Gut, 1961, 2, 85

The annual meeting of the British Societyof Gastroenterology

The annual meeting of the British Society of Gastroenterology was held at King's College Hospital, London,on 4 and 5 November 1960 under the Presidency of Mr. Harold Edwards, with Dr. Bruce Pearson as thelocal secretary.At the general business meeting the following elections were made: President, E. Bulmer; Treasurer,

Hermon Taylor; Secretary, W. A. Bourne; Council Members, S. Sherlock and S. C. Truelove. The followingwere elected full members of the Society: Michael Atkinson, D. H. Cummack, David Douglas, C. W. A.Falconer, A. P. M. Forrest, Terence Fulton, J. B. Gibson, R. H. Girdwood, R. A. MacMynn, J. G. Murray,W. A. B. Nicholson, Brian Schofield, Geoffrey Slaney, and Ian Todd. The following were elected as

associate members: E. D. Acheson, H. T. F. Bamiville, E. V. Cox, C. W. Crane, G. P. Crean, I. E. Gillespie,F. E. Higgins, I. D. A. Johnston, W. G. Manderson, G. F. Matts, A. G. Melrose, Annette Rawson, H. I.Tankel, and R. S. Williams.

It was decided that the Society should play a more active role in international relations in respect ofgastroenterological work and that there was a need to keep in touch with other international societies andto assist in the coordination of education and research activities. It was decided to form a special committeewith T. C. Hunt, F. Avery Jones, Hermon Taylor, and Geoffrey Watkinson as members.On the Friday evening a most excellent dinner was held at the Apothecaries Hall and this had been

arranged by Professor Magnus. The President spoke of the work of the Society and welcomed the twovisitors, Dr. Grossman and Sir William Morrow.

After dinner the Clerk of the Apothecaries gave an account of the history of the beautiful hall.

Scientific meetingTHE EFFECT OF PROSTIGMINE ON

HUMAN COLONIC MOTILITY

N. A. CHAUDHARY AND S. C. TRUELOVE (oxFoRD) had madea comparative study of the patterns of colonic motilityfollowing a standard intramuscular dose of prostigminemethylsulphate in normal subjects, patients with irritablecolon syndrome, and patients with ulcerative colitis. Innormal subjects, the standard dose ofprostigmine methyl-sulphate provoked increased activity with a resultingpattern not dissimilar from that of the resting pattern ofpatients with spastic colon in a stage of symptoms.Patients in all clinical categories of the irritable colonsyndrome displayed more colonic activity after prostig-mine than normal subjects. This was so whether or notthey were in a stage of symptoms. By contrast, the res-ponse of patients with ulcerative colitis to a standarddose of prostigmine was little if any different from that ofnormal subjects. These results suggest that patients withspastic colon are subject to excessive parasympatheticstimulation or to increased reactivity to normal stimuli.

RADIOLOGICAL AND MANOMETRIC STUDIES OF CHANGES IN

MOTILITY OF THE ALIMENTARY TRACT IN DIFFUSE SYSTEMICSCLEROSIS AND POLYMYOSMS

D. A. W. EDWARDS (LONDON) said that in a group of 21patients with scleroderma, dermatomyositis, polymyositis,or systemic sclerosis, the motor activity of the gut had

been examined by radiology and by recording changes inintraluminal pressure with open tubes and miniatureballoons. The majority of patients were investigatedpersonally; information about the others was obtainedfrom hospital records. In all but two patients there wasevidence of a marked decrease in smooth muscle activityin some part of the gut, and, in a small group in whichhistological material became available, a decrease in theamount of smooth muscle was demonstrated.The commonest disturbance was loss of oesophageal

peristalsis, sometimes associated with stiffening of thelower end of the oesophagus and loss of tone in thecardiac sphincter. Changes in motility of the stomachwere difficult to distinguish from the normal, but thecharacteristic squashed out atonic immotile duodenalloop was present in six out of 13 patients adequatelyexamined. A similar appearance of flattened immotileloops of small intestine was seen in five out of 10 patients.Five out of six patients had saccular dilatations and adisorganized haustral pattern in the colon.The characteristic changes are valuable as a diagnostic

aid when biochemical or external manifestations of thisdisease complex are absent or equivocal, or when thedisease presents as a gastroenterological problem. Lossof smooth muscle appears to be an integral part of thedisease process.

GASTRIC SECRETION IN LIVER DISEASE

SOAD TABAQCHALI AND A. M. DAWSON (LONDON) It hasbeen claimed that there is a high incidence of peptic

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ulcer in patients with portal cirrhosis. Recently, it hasbeen suggested that this might be related to the fact thatin dogs which have undergone a portal systemic shuntprocedure there is a consistent increase in acid secretionfrom a Heidenhain pouch.The records of 200 consecutive patients with portal

cirrhosis were analysed and a probable increased incidenceof peptic ulcer, especially in women, was found, in con-trast to the greatly increased incidence in patients withprimary biliary cirrhosis. Gastric secretory function wasassessed in patients with portal cirrhosis, some of whomhad had a portacaval anastomosis operation, and inpatients with primary biliary cirrhosis. This was done bymeasuring basal acid secretion, maximal histaminesecretion, and the 24-hourly gastric pH. In all groups themaximal response to histamine was normal. However, inpatients with a portacaval anastomosis there was atendency to a low gastric pH at night, whereas patientswith uncomplicated portal cirrhosis and primary biliarycirrhosis did not differ from the controls in this respect.

A POSSIBLE EXPLANATION OF FAILURE OF RADIO-TRIOLEIN TO DIAGNOSE STEATORRHOEA

A G. COX (SHEFFIELD) In a clinical trial, radio-iodinatedtriolein failed to diagnose steatorrhoea in 50% of caseswith a high chemical faecal fat excretion. A possibleexplanation was instability of the radio-iodine label inthe alimentary tract. To investigate this point, a methodusing an anion exchange resin was evolved and appliedin vitro. When incubated with duodenal juice, six batchesof triolein tagged with the standard 1131 Cl. label showeda steady rise in the amount of the radio-isotope liberated.This demonstration of the instability of the label requiresstudy in vivo. The method also confirmed that the simple1131 label, still occasionally used, is highly unstable.

In the discussion N. Coghill noted that Lubran,working with him, had obtained good correlationand it was agreed that results varied appreciably indifferent places. Cooke pointed out that strictly speak-ing steatorrhoeawasdemonstrated andnot diagnosed.

OBSERVATIONS ON THE CLINICAL TESTING OF GASTRICANTISECRETORY DRUGS AND ANTACIDS

J. E. LENNARD-JONES (LONDON) had studied the effect oftwo gastric antisecretory drugs, a long-acting form ofpropantheline bromide and poldine methosulphate(Nacton), on thepH of hourly samples of gastric contentsin patients with uncomplicated duodenal ulcer. Both thedrugs significantly reduced the acidity of the samplewhen patients took hourly drinks of milk-cream withoutother food. When the same patients took a gastric-typediet, a small reduction in acidity was demonstrable withpropantheline but no reduction with Nacton. In otherpatients taking a diet, Nacton given alone did notreduce acidity even when given in doses large enough tocause unpleasant side-effects. Nacton potentiated theeffect of suboptimal doses of alkali and the combinationreduced acidity during waking hours. Although Nactondelayed gastric emptying at night, the effect of a dose ofalkali at bed-time was not prolonged. When patientssucked antacid tablets continuously a satisfactoryreduction in acidity of the gastric contents during wakinghours was achieved without the use of an antisecretorydrug.From this work it is concluded that the two anti-

secretory drugs studied are less effective in reducing theacidity of gastric contents under the conditions of clinicaluse than under experimental conditions. Antacids,sucked as tablets, satisfactorily reduce gastric acidityduring the day; the two antisecretory drugs do not use-fully reduce the pH of the gastric contents at night whena patient is taking a gastric-type diet.

In the discussion J. N. Hunt noted that the anti-secretory drugs had been given for a relatively shorttime, about five days before the observations weremade, and suggested that longer prior administrationmight have produced a different result. The speakerdid not support this view.

Sircus commented on the complexity of the factorsresulting in the final sampling figure.

SYMPOSIUM ON APPLIED PHYSIOLOGY OF THE STOMACH

There were four opening papers and these were given by Professor R. A. Gregory, J. G. Murray,M. R. Vane, and W. I. Card.

THE PHYSIOLOGY OF GASTRIC SECRETION

PROFESSOR R. A. GREGORY (LIVERPOOL) Studies duringthe last 10 years by Uvnas, Dragsted, Schofield, Gregory,and Tracy and others have led to a general acceptanceof the suggestion first made by Straaten that vagalactivity is important for the release of gastrin from thepyloric antrum. It is now agreed that in addition to itsdirect action on the gastric glands the vagus also excitesthe antrum and thus contributes, in combination withlocal stimulation by the swallowed food, to release thepyloric hormone. The 'cephalic phase', defined originally

by Pavlov, thus involves a hormonal component. Howlong the release of gastrin continues is uncertain, buttwo important controlling factors are now recognized toexist. One is the intragastric accumulation of acid whichinhibits further release of gastrin by a local action on thepyloric mucosa. The other, as recently shown by Gregoryand Tracy, is the action of the hormone enterogastroneliberated from the duodenum by such agencies as fat,acidity, and hypertonicity of the duodenal contents.

In addition to this hormonal mechanism, reflex controlof gastric secretion from the duodenum undoubtedlyexists, and the vagi are probably the efferent pathway, as

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indicated by the studies of Code and Watkinson. Thehighly purified preparation of gastrin obtained byGregory and Tracy stimulates acid but not pepsinsecretion in the conscious human subject, as well as inanimals. Its action resembles that of histamine, but differsfrom this substance in that it is strongly inhibited byatropine, and single intravenous injections are effectivein exciting secretion.

NERVOUS CONTROL OF GASTRIC FUNCTION

J. G. MURRAY (LONDON) Recent experimental work hasthrown new light on the composition of the vagus nerve.About 80 to 90% of the fibres supplying the abdominalviscera are afferent, some arising from stretch receptorsand others from chemoreceptors in the stomach.Combined anatomical and physiological observations

are consistent with the view that the intrinsic nerveplexuses contain local reflex arcs and mediate, forexample, peristalsis. At least two sets of enteric neuronsare involved: (a) sensory neurons, the processes of whichare distributed to the mucous membrane on the onehand, and to motor neurons on the other, and (b) motorneurons which innervate the muscle coats. Of all thenervous tissue in the stomach and gut, by far the largestpart is of intrinsic origin.

Lastly, the surprising plasticity of the autonomicnervous system following injury or disease has only beenappreciated over the last few years. If an organ is partiallydenervated, then the remaining intact nerve fibres arestimulated to give off tiny branches. These sproutsconnect up with denervated effector organs and resultin return of function. Even after complete denervation,nearby nerve fibres may sprout to produce quite bizarreeffects. This phenomenon was briefly described withparticular reference to vagotomy.

THE PHARMACOLOGY OF THE SMOOTHMUSCLE OF THE STOMACH

J. R. VANE (LONDON) Dale and Feldberg in 1934 demon-strated that excitation of the vagus nerves brought aboutthe release of acetylcholine in the wall of the stomach.However, the suggestion has often been made that vagaleffects in the stomach are mediated by the release ofhistamine. This suggestion was based on the highpotency of histamine as a stimulus for gastric secretionand for muscular contraction. Moreover, histamine isnormally present in the stomach wall. More recently,another hormone, 5-hydroxytryptamine, had beenisolated from the stomach. In consequence, the roles ofacetylcholine, histamine, and 5-hydroxytryptamine havebeen re-investigated.The release of acetylcholine from parasympathetic

nerve endings has been confirmed. It has also beenshown that the major effect of histamine on the smoothmuscle of the stomach, which is to increase its tone, isbrought about through an excitation of nerves.

CLINICAL APPLICATION

W. I. CARD (EDINBURGH) underlined the ideas foundvaluable in gastric physiology of the last 10 years. The

most important general advance in the last 10 years hasbeen the increasing application of the scientific methodto gastroenterology, and much of this advance has beendue to the introduction of better investigative techniques.With the introduction of the electron microscope

morphology has come into its own again, revealingalmost a new dimension of thought. The obstacle hereseems to be not that of resolution but of finding methodsof differentiating structure.

Gastric secretion continues to command much of ourattention, partly because it is simplest to measure andpartly because high secretions play a part in the causationof certain peptic ulcers. The evidence that histamine isthe actual pharmacological stimulant of the parietal cellscontinues to accumulate. The problem that has teas-dthe physiologist for so long of inferring from the mixedgastric secretion the original constituents as secretedcontinues to appear insoluble. Over the last 20 yearsacid output rather than acid concentration in gastricjuice has been generally adopted. Though the output isreproducible with the ordinary doses of histamine, theuse of 'maximal' histamine stimulation does allowcomparisons of one subject with another by excludingvariations in one parameter, and also makes for a morerigorous definition of achlorhydria. The output of acidin a given time can be considered as the product of therate of secretion and the number of secretory units,though the phrase 'rate of secretion' covers a number offactors. One of these which has been frequently over-looked is the blood flow to the mucosa which must,from consideration of energetics, be very large. Directlythe acid output is shown to be related to the number ofcells, the question immediately presents itself of account-ing for the origin of a large cell mass. There seems to bea need to consider the existence and the role of trophichormones, though it has not been possible to confirmthe trophic action of histamine as had been previouslyreported. The possibility has to be consideted thatgastrin acts as a trophic hormone. The discovery of agastrin-like hormone in the Zollinger-Ellison syndromeraised the question of whether this exists as a qualitativelydistinct syndrome, or whether it is simply a grosslyexaggerated form of a normal mechanism. Anotherhormone with a trophic action that had to be consideredis cortisone. It has been shown that complete achlor-hydria occurs in Addison's disease, that this may dis-appear after treatment with corticoids, and that evenpeptic ulceration may follow. Cortisone, given in anacute experiment, did not seem to produce an increasedresponse to histamine in human subjects, but given overa longer period, as in the treatment of Crohn's disease,it undoubtedly increases the output of acid. This can onlybe due to an increase in the number of secretory units percell, an increased number of cells, or an augmentationof secretory rate. The pituitary might also produce atrophic hormone from the gastric mucosa. There wasatrophy in clinical hypopituitarism, a diminution of theparietal cell count had been demonstrated followingexperimental hypophysectomy, while the prolonged ad-ministration ofcorticotrophin in man produced increasingamounts of acid which it was difficult to believe could bedue to anything else except hyperplasia ofthe parietal cells.

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DISCUSSION

Professor A. W. Kay commented that Mr. Murray'sfascinating studies on the intimate neuroanatomyof the stomach had an obvious bearing on theoperation of surgical vagotomy. His demonstrationof 'sprouting' from the divided ends of the vagalfibres rather suggested an appreciable chance ofvagal regeneration with a risk of late recurrentulceration. In this connexion it was of interest thatsecretion studies had been recently performed inSheffield on patients who had undergone vagotomyfrom a few months to some years previously.Analysis of these results showed that the greatmajority showed no tendency to a rising level ofacid secretion and indeed there was a general trendtowards a further reduction.With regard to Professor Gregory's magnificent

survey of the physiology of gastric secretion, wemust have some concern about various discre-pancies between the results of animal and humaninvestigations. For example, antrectomy in the doghas been shown by both American and Scandinavianinvestigators to have no effect on histamine-provokedacid secretion. On the contrary, antrectomy in mancauses a marked reduction not only of histaminesecretion but of maximally stimulated acid secretion.It may be that we should give more attention tophysiological studies in primates and there iscertainly room for a great deal more investigationof patients undergoing planned surgery for duodenalulcer.The influence of the advances in physiology and

pharmacology on surgical treatment demands thatcareful preoperative studies on gastric secretionshould be carried out and thereby the operationselected most suited to the individual case. Ingastrectomy, vagotomy with a drainage procedure,antrectomy with vagotomy, and gastrojejunostomywe have four operations of value in surgical therapy.Our task is to devise methods from which we canselect the appropriate operation for each patient.

J. N. Hunt drew attention to the threshold for theeffect of acid in reducing gastric secretion. Equalconcentrations of hydrochloric acid, acetic acid, andcitric acid were about equipotent, although the pHof the solutions were quite different.

Professor R. B. Welbourn referred to the influenceof the major endocrine glands on gastric acidsecretion, which Dr. Card mentioned. Hypophysec-tomy reduced secretion profoundly in the rat.Corticotrophin and growth hormone restored it.The latter observation does not appear to have beentaken up by others. Pharmacological doses of corti-sone, methyl prednisolone (a 'pure' glucocorticoid),and aldosterone all increase secretion similarly in the

dog. The effect might be a mineral corticoid one,since methyl prednisolone has slight salt-retainingproperties. However, they had recently investigatedtriamcinolone and dexamethasone, of which themineralocorticoids were minimal, and had foundthat they also increased secretion. It seems likely,therefore, that the gastric activity of the adrenalsteroids is not necessarily tied to their main metabolicactions. Cortisone increased by about 50% themaximal secretory capacity, in response to histamine,of Heidenhain pouches in dogs and it increased theparietal cell mass by a similar proportion. Thephysiological role of all these hormones appears tobe 'permissive'.M. I. Grossman said that the release of gastrin by

vagal impulses had been unequivocally established.Schofield had placed the keystone in the arch ofevidence supporting this conclusion. We should not,however, lose sight of the fact that vagal impulsesstimulate the secretion of gastric acid by anothermechanism, namely, direct cholinergic action on theacid-secreting glands. It is not yet possible to saywhich of these two vagal mechanisms for stimulationof acid secretion is quantitatively predominant.

Professor Gregory had introduced a new concepto'f the mode of action of enterogastrone. He believesthat it inhibits gastric secretion by suppressing therelease of gastrin. Inhibition of acid secretion byacid bathing the pyloric gland area is also attributableto prevention of gastrin release. Both of thesemechanisms for suppression of gastrin release actat the final step in the process, that is, the release ofgastrin by acetylcholine. It is unlikely that hydrogenions penetrate to the site where cholinergic releaseof gastrin is occurring; therefore, it is postulatedthat acid releases a local humoral agent whichinterfers with gastrin release.

Professor L. J. Witts spoke of the value of theaugmented histamine test in the differentiation ofthe anaemias. The essential defect in perniciousanaemia was loss of intrinsic factor but in adults itwas excessively rare to find free HCI in a provedcase of pernicious anaemia. In only four out of 30patients with pernicious anaemia studied did thetotal volume of gastric juice after histamine exceed20 ml. Electrometric measurements revealed a pre-histamine juice more alkaline than pH 7.0 in all butfour instances and the lowest reading was pH 6.71.In only two patients did the pH change to the acidside after histamine and the shift was less than 0.33units. In three there was no change in pH. In all theothers the pH rose after histamine and the meanmaximum pH change indicated an increased alka-linity of 0.52 units. One of the most interestingstudies at the moment was the detection of latent orpreclinical forms of pernicious anaemia. As a rule

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the sequence was loss of HCl, loss of intrinsic Dr. Avery Jones commented on the value of thefactor, and finally fall in serum vitamin B12, but this urinary pepsinogen test as a measure of gastricorder was not invariable. function.

CHEST DISEASE AND PEPTIC ULCER

B. G. RIDGEN (BRIGTrroN) describes an investigation of10,485 males of 21 years and upwards, attending a massradiography unit, with the object of determining whethercertain radiological abnormalities in the thorax wereseen more commonly amongst those with a history ofpeptic ulceration than in those without such a history.Each chest film was read in ignorance of the ulcer

state; and each ulcer history was assessed in ignoranceof the chest condition.Of the 10,485 men, 409 (3.9 %) were deemed to have a

valid history of peptic ulceration. The incidence ofemphysema (without radiological evidence of focal lungdisease) in the ulcer group was 6.35 %; in the remainderit was 1 87 %. Emphysema was thus seen more than threetimes as frequently in the ulcer patients. Intrathoracictuberculosis (all stages) was seen in 10-75 % of the ulcergroup as against 6.55% of those without an ulcer history.Congenital abnormalities (of the ribs, heart, and lungs)were seen rather less commonly in the ulcer groups thanin the others.

METABOLIC INFLUENCES IN THE DISSEMINATIONOF CANCER

JOHN D. GRIFFITHS (LONDON) said that the effect of dietarydeficiency in producing spontaneous tumours had beenwell described by Tannenbaum and Silverstone, whodemonstrated that prolonged restricted caloric intakeand malnutrition in laboratory animals would diminishinduction and growth in spontaneous tumours. However,the influence of acute metabolic changes had not beeninvestigated in relation to increased susceptibility ofthe host and its possible effect on the dissemination andsubsequent implantation of neoplastic cells. In thepresent investigation the effect of 'acute' metabolicchanges, such as starvation and dehydration, which canbe considered a form of metabolic 'stress', had beenstudied in relation to the rats' susceptibility to inoculationof Walker 256 carcinosarcoma.

Results of the experiment indicated that starvation anddehydration for 48 hours did not increase susceptibilityof the rat to subcutaneous inoculation of Walker tumour,but if starvation was continued for seven days there wasan increase in percentage 'takes' of the tumour as com-pared with the incidence in normal healthy animals.There was also an increase in 'takes' of implanted tumourin young rats.

CYTOLOGICAL STUDIES IN GASTRIC CARCINOMA

M. K. MASON (LONDON) said the investigations were beingmade to assess the value of cytology in the early diagnosisof carcinoma of the stomach. Two methods of approach

had been employed. The first consisted of gastric lavageusing normal saline in suspected or known cases ofcancer in order to identify any malignant cells exfoliatedfrom the lesions. A number of difficulties had beenencountered using this technique. The second methodwas to make smears from all stomach immediately afterresection and to examine the slides for the presence ofmalignant cells. By this means a number of early surfacecarcinomas had been identified. These growths in generalcannot be recognized macroscopically, and may be verysmall. By making smears, a considerably wider area ofmucosa is covered than is possible with sections alone.Surface carcinomas appear to be commoner than isusually realized, and are easily overlooked withoutcareful examination of the stomach.

THE MEDIASTINUM IN PORTAL HYPERTENSION

A. E. READ AND F. DOYLE (LONDON) had carried out aradiological study of the mediastinum in portal hyper-tension. The 'diameter' of the azygos vein had beenmeasured, using tomography, in a series of patientswith portal hypertension and in a group of normalcontrols. After correction for body weight differences asignificant increase in the size of this vessel had beenshown to exist in the portal hypertensive group. Therewas, however, no apparent correlation between the sizeof the azygos vein and various clinical manifestations ofportal hypertension, such as the presence of ascites,encephalopathy, and gastrointestinal bleeding.

Measurement of the left paravertebral shadow hadalso shown that in portal hypertension this is sometimeswidened. This measurement is, however, probably not areliable indication of the size of the hemiazygos veins.A very wide left paravertebral shadow is sometimesencountered in patients with ascites and may indicate thepresence of fluid in the mediastinum.

Attention was drawn to other abnormal mediastinalradiological appearances, recognition of which is ofimportance in avoiding diagnostic errors.

CHOLECYSTECTOMY FOR CARDIAC PAIN

G. E. SOWTON considered the relationship between cardiacsymptoms and gall bladder disease both theoretically andclinically, together with results of gall bladder surgery.A preliminary report on the cardiographic changes of

40 patients undergoing cholecystectomy was producedtogether with the results ofexercise tolerance cardiograms,blood cholesterol levels, and clinical details.The results of experimental stimulation of the biliary

tree during operation, using stronger distension stimulithan have previously been reported, were discussed, withparticular reference to the cardiac risk undergone by thepatient at operation.

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HISTOLOGICAL ABNORMALITIES IN THE JEJUNUM ANDILEUM IN THE MALABSORPTION SYNDROME

R. HOLMES, D. HOURIHANE, AND C. C. BOOTH (LONDON)described the results of intestinal biopsies in 120 patientsusing the Crosby biopsy capsule. The specimens wereusually examined first under the dissecting microscopeand histological sections were then prepared for con-ventional microscopy.

Thirty patients had idiopathic steatorrhoea. In 18there was subtotal atrophy of the villi, the biopsiesappearing flat and devoid of villi under the dissectingmicroscope. In the other 12 patients there was partialatrophy, histological sections revealing blunt, squat, andthickened 'villi'; under the dissecting microscope thesespecimens showed a remarkable ridged appearancewhich contrasted with the baldness of subtotal atrophy.Biopsies obtained from the ileum might be normal eventhough there was subtotal atrophy of the jejunal mucosa.

Biopsies from four patients with chronic tropical sprueshowed partial villous atrophy and a similar ridgedappearance under the dissecting microscope.The biopsy technique proved invaluable in the dif-

ferential diagnosis of steatorrhoea. It was also useful inassessing the response to treatment. The procedure wassafe and, apart from transient pyrexia after biopsy intwo patients, there were no complications.

THE EFFECT OF HAEMATEMESIS ON THE

HAEMOPOIETIC SYSTEM

W. M. DAVIDSON (LONDON) said that haematemesis wasusually due to primary disease of the oesophagus,stomach, or duodenum; less frequently disease in aneighbouring organ involving the upper part of thealimentary tract; and rarely generalized disease, includingdiseases of the blood.

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