Br. J. Surg. Vol. 69 (1982) 26-28 Printed in Great Britain

Hospital admissions for acute cholecystitis: changes in the age and sex distribution in Oxford in the post-war period

Admissions ,for acute cholecystitis to the Radclvfe Injirmary, Oxjord, during the period 1974-1978 have been reviewed and compared with jigures previously published for the period 1953- I962 (I).

There was a small overall increase in the annual rate of female admissions for acute cholecystitis between the two periods and this increase can be accounted jor bj' population changes in all age groups above the age of 40 years. However, there was a significant increase in the admission rate of women under the age of 40 which could not be accounted.for bqi changes in population alone. This apparent increase in acute gallbladder diseuse in young women coincides with the growth between 1960 and 1970 of the number of women taking oral contraceptives, and is further evidence of a causal relationship between the use of the contraceptive pill and the development of gallstones. Women taking oral contraceptive steroids had a higher rate o j common bile duct exploration and of sphincteroplusty than did those not taking oral contraceptives.

The annual rate of male admissions almost doubled between the two periods and this increase cannot be accounted fo r by population changes. There has also been a virtual disappearance of acute cholecystitis in children over the same time.

ANDREW MITCHELL AND PETER J. MORRIS

Nufield Department of Surgery. Unlverslty of

OX3 9DU Oxford, John Radcliffe Hospital, Oxford

Essenhigh ( I ) reviewed 429 consecutive admissions for acute cholecystitis to the Radcliffe Infirmary, Oxford, during the period 1953-1962. The female : male ratio of these admissions was 2.4: 1. Both male and female groups showed a unimodal age distribution with a peak incidence between 60 and 80 years of age (Fig. 1 ).

We have reviewed all admissions for acute cholecvstitis to the Radcliffe Infirmary during the period 1974-19f8 to assess whether the presentation and management of this condition has changed since Essenhigh's study some 20 years earlier. In this paper, we discuss the changes in age and sex distribution of admissions for acute cholecystitis in Oxford over the period spanned by the two studies.

Patients and methods The case notes of all patients admitted to the Radcliffe Infirmary, Oxford, with a diagnosis of acute cholecystitis. o r one of its compli- cations, during the 5 years from 1974 to 1978 inclusive were reviewed. Patients were included in the study if they were recorded as having tenderness and guarding in the right hypochondrium. a pyrexia of 37~5°C or more and an illness lasting more than 24 hours, or, alternatively, if the diagnosis of acute cholecystitis was made or confirmed at laparotomy. Over 800 case notes with an International Classification of Diseases (8th revision) code 575 (cholecystitis and cholangitis without mention of calculi) were examined and 304 of these patients met the above criteria for inclusion in the analysis. An examination of all case notes with ICD codes 574 (cholelithiasis), 576 (other diseases of the biliary tree) and 577 (pancreatitis) for the year 1974 gave no extra yield of cases, and case notes thus coded during the subsequent years covered by the study were not examined. A similarly thorough search of the case records and the same clinical criteria had been employed by Essenhigh in selecting cases for the 1953- 1962 study except that a fever of 37.5 'C was not made an absolute requirement for inclusion (Essenhigh, personal communication).

Ninety-seven items of information on the presentation, management and outcome were recorded for each of these 304 cases and stored on a computer file. Women were recorded as takers (past or present) or non- takers of the contraceptive pill where this had been clearly noted. If no note had been made they were placed in a 'not known' category. Neither the duration of oral contraceptive use nor the oestrogen contcnt of the oral contraceptive preparations used had been con- sistently recorded in the case notes.

The RadcliKe Infirmary was the major teaching hospital for the Oxford University Medical School and was the only hospital in the city to which acute surgical cases were admitted during this and the previous review periods. Consequently. most of these patients' records contained detailed admission notes by students and by house officers for each admission. Many had more than one admission and this increased the yield of information.

Population figures for the relevant catchment area of the hospital. broken down by age and sex, were obtained from the County Reports of the 1951 and 1971 censuses. This catchment area has shown only minor boundary changes during the past 30 years and its population increased from 293000 in 1951 to 399000 in 1971.

Results The overall average admission rate for patients with acute cholecystitis was 61 per year in the period 1974-1978 compared with 43 per year in the period 1953-1962. The fema1e:male ratio was 1.7: 1 for 1974-1978 compared with 2.4: 1 for 1953- 1962.

The annual admission rate by age for both review periods is shown in Fig. la (male) and Fig. l b (female). For the purpose of comparison, the admission rates shown in these figures for the period 1974- 1978 have been corrected for population changes within the catchment area of the Radcliffe Infirmary between 1951 and 1971 (the closest census years to the beginning of each review period). This has been done by scaling down the annual admission rates for 1974- 1978 in proportion to the population changes in each age and sex group. The corrected and uncorrected annual admission rates are plotted separately in Figs. l u and b.

Fig. la shows the striking increase in the annual rate of male admissions for acute cholecystitis between the two review periods. When correction is made for population changes, this increase is seen to be confined to the 40-70 year age range and to be greatest for men in their sixth decade. This increase has resulted in a shift of the peak admission age for male patients from the 70-80 year age group to the 50-60 year age group.

The female age distribution, which was similarly unimodal for 1953-1962, shows an early peak in the 20-40 year age group for 1974-1978 (Fig. Ib). The proportion of female

Hospital admission for acute cholecystitis 27

- 1953-62 - 1974-78

1974-78 (population E l corrected)

.-

2 2 -

- 1953-62 1974-: 1974--’

.- c

10 20 30 40 50 60 70 80 90 100 Age Age

Fig. 1. 1974- 1978 actual admission rates corrected for the increrise in population between the review periods.

Male ( a ) and,femule ( b ) admissions per annum ,for a w t e cholecystilis related to patient age. ‘Populution corrected’ plots ure tlw

patients under the age of 40 rose from 12.7 per cent in the earlier period to 25.3 per cent in the later period (1’ = 11.97; P < 0.00 I), whilst the proportion of male patients under the age of 40 years fell from 164 per cent in the earlier period to 5.3 per cent in the later period ( x 2 = 6.59; P<0 .01) . When correction is made for population changes, there is also an apparent fall in the annual admission rate of women in their seventh decade, but for all other age groups the admission rates remain virtually unchanged.

Information on the use of oral contraceptives was not available for 31 per cent of women under 40 years, but 50 per cent of women in this age group were recorded as ‘takers’ and 19 per cent as ‘non-takers’. As might be expected, the highest proportion of oral contraceptive users (74 per cent) was seen in women in their third decade. No woman over the age of 40 years was recorded as having taken oral contraceptives.

There was a high rate of common bile duct exploration in oral contraceptive users (Table r). All 14 ‘non-takers’ under 40 years who came to surgery had a cholecystectomy alone, whereas of the 19 ‘takers’ in the same age group, 9 (47 per cent) required exploration of the common bile duct and 3 of these patients also needed a sphincteroplasty. This group of 19 oral contraceptive users also contains 3 patients who were sub- sequently shown to have residual common bile duct stones and a fourth patient in whom a residual stone was strongly suspected but never proved. These 3 oral contraceptive users with residual stones represent 50 per cent of all patients with proved residual common bile duct stones in the 1974-1978 series.

Between 1953 and 1962 15 patients under the age of 20 years were admitted with acute cholecystitis to the Radcliffe Infirmary. Five of these patients were under the age of 10 years. In the 1974- 1978 period only 3 patients with acute cholecystitis were under 20 years and all 3 were girls in their late teens.

Discussion Our results show three significant changes in the age and sex distribution of patients admitted to hospital in Oxford for acute cholecystitis between the periods 1953- 1962 and 1974- 1978.

First, there has been a striking increase in the annual rate of male admissions. This increase is greatest for men in their fifth, sixth and sevenl.h decades. The admission rate in this age range has doubled between the 1950s and the 1970s, even when allowance is made for increases in the population at risk. The female : male ratio of hospital admissions for acute cholecystitis has consequently fallen from 2.4 : 1 to 1.7 : 1 despite a modest increase in the rate of female admissions. Leissner et al. (2) reported a similar fall in the female :male ratio of patients with surgically confirmed gallbladder disease in the two Swedish cities of Falun and Gothenberg between 1961 and 1971. The female preponderance dropped from 1.55 : 1 to 1 I6 : 1 in Gothenberg anti from 1.73 : 1 to 1.47 : 1 overall during the 10- year period, despite an apparent increase in gallbladder disease in young women.

Table I: OF AGE

OPERATIONS ON WOMEN UNDER 40 YEARS

~ ~

Oral Contraceptive pill Takers Non-taker

No n o No. O 0

~~ ~~ -~

Cholecystectomy 10 52 14 100 Cholecystectomy and 6 32 ~

Cholecystectomy, ECBD 3 16 -

Total 19 14

exploration of CBD

dnd sphincteroplasty

Published studies of acute cholecystitis report female : male ratios of between 1 1 : 1 (3) and 7 : 1 (4). These variations in the reported sex incidence of acute gallbladder disease may be due in part to differences in the age and sex distribution of the populations at risk from centre to centre and from time to time. In the catchment area of the Radcliffe Infirmary between 195 I and 1971 there was an overall population increase of 36 per cent but the alterations in age and sex distribution which occurred do not account for the different changes seen in male and female hospital admission rates for acute cholecystitis.

A significant change in hospital admission rates for acute cholecystitis does not necessarily indicate a corresponding change in the incidence of acute cholecystitis in the community, since a proportion of those patients who have clinically mild inflammatory episodes will be nursed at home. This proportion may vary from time to time because of changing social and economic factors. For example, a man with mild acute chole- cystitis is perhaps more likely to be referred to hospital if his wife goes out to work than if she is free to nurse him at home. Thus, the increase in the annual male admission rate to hospital for acute cholecystitis might be related in part to an increase in the proportion of working wives in the community.

A further possibility is that a proportion of men who had acute cholecystitis during the earlier period were nursed at home with a presumptive diagnosis of duodenal ulceration and that, as this latter condition has become less common and less severe in its clinical manifestations (9, the correct diagnosis of acute gallbladder disease has been made more readily. The decline in the incidence of perforated duodenal ulcer in Oxford between 1957 and 1963, reported by Sanders (6), is in keeping with this suggestion.

Dietary changes could be responsible for changing patterns of biliary disease but, although there have been some marked alterations in diet during the post-war period, figures for the consumption of individual commodities are not recorded separately for men and for women. No compelling explanation can be offered, on the basis of the present data. for the dramatic increase shown in the annuaf admission rate of middle-aged men with acute cholecystitis.

28

Secondly, there has been a highly significant increase in the proportion of female patients under the age of 40 years admitted with acute cholecystitis. This increase cannot be accounted for by population changes.

There is now considerable evidence that the use of oral contraceptive steroids results in an increased risk or chole- lithiasis. An association between the use of oral contraceptives and hospital admissions for gallbladder disease was first reported in 1973 (7). Vessey et al. (8), in a long term follow-up of contraceptive users, confirmed this association. Leissner et al. (2) found an increase in the cholecystectomy rate between 1961 and 1971 in young Swedish women but not in young men. Bennion et al. (9) recorded a consistent increase in cholesterol concentration in the bile of women taking oral contraceptives, thus providing a biochemical basis for the increased incidence of gallstones.

It might be assumed that an increased incidence of gallstones in young women. secondary to the increasing use of oral contraceptives, would lead to a corresponding increase in the incidence of acute cholecystitis in this group. This has not yet been confirmed, since previous studies (8,IO). in order to simplify data collection, have grouped patients according to their JCD coding which does not distinguish acute from chronic cholecystitis or these from cholangitis. We found that patients who came to cholecystectomy for gallstones, without any history of an acute inflammatory episode, had often been given an ICD code 575 because histology of the excised gallbladder had been reported as showing ‘chronic cholecystitis’.

Our finding of an increased admission rate for acute cholecystitis amongst young women following the widespread adoption of oral contraception in the 1960s lends support to the existing evidence for an association between oral contra- ceptive use and cholelithiasis. It further suggests that the lag period between the formation of stones and an acute inflam- matory episode is often short.

The high incidence of common bile duct exploration, sphinc- teroplasty and residual common bile duct stones amongst the oral contraceptive takers suggests a tendency for these patients to form multiple small stones which easily migrate into the bile ducts. This is disturbing because of the higher morbidity and mortality associated with common bile duct exploration (1 1).

The third significant finding is that no children were admitted to the Radcliffe Infirmary with acute cholecystitis during the period 1974-1978, whereas 20 years previously childhood cholecystitis was not uncommon in Oxford (1). This change may be related to the cause of acute cholecystitis in childhood. Most authors report a low incidence of gallstones in association with acute cholecystitis when it occurs in child- hood, up to 81 per cent of cases being acalculous (12). The aetiology of acalculous cholecystitis in children is a matter of

A. Mitchell and P. J. Morris

controversy but systemic bacterial infections have been con- sidered by many to be the underlying cause. Bonta and Lovingood (1 3) noted a fall in the number of reported cases between the 1940s and the 1950s. They suggested that acute cholecystitis in children was a complication of preceding infection elsewhere and that the use of antimicrobial agents had reduced the frequency of this complication. The introduction of more powerful antibiotics, and their widespread use for minor infections, may have been responsible for the decline in childhood cholecystitis in Oxford over the past 20 years.

Acknowledgements We wish to thank the consultant staff of the Radcliffe Infirmary for their permission to study the records of patients admittcd under their care, Professor Martin Vessey for advice on the presentation of this paper and Mr Iain Kidson, FRCS, for help with computer handling of the data. Population figures for the acute specialties’ catchment area of the Oxford Hospitals were kindly prepared by Mrs Sheila Rogers of the Statistics Department, Oxford Regional Health Authority.

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Essenhigh D. M.: Management of acute cholecystitis. Br. J . Sitrg. 1966; 53: 1032-8. Leissner K. H.. Wedel H. and Shersten T.: Comuarison between the use of oral contraceptives and the inciden’ce of surgically confirmed gallstone disease. Seand. J . Gustroenterol. 1977; 12: 893-6. Van dcr Linden W. and Sunzel H.: Early versus delayed operation for acute cholecystitis. Am. J . Surg. 1970; 120: 7-13. McArthur P., Cuschieri A,, Sells R. A. et a].: Controlled clinical trial comparing early with interval cholecystectomy for acute cholecystitis. Br. J . Surg. 1975; 62: 850-2. Smith M. P.: Decline in duodenal ulcer surgery. J A M A 1977; 237: 987-8. Sanders R.: Incidence of perforated gastric and duodenal ulcer in Oxford. Gut 1967; 8: 58-63. Boston Collaborative Drug Surveillance Programme: Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease, and breast tumours. Lancet 1973; 1: 1399-404. Vessey M., Doll R., Peto R et al.: A long-term follow-up study of women using different methods of contraception-an interim report. J . Biosoc. Sci. 1976; 8: 373-427. Bennion L. J., Ginsberg R. L., Garnick M. B. et al.: Effects of oral contraceptives on the gallbladder bile of normal women. N. Engi. J. Med. 1976: 294: 189-92. Royal College of General Practitioners: Oral Conrruceptives and Health. Tunbridge Wells: Pitman Medical. 1974. Bishop Y. M. M. and Mosteller F.: Smoothed contingency table analysis. In: Bunker J . P. (ed.): National Hulothunr Study. Bethesda, Md.: National Institutes of Health, 1969: 259-60. Pieretti R.. Auldist A. W. and Stephens C. A,: Acute cholecystitis in children. Surg. Gynccol. Obsret. 1975; 140: 16-18. Bonta J. A. and Lovingood C . G.: Acute cholecystitis in child- hood. Surgerj. 1952; 31: 309-11.

Paper accepted 4 Junc 1981.

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