Basal and meat extract plasma gastrin before and after parietal cell vagotomy and selective gastric vagotomy with drainage in patients with duodenal ulcer.

Basal and meat extract stimulated plasma gastrin (PG) levels and basal and stimulated gastric acid secretion were evaluated pre and postoperatively in duodenal ulcer patients who underwent parietal cell vagotomy without antral drainage (normal duodena) (PC, n=32) or selective vagotomy with drainage (pyloric stenosis) (SV +P, n=11). Before operation, both groups had comparable basal PG values of 52+/-13 pg/ml (PCVP) AND 51+/-18 PG/ML (SV+P), while the peak gastrin level to meat extract stimulation was 173+/-40 pg/ml for the total group of patients. After both operations basal PG levels increased (107+/-18 pg/ml (PCV) and 152+/-45 pg/ml (SV+P) and the gastrin response to meat extract stimulation was augmented after PCV, while the response after SV+P was the same as before operation. Patients with PCV often demonstrated an acid response following meat extract stimulation (3.6+/-0.9 mEq HC1/hr), and pentapeptide stimulation (18.8+/-2.0 mEq/hr) while patients with SV/P showed a minimal response (1.3+/-1.2 mEq HC1/hr meat extract), and 10.7+/-1.8 mEq/hr pentapeptide stimulation. The comparatively intact acid response in the PCV patients may augur a high ultimate recurrence rate.     

Variations in serum gastrin concentration after feeding in man, dog, and pig.

By employing a sensitive radioimmunoassay, the serum gastrin concentrations were measured in man, dog, and pig during fasting and after stimulation with a protein meal. The fasting levels of serum gastrin in the three species were of the same order of magnitude.After the meal, the patterns of variation in serum gastrin concentrations were very similar in man and dog, a steep rise occurring after 30 and 15 min, respectively. Thereafter the gastrin values decreased, and 90 min after the meal no significant difference compared to basal levels was observed. The pigs, on the other hand, showed a prolonged rise in serum gastrin concentration after the meal. This causes us to prefer the dog as a model in experimental surgery combined with gastrin studies.     

Sham feeding for testing gastric secretory capacities before and after parietal cell vagotomy

The usefulness of acid secretory data collected during a modified sham-feeding (MSF) test was examined in 50 patients suffering from duodenal ulcer before and after parietal cell vagotomy. In these patients basal acid output pentagastrin-stimulated acid output and MSF-stimulated acid output were measured. Preoperative MSF-stimulated acid output was found to be correlated with preoperative basal acid output, and postoperative MSF-stimulated acid output was correlated with both preoperative basal acid output and postoperative basal and pentagastrin-stimulated acid outputs. The addition of preoperative MSF-stimulated acid output to preoperative pentagastrin-stimulated acid output did not noticeably increase the close relationship between the latter and postoperative pentagastrin-stimulated acid output. It is concluded that basal and MSF-stimulated secretory rates overlap. Therefore, it is suggested that in both preoperative and postoperative conditions the addition of the sham-feeding test to the more simple basal and pentagastrin-stimulated studies could be discarded.     

Antrectomy for recurrent ulcer after parietal cell vagotomy

The results of antrectomy for recurrent ulcer after parietal cell vagotomy are reviewed. Eighteen patients underwent precise antrectomy between 6 months and 7 years after their primary operation. Fourteen patients were reconstructed with a gastroduodenostomy and 4 with a gastrojejunostomy. Eighteen patients were available for follow-up of between 18 months and 10 years. One patient (6.25 per cent) developed a recurrent ulcer 1 year after antrectomy. There was no operative mortality. Six patients (33 per cent) had minor complications in the immediate postoperative period, and one (5.5 per cent) had a major complication. According to Visick grading, 75 per cent had good or excellent results and 25 per cent poor results. Antrectomy following parietal cell vagotomy can be achieved with a low operative mortality, a low ulcer recurrence rate and a satisfactorily low incidence of post-gastrectomy problems.     

Recurrence after parietal cell vagotomy for peptic ulcer disease

The value of parietal cell vagotomy as a safe surgical procedure in the treatment of chronic peptic ulcer disease has been seemingly limited by the high recurrence rate usually reported. In this 10 year experience of 405 consecutive parietal cell vagotomy operations, 57 patients with recurrent ulceration were evaluated to try to answer the questions of where and why recurrent ulceration appears and how to treat it. Patients with pyloric or prepyloric ulcer disease had recurrence of disease earlier than did patients with chronic duodenal ulcer disease. Consequently, pyloric or prepyloric ulcer patients had a higher recurrence rate in the early postoperative period than chronic duodenal ulcer patients, but this difference disappeared after the seventh postoperative year. Patients with recurrent chronic duodenal ulcer disease have high postoperative acid secretion levels, indicating incomplete vagotomy as a causative factor. Patients with recurrent pyloric or prepyloric ulcer disease have postoperative acid secretion similar to that of patients without recurrence, suggesting another etiologic factor. Thirty of 57 patients with recurrent ulcer had successful medical treatment. A conservative attitude towards recurrences is justified, particularly when symptoms are few and the postoperative acid secretion tests indicate complete or partial vagotomy. Surgical therapy consisting of truncal vagotomy and pyloroplasty in cases of incomplete vagotomy and antrectomy in cases of complete vagotomy should be reserved for patients with symptoms and a disease course that cannot be controlled by conservative treatment.     

One hundred patients ten years after parietal cell vagotomy

One hundred patients with duodenal or pyloric/prepyloric ulcer disease were operated with parietal cell vagotomy (PCV) and followed for a minimum of 10 years. At 6 weeks, 1,5 and 10 years postoperatively gastric secretory tests, haematological work-up and clinical examination or telephone interview were performed. There was no operative mortality and the frequency of postoperative sequelae was minimal. The cumulative ulcer recurrence rate was 18 per cent and another 14 per cent had slight to moderate symptoms of epigastric pain without any signs of ulcer. Upper gastrointestinal endoscopy was used to reveal recurrences but was performed only if the patient had symptoms of recurrence. A rise in basal acid secretion and in pentagastrin-stimulated secretion was observed the first year postoperatively, whereas insulin-stimulated peak acid output increased during the first 5 years. We conclude that PCV has a low rate of per- and postoperative complications and an acceptable recurrence rate. Therefore, it seems that PCV is the method of choice in chronic duodenal ulcer disease.     

Gastrin cell populations after highly selective vagotomy in the dog.

Highly selective vagotomy was performed on five dogs. Postoperatively, gastrin cell (G cell) hyperplasia occurred in all dogs. Mean preoperative G cell numbers increased from 350 to 530/cm mucosal length (p less than 0.02). Antral tissue gastrin also increased by 100 per cent (6.7 x 10(6) to 13.7 x 10(6) pg/gm tissue, p less than 0.05). Basal and stimulated serum gastrin were unchanged following highly selective vagotomy. The cause for G cell hyperplasia is not clear, but is probably multifactorial.     

Morphologic and functional evidence of reinnervation of the gastric parietal cell mass after parietal cell vagotomy

The incidence of recurrent ulceration after parietal cell vagotomy varies greatly and the cause is largely unknown. Whether the vagus nerve can regenerate or reinnervate the gastric parietal cell mass after parietal cell vagotomy was investigated. Careful microscopic dissection of the neurovascular bundle in 130 rats allowed the vagus nerve to be divided to the gastric body with preservation of the antropyloric nerve and gastric vasculature. Gastric secretory tests were performed under basal and stimulated conditions after secretagogue and insulin hypoglycemia stimulation.Rats were killed weekly and the vagal nerve distribution examined by electron microscopy. Stimulated gastric acid output decreased from 164 to 26 μmol/hour immediately after operation (p < 0.001). One week after parietal cell vagotomy the nerves were swollen with fibroblast infiltration and collagen around axon groups showed degeneration. By the third week after parietal cell vagotomy, the axons were more densely packed with neurofilaments and acid output had increased to 183 μmol/hour. In the fourth and fifth weeks, the enlarged Schwann cell forum processes had more axons and acid output increased to 262 μmol/hour. By the seventh week, both large and small axons were identified and the acid output was 93 percent higher than the preoperative level (p < 0.001). The sequential neuropathologic changes of vagus nerve degeneration, regeneration and functional reinnervation of the gastric parietal cell mass after parietal cell vagotomy are shown by this study. If this occurs in man, it may be an important cause of recurrent peptic ulceration after parietal cell vagotomy.     

Our first 35 patients studied five years after parietal cell vagotomy.

Parietal cell vagotomy without drainage (PCV) was performed on 35 patients. The patients were evaluated at regular intervals for 60 months. A recurrent ulcer developed in four patients. One patient was reoperated on, one patient refused an operation, and in two patients, the ulcers healed and remained healed for four years after withdrawal of ulcerogenic drugs. Another patient was reoperated on for pyloric obstruction. Diarrhea was reported by no more than one patient at any reporting period. The number of patients who reported dumping at the various time periods ranged from two to four. At the time of each patient's last interview, 33 were considered to have excellent or good results. PCV is a safe and effective operation for treatment of duodenal ulcer. Instructions in the technique are necessary to avoid errors that might unnecessarily occur and lead to poor results with first operations.     

Human gastrin response to secretin after vagotomy.

The gastrin response to a liquid meal with and without secretin infusion was studied in nine patients undergoing selective or truncal vagotomy with pyloroplasty for duodenal ulcer disease. Fasting gastrin levels were significantly increased in eight of nine patients after vagotomy, but secretin infusion did not consistently suppress these basal gastrin levels either pre- or postoperatively. Infusion of secretin did significantly lower the integrated gastrin response to feeding both pre- and postoperatively in eight of nine patients. Vagotomy alone did not significantly alter the integrated gastrin response to feeding. This data gives evidence that secretin infusion remains a helpful diagnostic test, differentiating those patients with recurrent ulcer and elevated gastrin levels postvagotomy from those patients with occult Zollinger-Ellison syndrome.     

Regional gastric mucosal blood flow after parietal cell vagotomy in dogs

In this study we used the recently validated H2 clearance method to perform endoscopic measurements of gastric mucosal blood flow (MBF) in anesthetized dogs before and after parietal cell vagotomy (PCV). Under resting conditions, MBF in the gastric corpus before PCV was 72 +/- 5 ml/min/100 gm. This was not altered significantly at 4, 8, or 16 weeks after PCV, and there were not significant long-term changes in MBF on the greater or lesser curvatures of the corpus individually. Before PCV infusion of pentagastrin (8 micrograms/kg/hr) elicited increases in corpus MBF to 104 +/- 4 ml/min/100 gm, accompanied by increases in gastric acid output from resting levels of 2.1 +/- 0.9 to 38.6 +/- 2.4 mEq/hr (p less than 0.001). PCV significantly reduced pentagastrin-stimulated acid secretion by 50%, and secretory inhibition was accompanied by significant reductions in pentagastrin-stimulated MBF in the corpus. Pentagastrin did not alter antral MBFs before or after PCV. In summary PCV does not elicit significant long-term changes in resting MBF in different regions of the gastric corpus, and PCV significantly diminishes increases in acid output and corpus MBF that are normally stimulated by pentagastrin. These observations suggest that alterations in gastric MBF after PCV may be attributable to alterations in acid secretion.     

Effect of bethanechol on gastric acid secretion and serum gastrin concentration after proximal gastric vagotomy.

It has been suggested that maximal acid output decreases after vagotomy as a result of reduced cholinergic activity and that maximal acid secretion can be restored to prevagotomy levels with cholinergic agonists. To test this, a maximally tolerated dose of bethanechol (50 micrograms/kg/hr) or saline was infused intravenously in nine duodenal ulcer patients who had been treated by proximal gastric vagotomy. Bethanechol infusion significantly (p less than 0.05) increased basal acid secretion without affecting basal serum gastrin concentrations. Despite stimulation of basal acid secretion, bethanechol had no significant effect on maximal acid output in response to subcutaneous pentagastrin. Although bethanechol significantly increased maximal acid output in response to subcutaneous histamine, maximal acid secretion in response to histamine (or to pentagastrin) was not restored to the prevagotomy level in any patient. Thus, factors other than loss of cholinergic activity appear to be responsible for the large reduction in maximal secretory capacity after vagotomy.     

Serum pepsinogen before and after proximal gastric vagotomy in duodenal ulcer treatment

Serum pepsinogen (SP) behavior was evaluated under basal conditions and under betazole stimulation in 59 patients: 14 controls, nine unoperated duodenal ulcers (DU) and 36 DU after proximal gastric vagotomy (PGV), 14 with and 22 without recurrent ulcer. The mean follow-up of the 36 patients who underwent PGV was 38.7 months. SP was higher in unoperated DU than in the control group (p less than 0.05). After PGV in DU, there is a significant decrease of SP for both the patients with and without recurrent ulcer (p less than 0.05), being statistically similar to the control group. No difference of SP was observed between DU with and without recurrent ulcer after PGV. We concluded that SP can differentiate normal subjects from DU patients, although it is not a sensitive indicator of recurrent ulcer after PGV.     

Twenty years after parietal cell vagotomy or selective vagotomy antrectomy for treatment of duodenal ulcer. Final report.

OBJECTIVE: This study was a prospective, randomized evaluation of parietal cell vagotomy (PCV) and selective vagotomy-antrectomy (SV-A) in the treatment of duodenal ulcer. BACKGROUND DATA: Operative treatment of duodenal ulcer is associated with mortality and mechanical and metabolic morbidity. At the time that surgeons appear to have succeeded in developing operations with low morbidity and mortality, the number of patients requiring elective operation has decreased partly because of the simultaneous, dramatic improvement in medical therapy. Nevertheless, surgical therapy still is important, especially in certain socioeconomic environments. METHODS: After a pilot study of PCV, 200 patients with duodenal ulcers were randomized to PCV or SV-A. One surgeon was responsible for the operations and follow-up studies. An attempt was made to evaluate all patients annually in the hospital. Gastric analyses were performed on each visit, for which the patient gave his/her consent. RESULTS: There was no operative mortality. The recurrence rate-by-life table analysis was less (p < 0.003) after SV-A than PCV. Dumping was greater (p < 0.001), and there was no difference in the frequency of diarrhea after SV-A compared with PCV. The percentage of patients with grades Visick I or Visick II was not different for the two operations, but more patients were graded Visick I after PCV than after SV-A. CONCLUSIONS: Selective vagotomy-antrectomy and parietal cell vagotomy are effective and safe operations, when used appropriately. Selective vagotomy-antrectomy is preferable for patients with pyloric and prepyloric ulcers and pyloric obstruction. Parietal cell vagotomy is the authors' choice for duodenal ulcer patients because of the occasional patient who becomes disabled by SV-A.     

Interrelations between serum gastrin levels, gastric emptying and acid output before and after proximal gastric vagotomy and truncal vagotomy and antrectomy.

In a prospective study of proximal gastric vagotomy and truncal vagotomy and antrectomy measurements were made, before and after operation, of acid output, gastrin output and gastric emptying of a solid and a liquid meat extract meal. No relationships were demonstrable between acid output and gastrin output. Truncal vagotomy and antrectomy (TVA) produced rapid early emptying of both meals combined with gross prolongation of the overall emptying of the solid meal. Truncal vagotomy and antrectomy reduced the intergrated gastrin output after either meal. Proximal gastric vagotomy (PGV) produced rapid early emptying of the liquid meal with no alteration in the early emptying of the solid meal; however, overall solid meal emptying was delayed. Proximal gastric vagotomy increased basal, peak and integrated gastrin output. In preoperative patients slow solid meal emptying was associated with higher gastrin output but after PGV the reverse was found, the slowest emptiers having the lowest gastrin output. These findings do not support the contention that a pyloroplasty should be added to PGV to reduce the hypergastrinaemia produced by the operation.     

Vagal regeneration after parietal cell vagotomy: An experimental study in dogs

The gradual increase with time of the insulin-stimulated acid output, after a well-performed parietal cell vagotomy (PCV), has been thought to be produced by regeneration of the vagus nerves. A genuine regeneration of the gastric branches of the vagus connected to the intramural plexus has yet to be confirmed. Experiments have been carried out in dogs to determine if this type of regeneration takes place after PCV.The animals were divided into 3 groups (A, B, and C) of 4 mongrel dogs each. In all dogs, a PCV was performed and the Grassi test was used intraoperatively to check the completeness of vagotomy. During the experiments, an insulin stimulation test and a macroscopic and microscopic study of the esophagus and stomach were obtained at several points in time (in group A, at operation and after 2 weeks; in group B, after 6 months; and in group C., after 2 1/2 years).We found, 2 weeks after PCV, a complete degeneration pattern of the vagal branches in the gastric serosa. After 6 months, and more completely after 2 1/2 years, many nerve fibers are seen, macroscopically, crossing from the vagus nerves and the branches of Latarjet to the esophagus and the lesser curvature through the old ligatures. This regeneration can be confirmed microscopically. These pathological changes in the nervous system of the stomach were found to correlate with recovery of gastric secretion. It is suggested that the recovery of acid secretion after a well-performed PCV is accounted for by vagus nerves regeneration.

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Resumen El aumento gradual, en el curso del tiempo, de la production de ácido estimulada por insulina después de una bien ejecutada vagotomía de células parietales (VCP), ha sido considerado como el resultado de la regeneración de los nervios vagos. Pero la regeneración genuina de las ramas gástricas de los vagos conectados con el plejo intramural está aún por ser confirmada. Hemos realizado experimentos en perros con el fín de determinar si este tipo de regeneración ha tenido lugar después de la VCP.Los animales fueron divididos en 3 grupos (A, B, y C), cada uno de 4 perros. La VCP fue ejecutada en todos los perros y se utilizó la prueba de Grassi intraoperatoria para determinar si la vagotomía había sido completa. Se realizaron pruebas de estimulación con insulina y el estudio macroscópico y microscópico del esófago y del estómago en el curso de la investigación (en el grupo A, en el momento de la operación y a las 2 semanas; en el grupo B, a los 6 meses, y en el grupo C, a los 2 1/2 años).Dos semanas despues de la VCP, encontramos un patrón de degeneración total en las ramas vagales de la serosa gástrica. A los 6 meses, y en forma más completa a los 2 1/2 años, macroscópicamente se pueden observar muchas fibras nerviosas cruzando desde los nervios vagos y las ramas de Latarjet hacia el esófago y la curvatura menor a través de las antiguas ligaduras. Esta regeneración puede ser confirmada microscópicamente. Tales cambios patológicos en el sistema nervioso del estómago se correlacionan con la recuperación de la secreción gástrica. Se sugiere que la recuperación de la secreción ácida después de una bien ejecutada VCP puede ser atribuída a la regeneración de los nervios vagos.

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Résumé L'augmentation progressive au fil du temps du débit acide gastrique secondaire à l'injection d'insuline après vagotomie hypersélective parfaite (PCV) a été attribué à la régénération des fibres vagales mais cette régénération au niveau du plexus intramural n'a pas été confirmée jusqu'à ce jour.Une étude expérimentale a été entreprise chez le chien par les auteurs pour confirmer ou infirmer cette hypothèse. Les animaux d'expérience, des chiens bâtards, ont été répartis en 3 groupes de 4 (A, B, et C). Chez tous les chiens une vagotomie hypersélective fut pratiquée et contrôlée par le test de Grassi per-opératoire. Ultérieurement les chiens d'expérience furent soumis au test à l'insuline et à l'étude macroscopique et microscopique de l'oesophage et de l'estomac: le groupe A au moment de l'intervention et 2 semaines après celle-ci, le groupe B après 6 mois, le groupe C après 2 ans et 6 mois.Il a été observé 2 semaines après l'intervention l'absence complète d'éléments vagaux au niveau de la séreuse gastrique. En revanche 6 mois et 2 ans et 6 mois après l'intervention l'examen macroscopique a permis de constater que de nombreuses branches provenant des vagues et des nerfs de Latarjet traversaient les ligatures et se distribuaient à la petite courbure gastrique. Cette régénération a été confirmée par l'étude microscopique. Elle a coïncidé avec la récupération de la sécrétion gastrique. Ces constatations permettent de suggérer que la récupération de la sécrétion gastrique après une vagotomie hypersélective parfaitement réalisée est le fait de la régénération des fibres vagales.

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Presented at the 8th World Congress of the Collegium Internationale Chirurgiae Digestivae in Amsterdam, The Netherlands, September, 1984.     

Relationship between gastric acid secretion and clinical outcome after parietal cell vagotomy

Results of insulin and pentagastrin tests 2 months after parietal cell vagotomy were compared with clinical outcome in six patients with subsequent duodenal recurrence of ulcer, ten with pyloric or gastric recurrence, 43 with dyspepsia and 75 persistently symptom-free controls. The insulin-stimulated peak acid output (IPAO) and the pentagastrin-stimulated peak acid output (PAO), but not the basal acid output (BAO), were significantly higher in the duodenal recurrence group than in the controls. In the pyloric/gastric recurrence and dyspepsia groups, BAO, IPAO and PAO were similar to the control values. In the duodenal group the postvagotomy reductions of IPAO and PAO were significantly less than in the controls, indicating incomplete vagotomy. In the pyloric/gastric recurrence and dyspepsia groups, the postvagotomy BAO fall was significantly less than in the controls, but IPAO and PAO fell similarly in all three groups, indicating that pyloric or gastric recurrence was related only to inadequately reduced BAO.     

Treatment of recurrent ulcers after parietal cell vagotomy. Analysis of 18 cases]

One hundred and twenty seven patients had a follow-up of more than 4 years after parietal cell vagotomy for duodenal, pyloric or prepyloric ulcer. The recurrence rate is 15.8% (20 on 127). Eighteen patients who have recurred, had a follow-up of 2 years or more after treatment of the recurrent disease. Ten patients had a early recurrence (within 2 years); eight had a late one (more than 2 years). One patient had been operated as an emergency for perforation. Seventeen patients had first received a medical treatment. This treatment was sufficient for 10 out of 17. Seven patients were reoperated (3 partial gastrectomy), 4 partial gastrotomy associated with truncal vagotomy. Seven out of the 10 early recurrences was reoperated and only one of the 8 late recurrences was reoperated. The early recurrences seem to be more serious that the late ones. Medical treatment is always prescribed as first line therapy and a partial gastrectomy alone or with vagotomy is necessary in unsuccessful cases.