Association betweenHelicobacterspp. infections and hepatobiliary malignancies: A review

Abstract

Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma, the bile ducts intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, the gallbladder and the ampulla of Vater (collectively known as biliary tract cancers). These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies. Cholangiocarcinoma (CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available. Population genetics, geographical and environmental factors, cholelithiasis, obesity, parity, and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors. Other important factors affecting the carcinogenesis of these tumors include chronic inflammation, obstruction of the bile ducts, and impaired bile flow. It has been suggested that CCA is caused by infection with Helicobacter species, such as Helicobacter bilis and Helicobacter hepaticus, in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer. Due to the difficulty in culturing these Helicobacter species, molecular methods, such as polymerase chain reaction and sequencing, or immunologic assays have become the methods of choice for diagnosis. However, clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings, and the use of uniform and validated techniques is needed.

Management ofHelicobacter pyloriinfection—the Maastricht V/Florence Consensus Report

“…Some of them have been found in humans, including H. bilis , H. cinaedi , and H. fennelliae . Besides occasional associations with gastroenteritis,365 infection with these and other enterohepatic Helicobacter species have been associated with extraintestinal diseases, including extrahepatic cholangiocarcinoma for H. bilis and H. hepaticus 366 367 and bacteraemia 368. In addition to these enterohepatic Helicobacter species, gastric non- H. pylori Helicobacter species have also been detected in humans.…”

Incidental gallbladder cancer: Missing links in Pakistani population

“…Alterations in oncogenes, tumor suppressor genes, microsatellite instability and methylation of gene promoter areas act in synergy with recurrent or chronic mucosal inflammation to induce cancer although exact cause in not known [30]. Gallstones especially chronic one pose most significant risk although other suspected culprits [31] are advance age, female sex, positive family history, cholelithiasis, obesity (BMI > 30), parasitic infestations, chronic bacterial cholangitis especially by Salmonella and Helicobacter [32], porcelain gallbladder, large polyps >10 mm, heavy metals exposure and abnormal pancreaticobiliary duct junction [33] Clinical features are ominous but those harboring clue include persistent right upper quadrant pain, jaundice, nausea and weight loss [8]. Biochemical investigations are nonspecific.…”

Oxidative and nitrosative stress defences ofHelicobacterandCampylobacterspecies that counteract mammalian immunity

“…It is associated with chronic intestinal infection that in susceptible mice can lead to hepatitis and colonic and hepatic carcinomas (Falsafi and Mahboubi 2013;Segura-Lopez, Guitron-Cantu and Torres 2015). Helicobacter hepaticus is resistant to cephalothin and nalidixic acid but sensitive to metronidazole (Tanaka et al 2007).…”

“…Although first isolated from animals such as wild birds (H. valdiviensis), Bengal tigers and Australian marsupials, these so-called non-H. pylori species have been also found in humans (H. heilmannii, H. cinaedi, H. pullorum, H. bizzozeronii), and associated with a range of human diseases in children and adults including chronic gastritis (e.g. H. suis and H. felis), hepatobiliary malignancies, Crohn's disease and sepsis (H. cinaedi, H. bilis and H. canis) (Goldman and Mitchell 2010;Rossi and Hanninen 2012;Segura-Lopez, Guitron-Cantu and Torres 2015).…”