The burden of gallstone disease in Europe

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1 Aliment Pharmacol Ther 2003; 18 (Suppl. 3): doi: /j x The burden of gallstone disease in Europe R. AERTS & F. PENNINCKX Department of Abdominal Surgery, University Clinic Gasthuisberg, Leuven, Belgium INTRODUCTION Gallstones are common and may be associated with recurrent bouts of upper abdominal pain, often with nausea and or vomiting. The frequency of gallstones increases with age, female gender and obesity. The majority of gallstones are asymptomatic. Despite this, gallstone disease is the most common abdominal condition for which patients are admitted to hospital in developed countries. 1 Medical presentations usually result from complications or through routine investigations for abdominal pain. Complications attributable to gallstones include chronic inflammation infection of the gallbladder (cholecystitis), abscess formation, and biliary obstruction, which can result in jaundice or a severe ascending infection of the bile ducts and acute pancreatitis. Most uncomplicated cases that present to clinicians can be effectively treated by keyhole surgery (laparoscopic cholecystectomy), but patients with more severe disease often require multidisciplinary management, involving radiological, gastroenterological and surgical services. Medical management other than the use of antibiotics to treat infection are infrequently employed due to the poor long-term response rates. Although now uncommon, severe cases can be associated with significant morbidity and mortality, particularly in frail or elderly patients. 2 To determine the recent prevalence and incidence rates of gallstones, their complications and surgical treatments in Europe, a MedLine database search from 1989 to 2003 was performed. PREVALENCE AND INCIDENCE OF GALLSTONE DISEASE Cholelithiasis is a common disease in most developed countries and a frequent cause of abdominal surgery. Correspondence: Dr F. Penninckx, Department of Abdominal Surgery, University Clinic Gasthuisberg, Herestraat 49, Leuven B-3000, Belgium freddy.penninckx@uz.kuleuven.ac.be For many years, estimates of the frequency of gallstones have been made from necropsy studies or studies of clinically diagnosed cases of gallstones, which do not represent the true prevalence in the general population. As most gallstones stay asymptomatic during a lifetime, clinically diagnosed cases of gallstones represent less than half of the overall prevalence. Although autopsy studies have many drawbacks, they have shown that the prevalence of gallstone disease increases with age and is higher in women than in men. After standardization for age and sex, these studies also show large differences between countries in Europe (Table 1; according to Acalovschi et al. 3 ). Some authors have shown that autopsy data are comparable to ultrasonographic surveys in the same population when standardized for age and sex. 4 6 Necropsy data also enable definition of time trends in gallstone prevalence. In a retrospective study from a large town in Romania, a significant increase was found over a 100-year interval. 7 More recently, cross-sectional screening of the whole population for gallstone disease has become possible by the use of real-time ultrasonography, which is a noninvasive technique, and not only allows the evaluation of prevalence, but can also be repeated to give the gallstone incidence. Accurate data for both prevalence and incidence of gallstone disease are not available for every country in Europe; most studies come from Italy and Scandinavia. The median prevalence of gallstone disease in the largest population surveys in Europe ranges from 5.9 to 21.9%, 8 20 with the highest rates seen in Norway (21.9%) and former East Germany (19.7%), and the lowest rates in Italy (Chianciano 5.9% and Sirmione 6.9%) (Table 2). Most surveys show that the prevalence of gallstones increases with age. 12, 13, 16 Prevalence is also higher in 12, 13, 15, 16 women than in men. Prevalences of gallstone disease in men and women according to age are shown in Figures 1 and 2. Ó 2003 Blackwell Publishing Ltd 49

2 50 R. AERTS & F. PENNINCKX Table 1. Age-standardized necropsy prevalence of gallstones in Europe 3 Country Males Females Germany Czechoslovakia Sweden Scotland England Denmark Finland Ireland Norway Romania Greece The few prospective ultrasound surveys in Europe that have assessed gallstone incidence show an incidence < persons per year ( % in Italy, 0.93% in Denmark). 15, Incidence rates also increase with age and are higher in women than in men (southern Italy: 0.32 and 0.48% per year in year-old men and women, respectively; 1.66 and 1.86% per year in the year-old age group, mean 0.71% in men and 0.91% in women; 15 Denmark: 0.06 and 0.28% per year in 30-year-old men and women, respectively; 0.66 and 0.74% per year in the 60-yearold age group). 22 Incidences can also be calculated from prevalence data, and these show comparable results. 26 Incidence studies have shown that gallstones can also disappear due to dissolution or spontaneous passage in 4.5% of patients over 5 years. 22 Incidence rates are also Figure 1. Prevalence of gallstone disease in Europe: 8 12, 14, 17, men. time-dependent; in the Sirmione study, the gallstone incidence rate during was 0.60% per year and during was 0.34% per year, indicating a declining incidence in this town in northern Italy. 23 THE NATURAL HISTORY OF ASYMPTOMATIC AND SYMPTOMATIC CHOLELITHIASIS The large majority of gallstones remain asymptomatic during a lifetime. Several ultrasonographic population Table 2. Prevalence of gallstones in cross sectional ultrasound surveys in Europe City Country Number Males Females Global Ref. no Schwedt Neuruppin Norway [8] Neuruppin East Germany [9] Stockholm Sweden [10] Vidauban France [11] MICOL Italy [12] Poland [in 3] Sirmione Italy [13] Timisoara Romania [in 3] Guadalajara Spain [14] Castellana Italy [15] Rome Italy [16, 17] Copenhagen Denmark [18] Romerstein Germany [19] Bristol England [20] Chianciano Italy [in 3]

3 THE BURDEN OF GALLSTONE DISEASE IN EUROPE 51 eventually to undergo cholecystectomy. Of the women with initially asymptomatic gallstones, 15.4% experienced at least one episode of biliary pain, 23.1% underwent elective cholecystectomy and 61.5% remained asymptomatic. 25 The risk of developing an acute biliary complication (acute cholecystitis, acute pancreatitis, jaundice) was found to be 3.1% per year, much higher than the 3.0% risk over 10 years in the GREPCO study. In a prospective follow-up study in 153 patients with electively diagnosed symptomatic cholelithiasis, 28 a history of gallstone complication predicted further complications during follow-up Although an acute gallstone complication occurred in 15% of patients during the follow-up period (acute cholecystitis 18, acute pancreatitis 2 and jaundice 3), the authors concluded that an expectant management of patients with electively diagnosed cholelithiasis may be justified, but that young age and frequent attacks of biliary pain predicted the need for gallstone surgery. Figure 2. Prevalence of gallstone disease in Europe: 8 14, 16, 18, 19, 21 women. surveys have shown that severe pain in the right upper quadrant lasting for more than 30 min is the most typical symptom suggesting gallstone disease, but this is found in only a minority of people with gallstone disease. 8, 12, 13, 18, 20 Women are predisposed to having symptoms more often than men. Gallstones form earlier in life in women, who may have more severe 10, 11, 14, 20 symptoms. The GREPCO group studied the natural history of gallstones over a period of 10 years in an Italian population sample screened from 1981 to In the initially asymptomatic group (n ¼ 118), the cumulative probability of developing biliary colic was 11.9 ± 3.0 (mean % ± SE) at 2 years, 16.5 ± 3.5 at 4 years, and 25.8 ± 4.6 at 10 years. None of the variables associated with the occurrence of gallstones was found to modify the risk of developing biliary colic. The cumulative probability of developing complications after 10 years was 3.0 ± 1.8 in the initially asymptomatic group and 6.5 ± 4.4 in the initially symptomatic group (n ¼ 33). The difference was not statistically significant. It was concluded that the natural history of gallstones is less benign than had been generally considered. In a 10-year longitudinal follow-up study of a random sample of 426 women in a rural population in the south of Rome, a remarkable proportion of asymptomatic patients were found to become symptomatic and CHOLECYSTECTOMY RATES Reported data from Scotland The total cholecystectomy rate (open and laparoscopic) in Scotland was found to have increased by 18.7% from 1989 to 1993 with the advent of laparoscopic cholecystectomy. The largest increase (25%) was observed in the year-old age group, but was also particularly evident in elderly patients over 65 years (19%). In addition, symptomatic patients were more likely to undergo laparoscopic cholecystectomy if they were young and female. 29 In another study, the cholecystectomy rate in 51 Scottish public sector hospitals between January 1981 and June 1999 has been analysed and age-standardized with the European standard population. 30 The age-standardized cholecystectomy rate declined from 95 to 83 procedures per population in the decade before the introduction of laparoscopic cholecystectomy in The cholecystectomy rate increased from 83 to 98 per between 1990 and 1993, and remained at about that level until 1999, when it reached 100. The increases varied greatly by age and sex. The greatest increase was in women (17%), particularly those aged years (34%). In contrast, the overall increase in men was modest, 3%. It was also observed that emergency admissions slightly decreased from 20% in the 1980s to 17% in The fact that the cholecystectomy

4 52 R. AERTS & F. PENNINCKX rate did not fall back to the levels of the 1980s was attributed to either a widening of the indications for surgery, or to performing inappropriate surgery for asymptomatic gallstones found incidentally. Scandinavian countries Cholecystectomy rates were found to differ significantly between Scandinavian countries both before and after the introduction of laparoscopic cholecystectomy. 31 In Stockholm county, the cholecystectomy rate slowly increased from 1932 to In 1990 the rate was and increased to with the introduction of laparoscopic cholecystectomy. This increase was not associated with changed healthcare facilities or with changes in the rates of hernioraphy, appendicectomy, colonic resection for cancer and mastectomy for cancer. 32 Rates from other countries or regions are summarized in Table 3. CONCLUSIONS Gallstone disease increases with age and is for every age higher in women than in men. There are regional Table 3. Recent cholecystectomy rates in different countries or regions Country or region Period Cholecystectomy rate (per population) Ref. Scotland* [30] France? 133 à Belgium Belgium Denmark [31] Finland [31] Norway [31] Sweden [31] Stockholm [32] Scotland [29] L Aquila (Italy) [33] *Based on data from 51 public sector hospitals, estimated to cover 95% of all cholecystectomies. 44.3% operated on for colic(s), 9% for acute complications, 46.7% for dyspepsia or prophylaxis. àmentioned in [11]. Data from the Ministry for Society Affairs, Health and Environment. differences in prevalences, being highest in Norway and lowest in Italy, possibly reflecting variations in diet and obesity rates. In the 1990s, the cholecystectomy rate was found to be highly variable in different European countries regions, ranging from 62 to 213 per population. Different rates may be related to differences in the accessibility of surgery and to differences in the indications for surgery. The advent of laparoscopic cholecystectomy has had a significant effect on cholecystectomy rates. Its minimal invasiveness and its efficacy certainly changed the thresholds and or indications for surgery. An increased cholecystectomy rate was observed in elderly patients as well as in patients with asymptomatic disease or vague symptoms. However, differences in indications for surgery already existed before the introduction of laparoscopic cholecystectomy. In the second part of the 1990s the cholecystectomy rate seems to have stabilized, although remaining higher than the rate(s) observed in the prelaparoscopic era. REFERENCES 1 Beckingham IJ. ABC of diseases of liver, pancreas, and biliary system. Gallostone disease. Br Med J 2001; 322: Kang JY, et al. Gallstones an increasing problem: a study of hospital admissions in England between and Aliment Pharmacol Ther 2003; 17: Acalovschi M. Epidemiology of gallstone disease. In: M Acalovschi, G Paumgartner, eds. Hepatobiliary Diseases: Cholestasis and Gallstones Falk Workshop. London: Kluwer Academic Publishers, 2001: Jorgenson T, et al. Are autopsy studies reliable in assessing gallstone prevalence in the community? Int J Epidemiol 1994; 23: McFarlane MJ, et al. Supportive evidence for the validity of the epidemiologic necropsy for gallstones. J Gen Intern Med 1990; 5: Simonovis NJ, et al. In vivo and post-mortem gallstones: support for validity of the epidemiologic necropsy screening technique. Am J Epidemiol 1991; 133: Acalovschi M, et al. Increasing gallstone prevalence and cholecystectomy rate in a large Romanian town. A necropsy study. Dig Dis Sci 1995; 40: Glambek I, et al. Prevalence of gallstones in a Norwegian population. Scand J Gastroenterol 1987; 22: Berndt H, et al. Prävalenz der Cholelithiasis. Ergebnisse einer epidemiologischen Studie mittels Sonographie in der DDR. Z Gastroenterol 1989; 27: Muhrbeck O. Prevalence of gallstone disease in a Swedish population. Scand J Gastroenterol 1995; 30:

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