Early eCCA and GBC are hard to detect due to a lack of specific symptoms. However, fewer than 50% of GBC patients and 35–68% of eCCA patients are eligible for surgical resection. To date, surgical resection remains to be the most efficient treatment for eBTC. The main causes of GBC are gallstones and chronic cholecystitis and can therefore easily be confused with them due to similar symptoms. In contrast, GBC is one of the most common malignancies of the digestive system, accounting for approximately 1% of all cancers and 80–95% of all eBTCs. The risk factors for eCCA include primary sclerosing cholangitis, smoking, and heavy alcohol drinking.
The incidence of eCCA is similar to that of intrahepatic cholangiocarcinoma but lower than that of perihilar cholangiocarcinoma. Additional enhancements should be explored to improve the growth rate of PDOs and to preserve their immune microenvironment.Įxtrahepatic biliary tract carcinoma (eBTC), which comprises extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC), is a relatively rare malignancy that occurs in the digestive system.
Our study successfully established a series of eBTC PDOs, which contributed to the field of eBTC PDOs. Results from drug screening were confirmed to a certain extent by three clinical cases. In general, gemcitabine was found to be the most efficient drug for eBTC treatment, as it showed moderate or significant inhibitory impact on cancer growth. Three of the four PDOs exhibited a high degree of similarity when compared to the original specimens, except for GBC2 PDO, which only had a concordance of 74% in the proportion of single nucleotide polymorphisms in the coding sequence. Genetic profiles from the four original specimens, as well as paired cancer PDOs, were analyzed using whole exome sequencing. Immunohistological and periodic acid-schiff staining revealed that marker expression in cancer PDOs was similar to that of the original specimens. Hematoxylin and eosin staining demonstrated that the structures of most cancer PDOs retained the original structures of adenocarcinoma. Resultsĭifferent PDOs exhibited diverse growth rates during in vitro culture. Drug screening, including gemcitabine, 5-fluorouracil, cisplatin, paclitaxel, infigratinib, and ivosidenib, was measured and verified by clinical effects in certain cases. Whole exome sequencing (WES) was performed to analyze the genetic profiles of original tissues and cancer PDOs. Histological staining was used to compare structural features between the original tissues and cancer PDOs. We successfully established five GBC and one eCCA PDOs. We collected six samples of gallbladder carcinoma (GBC) and one sample of extrahepatic cholangiocarcinoma (eCCA) from seven patients to attempt to establish eBTC PDOs for drug screening.
However, to date, extrahepatic biliary tract carcinoma (eBTC) PDOs have not yet been fully established. Patient-derived organoids (PDO) have been proposed as a novel in vitro method of drug screening for different types of cancer.