1 GASTROENTEROLOGY 1981;81: Treatment of Bleeding Canine Duodenal and Esophageal Ulcers with Argon Laser and Bipolar Electrocoagulation GUSTAVO A. MACHICADO, DENNIS M. JENSEN, JORGE I. TAPIA, and WILLIAM MAUTNER Center for Ulcer Research and Education, Departments of Medicine, Veterans Administration, Wadsworth and the University of California, Los Angeles, California Although electrocoagulation and lasers are used by some endoscopists for control of bleeding from esophageal and duodenal lesions, no one has reported experimental or clinical comparative studies of efficacy or safety in either organ with power outputs and techniques that are used clinically. Our purpose was to compare the efficacy and histologic injury of bipolar electrocoagulation (BPEC) and argon laser photocoagulation (ALP) in the treatment of bleeding standard esophageal (EU) and duodenal ulcers (DU) in dogs. Clinically applied power output and techniques were used in these studies. After duodenotomy or esophagotomy, and heparinization, a standard ulcer maker was used to create acute ulcers to similar size, depth, and bleeding rate. Ulcers were randomly assigned to control or treatment with ALP or BPEG. Hemostatic effectiveness was determined acutely, and histologic injury was assessed after 7 days. Standard DUs were more difficult to treat than esophageal ulcers because of higher bleeding rates and less retraction of the submucosa with coagulation. BPEC and high-power ALP (6 or 10 W) had comparable efficacy in the duodenum although ALP caused more tissue injury. Standard EUs were easy to treat with either BPEC or ALP. For EU, high-power ALP (8-10 W) resulted in more tissue injury than BPEC or control. The mean duode- Received November 17, Accepted June 1, Address requests for reprints to: Dennis M. Jensen, M.D., Division of Gastroenterology CHS, UCLA Center for the Health Sciences, Los Angeles, California The authors wish to thank Anita Boesman and Dee Reynolds for secretarial assistance; Esther Braden for histologic preparation; Medi-Tech Corp. and Spectra-Physics Corp. for loan of equipment; Paul Franco for technical assistance; and J. Elashoff for statistical advice. This study was supported in part by NIH Grant AM (CURE--Center for Ulcer Research and Education) and by Veteran Administration Research Funds by the American Gastroenterological Association /81/ $02.50 na1 wall thickness of adult mongrel dogs was not significantly different from thickness of the esophagus (by micrometer, 2.52 ± 0.04 vs ± 0.05 mm or by histologic measurement 2.41 ± 0.05 vs ± 0.08 mm). The histologic injury seen with high-power ALP treatment in the esophagus or duodenum in this study was significantly greater than for the stomach of canines in previously reported studies. Histologic injury with BPEC was not significantly different. Why the duodenum, esophagus, and stomach respond differently to these thermal coagulation methods is uncertain. Both BPEC and lower-power ALP were effective and caused limited tissue damage in the esophagus and duodenum in this study. In our opinion, both should be considered for controlled human trials of endoscopic hemostatasis in the upper gastrointestinal (UGI) tract. Electrocoagulation and lasers are now being used by some clinicians for the endoscopic control of upper gastrointestinal (VGI) hemorrhage. In unselected, uncontrolled, and nonrandomized human series, monopolar electrocoagulation (MPEC) (1-7), argon laser (ALP) (8-10), and neodymium-yttrium-aluminum-garnet (YAG) laser (11-13) photocoagulation are reported to be effective for endoscopic treatment of bleeding VGI lesions. However, perforations have been reported with YAG (11-13) and MPEC (14,15), There are no systematic reports of the histology of human lesions treated with any endoscopic thermal hemostatic method. Although ALP, MPEC, and YAG are currently being used to treat bleeding lesions in the esophagus and duodenum of humans, no experimental comparative studies of efficacy or safety have been reported for lesion treatment in either organ using clinically applied power outputs and techniques. Papp et al. evaluated MPEC of nonbleeding canine esophageal and duodenal mucosa (16). For the same MPEC treatment parameters, transmucosal
2 860 MACHICADO ET AL. GASTROENTEROLOGY Vol. 81. No. 5 necrosis was more frequent in the canine esophagus than duodenum in that report. Fruhmorgen et a1. reported no perforations for ALP with a maximum power of 2 W applied to nonbleeding canine esophageal, gastric, small bowel, or colonic mucosa (17). Systematic evaluations of safety and efficacy have been reported in the stomach of canines at laparotomy with MPEC (18), BPEC (19-21) YAG (22 24), and ALP (25-28). Although the efficacy of these modalities was comparable, histologic damage was different. BPEC and ALP caused significantly less damage than MPEC or YAG (29). In the endoscopic treatment of standard ulcers of the canine stomach, BPEC and ALP have Leen shown by our group to cause significantly less histologic damage than YAG or MPEC (30). Before the clinical application of ALP and BPEC in the duodenum or esopagus, the present study was completed. The purpose was to compare the efficacy and histologic injury of BPEC and ALP in the treatment of bleeding standard esophageal and duodenal ulcers in the dog. Materials and Methods A 20-W argon laser (Spectra-Physics Corp., Mountainview, Calif.) with a 4oo-t.tm flexible lightguide (Quartz Products Corp., Plainfield, N.J.) and an angle of divergence of 8 _10 was used with coaxial carbon dioxide (C0 2 ) gas. The spot size, treatment distance, power density, and CO 2 back pr essure (100 mml-i.o) at the lesion were controlled as previously described (28). For laser-treated lesions, total treatment energy (power X treatment time) was calculated. A Valley Lab SSE2-K electrocoagulation unit (Valley Lab, Boulder, Colo.) was used with a prototype bipolar electrode (Medi-Tech Corp., Watertown, Mass.) as previously detailed (19). A coagulation setting of 3 was used. We did not have a method to measure total energy during bipolar electrocoagulation. Normal saline was infused (with a Harvard pump, Millis, Mass.) through the central lumen at 7 cm -/rnin, supplemented by pulses of saline for irrigation of ulcers. During coagulation, light touch was used. Half-second pulses of coagulating current were applied with an electronic timer. Argon laser and bipolar electrocoagulation were applied at laparotomy after duodenotomy or esophagotomy. The laser catheter was held with a handpiece which controlled treatment distance (28). The bipolar electrode was also hand held. Different adult mongrel dogs weighing between 40 and 60 lb were used for each of the studies outlined. Statistical comparisons were made using the Student's t-test or th e Fisher's exact test (31). The statistical signifi cance lev el (p < 0.05) was used throughout. Duodenal Studies Each dog was anesthetized with intravenous sodium pentobarbital and intubated. A sterile midline laparotomy was made. The duodenum was mobilized and two 5-cm duodenotomies on the antimesenteric side were made approximately 2 cm distal to the pylorus. For each animal, 10 different measurements of the duodenal wall thickness at the duodenotomies were made with a standard micrometer. Dogs were anticoagulated with intravenous sodium heparin (200 V/kg initially; then 100 V/ kg' h- 1 ). Standard ulcers (Quinton Corp., Seattle, Wash.) were made on the mucosal side by using a negative suction pressure of 6 in. Hg. Before randomization, the bleeding rate was immediately measured with a small graduated cylinder for a period of 15 s. Study I An extensive study was done to determine effectiv e coagulation (BPEC) and power density settings (ALP) for the treatment of standard ulcers in the duodenum of heparinized mongrel dogs. A total of 70 ulcers were studied in 4 dogs. The lowest effective coagulation setting was 3 for BPEC in the duodenum. In order to stimulate realistic clinical endoscopic treatment, distances of 1 and 2.0 cm were studied for ALP with the corresponding spot sizes (diameter) of 1.8 and 3.2 mm for the 8 divergent lightguide used. The lowest effective power setting for ALP was 4 W at 1 cm (power density of 157 W/cm") and 6 W at 2.0 ern (74 W/cm"). More effective, but higher power settings of 5.5 W at 1 ern (216 W/cm') and 10 W at 2.0 cm (124 W/cm') were also chosen for further testing in a histologic study. Study II Eleven dogs were used for this study. After duodenotomy and heparinization, standard ulcers were made as described above. Each ulcer was randomly assigned to one of five treatment groups (ALP 4 W, ALP 5.5 W, ALP 6W, ALP low, BPEC 3) or control. Ulcers were labeled with silk sutures. Control ulcers were observed for 3 min and also before surgical closure of the duodenotomies. Ulcer plug size and weight were determined for each lesion. Efficacy, defined as the ability to stop bleeding completely, was assessed at the time of each treatment. ALP treatment times greater than 120 s or BPEC treatments requiring more than 50- pulses were considered failures. As an indication of full thickness coagulation or injury, serosal whitening was also assessed acutely for each treatment or control lesion. After surgical closure, antibiotics were given for 48 h. The histologic damage was assessed grossly from I-mm sections of ulcers and from coded histologic sections at 7 days as previously described (29). Duodenal wall thickness (from the mucosa to the serosa) was also estimated from these sections for control and treated lesions using a calibrated microscopic eyepiece. Results Efficacy (Table 1) None of the control ulcers stopped bleeding during the observation period. All the BPEC and ALP 10 W treated lesions stopped bleeding, whereas
3 November 1981 LASER AND ELECTROCOAGULATION OF BLEEDING CANINE ULCERS 861 Table 1. Efficacy of Treatment for Duodenal Ulcers Modality Control BPEca ALP4 b ALP 5.5 ALP 6 ALp 10 Power density" Tx. distance (em)" # Stop/totale 0/20 21/21 16/20 21/24 21/24 23/23 Percent Applications' 30 ±4 Total energy (J)g 275 ± ± ± ± 82 a BPEC is bipolar electrocoagulation. b ALP 4-10 are argon laser photocoagulation 4-10 W. C Power density is in W/cm 2 d Tx is treatment. e Efficacy of treatment (# stop) is number of lesions with complete hemostasis for each treatment group., Applications are the mean (± SE) number of BPEC applications for hemostasis. g Total energy (J) is the mean (± SE) Jof ALP energy required for hemostasis. 80% of the ALP 4 W, 88% of the ALP 5.5 W, and 88% of the ALP 6 W lesions stopped bleeding with treatment. Although there was an arithmetic difference in the efficacy between lower- and higher-power argon laser treatment, the difference was not statistically significant. Subjectively, the acute duodenal ulcers were more difficult to treat with ALP and BPEC than standard ulcers in the stomach of our previously reported studies (19,22,28-30). There was more oozing and less retraction of submucosal tissue and vessels with thermal applications. Two to six bleeding vessels were seen in the base of each acute ulcer, similar to our experience with standard ulcers in the stomach (29). Histologic Damage Acute serosal whitening was not observed with any of the treatment modalities studied. At the time of autopsy, there was no evidence of perforation, penetration, obstruction, or abscess formation in any animal. Figure 1 shows the frequency of full-thickness external muscle layer damage (100% EMLD) for each treatment group. The frequency of 100% EMLD seen with ALP 10 Wand ALP 6 W was 60% and 55%, respectively. This contrasted with 30% for the ALP 5.5 W, 35% for ALP 4 W, 20% for BPEC, and 0% for control. The histologic damage seen with ALP 10 Wand ALP 6 W was significantly greater than that with BPEC or control. Other Determinations Duodenal thickness. The mean micrometer measurement (n = 10) in each animal was considered its duodenal wall thickness. The mean duodenal wall thickness (±SE) was 2.52 ± 0.04 mm for the 11 dogs. From histologic sections the mean thickness (±SE) was 2.41 ± 0.05 mm (p C) 70 <l; :E -c 0 60 * oj(- u'""'.* p <0.05 '" :=> 50 <l; '""' Z 0:: E-< 40 LO '0 S 30 :r: E-< '" 20 0 Z en '""' 10 0 t C 0 ALP low ALP 6w ALP 5. 5w ALP 4w BPEC Control Figure 1. Histogram of the incidence of DU with 100%EMLD for each treatment group or control. ALP is argon laser photocoagulation 4-10 W. BPEC is bipolar electrocoagulation. Incidence of tissue damage with ALP 6 W or 10 W was significantly greater (*) than for BPEC or control.
4 862 MACHICADO ET AL. GASTROENTEROLOGY Vol. 81, No.5 > 0.05). The mean standard ulcer depth from histologic sections was 1.16 ± 0.06 mm for control (n=20) and 1.12 ± 0.06 mm for treated ulcers (n = 20). Duodenal ulcer size, weight, and bleeding rate. The means (±SE) for plug size, plug we ight, and 15-s bleeding rate were 9.8 ± 2 mm, 56 ± 1 mg, and 0.41 ± 0.02 cc/15 s, respectively. There were no significant differences among control and treatment groups. Esophageal Studies Similar procedures (including heparinization) to those described for the duodenal studies were used except that a left thoracotomy was performed rather than a laparotomy. A volume respirator was used throughout the surgery. The distal esophagus was mobilized, and a single esophagotomy about 7 cm long was made 3-4 ern proximal to the gastroesophageal junction. Before standard ulcers were created, 10 different measurements of the esophageal wall thi ckness were made with a micrometer. Standard ulcers were made using a negative suction pressure of 10 in. Hg. Th e bleeding rate was quantitated for 30 s before randomization. Immediately after surgical closure of the thoracic cavity, the pneumothorax was evacuated with a 50 ern" syringe through percutaneous punctures. Study III A study was undertaken to determine effective coagulation (SPEC) and power setting (ALP) for treatment of standard bleeding ulcers in this organ. A 1.5-cm treatment distance was used for ALP with a 100 divergent Iightguide. The lowest consistently effective argon laser power was 4 W, but higher powers had shorter treatment times. The lowest effective coagulation setting for SPEC was 3. Five tr eatment groups were selected for further study: ALP 4 W, ALP 6 W, ALP 8 W, ALP 10 W, and SPEC 3. Study IV A chronic study was undertaken using 9 adult mongrel dogs. Each ulcer was randomly assigned to one of the five treatment groups or control. Efficacy was assessed acutely and histologic damage at 7 days similar to duodenal study II. Esophageal wall th ickness was estimated from these microscopic sections (mucosa to external muscle layer) for control and treated ulcers. Results Study VI Efficacy (Table 2) None of the control lesions stopped bleeding in the esophagus during the period of observation, whereas all lesions within the five treatment groups stopped bleeding. Subjectively, acute esophageal ulcers were much easier to treat than the acute duodenal or gastric ulcers in similar sized animals. For BPEC, the mean number of applications to achieve hemostasis of esophageal ulcers was 21 vs. 30 for duodenal ulcers (Tables 1 and 2). For ALP, significantly more total energy was required for treatment of duodenal than esophageal ulcers (Tables 1 and 2). Thermal application resulted in strong submucosal and blood vessel retraction in the esophagus. This was probably due to the strong adherence of the mucosa to the submucosa and muscle layers. This observation is attested to by the fact that a greater suction pressure had to be used in this organ in order to make standard ulcers comparable to those obtained in the duodenum. Histologic Damage At autopsy, no animal had mediastinitis, perforation, or obstruction. The frequencies of histologic 100% EMLD for esophageal lesions are illustrated in Figure 2. The frequency of 100% EMLD seen with ALP 10 W (74%) or ALP 8 W (47%) was significantly different than with BPEC (15%) or control (0%). Other Determinations Esophageal wall thickness. The mean (± SE) micrometer measurement for esophageal thickness was 2.52 ± 0.05 mm. From histologic sections (n = 30) the mean (± SE) thickness was 2.76 ± 0.08 mm. These differences are not statistically significant. The mean standard ulcer depth from histologic sections (n = 20 for each) was 0.90 ± 0.07 mm for contol and 0.89 ± 0.06 mm for treated ulcers (p > 0.05). Table 2. Efficacy of Treatment for Esophageal Ulcers Modality Control BPEC ALP4 ALP6 ALP8 ALP10 Power density Tx. distance # Stop/total 0/19 20/20 19/19 20/20 19/19 19/19 Percent Applications 21 ± 1 Total energy (J) 74± 3 74± 6 82 ± 8 77 ±4 Refer to Table 1 for details.
5 November 1981 LASER AND ELECTROCOAGULATION OF BLEEDING CANINE ULCERS 863 Esophageal ulcer size, weight, bleeding rate. The means (±SE) for plug size, plug weight, and 30-s bleeding rate were 6.3 ± 2 mm, 23 ± 1 mg, 0.42 ± 0.02 cm 3/30 s, respectively. There were no significant differences among control and treatment groups. Discussion For each organ, the ulcers randomized to each treatment group or control were not significantly different in bleeding rate, size, depth, or weight. They were standardized. However, there were statistically significant differences between esophageal and duodenal ulcers in mean bleeding rates (0.42 cm 3 / 30 s vs cm 3 / 15 s), size (6.3 mm vs, 9.8 mm), and weight (24.65 mg vs mg). These differences are opposite what we expected from the greater negative suction pressure used in the esophagus (10 in. Hg) than the duodenum (6 in. Hg). The mean depth of standard ulcers in these organs was 0.90 and 1.16 mm for esophagus and duodenum, respectively. Although the depth of EU and DU was similar to standard gastric ulcers, reported by Protell et al. (32), the bleeding rate and size of EU were different. Since the bleeding rate in the esophagus was significantly lower than in the duodenum, a longer period (30 s rather than 15 s) was chosen for quantitation in order to improve accuracy of blood collection. Bleeding rates decreased slightly with time for both duodenal and esophageal ulcers. All controls continued to bleed throughout the periods of observation and operation. However, as the heparin effect wore off, all controls eventually stopped bleeding and none of the dogs exsanguinated. For the esophagus, all treatment groups had equal efficacy. Esophageal ulcers subjectively responded to these thermal coagulation treatments with a stronger mucosa, submucosal, and vessel shrinkage than that seen with standardized gastric or duodenal ulcers. Although there were 2-6 small vessels around the submucosal ulcer margin, esophageal ulcers were easy to coagulate. For duodenal lesions, comparable efficacy was found with ALP 10 Wand BPEe 3. Lower-power argon was arithmetically less effective in this organ than in either the esophagus or stomach (27). Subjectively, these standard duodenal ulcers (DU) were more difficult to coagulate than either EU or GU. Although there were multiple bleeding vessels at the margins of both EU and DU, the bleeding rates were greater for DU than for esophageal ulcers. DU lesions continued bleeding unless meticulously treated. Also, with treatment, less retraction of the submucosa and vessels was evident than for comparable ulcers of the esophagus or stomach. This may be due to the relative looseness of the submucosa in the duodenum. Why the duodenum, esophagus, and stomach responded differently to these thermal coagulation modalities is uncertain. Differences in both efficacy and histologic damage probably represented different responses by these organs and their standard ulcers to treatment. The methods of application of both argon laser and bipolar electrocoagulation were the same as previously described (19). Also, the prototype bipolar electrode and argon laser lightguide are the same ones as we previously used in the stomach. There was no evidence that surgical manipula * * p ( Figure 2. The incidence of esophageal ulcers with 100% EMLD for control and treatment groups. See Figure 1 for ALP 4 10 Wand BPEC. The incidence of tissue damage with ALP 8 W or 10 W was significantly greater (*) than for BPEC or control. :c f-o Ul 20 QUl '"...J 10 '"o o ALP low ALP 8w ALP 6w ALP4w BPEC Control
6 864 MACHICADO ET AL. GASTROENTEROLOGY Vol. 81, No.5 tion itself resulted in any significant differences in efficacy because BPEC 3 and ALP 10 W were excellent throughout. There are some obvious differences of the duodenum, esophagus, and stomach that might have contributed: blood supply, muscle layer thicknesses, presence (stomach and duodenum) or absence of a serosa (esophagus), and submucosal structure. Tissue absorption of argon laser light and thermal conductivity might also differ. There was not a significant difference in the thickness of the duodenum and esophagus when measured with a micrometer: 2.52 ± 0.04 vs ± 0.05 mm. So, a difference in organ wall thickness did not contribute to the difference in tissue injury in these studies. The incidences of full-thickness injury to standard ulcers in the duodenum (30%-60%, Figure 1) and esophagus (30%-74%, Figure 2) were similar for argon laser treatment. The histologic results for 8 and 10 W in either the esophagus (Figure 2) or duodenum (Figure 1) differed significantly from our previous results with ALP treatment of standard ulcers in the stomach under similar conditions. For 1-cm treatment distance in the stomach, the mean incidence of 100% EMLD for 6, 9, and 12 W varied from 8% to 15% (28). In those experiments, histologic damage correlated directly with total energy used and inversely with animal weight. For neither the esophageal nor the duodenal ulcers in this study was there a good correlation between the degree of histologic damage and animal weight, bleeding rate, lesion weight, or energy required for hemostasis (total joules with ALP). The histologic injury with BPEC treatment of DU and EU in this study was similar to our previous experience with standard gastric ulcers. The mean incidences of 100% EMLD for gastric ulcers were 30% at laparotomy (19) and 17% at endoscopy (30). These results are not statistically different than for the esophagus or duodenum in the present study with incidences of 100% EMLD of 15% (Figure 2) and 20% (Figure 1), respectively. These models have allowed us to evaluate and compare efficacy and histologic damage of two promising hemostatic methods under controlled conditions. Such systematic studies are not possible in humans. For this multiple vessel model, it was evident that higher-power argon laser photocoagulation (8 or 10 W) was not necessary in the esophagus and should be avoided. If possible, high-power argon laser should be used with caution in the duodenum. BPEC was consistently as effective as high-power ALP and resulted in less tissue damage in the esophagus and duodenum. Although electrocoagulation is difficult to standardize, its advantages are portability, relative inexpensiveness, and the ability to use it with standard endoscopes and regular hospital electrical circuits (29). Bipolar electrocoagulation has several disadvantages. Lesion contact on vessels is required and this may worsen bleeding by disrupting clots or contacting friable surfaces. The electrode may stick during coagulation and upon withdrawal bleeding may occur. Effective endoscopic application may be difficult because precise contact with bleeding points is required. Coagulum builds up on the electrode tip during application, necessitating mechanical cleaning (29,30). Except for treatment of UGI telangiectasia by us (33), there are no reports of endoscopic applications of BPEC in patients. The prototype bipolar electrode used in these studies was fragile. Recently a more durable prototype bipolar probe in a hexagonal design was reported to cause limited tissue damage when applied to canine gastric standard ulcers at laparotomy (34). Endoscopic studies in animals with these prototype bipolar electrodes are needed in our opinion before initiation of controlled human trials. Although expensive and nonportable, argon laser can be standardized and easily used endoscopically without touching bleeding lesions. Argon laser has been used effectively and safely in uncontrolled, nonrandomized trials for actively bleeding and nonbleeding UGI lesions (8-10). Our preliminary results with argon laser for massive bleeders in separate controlled (35) and nonrandomized (33) trials are very favorable also. Both bipolar electrocoagulation and argon laser photocoagulation are very promising endoscopic methods for hemostasis. They offer equal efficacy yet wider margins of safety than monopolar electrocoagulation or YAG laser photocoagulation in the treatment of bleeding canine gastric ulcers (29,30). Both BPEC and lower-power ALP were effective and caused limited tissue damage in the esophagus and duodenum in this study. Both should be considered for controlled human trials of endoscopic hemostasis in the UGI tract, in our opinion. References 1. Papp JP. 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Presented at the International Medical Laser Symposium, Detroit, Michigan, March Kiefhaber P, Nath G, Moritz K. Endoscopic control of massive gastrointestinal hemorrhage by irradiation with a high power neodymium YAG laser. Prog Surg 1977;15: Kiefhaber P, Nath G, Moritz K. Endoscopic control of acute gastrointestinal hemorrhage by irradiation with high-power neodymium-yag laser. Presented at the International Medical Laser Sympsoium, Detroit, Michigan, March Koch H, Pesch JH, Bauerle H, et al. Erste experimentelle Untersuchungen und Klinische Erfahrungen zur Elektrokoagulation blutende Lasionen im oberen Gastrointestinaltrakt. Fortschr Endosk 1972;10: Stadelmann 0, Weisbart D, Zeus U. Blutende Lasionen im Gastrointestinaltrakt Elektrokoagulation. Symposium "Operativ e Endoskopie," Erlangen, Papp JP, Fox 1M, Nalbandian RM. Experimental electrocoagulation of dog esophageal and duodenal mucosa. Gastrointest Endosc 1976;23: Fruhmorgen P, Kaduk B, Reidenbach HD, et al. Long-term observations in endoscopic laser coagulations in the gastrointestinal tract. Endoscopy 1975;7: Piercey JRA, Auth DC, Silverstein FE, et al. Electrosurgical treatment of experimental bleeding gastric ulcers: development of a computer control and a better electrode. Gastroenterology 1978;74: Johnston JH, Jensen DM, Mautner W. A comparison of bipolar electrocoagulation and argon laser photocoagulation with coaxial CO 2 in the treatment of bleeding canine gastric ulcers (abstr). Gastrointest Endosc 1978:24: Moore JP, Silvis SE, Vennes JA. Evaluation of bipolar electrocoagulation in canine stomachs. Gastrointest Endosc 1978;24: Protell RL, Jensen DM, Silverstein FE, et al. Efficacy and safety of computer-controlled bipolar electrocoagulation in experimental acute gastric ulcer bleeding (abstr). Clin Res 1978;26:151A. 22. Johnston JH, Jensen DM, Mautner W, et al. YAG laser treatment of experimental gastric ulcers. Gastroenterology 1980;79: Dixon JA, Berenson MM, McCloskey DW. Neodymium-YAG laser treatment of experimental canine gastric bleeding. Acute and chronic studies of photocoagulation, penetration, and perforation. Gastroenterology 1979;77: Silverstein FE, Prot ell RL, Gilbert DA, et al. Argon vs. neodymium YAG laser photocoagulation of experimental canine gastric ulcers. Gastroenterology 1979;77: Silverstein FE, Auth D, Rubin CE, et al. High-power argon laser treatment via standard endoscopes. I. A preliminary study of efficacy in control of experimental erosive bleeding. Gastroenterology 1976;71: Silverstein FE, Prot ell RL, Piercey J, et al. Endoscopic laser treatment. II. Comparison of the efficacy of high and low power photocoagulation in control of severely bleeding experimental ulcers. Gastroenterology 1977;73: Silverstein FE, Prot ell RL, Gulacsik C, et aj. Endoscopic laser treatment. III. Development and testing of a gas-jet assisted argon laser waveguide in control of bleeding experimental ulcers. Gastroenterology 1978;74: Johnston JH, Jensen DM, Mautner W, et al. Argon laser treatment of bleeding canine ulcers: limitations and guidelines for endoscopic use. Gastroenterology 1981;80: Jensen DM. Endoscopic control of gastrointestinal bleeding. In: Berk JE, ed. Developments in digestive diseases. Vol. 3. Philadelphia: Lea & Febiger, 1980: Johnston JH, Jensen DM, Mautner W, et al. Comparison of laser photocoagulation and electrocoagulation in endoscopic treatment of UGI bleeding (abstr). Gastroenterology 1979; 76: Snedcor GW, Cochran WG. Statistical methods. 6th ed. Ames, Iowa : Iowa State University Press, Protell RL, Silverstein FE, Piercy 1. et al. A reproducible animal model of acute bleeding ulcer-the "ulcer maker." Gastroenterology 1976;71: Jensen D, Machicado G, Tapia J, et al. Endoscopic coagulation of telangiectasia with argon laser photocoagulation and bipolar electrocoagulation in patients with chronic gastrointestinal bleeding (abstr). Gastrointest Endosc 1980;26: Auth DC, Gilbert DA, Opi e EA, et al. The multipolar probe-a new endoscopic technique to control gastrointestinal bleeding (abstr). Gastrointest Endosc 1980;26: Jensen DM, Machicado GA. Mautner W, et al. Endoscopic argon laser photocoagulation of patients with severe gastrointestinal bleeding (abstr). Gastroenterology 1980;78:1188.