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1.  Practical Guidelines for the Surgical Treatment of Gallbladder Cancer 
Journal of Korean Medical Science  2014;29(10):1333-1340.
At present, surgical treatment is the only curative option for gallbladder (GB) cancer. Many efforts therefore have been made to improve resectability and the survival rate. However, GB cancer has a low incidence, and no randomized, controlled trials have been conducted to establish the optimal treatment modalities. The present guidelines include recent recommendations based on current understanding and highlight controversial issues that require further research. For T1a GB cancer, the optimal treatment modality is simple cholecystectomy, which can be carried out as either a laparotomy or a laparoscopic surgery. For T1b GB cancer, either simple or an extended cholecystectomy is appropriate. An extended cholecystectomy is generally recommended for patients with GB cancer at stage T2 or above. In extended cholecystectomy, a wedge resection of the GB bed or a segmentectomy IVb/V can be performed and the optimal extent of lymph node dissection should include the cystic duct lymph node, the common bile duct lymph node, the lymph nodes around the hepatoduodenal ligament (the hepatic artery and portal vein lymph nodes), and the posterior superior pancreaticoduodenal lymph node. Depending on patient status and disease severity, surgeons may decide to perform palliative surgeries.
Graphical Abstract
PMCID: PMC4214932  PMID: 25368485
Gallbladder; Neoplasm; General Surgery; Guideline
2.  Pneumomediastinum after Facial Bone Contouring Surgery 
Archives of Plastic Surgery  2014;41(4):443-445.
PMCID: PMC4113715  PMID: 25075378
3.  Immediately transcripted genes in various hepatic ischemia models 
To elucidate the characteristic gene transcription profiles among various hepatic ischemia conditions, immediately transcribed genes and the degree of ischemic injury were compared among total ischemia (TI), intermittent clamping (IC), and ischemic preconditioning (IPC).
Sprague-Dawley rats were equally divided into control (C, sham-operated), TI (ischemia for 90 minutes), IC (ischemia for 15 minutes and reperfusion for 5 minutes, repeated six times), and IPC (ischemia for 15 minutes, reperfusion for 5 minutes, and ischemia again for 90 minutes) groups. A cDNA microarray analysis was performed using hepatic tissues obtained by partial hepatectomy after occluding hepatic inflow.
The cDNA microarray revealed the following: interleukin (IL)-1β expression was 2-fold greater in the TI group than in the C group. In the IC group, IL-1α/β expression increased by 2.5-fold, and Na+/K+ ATPase β1 expression decreased by 2.4-fold. In the IPC group, interferon regulatory factor-1, osteoprotegerin, and retinoblastoma-1 expression increased by approximately 2-fold compared to that in the C group, but the expression of Na+/K+ ATPase β1 decreased 3-fold.
The current findings revealed characteristic gene expression profiles under various ischemic conditions. However, additional studies are needed to clarify the mechanism of protection against IPC.
PMCID: PMC3491232  PMID: 23166889
Reperfusion injury; Ischemic preconditioning; Necrosis; Apoptosis; Microarray analysis
4.  Is close monitoring in the intensive care unit necessary after elective liver resection? 
Many surgical patients are admitted to the intensive care unit (ICU), resulting in an increased demand, and possible waste, of resources. Patients who undergo liver resection are also transferred postoperatively to the ICU. However, this may not be necessary in all cases. This study was designed to assess the necessity of ICU admission.
The medical records of 313 patients who underwent liver resections, as performed by a single surgeon from March 2000 to December 2010 were retrospectively reviewed.
Among 313 patients, 168 patients (53.7%) were treated in the ICU. 148 patients (88.1%) received only observation during the ICU care. The ICU re-admission and intensive medical treatment significantly correlated with major liver resection (odds ratio [OR], 6.481; P = 0.011), and intraoperative transfusions (OR, 7.108; P = 0.016). Patients who underwent major liver resection and intraoperative transfusion were significantly associated with need for mechanical ventilator care, longer postoperative stays in the ICU and the hospital, and hospital mortality.
Most patients admitted to the ICU after major liver resection just received close monitoring. Even though patients underwent major liver resection, patients without receipt of intraoperative transfusion could be sent to the general ward. Duration of ICU/hospital stay, ventilator care and mortality significantly correlated with major liver resection and intraoperative transfusion. Major liver resection and receipt of intraoperative transfusions should be considered indicators for ICU admission.
PMCID: PMC3433552  PMID: 22977762
Hepatectomy; Major resection; Intensive care units; Intraoperative transfusion
5.  Synchronous double primary cancers associated with a choledochal cyst and anomalous pancreaticobiliary ductal union 
A 60-year-old female was admitted with epigastric pain lasting a month. Preoperative diagnosis was choledochal cyst with anomalous pancreaticobiliaryductal union (APBDU), C-P type. A papillary mass measuring 2.5 × 1.9 cm was found adjacent to the pancreaticocholedochal junction. Gallbladder (GB) cancer was also observed. Pyloric-preserving pancreaticoduodenectomy (PPPD) was performed. The patient received adjuvant chemotherapy/radiation therapy on the tumor bed. The gallbladder cancer showed serosal invasion, while the bile duct cancer extended into the pancreas. Although common bile duct (CBD) cancer lesion showed focally positive for p53 and the gallbladder cancer lesion showed negative for p53, the Ki-67 labeling index of the CBD cancer and GB cancer were about 10% and 30%, respectively. Nine months after curative resection, a stricture on the subhepatic colon developed due to adjuvant radiation therapy. Localized peritoneal seedings were incidentally found during a right hemicolectomy. The patient underwent chemotherapy and had no evidence of tumor recurrence for two years after PPPD.
PMCID: PMC3219855  PMID: 22111085
Choledochal cyst; Gallbladder neoplsms; Bile duct neoplasms; Synchronous multiple primary neoplasms
6.  The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats 
The Korean Journal of Hepatology  2011;17(2):139-147.
Ischemic preconditioning (IP) decreases severity of liver necrosis and has anti-apoptotic effects in previous studies using liver regeneration in normal rats. This study assessed the effect of IP on liver regeneration after hepatic resection in cirrhotic rats.
To induce liver cirrhosis, thioacetamide (300 mg/kg) was injected intraperitoneally into Sprague-Dawley rats twice per week for 16 weeks. Animals were divided into four groups: non-clamping (NC), total clamping (TC), IP, and intermittent clamping (IC). Ischemic injury was induced by clamping the left portal pedicle including the portal vein and hepatic artery. Liver enzymes alanine transaminase (ALT) and aspartate aminotransferase (AST) were measured to assess liver damage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining for apoptosis and proliferating cell nuclear antigen (PCNA) staining for cell replication were also performed.
Day-1 ALT and AST were highest in IP, however, levels in NC and IC were comparably low on days 1-7. There was no significant correlation of AST or ALT with experimental groups (P=0.615 and P=0.186). On TUNEL, numbers of apoptotic cells at 100× magnification (cells/field) were 31.8±24.2 in NC, 69.0±72.3 in TC, 80.2±63.1 in IP, and 21.2±20.8 in IC (P<0.05). When regeneration capacity was assessed by PCNA staining, PCNA-positive cells (cells/field) at 400× were 3.4±6.0 in NC, 16.9±69 in TC, 17.0±7.8 in IP and 7.4±7.6 in IC (P<0.05).
Although regeneration capacity in IP is higher than IC, the liver is vulnerable to ischemic damage in cirrhotic rats. Careful consideration is needed in applying IP in the clinical setting.
PMCID: PMC3304634  PMID: 21757985
Liver cirrhosis; Ischemic preconditioning; Liver regeneration; Hepatectomy; Apoptosis
7.  Solitary Extrahepatic Intraabdominal Metastasis from Hepatocellular Carcinoma after Liver Transplantation 
Yonsei Medical Journal  2010;52(1):199-203.
A liver transplantation is a treatment option in selected patients with hepatocellular carcinoma (HCC). Despite the adequate selection of candidates, recurrences of HCC may still develop. Solitary extrahepatic metastasis from HCC after a liver transplantation is rare. Here we report two cases of HCC demonstrated extrahepatic recurrence to the adrenal gland and spleen, respectively, within one year after a liver transplantation. Since the treatment of solitary extrahepatic metastasis from HCC after a liver transplantation is not standardized, surgical resection was performed. In the case of HCC adrenal metastasis, innumerable intrahepatic metastases were found two months after the adrenalectomy. And 16 months after adrenalectomy, the patient expired due to tumor progression and hepatic failure. In the case of HCC splenic metastasis, postoperative radiation therapy was performed. However, two recurrent HCC nodules were found 15 months after the splenectomy and received transarterial chemoembolization (TACE). And 29 month after the splenectomy, the patient also expired as same causes of former patient.
PMCID: PMC3017699  PMID: 21155056
Hepatocellular carcinoma; adrenal metastasis; splenic metastasis; liver transplantation
8.  The Efficacy of Hepatic Resection after Neoadjuvant Transarterial Chemoembolization (TACE) and Radiation Therapy in Hepatocellular Carcinoma Greater Than 5 cm in Size 
Journal of Korean Medical Science  2009;24(2):242-247.
In cases of large hepatocellular carcinoma (HCC), neoadjuvant treatment such as transarterial chemoembolization (TACE) and radiation therapy can be performed. The aim of this study was to evaluate the outcome of these treatments prior to hepatic resection. Between January 1994 and May 2007, 16 patients with HCC greater than 5 cm in size were treated with TACE and radiation therapy prior to hepatic resection. The clinicopathologic factors were reviewed retrospectively. Of the 16 patients, there were 14 men and two women, and the median age was 52.5 yr. TACE was performed three times in average, and the median radiation dosage was 45 Gy. The median diameter of tumor on specimen was 9.0 cm. The degree of tumor necrosis was more than 90% in 14 patients. The median survival time was 13.3 months. Five patients had survived more than 2 yr and there were two patients who had survived more than 5 yr. Although the prognosis of large HCC treated with neoadjuvant therapy is not satisfactory, some showed long-term survival loger than 5 yr. Further research will be required to examine the survival and disease control effect in a prospective randomized study.
PMCID: PMC2672123  PMID: 19399265
Carcinoma, Hepatocellular; TACE; Radiotherapy; Hepatic Resection
9.  Early Experiences of Robotic-assisted Laparoscopic Liver Resection 
Yonsei Medical Journal  2008;49(4):632-638.
The surgical robotic system is superior to traditional laparoscopy in regards to 3-dimensional images and better instrumentations. Robotic surgery for hepatic resection has not yet been extensively reported.
Patients and Methods
Between March and May 2007, we performed 3 robot-assisted left lateral sectionectomies of the liver. Case 1 had a hepatocellular carcinoma (HCC), case 2 had colon cancer with liver metastasis, and case 3 had intrahepatic duct stones.
All patients had successful operation and recovered without complications. Shorter length of hospital stays, earlier start of oral feeding and less amount of ascites were found. However, case 1 had recurrent HCC at 3 months after operation.
Robotic-assisted liver surgery is still a new field in its developing stage. In patients with small malignant tumors and benign liver diseases, robotic-assisted laparoscopic resection is feasible and safe. Through experience, the use of robotics is expected to increase in the treatment of benign diseases and malignant neoplsms. However, careful patient selection is important and long-term outcomes need to be evaluated.
PMCID: PMC2615291  PMID: 18729307
Hepatocellular carcinoma; robotic liver resection; minimally invasive surgery
10.  Comparison of CT and MRI for presurgical characterization of paraaortic lymph nodes in patients with pancreatico-biliary carcinoma 
AIM: To determine the accuracy of computed tomography (CT) and magnetic resonance (MR) for presurgical characterization of paraaortic lymph nodes in patients with pancreatico-biliary carcinoma.
METHODS: Two radiologists independently evaluated CT and MR imaging of 31 patients who had undergone lymphadenectomy (9 metastatic and 22 non-metastatic paraaortic nodes). Receiver operating characteristic (ROC) curve analysis was performed using a five point scale to compare CT with MRI. To re-define the morphologic features of metastatic nodes, we evaluated CT scans from 70 patients with 23 metastatic paraaortic nodes and 47 non-metastatic ones. The short axis diameter, ratio of the short to long axis, shape, and presence of necrosis were compared between metastatic and non-metastatic nodes by independent samples t-test and Fisher’s exact test. P < 0.05 was considered statistically significant.
RESULTS: The mean area under the ROC curve for CT (0.732 and 0.646, respectively) was slightly higher than that for MRI (0.725 and 0.598, respectively) without statistical significance (P = 0.940 and 0.716, respectively). The short axis diameter of the metastatic lymph nodes (mean = 9.2 mm) was significantly larger than that of non-metastatic ones (mean = 5.17 mm, P < 0.05). Metastatic nodes had more irregular margins (44.4%) and central necrosis (22.2%) than non-metastatic ones (9% and 0%, respectively), with statistical significance (P < 0.05).
CONCLUSION: The accuracy of CT scan for the characterization of paraaortic nodes is not different from that of MRI. A short axis-diameter (> 5.3 mm), irregular margin, and presence of central necrosis are the suggestive morphologic features of metastatic paraaortic nodes.
PMCID: PMC2703846  PMID: 18407595
Paraaortic lymph node; Pancreatico-biliary carcinoma; Computed tomography; Magnetic resonance imaging
11.  The Actual Five-year Survival Rate of Hepatocellular Carcinoma Patients after Curative Resection 
Yonsei Medical Journal  2006;47(1):105-112.
The five-year survival rate of patients after curative resection of hepatocellular carcinoma (HCC) has been reported to be 30 to 50%, however the actual survival rate may be different. We analyzed the actual 5-year survival rate and prognostic factors after curative resection of HCC. Retrospective analysis was performed on 63 HCC patients who underwent curative resection from 1998 to 1999. A total of 63 cases were reviewed, consisting of 53 men and 10 women, with a median age of 49 years. These cases included all four pathologic T stages (pT stage) and had the following representation: stage 1 (1 case), stage 2 (17 cases), stage 3 (38 cases), and stage 4 (7 cases). In our study, the actual 5-year survival rate was 57.0% and the median survival time was 60 months. In addition, the patients in our study had an actual 5-year disease-free survival rate of 50.2% and a median disease-free survival time of 46 months. Thirty-one patients had recurrences, with a majority occurring within one year (65%). These patients with early recurrences had a poor actual 5-year survival rate of 5%. A univariate analysis showed that the prognostic factors influencing survival rate were the presence of satellite nodules, increased pT stage, HCC recurrence, and the time to recurrence (within one year). Interestingly, microvascular invasion made a difference in survival rate but was not statistically significant (p = 0.08). Furthermore, factors influencing the disease free survival rate include the presence of satellite nodules, microvascular invasion, and pT stage. Multivariate analysis identified pT stage as the only statistically related factor in determining the disease-free survival rate. The most important prognostic factor of HCC is recurrence. Moreover, the major risk factor for recurrence is an advanced pT stage. Therefore, performing prospective studies of postoperative adjuvant therapy is necessary to prevent recurrences after hepatic resection. Furthermore, active preventative treatment and early diagnosis of recurrences should be of the highest priority in the care of high-risk patient groups that have an advanced pT stage.
PMCID: PMC2687566  PMID: 16502491
Hepatocellular carcinoma; hepatic resection; five-year survival rate
12.  Concurrent Chemoradiotherapy Shows Long-Term Survival after Conversion from Locally Advanced to Resectable Hepatocellular Carcinoma 
Yonsei Medical Journal  2014;55(6):1489-1497.
For locally unresectable hepatocellular carcinoma (HCC) patients, concurrent chemoradiotherapy (CCRT) has been applied as a loco-regional treatment. After shrinkage of tumors in selected patients, surgical resection is performed. The aim of this study was to evaluate prognostic factors and long-term survivors in such patients.
Materials and Methods
From January 2000 to January 2009, 264 patients with HCC were treated with CCRT (45 Gy with fractional dose of 1.8 Gy), and intra-arterial chemotherapy was administered during radiotherapy. Eighteen of these patients (6.8%) underwent hepatic resection after showing a response to CCRT. Cases were considered resectable when tumor-free margins and sufficient remnant volumes were obtained without extrahepatic metastasis. Prior to operation, there were six patients with complete remission, 11 with partial remission, and six with stable disease according to modified Response Evaluation Criteria in Solid Tumors.
In pathologic review, four patients (22.2%) showed total necrosis and seven patients (38.9%) showed 70-99% necrosis. A high level of necrosis (≥80%) was correlated with low risk for extrahepatic metastasis and long-term survival. In univariate analyses, vessel invasion and capsular infiltration were significantly correlated with disease free survival (DFS) (p=0.017 and 0.013, respectively), and vessel invasion was significantly correlated with overall survival (OS) (p=0.013). In multivariate analyses, capsule infiltration was a significant factor for DFS (p=0.016) and vessel invasion was significant for OS (p=0.015).
CCRT showed favorable responses and locally advanced HCC converted into resectable tumor after CCRT in selected patients. Long-term survivors showed the pathological features of near total necrosis, as well as negative capsule and vessel invasion.
PMCID: PMC4205687  PMID: 25323884
Hepatocellular carcinoma; concurrent chemoradiotherapy; intra-arterial chemotherapy; hepatic resection
13.  The Effect of Statin on Epithelial-Mesenchymal Transition in Peritoneal Mesothelial Cells 
PLoS ONE  2014;9(10):e109628.
Statins have recently been highlighted for their pleiotropic actions distinct from cholesterol-lowering effects. Despite this interest, it is currently unknown whether statin therapy inhibits peritoneal dialysis (PD)-related epithelial-mesenchymal transition (EMT).
In vitro, human peritoneal mesothelial cells (HPMCs) were exposed to 5.6 mM glucose (NG) or 100 mM glucose (HG) with or without simvastatin (1 µM). In vivo, PD catheters were inserted into 32 Sprague-Dawley rats, and saline (C, n = 16) or 4.25% peritoneal dialysis fluid (PDF) (PD, n = 16) was infused for 4 weeks. Eight rats from each group were treated with 5 mg/kg/day of simvastatin intraperitoneally. Changes in the protein expression of EMT markers such as E-cadherin, α-SMA, Snail, and fibronectin in HPMCs and the peritoneum were evaluated by Western blot analysis and immunofluorescence or immunohistochemical staining. We also explored whether activation of the mevalonate pathway and its downstream small GTPases were involved in dialysis-related peritoneal EMT and could be inhibited by statin treatment.
Compared to NG cells, E-cadherin expression was significantly decreased, while α-SMA, Snail, and fibronectin expression were significantly increased in HPMCs exposed to HG, and these changes were abrogated by simvastatin (p<0.05). In addition, the cobblestone-like appearance of normal HPMCs was converted into a fibroblast-like morphology after HG treatment, which was reversed by simvastatin. These EMT-like changes were also observed in HPMCs treated with geranyl-geranyl pyrophosphate (5 µM). HG significantly increased the protein expression of RhoA and Rac1 in the membrane fractions, and these increases were ameliorated by simvastatin (p<0.05). In PD rats, E-cadherin in the peritoneum was significantly decreased, whereas α-SMA, Snail, and fibronectin expression were significantly increased (p<0.05) compared to C rats. The thickness of the mesothelial layer in the peritoneum were also significantly greater in PD rats than in C rats (p<0.05). These changes of the peritoneum in PD rats were significantly attenuated by simvastatin.
This study demonstrated that PD-related EMT was mediated via the mevalonate pathway, and statin treatment inhibited the EMT changes in HG-treated HPMCs and PDF-stimulated PD rats. These findings suggest that statins may be a promising therapeutic strategy for preservation of peritoneal membrane integrity in long-term PD patients.
PMCID: PMC4183618  PMID: 25275561
14.  β-Catenin Activated Hepatocellular Adenoma: A Report of Three Cases in Korea 
Gut and Liver  2014;8(4):452-458.
Hepatocellular adenoma (HCA) is an uncommon benign hepatic tumor, and the use of oral contraceptives is known to contribute to the development of HCA. Recently, a genotype and phenotype classification system for HCA was suggested, and malignant transformation to hepatocellular carcinoma (HCC) was shown to be strongly associated with activating mutations in β-catenin. Here, we report three cases of HCA in Korean patients: 7-cm, inflammatory and β-catenin-activated HCA with HCC transformation in a 46-year-old man; 13-cm, β-catenin-activated HCA with cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and β-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear expression of β-catenin and diffuse cytoplasmic expression of glutamine synthetase upon immunohistochemical staining. All tumors were completely resected, and the patients were followed for 3 to 6 years with no evidence of local recurrence or metastasis.
PMCID: PMC4113041  PMID: 25071913
Adenoma; liver cell; Beta catenin; Carcinoma; hepatocellular; Glutamine synthetase
15.  Lesson from 610 liver resections of hepatocellular carcinoma in a single center over 10 years 
Recent advances in surgical techniques and perioperative management have led to improved surgical outcomes, especially perioperative outcomes. The aim of this study was to review our experience with hepatic resection for hepatocellular carcinoma (HCC) over a ten-year period to determine how to improve long-term surgical outcomes.
From January 1996 to December 2007, 610 patients underwent curative resection for HCC at Yonsei University Health System, Seoul, Korea. Prognostic factors for disease-free and overall survival were identified, and surgical outcomes were compared between two time periods: before 2003 and after 2003.
The 1-, 3-, and 5-year overall survival rates were 90.1%, 74.9% and 64.4%, respectively. The patients after 2003 tended to have improved overall survival. The survival rate after recurrence in patients with tumors > 3 cm was significantly greater after 2003. (P = 0.044).
The improved survival rates after 2003 may be explained by better selection of surgical candidates, a reduced perioperative transfusion rate due to improved surgical techniques, and active multimodal treatment for recurrent HCC.
PMCID: PMC4101710  PMID: 24961934
Hepatocellular carcinoma; Hepatectomy; Prognosis; Survival
16.  Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer 
Radiation Oncology Journal  2014;32(1):7-13.
To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival.
Materials and Methods
Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%).
The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively).
In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.
PMCID: PMC3977131  PMID: 24724046
Bile duct neoplasms; Adjuvant radiotherapy; Radiotherapy dosage
17.  The optimal follow-up period in patients with above 5-year disease-free survival after curative liver resection for hepatocellular carcinoma 
Although many patients with hepatocellular carcinoma experience recurrence within 2 years after hepatectomy, some patients with T1 and T2 hepatocellular carcinoma show recurrence-free survival for more than 5 years after surgery. This study was designed to analyze the optimal follow-up period on patients with T1 and T2 hepatocellular carcinoma (HCC) showing recurrence-free survival 5 years after surgery.
One hundred seventy patients underwent hepatectomy from January 1995 to December 1999. Numbers of patients with T1 and T2 HCC were 76 and 73, respectively. The recurrence patterns of patients experiencing recurrence more than 5 years after liver resection were analyzed in aspect of clinicopathological features and follow-up period.
Thirteen patients experienced recurrence more than 5 years after surgery. Only age was found as a significant factor for recurrence. Eight patients were checked regularly with 6-month intervals and the others were checked with 12-month or more intervals. The size of the recurrent tumors in the 6-month interval group had a median of 1.1 cm (range, 1 to 4.2 cm) and the size of the recurrent tumors in the 12-month or more interval group had a median of 3 cm (range, 1.6 to 4 cm). The tumor size was significantly smaller in the 6-month interval group.
Though the patients with early stage HCC showed high overall survival, some patients experienced a late recurrence of more than 5 years after surgery. Patients less than 60 years old with early stage HCC should be checked regularly with 6-month intervals even over 5 years after liver resection.
PMCID: PMC3868678  PMID: 24368984
Hepatocellular carcinoma; Recurrence; Surveillance
18.  Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B 
The incidence of multidrug-resistant (MDR) chronic hepatitis B (CHB) during sequential lamivudine (LAM) and adefovir dipivoxil (ADV) treatment is increasing. We investigated the antiviral efficacies of various rescue regimens in patients who failed sequential LAM-ADV treatment.
Forty-eight patients (83.3% of whom were HBeAg-positive) who failed sequential LAM-ADV treatment were treated with one of the following regimens: entecavir (ETV) (1 mg) monotherapy (n=16), LAM+ADV combination therapy (n=20), or ETV (1 mg)+ADV combination therapy (n=12). All patients had confirmed genotypic resistance to both LAM and ADV and were evaluated every 12 weeks.
The baseline characteristics and treatment duration did not differ significantly among the study groups. During the treatment period (median duration: 100 weeks), the decline of serum HBV DNA from baseline tended to be greatest in the ETV+ADV group at all-time points (week 48: -2.55 log10 IU/mL, week 96: -4.27 log10 IU/mL), but the difference was not statistically significant. The ETV+ADV group also tended to have higher virologic response rates at 96 weeks compared to the ETV monotherapy or LAM+ADV groups (40.0% vs. 20.0% or 20.0%, P=0.656), and less virologic breakthrough was observed compared to the ETV monotherapy or LAM+ADV groups (8.3% vs. 37.5% or 30.0%; P=0.219), but again, the differences were not statistically significant. HBeAg loss occurred in one patient in the ETV+ADV group, in two in the ETV monotherapy group, and in none of the LAM+ADV group. The safety profiles were similar in each arm.
There was a nonsignificant tendency toward better antiviral efficacy with ETV+ADV combination therapy compared to LAM+ADV combination therapy and ETV monotherapy for MDR CHB in Korea, where tenofovir is not yet available.
PMCID: PMC3622853  PMID: 23593607
Hepatitis B virus; Multidrug resistance; Hepatitis B; Entecavir; Adefovir
19.  Current Status of Laparoscopic Liver Resection in Korea 
Journal of Korean Medical Science  2012;27(7):767-771.
Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
PMCID: PMC3390725  PMID: 22787372
Laparoscopic Liver Resection; Laparoscopy; Anatomical Liver Resection; Liver Diseases; HCC
20.  Clinicopathological Characteristics in Combined Hepatocellular-Cholangiocarcinoma: A Single Center Study in Korea 
Yonsei Medical Journal  2011;52(5):753-760.
Combined hepatocellular-cholangiocarcinoma (CHCC) is an uncommon form of cancer, and its clinicopathological features have rarely been reported in detail. This study was undertaken to evaluate the clinicopathological characteristics and prognostic factors of CHCC.
Materials and Methods
The clinicopathological features of patients diagnosed with CHCC at Severance Hospital between January 1996 and December 2007 were retrospectively studied by comparing them with the features of patients with hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) who had undergone a hepatic resection during the same period.
Forty-three patients diagnosed with CHCC were included in this study (M : F=35 : 8, median age, 55 years). According to the parameters of the American Joint Committee on Cancer staging, there were 6 (14.0%), 9 (20.9%), 25 (58.1%), and 3 (7.0%) patients with stages I, II, III, and IV cancer, respectively. Thirty-two of the 43 patients underwent resection with curative intent. After resection, 27 patients (84.4%) had tumor recurrence during the follow-up period of 18 months (range: 6-106 months), and the median time to recurrence was 13 months. Overall median survival periods after hepatic resection of CHCC, HCC and CC were 34, 103 and 38.9 months, respectively (p<0.001). The median overall survival for all patients with CHCC was 21 months, and the 5-year survival rate was 18.1%. The presence of portal vein thrombosis and distant metastasis were independent prognostic factors of poor survival.
Even after curative hepatic resection, the presence of a cholangiocellular component appeared to be a poor prognostic indicator in patients with primary liver cancer.
PMCID: PMC3159948  PMID: 21786439
Combined hepatocellular and cholangiocarcinoma; hepatocellular carcinoma; cholangiocarcinoma
21.  Preoperative Radiologic and Postoperative Pathologic Risk Factors for Early Intra-Hepatic Recurrence in Hepatocellular Carcinoma Patients Who Underwent Curative Resection 
Yonsei Medical Journal  2009;50(6):789-795.
The risk of hepatocellular carcinoma (HCC) recurrence must be considered ahead of surgery. This study was undertaken to identify pre-operative risk factors for early intrahepatic recurrence of HCC after curative resection in a large-scale.
Materials and Methods
We retrospectively reviewed the preoperative three-phase multi-detector CT (MDCT) and laboratory data for 240 HCC patients who underwent curative resection; tumor size, number, gross shape, capsule integrity, distinctiveness of tumor margin, portal vein thrombosis (PVT), alpha-fetoprotein level (AFP), and protein induced by vitamin K absence-II (PIVKA-II) levels were assessed. Surgical pathology was reviewed; tumor differentiation, capsule, necrosis, and micro-vessel invasion were recorded.
HCC recurred in 61 patients within six months (early recurrence group), but not in 179 patients (control group). In univariate analysis, large tumor size (p = 0.018), shape (p = 0.028), poor capsule integrity (p = 0.046), elevated AFP (p = 0.015), and PIVKA-II (p = 0.008) were significant preoperative risk factors. Among the pathologic features, PVT (p = 0.023), Glisson's capsule penetration (p = 0.033), microvascular invasion (p < 0.001), and poor differentiation (p = 0.001) showed statistical significance. In multivariate analysis, only the histopathologic parameters of microvascular invasion and poor differentiation achieved statistical significance.
Preoperative CT and laboratory parameters showed limited value, while the presence of microscopic vascular tumor invasion and poorly differentiated HCC correlated with higher risk of early recurrence after curative resection.
PMCID: PMC2796405  PMID: 20046419
Hepatocellular carcinoma; preoperative CT; postoperative pathologic findings; early recurrence; curative resection
22.  Prediction of postoperative hepatic insufficiency by liver stiffness measurement (FibroScan®) before curative resection of hepatocellular carcinoma: a pilot study 
Hepatology International  2008;2(4):471-477.
Liver stiffness measurement (LSM) using transient elastography (FibroScan®) reflects the degree of hepatic fibrosis. This prospective study investigated how well LSM predicts the development of hepatic insufficiency after curative liver resection surgery for hepatocellular carcinoma.
The study enrolled 72 consecutive patients who underwent a preoperative LSM to assess the degree of liver fibrosis followed by curative liver resection surgery for hepatocellular carcinoma between July 2006 and December 2007. The primary end point was the development of hepatic insufficiency.
The mean age of the patients was 54.9 years. Twenty patients (27.7%) had chronic hepatitis and 52 (72.3%) had cirrhosis (44 and 8 patients showed Child-Pugh class A and B, respectively). The mean LSM was 17.1 kPa. Twelve patients (16.6%) had segmentectomy only, 16 patients (22.2%) had bisegmentectomy, and 44 patients (61.2%) had lobectomy. Nine patients (12.5%) had stage I tumor, 56 (77.7%) had stage II, and 7 (9.8%) had stage III. Univariate and subsequent multivariate analyses revealed that preoperative LSM was the only independent risk factor for predicting the development of postoperative hepatic insufficiency (cutoff, 25.6 kPa; P = 0.001; relative risk, 19.14; 95% confidence interval, 2.71–135.36).
LSM is potentially useful to predict the development of postoperative hepatic insufficiency in patients with hepatocellular carcinoma undergoing curative liver resection surgery.
PMCID: PMC2716908  PMID: 19669322
Liver stiffness measurement; Indocyanine green; Hepatic insufficiency; Hepatectomy
23.  Laparoscopic Enucleation of a Nonfunctioning Neuroendocrine Tumor of the Pancreas 
Yonsei Medical Journal  2008;49(5):864-868.
Laparoscopic approaches are increasingly used in pancreatic surgery. In the treatment of neuroendocrine tumors (NETs) of the pancreas, enucleation is one of the recommended surgery. Although many clinical experiences have reported the safety and efficacy of laparoscopic enucleation of functioning NETs, such as insulinomas, few reports have explored such treatment for non-functioning NETs. Here, we present a case of 70-year old female patient who underwent successful laparoscopic enucleation of a nonfunctioning NET located in the body of the pancreas.
PMCID: PMC2615360  PMID: 18972611
Laparoscopy; enucleation; neuroendocrine tumor; pancreas
24.  Gallbladder carcinoma associated with anomalous pancreaticobiliary duct junction 
Anomalous pancreaticobiliary ductal junction (APBDJ) is believed to be one of the risk factors for gallbladder carcinoma. The present study aims to delineate the gallbladder carcinoma characteristics associated with APBDJ.
Patients with gallbladder carcinoma associated with APBDJ between August 1992 and February 2005 were retrospectively reviewed. Two types of APBDJ classifications were considered: right-angle type (C-P) and acute-angle type (P-C).
Ten of 218 patients (4.6%) with gallbladder carcinomas were associated with APBDJ. All patients were female with a mean age of 55.4 years (range 41 to 72 years). Gallstones were absent in nine patients. Seven patients (70%) had the P-C type and three patients (30%) had the C-P type. Survival differences between the P-C type and the C-P type of gallbladder carcinomas were noted (P=0.0269). Patients with incidentally detected gallbladder carcinoma had superior survival (P=0.0316).
Gallbladder carcinomas associated with APBDJ were significantly related to relatively young female patients without gallbladder stones. Survival outcomes in these patients were not different from those of gallbladder carcinoma without APBDJ. In particular, the P-C type of APBDJ seemed to be more associated with relatively advanced gallbladder carcinomas, and patients with incidentally detected gallbladder carcinomas with APBDJ had superior survival.
PMCID: PMC2658122  PMID: 17571173
Anomalous pancreaticobiliary duct junction; Gallbladder carcinoma
25.  Hepatic Splenosis Preoperatively Diagnosed as Hepatocellular Carcinoma in a Patient with Chronic Hepatitis B: A Case Report 
Journal of Korean Medical Science  2008;23(2):336-341.
We report on a case of hepatic splenosis. A 32-yr-old man underwent a splenectomy due to trauma at the age of 6. He had been diagnosed as being a chronic hepatitis B-virus carrier 16 yr prior to the surgery. The dynamic computer tomography (CT) performed due to elevated serum alpha-fetoprotein (128 ng/mL) demonstrated two hepatic nodules, which were located near the liver capsule. A nodule in Segment IVa had a slight enhancement during both the arterial and portal phases, and another nodule in Segment VI showed a slight enhancement only in the portal phases. Dynamic magnetic resonance imaging (MRI) of the mass in Segment VI showed enhanced development in the arterial phases and slight hyperintensivity to the liver parenchyma in the portal phases. These imaging findings suggested a hypervascular tumor in the liver, which could be either focal nodular hyperplasia, adenoma, or hepatocellular carcinoma (HCC). Even though these lesions were diagnosed as HCC, some of the findings were not compatible with typical HCC. On dynamic CT and MRI, all lesions showed a slight arterial enhancement and did not show early venous washout. All lesions were located near the liver capsule. These findings, along with a history of splenectomy, suggested a diagnosis of hepatic splenosis.
PMCID: PMC2526445  PMID: 18437023
Hepatic Splenosis; Carcinoma, Hepatocellular

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