Bioartificial Liver System using a Fluidized-Bed Bioreactor

PURPOSE: Acute fulminant hepatic failure (FHF) is associated with high mortality. Recent studies have shown that a liver support system based on viable hepatocytes can prolong life in animal models of FHF and also in some FHF patients who were successfully bridged to liver transplantation. To be applied in humans, the bioartificial liver (BAL) system should have sufficient liver cell mass to provide adequate bioactive support. The most widely investigated bioreactor at present is based on hollow fiber membrane. However, it is difficult to build a scaledup module of this model. We devised a fluidized-bed bioreactor that is packed with isolated porcine hepatocytes, and these hepatcytes are immobilized in Ca-alginate hydrogel. METHODS: We isolated fresh porcine hepatocytes using a 2-step collagenase perfusion method, and they were suspended in 1.5% alginate solution. Through a drop-generator, this mixture was gelled in 135mM Cacl2. The resulting spherical beads (mean size: 500 micrometer) were embedded in a module. An average of 2x10(10) hepatocytes were present in the module. The efficacy of our design was tested in pigs that had undergone total hepatic devascularization and portocaval shunt. RESULTS: The BAL-treated group showed a significantly lower ammonium build-up rate compared to the control group (598.6+/-344.2 microgram/dl vs 1937.6+/-744.1 microgram/dl, respectively, at 8 hours after connecting to BAL). In addition, the intracranial pressure was well controlled in the BAL-treated group, whereas the control group showed a progressive increase of the intracranial pressure (16.9+/-1mmH2O vs 21.9+/-2.6mmH2O, respectively, at 8 hours after connecting to BAL). CONCLUSION: Our bioartificial liver system is a fluidized-bed bioreactor packed with immobilized porcine hepatocytes, and it seems to be a more effective scaled-up module.

Effect of Antibiotics on the Survival of Human Hepatocellular Carcinoma Cells under Hypoxic Conditions

PURPOSE: Antibiotics that kill or suppress the growth of bacteria also affect tumors directly or indirectly. The authors aimed to show whether some antibiotics can improve cancer cell survival under hypoxic conditions, and how the antibiotics improve the cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown at 1% oxygen concentration. Cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured at different incubation times, in the absence or presence of aminoglycosides, tetracyclines, quinolones, penicillins, cephalosporins, sulfonamides, or chloramphenicols. DNA fragmentation assay was performed to study the mechanism how some antibiotics improve the cell survival under hypoxic conditions. RESULTS: Of the antibiotics tested, only aminoglycosides, tetracyclines, quinolones and the chloramphenicol improved cell survival under hypoxic conditions. Geneticin (G418), an aminoglycoside chosen as an example, improved cell survival even if glucose in the medium was completely consumed. At the same time, the appearance of DNA ladder was delayed in the presence of geneticin, which was also the same for the other antibiotics that improved cell survival under hypoxic conditions. CONCLUSION: Some antibiotics improved hepatocellular carcinoma cells under ischemic conditions by inhibiting apoptosis. The results implies that the antibiotics might adversely affect solid tumors, by improving cancer cell growth where hypoxic or ischemic conditions occur in the core region. Therefore, we might be cautious in choosing antibiotics for cancer patients with solid tumors, especially when the patients should be treated with antibiotics for a long time.

The Comparative Results of Radiofrequency Ablation versus Surgical Resection for the Treatment of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC. METHODS: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups. RESULTS: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups. CONCLUSIONS: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results.

Idiosyncratic Portal Collateral Circulation during Hepatic Inflow Occlusion / 한국간담췌외과학회지

PURPOSE: Acute ligation of the portal vein in animals results in the pooling of blood in the splanchnic bed, and this is followed by rapid cardiovascular collapse and death. However, humans can withstand portal inflow occlusion because of portal collateral circulation. We tried to prove the development of portal collateral circulation for acute portal inflow occlusion through serial measurements of the portal pressure. METHODS: Our study was done on 187 patients who under went liver resection using portal triad clamping (PTC). We inserted a catheter into the right gastroepiploic vein and we measured the portal pressure before PTC, after PTC and just before the reperfusion of the last clamping. RESULTS: During liver resection, the portal pressure gradually decreased by 61.8 mmH2O in the normal liver group, 71.1 mmH2O in the chronic hepatitis group and 43.0 mmH2O in the cirrhosis group because of the development of collateral circulation. The differences among the three groups had no statistical significance. Moreover, there was no difference in the portal pressure decrease between the intermittent and continuous clamping groups. However, the decrease of portal pressure in the 21 patients with varices was much less than the decrease of portal pressure in those patients without varices (10 mmH2O vs. 62.7 mmH2O, p=0.008). In the more recent 20 cases, we additionally measured the portal pressure 15 minutes and 30 minutes after PTC. The pressure dereased rapidly for the first 15 minutes and the degree of pressure decrease after 15 minutes was minimal. CONCLUSION: The gradual decrease of portal pressure during PTC suggests the development of portal collateral circulation. This enables the patients to better tolerate liver ischemia during liver resection or transplantation. Most of the collateral circulations seemed to develop within the first 15 minutes of PTC.

A Comparison of the Clinicopathologic and Prognostic Differences in Patients Who Underwent Hepatic Resection with Hepatitis B- versus Hepatitis C-related Hepatocellular Carcinoma / 한국간담췌외과학회지

BACKGROUND/AIMS: The surgical outcomes for patients with HCC according to different hepatitis viral status have been inconsistently reported. This study evaluated the clinico-pathological and prognostic differences in patients with HBV- and HCV-related HCC. METHODS: Two hundred and eleven patients with HCC who underwent curative hepatic resection were categorized into three groups according to viral status: Group I (Hbs Ag (+) HCV Ab (-), n=116); Group II (Hbs Ag (-) HCV Ab (+), n=74); Group III (Hbs Ag (-) HCV Ab (-), n=17). The clinical manifestations, pathologic features, and treatment outcomes were compared. RESULTS: The average age at onset of HCV-related HCC is older than that of HBV-related HCC. Most HCV-related HCC is associated with liver cirrhosis as reflected by lower albumin level, platelet count, higher ICG R15 value, ALT levels. and frequency of minor resection (P<0.05). The incidence of portal vein invasion or intrahepatic metastasis did not differ among groups. In addition, HCV Ab (+) group had significantly lower disease free survival rates (P<0.05). CONCLUSION: This study suggests that the patients with HCV- related HCC have poorer liver function with more frequent recurrence.

The Effect of Preoperative Transcatheter Arterial Chemoembolization in Hepatocellular Carcinoma (prospective study) / 한국간담췌외과학회지

BACKGROUND/AIMS: The effect of preoperative Transcatheter Arterial Chemoembolization (TACE) in the management of Hepatocellular carcinoma (HCC) has remained controversial and lack of prospective study. To investigate the impact of preoperative TACE, we have performed a prospective study in HCC patients with tumor size below 5 cm. METHODS: From November 1998 through March 2002, 126 patients with HCC who had been referred for surgical resection were prospectively allocated to Group I (preoperative TACE, n=42) and Group II (simple hepatic angiography only, n=38). Patients who were underwent noncurative hepatic resection (n=4) were excluded and the groups with large tumor mass (above 5 cm) with or without TACE (n=64) were excluded from this analysis due to insufficient number. The impact of preoperative TACE on incidence of complication as well as long term overall and disease free survival rate were analyzed. RESULTS: Preoperative demographics and intraoperative data were compatible between two groups. There were no difference in complication rates between two groups. The 3 year survival rate of Group I and Group II were 88.10% and 58.32% respectively. The 3 year disease-free survival rate of Group I and Group II were 40.14% and 34.89% respectively. The 3 year overall rate was significantly high in Group I (p=0.0348), disease-free survival rate did not show difference between two groups (p=0.6132). CONCLUSION: Preoperative TACE can be done safely and showed improved overall survival rate in this prospective study, however fruther prospective study with longer period of follow up will be necessary to prove the effect of preoperative TACE.

Outcome of the Liver Resection of the Hepatocellular Carcinoma under Milan Criteria

PURPOSE: Liver resection (LR) has been the treatment of choice for hepatocellular carcinoma (HCC), but resection and survival rates remain low, and recurrence is common in cirrhotic patients. This study was designed to evaluate the outcome after resection of potentially transplantable early HCCs and compare it with that for liver transplantation (LT) as reported in the literature. METHODS: We studied 109 patients with HCC under the Milan criteria who underwent LR at Kyungpook National University Hospital from September 1997 to May 2002. The patients were divided into two groups: group A had a single tumor and group B had two or three tumors. RESULTS: The mean age was 56.1+/-8.1 years and the male-to-female ratio was 4.7: 1. Most of the patients had chronic liver disease due to viral hepatitis, but had preserved hepatic function. Overall survival rates (SR) at 1, 2, 3, and 4 years were 86.7, 69.4, 44.8, and 13.3%, respectively, and the corresponding disease-free survival rates (DFSR) were 74.2, 53.8, 41.6, and 23.7%. SR and DFSR were not significantly different between the two groups, although group B tended to have lower SR and DFSR. At a median follow-up of 25.3 months, 52 patients experienced recurrence, most of whom had intrahepatic recurrence within 2 years after resection. At the time of the diagnosis of recurrence, 34 patients were considered eligible for LT. CONCLUSION: Although most of the patients had preserved hepatic function, LR of early HCC showed low survival rates and high recurrence rates compared with those after LT reported in the literature and in our experiences. Therefore, in the absence of limiting factors, LT may be the better option for surgical treatment of patients with early HCC, even when preserved hepatic function is maintained.

Concomitant Splenectomy during Hepatectomy in Patients with Liver Cirrhosis and Thrombocytopenia / 한국간담췌외과학회지

BACKGROUND/AIMS: Resection of hepatocellular carcinoma in patients with liver cirrhosis and thrombocytopenia is risky. The benefit of concomitant splenectomy in cirrhotic patients is controversial. METHODS: To evaluate the efficacy of concomitant splenectomy in patients with liver cirrhosis and thrombocytopenia, 13 cirrhotic patients with thrombocytopenia (platelet count< or =80,000/mm3) were divided by two groups (Group I: the patients without concomitant splenectomy during hepatectomy, Group II: the patients with concomitant splenectomy). Intraoperative and postoperative parameters were retrospectively reviewed. RESULTS: Group II patients needed less amount of postoperative blood transfusion (Group I: 178.3+/-150 ml PRC in 3 patients, Group II: 107.1+/-100 ml in 2 patients, p=0.012, p= 0.041) and the platelet count was elevated to above 250,000/mm3 (p=0.003) and showed lower serum bilirubin level (p=0.037) within 1 week of operation in group II patients. CONCLUSION: The concomitant splenectomy during in patients of liver cirrhosis with thrombocytopenia may improve liver function and elevate platelet count.

Transduodenal Ampullectomy in Ampullary Neoplasm

PURPOSE: Periampullary malignant tumors become symptomatic at an early stage because of their particular location. For this reason, radical resection is possible in the majority of cases. Periampullary tumors can be removed either by a local resection, as performed by Halsted in 1899, or by a radical pancreaticoduodenectomy, as performed by Whipple et al. in 1935. Both techniques have been used, and their respective places in the treatment of benign or malignant periampullary tumors has been the subject of constant debate. Therefore, we reviewed the cases of four patients who had undergone a transduodenal ampullectomy for an ampullary tumor which was confined to the ampulla of Vater. METHODS: The clinical records of 4 patients who undergone a transduodenal ampullectomy were reviewed. All patients were diagnosed as having an ampullary mass based on gastroduodenoscopy, endoscopic retrograde cholangiopancreatography, or both. Clinical presentation, comparison of pathologic findings of preoperative endoscopic biopsy, operative frozen section, final pathologic examination, complications, follow-up period, and recurrence were reviewed. RESULTS: The two men and the two women studied had a median age of 59.3 (range, 49 to 64 years). Among the four patients who underwent a transduodenal ampullectomy, an adenocarcinoma was found at final pathologic examination in two patients with preoperative diagnoses of a villotubular adenoma and a villous adenoma, respectively. The other two cases were diagnosed as tubular adenomas at final pathologic examination as they had been at the preoperative diagnosis. No evidence of disease was observed in any of the four patients on follow-up at 29 months, 30 months36 months, and 4 months. None of these patients had major complications in the immediate postoperative period, transient hyperamylasemia without clinical significance developed in two patients. CONCLUSION: The transduodenal ampullectomy is a valuable tool in the treatment of ampullary lesions. The result of local excision of the Vater for ampullary tumors appears satisfactory, and this procedure may be particularly indicated for benign tumors, as well as for older or high-risk patients whose malignant lesions are confined to the ampulla of Vater. However, the selection of this procedure required judicious decision making and precise technique and should involve an experienced team of pathologists and surgeons. As a result, for patients in whom it is indicated, a transduodenal ampullectomy is an alternative to the pancreaticoduodenectomy and has good long-term results.

Pseudo-obstruction of the Portal Vein in Hepatic Transplantation and Liver Resection: Case Reports / 한국간담췌외과학회지

Confirmation of patency of the portal vein by either ultrasound or angiography is important for evaluating patients considered for living-related liver transplant(LRLT) and liver resection(LR). Portal vein thrombosis(PVT) in LRLT necessitates planning for a technically difficult operation because consideration must be given to obtaining an alternative for splanchnic inflow. When performing LR for hepatocellular carcinoma(HCC), portal vein tumor thrombus was usually thought of as a poor prognositic factor for tumor recurrence. Recently, we experienced two cases of pseudo-obstruction of the portal vein, one in LRLT and the other in LR. In the case of LRLT, a 16-month-old female patient was diagnosed as congenital biliary atresia. PVT had been preoperatively suggested, but the vein was actually open. The patient was successfully transplanted using the left lateral segment of the donor with ordinary portal vein anastomosis and the postoperative course was uneventful except for mild acute rejection episodes. In the case of LR, a 60-year-old male patient presented with incidental symptoms. Preoperative ultrasonography, computed tomography, and angiography showed a 9x8cm-sized mass in the right lobe of the liver with obstruction of the right portal vein, which suggested tumor thrombus. However, the operation disclosed the patency of the portal vein and a right lobectomy was subsequently done. Because of the scanty blood flow of the portal vein due to arterio-portal shunt, PVT was preoperatively suggested. Our experience indicates that more sophisticated image studies are needed for evaluating portal vein patency in the patient who needs hepatic transplant as well as liver resection, and that the surgeon should not hesitate to procede to operative procedures even though conventional studies suggest PVT.

A Case of Bleeding Vascular Malformation of the Jejunum

Vascular malformations are known by several names, such as angiodysplasia, vascular ectasia, arteriovenous malformation, and telangictasia. Arteriovenous malformations may occur anywhere in the gastrointestinal tract. The large intestine is the most commonly involved location, usually on the right side. Arteriovenous malformations, which consist of enlarged, tortuous and dilated, often thin-walled blood vessels, usually occur in the submucosa or mucosa. Occasionally, they can cause recurrent and even massive hemorrhage. The authors treated a case of angiodysplasia in the upper jejunum, which caused massive bleeding. A 67-year-old female patient was admitted because of massive lower gastrointestinal bleeding. The bleeding point was found by angiography, injection of methylene-blue dye, and intraoperative endoscopy. The bleeding lesion in jejunal segment was resected, and end-to-end anastomosis was performed. The postoperative course was uneventful, and the patient was discharged on the 10th postoperative day.

Clinical Analysis of 36 Appendectomies in Pregnant Women

Appendicitis is the most common acute abdominal condition that requires an operation during pregnancy. Variable clinical presentations in pregnant women make the diagnosis of acute appendicitis difficult, delay operative intervention, and cause many fetal or maternal complications. From January 1990 through December 1996, 36 appendectomies were performed on pregnant women at our hospital. This is a retrospective analysis of our cases compared to control group. 1. Thirty six pregnant women (0.1 %) from all labor cases during this period underwent appendectomies, representing 10.3 % of all appendectomies in women of childbearing age. 2. The age distribution was 21-25 (38.9 %), 26-30 (55.6 %) and 31-35 (5.5 %) years, which was similar to the age distribution of the non-pregnant group. 3. Acute appendicitis during pregnancy was most common in the spring. 4. No significant difference in the occurrences of various symptoms between the pregnant and the non-pregnant groups was observed. 5. The pregnant patients visited our hospital earlier, but underwent operations later, than the non-pregnant women. (p 0.05) 8. No significant differences between the pregnant and the non-pregnant groups were noticed in terms of operation time and types of anesthesia. (p > 0.05) 9. The wound infection rates were similar for the pregnant (16.7 %) and the non-pregnant (17.4 %)groups, but there were 3 fetal losses (8.3 %)from pregnant patients after their appendectomies. 10. The mean hospital stay was longer for the pregnant patients (7.6 days) than for the non-pregnant group (6.2 days).

Microcystic Adenoma of Pancreas: Case report

Microcystic adenoma, also known a glycogen rich or serous cystadenoma is very rare and usually presents grossly a large multiloculated mass, and the individual cystic cavities being small and filled with a clear(serous) fluid. The cut surface is spongy in appearance. Microscopically, cysts are composed of multiple small cysts lined by small, flat or cuboidal cells containing abundant glycogen but only an insignificant amount of mucin. The microcystic cystadenoma is benign, but mucinous cystadenoma is potentially malignant,so the two cysts should be differentiated, and should never be treated by-pass sugery in the case of mucinous cystadenoma. A 43-year-old female was admitted to this hospital with the palpable epigastric mass, postprandial nausea and weight loss for the preceeding 2 years, and increase in size in the past recent 8 months. Upper G.I series and ultrasonographic studies revealed a huge mass in the pancreatic head portion. Exploratory laparotomy was performed, which disclosed a round adult fist sized multicystic mass in the pancreatic head. Pancreaticoduodenectomy was performed. In gross specimen examination, the mass was 9x7.5x7 cm in size, the outer surface was smooth and grayish white, the cut surface was sponge- like with multiple small cysts. The content of cysts was serous fluid. Microscopically, the cystic mass was composed of small cysts, in which the lining of the cell shows flat and mild secretory activity. There was no malignant evidence. The patient was discharged uneventfully on the 22nd postoperative days.

One Case of Mucin Hypersecreting Papillary Adenocarcinoma of the Left Intrahepatic Duct / 한국간담췌외과학회지

A patient with mucin hypersecreting papillary adenocarcinoma of intrahepatic bile duct had jaundice and symptoms of cholangitis. Radiologic evaluations-ultrasonography and computerized tomographyrevealed passage disturbance of bile at the level of the distal common bile duct or ampulla of Vater. But, primary lesion was located at left intrahepatic duct proximal to the ductal dilatation. This peculiar phenomenon confused clinicians. A 59-year-old man was referred to our hospital for evaluation of recurrent cholangitis. Ultrasonogram, computerized tomogram and endoscopic retrograde cholangiography disclosed dilatation and amorphous filling defect extending from left intrahepatic bile duct to common bile duct suggesting choledochal cyst(type IVa). Preoperative endoscopic examination showed spillage of mucin through duodenal papilla. Abdominal exploration revealed mucin hypersecreting papillary adenocarcinoma of left intrahepatic duct and dilated distal common bile duct filled with tenacious mucin. Left hepatic lobectomy and Roux-en-Y hepaticojejunostomy were performed.

Hybrid Bioartificial Liver

No abstract available.

The Comparative Analysis of Therapeutic Results between a Laparoscopic Cholecystectomy and an Open cholecystectomy in Acute Cholecystitis

Laparoscopic cholecystectomy is now the treatment of choice for the surgical treatment of uncomplicated cholelithiasis. Application of this rule in acute cholecystitis is still controversal, in spite of the eagerness of the experts in the field of laparoscopic surgery.The role of a laparoscopic cholecystectomy in patients with acute cholecystitis was evaluated by comparing clinical data from a laparoscopic cholecystectomy group with those from an open cholecystectomy group.Clinical data for 24 patients with acute cholecystitis who underwent a laparoscopic cholecystectomy in the mid 1990, were compared with data for 31 patients with acute cholecystitis who went through an open cholecystectomy in the early 1990s. Preoperative clinical data showed no statistical difference between the laparoscopic cholecystectomy group and the open cholecystectomy group. The operating time, the postoperative hospitalization, the duration of drainage, and the returning time of intestinal motility were shorter in laparoscopic cholecystectomy group, and the incidence of wound infection was lower. However, the incidence of bile duct or bowel injury was larger in the laparoscopic cholecystectomy group. Laparoscopic cholecystectomy can be performed safely in most patients with acute cholecystitis, in spite of the difficulties in observation, traction and dissection, which can be overcome with complete understanding, confirmation of the biliary anatomy, and sufficient experience.