Rapid Regression of Advanced Hepatocellular Carcinoma Associated with Elevation of Des-Gamma-Carboxy Prothrombin after Short-Term Treatment with Sorafenib – A Report of Two Cases

Background: Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC), with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously. Case Reports: We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib. Results: HCC rapidly regressed, and both patients had a partial response (PR), despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP) was temporarily seen in both patients, with no elevation of alpha-fetoprotein. Conclusions: Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP

Late-onset benefit in progressive advanced hepatocellular carcinoma with continued sorafenib therapy: a case report

<p>Abstract</p> <p>Introduction</p> <p>In the past, no effective systemic therapy has existed for patients with advanced hepatocellular carcinoma. Sorafenib, an oral multikinase inhibitor, has recently been shown to improve overall survival in patients with advanced hepatocellular carcinoma in two randomized, double-blinded, placebo-controlled trials. This drug has been approved as the first-line therapy for advanced hepatocellular carcinoma patients. We report an intriguing case of advanced hepatocellular carcinoma in which the patient achieved late- onset partial response by prolonged administration of sorafenib in spite of progressive disease.</p> <p>Case presentation</p> <p>A 54-year-old Japanese man was treated with sorafenib for multiple lung metastases after surgical resection for advanced hepatocellular carcinoma accompanied by vascular invasion of the left branch of the portal vein. Although the effective diagnosis was progressive disease, almost all sites began to reduce or disappear eight months after the diagnosis of progressive disease. A dramatic reduction in alpha-fetoprotein and des-gamma-carboxy prothrombin levels was observed. The patient finally achieved partial response and his status remains unchanged.</p> <p>Conclusions</p> <p>If tolerated, prolonged sorafenib treatment may be beneficial.</p

A suspected case of Clostridium perfringens sepsis with intravascular hemolysis after transhepatic arterial chemoembolization: a case report

Abstract Introduction Sepsis due to Clostridium perfringens, one of several clostridial species, is an important cause of massive intravascular hemolysis in patients with underlying malignancies. Chronic liver diseases, immunosuppression, and presence of malignancies were risk factors for Clostridium perfringens sepsis. Therefore, Clostridium perfringens sepsis should always be considered in patients presenting with liver damage after chemo-embolic therapy for hepatocellular carcinoma. This case report focuses on findings characteristic of an intravascular hemolysis due to Clostridium perfringens after transhepatic arterial chemoembolization. Case presentation An 83-year-old Japanese man presented to our hospital because of a third recurrence of hepatocellular carcinoma. He had nonalcoholic steatohepatitis-related cirrhosis, and underwent radiofrequency ablation and transhepatic arterial chemoembolization therapy for hepatocellular carcinoma of S4/S8 and S2. He had a medical history of pancreatic carcinoma and underwent pylorus-preserving pancreaticoduodenectomy approximately 5 years ago. Because follow-up computed tomography showed a recurrence of the hepatocellular carcinoma, he underwent transhepatic arterial chemoembolization with a hepatic arterial infusion of 20 mg epirubicin, followed by 4 mL Lipiodol (ethiodized oil). On the sixth day after the procedure, he complained of fever and hematuria with jaundice. Laboratory findings indicated hemolysis and increased inflammatory response. Although we initiated antibiotic therapy combined with surgical debridement for infection after transhepatic arterial chemoembolization, he died within 6 hours. The autopsy showed a 4-cm local necrotic hepatic tumor. The cut surface revealed a tumor with an internal spongiform appearance, which was a pseudocystic and partially necrotic lesion. In addition, a diffuse spread of Gram-positive rods in multiple organs including the heart was histologically confirmed. The culture obtained by fluid aspiration from the hepatic abscess revealed Clostridium perfringens. Although the role of Clostridium perfringens was never established during the life of this patient, based on the clinical course and the culture from the hepatic abscess at postmortem, intravascular hemolysis secondary to Clostridium perfringens sepsis was suspected. Conclusion Intravascular hemolysis secondary to Clostridium perfringens should always be considered in patients presenting with liver damage after chemo-embolic therapy for hepatocellular carcinoma. Biliary reconstruction is an especially important risk factor for infection

Expression patterns of the Clq receptor (ClqRp) on the granulocytes and monocytes in peripheral blood mononuclear cells (PBMCs) from patients with liver diseases

肝臓疾患由来末梢血単核球(顆粒球および単球)表面上の補体レセプター(C1qRp)の発現パターンを我々が開発したC1qRpモノクローナル抗体(mNI-11)とフローサイトメトリー法を用いて解析した。その結果、肝硬変、慢性肝炎、肝細胞癌患者由来の顆粒球表面上のC1qRpの発現は、健常人に比べて有意に低下していた(P<0.01)。また、肝硬変患者由来単球表面上のC1qRpの発現も健常人に比べて有意に低下していた(P<0.01)。しかしながら、慢性肝炎、肝細胞癌患者由来の単球表面上のC1qRpの発現は健常人と比べて有意な差は認められなかった(P=0.079およびP=0.534)。以上の結果は、肝臓疾患由来の顆粒球および単球の免疫学的な機能を解析する上で非常に有益な情報を提供するものと考えられる。Human C1qRp, a receptor for complement component 1, subcomponent q (C1q), was shown to be selectively expressed by cells of myeloid lineage, was originally reported to be involved in the C1q-mediated enhancement of phagocytosis. However, its expression patterns on the granulocytes and monocytes in human peripheral blood mononuclear cells (PBMCs) isolated from patients with various diseases are still not well understood. In this study, focusing on the clinical significance of the expression of this receptor in patients with chronic liver diseases, we demonstrated the expression patterns of C1qRp on the granulocytes and monocytes in PBMCs prepared from patients with some liver diseases, using the C1qRp monoclonal antibody (mAb) mNI-11 and flow cytometry. Analysis of the expression patterns (percentage of expression) of C1qRp on the granulocytes of patients with liver cirrhosis, chronic hepatitis B or C and hepatocellular carcinoma revealed a significantly reduced expression of this receptor in these patients as compared with that in normal healthy donors (P<0.01, P<0.01 and P<0.01, respectively). On the other hand, in relation to the expression of C1qRp on the peripheral blood monocytes in patients with liver diseases, while the expression was significantly decreased in the cells of patients with liver cirrhosis as compared with that of normal healthy donors (P<0.01), the expression levels in the cells of patients with chronic hepatitis B or C and hepatocellular carcinoma were not significantly different from those of normal healthy donors (P=0.079 and P=0.534, respectively). Taken together, these findings indicate that the expression of C1qRp on the granulocytes or monocytes was, in general, decreased in patients with liver diseases, but more significantly so in patients with liver cirrhosis