SPENCER AND WELBOURN: MILK INTOLERANCE 26 I

REFERENCES BARNES, R. (1948),3. Bone3t Surg., 30B, 234. BRAIN, LORD (1963)~ Br. m d . 3 . , I, 771. BRAIN, W. R., NORTHPIELD, D., and WILKINSON, M.

BRITISH ASSOCIATION OF PHYSICAL MEDICINE (1966)~

CAMPBELL, A. M. G., and PHILLIPS, D. G. (1960)~ Zbid., 2,

CLOWARD, R. B. (1962)~ Clin. Neurosurg., 8, 93. FRYKHOLM, R. (1951), Acta chir. scad . , 102, 10. HAFT, H., and SHENKIN, H. A. (1963), 3 . Am. med. Ass.,

(I952), Bruin, 75, 187.

Review-Br. med. J., I, 253.

481.

186, 312. JEFFERSON, M. (I95I), Lancet, I, 129. KHAN, E. A. (1947), SOC. Neurosurg., 4, 191. KUHLENDAHL, H., and KUNERT, W. (1954), Medizinische,

14, 449.

LEt& F., and TURNER, J. W. A. (1963)~ Br. med. J., 2,

O'CONNELL, J. E. A. (1956)~ Proc. R. Soc. Med., 49,

ODOM, G. L., FINNEY, W., and WOODHALL, B. (1999,

PALLIS, C., JONES, A. M., and SPILLANE, J. 0. (1934)~

RUSSELL, W. R. (1956)~ Proc. R. SOC. Med., 49,

STOLTMANN, H. F., and BLACKWOOD, W. (1964)~ Bruin,

1607.

202.

3. Am. med. Ass., 166, 23.

Brain, 77, 274.

198.

87, 45. STOOPS, W. L., and KING, R. B. (1965),J. Am. med. Ass.,

192. 281. VOGUE, V. (1957)~ Modern Trends in Neurology, 2nd series,

WILKINSON, M. (1964, Proc. R. SOC. Med., 57, 159. p. 259. London: Butterworths.

MILK INTOLERANCE FOLLOWING GASTRIC OPERATIONS WITH SPECIAL REFERENCE TO LACTASE DEFICIENCY*

BY J. SPENCER AND R. B. WELBOURN DBPARTMENT OF SURGERY, ROYAL POSTGRADUATE MBDICAL SCHOOL, LONDON

MANY patients with peptic ulcer drink large quantities of milk by way of therapy. However, many who undergo partial gastrectomy can tolerate milk no longer (van Goidsenhoven, 1946; Gaviser, 1948;. Bernay and Blanchet, 1950; Meurling, 1953). The mcidence of milk intolerance reported after gastrectomy varies from 17 per cent to 56 per cent. Most of the patients experience specific symptoms when they drink milk, while some simply acquire a distaste for it as a result of long usage.

The nature of this milk intolerance which is precipitated by an operation on the stomach has never been explained. However, lactase deficiency has been recognized recently as a not uncommon cause of milk intolerance in the general population. The enzyme lactase is present in the mucosal cells of the small intestine and is necessary for the hydrolysis of lactose to glucose and galactose, both of which are absorbed readily. Deficiency of lactase produces the clinical syndrome of ' hypolactasia', the main features of which are illustrated in Fig. I. Ingested lactose is not hydrolysed and cannot be absorbed readily, most of it remaining within the bowel, where it acts as an osmotic purge and causes colicky abdominal pain and diarrhoea. Some lactose may be fermented in the colon, giving rise to frothy, acid stools. A little lactose may be absorbed as disaccharide, but it cannot be metabolized as such and is excreted in the urine.

For several reasons it seemed possible that post- gastrectomy milk intolerance might be due to hypo- lactasia. First, there were several reports of a high incidence of lactase deficiency in patients with peptic ulcer and in those who had had gastric operations (Auricchio, Rubino, Tosi, Semenza, Landolt, Kistler, and Prader, 1963; Kojecky, 1964; Dunphy, Littman, Hammond, Forstner, Dahlgrist, and Crane, 1965). Secondly, lactase deficiency in adults was often an

Based on a communication to the Surgical Research Society in November, 1966. I7

acquired condition, the enzyme disappearing after a bowel upset such as an attack of gastro-enteritis. It seemed possible that gastrectomy might have a similar effect, possibly by altering the intestinal flora. Thirdly, there was a suggestion that operations such

Colic. diarrhoea '7 ,w'

I Ingested lactose 1 -Fermentation-> Frothy acid r t o O k

Lactoruria

FIG. I .-Hypolactasia.

as Polya gastrectomy (in which the duodenum was by- passed) could produce a 'functionaly hypolactasia. Thus Heilskow (1952) found that in calves and rabbits the concentration of lactase was highest in the duodenum and that it diminished distally along the small intestine. Gryboski, Thayer, Gryboski, Gabrielson, and Spiro (1963) demonstrated a minor defect of lactose absorption after ptrojejunostomy and postulated that this was due to the by-passing of the high concentration of laaase in the duodenum. At this time the distribution of lactase in the human small intestine was not known.

This paper reports the results of our own investiga- tions to discover what role, if any, lactase deficiency plays in milk intolerance after gastrectomy and other gastric operations.

INVESTIGATIONS AND METHODS Four separate investigations were undertaken :- I. In order to discover the incidence of milk intoler-

ance after gastric operations a questionnaire was sent

262

OPERATION CASES

Polya 62 Billroth I 30 Others 8

Total IOO

BRIT. J. SURG., 1968,

WITH SYMPTOMS

24 (39 per cent) 13 (43 per cent) z (25 per cent)

39 (39 per cent)

assay lactase activity at different levels. The aim was to discover whether in man the highest concentrations were found in the duodenum or in other parts of the small intestine. These biopsies were obtained either at operation, as an incidental procedure whenever small bowel was opened or transected, or by peroral biopsy by means of the Crosby biopsy capsule (Crosby and Kugler, 1957). Some jejunal biopsies were obtained by the passage of a biopsy capsule through a pylorotomy during operations for duodenal ulcer. Altogether 70 biopsies were studied. The enzyme assays were performed by the method of Burgess, Levin, Mahalanabis, and Tonge (1964, the results being expressed in units of activity per gramme of wet tissue. A unit is defined as that activity required to hydrolyse I micromole (pmol.) of substrate in I minute at 37" C .

3. Lactose-tolerance tests were performed to assess lactose absorption, the method used being similar to that for standard oral glucose-tolerance tests. Venous blood was obtained for blood glucose estimation before an oral load of 50 g. of lactose, and half-hourly thereafter for 2 hours. A rise of blood glucose of less than 20 mg. per IOO ml. under these circumstances is considered abnormal.

Tolerance tests were performed on 5 healthy control subjects and on 10 patients after partial gastrectomy. Of the latter, 6 patients had milk intolerance, and 4 did not. Six had undergone Billroth-I operations, and the other 4 operations of the Polya type. (There was no correlation between the type of gastrectomy and the presence or absence of milk intolerance.) For purposes of comparison the rise in blood glucose in the first 30 minutes after the lactose load was noted. 4. Lactose-barium meals were carried out on

patients who had undergone gastrectomy. This test is a sensitive method for the diagnosis of lactase deficiency, the results correlating well with intestinal enzyme levels (Laws and Neale, 1966; Laws, Spencer, and Neale, 1967). Liquid micropaque barium sulphate, to which 25 g. of lactose has been added, is administered by mouth and a single film of the abdomen is taken after I hour. The result is compared with a similar film taken on a separate occasion after micropaque alone. In normal subjects on difference is seen between the two films. When lactase is deficient, however, two changes are noted in

Vol. 55, No. 4, APRIL

the film taken after lactose. First, the contrast medium is diluted by an osmotic effect, giving rise to a quite characteristic appearance. Secondly, the intestinal transit is more rapid, the medium often reaching the colon within an hour. These changes are diagnostic of lactase deficiency.

We performed this test on 20 patients who had undergone gastrectomy, 12 of whom had milk intolerance. In 3 patients milk intolerance preceded the operation by many years and was accompanied by diarrhoea; in these patients hypolactasia was suspected on clinical grounds.

aodanun 1~ ,- I j u r y n Ileum

l 2 t OD

20

1 . 0 1 f FIG. 2.-Lactase activity in small intestine.

RESULTS I. Incidence of Milk Intolerance.-Thirty-nine

of IOO patients who had had gastric operations stated that milk produced symptoms (Table I ) . The incidences after the different types of operation were similar.

The symptoms produced by milk in these patients are listed in Table I I . Most complained of a feeling of

Table II.-SYMPTOMS PRODUCED BY MILK IN 39 PATIENTS AFTER GASTRIC OPERATIONS

Sympromr No. 01 Patienrr Fullness Nausea Vomiting 7 Diarrhoea 7 Pain 4 Cramps 4

;:

Table III.-LACTASE ACTIVITY IN THE SMALL INTESTINE

Comparing jejunum with ileum, 1-0.643; P '0.5. Comparing duodenum with jejunum and ileum together,

1 ~ 3 ' 5 0 2 ; 0'01 . P , O ' O O I .

epigastric fullness and many others of nausea. A few complained of vomiting, diarrhoea, or abdominal cramps.

2. Lactase Assays on Intestinal Mucosa.-The results of the enzyme assays are shown in Table III and Fig. 2. I t is seen that the activity varies widely in

SPENCER AND WELBOURN: MILK INTOLERANCE 263 DISCUSSION

In common with others we have found that a high proportion of patients who have undergone gastric

3. Lactose-tolerance Tests.-The results of operations are intolerant of milk. We have not found any evidence to support the view that deficiency of

different biopsies, but that it is much greater in the jejunum and ileum than in the duodenum. Very few ileal biopsies were studied.

these tests are seen in Fig. 3, and are analysed in

A CONlllOLS i GASTRECIOMV B POLVA v 8lLLRDlHI CASlRttlOMV C MILK I N I O L E U N I i MILK TOLERANT AFTER GASIREClOMV

120 so 90 0 30

M 1 NU 1 E S analyses.)

Table IV. Absorption of lactose is not diminished after partial gastrectomy. The mean rise in blood glucose was actually greater than in the controls,

8-No intolerance-All normal

9 normal

\ 3 ahnormal'

/ '\ /'

20 Patients

rz-Milk intolerant,

' Intolerance preceded operation. FIG. 4.-Lactose-barium meals after gastrectomy.

although in the small numbers studied the difference was not quite significant.

The type of anastomosis made little difference to the speed of absorption. Those who were intolerant of milk showed no evidence of impairment.

lactase is a common cause of this condition. ( I ) In patients with known hypolactasia milk causes abdominal colic and diarrhoea, while in the patients whom we studied it usually caused abdominal full- ness and nausea. (2 ) Lactose-tolerance tests revealed that lactose, like glucose, is handled at least as efficiently in those who have had gastric operations as in healthy controls. (3) Lactose-barium meal examina- tions revealed evidence of hypolactasia in 3 patients only, and in each of these the symptoms had preceded the gastric operation by several years.

Further evidence against the view that the by- passing of the duodenum by a gastrojejunal anasto- mosis caused functional hypolactasia was provided by two further observations. (I) The incidence of milk tolerance was similar after operations of the Polya and of the Billroth-I types. ( 2 ) Lactase activity was

Table I V.-RESULTS OF LACTOSE TOLERANCE TESTS AFTER GASTRECTOMY

A. Healthy controls 1 versus

Postnastrectomv

1 81.2)1=1.36 1 z ; , ~ } t = 1.94

71'2 P>01 0 1 > P > O . O S

B. Postgastrectomy 86.7

Billroth I

C. Postgastrectomy: Milk intolerant I I 72.3)i-0.28 1 66.3 } t - O ~ I I

Milk tolerant 69.5 P>o.l 69.25 P.>o.g versus

4. Lactose-barium Meals.-The results of these considerably higher in the jejunum and ileum than in tests are seen in Fig. 4. Three of the 20 patients gave the duodenum. This had been suggested by early abnormal results, indicative of lactase deficiency. In absorption studies (Borgstrom, Lundh, and Sjovall, all of them the milk intolerance had preceded opera- 19.(7), and had been confirmed recently by enzyme tion by several years. The 9 other patients whose assays in the human foetus and newborn (Auricchio, milk intolerance had developed after gastrectomy gave Rubino, and Miirset, 1965) and in the adult (Auricchio normal results. and others, 1963; Sheehy and Anderson, 1965). It

264 BRIT. J. SURG., 1968,

seems clear from these studies and from our own that jejunal lactase is quite adequate for lactose absorption.

Several factors which may be involved in milk intolerance have been postulated (Stammers and Williams, 1963)~ but they await further investigation.

SUMMARY A survey of 100 patients after gastric operations

revealed that 39 per cent suffered from milk intoler- ance. Attempts were made to determine whether lactase deficiency, a not uncommon cause of milk intolerance in the general population, was responsible.

Assay of lactase in biopsies of small intestinal mucosa showed highest concentrations of the enzyme in the jejunum and ileum, and lower levels in the duodenum.

Lactose tolerance tests showed rapid lactose absorption in patients after gastrectomy, even in the presence of milk intolerance. Absorption was similar after Polya and Billroth-I operations.

Lactose-barium meals in 20 patients after gastrec- tomy did not reveal any lactase deficiency which had been induced by operation.

I t is concluded that lactase deficiency does not play an important part in the production of the milk intolerance which follows gastrectomy.

Acknowledgements.-We are grateful to Dr. J. Laws for performing the lactose meals and to Dr. J. Stevens and Miss G. Faulkner for their help with the lactase assays. We wish to thank the Department of Medical Illustration for the illustrations and Miss F. Gillingham for secretarial assi, Ftance.

Vol. 55, No. 4, APRIL

REFERENCES AURICCHIO, S., RUBINO, A., and MURSET, G. (1965),

Paediatrics, Springfield, 35, 944. ---- TOSI, R., SEMENZA, G., LANDOLT, M., KISTLER, H., and PRADER, A. (1963), Enzym. biol. clin.,

BERNAY, P., and BLANCHET, H. (195o),J. M i d . Lyon, 773, 615.

BORGSTROM, B., LUNDH, G., and SJOVALL, J. (I957), .7. clin. Invest., 36, 1521.

BURGESS, E. A., LEVIN, B., MAHALANABIS, D., and TONGE, R. E. (1964)~ A r c h Dis. Childh., 39, 431.

CROSBY, W. H., and KUGLER, H. W. (1957), A m . J . dig. Dis., 2, 236.

DUNPHY, J. V., LITTMAN, A., HAMMOND, J. B., FORSTNER, G., DAHLGRIST, A., and CRANE, R. K. (1965)~ Gastro- enterology, 49, 12.

GAVISER, D. (1948), Surgery, St Louis, 24, 873. GRYBOSKI, J. D., THAYER, W. R., GRYBOSKI, W. A.,

GABRIELSON, I. W., and SPIRO, H. M. (1963), New Engl. J . Med., 260, 78.

HEILSKOW, N. S. C. (I952), Acta physiol. scand., 24, 84.

KOJECKY, Z. (1964)~ personal communication to LITTMAN, A., and HAMMOND, J. B. (1969, Gastroenterology, 40, 237.

LAWS, J. W., and NEALE, G. (1966), Lancet, 2, 139. -- SPENCER, J., and NEALE, G. (1967)~ Br. J . Radiol.,

MEURLING, S . (1953), Acta SOC. Med. upsal., 59, Suppl. 3.

SHEEHY, T. W., and ANDERSON, P. (1969, Lancet, 2, I. STAMMERS, F. A. R., and WILLIAMS, J. A. (1963)~ Partial

Gastrectomy, Complications and Metabolic Consequences. London: Butterworths.

VAN GOIDSENHOVEN, F. (1946), Acta gasiro-enter. belg., 9, 254.

3J 193.

40, 594.

JEJUNAL DIVERTICULA IN THE PRESENCE OF SMALL-BOWEL OBSTRUCTION

BY D. J. PINTO IPSWICH A N D EAST SUPPOLK HOSPITAL

THE causal factors in the aetiology of jejunal diver- ticula have yet to be established. The work of some investigators (Lewis and Thyng, 1908) show that they are congenital in origin. Others have suggested that it is an acquired condition (Cooke, Cox, Fone, Meynell, and Gaddie, 1963) and part of a generalized intestinal disease (McCollum, 1959), probably due to ‘organic decline’ in predisposed subjects (Dubarry, Tounerie, and Dubarry, 1960).

Only 2 cases have been reported in the literature where jejunal diverticula were noted in the presence of a mechanical obstruction to the small bowel (Watson, 1924; Christ, 193z), and in these it was due to an enterolith either in a diverticulum or in the lumen of the small bowel.

Three cases in which obstruction of the small bowel may have resulted in jejunal diverticula formation are described.

CASE REPORTS Case I.-M. G., a woman, aged 67, had suffered with

coeliac disease from childhood. In November, 1950, she was admitted with iron-deficiency anaemia, diarrhoea, and oedema of the legs. Small-bowel meal (non-flocculating

barium) at the time revealed ‘gross flocculation and mucosal thickening of jejunum and upper ileum’. There was no radiological evidence of diverticula. She responded satisfactorily to medical treatment and was discharged 2 weeks later. In 1952 she was readmitted with a history of loss in

weight, the passage of frequent loose, fatty stools, and considerable abdominal distension. A small meal now revealed ‘a marked hold-up in the passage of meal through the lower ileum, with cpnsiderable dilatation of coils of small bowel proximally . No actual stricture was seen. Occult-blood test in stools were strongly positive on this occasion, and because of persistent blood-loss in the stools a laparotomy was performed. Crohn’s disease was found involving the ileum 3-18 in. from the ileocaecal valve. The bowel wall proximal to this was hypertrophied and dilated. The jejunum was studded with diverticula on its mesenteric aspect. The involved segment of Crohn’s disease was excised and an end-to-end anastomosis performed. Her postoperative convalescence was uneventful. Sections of the excised ileum confirmed the laparotomy findings. (This patient has been the subject of a previous report by Paulley, 1954.)

Case 2.-R. G., a woman, aged 73, was admitted with intestinal obstruction. Two years previously she had been investigated for change in bowel habit and a barium enema