Jeong-Moo Lee

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.

Hepatic venous congestion in living donor grafts in liver transplantation: Is there an effect on hepatocellular carcinoma recurrence?

A certain degree of graft congestion in living donor liver transplantation (LDLT) using a right liver graft may be inevitable because of the mismatch between the inflow and outflow structures of the liver. The subsequent inflammatory reaction and rapid regeneration of the graft have been suggested as causes of tumor recurrence. Therefore, we investigated the influence of graft congestion on hepatocellular carcinoma (HCC) recurrence after LDLT. Two hundred eighty‐nine LDLT patients for HCC within the University of California San Francisco criteria between November 1999 and February 2012 were investigated. Patients were assigned to groups on the basis of the degree of congestion (≤10% for group A and >10% for group B), which was determined by 3‐dimensional reconstruction of posttransplant multidetector helical computed tomography within 2 weeks. Perioperative characteristics, regeneration rates after 6 months, and recurrence rates were compared between the groups, and a multivariate analysis of the influence of congestion on tumor recurrence was subsequently completed. No significant difference in demographics was found. Group B had more elevated peak posttransplant levels of aspartate aminotransferase (296.26 versus 227.53, P = 0.05), alanine aminotransferase (382.91 versus 276.98, P = 0.04), and highly selective C‐reactive protein (5.41 versus 3.55, P < 0.001); a higher noncongestive section regeneration rate (25.8% versus 13.6%, P = 0.012); and a higher recurrence rate (30.4% versus 9.7%, P = 0.01) than group A. Graft congestion > 10% [hazard ratio (HR) = 3.10, 95% confidence interval (CI) = 1.15‐8.35, P = 0.03], microvascular invasion (HR = 5.43, 95% CI = 2.04‐14.44, P < 0.01), and an alpha‐fetoprotein level > 200 IU/L (HR = 2.98, 95% CI = 1.10‐8.03, P = 0.03) were significantly related to tumor recurrence. Liver congestion may promote the recurrence of HCC after LDLT; therefore, it should be minimized. Liver Transpl 20:784‐790, 2014.

Pediatric split liver transplantation after Fontan procedure in left isomerism combined with biliary atresia: A case report

LI is a subset of the heterotaxy syndrome and a rare birth defect that involves the heart and other organs. It can be combined with extracardiac abnormalities, especially BA. CHD can be associated with LI in up to 15% of cases, although it is rare in BA. Pediatric LT for a child with ESLD due to BA combined with LI and CHD is a challenging issue for a transplant surgeon. Herein, we report a successful split LT on a three‐yr‐old boy with LI who survived after a Fontan procedure due to single ventricle, but who suffered from HPS associated with BA.

Fulminant hepatitis linked to dapsone hypersensitivity syndrome requiring urgent living donor liver transplantation: A case report

Dapsone is a sulfone‐type drug used widely for different infectious, immune, and hypersensitivity disorders as an antibacterial treatment alone or in combination for leprosy and sometimes for infected skin lesions. DHS is a severe idiosyncratic adverse reaction with multi‐organ involvement. However, acute necrotic hepatitis requiring an emergent LT is rare. Herein, we report a case of 12‐yr‐old girl who suffered from fulminant hepatitis and multi‐organ failure due to DHS for PPD. She was saved by emergent LDLT. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal but rare disease.

Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

Background/Aims The dose of mycophenolate mofetil (MMF) has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT). Methods Two sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12) for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day) with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter), with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT. Results In the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day), and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively. Conclusions A reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

Reappraisal of the Role of Portacaval Shunting in the Growth of Patients With Glycogen Storage Disease Type I in the Era of Liver Transplantation.

Background Instead of dietary modification, surgical management is considered for correcting growth retardation, poor metabolic control, and hepatocellular adenoma (HCA) in glycogen storage disease (GSD) type I. Methods The records of 55 GSD type I patients were retrospectively reviewed. Thirty-two patients underwent only dietary management (group D) and 23 underwent surgical management (group S). In group S, 17 underwent portacaval shunting (PCS), 13 underwent liver transplantation (LT; 7 underwent both PCS and LT). Height-for-age and body mass index-for-age Z-scores based on World Health Organization data were used to compare growth patterns before and after surgery. Changes in metabolic abnormalities and HCA after operation were also investigated. Results Height-for-age Z-scores for group S were higher by an average of 0.377 compared to that for group D. Metabolic abnormalities often disappeared after LT but improved partially after PCS. De novo HCA was detected in 4 patients (13%) from group D, 12 (100%) who underwent PCS, and none who underwent LT. One case of hepatocellular carcinoma and one of hemorrhage from a HCA were noted in group D. Two cases of hepatocellular carcinoma, 2 of hemorrhage, and 1 of necrosis were noted after PCS. Conclusions Surgery yielded greater growth improvement than dietary management. However, after PCS, metabolic abnormalities remained unresolved, and the de novo HCA rate was high. Portacaval shunting can be used to improve growth in GSD type I patients when LT is not possible, but close observation for metabolic abnormalities and HCA is essential.

Living donor liver transplantation using a left liver extended to right anterior sector

In living donor liver transplantations, right liver grafts have been commonly used to meet the metabolic demands of the recipient. However, a small left remnant liver volume sometimes limits its use due to donor safety concerns. Here, we report an innovative living donor hepatectomy using a left liver extended to the right anterior sector (segments 2–5 and 8), which can be considered for donors who are unsuited for right liver donation.

Bile duct invasion can be an independent prognostic factor in early stage hepatocellular carcinoma

Backgrounds/Aims In hepatocellular carcinoma (HCC), bile duct invasion occurs far more rarely than vascular invasion and is not well characterized. In addition, the pathologic finding of bile duct invasion is not considered an independent prognostic factor for HCC following surgery. In this study, we determined the characteristics of HCC with bile duct invasion, and assessed the clinical significance of bile duct invasion. Methods We retrospectively reviewed the medical records of 363 patients who underwent hepatic resection for HCC at Seoul National University Hospital (SNUH) from January 2009 to December 2011. Preoperative, operative, and pathological data were collected. The risk factors for recurrence and survival were analyzed. Subsequently, the patients were divided into 2 groups according to disease stage (American Joint Committee on Cancer/International Union Against Cancer 7th edition): early stage (T1 and 2) and advanced stage (T3 and 4) group; and risk factors in the sub-groups were analyzed. Results Among 363 patients, 13 showed bile duct invasion on pathology. Patients with bile duct invasion had higher preoperative total bilirubin levels, greater microvascular invasion, and a higher death rate than those without bile duct invasion. In multivariate analysis, bile duct invasion was not an independent prognostic factor for survival for the entire cohort, but, was an independent prognostic factor for early stage. Conclusions Bile duct invasion accompanied microvascular invasion in most cases, and could be used as an independent prognostic factor for survival especially in early stage HCC (T1 and T2).