Başkent Üniversitesi Yayınları
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Item Long-term Survival After Liver Transplant for Recurrent Hepatocellular Carcinoma With Bile Duct Tumor Thrombus: Case Report(Başkent Üniversitesi, 2012-12) Liu, Chao; Wang, JieObjectives: Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. Materials and Methods: A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 µg/L, total bilirubin level was 327 µmol/L, direct bilirubin level was 261 µmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. Results: This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Conclusions: Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.Item Clinical Pharmacokinetics of Oral Versus Sublingual Administration of Tacrolimus in Adult Liver Transplant Recipients(Başkent Üniversitesi, 2012-12) Nasiri-Toosi, Zahra; Khalili, Hossein; Sadrai, Sima; Abdollahi, Alireza; Irajian, Hamideh; Jafarian, Ali; Nasiri-Toosi, Mohsen; Dashti-Khavidaki, SiminObjectives: Oral tacrolimus administration is the common route of drug delivery. Recent studies suggest sublingual administration of tacrolimus as an alternative route may produce comparable drug trough levels with similar or even lower doses than the oral route, especially in lung transplant recipients; however, most of this research does not encompass intraindividual variations compared between the 2 routes. This study sought to compare the bioavailability and blood trough concentrations of orally and sublingually administered tacrolimus in adult liver transplant recipients by considering intraindividual variations in tacrolimus pharmacokinetics properties. Materials and Methods: Six adult liver transplant recipients received their tacrolimus either orally or sublingually within 2 consecutive days. Blood samples to determine tacrolimus concentrations were gathered at 0, 0.5, 1, 2, 4, 6, and 12 hours after oral and sublingual tacrolimus administration. Mean data values were used to calculate the pharmacokinetics parameters via the feathering or residual method, using the 1-compartment, first-order elimination pharmacokinetics model. Compared pharmacokinetics parameters included drug bioavailability, maximum blood concentration (Cmax), time to reach maximum blood level (Tmax), and trough blood concentrations. Results: Trough whole blood levels, area under the concentration-time curve, Tmax, and Cmax after oral and sublingual administration of tacrolimus were not significantly different (10.4 ± 7.4 vs 11.2 ± 11.3 ng/mL for trough blood concentration, 181.5 ± 114.1 vs 160.8 ± 115.9 ng.h/mL for AUC, 1.9 ± 1.2 vs 1.4 ± 0.7 h for Tmax, and 19.9 ± 10.8 vs 17.2 ± 11.7 ng/mL for Cmax). A double-peak phenomenon was observed in some concentration-time profiles. Conclusions: Sublingual tacrolimus administration does provide therapeutic drug concentrations in adult liver transplant recipients. Therefore, sublingual tacrolimus may confidently be considered as an alternative route to oral administration in patients who are unable to swallow their drugs.Item Doppler Ultrasonography Findings of Splenic Arterial Steal Syndrome After Liver Transplant(Başkent Üniversitesi, 2012-08) Uslu, Nihal; Haberal, Mehmet; Arslan, Gulnaz; Boyvat, Fatih; Karakayali, Hamdi; Moray, Gokhan; Tore, Huseyin Gurkan; Aslan, HulyaObjectives: Splenic arterial steal syndrome is an important cause of morbidity and mortality after orthotopic liver transplant. Splenic arterial steal syndrome is characterized by arterial hypoperfusion of the graft; and if left untreated, causes ischemic biliary tract injury. Selective arterial embolization is important when treating splenic arterial steal syndrome. Doppler ultrasound has been used to follow-up liver transplant patients. This study sought to analyze alterations in portal vein velocity, peak systolic velocity, and resistivity index of the hepatic artery before diagnosis and after treatment of splenic arterial steal syndrome. Materials and Methods: We analyzed the Duplex Doppler ultrasonography results of 20 liver transplant recipients who developed angiographically proven splenic arterial steal syndrome between January 2005 and March 2009. Peak systolic velocity and resistivity index of the hepatic artery were noted during transplant surgery, before selective arterial embolization, and after embolization procedures. Results: A statistically significant decrease was found in peak systolic velocity and resistivity index of the hepatic artery between the intraoperative and pre-embolization values. In contrast to the statistically significant increase in peak systolic velocity of the hepatic artery, there were no significant changes in resistivity index after the selective arterial embolization. Portal vein velocity did not show a statistically significant change between intraoperative and preprocedure values. Portal vein velocity did show a tendency to decrease after coil embolization, but this was not significant. Conclusions: Doppler ultrasound surveillance is a valuable tool in early detection of hepatic arterial complications. A decrease in peak systolic velocity and resistivity index compared to the corresponding intraoperative data should raise suspicion of splenic arterial steal syndrome. Also Doppler ultrasound can be effectively used to examine the hepatic arterial inflow after selective arterial embolization.Item Twenty-Four Hour Steroid Avoidance Immunosuppressive Regimen in Liver Transplant Recipients(Başkent Üniversitesi, 2012-06) Ju, Wei-qiang; Zhu, Xiao-feng; Tai, Qiang; Han, Ming; Hu, An-bin; Wu, Lin-wei; He, Xiao-shun; Ling, Xiaoting; Guo, Zhi-yongObjectives: To investigate the efficacy and safety of an immunosuppressive regimen of steroid avoidance in combination with induction therapy and tacrolimus in liver transplant recipients. Materials and Methods: Eighty-two adult liver transplant recipients were randomized into 2 groups: standard protocol group (n=41) in which steroids were withdrawn 3 months after the operation, and a 24-hour steroid avoidance group (n=41) in which steroids were eliminated within 24-hours. The incidence of acute rejections, infections (bacterial, fungal, and cytomegalovirus), and metabolic complications were analyzed between the groups. Results: The incidence of early posttransplant diabetes mellitus and the average dosage of insulin consumption among diabetic recipients were significantly higher in recipients in the standard protocol group than in the 24-hour avoidance group (P < .05). In addition, the incidence of hypertension and infection during the follow-up were also higher in patients of the standard protocol group (P < .05). The incidence of hypertension in the early posttransplant period, hyperlipemia, and acute rejection during the follow-up were comparable between the groups (P > .05). Conclusions: Twenty-four hour steroid avoidance combined with induction therapy and tacrolimus maintenance is a safe and efficient immunosuppression strategy that can significantly reduce posttransplant infections and other complications owing to long-term use of steroids, without increasing the risk of acute rejection.Item Co-occurrence of Nonanastomotic Biliary Stricture and Acute Cellular Rejection in Liver Transplant(Başkent Üniversitesi, 2012-04) Sanada, Yukihiro; Egami, Satoshi; Kawarasaki, Hideo; Yasuda, Yoshikazu; Okada, Noriki; Yamada, Naoya; Wakiya, Taiichi; Ihara, Yoshiyuki; Urahashi, Taizen; Mizuta, KoichiBackground: Nonanastomotic biliary stricture is generally considered the most troublesome biliary complication after liver transplant. Nonanastomotic biliary stricture owing to immunologic cholangiopathy (such as acute cellular rejection) has not been reported. We describe 2 patients with the co-occurrence of nonanastomotic biliary stricture and acute cellular rejection after pediatric live-donor liver transplant. Case 1: A 13-month-old male infant with liver cirrhosis underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Eighty days after the live-donor liver transplant, fever with liver dysfunction and dilatation of the intrahepatic bile duct occurred. Percutaneous transhepatic biliary drainage and a liver biopsy were performed. The histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. Case 2: A 21-month-old female infant with biliary atresia underwent an ABO-identical live-donor liver transplant using a left lateral segment graft. Twenty-six days after the live-donor liver transplant, percutaneous transhepatic biliary drainage for B3 and a liver biopsy were performed, owing to fever, with liver dysfunction, and dilatation of the intrahepatic bile duct. Histopathologic evaluation indicated the presence of acute cellular rejection. After percutaneous transhepatic biliary drainage and steroid pulse treatment, the patient showed good clinical outcome. Conclusions: It is important for patients with nonanastomotic biliary stricture to undergo early liver biopsy because the nonanastomotic biliary stricture may be coincident with, or caused by, acute cellular rejection.Item Living-donor Liver Transplant in 3 Patients With Budd-Chiari Syndrome: Case Report(Başkent Üniversitesi, 2012-04) Bas, Koray; Tokat, Yaman; Yuzer, Yildiray; Dogusoy, Gulen Bulbul; Ulusoy, Onur Levent; Dayangac, Murat; Yaprak, OnurBudd-Chiari syndrome is a rare but life-threatening disorder characterized by obstruction of the hepatic venous outflow. Treatment depends on the underlying cause, the location, and extent of the obstruction, and the functional capacity of the liver. A stepwise therapeutic approach is commonly accepted. When all other therapy options are unsuccessful, or in case of end-stage liver disease, transplant should be considered. We present case reports of 3 patients with Budd-Chiari syndrome who underwent living-donor liver transplant. Characteristic features of Budd-Chiari syndrome, diagnostic and therapeutic interventions, complications, and overall outcomes are discussed. We believe that when a deceased donor graft is unavailable, a living-donor liver transplant can be a safe option for patients with end-stage liver disease associated with Budd-Chiari syndrome.Item Appropriate Donor Size for Porcine Liver Xenotransplant(Başkent Üniversitesi, 2012-04) Soleimani, Mehrdad; Yazdi, Seyed Hashem Fani; Mehrabi, Arianeb; Schmidt, Jan; Rahbari, Nuh N.; Hafezi, Mohammadreza; Golriz, Mohammad; Kashfi, Arash; Esmaeilzadeh, Majid; Fonouni, HamidrezaObjectives: Owing to an imbalance between demand and supply, which is more prominent in pediatric transplant, every year more patients lose their lives on waiting lists. In addition to the use of deceased-donor split and living-donor organs, xenotransplant could provide a solution if associated problems, such as immunologic and physiologic ones, are solved. This study sought to analyze the surgical aspects for liver xenotransplant in a porcine model. Materials and Methods: Landrace pigs (n=22, 23 to 37 kg) underwent a laparotomy under general anesthesia. The hepatic hilum was prepared and the common bile ducts, common hepatic artery, portal vein, supra- and infrahepatic inferior vena cava were identified. The length and diameter of each vessel and bile duct and the weight of the liver were measured. Results: Pearson tests showed a clear correlation between the increase of the pigs’ weight and the livers’ weight, and the length of the vessels and the bile ducts. We did not find a clear correlation between the increase of the pigs’ liver weight and the diameters of the vessels and the bile duct. Conclusions: As the first reporting, this study on xenotransplants from the surgical point of view, we postulate that it could be possible to estimate the size of the liver and the proper length of its vessels and bile duct by weighing only the pigs. It was not feasible to match the diameter of mentioned structures by the livers’ weight. However, the weight of pig’s liver as well as vascular anatomy of pigs appeared to be suitable alternative for the human liver.Item Hepatitis C Virus Infection Can Affect Lymphoproliferative Disorders Only as a Cofactor for Epstein-Barr Virus in Liver Transplant Recipients: PTLD.Int Survey(Başkent Üniversitesi, 2012-04) Khedmat, Hossein; Taheri, SaeedObjectives: Hepatitis C virus infection has a 10.5% frequency in liver transplant posttransplant lymphoproliferative disorders. Studies have suggested that hepatitis C virus infection plays a role in developing posttransplant lymphoproliferative disorders. Pooling data of posttransplant lymphoproliferative disorders developing in liver recipients from the literature, we analyzed and compared characteristics, behavior, and prognoses of posttransplant lymphoproliferative disorders arising in hepatitis C virus-positive versus negative liver graft recipients. Materials and Methods: We conducted a search for the available data though PubMed and Google Scholar for reports of posttransplant lymphoproliferative disorders and hepatitis C virus infection in liver transplant recipients. Overall, 29 studies were found and their data are included in the analyses. Results: Overall, data of 212 liver transplant patients were included. Sixty-three percent were male. No difference was found between hepatitis C virus-positive liver transplant patients with posttransplant lymphoproliferative disorders compared to their hepatitis C virus-negative counterparts regarding sex, time from transplant to lymphoma development, lymphoma cell type, remission, mortality rate, multiorgan involvement, disseminated posttransplant lymphoproliferative disorders, and histopathologic evaluations (P > .1 for all). Hepatitis C virus-positive liver transplant recipients representing posttransplant lymphoproliferative disorders who were concomitantly positive for Epstein-Barr virus were significantly more likely to develop lymphomas in the early posttransplant period (26 [67%] vs 16 [40%]; P = .024) and to complicate liver (19 [63%] vs 8 [30%]; P = .017) than hepatitis C virus-/Epstein-Barr virus+ patients. Conclusions: Hepatitis C virus infection alone has no significant effect on lymphoproliferative disorders after liver transplant; but when combined with Epstein-Barr virus infection, it represents some significant different presentations of the disease. However, no survival effect was found for hepatitis C virus with or without simultaneous Epstein-Barr virus infection, in the posttransplant lymphoproliferative disorders setting. Future prospective studies are needed for confirming our results.Item Sirolimus Conversion in Liver Transplant Recipients With Calcineurin Inhibitor-Induced Complications: Efficacy and Safety(Başkent Üniversitesi, 2012-04) Ju, Wei-qiang; Hu, An-bin; He, Xiaoshun; Zhu, Xiao-feng; Han, Ming; Tai, Qiang; Wu, Lin-wei; Liang, Wen-hua; Guo, Zhi-yongObjectives: To evaluate the efficacy and safety of conversion from calcineurin inhibitors to sirolimus among liver transplant recipients with calcineurin inhibitor-induced complications. Materials and Methods: After receiving liver transplants, 25 patients with calcineurin inhibitor-induced complications (22 renal dysfunction and 3 new-onset diabetes mellitus) were converted from sirolimus to tacrolimus. The serum creatinine, sirolimus trough level, liver function, acute rejection episodes, and drug-related adverse effects were monitored. Results: The patients were followed for 12 to 50 months (median, 25 months). The renal function of the 22 patients with renal dysfunction improved after sirolimus conversion. The serum creatinine levels were significantly lower at 3 months after conversion versus before conversion (113.2 ± 21.8 µmol/L vs 163.2 ± 45.3 µmol/L; P < .05). At the end of the follow-up, the average serum creatinine level was 101.9 ± 23.4 µmol/L among the 20 living recipients. Diabetes also was under control in 3 diabetic recipients after the conversion. Four patients experienced episodes of acute rejection, and intravenous steroid bolus therapy was administered in 2 of them. No graft was lost because of acute rejection. The adverse effects of sirolimus included hyperlipidemia (7/25), anemia (8/25), and mouth ulcers (9/25). All these adverse effects were relieved after a short-term symptomatic therapy, and no patient was withdrawn from the conversion trial. Conclusions: Sirolimus monotherapy is effective and safe in liver transplant recipients. Conversion to sirolimus was associated with a sustained improvement in renal function and diabetes mellitus without an increased incidence of acute rejection episodes.Item Kaposi Sarcoma of the Ureter After Liver Transplant: Case Report and Literature Review(Başkent Üniversitesi, 2012-02) Chen, Yu; He, Xiao-shun; Qiu, Shao-peng; Zhao, LiangKaposi sarcoma after an organ transplant is rare and infrequently involves internal organs. There are 2 reported cases in the English literature of Kaposi sarcoma originating from the transplant ureter after kidney transplant. We report a case of Kaposi sarcoma that occurred in the native ureter of the liver transplant recipient. Initially, the patient refused any further investigation and management and 2 years subsequent, had to undergo a left radical nephroureterectomy owing to the loss of renal function and distending pain. He recovered very well and no recurrence was detected at 47 months’ follow-up. To our knowledge, it is the first report in English. We review the literature on this topic and explore the therapeutic principles and histologic features of this sarcoma.