Hong-Shiue Chou

Surgical resection of centrally located large hepatocellular carcinoma.

BACKGROUND Centrally located large hepatocellular carcinoma (HCC) is a difficult issue in surgery. These HCCs can be treated by hemi-/extended or central hepatectomies. The aim of this study was to analyze the results of hemi-/extended and central hepatectomies. METHODS One hundred and four patients with centrally-located large tumors were retrospectively reviewed. Patients were divided into group 1 (n = 41) with hemi-/extended hepatectomies, and group 2 (n = 63) with central hepatectomies. Characteristics were analyzed between groups and survival rates were calculated. RESULTS Parenchyma resection was limited in group 2. The resection margin in 92.6% of group 2 patients was < 1 cm, compared with 78.9% of group 1 patients (p = 0.056). The 1- and 5-year disease-free survival rates were 50% and 38.9% for group 1, and 50% and 15% for group 2 (p = 0.279). The 1-, 5-year overall survival rates were 89.5% and 66.2% for group 1 and 87.5% and 53.1% for group 2 (p = 0.786). Cirrhosis, the preoperative aspartate aminotransferase (AST) level and lower resected liver weight were independent factors impairing survival. CONCLUSION Hemi-/extended and central hepatectomies have comparable complication rates and long-term survival rates for patients with centrally located large HCC. Cirrhosis, the AST level and resected liver weight were independent factors determining long-term survival.

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.

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.

Split liver transplantation in adults: preoperative estimation of the weight of right and left hemiliver grafts.

The application of split liver transplantation in adults effectively increases the pool of donor organs available for liver transplantation. The accurate estimation of the sizes of full right and left lobe grafts facilitates optimal matches with graft recipients and is a necessary requirement for successful split liver transplantation. We report an easy method for precisely estimating the sizes of full right and left lobe liver grafts to enable the selection of size-matched recipients. The basis of this method is that the relative sizes of the right and left hemilivers in the whole liver should correspond to the relative blood flow in the right and left portal veins. The blood flow in the right and left portal veins is proportional to the cross-sectional area of the respective vessels. The whole liver volume is calculated with the following equation: SLV 1⁄4 ð706:2 Body surface area ðm2Þ þ 2:4Þ

Endoscopic Management of Biliary Complications After Adult Right-Lobe Living Donor Liver Transplantation Without Initial Biliary Decompression

OBJECTIVES We sought to examine biliary complications in adult right-lobe living donor liver transplantation (LDLT) with duct-to-duct anastomosis (RL-LDLT-DD), evaluating the efficacy of endoscopic retrograde cholangiography (ERC) in the diagnosis and management of biliary complications following LDLT. METHODS Ninety adult RL-LDLT-DD were performed from June 2004 to August 2007, including 21 (23.3%) cases of biliary complications. RESULTS The endoscopic retrograde cholangiopancreatiography (ERCP) findings were stricture only (n = 8), stricture plus leakage (n = 9), and leakage only (n = 4). In the overall 13 cases of leakage, nine patients recovered after treatment by stent or endoscopic nasobiliary drainage. The time to resolution was 3.0 +/- 1.3 months with 2.2 +/- 1.3 endoscopic examinations. All bile duct complications were treated by ERC first. Among 17 cases with stricture, seven cases were successfully treated by endoscopy and three cases by percutaneous transhepatic cholangiography plus stent (PTCS). In the other seven cases, the treatment was still ongoing in five cases and two subjects died during treatment. The mean time to stricture resolution 7.2 +/- 3.3 months with 3.9 +/- 1.4 endoscopic examinations. The results of 21 cases were 5/21 mortalities (23.8%), successful ERC treatment in 9/21; (42.9%), successful PTCS treatment in 3/21 (14.3%), and ongoing ERC treatment in 5/21, (23.8%), including one case with successful ERC treatment who died of lung infection postoperatively. During follow-up (13.1 +/- 9.9 months), there was no recurrence in the stricture or leak. CONCLUSIONS When compared with the literature, RL-LDLT-DD without biliary drainage does not increase the incidence of biliary complications. From our study, ERC and PTC play a complementary roles in the treatment of bile duct complications.

The risk factors to predict acute rejection in liver transplantation.

PURPOSE The aim of this study was to evaluate risk factors for an acute cellular rejection episode (ARE) among adult liver transplant (OLT) patients. MATERIALS AND METHODS We retrospectively reviewed 110 consecutive patients who underwent OLT between May 2007 and December 2010. The diagnosis of ARE was based upon clinical and biochemical data; liver biopsy was only performed when clinical presentation was equivocal. We recorded donor and recipient characteristics, perioperative immune status, and postoperative laboratory data. Forty patients (36.4%) who suffered a clinical rejection episode and received pulsed or recycled steroid therapy (R group), were compared with 70 (63.6%) free of rejection (N group). RESULTS The mean age of R recipients was 46.61±9.97 years, which was younger than the N group (51.86±8.37, P=.005). R group patients displayed a lower pre-OLT creatinine (P=.016) and higher alanine aminotransferase (P=.048). Cox regression model showed recipient age to be the only significant factor to predict ARE (odds ratio=1.071, P=.003). The cutpoint of age was 46 years by receiver operating characteristic analysis. Patients younger than 46 years showed higher initial CD8+ T-cell counts (P=.038). CONCLUSION Recipient age was significantly associated with ARE; younger patients showed higher CD8+ lymphocyte counts than older patients. More aggressive immunosuppression should be considered for younger recipients to prevent ARE.

The Risk Factors for Early Infection in Adult Living Donor Liver Transplantation Recipients

OBJECTIVE The high rate of early major infections in liver transplantation recipients is due to their compromised immune-system. We examined the risk factors of early major infection in living donor liver transplantation (LDLT). MATERIALS AND METHODS From January 2004 to December 2010, 242 patients undergoing LDLT were enrolled in the prospective cohort. We prospectively collected their clinical and demographic variables, operative details, and posttransplant complications. RESULT One hundred thirty-nine patients (57.7%) experienced 252 episodes of early infection posttransplantation: bloodstream septicemia (n = 46, 18.3%), urinary tract (n = 34; 14.1%), pneumonia (n = 64; 25.4%), peritonitis (n = 62; 25.7%), and catheter related (n = 46; 19%). The most frequent Gram-positive bacteria were coagulase-negative staphylococci (n = 52; 16.9%), followed by Staphylococcus aureus (n = 32; 10.4%). The most common Gram-negative bacteria were Escherichia coli (n = 27; 8.8%); Acinetobacter baumannii (n = 29; 9.4%), Pseudomonas aureos (n = 18; 5.8%), and Sternotrophomonas maltophilia (n = 18; 5.8%). Upon multivariate logistic regression analysis, the risk factors for early major infection were a high creatinine level (odds ratio = 1.481), a long anhepatic arterial phase (1.01), a reoperation (6.417), young age (1.040), and non-hepatocellular carcinoma recipient (2.141). CONCLUSION Early major infection after LDLT was high with Gram-positive bacteria, the most common etiologies. Prolonged anhepatic arterial phase, renal insufficiency, and reoperation were risk factors for an early major infection.

Indicators and outcome of liver transplantation in acute liver decompensation after flares of hepatitis B.

Summary.  Non‐cirrhotic patients having acute liver decompensation in flares of hepatitis B can recover spontaneously or die without liver transplantation. Criteria for identifying patients in need of liver transplantation are lacking. Fifty‐one non‐cirrhotic patients having acute liver decompensation in flares of hepatitis B were retrospectively reviewed. The patients were divided into three groups: group A patients (n = 18) recovered from acute liver decompensation spontaneously; group B patients (n = 22) died of acute liver failure; and group C patients (n = 11) had liver transplantation. Model of end‐stage liver disease (MELD) scores were evaluated to identify the criteria for liver transplantation. The cut‐off point of MELD scores for liver transplantation was evaluated by receiver operating characteristic (ROC) curve. Comparing group A and B patients, MELD score was an independent factor to predict prognosis. By analysing ROC curve, a MELD score > 30 was the most optimal cut‐off point to indicate liver transplantation; however, the false positive rate was 11.1%. By weekly measurement of MELD scores, subsequent increase in MELD scores could help to avoid false positives. Moreover, a MELD score > 34 yielded 0% false positive rate and indicated the necessity of definite liver transplantation. For group C patients, ten of 11 patients were saved by liver transplantation. In conclusion, for the patients having acute liver decompensation in flares of hepatitis B, liver transplantation is definitely indicated by MELD scores > 34. Liver transplantation is also indicated if the MELD score increases in the subsequent 1–2 weeks. Liver transplantation has a good outcome if performed on time.

Suspect the Donor With Potential Infection in the Adult Deceased Donor Liver Transplantation

INTRODUCTION Liver transplantation is the treatment of choice for end-stage liver disease. However, the shortage of donors is still the major problem in most Asian countries. Using extended donor criteria may maximize the deceased donor pool, but some high-risk donors may show adverse recipient outcomes due to preexisting infection. MATERIALS AND METHODS This study included deceased donor liver transplant patients from June 2002 through June 2007. We retrospectively reviewed the clinical manifestations of donors and recipients. The donors showed no definite infection at the time the organs were matched to the recipients. Routine sputum, urine, blood, and bile cultures were obtained from the donor during the perioperative period. According to the final reports of the cultures, the recipients divided into two groups: donor infection (DI) and no donor infection (NDI). RESULTS This study included 59 donor and 72 recipients, including 34 who received a graft from a donor with a positive culture (47.2%) finally, defined as the DI groups, and 38 recipients (52.8%) as the NDI group. Most of them had positive sputum cultures, followed by urine cultures. Staphylococcus aureus was the most common pathogen. Using a stepwise logistical regression model to analyze the significant donor characteristics, donor admission to the intensive care unit (ICU) for 7 days or longer (P < or = .0001), previous cardiopulmonary cerebral resuscitation (CPCR) (P = .036), and inotropic agents (P = .022) were the only three independent factors to predict donor infection. To compare the outcomes between DI and NDI groups, the days of recipient ICU or hospital admission, the 1-week or 1-month mortality rate, and the overall survival showed no significant difference between both groups. However, the hospital mortality rate was mildly higher in the DI group (P = .050). CONCLUSION Donors with prolonged ICU admissions, rescue by CPCR, and use of inotropic agents carried an high risk of potential infections. Our data did not show a significant increase in adverse outcomes if the recipient received a graft from a potentially infected donor. However, there may be an increased risk of hospital mortality. We should be careful in using these potentially infected donors in selective recipients.