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Find video protocols related to scientific articles indexed in Pubmed.
Concurrent chemoradiotherapy shows long-term survival after conversion from locally advanced to resectable hepatocellular carcinoma.
Yonsei Med. J.
PUBLISHED: 10-18-2014
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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.
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?-Catenin activated hepatocellular adenoma: a report of three cases in Korea.
Gut Liver
PUBLISHED: 07-01-2014
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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 ?-catenin. Here, we report three cases of HCA in Korean patients: 7-cm, inflammatory and ?-catenin-activated HCA with HCC transformation in a 46-year-old man; 13-cm, ?-catenin-activated HCA with cytological atypia in a 23-year-old woman; and 10-cm, pigmented, inflammatory and ?-catenin-activated HCA in a 36-year-old man. All cases exhibited the nuclear expression of ?-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.
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Surgical resection after down-staging of locally advanced hepatocellular carcinoma by localized concurrent chemoradiotherapy.
Ann. Surg. Oncol.
PUBLISHED: 06-11-2014
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This study evaluated the down-staging efficacy and impact on resectability of concurrent chemoradiotherapy (CCRT) followed by hepatic arterial infusion chemotherapy (HAIC) in locally advanced hepatocellular carcinoma, and identified prognostic factors of disease-free survival (DFS) and overall survival (OS) after curative resection.
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Practical Guidelines for the Surgical Treatment of Gallbladder Cancer.
J. Korean Med. Sci.
PUBLISHED: 06-10-2014
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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.
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Pre-S mutations of hepatitis B virus affect genome replication and expression of surface antigens.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-01-2014
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In chronic hepatitis B virus (HBV) infection, quantitative HBV surface antigen (qHBsAg) is useful for monitoring viral replication and treatment responses. We aimed to determine whether pre-S mutations have any effect on circulating qHBsAg.
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[Efficacy of feeding pump for patients on enteral tube feeding: a systematic literature review and analysis].
Korean J Gastroenterol
PUBLISHED: 02-25-2014
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This study was conducted to establish a guideline on the utilizing of feeding pump in patients requiring enteral tube feeding.
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Histological subclassification of cirrhosis can predict recurrence after curative resection of hepatocellular carcinoma.
Liver Int.
PUBLISHED: 01-26-2014
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Recurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)-related HCC after curative resection.
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Postoperative radiotherapy dose correlates with locoregional control in patients with extra-hepatic bile duct cancer.
Radiat Oncol J
PUBLISHED: 01-13-2014
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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.
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Lesson from 610 liver resections of hepatocellular carcinoma in a single center over 10?years.
World J Surg Oncol
PUBLISHED: 01-04-2014
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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.
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The effect of statin on epithelial-mesenchymal transition in peritoneal mesothelial cells.
PLoS ONE
PUBLISHED: 01-01-2014
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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).
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Role of cholecystectomy and lymph node dissection in patients with T2 gallbladder cancer.
World J Surg
PUBLISHED: 08-21-2013
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Incidental findings of gallbladder cancer (GBCA) have dramatically increased as an initial presentation of the disease because of the expansion of laparoscopic cholecystectomy. However, the optimal management of T2 GBCA remains at issue.
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Surgical outcomes of hepatocellular carcinoma with bile duct tumor thrombus: a Korean multicenter study.
World J Surg
PUBLISHED: 07-16-2013
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The long-term outcomes after resection for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) are unclear. This multicenter study was conducted to determine the prognosis of HCC patients with macroscopic BDTT who underwent resection with curative intent.
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The optimal follow-up period in patients with above 5-year disease-free survival after curative liver resection for hepatocellular carcinoma.
J Korean Surg Soc
PUBLISHED: 05-21-2013
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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.
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High serum CA19-9 levels are associated with an increased risk of cholangiocarcinoma in patients with intrahepatic duct stones: a case-control study.
Surg Endosc
PUBLISHED: 05-10-2013
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Hepatolithiasis is a known risk factor for cholangiocarcinoma (CC). Due to the high risk of complications that accompany endoscopic and surgical stone removal, it is often difficult to decide whether it is beneficial to remove intrahepatic ductal stones. We conducted a case-control study to determine the risk of developing CC and the benefit of stone removal in patients with hepatolithiasis.
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Predictors of mortality in cirrhotic patients undergoing extrahepatic surgery: comparison of Child-Turcotte-Pugh and model for end-stage liver disease-based indices.
ANZ J Surg
PUBLISHED: 03-25-2013
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BACKGROUND: Underlying liver cirrhosis is associated with high morbidity and mortality after surgery. Previous studies have reported conflicting results about the value of Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores as predictors of post-operative mortality. This study was designed to compare the capacities of CTP, MELD and MELD-based indices in predicting mortality for patients with liver cirrhosis who underwent elective extrahepatic surgery. METHODS: The medical records of 79 patients with liver cirrhosis who underwent elective extrahepatic surgery under general anaesthesia from December 2000 to December 2009 were reviewed retrospectively. RESULTS: The median follow-up period was 21 months, and the mortality rate was 24.1% (n = 19). Among the 19 mortalities, nine (11.4%) occurred while the patient was hospitalized after surgery. Intraoperative transfusion amount (?700?mL; odds ratio 6.294, P = 0.004) and the integrated MELD score (?34; odds ratio 6.654, P = 0.007) were significantly correlated with post-operative mortality. CTP score (hazard ratio 1.575, P = 0.012) was significantly correlated with overall mortality. CONCLUSIONS: Integrated MELD may be a more accurate predictor of operative mortality in cirrhotic patients undergoing extrahepatic surgery than CTP and other MELD-Na based indices. However, overall mortality may be reflected more accurately by CTP score. Further large-scale study will be needed to validate this result.
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Antiviral efficacies of currently available rescue therapies for multidrug-resistant chronic hepatitis B.
Clin Mol Hepatol
PUBLISHED: 03-25-2013
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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.
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Prognostic significance of the worst grade in hepatocellular carcinoma with heterogeneous histologic grades of differentiation.
J. Gastroenterol. Hepatol.
PUBLISHED: 03-11-2013
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Although tumor differentiation is a known prognostic factor after the treatment of hepatocellular carcinoma (HCC), there have not been any studies on the prognostic significance of tumor differentiation in HCC with heterogeneous histologic grades. In this study, we attempted to ascertain whether the major or the worst grade in mixed histologic type HCC determines the prognosis after liver resection.
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Efficacy of concurrent chemoradiotherapy with 5-fluorouracil or gemcitabine in locally advanced biliary tract cancer.
Cancer Chemother. Pharmacol.
PUBLISHED: 02-25-2013
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There is no established standard treatment for patients with locally advanced biliary tract cancer (BTC).
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Early predictor of mortality due to irreversible posthepatectomy liver failure in patients with hepatocellular carcinoma.
World J Surg
PUBLISHED: 02-21-2013
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Although mortality after liver resection has declined, posthepatectomy liver failure (PHLF) remains a major cause of operative mortality. To date there is not consensus on a definition for PHLF. However, there have been many efforts to define PHLF causing operative mortality. In the present study we sought to identify early predictors of death from irreversible PHLF.
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Inhibition of tumour angiogenesis and growth by small hairpin HIF-1? and IL-8 in hepatocellular carcinoma.
Liver Int.
PUBLISHED: 02-19-2013
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Hypoxia-inducible factor-1? (HIF-1?), a key transcription factor in the cellular response to hypoxia, and interleukin 8 (IL-8), a key mediator of angiogenesis, are important in cancerous tumour growth. In this study, we evaluated the effects of HIF-1? and IL-8 knockdown on angiogenesis and tumour growth in hepatocellular carcinoma (HCC).
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Human liver carboxylesterase 1 outperforms alpha-fetoprotein as biomarker to discriminate hepatocellular carcinoma from other liver diseases in Korean patients.
Int. J. Cancer
PUBLISHED: 02-13-2013
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Although alpha-fetoprotein (AFP) is currently the major serologic biomarker for hepatocellular carcinoma (HCC), it cannot efficiently distinguish this cancer from other forms of liver disease in early diagnosis due to its low sensitivity. The aim of this study is to compare sensitivity and specificity of human carboxylesterase 1 (hCE1) and AFP biomarker. Antibody-based assays for hCE1 and AFP were used to test both biomarkers with respect to diagnostic efficiency, Youdens index and the area under the curve (AUC) through receiver operating characteristic (ROC) analysis in plasma from 208 patients with HCC (n=57), liver cirrhosis (n=27), chronic hepatitis (n=37), cholangiocarcinoma (n=22), gastric cancer (n=31) and pancreatic cancer (n=34), along with 52 healthy donors (HDs). The levels of hCE1 were significantly higher in patients with HCC than HDs and the other diseases (p<0.005), further verified by AUC values and Youdens index. In the set of HCC versus liver cirrhosis the AUC values were 0.744 (AFP), 0.918 (hCE1) and 0.938 (combination of AFP and hCE1), respectively. These results indicate that hCE1 is not only a more potent and specific marker in distinguishing cancer from liver diseases, in particular cirrhosis, but the combination of hCE1 and AFP shows also synergistic potential for greater sensitivity and specificity in early diagnosis. Therefore the antibody-based hCE1 assay appears to have high diagnostic efficiency for discriminating HCC from other forms of liver disease. It is now feasible to further validate this novel plasma-based biomarker in the large cohort we assembled.
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Relationship between severity of liver dysfunction and the relative ratio of liver to aortic enhancement (RE) on MRI using hepatocyte-specific contrast.
J Magn Reson Imaging
PUBLISHED: 02-06-2013
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To evaluate differences in liver enhancement among patients with low and high morbidity risks and to determine the relationship between severity of liver dysfunction and the relative ratio of liver to aortic enhancement (RE) on MRI using hepatocyte-specific contrast.
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Liver resection for Bismuth type I and Type II hilar cholangiocarcinoma.
World J Surg
PUBLISHED: 01-29-2013
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In patients with Bismuth type I and II hilar cholangiocarcinoma (HCCA), bile duct resection alone has been the conventional approach. However, many authors have reported that concomitant liver resection improved surgical outcomes.
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Comparison of the sixth and seventh editions of the AJCC TNM classification for gallbladder cancer.
J. Gastrointest. Surg.
PUBLISHED: 01-09-2013
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This study aimed to compare the seventh edition of the tumor node metastasis (TNM) staging system to the sixth edition to validate its usefulness in predicting prognosis for gallbladder cancer.
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[The safety of early enteral feeding after emergency gastrointestinal surgery].
Korean J Gastroenterol
PUBLISHED: 12-27-2011
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Postoperative early feeding has many advantages, and current guidelines recommend the early diet or enteral feeding after gastrointestinal surgery. However, there are controversies in emergency situation. The aim of this study was to assess the safety of early enteral feeding in patients underwent emergency gastrointestinal (GI) surgery.
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Hepatocellular carcinoma during pregnancy: is hepatocellular carcinoma more aggressive in pregnant patients?
J Hepatobiliary Pancreat Sci
PUBLISHED: 12-13-2011
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Hepatocellular carcinoma (HCC) during pregnancy is a very rare condition and is believed to have a worse prognosis than HCC in non-pregnant women. We evaluated the prognosis and the diagnostic and therapeutic strategies for HCC in pregnant women.
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Antimicrobial resistance and resistance genes in Escherichia coli strains isolated from commercial fish and seafood.
Int. J. Food Microbiol.
PUBLISHED: 08-23-2011
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The purpose of this study was to investigate the antimicrobial resistance and to characterize the implicated genes in Escherichia coli isolated from commercial fish and seafood. Fish and seafood samples (n=2663) were collected from wholesale and retail markets in Seoul, Korea between 2005 and 2008. A total of 179 E. coli isolates (6.7%) from those samples were tested for resistance to a range of antimicrobial agents. High rates of resistance to the following drugs were observed: tetracycline (30.7%), streptomycin (12.8%), cephalothin (11.7%), ampicillin (6.7%) and ticarcillin (6.1%). No resistances to amikacin, amoxicillin/clavulanic acid and cefoxitin were observed. Seventy out of 179 isolates which were resistant to one or more drugs were investigated by PCR for the presence of 3 classes of antimicrobial resistance genes (tetracycline, aminoglycosides and beta-lactams), class 1, 2 and 3 integrons. Gene cassettes of classes 1 and 2 integrons were further characterized by amplicon sequencing. The tetracycline resistance genes tetB and tetD were found in 29 (41.4%) isolates and 14 (20%) isolates, respectively. The beta-lactam resistance gene, bla(TEM) was found in 15 (21.4%) isolates. The aminoglycoside resistance gene, aadA was found in 18 (25.7%) isolates. Class 1 integron was detected in 41.4% (n=29) of the isolates, while only 2.9% (n=2) of the isolates were positive for the presence of class 2 integron. Two different gene cassettes arrangements were identified in class 1 integron-positive isolates: dfrA12-aadA2 (1.8 kb, five isolates) and aadB-aadA2 (1.6 kb, four isolates). One isolate containing class 2 integron presented the dfrA1-sat-aadA1 gene cassette array. These data suggest that commercial fish and seafood may act as the reservoir for multi-resistant bacteria and facilitate the dissemination of the resistance genes.
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MELD-based indices as predictors of mortality in chronic liver disease patients who undergo emergency surgery with general anesthesia.
J. Gastrointest. Surg.
PUBLISHED: 08-10-2011
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Underlying chronic liver disease is associated with high morbidity and mortality after emergency surgery, which complicates clinical decisions over performing such surgery. In addition, the Child-Turcotte-Pugh (CTP) score is limited in its ability to predict postoperative residual liver function. This study was designed to determine whether the scores of the Model for End-stage Liver Disease (MELD)-based indices are effective predictors of mortality following emergency surgery in patients with chronic liver disease.
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Adjuvant hepatic arterial infusional chemotherapy with 5-fluorouracil and cisplatin after curative resection of hepatocellular carcinoma.
Oncology
PUBLISHED: 08-09-2011
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We investigated whether adjuvant hepatic arterial infusional chemotherapy (HAIC) with 5-fluorouracil (5-FU) and cisplatin reduces the recurrence of hepatocellular carcinoma (HCC) after curative resection.
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Clinicopathological characteristics in combined hepatocellular-cholangiocarcinoma: a single center study in Korea.
Yonsei Med. J.
PUBLISHED: 07-26-2011
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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.
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The effect of preconditioning on liver regeneration after hepatic resection in cirrhotic rats.
Korean J Hepatol
PUBLISHED: 07-16-2011
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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.
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The effect of preoperative portal vein embolization on liver regeneration after extended hepatic resection.
Hepatogastroenterology
PUBLISHED: 06-14-2011
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This study was designed to evaluate the effect of portal vein embolization on liver regeneration after major liver resection.
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Portal venous invasion: the single most independent risk factor for immediate postoperative recurrence of hepatocellular carcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 05-20-2011
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Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection.
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Prediction of microvascular invasion of hepatocellular carcinoma: usefulness of peritumoral hypointensity seen on gadoxetate disodium-enhanced hepatobiliary phase images.
J Magn Reson Imaging
PUBLISHED: 05-04-2011
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To determine whether peritumoral hypointensity seen on hepatobiliary phase images of preoperative gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) is useful for predicting microvascular invasion of hepatocellular carcinoma (HCC).
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Solitary extrahepatic intraabdominal metastasis from hepatocellular carcinoma after liver transplantation.
Yonsei Med. J.
PUBLISHED: 05-04-2011
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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.
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Gadoxetic acid-enhanced MRI findings of early hepatocellular carcinoma as defined by new histologic criteria.
J Magn Reson Imaging
PUBLISHED: 04-29-2011
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To describe the imaging features of early hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in comparison with multidetector computed tomography (MDCT) examinations.
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The role of preoperative [18F]fluorodeoxyglucose positron emission tomography in predicting early recurrence after curative resection of hepatocellular carcinomas.
J. Gastrointest. Surg.
PUBLISHED: 04-27-2011
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(18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) scan reflects tumor differentiation and predicts clinical outcome in patients with hepatocellular carcinoma (HCC). We investigated the correlation of PET scans with tumor differentiation and early tumor recurrence (time-to-recurrence <1 year).
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Detection of liver metastases using gadoxetic-enhanced dynamic and 10- and 20-minute delayed phase MR imaging.
J Magn Reson Imaging
PUBLISHED: 03-22-2011
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To assess the incremental value of hepatobiliary phase images in gadoxetate disodium-enhanced magnetic resonance imaging (MRI), and to compare diagnostic accuracy and lesion conspicuity on 10- and 20-minute delayed images for preoperative detection of hepatic metastases with subgroup analysis according to size and history of chemotherapy.
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Prognostic value of the 7th edition of the AJCC staging system as a clinical staging system in patients with hepatocellular carcinoma.
Eur. J. Cancer
PUBLISHED: 02-08-2011
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In 2009, the American Joint Committee on Cancer (AJCC) published the 7th edition of the hepatocellular carcinoma (HCC) staging system. We investigated the prognostic value of the 7th AJCC staging system as a clinical staging system in patients with HCC.
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Foam sclerotherapy using polidocanol (aethoxysklerol) for preoperative portal vein embolization in 16 patients.
Cardiovasc Intervent Radiol
PUBLISHED: 02-03-2011
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To evaluate the clinical safety and effectiveness of foam sclerotherapy using polidocanol for preoperative portal vein embolization (PVE) before hemihepatectomy of the liver.
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Prognostic factors and 10-year survival in patients with hepatocellular carcinoma after curative hepatectomy.
J. Gastrointest. Surg.
PUBLISHED: 01-30-2011
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There were contrary results about the effects of hepatitis B e antigen (HBeAg) positivity on the long-term survival in patients with hepatocellular carcinoma (HCC) after curative resection.
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Synchronous double primary cancers associated with a choledochal cyst and anomalous pancreaticobiliary ductal union.
J Korean Surg Soc
PUBLISHED: 01-19-2011
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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.
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Preoperative serum CA 19-9 level as a predictive factor for recurrence after curative resection in biliary tract cancer.
Ann. Surg. Oncol.
PUBLISHED: 01-06-2011
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Complete surgical removal of biliary tract cancer (BTC) offers the only chance of cure; however, long-term survival remains very limited because of frequent recurrence after surgery. The purpose of our study was to evaluate whether the preoperative serum carbohydrate antigen (CA) 19-9 level could predict recurrence after curative resection of BTC.
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A new versatile peptide-based size exclusion chromatography platform for global profiling and quantitation of candidate biomarkers in hepatocellular carcinoma specimens.
Proteomics
PUBLISHED: 01-03-2011
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Disease biomarkers are predicted to be in low abundance; thus, the most crucial step of biomarker discovery is the efficient fractionation of clinical samples into protein sets that define disease stages and/or predict disease development. For this purpose, we developed a new platform that uses peptide-based size exclusion chromatography (pep-SEC) to quantify disease biomarker candidates. This new platform has many advantages over previously described biomarker profiling platforms, including short run time, high resolution, and good reproducibility, which make it suitable for large-scale analysis. We combined this platform with isotope labeling and label-free methods to identify and quantitate differentially expressed proteins in hepatocellular carcinoma (HCC) tissues. When we combined pep-SEC with a gas phase fractionation method, which broadens precursor ion selection, the protein coverage was significantly increased, which is critical for the global profiling of HCC specimens. Furthermore, pep-SEC-LC-MS/MS analysis enhanced the detection of low-abundance proteins (e.g. insulin receptor substrate 2 and carboxylesterase 1) and glycopeptides in HCC plasma. Thus, our pep-SEC platform is an efficient and versatile pre-fractionation system for the large-scale profiling and quantitation of candidate biomarkers in complex disease proteomes.
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Immunohistochemical analysis of claudin expression in pancreatic cystic tumors.
Oncol. Rep.
PUBLISHED: 01-03-2011
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Aberrant expression of the claudin family of proteins has been reported in many human cancers, including pancreatic ductal carcinoma. Intraductal papillary mucinous neoplasms of the pancreas (IPMN) and mucinous cystic neoplasms (MCN) are considered precancerous lesions that are able to progress towards pancreatic ductal adenocarcinoma. We analyzed the expression of several claudin family members using surgical IPMN and MCN specimens to clarify the relationships between claudin expression and clinicopathological features. Twenty-nine and 25 consecutive cases of IPMN and MCN were selected and the expression of claudin-2, -4 and -18 was analyzed by immunohistochemistry. In addition, IPMN and MCN histological grade as well as IPMN subtypes were analyzed in relation to claudin expression. The 29 cases of IPMN comprised of 3 (10.3%) adenomas, 18 (62.1%) borderline malignancies and 8 (27.6%) carcinomas. The 25 cases of MCN comprised of 13 (52%) adenomas, 5 (20%) borderline malignancies and 7 (28%) carcinomas. Claudin-2, -4 and -18 showed strong expression both in IPMN and MCN, with the exception of claudin-4 in MCN. The expression grades of claudin-2 in both IPMN and MCN became weaker with increased histological grade. On the other hand, the expression grades of claudin-4 and -18 became stronger with increased histological grade in both IPMN and MCN. With regard to histological subtype, claudin-4 expression was the strongest in pancreatobiliary type IPMN, and claudin-18 expression was the strongest in gastric type IPMN. The distinct expression patterns of claudin-2, -4 and -18 suggest that claudins may serve as useful molecular markers for tumor differentiation and progression in IPMN and MCN.
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Autologous bone marrow infusion activates the progenitor cell compartment in patients with advanced liver cirrhosis.
Cell Transplant
PUBLISHED: 06-03-2010
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Several clinical trials of bone marrow cell infusion in patients with liver cirrhosis (LC) have shown clinical improvement, despite conflicting results from animal models. We investigated serial pathological features and the clinical impact after autologous bone marrow infusion (ABMI) in patients with advanced LC. Ten patients with advanced LC due to chronic hepatitis B virus infection underwent ABMI. Serological tests, MRI, and liver biopsies were performed, and quality of life was assessed by a questionnaire. Median serum albumin and hemoglobin levels increased significantly after ABMI. All patients showed an improvement in quality of life, with no serious adverse events. Liver volume, measured by MRI, increased in 80% of the patients, and ascites decreased after ABMI. Child-Pugh scores were also significantly improved at 6 months after ABMI. In the serially biopsied livers, a gradually increasing activation of the hepatic progenitor cell (HPC) compartment, including HPC activation (ductular reaction) and HPC differentiation (intermediate hepatocyte), reached a peak after 3 months, with continued proliferation of hepatocytes, and returned to baseline levels after 6 months. There was no significant change in grade or stage of liver fibrosis or stellate cell activation after ABMI. ABMI is suggested to improve liver function and to activate the progenitor cell compartment. Although clinical improvement was sustained for more than 6 months, histological changes in the liver returned to baseline 6 months after ABMI. Further comparative studies are warranted.
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Surgical outcome of metachronous hepatic metastases secondary to gastric cancer.
Hepatogastroenterology
PUBLISHED: 04-29-2010
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The prognosis of hepatic metastasis from gastric carcinoma is dismal. A few patients are candidates for hepatic resection. The present study analyzed the oncologic outcomes of hepatic resection performed in metachronous hepatic metastasis from gastric cancer.
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Therapeutic potential of bone-marrow-derived mesenchymal stem cells differentiated with growth-factor-free coculture method in liver-injured rats.
Tissue Eng Part A
PUBLISHED: 04-07-2010
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Mesenchymal stem cell (MSC) differentiation by growth factors may be improper due to possibility of clinical risk. We have previously developed a growth-factor-free coculture method and observed rat MSCs differentiated into hepatic progenitor cells. This study was aimed to validate hepatic differentiation potential in vivo. MSCs from bone marrow of green fluorescent protein-transgenic Sprague-Dawley rats were cocultured with hepatocytes from normal Sprague-Dawley rats, sharing growth-factor-free media. After 14 days, cells were implanted into the spleen of carbon tetrachloride (CCl4)-injured rats and kept for 4 weeks. Fibrosis remarkably decreased in CCl4/cocultured MSC at weeks 1, 3, and 4. Immunohistochemistry revealed that albumin, alpha-fetoprotein, and cytokeratin 19 (CK19) expression was high in CCl4/cocultured MSC only at week 1. Reverse transcription-polymerase chain reaction and Western blot revealed that CCl4/cocultured MSC had reduced alpha-fetoprotein expression at week 4, whereas CK18 and CK19 exhibited stronger expression. Albumin in CCl4/cocultured MSC increased at week 4 only in protein level. We assume that cocultured MSCs had stayed at hepatic progenitor stage until week 3, and differentiated into hepatocytes or bile-ductal epithelial cells afterward. Hepatic progenitor cells from MSC differentiation in the growth-factor-free coculture system may contribute to the therapeutic effect for liver disease in vivo.
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Can preoperative diffusion-weighted MRI predict postoperative hepatic insufficiency after curative resection of HBV-related hepatocellular carcinoma? A pilot study.
Magn Reson Imaging
PUBLISHED: 03-05-2010
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Liver fibrosis determines the functional liver reserve. Several studies have reported that the apparent diffusion coefficient (ADC) values of diffusion-weighted magnetic resonance imaging (DW-MRI) can assess liver fibrosis. We investigated whether DW-MRI predicts postoperative hepatic insufficiency and liver fibrosis in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Twenty-six patients with HBV-related HCC who received preoperative DW-MRI on a 3-T MRI system were enrolled between July and December 2008. ADC values were measured twice by two observers. Three "b values" were used: 50, 400 and 800 s/mm(2). Postoperative hepatic insufficiency was defined as persistent hyperbilirubinemia (total bilirubin level >5 mg/dl for more than 5 days after surgery) or postoperative death without other causes. The mean age (21 men and 5 women) was 51.4 years. Three patients experienced postoperative hepatic insufficiency. liver stiffness measurement predicted postoperative hepatic insufficiency, advanced fibrosis (F3-4), and cirrhosis significantly [area under the receiving operator characteristic curve (AUROC)=0.942, 0.771 and 0.818, respectively, with P=.047, 0.048 and 0.006, respectively]; ADC values of DW-MRI, however, did not (AUROC=0.797, 0.648 and 0.491, respectively, with P=.100, 0.313 and 0.938, respectively). Reliability of ADC values between right and left hepatic lobes (rho=0.868 and rho=0.910 in the first and second measures of Observer A; rho=0.865 and rho=0.831 in the first and second measures of Observer B) was high and the intra- and interobserver reliability (rho=0.958 in observer A and rho=0.977 in observer B; rho=0.929 in the first measure and rho=0.978 in the second measure between the two observers) were high. All reliability was significant (P<.001). Our results suggest that DW-MRI on a 3-T MRI system is not suitable for predicting postoperative hepatic insufficiency, advanced liver fibrosis, and cirrhosis in patients with HBV-related HCC, despite significantly high reliability.
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Aberrant CpG island hypermethylation in dysplastic nodules and early HCC of hepatitis B virus-related human multistep hepatocarcinogenesis.
J. Hepatol.
PUBLISHED: 02-09-2010
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The concept of multistep hepatocarcinogenesis has been well-established, and an accumulation of methylating events has recently been demonstrated; however, the methylation status of low-grade dysplastic nodules (LGDN), high-grade dysplastic nodules (HGDN), and the recently introduced early hepatocellular carcinoma (eHCC) in hepatitis B virus (HBV)-related hepatocarcinogenesis has not yet been studied.
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Dynamic regulation of CFTR bicarbonate permeability by [Cl-]i and its role in pancreatic bicarbonate secretion.
Gastroenterology
PUBLISHED: 02-05-2010
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Pancreatic bicarbonate (HCO3-) secretion is important for a healthy pancreas as well as digestive physiology. However, how human pancreatic duct cells secrete copious amounts of HCO3- has long been a puzzle. Here, we report that a dynamic increase in the cystic fibrosis transmembrane conductance regulator (CFTR) HCO3- permeability by intracellular Cl- concentration ([Cl-]i)-sensitive mechanisms plays a pivotal role in pancreatic HCO3- secretion.
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Current status of hepatic surgery in Korea.
Korean J Hepatol
PUBLISHED: 12-29-2009
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Since the first liver resection was carried out in Korea in 1959, there have been remarkable changes in the field of surgery. With technical advancement and the improvement of perioperative care, liver resections are widely performed and surgical mortality is approaching zero. In the early 1990s, liver transplantation evolved as a feasible option in the treatment of end-stage liver disease in Korea, with successful adult living-donor liver transplantation (LDLT) as one of the greatest achievements. Various innovations in surgical approaches have been introduced. We review the current status of hepatic surgery in liver disease in Korea.
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Current status of liver diseases in Korea: hepatocellular carcinoma.
Korean J Hepatol
PUBLISHED: 12-29-2009
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Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. During the last two decades, the incidence rate of primary liver cancer has shown a modest decrease, but its mortality rate has slightly increased. The incidence of HCC, according to age, peaks in the late sixth decade in men and in the early seventh decade in women. Hepatitis B virus (HBV) is the most important risk factor, which represents approximately 70% of all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10 years earlier than HCV-associated HCC due to a more prolonged exposure to HBV, which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic area. National Cancer Control Institute, which was reorganized in 2005, is now working for several national projects such as National Cancer Registration Program, National R&D Program for Cancer Control and National Cancer Screening Program. International collaboration for the clinico-epidemiologic research would be needed to provide the specific measures for managing HCC in diverse etiologic situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular carcinogenesis might be clarified to provide insights into the advanced therapeutic and preventive approaches for HCC in Korea, where the majority of HCC originate from chronic HBV and HCV infections.
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The preoperative positivity for serum hepatitis B e antigen did not affect overall survival after curative resection of hepatitis B virus-related hepatocellular carcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 11-20-2009
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Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified.
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Intraductal ultrasonography combined with percutaneous transhepatic cholangioscopy for the preoperative evaluation of longitudinal tumor extent in hilar cholangiocarcinoma.
J. Gastroenterol. Hepatol.
PUBLISHED: 09-25-2009
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In hilar cholangiocarcinoma, an accurate assessment of preoperative resectability is important to optimize surgical resection. We investigated the accuracy of the combination of intraductal ultrasonography (IDUS) and percutaneous transhepatic cholangioscopy (PTCS) for evaluating longitudinal extent in hilar cholangiocarcinoma.
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Human plasma carboxylesterase 1, a novel serologic biomarker candidate for hepatocellular carcinoma.
Proteomics
PUBLISHED: 08-07-2009
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To identify and characterize a serologic glycoprotein biomarker for hepatocellular carcinoma (HCC), multi-lectin affinity chromatography was used to isolate intracellular N-linked glycoprotein fractions from five paired non-tumor and tumor tissues. From the series of 2-D DIGE targeted differentially expressed N-linked glycoproteins, we identified human liver carboxylesterase 1 (hCE1), which was remarkably down-regulated in tumor tissues, a finding confirmed by Western blot, a quantitative real-time RT-PCR, and immunohistochemical staining of non-tumor and tumor tissues from total 58 HCC patients. To investigate whether hCE1 is also present in human plasma, we employed a magnetic bead-based immunoprecipitation followed by nano-LC-MS/MS analysis, and we found for the first time that hCE1 is present in human plasma as opposed to that in liver tissues. That is, from normalization of hCE1 signal by the immunoprecipitation and Western blot analysis, hCE1 levels were increased in plasma specimens from HCC patients than in plasma from other disease patient groups (e.g. liver cirrhosis, chronic hepatitis, cholangiocarcinoma, stomach cancer, and pancreatic cancer). From the receiver operating characteristic analysis in HCC, both sensitivity and specificity were shown to be greater than 70.0 and 85.0%, respectively. Thus, the high-resolution proteomic approach demonstrates that hCE1 is a good candidate for further validation as a serologic glycoprotein biomarker for HCC.
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Synaptic scaffolding molecule binds to and regulates vasoactive intestinal polypeptide type-1 receptor in epithelial cells.
Gastroenterology
PUBLISHED: 07-31-2009
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Vasoactive intestinal polypeptide (VIP) is a principal regulator of fluid and electrolyte secretion in the gastrointestinal system. The VIP type-1 receptor (VPAC1), a class II G-protein-coupled receptor, contains a putative C-terminal PDZ-binding motif. A yeast 2-hybrid screen indicated that the C-terminus of VPAC1 bound to the PDZ domain of synaptic scaffolding molecule (S-SCAM, also known as membrane-associated guanylate kinase inverted-2 [MAGI-2]). We analyzed the association between S-SCAM and VPAC1.
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Comparative study of resection and radiofrequency ablation in the treatment of solitary colorectal liver metastases.
Am. J. Surg.
PUBLISHED: 07-02-2009
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We compared outcomes in patients with solitary colorectal liver metastases treated by either hepatic resection (HR) or radiofrequency ablation (RFA).
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Efficacy and safety of transarterial chemoembolization in recurrent hepatocellular carcinoma after curative surgical resection.
Am. J. Clin. Oncol.
PUBLISHED: 07-01-2009
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To evaluate the efficacy and safety of transarterial chemoembolization (TACE) for recurrent hepatocellular carcinoma (HCC) after curative resection and to examine the factors associated with the prognosis in a single center.
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Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice.
Stem Cells
PUBLISHED: 06-23-2009
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Various attempts have been made to develop stem cell-based therapy to alleviate type I diabetes using animal models. However, it has been a question whether human insulin produced from explanted cells is solely responsible for the normoglycemia of diabetic animals. In this study, we isolated neural crest-like stem cells from the human eyelid fat and examined their therapeutic potentials for diabetes. The human eyelid adipose-derived stem cells (HEACs) displayed characteristics of neural crest cells. Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments. Following differentiation in vitro, HEACs released insulin and c-peptide in a glucose-dependent manner. Upon their transplantation under kidney capsules of streptozotocin-treated immunocompetent mice, we observed normalization of hyperglycemia in 10 of 20 recipient mice until sacrifice after 2 months. Only the human, but not the mouse, insulin and c-peptide were detected in the blood of recipient mice. Removal of the kidneys transplanted with HEACs resulted in a sharp increase of blood glucose level. Removed kidney tissues showed distinct expression of various human genes including insulin, and colocalization of the human insulin and the human nuclear protein in many cells. However, they showed diminished or null expression of some immune-related genes. In conclusion, human insulin alone produced from eyelid-derived stem cells following differentiation into insulin-secreting cells and transplantation could normalize type I diabetes in mice.
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Chromosomal instability, telomere shortening, and inactivation of p21(WAF1/CIP1) in dysplastic nodules of hepatitis B virus-associated multistep hepatocarcinogenesis.
Mod. Pathol.
PUBLISHED: 05-22-2009
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Systemic analysis for chromosomal instability and inactivation of cell cycle checkpoints are scarce during hepatocarcinogenesis. We studied 24 patients with chronic B viral cirrhosis including 30 cirrhotic regenerative nodules, 35 low-grade dysplastic nodules, 15 high-grade dysplastic nodules, 7 dysplastic nodules with hepatocellular carcinoma foci, and 18 hepatocellular carcinomas. Eight normal livers were studied as the control group. Telomere length and micronuclei were detected by Southern blot and Feulgen-fast green dyeing technique, respectively, and p21(WAF1/CIP1) expression was studied by immunohistochemistry. Micronuclei >1 per 3000 hepatocytes were found in 17% of low-grade dysplastic nodules, 87% of high-grade dysplastic nodules, and 100% of high-grade dysplastic nodules with hepatocellular carcinoma foci and hepatocellular carcinomas in contrast to those of all normal livers, and 90% of cirrhosis showed no micronuclei. The micronuclei index showed a gradual increase during hepatocarcinogenesis and there was a significant increase between cirrhosis and low-grade dysplastic nodules, low-grade dysplastic nodules and high-grade dysplastic nodules, and high-grade dysplastic nodules and hepatocellular carcinomas. Telomere length showed a gradual shortening during hepatocarcinogenesis and a significant reduction was found in high-grade dysplastic nodules (P=0.024) and hepatocellular carcinomas (P=0.031) compared with normal and cirrhotic livers. The micronuclei index was correlated with telomere shortening (P=0.016). The p21(WAF1/CIP1) labeling index was significantly higher in cirrhosis than in normal livers (P=0.024) and markedly decreased in low-grade dysplastic nodules, high-grade dysplastic nodules, and hepatocellular carcinomas compared with cirrhosis (P<0.05). The p21(WAF1/CIP1) labeling index was associated with telomere length (P<0.001) but not micronuclei index. This study shows that telomere shortening, chromosomal instability, and inactivation of p21(WAF1/CIP1) checkpoint function occur in low-grade dysplastic nodules as well as in high-grade dysplastic nodules, and their cooperation is considered to be critical for malignant transformation during hepatitis B virus associated-multistep hepatocarcinogenesis.
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The efficacy of hepatic resection after neoadjuvant transarterial chemoembolization (TACE) and radiation therapy in hepatocellular carcinoma greater than 5 cm in size.
J. Korean Med. Sci.
PUBLISHED: 04-20-2009
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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.
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The prognosis and survival outcome of intrahepatic cholangiocarcinoma following surgical resection: association of lymph node metastasis and lymph node dissection with survival.
Ann. Surg. Oncol.
PUBLISHED: 03-20-2009
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Surgical resection has been shown to improve long-term survival for patients with intrahepatic cholangiocarcinoma (ICC). The benefit of lymph node dissection is still controversial. The aims of this study were to investigate the prognostic factors of ICC and to examine the impact of lymph node metastasis and extent of lymph node dissection on survival.
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Outcome after curative resection for a huge (>or=10 cm) hepatocellular carcinoma and prognostic significance of gross tumor classification.
Am. J. Surg.
PUBLISHED: 03-06-2009
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The purpose of this study was to investigate the surgical outcomes in patients with huge (>or=10 cm) hepatocellular carcinoma (HCC).
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Expression of Wnt target genes in solid pseudopapillary tumor of the pancreas: a pilot study.
Pancreas
PUBLISHED: 02-28-2009
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Solid pseudopapillary tumor (SPT) of the pancreas is very rare. This study was performed to analyze the expression of Wnt signal target genes (matrix metalloproteinase-7 [MMP-7], cyclin-D1, and c-myc) and Ki-67 in resected SPTs to determine their clinicopathologic characteristics according to their expression.
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The survival outcome and prognostic factors for middle and distal bile duct cancer following surgical resection.
J Surg Oncol
PUBLISHED: 02-20-2009
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The objective of this study was to analyze the survival outcome and the clinicopathological factors that influence survival and recurrence of middle and distal bile duct cancer after surgical resection.
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Detrimental effect of postoperative complications on oncologic efficacy of R0 pancreatectomy in ductal adenocarcinoma of the pancreas.
J. Gastrointest. Surg.
PUBLISHED: 01-28-2009
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Margin-negative resection of pancreatic cancers has proven to be the most effective treatment to date. Although there are frequent surgery-related complications following pancreatectomy, the oncologic effect of these complications following pancreatectomy for pancreatic cancer has not been studied.
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Can microvessel invasion of hepatocellular carcinoma be predicted by pre-operative MRI?
Eur Radiol
PUBLISHED: 01-24-2009
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Microvessel invasion is a major prognostic factor in hepatocellular carcinoma (HCC) that influences the suitability of surgery, but rarely can be evaluated preoperatively. This study was performed to identify preoperative MRI findings that reflect histopathological microvessel invasion in hepatocellular carcinoma. Gadobenate dimeglumine-enhanced four-arterial phase dynamic study and hepatobiliary phase images of preoperative MRI of 70 HCC lesions were retrospectively reviewed. Tumor size (cm), peritumoral enhancement, tumor margins, and radiological capsule were analyzed as radiological parameters reflecting microvessel invasion and were compared with histopathological references. The chi-square test and the independent t-test were used for univariate analysis, and a logistic regression analysis was performed for multivariate analysis. In univariate analysis, tumor size (p = 0.030), peritumoral enhancement (p < 0.001), and tumor margins (p = 0.007) were associated with microvessel tumor invasion. However, in multivariate analysis irregular circumferential peritumoral enhancement only showed statistical significance (odds ratio 13.0), suggesting a high probability of microvessel invasion of HCC. Irregular circumferential peritumoral enhancement on contrast-enhanced multi-arterial phase dynamic MRI could be a preoperative surrogate marker for microvessel tumor invasion.
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