The burden of gallstone disease in Europe

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. Cholelithiasis is a common disease in most developed countries and a frequent cause of abdominal surgery. 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 women than in men.12, 13, 15, 16 Prevalences of gallstone disease in men and women according to age are shown in 1, 2. Prevalence of gallstone disease in Europe: men.8-12, 14, 17,19-21 Prevalence of gallstone disease in Europe: women.8-14,16,18,19,21 The few prospective ultrasound surveys in Europe that have assessed gallstone incidence show an incidence < 1/100 persons per year (0.34–0.97% in Italy, 0.93% in Denmark).15, 22-25. Incidence rates also increase with age and are higher in women than in men (southern Italy: 0.32 and 0.48% per year in 30–39-year-old men and women, respectively; 1.66 and 1.86% per year in the 60–69-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-year-old 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 time-dependent; in the Sirmione study, the gallstone incidence rate during 1982–87 was 0.60% per year and during 1987–92 was 0.34% per year, indicating a declining incidence in this town in northern Italy.23 The large majority of gallstones remain asymptomatic during a lifetime. Several ultrasonographic population 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 symptoms.10, 11, 14, 20 The GREPCO group studied the natural history of gallstones over a period of 10 years in an Italian population sample screened from 1981 to 1984.27 In the initially asymptomatic group (n = 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 = 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 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. 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 45–65-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 100 000 population in the decade before the introduction of laparoscopic cholecystectomy in 1990. The cholecystectomy rate increased from 83 to 98 per 100 000 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 55–64 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 1997–99. The fact that the cholecystectomy 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. 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 1993. In 1990 the rate was 76/100 000 and increased to 90/100 000 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. Gallstone disease increases with age and is for every age higher in women than in men. There are regional 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 100 000 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.