Bile acid and lysolecithin concentrations in the stomach

Transcription

1 Gut, 1982, 23, Bile aid and lysoleithin onentrations in the stomah in patients with duodenal uler before operation and after treatment by highly seletive vagotomy, partial gastretomy, or trunal vagotomy and drainage P DEWAR,* R KING, and D JOHNSTON From the University Department of Surgery, The General Infirmary, Leeds SUMMARY Duodenogastri reflux of bile aids and lysoleithin in the ourse of a standard test meal was measured in normal people and in patients with duodenal uler before operation and more than one year after highly seletive vagotomy, Polya partial gastretomy, trunal vagotomy and pyloroplasty, and trunal vagotomy and gastrojejunostomy. Before operation, duodenal uler patients had signifiantly higher fasting, post-prandial, and peak bile aid onentrations in the stomah than had normal subjets. After Polya partial gastretomy, fasting, post-prandial, and peak onentrations of bile aids and lysoleithin were signifiantly higher than in preoperative duodenal uler patients. After highly seletive vagotomy, in ontrast, bile aid onentrations in the stomah were signifiantly lower than in preoperative duodenal uler patients and post-prandial and peak lysoleithin onentrations were less than half (NS) those reorded in preoperative duodenal uler patients. After highly seletive vagotomy, bile aid onentrations were also signifiantly lower than bile aid onentrations after Polya partial gastretomy, trunal vagotomy and pyloroplasty, and trunal vagotomy and gastrojejunostomy; and post-prandial and peak lysoleithin onentrations were signifiantly lower than after Polya partial gastretomy and trunal vagotomy and gastrojejunostomy. Thus, when used in the treatment of patients with duodenal uler, highly seletive vagotomy keeps 'bile' out of the stomah, probably through its effet on gastri smooth musle, ombined with the preservation of an intat antropyloroduodenal segment. In ontrast, Polya partial gastretomy, trunal vagotomy and gastrojejunostomy, and trunal vagotom' and pyloroplasty all lead to a signifiant inrease in reflux of bile aids and lysoleithin into the stomah. The linial importane of these findings is that both gastritis and, in the long term, gastri arinoma may prove to be less ommon after highly seletive vagotomy than after partial gastretomy or vagotomy with a drainage proedure. Traditional operative proedures for duodenal uler suh as partial gastretomy and vagotomy with a drainage proedure are known to inrease duodenogastri reflux.1 Duodenal ontent in the stomah breaks the gastri muosal barrier by its detergent ation and, with or without the aid of aid, pepsin, and agents suh as aspirin or alohol, produes a hroni gastri muosal reation or gastritis.>4 Suh 'bile reflux gastritis' may produe symptoms suh as ' Address for orrespondene: Mr E P Dewar, Department of Surgery, Royal Naval Hospital, Haslar, Gosport, Hants P012 2AA. Reeived for publiation 19 Otober 1981 epigastri pain, nausea, vomiting, and loss of weight5-7 and, in the long term, there is an inreased risk of gastri arinoma. 10 Highly seletive vagotomy, unlike these proedures, preserves the pylorus" and might thus be expeted not to produe an inrease in duodenogastri reflux. In this paper we show that, after highly seletive vagotomy, reflux of bile aids 'and lysoleithin into the stomah is, in fat, signifiantly less than in patients with duodenal uler before operation. As expeted, both partial gastretomy and trunal vagotomy with a drainage proedure were followed by signifiant inreases in duodenogastri reflux. 569

2 570 Methods PATIENTS Six groups of patients were studied (Table 1). One group onsisted of 16 patients with ative duodenal uleration who had not been operated upon. A seond ontrol group omprised nine normal subjets with no history of disease of the gastrointestinal trat. The other four groups onsisted of patients who had been treated surgially for duodenal uler more than one year previously: 14 by highly seletive vagotomy, 11 by Polya partial gastretomy, nine by trunal vagotomy and Heineke-Mikuliz pyloroplasty, and eight by trunal vagotomy and gastrojejunostomy. The groups did not differ signifiantly with respet to age and sex. The mean interval between operation and these studies was four years in the highly seletive vagotomy group, eight years in the trunal vagotomy and drainage groups, and 20 years in the Polya partial gastretomy group. The results of operation were good (Visik grades 1 or 2)12 in all these postoperative patients. The diagnosis of duodenal uleration had been made in eah patient by barium meal examination and/or fibreopti endosopy and had been onfirmed at operation in eah patient who had undergone surgery. The nature and purpose of the investigations were arefully explained to eah patient and his or her onsent obtained. FIBREOPTIC OESOPHAGOGASTRODUODENOSCOPY Eah patient underwent this proedure, whih was performed for diagnosti purposes in the preoperative duodenal uler patients and in the postoperative patients both to onfirm that the uler had healed and to exlude the presene of any other pathologial ondition in the stomah and duodenum. At endosopy the presene or absene of bile reflux was reorded and multiple gastri and duodenal biopsies were taken in eah ase to form the basis of a separate report on the morphologial state of the gastri muosa in relation to 'bile' reflux. Table 1 Details ofpatients Dewar, King, and Johnston There was no evidene of gall bladder disease in any patient, either on oral holeystography or at operation. TEST MEAL AND SAMPLING TECHNIQUE After the patient had fasted overnight, a size 12 nasogastri tube was positioned in the stomah using the water reovery method. 13 Resting juie was aspirated and disarded. Three 8 ml samples of gastri juie were olleted by gentle sution with a syringe at 20 minute intervals during the 'basal' hour. A standard Lundh test meal was then given. It onsisted of 300 ml of water ontaining 13.5 g protein, 18 g orn oil, and 53 g arbohydrate, and was ingested over a five minute period. A further four samples of gastri ontent were then olleted at 20 minute intervals. The patient remained seated in a hair throughout the period of study. The proedure was well tolerated and none of the patients omplained of nausea during the test. The samples of gastri aspirate were plaed in tubes ontaining 0O002 M ethylenediaminetetraeti aid and M alium hloride to inhibit phospholipase A ativity. This prevented in vitro hydrolysis of leithin to lysoleithin, a proess atalysed by phospholipase A and ativated by bile aids and trypsin. MEASUREMENTS OF BILE ACIDS Conentrations of total bile aids were measured using a ommerial kit (Sterognost 3 R_Pho. Nyegaard).15 The method depends on the ativity of a non-speifi 3o-hydroxysteroid dehydrogenase linked to the redution of niotinamide adenine dinuleotide (NAD+). All 3o-hydroxysteroid bile aids, both free and onjugated, are onverted to the orresponding 3-ketosteroids with the formation of niotinamide adenine dinuleotide redued (NADH). Determinations were made in dupliate in a medium ontaining M NAD+, M hydrazine hydrate buffer, ph 9.5 and 20 gi of gastri aspirate in a final volume of 1.52 ml. The redution Length offollow-up (yr) Age (yr) after operation Sex Group n Mean Range (male) Mean Range Control DU HSV PG TV+P TV+GJ

3 Bile aid and Iysoleithin onentrations in stomah of NAD+ was followed at 340 nm using a Pye Uniam SP 1800 dual beam spetrophotometer. The smallest detetable differene in bile aid onentration was governed by the sensitivity of the spetrophotometer. For the instrument used this was equivalent to 10,mmol/l of bile aid. The between assay oeffiient of variation using this tehnique was 5%. Bile aid onentrations in eah 20 minute period were used to alulate the mean bile aid onentrations (1) in the fasting state for one hour, and (2) after the meal for 80 minutes. These values were termed the mean fasting onentration and the mean post-prandial onentration, respetively. The mean peak onentration was alulated from the highest onentration of bile aid reorded in eah patient. MEASUREMENT OF LYSOLECITHIN Phospholipids were extrated from 2 ml of aspirate by the method of Bligh and Dyer.16 Samples of this extrat (4 ml) were evaporated under nitrogen, redissolved in a small quantity of hloroform, and applied to thin layer hromatographi plates of silia gel H (thikness 0.5 mm) together with standards of lysoleithin. Plates were developed in hloroform/ methanol/water (65:25:4 by vol)17 and the separate lipid spots demonstrated by iodine vapour. Sample spots ontaining lysoleithin were sraped from the plate and assayed for phosphate after degradation. 18 To eah sample of silia gel was added 1. 1 ml 11.7 M perhlori aid. This mixture was heated on a sandbath and maintained at a temperature of approximately 230 C to ensure digestion of the lipid. After ooling, the original volume of perhlori aid was restored by weight and the liberated phosphate was assayed using a olorimetri tehnique.19 Standards of free phosphate were used in the alulation of the amount of phosphate liberated by aid degradation but the effiieny of extration of lysoleithin was determined by the addition of known quantities of pure lysoleithin to both low range and high range patient samples. In this way it was possible to quantify the loss of lysoleithin at all stages of the extration. The overall reovery was found to be 45±5% (mean± 1 SD) and this inluded the losses on extration, evaporation, transfer, thin layer hromatography, degradation, and assay. The fasting, post-prandial, and peak values of lysoleithin were alulated as for the bile aids. STATISTICAL METHODS The values reported represent the means of dupliate determinations on eah sample plus or minus one standard error of the mean. The signifiane of differenes between the groups was determined by means of the Wiloxon rank sum test.20 Results 571 BILE ACID CONCENTRATIONS IN STOMACH Bile aid onentrations in the stomah in the six groups of patients are shown in Figs. 1 and 2 and in Table 2. Patients with duodenal uler, before operation, had signifiantly higher fasting, post-prandial, and peak bile aid onentrations in the stomah than did normal subjets. In patients who had undergone highly seletive vagotomy fasting, post-prandial, and peak bile aid Gut: first published as /gut on 1 July Downloaded from Table 2 Bile aid onentrations (,umol 1-') Signifiane Post- Signifiane Signifiane Group Fasting of differene prandial of differene Peak of differene Control p<0-ool p<0-002 p<0-001 DU J 906p. p<o-ol 01 p<o-o1 p<o-o1 HSV p<o-oool 4 p<o-ooo1 p<o-loo PG 4880< J p<oo1 p<0-000 p<b-o TV+P NS p<0.001 p<0-01 TV+GJ HSV vs ontrol p<0-65 NS NS HSV vs TV+P p<0-01 p<0-05 p<0.05 HSV vs TV+GJ p<0-01 p< p< PG vs DU p<0-001 p< p< PG vs TV+GJ p<0-01 p<0-05 p<0.05 Mean fasting, post-prandial, and peak values for eah group of patients. The standard errors of the means are shown in Figs. 1 and 2. on 16 April 2019 by guest. Proteted by opyright.

4 572 Eg 700 D E500 E 400- C C U)S 100. T io iio 140 (minutes) Fig. 1 Bile aid onentrations in the stomah in the fasting state and after a Lundh test meal, in nine normal subjets (ontrol) (0), 16 preoperative duodenal uler patients (0), and 14 patients after highly seletive vagotomy (A). onentrations were signifiantly lower than those in duodenal uler patients (Fig. 1, Table 2). Postprandial and peak bile aid onentrations after highly seletive vagotomy were similar to those in normal ontrols (Fig. 1), but in the fasting state bile aid onentrations of highly seletive vagotomy patients were higher than in ontrols. Bile aid Lundh meal Sl E E 4000-, 2000 / (minutes) Fig. 2 Bile aid onentrations in the stomah in the fasting state and after a Lundh test meal, in 14 duodenal uler patients treated by highly seletive vagotomy (A), 11 by Polya partial gastretomy (0), nine by trunal vagotomy and pyloroplasty (E), and eight by trunal vagotomy and gastrojejunostomy (A). Note hange in salefrom Fig. 1. T I Dewar, King, and Johnston onentrations in the stomah were signifiantly less after highly seletive vagotomy than after trunal vagotomy and pyloroplasty or trunal vagotomy and gastrojejunostomy. After Polya partial gastretomy fasting, postprandial, and peak bile aid onentrations in the stomah were signifiantly greater than those of ontrols and duodenal uler patients before operation, and also signifiantly greater than those in patients treated by highly seletive vagotomy. Bile aid onentrations in the stomah after Polya partial gastretomy were signifiantly greater than those after trunal vagotomy and pyloroplasty and trunal vagotomy and gastrojejunostomy. Bile aid onentrations in the stomah of fasting patients were relatively low after trunal vagotomy and pyloroplasty and trunal vagotomy and gastrojejunostomy and high after Polya partial gastretomy. After the meal, bile aid onentrations were highest after Polya partial gastretomy, very high after trunal vagotomy and gastrojejunostomy, and high after trunal vagotomy and pyloroplasty. Duodenogastri reflux was muh less after trunal vagotomy and pyloroplasty than after trunal vagotomy and gastrojejunostomy or Polya partial gastretomy (Fig. 2). LYSOLECITHIN CONCENTRATIONS IN STOMACH Lysoleithin onentrations in the stomah in the six groups of patients are shown in Figs. 3 and 4 and in Table 3. E D E 100- E._ * p 50- o 40-.' 30- * 20- o5 10- J Lundh m I (minutes) * * Fig. 3 Lysoleithin onentrations in the stomah in the fasting state and after a Lundh test meal, in nine normal subjets (ontrol) (0), 16 preoperative duodenal uler patients (0), and 14 patients after highly seletive vagotomy (A).

5 Bile aid and Iysoleithin onentrations in stomah Table 3 Lysoleithin onentrations (,mol 1') Signifiane Post- Signifiane Signifiane Group Fasting of differene prandial of differene Peak of differene Control NS NS NS DU NS NS NS HSV p<0-ool p<o-oool p<0-oool PG p<0-0l p<o-ool p<0-ool TV+P J NS p<0-01 p<0-01 TV+GJ ] HSV vs TV+GJ NS p<0-001 p<0-001 PG vs ontrol p<0-01 p<0001 p< PG vs DU p<0-001 p< p< PG vs TV+GJ p<0-01 p<0-05 p<0.05 Mean fasting, post-prandial, and peak values for eah group of patients. Standard errors are shown in Figs. 3 and 4. Both in the fasting state and after the meal, lysoleithin onentrations in highly seletive vagotomy patients were very similar to those in normal subjets (Fig. 3). In duodenal uler patie-ts before operation, lysoleithin onentrations in the fasting state were similar to those of normal subjets and highly seletive vagotomy patients, but post-prandial and peak levels were more than double those in these two groups (Fig. 3, Table 3). (nimtes) Fig. 4 Lysoleithin onentrations in the stomah in the fasting state and after a Lundh test meal, in 14 patients after highly seletive vagotomy (A), 11 Polya partial gastretomy (0), nine trunal vagotomy and pyloroplasty (a), and eight trunal vagotomy and gastrojejunostomy (A). When the four postoperative groups of patients are onsidered (Fig. 4), lysoleithin onentrations were low in the fasting state in the highly seletive vagotomy, trunal vagotomy and pyloroplasty, and trunal vagotomy and gastrojejunostomy groups, and no signifiant differenes were found between these groups. The fasting lysoleithin onentrations in these three groups of patients were all signifiantly lower than the fasting lysoleithin onentrations in the Polya partial gastretomy group. After the meal, lysoleithin onentrations remained relatively low after highly seletive vagotomy and trunal vagotomy and pyloroplasty, but were greatly and signifiantly raised after both Polya partial gastretomy and trunal vagotomy and gastrojejunostomy (Fig. 4). After Polya partial gastretomy lysoleithin onentrations (fasting, post-prandial, and peak) were all signifiantly greater than lysoleithin onentrations after both trunal vagotomy and pyloroplasty and trunal vagotomy and gastrojejunostomy. Disussion 573 The method used to obtain samples of gastri ontent ould be ritiised on the grounds that the presene of a nasogastri tube may produe nausea and, in itself, influene duodenogastri reflux. The same onditions prevailed, however, in all subjets and the differenes observed between groups were in the main so great that it seems unlikely that the presene of the tube had muh influene on the results. Manifestly, the nasogastri tube did not ause muh reflux in the ontrol or in the highly seletive vagotomy groups. The use of radioisotopes and funtional sintigraphy21 has reently

6 574 been introdued to demonstrate duodenogastri reflux of bile. Suh a tehnique, however, does not at present permit aurate measurement of reflux and its use is thus omplementary to the method that we used, rather than a substitute for it. The findings of very low bile aid onentrations in the stomah in the ontrol group are in agreement with the findings of Rhodes et a122 and Fisher and Cohen.23 They again show the value of a normal antropyloroduodenal segment in preventing reflux of 'bile' into the stomah.24 The preoperative duodenal uler patients had signifiantly higher bile aid onentrations in the stomah than the ontrols, both in the fasting state and after a meal. These results onfirm, and give quantitative expression to, the previous observations of Capper and his olleagues25 that patients with duodenal uler show evidene of duodenogastri reflux more often than ontrol subjets. After highly seletive vagotomy, relatively low onentrations of bile aid were found in the stomah, only the fasting values being signifiantly greater than those of normal subjets. All three values of bile aid onentration (fasting, postprandial, and peak) were signifiantly lower after highly seletive vagotomy than in duodenal uler patients before operation (Table 2), and, as the two group of patients were well mathed, the differene is almost ertainly a real one. This finding is at first sight surprising and pre and postoperative studies on the same patients will be required to onfirm this point. The mehanism of duodenogastri reflux is not fully understood, but it may involve abnormalities of motility and pressure in the antropyloroduodenal omplex.23 Pressure inreases in the pylori sphinter of normal people on response to hormonal stimulation by seretin and holeystokinin, but there is no response in patients with gastri uler. Similarly, duodenal aidifiation redues duodenogastri reflux by inreasing pylori sphinter pressure in normal people, but in patients with gastri uler it produes little or no inrease in pressure. These findings suggest that dysfuntion of the pylori sphinter may be responsible, in whole or in part, for inreased reflux of duodenal ontent into the stomah. In patients with duodenal uler, the presene of the uler itself just beyond the pylorus ould be responsible for abnormal funtion of the pylorus. Presumably the normal pressure gradient aross the antropyloroduodenal omplex is altered beause of loss of normal pylori funtion. Entry of hyme into the duodenum not only stimulates the seretion of bile but also inreases duodenal motility and redues antral motility.26 Thus inreased pressure in the duodenum and Dewar, King, and Johnston dereased pressure in the antrum, in the presene of dysfuntion of the pylorus, may reate suitable onditions for duodenal ontent to enter the stomah. This may explain the similar findings for bile aid and lysoleithin onentrations in the preoperative duodenal uler and trunal vagotomy and pyloroplasty groups. Though many patients with duodenal uler probably have some dysfuntion of the pylorus, treatment by highly seletive vagotomy will at least preserve whatever normal funtion the antropyloroduodenal segment still possesses, beause the pylorus is neither destroyed nor by-passed and the motor innvervation of the antropyloroduodenal omplex is preserved.1' In addition, highly seletive vagotomy may atually improve the funtion of the pylorus by uring the uler and thereby diminishing oedema, musular spasm, and mehanial deformity. We think, however, that the best explanation for the finding of diminished duodenogastri reflux after highly seletive vagotomy is to be found in the effets of that operation on gastri smooth musle and on intragastri pressure. After vagal denervation of the body and fundus of the stomah, vagovagal inhibitory reflexes are destroyed,27 leading to impairment of reeptive relaxation and aommodation to distension by the musular walls of the stomah: the altered pressure/volume relationships after ingestion of a meal thus result in higher pressures than normal within the stomah.28 This inrease in intragastri pressure will tend to prevent reflux from the duodenum into the stomah, and it has also been shown to inrease the rate of gastri emptying of liquids,29 whih will itself disourage reflux. Thus, through its effet on gastri pressure/ volume relationships, by preservation of an intat antropyloroduodenal segment, and, perhaps, by uring the uler itself, highly seletive vagotomy keeps 'bile' out of the stomah. The results of the studies on lysoleithin suggest that lysoleithin onentrations in the stomah after highly seletive vagotomy are normal. Postprandial levels of lysoleithin in duodenal uler patients before operation were nearly three times those in normal subjets. Perhaps beause of the wide range of values reorded, however, there was no statistially signifiant differene between the two groups. The effetiveness of highly seletive vagotomy as an anti-reflux operation is apparent when it is ompared with Polya partial gastretomy, trunal vagotomy and pyloroplasty, and trunal vagotomy and gastrojejunostomy, all of whih are operations that either remove the pylorus or interfere with its

7 Bile aid and Iysoleithin onentrations in stomah funtions. The fasting, post-prandial, and peak bile aid onentrations in the stomah after highly seletive vagotomy were found to be highly signifiantly less than after eah of these three proedures. Not only was the degree of reflux muh less after highly seletive vagotomy, but the duration of exposure of the gastri muosa to inreased onentrations of 'bile' was muh longer after these other operations than after highly seletive vagotomy. Eighty minutes after the ingestion of the meal, onentrations of bile in the stomah remained high after both partial gastretomy and trunal vagotomy and gastrojejunostomy. The results of the lysoleithin estimations showed a pattern similar to the results of the bile aid estimations. The highest onentrations of lysoleithin in the stomah were found after partial gastretomy and trunal vagotomy and gastrojejunostomy, espeially after the meal. After trunal vagotomy and pyloroplasty the post-prandial and peak lysoleithin onentrations, though not signifiantly higher than after highly seletive vagotomy, were double those found after highly seletive vagotomy and remained so for at least 80 minutes after the meal. These findings suggest that removal or bypass of the pylorus, with gastrojejunal anastomosis, as in Polya partial gastretomy and trunal vagotomy and gastrojejunostomy, allows muh more duodenal ontent to enter the stomah than ours after pyloroplasty, whih produes less alteration of the normal anatomy. After partial gastretomy, onentrations of bile aids and lysoleithin in the stomah were signifiantly higher than after trunal vagotomy and gastrojejunostomy. This ould be due to the inhibitory effet of trunal vagotomy on biliary and panreati seretion. Again, refluxing duodenal ontent might be diluted to a greater extent by gastri seretions after trunal vagotomy and gastrojejunostomy than after partial gastretomy. Finally, the degree of reflux may be related to some extent to the size of the stoma, whih may be somewhat larger, on average, after partial gastretomy than after trunal vagotomy and gastrojejunostomy. Whatever fator or ombination of fators may be involved in the inreased duodenogastri reflux after partial gastretomy and trunal vagotomy with a drainage proedure, it is unlikely that the greater length of follow-up of the patients who underwent these proedures was responsible for the inreased reflux. If reflux is going to our it will probably be manifest soon after the operation, and all the patients studied had been operated upon more than one year before. Reports from many entres have highlighted the 575 importane of keeping 'bile' out of the stomah. The presene of bile aids and lysoleithin in the stomah has been shown to inrease the movement of hydrogen ions out of the lumen of the stomah into the muosa, where they ause histamine to be released and gastritis to develop. Lysoleithin is formed in the duodenum when phospholipase A of panreati juie hydrolyses the leithin in bile, the reation being ativated by bile aids and trypsin. The gastritis that is produed by exposure of the gastri muosa to the ombined ontents of the duodenum has been shown in dogs to be onsiderably worse than the gastritis that is aused by pure panreati juie alone or by pure bile alone It was for that reason that we measured both bile aids and lysoleithin. In a separate report the relationship between gastritis and the reflux of bile aids and lysoleithin is being examined. In man, regurgitation of 'bile' into the stoniah may lead to nausea and bilious vomiting, but of greater importane is the prolonged irritation of the gastri muosa, whih produes hroni superfiial gastritis and eventually hroni atrophi gastritis.38 These hanges in the gastri muosa produe a syndrome of 'bile reflux gastritis' or 'alkaline reflux gastritis' in a proportion of patients. The syndrome is haraterised by persistent epigastri pain, vomiting, anorexia, and loss of weight. In the longer term, prolonged ontat of 'bile' with the gastri muosa may well be a fator in the development of gastri arinoma. Gastritis progresses, with the development of intestinal metaplasia, whih some authors believe to be a pre-anerous lesion,38 though others doubt whether the presene of suh metaplasia is of value as a preditor of aner.39 Many reports have shown that the inidene of gastri 'stump' arinoma is signifiantly inreased more than 15 years after Billroth 1 partial gastretomy, Polya partial gastretomy, or even gastrojejunostomy alone The arinomatous hange usually develops lose to the stoma, where the damage to the gastri muosa is greatest, a fat that strongly suggests that 'bile' reflux may be an important fator in the genesis of the ondition. When Shrumpf and his olleaguesl' endosoped 108 asymptomati patients who had undergone partial gastretomy 20 to 25 years before, they found that four of them had infiltrating gastri arinoma and another three had arinoma-in-situ: all but one of the remaining patients had either severe hroni gastritis, intestinal metaplasia, or dysplasia. Thus it seems likely that loss of the pylorus and the exessive duodenogastri reflux that follows exposes the patient to a onsiderable risk of developing gastri arinoma in the long term. The severity of the gastritis that develops is

8 576 Dewar, King, and Johnston proportional to the amount of duodenal ontent that refluxes and to the duration of the exposure of the gastri muosa to the irritant.36 The results of this study suggest that when highly seletive vagotomy is used in the treatment of duodenal uler, both the quantity of bile in the stomah and the length of time that it is in ontat with the gastri muosa are signfiantly less than after other operations that destroy or bypass the pylorus. Metiulous, longterm studies are now needed to test our hypothesis that the redued duodenogastri reflux seen after highly seletive vagotomy benefits the patient in terms both of fewer symptoms of gastritis and a lower risk of gastri arinoma. Referenes 1 Lawson HH. The role of the pylori antrum and Hofmeister valve in the development of the hroni gastri muosal reation. Br J Surg 1976; 63: du Plessis DJ. Gastri muosal hanges after resetion of the stomah. S Afr Med J 1962; 36: Lawson HH. Effet of duodenal ontents on the gastri muosa under experimental onditions. Lanet 1964; 1: Orhard R, Reynolds K, Fox B, Andrews R, Parkins RA, Johnson AG. Effet of lysoleithin on gastri muosal struture and potential differene. Gut 1977; 18: Sudamore HH, Ekstam EE, Fenil WJ, Jaramillo CA. Bile reflux gastritis. Am J Gastroenterol 1973; 60: Drapanas T, Bethea M. Reflux gastritis following gastri surgery. Ann Surg 1974; 179: Keighley MRB, Asquith P, Alexander-Williams J. Duodenogastri reflux: A ause of gastri muosal hyperaemia and symptoms after operations for pepti uleration. Gut 1975; 16: Stalsberg H, Taksdal S. Stomah aner following gastri surgery for benign onditions. Lanet 1971; 2: Domellof L, Eriksson S, Janunger K-G. Late preanerous hanges and arinoma of the gastri stump after Billroth 1 resetion. Am J Surg 1976; 137: Shrumpf E, Stadaas J, Myren J, Serk-Hanssen A, Aune S, Osnes M. Muosal hanges in the gastri stump years after partial gastretomy. Lanet 1977; 2: Johnston D, Wilkinson AR. Highly seletive vagotomy without a drainage proedure in the treatment of duodenal uler. Br J Surg 1970; 57: Goligher JC, Pulvertaft CN, de Dombal FT, Conyers JH et al. Five to eight year results of Leeds/York ontrolled trial of eletive surgery for duodenal uler. Br Med J 1968; 2: Findlay JM, Presott RJ, Sirus W. Comparative evaluation of water reovery test and fluorosopi sreening in positioning a nasogastri tube during gastri seretory studies. Br Med J 1972; 4: Magee WL, Gallai-Hathard J, Sanders H. Thompson RHS. The purifiation and properties of phospholipase A from human panreas. Biohem J 1962; 83: Fausa 0, Skalhegg BA. Quantitative determination of bile aids and their onjugates using thin layer hromatography and a purified 3 o-hydroxysteroid dehydrogenase. Sand J Gastroenterol 1974; 9: Bligh EG, Dyer WJ. A rapid method of total lipid extration and purifiation. Can J Biohem Physiol 1959; 37: Nelson GJ. Quantitation, omposition and metabolism. In: Blood lipids and lipoproteins. New York: Wiley Intersiene, 1972: Marinetti GV. Chromatographi separation, identifiation and analysis of phosphatides. J Lipid Res 1962; 3: Fiske CH, Subbarrow Y. Colorimetri determination of phosphorus. J Biol Chem 1935; 66: Snedeor GW, Cohran WG. Statistial methods Ames, Iowa: Iowa State University Press, Makie CR, Wisbey M, Cushieri A. Milk 'TMEHIDA test for enterogastri bile reflux. Br J Surg 1981; 68: Rhodes J, Barnardo DE, Phillips SF, Rovelstad RA, Hofmann AF. Inreased reflux of bile into the stomah in patients with gastri uler. Gastroenterology 1969; 57: Fisher RS, Cohen S. Pylori sphinter dysfuntion in patients with gastri uler. N EngI J Med 1973; 288: Keighley MRB, Asquith P, Edwards JAC, Alexander- Williams J. The importane of an innervated and intat antrum and pylorus in preventing postoperative duodenogastri reflux and gastritis. Br J Surg 1975; 62: Capper WM, Airth GR, Kilby JO. A test for pylori regurgitation. Lanet 1966; 2: Brink BM, Shlegel JF, Code CF. The pressure profile of the gastroduodenal juntion zone in dogs. Gut 1965; 6: Martinson J. Studies on the efferent vagal ontrol of the stomah. Ata Physiol Sand 165; 65: suppl 255: Stadass J, Aune S. Intragastri pressure/volume relationship before and after vagotomy. Ata Chir Sand 1970; 136: Wilbur BG, Kelly KA. Effet of proximal gastri, omplete gastri, and trunal vagotomy on anine gastri eletri ativity, motility and emptying. Ann Surg 1973; 3: Malagelada JR, GO VLW, Summerskill WHJ. Altered panreati and biliary funtion after vagotomy and pyloroplasty. Gastroenterology 1974; 66: MaGregor IL, Parent J, Meyer JH. Gastri emptying of liquid meals and panreati and biliary seretion after subtotal gastretomy or trunal vagotomy and pyloroplasty in man. Gastroenterology 1977; 72: Lavigne ME, Wiley ZD, Martin P et al. A study of

9 Bile aid and lysoleithin onentrations in stomah 577 gastri, panreati and biliary seretion, and the rate of gastri emptying following parietal ell vagotomy. Am J Surg 1979; 138: Ivey KJ, DenBesten L, Clifton JA. Effet of bile salts on ioni movement aross the human gastri muosa. Gastroenterology 1970; 59: Davenport HW. Destrution of the gastri muosal barrier by detergents and urea. Gastroenterology 1968; 54: Davenport HW. Effet of lysoleithin, digitonin and phospholipase A upon the dog's gastri muosal barrier. Gastroenterology 1970; 59: Lawson HH. The effet of the duodenal ontents on the gastri muosa. S Afr J Surg 1965; 3: Dragstedt LR, Woodward ER, Seito T, Isaza J, Rodriguez JR, Samiian R. The question of bile regurgitation as a ause of gastri uler. Ann Surg 1971; 174: Morson BC, Dawson IMP. Gastrointestinal pathology. Oxford: Blakwell, Domellof L, Eriksson S, Janunger K-G. Carinoma and possible preanerous hanges of the gastri stump after Billroth II resetion. Gastroenterology 1977; 73: Siurala M, Lehtola J, Ihamaki T. Atrophi gastritis and its sequelae. Sand J Gastroenterol 1974; 9: Leading Artile. After gastretomy. Br Med J 1981; 282: Gut: first published as /gut on 1 July Downloaded from on 16 April 2019 by guest. Proteted by opyright.