Elsevier

Journal of Hepatology

Volume 37, Issue 6, December 2002, Pages 806-813
Journal of Hepatology

Changing international trends in mortality rates for liver, biliary and pancreatic tumours

https://doi.org/10.1016/S0168-8278(02)00297-0Get rights and content

Abstract

Background/Aims: The age-standardized mortality rate for hepatocellular carcinoma is increasing in several countries. However, in England and Wales we previously reported an increase in mortality rates from intrahepatic cholangiocarcinoma. Trends in cholangiocarcinoma in most other industrialized countries are unknown. To further study trends in hepatobiliary and pancreatic tumours, we analysed mortality data from the United States, Japan, Australia and Europe.

Methods: Age-standardized mortality rates for men and women for subcategories of liver tumours, tumours of the gall bladder and extrahepatic biliary tree and pancreas from 1979 to 1998 were obtained from the World Health Organization mortality database.

Results: We confirmed previously reported increases in hepatocellular carcinoma, but also found increases in other countries, particularly Australia (3-year average rise from 1.20 to 2.27, men). Mortality for intrahepatic cholangiocarcinoma increased in men in all countries studied, with the largest increases in Australia (from 0.10 to 0.70) and England and Wales (from 0.20 to 0.83).

Conclusions: We present a hitherto unreported rise in age-standardized mortality rates from intrahepatic cholangiocarcinoma across four continents. The cause remains uncertain. An impact on the observed trends of improved diagnostic techniques and death certificate misclassification cannot be completely ruled out. Future research should include epidemiological studies to examine possible case-clustering and investigation of potential aetiological and host factors.

Introduction

While investigating the mortality rates for primary liver tumours in England and Wales over the period 1968–1998 from the Office of National Statistics, we reported that deaths from all causes of malignant liver tumours had nearly doubled, but deaths from hepatocellular carcinoma had remained relatively static [1], [2]. Since the overall prognosis for liver and pancreatic tumours is extremely poor, mortality data may be considered a good proxy for incidence [3]. The rise in primary liver tumour deaths in England and Wales was explained by an unexpected and marked rise in age-standardized mortality rates (ASMR) for intrahepatic cholangiocarcinoma [2]. This, since the mid-1990s, has become the commonest recorded cause of death from a malignant liver tumour in England and Wales [1], [2], [4], [5]. We aimed to investigate whether a similar pattern was seen in other industrialized countries, using the official World Health Organization (WHO) mortality database.

Data from previous studies show rising mortality rates for liver tumours in the United States [6], France [7], [8], Italy [7] and Japan [9] and for pancreatic tumours in Japan and across several European countries [9], [10]. An increase in biliary tumours has also recently been reported in the United States [11], [12]. However, most epidemiological studies focus on only one tumour type, or on a group of tumours in general, and often only on a particular cohort within a country. McGlynn and associates [13] studied incidence rates for all primary liver cancers, grouped together, from 21 selected cancer registries, in selected cohorts around the world. For example, data from the United Kingdom were limited to the South Thames region only, while data from Spain were provided from Navarra. A substantial change in global time trends was extrapolated, with primary liver cancer incidence rates calculated to be increasing generally in the developed world and decreasing in some areas of the developing world. However, since the study examined data from ‘Cancer incidence in five continents’, [14] it was not possible to distinguish between sub-types of primary liver cancers. The data therefore aggregated information for hepatocellular carcinoma (HCC) and cholangiocarcinoma, for example. Given the possibility of diagnostic error and transfer between different categories of hepatobiliary and pancreatic tumours, it is important to examine all related sub-groups to properly assess trends in these diseases.

Changing patterns of mortality from individual sub-groups of hepatobiliary and pancreatic tumours, particularly cholangiocarcinoma, across most parts of the industrialized world have not previously been studied independently. The importance of studying specific individual tumours in the context of examining hepatobiliary cancer trends is borne out by the findings of Percy et al. [15] and Sharp et al. [16], namely that the more specific the International Classification of Disease (ICD) code, the greater its accuracy. We therefore examined ASMR for all sub-categories of liver tumours, as well as tumours of the extrahepatic bile ducts, gall bladder and pancreas in addition to intrahepatic cholangiocarcinoma. National mortality data were analysed from the United States, England and Wales, Scotland, France, Italy, Japan and Australia to elucidate and compare trends internationally. Countries were chosen to represent industrialized regions from Asia as well as Europe and North America, and to cover both hemispheres north and south of the equator. The inclusion of all sub-categories, including gall bladder and pancreatic cancer, in this study as with our last [2], was considered crucial as both may be diagnostically confused with cholangiocarcinoma.

Section snippets

Age-standardized mortality rates (ASMR)

ASMR from 1979 to 1998 were obtained from the official WHO mortality database [17] for the following International Classification of Diseases codes [4]:

  • ICD-9 155.0 (primary tumours of the hepatic parenchyma, including mainly HCC)

  • ICD-9 155.1 (intrahepatic cholangiocarcinoma)

  • ICD-9 155.2 (unspecified liver tumours)

  • ICD-9 156 (all extrahepatic biliary system tumours, including gall bladder)

  • ICD-9 157 (pancreatic tumours)

The WHO database is compiled from official data on causes of death, as reported

Results

The findings for all tumour types in the countries studied are summarized Table 1 (men) and Table 2 (women). All data points for ASMR were plotted on graphs to show mortality trends in men from 1979 onwards for ICD-9 155.0 (primary hepatic parenchymal cancer, including HCC), 155.1 (intrahepatic cholangiocarcinoma) and 156 (tumours of the gallbladder and extrahepatic biliary tree) in Figs. 1a, b and c, respectively. Tables and graphs giving annual rates by cause, sex and country are available on

Discussion

We have presented mortality trends for hepatobiliary and pancreatic tumours from various industrialized countries around the world between 1979 and 1998. Using the official WHO mortality database for nations, our findings confirm previously reported increasing mortality rates from HCC in the United States [6], France [7], [8], Italy [7], and Japan [9]; and pancreatic cancer in France, Italy and Japan [9], [10]. However, previous studies have not examined the changing patterns in HCC in relation

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