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gastrointestinal stromal tumors

Saurabh Zanwar, Vikas Ostwal, Arvind Sahu, Deepak Jain, Anant Ramaswamy, Avanish Saklani, Mukta Ramadwar, Nitin Shetty, Shailesh V Shrikande
INTRODUCTION: There is scarce data relating to methods to improve sphincter preservation in rectal gastrointestinal stromal tumor (GIST). Increasing the duration of neoadjuvant (NA) imatinib resulting in improved sphincter preservation rate has not been established. This retrospective analysis looks at the rates of sphincter preservation in rectal GIST with NA imatinib and effect of duration of NA imatinib on the same to find out optimum duration of NA with respect to sphincter preservation in rectal GIST patients...
October 26, 2016: Indian Journal of Gastroenterology: Official Journal of the Indian Society of Gastroenterology
Takayoshi Shinya, Ryota Inai, Takashi Tanaka, Noriaki Akagi, Shuhei Sato, Tadashi Yoshino, Susumu Kanazawa
PURPOSE: The purpose of the present study was to analyze the enhancement patterns of small bowel neoplasms on post-contrast multiphasic multidetector CT and to assess the diagnostic capacity for differentiating five tumor types. METHODS: We performed a retrospective study of data on 92 small bowel neoplasms. The neoplasms were categorized into five groups according to pathology findings, not imaging findings (23 adenocarcinomas; 22 lymphomas; 19 metastases; 18 gastrointestinal stromal tumors [GIST]; 10 neuroendocrine tumors [NET])...
October 25, 2016: Abdominal Radiology
Hengning Ke, Julhash U Kazi, Hui Zhao, Jianmin Sun
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...
2016: Cell & Bioscience
Yemarshet K Gebreyohannes, Patrick Schöffski, Thomas Van Looy, Jasmien Wellens, Lise Vreys, Jasmien Cornillie, Ulla Vanleeuw, Dana T Aftab, Maria Debiec-Rychter, Raf Sciot, Agnieszka Wozniak
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...
October 24, 2016: Molecular Cancer Therapeutics
Christelle Bahlawane, Martine Schmitz, Elisabeth Letellier, Karthik Arumugam, Nathalie Nicot, Petr V Nazarov, Serge Haan
Mutations in KIT or PDGFRA are responsible for >85% of gastrointestinal stromal tumors. The introduction of imatinib in the GIST therapy scheme revolutionized the patient outcome. Unfortunately, the therapy allows the disease stabilization instead of curation. Furthermore the resistance to the inhibitor arises in most cases within two first years of therapy. A thorough investigation of the signalling pathways activated by the major PDGFRA and KIT mutants encountered in the GIST landscape allowed to identify striking differences between the two receptor tyrosine kinases...
October 21, 2016: Cellular Signalling
Rita Vale Rodrigues, Filipa Santos, João Pereira da Silva, Inês Francisco, Isabel Claro, Cristina Albuquerque, Maria Manuel Lemos, Manuel Limbert, António Dias Pereira
Multiple gastrointestinal stromal tumors (GISTs) caused by germline KIT gene mutations are an extremely rare autosomal dominant disorder. We report a case of a 21-year-old woman who presented to the emergency department with a 2-week history of asthenia, palpitations and upper gastrointestinal bleeding. After further clinical evaluation one gastric and two small bowel GISTs were diagnosed, which were surgically resected after neoadjuvant therapy with Imatinib. Diffuse hyperplasia of the interstitial cells of Cajal was also seen in the background gastric and small intestinal walls...
October 22, 2016: Familial Cancer
Manuel Guerrero-Hernandez, Carlos A Hinojosa, Javier E Anaya-Ayala, Erika Elenes, Aldo Torre
Portal vein (PV) thrombosis (PVT) in the absence of liver disease or thrombophilia is rare. We report a 57-year-old male with a history of stage 3 chronic kidney disease who presented at the emergency department 18 months after abdominal surgery with progressive abdominal pain and distention. Computed tomography revealed PVT with multiple collaterals and moderate ascites. He had undergone partial gastrectomy and gastrojejunal anastomosis at an outside facility for gastrointestinal stromal tumors that caused an iatrogenic stenotic lesion in the PV...
October 20, 2016: Vascular and Endovascular Surgery
Yong-Sik Bong, Shahin Assefnia, Therese Tuohy, Deborah W Neklason, Randall W Burt, Jaeil Ahn, Hao-Wen J Jiang, Stephen W Byers
Vitamin D is implicated in the etiology of cancers of the gastrointestinal tract, usually characterized by alteration in the APC/β-catenin/TCF tumor suppressor pathway. The vitamin D receptor (VDR) is also implicated in cardiovascular and skin diseases as well as in immunity. Activated VDR can indirectly alter β-catenin nuclear localization and directly suppress β-catenin/TCF mediated transcriptional activity. We treated VDR null mice with the carcinogen azoxymethane (AOM) and generated mice bearing a mutated APC (hypomorph) on a VDR null background (Apc1638N/+Vdr-/-)...
October 19, 2016: Oncotarget
Achim Paulmichl, Dominik Summer, Claudia Manzl, Christine Rangger, Francesca Orlandi, Sabrina Niedermoser, Takahiro Taguchi, Björn Wängler, Clemens Decristoforo
The gastrointestinal stromal tumor (GIST) is a rare disease with limited therapeutic options when resistance to tyrosine kinase inhibitor (TKI) treatment occurs. The authors investigated binding of various (68)Ga-labeled peptides, targeting receptors reported to be overexpressed in GIST, in different cell lines. For this purpose, three GIST cell lines were tested: GIST-T1, GIST882 (Imatinib sensitive), and GIST430 (Imatinib resistant). DOTA-NT 8-13 (targeting NTR1), DOTA-TATE (targeting SSTR2), CP04 (a minigastrin derivative targeting CCK2-R), VIP-DOTA (targeting VPAC2-R), and 2 DOTA-bombesin derivatives [targeting gastrin releasing peptide receptors (GRPR)] were radiolabeled with (68)Ga and incubated with the respective tumor cell and control cell lines...
October 2016: Cancer Biotherapy & Radiopharmaceuticals
Elsa Iannicelli, Francesco Carbonetti, Giulia Francesca Federici, Isabella Martini, Salvatore Caterino, Emanuela Pilozzi, Francesco Panzuto, Chiara Briani, Vincenzo David
OBJECTIVES: The aim of this study was to correlate computed tomography (CT) findings with pathology in gastrointestinal stromal tumors (GISTs). METHODS: A retrospective evaluation of CT images of 44 patients with GISTs was performed. Computed tomography findings analyzed were location, size, margins, degree and pattern of contrast enhancement, angiogenesis, necrosis, signs of invasion, peritoneal effusion, peritoneal implants, surface ulceration, and calcifications...
October 7, 2016: Journal of Computer Assisted Tomography
Richard Quek, Mohamad Farid, Yada Kanjanapan, Cindy Lim, Iain Beehuat Tan, Sittampalam Kesavan, Tony Kiat Hon Lim, Lynette Lin-Ean Oon, Brian Kp Goh, Weng Hoong Chan, Melissa Teo, Alexander Yf Chung, Hock Soo Ong, Wai Keong Wong, Patrick Tan, Desmond Yip
AIM: 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. METHODS: In total, 142 GIST patients with complete clinicopathologic and mutational data from two sites were included...
October 17, 2016: Asia-Pacific Journal of Clinical Oncology
Olivier Mir, Thomas Brodowicz, Antoine Italiano, Jennifer Wallet, Jean-Yves Blay, François Bertucci, Christine Chevreau, Sophie Piperno-Neumann, Emmanuelle Bompas, Sébastien Salas, Christophe Perrin, Corinne Delcambre, Bernadette Liegl-Atzwanger, Maud Toulmonde, Sarah Dumont, Isabelle Ray-Coquard, Stéphanie Clisant, Sophie Taieb, Cécile Guillemet, Maria Rios, Olivier Collard, Laurence Bozec, Didier Cupissol, Esma Saada-Bouzid, Christine Lemaignan, Wolfgang Eisterer, Nicolas Isambert, Loïc Chaigneau, Axel Le Cesne, Nicolas Penel
BACKGROUND: Regorafenib is a multikinase inhibitor with proven activity in refractory gastrointestinal stromal tumours and chemotherapy-refractory advanced colorectal cancers. We assessed this agent's efficacy and safety in patients with metastatic soft tissue sarcomas previously treated with anthracycline. METHODS: In this randomised, double-blind, phase 2 trial undertaken in France and Austria, we enrolled patients aged 18 years and older with advanced soft tissue sarcomas who had received previous doxorubicin or other anthracycline treatment...
October 14, 2016: Lancet Oncology
Yasunori Minami, Tomohiro Minami, Hirokazu Chishina, Masashi Kono, Tadaaki Arizumi, Masahiro Takita, Norihisa Yada, Satoru Hagiwara, Hiroshi Ida, Kazuomi Ueshima, Naoshi Nishida, Masatoshi Kudo
OBJECTIVE: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. METHODS: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1)...
2016: Digestive Diseases
Tohru Takahashi, Yumiko Maruyama, Mayuko Saitoh, Hideto Itoh, Mitsuru Yoshimoto, Masayuki Tsujisaki, Masato Nakayama
A 64 year-old woman with steroid-dependent immune thrombocytopenia developed anemia. Esophagogastroduodenoscopy revealed the presence of a tumor, which was diagnosed to be diffuse large B-cell lymphoma, in the second portion of the duodenum. (18)F-fluorodeoxy glucose positron emission tomography showed an increased uptake mass in the pelvic cavity as well as in the duodenum. Though the duodenal tumor disappeared after 4 cycles of chemotherapy, the pelvic mass did not shrink in size. As a result, laparoscopic resection of the pelvic tumor was performed and the tumor was histologically diagnosed to be a gastrointestinal stromal tumor...
2016: Internal Medicine
Eun Jeong Gong, Do Hoon Kim
Subepithelial lesions occasionally found in the stomach of patients undergoing endoscopy may be either benign lesions or tumors with malignant potential. They may also appear due to extrinsic compression. Discrimination of gastric subepithelial lesions begins with meticulous endoscopic examination for size, shape, color, mobility, consistency, and appearance of the overlying mucosa. Accurate diagnosis can be achieved with endoscopic ultrasonography, which provides useful information on the exact size, layer-of-origin, and characteristic morphologic features to support a definitive diagnosis...
September 2016: Clinical Endoscopy
S F Lax
The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma)...
October 13, 2016: Der Pathologe
Susannah O'Sullivan, Mei Lin Tay, Jian-Ming Lin, Usha Bava, Karen Callon, Jillian Cornish, Dorit Naot, Andrew Grey
Nilotinib and imatinib are tyrosine kinase inhibitors (TKIs) used in the treatment of chronic myeloid leukemia (CML) and gastrointestinal stromal tumors (GIST). In vitro, imatinib and nilotinib inhibit osteoclastogenesis, and in patients they reduce levels of bone resorption. One of the mechanisms that might underlie these effects is an increase in the production of osteoprotegerin (OPG). In the current work we report that platelet-derived growth factor receptor beta (PDGFRβ) signaling regulates OPG production in vitro...
2016: PloS One
Dieter Zopf, Iduna Fichtner, Ajay Bhargava, Wolfram Steinke, Karl-Heinz Thierauch, Konstanze Diefenbach, Scott Wilhelm, Frank-Thorsten Hafner, Michael Gerisch
Regorafenib is an orally administered inhibitor of protein kinases involved in tumor angiogenesis, oncogenesis, and maintenance of the tumor microenvironment. Phase III studies showed that regorafenib has efficacy in patients with advanced gastrointestinal stromal tumors or treatment-refractory metastatic colorectal cancer. In clinical studies, steady-state exposure to the M-2 and M-5 metabolites of regorafenib was similar to that of the parent drug; however, the contribution of these metabolites to the overall observed clinical activity of regorafenib cannot be investigated in clinical trials...
October 13, 2016: Cancer Medicine
Yoshiaki Maeda, Toshiki Shinohara, Tomonari Katayama, Akihisa Nagatsu, Noriaki Futakawa, Tomonori Hamada
Gastrointestinal stromal tumors (GISTs) of the stomach presenting as an intra-abdominal abscess are extremely rare. We herein report a case that underwent successful laparoscopic resection of gastric GIST presenting with an intra-abdominal abscess. A 70-year-old man presented with a 3-day history of acute upper abdominal pain with a fever. Laboratory data showed an elevated white blood cell count and C-reactive protein level. A CT scan revealed a mass of mixed solid and fluid components, measuring 5.5 cm, in the adjacent lesser curvature of the stomach...
May 2016: Case Reports in Gastroenterology
Nikhil Sonthalia, Samit S Jain, Ravindra G Surude, Vinay B Pawar, Suhas Udgirkar, Pravin M Rathi
Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus...
2016: Clinical Medicine Insights. Gastroenterology
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