Search

Background Colorectal cancer (CRC) liver metastasis is highly unfavorable for patient outcome and is a leading cause of cancer-related death. Pre-clinical research of CRC liver metastasis predominately utilizes CRC cell lines grown in tissue culture. Here, we demonstrate that CRC liver metastases organoids derived from human specimens recapitulate some aspects of human disease. Methods Human CRC liver metastases pathological specimens were obtained following patient consent. Tumor disaggregates were plated and organoids were allowed to expand. CRC markers were identified by immunofluorescence. Stem cell genes were analysed by QPCR and flow cytometry. Response to drug therapy was quantified using time-lapse imaging and MATLAB analysis. Results Organoids showed global expression of the epithelial marker, EpCAM and the adenocarcinoma marker, CEA CAM1. Flow cytometry analysis demonstrated that organoids express the stem cell surface markers CD24 and CD44. Finally, we demonstrated that CRC liver metastases organoids acquire chemotherapy resistance and can be utilized as surrogates for drug testing. Conclusion These data demonstrate that CRC liver metastases organoids recapitulate some aspects of human disease and may provide an invaluable resource for investigating novel drug therapies, chemotherapy resistance and mechanism of metastasis., Highlights • Human colorectal cancer liver metastases can be cultured as organoids using rapid dissociation. • Organoids retain characteristics of human disease. • Organoids acquire chemotherapy resistance.

Two hundred ninety-three children suffering from acute appendicitis have been analyzed. Five deaths occurred in this group, two of which were nonoperative. This is a marked reduction in death rate as compared to previous reports from the same service. Among the outstanding reasons assigned for the lowered mortality rate are: (1) earlier hospitalization; (2) fewer cathartics; (3) more preoperative care aimed at correcting fluid balance, especially in toxic dehydrated patients with evidence of spreading peritonitis; (4) better anesthesia and (5) the use of the McBurney incision. This incision is likewise believed to have been the chief factor in reducing hospital stay from twenty-one days in the previous report to fifteen and six-tenth days in this series. Further followup observations in cases in which drainage was employed and in which only the peritoneum was sutured is reported, with a decreased incidence of hernia in this group.