Aralık 2024

43-48

Ferhat BACAKSIZ¹,Berat EBİK¹,Bayram YEŞİL²,Volkan GÖKBULUT³,Mahmut YÜKSEL³,Özlem AKDOĞAN³,Hale GÖKCAN⁴,Sabite KACAR³,Meral AKDOĞAN³,Ertuğrul KAYAÇETİN³

Department of ¹Gastroenterology, University of Health Sciences, Diyarbakır Gazi Yasargil Education and Research Hospital, Diyarbakır, Turkey
Department of ²Gastroenterology, Kırıkkale University School of Medicine, Kırıkkale, Turkey
Department of ³Gastroenterology, Ankara Bilkent City Hospital, Ankara, Turkey
Department of ⁴Gastroenterology, Ankara University School of Medicine, Ankara, Turkey

Giriş ve Amaç:Üst gastrointestinal kanama en sık görülen gastroenterolojikacil durumlardan biridir. Endoskopik tedavi yöntemlerine rağmen bazı has-talarda tekrar kanama görülebilir. Bu nedenle riskli hastalarda tekrarlayan ka-namaları öngörebilmek önemlidir. Bu çalışmamızda, peptik ülser kanamasıylatakip ettiğimiz ve hastanede yeniden kanaması olan hastalarda bu duruma etkieden faktörleri araştırarak, kendi deneyimimizi sunmayı amaçladık.Gereç ve Yöntem:Üst gastrointestinal sistem kanaması bulguları nedeniyle başvurupendoskopi yapılan ve peptik ülser kanaması teşhisi konulan 310 hasta çalış-maya dahil edildi. Üst gastrointestinal sistem kanaması tanısı alan hastalar,kanaması tekrar edenler ve tekrarlamayan hastalar olmak üzere iki gruba ay-rıldı. Her iki gruptaki hastaların laboratuvar parametreleri, kan grupları, yaşve cinsiyet gibi demografik verileri istatistiksel olarak analiz edildi.Bulgular:Yeniden kanama oranı, ülser çapı 10 mm ve 10 mm’den küçük olan hasta-larda anlamlı olarak daha azdı (p < 0.001). Forrest sınıflandırmasına göre,Forrest 1A’daki hastaların istatistiksel olarak anlamlı şekilde daha yüksek biryeniden kanama oranı vardı (p < 0.001). Endoskopik olarak kanama kontrolüiçin dual yöntemler uygulanan hastalarda yeniden kanamanın anlamlı şekildedaha fazla olduğu görüldü (p < 0.001). Öte yandan, yüksek üre seviyesininyeniden kanama olasılığında 1.1 kat artma ile ilişkili olduğu görüldü (p =0.023).Sonuç:Çalışmamız sonucunda yaş, kan hemoglobin ve üre düzeyle-ri, ülser boyutu ile Forrest sınıflandırması ve uygulanan endoskopik yöntemsayısının tekrar kanama oranlarında etkili faktörler olduğunu belirledik. Buparametrelerin birlikte kullanılmasıyla yüksek riskli hastalar belirlenebilir.Ayrıca erken veya tekrar endoskopisi hakkında öngörüde bulunulabilir.

Üst gastrointestinal sistem kanamaları, tekrarlayan ka-nama, risk faktörleri

Upper gastrointestinal (GI) bleeding is one of the most com-mon gastroenterological emergencies. However, gastroin-testinal bleeding accounts for 5% of emergency departmentadmissions and 2% to 3% of hospitalizations in developedcountries each year (1,2). The most common cause of upperGI bleeding is nonvariceal bleeding, and peptic ulcer bleedingoccurs in 28% to 59% of cases (3-5).Helicobacter pyloriin-fection and/or use of anti-inflammatory drugs, including low-dose aspirin use, are the most important risk factors (6,7). Endoscopic hemostatic therapy has been proposed as first-line therapy for ulcers with a high bleeding risk and availableendoscopic hemostatic modalities include mechanical treatments such as adrenaline injection therapy, thermal coagula-tion, and hemoclips (8). Despite these interventions, rebleeding may occur. The rateof rebleeding after endoscopic hemostasis interventions inpeptic ulcer bleeding varies between 6.3% and 25.2% (9).Rebleeding is a common complication of peptic ulcers, andthe possibility of rebleeding often precludes hospital dis-charge (10). Therefore, it is important to predict rebleedingclinically. Observational studies have identified predictors ofrebleeding, reoperation, and death in patients with peptic ul-cer bleeding (11-15). In this study, we aimed to present our own experience byinvestigating the predictors affecting this condition in our pa-tients with rebleeding.

 

<b>Study Design and Patient Population</b><br>Three hundred and ten patients who were admitted to ourhospital due to upper GI bleeding findings and underwentendoscopy and diagnosed with peptic ulcer bleeding were in-cluded in the study. The recorded files and electronic data ofthe patients were reviewed retrospectively.<br><br><p><b>Patient Data and Definitions</b></p><p>Patients diagnosed with upper GI bleeding were basicallydivided into two groups (with or without endoscopic treat-ment) as those with recurrent bleeding and those with non-re-currence. Demographic data such as laboratory parameters,blood groups, age and gender of the patients in both groupswere statistically analyzed. In addition, these patients weredivided into subgroups according to the location, size andseverity of the bleeding ulcer. </p><p>According to the location of theulcer; they were grouped as esophageal, stomach, duodenaland anastomotic ulcers.According to the size of the ulcer, it was grouped as 0-10 mm,between 11 mm and 20 mm, and greater than 20 mm.</p><p>While grouping according to the meeting of the ulcer; For-rest classification assessing the risk of rebleeding. Accordingly,Forrest Ia, in the gushing blood; Forrest Ib, oozing bleeding;Forrest IIa, presence of visible vessels that do not bleed; ForrestIIb, adherent clot; Forrest IIc was defined as having a hematinpigment base and Forrest III as a clean-based feature (2).</p><p>According to the endoscopic hemostasis methods appliedin the treatment of ulcers, those who did not apply any en-doscopic hemostasis method, those who applied only salineadrenaline, those who applied at least one endoscopic hemo-stasis method in addition to saline-adrenaline (hemoclips, ar-gon plasma coagulation or heater probe) and other methodswere grouped.</p><p>Patients with and without rebleeding were consistently an-alyzed in these subgroups. Thus, it was aimed to determinethe factors that affect the possibility of rebleeding in thesepatients.</p><p>Exclusion CriteriaPatients younger than 18 years of age, patients with bleed-ing etiologies other than peptic ulcer bleeding (oesophagitis,Mallory Weiss tear, varicose bleeding, patients with comor-bidities such as esophageal, stomach, duodenal malignancy,patients with endoscopic non-ulcer bleeding etiology, and endoscopic bleeding focus detection) patients were excludedfrom the study.</p><p><b>Ethics Committee:</b><br>Approval for this study was receivedfrom the Ethics Committee of Turkey Higher SpecializationHospital with the decision dated 24.01.2018 and numbered31/09.</p><p>Statistical AnalysisKolmogorov-Smirnov, Shapiro-Wilk test, coefficient of varia-tion, skewness and kurtosis methods were used to control thenormal distribution of patient data. While mean and standarddeviation values were expressed in continuous variables, cat-egorical variables were expressed as percentages. To comparedemographic and descriptive parameters such as age and gen-der of peptic ulcer patients with and without recurrent bleed-ing; Independent Samples T test or Mann Whitney U test wasused. Chi-square test was used to determine whether therewas a difference between the two groups in terms of bloodgroup. The Independent Samples T test was used for normallydistributed parameters and the Mann Whitney U test was usedfor non-normally distributed data for the difference betweenlaboratory data between groups. In the analysis of peptic ulcerpatients, who were divided into two groups according to re-bleeding status, according to the location of the ulcer, the sizeof the ulcer and Forrest Classification, one-way-ANOVA wasapplied to the groups with homogeneous variances, and Chi-Square test was applied to groups with non-homogeneousvariances. One-way ANOVA test was used to compare treat-ment methods between the two groups. Binary logistic regres-sion analysis was performed to determine the factors that mostaffect the probability of rebleeding of peptic ulcer. Exp(B) and95% CI values were determined. All tests were bilateral andp value < 0.05 was considered statistically significant. Statis-tical analyzes were performed using SPSS 24.0 for Windows(SPSSInc.Chicago, IL,USA) package program.</p>

<p>Demographic Characteristics and Laboratory </p><p><b>Findings</b></p><p>Rebleeding occurred in 44 (14.2%) of a total of 310 patients.There was no significant difference between the patients interms of gender (p = 0.560). The median age of the patientswith recurrent bleeding was 67 years and it was found tobe statistically significantly higher (p = 0.011). There was nosignificant difference between the groups in terms of bloodgroups (p = 0.169). Detailed data on demographic character-istics are presented in Table 1.</p><p>When the laboraory findings of the patients at the first ad-mission were evaluated, the mean hemoglobin value of thepatients with recurrent bleeding at the time of admission was 7.97 ± 2.48 g/dl, and it was found to be statistically signifi-cantly lower (p = 0.01). In these patients, the mean plateletvolume at the time of admission was 8.8 ± 1.29 fl, which wasfound to be significantly higher (p = 0.047). The mean urealevel was found to be significantly higher at 105 ± 78.8 mg/dl in patients with recurrent bleeding (p = 0.041) (Table 2).</p><p><b><br>Endoscopic Findings</b></p><p>When the bleeding localizations of the patients with recur-rent bleeding were evaluated, no difference was found interms of ulcer location, but it was found that the bleeding wassignificantly less in patients with ulcer diameters of 10 mmand less than 10 mm (p < 0.001). As expected, patients withgroup 1A according to Forrest classification had a statistical ly significant higher rate of rebleeding (p < 0.001). Detaileddata on ulcer location, size and Forrest classification are pre-sented in Table 3. When the endoscopic intervention meth-ods applied to the patients were compared, it was seen thatrebleeding was more common in the patients who receiveddual therapy (p < 0.001) (Table 4). In the logistic regressionanalysis, it was determined that patient age, urea level, ulcersize and Forrest classification were independent risk factorsfor rebleeding. Age increased the probability of rebleeding1.04 times in patients with peptic ulcer [p = 0.008; Exp(B)= 0.955]. High urea level, on the other hand, increased theprobability of rebleeding by 1.1 times [p = 0.023; Exp(B) =0.989]. The probability of rebleeding was 3.7 times higher inpatients with low hemoglobin [p = 0.001; Exp(B) = 3.709].  According to the Forrest Classification, Forrest 1A ulcerswere 2.58 times more likely to bleed again than Forrest 2 and3 ulcers [p = 0.001; Exp(B) = 2.584].  Considering the ulcer size, an ulcer larger than 20 mm was3.83 times more likely to bleed again than an ulcer smallerthan 10 mm [p < 0.001; Exp(B) = 0.261] (Table 5). </p>

<p>Despite the reduction in incidence, owing to the widespreaduse of modern endoscopic techniques in combination withproton pump inhibitors, the mortality rate associated withnon-variceal upper gastrointestinal bleeding is still high (16).Therefore, since it is important to evaluate the factors thatmay affect recurrent bleeding in the early period, we thoughtthat our experience would make an additional contributionto the literature.</p><p>In our study, we found that especially ulcer size less than 1cm significantly reduced the risk of recurrent bleeding. Wethought that the reason for this is that small ulcer bleedingcan be controlled more easily with endoscopic therapeutic in-terventions and there is a faster chance of healing. In parallelwith our study, Budimir et al. found that ulcers larger than 2cm significantly increased the risk of rebleeding (2).</p><p>We found that low hemoglobin level at the time of admissionincreased the risk of rebleeding. In such a case, we think thatthe ulcer causing bleeding may indicate an ulcer that is diffi-cult to control. It has been stated that a hemoglobin level be-low 10 g/dl has a predictive value in terms of rebleeding (17).In another study, it was reported that low hemoglobin levelpredicted life-threatening bleeding in patients with acute gas-trointestinal bleeding (18). We found that high blood urealevel at the time of admission also increased the risk of re-bleeding. High blood urea level has been reported to be asso-ciated with severe gastrointestinal bleeding (19,20). It is alsoknown that high urea impairs platelet functions and increasesthe tendency to coagulopathy (21).</p><p>It is known that advanced age and ulcer type in Forrest Clas-sification also increase the risk of rebleeding, as in Rockall</p><p>scoring (22,23). We found these data to be compatible withthe literature.</p><p>The limitations of our study were that it was retrospective,limited to a single center, comorbid conditions and the useof anticoagulants and antiaggregants were not known. Inpatients with upper GI bleeding due to peptic ulcer, thestrength of our study was to evaluate and analyze many pa-rameters, such as the patient, the lesion causing the bleeding,and the treatment applied, from the moment of admission tothe hospital.</p><p>When estimating the possibility of rebleeding in upper GIbleeding due to peptic ulcer, it would be more accurate toevaluate many parameters of the patient, as well as the sever-ity of bleeding, the diameter of the ulcer and the endoscopictreatment applied. By observing these parameters together,high-risk patients can be identified and more care can be tak-en in bleeding management. It can also give an idea aboutearly endoscopy again.</p><p>Ethics Committee:Approval for this study was received fromthe Ethics Committee of Turkey Higher Specialization Hospi-tal with the decision dated 24.01.2018 and numbered 31/09.</p><p>Conflict of Interest:The authors have no conflict of interestto declare.</p><p>Funding:The authors declared that this study has received nofinancial support.</p><p>Author Contributions:Consept-FB, BE; Design-BY, VG; Su-pervision-MY, ÖA; Data Collection and/or Processing-HG, SK;Analysis and/or Interpretation-MA, EK; Literature Search-BY,MY, MA; Writing Manuscript-FB, BE; Critical Review-VG,ÖA.</p>

1. Lanas A, Aabakken L, Fonseca J, Mungan ZA, et al. Clinical predictors of poor outcomes among patients with nonvariceal upper gastrointestinal bleeding in Europe. Aliment Pharmacol Ther. 2011;33(11):1225-33. <p>2. Budimir I, Stojsavljević S, Hrabar D, et al. Bleeding Peptic Ulcer - Tertiary Center Experience: Epidemiology, Treatment and Prognosis. Acta Clin Croat. 2017;56(4):707-14. <p>3. Holster IL, Kuipers EJ. Management of acute nonvariceal upper gastrointestinal bleeding: current policies and future perspectives. World J Gastroenterol. 2012;18(11):1202-7. </p><p>4. Budimir I, Nikolić M, Supanc V, et al. Secondary arterio-enteric fistula: case report and review of the literature. Acta Clin Croat. 2012;51(1):79-82.</p><p>5. Van Leerdam ME. Epidemiology of acute upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol. 2008;22(2):209-24. </p><p>6. De Groot NL, van Oijen MG, Kessels K, et al. Reassessment of the predictive value of the Forrest classification for peptic ulcer rebleeding and mortality: can classification be simplified? Endoscopy. 2014;46(1):46- 52.</p><p>7. Lau JY, Sung J, Hill C, et al Systematic review of the epidemiology of complicated peptic ulcer disease: incidence, recurrence, risk factors and mortality. Digestion. 2011;84(2):102-13 </p><p>8. Shi K, Shen Z, Zhu G, et al. Systematic review with network meta-analysis: dual therapy for high-risk bleeding peptic ulcers. BMC Gastroenterol. 2017;17(1):55. </p><p>9. Ogiyama H, Tsutsui S, Murayama Y, et al. Renal Dysfunction is an Independent Risk Factor for Rebleeding After Endoscopic Hemostasis in Patients with Peptic Ulcer Bleeding. Turk J Gastroenterol. 2021;32(8):622-30. </p><p>10. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol 2012;107(3):345-60. </p><p>11. Lolle I, Møller MH, Rosenstock SJ. Association between ulcer site and outcome in complicated peptic ulcer disease: a Danish nationwide cohort study. Scand J Gastroenterol. 2016;51(10):1165-71. </p><p>12. Lau JY, Sung J, Hill C, et al. Systematic review of the epidemiology of complicated peptic ulcer disease: incidence, recurrence, risk factors and mortality. Digestion. 2011;84(2):102-13.</p><p>13. Elmunzer BJ, Young SD, Inadomi JM, Schoenfeld P, Laine L. Systematic review of the predictors of recurrent hemorrhage after endoscopic hemostatic therapy for bleeding peptic ulcers. Am J Gastroenterol.2008;103(10):2625-32. </p><p> 14. García-Iglesias P, Villoria A, Suarez D, et al. Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding peptic ulcer. Aliment Pharmacol Ther. 2011;34(8):888-900. </p><p>15. Sung JJ, Tsoi KK, Ma TK, et al. Causes of mortality in patients with peptic ulcer bleeding: a prospective cohort study of 10,428 cases. Am J Gastroenterol. 2010;105(1):84-9. </p><p>16. Lazăr DC, Ursoniu S, Goldiş A. Predictors of rebleeding and in-hospital mortality in patients with nonvariceal upper digestive bleeding. World J Clin Cases. 2019;7(18):2687-703. </p><p>17. Wong SK, Yu LM, Lau JY, et al. Prediction of therapeutic failure after adrenaline injection plus heater probe treatment in patients with bleeding peptic ulcer. Gut. 2002;50(3):322-5. </p><p>18. Deutsch D, Romegoux P, Boustière C, et al. Clinical and endoscopic features of severe acute gastrointestinal bleeding in elderly patients treated with direct oral anticoagulants: a multicentre study. Therap Adv Gastroenterol. 2019;12:1756284819851677. </p><p>19. Tomizawa M, Shinozaki F, Hasegawa R, et al. Patient characteristics with high or low blood urea nitrogen in upper gastrointestinal bleeding. World J Gastroenterol. 2015;21(24):7500-5. </p><p>20. Bang CS, Lee YS, Lee YH, et al. Characteristics of nonvariceal upper gastrointestinal hemorrhage in patients with chronic kidney disease. World J Gastroenterol. 2013;19(43):7719-25. </p><p>21. Hedges SJ, Dehoney SB, Hooper JS, Amanzadeh J, Busti AJ. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3(3):138-53. </p><p>22. Kim MS, Choi J, Shin WC. AIMS65 scoring system is comparable to Glasgow-Blatchford score or Rockall score for prediction of clinical outcomes for non-variceal upper gastrointestinal bleeding. BMC Gastroenterol. 2019;19(1):136. </p><p>23. Stanley AJ, Laine L, Dalton HR, et al. Comparison of risk scoring systems for patients presenting with upper gastrointestinal bleeding: international multicentre prospective study. BMJ. 2017;356:i6432.</p></p>