• Title/Summary/Keyword: liver transplantation

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Current Trends and Recent Advances in Diagnosis, Therapy, and Prevention of Hepatocellular Carcinoma

  • Wang, Chun-Hsiang;Wey, Keh-Cherng;Mo, Lein-Ray;Chang, Kuo-Kwan;Lin, Ruey-Chang;Kuo, Jen-Juan
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3595-3604
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    • 2015
  • Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), descarboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Hepatic Vessel Segmentation using Edge Detection (Edge Detection을 이용한 간 혈관 추출)

  • Seo, Jeong-Joo;Park, Jong-Won
    • Journal of the Korea Society of Computer and Information
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    • v.17 no.3
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    • pp.51-57
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    • 2012
  • Hepatic vessel tree is the key structure for hepatic disease diagnosis and liver surgery planning. Especially, it is used to evaluate the donors' and recipients' liver for the LDLT(Living Donors Liver Transplantation) and estimate the volumes of left and right hepatic lobes for securing their life in the LDLT. In this study, we propose a method to apply canny edge detection that is not affected by noise to the liver images for automatic segmentation of hepatic vessels tree in contrast abdominal MDCT image. Using histograms and average pixel values of the various liver CT images, optimized parameters of the Canny algorithm are determined. It is more time-efficient to use the common parameters than to change parameters manually according to CT images. Candidates of hepatic vessels are extracted by threshold filtering around the detected the vessel edge. Finally, using a system which detects the true-negatives and the false-positives in horizontal and vertical direction, the true-negatives are added in candidate of hepatic vessels and the false-positives are removed. As a result of the process, the various hepatic vessel trees of patients are accurately reconstructed in 3D.

Development of α1,3-galactosyltransferase Inactivated and Human Membrane Cofactor Protein Expressing Homozygous Transgenic Pigs for Xenotransplantation (이종이식에 활용할 α1,3-galactosyltransferase 비활성화 및 Membrane Cofactor Protein 발현 동형접합 형질전환 돼지 개발)

  • Lee, Gunsup;Park, Sang Hyoun;Lee, Haesun;Ji, Soo-Jeong;Lee, Joo Yung;Byun, Sung-June;Hwang, Seongsoo;Kim, Kyung Woon;Ock, Sun A;Oh, Keon Bong
    • Journal of Embryo Transfer
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    • v.32 no.3
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    • pp.73-79
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    • 2017
  • Transplantation is considered to be a very useful approach to improve human welfare and to prolong life-span. Heterologous organ transplantation using pig organs which are similar to human beings and easy to make mass-production has known as one of the alternatives. To ensure potential usage of the pig organ for transplantation application, it is essentially required to generate transgenic pig modifying immuno-related genes. Previously, we reported production of heterozygous ${\alpha}1,3$-galactosyltransferase (GalT) knock-out and human membrane cofactor protein (MCP) expressing pig ($GalT^{-MCP/+}$), which is enforced for suppression of hyperacute and acute immunological rejection. In this study, we reported generation of homozygous pig ($GalT^{-MCP/-MCP}$) by crossbreeding $GalT^{-MCP/+}$ pigs. Two female founders gave birth to six of $GalT^{-MCP/-MCP}$, and seven $GalT^{-MCP/+}$ pigs. We performed quantitative real-time PCR, western blot, and flow cytometry analyses to confirm GalT and MCP expression. We showed that fibroblasts of the $GalT^{-MCP/-MCP}$ pig do not express GalT and its product Gal antigen, while efficiently express MCP. We also showed no expression of GalT, otherwise expression of MCP at heart, kidney, liver and pancreas of transgenic pig. Taken together, we suggest that the $GalT^{-MCP/-MCP}$ pig is a useful candidate to apply xenotransplantation study.

Adaptation of Feedlot Cattle to a High-energy Ration by Intraruminal Transplantation of Adapted Ruminal Fluid (제1위내용액 이식에 의한 비육우의 농후사료 적응법에 관한 연구)

  • 이현범;탁연빈;성은주;김기석;이영주;정재석;장종식;권오덕
    • Journal of Veterinary Clinics
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    • v.15 no.1
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    • pp.62-74
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    • 1998
  • In feedlot cattle the abrupt change of diet from roughage to a large quantity of grain for the purpose to improve production often results in increased occurrence of rumen acidosis or acute carbohydrate encouragement enterotoxemia, bloats diarrhea liver abscess and laminitis or robot disease. The common management practice to control these problem is to increase the amount of concentrates in the diet in a stepwise manner until the animals are adapted to a high-grain ration. However this practice requires at least about 3 weeks adaptation period and specially prepared adaptation rations which contain various amount of concentrates. Present experiment was undertaken in order to findout the more simple and rapid adaptation method of cattle to a high grain ration. Nineteen Korean calves aging from four to six month were fed artifical hay (Youngchoun Chuk-Hyup, Korea) which contains 10% of concentrates or alfalfa and rye grass hays for two months and randomly alloted to three experimental groups and two control groups. The experimental group-1 was inoculated by stomach tube for two days with li500 ml/day of ruminal fluid fished from Korean beef cattle that had been previously adapted to a high-energy ration. The experimental group-2 was inoculated by trocalization for two days with the same ruminal fluid. The experimental group-3 was inoculated by trocalization with 1,500 ml/day of bacterial culture which contained 2$\times $10$^{9}$/m1 of Gram-negative bacteria derived from adapted luminal fluid. The two control groups were treated with normal saline solution by the same methods. All animals were fed high-energy ration that contained 80% of grain ad libitum for 30-74 days beginning on the third of the treatment. The effect of the inoculation on the adaptation was observed clinicopathologically with the following results; All of the experimental calves inoculated with the ruminal fluid or Gram-negative bacterial culture derived from adapted cattle did not show any signs of rumen acidosis or other related diseases, while most of the control calves did show diarrhea and bloat and a calf laminitis. The average daily weight gain and feed efficiency of experimental calves were slightly improved compared with control calves. Following the feeding of high-grain rational the pH of the ruminal fluid was lowered in both the experimental and control groups. However severe acidosis with the pH of below 5.0 was observed in only a control group-2. The protozoal number in ruminal fluid was markedly decreased during the high-grain feeding in both the experimental and control calves. However the decrease was mere severe in control calves compared with the experimental calves. The activation of the protozoa were completely disappeared within nine hours at the refrigerator temperature (4"C). No significant differences in heamatological and blood chemical values between the experimental and control calves were recognized. However in one control calf which showed clinically laminitis marked elevations of serum glutamic oxaloacetate transaminase and lactic dehydrogenase activities and a decrease of serum glucose level were observed. From these results it would be concluded the intraruminal transplantation of unadapted calves with the adapted ruminal fluid from cattle previously adapted to a high-energy ration prevents disease problem associated with high-grain feeding and improve weight gain and feed efficiency.ency.

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Megakaryocyte Colony Formation of Fetal Liver Cells (태아 간세포의 거핵구 집락형성)

  • Kwon, Byung O;Ju, Hye Young;Kim, Chun Soo;Jeon, Dong Seok;Kim, Jong In;Kim, Heung Sik
    • Clinical and Experimental Pediatrics
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    • v.45 no.2
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    • pp.247-255
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    • 2002
  • Purpose : This study was undertaken to obtain basic data about the megakaryocyte colony formation of fetal liver cells by using immunocytochemical staining and ex vivo culture with growth factors. Methods : The mononuclear cells were isolated from fetal liver and bone marrow with idiopathic thrombocytopenic purpura(ITP) and pancytopenia. These mononuclear cells were cultured in $MegaCult^{TM}-C$(Stem Cell Tech, Canada) media in the presence of growth factors and CFU-Megakaryocyte( CFU-Mk) colonies were counted on day 12. The expansion of CD34+ and CD41+ cell was analyzed by flow cytometry after 5 days incubation using flask culture. Results : The numbers of CFU-Mk colonies of mononuclear cells obtained from fetal liver in the 11th week gestational age were more than those in the 19th week specimens; growth factors could not enhance the colony expansion in all cases. Total numbers of CFU-Mk colony of fetal liver cells were higher than bone marrow from ITP or pancytopenia groups. The numbers of pure or large CFU-Mk colonies of fetal liver cells were also higher than bone marrow specimens. The rate of CD34+ cell expression of fetal liver was increased after flask culture and the enhancement effect of epression was seen only in cases which added thrombopoietin. The rate of CD41+ cell expression of fetal liver was increased after incubation, but the enhancement effect of growth factors was unclear. Conclusion : This study revealed good results about the megakaryocyte colony assay of fetal liver mononuclear cells using $MegaCult^{TM}-C$ media. This study suggests that the fetal liver could be a good source of megakaryocytic progenitor cells for clinical application in hematopoietic stem cell transplantation.

The Use of Locally Applied Vibration to Minimize Pain during Fractional CO2 Laser Therapy in Living Liver-Donor Scar Management

  • Song, Sinyoung;Choi, Dong Hoon;Oh, Tae Suk
    • Archives of Plastic Surgery
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    • v.43 no.6
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    • pp.570-574
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    • 2016
  • Background Fractional $CO_2$ laser is an effective treatment for scars, but most patients complain about sharp burning pain, even after the application of lidocaine ointment. This study analyzed the impact of a vibrating device to nonpharmacologically reduce the acute pain of laser treatment, in accordance with the gate control theory of pain management. Methods This is a prospective study performed from May 2013 through March 2014. Fifty-three patients (mean age, 26.7 years; range, 16-44 years) who had donated livers for liver transplantation were treated with a fractional $CO_2$ laser (10,600 nm; model $eCO_2$, Lutronic Corp) for their abdomen scars. Laser treatment was applied 4 months after surgery. A commercially available, locally applied vibrating device (model UM-30M, Unix Electronics Co. Ltd.) was used, in an on-and-off pattern, together with the $CO_2$ laser. A visual analogue scale (VAS; 0, no pain; 10, most severe pain) of pain sensation was assessed and statistically analyzed using a paired t-test. Results The average VAS score for pain with the vibrating device was 4.60 and the average VAS score without the vibrating device was 6.11. The average difference between scores was 1.51 (P=0.001). Conclusions A locally applied vibrating device was demonstrated to be effective in reducing pain when treating with a fractional $CO_2$ laser. Vibration treatment could be helpful when treating scars with fractional $CO_2$ laser in pain-sensitive patients, particularly children.

Ultrastructural studies on the liver of rat treated with cyclosporin A; with the special reference to bile canaliculus (Cyclosporin A를 투여한 랫드 간장의 미세구조적 연구; 담세관을 중심으로)

  • Park, Chang-hyun;Kim, Yun-jeong;Jang, Byung-joon;Lim, Chang-hyeong;Yoon, Hwa-joong;Lee, Duck-yoon
    • Korean Journal of Veterinary Research
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    • v.35 no.4
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    • pp.659-670
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    • 1995
  • Cyclosporin A extracted from fungus Trichoderma polysporum Rifai and Cyclindrocarpon lucidum Booth serves as an important immunosuppressive drug in transplantation surgery. Systemic treatment with cyclosporin A induces an impairment of the biliary excretion of the bile salts and cholestasis. This study was designed to observe the Ultrastural changes of the hepatocytes and the bile canaliculi in cyclosporin A-induced intrahepatic cholestasis in rats. Cyclosporin A was injected into male Wistar rats intraperitoneally 50mg per kg body weight and rats were necropsied at 1, 3, 6, 9, 12, 24 hours. The liver tissues were observed with transmission and scanning electron microscopes and the results were as follows. Transmission electron microscopy: After cyclosporin A injection, SER and lysosomes were increased in the hepatocytes until 9 hours. At 12 hours after injection of cyclosporin A, RER with dilated cistern were increased, and SER, lysosomes in the cytoplasm were decreased. From 1 hour to 24 hours after injection of cyclosporin A, there were dilation of bile canalliculi and decreased or lost microvilli. At 24 hours the dilation of bile canaliculi were decreased. Scanning electron microsocopy: After cyclosporin A injection, the bile canaliculi were dilated and the microvilli were shortened, decreased or lost according to the sites. At 24 hours, the microvilli packing the bile canaliculi were observed. These observations suggest that cyclosporin A-induced cholestasis is associated with the dilation of bile canaliculi, increased microfilaments of the pericanalicular region and decreased or lost microvilli.

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ORAL CHARACTERISTIC OF ALAGILLE SYNDROME - A CASE REPORT (Alagille 증후군을 가진 환자의 구강내 특징에 대한 증례보고)

  • Kim, Tae-Wan;Kim, Young-Jin
    • The Journal of Korea Assosiation for Disability and Oral Health
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    • v.3 no.1
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    • pp.17-21
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    • 2007
  • Alagille syndrome is an autosomal dominant genetic disorder and occurs in approximately 1 in 100,000 live births. Diagnostic criteria was established by Alagille. It is mainly caused by a mutation in the Jagged1 gene. Major clinical features of this syndrome are paucity of intrahepatic bile duct with cholestasis, characteristic facies, cardiac murmur, defects of vertebrae, and embryotoxon. And minor clinical features are mental retardation, renal involvement, growth retardation, other skeletal abnormalities, a high-pitched voice. The surviving prognosis of Alagille syndrome patients depends on the severity of cardiovescular malformation in the early ages of infant. However, with the increasing years, it depends on the severity of the liver disease. Cholestasis causes congenital jaundice, malnutrition and growth retardation. Also, the increase of serum cholesterol level cause xanthoma and pruritus. Even though the severity of these problems are reduce with age, there is cases where there is no way but liver transplantation. For oral features of Alagille syndrome patients, green discoloration of entire dentition, induced by bilirubin infiltration into dentinal tubules, is especially. Also, xanthoma on gingiva and partial hypodontia have been reported. This report is on the oral features of an Alagille syndrome patient who visited to Kyung-Pook University Hospital.

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Alteration of MicroRNAs Targeted Integrins by PD-MSCs Transplantation Is Involved in Hepatic Regeneration in a Rat Model with BDL (담관결찰 쥐 모델에서 태반유래중간엽줄기세포 이식에 의한 miRNA 표적 인테그린 변화의 간재생 효과)

  • Park, Sohae
    • Journal of Life Science
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    • v.31 no.8
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    • pp.710-718
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    • 2021
  • Placenta-derived mesenchymal stem cells (PD-MSCs) are promising candidates for cell-based therapy in regenerative medicine. The migration and homing potential of PD-MSCs to injured sites is a critical property of MSC engraftment. MicroRNAs (miRNAs) have recently been shown to regulate the critical functions of MSCs, such as proliferation, survival, and migration. The objective of the present study was to identify the miRNA and target genes involved in PD-MSCs homing in a bile duct ligation (BDL) rat model. We selected candidate miRNAs targeting genes for PD-MSCs homing based on microarray analysis. PD-MSC engraftment in BDL-injured rat liver was identified by immunofluorescence assay and human-specific Alu gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) one week after transplantation. Compared with migrated naïve PD-MSCs under hypoxic and normoxic conditions (Hyp/Nor), the transplanted group with PD-MSCs (Tx) showed distinct differences in miRNA expressions in BDL-injured rat liver. We also validated the miRNAs and their target genes for PD-MSCs homing. The expressions of integrin α4 (ITGA4) and integrin α5 (ITGA5) target genes for miR-199a-5p and miR-148a-3p were significantly upregulated in the Tx group (p<0.05). In addition, integrin β1 (ITGB1) and integrin β8 (ITGB8) were upregulated by suppressing miR-183-5p and miR-145-5p, respectively. These results demonstrated that PD-MSCs regulate miRNA expression related to the integrin family for their homing effects on the BDL-injured rat liver. The findings further suggest that miRNA-mediated regulation of the integrin family contributes to the therapeutic efficacy of PD-MSCs in the rat hepatic fibrosis model by BDL.

Human Lung Cancer Cell Xenografts Implanted under the Capsule of Kidney, Spleen and Liver (폐암 세포주를 사용한 신, 비장 및 간 피막하 분식법의 비교)

  • 김수현;김종인;이해영;조봉균;박성달;김송명
    • Journal of Chest Surgery
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    • v.36 no.10
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    • pp.711-720
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    • 2003
  • Bakground : Complete resection by the surgery has been selected as the treatment of choice in lung cancer patients, but in cases of recurrence after excision or inoperable cases, the importance of anticancer chemotherapy has been emphasized. If one can select a set of the sensitive chemotherapeutic agents before anticancer chemotherapy, it will give more favourable results. Subrenal capsular assay has been recognized as a useful in-vivo chemosensitivity test of thoracic and abdominal tumors and it can be done in a short time for a rapid interpretation of tumor responsiveness to anticancer chemotherapeutic drugs. It has been reported that various kinds of cancer cells can be implantable to the kidney, but so far there is no comparative study of xenogeneic cell implantation on liver, spleen and kidney. The author implanted the human lung cancer cells under the capsule of S.D rat's liver, spleen and kidney respectively and compared the pattern of growth and histology. Material and Method: After incubation of human lung cancer cell line (SW-900 G IV) in RPMI 1640 (Leibovitz L-15 medium) culture media, 3${\times}$3${\times}$3 mm size fibrin clots which contain 108 cancer cells were made. Thereafter the fibrin clots were implanted at subcapsule area of liver, spleen and kidney of S.D. female rat. For immune suppression, cyclosporin-A (80 mg/Kg) was injected subcutaneously daily from post-implantation first day to sixth day. The body weight was measured at pre and post implantation periods. The growth pattern and the size of tumor mass were observed and the pathologic examination and serum tumor marker tests were performed. Result: Body weight increased in both of control and experimental groups. Serum Cyfra 21-1 was not detected. Serum levels of CEA and NSE revealed no significant change. The SCC-Ag increased significantly in implanted group. The growth rate of human lung cancer cells which was implanted on spleen was higher than on liver or kidney. The surface area, thickness, and volume of tumor mass were predominant at spleen. The success rates of implantation were 80% on kidney, 76.7% on spleen and 43.3% on liver. Pathologic examination of implanted tumors showed characteristic findings according to different organs. Tumors that were implanted on kidney grew in a round shape, small and regular pattern. In the spleen, tumors grew well and microscopic neovascularization and tumor thrombi were also found, but the growth pattern was irregular representing frequent daughter mass. Human lung cancer cells that were implanted in the liver, invaded to the liver parenchyme, and had low success rate of implantation. Microscopically, coagulation necrosis and myxoid fibrous lesion were observed. Conclusion: The success rate of implantation was highest in the kidney. And the mass revealed regular growth that could be measured easily. The SCC-Ag was presented earlier than CEA or Cyfra21-1. The Cyfra21-1 was not detected at early time after implantation. The best model for tumor implantation experiment for chemosensitivity test was subrenal capsular analysis than liver and spleen and the useful serum tumor marker in early period of implantation was the SCC-Ag.