Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats

Many orally administered phenolic drugs undergo enterohepatic recycling (EHR), presumably mediated by the hepatic phase II enzymes. However, the disposition of extrahepatically generated phase II metabolites is unclear. This paper aims to determine the new roles of liver and intestine in the disposition of oral phenolics. Sixteen representative phenolics were tested using direct portal vein infusion and/or intestinal perfusion. The results showed that certain glucuronides were efficiently recycled by liver. OATP1B1/1B3/2B1 were the responsible uptake transporters. Hepatic uptake is the rate-limiting step in hepatic recycling. Our findings showed that the disposition of many oral phenolics is mediated by intestinal glucuronidation and hepatic recycling. A new disposition mechanism ‘Hepatoenteric Recycling (HER)”, where intestine is the metabolic organ and liver is the recycling organ, was revealed. Further investigations focusing on HER should help interpret how intestinal aliments or co-administered drugs that alter gut enzymes (e.g. UGTs) expression/activities will impact the disposition of phenolics.

INTRABEAM intraoperative radiotherapy combined with portal vein infusion chemotherapy for treating hepatocellular carcinoma with portal vein tumor thrombus

Background: Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. Case Summary: We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with of FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 14 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely. Conclusions: IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.

INTRABEAM intraoperative radiotherapy combined with portal vein infusion chemotherapy for treating hepatocellular carcinoma with portal vein tumor thrombus

Background Portal vein tumor thrombus (PVTT) is common in hepatocellular carcinoma (HCC). Recent studies indicate that more aggressive treatments, including surgical resection or locoregional treatment, may benefit select HCC patients with PVTT. External radiation therapy and infusion chemotherapy were found to achieve good outcomes; however, the use of low-energy x-ray radiation system (INTRABEAM), intraoperative radiation therapy, and portal vein infusion chemotherapy for PVTT has not been reported. Case Summary We present a case of HCC with PVTT. The patient underwent hemihepatectomy and thrombectomy along with intraoperative radiotherapy (IORT) using a portable INTRABEAM radiation system. Subsequently, to treat PVTT, portal vein infusion chemotherapy with of FOLFOX (leucovorin [Folinic acid], fluorouracil, and oxaliplatin) regimen was administered. There were no obvious post-operative complications. After 14 months follow-up period, no obvious tumor recurrence had been observed, and PVTT gradually disappeared completely. Conclusions IORT using the INTRABEAM radiation system combined with portal vein infusion chemotherapy is promising for select patients with PVTT.