CLINICAL STUDY
Efficacy and Clinical Outcomes of Transcatheter Arterial Embolization for Gastrointestinal Bleeding from Gastrointestinal Stromal Tumor Hyun Jung Koo, MD, PhD, Ji Hoon Shin, MD, PhD, Sooyoung Shin, MD, Hyun-Ki Yoon, MD, PhD, Gi-Young Ko, MD, PhD, and Dong Il Gwon, MD
ABSTRACT Purpose: To evaluate the efficacy and clinical outcomes of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding from gastrointestinal stromal tumor (GIST). Materials and Methods: TAE was performed in 20 referred patients (male:female ¼ 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. Results: The sites of GIST-related bleeding or tumor staining were the jejunum (n ¼ 9), stomach (n ¼ 5), ileum (n ¼ 3), duodenum (n ¼ 2), and jejunum and colon (n ¼ 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. Conclusions: TAE is a safe and effective method for controlling GI bleeding from the GIST.
ABBREVIATIONS GI = gastrointestinal, GIST = gastrointestinal stromal tumor, INR = international normalized ratio, NBCA = N-butyl cyanoacrylate, pRBCs = packed red blood cells, PVA = polyvinyl alcohol, TAE = transcatheter arterial embolization
Gastrointestinal stromal tumor (GIST) is a tumor of mesenchymal origin in the gastrointestinal (GI) tract. Although it is the most common mesenchymal tumor of the GI tract, GIST accounts for only 2% of all GI tumors (1–4). The tumors are generally defined as spindled, From the Department of Radiology and Research Institute of Radiology (H.J.K., J.H.S., H.-K.Y., G.-Y.K., D.I.G.), Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea; and Department of Diagnostic Radiology (S.S.), University of Texas MD Anderson Cancer Center, Houston, Texas. Received January 26, 2015; final revision received May 29, 2015; accepted June 1, 2015. Address correspondence to J.H.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:1297–1304 http://dx.doi.org/10.1016/j.jvir.2015.06.005
epthelioid, mesenchymal tumors with overt mutations in the v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha gene; the rate of KIT positivity has been reported to be 95% and 98% in the stomach and small bowel, respectively (5). Although GIST can arise from any organ in the GI tract, the stomach and small bowel are most commonly involved (6,7). The primary treatment option for localized GIST is complete surgical resection. For patients with advanced disease or unresectable tumor, treatment with imatinib is recommended with or without surgery (8–10). GI bleeding from the GIST is rare and can manifest as asymptomatic occult bleeding. It is often found incidentally during imaging or endoscopic workups performed for other reasons, and the definitive diagnosis is made by pathology. However, life-threatening bleeding rarely occurs (11–13). If endoscopic intervention, including
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clipping, electrocoagulation, or epinephrine injection, fails to control the bleeding, emergency surgery can be performed, although it has significant morbidity or mortality (14). Embolization could be an alternative option for managing bleeding, especially in elderly patients who are at risk for postoperative morbidity because of their advanced age or generally poor health condition. There have been only a few previous case reports regarding the use of transcatheter arterial embolization (TAE) for GI bleeding from GIST (15–17). The purpose of the present study was to evaluate the efficacy and clinical outcomes of TAE for GI bleeding from GIST and show its usefulness as a palliative or preoperative management method.
MATERIALS AND METHODS Patient Characteristics and Study Design This study was approved by the hospital institutional review board; informed consent for data usage was waived because of the retrospective nature of the study.
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Informed consent from any patient who was treated with emergent TAE was obtained from either the patient or a family member before the procedure. Data used for this study were from electronic medical records. From January 2007 to December 2012, GIST was diagnosed in 2,078 patients, and among them, 20 (1.2%) patients (male:female = 13:7; mean age, 56.3 y) underwent TAE for GI bleeding from pathologically proven GIST. Pathologic diagnosis was made in 12 patients before embolization, and diagnosis in the remaining 8 patients was made following operations after embolization. The patient characteristics are noted in the Table. GI bleeding was detected as ongoing hematemesis, melena, or hematochezia. The cause of GI bleeding was diagnosed as GIST-related bleeding based on a review of the patient’s previous medical history and computed tomography (CT), endoscopic, or angiographic findings. Systolic and diastolic blood pressure; heart rate; hemoglobin; and coagulation profile including platelet count, prothrombin time, activated partial thromboplastin time, and international normalized ratio (INR) were also measured at the time of the patient’s initial presentation.
Table . Characteristics of Study Patients (N ¼ 20) Clinical Factors Age (y), median (IQR)
56.3 (50–64)
Male:female (n)
13:7
Systolic/diastolic blood pressure (mm Hg), median (IQR) Heart rate (beats/min), median (IQR)
123 (114–140)/68 (63–84) 87 (82–97)
Hemoglobin (g/dL), median (IQR)
7.7 (6.9–9.2)
Platelets (μL), median (IQR) PT (s), median (IQR)
163,000 (101,500–216,000) 12.6 (11.5–13.2)
aPTT (s), median (IQR)
27.2 (25.4–32.8)
INR, median (IQR) Coagulopathy (n)
1.1 (1.1–1.2) 1 (5%)
Multiplicity (n) Single lesion Multiple lesions
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History of endoscopic hemostatic attempt (n) Yes No
14 (60%) 6 (40%)
Interval between symptom and TAE (d), median (IQR)
0 (0–5)
Interval between CT scans and TAE (d), median (IQR) Interval between TAE and operation, median (IQR)
3 (1–12) 6 (2–7)
pRBC units before angiography (n)
4 (range, 0–24)
pRBC units after angiography (n) Treatment methods (n)
2 (range, 0–14)
Operation after TAE
11
Operation and medical treatment including imatinib after TAE Medical treatment including imatinib after TAE
3 4
Secondary TAE
1
Secondary operation Follow-up (y)
1 2.2 (0.6–3.0)
Note–IQR values are from the 25th to 75th percentile. aPTT ¼ activated partial thromboplastin time, INR ¼ international normalized ratio, IQR ¼ interquartile range, pRBC ¼ packed red blood cell, PT ¼ prothrombin time, TAE ¼ transcatheter arterial embolization.
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Embolization Procedures TAE was performed by four experienced interventional radiologists. Before each procedure, CT scans and endoscopy, if available, were thoroughly reviewed to localize the bleeding site. Using a 5-F catheter (RH catheter; Cook, Inc, Bloomington, Indiana) via the right common femoral artery, celiac artery, superior mesenteric artery, and inferior mesenteric artery angiograms were obtained to determine the focus of the GI bleeding. If upper GI bleeding or GIST involving the upper GI tract was suspected on CT or endoscopy, arteriograms of the celiac and superior mesenteric arteries were primarily obtained. To detect lower GI bleeding or GIST involving the lower GI tract, arteriograms of the superior and inferior mesenteric arteries were primarily obtained. Based on the tumor location noted on CT or endoscopy, feeding arteries were identified; tumor staining also helped to localize the site. Superselection of bleeding arteries was performed using a 2-F to 2.4-F microcatheter (Progreat [Terumo, Tokyo, Japan] or Renegade [Boston Scientific, Marlborough, Massachusetts]). The selection of embolic materials was based on the preference of the interventional radiologist and availability, and the types of materials were as follows: N-butyl cyanoacrylate (NBCA) (Histoacryl; B. Braun Melsungen AG, Melsungen, Germany) mixed with iodized oil (Lipiodol; Andre Guerbet, Aulnay-Sous-Bois, France), microcoils (Cook, Inc), polyvinyl alcohol (PVA) particles (Contour; Boston Scientific, Cork, Ireland), and gelatin sponge (SPONGOSTAN; Ferrosan Medical Devices, Søborg, Denmark). Because a mixture with a lower NBCA-to-lipiodol ratio may propagate more distally than a mixture with a higher ratio, NBCA was mixed with iodized oil at ratios ranging from 1:2 to 1:4 depending on the distance between the tip of the microcatheter and the target lesion and the interventionist’s
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preferences. Various sizes and types of microcoils were used, and PVA particles with diameters of 150–250 mm and 350–500 mm were used. To make gelatin sponge pledgets, operators cut a sheet of gelatin sponge into pledgets and used it in the wet state.
CT Technique Abdominopelvic CT images were obtained using one of five multidetector CT units: LightSpeed QX/i, LightSpeed Plus 16, LightSpeed Ultra 16, LightSpeed VCT (all GE Medical Systems, Milwaukee, Wisconsin), and Somatom Sensation 16 (Siemens Medical Solutions, Erlangen, Germany). The imaging parameters for CT examinations were 3.0–5.0 mm reconstruction slice thickness, 0.75–0.875:1 pitch, 0.5-second rotation time, 120 kVp, and 200–400 mA. All patients underwent unenhanced CT and contrast-enhanced CT at 120 seconds (portal phase) after the beginning of the bolus injection of intravenous contrast agent, 100–150 mL of iopromide (Ultravist 300 or Ultravist 370; Schering, Berlin, Germany) at a rate of 3.0 mL/s using a power injector.
Definitions and Study Endpoints Patients’ vital signs, including blood pressure, heart rate, respiratory rate, and blood oxygen level, were closely monitored. A platelet count less than 50,000/μL and an INR more than 1.5 before the initial embolization procedure were regarded as coagulopathic (18–21). Transfusions were administered to patients with a coagulopathy, hypovolemic shock, or hemodynamic instability caused by massive bleeding. The number of the packed red blood cells (pRBCs) was recorded before and 24 hours after TAE. TAE was considered as an emergent management for control of GI bleeding. All patients were evaluated for
Figure 1. Clinical course of 20 patients who underwent TAE for GIST-related GI bleeding or tumor staining.
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Figure 2. A 52-year-old man presented with hematochezia. (a) CT image obtained after administration of contrast material shows an enhanced, exophytic mass (asterisk) arising from the jejunum and with contrast extravasation (arrows). (b) Early phase and (c) late phase of superior mesenteric angiograms and (d) superselective angiogram of the jejunal artery branch show tumor staining (arrows) without bleeding. (e) Superior mesenteric arteriogram after TAE using gelatin sponge pledgets and two microcoils (arrow) shows no further visualization of tumor staining. Surgery was performed 2 days after TAE. (f) Hemorrhage (asterisk) with necrosis (arrowheads) in the GIST after embolization was proven by elective small bowel resection.
the possibility of tumor resection after embolotherapy. Patients were considered as surgical candidates for curative resection after obtaining stable hemodynamics or for secondary management for failure of bleeding control after embolization. Technical success was determined by cessation of contrast medium extravasation after embolization, as seen on angiography immediately after embolization, and cessation of bleeding within 24 hours after initial TAE. The clinical success of TAE was defined as the absence of the following three conditions for 30 days after the initial TAE: embolization-related complications, recurrent bleeding, and uncontrolled bleeding resulting in 30-day mortality. TAE-related complications such as bowel infarction or other organ damage as diagnosed with imaging modalities or based on clinical symptoms were graded based on the Society of Interventional Radiology (SIR) classification (22). Uncontrolled bleeding was suspected if a patient showed continuous bleeding-related symptoms, such as hematochezia, melena, or hematemesis with prolonged hypotension or anemia, even after initial TAE and having received
blood transfusions. Recurrent bleeding was defined as another episode of bleeding at the same site of the previous contrast extravasation or tumor staining within 24 hours of the successful initial TAE and requiring additional treatment. The overall patient survival rate was also determined.
Statistical Analysis Using descriptive statistics, patient age, gender, history of an endoscopic hemostatic attempt, interval number of days between symptom presentation and angiography, and the number of transfusions before and after TAE were demonstrated. Technical success, clinical success, 30-day mortality, and overall mortality were also assessed using descriptive methods. The Kaplan-Meier method was used to determine the cumulative survival period from the time of the initial TAE. SPSS for Windows, Version 18.0 (SPSS, Inc, Chicago, Illinois), was used for statistical analysis, and the results were expressed as medians with ranges.
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Figure 3. A 53-year-old man presented with hematemesis and hematochezia. Contrast-enhanced axial (a) and coronal, reconstructed (b) CT images show bleeding (arrow) from the large GIST (asterisk) involving the gastric fundus. A previous endoscopic hemostatic attempt failed because of the large mass with massive bleeding. (c, d) Celiac angiograms show contrast extravasation (arrow) from the left gastric artery. Note mild tumor staining (arrowheads) at the gastric fundus. (e) Selective angiogram of the left gastric artery branch shows contrast extravasation (arrow). (f) Embolization with PVA particles (150–250 μm) was performed successfully, and final angiogram shows no contrast extravasation.
RESULTS Clinical Characteristics The clinical courses of 20 patients who underwent TAE for GI bleeding from GIST are summarized in Figure 1. In all the study patients, GIST was pathologically proven by biopsy or surgery: small bowel resection (n ¼ 10), debulking operation (n ¼ 1), distal gastrectomy (n ¼ 1), pylorus-preserving pancreaticoduodenectomy (n ¼ 1), wedge resection of the stomach (n ¼ 3), and biopsy (n ¼ 4; liver [n ¼ 2], stomach [n ¼ 1], and duodenum [n ¼ 1]). Of the five patients who were treated medically after TAE, four patients had undergone biopsy, and the remaining patient had recurrent GIST with a history of previous small bowel resection. The main symptoms or signs of patients were hematochezia (n ¼ 7), melena (n ¼ 6), hematemesis (n ¼ 5), hemoperitoneum (n ¼ 1), and sudden hypotension (n ¼ 1). Of patients, 17 presented to the emergency department seeking management for the above-mentioned symptoms. The locations of GIST bleeding, as demonstrated on CT or angiography, were the jejunum
(n ¼ 9), stomach (n ¼ 5), ileum (n ¼ 3), duodenum (n ¼ 2), and both jejunum and colon (n ¼ 1). Coagulopathy was noted in one patient with jejunal GIST showing an INR of 1.83. The median INR of all patients was 1.11 (interquartile range, 1.1–1.2), and the median platelet count was 163,000/μL (interquartile range, 101,500–216,000/μL). Esophagogastroduodenoscopy was performed in 14 patients for initial management of GI bleeding. Five of these patients demonstrated bleeding refractory to the endoscopic treatment, and nine patients did not demonstrate bleeding sites. The remaining six patients did not undergo endoscopy before embolization. As seen on CT scans, 12 patients had solitary GIST involvement, and eight patients had multiple GIST involvement. In five patients, bleeding from tumors was noted on CT images (Fig 2a–f).
Angiographic Details In all patients, the median interval between symptom presentation and angiography was 0 days (range, 0–5 d).
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On angiography, 15 patients (75%) showed tumor staining without bleeding, and five patients (25%) showed tumor staining with bleeding (Fig 3a–f). In the five patients with bleeding seen on angiography, the bleeding was correlated on CT scans obtained before angiography in two patients, whereas evidence of bleeding was absent on the CT scans in three patients. The median interval between CT and angiography in these three patients was 7 days (range, 5.5–7.5 d). Embolization procedures for GIST bleeding were performed in 20 patients using various embolization materials, including gelatin sponge pledgets (n ¼ 7), NBCA (n ¼ 3), microcoils (n ¼ 2), PVA particles (n ¼ 2), and combined materials (ie, gelatin sponge pledgets and microcoil [n ¼ 3], microcoil and PVA [n ¼ 2], and NBCA and gelatin sponge pledgets [n ¼ 1]) (Table E1 [available online at www.jvir.org]). The location of the tumors, the number of patients who presented with contrast extravasation on angiography, the arteries that received embolization, and embolic materials are summarized in Table E1 (available online at www.jvir.org).
Technical Results and Clinical Outcomes Technical success of TAE was achieved in 19 (95.0%) patients. One patient with technical failure required a transfusion of 14 units of pRBCs within 24 hours of the initial TAE because of uncontrolled bleeding, although he eventually recovered after surgery for jejunal GIST-related bleeding. The clinical success rate was 90% (18 of 20 patients). There were no TAE-related complications such as bowel ischemia or infarction.
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In 15 patients, surgical resections of the tumors were performed after TAE. In all study patients, the median transfusion amount 24 hours before angiography was 4 units of pRBCs (range, 0–24 units), and the median transfusion amount after the procedure and after angiography was 2 units (range, 0–14 units), including one patient who needed 14 units after technical failure of TAE. With the exception of this patient, the range of transfusions was 0–4 units. The 30-day mortality rate was 10% (2 of 20 patients), and the overall mortality rate after initial TAE was 30% (6 of 20 patients) (Fig 4). The cause of death in the two patients who died within 30 days of the procedure was bleeding-related multiorgan failure. Another patient died 67 days after initial TAE secondary to multiorgan failure. Despite receiving medical intensive care this patient did not recover from multiorgan failure after the bleeding episode. The remaining causes of overall mortality from the initial TAE were disease progression (n ¼ 2) and hepatic failure (n ¼ 1). The median follow-up period from the initial TAE was 26.7 months (range, 6 mo to 8.2 y).
DISCUSSION The present study shows the usefulness of TAE for GI bleeding from GIST, with a technical success rate of 95% (19 of 20 patients) and a clinical success rate of 90% (18 of 20 patients). The incidence of GI bleeding secondary to GIST is rare; however, patients demonstrate asymptomatic occult bleeding as well as overt life-threatening bleeding (11–13). In our study, although only five patients showed contrast medium extravasation
Figure 4. Kaplan-Meier survival plot for all patients with GIST-related GI bleeding.
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at angiography, 17 patients (85%) presented to the emergency department with acute, unstable hemodynamics showing hematochezia, melena, hematemesis, hemoperitoneum, and sudden hypotension. Also, they required blood transfusion. In a hypovolemic condition, bleeding might not be detected on angiography. In addition, although 14 patients had undergone endoscopy, five presented with refractory bleeding, and bleeding sites were not discovered in nine patients. With these conditions, TAE was considered as a prompt management for control of GI bleeding. For patients who presented with GI bleeding symptoms, endoscopic intervention, including clipping, electrocoagulation, or epinephrine injection, is usually the primary management option. If endoscopic intervention fails to control the bleeding, embolization can be attempted to stop the bleeding. For life-threatening bleeding or refractory bleeding after less invasive management, emergency surgery is occasionally performed, although it is sometimes followed by significant morbidity or mortality (14). Surgical options are also limited in elderly patients and patients with a poor general health status. In these cases, embolization is an alternative for detecting and managing bleeding. Although endoscopy is the first choice for detecting and managing GI bleeding, small bowel bleeding might be difficult to detect using endoscopy. In our study, the jejunum was the most common GI bleeding site of GIST, and the bleeding sites could be successfully demonstrated and managed by TAE. TAE could be a good preoperative option for detecting and managing small bowel bleeding in areas where endoscopy usually cannot reach. Recurrent bleeding was noted in only one patient in this study, suggesting that TAE is effective in controlling GISTrelated bleeding. Also, there were no TAE-related complications. Considering the minimally invasive procedure and its availability, TAE could be used as an alternative option to surgery or as a preoperative treatment method. In the present study, TAE was performed before operation in15 patients with acute bleeding-related symptoms. In addition to its possible role for preoperative management, previous clinical trials have shown its efficacy as a palliative option for GIST with hepatic metastasis resistant to medical treatment, including imatinib (23,24). By decreasing the tumor burden, the addition of TAE to conventional therapy can improve the overall outcome of GIST, and this should be studied further in the future. The present study has several limitations. First, this is a retrospective study. Second, the number of patients with GI bleeding from GIST was small. Because the incidence of GIST is not high and bleeding cases are rare, this limitation could be an innate characteristic of the study. Third, 15 patients had surgical resections of GIST, which could overestimate the clinical success of TAE. Additionally, the lack of a standardized technique, particularly regarding various embolic materials, is a
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weak point. There were no data to suggest the preferred embolic agents for embolization of GIST-related GI bleeding; however, caution is necessary to avoid extensive embolization using NBCA to prevent potential bowel ischemia or infarction (25,26). In conclusion, the primary purpose of this study was to show the effectiveness of TAE for managing GI bleeding from GIST using long-term clinical experience. TAE for GI bleeding from GIST shows a high technical success rate and clinical effectiveness even for patients with failed endoscopic hemostasis. TAE could be a beneficial option for managing GIST-related GI bleeding including urgent situations where the bleeding needs to be stopped as well as preoperative or palliative management.
ACKNOWLEDGMENT This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (Grant No. 2014R1A2A2A01005857).
REFERENCES 1. Goettsch WG, Bos SD, Breekveldt-Postma N, Casparie M, Herings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumours is underestimated: results of a nation-wide study. Eur J Cancer 2005; 41: 2868–2872. 2. Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G. Management of malignant gastrointestinal stromal tumours. Lancet Oncol 2002; 3:655–664. 3. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 2005; 103:821–829. 4. Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005; 117:289–293. 5. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006; 23:70–83. 6. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29: 52–68. 7. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet 2007; 369:1731–1741. 8. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20–21 March 2004, under the auspices of ESMO. Ann Oncol 2005; 16:566–578. 9. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347:472–480. 10. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364:1127–1134. 11. Hwang JH, Fisher DA, Ben-Menachem T, et al. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc 2012; 75:1132–1138. 12. Seya T, Tanaka N, Yokoi K, Shinji S, Oaki Y, Tajiri T. Life-threatening bleeding from gastrointestinal stromal tumor of the stomach. J Nippon Med Sch 2008; 75:306–311. 13. Vats HS, Wengert TJ, Torbey CF. Gastrointestinal stromal tumor with Dieulafoy lesion: a novel association. Clin Med Res 2006; 4: 228–229.
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14. Clarke MG, Bunting D, Smart NJ, Lowes J, Mitchell SJ. The surgical management of acute upper gastrointestinal bleeding: a 12-year experience. Int J Surg 2010; 8:377–380. 15. Chikamori F, Kuniyoshi N, Okamoto H, Kuniyoshi K. A case of a gastric submucosal tumor treated with combined therapy using superselective TAE and endoscopic local resection. Surg Laparosc Endosc Percutan Tech 2012; 22:297–300. 16. Huang YW, Siao FY, Yen HH. Life-threatening bleeding from gastrointestinal stromal tumor: successful embolization with subsequent laparoscopic surgery. Am J Emerg Med 2014; 32:1150. 17. Kurihara N, Kikuchi K, Tanabe M, et al. Partial resection of the second portion of the duodenum for gastrointestinal stromal tumor after effective transarterial embolization. Int J Clin Oncol 2005; 10:433–437. 18. Strauss RG. Pretransfusion trigger platelet counts and dose for prophylactic platelet transfusions. Curr Opin Hematol 2005; 12:499–502. 19. Shander A, Goodnough LT. Update on transfusion medicine. Pharmacotherapy 2007; 27:57–68. 20. O’Connor SD, Taylor AJ, Williams EC, Winter TC. Coagulation concepts update. AJR Am J Roentgenol 2009; 193:1656–1664.
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21. Malloy PC, Grassi CJ, Kundu S, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol 2009; 20:240–249. 22. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14: S199–S202. 23. Cao G, Li J, Shen L, Zhu X. Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases. World J Gastroenterol 2012; 18:6134–6140. 24. Kobayashi K, Szklaruk J, Trent JC, et al. Hepatic arterial embolization and chemoembolization for imatinib-resistant gastrointestinal stromal tumors. Am J Clin Oncol 2009; 32:574–581. 25. Hur S, Jae HJ, Lee M, Kim HC, Chung JW. Safety and efficacy of transcatheter arterial embolization for lower gastrointestinal bleeding: a single-center experience with 112 patients. J Vasc Interv Radiol 2014; 25: 10–19. 26. Koo HJ, Shin JH, Kim HJ, et al. Clinical outcome of transcatheter arterial embolization with N-butyl-2-cyanoacrylate for control of acute gastrointestinal tract bleeding. AJR Am J Roentgenol 2015; 204:662–668.
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Table E1 . Tumor Location, Patients with Contrast Extravasation on Angiogram, Arteries that Received Embolization, and Embolic Materials Tumor Location
Patients with Contrast
Arteries that Received Embolization
Embolic Materials
Extravasation on Angiogram (n) Stomach (n ¼ 5)
Left gastric artery (n ¼ 5)
Gelatin sponge pledgets (n ¼ 3)
Left inferior phrenic artery (n ¼ 1)
NBCA (n ¼ 1) PVA (n ¼ 1)
Duodenum (n ¼ 2)
Pancreaticoduodenal artery (n ¼ 1)
Gelatin sponge pledgets þ coil (n ¼ 1)
Jejunum (n ¼ 9)
Duodenal branch (n ¼ 1) Jejunal branch (n ¼ 9)
NBCA (n ¼ 1) Coil (n ¼ 2)
1
3
Gelatin sponge pledgets þ coil (n ¼ 1) Gelatin sponge pledgets (n ¼ 3) NBCA (n ¼ 1) NBCA þ gelatin sponge pledgets (n ¼ 1) Ileum (n ¼ 3)
Jejunum þ colon (n ¼ 1)
1
Ileocolic (n ¼ 1)
Coil þ PVA (n ¼ 1) Coil þ PVA (n ¼ 1)
Ileal branch (n ¼ 2)
Gelatin sponge pledgets (n ¼ 1)
Colic and jejunal branch (n ¼ 1)
PVA (n ¼ 1) Gelatin sponge pledgets þ coil (n ¼ 1)
NBCA ¼ N-butyl cyanoacrylate, PVA ¼ polyvinyl alcohol.
Efficacy and Clinical Outcomes of Transcatheter Arterial Embolization for Gastrointestinal Bleeding from Gastrointestinal Stromal Tumor Hyun Jung Koo, MD, PhD, Ji Hoon Shin, MD, PhD, Sooyoung Shin, MD, Hyun-Ki Yoon, MD, PhD, Gi-Young Ko, MD, PhD, and Dong Il Gwon, MD
ABSTRACT Purpose: To evaluate the efficacy and clinical outcomes of transcatheter arterial embolization (TAE) for gastrointestinal (GI) bleeding from gastrointestinal stromal tumor (GIST). Materials and Methods: TAE was performed in 20 referred patients (male:female ¼ 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. Results: The sites of GIST-related bleeding or tumor staining were the jejunum (n ¼ 9), stomach (n ¼ 5), ileum (n ¼ 3), duodenum (n ¼ 2), and jejunum and colon (n ¼ 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. Conclusions: TAE is a safe and effective method for controlling GI bleeding from the GIST.
ABBREVIATIONS GI = gastrointestinal, GIST = gastrointestinal stromal tumor, INR = international normalized ratio, NBCA = N-butyl cyanoacrylate, pRBCs = packed red blood cells, PVA = polyvinyl alcohol, TAE = transcatheter arterial embolization
Gastrointestinal stromal tumor (GIST) is a tumor of mesenchymal origin in the gastrointestinal (GI) tract. Although it is the most common mesenchymal tumor of the GI tract, GIST accounts for only 2% of all GI tumors (1–4). The tumors are generally defined as spindled, From the Department of Radiology and Research Institute of Radiology (H.J.K., J.H.S., H.-K.Y., G.-Y.K., D.I.G.), Asan Medical Center, University of Ulsan College of Medicine, Olymphic-ro 43 gil 88, Songpa-Gu, Seoul 138-736, Korea; and Department of Diagnostic Radiology (S.S.), University of Texas MD Anderson Cancer Center, Houston, Texas. Received January 26, 2015; final revision received May 29, 2015; accepted June 1, 2015. Address correspondence to J.H.S.; E-mail: [email protected] None of the authors have identified a conflict of interest. Table E1 is available online at www.jvir.org. & SIR, 2015 J Vasc Interv Radiol 2015; 26:1297–1304 http://dx.doi.org/10.1016/j.jvir.2015.06.005
epthelioid, mesenchymal tumors with overt mutations in the v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) or platelet-derived growth factor receptor alpha gene; the rate of KIT positivity has been reported to be 95% and 98% in the stomach and small bowel, respectively (5). Although GIST can arise from any organ in the GI tract, the stomach and small bowel are most commonly involved (6,7). The primary treatment option for localized GIST is complete surgical resection. For patients with advanced disease or unresectable tumor, treatment with imatinib is recommended with or without surgery (8–10). GI bleeding from the GIST is rare and can manifest as asymptomatic occult bleeding. It is often found incidentally during imaging or endoscopic workups performed for other reasons, and the definitive diagnosis is made by pathology. However, life-threatening bleeding rarely occurs (11–13). If endoscopic intervention, including
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clipping, electrocoagulation, or epinephrine injection, fails to control the bleeding, emergency surgery can be performed, although it has significant morbidity or mortality (14). Embolization could be an alternative option for managing bleeding, especially in elderly patients who are at risk for postoperative morbidity because of their advanced age or generally poor health condition. There have been only a few previous case reports regarding the use of transcatheter arterial embolization (TAE) for GI bleeding from GIST (15–17). The purpose of the present study was to evaluate the efficacy and clinical outcomes of TAE for GI bleeding from GIST and show its usefulness as a palliative or preoperative management method.
MATERIALS AND METHODS Patient Characteristics and Study Design This study was approved by the hospital institutional review board; informed consent for data usage was waived because of the retrospective nature of the study.
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Informed consent from any patient who was treated with emergent TAE was obtained from either the patient or a family member before the procedure. Data used for this study were from electronic medical records. From January 2007 to December 2012, GIST was diagnosed in 2,078 patients, and among them, 20 (1.2%) patients (male:female = 13:7; mean age, 56.3 y) underwent TAE for GI bleeding from pathologically proven GIST. Pathologic diagnosis was made in 12 patients before embolization, and diagnosis in the remaining 8 patients was made following operations after embolization. The patient characteristics are noted in the Table. GI bleeding was detected as ongoing hematemesis, melena, or hematochezia. The cause of GI bleeding was diagnosed as GIST-related bleeding based on a review of the patient’s previous medical history and computed tomography (CT), endoscopic, or angiographic findings. Systolic and diastolic blood pressure; heart rate; hemoglobin; and coagulation profile including platelet count, prothrombin time, activated partial thromboplastin time, and international normalized ratio (INR) were also measured at the time of the patient’s initial presentation.
Table . Characteristics of Study Patients (N ¼ 20) Clinical Factors Age (y), median (IQR)
56.3 (50–64)
Male:female (n)
13:7
Systolic/diastolic blood pressure (mm Hg), median (IQR) Heart rate (beats/min), median (IQR)
123 (114–140)/68 (63–84) 87 (82–97)
Hemoglobin (g/dL), median (IQR)
7.7 (6.9–9.2)
Platelets (μL), median (IQR) PT (s), median (IQR)
163,000 (101,500–216,000) 12.6 (11.5–13.2)
aPTT (s), median (IQR)
27.2 (25.4–32.8)
INR, median (IQR) Coagulopathy (n)
1.1 (1.1–1.2) 1 (5%)
Multiplicity (n) Single lesion Multiple lesions
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History of endoscopic hemostatic attempt (n) Yes No
14 (60%) 6 (40%)
Interval between symptom and TAE (d), median (IQR)
0 (0–5)
Interval between CT scans and TAE (d), median (IQR) Interval between TAE and operation, median (IQR)
3 (1–12) 6 (2–7)
pRBC units before angiography (n)
4 (range, 0–24)
pRBC units after angiography (n) Treatment methods (n)
2 (range, 0–14)
Operation after TAE
11
Operation and medical treatment including imatinib after TAE Medical treatment including imatinib after TAE
3 4
Secondary TAE
1
Secondary operation Follow-up (y)
1 2.2 (0.6–3.0)
Note–IQR values are from the 25th to 75th percentile. aPTT ¼ activated partial thromboplastin time, INR ¼ international normalized ratio, IQR ¼ interquartile range, pRBC ¼ packed red blood cell, PT ¼ prothrombin time, TAE ¼ transcatheter arterial embolization.
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Embolization Procedures TAE was performed by four experienced interventional radiologists. Before each procedure, CT scans and endoscopy, if available, were thoroughly reviewed to localize the bleeding site. Using a 5-F catheter (RH catheter; Cook, Inc, Bloomington, Indiana) via the right common femoral artery, celiac artery, superior mesenteric artery, and inferior mesenteric artery angiograms were obtained to determine the focus of the GI bleeding. If upper GI bleeding or GIST involving the upper GI tract was suspected on CT or endoscopy, arteriograms of the celiac and superior mesenteric arteries were primarily obtained. To detect lower GI bleeding or GIST involving the lower GI tract, arteriograms of the superior and inferior mesenteric arteries were primarily obtained. Based on the tumor location noted on CT or endoscopy, feeding arteries were identified; tumor staining also helped to localize the site. Superselection of bleeding arteries was performed using a 2-F to 2.4-F microcatheter (Progreat [Terumo, Tokyo, Japan] or Renegade [Boston Scientific, Marlborough, Massachusetts]). The selection of embolic materials was based on the preference of the interventional radiologist and availability, and the types of materials were as follows: N-butyl cyanoacrylate (NBCA) (Histoacryl; B. Braun Melsungen AG, Melsungen, Germany) mixed with iodized oil (Lipiodol; Andre Guerbet, Aulnay-Sous-Bois, France), microcoils (Cook, Inc), polyvinyl alcohol (PVA) particles (Contour; Boston Scientific, Cork, Ireland), and gelatin sponge (SPONGOSTAN; Ferrosan Medical Devices, Søborg, Denmark). Because a mixture with a lower NBCA-to-lipiodol ratio may propagate more distally than a mixture with a higher ratio, NBCA was mixed with iodized oil at ratios ranging from 1:2 to 1:4 depending on the distance between the tip of the microcatheter and the target lesion and the interventionist’s
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preferences. Various sizes and types of microcoils were used, and PVA particles with diameters of 150–250 mm and 350–500 mm were used. To make gelatin sponge pledgets, operators cut a sheet of gelatin sponge into pledgets and used it in the wet state.
CT Technique Abdominopelvic CT images were obtained using one of five multidetector CT units: LightSpeed QX/i, LightSpeed Plus 16, LightSpeed Ultra 16, LightSpeed VCT (all GE Medical Systems, Milwaukee, Wisconsin), and Somatom Sensation 16 (Siemens Medical Solutions, Erlangen, Germany). The imaging parameters for CT examinations were 3.0–5.0 mm reconstruction slice thickness, 0.75–0.875:1 pitch, 0.5-second rotation time, 120 kVp, and 200–400 mA. All patients underwent unenhanced CT and contrast-enhanced CT at 120 seconds (portal phase) after the beginning of the bolus injection of intravenous contrast agent, 100–150 mL of iopromide (Ultravist 300 or Ultravist 370; Schering, Berlin, Germany) at a rate of 3.0 mL/s using a power injector.
Definitions and Study Endpoints Patients’ vital signs, including blood pressure, heart rate, respiratory rate, and blood oxygen level, were closely monitored. A platelet count less than 50,000/μL and an INR more than 1.5 before the initial embolization procedure were regarded as coagulopathic (18–21). Transfusions were administered to patients with a coagulopathy, hypovolemic shock, or hemodynamic instability caused by massive bleeding. The number of the packed red blood cells (pRBCs) was recorded before and 24 hours after TAE. TAE was considered as an emergent management for control of GI bleeding. All patients were evaluated for
Figure 1. Clinical course of 20 patients who underwent TAE for GIST-related GI bleeding or tumor staining.
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Figure 2. A 52-year-old man presented with hematochezia. (a) CT image obtained after administration of contrast material shows an enhanced, exophytic mass (asterisk) arising from the jejunum and with contrast extravasation (arrows). (b) Early phase and (c) late phase of superior mesenteric angiograms and (d) superselective angiogram of the jejunal artery branch show tumor staining (arrows) without bleeding. (e) Superior mesenteric arteriogram after TAE using gelatin sponge pledgets and two microcoils (arrow) shows no further visualization of tumor staining. Surgery was performed 2 days after TAE. (f) Hemorrhage (asterisk) with necrosis (arrowheads) in the GIST after embolization was proven by elective small bowel resection.
the possibility of tumor resection after embolotherapy. Patients were considered as surgical candidates for curative resection after obtaining stable hemodynamics or for secondary management for failure of bleeding control after embolization. Technical success was determined by cessation of contrast medium extravasation after embolization, as seen on angiography immediately after embolization, and cessation of bleeding within 24 hours after initial TAE. The clinical success of TAE was defined as the absence of the following three conditions for 30 days after the initial TAE: embolization-related complications, recurrent bleeding, and uncontrolled bleeding resulting in 30-day mortality. TAE-related complications such as bowel infarction or other organ damage as diagnosed with imaging modalities or based on clinical symptoms were graded based on the Society of Interventional Radiology (SIR) classification (22). Uncontrolled bleeding was suspected if a patient showed continuous bleeding-related symptoms, such as hematochezia, melena, or hematemesis with prolonged hypotension or anemia, even after initial TAE and having received
blood transfusions. Recurrent bleeding was defined as another episode of bleeding at the same site of the previous contrast extravasation or tumor staining within 24 hours of the successful initial TAE and requiring additional treatment. The overall patient survival rate was also determined.
Statistical Analysis Using descriptive statistics, patient age, gender, history of an endoscopic hemostatic attempt, interval number of days between symptom presentation and angiography, and the number of transfusions before and after TAE were demonstrated. Technical success, clinical success, 30-day mortality, and overall mortality were also assessed using descriptive methods. The Kaplan-Meier method was used to determine the cumulative survival period from the time of the initial TAE. SPSS for Windows, Version 18.0 (SPSS, Inc, Chicago, Illinois), was used for statistical analysis, and the results were expressed as medians with ranges.
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Figure 3. A 53-year-old man presented with hematemesis and hematochezia. Contrast-enhanced axial (a) and coronal, reconstructed (b) CT images show bleeding (arrow) from the large GIST (asterisk) involving the gastric fundus. A previous endoscopic hemostatic attempt failed because of the large mass with massive bleeding. (c, d) Celiac angiograms show contrast extravasation (arrow) from the left gastric artery. Note mild tumor staining (arrowheads) at the gastric fundus. (e) Selective angiogram of the left gastric artery branch shows contrast extravasation (arrow). (f) Embolization with PVA particles (150–250 μm) was performed successfully, and final angiogram shows no contrast extravasation.
RESULTS Clinical Characteristics The clinical courses of 20 patients who underwent TAE for GI bleeding from GIST are summarized in Figure 1. In all the study patients, GIST was pathologically proven by biopsy or surgery: small bowel resection (n ¼ 10), debulking operation (n ¼ 1), distal gastrectomy (n ¼ 1), pylorus-preserving pancreaticoduodenectomy (n ¼ 1), wedge resection of the stomach (n ¼ 3), and biopsy (n ¼ 4; liver [n ¼ 2], stomach [n ¼ 1], and duodenum [n ¼ 1]). Of the five patients who were treated medically after TAE, four patients had undergone biopsy, and the remaining patient had recurrent GIST with a history of previous small bowel resection. The main symptoms or signs of patients were hematochezia (n ¼ 7), melena (n ¼ 6), hematemesis (n ¼ 5), hemoperitoneum (n ¼ 1), and sudden hypotension (n ¼ 1). Of patients, 17 presented to the emergency department seeking management for the above-mentioned symptoms. The locations of GIST bleeding, as demonstrated on CT or angiography, were the jejunum
(n ¼ 9), stomach (n ¼ 5), ileum (n ¼ 3), duodenum (n ¼ 2), and both jejunum and colon (n ¼ 1). Coagulopathy was noted in one patient with jejunal GIST showing an INR of 1.83. The median INR of all patients was 1.11 (interquartile range, 1.1–1.2), and the median platelet count was 163,000/μL (interquartile range, 101,500–216,000/μL). Esophagogastroduodenoscopy was performed in 14 patients for initial management of GI bleeding. Five of these patients demonstrated bleeding refractory to the endoscopic treatment, and nine patients did not demonstrate bleeding sites. The remaining six patients did not undergo endoscopy before embolization. As seen on CT scans, 12 patients had solitary GIST involvement, and eight patients had multiple GIST involvement. In five patients, bleeding from tumors was noted on CT images (Fig 2a–f).
Angiographic Details In all patients, the median interval between symptom presentation and angiography was 0 days (range, 0–5 d).
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On angiography, 15 patients (75%) showed tumor staining without bleeding, and five patients (25%) showed tumor staining with bleeding (Fig 3a–f). In the five patients with bleeding seen on angiography, the bleeding was correlated on CT scans obtained before angiography in two patients, whereas evidence of bleeding was absent on the CT scans in three patients. The median interval between CT and angiography in these three patients was 7 days (range, 5.5–7.5 d). Embolization procedures for GIST bleeding were performed in 20 patients using various embolization materials, including gelatin sponge pledgets (n ¼ 7), NBCA (n ¼ 3), microcoils (n ¼ 2), PVA particles (n ¼ 2), and combined materials (ie, gelatin sponge pledgets and microcoil [n ¼ 3], microcoil and PVA [n ¼ 2], and NBCA and gelatin sponge pledgets [n ¼ 1]) (Table E1 [available online at www.jvir.org]). The location of the tumors, the number of patients who presented with contrast extravasation on angiography, the arteries that received embolization, and embolic materials are summarized in Table E1 (available online at www.jvir.org).
Technical Results and Clinical Outcomes Technical success of TAE was achieved in 19 (95.0%) patients. One patient with technical failure required a transfusion of 14 units of pRBCs within 24 hours of the initial TAE because of uncontrolled bleeding, although he eventually recovered after surgery for jejunal GIST-related bleeding. The clinical success rate was 90% (18 of 20 patients). There were no TAE-related complications such as bowel ischemia or infarction.
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In 15 patients, surgical resections of the tumors were performed after TAE. In all study patients, the median transfusion amount 24 hours before angiography was 4 units of pRBCs (range, 0–24 units), and the median transfusion amount after the procedure and after angiography was 2 units (range, 0–14 units), including one patient who needed 14 units after technical failure of TAE. With the exception of this patient, the range of transfusions was 0–4 units. The 30-day mortality rate was 10% (2 of 20 patients), and the overall mortality rate after initial TAE was 30% (6 of 20 patients) (Fig 4). The cause of death in the two patients who died within 30 days of the procedure was bleeding-related multiorgan failure. Another patient died 67 days after initial TAE secondary to multiorgan failure. Despite receiving medical intensive care this patient did not recover from multiorgan failure after the bleeding episode. The remaining causes of overall mortality from the initial TAE were disease progression (n ¼ 2) and hepatic failure (n ¼ 1). The median follow-up period from the initial TAE was 26.7 months (range, 6 mo to 8.2 y).
DISCUSSION The present study shows the usefulness of TAE for GI bleeding from GIST, with a technical success rate of 95% (19 of 20 patients) and a clinical success rate of 90% (18 of 20 patients). The incidence of GI bleeding secondary to GIST is rare; however, patients demonstrate asymptomatic occult bleeding as well as overt life-threatening bleeding (11–13). In our study, although only five patients showed contrast medium extravasation
Figure 4. Kaplan-Meier survival plot for all patients with GIST-related GI bleeding.
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at angiography, 17 patients (85%) presented to the emergency department with acute, unstable hemodynamics showing hematochezia, melena, hematemesis, hemoperitoneum, and sudden hypotension. Also, they required blood transfusion. In a hypovolemic condition, bleeding might not be detected on angiography. In addition, although 14 patients had undergone endoscopy, five presented with refractory bleeding, and bleeding sites were not discovered in nine patients. With these conditions, TAE was considered as a prompt management for control of GI bleeding. For patients who presented with GI bleeding symptoms, endoscopic intervention, including clipping, electrocoagulation, or epinephrine injection, is usually the primary management option. If endoscopic intervention fails to control the bleeding, embolization can be attempted to stop the bleeding. For life-threatening bleeding or refractory bleeding after less invasive management, emergency surgery is occasionally performed, although it is sometimes followed by significant morbidity or mortality (14). Surgical options are also limited in elderly patients and patients with a poor general health status. In these cases, embolization is an alternative for detecting and managing bleeding. Although endoscopy is the first choice for detecting and managing GI bleeding, small bowel bleeding might be difficult to detect using endoscopy. In our study, the jejunum was the most common GI bleeding site of GIST, and the bleeding sites could be successfully demonstrated and managed by TAE. TAE could be a good preoperative option for detecting and managing small bowel bleeding in areas where endoscopy usually cannot reach. Recurrent bleeding was noted in only one patient in this study, suggesting that TAE is effective in controlling GISTrelated bleeding. Also, there were no TAE-related complications. Considering the minimally invasive procedure and its availability, TAE could be used as an alternative option to surgery or as a preoperative treatment method. In the present study, TAE was performed before operation in15 patients with acute bleeding-related symptoms. In addition to its possible role for preoperative management, previous clinical trials have shown its efficacy as a palliative option for GIST with hepatic metastasis resistant to medical treatment, including imatinib (23,24). By decreasing the tumor burden, the addition of TAE to conventional therapy can improve the overall outcome of GIST, and this should be studied further in the future. The present study has several limitations. First, this is a retrospective study. Second, the number of patients with GI bleeding from GIST was small. Because the incidence of GIST is not high and bleeding cases are rare, this limitation could be an innate characteristic of the study. Third, 15 patients had surgical resections of GIST, which could overestimate the clinical success of TAE. Additionally, the lack of a standardized technique, particularly regarding various embolic materials, is a
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weak point. There were no data to suggest the preferred embolic agents for embolization of GIST-related GI bleeding; however, caution is necessary to avoid extensive embolization using NBCA to prevent potential bowel ischemia or infarction (25,26). In conclusion, the primary purpose of this study was to show the effectiveness of TAE for managing GI bleeding from GIST using long-term clinical experience. TAE for GI bleeding from GIST shows a high technical success rate and clinical effectiveness even for patients with failed endoscopic hemostasis. TAE could be a beneficial option for managing GIST-related GI bleeding including urgent situations where the bleeding needs to be stopped as well as preoperative or palliative management.
ACKNOWLEDGMENT This research was supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science, ICT and Future Planning (Grant No. 2014R1A2A2A01005857).
REFERENCES 1. Goettsch WG, Bos SD, Breekveldt-Postma N, Casparie M, Herings RM, Hogendoorn PC. Incidence of gastrointestinal stromal tumours is underestimated: results of a nation-wide study. Eur J Cancer 2005; 41: 2868–2872. 2. Joensuu H, Fletcher C, Dimitrijevic S, Silberman S, Roberts P, Demetri G. Management of malignant gastrointestinal stromal tumours. Lancet Oncol 2002; 3:655–664. 3. Nilsson B, Bumming P, Meis-Kindblom JM, et al. Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era—a population-based study in western Sweden. Cancer 2005; 103:821–829. 4. Tryggvason G, Gislason HG, Magnusson MK, Jonasson JG. Gastrointestinal stromal tumors in Iceland, 1990–2003: the Icelandic GIST study, a population-based incidence and pathologic risk stratification study. Int J Cancer 2005; 117:289–293. 5. Miettinen M, Lasota J. Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 2006; 23:70–83. 6. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29: 52–68. 7. Rubin BP, Heinrich MC, Corless CL. Gastrointestinal stromal tumour. Lancet 2007; 369:1731–1741. 8. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20–21 March 2004, under the auspices of ESMO. Ann Oncol 2005; 16:566–578. 9. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002; 347:472–480. 10. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364:1127–1134. 11. Hwang JH, Fisher DA, Ben-Menachem T, et al. The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointest Endosc 2012; 75:1132–1138. 12. Seya T, Tanaka N, Yokoi K, Shinji S, Oaki Y, Tajiri T. Life-threatening bleeding from gastrointestinal stromal tumor of the stomach. J Nippon Med Sch 2008; 75:306–311. 13. Vats HS, Wengert TJ, Torbey CF. Gastrointestinal stromal tumor with Dieulafoy lesion: a novel association. Clin Med Res 2006; 4: 228–229.
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14. Clarke MG, Bunting D, Smart NJ, Lowes J, Mitchell SJ. The surgical management of acute upper gastrointestinal bleeding: a 12-year experience. Int J Surg 2010; 8:377–380. 15. Chikamori F, Kuniyoshi N, Okamoto H, Kuniyoshi K. A case of a gastric submucosal tumor treated with combined therapy using superselective TAE and endoscopic local resection. Surg Laparosc Endosc Percutan Tech 2012; 22:297–300. 16. Huang YW, Siao FY, Yen HH. Life-threatening bleeding from gastrointestinal stromal tumor: successful embolization with subsequent laparoscopic surgery. Am J Emerg Med 2014; 32:1150. 17. Kurihara N, Kikuchi K, Tanabe M, et al. Partial resection of the second portion of the duodenum for gastrointestinal stromal tumor after effective transarterial embolization. Int J Clin Oncol 2005; 10:433–437. 18. Strauss RG. Pretransfusion trigger platelet counts and dose for prophylactic platelet transfusions. Curr Opin Hematol 2005; 12:499–502. 19. Shander A, Goodnough LT. Update on transfusion medicine. Pharmacotherapy 2007; 27:57–68. 20. O’Connor SD, Taylor AJ, Williams EC, Winter TC. Coagulation concepts update. AJR Am J Roentgenol 2009; 193:1656–1664.
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21. Malloy PC, Grassi CJ, Kundu S, et al. Consensus guidelines for periprocedural management of coagulation status and hemostasis risk in percutaneous image-guided interventions. J Vasc Interv Radiol 2009; 20:240–249. 22. Sacks D, McClenny TE, Cardella JF, Lewis CA. Society of Interventional Radiology clinical practice guidelines. J Vasc Interv Radiol 2003; 14: S199–S202. 23. Cao G, Li J, Shen L, Zhu X. Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases. World J Gastroenterol 2012; 18:6134–6140. 24. Kobayashi K, Szklaruk J, Trent JC, et al. Hepatic arterial embolization and chemoembolization for imatinib-resistant gastrointestinal stromal tumors. Am J Clin Oncol 2009; 32:574–581. 25. Hur S, Jae HJ, Lee M, Kim HC, Chung JW. Safety and efficacy of transcatheter arterial embolization for lower gastrointestinal bleeding: a single-center experience with 112 patients. J Vasc Interv Radiol 2014; 25: 10–19. 26. Koo HJ, Shin JH, Kim HJ, et al. Clinical outcome of transcatheter arterial embolization with N-butyl-2-cyanoacrylate for control of acute gastrointestinal tract bleeding. AJR Am J Roentgenol 2015; 204:662–668.
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Table E1 . Tumor Location, Patients with Contrast Extravasation on Angiogram, Arteries that Received Embolization, and Embolic Materials Tumor Location
Patients with Contrast
Arteries that Received Embolization
Embolic Materials
Extravasation on Angiogram (n) Stomach (n ¼ 5)
Left gastric artery (n ¼ 5)
Gelatin sponge pledgets (n ¼ 3)
Left inferior phrenic artery (n ¼ 1)
NBCA (n ¼ 1) PVA (n ¼ 1)
Duodenum (n ¼ 2)
Pancreaticoduodenal artery (n ¼ 1)
Gelatin sponge pledgets þ coil (n ¼ 1)
Jejunum (n ¼ 9)
Duodenal branch (n ¼ 1) Jejunal branch (n ¼ 9)
NBCA (n ¼ 1) Coil (n ¼ 2)
1
3
Gelatin sponge pledgets þ coil (n ¼ 1) Gelatin sponge pledgets (n ¼ 3) NBCA (n ¼ 1) NBCA þ gelatin sponge pledgets (n ¼ 1) Ileum (n ¼ 3)
Jejunum þ colon (n ¼ 1)
1
Ileocolic (n ¼ 1)
Coil þ PVA (n ¼ 1) Coil þ PVA (n ¼ 1)
Ileal branch (n ¼ 2)
Gelatin sponge pledgets (n ¼ 1)
Colic and jejunal branch (n ¼ 1)
PVA (n ¼ 1) Gelatin sponge pledgets þ coil (n ¼ 1)
NBCA ¼ N-butyl cyanoacrylate, PVA ¼ polyvinyl alcohol.
