Multipolar Electrocoagulation in the Treatment of Peptic Ulcers with Nonbleeding Visible Vessels

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1 Multipolar Electrocoagulation in the Treatment of Peptic Ulcers with Nonbleeding Visible Vessels A Prospective, Controlled Trial Loren Laine, MD Study Objective: To assess the efficacy and safety of treatment with endoscopic multipolar electrocoagulation in patients who have ulcers with nonbleeding visible vessels. Design: Prospective, randomized, sham-controlled trial; patients were followed until their discharge from the hospital. Setting: Urban, nonreferral county hospital. Patients: Consecutive sample of 75 patients who had a bloody nasogastric aspirate sample, melena, or hematochezia; unstable vital signs, a transfusion of at least two units of blood in 12 hours, or a drop in the hematocrit of at least 0.06 in 12 hours; and endoscopic evidence of an ulcer with a nonbleeding visible vessel. Intervention: Sham or real multipolar electrocoagulation at the time of diagnostic endoscopy. Measurements and Main Results: Compared with the control group, the group receiving multipolar electrocoagulation showed marked improvement in the following variables: rebleeding (18% compared with 41%, P < 0.05; difference, 23%; 95% CI, 3% to 43%); need for emergency surgery (8% compared with 30%, P < 0.05; difference, 22%; CI, 5% to 39%); mean number of hospital days (4.3 ± 0.4 compared with 6.2 ± 0.7, P < 0.05; difference, 1.9; CI, 0.4 to 3.4); and cost of hospitalization ($3790 ± $410 compared with $5730 ± $650, P < 0.05; difference, $1940; CI, $400 to $3480). The mean transfusion requirement in the treatment group was 1.6 ± 0.3 as compared with 3.0 ± 0.6 units in the control group (P = 0.13; difference, 1.4; CI, 0 to 2.8). The overall mortality was extremely low: Only 1 (1%) of 75 patients died. Bleeding was induced in 7 (18%) of the 38 patients treated with electrocoagulation, and 1 patient required urgent surgery. Conclusions: Endoscopic treatment with multipolar electrocoagulation is beneficial in patients who present with major upper gastrointestinal hemorrhage and are found to have an ulcer with a nonbleeding visible vessel. Oleeding, the commonest complication of peptic ulcer disease, occurs in approximately 15% to 20% of patients with ulcers (1). The incidence of emergency surgery for bleeding ulcers has not declined appreciably in recent years (2, 3) despite the development of medical therapy that effectively promotes the healing of ulcers. Because no medication has been clearly documented to stop bleeding or to prevent recurrent hemorrhage from ulcers, other forms of hemostatic treatment must be sought. The recent development of endoscopic therapy may offer an effective, nonsurgical alternative for the treatment of patients with bleeding ulcers. Most patients with bleeding ulcers stop bleeding spontaneously and have an uneventful recovery (4-6); hemostatic therapy cannot improve the course of hospitalization in these patients. A smaller number of patients, however, have persistent or recurrent bleeding. Identification of these high-risk patients is important because they are the ones most likely to benefit from intervention. Clinical characteristics, such as vital signs, transfusion requirements, age, and concurrent illnesses, are helpful in predicting a patient's outcome (4). The appearance of an ulcer crater at endoscopy, however, provides perhaps the best prognostic information available. Patients who have endoscopically verified active bleeding have a high morbidity (6-9) and appear to benefit from endoscopic therapy (8). On the other hand, patients with a clean ulcer base or stigmata of recent hemorrhage, such as a flat red spot, are unlikely to have recurrent bleeding and are therefore unlikely to benefit from hemostatic treatment (9-14). Patients with a nonbleeding visible vessel in an ulcer crater comprise an intermediate group, who have approximately a 45% chance of recurrent bleeding (11-22). The potential benefit of endoscopic intervention in these patients has been assessed in this prospective, controlled trial of multipolar electrocoagulation for the treatment of patients who have ulcers with nonbleeding visible vessels. Methods Annals of Internal Medicine. 1989;110: From the University of Southern California School of Medicine and Los Angeles County-University of Southern California Medical Center, Los Angeles, California. For current author address, see end of text. Patients were considered for inclusion if they had a bloody nasogastric aspirate sample, melena, or hematochezia, and a systolic blood pressure no higher than 90 mm Hg, a heart rate of at least 110 beats/min, or orthostatic changes in systolic blood pressure of at least 20 mm Hg or a heart rate of at least 20 beats/min; a transfusion of at least two units of blood in 12 hours; or a drop in the hematocrit of at least 0.06 in 12 hours. Patients meeting these clinical criteria had en American College of Physicians

2 doscopy of the upper gastrointestinal tract. When debris or a clot was present in an ulcer base, forceful irrigation with the multipolar electrocoagulation probe was used to clear the base and to look for a visible vessel. Patients with a nonbleeding visible vessel (appearing at endoscopy as a raised, rounded, relatively smooth-surfaced plug) in an ulcer crater were then randomly assigned to receive either multipolar electrocoagulation or sham multipolar electrocoagulation (a computer-generated randomization sequence was used). The author was blinded to the treatment that would be assigned when he made the decision to enroll a patient in the study. Patients were neither screened for this study nor enrolled if the author was out of town. Patients were excluded if they were younger than 18 years of age, were unable or unwilling to give informed consent, were pregnant, or were receiving anticoagulant therapy; if they had a severe coagulopathy (prothrombin time, less than 30%); if endoscopy could not be done; if the bleeding site could not be visualized; if there were two or more bleeding lesions; or if it was likely that the performance of endoscopy might jeopardize the patient's survival. A 25-W BICAP unit (Circon-ACMI, Stamford, Connecticut) was used at a setting of 9 W for multipolar electrocoagulation therapy in the initial portion of the study. Subsequently, the 50-W unit was used at a setting of 5 to 6 W (The watts delivered with each application varied no more than 15% throughout the study, and no significant differences in results occurred with the two units.) A large (3.2 mm) BICAP probe was used with a GIF-IT10 or GIF-2T10 endoscope (Olympus Corporation of America, New Hyde Park, New York). In patients assigned to receive multipolar electrocoagulation, 2-second bursts of electrocoagulation were administered to the visible vessel and the immediately surrounding area to a radius of at least 0.5 cm with application of the BICAP probe as forcefully as possible. The mean number of seconds of electrocoagulation per patient was 41 (range, 20 to 80). Coagulation was continued until the area treated was completely covered with a whitish "coagulum" and then several additional 2-second bursts were applied to the same region. Sham multipolar electrocoagulation was accomplished by activating the BICAP unit with the probe in the lumen of the gut. Endoscopic treatments were done by the author in all cases. The patients and those caring for them were blinded to the nature of the treatment. Only the endoscopist was aware of a patient's endoscopic therapy, and he did not participate in the further care of the patient. The patients' physicians Table 1. Characteristics of Patients at Presentation Who Have Nonbleeding Visible Vessels in Peptic Ulcers Characteristic Sham Multipolar Treatment I Electrocoagulation (n = 37) (n = 38) Age,y 42 ±3* 47 ±3 Patients with unstable vital signsf, n(%) 35 (95) 36 (95) Patients who were hospitalized at the onset of bleeding, n(%) 2(5) 2(5) Patients with alcoholism, n(%) 8(22) 6(16) Blood transfusions, units Hematocrit 1.8 ± ± ± ± 0.01 Blood urea nitrogen, mmol/l Patients with duodenal 12 ± 1 11±1 ulcers, n(%) 26 (70) 26 (66) Patients with gastric ulcers, n(%) 11 (30) 13 (34) * Where appropriate, data are mean ± SE. t Systolic blood pressure, <, 90 mm Hg; heart rate, ^ 110 beats/min; or orthostatic changes in blood pressure, ^ 20 mm Hg; or heart rate, ^ 20 beats/min. were informed that endoscopy had shown a nonbleeding visible vessel. Patients were followed until their discharge or death, and they received only one course of real or sham treatment. An episode of rebleeding was defined as a recurrence of bloody emesis or nasogastric aspirate sample, melena, or hematochezia, coupled with a recurrence of unstable vital signs or a drop in the hematocrit after stabilization of at least 0.04 in 24 hours. The hospital costs presented reflect the official charges of the Los Angeles County-University of Southern California Medical Center for each patient from the day of entry into the trial. Charges were billed on a daily basis and differed according to the degree of care (ward or intensive care unit) and the service caring for the patient (medical or surgical). Quantitative data (expressed as mean ± SE) were compared by a Wilcoxon two-tailed, nonpaired, rank-sum test. Integral data were analyzed with a Fisher exact test. A difference was regarded as significant if P was less than Differences in outcome measures were also calculated along with the 95% CI for the differences between the two independent means or two independent proportions. This study was approved by the Research Committee of the Los Angeles County-University of Southern California Medical Center. All patients who entered received an explanation of the protocol in their native language and signed a consent form. Results From September 1984 to December 1987, 588 patients meeting the clinical criteria for entry were screened. Seventy-five of these patients, who had an ulcer with a nonbleeding visible vessel, were randomly assigned to receive either multipolar electrocoagulation or sham multipolar electrocoagulation. The other 513 patients were excluded: 38 patients because they had an actively bleeding ulcer; 104 patients because they had a nonbleeding ulcer without a visible vessel; 260 because they bled from another lesion (varices, 155; Mallory- Weiss tear, 67; hemorrhagic or erosive "gastritis," 15; and other lesions, 23); 35 because no lesion was visualized; 22 because they were bleeding from two or more sites; 22 because they were unable to give consent; 14 because they refused consent; 3 because they had a severe coagulopathy; 2 because the physician refused to consent; and 13 because endoscopy could not be done (hemodynamic instability, 8; agitation or lack of cooperation, 5). The treatment and control groups did not differ significantly in any of 21 characteristics evaluated at the time of presentation (selected characteristics are shown in Table 1). These characteristics included age, number of gastric compared with number of duodenal ulcers, transfusion requirements, vital signs, use of alcohol or nonsteroidal anti-inflammatory drugs, hours from presentation to entry, number of patients already hospitalized at the onset of bleeding (a characteristic associated with a greatly increased mortality [4, 6]), and the results of laboratory studies. The results after randomization, however, showed marked differences in favor of the group treated with multipolar electrocoagulation (Table 2). The incidence of recurrent bleeding in the multipolar electrocoagulation patients was less than half that in the controls (7/38 [18%] compared with 15/37 [41%], P < 0.05; difference, 23%; CI, 3% to 43%), and the 1 April 1989 Annals ofinternal Medicine Volume 110 Number 7 511

3 Table 2. Results of Endoscopic Multipolar Electrocoagulation Compared with Sham Treatment in Patients Who Have Peptic Ulcers with Nonbleeding Visible Vessels* Characteristic Patients with rebleeding, % Blood transfusions, units Patients with emergency surgery, % Hospital stay, d Hospital cost, $ Deaths, % Sham (n = 37) 41f 3.0 ± f 6.2 ± 0.7 t 5730 ± 650f 0 Multipolar Electrocoagulation (n = 38) ± ± ± Difference (95% CI) 23 (3 to 43) 1.4(0 to 2.8) 22 (5 to 39) 1.9 (0.4 to 3.4) 1940 (400 to 3480) 3 (...)t * Where appropriate, values are mean ± SE. t P < 0.05 for sham treatment compared with multipolar electrocoagulation. % Data do not allow use of normal approximation to calculate 95% CI for the difference in proportions of deaths between the two groups. incidence of urgent surgery for recurrent bleeding in the multipolar electrocoagulation group was approximately one third the rate in the sham-treated group (3/38 [8%] compared with 11/37 [30%], P < 0.05; difference, 22%; CI, 5% to 39%). Patients treated with multipolar electrocoagulation had a mean hospital stay almost 2 days shorter than that of controls (4.3 ± 0.4 compared with 6.2 ± 0.7 days, P < 0.05; difference, 1.9; CI, 0.4 to 3.4); patients receiving multipolar electrocoagulation also tended to stay fewer days in an intensive care unit (1.3 ±0.1 compared with 1.7 ± 0.2 days, P = 0.09; difference, 0.4; CI, 0.1 to 0.9). In addition, multipolar electrocoagulation treatment was associated with a significant savings in the cost of hospitalization ($3790 ± $410 compared with $5730 ± $650, P < 0.05; difference, $1940; CI, $400 to $3480). The mean transfusion requirement in patients treated with multipolar electrocoagulation was approximately half that in the control patients, but this difference was not statistically significant (1.6 ±0.3 compared with 3.0 ± 0.6 units, P = 0.13; difference, 1.4; CI, 0 to 2.8). Only one patient died in this study; the overall mortality rate was thus 1%. The patient who died was an elderly woman with cirrhosis and a previous portacaval shunt. She was assigned to the treatment group, and she had no further bleeding after multipolar electrocoagulation therapy. Unfortunately, she died from shock liver related to bleeding before endoscopy (a blood sample drawn immediately before endoscopy had shown increased transaminase levels). Bleeding was induced by the application of the multipolar electrocoagulation probe in 7 (18%) of the 38 patients treated with electrocoagulation. The bleeding was controlled with continued multipolar electrocoagulation treatment in 6 of these patients, but 1 patient required urgent surgery. No perforations occurred in this trial. Discussion A visible vessel is as an elevated "plug" noted in the ulcer crater of 4% to 39% of patients presenting with upper gastrointestinal hemorrhage due to an ulcer (9-11, 20, 23, 24). Histologically, visible vessels are characterized by an eroded artery, with the vessel or a clot, or both protruding above the ulcer base in approximately 75% of cases (10). The results of previous prospective trials have shown that approximately 45% of patients with nonbleeding visible vessels will have a recurrence of bleeding (range, 13% to 81%) (11-22). The presence of a visible vessel in an ulcer crater indicates not only an increased risk for recurrent bleeding but also an increase in morbidity and perhaps mortality (9, 10). This study was designed to evaluate the effect of multipolar electrocoagulation treatment in patients who present with clinical evidence of major upper gastrointestinal hemorrhage and who are found to have an ulcer with a nonbleeding visible vessel by endoscopic means. Seventy-five patients received either multipolar electrocoagulation or sham multipolar electrocoagulation, and the trial was blinded neither the patients nor their physicians knew which treatment had been given. The characteristics of patients in the treatment and control groups were similar at the time of randomization. After randomization, however, patients treated with multipolar electrocoagulation had a marked improvement in their hospital course compared with the patients given the sham treatment. In the multipolar electrocoagulation group, the rate of recurrent bleeding and mean requirement for transfusion were approximately half that in the control group. In addition, the need for emergency surgery, length of hospital stay, and cost of hospitalization were all significantly less in the treatment group. Only 1 patient died in the study, and the overall mortality rate was 1%. This statistic may be explained, at least in part, by the relative youth of the patients (mean age, 44 years) and the low incidence of serious, concurrent illness, as indicated by the small number of patients (5%) who already were hospitalized when bleeding began. Eleven previous prospective, controlled trials (11-18, 21, 22, 24) of endoscopic hemostatic therapy have included specific information on the treatment of patients who have ulcers with nonbleeding visible vessels, although just two trials (15, 21) dealt exclusively with this group. Only two studies (16, 21) included as many patients with nonbleeding visible vessels, and none used the stringent clinical entry criteria that were used in the present study. (Because clinical characteristics such as vital signs and transfusion requirements are prognostic [4], trials without clinical entry criteria April 1989 Annals of Internal Medicine Volume 110 Number 7

4 other than evidence of gastrointestinal bleeding may include many patients with a relatively low morbidity; the inclusion of these patients thus decreases the chance that a significant benefit will be seen with treatment.) O'Brien and colleagues (16), using a small (2.3 mm) multipolar electrocoagulation probe at a lower power setting than the present study, showed significantly less recurrent bleeding in patients with nonbleeding visible vessels who were treated with multipolar electrocoagulation (7/43 [16%]) compared with controls (16/43[37%]; P < 0.05), but they did not report an improvement in variables, such as emergency surgery, blood transfusions, or mortality. Brearley and coauthors (24) found no benefit with multipolar electrocoagulation treatment in a controlled trial of 41 patients with hemorrhage of the upper gastrointestinal tract due to an ulcer; most of these patients had nonbleeding visible vessels, but the authors also included 4 patients with other stigmata of hemorrhage. In contrast to the present study, Brearley and coworkers required no clinical entry criteria other than hematemesis or melena, and they delivered fewer applications of multipolar electrocoagulation at a lower setting. In addition, compared with the control group, the treatment group had significantly more patients with systolic blood pressure below 100 mm Hg. This prerandomization inequality favored the control group. Although differences in clinical characteristics exist between the patients in the present study and those in the previous trials of multipolar electrocoagulation, differences in technique may be the most likely explanation for the current study's better results. By the use of forceful application of the probe to the ulcer base, hemostatic efficacy may have been increased (25). Also, the application of electrocoagulation for a longer period than that used in previous trials may account for improved results. In addition, a large (3.2 mm) probe was used in all patients. Not only does this probe cover a greater surface area than the small (2.3 mm) probe, but the results of a canine study have shown that the large probe is significantly more effective than the small probe in controlling arterial hemorrhage from larger vessels and leads to no increase in the depth of tissue injury (26). Swain and colleagues (12) reported significantly less recurrent bleeding in patients with nonbleeding visible vessels treated with the argon laser and the neodymium-yttrium aluminum garnet (Nd-YAG) laser (13), but they did not document benefit in any other variable of outcome for this group. Three other studies (11, 17, 21) of laser therapy failed to show a significant benefit in patients with nonbleeding visible vessels. (Buset and coworkers (21) [21] did report significantly less recurrent bleeding in the gastric ulcer group but not in the overall ulcer group; other variables were not significantly different in the treatment and control groups.) Multipolar electrocoagulation has several advantages over laser photocoagulation in the treatment of upper gastrointestinal hemorrhage: Multipolar electrocoagulation is more effective than the Nd-YAG laser in coagulating canine arteries of 0.5 to 2.0 mm in diameter (27) (similar to the size range of visible vessels [10]); it causes significantly less tissue injury than the Nd-YAG laser (27, 28), thereby decreasing the risk for perforation; because it is portable, it can be taken to a critically ill patient; and it is much less expensive. The use of another form of endoscopic thermal treatment, monopolar electrocoagulation, has also been evaluated in patients with nonbleeding visible vessels. Two of three studies (14, 15, 18) using monopolar electrocoagulation showed a significant benefit in favor of the treatment group; rates of recurrent bleeding and emergency surgery were lower in patients with nonbleeding visible vessels who received monopolar electrocoagulation. One important factor, however, limits the usefulness of monopolar electrocoagulation in the treatment of patients with bleeding ulcers: It causes significantly greater tissue injury than multipolar electrocoagulation (27-30). Not only does this greater tissue injury increase the risk for perforation but, in the animal model, the vessel erosion produced by the monopolar probe sometimes interferes with the coagulation of arteries more than 0.5 mm in diameter and induces bleeding (27). A nonthermal method of endoscopic hemostasis, injection therapy, has recently been introduced. Treatment is delivered by injection of the ulcer base with absolute ethanol, other sclerosing agents, or epinephrine through a sclerotherapy needle. One prospective, controlled trial (22) provided data on the use of injection therapy for nonbleeding visible vessels. Thirty-nine patients with nonbleeding visible vessels were included in this trial, and the treatment group had significantly less "major" (but not "minor") recurrent bleeding and a marked reduction in transfusion requirements; other variables were not significantly different. The physicians caring for the patients in this trial were not blinded in all cases they were informed of a patient's treatment if there was a major recurrence of bleeding. In addition, bleeding was precipitated by injection in 10 (56%) of the 18 patients treated (although only 1 required emergency surgery for persistent hemorrhage). The advantages of injection therapy include its low cost and ease of transport: Only a sclerotherapy needle and injection solution are needed. The disadvantages include the severe tissue injury caused by absolute ethanol and other sclerosing agents (31, 32) (which thus increases the chance of perforation), and the lack of an irrigation system to wash the bleeding lesion. Trials should be done to compare endoscopic injection therapy with thermal devices, such as multipolar electrocoagulation. The complications of multipolar electrocoagulation treatment must be addressed. Almost 20% of patients in this study had bleeding induced by the multipolar electrocoagulation probe. In six of seven cases, hemorrhage was controlled with continued multipolar electrocoagulation, but one patient did require emergency surgery early in the trial. Thus, although multipolar electrocoagulation improves the hospital course of patients with nonbleeding visible vessels, it may worsen the course of an individual patient. No perforations 1 April 1989 Annals of Internal Medicine Volume 110 Number 7 513

5 were noted in this study, and only one perforation has been reported immediately after multipolar electrocoagulation treatment for hemorrhage of the upper gastrointestinal tract (24). No study has documented that the excellent diagnostic yield of endoscopy leads to an improvement in the outcome of patients. This lack of demonstrable benefit is not surprising for two reasons: Most patients with hemorrhage of the upper gastrointestinal tract do well with conservative management alone, and before the development of endoscopic therapy, no effective alternative to surgery was available for patients whose bleeding persisted or recurred. Endoscopy, however, does have potential prognostic and therapeutic usefulness in patients with clinical evidence of a major hemorrhage of the upper gastrointestinal tract. When endoscopy shows a lesion with a low likelihood of recurrent bleeding, such as an ulcer with a clean base or a nonbleeding Mallory-Weiss tear, the patient can probably be discharged after a short hospital stay, resulting in reduced costs. On the other hand, if endoscopic examination shows a high-risk lesion, such as an actively bleeding ulcer or esophageal varices, the application of hemostatic therapy can be beneficial, as shown by the results of previous trials (8, 33, 34). The findings in the present study help to broaden the indications for endoscopic therapy in gastrointestinal bleeding by documenting that multipolar electrocoagulation decreases morbidity and cost in patients who present with major hemorrhage of the upper gastrointestinal tract and are found to have an ulcer with a nonbleeding visible vessel. Acknowledgments: The author thanks the nursing and medical staffs of the medical admitting area and the gastrointestinal unit of the Los Angeles County-University of Southern California Medical Center for assistance; Dr. Hartley Cohen for thoughtful criticism; Dr. John Weiner for preparation of the randomization sheets; Dr. Madeline Bauer for statistical advice; and Angie Garcia for help in preparation of the manuscript. Grant Support: Computational assistance was provided by the CLINFO Project, funded by the Division of Research Resources of the National Institutes of Health (under grant no. RR-00043) with the aid of Ken Anderson (CLINFO Manager). Requests for Reprints: Loren Laine, MD, Gastroenterology Section, Department of Medicine, University of Southern California School of Medicine, 2025 Zonal Avenue, Los Angeles, CA Current Author Address: Dr. Laine: Gastroenterology Section, Department of Medicine, University of Southern California School of Medicine, Los Angeles, CA References 1. Walker C. Complications of peptic ulcer disease and indications for surgery. In: Sleisenger MH, Fordtran JS, eds. Gastrointestinal Disease: Pathophysiology, Diagnosis, Management. 3rd ed. Philadelphia: W.B. Saunders Company; 1983: Gustavsson S, Kelly KA, Melton LJ m, Zinsmeister AR. Trends in peptic ulcer surgery: a population-based study in Rochester, Minnesota, Gastroenterology. 1988;94: Christensen A, Bonafleld R, Christiansen J. Incidence of perforated and bleeding peptic ulcers before and after the introduction of ^-receptor antagonists. Ann Surg. 1988;207: Silverstein FE, Gilbert DA, Tedesco FJ, Buenger NK, Persing J. The national ASGE survey on upper gastrointestinal bleeding. II. Clinical prognostic factors. Gastrointest Endosc. 1981;27: Schiller KFR, Truelove SC, Williams DG. Haematemesis and melaena, with special reference to factors influencing the outcome. Br Med J. 1970;2: Fleischer D Etiology and prevalence of severe persistent upper gastrointestinal bleeding. Gastroenterology. 1983;84: Gilbert DA, Silverstein FE, Tedesco FJ, Buenger NK, Persing J. The national ASGE survey on upper gastrointestinal bleeding. III. Endoscopy in upper gastrointestinal bleeding. Gastrointest Endosc. 1981;27: Laine L. Multipolar electrocoagulation in the treatment of active upper gastrointestinal tract hemorrhage: a prospective controlled trial. N Engl J Med. 1987;316: Kovacs TOG, Jensen DM. Endoscopic control of gastroduodenal hemorrhage. Ann Rev Med. 1987;38: Swain CP, Storey DW, Sown SG, et at Nature of the bleeding vessel in recurrently bleeding gastric ulcers. Gastroenterology. 1986;90: Vallon AG, Cotton PB, Laurence BH, Armengol Miro JR, Salord Oses JC. Randomised trial of endoscopic argon laser photocoagulation in bleeding peptic ulcers. Gut. 1981;22: Swain CP, Bown SG, Storey DW, Kirkham JS, Northfleld TC, Salmon PR. Controlled trial of argon laser photocoagulation in bleeding peptic ulcers. Lancet 1981;2: Swain CP, Kirkham JS, Salmon PR, Bown SG, Northfleld TC. Controlled trial of Nd- YAG laser photocoagulation in bleeding peptic ulcers. Lancet. 1986;1: Freitas D, Donate A, Monteiro JG. Controlled trial of liquid monopolar electrocoagulation in bleeding peptic ulcers. Am J Gastroenterol. 1985;80: Papp JP. Endoscopic electrocoagulation in the management of upper gastrointestinal tract bleeding. Surg Clin North Am. 1982; 62: O'Brien JD, Day SJ, Burnham WR. Controlled trial of small bipolar probe in bleeding peptic ulcers. Lancet. 1986;1: Krejs GJ, Little KH, Westergaard H, Hamilton JK, Spady DK, Polter DE. Laser photocoagulation for the treatment of acute peptic-ulcer bleeding: a randomized controlled clinical trial. N Engl J Med. 1987;316: Moreto M, Zaballa M, Ibanez S, Setien F, Figa M. Efficacy of monopolar electrocoagulation in the treatment of bleeding gastric ulcer: a controlled trial. Endoscopy. 1987;19: Rutgeerts P, Broeckaert L, Coremans G, Janssens J, Van Isveldt J, Vantrappen G. Randomized comparison of three hemostasia modalities for severely bleeding peptic ulcers: epinephrine 1% injection alone (1), epinephrine + polidocanol 1% injection (2), epinephrine injection followed by YAG laser (3) [Abstract]. Gastrointest Endosc. 1987;30: Wara P. Endoscopic prediction of major rebleeding a prospective study of stigmata of hemorrhage in bleeding ulcer. Gastroenterology. 1985;88 (5 pt 1): Buset M, Des Marez B, Vandermeeren A, Baize M, Cremer M. Laser therapy for nonbleeding visible vessels in peptic ulcer hemorrhage: a prospective randomized study [Abstract]. Gastrointest Endosc. 1988;34: Panes J, Viver J, Forne M, Garda-Olivares E, Marco C, Garau J. Controlled trial of endoscopic sclerosis in bleeding peptic ulcers. Lancet. 1987;2: Brearley S, Morris DL, Hawker PC, Dykes PW, Keighley MRB. Prediction of mortality at endoscopy in bleeding peptic ulcer disease. Endoscopy. 1985;17: Brearley S, Hawker PC, Dykes PW, Keighley MRB. Per-endoscopic bipolar diathermy coagulation of visible vessels using a 3.2 mm probe a randomised clinical trial. Endoscopy. 1987;19: Sigel B, Hatke FL. Physical factors in electrocoaptation of blood vessels. Arch Surg. 1967;95: Morris DL, Brearley S, Thompson H, Keighley MRB. A comparison of the efficacy and depth of gastric wall injury with 3.2- and 2.3- mm bipolar probes in canine arterial hemorrhage. Gastrointest Endosc. 1985;31: Johnston JH, Jensen DM, Auth D. Experimental comparison of endoscopic ytrrium-aluminum-garnet laser, electrosurgery, and heater probe for canine gut arterial coagulation: importance of compression and avoidance of erosion. Gastroenterology. 1987;92(5 pt 1): Johnston JH, Jensen DM, Mautner W. Comparison of endoscopic electrocoagulation and laser photocoagulation of bleeding canine gastric ulcers. Gastroenterology. 1982;82 (5 pt 1): Protell RL, Gilbert DA, Silverstein FE, Jensen DM, Hulett FM, Auth DC. Computer-assisted electrocoagulation: bipolar vs. monopolar in the treatment of experimental canine gastric ulcer bleeding. Gastroenterology. 1981;80: Swain CP, Mills TN, Shemesh E, et al. Which electrode? A comparison of four endoscopic methods of electrocoagulation in experimental bleeding ulcers. Gut 1984;25: Rutgeerts P, Geboes K, Vantrappen G. Tissue damage produced by hemostatic injections [Abstract]. Gastrointest Endosc. 1986;32: Randall GM, Jensen DM, Hirabayashi K, Machicado GA. Controlled trial of sclerosing agents for hemostasia of canine gut arteries [Abstract]. Gastrointest Endosc. 1987;33: Larson AW, Cohen H, Zweiban B, et al. Acute esophageal varices! sclerotherapy: results of a prospective randomized controlled trial. JAMA. 1986;255: Paquet KJ, Feussner J. Endoscopic sclerosis and esophageal balloon tamponade in acute hemorrhage from esophagogastric varices: a prospective controlled randomized trial. Hepatology. 1985;5: April 1989 Annals of Internal Medicine Volume 110 Number 7

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