Selection of patients with esophageal varices for liver resection of hepatocellular carcinoma.

The presence of esophageal varices (EV) is a phenotype of portal hypertension, and the indications of liver resection for hepatocellular carcinoma (HCC) in patients with concomitant EV are conflicting. This retrospective study aimed to elucidate if there is justification for liver resection in patients with EV. The surgical outcomes were compared between the patients who underwent resection for HCC with EV (EV group) and those without EV (non-EV group) after propensity-score matching. More bleeding was prevalent (P < 0.001) and refractory ascites was more frequently observed (P = 0.031) in the EV group (n = 277) compared with the non-EV group (n = 277); however, the numbers of patients with morbidities (P = 0.740) and re-operation (P = 0.235) were not significantly different between the two groups. After a median follow-up period of 3.0 years, the median overall and recurrencefree survival periods of patients with EV were 4.8 years (95% confidence interval [CI], 4.1-5.9) and 1.7 years (1.5-2.0), respectively, and were significantly shorter than those of patients without EV (7.6 years [95% CI, 6.3.9.7], P < 0.001, and 2.2 years [1.9-2.5], P = 0.016). On multivariate analysis, the independent factors for overall survival in the EV group were indocyanine green clearance rate at 15 minutes, des-gamma carboxyprothrombin, and the presence of multiple tumors. Considering that liver resection for patients with EV can be safely performed, it should not be contraindicated. However, surgical outcomes of these patients were unsatisfactory, suggesting that candidates for resection for HCC should be carefully selected.

Comparison of the surgical outcomes in patients with synchronous versus metachronous multiple hepatocellular carcinoma.

Multiplicity is one of the characteristics of hepatocellular carcinoma (HCC), and patients with multiple HCC (≤ 3 nodules) are recommended as candidates for liver resection. To confirm the validity of resecting multiple HCC, we compared the surgical outcomes in patients with synchronous and metachronous multiple HCC. Patients who underwent resection for multiple HCC (2 or 3 nodules) were classified into the "synchronous multiple HCC" group, while those undergoing resection for solitary HCC and repeated resection for 1 or 2 recurrent nodules within 2 years after initial operation were classified into the "metachronous multiple HCC" group. After one-to-one matching, longer operation time and more bleeding were seen in the synchronous multiple HCC group (n = 98) than those in the metachronous multiple HCC group (n = 98); however, the complication rates were not different between the two groups. The median overall survival times were 4.0 years (95% CI, 3.0-5.9) and 5.9 years (4.0-NA) for the synchronous and metachronous multiple HCC (after second operation) groups, respectively (P = 0.041). The recurrence-free survival times were shorter in the synchronous multiple HCC group than in the metachronous multiple HCC group (median, 1.5 years [95% CI, 0.9-1.8] versus 1.8 years, [1.3-2.2]) (P = 0.039). On multivariate analysis, independent factors for overall survivals in the synchronous multiple HCC group were older age, cirrhosis, larger tumor, and tumor thrombus. Taken together, resection of metachronous multiple HCC still has good therapeutic effect, even better than synchronous multiple HCC, so resection is suggested for metachronous multiple HCC.

High platelet count as a poor prognostic factor for liver cancer patients without cirrhosis.

A low platelet count, one of parameters of portal hypertension, is clinically a predictor of postoperative mortality, while platelets induce tumor development during growth factor secretion. In this study, we retrospectively investigated whether high platelet count negatively affects the survival of patients with hepatocellular carcinoma (HCC). Patients undergoing initial and curative resection for HCC were included. Surgical outcomes were compared between the high platelet (platelet count ≥ 20 × 104/µL) and control (< 20 × 104/µL) groups in patients without cirrhosis and between the low platelet (< 10 × 104/µL) and control (≥ 10 × 104/µL) groups in patients with cirrhosis. Among patients without cirrhosis, tumor was larger (P < 0.001) and tumor thrombus was more frequent (P < 0.001) in the high-platelet group than in the control group. After a median follow-up period of 3.1 years (range 0.2-16.2), median overall survival was 6.3 years (95% confidence interval [CI], 5.3-7.8) and 7.6 years (6.6-10.9) in the high-platelet (n = 273) and control (n = 562) groups, respectively (P = 0.027). Among patients with cirrhosis, liver function was worse (P < 0.001) and varices were more frequent (P < 0.001) in the low-platelet group. The median overall survival of patients in the low-platelet group (n = 172) was significantly shorter than that of patients in the control group (n = 275) (4.5 years [95% CI, 3.7-6.0] vs. 5.9 years [4.5-7.5], P = 0.038). Taken together, thrombocytopenia indicates poor prognosis in HCC patients with cirrhosis, while thrombocytosis is a poor prognostic predictor for those without cirrhosis.

Favorable outcomes of surgical resection for extrahepatic recurrent hepatocellular carcinoma.

AIM: Repeat resection for intrahepatic recurrent hepatocellular carcinoma (HCC) is effective for the long-term survival of patients; however, little is known about the surgical outcomes of extrahepatic nodules. The aim of this study is to investigate whether resection can contribute to the survival of patients with extrahepatic recurrent HCC. METHODS: Under the conditions that intrahepatic recurrent HCC was absent or controlled by locoregional therapies, patients who had resectable extrahepatic recurrent HCC in the lymph nodes, adrenal gland, peritoneum, lung, or brain were included in this study. The survival of patients who did (Surgical group) and did not (Non-surgical group, underwent other therapies) undergo resection for extrahepatic recurrent HCC was compared. RESULTS: Thirty-eight and 26 patients were included in the Surgical and Non-surgical groups, respectively. No patient had severe postoperative complications. After a median follow-up of 1.2 (range, 0.2-8.8) years, the median cumulative incidence of extrahepatic recurrent HCC was 1.2 years (95% confidence interval [CI], 0.4-3.5) in the Surgical group. The median overall survival was 5.3 (95% CI, 2.5-8.8) and 1.1 (0.8-2.3) years in the Surgical and Non-surgical groups, respectively (P < 0.001). The 5-year rates of survival were 60.5% and 9.1% in the Surgical and Non-surgical groups, respectively. Surgical resection, α-fetoprotein, disease-free interval, and metastasis at the adrenal gland were the independent factors for overall survival. CONCLUSIONS: Due to the favorable surgical outcomes, resection should be considered as one of the therapeutic choices for patients with extrahepatic recurrent HCC if intrahepatic recurrent HCC can be controlled by locoregional therapies.

Patients' prognosis of intrahepatic cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma after resection.

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) are classified into one category, but comparison of prognosis of the two carcinomas remains controversial. The aim of the current study was to investigate surgical outcomes for patients with ICC or cHCC-CC who underwent resection in order to elucidate whether the classification of ICC and cHCC-CC is justified. Subjects were 61 patients with ICC and 29 patients with cHCC-CC who underwent liver resection from 2001 to 2017. Clinic-pathological data from the two groups were compared. Tumor number and vascular invasion were independent risk factors for recurrence-free survival (RFS) in both groups (P < .001 for both). Of note, for patients with ICC, tumor cut-off size of 5 cm showed statistical significance in median RFS (>5 cm vs ≤5 cm, 0.5 years vs 4.0 years, P = .003). For patients with cHCC-CC, tumor cut-off size of 2 cm showed statistical significance in median RFS (>2 cm vs ≤2 cm, 0.6 years vs 2.6 years, P = .038). The median RFS of patients with cHCC-CC was 0.9 years (95% confidence interval: 0.3-1.6), which was poorer than that of patients with ICC (1.3 years, 0.5-2.1) (P = .028); the rate of RFS at 5 years was 0% and 37.7% respectively. Our study supports the concept of classifying ICC and cHCC-CC into different categories because of a significant difference in RFS between the two.

Paraneoplastic extralimbic encephalitis associated with thymoma: a case report.

Here we a report a rare case of extralimbic encephalitis associated with thymoma. A 66-year-old woman was admitted to our hospital with cramping in her right leg and inability to walk. Magnetic resonance imaging of the brain showed multifocal high intensity signals on T2 flare images in the cerebral cortex, and chest computed tomography showed a 5-cm anterior mediastinal mass, which was considered to be a thymoma. We speculated that she had paraneoplastic encephalitis associated with thymoma. She underwent a thymectomy and was diagnosed with type B1 thymoma. On postoperative day 6, her neurological symptoms began to improve. On postoperative day 31, she was discharged without complications. Limbic encephalitis is a paraneoplastic neurological syndromeassociated with thymoma, but extralimbic encephalitis has been described in the literature very rarely. We report the case of extralimbic encephalitis associated with thymoma along with a literature review.

[A case of pancreatic mucinous carcinoma invading the common bile duct with obstructive jaundice].

A 75-year-old man was admitted to our hospital for further investigation of obstructive jaundice due to a mucin-producing bile duct tumor. ERCP revealed dilatation of the common bile duct and a filling defect in the bile duct. Because of obstructive jaundice, an EBD tube was placed and bile was drained. Contrast-enhanced CT showed a low density 2-cm mass, in the pancreatic head containing some enhanced parts in the tumor. MRI revealed the tumor to be a low-intensity mass on T2-weighted image. After recovery from the obstructive jaundice, pancreaticoduodenectomy was performed under a diagnosis of invasive mucinous carcinoma penetrating the common bile duct from the pancreatic head, resulting in obstruction of the common bile duct. Postoperatively histopathological diagnosis of the resected specimen showed mainly mucinous carcinoma originating from the pancreatic head without a component of intraductal papillary-mucinous tumor.

Pancreatoduodenectomy after coronary artery bypass grafting using the right gastroepiploic artery: a case report.

We herein report the case of an advanced ampullary cancer developed 80 months after coronary artery bypass grafting (CABG) using the right gastroepiploic artery (RGEA) and successfully treated by pancreaticoduodenectomy (PD) with revascularization using the great saphenous vein. A 69-year-old Japanese male was admitted for examination with one-month history of nausea and appetite loss. He underwent three vessel CABG, involving bypassing between the right coronary artery and RGEA about 80 months before. The preoperative diagnosis with CT scan and gastric endoscope was carcinoma of the papilla of Vater. Preoperative abdominal angiography showed the RGEA graft remained well patent. He underwent PD with regional lymph node dissection after revascularization of the RGEA. The postoperative clinical course was uneventful. The histopathological examinations of the resected specimen revealed adenocarcinoma of the ampulla, pT2, pN0, M0 stage IB. The patient is currently alive without any further signs of ischemic heart disease several months after his operation. This case report demonstrates that the radical PD with revascularization using other vein graft can be safely performed after CABG using the RGEA.

A novel method of mouse ex utero transplantation of hepatic progenitor cells into the fetal liver.

Avoiding the limitations of the adult liver niche, transplantation of hepatic stem/progenitor cells into fetal liver is desirable to analyze immature cells in a hepatic developmental environment. Here, we established a new monitor tool for cell fate of hepatic progenitor cells transplanted into the mouse fetal liver by using ex utero surgery. When embryonic day (ED) 14.5 hepatoblasts were injected into the ED14.5 fetal liver, the transplanted cells expressed albumin abundantly or alpha-fetoprotein weakly, and contained glycogen in the neonatal liver, indicating that transplanted hepatoblasts can proliferate and differentiate in concord with surrounding recipient parenchymal cells. The transplanted cells became mature in the liver of 6-week-old mice. Furthermore, this method was applicable to transplantation of hepatoblast-like cells derived from mouse embryonic stem cells. These data indicate that this unique technique will provide a new in vivo experimental system for studying cell fate of hepatic stem/progenitor cells and liver organogenesis.

Endoscopic thermal ablation therapies for hepatocellular carcinoma: a multi-center study.

AIM: The differing efficacies of radiofrequency ablation and microwave coagulation for hepatocellular carcinoma (HCC) are unknown. Therefore, we performed a multi-center study to assess the factors contributing to survival and local recurrences of HCC among patients with solitary tumors who underwent endoscopic thermal ablation as their primary treatment. METHODS: From six institutions, 391 patients with solitary HCC who were first treated by endoscopic thermal ablation were enrolled in this study and assessed retrospectively. We investigated age, gender, location of tumor, longest diameter of tumor, method of anesthesia, type of endoscope, method of thermal ablation, Child-Pugh classification, the Japan Integrated Staging score and the Cancer of the Liver Italian Program score. Statistical analyses were performed using univariate analysis with log-rank test and multivariate analysis with the Cox proportional hazards model. RESULTS: On univariate analysis, advanced Child-Pugh score, advanced Italian Program score and local recurrences were significant predictors of poor survival. Young age (30 mm) and the use of the thoracoscopic approach were significant predictors for the development of local recurrence. On multivariate analysis, local anesthesia and advanced Child-Pugh score were independent predictors of poor survival. Young age, large tumor, local anesthesia and the use of the thoracoscopic approach were independent predictors for the development of local recurrence. The method of thermal ablation did not influence survival or local recurrence. CONCLUSIONS: Differences in the effect on survival and local recurrence between microwave and radiofrequency were not observed in this retrospective, multi-center study of endoscopic thermal ablation for HCC.

Influence of risk factors for metabolic syndrome and non-alcoholic fatty liver disease on the progression and prognosis of hepatocellular carcinoma.

BACKGROUND/AIMS: We investigated a relationship between the risk factors for metabolic syndrome, such as obesity, diabetes mellitus, hypertension, and hyperlipidemia, and the pathogenesis and outcome of hepatocellular carcinoma (HCC). METHODOLOGY: One hundred twenty four patients who underwent curative resections for HCC were classified into 3 groups: those patients who were positive for hepatitis B surface antigen (group B), those positive for antibody to hepatitis C virus (group C), and those negative for both of them (non-B non-C) (group NBNC). The preoperative laboratory data, risk factors for metabolic syndrome, history of alcohol abuse, and outcome after surgery were investigated. The presence of non-alcoholic steatohepatitis (NASH) was also evaluated. RESULTS: The incidence of diabetes mellitus, hyperlipidemia, and alcohol abuse, and the serum level of triglyceride were significantly higher in group NBNC than in groups B or C. The risk factors for metabolic syndrome tended to lower the survival rates in group B and C, but not in group NBNC. Three of the 37 non-B non-C patients were associated with NASH. CONCLUSIONS: It is suggested that the pathogenesis of non-B non-C HCC may be more closely associated with the risk factors for metabolic syndrome than that of hepatitis virus related HCC.

Strong association between frequency of intermittent inflow occlusion and transient increase in serum liver enzymes after hepatic resection.

BACKGROUND/AIMS: Although significantly higher serum levels of liver transaminases are commonly observed after hepatic resection, the factors responsible for the increase and the association between the increase and the postoperative course remain unclear. METHODOLOGY: The study population comprised 70 patients who had undergone hepatic resection except hepatectomy with vascular and biliary reconstruction. The relation between the perioperative factors and postoperative aspartic aminotransferase (AST) and alanine aminotransferase (ALT) elevations were analyzed. Outcome parameters, i.e., postoperative total bilirubin level, hospital stay and complications were also analyzed. RESULTS: The average maximum postoperative serum AST and ALT levels were 444.6 IU/L and 390.1 U/L. None of the preoperative factors examined, such as AST, ALT, associated liver disease, Liver Damage Classification, intraoperative hypotension, intraoperative blood loss or types of liver resection, were significantly correlated with liver enzyme elevations. The only factor that was significantly correlated was frequency of intermittent inflow occlusion (p < 0.001). The elevations of AST and ALT were not significantly correlated with length of hospital stay and postoperative serum bilirubin level. ALT also was not correlated to complications, whereas AST was significantly correlated to the frequency of the postoperative complications. CONCLUSIONS: The frequency of intermittent inflow occlusion is the only factor that affects the postoperative enzyme elevation.

Vascular endothelial growth factor promotes proliferation and function of hepatocyte-like cells in embryoid bodies formed from mouse embryonic stem cells.

BACKGROUND/AIMS: Embryoid bodies (EBs) formed from embryonic stem cells (ESCs) differentiate into hepatocyte-like cells (HLCs), and are thus thought to be a useful cell source for drug testing and bioartificial liver. The aim of this study was to induce proliferation and function of ESC-derived HLCs in EBs using HLC-endothelial cell interaction. METHODS: EBs were cultured in the presence of vascular endothelial growth factor (VEGF) and/or VEGF receptor (VEGFR) inhibitors. To reproduce HLC-endothelial cell interaction, we overexpressed VEGF in ESC-derived HLCs under the control of Cyp7a1 gene in EBs. RESULTS: VEGF added to the cultured EBs increased the proliferation of ESC-derived endothelial cells, resulting in the promotion of proliferation and function of ESC-derived HLCs. In EBs, the VEGFR2 inhibitor suppressed expression of albumin and endothelial cell marker genes, whereas the inhibitor for both VEGFR1 and VEGFR2 suppressed expression of Cyp7a1 and hepatocyte growth factor (Hgf) genes. Upon exposure to VEGF, the endothelial cells in EBs increased Hgf mRNA expression. Forced VEGF expression in ESC-derived HLCs in EBs induced angiogenesis around the HLCs and resulted in an increase in the amount of HLCs. CONCLUSIONS: VEGF indirectly induces the proliferation and function of ESC-derived HLCs through VEGFR1 and VEGFR2 signaling in endothelial cells.

Left-sided portal hypertension caused by serous cystadenoma of the pancreas: report of a case.

We report a case of serous cystadenoma of pancreas causing left-sided portal hypertension and gastric varices. A 68-year-old man was admitted for treatment of a pancreatic body tumor. Contrast-enhanced computed tomography (CT) showed a honeycombed cystic mass. A celiac angiogram showed a hypervascular tumor supplied mainly by a dilated splenic artery and dorsal pancreatic artery. In the venous phase, the patent splenic vein had a large hepatopetal collateral vein via the coronary gastric vein. Upper gastrointestinal endoscopy showed isolated varices of the gastric fundus. We made a preoperative diagnosis of a serous cystic tumor of the pancreas with left-sided portal hypertension and performed distal pancreatectomy with splenectomy. The resected tumor was 8 cm in diameter and had a typical honeycombed microcystic pattern with central stellate scarring. The spleen was not enlarged. Histopathological examination confirmed a diagnosis of serous cystadenoma without any sign of malignancy. Postoperative endoscopy showed disappearance of the gastric varices.

Sensitization to enhanced green fluorescence protein minor histocompatibility antigen by gene transduction into dendritic cells and peritoneal exudate macrophages.

Enhanced green fluorescence protein (EGFP) has been widely applied to gene transduction in cellular and molecular biology as a reporter element. When applied to cell transplantation, it raises fundamental issues concerning cell-associated antigens, in particular, a model of minor histocompatibility antigen(s). Although it is well known that immunological behavior of minor histocompatibility antigens mimic tumor associated antigens (TAA), identified genes coding minor histocompatibility antigens are few and far between. Inasmuch as immunity and tolerance to TAA are provided by immunological behavior of minor histocompatibility antigen such as histocompatibility antigen of the Y chromosome, H-Y, it occurs to us that transgenic as well as transduced EGFP provides a useful model system to be applied to tumor immunology. In this respect, genetic modification of specialized antigen-presenting cells (APC), i.e., dendritic cells (DC), such as gene transduction of EGFP into DC, would provide one of the most important strategies in transplantation as well as tumor immunology inasmuch as DC play a key role in initiating primary immune responses, As far as gene transduction into DC is concerned, others have reported that successful gene transduction occurs in DC by adenoviral vector systems. However, our previous studies concerning EGFP transduction into DC suggested that this view should be carefully examined and interpreted. Employing adenoviral and lentiviral vector systems as well as specialized APC of rat DC and peritoneal exudate macrophages (PEM), EGFP-transduced APC were examined to determine whether and to what extent the EGFP-transduced APC were able to sensitize non-transgenic littermates against transgenic EGFP as antigen(s). Thus EGFP-transgenic cardiac isografts were transplanted to non-transgenic littermates and examined to determine if sensitization of non-transgenic littermate recipients with the EGFP-transduced APC was able to reject the test grafts in an accelerated manner. In this study, we examined this and provide further evidence that widely used viral vector systems are unable to transfer the reporter gene EGFP into mature rat DC generated from bone marrow cells (BMC), driven by Flt3/Flk2 ligand and IL-6. Nevertheless, successful gene transduction was obtained by either applying a lentiviral vector system to the developing DC progenitor cells during a long-term culture of rat BMC or by applying an adenoviral vector system to PEM. Thus, successful gene transduction into specialized APC was verified by in vivo priming of non-transgenic littermates with the EGFP-transduced APC, followed by accelerated rejection of EGFP-transgenic cardiac isografts.

Hepatic progenitor cells in the mouse extrahepatic bile duct after a bile duct ligation.

The intrahepatic bile duct has been suggested to be a source of hepatic progenitor cells in the severely damaged liver. In contrast, little attention has been paid to the question of whether hepatic progenitor cells exist in the extrahepatic bile duct (EHBD). In the present study, we examined the phenotypic changes of the mouse EHBD following bile duct ligation. After bile duct ligation, the number of c-Kit-positive epithelial cells increased in the EHBD. The ligated EHBD expressed mRNA for hepatic progenitor cell markers, including c-Kit and Thy-1. Hepatocyte markers such as albumin and cytochrome P450 7a1 were also transiently detected in the EHBD after a bile duct ligation. In a culture of EHBD cells, we detected hepatic progenitor cells that were positive for both staining with anti-albumin antibodies and Dolichos biflorus agglutinin, a biliary epithelial cell-specific lectin. Furthermore, hepatic progenitor cells positive for both c-Kit and albumin were found in the cultured EHBD population. Additionally EHBD-derived hepatocyte-like cells were also observed in the culture. A transplantation study revealed that EHBD cells integrate into the parenchyma and are albumin positive. These data suggest that hepatic progenitor cells emerge in the EHBD following bile duct ligation, that subsequently give rise to hepatocyte-like cells. We also observed that the gall bladder transiently expressed hepatocyte markers after bile duct ligation. Our results suggest a potential of the EHBD and gall bladder as useful transplantable sources for liver injury.

Evaluation of tumor growth in vivo in a rat model of liver metastasis, using a newly devised index obtained by positron emission tomography with [18F] FDG.

BACKGROUND/PURPOSE: [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) is regarded as a unique imaging modality, because the images reflect tumor activity. This characteristic of PET encouraged us to use it to develop a novel method of quantitatively measuring liver metastasis viability. METHODS: F344 rats were injected with rat colon adenocarcinoma cells (RCN-9 cell line) via the portal vein, and some of them were treated with 5-fluorouracil (5-FU). Tumor growth and tumor activity were measured by PET. We used a tumor viability index (TVI) to evaluate changes in tumor activity and to quantitatively evaluate tumor proliferation activity, instead of using the standardized uptake value (SUV) of the tumor tissue. The TVI was compared with the number of tumor nodules and the proliferating cell nuclear antigen (PCNA) index 28 days after RCN-9 cell inoculation. RESULTS: [(18)F] FDG uptake by the liver tumors was measured by PET, and the TVI was found to increase as the tumor nodules increased in number and size. The TVI values in the experimental model represented the viability of tumors suppressed by chemotherapy, and the values were significantly correlated with the number of nodules and the PCNA index. CONCLUSIONS: The TVI was concluded to be superior to the SUV, the commonly used indicator, for evaluating tumor growth, especially that of multiple, small tumors.

Mucinous cystadenocarcinoma of the pancreas developing during hormone replacement therapy.

Hormone replacement therapy (HRT) containing estrogens is generally used to relieve climacteric symptoms and to prevent osteoporosis and coronary heart disease [1], however, there has been increasing evidence of the HRT as the risk of hormone-dependent neoplasms including breast cancer [2], uterine endometrial cancer [3], ovarian cancer [4], and even lung cancer [5]. Noteworthy is mucinous cyst neoplasms (MCNs) of the pancreas, characterized by mucin-producing columnar epithelium supported by "ovarian-like" mesenchymal stroma, occur mostly in females expressing estrogen receptors [6, 7]. Although several reports regarding the closed relationship between MCNs and pregnancy [8, 9] might imply potential sex hormone-dependency of the MCNs [10], no correlation has been reported. This is the first case report of malignant MCN developing during continuous HRT after hysterectomy.

Outcomes and recurrence of initially resectable hepatocellular carcinoma meeting milan criteria: Rationale for partial hepatectomy as first strategy.

BACKGROUND: Partial hepatectomy and liver transplantation are considered curative treatments for small hepatocellular carcinoma (HCC) meeting the Milan criteria (solitary tumor <5 cm or up to 3 nodules <3 cm). This study was designed to clarify whether partial hepatectomy can be the first option in patients eligible for both treatments. STUDY DESIGN: All patients (n = 152) underwent curative surgical operation for primary HCC during 2000 to 2005 at our hospital. Eighty-seven patients met Milan criteria and the remaining 65 did not. Outcomes were examined according to Milan criteria. RESULTS: After partial hepatectomy, 3-year survival rate was 89.6% for the group that met Milan criteria, compared with 60.8% for the group that did not (p = 0.0044). Among patients with HCC who initially met the criteria, tumor recurrences were observed in 30 patients; 23 patients met criteria and 7 patients exceeded the criteria at first diagnosis of recurrence. Patients with recurrence within the criteria showed a higher 3-year survival rate compared with patients with recurrence exceeding the criteria (100% versus 19.8%; p < 0.0001). Analysis of clinicopathologic variables to predict mode of recurrence revealed tumor size (p < 0.0001) and lower histologic differentiation (p = 0.0326) as positive factors for recurrence exceeding Milan criteria. CONCLUSIONS: Our results suggest that it is an appropriate strategy to treat HCC patients who meet Milan criteria with partial hepatectomy. It should be noted that approximately one-tenth of patients who initially met Milan criteria experienced postoperative recurrence that exceeded the criteria.

The close participation of ET-1 and NO in human hepatic hemodynamics.

BACKGROUND: Nitric oxide and endothelin-1 (ET-1) are believed to closely participate in the hepatic circulation. However, there are no clinical studies evaluating the participation of these two molecules in the hepatic circulation. PATIENTS AND METHODS: All 27 patients had liver tumors; 6 liver tumors were associated with liver cirrhosis and 12 patients had chronic hepatitis. Portal vein and hepatic arterial blood flow was measured with an electromagnetic flowmeter. Blood was sampled to quantitate endothelin-1 and nitrate/nitrite (NO(x)) from portal veins, peripheral veins and peripheral arteries. RESULTS: Serum ET-1 levels tended to be higher in patients with liver cirrhosis than patients with chronic hepatitis or patients with normal livers. There were no apparent differences in NO(x) concentrations among underlying liver disease states. Portal blood flow and estimated total hepatic blood flow was adversely correlated with ET-1 in portal veins with relatively higher correlation coefficients whereas arterial blood flow was not correlated to ET-1. On the other hand, arterial plasma ET-1 concentrations were not correlated to any type of blood flow. NO(x) concentrations were not correlated with any type of hepatic blood flow. The ratio of NO(x) to ET-1 in portal veins was correlated with portal blood flow and estimated hepatic blood flow. This correlation coefficients were higher than correlation coefficients between ET-1 concentrations in portal veins, and portal and hepatic blood flow. CONCLUSION: ET-1 levels in portal blood are significantly associated with portal blood flow and total hepatic blood flow in humans, and ratio of NO(x) to ET-1 is better indicators than either ET-1 or NO(x) alone. Although this study has limitations because it was carried out in a clinical setting, the data may contribute to the understanding of human hepatic hemodynamics.