Liver transplantation has become a lifesaving procedure for patients who have chronic end-stage liver disease and acute liver failure. The satisfactory outcome of liver transplantation has led to insufficient supplies of deceased donor organs, particularly in East Asia. Hence, East Asian surgeons are concentrating on developing and performing living-donor liver transplantation (LDLT). This review article describes an update on the present status of liver transplantation, mainly in adults, and highlights some recent developments on indications for transplantation, patient selection, donor and recipient operation between LDLT and deceased-donor liver transplantation (DDLT), immunosuppression, and long-term management of liver transplant recipients. Currently, the same indication criteria that exist for DDLT are applied to LDLT, with technical refinements for LDLT. In highly experienced centers, LDLT for high-scoring (>30 points) Model of End-Stage Liver Disease (MELD) patients and acute-on-chronic liver-failure patients yields comparably good outcomes to DDLT, because timely liver transplantation with good-quality grafting is possible. With increasing numbers of liver transplantations and long-term survivors, specialized attention should be paid to complications that develop in the long term, such as chronic renal failure, hypertension, diabetes mellitus, dyslipidemia, obesity, bone or neurological complications, and development of de novo tumors, which are highly related to the immunosuppressive treatment.
Liver transplantation; Deceased donor liver transplantation; Living donor liver transplantation
In this study, we investigated the therapeutic potential of regulated negative pressure vacuum-assisted wound therapy for inguinal lymphatic complications in critically ill, liver transplant recipients.
The great saphenous vein was harvested for hepatic vein reconstruction during liver transplantation in 599 living-donor liver transplant recipients. Fourteen of the recipients (2.3%) developed postoperative inguinal lymphatic complications and were treated with negative pressure wound therapy, and they were included in this study.
The average total duration of negative pressure wound therapy was 23 days (range, 11 to 42 days). Complete resolution of the lymphatic complications and wound healing were achieved in all 14 patients, 5 of whom were treated in hospital and 9 as outpatients. There was no clinically detectable infection, bleeding or recurrence after an average follow-up of 27 months (range, 7 to 36 months).
Negative pressure wound therapy is an effective, readily-available treatment option that is less invasive than exploration and ligation of leaking lymphatics and provides good control of drainage and rapid wound closure in critically ill patients.
Wound; Lymphatic; Complication; Negative pressure; Therapy
Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is characterized by a severe idiosyncratic reaction including rash and fever, often with associated hepatitis, arthralgias, lymph node enlargement, or hematologic abnormalities. The mortality rate is approximately 10%, primarily owing to liver failure with massive or multiple disseminated focal necrosis. Here, we report a case of a 14-year-old girl treated with vancomycin because of a wound infection by methicillin-resistant Staphylococcus aureus, who presented with non-specific symptoms, which progressed to acute liver failure, displaying the hallmarks of DRESS syndrome. With the presence of aggravated hepatic encephalopathy and azotemia, the patient was refractory to medical treatments, she received a living-donor liver transplantation, and a cure was achieved without any sign of recurrence. Vancomycin can be a cause of DRESS syndrome. A high index of suspicion and rapid diagnosis are necessary not to miss this potentially lethal disease.
DRESS syndrome; Vancomycin; Acute liver failure; Liver transplantation
Pediatric liver transplantation is the standard of care for treatment of liver failure in children. The aim of this study was to identify the characteristics of pediatric liver transplantation in centers located in Korea and determine factors that influence outcomes. This retrospective study was performed using data from between 1988 and 2010 and included all recipients 18 yr old and younger who underwent pediatric liver transplantation in Korea during that period. Our data sources were hospital medical records and the outcome measure was overall patient survival. Univariate and multivariate statistical analyses were undertaken using the Cox proportional hazards model. Five hundred and thirty-four pediatric liver transplantations were performed in 502 children. Median age and average pediatric end-stage liver disease (PELD) score were 20 months and 18 point, respectively. Biliary atresia (57.7%, 308/534) was the most common cause of liver disease. Eighty-two (15.3%) were deceased donor liver transplantations and 454 (84.7%) were living donor liver transplantations. Retransplantation was performed in 32 cases (6%). Overall, 1-, 5-, and 10-yr patient survival rates were 87.8%, 82.2%, and 78.1%, respectively. In multivariate analysis, independent significant predictors of poor patient survival were chronic rejection and retransplantation. This study presents the epidemiologic data for nearly all pediatric liver transplantation in Korea and shows that the independent prognostic factors in patient survival are chronic rejection and retransplantation.
Liver Transplantation; Children; Survival; Rejection; Retransplantation
Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.
Liver transplantation; Acute-on-chronic liver failure; Erythropoietic protoporphyria
The surface of proteins can be charged with zinc ions and the anomalous signals from these zinc ions can be used for structure determination of proteins.
Zinc is a suitable metal for anomalous dispersion phasing methods in protein crystallography. Structure determination using zinc anomalous scattering has been almost exclusively limited to proteins with intrinsically bound zinc(s). Here, it is reported that multiple zinc ions can easily be charged onto the surface of proteins with no intrinsic zinc-binding site by using zinc-containing solutions. Zn derivatization of protein surfaces appears to be a largely unnoticed but promising method of protein structure determination.
zinc anomalous scattering; phasing; Zn derivatization
The antioxidant activities of fermented red ginseng (FRG) were investigated in vitro and in vivo. The contents of total polyphenol and total flavonoid in FRG extracts were 17.01±2.00 μg/mg and 18.42±3.97 μg/mg, respectively. These extracts were capable of directly scavenging α, α-diphenyl-picrylhydrazyl free radicals. The antioxidative effects of the FRG extracts in streptozotocin (STZ)-induced diabetic rats were also investigated. The activities of plasma alanine transaminase, aspartate transaminase, and γ-glutamyltransferase were significantly decreased by extract administration as compared to an STZ control group. Hepatic glutathione content depleted by STZ treatment was significantly increased by treatment of the FRG extracts, but the elevation of lipid peroxide content induced by STZ was significantly decreased by the extracts. Activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase decreased after STZ-treatment were recovered by the treatment of the FRG extracts. These results indicate that FRG extracts have antioxidative effets in STZ-induced diabetic rats.
Panax ginseng; Red ginseng; Fermentation; Antioxidant effect; Streptozotocin
Hepatitis B virus X (HBx) protein has been known to play an important role in development of hepatocellular carcinoma (HCC). The aim of this study is to find out whether HBx protein expression affects antiproliferative effect of an epidermal growth factor receptor-tyrosine kinase (EGFR-TK) inhibitor and a MEK inhibitor in HepG2 and Huh-7 cell lines. We established HepG2 and Huh-7 cells transfected stably with HBx gene. HBx protein expression increased pERK and pAkt expression as well as β-catenin activity in both cells. Gefitinib (EGFR-TK inhibitor) inhibited pERK and pAkt expression and β-catenin activity in both cells. Selumetinib (MEK inhibitor) reduced pERK level and β-catenin activity but pAkt expression was rather elevated by selumetinib in these cells. Reduction of pERK levels was much stronger with selumetinib than gefitinib in both cells. The antiproliferative efficacy of selumetinib was more potent than that of gefitinib. However, the antiproliferative effect of gefitinib, as well as selumetinib, was not different between cell lines with or without HBx expression. Signal pathway activation by HBx might not be strong enough to attenuate the antiproliferative effect of EGFR-TK inhibitor. Future experiments are needed to understand the role of HBx protein expression in HCC treatment using molecular targeting agent.
Hepatocellular Carcinoma; HBx protein; Gefitinib; Selumetinib; EGFR; MEK
Endometritis is one of the primary reasons for reproductive failure. In order to investigate endometritis-associated marker proteins, proteomic analysis was performed on bovine endometrium with endometritis. In bovine endometritis, desmin, α-actin-2, heat-shock protein (HSP) 27, peroxiredoxin-6, luteinizing hormone receptor isoform 1, collectin-43 precursor, deoxyribonuclease-I (DNase-I), and MHC class I heavy chain (MHC-Ih) were up-regulated. In contrast, transferrin, interleukin-2 precursor, hemoglobin β subunit, and potassium channel tetramerisation domain-containing 11 (KCTD11) were down-regulated in comparison to normal endometrium. The proteomic results were validated by semiquantitative-PCR and immunoblot analysis. The mRNA levels of desmin, transferrin, α-actin-2, HSP27, KCTD11, and MHC-Ih were up-regulated by over 1.5-fold, and showed a pattern similar to their proteomic profiles. Desmin and α-actin-2 protein showed positive correlations between proteomic analysis and immunoblot analysis. These results suggest that desmin and α-actin-2 may play important roles in endometritis-related function, and could be useful markers for the diagnosis of bovine endometritis.
Actin; Desmin; Endometritis; Proteomics
The aim of this study was to evaluate the infectious complications after living donor liver transplantation (LDLT) in children. We enrolled 95 children (38 boys and 57 girls) who underwent LDLT from 1994 to 2004. The median age was 22 months (range, 6 months to 15 yr). We retrospectively investigated the proven episodes of bacterial, viral, and fungal infection. There occurred 150 infections in 67 (70%) of 95 patients (1.49 infections/patient); 74 in 43 patients were bacterial, 2 in 2 were fungal, and 74 in 42 were viral. The most common sites of bacterial infection were the bloodstream (33%) and abdomen (25%). Most of the bacterial infections occurred within the first month after LDLT. Bacterial and fungal infections did not result in any deaths. The most common causes of viral infection were Epstein-Barr virus in 37 patients and cytomegalovirus in 18. Seven of the 14 deaths after LDLT were associated with viral infection. Our study suggests that infection is one of the important causes of morbidity and mortality after LDLT. Especially careful monitoring and management of viral infections is crucial for improving the outcome of LDLT in children.
Infection; Liver Transplantation; Living Donors; Child
EC-18 (monoacetyldiacylglyceride) stimulates T cell production of IL-2, IL-4, IL-12, IFN-γ, and GM-CSF in vitro. To study the effects of these cytokines stimulated by EC-18 on cancer cells, we applied hamster biliary cancer model, a difficult cancer to treat. Cancer (KIGB-5) cells were given intravenously to produce hematogenous metastatic lung lesions which were treated with EC-18 at 10, 25, and 50 mg/kg/day respectively. The fourth group was untreated control. At 4th, 8th, and 12th week the lungs were examined. EC-18 treated groups showed only a few microscopic lung lesions and no evidence of metastatic lesion with highest dose whereas widespread gross lung lesions were observed in untreated control. To investigate whether the anti-tumor effect of EC-18 is associated with suppression of tumor cell Toll-like receptor 4 (TLR-4) expression in addition to stimulation of the immune cells, KIGB-5 cells were exposed to LPS with or without EC-18. TLR-4 mRNA and protein expression, measured by reverse transcriptase PCR (RT-PCR), real-time quantitative PCR and western blot analysis, showed suppression of TLR-4 expression in KIGB-5 cells treated with EC-18 compared with control. In conclusion, EC-18 has a significant anti-tumor effect in this experimental model of biliary cancer suggesting potential for clinical application to this difficult cancer.
EC-18; Anti-Tumor Effect; TLR-4; Biliary Cancer
Glycogen storage disease type IV (GSD-IV) is an autosomal recessive disease caused by a deficient glycogen branching enzyme (GBE), encoded by the GBE1 gene, resulting in the accumulation of abnormal glycogen deposits in the liver and other tissues. We treated a 20-month-old girl who presented with progressive liver cirrhosis and was diagnosed with GSD-IV, as confirmed by GBE1 gene mutation analysis, and underwent living related heterozygous donor liver transplantation. Direct sequencing of the GBE1 gene revealed that the patient was compound heterozygous for a known c.1571G>A (p.Gly264Glu) mutation a novel c.791G>A (Arg524Gln) mutation. This is the first report of a Korean patient with GSD-IV confirmed by mutation analysis, who was treated successfully by liver transplantation.
Glycogen storage disease type IV; GBE1; DNA analysis; Liver transplantation; Living donors
Orthotopic liver transplantation (OLT) is the best available option for early hepatocellular carcinoma (HCC), although its application is limited by stringent selection criteria, costs, and deceased donor graft shortage, particularly in Asia, where living donor liver transplant (LDLT) has been developed.
This article reviews the present standards for patient selection represented by size-and-number criteria with particular references to Milan Criteria and novel prediction models based on results achieved in patients exceeding those limits, with consideration of the expanded indication represented by the UCSF Criteria.
The expected outcomes after deceased donor liver transplant (DDLT) or LDLT are favorable if predetermined selection criteria are applied. However, selection bias, difference in waiting time, and ischemia-regeneration injuries of the graft among DDLT vs LDLT may influence long-term results. In the article, the differences between East and West in first-line treatments for HCC (resection vs transplantation), indications, and ethics for the donor, are summarized as well as possible novel predictors of tumor biology (especially DNA mutation and fractional allelic loss, FAI) to be considered for better outcome prediction.
Liver transplantation remains the most promising product of modern surgery and represents a cornerstone in the management of patients with HCC.
Hepatocellular; Hepatoma; Transplantation
Major resection of cirrhotic livers can result in hepatic failure, but no supportive treatment has been found to be generally effective. We successfully treated a 63-year-old woman with post-hepatectomy liver failure with plasmapheresis. Following right hepatectomy, the initial postoperative recovery of liver function was favorable, except for ascites. One month later, however, the amount of drained ascites increased up to 2 l/day. In addition, serum cholesterol concentration gradually decreased to around 30 mg/dl, and serum total bilirubin rose to 11.1 mg/dl. Plasmapheresis was performed, and after just 2 sessions, serum cholesterol level was rapidly corrected and prothrombin time was restored. After 3 sessions of plasmapheresis, the usual rebound rise of serum bilirubin disappeared, and the amount of ascites drained also decreased slowly. The patient underwent a total of 5 sessions of plasmapheresis over 2 weeks, after which liver function improved slowly, and she was finally discharged 72 days after liver resection. Mild ascites requiring diuretic therapy persisted over 3 months. She is doing well to date 10 months after liver resection without tumor recurrence or hepatic decompensation. This limited experience suggests that plasmapheresis can be a useful liver support for post-hepatectomy liver failure.
Plasmapheresis; Hepatectomy; Liver cirrhosis; Hepatic failure
We report a rare case of lower limb swelling due to compression of the superficial femoral vein by a solitary deep femoral artery aneurysm. The patient was a 58-year-old man presenting with acute swelling of the right lower limb caused by deep venous thrombosis. A multi-detector computed tomographic scan (CT) confirmed the diagnosis of a deep femoral artery aneurysm and revealed no evidence of aneurysms or occlusive lesions in the other arteries. Aneurysmectomy and ligation of the deep femoral artery were successfully performed. Preoperative multi-detector CT scanning is a valuable, non-invasive diagnostic tool to delineate not only the state of the aneurysm, but also that of the distal arterial tree.
Deep femoral artery; aneurysm; computed tomography
Torsion of the gallbladder is a rare entity that is difficult to diagnose preoperatively. The condition occurs most often in the elderly. Although its etiology is unknown, a constant finding is the presence of the gallbladder on a mobile mesentery (floating gallbladder). Torsion, or volvulus, of the gallbladder occurs when it twists axially, with the subsequent occlusion of bile and/or blood flow. Herein, a case of torsion of the gallbladder is presented where preoperative computed tomographic scan and laparoscopy were successfully used to diagnose and treat this condition without the usual requirement of open exploration. Given the possibility of laparoscopic cholecystectomy and the increasing incidence with which torsion of the gallbladder is being witnessed today, the importance of a preoperative computed tomographic scan is emphasized when there is a high index of clinical suspicion.
Torsion; gallbladder; computed tomography; x-ray; laparoscopy; cholecystectomy
In order to determine the influence of living donor liver transplantation (LDLT) on long-term growth, we studied the progress of 36 children who had survived more than 5 yr after LDLT from 1994 to 1999. The median age at the transplantation was 1.5 yr (range: 6 months-15 yr) and the median follow-up period was 6.5 yr (range: 5-9 yr). A height standard deviation score (zH) was analyzed for each patient according to medical records. Significant catch-up growth occurred within 2 yr after LDLT with a mean zH changing from -1.2 to 0.0 and was maintained for up to 7 yr post-transplantation (zH-0.1). Younger children (<2 yr) were more growth-retarded at the time of LDLT, but showed higher catch-up growth rates and their final zH was greater than that of older children. Children with liver cirrhosis were more growth-retarded at the time of LDLT, but showed significant catch-up growth and their final height was similar to children with fulminant hepatitis. Growth in children who experienced significant hepatic dysfunction after LDLT was not significantly different from those without graft dysfunction. There was no difference between the types of immunosuppressants used. Our finding suggests that LDLT can result in adequate catch-up linear growth, and this effect can persist even after 7 yr post-transplantation.
Living Donor; Liver Transplantation; Child; Growth
The purpose of this study was to evaluate the early outcome of endovascular management in patients with iliofemoral deep venous thrombosis (DVT) due to iliac vein compression syndrome (IVCS) and protein C and/or S deficiency. Between September 2000 and January 2003, catheter-directed thrombolysis was performed in 11 patients with a diagnosis of acute iliofemoral DVT: 7 with protein C and/or S deficiency and 4 without protein C and/or S deficiency. After thrombolysis, the diagnosis of IVCS was confirmed in 6 patients: 4 with protein C and/or S deficiency and 2 without protein C and/or S deficiency. Further intervention consisted of angioplasty and stent placement was performed. Four patients with IVCS and protein C and/or S deficiency were included in this study. The immediate technical and clinical success rates were 100% in all 4 patients. There were no complications or clinically detectable pulmonary emboli. This initial experience suggests that endovascular management of iliofemoral DVT due to IVCS in patients with protein C and/or S deficiency is safe and effective.
Thrombolytic Therapy; Venous Thrombosis; Protein C Deficiency; Protein S Deficiency
To analyze the causes of arterial bleeding after living donor liver transplantation (LDLT) and to evaluate the efficacy of transcatheter arterial embolization (TAE).
Materials and Methods
Forty-two sessions of conventional arteriography were performed in 32 of the 195 patients who underwent LDLT during the past 2 years. This was done in search of bleeding foci of arterial origin. TAE was performed with microcoils or gelatin sponge particles. The causes of arterial bleeding, the technical and clinical success rates of TAE and the complications were retrospectively evaluated.
Forty-two bleeding foci of arterial origin were identified on 30 sessions of arteriography in 21 patients. The most common cause of bleeding was percutaneous procedures in 40% of the patients (17 of the 42 bleeding foci) followed by surgical procedures in 36% (15/42). The overall technical and clinical success rates of TAE were 21 (70%) and 20 (67%) of the 30 sessions, respectively. The overall technical success rate of TAE for the treatment of bleeding from the hepatic resection margin, hepatic artery anastomotic site and hepaticojejunostomy was only 18% (2/11), whereas for the treatment of bleeding in the other locations the technical and clinical success rates of TAE were 100% and 95%, respectively. No procedure-related major complications occurred.
In the case of arterial bleeding after LDLT, percutaneous procedure-related hemorrhages were as common as surgery-related hemorrhages. There were technical difficulties in using TAE for the treatment of hepatic arterial bleeding. However, in the other locations, TAE seems to be safe and effective for the control of arterial bleeding in LDLT recipients.
Liver, transplantation; Arteries, therapeutic embolization; Hemorrhage; Surgery, complications
Aortoenteric fistula is one of the most challenging problems that confront the vascular surgeons. Controversy remains over the optimal treatment because of the continued publication of series with high mortality, amputation, and aortic disruption rates. A positive preoperative blood culture is the best predictor of mortality with increased amputation rates due to infection of the extra-anatomic bypass. Therefore, in selected cases with sepsis, a prudent management protocol is required. We report a 68-yr-old male presenting with a chronic primary aortoduodenal fistula extensively involving the duodenum and Gram-negative sepsis. We planned a staged operation. Initially, an emergency laparotomy and control of the aorta allowed stabilization of the patient, identification of the fistula, and direct in situ placement of the prosthetic graft followed by an en bloc resection of the aneurysm and the surrounding structures. After he recovered from sepsis and had been stabilized, a staged extra-anatomic bypass followed by transabdominal removal of the temporarily placed graft was done. This management plan will allow the highest success rate and may be a prudent management protocol for these difficult cases.
Aortic Aneurysm; Fistula; Duodenum; Sepsis; Surgery
With acupuncture treatment becoming an increasingly popular analgesic, there have been increasing reports on its associated complications. Although pneumothorax is the most frequently reported injury caused by acupuncture needles, infectious complications may not be uncommon. Most infectious complications show less serious clinical manifestations than pneumothorax, but retroperitoneal or intraabdominal abscess caused by acupuncture may be much more serious conditions. We experienced a 56-yr-old male diabetic patient presenting with serious retroperitoneal abscess after acupuncture treatments. Emergency operative drainage with adequate antibiotic therapy was performed. Bacterial culture of blood and closed pus specimens recovered Klebsiella pneumoniae. In addition to application of better knowledge on anatomy, appropriate antiseptic practice by practitioners will reduce many serious complications associated with acupuncture.
Postoperative leakage is a serious complication in patients after gastric surgery. It can lead to a rapid deterioration in the patient's condition and quality of life. Treatment is guided by the type of anastomosis and the patient's clinical status. The role of interventional radiology in gastrointestinal tract is evolving. Metallic stent placement has shown encouraging results for the palliation of gastrointestinal tract obstruction and fistula in malignant patients. We encountered a case of the leakage of jejunal end of Roux limb after total gastrectomy. This patient required a drainage procedure with long-term parenteral nutrition. We performed peroral placement of a covered metallic stent to avoid surgery and long-term parenteral nutrition, and he resumed adequate oral intake immediately after stent placement. This minimally invasive procedure is very promising for the treatment of a gastrointestinal fistula to avoid surgery and long-term parenteral nutritional support in selected cases.