R.L. Protell

A Reproducible Animal Model of Acute Bleeding Ulcer—The “Ulcer Maker”

An instrument has been developed which creates an experimental model of an acute bleeding gastric ulcer. The diameter and depth of these gastric ulcers are reproducible. The instrument can be used endoscopically or at laparotomy. Using this ulcer model nonsurgical modalities for the treatment of upper gastrointestinal bleeding can be compared in a controlled manner. This standard experimental model may also facilitate comparison of results among different research groups.

High Power Argon Laser Treatment Via Standard Endoscopes: I. A preliminary study of efficacy in control of experimental erosive bleeding

With minimal transmission loss a high power argon laser (10 w) was coupled to a waveguide consisting of a flexible, single, coated, quartz fiber encased in a protective polyethylene tube. This waveguide can be passed down the biopsy channel of any standard fiberoptic endoscope. An aiming light improves accuracy. Safety devices were developed to protect the subject and the operator. Each of 8 heparinized mongrel dogs had three superficial erosions created endoscopically in the fundal gland mucosa by a jet of warm 0.1 N HC1. In each animal two lesions were photocoagulated with the laser and the third was left as a control. The animals were killed at 0, 4, 7, 10, and 14 days, and the erosions were examined histologically. By 14 days all lesions were covered by normal surface epithelium. Parietal and chief cells had returned to untreated erosions at 14 days but not to all lasered lesions. Only rarely did the lasered lesions penetrate through the muscularis mucosae into the submucosa. High power argon laser photocoagulation is now feasible through standard endoscopes. These data are sufficiently promising to encourage further evaluation of laser photocoagulation in a variety of animal models.

Evaluation of electrofulguration in control of bleeding of experimental gastric ulcers.

The safety and efficacy of electrofulguration for control of bleeding from standard canine experimental gastric ulcers was studied. At settings of 2, 5, and 8 on a Valleylab SSE-3 generator, 0.5-sec applications provided effective hemostasis. However, a setting of 2 required an excessive number of applications. Settings of 5 and 8 showed deep injury to the muscularis externa when examined histologically. In an attempt to reduce the depth of injury, a more easily ionizable gas mixture of 50% argon gas and 50% CO2 was compared to CO2 alone. At a generator setting of 5 with 0.5-sec applications the argon-CO2 mixture produced slightly less deep injury than CO2 alone, but the difference was not significant. Although electrofulguration was effective in stopping bleeding in these experiments, the tissue injury was unpredictable and deep.

Failure of cyanoacrylate tissue glue (Flucrylate, MBR4197) to stop bleeding from experimental canine gastric ulcers

A plastic tissue adhesive, trifluoroisopropyl 2-cyanoacrylate (FlucrylateTM, MBR4197), was tested for hemostatic efficacy in acute laparotomy experiments using a canine model of acute bleeding gastric ulcer. An improved delivery system suitable for endoscopic use was developed. Hemostatic efficacy of the adhesive was tested in both briskly bleeding ulcers and in oozing ulcers after partial treatment with a heater probe. In pilot studies at laparotomy, primary and adjunctive cyanoacrylate therapy of 81 bleeding ulcers were evaluated in seven unheparinized foxhounds. Hemostasis was produced in 11% of ulcers treated with cyanoacrylate alone and in 31% of ulcers treated with cyanoacrylate as an adjunctive after partial heater-probe treatment; no sham-treated control ulcers stopped bleeding under the conditions of the experiment. To evaluate FlucrylateTM using our standard heparinized ulcer model, a randomized study was performed in six heparinized foxhounds at laparotomy. Ulcers were randomized to treatment with cyanoacrylate alone, adjunctive cyanoacrylate, heater probe alone or untreated control. Sham-treated control ulcers or ulcers treated with cyanoacrylate alone did not stop bleeding; 42% of ulcers treated with cyanoacrylate as an adjunctive stopped bleeding; all ulcers treated with a heater probe stopped bleeding. In this experimental model of acute bleeding gastric ulcer, trifluoroisopropyl 2-cyanoacrylate (FlucrylateTM, MBR4197) did not stop severe bleeding and was unpredictable as an adjunctive treatment.

The multisection tissue slicer: A simpler technique for assessing the maximal depth of experimental injury

A new device, the multisection tissue sampler, has been developed to accurately identify the area of maximal tissue damage after experimental coagulation of bleeding ulcers. Fixed ulcers are sliced into 1-mm strips and then examined with a dissecting microscope. The technique was validated by comparing visible changes in one ulcer slice with changes observed microscopically in the mirror image slice. This device is a less time-consuming method of histologic analysis that may be of value in other areas of endoscopic research.

Use of Gas Jet Appositional Pressurization in Endoscopic Laser Photocoagulation

A hybrid optical fiber catheter has been developed which is capable of simultaneously emitting from its distal end 20 W of continuous laser radiation and a jet stream of CO2 gas. The catheter can be readily inserted into the biopsy channel of conventional flexible endoscopes for control of gastric bleeding. Experiments on bleeding animal ulcers and an artificial bleeding vessel model show that a catheter which delivers a simultaneous jet of gas with laser radiation is much more effective in achieving hemostasis than laser radiation alone. The laser/gas catheter also incorporates other improvements in device durability. Results of controlled animal trials are discussed.

Endoscopic Treatment of Nonvariceal Upper Gastrointestinal Bleeding

The advent of flexible fiberoptic endoscopy has stimulated the development of numerous nonsurgical methods to stop bleeding in patients with upper gastrointestinal hemorrhage. Our laboratory has evaluated several of these techniques in studies using standard-sized bleeding canine gastric ulcers. Gas-assisted argon and the neodymium YAG laser photo-coagulation, computer-assisted monopolar and bipolar electrocoagulation, and a new device, the heater probe, are all highly effective for stopping bleeding from this model. Of these, the gas-assisted argon laser produces the least injury to tissue underlying the treated ulcer. A topical hemostatic spray, Flucrylate, proved ineffective in this model. Uncontrolled clinical experience with laser photocoagulation and monopolar electrocoagulation indicates that each stops upper gastrointestinal hemorrhage in more than 90% of treated patients. Based on available experimental and clinical data, we are now undertaking a controlled clinical trial of gas-assisted argon laser photocoagulation in patients with bleeding gastric, stomal, or duodenal ulcers.

The role of ERCP in the diagnosis of pancreatic malignancy presenting as steatorrhea

Of 29 patients whose endoscopic retrograde cholangiopancreatogram (ERCP) led to a diagnosis of pancreatic neoplasia, 7 presented with steatorrhea. Steatorrhea may be the initial sign of pancreatic malignancy and aggressive evaluation including ERCP should be considered.