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1.  Efficacy of Oxidized Regenerated Cellulose, SurgiGuard®, in Porcine Surgery 
Yonsei Medical Journal  2016;58(1):195-205.
Adequate hemostasis is important for postoperative outcomes of abdominal surgery. This study evaluated the hemostatic effects and accompanying histopathological changes of a novel oxidized regenerated cellulose, SurgiGuard®, during abdominal surgery.
Materials and Methods
Ten pigs underwent wedge resection of the spleen (1×1 cm) and liver (1.5×1.5 cm). The resected surface was covered with Surgicel® fabric or fibril type (Group A) or SurgiGuard® fabric or fibril type (Group B). Surgicel® and SurgiGuard® were randomized for attachment to the resected surface by fabric type (n=5) or fibril type (n=5). Blood loss was measured 5, 7, and 9 min after resection. Pigs were necropsied 6 weeks postoperatively to evaluate gross and histopathological changes.
There was no significant difference in total blood loss between groups [spleen fabric: Group A vs. Group B, 4.38 g (2.74–6.43) vs. 3.41 g (2.46–4.65), p=0.436; spleen fibril: Group A vs. Group B, 3.44 g (2.82–6.07) vs. 3.60 g (2.03–6.09), p=0.971; liver fabric: Group A vs. Group B, 4.51 g (2.67–10.61) vs. 6.93 g (3.09–9.95), p=0.796; liver fibril: Group A vs. Group B, 3.32 g (2.50–8.78) vs. 3.70 g (2.32–5.84), p=0.971]. Histopathological analysis revealed no significant difference in toxicities related to Surgicel® or SurgiGuard® [inflammation, fibrosis, foreign bodies, and hemorrhage (spleen: p=0.333, 0.127, 0.751, and 1.000; liver: p=0.155, 0.751, 1.000, and 1.000, respectively)].
SurgiGuard® is as effective and non-toxic as Surgicel® in achieving hemostasis after porcine abdominal surgery.
PMCID: PMC5122638  PMID: 27873514
Animal model; blood loss; hemostatics; histopathology; oxidized regenerated cellulose
2.  Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer 
Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal.
Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed.
Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively).
Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases.
PMCID: PMC5018949  PMID: 27621747
Colorectal cancer; Liver cancer; Lung cancer; Metastasis
3.  Efficacy evaluation of SurgiGuard® in partially hepatectomized pigs 
This study evaluated the hemostatic effects of a novel oxidized regenerated cellulose, SurgiGuard®, during liver surgery, using a reproducible and clinically relevant animal model.
Fifteen mini-pigs underwent left partial hepatectomy. They were randomized to treatment of the resected surface with SurgiGuard® (Group C [test], n=5), Surgicel® (Group B [reference], n=5), or nothing (Group A [control], n=5). Blood loss was measured 5, 7 and 9 min after resection. Time to hemostasis was recorded. Mini-pigs were necropsied 4 or 6 weeks postoperatively to evaluate toxicity changes and material dissolution.
The median resected liver weight was 2.13 g (2.02-2.20) in control group, 2.04 g (2.01-2.13) in reference group, and 2.01 g (1.99-2.12) in test group (p=0.024). Median total blood loss was 57.18 g (52.02-59.54) in control group, 32.52 g (27.66-35.10) in reference group, and 35.52 g (25.70-38.71) in test group (p=0.008). Blood loss at 0-5 minutes and 7-9 minutes was significantly different between groups (p=0.009 and p=0.006, respectively). At necropsy, no hematomas, granulomas, or adhesions were noted in any group. Histopathological analysis revealed no changes suggesting toxicity related to SurgiGuard®.
SurgiGuard® is as effective as Surgicel® in achieving hemostasis after porcine partial liver resection.
PMCID: PMC5018953  PMID: 27621746
Animal model; Hemostatic; Hepatectomy; Histopathology; Oxidized regenerated cellulose
4.  Management of portal hypertension derived from uncommon causes 
Portal hypertension can arise from any condition interfering with normal blood flow at any level within the portal system. Herein, we presented two uncommon cases of the portal hypertension and its treatment with brief literature review. A 71-year-old man who underwent right hemihepatectomy revealed a tumor recurrence adjacent to the inferior vena cava (IVC). After radiofrequency ablation (RFA) with lymph node dissection, he was referred for abdominal distension. The abdomen computed tomography scan showed severe ascites with a narrowing middle hepatic vein (MHV) and IVC around the RFA site. After insertion of two stents at the IVC and MHV, the ascites disappeared. Another 73-year-old man underwent right trisectionectomy of liver and segmental resection of the portal vein (PV). After operation, he underwent conservative management due to continuous abdominal ascites. The abdomen computed tomography scan showed severe ascites with obliteration of the left PV. After insertion of stent, the ascites disappeared. A decrease of the pressure gradient between the PV and IVC is one of the important treatment strategies for portal hypertension. Vascular stent is useful in the reduction of pressure gradient and thus, can be a treatment option for portal hypertension.
PMCID: PMC4874045  PMID: 27212996
Portal hypertension; Radiofrequency ablation; Stenosis; Stents
5.  Incidental detection of pancreatic hemangioma mimicking a metastatic tumor of renal cell carcinoma 
Adult pancreatic hemangioma is a rare disease. We presented a case of a woman with pancreatic tail mass mimicking a distant metastasis from the kidney. A 68-year-old woman was found with a left kidney mass on medical checkup. Computed tomography scan showed a 4.3 cm-sized mass in the left kidney, suggesting renal cell carcinoma (RCC), and a strongly enhancing tiny nodule in the pancreatic tail. We could not rule the possibility of RCC metastasis, hence, surgical resection of the pancreatic mass simultaneously with radical nephrectomy for RCC was conducted. Gross pathologic examination revealed hemangioma. Immunohistochemistry revealed that the tumor was positive for CD34, CD31 and factor VIII-related antigen. There were no significant postoperative events, and the patient was discharged on postoperative day 7 without any complications. Treatment strategies for pancreatic hemangioma have not been established. To our knowledge, this was the first case report of asymptomatic pancreatic hemangioma. In previous literature, treatment differed on a case-by-case basis, ranging from observation to surgical resection. The most important factor in deciding whether to perform surgery is possibly risk-benefit effectiveness; however, tumor location, patient symptoms, and other factors are also important.
PMCID: PMC4874050  PMID: 27212999
Pancreas; Hemangioma; Adult hemangioma; Incidental discovery; CD34
6.  Influencing factors on postoperative hospital stay after laparoscopic cholecystectomy 
Laparoscopic cholecystectomy can reduce postoperative pain and recovery time. However, some patients experience prolonged postoperative hospital stay. We aimed to identify factors influencing the postoperative hospital stay after laparoscopic cholecystectomy.
Patients (n=336) undergoing laparoscopic cholecystectomy for gallbladder pathology at 8 hospitals were enrolled and divided into 2 groups: 2 or less and more than 2 days postoperative stay. Perioperative factors and patient factors were retrospectively analyzed.
The patient population median age was 52 years, and consisted of 32 emergency and 304 elective operations. A univariate analysis of perioperative factors revealed significant differences in operation time (p<0.001), perioperative transfusion (p=0.006), emergency operation (p<0.001), acute inflammation (p<0.001), and surgical site infection (p=0.041). A univariate analysis of patient factors revealed significant differences in age (p<0.001), gender (p=0.036), diabetes mellitus (p=0.011), preoperative albumin level (p=0.024), smoking (p=0.010), and American Society of Anesthesiologists score (p=0.003). In a multivariate analysis, operation time (p<0.001), emergency operation (p<0.001), age (p=0.014), and smoking (p=0.022) were identified as independent factors influencing length of postoperative hospital stay.
Operation time, emergency operation, patient age, and smoking influenced the postoperative hospital stay and should be the focus of efforts to reduce hospital stay after laparoscopic cholecystectomy.
PMCID: PMC4767266  PMID: 26925145
Laparoscopic cholecystectomy; Hospital stay; Postoperative complications
7.  The role of prophylactic antibiotics on surgical site infection in elective laparoscopic cholecystectomy 
Although laparoscopic cholecystectomy is a common and widely accepted technique, the use of prophylactic antibiotics in elective laparoscopic cholecystectomy still remains controversial. The aim of this study is to determine whether prophylactic antibiotics could prevent surgical site infection after elective laparoscopic cholecystectomy and to identify any risk factors for surgical site infection.
This study included 471 patients undergoing laparoscopic cholecystectomy between January 2009 and May 2012. Period 1 patients (279) received second generation cephalosporin 1 g intravenously after induction of anesthesia, and Period 2 patients (192) were not given prophylactic antibiotics. The characteristics and surgical site infections of the patients were compared and analyzed.
The overall rate of surgical site infection was 1.69% for the total of 471 patients. The incidence of surgical site infection was similar for the two Periods: 5 of 279 patients (1.79%) in Period 1, 3 of 192 patients (1.56%) in Period 2 (p=0.973). All of the patients with surgical site infections were well treated under conservative treatments without any sequelae. The preoperative albumin level (p=0.023) contributed to surgical site infection.
Prophylactic antibiotics are not necessary for elective laparoscopic cholecystectomy but patients in poor nutritional state with low albumin level should consider prophylactic antibiotics.
PMCID: PMC4683922  PMID: 26693239
Laparoscopic cholecystectomy; Antibiotic prophylaxis; Surgical wound infection; Nutrition assessment
8.  Toward angiogenesis of implanted bio-artificial liver using scaffolds with type I collagen and adipose tissue-derived stem cells 
Stem cell therapies for liver disease are being studied by many researchers worldwide, but scientific evidence to demonstrate the endocrinologic effects of implanted cells is insufficient, and it is unknown whether implanted cells can function as liver cells. Achieving angiogenesis, arguably the most important characteristic of the liver, is known to be quite difficult, and no practical attempts have been made to achieve this outcome. We carried out this study to observe the possibility of angiogenesis of implanted bio-artificial liver using scaffolds.
This study used adipose tissue-derived stem cells that were collected from adult patients with liver diseases with conditions similar to the liver parenchyma. Specifically, microfilaments were used to create an artificial membrane and maintain the structure of an artificial organ. After scratching the stomach surface of severe combined immunocompromised (SCID) mice (n=4), artificial scaffolds with adipose tissue-derived stem cells and type I collagen were implanted. Expression levels of angiogenesis markers including vascular endothelial growth factor (VEGF), CD34, and CD105 were immunohistochemically assessed after 30 days.
Grossly, the artificial scaffolds showed adhesion to the stomach and surrounding organs; however, there was no evidence of angiogenesis within the scaffolds; and VEGF, CD34, and CD105 expressions were not detected after 30 days.
Although implantation of cells into artificial scaffolds did not facilitate angiogenesis, the artificial scaffolds made with type I collagen helped maintain implanted cells, and surrounding tissue reactions were rare. Our findings indicate that type I collagen artificial scaffolds can be considered as a possible implantable biomaterial.
PMCID: PMC4494077  PMID: 26155277
Tissue scaffolds; Liver; Artificial; Neovascularization; Physiologic; Biocompatible materials
9.  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
10.  Pneumomediastinum after Facial Bone Contouring Surgery 
Archives of Plastic Surgery  2014;41(4):443-445.
PMCID: PMC4113715  PMID: 25075378
11.  Duodenum-preserving pancreatic head resection in benign and low-grade malignant pancreatic tumors 
With development of imaging techniques, pancreatic tumors are being diagnosed more frequently. Applying the standard surgical procedures for pancreatic head tumors, such as pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy may seem too extensive for benign or low-grade malignant pancreas head tumors. Duodenum-preserving pancreatic head resection (DPPHR) has been safely performed in patients with chronic pancreatitis. Recently, DPPHR has been used as a limited surgical procedure to remove benign or low-grade malignant pancreatic head lesions. This study is aimed to evaluate the results of DPPHR in benign or low-grade malignant tumors.
Between 2004 and 2012, six patients underwent DPPHR due to benign or low-grade malignant pancreas tumor. We performed this retrospective analysis based on the medical records.
Five of six patients were diagnosed as intraductal papillary mucinous neoplasms. Remaining one patient was diagnosed as solid pseudopapillary neoplasm. The median age of patients was 60.3 (27-75) years, and the median follow-up period was 24 months. The operation time, blood loss and length of stay were 442.5 minutes, 680 ml and 19.2 days, respectively. There was no mortality. Five patients experienced complications including 1 delayed gastric empting, 2 bile duct strictures, 1 pancreatic fistula and 1 duodenal stricture. No recurrence or metastasis was found during follow-up.
In benign and low-grade malignant lesions of pancreatic head, DPPHR could be alternative to traditional surgery. For applying DPPHR in pancreas tumor, a thorough preoperative examination and utilization of frozen section for sufficient resection margin are required.
PMCID: PMC4304526  PMID: 26155226
Pancreatectomy; Duodenum; Organ preservation; Duodenum-preserving pancreatic head resection
12.  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
13.  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
14.  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
15.  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
16.  Ideal Experimental Rat Models for Liver Diseases 
There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.
PMCID: PMC4582547  PMID: 26421020
Liver disease; Animal model; Rat
17.  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
18.  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
19.  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
20.  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
21.  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
22.  Impaired Lymphocytes Development and Xenotransplantation of Gastrointestinal Tumor Cells in Prkdc-Null SCID Zebrafish Model1 
Neoplasia (New York, N.Y.)  2016;18(8):468-479.
Severe combined immunodeficiency (SCID) mice have widely been used as hosts for human tumor cell xenograft study. This animal model, however, is labor intensive. As zebrafish is largely emerging as a promising model system for studying human diseases including cancer, developing efficient immunocompromised strains for tumor xenograft study are also demanded in zebrafish. Here, we have created the Prkdc-null SCID zebrafish model which provides the stable immune-deficient background required for xenotransplantation of tumor cell. In this study, the two transcription activator-like effector nucleases that specifically target the exon3 of the zebrafish Prkdc gene were used to induce a frame shift mutation, causing a complete knockout of the gene function. The SCID zebrafish showed susceptibility to spontaneous infection, a well-known phenotype found in the SCID mutation. Further characterization revealed that the SCID zebrafish contained no functional T and B lymphocytes which reflected the phenotypes identified in the mice SCID model. Intraperitoneal injection of human cancer cells into the adult SCID zebrafish clearly showed tumor cell growth forming into a solid mass. Our present data show the suitability of using the SCID zebrafish strain for xenotransplantation experiments, and in vivo monitoring of the tumor cell growth in the zebrafish demonstrates use of the animal model as a new platform of tumor xenograft study.
PMCID: PMC5018095  PMID: 27566103
23.  Prognostic implications of PD-L1 expression in patients with soft tissue sarcoma 
BMC Cancer  2016;16:434.
The PD-1/PD-L1 axis plays a paramount role in the immune escape of tumor cells by negative regulation of T-cell functions. The aim of the present study was to characterize the PD-L1 expression pattern and its clinical implication in soft-tissue sarcomas (STS).
We analyzed PD-L1 expression in 82 STS patients with 5 subtypes: rhabdomyosarcoma, synovial sarcoma, Ewing sarcoma, epithelioid sarcoma, and mesenchymal chondrosarcoma.
The median age at diagnosis was 26 (range: 1–78) and the male to female ratio was 1.6. The majority (80 %) of patients showed locoregional disease rather than metastatic disease at diagnosis. Thirty-five cases (43 %) showed PD-L1 expression and the proportion of PD-L1 expression was significantly different according to histologic subtypes (P = 0.004); highest in epithelioid sarcoma (100 %, 7/7), followed by synovial sarcoma (53 %, 10/19), rhabdomyosarcoma (38 %, 12/32), and Ewing sarcoma (33 %, 6/18), while it was not expressed in mesenchymal chondrosarcoma (0 %, 0/6). STS patients with PD-L1 expression had worse overall survival compared with those without PD-L1 expression (5-year survival rate: 48 % vs. 68 %, P = 0.015). The Cox proportional hazard model adjusted for histologic subtype, initial metastasis, and PD-L1 expression showed that PD-L1 expression was significantly associated with shorter overall survival (P = 0.037, HR 2.57, 95 % CI 1.060–6.231).
We have confirmed PD-L1 expression in various STS of young population and demonstrated its independent negative prognostic role, thereby suggesting the PD-1/PD-L1 axis as a potential therapeutic target for the treatment of young STS patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12885-016-2451-6) contains supplementary material, which is available to authorized users.
PMCID: PMC4938996  PMID: 27393385
Soft tissue sarcoma; PD-L1; Biomarker; Prognosis
24.  Prognostic implications of PIK3CA amplification in curatively resected liposarcoma 
Oncotarget  2016;7(17):24549-24558.
We investigated the epidemiologic characteristics and prognostic significance of PIK3CA mutations/amplifications in curative resected liposarcoma.
Patients and methods
A total of 125 liposarcoma tissue samples were collected over a 12-year period. PIK3CA mutations and gene copy number amplifications were analyzed by pyrosequencing and fluorescence in situ hybridization (FISH).
Nine of the 105 liposarcomas (8.6%) had activating PIK3CA mutation. PIK3CA mutations were more frequent in myxoid/round cell and pleomorphic tumors compared with well-differentiated/dedifferentiated tumors (13.3% vs. 2.2%, P=0.043). In FISH PIK3CA analysis, copy number gain was detected in 14 of the 101 tumors (13.9%): 11 (10.9%) tumors had increased gene copy number (polysomy) and 3 (3.0%) exhibited gene amplification. In survival analysis, patients with PIK3CA copy number gain had a worse prognosis compared to patients without PIK3CA amplification (median disease-free survival [DFS] 22.2 vs. 107.6 months p=0.005). By multivariate analysis, PIK3CA copy number gain was an independent prognostic factor for worse DFS (P=0.027; hazard ratio, 2.400; 95% confidence interval 1.105 to 5.213). PIK3CA mutation was not associated with DFS and overall survival.
We demonstrated PIK3CA mutation and amplification in liposarcoma. PIK3CA copy number gain was an independent poor prognostic factor for DFS. Further studies are needed to evaluate the potential diagnostic and therapeutic role of PIK3CA mutations and amplifications in liposarcoma.
PMCID: PMC5029721  PMID: 27016421
liposarcoma; PIK3CA; amplification; mutation
25.  Surgery Alone Versus Surgery Followed by Chemotherapy and Radiotherapy in Resected Extrahepatic Bile Duct Cancer: Treatment Outcome Analysis of 336 Patients 
This study analyzed the outcomes of patients with resected extrahepatic bile duct cancer (EHBDC) in order to clarify the role of adjuvant treatments in these patients.
Materials and Methods
A total of 336 patients with EHBDC who underwent curative resection between 2001 and 2010 were analyzed retrospectively. The treatment types were as follows: surgery alone (n=168), surgery with chemotherapy (CTx, n=90), surgery with radiotherapy (RT) alone (n=29), and surgery with chemoradiotherapy (CRT, n=49).
The median follow-up period was 63 months. The 5-year rates of locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival (OS) for all patients were 56.5%, 59.7%, 36.6%, and 42.0%, respectively. In multivariate analysis, surgery with RT and CRT was a significant prognostic factor for LRFFS, and surgery with CTx was a significant prognostic factor for DMFS, and surgery with CTx, RT, and CRT was a significant prognostic factor for PFS (p < 0.05). Surgery with CTx and CRT showed association with superior OS (p < 0.05), and surgery with RT had marginal significance (p=0.078). In multivariate analysis of the R1 resection patients, surgery with CRT showed significant association with OS (p < 0.05).
Adjuvant RT and CTx may be helpful in improving clinical outcomes of patients with resected EHBDC who have a high risk of disease recurrence, particularly R1 resection patients. Conduct of additional prospective, larger-scale studies will be required in order to confirm the benefit of adjuvant RT and CTx in these patients.
PMCID: PMC4843751  PMID: 26323644
Extrahepatic bile duct cancer; Cholangiocarcinoma; Adjuvant radiotherapy; Drug therapy; Survival; Biliary tract neoplasms

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