Five- to Eight-year Results of Truncal Vagotomy and Pyloroplasty for Duodenal Ulcer

From January 1963 to December 1965 inclusive 192 men with duodenal ulcer were treated by elective truncal vagotomy and pyloroplasty with one death. Ten subsequent deaths were due to causes unrelated to the ulcer or operation, and 17 patients became untraceable. The remaining 164 patients have been followed up for five to eight years. The late results have been compared with those obtained in a previous study of patients five to eight years after truncal vagotomy and gastroenterostomy, truncal vagotomy and antrectomy, and subtotal gastrectomy respectively for duodenal ulcer.Of the various postgastric operation syndromes early dumping, late dumping, bilious vomiting, and diarrhoea were all less frequent, but not significantly so, after vagotomy and pyloroplasty than after vagotomy and gastroenterostomy.Recurrent ulceration was commoner after vagotomy and pyloroplasty than after all the other operations, the incidence of proved and suspected recurrent ulcers being respectively 6·7 and 7·3% after vagotomy and pyloroplasty, but only 2·5 and 5·9% after vagotomy and gastroenterostomy, 0 and 5·2% after vagotomy and antrectomy, and 0·9 and 3·7% after subtotal gastrectomy. The differences between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy are statistically significant, but those between vagotomy and pyloroplasty and vagotomy and gastroenterostomy are not.Overall assessment (Visick grading) of the outcome gave poorer results after vagotomy and pyloroplasty than after any other operation, with 14% of category IV cases after vagotomy and pyloroplasty, 11% after vagotomy and gastroenterostomy, 8% after vagotomy and antrectomy, and 6% after subtotal gastrectomy—differences that are significant between vagotomy and pyloroplasty and vagotomy and antrectomy or subtotal gastrectomy but not between vagotomy and pyloroplasty and vagotomy and gastroenterostomy.In the light of these findings it is suggested that truncal vagotomy and pyloroplasty has not lived up to expectations and its place as the currently most popular procedure in the elective surgical treatment of duodenal ulcer should be reconsidered.     

Gastrin and the vagus interact in the trophic control of the rat oxyntic mucosa

Gastrin is a trophic hormone for the stomach, and permanent reduction of circulating gastrin by antrectomy leads to atrophy of the oxyntic mucosa, including a reduced density of histamine-storing endocrine cells (so-called ECL cells). Recently, it was proposed that also the vagal nerve has a trophic influence on the stomach. The two vagal trunks innervate the anterior and posterior side of the gastric wall, respectively. This arrangement makes it possible to denervate one side of the stomach selectively. The objective of the present study was to examine the consequences of combined antrectomy and vagotomy (unilateral or bilateral). Male Sprague-Dawley rats were subjected to unilateral or bilateral subdiaphragmatic truncal vagotomy with or without antrectomy. Control rats were sham-operated. The rats were killed 8 weeks after the operation. Bilateral vagotomy raised the basal serum gastrin concentration (fasting level). The thickness of the oxyntic mucosa and the density of ECL cells were not significantly different from age-matched vagally intact controls. Unilateral vagotomy induced no change in the basal serum gastrin concentration, nor did it affect the mucosa on the intact side. On the denervated side, however, there was reduced mucosal thickness and a greatly reduced ECL cell density. With a combination of antrectomy and vagal denervation the decrease in ECL cell density was exaggerated compared to the effect of antrectomy or unilateral vagotomy alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of truncal,selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part II-Comparison of response to oral and intravenous glucose.

Paired oral and intravenous glucose tolerance tests were carried out in patients who had undergone truncal vagotomy and pyloroplasty, selective vagotomy and pyloroplasty, or highly selective vagotomy at least six months earlier. Intravenous glucose tolerance was similar in all three groups. Oral glucose elicited significantly higher concentrations of plasma insulin in patients who had undergone selective and highly selective vagotomy than in those treated by truncal vagotomy. When the same amount of glucose was given intravenously, however, plasma insulin concentrations were similar in all three groups of patients. The insulin secreted in response to intravenous glucose expressed as a percentage of that secreted in response to oral glucose was 112% for truncal vagotomy, 51% for selective vagotomy, and 52% for highly selective vagotomy. Truncal vagotomy thus led to a diminished insulin response to oral glucose, which was probably due to impaired release of small-bowel hormones.     

Effects of truncal,selective, and highly selective vagotomy on glucose tolerance and insulin secretion in patients with duodenal ulcer. Part I-Effect of vagotomy on response to oral glucose.

An oral glucose tolerance test was performed in patients who had undergone truncal vagotomy and pyloroplasty, bilateral selective vagotomy and pyloroplasty, or highly selective vagotomy without a drainage procedure at least six months earlier. The results were compared with those from patients with chronic duodenal ulcer before operation. In all three groups of patients after vagotomy more rapid rates of rise of blood glucose and higher peak concentrations were observed than in patients who were tested before operation. These differences were statistically significant only in patients who had undergone truncal or selective vagotomy with pyloroplasty and were probably due to more rapid rates of gastric emptying after these operations. Plasma insulin concentrations were lower after truncal vagotomy than after selective or highly selective vagotomy, the difference between truncal vagotomy and highly selective vagotomy being statistically significant. Truncal vagotomy resulted in a diminished insulin response to oral glucose, which could have been due to vagal denervation of the pancreas or, more probably, impaired release of small-bowel hormones which normally augment the pancreatic insulin response.     

Changes in intestinal endocrine cells in the mouse after unilateral cervical vagotomy

The effect of right or left unilateral cervical vagotomy on the intestinal endocrine cells was studied in 23 mice at 2 and 8 weeks after operation, respectively. The results were compared with that from 10 sham operated mice. Various types of endocrine cells in duodenum and proximal colon were detected by immunohistochemistry and quantified by computerized image analysis. In mouse duodenum, chromogranin-, CCK/gastrin-, GIP- and somatostatin-cells were significantly decreased at 2 weeks after right vagotomy, but returned to the control levels at 8 weeks. Serotonin-cells were reduced at both 2 and 8 weeks after right vagotomy. The amount of the duodenal endocrine cells did not change after left vagotomy with the exception of secretin-cells, which were diminished at 8 weeks after both right and left vagotomy. In the proximal colon, chromogranin-cells were also decreased at 2 weeks after right vagotomy. Serotonin-cells were reduced at 8 weeks after left vagotomy but not right vagotomy. There was no significant difference between the unilaterally vagotomized and the sham operated mice with regard to PYY- and glucagon-cells. It was concluded that vagotomy affected the intestinal endocrine cells in mouse. The influence was more pronounced in the small intestine than the proximal colon. The right vagus nerves seemed to exert more effect on the intestinal endocrine cells than the left ones.     

Vagotomy without Diarrhoea

The incidence of diarrhoea after three types of vagotomy was assessed “blind” at a gastric follow-up clinic one year after operation. Diarrhoea was recorded in 24% of patients after truncal vagotomy and pyloroplasty, in 18% after selective vagotomy and pyloroplasty, but in only 2% of patients after highly selective vagotomy without a drainage procedure. The incidence of diarrhoea was significantly less (P < 0·01) after highly selective vagotomy than after either of the other procedures.Hypertonic glucose solution given by mouth to 15 representative patients from each group and to 15 patients before operation provoked the onset of diarrhoea in 67% of the patients who had undergone truncal vagotomy and pyloroplasty, in 60% of those who had undergone selective vagotomy and pyloroplasty, in 13% of those who had undergone highly selective vagotomy without a drainage procedure, and in none of the preoperative patients. Again the difference between the “highly selective” group and the other two groups of vagotomized patients was statistically significant.It is suggested that postvagotomy diarrhoea is attributable both to unregulated gastric emptying after truncal or selective vagotomy with a drainage procedure and to the extragastric denervation produced by truncal vagotomy. “Postvagotomy” diarrhoea can be virtually eliminated by using highly selective vagotomy without a drainage procedure.     

Incidence of Dumping after Truncal and Selective Vagotomy with Pyloroplasty and Highly Selective Vagotomy without Drainage Procedure

The incidence of dumping after truncal or selective vagotomy with pyloroplasty and highly selective vagotomy without a drainage procedure was assessed both clinically and experimentally. At a gastric follow-up clinic dumping was found to be significantly less frequent in patients who had undergone highly selective vagotomy without a drainage procedure than in patients who had undergone truncal or selective vagotomy with pyloroplasty (P < 0·05 or < 0·001, respectively). Hypertonic glucose given by mouth provoked the onset of dumping in 20% of patients with duodenal ulcer before operation, in 73% after truncal vagotomy and pyloroplasty, in 80% after selective vagotomy and pyloroplasty, and in 47% after highly selective vagotomy. The test meal also produced significantly greater decreases in blood pressure and increases in pulse rate in patients who had undergone vagotomy with pyloroplasty than in patients who had undergone highly selective vagotomy.     

Epitheliocytes of fundal glands and the relative volume of the parietal microflora of the stomach and small intestine mucosa in experimental chronic duodenal ulcer

The effect of experimental chronic duodenal ulcers and vagotomy on fundal gland epitheliocytes and membrane microflora has been studied in rats using light microscopy and stereometry on semithin sections. It is shown that in ulcers the relative amount of perietal and zymogen cells increases, while the volume of mucocytes decreases. Vagotomy leads to a decrease in the relative amount of parietal and zymogen cells and increases the relative amount of mucocytes. The relative volume of membrane microflora in gastric fundal and pyloroantral regions, duodenum and jejunum diminishes in ulcers and increases in vagotomy, as compared to the control.     

The Immediate Results of Operations for Duodenal Ulcer: A Comparative Study of the Morbidity and Mortality of Vagotomy and Pyloroplasty versus Subtotal Gastrectomy

Immediate postoperative results of vagotomy and pyloroplasty were compared with those of subtotal gastrectomy. Ulcer recurrence rate and the long-term complications of the two procedures were not studied. Age and sex distribution, and preoperative indications in the two groups of patients were almost identical. Vagotomy and pyloroplasty has gradually superseded subtotal gastrectomy at St. Michael''s Hospital, Toronto. One hundred and seventy vagotomy and drainage procedures were compared with 173 subtotal gastric resections performed over a five-year period. There were 39 postoperative complications and five deaths in the subtotal gastrectomy group, an overall mortality of 2.8% and an elective mortality of 2.4%. In the vagotomy and pyloroplasty group there were 31 postoperative complications and two deaths, an overall mortality of 1.2% and an elective mortality of zero. Vagotomy and pyloroplasty is a relatively safe procedure, associated with fewer complications, shorter hospital stay and a lower mortality than subtotal gastrectomy.     

Vagotomy or Gastrectomy for Gastric Ulcer

Patients treated in a randomized controlled comparison of management of benign gastric ulcer of the body of the stomach, comprising 50 patients treated by Billroth I partial gastrectomy and 50 patients treated by vagotomy and pyloroplasty and biopsy of the ulcer, were followed up for about five years (range one and a half to eight and a half years). No statistically significant difference has been found between the functional results (Visick grading) of the two groups. There was no operative mortality. Postoperative morbidity (17 against 5) and length of stay in hospital (14 against 10 days) were significantly greater after gastrectomy. Seven patients after vagotomy have been submitted to gastrectomy (three for recurrent gastric ulceration, three for gastric cancer, and one for bleeding), which is a statistically significant excess compared with no reoperation after gastrectomy. While vagotomy and pyloroplasty can be useful to avoid a technically difficult gastrectomy, it cannot be said to replace partial gastrectomy in the treatment of gastric ulcer.     

Calcium binding properties of purified zymogen granule membrane of pig pancreas. Evidence for calcium binding proteins

Ca2+ binding properties of purified zymogen granule membranes of pig pancreas have been measured: Binding increased linearly with Ca2+ concentration in the medium up to the micromolar range; in the millimolar range a sharp rise in binding capacity was observed. Binding increased with pH both at low and high concentrations of Ca2+. It was insensitive to Na+ and K+ ions at concentrations up to 100 mM. Mg2+ was inhibitory in the millimolar range whereas La2+ and Tb3+ were inhibitory in the micromolar range. The Ca2+ binding components of zymogen granule membranes were identified by two methods: (1) by measuring 45Ca2+ binding after counter-ion electrophoresis and (2) by Stain's-all (forms a complex with Ca2+ binding proteins absorbing maximally at 600 nm), after SDS-polyacrylamide gel electrophoresis. The first method, counter-ion electrophoresis, indicated that most of the 45Ca2+ was associated with an acidic band which could be subsequently subfractionated by SDS-polyacrylamide gel electrophoresis in five bands: 66, 57, 30, 27 and 22.5 kDa. The second method, Stain's-all, revealed six positive polypeptides after SDS-polyacrylamide gel electrophoresis of native zymogen granule membranes' two were unreactive after neuraminidase treatment (130 and 92 kDa, respectively), whereas four other bands were still reactive (66, 57, 43, 30 kDa, respectively.) Ca2+ binding was also measured on intact zymogen granules: the binding capacity was higher than for zymogen granule membranes. Among the Ca2+ binding proteins of the zymogen granule membrane only one is apparently located on the granule external surface: the 30 kDa polypeptide. If Ca2+ directly facilitates fusion of zymogen granules with plasma membrane by a Ca2+-protein interaction, then this protein is a presumptive candidate to play such a key role.     

Vagotomy and accompanying pyloroplasty down-regulates ghrelin mRNA but does not affect ghrelin secretion

In this study, we have examined how the lack of vagus activity affects the long-term secretion of total and active ghrelin. We subjected mice to sham-operation, pyloroplasty or vagotomy and pyloroplasty. The study lasted for 2 weeks, during which body weight development and daily food intake was monitored. At the end of the study, the mice were sacrificed, and serum and fundus were collected. Measurements of total and active serum ghrelin revealed no difference between the surgical groups and sham-operated mice, despite the fact that fundic ghrelin mRNA was down-regulated. The results presented here suggest that the vagus activity is not required for the long-term secretion of neither total nor active ghrelin in mice. They also suggest that fundic ghrelin mRNA expression is affected by pyloroplasty and vagotomy but that this effect does not translate into changes in ghrelin levels in the circulation.     

Effect of cholecystokinin blockade on the recovery of alterations induced by acute pancreatitis in glycoconjugates of rat zymogen granules

Lectin-binding studies have been performed on rat zymogen granules to investigate alterations in the carbohydrate membrane composition that occur in acute pancreatitis induced by caerulein. The influence of treatment with hydrocortisone for seven days before inducing pancreatitis was also studied. Lectin labeling on zymogen granules was also analyzed seven days after inducing pancreatitis in rats that had previously received a hydrocortisone treatment. During this period L 364,718 (0.1 mg/kg)—specific cholecystokinin (CCK) receptor antagonist—was administered daily to some of the rats, and no treatment was applied to others. Using fluorescein-labelled T. purpureus (TP)lectin, a significant decrease in the amount of L-fucose in the granule membrane was observed in rats with caerulein-induced pancreatitis. This effect was directly caused by the pancreatitis and was not influenced by previous hydrocortisone treatment. Seven days later, the density of TP receptors in the granule membrane was similar to the controls both in L-364,718-treated and untreated rats. Therefore, we suggest that endogenous CCK is not an essential factor in the recovery of L-fucose containing glycoconjugates the granule membrane after pancreatitis. Acute pancreatitis did not alter the expression of wheat germ agglutinin (WGA) receptors in the zymogen granule membrane. WGA specifically binds N-acetyl glucosamine and sialic acids. L 364,718 administered for seven days after inducing pancreatitis significantly reduced WGA binding, untreated rats showed a normal zymogen granule membrane. Therefore, the blockade of CCK-induced alterations in membrane glycoconjugates enriched in N-acetyl glucosamine and sialic acid of newly formed granules after pancreatitis, a finding that could explain the delay in the regression of the disease.     

Emergency Vagotomy and Pyloroplasty for Perforated Duodenal Ulcer: Study of 73 Cases

Seventy-three unselected patients with perforated duodenal ulcer were treated by vagotomy and pyloroplasty in a six-year period. Postoperative complications were commoner when the operation was carried out after more than six hours after perforation. The follow-up results were similar to those for elective vagotomy and pyloroplasty carried out in the hospital during the past nine years.     

RESTITUTION OF PANCREATIC ACINAR CELLS FOLLOWING ETHIONINE

The regeneration of the pancreatic acinar cell was studied at four time periods after ethionine had destroyed most of the acinar cells. Within 2 days of the last ethionine injection, small basophilic cells (pre-acinar cells) with whorls of ergastoplasm or nebenkern were present. These cells also contained a decreased amount of Golgi substance, small zymogen granules, and a fine granularity of the nuclear matrix. They showed persistence of the characteristic ergastoplasm lesion produced by ethionine. Eight days after the last ethionine injection, the nebenkern was replaced by approximately normal appearing ergastoplasm and the nucleoli and Golgi bodies were enlarged. Zymogen granules were less dense but more abundant. Mitochondria were considerably enlarged. Most cells showed no ethionine lesions or only small foci of damage. Eighteen days after the cessation of ethionine, a good approximation of the normal acinar cell was present. The whorls of ergastoplasm appeared at a time (day 12) when basophilia was pronounced. Other studies showed that nucleic acid and protein precursors began to show an increased concentration in acinar cells at this time. The appearance of nebenkern during a phase of cellular recovery and its absence during a phase of replication when mitotic indices were high suggest that its presence is more indicative of ergastoplasmic synthesis than of cell multiplication as such. Possibly the increased density of zymogen granules was a reflection of this increased protein synthesis. The increase in size of Golgi apparatus occurred prior to the replenishment of zymogen granules and thus satisfied a precursor relationship for a possible role in the formation of these secretory structures. Evidence suggests that some injured acinar cells recover from the ethionine and protein-free regimen and give rise to most of the new acinar cells formed. It is possible that, under the severe conditions which prevailed, the centroacinar ductule cells may also have given rise to some acinar cells.     

Effects of hypothyroidism on the ultrastructure of rat pancreatic acinar cells: a stereological analysis.

The morphological and stereological characteristics of the exocrine pancreas subcellular organelles from healthy and thyroidectomized rats have been studied. The acinar tissue from hypothyroid rats showed an interstitial edema and evidence of degenerative processes. Stereological parameters of zymogen granules were significantly reduced in thyroidectomized rats. The hypothyroidism induced degenerative changes in the pancreatic acinar cells as well as a decrease in the number and size of the zymogen granules. These modifications probably cause functional alterations.     

What is the Best Elective Operation for Duodenal Ulcer?

During the past 40 years, after gastroenterostomy and pyloroplasty for duodenal ulcer had been replaced by partial gastrectomy in many centres, partial gastrectomy itself gave way to combinations of vagotomy with gastroenterostomy, pyloroplasty or antrectomy. Opinions differ concerning the procedure of choice and in this paper the author examines the causes of this diversity of opinion and assesses the reliability of conclusions that can be drawn about the elective treatment of duodenal ulcer today. Most reports of results from various operations have come from retrospective studies, and the causes of variability among such reports are analyzed to point out the great difficulty in making a valid judgment about the relative worth of the various operations used to treat duodenal ulcer. Results of some of the few prospective studies with randomized operations assessed blindly are then presented and note is taken of the surprising observation that greatly different operations appear to give remarkably similar results. From the data available the author develops a logical way of approaching the choice of operation for the various problems related to duodenal ulcer that require elective surgical treatment.     

Zymogen granule size in pancreas of nursing rats

Dramatic depression in granule volume density and size was measured in acinar cells of postnatal rat pancreas following the initiation of feeding. Volume density decreased about threefold from 45% at birth to 16% 2 days thereafter. Mean granule diameter decreased from 1.50 micron to 0.80 micron, an 85% decrease in corresponding granule volume. At the same time, numerical density approximately doubled. At 2 days after birth, cells with smaller granules had lower volume densities, and differences in mean granule volume between cells accounted for most of the differences in volume density. Although the distribution of granule diameter in newborns was lognormal, the distribution at 2 days was heavily skewed to larger sizes. This was the result of skewed distributions within individual cells and not an artifact of sampling. The results corroborate the central role of granule volume in determining changes in the volume density of zymogen granules in the pancreas and suggest that zymogen granules can act as capacitors that can change size as a function of the enzyme contained within.     

Synthesis and discharge of secretions in the pancreas of the white rat in the presence of excessive hydrocortisone

Under conditions of physiological loading at feeding, histologically and radio-autographically (35S-methionine), granuloformation and protein metabolism have been studied in exocrinic pancreocytes in mature white rats under abundant injection of hydrocortisone (6 daily injections, 1 mg per 100 g of body mass). The procedure stimulates formation of zymogen granules, but intensity of the excretion remains unchanged. This results in overfilling the cell with the secretory product, considered as the base of the alterative changes, that in their turn could stimulate the development of the steroid pancreatitis.     

Localization and neurophysiological properties of motoneurones of the M. triceps surae of the rat after retrograde labelling with evans blue

Summary The effect of vinblastine on the intracellular transport of newly synthesized protein in the mouse exocrine pancreas in vivo was studied by electron microscopic autoradiography after administration of ³H-leucine. Vinblastine (1.1 mole/mouse; i.v. injection) was in general given 1 h before radioleucine and 2–4 h before fixation of the pancreas by perfusion with glutaraldehyde.Vinblastine causes the disappearance of microtubules, mainly present in controls in the apical portion of the acinar cell. After injection of vinblastine, zymogen granules form clusters located throughout the cell but often associated with Golgi areas. The latter are enlarged mainly due to the accumulation of small vesicles. In addition, Golgi areas are displaced, most often in an apical direction.Electron microscopic autoradiography demonstrated that vinblastine delays the appearance of labeled protein in zymogen granules; even 2 h after injection of radioleucine the majority of silver grains is located over the rough endoplasmic reticulum while very few grains are related to zymogen granules. This finding might be related to the structural changes of the Golgi areas observed. Although intracellular migration of protein is retarded, zymogen granules are formed. However, many of the labeled granules are found in peculiar locations, often distant from the acinar lumen.The present study suggests that vinblastine, possibly due to its effect on microtubules, influences both the formation and the translocation of zymogen granules.Supported by Swedish Medical Research Council, Grant No. 12X-537