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How can HAI therapy reduce severe hepatobiliary toxicity by improving chemotherapy drug combinations?
Hepatic arterial infusion (HAI) is a medical procedure that delivers chemotherapy drugs directly to the liver. The procedure is primarily used in combination with systemic chemotherapy and plays an important role in the treatment of liver metastases in patients with colorectal cancer (CRC). Although surgical resection remains the standard of care for these liver metastases, the disease is unresectable in the majority of patients. The liver's blood supply comes from two sources - the hepatic arterial circulation and the portal venous circulation. Liver metastases receive their blood supply primarily through the hepatic artery, whereas normal hepatocytes receive their blood supply primarily through the portal vein. This allows chemotherapy drugs to be delivered directly to cancer cells if they are injected into the hepatic artery.
Several trials have compared HAIs (with various chemotherapy agents) with systemic chemotherapy. Compared with systemic fluoropyrimidines, the use of fluorouracil (FUDR) in HAI has a higher response rate but fails to significantly improve the overall survival of patients.
To increase the safety and effectiveness of HAI chemotherapy, researchers have tried some new combinations. When HAI was treated with a combination of FUDR and dexamethasone, the response rate and median survival of patients were significantly improved. In another study, combining FUDR with an amino acid (leucovorin) resulted in an improved response rate and reduced hepatobiliary toxicity.
Given improvements in surgical placement of HAI pumps, and further studies showing even more promising results when HAI therapy is combined with systemic treatments such as oxaliplatin or irinotecan, , HAI has once again become one of the treatment options for patients with unresectable CRC liver metastases. However, the study suggests that this treatment should be limited to medical centers with relevant expertise.
HAI Operation Process
Before HAI pump placement, patients undergo hepatic arteriography to confirm blood supply to the liver and identify potential anatomic variations. The surgical team will then perform an exploratory laparotomy to confirm the unresectable nature of the tumor, and a cholecystectomy will be performed to prevent post-treatment cholecystitis.
During the surgery, the distal gastroduodenal artery, the right gastric artery, and the small branches supplying the stomach and duodenum are ligated, which greatly reduces the risk of any extrahepatic perfusion.
Once the catheter is positioned in the correct position in the hepatic artery, the HAI pump is inserted into a subcutaneous pocket. To confirm adequate perfusion and exclude extrahepatic perfusion, a dye (such as fluorescein or meckrodine) is then injected into the pump.
Complications of HAI Treatment
Complications of HAI therapy can be divided into complications related to surgical placement of the pump, technical catheterization, and chemotherapy administration. Early surgical complications include hepatic artery thrombosis due to damage to the hepatic artery; late complications are more common and include inflammation or ulcers of the stomach or duodenum and pump bag infection.
It has been reported that the most common toxic symptoms in HAI treatment include gastrointestinal discomfort, chemical hepatitis and bone marrow suppression. The most clinically significant and dose-limiting complication is hepatobiliary toxicity, which is particularly evident when FUDR is used for treatment.
Therefore, patients receiving HAI therapy frequently require liver function tests to monitor liver damage. In order to reduce the serious side effects of hepatobiliary toxicity, studies have found that the combination of amino acids and FUDR can not only reduce biliary toxicity but also improve the response rate.
ConclusionWith the advancement of HAI technology, this treatment option is expected to become a lifeline for many patients facing difficult-to-resectable liver metastases. However, how to ensure effectiveness while reducing harm is still an important issue that the medical community needs to consider?
