102 11 October 1969 Peptic Ulcer-Langman BRITSHMEDICAL JOURNALj

healing, probably owing in part to the difficulty of assessingchanges in a deformed duodenal cap and in part becausethe doses required of anticholinergic drugs may be considerablyhigher than those commonly recommended. The newer anti-cholinergic preparations (such as glycopyrrolate, isopropamide,poldine, and propantheline) probably have a more selectiveaction on the stomach than atropine, but similar side-effectsdo occur.

It has been claimed that when given in the maximum tolerateddoses anticholinergic preparations will reduce the gastric acidsecretory response by half3" and that they will reduce thesymptomatic relapse rate and complication rates36; the drugsused in these studies were poldine and propantheline, respec-tively. More recently a controlled trial has been reported inwhich glycopyrrolate was found to have no better effect thanplacebo tablets in preventing relapse.37 The results are difficultto equate with those obtained by Sun, for the drugs used,though different, are probably similar in effect.

In general, anticholinergic drugs should be used in thosepatients whose pain is poorly controlled by alkali administrationalone. It is probably also reasonable to try them as a long-termmeasure in patients with frequent symptomatic relapse but inwhom surgery is thought inadvisable.

Other DrugsCarbenoxolone.-Carbenoxolone in tablet form is ineffective

in duodenal ulcer, possibly because it has a direct local effectupon the mucosa but does not usually reach the duodenum insufficiently high concentration. A capsule claimed to burst inthe gastric antrum and release its contents into the duodenumhas now been developed (Duogastrone). Conflicting resultshave been obtained in two double-blind trials, varying from aclear and statistically significant advantage in the duogastrone-treated group38 to no advantage in the test group,39 with twoopen trials showing some advantage to the test group.40 41

In view of this conflict and evidence that under the normalconditions of use the capsules burst in the gastric fundus andnot the antrumrn9 the preparation cannot yet be recommendedfor routine use.

Deglycyrrhizinated Liquorice and Gefarnate.-There islimited evidence from one trial that deglycyrrhizinated

liquorice may be useful in obtaining symptomatic relief induodenal ulcer,27 but further data are required before thepreparation can be recommended for general use. As yet thereis no clear evidence on which to base an opinion of the valueof gefarnate.

Antipepsins and Antigastrins.-Initial experience with anti-pepsins was unfavourable, probably because they were found tobe bound and inactivated by food. More recently a syntheticsulphated polysaccharide SN 263 (Depepsen) has been describedwhich inhibits intraluminal peptic activity to a considerabledegree for 30 minutes to an hour after a single oral dose of05 g.42 There is some preliminary evidence suggesting thatthis may have a place in the treatment of duodenal as well asgastric ulcer.43At least one compound possessing antisecretory and anti-

gastrin properties has been described,44 but oral preparations foruse in man are not yet available.Oestrogens.-Though Truelove4 found stilboestrol to be an

effective treatment in duodenal ulcer in men, there is a highincidence of side-effects of mastitis and impotence. Oestro-genic preparations which are free of side-effects and of thera-peutic value have yet to be found, and hence drugs of this groupdo not seem to have any clear place in routine management.

Gastric Freezing and IrradiationThese forms of treatment are essentially based on the hope

that they will induce necrosis and hypoplasia, which is particu-larly prominent in mucosal secretory cells. The initial promiseof gastric freezing (carried out by circulating alcohol at -20°C. through an intragastric balloon connected to peroral can-nulae) has not been borne out by further experience, and adisturbing feature of the treatment has been the incidence ofcomplications-which include melaena, pyloric obstruction,oesophageal rupture or stricture, and gastric ulcer. Gastricacidity can be reduced to a variable and unpredictabledegree by x-ray treatment. The treatment involves a high doseof radiation, and in consequence there is a risk of late com-plications of leukaemia and perhaps cancer. Radiation therapymay have a limited place in the treatment of patients withintractable symptoms in whom surgery is for other reasonsinadvisable.

Surgical Treatment

J. L. DAWSON,* M.S., F.R.C.S.

British Medical Journal, 1969, 4, 102-105

Any current surgical journal is likely to contain several articleson the surgical treatment of peptic ulcer. Unfortunately almostall of these contributions represent the results of a particularoperation, applied to a selected group of patients, followed upby the surgeons who did the operation.The various operations are judged by (1) their mortality and

recurrent ulcer rates; (2) the presence of any postoperativegastrointestinal symptoms ; and (3) any late nutritional disturb-ances. The patient's own assessment of his condition providesmuch of the information on which a judgement of any pro-cedure is made. The only valid way in which various opera-tions can be compared is by a controlled trial with an objectivepostoperative assessment made by clinicians who have no know-ledge of the type of operation done. It may be fallacious tocompare results of surgery for duodenal ulcer in one part

of the world with another or even one part of a country withanother, because the incidence of the disease varies consider-ably-for example, the incidence of duodenal ulcer in the malepopulation is higher in Scotland than in the southeastern areaof England. The incidence of duodenal ulcer has risen sharplysince the beginning of this century, so that the results of surgeryin past decades are not necessarily valid today.The value of a properly controlled trial was demonstrated by

a recent series reported from Leeds,46 47 which showed that mostof the currently employed operations produced almost iden-tical results. The success of surgery depends less on the par-ticular operation chosen and much more on the patient chosenfor the operation. Patients with personality and mood dis-orders-especially those who are obsessional-have beenreported to do badly whatever the operation.'4' It has alsobeen found that the results of gastric surgery are poorer inwomen whatever the operation. '7"Consultant Surgeon, King's College Hospital, London.

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Peptic Ulcer-DawsonzGastric Secretion Tests

The augmented histamine test is widely employed to assessthe basal gastric secretion and the maximal acid secretion (whichis related to the size of secretory cell mass), but pentagastrinmay well supersede histamine in this test.5051 Secretion studiesare not diagnostic except in the rare Zollinger-Ellison syn-drome, in which the high levels of endogenous gastrin producea high basal secretion rate which is not much affected by furtherexogenous stimuli.Some surgeons have shown that surgery may be tailored to

an individual patient on the result of gastric secretion tests withvery satisfactory results,52 53but no properly controlled trialhas been done to establish that such methods produce superiorresults to carrying out the same operation on every patient.The insulin test is used mainly postoperatively as a test of

the completeness of vagal section,5 though bile reflux maymake interpretation of the results difficult. It has been sug-gested that the criteria for diagnosing incomplete vagotomy inmen should be different from those in women, as the formerhave a much higher secretory response to insulin.55 Morerecently it has been reported that if insulin tests are repeatedsome years after operation some patients who in the immediatepostoperative period had a negative response will then showa positive response.56

Operative Treatment of Duodenal Ulcer

Partial Gastrectomy

The mortality rate of this operation is very low in experthands, but in Britain as a whole it is higher than for vagotomyand a drainage procedure. The recurrent ulcer rate is low-somewhere between 2 and 5 % in most big series. The antrumand part of the body of the stomach is excised and the gastricremnant anastomosed to the first loop of jejunum, with or,A ithout a valve. Poor mixing of food and duodenal contentsis probably minimized by a short afferent loop, and somesurgeons advocate anastomosing the gastric remnant to thethird part of the duodenum.

In the years after gastrectomy reflux of jejunal contents pro-duces a progressive gastric atrophy, so that most stomal ulcersoccur within three years of operation.57 Decreased gastricsecretion leads to defective iron absorption, which if left un-

corrected is associated with further mucosal atrophy, andvitamin B12 deficiency may develop 10-15 years after oper-

ation.58 59 Loss of weight occurs in many patients, mainlybecause they eat less after operation. Disturbances of calciummetabolism were found in 28% of patients in one series.60 Inanother careful study of 1,228 patients the alkaline phosphatasewas found to be raised in 12 %, but only 3 % of women and1% of men were found to have osteomalacia.61Bilious vomiting is a persistent problem in a minority of

patients after gastrectomy, who seem to be intolerant of bile inthe gastric remnant. A Roux conversion may be necessary torelieve these symptoms.62 Almost all patients have symptoms

related to the loss of pyloric control of gastric emptying-thatis, early postcibal dumping-but these symptoms tend to regress

in the first few months after partial gastrectomy, and in onlya minority is this a real handicap.6'

Vagotomy and Drainage

Vagal section abolishes the appetite juice and interferes withthe gastric phase of secretion by decreasing the release of gastrinand the responsiveness of the secretory cell mass to endogenousgastrin. Gastric emptying is also delayed, so that a pyloro-plasty or a gastroenterostomy is usually added; a pyloromy-otomy has been tried but found to be unsatisfactory as a drain-age operation.6' Selective vagotomy-that is, a section of the

BRITISHMEDICAL JOURNAL 103

gastric branches of the vagus nerves-is advocated as a more

logical operation, for to reduce gastric secretion only the vagalsupply of the stomach has to be interrupted. Recently experi-mental evidence has suggested that truncal vagotomy mayinterfere with the inhibitory reflexes normally controllinggastric secretion, and is therefore a less effective procedure thanselective vagotomy in controlling gastric hypersecretion.6'Selective vagotomy is claimed to lead to a lower recurrentulcer rate; in part this probably reflects the fact that a morecareful dissection of the hiatus has been carried out,66 thoughothers have reported a higher incidence of incomplete vago-tomy.67The incidence of diarrhoea after truncal vagotomy has been

variously estimated, depending on the particular definition ofdiarrhoea, but most surgeons find that many patients regardsome looseness of the bowels as an added benefit of the oper-ation, and only a few patients are really troubled-probably1% or 2 %.46 47 68 69 The sponsors of selective vagotomy claimthat the incidence of postoperative diarrhoea is much reduced,70but no statistically significant difference was found in two recentseries.68 71 A practical point is that selective vagotomy takesmuch longer to perform, and in a fat patient may be a tediousand difficult operation. Recently selective vagotomy retainingthe antral nerve supply has been used in 15 patients without a

drainage procedure.72 Though the immediate results appearsatisfactory judgement must wait on long-term results.The mortality rate of vagotomy and pyloroplasty is lower

than for partial gastrectomy, but the recurrent ulcer rate isprobably higher-somewhere between 5 and 10%-though inexpert hands, when complete vagal section is more likely, it iscomparable with partial gastrectomy. The use of a nervestimulator has been advocated to ensure a complete vagotomy,73but has not found general acceptance probably because it re-quires some perseverance and attention to detail to achievesatisfactory results. Vagotomy combined with antrectomy hasa more profound effect on gastric secretion, and most seriesreport a very low recurrent ulcer rate.7' Undesirable post-operative sequelae might be expected to be more frequent whennerve section is added to gastric resection, but this was notfound by the only controlled trial of this operation.'6 '7

Gastrointestinal symptoms (nausea, vomiting, early post-cibal dumping, flatulence, etc.) occur with much the samefrequency after vagotomy and drainage operations as they doafter partial gastrectomy.46 47 68 In the present state of know-ledge the surgeon may reasonably employ any of the standardprocedures, remembering that the simplest will probably be thesafest for the patient.

Operative Treatment of Gastric UlcerThe most commonly employed operation, the Billroth I

partial gastrectomy, has a very low recurrent ulcer rate-lessthan 1 % .7 For high gastric ulcers, proved benign by histo-logical section, a Polya gastrectomy below the ulcer almostinvairiably produces healing.76 Recently some authors haveadvocated vagotomy and pyloroplasty for gastric ulcer. Pro-vided vagotomy is complete recurrence of gastric ulcer is lowin most series,77 78 but not all,79 and recently gastric ulcer was

reported as developing in 9 out of 500 patients who had under-gone vagotomy and pyloroplasty for duodenal ulcer.80 Never-theless, there is no large series with a sufficiently long follow-up to make any definite judgement. The interim results of a

controlled trial comparing vagotomy and pyloroplasty withBillroth 1 partial gastrectomy show that there was little tochoose between the early results but there was a slight bias infavour of partial gastrectomy.81A more serious criticism of not resecting a gastric ulcer is

that early carcinoma of the stomach may be wrongly treated in5-10% of patients or even higher.82 If vagotomy isemployeda careful four-quadrant biopsy of the ulcer and frozen-sectionexamination is essential at the time of operation.

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104 1 1 October 1969 Peptic Ulccr-Dawson BRIIrriSMEDICAL JOURNAL

Haematemesis and Melaena

The only real yardstick of success of different methods oftreating haematemesis and melaena is whether the mortalityrate of all admissions for gastroduodenal haemorrhage isinfluenced by a particular policy. Most centres employ a policyof selective surgical intervention-that is, selecting thosepatients who from experience are known to fare badly, andoperating on them as early as possible before they deterioratefrom repeated episodes of haemorrhage and resuscitation.

Haemorrhage from a gastric ulcer carries a serious prognosis,for even if the patient recovers from conservative managementthe likelihood of further trouble or serious symptoms is highover the next five years.83 Until recently the accepted oper-ative treatment for bleeding ulcer either gastric or duodenal waspartial gastrectomy. Recently vagotomy and pyloroplasty havebeen advocated, with underrunning of the bleeding vessels inthe ulcer base. Though the immediate mortality rate for thisoperation is probably lower than partial gastrectomy, it carriesthe real risk of a secondary haemorrhage 7-10 days later, prob-ably because nonabsorbable sutures are left in the ulcer base incontinuity with the bowel contents.84 There is no randomizedseries including all patients treated by all methods to showwhich surgical policy is better. Much depends on the operator'sexperience, as bleeding ulcers tend to be penetrating and tech-nically much more difficult to resect safely. Most publishedseries come from centres interested in the problem, and maynot reflect the overall situation over the country as a whole.

Perforation

Perforation of a peptic ulcer produces a chemical peritonitiswhich usually remains sterile for many hours, though finallysecondary bacterial contamination does occur.85 The surfacearea of the peritoneum is roughly that of the whole body, sothat the resulting peritoneal exudate may represent a consider-able fraction of the plasma volume. Hence replacement of thissequestered fluid by plasma expanders is a vital step in resus-citating the patient before operation. Provided that theoperator is experienced, perforated gastric ulcers are probablybest dealt with by immediate resection, as the result of simplesuture are usually poor owing to overlooked carcinoma,86reperforation, haemorrhage, and further subsequent severe ulcersymptoms, often with complications.8 7-89

Perforation occurring in a longstanding duodenal ulcer isprobably best dealt with by definitive operation, either partialgastrectomy87 88 or vagotomy and drainage.90 Those with nopast history are best treated by simple suture, as follow-upseries show that they have only a small chance of further symp-toms over the next ten years.5'

Pyloric Stenosis

The metabolic deficit in pyloric stenosis secondary to duo-denal ulceration must be corrected before any operative treat-ment is considered, and this may require considerable volumesof normal saline92 (but potassium deficits are probably muchsmaller than previously thought).93 Gastric lavage with a wide-bore tube, followed by nasogastric suction, frequently causesresolution of the retention gastritis and mucosal oedema, sothat the stomach can empty again; the final correction of thefluid balance and starvation is then achieved by oral fluids.Once the patient is fit operation should be undertaken, as

otherwise further episodes of pyloric obstruction and metabolicupset are almost inevitable. Duodenal ulcer may be treatedby any of the conventional operations. In a recent series of 21consecutive patients with pyloric obstruction treated by vag-otomy and drainage no patients developed prolonged gastricretention even though no nasogastric suction was used in theirpostoperative care.94

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J. J., and Langman, M. J. S., in Carbenoxolone Sodium: A Sym-posium, 1968, p. 209, edited by J. M. Robson and F. M. Sullivan.London, Butterworths.

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Lancet, 1964, 1, 734.61 Morgan, D. B., Paterson, C, R., Woods, C. G., Pulvertaft, C. N., and

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3 Burge, H., Vagotomy, 1964. London, Arnold.74 Thoroughman, J. C., Walker, L. G., and Raft, D., Surgery, Gyneco-

logy and Obstetrics, 1964, 119, 257.' Tanner, N. C., British Yournal of Surgery, 1964, 51, 5.76 Gammie, W. F. P., Proceedings of the Royal Society of Medicine,

1963, 56, 500.Farris, J. M., and Smith, G. K., Annals of Surgery, 1963, 158, 461.

78 McNeill, A. D., McAdam, W. A. F., and Hutchison, J. S. F., Surgery,Gynecology and Obstetrics, 1969, 128, 91.

9 Herrington, J. L., American Yournal of Surgery, 1967, 113, 11.80 Bank, S., Marks, I. N., Louw, J. H., and Brom, B., Gut, 1969, 10,460.

S1 Duthie, H. L., and Smith, G. H., Yournal of the Royal College ofSurgeons of Edinburgh, 1968, 13, 324.

82 Marshall, S. F., Jensen, A., and Davidson, C. M., American 7ournal ofSurgery, 1961, 101, 273.

" Avery-Jones, F. A., Gastroenterology, 1956, 30, 166.84 Carruthers, R. K., Giles, G. R., Clark, C. G., and Goligher, J. C.,British Medical Yournal, 1967, 1, 80.

85 Hamilton, J. E, and Harbrecht, P. J., Surgery, Gynecology and Ob-stetrics, 1967, 124, 61.

86 Antila, L. E., Acta Chirurgica Scandinavica, 1964, 128, 406.87 Jordan, G. L., Angel, R. T., and Debakey, M. E., Archives of Sur-gery, 1966, 92, 449.

88 Desmond, A. M., and Seargeant, P. W., British Yournal of Surgery,1957, 45, 283.

89 Gall, W. J., and Talbot, C. H., British Yournal of Surgery, 1964, 51,500.

90 Hinshaw, D. B., Pierandozzi, J. S., Thompson, R. J., and Carter, R.,American Journal of Surgery, 1968, 115, 173.

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92 Black, D. A. K., and Jepson, R. P., Quarterly Journal of Medicine,1954, 23, 367.

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Ellis, H., Starer, F., Venables, C., and Ware, C., Gut, 1966, 7, 671.

HOSPITAL TOPICS

Northwick Park Hospital and Clinical Research CentreOn 6 October a press conference was heldby the Medical Research Council and theNorth-west Metropolitan Regional HospitalBoard about progress at Northwick ParkHospital. Building of this project, whichcomprises Northwick Park Hospital andClinical Research Centre,' started in 1966and will not be fully completed before 1973.Nevertheless, in the next few weeks the firstof the buildings to reach completion will behanded over to the staff, and it is hoped toadmit the first patients by the middle of 1970.A joint statement issued by the M.R.C.

and the North-west Metropolitan RegionalHospital Board says that the hospital, whichwill eventually provide 815 beds, has twomain tasks-a " district " task and a" national " task. The former is to providea new general hospital service for the district,the population ultimately to be served beingestimated at 182,000, mainly from theboroughs of Harrow, Brent, and Ealing.The inpatient and outpatient services to beprovided include general medicine, surgery,orthopaedic surgery, gynaecology, maternity,psychological medicine, communicable dis-eases, the treatment of children and theelderly, and rehabilitation. Consultant out-patient services will also be provided for ear,nose, and throat surgery, ophthalmology, anddermatology, which will be supported by bedsfor inpatients at existing centres serving thatpart of the region. When the hospital isfully completed in 1973 there will be 630" district" beds with associated full accidentand outpatient services.The " national " task of the hospital will

be carried out in partnership with the ClinicalResearch Centre, and will contain 185 beds.The admission of patients to these beds andto associated clinics will be governed, thestatement says, by their need for morespecialized treatment or further diagnosticinvestigation. Some of these patients willalready have been admitted to " district "beds ; others will be referred directly from

the local community by their own doctors;some patients may be referred eventually fromother parts of the country.

Stages of DevelopmentThe hospital and research centre will be

complete in three distinct stages.Stage I (date of completion 1970).-There

will be an initial 204 "district" beds and60 " national " hospital beds, some outpatientclinics and operating-theatres, and fullysupporting diagnostic services. The buildingsfor the Clinical Research Centre will com-prise the central building of laboratories,special environment rooms, and radio-chemistry service.

Stage 2 (date of completion 1971).-Thetotal of hospital beds will be 323 " district "and 125 " national " beds. In this stage thematernity department (125 beds and a special-care baby unit) and the main operating-theatres will be added. The Clinical ResearchCentre buildings to be completed are furtherbuildings for laboratories.

Stage 3 (date of completion 1973).-Addi-tional beds will be provided to bring the totalsto 630 " district " beds, 185 " national "beds, as well as full accident and emergency,outpatient, and diagnostic and treatment ser-vices. At this stage additional buildings willalso be provided for the third general wardbuilding, psychological medicine department,and rehabilitation. At the Clinical ResearchCentre the Institute will be completed by theaddition of the third building for laboratories,and the provision of the large lecture halland library.

Clinical Research Centre

The press statement says that the mainbuildings of the Clinical Research Centre willconsist of a research institute, comprisingmany serviced modular laboratories, special

environment rooms and workshops, a library/lecture hall, and laboratories adjoining thewards of the hospital containing 185" national " beds. Nevertheless, the centrewill be so closely integrated with the hospitalthat much of its work will be carried outin special accommodation within the appro-priate hospital department. With the openingof the centre in 1970 in mind, the MedicalResearch Council has already appointed anumber of scientists and clinicians so thatdefinite research programmes would be set upwell in advance of the opening. The follow-ing research divisions (with the names of theirdirectors in brackets) have been establishedat the centre.

Division of anaesthesia (Professor J. F.NUNN).

Animal division (Dr. CHARLES COID).Division of bioengineering (Mr. H. S.

WOLFF).Division of cell pathology (Dr. A. C.

ALLISON).Division of clinical chemistry (Dr. F. L.

MITCHELL).Division of communicable diseases (Dr.

D. A. J. TYRRELL).Division of computing and statistics (Mr.

M. J. HEALY).Electron microscopy section (Dr. R.

DOURMASHKIN).Haematology section (Dr. I. CHANARIN).Division of immunology (Dr. GEOFFREY L.

ASHERSON).Division of low temperature biology (Dr.

A. U. SMITH).Division of metabolism (Professor G. M.

BULL, who is also Director of the ClinicalResearch Centre).

Radioisotopes division (Mr. N. VEALL).Radiology section (Dr. L. KREEL).Surgical division (Dr. EUGENE LANCE).

REFERENCE1 British Medical 7ournal, 1966, 1, 535.

on 19 August 2021 by guest. P

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.bmj.com

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r Med J: first published as 10.1136/bm

j.4.5675.102 on 11 October 1969. D

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