C.-L. Chen

Preoperative Imaging Evaluation of Potential Living Liver Donors: Reasons for Exclusion From Donation in Adult Living Donor Liver Transplantation

Accurate pretransplant evaluation of a potential donor in living donor liver transplantation (LDLT) is essential in preventing postoperative liver failure and optimizing safety. The aim of this study was to investigate the reasons for exclusion from donation of potential donors in adult LDLT. From September 2003 to June 2006, 266 potential donors were evaluated for 215 recipients: 220 potential donors for 176 adult recipients; 46 for 39 pediatric recipients. Imaging modalities including Doppler ultrasound, computerized tomography (CT), and magnetic resonance (MR) angiography provided vascular evaluation and MR cholangiopancreatography to evaluate biliary anatomy. Calculation of liver volume and assessment of steatosis were performed by enhanced and nonenhanced CT, respectively. In the adult group, only 83 (37.7%) potential donors were considered suitable for LDLT. Of the 137 unsuitable potential donors, 36 (26.2%) candidates were canceled because of recipient issues that included death of 15 recipients (10.9%), main portal vein thrombosis (8%), recipient condition beyond surgery (5%), and no indication for liver transplantation due to disease improvement (2%). The remaining 101 (73.8%) candidates who were excluded included steatosis (27.7%), an inadequate remnant volume (57.4%), small-for-size graft (8.9%), HLA-homozygous donor leading to one-way donor-recipient HLA match (3%), psychosocial problems (4%), as well as variations of hepatic artery (4%), portal vein (1%), and biliary system anatomy (5%). Anatomic considerations were not the main reason for exclusion of potential donors. An inadequate remnant liver volume (< 30%) is the crucial point for the adult LDLT decision.

Hepatocellular Carcinoma Downstaging in Liver Transplantation

BACKGROUND Hepatocellular carcinoma (HCC) is the leading malignant tumor in Taiwan. The majority of HCC patients are diagnosed in late stages and therefore in eligible for potentially curative treatments. Locoregional therapy has been advocated as an effective treatment for patients with advanced HCCs. PURPOSE The aim of this study was to evaluate the outcomes of HCC downstaged patients after locoregional therapy to allow eligibility for liver transplantation. METHODS AND MATERIALS From January 2004 to June 2010, 161 patients with HCCs underwent liver transplantation including 51 (31.6%) who exceeded the University of California-San Francisco (UCSF) who had undergone successful locoregional therapy to be downstaged within these criteria. Among the downstaged patients, 48 (94.1%) underwent transarterial embolization; 7 (13.8%), percutaneous ethanol injection; 24 (47.1%), radiofrequency ablation; 15 (29.4%), surgical resection, and 34 (66.7%), combined treatment. RESULTS The overall 1- and 5-year survival rates of all HCC patients (n=161) were 93.2% and 80.5%. The overall 1- and 5-year survival rates of downstaged (n=51) versus non-downstaged (n=110) subjects were 94.1% versus 83.7% and 92.7% versus 78.9%, respectively (P=.727). There are 15 (9.2%) HCC recurrences. The overall 1- and 5-year tumor-free rates of all HCC patients were 94.8% and 87.2%. The overall 1- and 5-year tumor-free rates between downstaged versus non-downstaged patients were 93.9% and 90.1% versus 95.2% and 86.0%, respectively (P=.812). CONCLUSION Patients with advanced HCC exceeding the UCSF/Milan criteria can be downstaged to fit the criteria using locoregional therapy. Importantly, successfully downstaged patients who are transplanted show excellent tumor-free and overall survival rates, similar to fit-criteria group.

High-mobility group box 1 protein activates hepatic stellate cells in vitro.

OBJECTIVES Our previous study noticed remarkably elevated titers of anti-high-mobility group box 1 (HMGB1) antibodies in sera during the tolerance induction phase of a rat tolerogenic orthotopic liver transplantation (OLT) as well as in sera of clinically drug-free patients. We hypothesized that the release of nonhistone nuclear protein HMGB1 during rejection may play a pathogenic role in deteriorating post-OLT graft functions, such as inducing liver fibrosis. This study sought to investigate whether HMGB1 can directly activate hepatic stellate cells (HSCs) and drive them toward fibrogenesis. METHODS The cultured HSCs were treated with recombinant HMGB1. RT-PCR and Western blotting analysis were used to measure alpha-smooth muscle actin (alpha-SMA) expression. Conditioned media were collected for gelatin zymography to monitor the activities of collagen-degrading matrix metalloproteinases (MMPs). RESULTS HMGB1 at concentrations > 1 ng/mL significantly stimulated HSC growth as revealed by proliferation and BrdU assays. alpha-SMA gene and protein expression were significantly up-regulated by HMGB1, whereas the MMP-2, but not MMP-9, activity was suppressed by HMGB1 treatment. CONCLUSION Our data suggested that HMGB1 protein, once released during the rejection phase of OLT, activated HSCs and exhibited profibrogenic effects on liver grafts either by increasing the HSC population and extracellular matrix content in liver grafts, or by transforming HSCs into myofibroblasts. Neutralization with anti-HMGB1 antibody was suggested to be a therapeutic modality applicable to prevent fibrogenesis in post-OLT liver grafts.

Doppler Ultrasound Evaluation of Postoperative Portal Vein Stenosis in Adult Living Donor Liver Transplantation

AIM To evaluate the postoperative portal vein stenosis (PVS) and the diagnostic efficiency of Doppler ultrasound (DUS) in adult living donor liver transplantation (ALDLT). MATERIALS AND METHOD From January 2007 to December 2008, 103 ALDLTs were performed and postoperatively followed by routine DUS. The morphologic narrowing at the anastomotic site (AS) of the PVS was analyzed. We calculated the PV stenotic ratio (SR) using the following formula: SR (%)=PRE-AS/PRE (PRE=pre-stenotic caliber). An SR>50% was defined as the critical point for PVS. We also calculated the velocity ratio (VR) between the AS and PRE, and set the significant VR as >3:1. Statistical analyses were carried out to determine clinical significance. RESULTS Using the definition of morphologic PVS by DUS, there were total 20 cases (19.4%) in this series with SR>50%, which included 17 cases with VR>3:1. Eight cases of severe PVS had a stenotic AS>5 mm and subsequently underwent interventional management. Doppler criteria of SR and VR values were elevated up to 75.8% and 7.5:1, respectively, in these treated cases. Two cases of severe PVS subsequently developed PV thrombosis. Intervention by balloon dilation and/or stenting was performed successfully in this PVS case. CONCLUSION DUS is the most convenient and efficient imaging modality to detect and follow postoperative PVS in ALDLT. The Doppler criteria of SR and VR are both sensitive but less specific. Cases of AS<5 mm require interventional management for good long-term graft survival.

Ovulation induction with tamoxifen and alternate-day gonadotrophin in patients with thin endometrium

Tamoxifen has been reported to be oestrogenic on the lower genital tract. To evaluate its potential positive effect on the endometrium, and consequently early miscarriage and ongoing pregnancy rate, a prospective study was employed in patients for intrauterine insemination who failed to develop an adequate endometrial thickness in a previous ovulatory cycle. Ovarian stimulation was initiated with tamoxifen 40 mg/day from day 3 of the menstrual cycle for 7 days or clomiphene 100 mg/day for 5 days, in combination with 150 IU of human menopausal gonadotrophin on alternate days starting on day 4. Human chorionic gonadotrophin (HCG) was administered when at least one leading follicle was larger than 20 mm. Intrauterine insemination was accomplished 24-36 h after HCG injection and luteal phase supplement was achieved with micronized progesterone 200 mg transvaginally per day. It was found that tamoxifen-treated patients required more stimulation days and used more gonadotrophin, but recruited less follicles larger than 14 mm than clomiphene-treated patients. However, a significantly increased endometrial thickness (P < 0.001) and pregnancy rate (P = 0.015), decreased early miscarriage rate (P = 0.001) and thus improved ongoing pregnancy (P < 0.001) rate were noted in tamoxifen-treated patients. These results suggest that although tamoxifen may not be a first-line treatment in patients with adequate endometrium, it may be a promising alternative for patients with thin endometrium.

Bispectral Index Monitoring in Healthy, Cirrhotic, and End-Stage Liver Disease Patients Undergoing Hepatic Operation

The purpose of this study was to assess factors influencing the end-tidal concentrations of isoflurane within a bispectral index (BIS) range of 45-55 among healthy live liver donors (n = 11), chronic hepatitis B patients undergoing hepatectomy hepatocellular carcinoma (n = 10), and end-stage liver disease patients undergoing liver transplantation (n = 7). Patients data collected prospectively were compared among the groups using one-way analysis of variance as well as univariate and multivariate techniques. The results showed that end-stage liver disease patients required the least end-tidal isoflurane concentration. Patients with hepatocellular carcinoma with cirrhosis required intermediate end-tidal isoflurane concentrations; healthy live liver donors required the highest end-tidal isoflurane concentrations to provide sufficient anesthetic depth, as monitored by a target BIS (range, 45-55). Upon multivariate analysis, liver function was the only significant factor influencing the likelihood of lowering the end-tidal isoflurane concentration by 4 hours after anesthesia induction (P = .026). In conclusion, we recommend a preset target BIS within the range of 45-55 to monitor the depth of anesthesia during partial hepatectomy and liver transplantation because end-tidal isoflurane concentration requirements are different for patients with various liver status. This strategy may protect the patients from intraoperative recall or anesthesia over-depth as a consequence of insufficient or overdose of anesthesia, respectively.

Correlation Between Imaging and Pathologic Findings in Explanted Livers of Hepatocellular Carcinoma Cases

PURPOSE We sought investigate the accuracy of preoperative computed tomography angiography (CTA) and magnetic resonance imaging (MRI) to evaluate tumor-related prognostic factors, including tumor size, number, portal vein (PV) thrombosis, and bile duct invasion. MATERIALS AND METHODS From March 2006 to October 2008, we enrolled 57 patients with hepatocellular carcinoma (HCC) who were undergoing liver transplantation at our institute. Imaging was performed with multidetector 64 slice CTA and MRI within 1 month preoperatively. Imaging findings including tumor size, number, PV thrombosis, and bile duct invasion were correlated with histopathologic features from the explanted livers. RESULTS We included 128 HCCs in 57 patients in this study. The sensitivities to detect tumor number and size were 83.6% and 88.8% for CTA, and 75.8% and 88.7% for MRI. In addition, CTA and MRI were both accurate to determine whether patients were beyond or within the Milan and UCSF criteria. Fifteen patients with PV microthrombosis and 1 with bile duct microinvasion were not found on CTA or MRI preoperatively; negative predictive value of PV microthrombosis and bile duct microinvasion were 73.68% and 98.25%, respectively. During follow-up, 2 patients experienced recurrence, one of which was associated with PV microthrombosis, and 4 patients died of causes unrelated to HCC. CONCLUSION CTA and MRI were both accurate to determine whether patients fit within the Milan or UCSF criteria, but CTA was slightly better than MRI to evaluate tumor number and size. However, pretransplant diagnostic pitfalls were PV microthrombosis and bile duct microinvasion.

Pain Management of Living Liver Donors With Morphine With or Without Ketorolac

BACKGROUND To compare the efficacy and dose requirements for intravenous (IV) patient-controlled analgesia (PCA) with morphine only versus morphine with ketorolac for living liver donors after partial hepatectomy. PATIENTS AND METHODS Eighty living liver donors who had undergone partial hepatectomy received 3 days of IV PCA for postoperative pain control. Some were prescribed a PCA with morphine alone (group I) or morphine with ketorolac (group II), while both had a rescue dose of IV fentanyl (25 μg). The daily consumption of morphine, pain score, and frequency of rescue fentanyl doses were compared retrospectively using the Mann-Whitney U test and the incidence of side effects with chi-square tests; a P value of .05 was regarded as significant. All the data are shown as mean values±standard deviations. RESULTS The 80 subjects were distributed as 57 group I and in 23 group II patients. The daily consumption of morphine, Visual Analogue Scale (VAS) and side effects were not different between the groups, but group II required significantly fewer rescue doses to achieve pain relief. CONCLUSION Both regimens provided acceptable pain control with daily VAS less than 3. The use of ketorolac in the PCA did not reduce the daily total morphine requirements with a similar incidence of side effects but a significantly reduced requirement for rescue doses, which subsequently reduced the work load of personnel in the pain control service.

Correlation Between Hepatic Steatosis, Hepatic Volume, and Spleen Volume in Live Liver Donors

INTRODUCTION The purpose of this study was to evaluate the changes in liver fatty content and the volumes of liver and spleen after body weight reduction in potential living liver donors. MATERIALS AND METHODS Twenty-three potential living donors had fatty livers at pretransplantation sonography and computed tomography (CT). All were advised to undergo body weight reduction by exercise and diet control. A percutaneous core liver biopsy was performed in segment 5 of the liver in 22 donors to evaluate the hepatic fat content before and after body weight reduction. We compared the changes in the liver CT attenuation values and volume changes in the left and right lobes of the liver and the spleen before and after body weight reduction. RESULTS The mean (SD) body weight, body mass index, and fatty content of the liver biopsy specimens were 73 (17) kg, 26.8 (4.4), and 16.9% (12.7%), respectively, before body weight reduction and 70 (15) kg, 25.3 (3.8), and 6.6% (3.7%), respectively, thereafter. These changes were significant. The CT attenuation values of the left and right lobes of the liver and spleen were 54 (11), 51 (11), and 52 (5) HU, respectively, before body weight reduction and 60 (8), 58 (6), and 53 (5) HU, respectively, thereafter. The mean CT attenuation value of the left lateral segment was greater than that of the right lobe both before and after body weight reduction. The volume of the left and right lobes and spleen changed from 497 (129) cm3 to 452 (99) cm3, 927 (237) cm3 to 846 (173) cm3, and 185 (65) cm3 to 186 (63) cm3, respectively, thereafter. The right and left lobe volume change ratios were 7.0% (10.6%) and 7.6% (11.1%), respectively, but showed no significant difference. Twenty of the 23 candidates were able to donate part of their liver. CONCLUSION Body weight reduction by exercise and diet control in potential living liver donors is effective to reduce the fatty content of the liver. Reversed percentage of the fatty content and volume of the liver was observed in these donors. The volumes of the right and left lobes of liver decreased significantly after body weight reduction. The volume changes were proportional.

Biliary complications and management in pediatric living donor liver transplantation for underlying biliary atresia.

BACKGROUND Biliary complications are a major problem in pediatric liver transplantation. The aim of this study was to evaluate the management and outcomes of biliary complication after pediatric living donor liver transplantation (LDLT). METHODS From 1994 to 2010, 157 pediatric LDLT due to biliary atresia were performed in our center. Doppler ultrasound was initially performed daily for 2 weeks postoperatively to evaluate biliary and vascular complications. Computed tomography and or magnetic resonance cholangiography were performed when complications were suspected. They were treated using radiological or surgical interventions. RESULTS Among the 157 cases, we observed 10 (6.3%) biliary complications, which were divided into three groups: bile leakage (n=3); biliary stricture without vascular complication (n=4); and biliary stricture with vascular complication (n=3). The three cases bile leakages recovered after interventional procedures. The seven biliary strictures underwent percutaneous transhepatic cholangial drainage (PTCD). All cases without vascular complications were completely cured after PTCD or a subsequent surgical re-anastomosis. In the vascular complication group, early recorrection of the HA occlusion with successful PTCD treatment were performed in two cases, but one other case with diffuse ischemic biliary destruction had a poor result. CONCLUSION Successful interventional radiographic approaches are effective for anastomotic biliary complications but with poor results in diffuse ischemic biliary destruction.