Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding | Gastrointestinal kanama odaǧi{dotless}ni{dotless}n saptanmasi{dotless}nda işaretli eritrosit sintigrafisinin rolü

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Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding | Gastrointestinal kanama odaǧi{dotless}ni{dotless}n saptanmasi{dotless}nda işaretli eritrosit sintigrafisinin rolü

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  225Turkish Journal of Trauma & Emergency SurgeryOriginal Article Klinik Çalışma Ulus Travma Acil Cerrahi Derg 2012;18 (3):225-230 Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding Gastrointestinal kanama odağının saptanmasında işaretli eritrosit sintigrafisinin rolü Yasemin ŞANLI, 1  Zeynep Gözde ÖZKAN, 1  Serkan KUYUMCU, 1  Hakan YANAR , 2  Emre BALIK , 2   Handan TOKMAK, 1  Cüneyt TÜRKMEN, 1  Işık ADALET 1 Departments of 1 Nuclear Medicine, 2 General Surgery, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey. İstanbul Üniversitesi, İstanbul Tıp Fakültesi, 1 Nükleer Tıp Anabilim Dalı, 2 Genel Cerrahi Anabilim Dalı, İstanbul. Correspondence (İletişim):  Zeynep Gözde Özkan, M.D. İÜ İstanbul Tıp Fakültesi Nükleer Tıp Anabilim Dalı Sekreterliği, Çapa-Fatih 34390 İstanbul, Turkey.Tel: +90 - 212 - 414 20 00 / 32963 e-mail (e-posta):  zgozdeozkan@yahoo.com  AMAÇ  Gastrointestinal sistem (GİS) kanamalarında kanama odağı - nın saptanmasında, Tc-99m ile işaretli eritrosit (RBC) sintig - rasinin rolü klinik deneyimlerimiz ışığında değerlendirildi. GEREÇ VE YÖNTEM  1995-2010 yılları arasında GİS kanaması odağının belir  - lenmesi amacıyla kliniğimize gönderilen 57 hasta (27 ka - dın, 30 erkek; ortalama yaş 43.9±24; dağılım 1-91 yıl) ge - riye dönük olarak çalışmaya alındı. Sintigra öncesi has - taların 51’ine gastroskopi, 45’ine kolonoskopi, 9’una anji - yogra yapılmıştı.  BULGULAR RBC sintigrasi hastaların 31’inde pozitif ve 26’sında ne - gatifti. Pozitif sintigrak bulgular, 19 hastada ilk bir saatlik dinamik imajlarda, 7 hastada 1-4. saatler arası statik imaj - larda, 5 hastada ise 4-24. saatler arasında alınan statik imaj - larda kaydedildi. Toplam 14 hasta GİS kanaması nedeniyle ameliyat edildi. On üç hastada kanama yeri RBC sintigra - si tanısıyla doğrulandı (doğruluk: %92,8). Ameliyat edilme - yen 43 hastanın 12’sinde nedeni bilinmeyen demir eksikli - ği anemisi vardı ki bu hastaların tümünde sintigra negatif olarak sonuçlandı. Yoğun kanama bulguları olan 4 hasta me - dikal takip sürecinde kaybedildi, geri kalan 27 hastanın ka - namaları kendiliğinden ya da konservatif tedavilerle durdu.  SONUÇ  Çalışmamız aktif GİS kanamalarında kanama odağının be - lirlenmesinde sintigranin primer yöntem olması gereklili - ğini göstermektedir. Özellikle ilk 1 saatlik dinamik görün - tüleme esnasında saptanan pozitif imajlar, kanama odağı - nın doğru yerinin saptanmasında ve cerrahi gerekliliğin be - lirlenmesinde yol göstericidir.  Anahtar Sözcükler: Gastrointestinal kanama; işaretli eritrosit sin - tigrasi; endoskopik girişimler.  BACKGROUND We aimed to evaluate the role of Tc-99m labeled red blood cell (RBC) scintigraphy for determination of localization of gastrointestinal system (GIS) bleeding.  METHODS  Fifty-seven cases (27 females, 30 males; mean age 43.9±24; range 1 to 91 years) who referred to our clinic  between 1995-2010 were evaluated for determination of localization of GIS bleeding with RBC scintigraphy. Prior to scintigraphy, gastroscopy in 51, colonoscopy in 45, and angiography in 9 patients were performed.  RESULTS  RBC scintigraphies were positive and negative in 31 and 26 patients, respectively. Positive scintigraphic ndings were obtained within the 1st hour of dynamic imaging in 19 patients, within the 1st-4th hour static images in 7, and within the 4th-24th hour images in 5 patients. Fourteen  patients underwent surgical exploration. In 13 patients, the surgery conrmed the diagnosis by RBC scintigraphy (ac - curacy: 92.8%). Of 43 patients without surgical explora - tion, 12 had anemia due to iron deciency and their scin - tigraphic evaluation were negative. Four patients died and in 27 patients, GIS bleeding ceased spontaneously or with conservative measures. CONCLUSION  Scintigraphy should be the primary tool for accurate di - agnosis of patients with active GIS bleeding. Positive dy - namic images obtained within the rst hour of imaging may be more accurate for demonstrating bleeding local - ization and a good predictor of requirement of surgical exploration.  Key Words:  Gastrointestinal bleeding; red blood cell scintigraphy; endoscopic intervention. doi: 10.5505/tjtes.2012.55553  Ulus Travma Acil Cerrahi Derg Gastrointestinal hemorrhage is a common indica - tion for hospital admission. While the great majority of the bleedings are observed to be from the upper gas - trointestinal system (GIS), about 20% of them srci - nate from the lower GIS. [1]  In the upper GIS bleedings, the source of bleeding can be localized in 80-97% with endoscopy and 75% of these will either stop sponta - neously or will respond to the medical therapy, while 10% of them will require urgent operation. [2]  In the case of lower GIS bleedings, 80% will cease spon - taneously without further intervention, about 25% of them will start to bleed again, and about 10-15% will require urgent operation. [3]   It is essential to locate the site of bleeding before any intervention. The current methods for this pur  -  pose are endoscopy, angiography, and scintigraphic techniques. Among these, as a major advantage, scin - tigraphic methods permit the rendering of the visual image of the whole abdomen at the same time. [4]  For this reason, some authors advocate the evaluation of  patients with scintigraphic methods before undergoing endoscopy or angiography. [3,5-8]   The aim of this retrospective study is to report our clinical experience with red blood cell (RBC) scintig - raphy and to discuss the role of this method in light of the contemporary literature. MATERIALS AND METHODS Scintigraphic ndings of a total of 57 cases (27 fe - males, 30 males), with a mean age of 43.9±24 (1-91) years, who were referred to our clinic between 1995 and 2010 were evaluated retrospectively. The patients who were referred to our clinic had at least one diag - nostic examination, such as gastroscopy, colonoscopy or angiography, and the results of the examinations were interpreted as either “normal” or as “no bleeding focus could be found”.  Red Blood Cell Labeling Technique:  In this study, in vivo and the modied in vitro erythrocyte labeling techniques were used. Briey, in the in vivo  technique, 20 minutes (min) after the injection of stannous agent, 20 millicurie (mCi) (in children 0.2 mCi/kg) Tc-99m injection was performed. [8]  On the other hand, in the modied in vitro technique, 10-15 min after the in -  jection of stannous agent, 3-5 ml of blood was drawn from the patient into a heparin-washed injector and transferred to a sterile tube containing 20 mCi (in chil - dren 0.2 mCi/kg) Tc-99m. The sample was then incu -  bated either at 37ºC for 10 min or at room temperature for 20 min before its reinjection to the patient. [9]    Imaging Procedures:  The images were obtained  by using low-energy all-purpose collimators (ADAC Vertex Plus, Milpitas, CA). The images obtained after the injection were taken from the anterior position in which the camera’s area of focus included the entire abdominal region. The images of the rst hour were recorded as dynamic images in 60 frames, each with a duration of 60 seconds (s). In the following hours (rst 4-6 hours), images were obtained at the beginning of each hour as static images of 300 s. When necessary, a late image was obtained up to the 24th hour.  Interpretation:  In the images obtained, the detec - tion of an abnormal activity pattern in the abdominal region was evaluated as positive. Changes in localiza - tion of activity in static images were accepted as due to intraintestinal activities. If focal activity remained xed and did not change in conguration over time, then it was not interpreted as representing a bleeding site. The scintigraphic results as well as endoscopic, colonoscopic, angiographic, and operational ndings were evaluated together with the available follow-up of the patients. RESULTS Twenty-three of the patients had a complaint of hematochezia, while 34 complained of melena. The mean hemoglobin level of the patients with GIS  bleeding was found to be 7.3±1.2 (4.1-9.6) mg/dl. In their histories, 10 patients were on steroids, 6 were on non-steroid anti-inammatory drugs, 2 were on acetylsalicylic acid, and 1 patient was on oral anti-coagulants. Prior to scintigraphy, gastroscopy in 51 (89.4%), colonoscopy in 45 (78.9%) and angiogra -  phy in 9 (15.7%) patients were performed. Of the 57 scintigraphies, 31 (54.4%) were found to be positive, while 26 (45.6%) were found to be negative. Four  - teen of 31 patients underwent urgent surgical explo - ration due to lower GIS bleeding primarily based on the scintigraphic ndings. Operational ndings of 13  patients conrmed the diagnosis of the scintigraphic ndings, giving an accuracy of 92.8% for the scinti - graphic technique. The result of the scintigraphy of one case was interpreted as a bleeding of the small intestine; however, the site of bleeding was found to  be her hemorrhoids (Table 1). Scintigraphies of 19 patients were positive in the 1st hour dynamic images. Scintigraphies were positive in the initial 1st-4th hour static images in 7 patients and in the 4th-24th hour static images in 5 patients. Of 19 patients with positive scintigraphies within the 1st hour dynamic images, 10 were operated and 9 were treated medically (Fig. 1). Unfortunately, 3 patients died after obtaining posi - tive scintigraphic ndings. Of the 7 patients with posi - tive scintigraphic ndings in the 1st-4th hour static images, 2 were operated and 5 received medical treat - ment. Two of 5 patients with positive scintigraphic ndings in the 4th-24th hour static images were oper  - ated, and the remaining 3 patients were treated medi - 226 Mayıs - May   2012  Role of red blood cell scintigraphy for determining the localization of gastrointestinal bleeding cally (Table 2). As a result, of 31 cases who had posi - tive scintigraphic ndings, 14 were operated, and in 13 (92.8%) of the patients, it was noted that the cor  - rect foci of the bleeding was determined with RBC scintigraphy. From another aspect, among patients whose sites of bleeding were localized with scinti - graphic methods, 48.1% required surgical interven - tion (Table 3).Of the 43 patients who were not operated, 2 pa - tients died due to abundant bleeding, 1 patient died due to pneumonia, and 1 patient who was evaluated as negative died due to hemolytic uremia syndrome. The GIS bleeding of the remaining 39 patients ceased spontaneously or with conservative measures (i.e.,  blood transfusion, vitamin K injection, iron supple - ments, suppositories for internal hemorrhoids). Cilt - Vol.  18 Sayı - No.  3227 Table 1.  Features of patients who underwent surgery for gastrointestinal system bleeding No Age/Sex Scan localization Operation Pathologic nding 1 60/F Small intestine Partial ileal resection Primary non-Hodgkin lymphoma2 62/M Small intestine Partial ileal resection Metastases of lung carcinoma3 34/M Rectum Hemorrhoid Hyperplastic polyps4 42/F Small intestine Internal hemorrhoid Hyperplastic polyps5 63/M Diffuse colon Right hemicolectomy Hemorrhagic diverticulosis6 63/M Small intestine Partial ileal resection Jejunal diverticulosis 7 72/F Small intestine Partial ileal resection Small intestinal segment with focal hemorrhagic necrosis8 75/F Ascending colon Right hemicolectomy Hemorrhagic diverticulosis9 10/F Small intestine Diverticulectomy + Partial ileal resection Meckel’s diverticulum10 53/M Small intestine Partial ileal resection Gastrointestinal stromal tumor 11 14/M Small intestine Partial ileal resection Hemangioma12 44/M Small intestine Partial ileal resection Small intestinal segment with focal hemorrhagic necrosis13 12/M Small intestine Partial ileal resection Hemangioma14 5/F Small intestine Partial ileal resection Small intestinal segment with focal hemorrhagic necrosis Table 2.  Scintigraphy timing and requirement of urgent surgical exploration 1st hour 1st - 4th hour 4th - 24th hour  dynamic images (n) static images (n) static images (n) Requirement of surgical exploration 10 2 2Conservative therapy 9* 5 3 * Three patients died while under conservative treatment without surgical intervention. Fig. 1.  A 58-year-old patient was admit - ted to the emergency room with the complaint of hematochezia. Tc-99m labeled RBC scintigraphy was per  - formed to detect a possible lower gastrointestinal bleeding. In the early dynamic images, bleeding was de - tected on the right side of the iliac  bifurcation (small arrow) with signi - cant increased activity in the follow - ing frames (arrow). The localization of the bleeding was interpreted in the region of the small intestine. Based on the scintigraphic ndings, the patient was operated. In the surgical explora - tion, a bleeding jejunal diverticulum was seen and resected, with the con - rmation of a negative surgical mar  - gin (Table 1, patient number 6).  Ulus Travma Acil Cerrahi Derg DISCUSSION In the determination of the localization of bleed - ings in the GIS, scintigraphic methods have been used over the last 20 years. Some studies have recommend - ed scintigraphic evaluation as the rst method to be employed. [3,5-8]  In the present study, RBC scintigraphy was not the initial diagnostic method, since all patients had received at least one radiological examination pri - or to their referral to our clinic. However, no positive result was obtained in any of these examinations for the foci of the bleeding. At this point, the question is whether the scintigraphic techniques for GIS bleeding should be an initial step for the diagnosis or an assist - ing technique to the other diagnostic tools such as en - doscopy and angiography. Although for most centers, RBC scintigraphy is an assisting technique, clinicians should keep in mind that a signicant portion of the  patients with GIS bleeding are diagnosed with scin - tigraphy. For this reason, it may be rational to carry this minimally invasive technique to one of the rst steps of the algorithm for the management of a bleed - ing patient.In the literature, the ratio of detection of lower GIS  bleedings with scintigraphy has been reported as be - tween 75-92%. [6]  In our study, 31 of the 57 patients (54.3%) with GIS bleedings were found to be positive with scintigraphy. Gunderman et al. [10]  reported that, of the 249 cases evaluated with GIS bleeding scans, 115 (51.3%) were found to be positive, and of them, 37 positive cases underwent surgical exploration. In 36 patients (97.3%), an accurate bleeding localization was determined through scintigraphy. The require - ment for surgical treatment was determined to be 5 times greater for the patients who were positive on scintigraphic evaluation. In our study, of the 31 cases with positive scintigraphic ndings, 14 were operated, and in 13 (92.8%) of them, it was noted that the correct foci of the bleeding was determined with RBC scin - tigraphy. From another aspect, among patients whose sites of bleeding were localized with scintigraphic methods, 48.1% required surgical intervention. Many investigators claim that the rst method of choice in the determination of lower GIS bleedings should be colonoscopy, since it facilitates not only the diagnosis but also effective treatments with elec - trocautery and similar interventions. [11,12]  However, in acute bleedings requiring urgent management, since colon cleaning cannot be done, colonoscopy may not localize the focus of the bleeding. Vernava et al. [13]  reported the ratio of determining the localiza - tion of bleeding in patients with severe hematochezia as between 74-82%. In the present study, of 51 and 45 patients with initial gastroscopic and colonoscopic evaluations, respectively, who were referred to our de -  partment, none had a demonstrable bleeding site with these techniques. Mesenteric angiography is capable of providing high resolution images and showing the vascular anat - omy in the denitive localization of the focus point of the bleeding, and hence is far superior to scintigra -  phy. During the procedure, therapeutic interventions can also be done. While bleedings over 0.05 ml/min can be determined with scintigraphic methods, bleed - ings over 0.5 ml/min can be determined with angiog - raphy. [14,15]  Therefore, if the scintigraphy proves to be negative, there is no practical benet in performing an angiography. [16-18]  In addition, RBC scintigraphy may  be helpful in establishing the correct timing of the an - giography. [19]  In the present study, angiography was  performed in nine patients with negative results be - fore referral to our center. In all of these patients, RBC scintigraphies were found to be positive, and three  patients underwent surgical exploration. Conservative measures were applied in the remaining patients.Endoscopy and angiography are generally unsuc - cessful for demonstrating intermittent bleedings. How - ever, scintigraphy is quiet helpful due to its ability to demonstrate intermittent bleedings. Moreover, com -  pared with the above-mentioned diagnostic methods, scintigraphy has the advantage of high tolerability due to its minimally invasive nature. 2-3 ml of extrava - sated blood is sufcient for detection. [20,21]  Another advantage brought about by this technique is the ca -  pability of long-term imaging (up to 24 hours) due to circulation of radioactively marked erythrocytes in the  blood pool. [22-24]   Timing for scintigraphy is important for determin - ing bleeding localization correctly. Ten of 19 (52.6%)  patients with positive scintigrams in the rst hour un - derwent surgical exploration. In all patients, bleeding sites had been demonstrated with scintigraphic meth - 228 Mayıs - May   2012 Table 3. Proportion of positive scan results: surgical versus non-operative casesScan results Operative  Non-operative % Requiring [no. (%)] [no. (%)] surgeryPositive / localizing (27) 13 (92.8 %) 14 (32.5%) 48.1Positive / non-localizing (4) 1 (7.2%) 3 (7%) 25 Negative (26) – 26 (60.5%) – Total (57) 14 (100%) 43 (100%) 24.5  ods accurately. The single case of an incorrect posi - tive scan, in which an internal hemorrhoid was inter  -  preted as a small intestine bleeding, was observed in the 4th-24th hour static images. In addition, other non-localizing scans were found in the same time interval. Although Jacobson et al. [25]  reported that patients with late positive scans had a higher rate of surgery than late negative patients, according to the present study, a  positive dynamic image obtained within the rst hour is a mainstay for accurate localization of the bleeding and higher rate of requirement of surgery.The use of RBC scintigraphy as a tool for risk strat - ication may assist an algorithmic approach to man - agement and may also help to prevent an overaggres - sive surgical approach to management, which may reduce both morbidity and mortality. [19]  A negative scintigraphic study is predictive of a good outcome and may be a very useful means of risk stratication in patients who do not need to be put at an unneces - sary risk of emergency surgery. [26]  Consistent with the above-mentioned opinion, in the present study, no pa - tient with negative RBC scintigraphy underwent ur  - gent surgical exploration. Schillaci et al. [27]  performed a study with Tc-99m RBC scintigraphy using a single- photon emission computed tomography (SPECT)/CT hybrid imaging system in patients with lower GI bleeding. This sys - tem was used only for patients with positive planar scintigraphy and the authors found that SPECT/CT images may yield a better localization of GI bleeding in comparison with the standard planar scan. Glucagon can be used in conjunction with RBC scintigraphy for improving detection and localization of the bleeding site. Further, the use of subtraction scintigraphy during RBC imaging may improve the contrast. [28] In conclusion, the present study addresses the im -  portance of RBC scintigraphy in determination of the correct localization of GIS bleedings. For this reason, RBC scintigraphy could be the primary tool for the diagnosis of patients with GIS bleeding, especially in centers without immediate availability to angiograph - ic intervention. Moreover, positive dynamic images obtained within the rst hours of the imaging are prob - ably more accurate for demonstrating the bleeding lo - calization and are a good predictor of the requirement of surgical exploration. REFERENCES 1. Friedman LS, Martin P. The problem of gastrointestinal  bleeding. Gastroenterol Clin North Am 1993;22:717-21.2. Fuad H, Sleiman N, Al-Enizi E. Gastrointestinal bleeding. In: Elgazzar A, editor. The pathophysiologic basis of nuclear medicine. Berlin: Springer Verlag; 2001. p. 289-290.3. Al Qahtani AR, Satin R, Stern J, Gordon PH. Investiga - tive modalities for massive lower gastrointestinal bleeding. World J Surg 2002;26:620-5.4. Alavi A, Worsley D, Zhuang H. Scintigraphic detection and localization of gastrointestinal bleeding sites. In: Sandler MP, editor. Diagnostic nuclear medicine. 4th ed., Philadel -  phia: Lippincott Williams & Wilkins; 2003. p. 531-51.5. Winzelberg GG, McKusick KA, Froelich JW, Calla - han RJ, Strauss HW. Detection of gastrointestinal bleed - ing with 99mTc-labeled red blood cells. Semin Nucl Med 1982;12:139-46.6. Orecchia PM, Hensley EK, McDonald PT, Lull RJ. Localiza - tion of lower gastrointestinal hemorrhage. Experience with red blood cells labeled in vitro with technetium Tc 99m. Arch Surg 1985;120:621-4.7. Treves ST, Grand RJ. Gastrointestinal bleeding. In: Treves ST, editor. Pediatric nuclear medicine. 2nd ed., New York: Springer-Verlag; 1994. p. 453-462.8. Kostamo KL. Evaluation of gastrointestinal bleeding by nu - clear medicine techniques. In: Henkin RE, Boles MA, Dille - hay GL, editors. Nuclear medicine. Vol II, St. Louis: Mosby, Inc., 1996. p. 1016-1022.9. Suzman MS, Talmor M, Jennis R, Binkert B, Barie PS. Ac - curate localization and surgical management of active lower  gastrointestinal hemorrhage with technetium-labeled eryth - rocyte scintigraphy. Ann Surg 1996;224:29-36.10. Gunderman R, Leef J, Ong K, Reba R, Metz C. 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Am J Gastroenterol 1989;84:878-81.16. Nicholson ML, Neoptolemos JP, Sharp JF, Watkin EM, Fos - sard DP. Localization of lower gastrointestinal bleeding us - ing in vivo technetium-99m-labelled red blood cell scintigra -  phy. Br J Surg 1989;76:358-61.17. Zuckerman GR, Prakash C. Acute lower intestinal bleeding:  part I: clinical presentation and diagnosis. Gastrointest En - dosc 1998;48:606-17.18. Baum S. Angiography and the gastrointestinal bleeder. Radi - ology 1982;143:569-72.19. Howarth DM. The role of nuclear medicine in the detec - tion of acute gastrointestinal bleeding. Semin Nucl Med 2006;36:133-46.20. Thrall JH, Ziessman HA. Gastrointestinal system. In: Thrall JH, Ziessman HA, editors. Nuclear medicine. The Requi - sites. 2nd ed., St Louis: Mosby, Inc., 2001. p. 280-91.21. Hoedema RE, Luchtefeld MA. The management of lower gas - trointestinal hemorrhage. Dis Colon Rectum 2005;48:2010-24. 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