Donor sex and donor-recipient sex disparity do not affect hepatocellular carcinoma recurrence after living donor liver transplantation

Purpose@#Studies have yielded contradictory results on whether donor sex and donor-recipient sex disparity affect hepatocellular carcinoma (HCC) recurrence after living donor liver transplantation (LDLT). The present study assessed whether donor sex or donor-recipient sex disparity affects HCC recurrence after LDLT at a high-volume center. @*Methods@#This study included 772 HCC patients who underwent LDLT between January 2006 and December 2015 at Asan Medical Center. Patients were divided into 4 groups based on the sex of the donor and recipient: male-to-male (n = 490, 63.5%), male-to-female (n = 75, 9.7%), female-to-male (n = 170, 22.0%), and female-to-female (n = 37, 4.8%). @*Results@#Disease-free survival (DFS; P = 0.372) and overall survival (OS; P = 0.591) did not differ significantly among the 4 groups. DFS also did not differ significantly between LDLT recipients with male and female donors (P = 0.792) or between male and female recipients (P = 0.084). After patient matching with an α-FP/des-γ-carboxy prothrombin/tumor volume score cutoff of 5logs, donor-recipient sex disparity did not significantly affect DFS (P = 0.598) or OS (P = 0.777). There were also no differences in DFS in matched LDLT recipients with male and female donors (P = 0.312) or between male and female recipients (P = 0.374). @*Conclusion@#Neither donor sex nor donor-recipient sex disparity significantly affected posttransplant HCC recurrence.

Prognostic impact of serum soluble PD-1 and ADV score for living donor liver transplantation in patients with previously untreated hepatocellular carcinoma

Purpose@#The programmed death protein 1 (PD-1) pathway is the critical mechanism in development of hepatocellular carcinoma (HCC). The present study analyzed the prognostic impact of pretransplant serum soluble PD-1 (sPD-1) concentration and α-FP–des-γ- –tumor volume (ADV) score in patients with previously untreated HCC undergone liver transplantation (LT). @*Methods@#This retrospective single-center study enrolled 100 patients with HCC who underwent living donor LT from 2010 to 2016. Concentrations of sPD-1 were measured in stored serum samples. @*Results@#Receiver operating characteristic curve analysis of 2-year tumor recurrence resulted in an sPD-1 cutoff of 177.1 µg/mL, which was associated with higher rates of tumor recurrence (P = 0.022), but not with overall patient survival (P = 0.460). The derived cutoff for pretransplant ADV score was 5.4log, which was associated with higher tumor recurrence rate (P 177.1 µg/mL (hazard ratio [HR], 2.26; P = 0.020) and pretransplant ADV score of >5.4log (HR, 3.56; P < 0.001) were independent risk factors for posttransplant HCC recurrence. The combination of these 2 factors enabled the stratification of patients into 3 groups, with groups having 0, 1, and 2 risk factors differing significantly in the prognosis of tumor recurrence (P < 0.001) and overall patient survival (P = 0.006). @*Conclusion@#Both sPD-1 concentration and ADV score have prognostic impacts in patients who underwent LT for untreated HCCs. These factors, both individually and combined, can help in predicting posttransplant prognosis.

Diagnostic and prognostic impact of fluorodeoxyglucosepositron emission tomography in diagnosing intraductal papillary neoplasms of the bile duct of the liver

Purpose@#Malignant intraductal papillary neoplasm of the bile duct of the liver (IPNB-L) cannot readily be diagnosed through preoperative CT or MRI, but fluorodeoxyglucose (FDG)-PET is a viable alternative. This study evaluated the diagnostic and prognostic impacts of FDG-PET in patients with IPNB-L. @*Methods@#This was a retrospective single-center study of 101 IPNB-L patients who underwent hepatectomy between 2010 and 2019. @*Results@#Mean age was 64.4 ± 8.3 years and 76 (75.2%) were male. Anatomical hepatic resection was performed in 99 (98.0%). Concurrent bile duct resection and pancreaticoduodenectomy were performed in 41 (40.6%) and 1 (1.0%), respectively. R0 and R1 resections were performed in 88 (87.1%) and 13 (12.9%), respectively. Low-grade intraepithelial neoplasia and high-grade neoplasia/invasive carcinoma were diagnosed in 19 (18.8%) and 82 (81.2%), respectively. Median FDG-PET maximal standardized uptake values (SUVmax) in low-grade neoplasia and high-grade neoplasia/carcinoma were 3.6 (range, 1.7–7.6) and 5.2 (range, 1.5–18.7) (P = 0.019), respectively. Receiver operating characteristic curve analysis of SUVmax showed area under the curve of 0.674, with sensitivity of 84.2% and specificity of 47.4% at SUVmax cutoff of 3.0. This cutoff had no significant influence on tumor recurrence (P = 0.832) or patient survival (P = 0.996) in patients with IPNB-L of high-grade neoplasia or invasive carcinoma. @*Conclusion@#IPNB-L is a rare type of biliary neoplasm and encompasses a histological spectrum ranging from benign disease to invasive carcinoma. An FDG-PET SUVmax cutoff of 3.0 appears to effectively discern high-grade neoplasia/ carcinoma from low-grade neoplasia, which will assist with the surgical strategy for these cases.

Outcomes after liver transplantation in Korea: Incidence and risk factors from Korean transplantation registry

Background/Aims@#To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. @*Methods@#This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. @*Results@#A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. @*Conclusions@#This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

Postresection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma according to the 2010World Health Organization classification: single-center experience of 168 patients

Purpose@#Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. @*Methods@#The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. @*Results@#During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. @*Conclusion@#Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft

Purpose@#When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. @*Methods@#This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. @*Results@#The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. @*Conclusion@#The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Efficacy of Living Donor Liver Transplantation in Patients with Methylmalonic Acidemia / 대한소아소화기영양학회지

Purpose@#Despite aggressive medical and nutritional management, patients with methylmalonic acidemia (MMA) often suffer from multi-organ damage. Early deceased donor liver transplantation (DDLT) has emerged as an intervention to prevent disease progression. We investigated the efficacy of living donor LT (LDLT) with a potential carrier of MMA and a small volume of graft in patients with MMA as an alternative to DDLT. @*Methods@#Of five patients (three male, two female; median age 5.7 years; range, 1.3–13.7 years), four underwent carrier LDLT, while one underwent non-carrier auxiliary LDLT. All patients received pre- and post-LT continuous renal replacement therapy and were provided with minimal restriction diet according to serum MMA level after LT. MMA levels in the serum and urine, the incidence of metabolic crisis, and clinical findings before and after LT were compared. @*Results@#The survival rate was 100% during 2.2 years of follow up period after LT. In all five cases, MMA titer in the serum after transplantation decreased with less restrictive diet. Metabolic crisis was not observed during the follow-up period. In addition, no patient showed progression of severe renal impairment requiring hemodialysis. Progression of delayed cognitive development was not observed. Social functioning with improved neuropsychiatric development was observed. @*Conclusion@#This study showed that LDLT achieved improved quality of life with less restrictive diet, therefore it could be a feasible alternative option to DDLT for the treatment of patients with MMA, even with an auxiliary LT.

Effects of Voice Therapy Using Gliding and Humming in Dysphonic Patients With Glottal Gap

Background and Objectives@#Therapies have been reported to treat the glottal gap previously. However, these voice therapies showed the limits because many techniques focused only on one among breathing, resonance and phonation. In addition patients often have difficulties visiting hospital frequently. ‘Gliding and humming’ is vocal training technique that readjusts total vocal patterns such as breathing, resonance and phonation. This technique can be easily applied during short term sessions. The purpose of this study is to evaluate the efficiency of voice therapy with ‘gliding and humming’ for patients with glottic gap during short-term treatment sessions.Materials and Method Twenty-three patients with glottal gap were selected. Of all patients, 14 patients had sulcus vocalis and 12 patients had muscle tension dysphonia (MTD). Voice therapies were performed 1.9 sessions in average. GRBAS, jitter, shimmer, noise to harmonic ratio, semitone range, closed quotient_vowel and maximum phonation time were compared before and after the therapies. In addition, changes of glottal gap and MTD severity were evaluated. @*Results@#Statistically significant improvement was observed. MTD improvement was observed only among the patients with glottal gap improvement. Also sulcus vocalis group showed the statistically significant improvement. @*Conclusion@#‘Gliding and humming’ was effective to the patients with glottic gap and sulcus vocalis. Also, among patients who have both glottic gap and MTD, the data suggests that voice therapy for glottic gap also makes improvement in MTD.

Prediction of Post-resection Prognosis Using the ADV Score for Huge Hepatocellular Carcinomas ≥13 cm

Background/Aims@#Multiplication of α-fetoprotein, des-γ-carboxy prothrombin, and tumor volume (ADV score) is a surrogate marker for post-resection prognosis of hepatocellular carcinoma (HCC). This study aimed to validate the predictive power of the ADV score-based prognostic prediction model for patients with solitary huge HCC. @*Methods@#Of 3,018 patients, 100 patients who underwent hepatic resection for solitary HCC ≥13 cm between 2008 and 2012 were selected. @*Results@#The median tumor diameter and tumor volume were 15.0 cm and 886 mL, respectively. Tumor recurrence and overall survival (OS) rates were 70.7% and 66.0% at one year and 84.9% and 34.0% at five years, respectively. Microvascular invasion (MVI) was the only independent risk factor for disease-free survival (DFS) and OS. DFS and OS, stratified by ADV score with 1-log intervals, showed significant prognostic contrasts (P=0.007 and P=0.017, respectively). DFS and OS, stratified by ADV score with a cut-off of 8-log, showed significant prognostic contrasts (P=0.014 and P=0.042, respectively). The combination of MVI and ADV score with a cut-off of 8-log also showed significant prognostic contrasts in DFS (P<0.001) and OS (P=0.001) considering the number of risk factors. Prognostic contrast was enhanced after combining the MVI and ADV score. @*Conclusions@#The prognostic prediction model with the ADV score could reliably predict the risk of tumor recurrence and long-term patient survival outcomes in patients with solitary huge HCC ≥13 cm. The results of this study suggest that our prognostic prediction models can be used to guide surgical treatment and post-resection follow-up for patients with huge HCCs.

Outcomes after liver transplantation in Korea: Incidence and risk factors from Korean transplantation registry

Background/Aims@#To analyze the incidence and risk factors of outcomes after liver transplantation (LT) in the Korean population. @*Methods@#This study analyzed data from the liver cohort of Korean Organ Transplantation Registry (KOTRY) who had LT between May 2014 and December 2017. Study measures included the incidence of post-LT outcomes in recipients of living donor LT (LDLT) and deceased donor LT (DDLT). Cox multivariate proportional hazards model was used to determine the potential risk factors predicting the outcomes. @*Results@#A total of 2,563 adult recipients with LT (LDLT, n=1,956; DDLT, n=607) were included, with mean±standard deviation age of 53.9±8.9 years, and 72.2% were male. The post-LT outcomes observed in each LDLT and DDLT recipients were death (4.0% and 14.7%), graft loss (5.0% and 16.1%), rejection (7.0% and 12.0%), renal failure (2.7% and 13.8%), new onset of diabetes (12.5% and 15.4%), and hepatocellular carcinoma (HCC) recurrence (both 6.7%). In both LDLT and DDLT recipients, the most common post-LT complications were renal dysfunction (33.6% and 51.4%), infection (26.7% and 48.4%), and surgical complication (22.5% and 23.9%). Incidence of these outcomes were generally higher among recipients of DDLT than LDLT. Multivariate analysis indicated recipient age and DDLT as significant risk factors associated with death and graft loss. DDLT and ABO incompatible transplant were prognostic factors for rejection, and HCC beyond Milan criteria at pre-transplant was a strong predictor of HCC recurrence. @*Conclusions@#This study is a good indicator of the post-LT prognosis in the Korean population and suggests a significant burden of post-LT complications.

Postresection prognosis of combined hepatocellular carcinoma-cholangiocarcinoma according to the 2010World Health Organization classification: single-center experience of 168 patients

Purpose@#Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC) has wide histologic diversity. This study investigated the effects of cHCC-CC histology, according to the 2010 World Health Organization (WHO) classification, on patient prognosis. @*Methods@#The medical records of patients who underwent surgical resection for cHCC-CC at our institution between July 2012 and June 2019 were retrospectively evaluated. @*Results@#During the study period, 168 patients, 122 males (72.6%) and 46 females (27.4%), underwent surgical resection for cHCC-CC, including 159 patients (94.6%) who underwent R0 resection. Mean tumor diameter was 4.4 ± 2.8 cm, and 161 patients (95.8%) had solitary tumors. Histologically, 86 patients (51.2%) had classical type, and 82 (48.8%) had tumors with stem cell (SC) features, including 33 (19.6%) with intermediate-cell and 23 (13.7%) each with typical SC and cholangiolocellular features; 3 tumors (1.8%) were unclassifiable. At 1, 3, and 5 years, tumor recurrence rates were 31.9%, 49.6%, and 58.1%, respectively, and patient survival rates were 91.0%, 70.2%, and 60.3%, respectively. Univariate analysis showed that tumor size of >5 cm, microscopic and macroscopic vascular invasion, lymph node metastasis, 8th edition of the American Joint Committee on Cancer (AJCC) tumor stage, and 2010 WHO classification were significantly prognostic. Multivariate analysis showed that the 8th AJCC tumor stage and 2010 WHO histologic classification were independently prognostic for tumor recurrence and patient survival. There were no significant prognostic differences among the 3 SC subtypes. @*Conclusion@#Postresection outcomes are better in patients with SC-type than with classical-type cHCC-CC.

Fates of retained hepatic segment IV and its prognostic impact in adult split liver transplantation using an extended right liver graft

Purpose@#When splitting a liver for adult and pediatric graft recipients, the retained left medial section (S4) will undergo ischemic necrosis and the right trisection graft becomes an extended right liver (ERL) graft. We investigated the fates of the retained S4 and its prognostic impact in adult split liver transplantation (SLT) using an ERL graft. @*Methods@#This was a retrospective analysis of 25 adult SLT recipients who received split ERL grafts. @*Results@#The mean model for end-stage liver disease (MELD) score was 27.3 ± 10.9 and graft-recipient weight ratio (GRWR) was 1.98 ± 0.44. The mean donor age was 26.5 ± 7.7 years. The split ERL graft weight was 1,181.5 ± 252.8 g, which resulted in a mean GRWR of 1.98 ± 0.44. Computed tomography of the retained S4 parenchyma revealed small ischemic necrosis in 16 patients (64.0%) and large ischemic necrosis in the remaining 9 patients (36.0%). No S4-associated biliary complications were developed. The mean GRWR was 1.87 ± 0.43 in the 9 patients with large ischemic necrosis and 2.10 ± 0.44 in the 15 cases with small ischemic necrosis (P = 0.283). The retained S4 parenchyma showed gradual atrophy on follow-up imaging studies. The amount of S4 ischemic necrosis was not associated with graft (P = 0.592) or patient (P = 0.243) survival. A MELD score of >30 and pretransplant ventilator support were associated with inferior outcomes. @*Conclusion@#The amount of S4 ischemic necrosis is not a prognostic factor in adult SLT recipients, probably due to a sufficiently large GRWR.

Efficacy of Living Donor Liver Transplantation in Patients with Methylmalonic Acidemia / 대한소아소화기영양학회지

Purpose@#Despite aggressive medical and nutritional management, patients with methylmalonic acidemia (MMA) often suffer from multi-organ damage. Early deceased donor liver transplantation (DDLT) has emerged as an intervention to prevent disease progression. We investigated the efficacy of living donor LT (LDLT) with a potential carrier of MMA and a small volume of graft in patients with MMA as an alternative to DDLT. @*Methods@#Of five patients (three male, two female; median age 5.7 years; range, 1.3–13.7 years), four underwent carrier LDLT, while one underwent non-carrier auxiliary LDLT. All patients received pre- and post-LT continuous renal replacement therapy and were provided with minimal restriction diet according to serum MMA level after LT. MMA levels in the serum and urine, the incidence of metabolic crisis, and clinical findings before and after LT were compared. @*Results@#The survival rate was 100% during 2.2 years of follow up period after LT. In all five cases, MMA titer in the serum after transplantation decreased with less restrictive diet. Metabolic crisis was not observed during the follow-up period. In addition, no patient showed progression of severe renal impairment requiring hemodialysis. Progression of delayed cognitive development was not observed. Social functioning with improved neuropsychiatric development was observed. @*Conclusion@#This study showed that LDLT achieved improved quality of life with less restrictive diet, therefore it could be a feasible alternative option to DDLT for the treatment of patients with MMA, even with an auxiliary LT.

Effects of Voice Therapy Using Gliding and Humming in Dysphonic Patients With Glottal Gap

Background and Objectives@#Therapies have been reported to treat the glottal gap previously. However, these voice therapies showed the limits because many techniques focused only on one among breathing, resonance and phonation. In addition patients often have difficulties visiting hospital frequently. ‘Gliding and humming’ is vocal training technique that readjusts total vocal patterns such as breathing, resonance and phonation. This technique can be easily applied during short term sessions. The purpose of this study is to evaluate the efficiency of voice therapy with ‘gliding and humming’ for patients with glottic gap during short-term treatment sessions.Materials and Method Twenty-three patients with glottal gap were selected. Of all patients, 14 patients had sulcus vocalis and 12 patients had muscle tension dysphonia (MTD). Voice therapies were performed 1.9 sessions in average. GRBAS, jitter, shimmer, noise to harmonic ratio, semitone range, closed quotient_vowel and maximum phonation time were compared before and after the therapies. In addition, changes of glottal gap and MTD severity were evaluated. @*Results@#Statistically significant improvement was observed. MTD improvement was observed only among the patients with glottal gap improvement. Also sulcus vocalis group showed the statistically significant improvement. @*Conclusion@#‘Gliding and humming’ was effective to the patients with glottic gap and sulcus vocalis. Also, among patients who have both glottic gap and MTD, the data suggests that voice therapy for glottic gap also makes improvement in MTD.

Prediction of Post-resection Prognosis Using the ADV Score for Huge Hepatocellular Carcinomas ≥13 cm

Background/Aims@#Multiplication of α-fetoprotein, des-γ-carboxy prothrombin, and tumor volume (ADV score) is a surrogate marker for post-resection prognosis of hepatocellular carcinoma (HCC). This study aimed to validate the predictive power of the ADV score-based prognostic prediction model for patients with solitary huge HCC. @*Methods@#Of 3,018 patients, 100 patients who underwent hepatic resection for solitary HCC ≥13 cm between 2008 and 2012 were selected. @*Results@#The median tumor diameter and tumor volume were 15.0 cm and 886 mL, respectively. Tumor recurrence and overall survival (OS) rates were 70.7% and 66.0% at one year and 84.9% and 34.0% at five years, respectively. Microvascular invasion (MVI) was the only independent risk factor for disease-free survival (DFS) and OS. DFS and OS, stratified by ADV score with 1-log intervals, showed significant prognostic contrasts (P=0.007 and P=0.017, respectively). DFS and OS, stratified by ADV score with a cut-off of 8-log, showed significant prognostic contrasts (P=0.014 and P=0.042, respectively). The combination of MVI and ADV score with a cut-off of 8-log also showed significant prognostic contrasts in DFS (P<0.001) and OS (P=0.001) considering the number of risk factors. Prognostic contrast was enhanced after combining the MVI and ADV score. @*Conclusions@#The prognostic prediction model with the ADV score could reliably predict the risk of tumor recurrence and long-term patient survival outcomes in patients with solitary huge HCC ≥13 cm. The results of this study suggest that our prognostic prediction models can be used to guide surgical treatment and post-resection follow-up for patients with huge HCCs.

Post-resection prognosis of patients with hepatic epithelioid hemangioendothelioma

Purpose@#Epithelioid hemangioendothelioma (EHE) is a rare borderline vascular tumor. This retrospective, single-center study evaluated the outcomes of hepatic resection (HR) in patients with hepatic EHE. @*Methods@#Over the 10-year period from 2009 to 2018, 11 patients with hepatic EHE underwent HR, accounting for 0.1% of the 11,979 adults who underwent HR at our center. Diagnosis of hepatic EHE was confirmed by immunohistochemical staining for CD34, CD31, and factor VIII-related antigen. @*Results@#The 11 patients included 9 females (81.8%) and 2 males (18.2%) with mean age of 43.5 ± 13.6 years. Preoperative imaging resulted in a preliminary diagnosis of suspected liver metastasis or EHE, with 9 patients (81.8%) undergoing liver biopsy. No patient presented with abnormally elevated concentrations of liver tumor markers. The extents of HR were determined by tumor size and location from trisectionectomy to partial hepatectomy. All patients recovered uneventfully from HR. Five patients showed tumor recurrence, with 4 receiving locoregional treatments for recurrent lesions. The 1-, 3-and 5-year disease-free survival rates were 90.9%, 54.5%, and 54.5%, respectively. Currently, all patients remain alive and are doing well. Univariate analysis on tumor recurrence showed that tumor size ≥ 4 cm was significantly associated with tumor recurrence (P = 0.032), but tumor number ≥ 4 was not related to (P = 0.24). @*Conclusion@#Hepatic EHE is a rare form of primary liver tumor often misdiagnosed as a metastatic tumor. Because of its malignant potential, HR is indicated if possible. HR plus, when necessary, treatment of recurrence yields favorable overall survival rates in patients with hepatic EHE.

Validation of prognostic impact of ADV score for resection of hepatocellular carcinoma: analysis using Korea Liver Cancer Registry Database

Purpose@#We aimed to validate the prognostic predictive power of ADV score (α-FP-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score, calculated as α-FP [ng/mL] × DCP [mAU/mL] × TV [mL] and expressed in log10) for predicting patient survival after resection of hepatocellular carcinoma (HCC). @*Methods@#This study included 1,390 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection between 2008 and 2012 and were followed up until December 2016. They were divided into 4 groups according to the number of tumors and preoperative treatment. @*Results@#There was no significant correlation among α-FP, DCP, and TV values (r2 ≤ 0.04, P < 0.001). In group 1 with single treatment-naive tumor (n = 1,154), patient stratification with postoperative ADV 1log-interval and cutoffs of 5log, 7log, and 10log showed great prognostic contrast (P < 0.001). In group 2 with multiple treatment-naive tumors (n = 170), patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs also showed great prognostic contrast (P < 0.001). In group 3 (n = 50) and group 4 (n = 16) with preoperative-treated tumors, patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs showed noticeable prognostic contrast (P ≤ 0.031). Preoperative ADV score based on preoperative findings also showed great prognostic contrast in 1,106 patients preoperatively diagnosed as having single treatment-naive tumor (P < 0.001). Confining patients to tumor-node-metastasis stages I and II (n = 1,072) as well as Barcelona Clinic Liver Cancer stage 0 and A (n = 862), postoperative ADV cutoffs showed further prognostic stratification. @*Conclusion@#This validation study strongly suggests that ADV score is an integrated surrogate marker for postresection prognosis in patients with HCC.

Pretransplant Hepatic Malignancy Increases Risk of De Novo Malignancy after Liver Transplantation

BACKGROUND@#Hepatocellular carcinoma (HCC) recurrence and development of de novo malignancy (DNM) after liver transplantation (LT) are the major causes of late recipient death.@*METHODS@#We analyzed the incidence of extrahepatic DNM following living donor LT according to the status of pretransplant hepatic malignancy. We selected 2,076 adult patients who underwent primary LDLT during 7 years from January 2010 to December 2016.@*RESULTS@#The pretransplant hepatic malignancy group (n = 1,012) showed 45 cases (4.4%) of the following extrahepatic DNMs: posttransplant lymphoproliferative disease (PTLD) in 10; lung cancer in 10; stomach cancer in 6; colorectal cancer in 5; urinary bladder cancer in 3; and other cancers in 11. The pretransplant no hepatic malignancy group (n = 1,064) showed 25 cases (2.3%) of the following extrahepatic DNMs: colorectal cancer in 3; stomach cancer in 3; leukemia in 3; lung cancer in 3; PTLD in 2; prostate cancer in 2; and other cancers in 9. Incidences of extrahepatic DNM in the pretransplant hepatic malignancy and no hepatic malignancy groups were as follows: 1.1% and 0.5% at 1 year, 3.2% and 2.0% at 3 years, 4.6% and 2.5% at 5 years, and 5.4% and 2.8% at 8 years, respectively (P = 0.006). Their overall patient survival rates were as follows: 97.3% and 97.2% at 1 year, 91.6% and 95.9% at 3 years, 89.8% and 95.4% at 5 years, and 89.2% and 95.4% at 8 years, respectively (P < 0.001). Pretransplant hepatic malignancy was the only significant risk factor for posttransplant extrahepatic DNM.@*CONCLUSION@#Our results suggest that patients who had pretransplant hepatic malignancy be followed up more strictly because they have a potential risk of primary hepatic malignancy recurrence as well as a higher risk of extrahepatic DNM than patients without pretransplant hepatic malignancy.

Hepatitis B Prophylaxis after Liver Transplantation in Korea: Analysis of the KOTRY Database

BACKGROUND@#Prophylaxis for hepatitis B virus (HBV) recurrence is essential after liver transplantation (LT) in HBV-associated recipients. We conducted real-world analysis of HBV prophylaxis after LT in the Korean population.@*METHODS@#Korean Organ Transplantation Registry (KOTRY) database and additionally collected data (n = 326) were analyzed with special reference to types of HBV prophylaxis.@*RESULTS@#The study cohort comprised 267 cases of living-donor LT and 59 cases of deceased-donor LT. Hepatocellular carcinoma (HCC) was diagnosed in 232 (71.2%) of these subjects. Antiviral agents were used in 255 patients (78.2%) prior to LT. HBV DNA was undetectable in 69 cases (21.2%) and detectable over wide concentrations in the other 257 patients (78.8%) prior to LT. Polymerase chain reaction analysis of the store blood samples detected HBV DNA in all patients, with 159 patients (48.9%) showing concentrations > 100 IU/mL. Post-transplant HBV regimens during the first year included combination therapy in 196 (60.1%), hepatitis B immunoglobulin (HBIG) monotherapy in 121 (37.1%), and antiviral monotherapy in 9 (2.8%). In the second post-transplant year, these regimens had changed to combination therapy in 187 (57.4%), HBIG monotherapy in 112 (34.4%), and antiviral monotherapy in 27 (8.3%). Trough antibody to hepatitis B surface antigen titers > 500 IU/mL and >1,000 IU/mL were observed in 61.7% and 25.2%, respectively. The mean simulative half-life of HBIG was 21.6 ± 4.3 days with a median 17.7 days. Up to 2-year follow-up period, HCC recurrence and HBV recurrence developed in 18 (5.5%) and 6 (1.8%), respectively. HCC recurrence developed in 3 of 6 patients with HBV recurrence.@*CONCLUSION@#Combination therapy is the mainstay of HBV prophylaxis protocols in a majority of Korean LT centers, but HBIG was often administered excessively. Individualized optimization of HBIG treatments using SHL is necessary to adjust the HBIG infusion interval.

Validation of prognostic impact of ADV score for resection of hepatocellular carcinoma: analysis using Korea Liver Cancer Registry Database

Purpose@#We aimed to validate the prognostic predictive power of ADV score (α-FP-des-γ-carboxyprothrombin [DCP]-tumor volume [TV] score, calculated as α-FP [ng/mL] × DCP [mAU/mL] × TV [mL] and expressed in log10) for predicting patient survival after resection of hepatocellular carcinoma (HCC). @*Methods@#This study included 1,390 patients with HCC registered in the Korea Liver Cancer Registry. Patients underwent hepatic resection between 2008 and 2012 and were followed up until December 2016. They were divided into 4 groups according to the number of tumors and preoperative treatment. @*Results@#There was no significant correlation among α-FP, DCP, and TV values (r2 ≤ 0.04, P < 0.001). In group 1 with single treatment-naive tumor (n = 1,154), patient stratification with postoperative ADV 1log-interval and cutoffs of 5log, 7log, and 10log showed great prognostic contrast (P < 0.001). In group 2 with multiple treatment-naive tumors (n = 170), patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs also showed great prognostic contrast (P < 0.001). In group 3 (n = 50) and group 4 (n = 16) with preoperative-treated tumors, patient stratification with postoperative ADV 1log-interval and above-mentioned 3 cutoffs showed noticeable prognostic contrast (P ≤ 0.031). Preoperative ADV score based on preoperative findings also showed great prognostic contrast in 1,106 patients preoperatively diagnosed as having single treatment-naive tumor (P < 0.001). Confining patients to tumor-node-metastasis stages I and II (n = 1,072) as well as Barcelona Clinic Liver Cancer stage 0 and A (n = 862), postoperative ADV cutoffs showed further prognostic stratification. @*Conclusion@#This validation study strongly suggests that ADV score is an integrated surrogate marker for postresection prognosis in patients with HCC.