ABSTRACT
BACKGROUND: The intrahepatic recurrence rate after curative hepatectomy for hepatocellular carcinoma (HCC) is high, and management of recurrence is thus important for long-term survival. The use of radiation therapy has been relatively uncommon in the treatment of recurrent HCC. METHODS: Eight patients underwent radiation therapy for recurrent HCC 12-98 months after hepatectomy. Five of them were treated with protons (250 MeV; 68.8-84.5 Gy), and three were treated with X-rays (6 MV; 60 or 70 Gy). One patient received radiation therapy twice for another lesion with a 79-month interval. The target tumors were 1.2-4.5 cm. All patients also underwent transcatheter arterial embolization or other regional therapy. RESULTS: Although transient ascites was found in three patients after radiation therapy, no patient died as a result of the irradiation. Seven patients died 9 months to 4 years (median 1 year 6 months) after radiation therapy. Re-recurrence was observed in the irradiated liver in two patients (local control 78%). Four patients died of lung metastasis after radiation therapy. The median survival time was 3 years 3 months (range 1 year 1 month to 8 years 6 months) after recurrence. CONCLUSION: Multimodality therapy is necessary for the management of recurrence. Radiation therapy could be beneficial when other therapies present some difficulty regarding application or are performed incompletely. It must be emphasized that radiation therapy should be considered in addition to other regional therapies for the treatment of recurrent or re-recurrent HCC, and that radiation therapy can be repeated in selected patients.
Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/radiotherapy , Aged , Biopsy, Needle , Brachytherapy/methods , Carcinoma, Hepatocellular/pathology , Female , Follow-Up Studies , Hepatectomy/methods , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Staging , Radiation Dosage , Retrospective Studies , Risk Assessment , Sampling Studies , Survival Analysis , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: In hepatolithiasis, chronic proliferative cholangitis may influence the progression of the disease. Prostaglandin (PG) E(2) experimentally causes morphologic changes to intrahepatic bile ducts, analogous to the changes found in cholangitis. This study was designed to gain an understanding of the involvement of PGE(2) and PGE receptor (EP) subtypes in the development of cholangitis. METHODS: The expression levels of secretory-type group IIA phospholipase A(2) (sPLA(2)-IIA) and cyclooxygenase (COX)-2 as well as EP subtypes were determined in the bile ducts with change of cholangitis. In in vitro experiments, growth promotion and mucin secretagogue properties of biliary epithelial cells in response to EP-selective agonists or antagonists were studied. RESULTS: The messenger RNA (mRNA) level of sPLA(2)-IIA and the protein and mRNA levels of COX-2 were significantly increased in the bile ducts of patients with hepatolithiasis compared with the levels of the bile ducts of control subjects. These changes were associated with a concomitant increase in PGE(2) and total mucin concentrations in the bile. The mRNAs of EP subtypes EP(2), EP(3), and EP(4) but not EP(1) were amplified in the bile ducts. Treatment with an EP(4)-selective agonist (ONO-AE1-329) caused a dose-dependent increase in DNA synthesis, colony number, and mucin secretion in the cells. Conversely, treatment with an EP(4)-selective antagonist (ONO-AE3-208) abolished the biological effects of PGE(2) on the cells. CONCLUSIONS: In hepatolithiasis, an enhanced synthesis of sPLA(2)-/COX-2-derived PGE(2) and its actions mediated via the EP(4) receptor in the bile ducts may be of pathobiological significance for chronic proliferative cholangitis.
