Suk-Won Suh

Living-donor liver transplantation associated with higher incidence of hepatocellular carcinoma recurrence than deceased-donor liver transplantation.

Background Living-donor liver transplantation (LDLT) is becoming an important tool in hepatocellular carcinoma (HCC) treatment. However, the oncologic outcome between LDLT and deceased-donor LT (DDLT) for HCC remains controversial. This study aims to compare the HCC recurrence rates after LDLT versus DDLT. Methods Two hundred sixteen patients (166 LDLTs and 50 DDLTs) who underwent LT for HCC within University of California-San Francisco criteria were retrospectively reviewed. LDLT patients were divided into two groups: small living-donor graft (LDG; graft-to-recipient body weight ratio<1.0, n=59) and nonsmall LDG (graft-to-recipient body weight ratio≥1.0, n=107). Patients were further stratified into low- and high-risk settings by the number of risk factors for recurrence. Results The recurrence-free survival was lower in LDLT compared with DDLT (88.6% and 80.7% vs. 96.0% and 94.0% at 1 and 5 years; P=0.045). There was no significant difference between two groups regarding the majority of clinical and tumor characteristics, with the exception of a higher proportion of microvascular invasion presence in LDLT. After the adjustment for microvascular invasion, LDLT was identified as an independent risk factor for recurrence. Moreover, recurrence-free survival between small and nonsmall LDG was not statistically significant. In low-risk setting (⩽1 risk factor), LDLT showed comparable outcome with DDLT. However, the risk of recurrence was higher in LDLT than DDLT in high-risk patients. Conclusion In conclusion, LDLT showed poorer outcome than DDLT. This should be considered to select optimal strategy for HCC.

Alpha-fetoprotein and 18F-FDG positron emission tomography predict tumor recurrence better than Milan criteria in living donor liver transplantation

BACKGROUND & AIMS Given the organ shortage for liver transplantation (LT) and the limitations of the current morphology-based selection criteria, improved criteria are needed to achieve the maximum benefit of LT for hepatocellular carcinoma (HCC). We hypothesized that a combination of biological markers may better predict the prognosis than the Milan criteria. METHODS HCC patients (n=123) with preoperative data on serum alpha-fetoprotein (AFP) levels and (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) positivity underwent live-donor LT between January 2003 and December 2009. The cut-off values for serum AFP levels (200 ng/ml) and (18)F-FDG PET positivity (1.10) for tumor recurrence were determined by c-statistics using receiver operating characteristic curves. Univariate and multivariate analyses with preoperative variables were performed to find pre-transplant prognostic factors. Disease-free survival rates and overall survival rates were analysed with regard to serum AFP levels and (18)F-FDG PET positivity. RESULTS The 5-year disease-free survival rates and overall survival rates were 80.3% and 81.6% respectively. (18)F-FDG PET positivity (hazard ratio (HR) 9.766, 95% CI 3.557-26.816; p<0.001) and serum AFP level (HR 6.234, 95% CI 2.643-14.707; p<0.001) were the only significant pre-transplant prognostic factors in the multivariate analysis; tumor number and size were not significant. A combination of criteria showed that the biologically high-risk group (AFP level ⩾200 ng/ml and PET-positive) had an HR of 29.069 (95% CI 8.797-96.053; p<0.001) compared with the double-negative group. Use of the Milan criteria yielded an HR of 1.351 (95% CI 0.500-3.652; p=0.553). CONCLUSIONS The combination of the serum AFP level and (18)F-FDG PET data predicted better outcomes than those using the Milan criteria, improving objectivity when adult-to-adult living donor LT is contemplated.

Prediction of aggressiveness in early-stage hepatocellular carcinoma for selection of surgical resection

BACKGROUND & AIMS In early-stage hepatocellular carcinoma (eHCC), radiofrequency ablation (RFA) has comparable outcomes to surgical resection (SR); however, micrometastases may be present, resulting in tumor recurrence after local ablation. Therefore, we investigated predictors of aggressiveness in eHCC to select patients at high risk of recurrence after RFA who would benefit from SR. METHODS First, we analyzed 128 patients with newly diagnosed eHCC (single tumor with a diameter <3 cm) who underwent SR between January 2006 and December 2011. Risk factors for micrometastasis (representative of tumor aggressiveness) such as microvascular invasion or poor histologic grade were investigated. We then analyzed 201 eHCC patients who underwent RFA between July 2007 and December 2011. Identified risk factors were validated to determine their influence on tumor recurrence. RESULTS The only significant risk factor for tumor aggressiveness in the SR group was the product of serum levels of α-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) (A∗P ≥1600; hazard ratio [HR] 4.764; 95% confidence interval [CI], 1.867-12.161; p=0.001). This product also showed statistical significance for predicting recurrence in the RFA group (HR 2.296; 95% CI, 1.237-4.262; p=0.008). Patients with RFA and A∗P ≥1600 had significant early tumor recurrence (p=0.008) and poor late survival outcomes (p=0.001) compared with other patients. CONCLUSIONS The product of AFP and PIVKA-II levels is a useful predictor of aggressiveness in eHCC, which predicts tumor recurrence after RFA. Therefore, it should be considered when selecting SR as first-line treatment.

Recent advancements in and views on the donor operation in living donor liver transplantation: A single‐center study of 886 patients over 13 years

Donor safety remains an important concern in living donor liver transplantation (LDLT). In the present study, we assessed recent advancements in the donor operation for LDLT through our experience with this procedure. A total of 886 donor hepatectomies performed between January 1999 and December 2012 were analyzed. Three chronological periods were investigated: the initial period (1999‐2004, n = 239), the period in which the right liver with middle hepatic vein reconstruction was primarily used (2005‐2010, n = 422), and the period in which the right liver with a standardized protocol, including a preoperative donor diet program, an evaluation of steatosis with magnetic resonance spectroscopy, no systemic heparin administration or central venous pressure monitoring, exact midplane dissection, and incremental application of minimal incisions, was exclusively used (2011‐2012, n = 225). The proportion of patients > 50 years old increased (2.5% versus 4.7% versus 8.9%), whereas the proportion of patients with a remnant liver volume ≤ 30% (6.5% versus 13.9% versus 6.3%) and with macrosteatosis ≥ 10% (7.9% versus 11.1% versus 4.4%) decreased throughout the periods. The operative time (292.7 versus 290.0 versus 272.8 minutes), hospital stay (12.4 versus 11.2 versus 8.5 days), and overall morbidity rate (26.4% versus 13.3% versus 5.8%), including major complications (>grade 3; 1.7% versus 1.9% versus 0.9%) and biliary complications (7.9% versus 5.0% versus 0.9%), were markedly reduced in the most recent period. No intraoperative transfusion was required. No cases of irreversible disability or mortality were noted. In conclusion, the quality of the donor operation has recently been standardized through a large volume of experience, and the operation has been proven to have minimal risk. However, a constant evaluation of our experience is critical for remaining prepared for any unavoidable crisis. Liver Transpl 21:329–338, 2015.

Clinical outcomes of and patient satisfaction with different incision methods for donor hepatectomy in living donor liver transplantation

With the decrease in the average donor age and the increase in the proportion of female donors, both donor safety and cosmetic appearance are major concerns for some living donors in living donor liver transplantation (LDLT) because a large abdominal incision is needed that may influence the donors quality of life. In all, 429 donors who underwent donor hepatectomy for LDLT from April 2010 to February 2013 were included in the study. Donors were divided into 3 groups based on the type of incision: conventional inverted L incision (n = 268; the C group), upper midline incision (n = 147; the M group), and transverse incision with laparoscopy (n = 14; the T group). Demographics, perioperative outcomes, postoperative complications for donors and recipients, and questionnaire‐derived donor satisfaction with cosmetic appearance were compared. The mean age was lower (P < 0.001), the female ratio was higher (P < 0.001), and the body mass index (BMI) was lower (P = 0.017) in the M and T groups versus the C group. The operation time (P < 0.001) and the hospital stay duration (P = 0.010) were lowest in the M group. The postoperative complications did not differ by the type of incision and also did not show any significant effect in a multivariate analysis (P = 0.867). In the assessment of questionnaire‐derived donor satisfaction matched by age (±5 years), sex, graft, height, weight, and BMI, a more satisfactory cosmetic result and more self‐confidence were noted in the M and T groups versus the C group. In conclusion, the use of a minimal incision is technically feasible for some donor hepatectomy cases with a favorable safety profile. The patient satisfaction levels were greater with improved cosmetic outcomes in cases of minimal incision versus cases of conventional incision. Liver Transpl 21:72‐78, 2015.

Liver transplantation for HBsAg-positive recipients using grafts from HBsAg-positive deceased donors.

This study reports our experience using deceased donor liver grafts from HBsAg‐positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg‐positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26–64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(−) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46–76) at LT. Post‐LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow‐up period was 25.5 months (range: 14–82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV‐unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow‐up biopsies. This experience shows that LT using grafts from deceased HBsAg‐positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring.

The Model for End-Stage Liver Disease Score-Based System Predicts Short Term Mortality Better Than the Current Child- Turcotte-Pugh Score-Based Allocation System during Waiting for Deceased Liver Transplantation

To adopt the model for end-stage liver disease (MELD) score-based system in Korea, the feasibility should be evaluated by analysis of Korean database. The aim of this study was to investigate the feasibility of the MELD score-based system compared with the current Child-Turcotte-Pugh (CTP) based-system and to suggest adequate cut-off to stratify waiting list mortality among Korean population. We included 788 adult patients listed in waiting list in Seoul National University Hospital from January 2008 to May 2011. The short-term survival until 6 months after registration was evaluated. Two hundred forty six (31.2%) patients underwent live donor liver transplantation and 353 (44.8%) patients were still waiting and 121 (15.4%) patients were dropped out due to death. Significant difference was observed when MELD score 24 and 31 were used as cut-off. Three-months survival of Status 2A was 70.2%. However, in Status 2A patients whose MELD score less than 24 (n=82), 86.6% of patients survived until 6 month. Furthermore, patients with high MELD score (≥31) among Status 2B group showed poorer survival rate (45.8%, 3-month) than Status 2A group. In conclusion, MELD score-based system can predict short term mortality better and select more number of high risk patients in Korean population.

Outcome and technical aspects of liver retransplantation: analysis of 25-year experience in a single major center.

BACKGROUND The need for liver retransplantation (re-LT) has been increasing. Here we describe the outcome and technical aspects of re-LT during 25 years in a single major center. METHODS We retrospectively reviewed patients who underwent LT from March 1988 to February 2013. Among 1,312 LTs during 25 years, 38 (2.9%) were re-LTs, including 28 adults (mean age 52.0 y) and 10 children (mean age 5.7 y). RESULTS The most common indication was primary nonfunction in early re-LT and biliary complication in late re-LT. Preoperative major comorbidity was very common (81.6%). Among them, infection was the most frequent (52.6%). Living-donor re-LT constituted 21.1%. In operative technique, nonconventional methods were substantially performed, including high hilar dissection for hepatectomy (>50%), arterial anastomosis with the use of right gastroepiploic or jump graft (23.7%), and hepaticoenterostomy (60.5%). Several reanastomoses were needed in 10.5% for artery and 5.3% for duct. In adults and children, mean estimated blood losses were 9,541 mL and 977 mL, respectively. Mean operative times for adults and children were 508 and 432 minutes, respectively. In-hospital mortality was 35.7% in adults and 40.0% in children. The main cause of death was sepsis for both adults and children. Survival rates at 1 month and 1, 3, and 5 years were, respectively, 89.4%, 56.5%, 50.3%, and 50.3% in adults, and 70.0%, 60.0%, 60.0%, and 60.0% in children. CONCLUSIONS Outcome of re-LT is poorer than primary LT regardless of the cause of graft failure. Therefore, more technical concerns need to be considered. We also need more efforts to control perioperative infections to improve survival after re-LT.

Macrovascular invasion is not an absolute contraindication for living donor liver transplantation

The indication of liver transplantation (LT) for the treatment of advanced hepatocellular carcinoma (HCC) is expanding. However, portal vein tumor thrombus (PVTT) has been still accepted as an absolute contraindication. We experienced an unexpectedly good prognosis in selected patients. Therefore, we tried to identify the prognostic factors after LT for HCC with major PVTT. Among 282 patients who underwent living donor liver transplantation (LDLT) for HCC from January 2009 to December 2013, 11 (3.9%) patients with major PVTT that was preoperatively diagnosed were investigated. The 1‐, 3‐, and 5‐year recurrence‐free survival rates were 63.6%, 45.5%, and 45.5%, respectively, and all recurrent cases showed intrahepatic and extrahepatic recurrence. The 1‐, 3‐, and 5‐year overall survival rates were 72.7%, 63.6%, and 63.6%, respectively, and 2 patients with delayed recurrence survived approximately 5 years after LT. Main portal vein (PV) invasion (P < 0.01), high alpha‐fetoprotein × protein induced by vitamin K absence/antagonist‐II (AP) score (≥20,000; P < 0.01), high standardized uptake value (SUV) ratio (tumor/background liver) in positron emission tomography (≥2.1; P < 0.01), and a large original tumor (≥7 cm; P = 0.03) were significant risk factors for recurrence. In conclusion, if the PVTT has not expanded to the main PV and the AP score is not high, we can consider LDLT as a curative treatment option. Liver Transplantation 23:19–27 2017 AASLD.

Histopathologic factors affecting tumor recurrence after hepatic resection in colorectal liver metastases

Purpose Hepatic resection is a standard method of treatment for colorectal liver metastases (CRLM). However, the pathologic factors of metastatic lesions that affect tumor recurrence are less well defined in CRLM. The aim of this study was to evaluate the risk factors for recurrence of CRLM, focusing on histopathologic factors of metastatic lesions of the liver. Methods From January 2003 to December 2008, 117 patients underwent curative hepatic resection for CRLM were reviewed. Tumor size and number, differentiation, tumor budding, angio-invasion, dedifferentiation and tumor infiltrating inflammation of metastatic lesions were investigated. Results The mean number of hepatic tumors was 2 (range, 1-8). The mean size of the largest tumor was 2.9 cm (range, 0.3-18.5 cm) in diameter. The moderate differentiation of the hepatic tumor was the most common in 86.3% of the patients. Tumor budding, angio-invasion, and dedifferentiation were observed in 81%, 34%, and 12.8% of patients. Inflammation infiltrating tumor was detected in 6.8% of patients. Recurrence after hepatic resection appeared in 69 out of 117 cases (58.9%). Recurrence-free survival at 1, 2 and 5 years were 62.4%, 43.6%, and 34.3%. The multivariate analysis showed the number of metastases ≥3 (P = 0.007), the tumor infiltrating inflammation (P = 0.047), and presence of dedifferentiation (P = 0.020) to be independent risk factors for tumor recurrence. Conclusion Histopathological factors, i.e., dedifferentiation and tumor infiltrating inflammation of the metastatic lesion, could be one of the risk factors of aggressive behavior as well as the number of metastases even after curative resection for CRLM.