Naritaka Yamamoto

Cholangitis and Liver Abscess after Percutaneous Ablation Therapy for Liver Tumors: Incidence and Risk Factors

PURPOSE To determine the risk factors of cholangitis and liver abscess occurring after percutaneous ablation therapy for liver tumors. MATERIALS AND METHODS Between October 1995 and September 2002, 358 patients with 455 liver tumors underwent a total of 683 ablation procedures, such as percutaneous ethanol injection (PEI), percutaneous microwave coagulation (PMC), and radiofrequency (RF) ablation therapy. With a retrospective review of medical records, the rates and outcomes of cholangitis and/or liver abscess occurring after ablation therapy were evaluated. The relationship between cholangitis and/or liver abscess and multiple variables (age, disease, Child-Pugh class, size of nodules, multiplicity of nodules, history of transcatheter arterial embolization, presence of bilioenteric anastomosis, and lack of prophylactic antibiotics administration) were statistically analyzed. RESULTS Cholangitis and/or liver abscess occurred in 10 sessions (1.5%) in 10 patients: six sessions after PEI, three sessions after PMC, and one session after RF ablation. Both cholangitis and liver abscess were noted in seven sessions, cholangitis was noted in two, and liver abscess was noted in one. Six patients recovered, but two developed recurrent cholangitis and liver abscess, one developed lung abscess complicated with liver abscess, and one died of septic shock associated with cholangitis. On stepwise regression analysis, bilioenteric anastomosis was the sole significant predictor of cholangitis and/or liver abscess formation (P <.001; odds ratio = 36.4; 95% CI = 9.67-136.9). CONCLUSION Bilioenteric anastomosis strongly correlated with the development of cholangitis and/or liver abscess after percutaneous ablation therapy. Close posttreatment attention should be paid to this subgroup of patients.

Results of hepatic resection for hepatocellular carcinoma invading major portal and/or hepatic veins

Nonsurgical therapy for patients with advanced hepatocellular carcinoma (HCC) has yielded poor long-term survival. This study evaluates the effects of surgical treatments for patients with HCC invading major portal and/or hepatic veins. The surgical results of 112 patients with HCC invading major portal and/or hepatic veins who underwent hepatic resection between 1985 and 2001 were studied to evaluate the feasibility of hepatic resection as a local treatment.

Management of Adrenal Metastasis from Hepatocellular Carcinoma

Abstract.Purpose: Although the adrenal gland is a common site of extrahepatic metastasis from hepatocellular carcinoma (HCC), there are no definitive guidelines for the treatment of adrenal metastasis. This study examines the effectiveness of various treatments for this disease. Methods: We retrospectively analyzed 20 patients treated for adrenal metastasis of HCC by adrenalectomy (n = 13), transarterial chemoembolization (TACE), or percutaneous ethanol injection therapy (PEIT) (n = 7). Results: There were no significant differences in cumulative survival rates between patients given adrenalectomy and those given TACE or PEIT, either after completing treatment for primary HCC or after the first treatment for adrenal metastasis. Six of seven patients with tumor thrombi in the inferior vena cava (IVC) from adrenal metastasis underwent adrenalectomy combined with intracaval thrombectomy, five of whom survived for more than 1 year after surgery, and two of whom are still alive without any recurrence more than 3 years after surgery. PEIT showed good results for small adrenal metastasis. Conclusion: These findings suggest that therapeutic modalities should be chosen according to the clinical features of each individual, including the size of the metastatic tumor, whether there is invasion into the IVC, the function of the remaining liver, and the existence of intra- and/or nonadrenal extrahepatic lesions. Furthermore, intracaval tumor thrombectomy could be indicated for patients with IVC thrombus if they are suitable candidates for surgery.

Arterial ketone body ratio as a possible indicator for liver transplantation in fulminant hepatic failure.

Arterial ketone body ratio (AKBR [acetoacetate/beta-hydroxybutyrate]) was measured in nineteen patients under medical supportive therapy for fulminant hepatic failure (FHF), in order to evaluate its predictive value relative to liver transplantation. Of the 19 patients 8 (42%) were salvaged and 11 (58%) died. Seven of 8 survivors showed an increased AKBR over 0.6 at 24-hr after admission, and all of them showed AKBR over 0.8 at 48-hr with subsequent maintenance of the value over 1.0. By contrast, all 11 nonsurvivors demonstrated sustained suppression of AKBR below 0.4 from 24 to 72 hr after admission. AKBR values at 24 and 48 hr showed statistically significant differences between survivors and nonsurvivors. Neither the grade of portal systemic encephalopathy (PSE) nor other conventional laboratory parameters--such as AST, bilirubin, ammonia, prothrombin time, hepaplastin test, fibrinogen, and platelet count--could discriminate between survivors and nonsurvivors by univariate analysis. These results indicate that AKBR can accurately predict the prognosis of FHF at the initial 24-48 hr after admission, and that it can play an important role in setting the indication of FHF for liver transplantation.

Inactivation of the small GTPase Rac1 protects the liver from ischemia/reperfusion injury in the rat.

BACKGROUND In ischemia/reperfusion (I/R) injury, a massive generation of reactive oxygen species (ROS) after reperfusion is a critical factor. Rac, a member of the Rho GTPase superfamily, plays important roles in the production of ROS and activation of nuclear factor-kappaB (NF-kappaB) in vitro. However, the exact role of Rac in the ROS production and NF-kappaB activation in vivo after I/R is still obscure. METHODS We blocked Rac1 activity in the rat liver using adenovirus encoding a dominant negative rac1 mutant (Ad5N17Rac1) and examined whether inactivation of Rac1 could prevent ROS generation in the hepatic I/R injury. Seventy-two hours after the adenoviral infection, hepatic I/R was induced by Pringles maneuver for 20 minutes, followed by reperfusion in the rats. RESULTS Ad5N17Rac1 infection significantly attenuated ROS production after reperfusion and suppressed the hepatic injury. Furthermore, N17Rac1 suppressed NF-kappaB activation and messenger RNA expression of tumor necrosis factor-alpha (TNF-alpha) and inducible nitric oxide synthetase (iNOS). Ad5LacZ, a control adenovirus, had no effect on the induced hepatic I/R injury, nor did it affect NF-kappaB activation. Immunohistochemical analysis of NF-kappaB (p65) revealed that translocation of p65 to the nucleus after reperfusion was blocked in many of non-parenchymal cells (NPCs) and in hepatocytes in the Ad5N17Rac1-infected liver. CONCLUSION We conclude that Rac1 is required in ROS generation and NF-kappaB activation after hepatic I/R in vivo, and that inactivation of NF-kappaB in NPCs and suppression of ROS generation in NPCs and hepatocytes possibly account for the protective effect of N17Rac1 in this study.

Seventy-two-hour preservation of porcine liver by continuous hypothermic perfusion with UW solution in comparison with simple cold storage.

Porcine livers preserved for 72 hr using continuous hypothermic perfusion (CHP) were studied in order to compare the effects of CHP on energy metabolism with those of simple cold storage (SCS). The livers of the CHP group were perfused in situ for 72 hr at 7 degrees C with University of Wisconsin (UW) solution and FC-43 as an oxygen carrier, while those of the S1 group were stored ex situ for 48 hr at 4 degrees C in UW solution, and those of the S2 group for 72 hr. They were then recirculated with human blood at 37 degrees C for 2 hr for the evaluation of their viability. At the end of preservation, significantly higher levels of total adenine nucleotides (TAN) and energy charge (EC) were observed in the CHP group compared with the S1 and S2 groups. At 2 hr recirculation, the level of TAN was significantly higher in the CHP group than in the S1 and S2 groups. The EC level was also higher in the CHP group than in the S2 group. During recirculation, the ketone body ratio (acetoacetate/beta-hydroxybutyrate) was higher in the CHP group than in the S2 group. The values in the CHP group were above 1.0 after 45 min recirculation. There were no significant differences in the pyruvate/lactate ratio and lactate level between the CHP and S1 groups. However, these values were significantly different from those in the S2 group. The present findings demonstrate that CHP using UW solution and the oxygen carrier was better able to preserve the energy metabolism of the porcine liver for 72 hr than 48-hr SCS in UW solution.

Extrinsic sympathetic reinnervation after intestinal transplantation in rats

Although extrinsic denervation is inevitable after intestinal transplantation and leads to poor intestinal function, little is known about the occurrence of extrinsic reinnervation. In this study, extrinsic sympathetic reinnervation was investigated morphologically following syngeneic intestinal transplantation performed on male Lewis strain rats. At 1, 3, 6, 9, 15, and 27 weeks after transplantation, the graft mesenteric arteries and their branches in the intestinal wall were histochemically examined by a glyoxylic acid method demonstrating perivascular sympathetic nerve fibers. At 3 weeks after transplantation, extrinsic sympathetic reinnervation was recognized in the graft mesenteric arteries, where it traversed the arterial anastomosis and extended along the course of the mesenteric arteries from proximal to distal. The degree of reinnervation in the mesenteric arteries was similar to the results obtained in the simple denervation model. The transplanted intestinal tract itself was sympathetically denervated for at least 9 weeks after transplantation, and reinnervation was not recognized until 15 weeks after transplantation. Reinnervation extended into the intestinal wall in every preparation, and the enteric nerves began to be rein-nervated at 27 weeks after transplantation, but the density was still at a low level and complete extrinsic reinnervation of the graft would seem to require a much longer time to reestablish itself.

In situ pedicle resection in left trisegmentectomy of the liver combined with reconstruction of the right hepatic vein to an inferior vena caval segment transpositioned from the infrahepatic portion.

A combination of an in situ pedicle resection of the liver and a hepatic vein reconstruction using a cranially transpositioned segment of the IVC after implantation of an ePTFE graft at the missing IVC was useful in treating a patient who suffered from a huge liver tumor involving all of the hepatic venous confluence and the IVC. Although early tumor recurrence remains an unresolved problem for such patients, a surgical approach is feasible. This technique can be justified as a therapeutic modality, not only because it improves quality of life, but also because it provides patients with an opportunity for additional treatment.

Increased expression of collagenase in the liver induces hepatocyte proliferation with cytoplasmic accumulation of β-catenin in the rat

BACKGROUND/AIMS Since the hepatic extracellular matrix is remodeled in liver regeneration, we investigated whether increased collagenase activity in the liver can induce hepatocyte proliferation in vivo. METHODS To increase hepatic collagenase activity, human matrix metalloproteinase-1 was delivered to the rat liver by the recombinant adenoviral vector Ad5MMP-1. RESULTS Hepatic delivery of Ad5MMP-1 increased the 5-bromo-2-deoxyuridine labeling index and mitotic index in hepatocytes, causing an increase in the dry liver weight; control adenovirus, Ad5LacZ, had minimal effect. Hepatocyte proliferation started approximately 48 h after infection with Ad5MMP-1 and ended after about 2 weeks. The increase in the dry liver weight also returned to baseline after 2 weeks. Transient liver injury by Ad5MMP-1, reflected by increased aspartate and alanine aminotransferase levels, peaked around 1 week, and was associated with hepatocyte apoptosis. Collagenase-induced hepatocyte proliferation was accompanied by cytoplasmic accumulation of beta-catenin and a transient decrease in E-cadherin expression. CONCLUSIONS Modification of the hepatic extracellular matrix by collagenase induces transient hepatocyte proliferation in vivo, suggesting that the condition of the hepatic extracellular matrix per se plays a pivotal role in regulating hepatocyte proliferation.

Myoglobin gene expression attenuates hepatic ischemia reperfusion injury

BACKGROUND Cellular functions are maintained by a continuous supply of ATP, which is supplied efficiently by mitochondrial oxidative phosphorylation. Since myoglobin, found in cardiac myocytes and red skeletal muscle, but not in the liver, facilitates oxygen diffusion under low oxygen conditions and enhances oxidative phosphorylation, this study seeks to enhance hepatic ATP levels and attenuate ischemia-reperfusion injury in rodent livers by adenovirus-mediated myoglobin expression. MATERIAL AND METHODS After infecting Hep3B and rodent livers with adenovirus carrying CMV promoter sequences linked to the human myoglobin gene (AdCMVMyo), reverse transcriptase-PCR and immunodetection for myoglobin, and cellular and hepatic ATP levels were examined. The effect of myoglobin was evaluated in a hepatic ischemia-reperfusion model in the rat. RESULTS Myoglobin expression was confirmed in Hep3B and rat livers after AdCMVMyo infection. The ATP levels in Hep3B cells and C57BL/6 mice livers 72 h after AdCMVMyo transfection were significantly higher than control levels and those after adenovirus-mediated beta-galactosidase transfection. Finally, expression of myoglobin attenuated ischemia-reperfusion injury in the rat liver. CONCLUSION These results indicate that myoglobin gene transfer to the liver enhanced ATP levels both in vitro and in vivo and might be a novel strategy to reduce ischemia-reperfusion injury.