BACKGROUND/AIMS: In the immunological and functional aspects, freshly isolated human hepatocytes are better than animal hepatocytes from other species such as the pig and hepatocytes from human tumor cell lines. Human liver tissue for hepatocyte isolation can be obtained either from surgical specimens of patients with liver disease, such as hepatocellular carcinoma or from donor livers that are not suitable for transplantation. In the latter case, the liver may be preserved in 4 degrees C UW solution. Therefore, studies of the limit on the preservation time to get clinically applicable hepatocytes, and proper isolation techniques improving cell viability are needed. In this study, the authors isolated hepatocytes from a few kinds of the liver with different UW preservation times and different isolation techniques. METHODS: Male Sprague-Dawley rats weighing 200g-250g were used. The hepatocytes were isolated from unpreserved livers(control), livers preserved for 24 hours in UW solution, and livers preserved for 48 hour in UW solution, with a modified Seglen's two step method. To improve cell viability, 5mM glycin was added to the EDTA solution in one group and in another, the pH of the EDTA solution was slowly changed from 6.5 to 7.25. RESULTS: The control group showed 80.0% of cell viability. 53.8% of isolated hepatocytes were viable even after 24 hours of preservation. The cell viability decreased to 36.1% and severe cellular damage was observed after 48 hours preservation. The glycin and pH change showed no protective effect on the isolation of hepatocytes from UW preserved livers. CONCLUSION: After 24 hours preservation in UW solution, many clinically useful hepatocytes were isolated with a modified Seglen's two step method. Further studies concerning the preservation of functions of hepatocytes isolated from UW preserved livers and on the technique of cell culture and cryopreservation are needed.
Animals ; Carcinoma, Hepatocellular ; Cell Culture Techniques ; Cell Line, Tumor ; Cell Survival ; Cryopreservation ; Edetic Acid ; Hepatocytes* ; Humans ; Hydrogen-Ion Concentration ; Liver Diseases ; Liver* ; Male ; Rats* ; Rats, Sprague-Dawley ; Tissue Donors

BACKGROUND/AIMS: Auxiliary liver transplantation means a procedure in which part of the native liver is left in situ. In this method, it has been suggested that blocking of portal flow to the native liver (arterialized liver) could potentiate the regeneration of the graft liver. In this study, we evaluate the effect on regeneration capacity of graft liver by blocking the portal flow to the native liver in auxiliary heterotopic liver transplantation in pig. METHODS: Female pigs weighing 25 kg and 30 kg were used as the donor and the recipient for liver transplantation, respectively. After total hepatectomy in the donor pig, graft liver was placed inferior to right liver and superior to right kidney of the recipient. The donor's hepatic vein was anastomosed to infrahepatic inferior vena cava superior to renal vein. The portal vein of the recipient was divided at the hilum and anastomosed with donor's portal vein. The donor's hepatic artery was anastomosed to the aorta below the renal artery. After 1, 3, 5, 7, 15th postoperative days, the weights of native and graft liver, proliferative cell nuclear antigen (PCNA) indices of both livers, and liver function test were checked. RESULTS: During the procedure, hemodynamic status was stable without using venovenous bypass. There was no postoperative death and no severe deterioration of hepatic function. During 5th and 15th postoperative days, PCNA indices of graft liver (40~60%) were higher than those of native liver (30%). The weight of graft liver was increased more than 80% of preoperative value on day 7 and 15. CONCLUSION: By arterialization of the native liver, the regeneration of the small graft liver could be accomplished smoothly without metabolic burden. This animal model is useful for studying graft liver physiology of liver transplantation in preclinical setting. With this study, the first case of auxiliary partial orthotopic liver transplantation was performed successfully in the patients who suffered from metabolic liver disease.
Aorta ; Female ; Hemodynamics ; Hepatectomy ; Hepatic Artery ; Hepatic Veins ; Humans ; Kidney ; Liver Diseases ; Liver Function Tests ; Liver Regeneration ; Liver Transplantation* ; Liver* ; Models, Animal ; Physiology ; Portal Vein ; Proliferating Cell Nuclear Antigen ; Regeneration ; Renal Artery ; Renal Veins ; Swine ; Tissue Donors ; Transplants ; Vena Cava, Inferior ; Weights and Measures

BACKGROUND/AIMS: The c-met proto-oncogene encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), a potent mitogen and motogen for epithelial cells. Because of its profound effects on cell growth and motility, HGF may be important in the development of cancer metastases in hepatocellular carcinoma (HCC). We examined the expression of the c-met proto-oncogene product (c-Met) in the patients with HCCs to determine the relationship between the level of expression of c-Met and clinicopathological features, and patient outcome following hepatectomy. METHODS: Fifty patients with surgically resected hepatocellular carcinoma at Seoul National University Hospital from January 1997 to December 1998 were included in this study. Western blotting was used to examine the c-Met expression of tumor and surrounding tissues. The clinicopathologic features and treatment results of the patients were analyzed by medical records. Patients were divided into two groups, low c-met HCC and high c-met HCC. RESULTS: c-Met was not overexpressed in HCC compared to surrounding tissue. The expression of c- Met in tumor tissue was correlated with well-differentiated HCCs, and adversely correlated with tumor necrosis by transcatheter arterial chemoembolization (TACE). There was no correlation between c-Met expression and intrahepatic recurrence. CONCLUSION: In conclusion, these results indicate that c-Met expression in HCC is not correlated with intrahepatic recurrence, and tumor necrosis by TACE reduces c-Met expression in tumor tissue. More large-scaled study is needed for exact relation between c-Met expression and clinicopathologic features of HCCs.
Blotting, Western ; Carcinoma, Hepatocellular* ; Epithelial Cells ; Hepatectomy ; Hepatocyte Growth Factor ; Humans ; Medical Records ; Necrosis ; Neoplasm Metastasis ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Recurrence ; Seoul

BACKGROUND: Intraductal papillary mucinous tumor (IPMT) of the pancreas is a rare tumor arising in the main pancreatic duct or its subbranches. It is characterized by a diffusely or focally dilated main pancreatic duct filled with mucus and a mucus secretion through a patulous duodenal papilla. METHODS: The clinicopathologic characteristics of eight IPMT cases which were resected surgically from January 1994 to August 1998 at Seoul National University Hospital were reviewed to consider the optimal surgical treatment. RESULTS: The range of ages was from 49 to 70 years with a mean age of 59.3. Five were men and three were women. The prominent symptom was upper abdominal pain. Seven patients had been treated for pancreatitis before. Tumor markers didn't correlate with the pathologic status. In all the cases, a dilated pancreatic duct with secretion of mucin was found in the radiologic studies. Four lesions were located in the uncinate process, 3 in the body, and 1 diffusely. One total pancreatectomy, 1 Whipple's procedure, 3 pylorus-preserving pancreatoduodenectomies, 1 duodenum-preserving resection of the head of the pancreas, and 2 subtotal pancreatectomies were performed. Three lesions were malignant, another three were borderline malignant, and the remaining two were benign. Three were multiple lesions. Lesions for which the main pancreatic duct was dilated more than 0.5 cm, lesions greater than 2.5 cm, lesions with a mural nodule greater than 1.0 cm, or type 1, 2, 3 lesions were borderline malignant or malignant. There was no lymphatic metastasis. After a follow-up duration from 1 month to 56months, all patients are alive at the time of study and have experienced no locoregional recurrence or distant metastasis. CONCLUSIONS: In the radiologic studies, an IPMT should be considered in a multilobulating cystic lesion with the dilated main pancreatic duct. The lesions are variable from benign to malignant and often spread intraductally. When the lesion seems to be malignant, an aggressive resection is recommended.
Abdominal Pain ; Biomarkers, Tumor ; Female ; Follow-Up Studies ; Head ; Humans ; Lymphatic Metastasis ; Male ; Mucins* ; Mucus ; Neoplasm Metastasis ; Pancreas* ; Pancreatectomy ; Pancreatic Ducts ; Pancreaticoduodenectomy ; Pancreatitis ; Recurrence ; Seoul

PURPOSE: To draw attention to patient safety and increase its awareness among medical students, we developed a program that teaches patient safety based on common medical error cases. The aim of this study is to introduce this program and improve student receptivity to it. METHODS: As part of the "Patient, Doctor, and Society" course, third-year medical students participated in 8 hours of a medical error education program. Students discussed recent, typical medical lawsuits that were generated from internal medicine, surgery, pediatrics, obstetrics and gynecology, neurosurgery, medication, anesthesia, and blood transfusion cases. Students weighed these issues in small groups, using various discussion methods. After finishing the program, students completed a course evaluation questionnaire. RESULTS: The students rated this program as satisfactory, highly motivating, and helpful in preparing their future practices. They responded that although the cases were interesting, some were difficult. They stated that the small group discussion techniques encouraged them to take active part in the discussion and to consider the cases more deeply. CONCLUSION: Small group discussion of medical error cases is an effective method for students to study patient safety.
Anesthesia ; Blood Transfusion ; Group Processes ; Gynecology ; Humans ; Internal Medicine ; Malpractice ; Medical Errors ; Neurosurgery ; Obstetrics ; Patient Safety ; Pediatrics ; Safety Management ; Students, Medical ; Surveys and Questionnaires

BACKGROUND/AIMS: There are many reports in which perioperative transfusion was closely related to the survival of cancer. The long-term survival rate of patients with hepatocellular carcinoma undergoing hepatectomy has improved, and it may be related to the reduction of intraoperative transfusion. The aim of this study is to evaluate the effect of intraoperative transfusion on the prognosis in the hepatectomized hepatocellular carcinoma patients and the relationship between the survival improvement and reduction of intraoperative transfusion. METHODS: From 1988 Jan. to 1995 Dec., 507 cases in which the amount of intraoperative transfusion was known were reviewed. Operative transfusion of whole blood or packed red cells was included in this study. The clinical, operative, and pathological factors were analyzed to identify factors that affected long-term survival and disease free survival. RESULTS: By multivariate analysis, Child classification, the extent of resection, portal vein invasion, and blood transfusion(more than 7 units) were shown to be independent factors in overall survival. Child classification, the number of tumors, portal vein invasion, and blood transfusion(more than 7 units) were shown to be independent factors in disease free survival. CONCLUSION: Operative blood transfusion affects the long-term survival and the disease free survival. Therefore, the intraoperative transfusion should be reduced if possible. Through the improvement of surgical technique and instrument, surgeon can reduce the intraoperative bleeding, and this reduction of intraoperative bleeding may contribute the improvement of survival through the reduction of intraoperative transfusion.
Blood Transfusion ; Carcinoma, Hepatocellular* ; Child ; Classification ; Disease-Free Survival ; Hemorrhage ; Hepatectomy ; Humans ; Multivariate Analysis ; Portal Vein ; Prognosis* ; Survival Rate

BACKGROUND/AIMS: The role of hepatic resection for metastatic gastric cancer is less well defined due to its tendency of multiple intra- and extra-hepatic metastatic patterns. We have reviewed our experiences in the gastric cancer patients with liver metastases to define good candidates for the prolonged survival by hepatic resection. METHODS: Records of eleven patients who underwent hepaatic resection for metastatic gastric cancer from January 1988 to December 1996 at Seooul National University Hospital were reviewed. The clinicopathologic features and their long-term results were analysed. RESULTS: All resected hepatic metastases were solitary mass. Among eight patients with synchronous liver metastases, only one patient who had early gastric cancer with lymph node metastases (T1N2M1) was alive for 9 years 6 months after hepatic resection without recurrence. Among three patients with metachronous liver metastases, two patients who had advanced gastric cancer with lymph node metastases (T3N2M0, T2N1M0 at initial operation, respectively) survived 8 years 6 months and 3 years after hepatic resection, respectively. Median survival time of synchronous and metachronous liver metastases were 13.0 and 74.3 months, respectively. CONCLUSION: Good prognosis may be expected in some selected patients who underwent hepatic resection for metastatic gastric cancer.
Hepatectomy ; Humans ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Stomach Neoplasms* ; Treatment Outcome

BACKGROUND/AIMS: With the advances in imaging modalities, the incidental diagnoses of solitary cystic lesions of the liver are increasing. The aim of this study is to establish the strategy of differential diagnosis and treatment in the patients with solitary cystic lesions of the liver METHODS: Forty three solitary cystic lesions of the liver treated surgically at Seoul National University Hospital from January 1981 to December 1998 were reviewed retrospectively. The clinicopathologic features, postoperative courses and their long-term results were analysed. RESULTS: There were fifteen congenital nonparasitic cysts (simple cysts), 3 Caroli's diseases, 4 hydatid cysts, 2 traumatic cysts, 1 cystic hamartoma, 10 biliary cystadenomas, and 8 biliary cystadenocarcinomas. Twenty six hepatic resections, 12 excisions, 3 marsupializations, 1 cystojejunostomy, and 1 cystic wall biopsy were performed. There were 4 biliary leakages and 2 intraabdominal abscesses after surgery, and three out of them resulted from the communications with the biliary trees. Cystic fluid analysis or radiologic study could not offer the accurate diagonosis. Two patients who had biliary cystadenoma and biliary cystadenocarcinoma, respectively, and underwent marsupializations with preoperative misdiagnosis of simple cyst resulted in death due to recurrent tumors. CONCLUSION: In exploring every case of solitary cystic lesion of the liver, presence of biliary communication and cystic malignancy should be considered unless simple cyst is highly suggested.
Abscess ; Biopsy ; Bone Cysts* ; Cystadenocarcinoma ; Cystadenoma ; Diagnosis* ; Diagnosis, Differential ; Diagnostic Errors ; Echinococcosis ; Hamartoma ; Humans ; Liver* ; Retrospective Studies ; Seoul

This study was conducted to compare the multiple low-dose streptozotocin (MLDS)-induced diabetic patterns of Korl:ICR, A:ICR, and B:ICR mice obtained from three different sources. Six-week-old male ICR mice were obtained from three difference sources. Korl:ICR mice were kindly provided by the National Institute of Food and Drug Safety Evaluation (NIFDS). The other two groups of ICR mice were purchased from different vendors located in the United States (A:ICR) and Japan (B:ICR). All ICR mice that received MLDS exhibited overt diabetic symptoms throughout the study, and the incidence and development of diabetes mellitus were similar among the three ICR groups. The diabetic mice exhibited hyperglycemia, loss of body weight gain, decreased plasma insulin levels, impaired glucose tolerance, decreased number of insulin-positive cells, and decreased size of β-cells in the pancreas. The diabetes symptoms increased as the blood glucose level increased in the three ICR groups. In particular, the level of blood glucose in the STZ-treated group was higher in Korl:ICR and A:ICR mice than in B:ICR mice. The plasma insulin levels, glucose tolerance, blood chemistry, and morphological appearance of the pancreas were very similar in the ICR groups obtained from the three different sources. In conclusion, our results suggest that Korl:ICR, A:ICR, and B:ICR mice from different sources had similar overall responses to multiple low-dose STZ to induce diabetes mellitus.
Animals ; Blood Glucose ; Body Weight ; Chemistry ; Commerce ; Diabetes Mellitus* ; Glucose ; Humans ; Hyperglycemia ; Incidence ; Insulin ; Japan ; Male ; Mice ; Mice, Inbred ICR* ; Pancreas ; Plasma ; Streptozocin ; United States

PURPOSE: Recently, the Liver Cancer Study Group of Japan classified intrahepatic cholangiocarcinoma into three types: mass forming type, periductal infiltrating type and intraductal growth type. The clinical features of these three types are not well known. The purpose of this study was to define the clinical features of intrahepatic cholangiocarcinoma according to gross morphology. METHODS: We retrospectively reviewed the clinical records of 98 patients with intrahepatic cholangiocarcinoma who had undergone surgery at the Department of Surgery, Seoul National University Hospital from January 1980 to December 1998. The tumors were classified into mass forming type (MF, n=42), periductal infiltrating type (PI, n=22), intraductal growth type (IG, n=21) and Mixed type (n=13) by gross appearance. RESULTS: There were no differences in age, sex ratio, symptoms or laboratory findings. Intrahepatic stones were highly associated with the PI type (31.8% vs 2.4% in MF p=0.02). Hepatitis B surface antigen was more frequently found in the MF type (21.4% vs 4.5% in PI, 4.8% in IG, p=0.04). The size of tumor in the MF type was larger than those of the PI and IG types. In PI type, the rate of lymph node metastasis was higher (45.5% vs 19% in MF, 0% in IG, p=0.01). In IG type, the tumors were associated with adenomatous hyperplasia at a 95% rate. The cumulative five year survival rate of the MF and IG types were 23.3% and 76.2% (p<0.001), respectively. There were no five year survivors in the PI type. CONCLUSION: Intrahepatic cholangiocarcinoma has quite different clinical features and prognoses according to the grosstypes. Therefore we must choose appropriate treatment strategies according to gross type.