This multicenter retrospective study investigated the clinical utility of patient-derived tumor organoids (PDOs) in guiding adjuvant chemotherapy for intrahepatic cholangiocarcinoma (ICC) patients. A total of 82 ICC patients at the Shanghai Eastern Hepatobiliary Surgery Hospital and the Shanghai Tenth People’s Hospital between 2021 and 2022 were included in the study. All of these patients underwent surgical resection and were pathologically confirmed to have high-risk factors for recurrence. Therefore, they received adjuvant chemotherapy post-surgery. Sixty-one PDOs were successfully established from resected tumor tissues and tested against four common regimens: Gemcitabine + cisplatin, gemcitabine + oxaliplatin, capecitabine, and S-1. A novel fluorescence-based method was developed for drug sensitivity testing, showing significant concordance with conventional half-maximal inhibitory concentration quantification. Patients were stratified into matched (n=26) and unmatched (n=35) groups based on alignment between PDOs-based drug sensitivity results and actual chemotherapy received. The matched group demonstrated significantly improved recurrence-free survival (RFS) (hazard ratio = 2.52, p=0.007), with 63% versus 17% experiencing recurrence events. Through eXtreme Gradient Boosting machine learning and Cox regression analyses, we identified PDOs-based drug sensitivity, tumor multiplicity, and vascular invasion as key predictors of 2-year recurrence. A clinical nomogram incorporating these factors showed that patients with matched PDO-guided therapy had 46% 12-month RFS probability versus 28% in unmatched cases. This study provides a clinically translatable platform to guide adjuvant chemotherapy decisions and predict the prognosis of ICC patients with a high recurrence risk after surgery.

With the emergence of new virus variants, limited data are available on the impact of SARS-CoV-2 Omicron infection on surgery outcomes in cancer patients who have been widely vaccinated. This study aimed to determine whether undergoing hepatectomy poses a higher risk of postoperative complications for liver cancer patients who have had mild Omicron infection before surgery. A propensity-matched cohort study was conducted at a tertiary liver center from 8 October 2022 to 13 January 2023. In total, 238 liver cancer patients who underwent hepatectomy were included, with 57 (23.9%) recovering from preoperative SARS-CoV-2 Omicron infection and 190 (79.8%) receiving COVID-19 vaccination. Pre- and post-matching, there was no significant difference in the occurrence of postoperative outcomes between preoperative COVID-19 recovered patients and COVID-19 negative patients. Multivariate logistic regression showed that the COVID-19 status was not associated with postoperative major pulmonary and cardiac complications. However, preexisting comorbidities (odds ratio [OR], 4.645; 95% confidence interval [CI], 1.295–16.667), laparotomy (OR, 10.572; 95% CI, 1.220–91.585), and COVID-19 unvaccinated (OR, 5.408; 95% CI, 1.489–19.633) had increased odds of major complications related to SARS-CoV-2 infection. In conclusion, liver cancer patients who have recovered from preoperative COVID-19 do not face an increased risk of postoperative complications.