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Needle tract seeding and abdominal recurrence following pre-treatment biopsy of gastrointestinal stromal tumors (gist): results of a systematic review

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BMC SURGERY 2022年第1期22卷 1-9页

作者： Jakob, Jens Salameh, Rashad Wichmann, David Charalambous, Nicos Zygmunt, Anne-Christine Kreisel, Inga Heinz, Judith Ghadimi, Michael Ronellenfitsch, Ulrich Univ Med Ctr Mannheim Dept Surg Sarcoma Unit Th Kutzer Ufer 1-3 D-68163 Mannheim Germany Univ Hosp Dresden Dept Visceral Thorac Vasc & Transplant Surg Dresden Germany Univ Med Ctr Dept Gen Visceral & Pediat Surg Gottingen Germany Univ Med Ctr Goettingen Dept Med Stat Gottingen Germany Univ Hosp Halle Dept Surg Halle Germany

Background Gastrointestinal stromal tumors (gist) are rare abdominal tumors. Pretreatment biopsies may be used to diagnose a gist and enable tailored treatment. Some experts are skeptical about biopsies because they fear tumor cell seeding. The objective of this study was to determine if pretreatment biopsy is associated with increased tumor recurrence. Methods We performed a systematic literature search and included studies assessing the oncological outcome of gist patients who underwent a pre-treatment core needle biopsy or fine needle aspiration. We assessed methodological quality with the Newcastle-Ottawa-Scale for non-randomized studies. This review was registered in the PROSPERO database (CRD42021170290). Results Three non-randomized studies and eight case reports comprising 350 patients were eligible for inclusion. No prospective study designed to answer the review question was found. One case of needle tract seeding after percutaneous core needle biopsy of gist was reported. None of the studies reported an increased rate of abdominal recurrence in patients with pretreatment biopsy. Conclusions The existing evidence does not indicate a relevant risk of needle tract seeding or abdominal recurrence after pre-treatment biopsy of gist. Biopsy can safely be done to differentiate gist from other tumors and to select the most appropriate treatment.

关键词： Core needle biopsy Fine needle aspiration FNA Preoperative biopsy Metastasis gist

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Gastrointestinal stromal tumors (gist):: the yield of endoscopic ultrasonography and fine needle aspiration

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ACTA ENDOSCOPICA 2006年第1期36卷 81-86页

作者： Boustiere, Ch. Hop St Joseph Serv Hepatogastroenterol Marseille France

Stromal tumors or gist are unfrequent tumors either incidentally found or diagnosed in case of complications. Endoscopic ultrasonography (EUS) is actually the best examination to confirm the diagnosis of solid submucosal tumors mainly represented by gists, whereas the leiomyomas are snore frequent in esophagus. The fine needle aspiration (FNA) can easily confirm the diagnosis of gist with the presence of a specific marker (C-Kit) on the cytologic specimens. However the prognosis of such tumors remains difficult to assess despite histologic analysis and the potential risk of maligancy usually requires a surgical treatment. Targeted therapies, and especially imatinib mesylate, have radically changed the outcome of most severe diseases.

关键词： endoscopic ultrasonography (EUS) fine needle aspiration stromal tumors gist

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Barriers to mutational testing in patients with gastrointestinal stromal tumors (gist) - a survey of life raft group members

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BMC GASTROENTEROLOGY 2022年第1期22卷 1-10页

作者： Montoya, Denisse Call, Jerry W. Eshak, Jennily Knox, Pete Luedke, Maeven Kaur, Sahibjeet Rothschild, Sara Garland, Mary Scherzer, Norman J. Life Raft Grp 155 US 46 HighwaySuite 202 Wayne NJ 07470 USA

Background Due to the low mutational testing rate in patients with Gastrointestinal Stromal Tumors (gist), The Life Raft Group (LRG), a non-profit organization that provides support, advocacy and conducts research for patients with gist, analyzed various factors that may have an impact on patients' ability to receive mutational testing. Methods A survey about mutational testing for patients with gist or their caregivers, was conducted in June 2020. The survey, sent to 1004 gist patients and caregivers through email, was promoted through social media with instructions to contact the LRG to participate. The survey was designed by the LRG Patient Registry Department. Members of the LRG, regardless of Patient Registry status, were eligible to participate. Results A total of 295 patients/caregivers participated in this study (response rate: 29.4%). The percentage of patients who indicated they had received mutational testing was much higher in this survey (80%) than in the general gist community (26.7%). Several reasons were cited for having a test, including: "My doctor ordered/suggested that I have it done" (54%);"The Life Raft Group advised/suggested I have it done" (25%);"I asked my doctor to have it done" (22%);"I had it done as part of a clinical trial" (5%);"I am not sure" (3%) and "Other" (14%). Mutational testing resulted in a treatment change in 25% of cases. Patients were able to select more than one option when completing this question resulting in a percentage greater than 100. Conclusions The LRG membership is voluntary and proactive;patients who join are more likely to participate in surveys and mutational testing, as well as more likely to have a gist specialist. Mutational testing can influence understanding of a patient's gist and the treatment best suited to each case. These are extremely important findings, as it helps ensure that patients are on the proper treatment, which should lead to better outcomes.

关键词： Gastrointestinal Stomal tumors gist Mutational testing Biomarker testing Survey

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Circulating cKIT and PDGFRA DNA indicates disease activity in Gastrointestinal Stromal Tumor (gist)

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INTERNATIONAL JOURNAL OF CANCER 2019年第8期145卷 2292-2303页

作者： Jilg, Stefanie Rassner, Michael Maier, Jacqueline Waldeck, Silvia Kehl, Victoria Follo, Marie Philipp, Ulrike Sauter, Andreas Specht, Katja Mitschke, Jan Lange, Thoralf Bauer, Sebastian Jost, Philipp J. Peschel, Christian Duyster, Justus Gaiser, Timo Hohenberger, Peter von Bubnoff, Nikolas Tech Univ Munich Klinikum Rechts Isar Med Dept Hematol & Oncol 3 Munich Germany Univ Freiburg Fac Med Med Ctr Dept Hematol Oncol & Stem Cell Transplantat Freiburg Germany Univ Leipzig Ctr Internal Med Dept Hematol Oncol & Hemostaseol Leipzig Germany German Canc Consortium DKTK Partner Site Freiburg Heidelberg Germany German Canc Res Ctr Heidelberg Germany Univ Freiburg Fac Biol Freiburg Germany Tech Univ Munich Klinikum Rechts Isar Inst Med Informat Stat & Epidemiol Munich Germany Tech Univ Munich Klinikum Rechts Isar Dept Diagnost & Intervent Radiol Munich Germany Tech Univ Munich Klinikum Rechts Isar Inst Pathol Munich Germany Asklepios Klin Weissenfels Weissenfels Germany Univ Duisburg Essen Univ Hosp Essen West German Canc Ctr Sarcoma Ctr Essen Germany Ruprecht Karl Univ Heidelberg Univ Med Ctr Mannheim Inst Pathol Mannheim Germany Ruprecht Karl Univ Heidelberg Univ Med Ctr Mannheim Div Surg Oncol & Thorac Surg Mannheim Germany Univ Schleswig Holstein Med Ctr Dept Hematol & Oncol Campus LubeckRatzeburger Allee 160 D-23538 Lubeck Germany

This prospective trial aimed to investigate whether tumor-specific cKIT and PDGFRA mutations can be detected and quantified in circulating tumor (ct)DNA in patients with active gist, and whether detection indicates disease activity. We included 25 patients with active disease and cKIT or PDGFRA mutations detected in tissue. Mutant ctDNA was detected in the peripheral blood plasma using allele-specific ligation (L-)PCR and droplet digital (d)PCR. CtDNA harboring tumor-specific cKIT or PDGFRA mutations was detected at least once in 16 out of 25 patients using L-PCR (64%) and in 20 out of 25 patients with dPCR (80%). Using dPCR, the absolute numbers of ctDNA fragments (DNA copies/ml) and the mutant allele frequency (MAF;in percent of wild-type control) strongly correlated with tumor size expressed as RECIST1.1 sum of diameter (SOD) in mm (rho = 0.3719 and 0.408, respectively, p < 0.0001) and response status (rho = 0.3939 and 0.392, respectively, p < 0.0001 and p < 0.001). Specificity of dPCR for detection of progression was 79.2% with a sensitivity of 55.2% and dPCR discriminated CR from active disease with a specificity of 96% and s sensitivity of 44.7%. With L-PCR, correlations of MAF with tumor size and response status were less prominent. Serial ctDNA measurement reflected individual disease courses over time. Targeted panel sequencing of four patients detected additional driver mutations in all cases and secondary resistance mutations in two cases. Thus, ctDNA indicates disease activity in patients with gist and should be incorporated as companion biomarker in future prospective trials.

关键词： liquid biopsy circulating tumor DNA gist cancer biomarker

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Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in gist patients

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ANNALS OF ONCOLOGY 2008年第7期19卷 1293-1298页

作者： Braconi, C. Bracci, R. Bearzi, I. Bianchi, F. Sabato, S. Mandolesi, A. Belvederesi, L. Cascinu, S. Valeri, N. Cellerino, R. Univ Politecn Marche Ctr Reg Genet Oncol Oncol Med Ist Med Clin & Biotecnol Applicate I-60100 Ancona Italy Osped Riuniti Ancona Clin Oncol Med Ancona Italy Univ Politecn Marche Scuola Specializzaz Oncol I-60100 Ancona Italy

Background: The expression of the insulin-like growth factor (IGF) system has never been studied in gastrointestinal stromal tumors (gists). Patients and methods: We studied the immunohistochemical expression of IGF1 receptor (IGFR-I), IGF1 and IGF2 in 94 samples of gists. IGF1 and IGF2 expression was scored in three classes: negative (N), moderate (M) and strong (S), according to staining intensity and extent. Results: IGFR-I was overexpressed in all cases. IGF1 and IGF2 expression was absent in 25 and 48 cases, moderate in 29 and 16 cases and strong in 40 and 30 cases, respectively. Strong IGF1 expression significantly correlated with higher mitotic index (P = 0.0001), larger (P = 0.01), higher risk (P = 0.0002), metastatic (P = 0.0001) and relapsed (P = 0.04) gists. Strong IGF2 expression correlated with higher mitotic index (P = 0.05) and higher risk gists (P = 0.001). The Kaplan-Meier analysis (N versus M versus S) showed a significant worsening of the disease-free survival (DFS) with the increase of IGF1 (P = 0.02) and IGF2 (P = 0.02) expression. In the subgroup of patients with operated high-risk gists, there was a better trend in DFS for patients affected by gists with negative IGF1 and IGF2. Conclusions: The expression of IGF1 and IGF2 seems to predict relapse in gist patients.

关键词： gist IGF1 IGF2

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Getting the gist: a pictorial review of the various patterns of presentation of gastrointestinal stromal tumors on imaging

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ABDOMINAL RADIOLOGY 2017年第5期42卷 1350-1364页

作者： Scola, Dominic Bahoura, Lawrence Copelan, Alexander Shirkhoda, Ali Sokhandon, Farnoosh Beaumont Hlth Dept Diagnost Radiol & Mol Imaging Diagnost Radiol 3601 W Thirteen Mile Rd2CT Royal Oak MI 48073 USA Univ Calif Irvine Dept Radiol & Diagnost Imaging Irvine CA 92697 USA

Gastrointestinal stromal tumors (gists), the most common mesenchymal tumors of the gastrointestinal tract, are a relatively recently described entity. Most exhibit a mutated tyrosine kinase receptor gene and in some capacity are treated by tyrosine kinase inhibitors. gists can occur across the age spectrum but are more common in patients older than 40 years. They exhibit a wide range of clinical presentations and imaging characteristics. All patterns of enhancement on contrast enhanced computed tomography (CECT) can be seen with gists, including hypoenhancing, isoenhancing, and hyperenhancing tumors. They can be large or small, endoluminal or exophytic. Clinical presentations include asymptomatic patients, nonspecific symptoms, obstruction, and bleeding. Bleeding can take the form of slow, intraluminal GI bleeding or massive intraperitoneal bleeding secondary to rupture and can be seen regardless of the enhancement pattern. Some can cavitate, ulcerate, rupture or cause fistulae. The radiologist's knowledge of the variety of combinations of presentations can narrow the differential diagnosis and ultimately lead to faster diagnosis and treatment.

关键词： gist Focal small bowel lesions CT-enterography

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Long noncoding RNA HOTAIR is upregulated in an aggressive subgroup of gastrointestinal stromal tumors (gist) and mediates the establishment of gene-specific DNA methylation patterns

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GENES CHROMOSOMES & CANCER 2018年第11期57卷 584-597页

作者： Bure, Irina Geer, Sandra Knopf, Jasmin Roas, Maike Henze, Sabine Stroebel, Philipp Agaimy, Abbas Wiemann, Stefan Hoheisel, Joerg D. Hartmann, Arndt Haller, Florian Moskalev, Evgeny A. Friedrich Alexander Univ Inst Pathol Diagnost Mol Pathol Erlangen Germany German Canc Res Ctr Genom & Prote Core Facil Heidelberg Germany Georg August Univ Inst Pathol Gottingen Germany German Canc Res Ctr Mol Genome Anal Heidelberg Germany German Canc Res Ctr Funct Genome Anal Heidelberg Germany IM Sechenov First Moscow State Med Univ Sechenov Human Mol Genet Lab Moscow Russia

Aberrant alterations of DNA methylation are common events in oncogenesis. The origin of cancer-associated epigenetic defects is of interest for mechanistic understanding of malignant transformation andin the long runtherapeutic modulation of DNA methylation in a locus-specific manner. Given the ability of certain long noncoding RNAs to operate as an interface between DNA and the epigenetic modification machinery which can interact with DNA methyltransferases, we hypothesizedconsidering HOTAIR as an examplethat this transcript may contribute to gene specificity of DNA methylation. Using gastrointestinal stromal tumors (gists, n=67) as a model, we confirmed upregulation of HOTAIR in tumors with high risk of recurrence and showed high abundance of the transcript in gist cell lines. HOTAIR knockdown in gist-T1 cells triggered transcriptional response of genes involved in the organization and disassembly of the extracellular matrix and, notably, induced global locus-specific alterations of DNA methylation patterns. Hypomethylation was induced at a total of 507 CpG sites, whereas 382 CpG dinucleotides underwent gain of methylation upon HOTAIR depletion. Importantly, orchestrated gain or loss of methylation at multiple individual CpG sites was shown for cancer-related DPP4, RASSF1, ALDH1A3, and other targets. Collectively, our data indicate that HOTAIR enables target specificity of DNA methylation in gist and is capable of dual (hypo- and hypermethylation) regulation by a yet to be defined mechanism. The results further suggest the feasibility of manipulating DNA methylation in a targeted manner and are of interest in the context of epigenetic cancer therapy.

关键词： DNA methylation gist HOTAIR long noncoding RNAs

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Age differences in hippocampal activation during gist-based false recognition

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NEUROBIOLOGY OF AGING 2016年 46卷 76-83页

作者： Paige, Laura E. Cassidy, Brittany S. Schacter, Daniel L. Gutchess, Angela H. Brandeis Univ Dept Psychol 415 South StMS 062 Waltham MA 02453 USA Indiana Univ Dept Psychol & Brain Sci Bloomington IN USA Harvard Univ Dept Psychol William James Hall 33 Kirkland St Cambridge MA 02138 USA

Age-related increases in reliance on gist-based processes can cause increased false recognition. Understanding the neural basis for this increase helps to elucidate a mechanism underlying this vulnerability in memory. We assessed age differences in gist-based false memory by increasing image set size at encoding, thereby increasing the rate of false alarms. False alarms during a recognition test elicited increased hippocampal activity for older adults as compared to younger adults for the small set sizes, whereas the age groups had similar hippocampal activation for items associated with larger set sizes. Interestingly, younger adults had stronger connectivity between the hippocampus and posterior temporal regions relative to older adults during false alarms for items associated with large versus small set sizes. With increased gist, younger adults might rely more on additional processes (e.g., semantic associations) during recognition than older adults. Parametric modulation revealed that younger adults had increased anterior cingulate activity than older adults with decreasing set size, perhaps indicating difficulty in using monitoring processes in error-prone situations. (C) 2016 Elsevier Inc. All rights reserved.

关键词： gist False memory Aging Memory fMRI Hippocampus

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GEIS guidelines for gastrointestinal sarcomas (gist)

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CANCER TREATMENT REVIEWS 2017年 55卷 107-119页

作者： Poveda, Andres Garcia del Muro, Xavier Antonio Lopez-Guerrero, Jose Cubedo, Ricardo Martinez, Virginia Romero, Ignacio Serrano, Cesar Valverde, Claudia Martin-Broto, Javier Inst Valenciano Oncol Calle Prof Beltran Baguena 8 Valencia 46009 Spain Inst Catala Oncol Avinguda Granvia Hosp 199-203 Barcelona 08907 Spain Fdn Inst Valenciano Oncol C Prof Baguena 19 Valencia 46009 Spain Hosp Puerta de Hierro Calle Manuel de Falla 1 Madrid 28222 Spain Hosp La Paz Paseo Castellana 261 Madrid 28046 Spain Hosp Valle De Hebron Passeig Vail dHebrdn 119-129 Barcelona 08035 Spain Hosp Virgen del Rocio Av Manuel Siurot S-N Seville 41013 Spain

Gastrointestinal stromal sarcomas (gists) are the most common mesenchymal tumours originating in the digestive tract. They have a characteristic morphology, are generally positive for CD117 (c-kit) and are primarily caused by activating mutations in the KIT or PDGFRA genes(1). On rare occasions, they occur in extravisceral locations such as the omentum, mesentery, pelvis and retroperitoneum. gists have become a model of multidisciplinary work in oncology: the participation of several specialties (oncologists, pathologists, surgeons, molecular biologists, radiologists...) has forested advances in the understanding of this tumour and the consolidation of a targeted therapy, imatinib, as the first effective molecular treatment in solid tumours. Following its introduction, median survival of patients with advanced or metastatic gist increased from 18 to more than 60 months. Sunitinib and Regorafenib are two targeted agents with worldwide approval for second-and third-line treatment, respectively, in metastatic gist. (C) 2017 GEIS (GRUPO ESPA7OL DE INVESTIGACION EN SARCOMAS). Published by Elsevier Ltd.

关键词： gist Imatinib Sunitinib Regorafenib GEIS CD117 KIT PDGFRA DOG1

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Management of liver metastases of gastrointestinal stromal tumors (gist)

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ANNALS OF HEPATOLOGY 2015年第4期14卷 531-539页

作者： Vassos, Nikolaos Againny, Abbas Hohenberger, Werner Croner, Roland S. Univ Hosp Erlangen Dept Surg D-91054 Erlangen Germany Univ Hosp Erlangen Inst Pathol D-91054 Erlangen Germany

Introduction. Liver metastases (LM) are crucial prognostic manifestation of gastrointestinal stromal tumors (gist). With the advent of tyrosine kinase inhibitors (TKI), management of metastatic gist has radically changed. Long clinical follow-up provides an increased proportion of gist patients with LM who are candidates for potentially curative therapy. Material and methods. Patients who underwent treatment for liver metastases of gist between 2000-2009 in our department were included in the study. Mean follow-up was 84 months (range 40-145) months. In retrospective analysis we investigated clinical, macro-/microscopic and immunohistochemical criteria, surgical, interventional and TKI therapy as well. Results. In 87 gist-patients we identified 25 (29%) patients with metastatic disease. Of these, 12 patients (14%) suffered from LM with a mean age of 60.5 (range, 35-75) years. Primary gist were located at stomach (n = 4, 33%) or small intestine (n = 8, 67%);all of them expressed CD117 and/or CD34. LM were multiple (83%), distributed in both lobes (67%). They were detected synchronously with primary tumor in 33% and nnetachronously in 77%. All patients with liver involvement were considered to treatment with TKI. LM were resected (RO) in 4 patients (33%). In recurrent (2/4) and TKI resistant cases, interventional treatment (radiofrequency ablation) and TKI escalation were carried out. During a median follow-up of 84 months (range 30-152), 2 patients died (16.5%) for progressive disease and one patient for other reasons. Nine patients (75%) were alive. Conclusion. Treatment of LM from gist needs a multimodal approach. TKI-therapy is required at any case. In case of respectability, surgery must be carried out. In unresectable cases or recurrent/progressive disease, interventional treatment or TKI escalation should be considered. Therefore, these patients need to be treated in experienced centres, where multimodal approaches are established.

关键词： gist Liver Metastases

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