식도정맥류 밴드결찰술 후 궤양 치유에 대한 양성자 펌프 억제제의 효과 = The Effect of Proton Pump Inhibitor on Healing of Post-esophageal Variceal Ligation Ulcers

국문 초록 (Abstract)

목적: 식도정맥류 출혈 치료에서 식도정맥류밴드결찰술(esophageal band ligation, EVL)은 합병증의 적은 발생 빈도 때문에 최근에 가장 널리 시행되는 치료방법이다. 그러나 EVL 시술 후 거의 대부분에서 의인성의 식도궤양이 발생하기 때문에 출혈, 흉통, 흉골하 작열감, 연하통 등의 합병증이 있다. 이번 연구에서는 양성자펌프억제제(Proton pump inhibitor, PPI)제제의 일종인 pantoprazole을 사용하여 위산분비를 억제하고 EVL 시행 후 궤양의 치유에 대한 효과를 알아보고자 하였다. 대상 및 방법: 전체 47명의 간경변으로 인한 식도정맥류 출혈 환자들을 PPI 투여군과 대조군으로 무작위로 나누었다. PPI 투여군에서는 EVL 시행 후 pantoprazole 3일간 40 mg을 하루 한번 정맥 투여하였고 이후 11일간 40 mg을 경구 투여하였다. 대조군에서는 동일한 기간 동안 위약을 정맥 및 경구 투여하였다. 2회의 추적 내시경 검사를 EVL 후 7일째와 14일째 각각 시행하였다. 연구의 결과물로 식도궤양의 크기를 측정하고 설문지를 통한 증상 점수를 구한 후 두 군 간에 비교하였다. 결과: 47명 모든 환자(PPI투여군 25명, 대조군 22명)가 EVL 후 7일째 추적 내시경 검사를 시행하였고, 26명의 환자(PPI 투여군 16명, 대조군 10명)에서 14일째 추적 내시경 검사를 시행하였다. 19명(PPI투여군 9명, 대조군 10명)의 환자들이 14일째 검사를 거부하였으며, 대조군 중 2명의 환자에서 합병증이 발생되어 검사를 시행 못하였는데 그 중 한 명은 간부전으로, 다른 한 명은 EVL 후 궤양에서의 출혈과 함께 패혈증으로 사망하였다. 두 군 간에 환자 특성들에서는 차이가 없었고, EVL 후 식도 궤양 크기의 비교에서 7일째와 14일째 모두에서 유의한 수준에서 PPI 투여군이 대조군보다 작았다(7일째; 98.7 mm2：119.4 mm2, 14일째; 32.3 mm2：42.8 mm2, p＜0.001). 설문지를 통한 흉통, 흉골하 작열감, 연하통의 증상 점수의 비교에서는 두 군 간에 차이가 없었다. 결론: EVL 시술 후 발생된 식도궤양의 크기 비교에서 시술 후 7일째와 14일째 모두에서 PPI 투여군이 대조군보다 의미 있게 궤양의 크기가 작았다. 따라서 EVL 시행 후 PPI의 투여는 궤양 치유에 도움이 될 것으로 생각한다.

다국어 초록 (Multilingual Abstract)

Background/Aims: Esophageal variceal ligation (EVL) is the most preferable method for controling variceal bleeding. However, EVL is associated with complications such as hemorrhage, chest pain, dysphagia, and odynophagia due to post-EVL ulcers in the esophageal mucosa. The aim of this study was to assess the effect of proton pump inhibitor (PPI), pantoprazole on the healing of post-EVL ulcers. Methods: Forty seven patients were randomly allocated into PPI group and control group. Patients in PPI group received 40 mg of pantoprazole intravenously for 3 days after EVL, then 40 mg of oral pantoprazole for 11 days consecutively. Control patients received intravenous and oral placebo. Endoscopic examinations were performed twice at 7±2 days and 14±2 days after EVL respectively. Clinical outcomes include the size of ulcers, symptoms reported by patients; chest pain, dysphagia, and odynophagia. Results: Forty seven patients completed the 7 days protocol (PPI/control; 25/22), and twenty six patients completed the 14 days protocol (PPI/control; 16/10). Post-EVL ulcers in PPI group were significantly smaller than those in control group (7 days; 98.7 mm2/119.4 mm2, 14 days; 32.3 mm2/43.8 mm2, p＜0.01). No difference was observed between two the groups with respect to summations of symptom scores (p＞0.05). Nineteen patients (PPI/control; 9/10) did not complete the 14 days protocol due to patients`` refusal and adverse outcomes, such as hepatic failure and sepsis with bleeding from post-EVL ulcer occurred in two patients of control group. Conclusions: PPI treatment following EVL may be effective in healing post-EVL ulcer. (Korean J Gastroenterol 2008;51:232-240)

참고문헌 (Reference)

1 Lee DH, "치핵의 고무밴드 결찰요법 및 적외선 응고법" 12 : 651-652, 1995

2 Yoo K, "간경변 합병증 치료 가이드라인: 정맥류 출혈의 치료 가이드라인" 11 : 139-149, 2005

3 Singal AK, "Ulceration after esophageal and gastric variceal sclerotherapy: influence of sucralfate and other factors on healing" 20 : 238-240, 1988

4 Roark G, "Treatment of postsclerotherapy esophageal ulcers with sucralfate" 30 : 9-10, 1984

5 Chen WC, "Symptomatic esophageal stricture after endoscopic variceal ligation--success of endoscopic balloon dilation" 63 : 144A-147A, 2000

6 Polson RJ, "Sucralfate for the prevention of early rebleeding following injection sclerotherapy for esophageal varices" 10 : 279-282, 1989

7 Van Vlierberghe H, "Severe bleeding following endoscopic variceal ligation: should EVL be avoided in Child C patients?" 62 : 175-177A, 1999

8 Tabibian N, "Sclerotherapy-associated esophageal ulcers: lessons from a double-blind, randomized comparison of sucralfate suspension versus placebo" 35 : 312-315, 1989

9 Garg PK, "Role of omeprazole in prevention and treatment of postendoscopic variceal sclerotherapy esophageal complications. Double-blind randomized study" 40 : 1569-1574, 1995

10 Guglielmi A, "Risk assessment and prediction of rebleeding in bleeding gastroduodenal ulcer" 34 : 778-786, 2002

11 Pierre AF, "Results of laparoscopic repair of giant paraesophageal hernias: 200 consecutive patients" 74 : 1909-1915, 2002

12 Gimson AE, "Randomised trial of variceal banding ligation versus injection sclerotherapy for bleeding esopahgeal varices" 342 : 391-394, 1993

13 Velanovich V, "Quality of life scale for gastroesopahgeal reflux disease" 183 : 217-224, 1996

14 Tamura S, "Prospective randomized study on the effect of ranitidine against injection ulcer after endoscopic injection sclerotherapy for esophageal varices" 86 : 477-480, 1991

15 Pulanić R, "Prophylactic administration of ranitidine after sclerotherapy of esophageal varices" 29 : 347A-351A, 1991

16 Chiu PW, "Predictors of peptic ulcer rebleeding after scheduled second endoscopy: clinical or endoscopic factors?" 38 : 726-729, 2006

17 Shaheen NJ, "Pantoprazole reduces the size of postbanding ulcers after variceal band ligation: a randomized, controlled trial" 41 : 588-594, 2005

18 Jaspersen D, "Omeprazole in the management of sclerotherapy-induced esophageal ulcers resistant to H2 blocker treatment" 30 : 128-130, 1995

19 Gimson A, "Omeprazole in the management of intractable esophageal ulceration following injection sclerotherapy" 99 : 1829-1831, 1990

20 Johlin FC, "Omeprazole heals mucosal ulcers associated with endoscopic injection sclerotherapy" 37 : 1373-1376, 1992

21 Nijhawan S, "Natural history of postligation ulcers" 89 : 2281-2282, 1994

22 Schoonbroodt D, "Local necrosis and fatal perforation of oesophagus after endoscopic ligation" 344 : 1365-, 1994

23 Müller JM, "Ligation with elastic ligature: an alternative in the treatment of hemorrhoidal diseases" 33 : 759A-762A, 1978

24 Schmitz RJ, "Incidence and management of esophageal stricture formation, ulcer bleeding, perforation, and massive hematoma formation from sclerotherapy versus band ligation" 96 : 437-441, 2001

25 Lee SY, "Healing rate of EMR-induced ulcer in relation to the duration of treatment with omeprazole" 60 : 213-217, 2004

26 Toyoda H, "Fatal bleeding from a residual vein at the esophageal ulcer base after successful endoscopic variceal ligation" 32 : 158-160, 2001

27 Stiegmann GV, "Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices" 326 : 1527-1532, 1992

28 Laine L, "Endoscopic ligation compared with sclerotherapy for the treatment of bleeding esophageal varices" 119 : 87-88, 1993

29 Stiegmann GV, "Endoscopic esophageal varix ligation: prelinimary clinical experience" 34 : 113-117, 1988

30 Esaki M, "Effects of omeprazole and famotidine on fibroblast growth factor-2 during artificial gastric ulcer healing in humans" 14 : 365-369, 2002

31 Yang WG, "Effect of sucralfate granules in suspension on endoscopic variceal sclerotherapy induced ulcer: analysis of the factors determining ulcer healing" 13 : 225-231, 1998

32 Nijhawan S, "Does post-ligation oesophageal ulcer healing require treatment?" 343 : 116-117, 1994

33 Young MF, "Comparison and characterization of ulcerations induced by endoscopic ligation of esophageal varices versus endoscopic sclerotherapy" 39 : 119-122, 1993

34 Baroncini D, "A prospective randomized trial of sclerotherapy versus ligation in the elective treatment of bleeding esophageal varices" 29 : 2352-2340, 1997

35 Paquet KJ, "A comparison of sucralfate with placebo in the treatment of esophageal ulcers following therapeutic endoscopic sclerotherapy of esophageal varices.: a prospective controlled randomized trial" 91 : 147S-150S, 1991