promoting tissue healing and regeneration. For this reason, mesenchymal stromal cells have been widely used in regenerative medicine, both in preclinical and clinical settings. Another clinical application of mesenchymal stromal cells is the targeted delivery of chemotherapeutic agents to neoplastic cells, maximizing the cytotoxic activity against cancer cells and minimizing collateral damage to non-neoplastic tissues. Mesenchymal stem cells are home to the stroma of several primary and metastatic neoplasms and hence can be used as vectors for targeted delivery of antineoplastic drugs to the tumour microenvironment, thereby reducing systemic toxicity and maximizing antitumour effects. Paclitaxel and gemcitabine are the chemotherapeutic drugs best loaded by mesenchymal stromal cells and delivered to neoplastic cells, whereas other agents, like pemetrexed, are not internalized by mesenchymal stromal cells and therefore are not suitable for advanced antineoplastic therapy. This review focuses on the state of the art of advanced antineoplastic cell therapy and its future perspectives, emphasizing in vitro and in vivo preclinical results and future clinical applications.

Contribution of immunomodulators to gastroesophageal reflux disease and its complications: stromal cells, interleukin 4, and adiponection

PubMed Central

Li, Jing; Chen, Xiaoxin; Shaker, Anisa; Oshima, Tadayuki; Shan, Jing; Miwa, Hiroto; Feng, Cheng; Zhang, Jun

2016-01-01

Gastroesophageal reflux disease (GERD) has become the most commonly seen gastrointestinal disorder in outpatient clinics. In the United States, around 20% of the general population experience heartburn on a weekly basis. Although clinical complaints can be mild or moderate, patients with GERD may develop further complications, such as peptic strictures, Barrett's esophagus (BE), and even esophageal adenocarcinoma (EAC). Pathologically, GERD is developed as a result of chronic and enhanced exposure of the esophageal epithelium to noxious gastric refluxate. In this review article, we provide an overview of GERD, and then focus on the roles of stromal cells, interleukin 4 (IL-4), and adiponectin in GERD and BE. The importance of inflammation and immunomodulators in GERD pathogenesis is highlighted. Targeting the immunomodulators or inflammation in general may improve the therapeutic outcome of GERD, in particular, in those refractory to proton pump inhibitors. PMID:27441783

75 FR 68767 - Taking of Threatened or Endangered Marine Mammals Incidental to Commercial Fishing Operations

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-09

...-based groundfish fisheries to incidentally take individuals from five marine mammal stocks listed as... or endangered marine mammals are not taken incidental to groundfish fisheries in Alaska, no other... marine mammals incidental to commercial fishing operations. Detailed descriptions of these fisheries can...

76 FR 33704 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

... 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, may...

Intracranial incidental findings on brain MR images in a pediatric neurology practice: a retrospective study.

PubMed

Gupta, Surya N; Belay, Brook

2008-01-15

Previous studies have addressed the prevalence of incidental findings largely in healthy adult and pediatric populations. Our study aims to elucidate the prevalence of incidental findings in a pediatric neurology practice. We reviewed the charts of 1618 patients seen at a pediatric neurology practice at a tertiary care center from September 2003 to December 2005 for clinical data and incidental intracranial findings on brain magnetic resonance imaging reports. Incidental findings were divided into two categories: normal or abnormal variants. Clinical and demographic data were assessed for associations with incidental findings. From 1618 charts reviewed, only 666 patients (41% of all patients) had brain MRIs ordered. One-hundred and seventy-one (171) patients (25.7% of all patients; 95% CI: 22.6, 29.0) had incidental findings. Of these, 113 (17.0%; 95% CI: 14.1, 19.8) were classified as normal-variants and 58 (8.7%; 95% CI: 6.6, 10.9) were classified as abnormal. The nature of incidental findings was not related to age group, sex or clinical diagnosis (p=0.29, p=0.31 and p=0.69 respectively). Two patients (0.3%; 95% CI: approximately 0.0, 0.7) required neurosurgical referral. We report a high prevalence of and a low rate of referrals for incidental findings in comparison to previous studies. The present study may help guide management decisions and discussions with patients and families. Future studies should attempt to address issues of associations between primary or secondary diagnoses and intracranial incidental findings in a controlled, prospective fashion.

Incidental Findings on Cone Beam Computed Tomography Studies outside of the Maxillofacial Skeleton

PubMed Central

2016-01-01

Objective. To define the presence and prevalence of incidental findings in and around the base of skull from large field-of-view CBCT of the maxillofacial region and to determine their clinical importance. Methods. Four hundred consecutive large fields of view CBCT scans viewed from January 1, 2007, to January 1, 2014, were retrospectively evaluated for incidental findings of the cervical vertebrae and surrounding structures. Findings were categorized into cervical vertebrae, intracranial, soft tissue, airway, carotid artery, lymph node, and skull base findings. Results. A total of 653 incidental findings were identified in 309 of the 400 CBCT scans. The most prevalent incidental findings were soft tissue calcifications (29.71%), followed by intracranial calcifications (27.11%), cervical vertebrae (20.06%), airway (11.49%), external carotid artery calcification (10.41%), lymph node calcification (0.77%), subcutaneous tissue calcification and calcified tendonitis of the longus colli muscle (0.3%), and skull base finding (0.15%). A significant portion of the incidental findings (31.24%) required referral, 17.76% required monitoring, and 51% did not require either. Conclusion. A comprehensive review of the CBCT images beyond the region of interest, especially incidental findings in the base of skull, cervical vertebrae, pharyngeal airway, and soft tissue, is necessary to avoid overlooking clinically significant lesions. PMID:27462350

Increase in incidental detection of thyroid cancer in Osaka, Japan.

PubMed

Toyoda, Yasuhiro; Tabuchi, Takahiro; Nakata, Kayo; Morishima, Toshitaka; Nakayama, Tomio; Miyashiro, Isao; Hojo, Shigeyuki; Yoshioka, Setsuko

2018-05-22

We examined age-specific and age-adjusted incidence rates of thyroid cancer according to the route of thyroid cancer detection from 1992-2012, using Osaka Cancer Registry data. The detection routes were categorized into 'symptomatic' and 'incidental detection'. Age-specific incidence rates of incidentally-detected thyroid cancer consistently increased during the study period, especially after 2001, for all sex and age groups other than childhood. The rate of symptomatic thyroid cancer did not largely differ. Age-adjusted incidence rates of symptomatic thyroid cancer were around 1.5 and 4.5 per 100,000 among men and women, respectively. The rate of incidentally-detected thyroid cancer increased from 0.1 and 0.1 per 100,000 person-years among men and women in 1992-1994 to 2.0 and 4.9, respectively in 2010-2012. Age-adjusted mortality rates among both sexes during study period leveled off. This finding suggests that the thyroid cancer incidence rate in Osaka increased with incidental detection. We need to continue careful monitoring to confirm these findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

76 FR 12751 - Endangered and Threatened Wildlife and Plants; Receipt of Applications for Incidental Take...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-08

...] Endangered and Threatened Wildlife and Plants; Receipt of Applications for Incidental Take Permits... coerulescens) (scrub- jay) breeding, feeding, and sheltering habitat incidental to land preparation for the... approximately 1.75 acres (0.71 hectares (ha)) of scrub-jay breeding, feeding, and sheltering habitat incidental...

Incidental experiences of regulatory fit and the processing of persuasive appeals.

PubMed

Koenig, Anne M; Cesario, Joseph; Molden, Daniel C; Kosloff, Spee; Higgins, E Tory

2009-10-01

This article examines how the subjective experiences of "feeling right" from regulatory fit and of "feeling wrong" from regulatory non-fit influence the way people process persuasive messages. Across three studies, incidental experiences of regulatory fit increased reliance on source expertise and decreased resistance to counterpersuasion, whereas incidental experiences of regulatory non-fit increased reliance on argument strength and increased resistance to counterpersuasion. These results suggest that incidental fit and non-fit experiences can produce, respectively, more superficial or more thorough processing of persuasive messages. The mechanisms underlying these effects, and the conditions under which they should and should not be expected, are discussed.

Memory for Central and Incidental Information from Newspaper and Television News.

ERIC Educational Resources Information Center

Bellack, Daniel R.; And Others

A study was conducted to examine the hypothesis that the distracting nature of incidental information inherent to television news, combined with the absence of headlines, might result in television viewers remembering less central and more incidental information than they would when reading a newspaper article that uses headlines to condense the…

Clinicopathological characteristics of KIT and protein kinase C-δ expression in adenoid cystic carcinoma: comparison with chromophobe renal cell carcinoma and gastrointestinal stromal tumour.

PubMed

Park, Cheol Keun; Kim, Won Kyu; Kim, Hoguen

2017-10-01

KIT overexpression is frequently observed in adenoid cystic carcinomas (AdCCs), chromophobe renal cell carcinomas (ChRCCs), and gastrointestinal stromal tumours (GISTs). Persistent KIT activation has been reported to be mediated by protein kinase C (PKC)-δ in a subset of colon cancers with wild-type KIT overexpression, and by PKC-θ in GISTs with mutant KIT overexpression. To elucidate the clinical implications of PKC-δ and PKC-θ expression in KIT-expressing tumours, we investigated the expression of KIT, PKC-δ and PKC-θ in AdCCs and ChRCCs in comparison with GISTs. KIT expression, PKC-δ expression and PKC-θ expression were analysed in whole sections from 41 AdCCs, 40 ChRCCs and 56 GISTs by immunohistochemistry. Membranous expression of KIT was found in 34 AdCCs and all ChRCCs, whereas cytoplasmic expression of KIT was found in 46 GISTs. In AdCCs, PKC-δ expression was associated with histological grade (P = 0.049), lymphovascular invasion (P = 0.004), perineural invasion (P = 0.002), and KIT positivity (P = 0.002). PKC-δ positivity was associated with shorter relapse-free survival (RFS) (P = 0.017) and a tendency for there to be shorter overall survival (OS) (P = 0.090) in patients with AdCCs. No clinicopathological associations were observed between PKC-δ and KIT expression in ChRCCs. In GISTs, PKC-θ expression was associated with higher mitotic count (P = 0.011) and high grade according to the modified National Institutes of Health criteria (P < 0.001). PKC-θ positivity was associated with shorter RFS (P = 0.016) and a tendency for there to be shorter OS (P = 0.051) in patients with GISTs. PKC-δ expression is associated with KIT expression and the prognosis of patients with AdCCs, suggesting that PKC-δ may be a potential therapeutic target for AdCCs. © 2017 The Authors. Histopathology published by John Wiley & Sons Ltd.

Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior: KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors.

PubMed

Antonescu, Cristina R; Sommer, Gunhild; Sarran, Lisa; Tschernyavsky, Sylvia J; Riedel, Elyn; Woodruff, James M; Robson, Mark; Maki, Robert; Brennan, Murray F; Ladanyi, Marc; DeMatteo, Ronald P; Besmer, Peter

2003-08-15

Activating mutations of the KIT juxtamembrane region are the most common genetic events in gastrointestinal stromal tumors (GISTs) and have been noted as independent prognostic factors. The impact of KIT mutation in other regions, such as the extracellular or kinase domains, is not well-defined and fewer than 30 cases have been published to date. One hundred twenty GISTs, confirmed by KIT immunoreactivity, were evaluated for the presence of KIT exon 9, 11, 13, and 17 mutations. The relation between the presence/type of KIT mutation and clinicopathological factors was analyzed using Fisher's exact test and log-rank test. Forty-four % of the tumors were located in the stomach, 47% in the small bowel, 6% in the rectum, and 3% in the retroperitoneum. Overall, KIT mutations were detected in 78% of patients as follows: 67% in exon 11, 11% in exon 9, and none in exon 13 or 17. The types of KIT exon 11 mutations were heterogeneous and clustered in the classic "hot spot" at the 5' end of exon 11. Seven % of cases showed internal tandem duplications (ITD) at the 3' end of exon 11, in a region that we designate as a second hot spot for KIT mutations. Interestingly, these cases were associated with: female predominance, stomach location, occurrence in older patients, and favorable outcome. There were significant associations between exon 9 mutations and large tumor size (P < 0.001) and extragastric location (P = 0.02). Ten of these 13 patients with more than 1-year follow-up have developed recurrent disease. Most KIT-expressing GISTs show KIT mutations that are preferentially located within the classic hot spot of exon 11. In addition, we found an association between a second hot spot at the 3'end of exon 11, characterized by ITDs, and a subgroup of clinically indolent gastric GISTs in older females. KIT exon 9 mutations seem to define a distinct subset of GISTs, located predominantly in the small bowel and associated with an unfavorable clinical course.

Study of the Glutaminase Inhibitor CB-839 in Solid Tumors

ClinicalTrials.gov

2016-08-18

Solid Tumors; Triple-Negative Breast Cancer; Non Small Cell Lung Cancer; Renal Cell Carcinoma; Mesothelioma; Fumarate Hydratase (FH)-Deficient Tumors; Succinate Dehydrogenase (SDH)-Deficient Gastrointestinal Stromal Tumors (GIST); Succinate Dehydrogenase (SDH)-Deficient Non-gastrointestinal Stromal Tumors; Tumors Harboring Isocitrate Dehydrogenase-1 (IDH1) and IDH2 Mutations; Tumors Harboring Amplifications in the cMyc Gene

Marginal reticular cells: a stromal subset directly descended from the lymphoid tissue organizer

PubMed Central

Katakai, Tomoya

2012-01-01

The architecture of secondary lymphoid organs (SLOs) is supported by several non-hematopoietic stromal cells. Currently it is established that two distinct stromal subsets, follicular dendritic cells and fibroblastic reticular cells, play crucial roles in the formation of tissue compartments within SLOs, i.e., the follicle and T zone, respectively. Although stromal cells in the anlagen are essential for SLO development, the relationship between these primordial cells and the subsets in adulthood remains poorly understood. In addition, the roles of stromal cells in the entry of antigens into the compartments through some tissue structures peculiar to SLOs remain unclear. A recently identified stromal subset, marginal reticular cells (MRCs), covers the margin of SLOs that are primarily located in the outer edge of follicles and construct a unique reticulum. MRCs are closely associated with specialized endothelial or epithelial structures for antigen transport. The similarities in marker expression profiles and successive localization during development suggest that MRCs directly descend from organizer stromal cells in the anlagen. Therefore, MRCs are thought to be a crucial stromal component for the organization and function of SLOs. PMID:22807928

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.

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

... Drilling Program in the Chukchi Sea, Alaska AGENCY: National Marine Fisheries Service (NMFS), National... numbers of marine mammals, by harassment, incidental to conducting offshore exploration drilling on Outer... offshore exploration drilling on OCS leases in the Chukchi Sea, Alaska, during the 2014 open-water season...

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

... Drilling Program in the Chukchi Sea, Alaska AGENCY: National Marine Fisheries Service (NMFS), National... conducting offshore exploration drilling on Outer Continental Shelf (OCS) leases in the Chukchi Sea, Alaska... incidental to COP's offshore exploration drilling in the Chukchi Sea during the 2014 open- [[Page 24732...

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

... Drilling Programs in the Chukchi and Beaufort Seas, AK AGENCY: National Marine Fisheries Service (NMFS... harassment, by Shell Offshore Inc. (Shell) incidental to offshore exploration drilling on Outer Continental... drilling programs in 2010. ADDRESSES: The applications related to this action are available by writing to...

Stromal p16 expression is significantly increased in endometrial carcinoma

PubMed Central

Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

2017-01-01

p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC. PMID:27902476

Relative Preference and Localized Food Affect Predator Space Use and Consumption of Incidental Prey.

PubMed

Schartel, Tyler E; Schauber, Eric M

2016-01-01

Abundant, localized foods can concentrate predators and their foraging efforts, thus altering both the spatial distribution of predation risk and predator preferences for prey that are encountered incidentally. However, few investigations have quantified the spatial scale over which localized foods affect predator foraging behavior and consumption of incidental prey. In spring 2010, we experimentally tested how point-source foods altered how generalist predators (white-footed mice, Peromyscus leucopus) utilized space and depredated two incidental prey items: almonds (Prunus dulcis; highly profitable) and maple seeds (Acer saccharum; less profitable). We estimated mouse population densities with trapping webs, quantified mouse consumption rates of these incidental prey items, and measured local mouse activity with track plates. We predicted that 1) mouse activity would be elevated near full feeders, but depressed at intermediate distances from the feeder, 2) consumption of both incidental prey would be high near feeders providing less-preferred food and, 3) consumption of incidental prey would be contingent on predator preference for prey relative to feeders providing more-preferred food. Mouse densities increased significantly from pre- to post-experiment. Mean mouse activity was unexpectedly greatest in control treatments, particularly <15 m from the control (empty) feeder. Feeders with highly preferred food (sunflower seeds) created localized refuges for incidental prey at intermediate distances (15 to 25m) from the feeder. Feeders with less-preferred food (corn) generated localized high risk for highly preferred almonds <10 m of the feeder. Our findings highlight the contingent but predictable effects of locally abundant food on risk experienced by incidental prey, which can be positive or negative depending on both spatial proximity and relative preference.

Relative Preference and Localized Food Affect Predator Space Use and Consumption of Incidental Prey

PubMed Central

Schartel, Tyler E.; Schauber, Eric M.

2016-01-01

Abundant, localized foods can concentrate predators and their foraging efforts, thus altering both the spatial distribution of predation risk and predator preferences for prey that are encountered incidentally. However, few investigations have quantified the spatial scale over which localized foods affect predator foraging behavior and consumption of incidental prey. In spring 2010, we experimentally tested how point-source foods altered how generalist predators (white-footed mice, Peromyscus leucopus) utilized space and depredated two incidental prey items: almonds (Prunus dulcis; highly profitable) and maple seeds (Acer saccharum; less profitable). We estimated mouse population densities with trapping webs, quantified mouse consumption rates of these incidental prey items, and measured local mouse activity with track plates. We predicted that 1) mouse activity would be elevated near full feeders, but depressed at intermediate distances from the feeder, 2) consumption of both incidental prey would be high near feeders providing less-preferred food and, 3) consumption of incidental prey would be contingent on predator preference for prey relative to feeders providing more-preferred food. Mouse densities increased significantly from pre- to post-experiment. Mean mouse activity was unexpectedly greatest in control treatments, particularly <15 m from the control (empty) feeder. Feeders with highly preferred food (sunflower seeds) created localized refuges for incidental prey at intermediate distances (15 to 25m) from the feeder. Feeders with less-preferred food (corn) generated localized high risk for highly preferred almonds <10 m of the feeder. Our findings highlight the contingent but predictable effects of locally abundant food on risk experienced by incidental prey, which can be positive or negative depending on both spatial proximity and relative preference. PMID:26978659

78 FR 79403 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-30

...), National Oceanic and Atmospheric Administration (NOAA), Commerce. ACTION: Notice; issuance of an incidental... permanent study plots. Disturbance may result in reactions ranging from an animal simply becoming alert to... the haul-out site into the water. NMFS does not consider the lesser reactions to constitute behavioral...

Targeting stromal glutamine synthetase in tumors disrupts tumor microenvironment-regulated cancer cell growth

USDA-ARS?s Scientific Manuscript database

Reactive stromal cells are an integral part of tumor microenvironment (TME) and interact with cancer cells to regulate their growth. Although targeting stromal cells could be a viable therapy to regulate the communication between TME and cancer cells, identification of stromal targets that make canc...

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

Androgen Receptor Expression in Epithelial and Stromal Cells of Prostatic Carcinoma and Benign Prostatic Hyperplasia.

PubMed

Filipovski, Vanja; Kubelka-Sabit, Katerina; Jasar, Dzengis; Janevska, Vesna

2017-08-15

Prostatic carcinoma (PCa) derives from prostatic epithelial cells. However stromal microenvironment, associated with malignant epithelium, also plays a role in prostatic carcinogenesis. Alterations in prostatic stromal cells contribute to the loss of growth control in epithelial cells that lead to progression of PCa. To analyse the differences between Androgen Receptor (AR) expression in both epithelial and stromal cells in PCa and the surrounding benign prostatic hyperplasia (BPH) and to compare the results with tumour grade. Samples from 70 cases of radical prostatectomy specimens were used. The expression and intensity of the signal for AR was analysed in the epithelial and stromal cells of PCa and BPH, and the data was quantified using histological score (H-score). AR showed significantly lower expression in both epithelial and stromal cells of PCa compared to BPH. In PCa a significant positive correlation of AR expression was found between stromal and epithelial cells of PCa. AR expression showed a correlation between the stromal cells of PCa and tumour grade. AR expression is reduced in epithelial and stromal cells of PCa. Expression of AR in stromal cells of PCa significantly correlates with tumour grade.

Transcriptome-derived stromal and immune scores infer clinical outcomes of patients with cancer.

PubMed

Liu, Wei; Ye, Hua; Liu, Ying-Fu; Xu, Chao-Qun; Zhong, Yue-Xian; Tian, Tian; Ma, Shi-Wei; Tao, Huan; Li, Ling; Xue, Li-Chun; He, Hua-Qin

2018-04-01

The stromal and immune cells that form the tumor microenvironment serve a key role in the aggressiveness of tumors. Current tumor-centric interpretations of cancer transcriptome data ignore the roles of stromal and immune cells. The aim of the present study was to investigate the clinical utility of stromal and immune cells in tissue-based transcriptome data. The 'Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data' (ESTIMATE) algorithm was used to probe diverse cancer datasets and the fraction of stromal and immune cells in tumor tissues was scored. The association between the ESTIMATE scores and patient survival data was asessed; it was indicated that the two scores have implications for patient survival, metastasis and recurrence. Analysis of a colorectal cancer progression dataset revealed that decreased levels immune cells could serve an important role in cancer progression. The results of the present study indicated that trasncriptome-derived stromal and immune scores may be a useful indicator of cancer prognosis.

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

... Operation of the Northeast Gateway Liquefied Natural Gas Port Facility in Massachusetts Bay AGENCY: National... application from Tetra Tech EC, Inc., on behalf of the Northeast Gateway[supreg] Energy Bridge TM L.P. (Northeast Gateway or NEG), for authorization to take marine mammals, by harassment, incidental to operating...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...). SUMMARY: In accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...). SUMMARY: In accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...). SUMMARY: In accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations...

76 FR 12070 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-04

... Energy's EROS operations in 2010: Marine mammals Biological impacts Company Structure Dates sighted... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...). SUMMARY: In accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and...: In accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification...

System-Level Process Change Improves Communication and Follow-Up for Emergency Department Patients With Incidental Radiology Findings.

PubMed

Baccei, Steven J; Chinai, Sneha A; Reznek, Martin; Henderson, Scott; Reynolds, Kevin; Brush, D Eric

2018-04-01

The appropriate communication and management of incidental findings on emergency department (ED) radiology studies is an important component of patient safety. Guidelines have been issued by the ACR and other medical associations that best define incidental findings across various modalities and imaging studies. However, there are few examples of health care facilities designing ways to manage incidental findings. Our institution aimed to improve communication and follow-up of incidental radiology findings in ED patients through the collaborative development and implementation of system-level process changes including a standardized loop-closure method. We assembled a multidisciplinary team to address the nature of these incidental findings and designed new workflows and operational pathways for both radiology and ED staff to properly communicate incidental findings. Our results are based on all incidental findings received and acknowledged between November 1, 2016, and May 30, 2017. The total number of incidental findings discovered was 1,409. Our systematic compliance fluctuated between 45% and 95% initially after implementation. However, after overcoming various challenges through optimization, our system reached a compliance rate of 93% to 95%. Through the implementation of our new, standardized communication system, a high degree of compliance with loop closure for ED incidental radiology findings was achieved at our institution. Copyright © 2017 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Uncommon incidental pseudoaneurysm. Diagnostic and management challenges.

PubMed

Hadidy, Azmy M; Samara, Osama A; Takrouri, Heba S; Al-Ryalat, Nosaiba T; Al-Smady, Moaath M; Ryalat, Soukaina T; Abu-Khalaf, Mahmoad M

2009-08-01

To analyze patients with uncommon incidental pseudoaneurysms, secondary to non-catheterization causes, and to discuss the peculiar clinical spectrum, and focus on some aspects of difference from post-catheterization pseudoaneurysms. Eleven patients, 8 males and 3 females, were studied retrospectively in Jordan University Hospital, Amman, Jordan, between 2002-2008. Radiological studies performed included duplex sonography (DS), computed tomography (CT), conventional angiography, magnetic resonance imaging (MRI), and magnetic resonance angiography (MRA). Pseudoaneurysms were most commonly encountered in young males (63.6%), especially in the lower limb vessels (36%). Clinical findings were suggestive of pseudoaneurysms in 27% of our cases. Four out of the 8 DS scans showed the neck of pseudoaneurysms, and the to and fro waveform, the strongest indicators for pseudoaneurysms. Both CT with intravenous contrast and angiography failed to establish the diagnosis in one out of 5 cases. The MRI with MRA showed the pseudoaneurysms in 2 patients that underwent the scan. Incidental pseudoaneurysms are considered following iatrogenic procedures, penetrating, or blunt traumas with variable delay time. Young healthy males are at increased risks, as opposed to elderly females with calcified vessels in post-catheterization cases. Duplex sonography is less sensitive in incidental than post-catheterization pseudoaneurysms. The CT scan with intravenous contrast has high accuracy in establishing the diagnosis in small, or medium sized pseudoaneurysms. The MRI and MRA are accurate valuable studies and comparable to conventional angiography.

Contribution of immunomodulators to gastroesophageal reflux disease and its complications: stromal cells, interleukin 4, and adiponectin.

PubMed

Li, Jing; Chen, Xiaoxin Luke; Shaker, Anisa; Oshima, Tadayuki; Shan, Jing; Miwa, Hiroto; Feng, Cheng; Zhang, Jun

2016-09-01

Gastroesophageal reflux disease (GERD) has become the most commonly seen gastrointestinal disorder in outpatient clinics. In the United States, around 20% of the general population experience heartburn on a weekly basis. Although clinical complaints can be mild or moderate, patients with GERD may develop further complications, such as peptic strictures, Barrett's esophagus (BE), and even esophageal adenocarcinoma. Pathologically, GERD is developed as a result of chronic and enhanced exposure of the esophageal epithelium to noxious gastric refluxate. In this review article, we provide an overview of GERD and then focus on the roles of stromal cells, interleukin 4, and adiponectin in GERD and BE. The importance of inflammation and immunomodulators in GERD pathogenesis is highlighted. Targeting the immunomodulators or inflammation in general may improve the therapeutic outcome of GERD, in particular, in those refractory to proton pump inhibitors. © 2016 New York Academy of Sciences.

Bone marrow stromal-B cell interactions in polycyclic aromatic hydrocarbon-induced pro/pre-B cell apoptosis.

PubMed

Allan, Lenka L; Mann, Koren K; Matulka, Raymond A; Ryu, Heui-Young; Schlezinger, Jennifer J; Sherr, David H

2003-12-01

Environmental polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons are immunotoxic in a variety of systems. In a model system of B lymphopoiesis, PAH exposure rapidly induces apoptosis in CD43- pre-B and CD43+ pro/pre-B cells. Apoptosis induction by 7,12-dimethylbenzo[a]anthracene (DMBA) is dependent upon AhR+ bone marrow stromal cells and likely involves DMBA metabolism within the stromal cell. However, it is not known if PAH-treated stromal cells release free metabolites or soluble factors that may directly induce B cell death or if the effector death signal is delivered by stromal cell-B cell contact. Here, we demonstrate that supernatants from DMBA-treated bone marrow stromal cells contain an activity capable of inducing apoptosis in pro/pre-B cells cocultured with stromal cells. This activity (1) is not produced when stromal cells are cotreated with DMBA and alpha-naphthoflavone (alpha-NF), an aryl hydrocarbon receptor (AhR) and cytochrome P-450 inhibitor, (2) is > or = 50 kDa, (3) is trypsin and heat sensitive, and (4) is dependent on AhR+ stromal cells, which in turn deliver the effector death signal to pro/pre-B cells. The results (1) argue against a role for a soluble, stromal cell-derived cytokine as the effector of PAH-induced pro/pre-B cell death, (2) exclude the possibility of a free metabolite acting directly on AhR- pro/pre-B cell targets, and (3) suggest the elaboration by stromal cells of a relatively stable, DMBA metabolite-protein complex capable of acting on other stromal cells at some distance. Collectively, these studies suggest that, while stromal cell products, e.g., metabolite-protein complexes, may affect the function of distant stromal cells, the effector death signal delivered by stromal cells to bone marrow B cells is mediated by cell-cell contact.

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

... Aerospace Corporation (AAC) to take two species of pinnipeds incidental to space vehicle and missile launch... Importing Marine Mammals; Taking Marine Mammals Incidental to Space Vehicle and Missile Launch Operations at... harbor seals (Phoca vitulina) (adults by harassment and pups by injury or mortality), incidental to space...

77 FR 11492 - Notice of Availability of a Draft Environmental Assessment for the Issuance of Incidental...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-27

... Shell for the take of marine mammals incidental to offshore oil and gas exploratory drilling programs in... Mammals by Harassment Incidental to Conducting Exploratory Drilling Programs in the U.S. Beaufort and... take of marine mammals incidental to conducting offshore exploratory drilling programs in the U.S...

78 FR 51147 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... monitoring systems; and (5) exacting funds from TGS to support accelerated mitigation research in this area... (2D) seismic survey program in the Chukchi Sea, Alaska, during the 2013 Arctic open-water season... small numbers of marine mammals incidental to conducting an open-water 2D seismic survey in the Chukchi...

Incidental findings in children with blunt head trauma evaluated with cranial CT scans.

PubMed

Rogers, Alexander J; Maher, Cormac O; Schunk, Jeff E; Quayle, Kimberly; Jacobs, Elizabeth; Lichenstein, Richard; Powell, Elizabeth; Miskin, Michelle; Dayan, Peter; Holmes, James F; Kuppermann, Nathan

2013-08-01

Cranial computed tomography (CT) scans are frequently obtained in the evaluation of blunt head trauma in children. These scans may detect unexpected incidental findings. The objectives of this study were to determine the prevalence and significance of incidental findings on cranial CT scans in children evaluated for blunt head trauma. This was a secondary analysis of a multicenter study of pediatric blunt head trauma. Patients <18 years of age with blunt head trauma were eligible, with those undergoing cranial CT scan included in this substudy. Patients with coagulopathies, ventricular shunts, known previous brain surgery or abnormalities were excluded. We abstracted radiology reports for nontraumatic findings. We reviewed and categorized findings by their clinical urgency. Of the 43,904 head-injured children enrolled in the parent study, 15,831 underwent CT scans, and these latter patients serve as the study cohort. On 670 of these scans, nontraumatic findings were identified, with 16 excluded due to previously known abnormalities or surgeries. The remaining 654 represent a 4% prevalence of incidental findings. Of these, 195 (30%), representing 1% of the overall sample, warranted immediate intervention or outpatient follow-up. A small but important number of children evaluated with CT scans after blunt head trauma had incidental findings. Physicians who order cranial CTs must be prepared to interpret incidental findings, communicate with families, and ensure appropriate follow-up. There are ethical implications and potential health impacts of informing patients about incidental findings.

75 FR 8921 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-26

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

76 FR 23570 - Incidental Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-27

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

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

... Taking of Marine Mammals; Taking of Marine Mammals Incidental to the Explosive Removal of Offshore Structures in the Gulf of Mexico AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and... accordance with the Marine Mammal Protection Act (MMPA) and implementing regulations, notification is hereby...

The corneal fibrosis response to epithelial-stromal injury

PubMed Central

Torricelli, Andre A. M.; Santhanam, Abirami; Wu, Jiahui; Singh, Vivek; Wilson, Steven E.

2014-01-01

The corneal wound healing response, including the development of stromal opacity in some eyes, is a process that often leads to scarring that occurs after injury, surgery or infection to the cornea. Immediately after epithelial and stromal injury, a complex sequence of processes contributes to wound repair and regeneration of normal corneal structure and function. In some corneas, however, often depending on the type and extent of injury, the response may also lead to the development of mature vimentin+ α-smooth muscle actin+ desmin+ myofibroblasts. Myofibroblasts are specialized fibroblastic cells generated in the cornea from keratocyte-derived or bone marrow-derived precursor cells. The disorganized extracellular matrix components secreted by myofibroblasts, in addition to decreased expression of corneal crystallins in these cells, are central biological processes that result in corneal stromal fibrosis associated with opacity or “haze”. Several factors are associated with myofibroblast generation and haze development after PRK surgery in rabbits, a reproducible model of scarring, including the amount of tissue ablated, which may relate to the extent of keratocyte apoptosis in the early response to injury, irregularity of stromal surface after surgery, and changes on corneal stromal proteoglycans, but normal regeneration of the epithelial basement membrane (EBM) appears to be a critical factor determining whether a cornea heals with relative transparency or vision-limiting stromal opacity. Structural and functional abnormalities of the regenerated EBM facilitate prolonged entry of epithelium-derived growth factors such as transforming growth factor β (TGF-β) and platelet-derived growth factor (PDGF) into the stroma that both drive development of mature myofibroblasts from precursor cells and lead to persistence of the cells in the anterior stroma. A major discovery that has contributed to our understanding of haze development is that keratocytes and

Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells

PubMed Central

VÊNCIO, ENEIDA F.; PASCAL, LAURA E.; PAGE, LAURA S.; DENYER, GARETH; WANG, AMY J.; RUOHOLA-BAKER, HANNELE; ZHANG, SHILE; WANG, KAI; GALAS, DAVID J.; LIU, ALVIN Y.

2014-01-01

The prostate stromal mesenchyme controls organ-specific development. In cancer, the stromal compartment shows altered gene expression compared to non-cancer. The lineage relationship between cancer-associated stromal cells and normal tissue stromal cells is not known. Nor is the cause underlying the expression difference. Previously, the embryonal carcinoma (EC) cell line, NCCIT, was used by us to study the stromal induction property. In the current study, stromal cells from non-cancer (NP) and cancer (CP) were isolated from tissue specimens and co-cultured with NCCIT cells in a trans-well format to preclude heterotypic cell contact. After 3 days, the stromal cells were analyzed by gene arrays for microRNA (miRNA) and mRNA expression. In co-culture, NCCIT cells were found to alter the miRNA and mRNA expression of NP stromal cells to one like that of CP stromal cells. In contrast, NCCIT had no significant effect on the gene expression of CP stromal cells. We conclude that the gene expression changes in stromal cells can be induced by diffusible factors synthesized by EC cells, and suggest that cancer-associated stromal cells represent a more primitive or less differentiated stromal cell type. PMID:20945389

Innate lymphoid cells and their stromal microenvironments.

PubMed

Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

2017-09-01

In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Incidental Learning: A Brief, Valid Measure of Memory Based on the WAIS-IV Vocabulary and Similarities Subtests.

PubMed

Spencer, Robert J; Reckow, Jaclyn; Drag, Lauren L; Bieliauskas, Linas A

2016-12-01

We assessed the validity of a brief incidental learning measure based on the Similarities and Vocabulary subtests of the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV). Most neuropsychological assessments for memory require intentional learning, but incidental learning occurs without explicit instruction. Incidental memory tests such as the WAIS-III Symbol Digit Coding subtest have existed for many years, but few memory studies have used a semantically processed incidental learning model. We conducted a retrospective analysis of 37 veterans with traumatic brain injury, referred for outpatient neuropsychological testing at a Veterans Affairs hospital. As part of their evaluation, the participants completed the incidental learning tasks. We compared their incidental learning performance to their performance on traditional memory measures. Incidental learning scores correlated strongly with scores on the California Verbal Learning Test-Second Edition (CVLT-II) and Brief Visuospatial Memory Test-Revised (BVMT-R). After we conducted a partial correlation that controlled for the effects of age, incidental learning correlated significantly with the CVLT-II Immediate Free Recall, CVLT-II Short-Delay Recall, CVLT-II Long-Delay Recall, and CVLT-II Yes/No Recognition Hits, and with the BVMT-R Delayed Recall and BVMT-R Recognition Discrimination Index. Our incidental learning procedures derived from subtests of the WAIS-IV Edition are an efficient and valid way of measuring memory. These tasks add minimally to testing time and capitalize on the semantic encoding that is inherent in completing the Similarities and Vocabulary subtests.

Endometrial stromal tumours revisited: an update based on the 2014 WHO classification.

PubMed

Ali, Rola H; Rouzbahman, Marjan

2015-05-01

Endometrial stromal tumours (EST) are rare tumours of endometrial stromal origin that account for less than 2% of all uterine tumours. Recent cytogenetic and molecular advances in this area have improved our understanding of ESTs and helped refine their classification into more meaningful categories. Accordingly, the newly released 2014 WHO classification system recognises four categories: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma (LGESS), high-grade endometrial stromal sarcoma (HGESS) and undifferentiated uterine sarcoma (UUS). At the molecular level, these tumours may demonstrate a relatively simple karyotype with a defining chromosomal rearrangement (as in the majority of ESNs, LGESSs and YWHAE-rearranged HGESS) or demonstrate complex cytogenetic aberrations lacking specific rearrangements (as in UUSs). Herein we provide an update on this topic aimed at the practicing pathologist. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Identification of the 64 kilodalton chloroplast stromal phosphoprotein as phosphoglucomutase. [Pisum sativum

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salvucci, M.E.; Drake, R.R.; Broadbent, K.P.

1990-05-01

Phosphorylation of the 64 kilodalton stromal phosphoprotein by incubation of pea (Pisum sativum) chloroplast extracts with ({gamma}-{sup 32}P)ATP decreased in the presence of Glc-6-P and Glc-1,6-P{sub 2}, but was stimulated by glucose. Two-dimensional gel electrophoresis following incubation of intact chloroplasts and stromal extracts with ({gamma}-{sup 32}P)ATP, or incubation of stromal extracts and partially purified phosphoglucomutase (EC 2.7.5.1) with ({sup 32}P)Glc-1-P showed that the identical 64 kilodalton polypeptide was labeled. A 62 kilodalton polypeptide was phosphorylated by incubation of tobacco (Nicotiana sylvestris) stromal extracts with either ({gamma}-{sup 32}P)ATP or ({sup 32}P)Glc-1-P. In contrast, an analogous polypeptide was not phosphorylated in extractsmore » from a tobacco mutant deficient in plastid phosphoglucomutase activity. The results indicate that the 64 (or 62) kilodalton chloroplast stromal phosphoprotein is phosphoglucomutase.« less

The role of verbal and pictorial information in multimodal incidental acquisition of foreign language vocabulary.

PubMed

Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

2015-01-01

This study used eye tracking to investigate the allocation of attention to multimodal stimuli during an incidental learning situation, as well as its impact on subsequent explicit learning. Participants were exposed to foreign language (FL) auditory words on their own, in conjunction with written native language (NL) translations, or with both written NL translations and pictures. Incidental acquisition of FL words was assessed the following day through an explicit learning task where participants learned to recognize translation equivalents, as well as one week later through recall and translation recognition tests. Results showed higher accuracy scores in the explicit learning task for FL words presented with meaning during incidental learning, whether written meaning or both written meaning and picture, than for FL words presented auditorily only. However, participants recalled significantly more FL words after a week delay if they had been presented with a picture during incidental learning. In addition, the time spent looking at the pictures during incidental learning significantly predicted recognition and recall scores one week later. Overall, results demonstrated the impact of exposure to multimodal stimuli on subsequent explicit learning, as well as the important role that pictorial information can play in incidental vocabulary acquisition.

The role of verbal and pictorial information in multimodal incidental acquisition of foreign language vocabulary

PubMed Central

Bisson, Marie-Josée; van Heuven, Walter J. B.; Conklin, Kathy; Tunney, Richard J.

2015-01-01

This study used eye tracking to investigate the allocation of attention to multimodal stimuli during an incidental learning situation, as well as its impact on subsequent explicit learning. Participants were exposed to foreign language (FL) auditory words on their own, in conjunction with written native language (NL) translations, or with both written NL translations and pictures. Incidental acquisition of FL words was assessed the following day through an explicit learning task where participants learned to recognize translation equivalents, as well as one week later through recall and translation recognition tests. Results showed higher accuracy scores in the explicit learning task for FL words presented with meaning during incidental learning, whether written meaning or both written meaning and picture, than for FL words presented auditorily only. However, participants recalled significantly more FL words after a week delay if they had been presented with a picture during incidental learning. In addition, the time spent looking at the pictures during incidental learning significantly predicted recognition and recall scores one week later. Overall, results demonstrated the impact of exposure to multimodal stimuli on subsequent explicit learning, as well as the important role that pictorial information can play in incidental vocabulary acquisition. PMID:25383918

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

PubMed Central

Ishii, Genichiro; Aoyagi, Kazuhiko; Sasaki, Hiroki; Ochiai, Atsushi

2015-01-01

Background Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body. Methods Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup. Results In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling. Conclusions GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract. PMID:26046848

Protection of Brain Injury by Amniotic Mesenchymal Stromal Cell-Secreted Metabolites.

PubMed

Pischiutta, Francesca; Brunelli, Laura; Romele, Pietro; Silini, Antonietta; Sammali, Eliana; Paracchini, Lara; Marchini, Sergio; Talamini, Laura; Bigini, Paolo; Boncoraglio, Giorgio B; Pastorelli, Roberta; De Simoni, Maria-Grazia; Parolini, Ornella; Zanier, Elisa R

2016-11-01

To define the features of human amniotic mesenchymal stromal cell secretome and its protective properties in experimental models of acute brain injury. Prospective experimental study. Laboratory research. C57Bl/6 mice. Mice subjected to sham or traumatic brain injury by controlled cortical impact received human amniotic mesenchymal stromal cells or phosphate-buffered saline infused intracerebroventricularly or intravenously 24 hours after injury. Organotypic cortical brain slices exposed to ischemic injury by oxygen-glucose deprivation were treated with human amniotic mesenchymal stromal cells or with their secretome (conditioned medium) in a transwell system. Traumatic brain injured mice receiving human amniotic mesenchymal stromal cells intravenously or intracerebroventricularly showed early and lasting functional and anatomical brain protection. cortical slices injured by oxigen-glucose deprivation and treated with human amniotic mesenchymal stromal cells or conditioned medium showed comparable protective effects (neuronal rescue, promotion of M2 microglia polarization, induction of trophic factors) indicating that the exposure of human amniotic mesenchymal stromal cells to the injured tissue is not necessary for the release of bioactive factors. Using sequential size-exclusion and gel-filtration chromatography, we identified a conditioned medium subfraction, which specifically displays these highly protective properties and we found that this fraction was rich in bioactive molecules with molecular weight smaller than 700 Da. Quantitative RNA analysis and mass spectrometry-based peptidomics showed that the active factors are not proteins or RNAs. The metabolomic profiling of six metabolic classes identified a list of molecules whose abundance was selectively elevated in the active conditioned medium fraction. Human amniotic mesenchymal stromal cell-secreted factors protect the brain after acute injury. Importantly, a fraction rich in metabolites, and

Incidental genetic findings in randomized clinical trials: recommendations from the Genomics and Randomized Trials Network (GARNET)

PubMed Central

2013-01-01

Recommendations and guidance on how to handle the return of genetic results to patients have offered limited insight into how to approach incidental genetic findings in the context of clinical trials. This paper provides the Genomics and Randomized Trials Network (GARNET) recommendations on incidental genetic findings in the context of clinical trials, and discusses the ethical and practical issues considered in formulating our recommendations. There are arguments in support of as well as against returning incidental genetic findings in clinical trials. For instance, reporting incidental findings in clinical trials may improve the investigator-participant relationship and the satisfaction of participation, but it may also blur the line between clinical care and research. The issues of whether and how to return incidental genetic findings, including the costs of doing so, should be considered when developing clinical trial protocols. Once decided, plans related to sharing individual results from the aim(s) of the trial, as well as incidental findings, should be discussed explicitly in the consent form. Institutional Review Boards (IRBs) and other study-specific governing bodies should be part of the decision as to if, when, and how to return incidental findings, including when plans in this regard are being reconsidered. PMID:23363732

An Incidental Renal Oncocytoma: 18F-Choline PET/MRI

PubMed Central

Mallia, Andrew; Bashir, Usman; Stirling, James; Wolfe, Konrad; Goh, Vicky; Cook, Gary

2016-01-01

PET/MRI is a new hybrid imaging modality and has the potential to become a powerful imaging tool. It is currently one of the most active areas of research in diagnostic imaging. The characterisation of an incidental renal lesion can be difficult. In particular, the differentiation of an oncocytoma from other solid renal lesions such as renal cell carcinoma (RCC) represents a diagnostic challenge. We describe the detection of an incidental renal oncocytoma in a 79-year gentleman who underwent a re-staging 18F-Choline PET/MRI following a rise in PSA values (4.07, nadir 1.3).

[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. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

78 FR 44539 - Takes of Marine Mammals Incidental to Specified Activities; Taking Marine Mammals Incidental to a...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-24

... (NOAA), Commerce. ACTION: Notice; issuance of an incidental harassment authorization. SUMMARY: In... likely to result from pile driving at NBPL, studies with similar properties to the proposed action were...-water work window (n = 13) and from the specific action area are used, and we attempt to quantify the...

How could disclosing incidental information from whole-genome sequencing affect patient behavior?

PubMed Central

Christensen, Kurt D; Green, Robert C

2013-01-01

In this article, we argue that disclosure of incidental findings from whole-genome sequencing has the potential to motivate individuals to change health behaviors through psychological mechanisms that differ from typical risk assessment interventions. Their ability to do so, however, is likely to be highly contingent upon the nature of the incidental findings and how they are disclosed, the context of the disclosure and the characteristics of the patient. Moreover, clinicians need to be aware that behavioral responses may occur in unanticipated ways. This article argues for commentators and policy makers to take a cautious but optimistic perspective while empirical evidence is collected through ongoing research involving whole-genome sequencing and the disclosure of incidental information. PMID:24319470

How could disclosing incidental information from whole-genome sequencing affect patient behavior?

PubMed

Christensen, Kurt D; Green, Robert C

2013-06-01

In this article, we argue that disclosure of incidental findings from whole-genome sequencing has the potential to motivate individuals to change health behaviors through psychological mechanisms that differ from typical risk assessment interventions. Their ability to do so, however, is likely to be highly contingent upon the nature of the incidental findings and how they are disclosed, the context of the disclosure and the characteristics of the patient. Moreover, clinicians need to be aware that behavioral responses may occur in unanticipated ways. This article argues for commentators and policy makers to take a cautious but optimistic perspective while empirical evidence is collected through ongoing research involving whole-genome sequencing and the disclosure of incidental information.

78 FR 4428 - Endangered and Threatened Wildlife and Plants; Receipt of an Application for an Incidental Take...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-22

...-FF04EF2000] Endangered and Threatened Wildlife and Plants; Receipt of an Application for an Incidental Take... (Eumeces egregius lividus) (skinks) foraging, breeding, and sheltering habitat incidental to land... and blue-tailed mole skink breeding, feeding, and sheltering habitat incidental to land preparation...

Stromal vascular cells and adipogenesis: Cells within adipose depots regulate adipogenesis

USDA-ARS?s Scientific Manuscript database

A collection of investigations indicate the importance of adipose tissue stromal/stem cells to vasculogenesis and angiogenesis during adipogenesis. Early in development the stromal-vascular (S-V) elements control and dictate the extent of adipogenesis in a depot dependent manner. For instance, the...

Combining lymphovascular invasion with reactive stromal grade predicts prostate cancer mortality.

PubMed

Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

2016-09-01

Previous studies suggest that lymphovascular invasion (LVI) has a weak and variable effect on prognosis. It is uncertain whether LVI, determined by diagnostic prostate biopsy, predicts prostate cancer death. Data from experimental studies have indicated that carcinoma-associated fibroblasts in the reactive stroma could promote LVI and progression to metastasis. Thus, combining LVI with reactive stromal grade may identify prostate cancer patients at high risk of an unfavorable outcome. The purpose of the present study was to examine if LVI, determined by diagnostic biopsy, alone and in combination with reactive stromal grade could predict prostate cancer death. This population-based study included 283 patients with prostate cancer diagnosed by needle biopsy in Aust-Agder County (Norway) from 1991 to 1999. Clinical data were obtained by medical charts review. Two uropathologists evaluated LVI and reactive stromal grade. The endpoint was prostate cancer death. Patients with LVI had marginally higher risk of prostate cancer death compared to patients without LVI (hazard ratio: 1.8, P-value = 0.04). LVI had a stronger effect on prostate cancer death risk when a high reactive stromal grade was present (hazard ratio: 16.0, P-value <0.001). Therefore, patients with concomitant LVI and high reactive stromal grade were at particularly high risk for prostate cancer death. Evaluating LVI together with reactive stromal grade on diagnostic biopsies could be used to identify patients at high risk of death from prostate cancer. Prostate 76:1088-1094, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

30 CFR 750.21 - Coal extraction incidental to the extraction of other minerals.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Coal extraction incidental to the extraction of... ENFORCEMENT, DEPARTMENT OF THE INTERIOR INDIAN LANDS PROGRAM REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS ON INDIAN LANDS § 750.21 Coal extraction incidental to the extraction of other minerals...

30 CFR 750.21 - 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 Coal extraction incidental to the extraction of... ENFORCEMENT, DEPARTMENT OF THE INTERIOR INDIAN LANDS PROGRAM REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS ON INDIAN LANDS § 750.21 Coal extraction incidental to the extraction of other minerals...

30 CFR 750.21 - 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 Coal extraction incidental to the extraction of... ENFORCEMENT, DEPARTMENT OF THE INTERIOR INDIAN LANDS PROGRAM REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS ON INDIAN LANDS § 750.21 Coal extraction incidental to the extraction of other minerals...

30 CFR 750.21 - Coal extraction incidental to the extraction of other minerals.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Coal extraction incidental to the extraction of... ENFORCEMENT, DEPARTMENT OF THE INTERIOR INDIAN LANDS PROGRAM REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS ON INDIAN LANDS § 750.21 Coal extraction incidental to the extraction of other minerals...

30 CFR 750.21 - Coal extraction incidental to the extraction of other minerals.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Coal extraction incidental to the extraction of... ENFORCEMENT, DEPARTMENT OF THE INTERIOR INDIAN LANDS PROGRAM REQUIREMENTS FOR SURFACE COAL MINING AND RECLAMATION OPERATIONS ON INDIAN LANDS § 750.21 Coal extraction incidental to the extraction of other minerals...

Incidental Learning of Melodic Structure of North Indian Music.

PubMed

Rohrmeier, Martin; Widdess, Richard

2017-07-01

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. Copyright © 2016 Cognitive Science Society, Inc.

Treatment of advanced gastrointestinal tumors with genetically modified autologous mesenchymal stromal cells (TREAT-ME1): study protocol of a phase I/II clinical trial.

PubMed

Niess, Hanno; von Einem, Jobst C; Thomas, Michael N; Michl, Marlies; Angele, Martin K; Huss, Ralf; Günther, Christine; Nelson, Peter J; Bruns, Christiane J; Heinemann, Volker

2015-04-08

Adenocarcinoma originating from the digestive system is a major contributor to cancer-related deaths worldwide. Tumor recurrence, advanced local growth and metastasis are key factors that frequently prevent these tumors from curative surgical treatment. Preclinical research has demonstrated that the dependency of these tumors on supporting mesenchymal stroma results in susceptibility to cell-based therapies targeting this stroma. TREAT-ME1 is a prospective, uncontrolled, single-arm phase I/II study assessing the safety and efficacy of genetically modified autologous mesenchymal stromal cells (MSC) as delivery vehicles for a cell-based gene therapy for advanced, recurrent or metastatic gastrointestinal or hepatopancreatobiliary adenocarcinoma. Autologous bone marrow will be drawn from each eligible patient after consent for bone marrow donation has been obtained (under a separate EC-approved protocol). In the following ~10 weeks the investigational medicinal product (IMP) is developed for each patient. To this end, the patient's MSCs are stably transfected with a gamma-retroviral, replication-incompetent and self-inactivating (SIN) vector system containing a therapeutic promoter - gene construct that allows for tumor-specific expression of the therapeutic gene. After release of the IMP the patients are enrolled after given informed consent for participation in the TREAT-ME 1 trial. In the phase I part of the study, the safety of the IMP is tested in six patients by three treatment cycles consisting of re-transfusion of MSCs at different concentrations followed by administration of the prodrug Ganciclovir. In the phase II part of the study, sixteen patients will be enrolled receiving IMP treatment. A subgroup of patients that qualifies for surgery will be treated preoperatively with the IMP to verify homing of the MSCs to tumors as to be confirmed in the surgical specimen. The TREAT-ME1 clinical study involves a highly innovative therapeutic strategy combining cell

Incidental L2 Vocabulary Acquisition "from" and "while" Reading: An Eye-Tracking Study

ERIC Educational Resources Information Center

Pellicer-Sánchez, Ana

2016-01-01

Previous studies have shown that reading is an important source of incidental second language (L2) vocabulary acquisition. However, we still do not have a clear picture of what happens when readers encounter unknown words. Combining offline (vocabulary tests) and online (eye-tracking) measures, the incidental acquisition of vocabulary knowledge…

WINGLESS (WNT) signaling is a progesterone target for rat uterine stromal cell proliferation

PubMed Central

Talbott, Alex; Bhusri, Anuradha; Krumsick, Zach; Foster, Sierra; Wormington, Joshua; Kimler, Bruce F

2016-01-01

Preparation of mammalian uterus for embryo implantation requires a precise sequence of cell proliferation. In rodent uterus, estradiol stimulates proliferation of epithelial cells. Progesterone operates as a molecular switch and redirects proliferation to the stroma by down-regulating glycogen synthase kinase-3β (GSK-3β) and stimulating β-catenin accumulation in the periluminal stromal cells. In this study, the WNT signal involved in the progesterone-dependent proliferative switch was investigated. Transcripts of four candidate Wnt genes were measured in the uteri from ovariectomized (OVX) rats, progesterone-pretreated (3 days of progesterone, 2mg/daily) rats, and progesterone-pretreated rats given a single dose (0.2µg) of estradiol. The spatial distribution of the WNT proteins was determined in the uteri after the same treatments. Wnt5a increased in response to progesterone and the protein emerged in the periluminal stromal cells of progesterone-pretreated rat uteri. To investigate whether WNT5A was required for proliferation, uterine stromal cell lines were stimulated with progesterone (1µM) and fibroblast growth factor (FGF, 50ng/mL). Proliferating stromal cells expressed a two-fold increase in WNT5A protein at 12h post stimulation. Stimulated stromal cells were cultured with actinomycin D (25µg/mL) to inhibit new RNA synthesis. Relative Wnt5a expression increased at 4 and 6 h of culture, suggesting that progesterone plus FGF preferentially increased Wnt5a mRNA stability. Knockdown of Wnt5a in uterine stromal cell lines inhibited stromal cell proliferation and decreased Wnt5a mRNA. The results indicate that progesterone initiates and synchronizes uterine stromal cell proliferation by increasing WNT5A expression and signaling. PMID:26975616

Incidental prostate cancer in radical cystoprostatectomy specimens.

PubMed

Jin, Xiao-Dong; Chen, Zhao-Dian; Wang, Bo; Cai, Song-Liang; Yao, Xiao-Lin; Jin, Bai-Ye

2008-09-01

To investigate the rates of prostate cancer (PCa) in radical cystoprostatectomy (RCP) specimens for bladder cancer in mainland China. To determine the follow-up outcome of patients with two concurrent cancers and identify whether prostate-specific antigen (PSA) is a useful tool for the detection of PCa prior to surgery. From January 2002 to January 2007, 264 male patients with bladder cancer underwent RCP at our center. All patients underwent digital rectal examination (DRE) and B ultrasound. Serum PSA levels were tested in 168 patients. None of the patients had any evidence of PCa before RCP. Entire prostates were embedded and sectioned at 5 mm intervals. Incidental PCa was observed in 37 of 264 (14.0%) RCP specimens. Of these, 12 (32.4%) were clinically significant according to an accepted definition. The PSA levels were not significantly different between patients with PCa and those without PCa, nor between patients with significant PCa and those with insignificant PCa. Thirty-four patients with incidental PCa were followed up. During a mean follow-up period of 26 months, two patients with PSA > 4 ng/mL underwent castration. None of the patients died of PCa. The incidence of PCa in RCP specimens in mainland China is lower than that in most developed countries. PSA cannot identify asymptomatic PCa prior to RCP. In line with published reports, incidental PCa does not impact the prognosis of bladder cancer patients undergoing RCP. (c) 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.

Returning Incidental Findings in Low-Resource Settings: A Case of Rescue?

PubMed

Mackay, Douglas

2018-05-01

In a carefully argued article, Haley K. Sullivan and Benjamin E. Berkman address the important question of whether investigators have a duty to report incidental findings to research participants in low-resource settings. They suggest that the duty to rescue offers the most plausible justification for the duty to return incidental findings, and they explore the implications of this duty for the context of research in low-resource settings. While I think they make valuable headway on an important problem, in this commentary, I identify a significant difference between the paradigmatic rescue case and the return of incidental findings in low-resource settings. This difference, I suggest, implies that their framework may be too narrow in scope. If investigators (and their sponsors) really wish to fulfill their duty to rescue, they must consider factors that are left out of Sullivan and Berkman's framework. © 2018 The Hastings Center.

The Development of Visual and Auditory Selective Attention Using the Central-Incidental Paradigm.

ERIC Educational Resources Information Center

Conroy, Robert L.; Weener, Paul

Analogous auditory and visual central-incidental learning tasks were administered to 24 students from each of the second, fourth, and sixth grades. The visual tasks served as another modification of Hagen's central-incidental learning paradigm, with the interpretation that focal attention processes continue to develop until the age of 12 or 13…

Incidental Sequence Learning across the Lifespan

ERIC Educational Resources Information Center

Weiermann, Brigitte; Meier, Beat

2012-01-01

The purpose of the present study was to investigate incidental sequence learning across the lifespan. We tested 50 children (aged 7-16), 50 young adults (aged 20-30), and 50 older adults (aged >65) with a sequence learning paradigm that involved both a task and a response sequence. After several blocks of practice, all age groups slowed down…

Stromal cells in chronic inflammation and tertiary lymphoid organ formation.

PubMed

Buckley, Christopher D; Barone, Francesca; Nayar, Saba; Bénézech, Cecile; Caamaño, Jorge

2015-01-01

Inflammation is an unstable state. It either resolves or persists. Why inflammation persists and the factors that define tissue tropism remain obscure. Increasing evidence suggests that tissue-resident stromal cells not only provide positional memory but also actively regulate the differential accumulation of inflammatory cells within inflamed tissues. Furthermore, at many sites of chronic inflammation, structures that mimic secondary lymphoid tissues are observed, suggesting that chronic inflammation and lymphoid tissue formation share common activation programs. Similarly, blood and lymphatic endothelial cells contribute to tissue homeostasis and disease persistence in chronic inflammation. This review highlights our increasing understanding of the role of stromal cells in inflammation and summarizes the novel immunological role that stromal cells exert in the persistence of inflammatory diseases.

Gastrointestinal tuberculosis.

PubMed

Galloway, D J; Scott, R N

1986-10-01

In the developed countries gastrointestinal tuberculosis is no longer common in clinical practice. In this setting the importance of the condition lies in the vagaries of its presentation and the fact that it is eminently treatable, usually by a combination of chemotherapy and surgery. The clinical features and complications of gastrointestinal tuberculosis are highlighted by the seven cases which we report. Diagnosis and treatment of this condition is discussed and attention is drawn to the importance of case notification. Clinicians should bear in mind the diagnosis of gastrointestinal tuberculosis when dealing with any patient with non-specific abdominal symptoms.

Progressive Enrichment of Stemness Features and Tumor Stromal Alterations in Multistep Hepatocarcinogenesis.

PubMed

Yoo, Jeong Eun; Kim, Young-Joo; Rhee, Hyungjin; Kim, Haeryoung; Ahn, Ei Yong; Choi, Jin Sub; Roncalli, Massimo; Park, Young Nyun

2017-01-01

Cancer stem cells (CSCs), a subset of tumor cells, contribute to an aggressive biological behavior, which is also affected by the tumor stroma. Despite the role of CSCs and the tumor stroma in hepatocellular carcinoma (HCC), features of stemness have not yet been studied in relation to tumor stromal alterations in multistep hepatocarcinogenesis. We investigated the expression status of stemness markers and tumor stromal changes in B viral carcinogenesis, which is the main etiology of HCC in Asia. Stemness features of tumoral hepatocytes (EpCAM, K19, Oct3/4, c-KIT, c-MET, and CD133), and tumor stromal cells expressing α-smooth muscle actin (α-SMA), CD68, CD163, and IL-6 were analyzed in 36 low grade dysplastic nodules (DNs), 48 high grade DNs, 30 early HCCs (eHCCs), and 51 progressed HCCs (pHCCs) by immunohistochemistry or real-time PCR. Stemness features (EpCAM and K19 in particular) were progressively acquired during hepatocarcinogenesis in combination with enrichment of stromal cells (CAFs, TAMs, IL-6+ cells). Stemness features were seen sporadically in DNs, more consistent in eHCCs, and peaked in pHCCs. Likewise, stromal cells were discernable in DNs, showed up as consistent cell densities in eHCCs and peaked in pHCCs. The stemness features and tumor stromal alterations also peaked in less differentiated or larger HCCs. In conclusion, progression of B viral multistep hepatocarcinogenesis is characterized by an enrichment of stemness features of neoplastic hepatocytes and a parallel alteration of the tumor stroma. The modulation of neoplastic hepatocytes and stromal cells was at low levels in precancerous lesions (DNs), consistently increased in incipient cancer (eHCCs) and peaked in pHCCs. Thus, in B viral hepatocarcinogenesis, interactions between CSCs and the tumor stroma, although starting early, seem to play a major role in tumor progression.

Interpretability of the PedsQL gastrointestinal symptoms scales and gastrointestinal worry scales in pediatric patients with functional and organic gastrointestinal diseases

USDA-ARS?s Scientific Manuscript database

The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventor (PedsQL) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls....

Influence of stromal refractive index and hydration on corneal laser refractive surgery.

PubMed

de Ortueta, Diego; von Rüden, Dennis; Magnago, Thomas; Arba Mosquera, Samuel

2014-06-01

To evaluate the influence of the stromal refractive index and hydration on postoperative outcomes in eyes that had corneal laser refractive surgery using the Amaris laser system. Augenzentrum Recklinghausen, Recklinghausen, Germany. Comparative case series. At the 6-month follow-up, right eyes were retrospectively analyzed. The effect of the stromal refractive index and hydration on refractive outcomes was assessed using univariate linear and multilinear correlations. Sixty eyes were analyzed. Univariate linear analyses showed that the stromal refractive index and hydration were correlated with the thickness of the preoperative exposed stroma and was statistically different for laser in situ keratomileusis and laser-assisted subepithelial keratectomy treatments. Univariate multilinear analyses showed that the spherical equivalent (SE) was correlated with the attempted SE and stromal refractive index (or hydration). Analyses suggest overcorrections for higher stromal refractive index values and for lower hydration values. The stromal refractive index and hydration affected postoperative outcomes in a subtle, yet significant manner. An adjustment toward greater attempted correction in highly hydrated corneas and less intended correction in low hydrated corneas might help optimize refractive outcomes. Mr. Magnago and Dr. Arba-Mosquera are employees of and Dr. Diego de Ortueta is a consultant to Schwind eye-tech-solutions GmbH & Co. KG. Mr. Rüden has no financial or proprietary interest in any material or method mentioned. Copyright © 2014 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Interpretability of the PedsQL™ Gastrointestinal Symptoms Scales and Gastrointestinal Worry Scales in Pediatric Patients With Functional and Organic Gastrointestinal Diseases

PubMed Central

Bendo, Cristiane B.; Shulman, Robert J.; Self, Mariella M.; Nurko, Samuel; Franciosi, James P.; Saps, Miguel; Saeed, Shehzad; Zacur, George M.; Vaughan Dark, Chelsea; Pohl, John F.

2015-01-01

Objective The present study investigates the clinical interpretability of the Pediatric Quality of Life Inventory™ (PedsQL™) Gastrointestinal Symptoms Scales and Worry Scales in pediatric patients with functional gastrointestinal disorders or organic gastrointestinal diseases in comparison with healthy controls. Methods The PedsQL™ Gastrointestinal Scales were completed by 587 patients with gastrointestinal disorders/diseases and 685 parents, and 513 healthy children and 337 parents. Minimal important difference (MID) scores were derived from the standard error of measurement (SEM). Cut-points were derived based on one and two standard deviations (SDs) from the healthy reference means. Results The percentages of patients below the scales’ cut-points were significantly greater than the healthy controls (most p values ≤ .001). Scale scores 2 SDs from the healthy reference means were within the range of scores for pediatric patients with a gastrointestinal disorder. MID values were generated using the SEM. Conclusions The findings support the clinical interpretability of the new PedsQL™ Gastrointestinal Symptoms Scales and Worry Scales. PMID:25682210

Gastric Glomus Tumour Misdiagnosed as Gastric Carcinoid: An Unfamiliar Entity with Aids to Diagnosis and Review of Literature.

PubMed

Vig, Tanush; Bindra, Mandeep Singh; Kumar, Ramani Manoj; Alexander, Suceena

2017-05-01

Glomus tumour (GT) is a rare mesenchymal tumour of the stomach with Gastrointestinal Stromal Tumour (GIST), leiomyoma and schwannoma being far more common and comprising more than 90% of all gastric mesenchymal tumours. As glomus bodies are located in the peripheral parts of the human body, these tumours are peripherally located, classically the subungual region, hands, feet and trunk. While being evaluated for renal problems, a middle aged lady was incidentally found to have a gastric tumour. This was submucosal in location and was excised by a wedge resection and reported elsewhere as carcinoid tumour. The patient came to our hospital for further management. The biopsy was reviewed here and the modified diagnosis given was GT, confirmed by panel of immunohistochemistry. Two years after regular clinical follow up the patient is free of disease or any distant metastasis. In this paper the authors discuss the potential pitfalls, differential diagnoses and diagnostic clues that help in diagnosing this gastric tumour.

Gastric Glomus Tumour Misdiagnosed as Gastric Carcinoid: An Unfamiliar Entity with Aids to Diagnosis and Review of Literature

PubMed Central

Bindra, Mandeep Singh; Kumar, Ramani Manoj; Alexander, Suceena

2017-01-01

Glomus tumour (GT) is a rare mesenchymal tumour of the stomach with Gastrointestinal Stromal Tumour (GIST), leiomyoma and schwannoma being far more common and comprising more than 90% of all gastric mesenchymal tumours. As glomus bodies are located in the peripheral parts of the human body, these tumours are peripherally located, classically the subungual region, hands, feet and trunk. While being evaluated for renal problems, a middle aged lady was incidentally found to have a gastric tumour. This was submucosal in location and was excised by a wedge resection and reported elsewhere as carcinoid tumour. The patient came to our hospital for further management. The biopsy was reviewed here and the modified diagnosis given was GT, confirmed by panel of immunohistochemistry. Two years after regular clinical follow up the patient is free of disease or any distant metastasis. In this paper the authors discuss the potential pitfalls, differential diagnoses and diagnostic clues that help in diagnosing this gastric tumour. PMID:28658787

Incidental findings on MRI scans of patients presenting with audiovestibular symptoms.

PubMed

Papanikolaou, Vasileios; Khan, Mohammad H; Keogh, Ivan J

2010-06-07

The evaluation of patients presenting with audiovestibular symptoms usually includes MRI of the internal auditory meatus, the cerebellopontine angle and the brain. A significant percentage of these scans will present unexpected, incidental findings, which could have important clinical significance. To determine the frequency and clinical significance of incidental findings on MRI scans of patients with audiovestibular symptoms. A retrospective analysis of 200 serial MRI scans. Gender distribution: equal. Age range: 17-82 years. One-hundred and four scans (52%) were normal and 1 scan (0.5%) demonstrated a unilateral vestibular schwannoma. Ninety-five scans (47.5%) demonstrated incidental findings. Sixty-six of these (33%) were considered of ishaemic origin and did not require further action. Five (2.5%) scans demonstrated significant findings which warranted appropriate referral; Two Gliomas (1%), 2 cases of extensive White Matter Lesions (1%), 1 lipoma (0.5%). The remaining scans demonstrated various other findings. Investigation of patients with audiovestibular symptoms with MRI scans revealed incidental findings in a significant percentage (47.5%). The majority of these findings were benign warranting no further action and only 2.5% required further referral. It is the responsibility of the referring Otolaryngologist to be aware of these findings, to be able to assess their significance, to inform the patient and if needed to refer for further evaluation.

Incidental Prostate Adenocarcinoma in Cystoprostatectomy Specimens: Partial Versus Complete Prostate Sampling.

PubMed

Filter, Emily R; Gabril, Manal Y; Gomez, Jose A; Wang, Peter Z T; Chin, Joseph L; Izawa, Jonathan; Moussa, Madeleine

2017-08-01

The rate of incidental prostate adenocarcinoma (PCa) detection in radical cystoprostatectomy (RCP) varies widely, ranging from 15% to 54%. Such variability may be explained by institutional differences in prostate grossing protocols. Either partial or complete submission of the prostate gland in RCP may result in detection of clinically insignificant or significant incidental PCa. The aim of the study was to compare the clinical significance of PCa in RCP specimens in partial versus complete sampling. Seventy-two out of 158 RCP cases showed incidental PCa. The pathologic features, including Gleason score, margin status, extraprostatic extension (EPE), seminal vesicle invasion (SVI), PCa stage, and tumor volume, were assessed. The 72 cases were divided into partial (n = 21, 29.1%) and complete sampling (n = 51, 70.8%) groups. EPE was detected in 13/72 (18.1%) with 11/13 (84.6%) cases in the complete group. Positive margins were present in 11/72 (15.3%) with 9/11 (81.8%) in the complete group. SVI was detected in 4/72 (5.6%) with 3/4 (75.0%) in the complete group. Overall, 4/72 (5.6%) had a Gleason score >7, all of which were in the complete group. Our data suggest that complete sampling of the prostate may be the ideal approach to grossing RCP specimens, allowing for greater detection of clinically significant incidental PCa.

Risk of appendicitis in patients with incidentally discovered appendicoliths.

PubMed

Khan, Muhammad Sohaib; Chaudhry, Mustafa Belal Hafeez; Shahzad, Noman; Tariq, Marvi; Memon, Wasim Ahmed; Alvi, Abdul Rehman

2018-01-01

An appendicolith-related appendiceal obstruction leading to appendicitis is a commonly encountered surgical emergency that has clear evidence-based management plans. However, there is no consensus on management of asymptomatic patients when appendicoliths are found incidentally. The objective of this study was to determine the risk of appendicitis in patients with an incidental finding of the appendicolith. A retrospective matched cohort study of patients with appendicolith discovered incidentally on computed tomographic scan from January 2008 to December 2014 at our institution was completed. The size and position of the appendicolith were ascertained. The study group was matched by age and gender to a control group. Both groups were contacted and interviewed regarding development of appendicitis. In total, 111 patients with appendicolith were successfully contacted and included in the study. Mean age was found to be 38 ± 15 y with 36 (32%) of the study population being females. Mean length of appendix was 66 ± 16 mm, and mean width was 5.8 ± 0.9 mm. Mean size of the appendicolith was 3.6 ± 1.1 mm (1.4-7.8 mm). Fifty-eight percent of appendicoliths was located at the proximal end or whole of appendix, 31% at mid area, and 11% at the distal end of appendix. All patients of the study and control groups were contacted, and at a mean follow-up of 4.0 ± 1.7 y, there was no occurrence of acute appendicitis in either group. Patients with incidentally discovered appendicolith on radiological imaging did not develop appendicitis. Hence, the risk of developing acute appendicitis for these patients does not seem higher than the general population. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of Incidental Emotions on Moral Dilemma Judgments: An Analysis Using the CNI Model.

PubMed

Gawronski, Bertram; Conway, Paul; Armstrong, Joel; Friesdorf, Rebecca; Hütter, Mandy

2018-02-01

Effects of incidental emotions on moral dilemma judgments have garnered interest because they demonstrate the context-dependent nature of moral decision-making. Six experiments (N = 727) investigated the effects of incidental happiness, sadness, and anger on responses in moral dilemmas that pit the consequences of a given action for the greater good (i.e., utilitarianism) against the consistency of that action with moral norms (i.e., deontology). Using the CNI model of moral decision-making, we further tested whether the three kinds of emotions shape moral dilemma judgments by influencing (a) sensitivity to consequences, (b) sensitivity to moral norms, or (c) general preference for inaction versus action regardless of consequences and moral norms (or some combination of the three). Incidental happiness reduced sensitivity to moral norms without affecting sensitivity to consequences or general preference for inaction versus action. Incidental sadness and incidental anger did not show any significant effects on moral dilemma judgments. The findings suggest a central role of moral norms in the contribution of emotional responses to moral dilemma judgments, requiring refinements of dominant theoretical accounts and supporting the value of formal modeling approaches in providing more nuanced insights into the determinants of moral dilemma judgments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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

Rapid Selection of Mesenchymal Stem and Progenitor Cells in Primary Prostate Stromal Cultures

PubMed Central

Brennen, W. Nathaniel; Kisteman, L. Nelleke; Isaacs, John T.

2016-01-01

BACKGROUND Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. METHODS Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (>25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. RESULTS MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 μm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. CONCLUSIONS Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when

Rapid selection of mesenchymal stem and progenitor cells in primary prostate stromal cultures.

PubMed

Brennen, W Nathaniel; Kisteman, L Nelleke; Isaacs, John T

2016-05-01

Carcinoma-associated fibroblasts (CAFs) are a dominant component of the tumor microenvironment with pro-tumorigenic properties. Despite this knowledge, their physiologic origins remain poorly understood. Mesenchymal stem cells (MSCs) can be recruited from the bone marrow to areas of tissue damage and inflammation, including prostate cancer. MSCs can generate and have many overlapping properties with CAFs in preclinical models. Multiparameter flow cytometry and multipotent differentiation assays used to define MSCs in primary prostate stromal cultures derived from young (<25 yrs) organ donors and prostate cancer patients compared with bone marrow-derived stromal cultures. Population doubling times, population doublings, cell size, and differentiation potential determined under multiple culture conditions, including normoxia, hypoxia, and a variety of media. TGF-β measured by ELISA. MSCs and stromal progenitors are not only present in normal and malignant prostate tissue, but are quickly selected for in primary stromal cultures derived from these tissues; becoming the dominant population within just a few passages. Growth potential inversely associated with TGF-β concentrations. All conditions generated populations with an average cell diameter >15 µm. All cultures tested had the ability to undergo osteogenic and chondrogenic differentiation, but unlike bone marrow-derived MSCs, primary stromal cultures derived from normal prostate tissue lack adipogenic differentiation potential. In contrast, a subset of stromal cultures derived from prostate cancer patients retain the ability to differentiate into adipocytes; a property that is significantly suppressed under hypoxic conditions in both bone marrow- and prostate-derived MSCs. Primary prostate stromal cultures are highly enriched in cells with an MSC or stromal progenitor phenotype. The use of primary cultures such as these to study CAFs raises interesting implications when considering their overlapping

Incidental findings found in “healthy” volunteers during imaging performed for research: current legal and ethical implications

PubMed Central

Booth, T C; Jackson, A; Wardlaw, J M; Taylor, S A; Waldman, A D

2010-01-01

Incidental findings found in “healthy” volunteers during research imaging are common and have important implications for study design and performance, particularly in the areas of informed consent, subjects' rights, clinical image analysis and disclosure. In this study, we aimed to determine current practice and regulations concerning information that should be given to research subjects when obtaining consent, reporting of research images, who should be informed about any incidental findings and the method of disclosure. We reviewed all UK, European and international humanitarian, legal and ethical agencies' guidance. We found that the guidance on what constitutes incidental pathology, how to recognise it and what to do about it is inconsistent between agencies, difficult to find and less complete in the UK than elsewhere. Where given, guidance states that volunteers should be informed during the consent process about how research images will be managed, whether a mechanism exists for identifying incidental findings, arrangements for their disclosure, the potential benefit or harm and therapeutic options. The effects of incidentally discovered pathology on the individual can be complex and far-reaching. Radiologist involvement in analysis of research images varies widely; many incidental findings might therefore go unrecognised. In conclusion, guidance on the management of research imaging is inconsistent, limited and does not address the interests of volunteers. Improved standards to guide management of research images and incidental findings are urgently required. PMID:20335427

Know thy neighbor: stromal cells can contribute oncogenic signals

NASA Technical Reports Server (NTRS)

Tlsty, T. D.; Hein, P. W.

2001-01-01

Although the stroma within carcinogenic lesions is known to be supportive and responsive to tumors, new data increasingly show that the stroma also has a more active, oncogenic role in tumorigenesis. Stromal cells and their products can transform adjacent tissues in the absence of pre-existing tumor cells by inciting phenotypic and genomic changes in the epithelial cells. The oncogenic action of distinctive stromal components has been demonstrated through a variety of approaches, which provide clues about the cellular pathways involved.

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…

The Role of Repeated Exposure to Multimodal Input in Incidental Acquisition of Foreign Language Vocabulary.

PubMed

Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

2014-12-01

Prior research has reported incidental vocabulary acquisition with complete beginners in a foreign language (FL), within 8 exposures to auditory and written FL word forms presented with a picture depicting their meaning. However, important questions remain about whether acquisition occurs with fewer exposures to FL words in a multimodal situation and whether there is a repeated exposure effect. Here we report a study where the number of exposures to FL words in an incidental learning phase varied between 2, 4, 6, and 8 exposures. Following the incidental learning phase, participants completed an explicit learning task where they learned to recognize written translation equivalents of auditory FL word forms, half of which had occurred in the incidental learning phase. The results showed that participants performed better on the words they had previously been exposed to, and that this incidental learning effect occurred from as little as 2 exposures to the multimodal stimuli. In addition, repeated exposure to the stimuli was found to have a larger impact on learning during the first few exposures and decrease thereafter, suggesting that the effects of repeated exposure on vocabulary acquisition are not necessarily constant.

The Role of Repeated Exposure to Multimodal Input in Incidental Acquisition of Foreign Language Vocabulary

PubMed Central

Bisson, Marie-Josée; van Heuven, Walter J B; Conklin, Kathy; Tunney, Richard J

2014-01-01

Prior research has reported incidental vocabulary acquisition with complete beginners in a foreign language (FL), within 8 exposures to auditory and written FL word forms presented with a picture depicting their meaning. However, important questions remain about whether acquisition occurs with fewer exposures to FL words in a multimodal situation and whether there is a repeated exposure effect. Here we report a study where the number of exposures to FL words in an incidental learning phase varied between 2, 4, 6, and 8 exposures. Following the incidental learning phase, participants completed an explicit learning task where they learned to recognize written translation equivalents of auditory FL word forms, half of which had occurred in the incidental learning phase. The results showed that participants performed better on the words they had previously been exposed to, and that this incidental learning effect occurred from as little as 2 exposures to the multimodal stimuli. In addition, repeated exposure to the stimuli was found to have a larger impact on learning during the first few exposures and decrease thereafter, suggesting that the effects of repeated exposure on vocabulary acquisition are not necessarily constant. PMID:25558094

Disclosure of Incidental Findings From Next-Generation Sequencing in Pediatric Genomic Research

PubMed Central

Abdul-Karim, Ruqayyah; Berkman, Benjamin E.; Wendler, David; Rid, Annette; Khan, Javed; Badgett, Tom

2013-01-01

Next-generation sequencing technologies will likely be used with increasing frequency in pediatric research. One consequence will be the increased identification of individual genomic research findings that are incidental to the aims of the research. Although researchers and ethicists have raised theoretical concerns about incidental findings in the context of genetic research, next-generation sequencing will make this once largely hypothetical concern an increasing reality. Most commentators have begun to accept the notion that there is some duty to disclose individual genetic research results to research subjects; however, the scope of that duty remains unclear. These issues are especially complicated in the pediatric setting, where subjects cannot currently but typically will eventually be able to make their own medical decisions at the age of adulthood. This article discusses the management of incidental findings in the context of pediatric genomic research. We provide an overview of the current literature and propose a framework to manage incidental findings in this unique context, based on what we believe is a limited responsibility to disclose. We hope this will be a useful source of guidance for investigators, institutional review boards, and bioethicists that anticipates the complicated ethical issues raised by advances in genomic technology. PMID:23400601

Prostate stromal cells express the progesterone receptor to control cancer cell mobility.

PubMed

Yu, Yue; Lee, Jennifer Suehyun; Xie, Ning; Li, Estelle; Hurtado-Coll, Antonio; Fazli, Ladan; Cox, Michael; Plymate, Stephen; Gleave, Martin; Dong, Xuesen

2014-01-01

Reciprocal interactions between epithelium and stroma play vital roles for prostate cancer development and progression. Enhanced secretions of cytokines and growth factors by cancer associated fibroblasts in prostate tumors create a favorable microenvironment for cancer cells to grow and metastasize. Our previous work showed that the progesterone receptor (PR) was expressed specifically in prostate stromal fibroblasts and smooth muscle cells. However, the expression levels of PR and its impact to tumor microenvironment in prostate tumors are poorly understood. Immunohistochemistry assays are applied to human prostate tissue biopsies. Cell migration, invasion and proliferation assays are performed using human prostate cells. Real-time PCR and ELISA are applied to measure gene expression at molecular levels. Immunohistochemistry assays showed that PR protein levels were decreased in cancer associated stroma when compared with paired normal prostate stroma. Using in vitro prostate stromal cell models, we showed that conditioned media collected from PR positive stromal cells inhibited prostate cancer cell migration and invasion, but had minor suppressive impacts on cancer cell proliferation. PR suppressed the secretion of stromal derived factor-1 (SDF-1) and interlukin-6 (IL-6) by stromal cells independent to PR ligands. Blocking PR expression by siRNA or supplementation of exogenous SDF-1 or IL-6 to conditioned media from PR positive stromal cells counteracted the inhibitory effects of PR to cancer cell migration and invasion. Decreased expression of the PR in cancer associated stroma may contribute to the elevated SDF-1 and IL-6 levels in prostate tumors and enhance prostate tumor progression.

Gastrointestinal Morbidity in Obesity

PubMed Central

Acosta, Andres; Camilleri, Michael

2014-01-01

Obesity is a complex disease that results from increased energy intake and decreased energy expenditure. The gastrointestinal system plays a key role in the pathogenesis of obesity and facilitates caloric imbalance. Changes in gastrointestinal hormones and the inhibition of mechanisms that curtail caloric intake result in weight gain. It is not clear if the gastrointestinal role in obesity is a cause or an effect of this disease. Obesity is often associated with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD). Obesity is also associated with gastrointestinal disorders, which are more frequent and present earlier than T2DM and CVD. Diseases such as gastro-esophageal reflux disease, cholelithiasis or non-alcoholic steatohepatitis are directly related to body weight and abdominal adiposity. Our objective is to assess the role of each gastrointestinal organ in obesity and the gastrointestinal morbidity resulting in those organs from effects of obesity. PMID:24602085

Endometrial stromal sarcoma diagnosed after uterine morcellation in laparoscopic supracervical hysterectomy.

PubMed

Della Badia, Carl; Karini, Homa

2010-01-01

Endometrial stromal sarcoma is a rare uterine cancer with no reliable method for preoperative diagnosis. A 30-year-old parous woman underwent laparoscopic supracervical hysterectomy because of a leiomyoma. The uterus was removed from the abdominal cavity with an electric morcellator with a spinning blade. The pathology report revealed low-grade endometrial stromal sarcoma. Two months after the initial surgery, a second laparoscopic procedure was performed. The final pathology report confirmed low-grade endometrial stromal sarcoma involving the ovary, fallopian tube, and ovarian artery. It was concluded that morcellation of leiomyomas at laparoscopic supracervical hysterectomy may potentially increase metastasis if the tumor is a sarcoma. Copyright © 2010 AAGL. Published by Elsevier Inc. All rights reserved.

Mixed-handedness advantages in episodic memory obtained under conditions of intentional learning extend to incidental learning.

PubMed

Christman, Stephen D; Butler, Michael

2011-10-01

The existence of handedness differences in the retrieval of episodic memories is well-documented, but virtually all have been obtained under conditions of intentional learning. Two experiments are reported that extend the presence of such handedness differences to memory retrieval under conditions of incidental learning. Experiment 1 used Craik and Tulving's (1975) classic levels-of-processing paradigm and obtained handedness differences under incidental and intentional conditions of deep processing, but not under conditions of shallow incidental processing. Experiment 2 looked at incidental memory for distracter items from a recognition memory task and again found a mixed-handed advantage. Results are discussed in terms of the relation between interhemispheric interaction, levels of processing, and episodic memory retrieval. Copyright © 2011 Elsevier Inc. All rights reserved.

Correlation of KIT and PDGFRA mutational status with clinical benefit in patients with gastrointestinal stromal tumor treated with sunitinib in a worldwide treatment-use trial.

PubMed

Reichardt, Peter; Demetri, George D; Gelderblom, Hans; Rutkowski, Piotr; Im, Seock-Ah; Gupta, Sudeep; Kang, Yoon-Koo; Schöffski, Patrick; Schuette, Jochen; Soulières, Denis; Blay, Jean-Yves; Goldstein, David; Fly, Kolette; Huang, Xin; Corsaro, Massimo; Lechuga, Maria Jose; Martini, Jean-Francois; Heinrich, Michael C

2016-01-15

Several small studies indicated that the genotype of KIT or platelet-derived growth factor receptor-α (PDGFRA) contributes in part to the level of clinical effectiveness of sunitinib in gastrointestinal stromal tumor (GIST) patients. This study aimed to correlate KIT and PDGFRA mutational status with clinical outcome metrics (progression-free survival [PFS], overall survival [OS], objective response rate [ORR]) in a larger international patient population. This is a non-interventional, retrospective analysis in patients with imatinib-resistant or intolerant GIST who were treated in a worldwide, open-label treatment-use study (Study 1036; NCT00094029) in which sunitinib was administered at a starting dose of 50 mg/day on a 4-week-on, 2-week-off schedule. Molecular status was obtained in local laboratories with tumor samples obtained either pre-imatinib, post-imatinib/pre-sunitinib, or post-sunitinib treatment, and all available data were used in the analyses regardless of collection time. The primary analysis compared PFS in patients with primary KIT exon 11 versus exon 9 mutations (using a 2-sided log-rank test) and secondary analyses compared OS (using the same test) and ORR (using a 2-sided Pearson χ(2) test) in the same molecular subgroups. Of the 1124 sunitinib-treated patients in the treatment-use study, 230 (20%) were included in this analysis, and baseline characteristics were similar between the two study populations. Median PFS was 7.1 months. A significantly better PFS was observed in patients with a primary mutation in KIT exon 9 (n = 42) compared to those with a primary mutation in exon 11 (n = 143; hazard ratio = 0.59; 95 % confidence interval, 0.39-0.89; P = 0.011), with median PFS times of 12.3 and 7.0 months, respectively. Similarly, longer OS and higher ORR were observed in patients with a primary KIT mutation in exon 9 versus exon 11. The data available were limited to investigate the effects of additional KIT or PDGFRA mutations on the efficacy

Inflammatory responses of stromal fibroblasts to inflammatory epithelial cells are involved in the pathogenesis of bovine mastitis.

PubMed

Zhang, Wenyao; Li, Xuezhong; Xu, Tong; Ma, Mengru; Zhang, Yong; Gao, Ming-Qing

2016-11-15

Hypernomic secretion of epithelial cytokines has several effects on stromal cells. The contributions of inflammatory epithelial cells to stromal fibroblasts in bovine mammary glands with mastitis remain poorly understood. Here, we established an inflammatory epithelial cell model of bovine mastitis with gram-negative lipopolysaccharide (LPS) and gram-positive lipoteichoic acid (LTA) bacterial cell wall components. We characterized immune responses of mammary stromal fibroblasts induced by inflammatory epithelial cells. Our results showed that inflammatory epithelial cells affected stromal fibroblast characteristics by increasing inflammatory mediator expression, elevating extracellular matrix protein deposition, decreasing proliferation capacity, and enhancing migration ability. The changes in stromal fibroblast proliferation and migration abilities were mediated by signal molecules, such as WNT signal pathway components. LPS- and LTA-induced inflammatory epithelial cells triggered different immune responses in stromal fibroblasts. Thus, in mastitis, bovine mammary gland stromal fibroblasts were affected by inflammatory epithelial cells and displayed inflammation-specific changes, suggesting that fibroblasts play crucial roles in bovine mastitis. Copyright © 2016 Elsevier Inc. All rights reserved.

75 FR 13498 - Small Takes of Marine Mammals Incidental to Specified Activities; Dumbarton Bridge Seismic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-22

... of Marine Mammals Incidental to Specified Activities; Dumbarton Bridge Seismic Retrofit Project... pile driving associated with the Dumbarton Bridge Seismic Retrofit Project. DATES: Effective August 15... request from Caltrans to harass marine mammals incidental to the Dumbarton Bridge Seismic Retrofit Project...

[Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality].

PubMed

Zaimov, K; Kokoshkarova, A

1978-10-01

A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.

Imagery Based Elaboration as an Index of EMR Children's Creativity and Incidental Associative Learning.

ERIC Educational Resources Information Center

Greeson, Larry E.; Vane, Raymond J.

1986-01-01

Educable mentally retarded (EMR) 13- to 15-year-olds (N=19) and matched mental-age comparison subjects (N=22) participated in an imagery-based, associative learning pictorial elaboration task, followed by a delayed test of incidental learning. Both groups were able to generate original elaborations, although fluency and incidental learning scores…

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…

Mesenchymal stromal cells support the viability and differentiation of thymocytes through direct contact in autologous co-cultures.

PubMed

Azghadi, Seyed Mohammad Reza; Suciu, Maria; Gruia, Alexandra Teodora; Barbu-Tudoran, Lucian; Cristea, Mirabela Iustina; Mic, Ani Aurora; Muntean, Danina; Nica, Dragos Vasile; Mic, Felix Aurel

2016-08-01

The development of thymocytes and generation of mature T cells is a complex process that requires spatio-temporal interactions of thymocytes with the other cells of the thymus microenvironment. Recently, mesenchymal stromal cells were isolated from the neonatal human thymus and differentiated into chondrogenic, osteogenic, and adipogenic lineages, just like their bone marrow counterparts. However, their function in thymocyte homeostasis is unknown. In our autologous co-cultures of rat mesenchymal stromal cells and thymocytes, the stromal cells preserve the viability of cultured thymocytes and stimulate the development of CD4-CD8- double-negative and the maturation of mainly CD4+ single-positive thymocytes. Thymocytes also influence the stemness of bone marrow mesenchymal stromal cells, as their expression of CD44, a marker associated with cellular proliferation and migration, is reduced in co-cultures. Mesenchymal stromal cells' influence on thymocyte development requires direct physical contact between the two cells and is not mediated by a soluble factor. When the two types of cells were physically separated, the stimulative effects of mesenchymal stromal cells on thymocytes did not occur. Electron microscopy confirmed the close contact between the membranes of thymocytes and mesenchymal stromal cells. Our experiments suggest that membrane exchanges could occur between mesenchymal stromal cells and thymocytes, such as the transfer of CD44 from mesenchymal stromal cells to the thymocytes, but its functional significance for thymocytes development remains to be established. These results suggest that mesenchymal stromal cells could normally be a part of the in vivo thymic microenvironment and form a niche that could sustain and guide the development of thymocytes.

Gap junction blockade induces apoptosis in human endometrial stromal cells.

PubMed

Yu, Jie; Berga, Sarah L; Zou, Wei; Sun, He-Ying; Johnston-MacAnanny, Erika; Yalcinkaya, Tamer; Sidell, Neil; Bagchi, Indrani C; Bagchi, Milan K; Taylor, Robert N

2014-07-01

One of the most dynamic adult human tissues is the endometrium. Through coordinated, cyclical proliferation, differentiation, leukocyte recruitment, apoptosis, and desquamation, the uterine lining is expanded and shed monthly, unless pregnancy is established. Errors in these steps potentially cause endometrial dysfunction, abnormal uterine bleeding, failed embryonic implantation, infertility, or endometrial carcinoma. Our prior studies showed that gap junctions comprised of Gap junction alpha-1 (GJA1) protein, also known as connexin 43 (CX43), subunits are critical to endometrial stromal cell differentiation. The current studies were undertaken to explore the mechanism of endometrial dysfunction when gap junction intercellular communication (GJIC) is disrupted. Gap junction blockade by two distinct GJIC inhibitors, 18α-glycyrrhetinic acid (AGA) and octanol (OcOH), suppressed proliferation and induced apoptosis in endometrial stromal cells, as manifested by reduced biomarkers of cell viability, increased TUNEL staining, caspase-3 activation, sub-G1 chromosomal DNA complement, as well as shortened telomere length. Unexpectedly, we also observed that the chemical inhibitors blocked CX43 gene expression. Moreover, when endometrial stromal cells were induced to undergo hormonal decidualization, following a 7-day exposure to 10 nM 17β-estradiol + 100 nM progesterone + 0.5 mM dibutyryl cAMP, characteristic epithelioid changes in cell shape and secretion of prolactin were blunted in the presence of AGA or OcOH, recapitulating effects of RNA interference of CX43. Our findings indicate that endometrial stromal cell proliferation and maintenance of decidualized endometrial function are GJIC-dependent, and that disruption of gap junctions induces endometrial stromal cell apoptosis. These observations may have important implications for several common clinical endometrial pathologies. © 2014 Wiley Periodicals, Inc.

Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar.

PubMed

Jain, Abhinav; Gandhi, Shrey; Koshy, Remya; Scaria, Vinod

2018-03-20

Incidental findings in genomic data have been studied in great detail in the recent years, especially from population-scale data sets. However, little is known about the frequency of such findings in ethnic groups, specifically the Middle East, which were not previously covered in global sequencing studies. The availability of whole exome and genome data sets for a highly consanguineous Arab population from Qatar motivated us to explore the incidental findings in this population-scale data. The sequence data of 1005 Qatari individuals were systematically analyzed for incidental genetic variants in the 59 genes suggested by the American College of Medical Genetics and Genomics. We identified four genetic variants which were pathogenic or likely pathogenic. These variants occurred in six individuals, suggesting a frequency of 0.59% in the population, much lesser than that previously reported from European and African populations. Our analysis identified a variant in RYR1 gene associated with Malignant Hyperthermia that has significantly higher frequency in the population compared to global frequencies. Evaluation of the allele frequencies of these variants suggested enrichment in sub-populations, especially in individuals of Sub-Saharan African ancestry. The present study thereby provides the information on pathogenicity and frequency, which could aid in genomic medicine. To the best of our knowledge, this is the first comprehensive analysis of incidental genetic findings in any Arab population and suggests ethnic differences in incidental findings.

Patient Health Communication Mediating Effects Between Gastrointestinal Symptoms and Gastrointestinal Worry in Pediatric Inflammatory Bowel Disease.

PubMed

Varni, James W; Shulman, Robert J; Self, Mariella M; Saeed, Shehzad A; Patel, Ashish S; Nurko, Samuel; Neigut, Deborah A; Saps, Miguel; Zacur, George M; Dark, Chelsea V; Bendo, Cristiane B; Pohl, John F

2017-05-01

To investigate the effects of patient health communication regarding their inflammatory bowel disease (IBD) to their health care providers and significant others in their daily life as a mediator in the relationship between gastrointestinal symptoms and gastrointestinal worry in pediatric patients. The Pediatric Quality of Life Inventory Gastrointestinal Symptoms, Gastrointestinal Worry, and Communication Scales, and Pediatric Quality of Life Inventory 4.0 Generic Core Scales were completed in a 9-site study by 252 pediatric patients with IBD. Gastrointestinal Symptoms Scales measuring stomach pain, constipation, or diarrhea and patient communication were tested for bivariate and multivariate linear associations with Gastrointestinal Worry Scales specific to patient worry about stomach pain or bowel movements. Mediational analyses were conducted to test the hypothesized mediating effects of patient health communication as an intervening variable in the relationship between gastrointestinal symptoms and gastrointestinal worry. The predictive effects of gastrointestinal symptoms on gastrointestinal worry were mediated in part by patient health communication with health care providers/significant others in their daily life. In predictive models using multiple regression analyses, the full conceptual model of demographic variables, gastrointestinal symptoms (stomach pain, constipation, or diarrhea), and patient communication significantly accounted for 46, 43, and 54 percent of the variance in gastrointestinal worry (all Ps < 0.001), respectively, reflecting large effect sizes. Patient health communication explains in part the effects of gastrointestinal symptoms on gastrointestinal worry in pediatric patients with IBD. Supporting patient disease-specific communication to their health care providers and significant others may improve health-related quality of life for pediatric patients with IBD.

Carbon Monoxide Improves Efficacy of Mesenchymal Stromal Cells During Sepsis by Production of Specialized Proresolving Lipid Mediators.

PubMed

Tsoyi, Konstantin; Hall, Sean R R; Dalli, Jesmond; Colas, Romain A; Ghanta, Sailaja; Ith, Bonna; Coronata, Anna; Fredenburgh, Laura E; Baron, Rebecca M; Choi, Augustine M K; Serhan, Charles N; Liu, Xiaoli; Perrella, Mark A

2016-12-01

Mesenchymal stromal cells are being investigated as a cell-based therapy for a number of disease processes, with promising results in animal models of systemic inflammation and sepsis. Studies are ongoing to determine ways to further improve the therapeutic potential of mesenchymal stromal cells. A gas molecule that improves outcome in experimental sepsis is carbon monoxide. We hypothesized that preconditioning of mesenchymal stromal cells with carbon monoxide ex vivo would promote further therapeutic benefit when cells are administered in vivo after the onset of polymicrobial sepsis in mice. Animal study and primary cell culture. Laboratory investigation. BALB/c mice. Polymicrobial sepsis was induced by cecal ligation and puncture. Mesenchymal stromal cells, mesenchymal stromal cells-conditioned with carbon monoxide, fibroblasts, or fibroblasts-conditioned with carbon monoxide were delivered by tail vein injections to septic mice. The mice were assessed for survival, bacterial clearance, and the inflammatory response during sepsis in each of the groups. Mesenchymal stromal cells were also assessed for their ability to promote bacterial phagocytosis by neutrophils, the production of specialized proresolving lipid mediators, and their importance for mesenchymal stromal cells function using gene silencing. Ex vivo preconditioning with carbon monoxide allowed mesenchymal stromal cells to be administered later after the onset of sepsis (6 hr), and yet maintain their therapeutic effect with increased survival. Carbon monoxide preconditioned mesenchymal stromal cells were also able to alleviate organ injury, improve bacterial clearance, and promote the resolution of inflammation. Mesenchymal stromal cells exposed to carbon monoxide, with docosahexaenoic acid substrate, produced specialized proresolving lipid mediators, particularly D-series resolvins, which promoted survival. Silencing of lipoxygenase pathways (5-lipoxygenase and 12/15-lipoxygenase), which are

Decidualized Human Endometrial Stromal Cells Mediate Hemostasis, Angiogenesis, and Abnormal Uterine Bleeding

PubMed Central

Lockwood, Charles J.; Krikun, Graciela; Hickey, Martha; Huang, S. Joseph; Schatz, Frederick

2011-01-01

Factor VII binds trans-membrane tissue factor to initiate hemostasis by forming thrombin. Tissue factor expression is enhanced in decidualized human endometrial stromal cells during the luteal phase. Long-term progestin only contraceptives elicit: 1) abnormal uterine bleeding from fragile vessels at focal bleeding sites, 2) paradoxically high tissue factor expression at bleeding sites; 3) reduced endometrial blood flow promoting local hypoxia and enhancing reactive oxygen species levels; and 4) aberrant angiogenesis reflecting increased stromal cell-expressed vascular endothelial growth factor, decreased Angiopoietin-1 and increased endothelial cell-expressed Angiopoietin-2. Aberrantly high local vascular permeability enhances circulating factor VII to decidualized stromal cell-expressed tissue factor to generate excess thrombin. Hypoxia-thrombin interactions augment expression of vascular endothelial growth factor and interleukin-8 by stromal cells. Thrombin, vascular endothelial growth factor and interlerukin-8 synergis-tically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. The resulting enhanced vessel fragility promotes abnormal uterine bleeding. PMID:19208784

Incidental parathyroidectomy during thyroidectomy increases the risk of postoperative hypocalcemia.

PubMed

Lin, Yann-Sheng; Hsueh, Chuen; Wu, Hsin-Yi; Yu, Ming-Chin; Chao, Tzu-Chieh

2017-09-01

The correlation between incidental parathyroidectomy (IP) during thyroidectomy and postoperative hypocalcemia remains controversial. Our aim was to investigate the incidence of IP, risk factors, and impact on patient outcomes. Retrospective cohort study. This was a retrospective observational study including 3,186 consecutive patients who underwent thyroidectomy between January 2007 and December 2014. The patients were divided into two groups: the IP group and the non-IP. Numerous clinical parameters were collected and analyzed. The overall incidence of incidentally excised parathyroid glands during thyroidectomy was 6.4%. Patients with IP had significantly higher incidences of postoperative hypocalcemia and hypoparathyroidism than those without IP (P < 0.001). Intrathyroidal parathyroid glands presented only 2.2% of all removed parathyroid glands. Total thyroidectomy, central compartment lymph node dissection, and reoperation were independent risk factors for IP. Incidental parathyroidectomy during thyroidectomy is associated with the increased likelihood of postoperative hypocalcemia. All independent risk factors examined in the study for IP are surgery-related. Surgeons should perform meticulous dissection with the intention of avoiding IP and resultant hypocalcemia. 4. Laryngoscope, 127:2194-2200, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Guidance of spatial attention by incidental learning and endogenous cuing

PubMed Central

Jiang, Yuhong V.; Swallow, Khena M.; Rosenbaum, Gail M.

2012-01-01

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, and examined the interaction between endogenous cuing and probability cuing. Participants searched for a target (T) among distractors (L’s). The target was more often located in one region of the screen than in others. We found that search RT was faster when the target appeared in the high-frequency region rather than the low-frequency regions. This difference increased when there were more items on the display, suggesting that probability cuing guides spatial attention. Additional data indicated that on their own, probability cuing and endogenous cuing (e.g., a central arrow that predicted a target’s location) were similarly effective at guiding attention. However, when both cues were presented at once, probability cuing was largely eliminated. Thus, although both incidental learning and endogenous cuing can effectively guide attention, endogenous cuing takes precedence over incidental learning. PMID:22506784

76 FR 37142 - Endangered and Threatened Wildlife and Plants; Incidental Take Permit Application; Proposed Low...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-24

...] Endangered and Threatened Wildlife and Plants; Incidental Take Permit Application; Proposed Low-Effect... (Aphelocoma coerulescens) (scrub-jay) breeding, feeding, and sheltering habitat incidental to lot preparation... taking approximately 0.23 acre (0.1 hectares (ha)) of Florida scrub-jay breeding, feeding, and sheltering...

75 FR 8677 - Takes of Marine Mammals Incidental to Specified Activities; Seabird and Pinniped Research...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-25

... Marine Mammals Incidental to Specified Activities; Seabird and Pinniped Research Activities in Central... forth the permissible methods of taking, other means of effecting the least practicable adverse impact... the taking by harassment, of marine mammals incidental to conducting seabird and pinniped research...

Malignant lymphoma incidentally diagnosed due to the perforation of the small intestine caused by a fish bone: A case report.

PubMed

Hiraki, Masatsugu; Miyoshi, Atsushi; Anegawa, Go; Kubo, Hiroshi; Ikeda, Osamu; Ohira, Keiichi; Azama, Shinya; Kido, Shinichi; Mori, Daisuke; Aibe, Hitoshi; Tanaka, Toshiya; Kitahara, Kenji; Sato, Seiji

2017-01-01

The ingestion of a foreign body is relatively common. However, it rarely results in the perforation of gastrointestinal tract. We herein report an unusual case of malignant lymphoma incidentally diagnosed after the perforation of the small intestine by a fish bone. A 90-year-old woman was admitted to our hospital because of abdominal pain and vomiting. Abdominal computed tomography demonstrated free air and ascites in the abdominal cavity. In the pelvic cavity, a radiopaque linear shadow about 35mm in diameter was shown in the small intestine, and the stricture was exposed to the abdominal cavity. Therefore, a diagnosis of perforation of the small intestine due to ingestion of a foreign body and panperitonitis was made. Emergent laparotomy was performed. The intraoperative findings revealed perforation of the small intestine with a fish bone in the jejunum. Local inflammation at the perforation site was seen, and circulated wall thickness was observed at the distal side of the jejunum. Partial resection of the jejunum and anastomosis of jejuno-jejunostomy was performed. A pathological examination and immunohistochemical study of the resected specimen resulted in a diagnosis of malignant lymphoma of follicular lymphoma Grade 1. It is very difficult to identify the existence malignancy accompanied with gastrointestinal perforation with ingestion of a foreign body. In cases suspected of involving malignancy, careful observation during surgery is needed in order to avoid missing the accompanying malignancy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Learning L2 Collocations Incidentally from Reading

ERIC Educational Resources Information Center

Pellicer-Sánchez, Ana

2017-01-01

Previous studies have shown that intentional learning through explicit instruction is effective for the acquisition of collocations in a second language (L2) (e.g. Peters, 2014, 2015), but relatively little is known about the effectiveness of incidental approaches for the acquisition of L2 collocations. The present study examined the incidental…

Awareness and Learning under Incidental Learning Conditions

ERIC Educational Resources Information Center

Rogers, John

2017-01-01

Recent years have witnessed a strong and increasing interest in the incidental learning of second language grammar. While much of this research has focused on the acquisition of second language word order or noun-determiner systems, relatively fewer studies have examined the learning of second language morphology. Results of studies that have…

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…

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. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Laser-supported diaphanoscopy: an innovative technique for locating gastric stromal tumors in gastroscopic-laparoscopic rendezvous: a case series.

PubMed

Patrzyk, M; Schreiber, A; Heidecke, C D; Glitsch, A

2009-12-01

Development of an innovative method of endoscopic laser-supported diaphanoscopy, for precise demonstration of the location of gastrointestinal stromal tumors (GISTs) at laparoscopy is described. The equipment consists of a light transmission cable with an anchoring system for the gastric mucosa, a connecting system for the light source, and the laser light source itself. During surgery, transillumination by laser is used to show the shape of the tumor. The resection margins are then marked by electric coagulation. Ten patients have been successfully treated using this technique in laparoscopic-endoscopic rendezvous procedures. Average time of surgery was 123 minutes. The time for marking the shape of the tumor averaged 16 minutes. Depending on tumor location and size, 4-7 marks were used, and resection margins were 4-15 mm. This new and effective technique facilitates precise locating of gastric GISTs leading to exact and tissue-sparing transmural laparoscopic resections. Georg Thieme Verlag KG Stuttgart New York.

Upper Gastrointestinal Complications and Cardiovascular/Gastrointestinal Risk Calculator in Patients with Myocardial Infarction Treated with Aspirin.

PubMed

Wen, Lei

2017-08-20

Aspirin is widely used for the prevention of cardiovascular and cerebrovascular diseases for the past few years. However, much attention has been paid to the adverse effects associated with aspirin such as gastrointestinal bleeding. How to weigh the benefits and hazards? The current study aimed to assess the feasibility of a cardiovascular/gastrointestinal risk calculator, AsaRiskCalculator, in predicting gastrointestinal events in Chinese patients with myocardial infarction (MI), determining unique risk factor(s) for gastrointestinal events to be considered in the calculator. The MI patients who visited Shapingba District People's Hospital between January 2012 and January 2016 were retrospectively reviewed. Based on gastroscopic data, the patients were divided into two groups: gastrointestinal and nongastrointestinal groups. Demographic and clinical data of the patients were then retrieved for statistical analysis. Univariate and multiple logistic regression analyses were used to identify independent risk factors for gastrointestinal events. The receiver operating characteristic (ROC) curves were used to assess the predictive value of AsaRiskCalculator for gastrointestinal events. A total of 400 MI patients meeting the eligibility criteria were analyzed, including 94 and 306 in the gastrointestinal and nongastrointestinal groups, respectively. The data showed that age, male gender, predicted gastrointestinal events, and Helicobacter pylori (HP) infection were positively correlated with gastrointestinal events. In multiple logistic regression analysis, predicted gastrointestinal events and HP infection were identified as risk factors for actual gastrointestinal events. HP infection was highly predictive in Chinese patients; the ROC curve indicated an area under the curve of 0.822 (95% confidence interval: 0.774-0.870). The best diagnostic cutoff point of predicted gastrointestinal events was 68.0‰, yielding sensitivity and specificity of 60.6% and 93

12 CFR 1501.2 - What activities has the Secretary determined to be financial in nature or incidental to a...

Code of Federal Regulations, 2010 CFR

2010-01-01

... be financial in nature or incidental to a financial activity? 1501.2 Section 1501.2 Banks and Banking... Secretary determined to be financial in nature or incidental to a financial activity? (a) Activities... of activities are financial in nature or incidental to a financial activity when conducted pursuant...

12 CFR 1501.2 - What activities has the Secretary determined to be financial in nature or incidental to a...

Code of Federal Regulations, 2012 CFR

2012-01-01

... be financial in nature or incidental to a financial activity? 1501.2 Section 1501.2 Banks and Banking... Secretary determined to be financial in nature or incidental to a financial activity? (a) Activities... of activities are financial in nature or incidental to a financial activity when conducted pursuant...

12 CFR 1501.2 - What activities has the Secretary determined to be financial in nature or incidental to a...

Code of Federal Regulations, 2014 CFR

2014-01-01

... to be financial in nature or incidental to a financial activity? 1501.2 Section 1501.2 Banks and... the Secretary determined to be financial in nature or incidental to a financial activity? (a... following types of activities are financial in nature or incidental to a financial activity when conducted...

12 CFR 1501.2 - What activities has the Secretary determined to be financial in nature or incidental to a...

Code of Federal Regulations, 2013 CFR

2013-01-01

... be financial in nature or incidental to a financial activity? 1501.2 Section 1501.2 Banks and Banking... Secretary determined to be financial in nature or incidental to a financial activity? (a) Activities... of activities are financial in nature or incidental to a financial activity when conducted pursuant...

12 CFR 1501.2 - What activities has the Secretary determined to be financial in nature or incidental to a...

Code of Federal Regulations, 2011 CFR

2011-01-01

... be financial in nature or incidental to a financial activity? 1501.2 Section 1501.2 Banks and Banking... Secretary determined to be financial in nature or incidental to a financial activity? (a) Activities... of activities are financial in nature or incidental to a financial activity when conducted pursuant...

77 FR 17033 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy's Training...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-23

... take marine mammals by harassment incidental to its training activities at the Gulf of Mexico (GOMEX... Importing Marine Mammals: Taking Marine Mammals Incidental to Navy's Training Activities at the Gulf of Mexico Range Complex AGENCY: National Marine Fisheries Service (NMFS), National Oceanic and Atmospheric...

The Influence of Two Cognitive-Linguistic Variables on Incidental Word Learning in 5-Year-Olds

ERIC Educational Resources Information Center

Abel, Alyson D.; Schuele, C. Melanie

2014-01-01

The relation between incidental word learning and two cognitive-linguistic variables--phonological memory and phonological awareness--is not fully understood. Thirty-five typically developing, 5-year-old, preschool children participated in a study examining the association between phonological memory, phonological awareness, and incidental word…

Stromal loss of TGFβ drives cancer growth in the epithelium via inflammation | Center for Cancer Research

Cancer.gov

Interactions between epithelial and stromal cells play an important role in cancer development and progression. Epithelial cancers develop when changes occur to tumor suppressor genes in stromal fibroblast cells. For example, loss of tumor suppressor, p53, in stromal fibroblasts leads to p53 inactivation in the epithelium in a prostate cancer model, and disruption of the transforming growth factor-b receptor II (TGF-βRII) in stromal fibroblasts results in intraepithelial dysplasia in prostate cancer and invasive squamous cell carcinoma (SCC) in mouse forestomach.

Activation of NK Cells in Mixed Cultures of Wharton's Jelly Mesenchymal Stromal Cells and Peripheral Blood Lymphocytes.

PubMed

Svirshchevskaya, E V; Poltavtsev, A M; Os'mak, G Zh; Poltavtseva, R A

2018-01-01

Mesenchymal stromal cells possess immunosuppressive properties that might be used for the therapy of inflammatory diseases of various geneses. The effects of mesenchymal stromal cells depend on their lifetime in the recipient tissues. During heterologous transplantation, mesenchymal stromal cells are eliminated by NK cells. We studied NK cell formation in mixed cultures of Wharton's jelly mesenchymal stromal cells and peripheral blood lymphocytes from an autologous donor. Lymphocytes were activated by a mitogen or IL-2. The lifetime of mesenchymal stromal cells was estimated by MTT test. Cytotoxic activity and phenotype of NK cells were evaluated by flow cytometry. It was found that activation of NK cells depended on IL-2 and was registered on day 2 of incubation with IL-2. In cultures with mitogen-activated lymphocytes, cytotoxicity was observed after 5-6 days. Cytotoxicity of NK correlated with significant decrease in CD16+ and increase in CD56+ NK and with reduction of mesenchymal stromal cell viability. Thus, the main mechanism of elimination of mesenchymal stromal cells is cytotoxicity of NK cells that depended on IL-2 production.

Breast tumors educate stromal tissue with individualized but coordinated proteomic signatures

PubMed Central

Wang, Xuya; Mooradian, Arshag D.; Erdmann-Gilmore, Petra; Zhang, Qiang; Viner, Rosa; Davies, Sherri R.; Huang, Kuan-lin; Bomgarden, Ryan; Van Tine, Brian A.; Shao, Jieya; Ding, Li; Li, Shunqiang; Ellis, Matthew J.; Rogers, John C.; Townsend, R. Reid; Fenyö, David; Held, Jason M.

2017-01-01

Cancer forms specialized microenvironmental niches that promote local invasion and colonization. Engrafted patient-derived xenografts (PDXs) locally invade and colonize naïve stroma, while enabling unambiguous molecular discrimination of human proteins in the tumor from mouse proteins in the microenvironment. To characterize how patient breast tumors form a niche and educate naïve stroma, subcutaneous breast cancer PDXs were globally profiled using species-specific quantitative proteomics. Regulation of PDX stromal proteins by breast tumors was extensive, with thirty-five percent of the stromal proteome consistently altered by tumors across different animals and passages. Differentially regulated proteins in the stroma clustered into six signatures that included both known and novel contributors to tumor invasion and colonization. Stromal proteomes were coordinately regulated, though the sets of proteins altered by each tumor were highly distinct. Integrated analysis of tumor and stromal proteins, a comparison possible in xenograft models, indicated that the known hallmarks of cancer contribute pleiotropically to establishing and maintaining the tumor’s microenvironmental niche. Tumor education of the stroma is therefore an intrinsic property of breast tumors that is highly individualized, yet proceeds by consistent, non-random and defined tumor-promoting molecular alterations. PMID:28790197

Changing the Properties of Multipotent Mesenchymal Stromal Cells by IFNγ Administration.

PubMed

Petinati, N A; Kapranov, N M; Bigil'deev, A E; Popova, M D; Davydova, Yu O; Gal'tseva, I V; Drize, N I; Kuz'mina, L A; Parovichnikova, E N; Savchenko, V G

2017-06-01

We studied changes in the population of human multipotent mesenchymal stromal cells activated by IFNγ. The cells were cultured under standard conditions; IFNγ was added in various concentrations for 4 h or over 2 passages. It was shown that the total cell production significantly decreased after long-term culturing with IFNγ, but 4-h exposure did not affect this parameter. After 4-h culturing, the expression levels of IDO1, CSF1, and IL-6 increased by 300, 7, and 2.4 times, respectively, and this increase persisted 1 and 2 days after removal of IFNγ from the culture medium. The expression of class I and II MHC (HLA) on cell surface practically did not change immediately after exposure to IFNγ, but during further culturing, HLA-ABC (MHC I) and HLA-DR (MHC II) expression significantly increased, which abolished the immune privilege in these cells, the property allowing clinical use of allogenic multipotent mesenchymal stromal cells. Multipotent mesenchymal stromal cells can suppress proliferation of lymphocytes. The degree of this suppression depends on individual properties of multipotent mesenchymal stromal cell donor. Treatment with IFNγ did not significantly affect the intensity of inhibition of lymphocyte proliferation by these cells.

Psychosocial consequences and severity of disclosed incidental findings from whole-body MRI in a general population study.

PubMed

Schmidt, Carsten Oliver; Hegenscheid, Katrin; Erdmann, Pia; Kohlmann, Thomas; Langanke, Martin; Völzke, Henry; Puls, Ralf; Assel, Heinrich; Biffar, Reiner; Grabe, Hans Jörgen

2013-05-01

Little is known about the psychosocial impact and subjective interpretation of communicated incide ntal findings from whole-body magnetic resonance imaging (wb-MRI). This was addressed with this general population study. Data was based on the Study of Health in Pomerania (SHIP), Germany. SHIP comprised a 1.5-T wb-MRI examination. A postal survey was conducted among the first 471 participants, aged 23-84 years, who received a notification about incidental findings (response 86.0 %, n = 405). The severity of incidental findings was assessed from the participants' and radiologists' perspective. In total, 394 participants (97.3 %) wanted to learn about their health by undergoing wb-MRI. Strong distress while waiting for a potential notification of an incidental finding was reported by 40 participants (9.9 %), whereas 116 (28.6 %) reported moderate to severe psychological distress thereafter. Strong disagreement was noted between the subjective and radiological evaluation of the findings' severity (kappa = 0.02). Almost all participants (n = 389, 96.0 %) were very satisfied with their examination. Despite the high satisfaction of most participants, there were numerous adverse consequences concerning the communication of incidental findings and false expectations about the likely potential benefits of whole-body-MRI. • Disclosed incidental findings from MRI may lead to substantial psychosocial distress. • Subjective and radiological evaluations of incidental findings' severity differ strongly. • Disclosing incidental findings is strongly endorsed by study volunteers. • Study volunteers tend to have false expectations about potential benefits from MRI. • Minimizing stress in study volunteers should be a key aim in MRI research.

Inflammatory response of a prostate stromal cell line induced by Trichomonas vaginalis.

PubMed

Im, S J; Han, I H; Kim, J H; Gu, N Y; Seo, M Y; Chung, Y H; Ryu, J S

2016-04-01

While Trichomonas vaginalis, a cause of sexually transmitted infection, is known as a surface-dwelling protozoa, trichomonads have been detected in prostatic tissue from benign prostatic hyperplasia and prostatitis by immunoperoxidase assay or PCR. However, the immune response of prostate stromal cells infected with T. vaginalis has not been investigated. Our objective was to investigate whether T. vaginalis could induce an inflammatory response in prostate stromal cells. Incubation of a human prostate stromal myofibroblast cells (WPMY-1) with live T. vaginalis T016 increased expression of the inflammatory chemokines CXCL8 and CCL2. In addition, TLR4, ROS, MAPK and NF-κB expression increased, while inhibitors of TLR4, ROS, MAPKs and NF-κB reduced CXCL8 and CCL2 production. Medium conditioned by incubation of WPMY-1 cells with T. vaginalis stimulated the migration of human neutrophils and monocytes (THP-1 cells). We conclude that T. vaginalis increases CXCL8 and CCL2 production by human prostate stromal cells by activating TLR4, ROS, MAPKs and NF-κB, and this in turn attracts neutrophils and monocytes and leads to an inflammatory response. This study is the first attempt to demonstrate an inflammatory reaction in prostate stromal cells caused by T. vaginalis. © 2016 John Wiley & Sons Ltd.

A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development

DTIC Science & Technology

2016-05-01

1 AWARD NUMBER: W81XWH-15-1-0082 TITLE: A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development PRINCIPAL INVESTIGATOR: Qinglei Li...5a. CONTRACT NUMBER A New Paradigm for Ovarian Sex Cord-Stromal Tumor Development 5b. GRANT NUMBER W81XWH-15-1-0082 5c. PROGRAM ELEMENT NUMBER 6...role of sustained activation of oocyte TGFBR1 in ovarian tumor development using an in vitro approach. 2. Keywords Ovarian tumor, Sex cord

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

PubMed

Bellera, C A; Penel, N; Ouali, M; Bonvalot, S; Casali, P G; Nielsen, O S; Delannes, M; Litière, S; Bonnetain, F; Dabakuyo, T S; Benjamin, R S; Blay, J-Y; Bui, B N; Collin, F; Delaney, T F; Duffaud, F; Filleron, T; Fiore, M; Gelderblom, H; George, S; Grimer, R; Grosclaude, P; Gronchi, A; Haas, R; Hohenberger, P; Issels, R; Italiano, A; Jooste, V; Krarup-Hansen, A; Le Péchoux, C; Mussi, C; Oberlin, O; Patel, S; Piperno-Neumann, S; Raut, C; Ray-Coquard, I; Rutkowski, P; Schuetze, S; Sleijfer, S; Stoeckle, E; Van Glabbeke, M; Woll, P; Gourgou-Bourgade, S; Mathoulin-Pélissier, S

2015-05-01

The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Bevacizumab in Treating Patients With Recurrent Sex Cord-Stromal Tumors of the Ovary

ClinicalTrials.gov

2018-03-20

Malignant Ovarian Epithelial Tumor; Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

Incidental Testicular Irradiation From Prostate IMRT: It All Adds Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, Christopher R., E-mail: crking@stanford.ed; Maxim, Peter G.; Hsu, Annie

Purpose: To identify the technical aspects of image-guided intensity-modulated radiation therapy (IMRT) for localized prostate cancer that could result in a clinically meaningful incidental dose to the testes. Methods and Materials: We examined three sources that contribute incidental dose to the testes, namely, from internal photon scattering from IMRT small field and large pelvic nodal fields with 6 or 15 MV, from neutrons when >10-MV photons are used, and from daily image-guided fiducial-based portal imaging. Using clinical data from 10 patients who received IMRT for prostate cancer, and thermo-luminescent dosimeter measurements in phantom, we estimated the dose to the testesmore » from each of these sources. Results: A mean testicular dose of 172 and 220 cGy results from internal photon scatter for pelvic nodal fields and 68 and 93 cGy for prostate-only fields, for 6- and 15-MV energies, respectively. For 15-MV photon energies, the mean testicular dose from neutrons is 60 cGy for pelvic fields and 31 cGy for prostate-only fields. From daily portal MV image guidance, the testes-in-field mean dose is 350 cGy, whereas the testes-out-of-field scatter dose is 16 cGy. Dosimetric comparisons between IMRT using 6-MV and 15-MV photon energies are not significantly different. Worst-case scenarios can potentially deliver cumulative incidental mean testicular doses of 630 cGy, whereas best-case scenarios can deliver only 84 cGy. Conclusions: Incidental dose to the testes from prostate IMRT can be minimized by opting to restrict the use of elective pelvic nodal fields, by choosing photon energies <10 MV, and by using the smallest port sizes necessary for daily image guidance.« less

78 FR 26751 - Taking of Threatened or Endangered Marine Mammals Incidental to Commercial Fishing Operations...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... years to authorize the incidental, but not intentional, taking of three stocks of marine mammals listed..., shall for a period of up to three years allow the incidental taking of marine mammal species listed... full year post- Take Reduction Plan implementation (October 30, 1997)), through December 31, 2011. This...

77 FR 55645 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to Construction and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

... Incidental to Construction and Operation of a Liquefied Natural Gas Deepwater Port in the Gulf of Mexico... Incidental to Construction and Operation of a Liquefied Natural Gas Deepwater Port in the Gulf of Mexico...), Commerce. ACTION: Proposed rule; request for comments. SUMMARY: NMFS has received a request from Port...

Prevalence and histopathological characteristics of corneal stromal dystrophies in Saudi Arabia.

PubMed

Alzuhairy, Sultan; Alkatan, Hind M; Al-Rajhi, Ali A

2015-01-01

The aim was to determine the frequency and describe the main histopathologic features of corneal stromal dystrophy in Saudi Arabia. A single-center, retrospective analysis of 193 corneal specimens diagnosed with stromal dystrophy. All samples were retrieved from the Histopathology Department at King Khaled Eye Specialist Hospital over a 10-year period (2002 to December 31, 2011). Cases of stromal dystrophy undergoing keratoplasty were included in the study. Routine histopathologic stains and specific stains were used to determine a diagnosis. The corresponding demographic data and basic clinical/surgical information were collected via chart review. The study sample was comprised of 193 eyes. The final diagnoses were macular corneal dystrophy (MCD) in 180 (93.26%) eyes, granular corneal dystrophy (GCD) in 9 (4.66%) and lattice corneal dystrophy (LCD) in 4 (2.07%) eyes. The mean age at presentation was 27.03 years for MCD, 26.33 years for GCD and 53.75 years for LCD. The interval between diagnosis and surgical intervention was not statistically different between the macular and granular groups (P = 0.141). There was a positive family history for the MCD (37.22%) and GCD (44.44%) groups. All eyes underwent penetrating keratoplasty (PKP) except 10 MCD cases that underwent lamellar keratoplasty. Diffuse stromal deposits were present in 87.2% of MCD corneas and 66.67% of GCD corneas. Seventeen eyes with MCD were misdiagnosed as GCD. None of the LCD cases were clinically identified since all of these cases were diagnosed as corneal scarring. In eyes with MCD that underwent PKP, there was diffuse stromal involvement (in 87.22% eyes) and changes in Descemet's membrane (in 53.5% eyes). This pathological study suggested that MCD was the most common corneal stromal dystrophy that required keratoplasty in Saudi Arabia. Patient with MCD and GCD presented at a significantly younger age than LCD. The clinical diagnosis of MCD is not achieved in all cases likely due to a more

Prevalence and Histopathological Characteristics of Corneal Stromal Dystrophies in Saudi Arabia

PubMed Central

Alzuhairy, Sultan; Alkatan, Hind M.; Al-Rajhi, Ali A.

2015-01-01

Purpose: The aim was to determine the frequency and describe the main histopathologic features of corneal stromal dystrophy in Saudi Arabia. Methods: A single-center, retrospective analysis of 193 corneal specimens diagnosed with stromal dystrophy. All samples were retrieved from the Histopathology Department at King Khaled Eye Specialist Hospital over a 10-year period (2002 to December 31, 2011). Cases of stromal dystrophy undergoing keratoplasty were included in the study. Routine histopathologic stains and specific stains were used to determine a diagnosis. The corresponding demographic data and basic clinical/surgical information were collected via chart review. Results: The study sample was comprised of 193 eyes. The final diagnoses were macular corneal dystrophy (MCD) in 180 (93.26%) eyes, granular corneal dystrophy (GCD) in 9 (4.66%) and lattice corneal dystrophy (LCD) in 4 (2.07%) eyes. The mean age at presentation was 27.03 years for MCD, 26.33 years for GCD and 53.75 years for LCD. The interval between diagnosis and surgical intervention was not statistically different between the macular and granular groups (P = 0.141). There was a positive family history for the MCD (37.22%) and GCD (44.44%) groups. All eyes underwent penetrating keratoplasty (PKP) except 10 MCD cases that underwent lamellar keratoplasty. Diffuse stromal deposits were present in 87.2% of MCD corneas and 66.67% of GCD corneas. Seventeen eyes with MCD were misdiagnosed as GCD. None of the LCD cases were clinically identified since all of these cases were diagnosed as corneal scarring. In eyes with MCD that underwent PKP, there was diffuse stromal involvement (in 87.22% eyes) and changes in Descemet's membrane (in 53.5% eyes). Conclusion: This pathological study suggested that MCD was the most common corneal stromal dystrophy that required keratoplasty in Saudi Arabia. Patient with MCD and GCD presented at a significantly younger age than LCD. The clinical diagnosis of MCD is not achieved

Views of nonmedical, health system professionals regarding the return of whole genome sequencing incidental findings.

PubMed

Strong, Kimberly A; Zusevics, Kaija L; Bick, David P; Veith, Regan

2014-10-01

Use of genome sequencing in the clinic continues to increase. In addition to its potential to provide findings of clinical benefit, it also has the potential to identify findings unrelated to the indication for testing (incidental findings). Incidental findings are the subject of considerable debate, particularly following the publication of recommendations by the American College of Medical Genetics and Genomics. This debate involves how and which results should be returned as well as stakeholders' desires for such results. Part of the difficulty in determining best practice in relation to returning incidental findings is the dearth of empirical data available regarding laypersons' attitudes and desire for the sometimes controversial information. In an effort to contribute data on views regarding the return of incidental findings following genome sequencing in a clinical setting, a survey specifically designed around the various types of incidental findings that occur, ranging from clinically actionable to nonactionable, was administered to a nonmedical population of medical coders working at a medical school (N = 97). Almost all (98%) of the respondents were women, 80% had 6 or more years of experience as a medical coder, and about three-fourths (74%) of participants reported that they had children. The group surveyed was considerably more interested in receiving all types of results for both themselves and their children than previously surveyed genetics professionals. Results from this study offer a snapshot of opinions beyond those of the professional genetic community and demonstrate a striking difference between genetic professionals and a more lay population in terms of their attitudes and desires regarding the return of incidental findings. Additional research is needed to explain the nuances in the perspectives motivating these variations.

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed Central

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T.

2013-01-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. PMID:23770322

TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?

PubMed

Piao, Yun-shang; Wiesenfeld, Paddy; Sprando, Robert; Arnold, Julia T

2013-11-01

The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. Published by Elsevier Ltd.

The role of demographic compensation theory in incidental take assessments for endangered species

USGS Publications Warehouse

McGowan, Conor P.; Ryan, Mark R.; Runge, Michael C.; Millspaugh, Joshua J.; Cochrane, Jean Fitts

2011-01-01

Many endangered species laws provide exceptions to legislated prohibitions through incidental take provisions as long as take is the result of unintended consequences of an otherwise legal activity. These allowances presumably invoke the theory of demographic compensation, commonly applied to harvested species, by allowing limited harm as long as the probability of the species' survival or recovery is not reduced appreciably. Demographic compensation requires some density-dependent limits on survival or reproduction in a species' annual cycle that can be alleviated through incidental take. Using a population model for piping plovers in the Great Plains, we found that when the population is in rapid decline or when there is no density dependence, the probability of quasi-extinction increased linearly with increasing take. However, when the population is near stability and subject to density-dependent survival, there was no relationship between quasi-extinction probability and take rates. We note however, that a brief examination of piping plover demography and annual cycles suggests little room for compensatory capacity. We argue that a population's capacity for demographic compensation of incidental take should be evaluated when considering incidental allowances because compensation is the only mechanism whereby a population can absorb the negative effects of take without incurring a reduction in the probability of survival in the wild. With many endangered species there is probably little known about density dependence and compensatory capacity. Under these circumstances, using multiple system models (with and without compensation) to predict the population's response to incidental take and implementing follow-up monitoring to assess species response may be valuable in increasing knowledge and improving future decision making.

HOX and TALE signatures specify human stromal stem cell populations from different sources.

PubMed

Picchi, Jacopo; Trombi, Luisa; Spugnesi, Laura; Barachini, Serena; Maroni, Giorgia; Brodano, Giovanni Barbanti; Boriani, Stefano; Valtieri, Mauro; Petrini, Mario; Magli, Maria Cristina

2013-04-01

Human stromal stem cell populations reside in different tissues and anatomical sites, however a critical question related to their efficient use in regenerative medicine is whether they exhibit equivalent biological properties. Here, we compared cellular and molecular characteristics of stromal stem cells derived from the bone marrow, at different body sites (iliac crest, sternum, and vertebrae) and other tissues (dental pulp and colon). In particular, we investigated whether homeobox genes of the HOX and TALE subfamilies might provide suitable markers to identify distinct stromal cell populations, as HOX proteins control cell positional identity and, together with their co-factors TALE, are involved in orchestrating differentiation of adult tissues. Our results show that stromal populations from different sources, although immunophenotypically similar, display distinct HOX and TALE signatures, as well as different growth and differentiation abilities. Stromal stem cells from different tissues are characterized by specific HOX profiles, differing in the number and type of active genes, as well as in their level of expression. Conversely, bone marrow-derived cell populations can be essentially distinguished for the expression levels of specific HOX members, strongly suggesting that quantitative differences in HOX activity may be crucial. Taken together, our data indicate that the HOX and TALE profiles provide positional, embryological and hierarchical identity of human stromal stem cells. Furthermore, our data suggest that cell populations derived from different body sites may not represent equivalent cell sources for cell-based therapeutical strategies for regeneration and repair of specific tissues. Copyright © 2012 Wiley Periodicals, Inc.

75 FR 18160 - Small Takes of Marine Mammals Incidental to Specified Activities; Antioch Bridge Seismic Retrofit...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-09

... of Marine Mammals Incidental to Specified Activities; Antioch Bridge Seismic Retrofit Project... pile driving associated with the Antioch Bridge Seismic Retrofit Project. DATES: Effective August 15... request from Caltrans to harass marine mammals incidental to the Antioch Bridge Seismic Retrofit Project...

The influence of two cognitive-linguistic variables on incidental word learning in 5-year-olds.

PubMed

Abel, Alyson D; Schuele, C Melanie

2014-08-01

The relation between incidental word learning and two cognitive-linguistic variables--phonological memory and phonological awareness--is not fully understood. Thirty-five typically developing, 5-year-old, preschool children participated in a study examining the association between phonological memory, phonological awareness, and incidental word learning. Children were exposed to target words in a read-aloud story that accompanied a wordless picture book. Target word comprehension was assessed before and after two readings of the story. Phonological awareness predicted incidental word learning but phonological memory did not. The influence of phonological awareness and phonological memory on word learning may be dependent on the demands of the word learning task.

30 CFR 937.702 - 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. 937.702 Section 937.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of Other...

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 Other...

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 Other...

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 of...

30 CFR 941.702 - 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. 941.702 Section 941.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

30 CFR 947.702 - 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. 947.702 Section 947.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

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 of...

30 CFR 912.702 - 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. 912.702 Section 912.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of Other...

30 CFR 942.702 - 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. 942.702 Section 942.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of Other...

30 CFR 939.702 - 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. 939.702 Section 939.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

30 CFR 933.702 - 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. 933.702 Section 933.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... other minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of...

30 CFR 910.702 - 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. 910.702 Section 910.702 Mineral Resources OFFICE OF SURFACE MINING RECLAMATION... minerals. Part 702 of this chapter, Exemption for Coal Extraction Incidental to the Extraction of Other...

Stromal loss of TGFβ drives cancer growth in the epithelium via inflammation | Center for Cancer Research

Cancer.gov

Interactions between epithelial and stromal cells play an important role in cancer development and progression. Epithelial cancers develop when changes occur to tumor suppressor genes in stromal fibroblast cells. For example, loss of tumor suppressor, p53, in stromal fibroblasts leads to p53 inactivation in the epithelium in a prostate cancer model, and disruption of the

Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate