Histologic, immunohistochemical and morphometric study of the mucosa of the total gastric antrum in patients with carcinoma of the stomach.

Examination of gastrin-immunoreactive G-cells, somatostatin-immunoreactive D-cells, enterochromaffin cells and 5-hydroxytryptamine-immunoreactive (5-HT-immunoreactive) cells of the completely mapped histologic antrum (70 to 100 tissue blocks) was done in 20 normal stomachs of persons between 17 and 94 years of age (from forensic autopsy). Results were compared with those of nine patients between 48 and 76 years of age with total gastrectomy for carcinoma of the proximal part of the stomach. Cell counts and morphometric examinations were performed. Results were summarized for the proximal (I), middle (II) and distal (III) one-third of the antrum and for the major (A) and minor (B) curvature side. In normal stomachs, the G-cell count was 2.52 percent of the total gland cell count in AI; 4.25 percent in AII and 4.77 percent in AIII. In BI, the numbers were 2.5 percent, in BII, 3.73 percent and 4.06 percent in BIII. The D-cell count was 0.47 percent in AI, 0.62 percent in AII and 0.58 percent in AIII. The numbers were 0.44 percent in BI, 0.51 percent in BII and 0.51 percent in BIII. In the antrum of the stomach with carcinoma, the G-cells revealed a non-significant 20 to 70 percent lower cell count, while the D-cell count was reduced insignificantly by as much as 35 percent in all areas. The 5-HT-immunoreactive cell count in normal stomachs is 0.25 percent in AI of the total gland cells, 0.32 percent in AII and 0.39 percent in AIII. In B, it shows numerically no difference to that of A. Contrary to the cell count in normal stomachs, the carcinoma antrum revealed a 200 to 400 percent increase in 5-HT-immunoreactive cell count, highly significant in every area of the antrum. Because 5-HT is known as a growth stimulant, especially for tumors, an increase in 5-HT-immunoreactive cells may be a factor that contributes to the initial histologic changes observed during the early phase of gastric tumor.

Effects of superior mesenteric and coeliac ganglionectomy on the small intestinal mucosa in the Hanford mini pig. I. Histological and enzyme-histochemical study.

The effects of total superior mesenteric and coeliac ganglionectomy on the thickness of the mucosa, the cell composition of the epithelium and the enzyme activity of the absorptive cells was studied in 10 Hanford mini pigs 3 weeks and 6 months after ganglionectomy. The mucosal thickness increased after ganglionectomy by 10-33% (P less than 0.02) mainly due to increase in the villus height. Differential cell counts showed a postganglionectomy decrease in percentage of goblet cells of 20-40%. Absorptive cell counts increased significantly (P less than 0.05). Enterochromaffin cells (stained with the Masson-Fontana method) and 5-hydroxytryptamine (5-HT)-immunoreactive cells did not change significantly in the small intestine. The activity of L-leucine-amino-peptidase, non-specific alkaline phosphatase, adenosintriphosphatase, non-specific acid phosphatase, non-specific esterase and succinate dehydrogenase, as assessed by absorption photometry, increased by 2-18% (P less than 0.01) after ganglionectomy. Total ganglionectomy thus results in a rise in villus height and in an increase in the number of absorptive cells which, by their enzymatic activity, appear to be fully mature.

Effects of superior mesenteric and coeliac ganglionectomy on peptide-producing cells of the small intestinal mucosa in the Hanford mini pig. II. Immunohistochemical study.

Superior mesenteric and coeliac ganglionectomy was performed in 5 Hanford mini pigs and cholecystokinin (CCK)-immunoreactive I-cells, neurotensin (NT)-immunoreactive N-cells, glucagon (Glu)-immunoreactive L-cells, glicentin (Glic)-immunoreactive L-cells and somatostatin (Som)-immunoreactive D-cells were quantitatively evaluated in the duodenum, the upper, middle and lower jejunum and the ileum before, 3 weeks and 6 months after ganglionectomy. Three additional animals served as controls. After ganglionectomy, I-cell numbers increase by 110% in the upper jejunum and duodenum; N-cells increase by 86% in the lower jejunum. Glu- and Glic-immunoreactive L-cells decrease slightly in the jejunum. In contrast, D-cells decrease in all sections of the small intestine by 44-76% (P less than 0.05 and P less than 0.001). All the examined entero-endocrine cells, except the D-cells in the duodenum and upper jejunum, develop hypertrophy after ganglionectomy. No changes either in number or size are found in the ganglia and neurons of the myenteric plexus. From these and the recently described increase in villus height and absorptive cells and absorptive cell enzymes after ganglionectomy (Holle, G.E. et al. Effects of superior mesenteric and coeliac ganglionectomy on the mucosa of the small intestine in the Hanford mini pig. I. Histological and enzymhistochemical study, J. Auton. Nerv. Syst., 26 (1988) 135-145), we conclude that the extrinsic nervous system takes suppressive influence on structure and probably function of the small intestinal mucosa by modifying its cellular organization.

Recurrence of peptic ulcer after selective proximal vagotomy and pyloroplasty in relation to changes in clinical signs and symptoms between 1969 and 1983.

Only those patients who were examined endoscopically were evaluated. Concomitant examinations, such as biopsy, histologic studies, roentgenograms, scintiscanning, acid secretion, serum gastrin and review of the operative reports, were done. Duodenal ulcers (1,219) and gastric ulcers (421) were examined preoperatively. Of these, selective proximal vagotomy and pyloroplasty and excision of the ulcer were performed for 1,018 duodenal ulcers. Forty-three per cent were examined postoperatively. Selective proximal vagotomy and pyloroplasty and excision of ulcer were performed for 315 gastric ulcers. Thirty-nine per cent were examined postoperatively. Recurrence was calculated in relation with the patients examined postoperatively. Recurrence of duodenal ulcer occurred in 6.3 per cent; of these, 0.9 per cent had duodenal ulcers develop into gastric ulcers. The recurrence rate of gastric ulcer is 8.1 per cent; of these, 0.8 per cent developed into duodenal ulcers, and 0.8 per cent to carcinoma of the stomach. Data of recurrent ulcers were compared with the data for the total number of patients who underwent surgical treatment. The possible causes for a recurrence are demonstrated. In duodenal ulcers, 79 per cent of recurrences are due to technical error (inadequate vagotomy and incomplete drainage); in gastric ulcers, 90 per cent of recurrences are due to technical error. In both duodenal and gastric ulcers, causes are partly based on advanced clinical symptoms. Recurrence rates showed a tendency to increase between 1969 and 1975 and 1976 and 1983. This correlated directly with the deterioration of the clinical signs and symptoms between 1969 and 1983, shown in increased acid secretion, increase and shift of ulcers and stenoses, increase in bleeding and changed epidemiologic findings.

Behavior of somatostatin-immunoreactive cells in the gastric mucosa before and after selective proximal vagotomy and pyloroplasty in treatment of gastric and duodenal ulcers.

Antral somatostatin-immunoreactive cells (D cells) were counted pre- and postoperatively in 20 patients with duodenal ulcer and in 8 patients with gastric ulcer. Counts were obtained either over a 2-yr postoperative period (duodenal ulcer patients) at intervals of 0.5, 1, and 2 yr or over a greater than or equal to 4-yr postoperative period (gastric ulcer patients) at intervals of 1-2 yr. In patients with a normal population of gastrin-immunoreactive cells (G cells), the D cells were within the normal range (mean value 0.53% in duodenal ulcer patients and 0.67% in gastric ulcer patients). High G-cell values were accompanied by high D-cell values (e.g., in gastrin-cell hyperplasia) and low G-cell values were accompanied by low D-cell values. The G-cell to D-cell ratio was 8:1 and 6.6:1 in duodenal and gastric ulcer patients, respectively. After selective proximal vagotomy and pyloroplasty, the following observations were made: the relation of number of G cells to number of D cells remained unchanged; the postoperative rise in G-cell population was accompanied by a rise in D-cell population; hypertrophy of the D cells was apparent as was postoperative hyperplasia, with a postoperative increase in D-cell size. Morphologic coupling of the gastrin-somatostatin system in the antrum is assumed. This is constant in ulcer disease both before and after vagotomy.

Changes of cell population in the antrum after selective proximal vagotomy and pyloroplasty in gastroduodenal ulcer.

A marked increase in the number and size of the antral gastrin cells and parietal cells could be shown in long term examinations of the antrum mucosa after SPV and pyloroplasty. Twenty-five patients with UD, 12 with UV and five with Dragstedt combination (UV and UD) were examined over a period of five to seven years. A significant correlation of parietal cell increase and a positive reaction to insulin was found. The findings were compared with the changes in the fundic mucosa, where a marked decrease of parietal cells occur after SPV.

[Nonresecting technic in uncomplicated and complicated gastroduodenal ulcer]. / Die nichtresezierende Technik bei unkompliziertem und kompliziertem Gastro-Duodenal-Ulcus.

The technique of the nonresective surgical treatment of peptic ulcer disease is based on the recognition of the autonomous innervation of the stomach and of its musculature, especially in the pyloric region. A correct performance is of very high relevance. The tactics are a combination of a neurosurgical and plastic restorative procedure. This is contrary to the technique of the resective methods. A prospective study pointed out the following healing rates: lethality: phi, healing: 94% objective, 98% subjective; dumping: healing 86%, medium 13%, bad 1% - risk of recurrency: 4%, for the total number of ulcers.

Adequate selective proximal vagotomy with pyloroplasty as nonresective surgery for peptic ulcer disease: a 20 year review.

Nonresective surgery for gastro-duodenal ulcers (GDU) is the operation of choice in 95% of cases of duodenal ulcer (DU) and approximately 50% of cases of gastric ulcer (GU), with a good probability of permanent success if an adequate selective proximal vagotomy (a-SPV) is combined with a pyloroplasty based on form and function (ff-Py). The result is the elimination of local foci and secretion and motility disturbances.

[Changes in microcirculation of various layers and regions of the stomach wall following selective proximal vagotomy. Animal experiments using radioactive-labeled plastic particles]. / Anderungen der Mikrozirkulation in unterschiedlichen Schichten und Regionen der Magenwand nach selektiv-proximaler Vagotomie. Tierexperimentelle Untersuchungen mit radioaktiv markierten Kunststoffpartikeln.

Changes of the blood flow in the different layers and regions were determined with radioactively labelled microspheres after proximal vagotomy. Under normal conditions and vagal stimulation a significant reduction of the flow in corpus and antrum up to 74% can be observed at least over the time of 3 weeks. This decrease of bloodflow in the stomach together with a reduction in secretion can possibly be responsible for the successful treatment of diffuse bleeding in erosive gastritis by selective vagotomy.

[Bile acid reflux following stomach surgery on rats (author's transl)]. / Gallensäurenreflux nach operativen Eingriffen am Rattenmagen.

Using rats in a standardized animal experiment, the extent of duodenogastric reflux was studied eight months postoperatively following SPV with and without pyloroplasty. The reflux was determined by enzymatically testing the concentration of bile acid secretion withdrawn from the stomach intraoperatively. Serving as comparison were laparotomies, simple pyloroplasties, and the obligatory reflux models: resection after BII without enteroanastomosis. After SPV with and without pyloroplasty, the extent of duodenogastric reflux was less than in the control group. Specimens with simple pyloroplasty displayed a significantly greater reflux. The BII group had fivefold higher reflux than the control group. Since pyloroplasty can be considered a drainage operation, there is no retention of food particles in the stomach of the rat following SPV--an occurrence expected after SPV without pyloroplasty. However, due to the retarded stomach motility, the thickened chyme tends to linger at the opening of the stomach, thus reducing the duodenogastric reflux. According to our investigations, an increased duodenogastric reflux following SPV with or without pyloroplasty does not induce changes in the mucosa of the stomach.

[Acid reduction after SPV and after H2 receptor blocking substance cimetidine. Comparative studies in Shay-rats)]. / Säurereduktion nach SPV und nach H2-Rezeptoren-Blockade. Vergleichsstudie an der Shay-Ratte.

The effect of a complete selective proximal vagotomy on stomach acidity has been compared experimentally to that of the H2 receptor blocking agent cimetidine in the rat. Both methods produced a significant reduction of total acid as compared to controls, a reduction to 0.5 % for cimetidine and to 0.1 % for SPV. The acid reduction following SPV is a result of decreased production of stomach fluid as well as a decrease in degree of acidity. The acid reduction following administration of cimetidine is mainly a result of an increase in pH without any change in volume of stomach fluid production.

Are bloodflow changes after selective proximal vagotomy responsible for a necrosis in the gastric wall?

Animal experiments were performed to investigate bloodflow distribution before and after selective vagotomy to explain gastric mucosa necrosis found in some patients after vogtomy. Flow measurements were made using the microsphere technique. Changes in the microcirculation were determined under basal and stimulated conditions (250 mg 2-desoxy-D-glucose). After selective vagotomy a reduction in bloodflow of up to 50% could be observed in all layers of the stomach. There were no differences in the bloodflow along either the lesser or greater curvature under basal conditions. In the stimulated stomach, however, the increase in bloodflow along the lesser curvature was higher, although the vessels of this region were mostly altered by SPV operative procedure. From these results it can be concluded that a reducton of arterial input after selective proximal vagotomy is probably compensated for by intramucosal or submucosal anastomoses. Therefore, necrosis in the gastric wall is not due to SPV but probably to other accompanying diseases.

[Studies of gastric motility following SPV and pyloroplasty in dogs (author's transl)]. / Veränderung der Magenmotilität durch SPV mit Pyloroplastik-Untersuchungen am Hundemagen.

UNLABELLED: In unanesthetized dogs, the mechanical activity of the antrum and pylorus was studied by means of strain gauge force transducers during fasting condition, after feeding, and following application of metoclopramide (Paspertin), before and after SPV without pyloroplasty, and after SPV with pyloroplasty respectively. RESULTS: 1) The mechanical activity during fasting condition differs from that after feeding. 2) During fasting, the contractile force is decreased for about 15%-20% after SPV without pyloroplasty and for about 50% after SPV with pyloroplasty. The frequency remains unchanged. 3) After feeding, the contractile force is decreased by about 50%, the frequency shows an increase of 100%. The same results can be obtained after SPV with or without pyloroplasty. 4) After metoclopramide the contractile force is increased up to 30%, during fasting, after feeding, and also before and after SPV. The frequency, however, shows no significant change. 5) The postoperative findings remained unchanged throughout the entire observation period (up to the 20th postoperative month).

[Inhibition of stimulated gastric secretion with simultaneous administration of cimetidine and somatostatin]. / Hemmung der stimulierten Magensekretion durch simultane Gabe von Cimetidin und Somatostatin.

In four gastric fistula dogs we studied the effect of cimetidine (5 mg/kg/h) and somatostatin (10 microgram/kg/h), alone or in combination, on gastric secretion stimulated by histamine (160 microgram/kg/h) or pentagastrin (6 microgram/kg/h). Acid and pepsin output after histamine stimulation was more reduced by cimetidine than after pentagastrin stimulation. Somatostatin showed an inhibitory effect only after pentagastrin stimulation. The most effective reduction, both on the degree of inhibition and on duration after cessation of the inhibitors, was seen after the combination of cimetidine/somatostatin. These results give some clinical aspects for the use of these two agents.

The definitive technique of selective proximal vagotomy with pyloroplasty appropriate to form and function in surgery of peptic ulcer disease.

The overall efficiency of the ff-PYPL is most apparent when we compare our own large series of long-term observations of SPV, accompanied with these pyloroplasty forms with all types of DU, in contrast to the series of SPV without pyloroplasty of some other authors with a smaller number of patients and a shorter observation period (Table 1). The table shows that the combination operation of complete SPV with ff-PYPL (Fig. 17) assures the clinical permanent healing of DU. In GU the results of the nonresecting method are less satisfying. Twenty-two percent of the GU patients must have selective vagotomy with antrectomy because of antral disorder, destroyed antral innervation, or suspicion of malignancy.

The physiopathologic background and standard technique of selective proximal vagotomy and pyloroplasty.

The observations collected on selective proximal vagotomy plus functionally and structurally appropriate pyloroplasty during a period of 13 years have demonstrated that inadequate selective proximal vagotomy results in an excessive rate of relapses and that adequate selective proximal vagotomy without drainage leads to stasis, resulting in retention difficulites or secondary gastric ulcers. In both instances, reoperations are to be expected. If complete healing without resection is what one wishes to accomplish, and who doesn't, adequate selective proximal vagotomy combined with structurally and functionally appropriate pyloroplasty is indicated. This combination can now be considered a reliable standardized procedure of curative nonresection surgical therapy for gastroduodenal ulcers.

[Prevention and treatment of upper gastrointestinal haemorrhage with cimetidine and somatostatin in intensiv care patients (author's transl)]. / Kasuistische Mitteilung über Möglichkeiten der Prophylaxe und Therapie gastrointestinaler Blutungen mit Cimetidin oder Somatostatin bei Schwerstkranken.

Upper gastrointestinal haemorrhage is a severe problem in patients in surgical intensive care units. Good experimental and clinical results are reported with somatostatin (somatotropin release inhibitoring factor) and cimetidine (H2-receptor antagonist) in prevention and treatment of acute gastrointestinal bleeding, by blocking gastric acid secretion. These experiences are confirmed with an open trial in 13 seriously ill surgical patients. First of all cimetidine can be recommended because of its mode of action and application.

[Radioactive microsphere studies of stomach wall blood flow in dogs following truncular vagotomy]. / Messung der Magenwanddurchblutung beim Hund mit radioaktiven Microspheres nach trunculärer Vagotomie.

Blood flow in the mucosa of fundus and antrum behave quite contrary after TV: Whereas mucosal flow of the fundus is reduced, mucosal flow of the antrum increases significantly. But 3 weeks after TV flow values of the fundus are in the range of the initial blood flow and are decreased significantly in the antrum. The early diminution of the blood flow in the mucosa of the fundus can be partly responsible for the favourable effect of TV, which is observed on erosive bleedings in this region.