Current status of surgical treatment for hepatocellular carcinoma

The therapeutic modalities for hepatocellular carcinoma (HCC) have diversified during the past decades, and in particular, the treatment has mainly been concentrated on small HCC of 3 cm or less. Therefore, it has become very important for surgeons to be able to identify the clinical indications for liver resection in HCC. We reviewed data on liver resection for HCC using the National Primary Hepatic Cancer follow-up survey report of the Liver Cancer Study Group of Japan, indicating problem associated with liver resection for HCC. As a result, the indications of surgical treatment for HCC are as follows:(1) In patients with HCC of 3 cm or less in diameter, a solitary HCC indicates liver resection. However, priority should be given to medical treatment such as percutaneous transhepatic ethanol injection therapy, microwave coagulative necrosis therapy for multiple HCC and patients with clinical states II or III. (2) HCC between 3 cm and 5 cm in diameter is a good indicator for liver resection. Solitary HCC indicates liver resection as a first choice. (3) HCC greater than 5 cm in diameter and cases with tumor stages II or III indicate liver resection. (4) There are limits to treating HCC with tumor thrombus in the second branch of the portal vein (Vp2) and tumor thrombus in the first branch, the trunk of the portal vein or in a branch on the opposite side (Vp3) only by liver resection. (5) HCC with tumor thrombus in the right, middle or left hepatic vein trunk, posterior inferior hepatic vein trunk or short hepatic vein (Vv2) and with tumor thrombus in the inferior vena cava (Vv3) are indicators for liver resection. A limited resection according to Glissons structure and with a negative surgical margin can be performed in HCC of 5 cm or less, however an extended resection is required for HCC greater than 5 cm. Furthermore, the extent of liver resection should be considered according to the hepatitis virus. Finally, it was emphasized that effective measures against the postoperative recurrence was essential in order to improve the outcome of HCC

Changes of lymphatic flow in case of pancreatic duct obstruction in the pig : as a model of pancreatic cancer

To investigate the lymph network change in pancreatic duct obstruction in pigs as a model of pancreatic cancer invading pancreatic duct, six domestic pigs weighing 17-40 kg underwent surgery as protocol. Two of them were controls, and the others underwent ligation of the pancreatic duct as a model of ductal obstruction. A CH 40 and lipiodol mixture was injected in their pancreas at 7 or 21 Days after first operation. Radiographic examination had been also performed. Five or 14 days later, they were examined radiographically, and sacrificed for histological examination. Ligation of the pancreatic duct caused experimental pancreatitis. Dilatation of the pancreatic duct and dilatation of the lymph canal in the interlobular space of pancreas was demonstrated in the ligation group. CH 40 and lipiodol showed discrepancies in the distribution. There were not distinct differences between the two groups in a route of CH 40 traveling. Only fluoroscopic examination revealed an image of lipiodol enlargement to the caudal site in the ligated group. The congestive lymph system may have impaired flow like reflux

Remedy for improving ICC prognosis

The prognosis of patients with intrahepatic cholangiocarcinoma (ICC) is still poor, and the 5-year survival rate in patients undergoing radical surgery (R0) is less than one-third. Since the prognosis depends mainly on tumor factors, so early diagnosis is necessary. To extend the survival time of these patients with a poor prognosis, cases of long-term survival were examined based on the results of our experiences and the literature. It was found that the hepatitis virus was highly involved in the carcinogenesis of ICC, and patients who were infected with hepatitis virus had rather good survival

Direct lymphatic spreading route into the liver from the gallbladder : an animal experiment using pig

In the special occasion that the physiological lymphatic flow is obstructed, gallbladder carcinoma (GBC)may spread into the liver via lymphatic route. Therefore, this study was conducted to find out the direct lymphatic route draining into the liver from the gallbladder using pigs with ligated cystic ducts. After injecting the carbon particle suspension (CH40) or the contrast medium (Lipiodol) into the subserosal layer of the gallbladder, the lymphatic route into the liver was examined both macroscopically and histologically. In controls, CH40 or Lipiodol drained along the cystic duct toward the hepatoduodenal ligament. After occlusion of cystic duct, CH40 was interrupted at the ligated point, and then spread into the liver nearby the gallbladder bed, running off to the liver hilus, toward the hepatoduodenal ligament. This route was confirmed by the Lipiodol drainage into the right median lobe of the liver, equivalent to the segments Vand IV a in humans. We presented for the first time the emergence of lymphatic drainage from the gallbladder into the liver after the occlusion of physiological lymphatic route using pigs. This implies that the direct spread into the segments Vand IVa of liver should be considered in the surgical treatment of advanced GBC

Prognostic significance of Ki-67 and p53 antigen expression in carcinomas of bile duct and gallbladder

Ki-67 and p53 protein expression was evaluated immunohistochemically in 32 patients with intrahepatic, extrahepatic bile duct and gallbladder carcinomas, who underwent surgery at First Department of Surgery, The University of Tokushima School of Medicine. p53 expression was found more in the well differentiated group than poorly differentiated group (p=0.007). MIB1 labelling index (MIB1 LI) was higher in EHC than in GBC (p=0.0061). MIB1 LI (T), (MIB1 LI in tumor) was higher in cases with lymph node metastasis than in those without lymph node metastasis (p=0.0189). Moreover, MIB1LI (L) (MIB1 LI in metastasized lymph node) was higher in poorly differentiated than in well differentiated carcinoma (p=0.0404). Prognostically, patients with high MIB1 LI (T) (>56.93) had a worse prognosis after surgery than those with low MIB1 LI (T) (p<0.05). There was no association between p53 positive tumors and MIB1 expression. These results suggest that cancer cell proliferative activity was markedly increased in cases with EHC compared to those with GBC and the poorly differentiated and lymph node metastasis group. MIB1 LI in tumor was found to be a good prognostic indicator whereas there was no association of p53 positive tumor with MIB1 expression and prognosis of the patients

スイタイブ ヒシンジュンセイ スイカンナイ ニュウトウセンガン ニ タイシ ヒ オンゾン スイタイ ビブ セツジョジュツ オ シコウ シタ 1レイ

We report a case of non-invasive intraductal papillary-mucinous carcinoma that was performed spleen-preserving distal pancreatectomy. A 74-year-old man was admitted to our hospital because he was pointed out a cystic tumor of the pancreatic body by near doctor. Abdominal ultrasonography and endoscopic ultrasonography showed a cystic tumor with papillary elevated lesion. But there were no evidence of infiltration to another organs. Based on these various examinations a diagnosis non-invasive intraductal papillary-mucinous carcinoma was determined. Then we determined to perform a minimal invasive operation, and underwent spleen-preserving distal pancreatectomy. After the operation there were no major complications and he discharged on 45th post operative days. To determine the surgical procedure of non-invasive intraductal papillary-mucinous carcinoma, because of the high incidence of postoperative infections after splenectomy, we should try to preserve the organ function. It was considered that this procedure was a useful method for non-invasive intraductal papillary-mucinous carcinoma of the pancreas body

Protective effect of FK506 and Thromboxane synthase inhibitor on ischemia-reperfusion injury in non-heart-beating donor in rat orthotopic liver transplantation

The study investigated the possibility of pharmacologically modulating hepatic allograft function from non-heart-beating donors (NHBDs)using male Lewisrats. The donors were divided into 4 groups :Group 1 in which the vehicle was administered, Group 2 in which FK506 (tacrolimus a powerful immunosuppressive agent)was administered,Group3 in which OKY046 (a specific thromboxane synthetase inhibitor) was administered and Group 4 in which FK506 and OKY046 were administered. The recipients received orthotopic liver transplantation. The survival rates differed significantly between the recipients that had received liver transplantation from Groups1 and 4. The serum liver enzyme and inflammatory cytokine concentrations of the recipients which had received liver transplantation from Groups 2, 3 and 4 were significantly lower than those of the recipients that had received liver transplantation from Group1. Although there was no significant difference, all parameters were better in the recipients that had received transplantation from Group 4 than those that had received transplantation from Groups 2 and 3. The action mechanisms of FK506 and OKY046 are completely different. Therefore, concomitant use of FK506 and OKY046 might have additive effects on liver transplantation from NHBDs. In conclusion, we demonstrated that pretreatment of NHBDs using FK506 and OKY 046 ameliorated graft viability

Correlation of vascular endothelial cell proliferation with microvessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in hepatocellular carcinoma

Tumor-associated angiogenesis is essential for tumor growth or metastasis, and consists of multiple and sequential steps regulated by proangiogenic and antiangiogenic factors. Vascular endothelial cell proliferation is involved in this process. We investigated the correlation of vascular endothelial cell proliferation with microvessel density (MVD) and expression of major proangiogenic molecules, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in hepatocellular carcinoma (HCC). Formalin-fixed paraffin-embedded specimens of surgically resectedHCCfrom67 patients were used. Proliferating endothelial cells were detected by immunofluorescence double staining for CD34 and proliferating cell nuclear antigen (PCNA). The proliferation activity of endothelial cells was determined by the rate of PCNA-positive endothelial cells, and evaluated at the periphery and center of the tumors and adjacent non-neoplastic livers. MVD and the expression of VEGF and bFGF in the tumors were also examined immunohistochemically. The proliferation activity of endothelial cells at the periphery of the tumors was significantly higher than that at the center of the tumors (35.8% vs.12.7%, P<0.0001). The rate of PCNA positive endothelial cells in the tumors with higher bFGF expression was significantly higher than that in the tumors with lower bFGF expression (44.8% vs. 32.5%,P<0.005) at the periphery of the tumors. There was no significant correlation between the rate of PCNA-positive endothelial cells and clinicopathological findings or MVD. InHCC, the proliferation activity of vascular endothelial cells is suggested to be heterogeneous in the tumor and higher at the periphery of the tumor, and bFGF may play an important role in the positive regulation of tumor-associated vascular endothelial cell proliferation

Experimental study of the evaluation of liver function on the opposite side during portacaval anastomosis and ligation of the left portal branch

Background. Hepatocellular carcinoma is likely to accompany liver cirrhosis in which the portal pressure increases with portasystemic shunt. When portal tumor thrombus is present in the primary bifurcation, blood flow differs between the thrombolic lobe and the non-thrombolic lobe. In those cases, it is difficult to evaluate exactly residual liver function by conventional test. Therefore, the following studies were performed. Materials and Methods. Adult mongrel dogs are divided into a control group(Cgroup), group undergoing ligation of the left portal branch(PL group), group undergoing portacaval anastomosis (PCS group) and group undergoing both ligation of the left portal branch and portacaval anastomosis (PL+PCSgroup)(n=5). ICG-R15 andMEGX15 in peripheral venous blood and right hepatic venous blood were determined. Mitchondrial metabolic capacity (adenosine triphosphate level, energy charge)was measured by high-performance liquid chromatography using liver biopsied specimens. Results. The MEGX ratio (right hepatic venous blood MEGX15/peripheral venous blood MEGX 15) positively correlated with energy charge in the right hepatic lobe. Conclusions. In evaluating liver function of the right hepatic lobe during portacaval shunt and the left portal branch ligation, the MEGX ratio may sensitively reflect the mitochondrial function