Randomized, multicenter trial comparing tacrolimus plus mycophenolate mofetil to tacrolimus plus steroids in hepatitis C virus-positive recipients of living donor liver transplantation.

The purpose of this prospective, randomized, multicenter trial was to evaluate the effects of a steroid-avoiding immunosuppression protocol on hepatitis C virus (HCV)-positive recipients of living donor liver transplantation (LDLT). Seventy-five HCV-positive LDLT recipients were included in this study, and they were randomized to receive tacrolimus (TAC) plus a corticosteroid (ST; n = 35) or TAC plus mycophenolate mofetil (MMF; n = 40). Biopsy-proven acute rejection (BPAR) was treated with steroid pulse therapy in both groups. Protocol biopsy was performed 3, 6, and 12 months after LDLT and annually thereafter. Histological recurrence of HCV (fibrosis stage ≥ F1 according to the METAVIR score), BPAR resistant to 2 sets of steroid pulse therapy, hepatocellular carcinoma (HCC) recurrence, retransplantation, and patient death were defined as events, and the primary endpoint was event-free survival. The median follow-up was 55 months. The event-free survival rates at 1, 3, and 5 years were 38.2%, 11.8%, and 5.9%, respectively, for the ST group and 25.0%, 17.5%, and 14.6%, respectively, for the MMF group (P = 0.45). The overall 5-year patient survival rates were similar for the ST group (82.7%) and the MMF group (81.0%, P = 0.28). Steroid-resistant BPAR occurred in only 1 patient from the MMF group. HCC recurrence occurred for 1 patient from the ST group and 2 patients from the MMF group. HCV recurrence rates with a fibrosis stage ≥ F1 1 and 3 years after LDLT were 59.4% and 85.9%, respectively, for the ST group and 74.2% and 81.9%, respectively, for the MMF group (P = 0.57). In conclusion, our steroid-avoidance regimen had no apparent impact on LDLT outcomes for HCV-positive recipients.

Immunogenicity of inactivated seasonal influenza vaccine in adult and pediatric liver transplant recipients over two seasons.

Immunological responses to influenza vaccination administered to liver transplantation recipients are not fully elucidated. To compare inactivated influenza vaccine's immunogenicity between adult and pediatric recipients, 16 adult and 15 pediatric living donor liver transplantation recipients in the 2010-11 influenza season, and 53 adult and 21 pediatric recipients in the 2011-12 season, were investigated. Seroprotection rates (hemagglutinin-inhibition [HI] antibody titer 1:40) were 50-94% to all three antigens among adults and 27-80% among children in both seasons. Seroconversion rates (fourfold or more HI antibody rise) were 32-56% among adults and 13-67% among children in both seasons. No significant differences were observed between the two groups. In addition, 20/53 adult and 13/21 pediatric recipients received a vaccine containing identical antigens in both of these seasons. Geometric mean titer fold increases of all three antigens in adult recipients were significantly lower than those in recipients who had not received a preceding vaccination. In contrast, in pediatric recipients, there were no significant differences between the groups who had and had not received preceding vaccinations. The number of patients with rejection did not differ significantly between the two groups (0/53 vs. 1/21) in the 2011-12 season. The incidence of influenza after vaccination was significantly different between adult and pediatric recipients (0/16 vs. 5/15 in 2010-11 and 0/53 vs. 3/21 in 2011-12, respectively). Overall, there were no significant differences in antibody responses between adult and pediatric groups. Influenza infection was more frequent in pediatric recipients. Long-term response to preceding vaccinations appeared to be insufficient in both groups.

Impact of recipient age and preoperative fasting blood glucose level as the risk factors of living donor liver transplantation in cirrhotic patients in the recent comprehensive era with knowledge of indications: Recent status in a Japanese single center.

AIM: Recently, knowledge for indications of living donor liver transplantation (LDLT) has been robustly accumulated in. For further improvement, risks should be reexamined in recent cases. In this study, we investigated preoperative risk factors in cirrhotic patients who underwent LDLT in recent era. METHODS: Seventy-four cirrhotic patients who underwent LDLT at our institution between 2003 and 2011 were included. Recipient and donor age and sex, existence of hepatocellular carcinoma (HCC), preoperative Model for End-Stage Liver Disease score, fasting blood glucose (FBG), triglyceride, total cholesterol, serum creatinine, hemoglobin A1c, graft : recipient weight ratio, ABO compatibility and choice of calcineurin inhibitor were analyzed. A proportional hazard model was applied and P < 0.05 was considered statistically significant. RESULTS: In multivariate analysis, recipient age (hazard ratio = 1.188, P = 0.011) and FBG (hazard ratio = 1.009, P = 0.016) showed as significant independent factors. Theoretical mortalities were 9.2%, 21.9% and 51.7% in patients with normal FBG at 55, 60 and 65 years old, respectively, and 34.3% and 53.6% in patients with FBG of 150 and 200 mg/dL, respectively, at 60 years old. CONCLUSION: Recipient age and FBG remain important risk factors for LDLT in cirrhotic patients even in the recent era. These factors should be considered for selecting liver transplant candidates in cirrhotic patients.

Prognostic significance of changes in serum thyroglobulin antibody levels of pre- and post-total thyroidectomy in thyroglobulin antibody-positive papillary thyroid carcinoma patients.

Although postoperative serum thyroglobulin (Tg) is a prognostic indicator for papillary thyroid carcinoma (PTC), it is unreliable when Tg antibody (TgAb) is positive. We evaluated the prognostic significance of changes in serum TgAb levels of pre- and post-total thyroidectomy in TgAb-positive PTC patients. We reviewed our medical charts of 225 TgAb-positive PTC patients in whom TgAb levels were measured before and 1-2 years after total thyroidectomy, performed between April 2002 and March 2007. We divided them into 3 groups based on changes in TgAb levels. Postoperative serum TgAb levels decreased by ≥ 50% in 181 patients (80.4%) (Group 1), by <50% in 22 patients (9.8%) (Group 2), and increased in 22 patients (9.8%) (Group 3). During the follow-up, 3 patients died of the disease and 14 patients had recurrences. All 3 patients who died of PTC were seen only in Groups 2 and 3. Groups 2 and 3 showed similar prognostic outcomes, thus were analyzed together as Group 2+3. Group 1 had significantly better lymph node recurrence-free survival and distant recurrence-free survival than Group 2+3 (96.9% vs. 90.5%, p <0.001, and 98.9% vs. 90.1%, p = 0.004, respectively at 5 years). Multivariate analyses on prognostic factors revealed that classification to Group 2+3 was the strongest indicator for poor prognosis. The present results suggest that changes in TgAb levels following total thyroidectomy can be an important dynamic prognostic factor of PTC patients. Prospective periodical measurements of TgAb are necessary to confirm these findings.

Long-term results of surgery for papillary thyroid carcinoma with local recurrence.

PURPOSE: Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. METHODS: A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. RESULTS: The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. CONCLUSIONS: Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.

Impact of aging on the progression of neuropathy after liver transplantation in transthyretin Val30Met amyloidosis.

INTRODUCTION: Information related to the long-term follow-up of neuropathy in patients with familial amyloid polyneuropathy after liver transplantation is still scarce. METHODS: We describe the neuropathic features of 3 patients with the transthyretin Val30Met mutation. Each patient underwent liver transplantation at an early stage of neuropathy, as indicated by the absence of motor dysfunction and relative preservation of myelinated fibers in sural nerve biopsy specimens. RESULTS: Although the patient with late-onset disease (at age 60 years) presented with the least amount of amyloid deposition, he had neuropathic progression after liver transplantation. An older early-onset (at age 40 years) patient reported a slight exacerbation of both somatic and autonomic neuropathic symptoms 10 years after transplantation. However, the younger early-onset (at age 28 years) patient did not exhibit characteristics suggestive of neuropathy 7 years after transplantation. CONCLUSION: Aging may determine the progression of neuropathy after liver transplantation.

[Psychosocial indication of liver transplantation for alcohol-related liver failure: current controversies and imminent issues in Japanese society].

Organ transplant therapy is becoming a usual practice also in Japan, which dramatically improves the length and quality of life in patients with end-stage organ disease. Liver transplantation was resumed in Japan much later than that in the West and is continued now under unique circumstances where more than 90% of grafts come from living donors. Nevertheless the number of liver transplantation for alcohol-related liver failure shows a sharp rise to the level comparable to the West, and not a few physical and/or psychosocial problems caused by recidivism after transplantation are coming up. To find appropriate solutions to how to predict recidivism and define psychosocial indication of liver transplantation in our society, and to how to monitor and support sobriety after transplantation, there is an urgent need for multidisciplinary management by hepatologist, transplant surgeon, psychiatrist, and dependence specialist. Life-saving therapy and dependence management are expected to work closely together from the viewpoints of transparency, equity, utility, and autonomy requested in transplant therapy, protection of living donors, and consideration for donor family and public emotion.

Identification of Epstein-Barr virus-infected CD27+ memory B-cells in liver or stem cell transplant patients.

To analyse the phenotype of Epstein-Barr virus (EBV)-infected lymphocytes in EBV-associated infections, cells from eight haematopoietic stem cell/liver transplantation recipients with elevated EBV viral loads were examined by a novel quantitative assay designed to identify EBV-infected cells by using a flow cytometric detection of fluorescent in situ hybridization (FISH) assay. By this assay, 0.05-0.78% of peripheral blood lymphocytes tested positive for EBV, and the EBV-infected cells were CD20+ B-cells in all eight patients. Of the CD20+ EBV-infected lymphocytes, 48-83% of cells tested IgD positive and 49-100% of cells tested CD27 positive. Additionally, the number of EBV-infected cells assayed by using FISH was significantly correlated with the EBV-DNA load, as determined by real-time PCR (r2  = 0.88, P < 0.0001). The FISH assay enabled us to characterize EBV-infected cells and perform a quantitative analysis in patients with EBV infection after stem cell/liver transplantation.

Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation.

As familial amyloid polyneuropathy (FAP) is an adult-onset disease, a long period is expected between domino liver transplantation (DLT) and the occurrence of amyloidosis in recipients of a FAP liver. However, as time passes, and increased numbers of patients have undergone DLT, patients with symptoms suggesting amyloidosis have been reported. The authors describe, for the first time, pathological findings in an autopsy case of a recipient of a FAP liver. A male patient with primary sclerosing cholangitis received a liver graft from a FAP patient with the transthyretin (TTR) Tyr114Cys mutation when he was 30 years old. Although a recurrence of primary sclerosing cholangitis was detected at age 34, he had no symptoms indicating amyloidosis. He died from Burkitt's lymphoma at 38 years of age. TTR immunoreactive amyloid was found in various organs including the heart, lung, gastrointestinal tract, pancreas, spleen, reproductive system and skeletal muscles. In the nervous system, TTR immunoreactive amyloid deposition was obvious in the sympathetic ganglia and the median nerve within the carpal tunnel, while loss of neurons or nerve fibres was not apparent. This case allows for the characterisation of amyloid deposition during the asymptomatic stage of FAP. Widespread amyloid deposition may occur before tissue damage in this disease.

Donor screening algorithm for exclusion of thrombophilia during evaluation of living donor liver transplantation.

Living donor liver transplantation (LDLT) has evolved based on the premise that donor safety is most important. In 2005, we encountered a donor who developed a pulmonary embolism during the early post-operative period. As it is important for donors to be healthy, most risk factors related to perioperative thrombosis, such as obesity, age, and malignancy are used as exclusion criteria during the evaluation process. We speculated that thrombophilia not detected by conventional laboratory examinations may cause post-operative thrombotic complications and should be investigated by application of additional parameters, including protein S, protein C, antithrombin III, anti-ß2-glycoprotein I antibodies (anti-ß2GPI), and lupus anticoagulant. From July 2005 to June 2007, we evaluated 44 donor candidates for LDLT using our novel algorithm for screening of thrombophilia, which revealed two suspected candidates (one with low protein S, one with low protein C, and positive anti-ß2GPI findings), who were subsequently excluded from the donor pool. Thereafter, all donor hepatectomies, which included two borderline donors given anticoagulants perioperatively, were performed without complications. Four donors (two suspected, two borderline) would not have been recognized without additional screening. In conclusion, we were able to detect thrombophilia and avoid donor thrombosis using additional screening criteria and our novel algorithm.

Effectiveness and safety of inactivated influenza vaccination in pediatric liver transplant recipients over three influenza seasons.

Annual influenza vaccination is recommended for pediatric liver transplant recipients, who are at high risk of influenza-related complications. However, effectiveness and safety of vaccination may differ among influenza seasons in this population and have not been fully evaluated. Subjects comprised 38 pediatric liver transplant recipients with or without influenza vaccination through the 2006-2007, 2007-2008 and 2008-2009 influenza seasons. Recipients received inactivated trivalent (AH1/AH3/B) influenza vaccine, and comparisons were made to non-vaccinated recipients with regard to effectiveness and safety. No significant differences were seen between recipient groups for acute allograft rejection, acute febrile illness, or influenza virus infection. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rate (defined as the proportion of recipients with HI antibody titer ≥ 1:40), seroconversion rate (proportion of recipients with a ≥ 4-fold increase in HI titers), and geometric mean titers were mostly elevated after vaccination for the three influenza antigens in each season. These three indicators of immunogenicity showed similar results in both vaccinated recipients and vaccinated healthy children in the 2007-2008 season. These findings suggest that pediatric liver transplant patients may respond safely to inactivated seasonal influenza vaccines in a similar manner to healthy children, and effectiveness varies among influenza seasons.

Patterns of lymph node metastases in papillary thyroid carcinoma: results from consecutive bilateral cervical lymph node dissection.

BACKGROUND: In patients with papillary thyroid carcinoma (PTC), the appropriate extent of lymph node dissection has not yet been established due to lack of accurate patterns of lymph node metastases (LNM). The aim of this study was to clarify the LNM pattern in PTC patients based on our institution's experience with a consistent technique of bilateral neck dissection, and to consider the rational extent of lymph node dissection. METHODS: Between 1990 and 1999, 152 consecutive patients with PTC who underwent curative total thyroidectomy and bilateral neck dissection as initial treatment were analyzed. The patterns of LNM according to clinicopathological classification were analyzed using the lymph node ratio (LNR; number of metastatic lymph nodes/number of dissected nodes) and frequency (FLNM; number of patients with LNM/number of dissected patients) in cervical compartments. RESULTS: Regardless of clinicopathological classification, LNR in the central compartment was consistently higher than in other compartments, and FLNM in the ipsilateral lateral compartment was consistently higher than in other compartments except for multifocal tumors. The LNR and FLNM in the contralateral lateral compartment were significantly higher in advanced (≥T3) cases than in cases with smaller tumors (T1) and were comparable to those in the ipsilateral lateral compartment in advanced (≥T3) cases. CONCLUSIONS: The pattern of LNR provided a better reflection of the patterns of LNM. In terms of the LNR, central neck dissection is the basic extent of lymph node dissection for all clinically apparent PTC. In advanced patients, it is also advisable to include bilateral lateral neck dissection.

Immunologic and virologic analyses in pediatric liver transplant recipients with chronic high Epstein-Barr virus loads.

BACKGROUND: Long-term Epstein-Barr virus (EBV) monitoring for potentially life-threatening posttransplant lymphoproliferative disorder (PTLD) has identified asymptomatic patients who maintain high EBV loads over long periods. METHODS: Thirty-one pediatric liver transplant recipients were designated as 11 chronic high EBV load carriers (EBV DNA level >5000 copies/mL of whole blood for >6 months) and 20 control recipients. Serial quantification of EBV DNA, measurement of interleukin 10 (IL-10) concentrations, EBV-specific tetramer staining, and relative quantification of EBV gene expression in peripheral blood mononuclear cells were performed. RESULTS: Most of the chronic high EBV load carriers were seronegative at transplant, the median time to resolution of a chronic high EBV load was 23 months, and no recipient developed late-onset PTLD. EBV DNA was detected predominantly in CD19(+) cells. The plasma concentration of IL-10 and the EBV-specific CD8(+) cell frequency did not differ significantly between the chronic high EBV load carriers and the control recipients. Analysis of gene expression showed that EBV-encoded small RNA 1, BamHI A rightward transcripts, and latent membrane protein 2 were positive in peripheral blood mononuclear cells from chronic high EBV load carriers. CONCLUSIONS: EBV-infected cells in the blood of chronic high EBV load carriers expressed a highly restricted set of latency genes, suggesting that the EBV-infected cells escaped from a T cell response.

Indirect immunohistochemical evaluation of graft fibrosis and interface hepatitis after pediatric liver transplantation.

Fibrosis or IH following pediatric liver transplantation is recognized as major causes of graft loss, but the etiology remains unclear. To determine this issue, we used an indirect immunohistochemistry technique with post-transplant serum samples from recipients and normal human liver tissues from living liver donors, and the association between occult antibody reaction to the liver and the occurrence of fibrosis or IH was evaluated. Forty-three recipients were evaluated, and both hepatocytes and biliary epithelial cells were evaluated for staining intensity. Fibrosis and IH occurred in 13 and six patients, respectively. According to staining results for the hepatocytes and biliary epithelial cells, 18 and 11 patients, respectively, were classified into the positive group. According to log-rank analysis, positive reaction for hepatocytes was associated with increased rates of fibrosis and IH (p = 0.002 and 0.048, respectively), while positive reaction for biliary epithelial cells was associated with an increased rate of fibrosis (p = 0.014). Multivariate analysis revealed that positive reaction for hepatocytes and biliary epithelial cells was independently associated with fibrosis occurrence (p = 0.020 and 0.047, respectively). In conclusion, immune-mediated reactions by occult antibodies may underlie the pathogeneses of fibrosis and IH.

Gray-scale ultrasonography shows serial changes of the congestive area after living donor liver transplantation using right lobe graft.

BACKGROUND/AIMS: Hepatic venous congestion after living donor liver transplantation using right lobe graft produces various abnormalities on ultrasonography. Doppler sonography can reveal reversal of the portal flow direction in patients with acute and severe venous congestion and can show the presence of a functional intrahepatic anastomosis between the hepatic vein tributaries during the follow-up period in those people with improved congestion. However, few abnormal findings have so far been observed using gray-scale ultrasonography. METHODOLOGY: Thirteen patients who underwent living-donor liver transplantation using right lobe graft enrolled in this study. Postoperative ultrasonography was performed during the first 14 days after surgery. The serial changes of the congestive area indicated by gray-scale ultrasonography were quantitatively and qualitatively analyzed. RESULTS: Gray-scale ultrasonography showed the congestive areas as hyperechoic lesion in comparison to normal hepatic parenchyma. Congestive areas were seen in 4 patients in the early postoperative period (1-3 postoperative days). The acoustic intensity was higher in the congestive areas than in non-congestive areas (19.7 +/- 1.6 vs. 9.7 +/- 1.8 dB, respectively) in the early postoperative period. However, there was no difference between the congestive and non-congestive areas (21.3 +/- 5.0 vs. 19.8 +/- 2.6 dB, respectively) in the late postoperative period (8-14 postoperative days). Interestingly, the acoustic intensity in the congestive area in the early postoperative period was similar to that in the non-congestive area in the late postoperative period (19.7 +/- 1.6 vs. 19.8 +/- 2.6 dB, respectively). In nine patients who had no congestive area, acoustic intensity was similar throughout the postoperative period. CONCLUSIONS: Congestive areas can be seen in gray-scale ultrasonography. A congestive area may spread to a non-congestive area in patients whose congestive area can be seen on gray-scale ultrasonography in the early postoperative period.

Risk factors of recipient receiving living donor liver transplantation in the comprehensive era of indication and perioperative managements.

Living donor liver transplantation (LDLT) has become one of the chief methods of saving patients with end-stage liver disease due to liver cirrhosis. Accumulation of knowledge about indication and perioperative managements improve outcome of this treatment. In this study, we elucidate the risk factors of LDLT, which still exist today. Sixty-one patients received LDLT in our institute between 2003 and 2009 were included in this study. Recipient age and sex, donor age and sex, etiology, preoperative model of end-stage liver disease (MELD) score, hepatocellular carcinoma (HCC), graft versus recipient weight ratio (GRWR), cold and warm ischemic time, operation time, blood loss, ABO compatibility, rejection, cytomegalovirus (CMV) infection, biliary stricture, and calcineurin inhibitor (FK506 or cyclosporin A) were the factors investigated. p < 0.05 was considered as statistically significant in the proportional hazard model. In univariate analysis, the recipients' age (p = 0.024) and rejection episode (p = 0.046) were selected as significant risk factors. In multivariate analysis including the factors that showed p < 0.2 (recipient age, GRWR, ABO compatibility, rejection episode) in univariate analysis, recipient age (p = 0.008, HR: 1.40; 95% CI: 1.09-1.80) and rejection episodes (p = 0.002, HR: 13.33; 95% CI: 2.53-71.43) were still selected as significant independent risk factors after LDLT. Recipient age was shown to be 1.40 times risk per 1 year older and the rejection episode was shown to be 13.33 times risk in the recent era with comprehensive indication and preoperative management for LDLT. Indication must be cautious for elderly patients, and prevention of rejection is crucial for the improvement of results for LDLT.

Serial measurement of Doppler hepatic hemodynamic parameters for the diagnosis of acute rejection after live donor liver transplantation.

To elucidate the role of Doppler hepatic hemodynamic parameters as surrogate markers of acute rejection (AR) after live donor liver transplantation (LDLT), serial Doppler measurements were prospectively performed during the first 2 weeks after LDLT to compare the longitudinal hepatic hemodynamic changes between patients with histologically proven AR and patients without histologically proven AR. Forty-six patients that had undergone adult-to-adult LDLT using a right lobe graft were enrolled in this study. The portal venous maximum velocity (PVV; cm/second), portal venous flow volume, hepatic arterial peak systolic velocity, hepatic arterial pulsatility index, hepatic venous maximum velocity, hepatic venous pulsatility index, and splenic arterial pulsatility index were measured. Fourteen patients were diagnosed by biopsy to have clinically relevant AR. Markedly increased PVV was seen soon after surgery and gradually decreased in both patients with clinically relevant AR and patients without clinically relevant AR. This serial change of decreasing PVV was significantly greater in patients with clinically relevant AR (P < 0.0001). After postoperative day 6, the PVV in patients with clinically relevant AR was significantly lower than that in patients without clinically relevant AR (PVV on postoperative day 6: 35.6 +/- 21.3 versus 58.3 +/- 27.1 cm/second, respectively, P = 0.0080). A PVV cutoff value of 20.2 cm/second demonstrated the best accuracy for predicting clinically relevant AR. The sensitivity and specificity for predicting clinically relevant AR were 92.9% and 87.1%, respectively. The area under the curve was 0.94. In conclusion, serial Doppler measurement of hepatic parameters in LDLT is useful for the diagnosis of clinically relevant AR. Clinically relevant AR should therefore be suspected when a marked unexpected decrease in the PVV is observed.

Two cases of central venous catheter-related thrombosis in living liver donors: how can the risk be minimized?

A central venous catheter (CVC) is commonly used for intraoperative management by anesthetists and surgeons during major operations, including donor operations for living donor liver transplantation (LDLT), in which donor safety is of utmost importance. Reasons for use of CVC for donors include measurement of central venous pressure and drug infusion when necessary. A potentially serious complication of a major operation is pulmonary thromboembolism. We report two cases of LDLT donors complicated by catheter related thrombosis (CRT) of the jugular vein, who were eventually discharged without long-term complications. To the best of our knowledge, there has been no report of CRT among LDLT donor population. In this report, in order to minimize the risks related to CRT in LDLT donors, we propose thorough screening for thrombophilic disorders, use of a silicone or polyurethane double-lumen CVC as thin as possible, placement of the tip of the CVC at the superior vena cava via the right jugular vein using ultrasonography as a guide for puncture, and removal of the catheter at the end of the operation based on our experience of CRT among LDLT donors.

Possible involvement of BRAFV600E in altered gene expression in papillary thyroid cancer.

Somatic mutations in BRAF, especially BRAFV600E, are frequently identified in papillary thyroid cancer (PTC) tumors. It has been established that expression levels of numbers of genes are characteristically altered in PTC, however, the link between BRAF mutation and gene expression patterns are still elusive. In the present study, we analyzed relative expression levels of the wild type BRAF and BRAFV600E mRNA by using quantitative PCR (qPCR) and cDNAPCR- RFLP in 19 PTC specimens and adjacent normal thyroid tissues. BRAFV600E mRNA was detected in 17 out of 19 PTC specimens, and the expression levels were valuable among the specimens, suggesting alternative expression of BRAFV600E in each cell and/or alternative population of BRAFV600E-positive clones in the tumor. We then analyzed expression levels of 20 genes by qPCR, and analyzed for possible correlation with expression levels of BRAFV600E mRNA. Expression levels of fibronectin, vimentin and CITED1 (Cbp/p300 interacting protein with glutamic acid and aspartic acid rich carboxyl terminal domain) were positively correlated with those of BRAFV600E, suggesting pathophysiological links between activated BRAF and overexpression of these genes. Among these genes expression of vimentin was decreased by inhibiting BRAF expression in NPA cells that express BRAFV600E by means of siRNA, suggesting activated BRAF positively regulate expression of vimentin. Collectively, our analyses illustrated the possibilities that variable expression of BRAFV600E may modify characters of PTC through its effects on gene expression.

Long term parathyroid function following total parathyroidectomy with autotransplantation in adult patients with MEN2A.

While there is no doubt that total thyroidectomy is necessary for medullary thyroid carcinoma (MTC) in multiple endocrine neoplasia type 2A (MEN2A) patients, there is still controversy regarding the management of the parathyroid glands. Although most, but not all, endocrine surgeons leave normal-appearing parathyroid glands in situ during thyroid surgery for MEN2A, we have employed total parathyroidectomy with autotransplantation. Between 1994 and 2006, 12 MEN2A patients underwent therapeutic total or completion thyroidectomy and lymph nodes dissection at least in the central compartment for MTC. Total or completion parathyroidectomy with autotransplantation was performed concurrently with above-mentioned surgery. All patients were over 25 years old, and the median age was 48.5 years. There were 5 males and 7 females from 8 families. The average number of transplanted parathyroid glands was 3. Serum calcium and intact PTH levels have been maintained during the median follow up of 107 months in all patients except for one who of died of advanced MTC one year after surgery. Total parathyroidectomy with autotransplantation at the time of primary surgery for MTC, i.e. total thyroidectomy with bilateral central neck dissection, is a feasible approach for managing the risk of hyperparathyroidism.