Ting-Jung Wu

Minor versus major hepatic resection for small hepatocellular carcinoma (HCC) in cirrhotic patients: A 20-year experience

BACKGROUND The choice between minor versus major resection or anatomic versus nonantatomic resection for small (<5 cm) solitary hepatocellular carcinoma (HCC) in patients with cirrhosis is controversial. The aim of our study was to evaluate the long-term disease-free survival (DFS) and overall survival (OS) after minor or major hepatic resection for small solitary HCC in cirrhotic patients. METHODS Between January 1983 and December 2002, patients with solitary HCC of < or = 5 cm in size who had histologically proven liver cirrhosis and microscopically tumor-free margin were included. These selected patients underwent either minor (< or = 2 segments) or major (> or = 3 segments) hepatectomy. RESULTS In 373 patients, 259 underwent minor and 114 underwent major hepatectomy. Patients in the minor resection group had more severe underlying liver disease (P = .005). Therefore, only 29.3% received anatomic resection in the minor resection group in comparison with 72.8% in the major hepatectomy group (P = .0001). No difference was found in postoperative morbidity (P = .105), mortality (P =.222), intrahepatic recurrence (P = .742), and 5-year DFS and OS (31.6% vs 31.8%, P = .932 and 50.7% vs 44.0%, P = .114) in both groups. The type of operative resection was not found to be a significant factor affecting survival in univariate analysis, but the preoperative liver function (alanine aminotransferase [AST] or alanine aminotransferase [ALT], serum albumin, or Child-Pugh status), tumor characteristics (alpha-feto protein, size, and presence of daughter nodules), and blood transfusion were found to be independent factors that affect the DFS and OS in a multivariate analysis. CONCLUSION The severity of cirrhosis and tumor characteristics depicts long-term survival rather than the type of resection in HCC.

Clinical perspective of acute humoral rejection after blood type-compatible liver transplantation.

Acute humoral rejection (AHR) is antibody-mediated rejection caused by complement activation and antibodies against the donor graft, and it usually occurs immediately (hyperacute) or during the first week (acute) after organ transplantation (1). The liver allograft has been considered relatively resistant to immunologic rejection, and most liver graft rejections are cellular rejections (2). Although AHR is well described in blood type-incompatible liver transplantation (LT) (3), its occurrence in blood type-compatible LT is an uncommon complication. Clinically, AHR diagnosis currently relies on histologic findings, presence of donor-specific antibodies, and graft dysfunction (1, 4). However, early detection and treatment of AHR after LT remains uncertain. Among 316 LTs, 6 patients (1.9%) had AHR within 2 weeks after LT (range 5–14 days). Table 1 summarizes the clinical features of AHR patients after LT. All patients first presented with rapid increase of liver enzymes, which increased by 2or 3-fold every 6 hr (see Figure 1A, Supplemental Digital Content 1, http://links.lww.com/TP/A348). However, increased liver enzymes levels were refractory to pulse therapy and recycling steroids. Main portal vein stenosis or thrombosis were not observed; however, Doppler sonography showed a markedly decreasing portal flow (see Figure 1B, Supplemental Digital Content 1, http://links.lww.com/TP/A348). Furthermore, examination of artery flow revealed no significant variation. Tissue biopsies of liver grafts for histologic examinations were obtained from three patients; all demonstrated massive coagulative necrosis of the liver parenchyma and occluded small branches of portal vessels. However, no inflammatory cell infiltration existed in the remaining portal tracts, and immunohistochemical examinations were all positive for C4d deposition in vessel walls. These finding indicate that the deterioration of liver function was not because of vascular complication but likely related to AHR. Five (83%) of six patients with AHR died because of inappropriate management, and only one patient was successfully rescued by early plasmapheresis combined with bortezomib therapy. At the start of AHR, this patient also exhibited extensive increase of liver enzymes, followed by decreased portal flow. There-

The impact of CD4+CD25+ T cells in the tumor microenvironment of hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma (HCC) is the most common liver cancer. Therapeutic results are usually unsatisfactory because liver tumors recur often. Immunologic factors may be related to the recurrence of HCC; however, this possibility is mentioned only rarely. METHODS Thirty HCC patients undergoing hepatectomies were divided into 3 groups according to the diameters of their HCCs: group A (n = 8), diameter ≤3 cm; group B (n = 8), diameter >3 cm and ≤5 cm; and group C (n = 14), diameter >5 cm. T-lymphocytes from peripheral blood, nontumor liver tissue, and the HCC were analyzed. RESULTS The percentage of CD25+ in the CD4+ T cells did not differ between the peripheral blood and the nontumor liver tissue among the 3 groups. CD25+ cells were increased in the tumor tissue in group C patients (range, 6-41%; median, 22.9%; P = .003), compared to group A patients. The percentage of CD25+ in the CD4+ T cells in tumor tissue was positively correlated with tumor sizes (r = 0.556). These CD4+ CD25+ lymphocytes produced transforming growth factor-β and interferon-γ but not interleukin-10, and were anergic to plate-coated monoclonal antibodies (anti-CD3/anti-CD28). The characteristics of these antibodies were comparable to those of regulatory T cells. When the infiltration lymphocytes including CD4+ CD25+ T cells were added to the mixed lymphocyte reaction activated by autologous tumor lysate-pulsed dendritic cells, the proliferation of lymphocytes was inhibited. CONCLUSION The increase of CD4+ CD25+ T cells in the tumor microenvironment correlates with tumor sizes. These CD4+ CD25+ regulatory T cells appeared to suppress the immune response activated by dendritic cells.

Encapsulation is a significant prognostic factor for better outcome in large hepatocellular carcinoma.

The aim of this study was to determine the effect of tumor encapsulation of hepatocellular carcinoma (HCC) on long‐term survival.

Impact of portal venous hemodynamics on indices of liver function and graft regeneration after right lobe living donor liver transplantation

The aim of this study was to evaluate the effects of portal hemodynamics on indices of liver function and graft regeneration in patients after adult right lobe living donor liver transplantation (R‐LDLT). Sixty‐four patients who underwent R‐LDLT and had an uneventful postoperative course were enrolled in this study. The contribution of portal flow was greater to the recipient grafts versus the donor livers (90.74% versus 69.12%, P < 0.0001). Portal flow variations decreased significantly during the first 10 days after R‐LDLT (P < 0.0001); variations in the hepatic arterial flow were more constant during this period (P = 0.812). The mean portal venous pressure (PVP) before recipient hepatectomy (the initial PVP) was 23.1 ± 4.0 mm Hg; the mean PVP after reperfusion (the final PVP) was 15.0 ± 4.3 mm Hg (P < 0.0001). Furthermore, the mean hepatic portal venous gradient (ie, PVP − central venous pressure) before recipient hepatectomy was 17.1 ± 4.3 mm Hg; it decreased to 10.6 ± 4.5 mm Hg after reperfusion (P < 0.0001). These findings suggest that after graft reperfusion, the vascular resistance of the hepatic parenchyma decreased, and there was an associated mild decrease in the portal hypertension. Multiple regression analysis indicated that PVPs correlated significantly with indices of liver function after living donor liver transplantation (P < 0.05). Patients were separated into 4 groups according to their PVP values: group A (initial PVP ≥ 23 mm Hg, final PVP ≥ 15 mm Hg), group B (initial PVP < 23 mm Hg, final PVP ≥ 15 mm Hg), group C (initial PVP ≥ 23 mm Hg, final PVP < 15 mm Hg), and group D (initial PVP < 23 mm Hg, final PVP < 15 mm Hg). Immediately after R‐LDLT, the peak values for aspartate aminotransferase, alanine aminotransferase, the international normalized ratio and the average ascites production varied appreciably in these groups. The regeneration rate of the liver graft 3 months after R‐LDLT was significantly greater in group A versus the other groups. In conclusion, PVP is a significant hemodynamic factor that influences the functional status of the liver and graft regeneration after R‐LDLT. Liver Transpl 17:1035–1045, 2011.

Preoperative estimation of the liver graft weight in adult right lobe living donor liver transplantation using maximal portal vein diameters

An accurate preoperative estimate of the graft weight is vital to avoid small‐for‐size syndrome in the recipient and ensure donor safety after adult living donor liver transplantation (LDLT). Here we describe a simple method for estimating the graft volume (GV) that uses the maximal right portal vein diameter (RPVD) and the maximal left portal vein diameter (LPVD). Between June 2004 and December 2009, 175 consecutive donors undergoing right hepatectomy for LDLT were retrospectively reviewed. The GV was determined with 3 estimation methods: (1) the radiological graft volume (RGV) estimated by computed tomography (CT) volumetry; (2) the computed tomography–calculated graft volume (CGV‐CT), which was obtained by the multiplication of the standard liver volume (SLV) by the RGV percentage with respect to the total liver volume derived from CT; and (3) the portal vein diameter ratio–calculated graft volume (CGV‐PVDR), which was obtained by the multiplication of the SLV by the portal vein diameter ratio [PVDR; ie, PVDR = RPVD2/(RPVD2 + LPVD2)]. These values were compared to the actual graft weight (AGW), which was measured intraoperatively. The mean AGW was 633.63 ± 107.51 g, whereas the mean RGV, CGV‐CT, and CGV‐PVDR values were 747.83 ± 138.59, 698.21 ± 94.81, and 685.20 ± 90.88 cm3, respectively. All 3 estimation methods tended to overestimate the AGW (P < 0.001). The actual graft‐to‐recipient body weight ratio (GRWR) was 1.00% ± 0.19%, and the GRWRs calculated on the basis of the RGV, CGV‐CT, and CGV‐PVDR values were 1.19% ± 0.25%, 1.11% ± 0.22%, and 1.09% ± 0.21%, respectively. Overall, the CGV‐PVDR values better correlated with the AGW and GRWR values according to Lins concordance correlation coefficient and the Landis and Kock benchmark. In conclusion, the PVDR method is a simple estimation method that accurately predicts GVs and GRWRs in adult LDLT. Liver Transpl, 2011.

Significance of Tumor Necrosis for Outcome of Patients with Hepatocellular Carcinoma Receiving Locoregional Therapy Prior to Liver Transplantation

BackgroundLocoregional therapy has been advocated as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), and the majority of patients with HCC receive locoregional therapy prior to liver transplantation (LT). We herein aim to determine the prognostic factors affecting the outcome in patients who receive pretransplantation therapy.MethodsWe conducted a retrospective study of the prospective data of patients who received locoregional therapy before undergoing LT for HCC. The clinicopathologic features of the patients were studied using univariate and multivariate analysis to determine prognostic factors.ResultsUnivariate and multivariate analysis of clinicopathologic features identified mean tumor necrosis (TN) ≥60% as the sole independent factor associated with lower HCC recurrence following LT. Further, the groups of patients with mean TN ≥60% who were within the University of California, San Francisco (UCSF) criteria and whose tumors beyond UCSF criteria were downstaged by TN following locoregional therapy had significantly better survival rates than the opposite groups. In-depth exploration of treatment modalities and pathological features indicated that HCC showed marked TN, while tumor nodules were well treated by locoregional therapy, and no viable tumors could be detected on radiological examination.ConclusionsMean TN ≥60% of tumor by locoregional therapy could offer better outcomes for patients with HCC undergoing LT. Therefore, locoregional therapy should be considered for patients with HCC awaiting LT or potential candidates for LT in order to induce TN as well as leading to diminished viable tumor burden and reducing the odds of HCC recurrence following LT.

Feasibility of split liver transplantation for 2 adults in the model of end-stage liver disease era.

Objective: To examine the results of split liver transplantation for 2 adults in the model of end-stage liver disease (MELD) era. Background: In the MELD era, liver allografts are first allocated to recipients with the highest MELD scores. However, the application of split liver transplantation for 2 adults in urgent condition has doubled and has become a matter of concern. Methods: Twenty-one deceased liver grafts were split into full right and full left lobes for 42 adult recipients. One of the hemiliver grafts was allocated to the recipient with the highest MELD score in the waiting list. The results of split liver transplantation were examined and compared with those of living donor liver transplantation. Results: Among 42 recipients, 24 (57.1%) had MELD scores higher than 20. The median (interquartile) MELD score for the recipients with split liver transplantation was 22 (15–30), which was higher than that for the recipients with living donor liver transplantation (P < 0.001). The 1-, 3-, and 5-year survival rates for split liver transplantation were comparable with those of living donor transplantation (P = 0.489). Nevertheless, 10 of 42 split liver recipients died within 3 months after transplantation. By receiver operating characteristic curve analysis, the safe graft-recipient weight ratio was better more than 1% to avoid early patient death for split liver transplantation. Conclusions: Although most of the recipients with split liver transplantation had high MELD scores, the results were comparable with those of living donor liver transplantation. Split liver transplantation for 2 adults is still feasible in the MELD era.

Liver resection for complicated hepatocellular carcinoma: challenges but opportunity for long-term survivals.

Hepatocellular carcinoma (HCC) is often diagnosed late because of the lack of pathognomonic symptoms. This study evaluated outcomes following liver resection (LR) for patients with HCC presenting with large tumor size (over 10 cm), adjacent organ invasion, or ruptured tumor, which we termed as complicated HCC (cHCC).

Hepatic Resection for Hepatocellular Carcinoma With Lymph Node Metastasis: Clinicopathological Analysis and Survival Outcome

OBJECTIVE Lymph node metastasis (LNM) rarely occurs in hepatocellular carcinoma (HCC). Few studies have reported the potential risk factors of LNM and the influence of LNM on the progression and prognosis of HCC. The purposes of this study were to explore the clinicopathological characteristics of operable HCC with LNM and to demonstrate the effects of LNM on HCC prognosis. METHODS A retrospective review of 2,034 HCC patients undergoing surgery from 1982 to 2005 was performed. The influence of LNM was assessed by clinicopathological factors, tumour recurrence, and overall survival. A total of 66 randomly selected patients matched for clinicopathological variables were used to analyse the difference in survival. RESULTS A total of 25 patients (1.23%) were reported to have LNM. Higher preoperative carcinoembryonic antigen levels (> 10 ng/mL) were significantly associated with a higher incidence of LNM than were low preoperative carcinoembryonic antigen levels (≤ = 10 ng/mL) (15.38%vs. 3.79%, p = 0.042). Furthermore, HCC with LNM (N1 disease) was larger in size (mean, 9.44 vs. 5.85 cm, p = 0.016) and significantly associated with vascular invasion, worse histological grade, and nonencapsulation (p = 0.002, < 0.001, and < 0.001, respectively). Finally, patients with HCC accompanied by LNM had shorter mean disease-free survival and overall survival (p = 0.001 and < 0.001, respectively). CONCLUSION This study identified the worst prognosis of HCC in a population with LNM. HCC with LNM tends to be the infiltrating type with larger tumour size (> 5 cm), presence of microvascular invasion, and worse histological grade. Liver resection with lymphadenectomy is possibly beneficial for patients with HCC accompanied by LNM.