Title: Argon Plasma Electrocoagulation Versus Gold Probe in Arresting Ulcer Bleeding

Title: Argon plasma electrocoagulation versus gold probe in arresting ulcer bleeding, a 3-yr project

INTRODUCTION A bleeding peptic ulcer remains a serious medical problem with significant morbidity and mortality. Endoscopic therapy significantly reduces further bleeding, surgery, and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients (1). Endoscopic injection and thermal coagulation reduce recurrent bleeding rates, the need for surgery, and the mortality rates from peptic ulcer bleeding (1). A potential drawback of these methods is the possibility of tissue injury, leading to perforation (2). Endoscopic placement of metallic clips to a bleeder is an appealing alternative that avoids the above complication. Endoscopic placement of a hemoclip is effective in achieving hemostasis with a low rebleeding rate (3–8). However, it may be difficult to apply in patients with a poorly located bleeder (3). At present, there is a new device with three prongs in one clip (triclip). It may have the advantage in arresting bleeding for such bleeders. Triclip was found to be comparable to hemoclip with respect to hemostatic efficacy in an experimental setting (9). So far, there is only one case report concerning triclip placement (10). The objective of this study was to compare the hemostatic efficacy between hemoclip and triclip in patients with highrisk peptic ulcer bleeding. In addition, requirement of blood transfusion, surgery, mortality, and length of hospital stay between these two groups were compared. METHODS Patients were accepted for endoscopic therapy if a peptic ulcer with active bleeding or a nonbleeding visible vessel (NBVV) was observed within 12 h of hospital admission. Patients with anNBVVhad to showone of the following signs of recent bleeding: “coffee grounds” or blood in the stomach or duodenum; shock; or initial Hb<10 g/L. The possibility of endoscopic therapy was discussed with patients and/or their relatives and written informed consent was obtained before the trial. The study was approved by the Clinical Research Committee of the Veterans General Hospital, Taipei, Taiwan. Patients were excluded from the study if they were pregnant, did not give written informed consent, or had a bleeding tendency (platelet count <50 × 109/L, serum prothrombin. <30% of normal, or were taking anticoagulations), uremia, or bleeding gastric cancer. For enrolled patients, an Olympus GIF-XQ240 videoendoscope was used and endoclip placement was performed by a single experienced endoscopist (HJ Lin). Patients were randomized using numbered envelopes to either the hemoclip group or the triclip group according to a randomization table. The randomization methodology balanced the number in each group and was prepared by a statistician who was not involved in the study. Patients were cared for by us and other doctors who were not involved in the study.

In the hemoclip group,we used a hemoclip (135◦, HX-600- 135, HX-5LR-1, Olympus Optical, Tokyo, Japan) to treat the patients. The hemoclip was applied directly to the bleeding vessel. If bleeding was persistent, the same procedure was repeated until hemostasis was achieved. If there was a large blood clot over the bleeder, the clotwas removed with a biopsy forceps or a three-pronged device. Hemoclip was placed over the NBVV as mentioned earlier. In theArgon plasma group, we use argon plasma to treat the patients. The dution was about 10-20 second. Endoscopy was undertaken 72 h after enrollment. If no blood clot or hemorrhage was observed at the ulcer base, the patient was discharged and followed up in the outpatient department. Patients’ vital signs ere checked every hour for the first 12 h, every 2 h for the second 12 h, and every 4 h for the following 24 h until they became stable, then four times daily. The hemoglobin level and hematocrit were checked at least once daily, and a blood transfusion was given if the hemoglobin level decreased to lower than 90 g/L or if the patient’s vital signs deteriorated. The attending physicians or surgeonswere made aware of the exact endoscopic finding and treatment given each case. Active bleeding was defined as a continuous blood flow spurting or oozing from the ulcer base. An NBVV at endoscopy was defined as a discrete protuberance at the ulcer base that was resistant to washing and was often associated with the freshest clot in the ulcer base. Shock was defined as systolic blood pressure lower than 100 mmHg and a pulse rate of more than 100/minute accompanied by cold sweats, paleness, and oliguria. Initial hemostasis was defined as no visible hemorrhage lasting for 5 minutes after metallic clip placement. Ultimate hemostasiswas defined as no rebleeding during the 14 days after endoscopic therapy. Rebleeding was suspected if unstable vital signs, continuous tarry, bloody stools, or a drop in the hemoglobin level of more than 20 g/L within 24 h was observed during hospitalization. For these patients, an emergency endoscopy was performed immediately. Rebleeding was concluded if either blood in the stomach 24 h after therapy or a fresh blood clot or bleeding in the ulcer base was found. For ethical reasons, treatment regimens were discussed with patients who rebled. Therapeutic options included a second hemoclip or triclip placement, injection, heat probe thermocoagulation, embolization, or surgery. One biopsy specimen from the gastric antrum was obtained for a rapid urease test. Omeprazole 40 mg was given as intravenous infusion every 12 h for 3 days, then esomeprazole 40 mg/day per os for 2 months. Patients who had a positive urease test received a 1-wk course of esomeprazole (40 mg twice daily), clarithromycin (500 mg twice daily), and amoxicillin (1 g twice daily) after discharge. At entry to the study, the following datawere recorded: age, sex, the location of the ulcer (esophagus, stomach, duodenum, or gastrojejunal anastomosis), ulcer size, the appearance of gastric contents (clear, coffee grounds, and blood), stigmata of bleeding (spurting, oozing, and NBVV), volume of blood transfusion at entry, presence of shock, hemoglobin, nonsteroidal anti-inflammatory drug ingestion, cigarette smoking, alcohol drinking, and comorbid illness. The primary end pointswere hemostatic efficacy and recurrent bleeding before discharge and within 14 days. At day 14, volume of blood transfused, number of surgeries performed, and the mortality rates of the two groups were compared as well. The sample size estimation was based on an expected rebleeding rate of 30% in the triclip group. The trial was designed to detect a 25% difference in favor of the hemoclip group with a type I error of 0.05 and type II error of 0.2. At least 43 patients were essential for each group. The Mann-Whitney rank sum test was used for the analysis of nonparametric quantitative data (age, volume of blood transfusion, ulcer size, hemoglobin, and length of hospital stay).

The χ2 test, with or without Yates’s correction, and Fisher exact testwere usedwhen appropriate to compare the location of the bleeders, endoscopic findings, gastric contents, number of patients with Helicobacter pylori infection, shock, medical illness, hemostasis, emergency operation, and mortality between the two groups. A probability value of less than 0.05 was considered significant

First year: 20 each for each group.

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