Excretion of heavy metals from the biliary tract and its association with pancreato-biliary malignancy

Abstract

Biliary and pancreatic cancers are associated with poor prognosis and high mortality. A variety of genetic and environmental factors have been implicated as possible causes of these cancers. New epidemiological studies are looking into the possible role of heavy metals such as lead, chromium, nickel and cadmium as carcinogens. Studies from areas of wide geographical differences such as Egypt, USA and India have reported a possible association of heavy metals such as lead and cadmium with pancreato-biliary malignancy. These studies were from areas of significant environmental pollution with these metals due to the proximity of heavy industry or mining activities. No association has been demonstrated between metal exposure and pancreato-biliary malignancy in areas of low environmental pollution. Aim The aim of this study was to look at a possible association between excretion of heavy metals from the biliary tract and pancreato-biliary malignancy in an industrial area in the North-East of England. Materials and Methods Patients with malignant biliary obstruction admitted to a tertiary referral centre were identified prospectively. Bile was collected either during endoscopic retrograde cholangiography (ERC), percutaneous transhepatic 10 cholangiography (PTC) or during biliary tract surgery. Bile was also collected from patients with benign biliary disease to act as controls. The bile samples were analyzed for concentrations of lead, copper, zinc, cadmium, chromium and nickel using atomic absorption spectrometry after pre-treatment by the acid digestion method. The mean levels of every metal in the study groups (biliary malignancy and pancreatic malignancy) and the control group were compared by using SPSS 16© (SPSS Inc) statistical software. It was uncertain whether there would be a measurable quantity of heavy metals in the bile collected during the above procedures and therefore it was felt necessary to perform a small pilot study to standardize the methods and address any possible difficulties. Results Bile samples collected from 107 patients over a period of 18 months were included in this study. As part of the pilot study two different methods of purification of bile (acid digestion vs syringe filtration) were evaluated and acid digestion was chosen as a more reliable method. For the main study, after exclusion due to inadequate volume of sample, a total of 127 bile samples from 98 patients (43 male, 55 female, median age 65.82 years, range 20-82 years) were analyzed. On final analysis, the malignant group comprised of 3 subgroups: pancreatic cancer, biliary cancer and periampullary cancer. Results from these 3 groups were compared with those from the benign control group. The groups were sex-matched but there was a significant difference in age distribution between the benign and 11 malignant groups (p<0.001). Bile samples were obtained from both gallbladder (GB) and common bile duct (CBD) in 33 patients and from either of these sources in the remainder. There was a strong positive correlation between the concentration of each metal when obtained from either GB or CBD. The main results of this study have shown that copper was present at significantly higher levels in the benign control group (p=0.004) and that cadmium was present at significantly higher levels in the malignant groups (p=0.02). There was no significant difference amongst the groups for the other heavy metals. Discussion Cadmium has been implicated as a possible environmental carcinogen for various malignancies, including pancreatic cancer. Most studies that show this association are from areas of high environmental pollution. The present study supports this association. There is evidence of excess environmental exposure to heavy metals, including cadmium, in the North-East of England. This exposure is mainly in relation to mining activities in the past in this region and is mainly noticed downstream along the rivers draining the areas with significant mining history. The results of this study support the possible association between heavy metal exposure and pancreatic and biliary malignancy. Further research is needed to establish the specific carcinogenic role of heavy metals such as cadmium in pancreato-biliary malignancies.