Tomonobu Gion

Postoperative liver failure after major hepatic resection for hepatocellular carcinoma in the modern era with special reference to remnant liver volume

BACKGROUND Postoperative liver failure is a life-threatening complication after hepatic resection. Because of recent advances in liver surgery technique and a more stringent patient selection, mortality after hepatic resection has steadily decreased, but its incidence still ranges from 10% to 20%. The factors linked to postoperative liver failure in major hepatic resection in the modern era should be reevaluated. STUDY DESIGN Of 80 patients with viral markers (hepatitis C viral antibody or hepatitis B surface antigen) who underwent major hepatic resections (no less than bisegmentectomies) for hepatocellular carcinoma between 1990 and 1996, 7 patients (8.8%) died of postoperative liver failure within 6 months after hepatectomy. The cause of liver failure was analyzed based on both the preoperative data and the intraoperative findings. In addition, since all the patients who died of liver failure underwent a right hepatic lobectomy, a further data analysis was also done in 47 patients who underwent a right lobectomy of the liver. A volumetric analysis by CT was then done to evaluate the remnant liver volume. RESULTS Between the patients with liver failure and those without liver failure who underwent a right lobectomy, there were no significant differences in preoperative data or intraoperative findings. Volumetric analysis revealed that the remnant liver volume of patients who died of liver failure was significantly smaller than that of patients who lived (p = 0.008). The incidence of liver failure in patients with a remnant liver volume of less than 250 mL/m2 was 7 of 20 (38%), while it was 0 of 27 in patients with a liver volume of no less than 250 mL/m2 (p = 0.0012). The only significant risk factor for liver failure in patients with a remnant liver volume of less than 250 mL/m2 was diabetes mellitus (p = 0.0072). CONCLUSIONS The expected remnant liver volume appears to be a good predictor for liver failure in patients who undergo a right lobectomy of the liver. In patients with diabetes mellitus and an expected remnant liver volume of less than 250 mL/m2, a major hepatectomy should be avoided. Careful patient selection based on volumetric analysis in major hepatectomy cases could help prevent the occurrence of postoperative liver failure.

Prognostic factors after repeat hepatectomy for recurrent hepatocellular carcinoma.

OBJECTIVE The aims of this study were to identify prognostic factors in patients who developed recurrent hepatocellular carcinoma (HCC) after repeat hepatectomy and to elucidate the role of multicentric occurrence in the second tumor after a first hepatectomy. SUMMARY BACKGROUND DATA A repeat hepatectomy for recurrent HCC has been established as the most effective treatment modality, whenever it is possible. However, the prognostic factors for recurrent HCC after repeat hepatectomy have yet to be clarified. METHODS Forty-one patients who underwent a curative repeat hepatectomy were retrospectively studied. Patient survival and disease-free survival after recurrence were univariately and multivariately analyzed using 38 clinicopathologic variables. The histologic grade of HCC at repeat hepatectomy was also compared with that at first hepatectomy. RESULTS Patient survival after repeat hepatectomy did not differ substantially from that in 312 patients undergoing primary hepatectomy. However, the disease-free survival after repeat hepatectomy was significantly lower than that in patients with only a primary hepatectomy (p < 0.05). Multivariate analysis revealed only portal vein invasion in the first hepatectomy to be an independent and significantly poor prognostic factor. Regarding multicentric occurrence at repeat hepatectomy, only 6 of 40 patients (15%) whose specimens could be evaluated histologically were determined to be Edmondson and Steiners Grade 1. CONCLUSIONS The only prognostic factor identified in patients with recurrent HCC after repeat hepatectomy was portal vein invasion in the first hepatectomy. Most second tumors after the first hepatectomy are considered to be caused by metastatic recurrence, not by multicentric occurrence.

Validity of preoperative volumetric analysis of congestion volume in living donor liver transplantation using three-dimensional computed tomography

Reconstruction of middle hepatic vein (MHV) tributaries is controversial in right‐lobe living donor liver transplantation (LDLT). This study aimed to evaluate the appropriateness of reconstructing MHV tributaries by volumetry using 3‐dimensional computed tomography (3D‐CT). Between November 2003 and January 2005, 42 donor livers (right‐lobe graft, n = 25; left‐lobe graft, n = 17) were evaluated using this software. The total congestion volume (CV) associated with the MHV tributaries and the inferior right hepatic vein (IRHV), and graft volume (GV) were calculated. In recipients with right‐lobe grafts, CV/(right liver volume [RLV]) and (GV − CV)/(standard liver volume [SLV]) were compared between 2 groups: with reconstruction (n = 16) and without reconstruction (n = 9). To evaluate the influence of CV on the remnant right lobe in donors, total bilirubin was compared between 2 groups: high CV (CV > 20%, n = 13) or low CV (CV ≤ 20%, n = 4). The mean CV/RLV ratio was 32.3 ± 17.1% (V5, 15.2 ± 9.9%; V8, 9.2 ± 4.1%; and IRHV, 8.5 ± 11.4%) and the maximum ratio was as high as 80.8%. The mean (GV − CV)/SLV ratio before reconstruction in patients with or without reconstruction resulted in 33.5 ± 12.8% and 55.4 ± 12.9%, respectively (P < 0.01). In donors, total bilirubin was significantly high in the high CV group on postoperative day 1 compared with the low CV group (P < 0.05). In conclusion, calculation of CV using 3D‐CT software proved to be very useful. We concluded that this evaluation should be an integral part of procedure planning, especially for right‐lobe LDLT. (Liver Transpl 2005;11:1556–1562.)

Suppressed MKP-1 Is an Independent Predictor of Outcome in Patients with Hepatocellular Carcinoma

Objective: An increase in the activity of mitogen-activated protein kinases (MAPKs) has been correlated with a more malignant phenotype in several tumor models in vivo. This study was designed to clarify the expression of MKP-1 in surgically resected hepatocellular carcinoma (HCC). Methods: We reviewed the cases of 77 patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemical analysis of MKP-1 was performed on paraffin-embedded tissues. The correlation between MKP-1 expression and clinical outcome was investigated. Results: Tumor cells were immunohistochemically stained for MKP-1 expression, and the same levels as in normal hepatocytes were detected in 66 (85%) of 77 HCC patients, being decreased in 11 (15%) HCCs. Decreased MKP-1 expression significantly correlated with serum α-fetoprotein levels and tumor size (p < 0.05). The disease-free survival rates in MKP-1-negative and -positive patients were 0 and 31.0% at 5 years, respectively (p < 0.01). The survival rates after a surgical resection in MKP-1-negative and -positive patients were 18.2 and 65.5% at 5 years, respectively (p < 0.01). Conclusions: The MKP-1 expression in HCC was an independent prognostic factor for outcome in HCC patients. In the future, it will be useful to explore whether the phosphatase expression might account for the response to HCC treatments targeting at MAPK activation.

Expression of matrix metalloproteinase-9 in surgically resected intrahepatic cholangiocarcinoma

BACKGROUND Matrix metalloproteinase-9 (MMP-9) has recently been reported to be related to cancer cell invasion. This study was performed to clarify the expression of MMP-9 in surgically resected intrahepatic cholangiocarcinoma (IHCC). METHODS In 37 patients with IHCC who underwent a surgical resection, the expression of MMP-9 and the clinicopathologic characteristics of MMP-9-positive IHCC were investigated. The expression of MMP-9 was immunohistochemically detected in 16 (43%) of 37 IHCC. The patients were divided into MMP-9 (-) IHCC (n = 21), MMP-9 (+) IHCC (n = 12), and MMP-9 (++) IHCC (n = 4). RESULTS The survival rate after surgical resection in patients with MMP-9 (-), (+), and (++) IHCC, was 66%, 39%, and 0% at one year, 50%, 32% and 0% at 3 years, respectively (P = .001). The incidence rate of lymph node metastasis was 6 (28%) of 21 in MMP-9 (-) patients, 7 (58%) of 12 in MMP-9 (+) patients and 4 (100%) of 4 in MMP-9 (++) patients. The incidence rate of lymph node metastasis increased in proportion to an increase in the expression of MMP-9 in IHCC (P = .02). Recurrence in the lymph node was more common in patients with MMP-9 (+) and (++) cancers than in those with MMP-9 (-) cancers. CONCLUSIONS The expression of MMP-9 in IHCC was a prognostic factor related to lymph node metastasis.

Significance of alpha-fetoprotein levels for detection of early recurrence of hepatocellular carcinoma after hepatic resection.

The recurrence of hepatocellular carcinoma (HCC) after surgery is common. The present study was conducted in order to clarify the significance of alpha‐fetoprotein (AFP) in the detection of the early recurrence of HCC after surgery.

Fascin expression in progression and prognosis of hepatocellular carcinoma

Fascin is an actin‐bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry.

The role of telomerase activity in hepatocellular carcinoma

OBJECTIVE:The aim of this study was to clarify the role of telomerase activity in hepatocellular carcinoma (HCC).METHODS:Specimens from both HCC and noncancerous liver were obtained from 39 patients with HCC using a 14-gauge biopsy needle immediately after laparotomy. Telomerase activity was determined using a telomeric repeat amplification protocol assay. The 3+ of telomerase activity in HCC was defined as a high telomerase group, and 2+ or less of HCC telomerase activity was defined as a low telomerase group. In noncancerous liver, 2+ or more of telomerase activity was defined as an increased telomerase group, and 1+ or less of telomerase activity was defined as a nonincreased telomerase group. The correlation between telomerase activity in HCC or noncancerous liver and clinicopathological factors, including prognosis, was investigated.RESULTS:Telomerase activities in HCCs were 0 in one patient, 1+ in two, 2+ in seven, and 3+ in 29 patients. The disease-free survival rate in the high telomerase group was significantly worse than that in the low telomerase group. The des-γ-carboxy prothrombin level in a high telomerase group (median, 330 mAU/ml) was significantly higher than that in the low telomerase group (median, 150 mAU/ml). A multivariate analysis revealed that higher TNM stage, high telomerase activity in HCC, female gender, and high α-fetoprotein value were independent significant factors related to be early recurrence. The incidence of multicentric HCC occurrence in the increased telomerase group (53.3%) tended to be higher than that in the nonincreased telomerase group (27.3%).CONCLUSION:A high telomerase activity in HCC correlated with the potential of HCC to be more malignant, which was expressed as both a high level of des-γ-carboxy prothrombin and an earlier recurrence after hepatectomy than that of HCC with a low telomerase activity.

Hepatic resection for the treatment of liver metastases in gastric carcinoma: review of the literature.

This article presents a review of the literature on hepatic resection for the treatment of liver metastases in gastric carcinoma, and discusses the indications, mortality rates, prognostic factors and long-term results. Reports on hepatectomy for liver metastases from gastric cancer are rare, the results are disappointing, and further studies are required.

New prediction factors of small-for-size syndrome in living donor adult liver transplantation for chronic liver disease.

Small‐for‐size syndrome (SFSS), which is characterized by synthetic dysfunction and prolonged cholestasis, is a major cause of worse short‐term prognoses after living donor adult liver transplantation (LDALT). However, the risks of SFSS remain unclear. The aim of this study was to clarify the risks of SFSS, which were analysed in 172 patients who underwent LDALT for chronic liver disease. Graft types included left lobe with caudate lobe graft (n = 110) and right lobe graft (n = 62). Thirty‐four cases (24 with left lobe grafts and 10 with right lobe grafts) were determined as SFSS. SFSS developed even if the actual graft‐to‐recipient standard liver volume ratio was >40%. Logistic regression analysis revealed three independent factors associated with SFSS development in left and right lobe grafts: donor age, actual graft‐to‐recipient native liver volume ratio, and Child’s score. Donor age and actual graft‐to‐recipient native liver volume ratio may become predictive factors for SFSS development in left and right lobe grafts in patients undergoing LDALT.