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Protective effect of gastroduodenostomy (jaboulay) and truncal vagotomy against formation of peptic ulcers induced by histamine beeswax in dogs
Protective Effect of Gastroduodenostomy (Jaboulay) and Truncal Vagotomy against Formation of Peptic Ulcers Induced by Histamine Beeswax in Dogs Isaac Egozi, MD, Miami, Florida Alfred Hurwitz, MD, Miami Beach, Florida
Pyloroplasty or gastrojejunostomy with truncal vagotomy in the treatment of duodenal ulcer has been followed by the redevelopment of ulcers in approximately 10 per cent of cases [I]. Side to side gastroduodenostomy with vagotomy has been employed to a limited degree but with increasing frequency. Because of the paucity of cases and the lack of longterm follow-up examinations, the efficacy of this operation is unknown. It was our aim to determine the efficacy of gastroduodenostomy with vagotomy in the dog. The following experiments were designed for this purpose. Methods and Results
In this study prolonged histamine action was obtained by embedding histamine in a beeswax-mineral oil mixture. This mixture, which melts at a temperature ranging from 40” to 50” C, remains a semisolid mass when injected intramuscularly, and thus permits a slow and gradual liberation of the embedded histamine. This method was devised in 1940 for the study of prolonged histamine stimulation [2]. Thirty-four adult mongrel dogs, weighing from 22 to 40 pounds were injected daily with 40 mg of histamine, * suspended in beeswax base. These dogs were divided into three groups. Group I. This was the control group to determine the incidence of ulcer formation after two to fifty-two *Code 49767, City Chemical Corporation, New York, New York.
From the Department of Surgery, Mount Sinai Medical Center, Miami Beach, Florida 33140. Reprint requests should be addressed to Dr Hurwitz, Director, Surgical %WiCeS, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140.
Volume 123, June 1972
injections of histamine in beeswax. (Table I.) Twenty-three dogs were given daily injections. Dog number 14 demonstrated ulcer after two daily doses. Most of the dogs presented symptoms of gastrointestinal bleeding, and at laparotomy all but one dog (dog number 3) exhibited duodenal or gastric ulcers. The ulcers occurred on the average after three weeks of histamine injections. Group II. Seven dogs received seven to fifty-two injections of histamine in beeswax (Table II) and when symptoms (such as weight loss or gastrointestinal bleeding) developed, laparotomy was performed. All dogs exhibited peptic ulcer. Side to side gastroduodenostomy and truncal vagotomy were performed. A week later the injections were recommenced and continued for twenty-five days. When re-exploration was carried out, no ulcers were found. These experiments demonstrated that gastroduodenostomy with vagotomy is effective in healing ulcers previously produced, and in perpetuating the remission, even though the animals were receiving the same stimulus that originally induced the ulcer. Group III. In this last group (Table III) gastroduodenostomy and vagotomy were performed in four dogs. Ten days later a series of twenty-five daily injections of histamine in beeswax was initiated, after which exploratory laparotomy was performed and no ulcers were seen. One week after operation a second series of injections was given for thirty more days, and again no ulcers were found on re-exploration. This operation is an effective method in preventing formation of peptic ulcer since the first group demonstrated that in all but one of the twenty-three dogs ulcers developed after similar histamine beeswax injections.
649
Egozi and Hurwitz
TABLE I
Group I: Production, of Ulcer in Dogs by Daily Injections of 40 Mg of Histamine-Beeswax Number of Injections (one per day)
Reason for Exploration
1 2
20 17
Melena, weakness Weakness, weight loss
3 4
6 38 16 20 30 30 24 21 18 10 5 2 8 52 24 51 7 59 14 14 25
Melena Melena Vomiting, melena Weakness, melena No symptoms No symptoms Gastrointestinal bleeding No symptoms Vomiting, weight loss
Dog Number
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
TABLE II
Melena Melena Weight loss Melena Melena Melena No symptoms Melena Melena Gastrointestinal
bleeding
Operative
Findings
Group II: Results Obtained with Gastroduodenostomy and Vagotomy after Experimental Production of Ulcers Followed by a Second Course of Injections Number of Injections after Exploration
Dog Number 1 2 3 4
24 52 51 14
Two small duodenal ulcers Two duodenal ulcers; pyloric ulcer Two duodenal ulcers Duodenal ulcer
33 25 25 21
5 6 7
21 27 18
Gastric ulcer Duodenal ulcer Two duodenal ulcers
25 25 25
*Gastroduodenostomy
and vagotomy
Operative
Findings*
Findings at Exploration at Time of Last Injection No ulcers No ulcers No ulcers Gastric erythema; no ulcers No ulcers No ulcers No ulcers
performed.
Group Ill: Prevention of Peptic Ulcer after Side to Side Gastroduodenostomy and Vagotomy
Dog Number 1 2
Number of Injections after Surgery* 25 25
3
25
4
22
*Gastroduodenostomy
650
or Postmortem
Small ulcer, second portion of duodenum Two duodenal ulcers; multiple areas of gastric hemorrhage Congestive gastric mucosa; no ulcer Large antral ulcer Multiple duodenal ulcer Ulcer of second portion of duodenum Two gastric ulcers Three duodenal ulcers Two small duodenal ulcers Necrotizing gastritis Duodenal ulcer Perforated duodenal ulcer Perforated duodenal ulcer Large duodenal ulcer Duodenal ulcer Two duodenal ulcers Duodenal ulcer Two duodenal ulcers Two duodenal ulcers Perforated gastric ulcer Duodenal ulcer Duodenal ulcer Duodenal ulcer
Number of Injections
TABLE III
Mixture
Findings at Exploration No ulcers Erythema gastric mucosa; no ulcers No ulcers No ulcers
Number of Injections after Exploration
Findings at Exploration
25 25
No ulcers Erythema;
25 25
No ulcers No ulcers
no ulcers
and vagotomy.
The American
Journal of Surgery
Gastroduodenostomy
and Vagotomy
Protecting
against Peptic Ulcers
Comments
Summary
The type of operation employed in the treatment of duodenal ulcer should be tailored to the clinical and anatomic findings. Although hemigastrectomy and vagotomy are followed by the lowest incidence of postoperative ulcer formation [3,4], the immediate operative mortality is approximately four to eight times greater than that after any drainage procedure combined with vagotomy. On the other hand, drainage procedures combined with vagotomy exhibit an incidence of marginal ulcer at least eight to ten times greater than that of hemigastrectomy and vagotomy. Heupel and Hay [5], using the same dosage of histamine that we employed, reported the development of histamine-induced ulcers in six of ten control dogs, in none of twelve dogs with vagotomy-pyloroplasty, and in nine of nine dogs with vagotomygastrojejunostomy. In the latter group they excised the pylorus, closed the duodenum and performed gastrojejunostomy in the nine dogs that survived previous pyloroplasty and vagotomy. They also showed that marked inhibition of gastric secretion from a denervated pouch occurred when the duodenum was perfused with acid. Since gastric secretions empty directly into the duodenum in gastroduodenostomies, acid secretion may be diminished by the aforementioned mechanism. We plan to compare the results of gastrojejunostomy-vagotomy performed without excision of the pylorus with the results reported in the present series of gastroduodenostomyvagotomy. It would be highly desirable to have in our armamentarium a drainage operation which is easy to perform and is followed by a lower incidence of development of marginal ulcer [6]. Gastroduodenostomy is easy to perform. It has the theoretical advantages of permitting easy flow of gastric contents into the duodenum, which, because of its proximity to the stomach, is a more physiologic recipient of gastric secretions than is the jejunum [ 7].
There has not been a long-term study (ten or more years) of the efficacy of gastroduodenostomy and vagotomy in patients. Although the results obtained in dogs may not be emulated in man, our animal studies, as shown in Tables I, II and III, reveal that: (1) peptic ulcer was induced by histamine in beeswax in twenty-two of twenty-three dogs; (2) once the ulcer has developed, gastroduodenostomy with vagotomy was effective in healing it, and the ulcer remained healed after a second continuous course of daily histamine injections in seven dogs; (3) in four dogs gastroduodenostomy with vagotomy protected the dog against the formation of ulcers even after fifty daily injections of histamine in beeswax. Side to side gastroduodenostomy (Jaboulay) with truncal vagotomy is an effective method in preventing formation pf peptic ulcer in dogs, in healing ulcers previously produced by injections of histamine in beeswax, and in maintaining healing even after a prolonged second course of injections in dogs.
Volume 123. June 1972
References 1. Small WT, Jahadi Ml?: Pyloroplasty and vagotomy for duodenal ulcer. Amer J Surg 119: 372, 1970. 2. Hay W, Varco RL, Code CF. Wangensteen OH: Experimental production of gastric and duodenal ulcers in laboratory animals by intramuscular injection of histamine in beeswax. Surg Gynec Obstet 75: 170. 1942. 3. Scott HW, Herrington JL Jr, Edwards LW, Shut1 HJ, Stephenson SE Jr, Sawyers JL, Classen KL: Results of vagotomy and antral resection in surgical treatment of duodenal ulcer. Gasfroenterology 39: 590, 1960. 4. Smithwick RH. Farmer DA: Procedures upon acidity and peptic activity of gastric contents. 1301 Asoc Med P Rico 44: 211, 1952. 5. Heupel HW, Hay W: Gastroenterostomy and pyloroplasty after vagotomy. Arch Surg 81: 419, 1960. 6. Eisenberg MM, Woodward ER, Carson TJ, Dragstedt LR: Vagotomy and drainage procedure for duodenal ulcer. Ann Sorg 170: 317, 1969. 7. Oi M, Miho 0, Endo M, Ohmura T: Relation of gastric mucosal boundary between fundic gland and pyloric gland areas to the development of anastomotic ulcers. Ann Surg 163: 35, 1966.
651
Pyloroplasty or gastrojejunostomy with truncal vagotomy in the treatment of duodenal ulcer has been followed by the redevelopment of ulcers in approximately 10 per cent of cases [I]. Side to side gastroduodenostomy with vagotomy has been employed to a limited degree but with increasing frequency. Because of the paucity of cases and the lack of longterm follow-up examinations, the efficacy of this operation is unknown. It was our aim to determine the efficacy of gastroduodenostomy with vagotomy in the dog. The following experiments were designed for this purpose. Methods and Results
In this study prolonged histamine action was obtained by embedding histamine in a beeswax-mineral oil mixture. This mixture, which melts at a temperature ranging from 40” to 50” C, remains a semisolid mass when injected intramuscularly, and thus permits a slow and gradual liberation of the embedded histamine. This method was devised in 1940 for the study of prolonged histamine stimulation [2]. Thirty-four adult mongrel dogs, weighing from 22 to 40 pounds were injected daily with 40 mg of histamine, * suspended in beeswax base. These dogs were divided into three groups. Group I. This was the control group to determine the incidence of ulcer formation after two to fifty-two *Code 49767, City Chemical Corporation, New York, New York.
From the Department of Surgery, Mount Sinai Medical Center, Miami Beach, Florida 33140. Reprint requests should be addressed to Dr Hurwitz, Director, Surgical %WiCeS, Mount Sinai Medical Center, 4300 Alton Road, Miami Beach, Florida 33140.
Volume 123, June 1972
injections of histamine in beeswax. (Table I.) Twenty-three dogs were given daily injections. Dog number 14 demonstrated ulcer after two daily doses. Most of the dogs presented symptoms of gastrointestinal bleeding, and at laparotomy all but one dog (dog number 3) exhibited duodenal or gastric ulcers. The ulcers occurred on the average after three weeks of histamine injections. Group II. Seven dogs received seven to fifty-two injections of histamine in beeswax (Table II) and when symptoms (such as weight loss or gastrointestinal bleeding) developed, laparotomy was performed. All dogs exhibited peptic ulcer. Side to side gastroduodenostomy and truncal vagotomy were performed. A week later the injections were recommenced and continued for twenty-five days. When re-exploration was carried out, no ulcers were found. These experiments demonstrated that gastroduodenostomy with vagotomy is effective in healing ulcers previously produced, and in perpetuating the remission, even though the animals were receiving the same stimulus that originally induced the ulcer. Group III. In this last group (Table III) gastroduodenostomy and vagotomy were performed in four dogs. Ten days later a series of twenty-five daily injections of histamine in beeswax was initiated, after which exploratory laparotomy was performed and no ulcers were seen. One week after operation a second series of injections was given for thirty more days, and again no ulcers were found on re-exploration. This operation is an effective method in preventing formation of peptic ulcer since the first group demonstrated that in all but one of the twenty-three dogs ulcers developed after similar histamine beeswax injections.
649
Egozi and Hurwitz
TABLE I
Group I: Production, of Ulcer in Dogs by Daily Injections of 40 Mg of Histamine-Beeswax Number of Injections (one per day)
Reason for Exploration
1 2
20 17
Melena, weakness Weakness, weight loss
3 4
6 38 16 20 30 30 24 21 18 10 5 2 8 52 24 51 7 59 14 14 25
Melena Melena Vomiting, melena Weakness, melena No symptoms No symptoms Gastrointestinal bleeding No symptoms Vomiting, weight loss
Dog Number
5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
TABLE II
Melena Melena Weight loss Melena Melena Melena No symptoms Melena Melena Gastrointestinal
bleeding
Operative
Findings
Group II: Results Obtained with Gastroduodenostomy and Vagotomy after Experimental Production of Ulcers Followed by a Second Course of Injections Number of Injections after Exploration
Dog Number 1 2 3 4
24 52 51 14
Two small duodenal ulcers Two duodenal ulcers; pyloric ulcer Two duodenal ulcers Duodenal ulcer
33 25 25 21
5 6 7
21 27 18
Gastric ulcer Duodenal ulcer Two duodenal ulcers
25 25 25
*Gastroduodenostomy
and vagotomy
Operative
Findings*
Findings at Exploration at Time of Last Injection No ulcers No ulcers No ulcers Gastric erythema; no ulcers No ulcers No ulcers No ulcers
performed.
Group Ill: Prevention of Peptic Ulcer after Side to Side Gastroduodenostomy and Vagotomy
Dog Number 1 2
Number of Injections after Surgery* 25 25
3
25
4
22
*Gastroduodenostomy
650
or Postmortem
Small ulcer, second portion of duodenum Two duodenal ulcers; multiple areas of gastric hemorrhage Congestive gastric mucosa; no ulcer Large antral ulcer Multiple duodenal ulcer Ulcer of second portion of duodenum Two gastric ulcers Three duodenal ulcers Two small duodenal ulcers Necrotizing gastritis Duodenal ulcer Perforated duodenal ulcer Perforated duodenal ulcer Large duodenal ulcer Duodenal ulcer Two duodenal ulcers Duodenal ulcer Two duodenal ulcers Two duodenal ulcers Perforated gastric ulcer Duodenal ulcer Duodenal ulcer Duodenal ulcer
Number of Injections
TABLE III
Mixture
Findings at Exploration No ulcers Erythema gastric mucosa; no ulcers No ulcers No ulcers
Number of Injections after Exploration
Findings at Exploration
25 25
No ulcers Erythema;
25 25
No ulcers No ulcers
no ulcers
and vagotomy.
The American
Journal of Surgery
Gastroduodenostomy
and Vagotomy
Protecting
against Peptic Ulcers
Comments
Summary
The type of operation employed in the treatment of duodenal ulcer should be tailored to the clinical and anatomic findings. Although hemigastrectomy and vagotomy are followed by the lowest incidence of postoperative ulcer formation [3,4], the immediate operative mortality is approximately four to eight times greater than that after any drainage procedure combined with vagotomy. On the other hand, drainage procedures combined with vagotomy exhibit an incidence of marginal ulcer at least eight to ten times greater than that of hemigastrectomy and vagotomy. Heupel and Hay [5], using the same dosage of histamine that we employed, reported the development of histamine-induced ulcers in six of ten control dogs, in none of twelve dogs with vagotomy-pyloroplasty, and in nine of nine dogs with vagotomygastrojejunostomy. In the latter group they excised the pylorus, closed the duodenum and performed gastrojejunostomy in the nine dogs that survived previous pyloroplasty and vagotomy. They also showed that marked inhibition of gastric secretion from a denervated pouch occurred when the duodenum was perfused with acid. Since gastric secretions empty directly into the duodenum in gastroduodenostomies, acid secretion may be diminished by the aforementioned mechanism. We plan to compare the results of gastrojejunostomy-vagotomy performed without excision of the pylorus with the results reported in the present series of gastroduodenostomyvagotomy. It would be highly desirable to have in our armamentarium a drainage operation which is easy to perform and is followed by a lower incidence of development of marginal ulcer [6]. Gastroduodenostomy is easy to perform. It has the theoretical advantages of permitting easy flow of gastric contents into the duodenum, which, because of its proximity to the stomach, is a more physiologic recipient of gastric secretions than is the jejunum [ 7].
There has not been a long-term study (ten or more years) of the efficacy of gastroduodenostomy and vagotomy in patients. Although the results obtained in dogs may not be emulated in man, our animal studies, as shown in Tables I, II and III, reveal that: (1) peptic ulcer was induced by histamine in beeswax in twenty-two of twenty-three dogs; (2) once the ulcer has developed, gastroduodenostomy with vagotomy was effective in healing it, and the ulcer remained healed after a second continuous course of daily histamine injections in seven dogs; (3) in four dogs gastroduodenostomy with vagotomy protected the dog against the formation of ulcers even after fifty daily injections of histamine in beeswax. Side to side gastroduodenostomy (Jaboulay) with truncal vagotomy is an effective method in preventing formation pf peptic ulcer in dogs, in healing ulcers previously produced by injections of histamine in beeswax, and in maintaining healing even after a prolonged second course of injections in dogs.
Volume 123. June 1972
References 1. Small WT, Jahadi Ml?: Pyloroplasty and vagotomy for duodenal ulcer. Amer J Surg 119: 372, 1970. 2. Hay W, Varco RL, Code CF. Wangensteen OH: Experimental production of gastric and duodenal ulcers in laboratory animals by intramuscular injection of histamine in beeswax. Surg Gynec Obstet 75: 170. 1942. 3. Scott HW, Herrington JL Jr, Edwards LW, Shut1 HJ, Stephenson SE Jr, Sawyers JL, Classen KL: Results of vagotomy and antral resection in surgical treatment of duodenal ulcer. Gasfroenterology 39: 590, 1960. 4. Smithwick RH. Farmer DA: Procedures upon acidity and peptic activity of gastric contents. 1301 Asoc Med P Rico 44: 211, 1952. 5. Heupel HW, Hay W: Gastroenterostomy and pyloroplasty after vagotomy. Arch Surg 81: 419, 1960. 6. Eisenberg MM, Woodward ER, Carson TJ, Dragstedt LR: Vagotomy and drainage procedure for duodenal ulcer. Ann Sorg 170: 317, 1969. 7. Oi M, Miho 0, Endo M, Ohmura T: Relation of gastric mucosal boundary between fundic gland and pyloric gland areas to the development of anastomotic ulcers. Ann Surg 163: 35, 1966.
651