Serum vascular endothelial growth factor-receptor 1 during liver regeneration.
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Animals↗
Biomedical subjects
Shinji Uemoto
Publications and source records attributed to Shinji Uemoto.
Classification of pancreatic cancer: comparison of Japanese and UICC classifications.
The Japan Pancreas Society (JPS) published the fifth Japanese edition of the General Rules for the Study of Pancreatic Cancer in 2002, the same year that the Union Internationale Contre le Cancer (UICC) published its sixth edition. The JPS fifth edition had been revised, based on data from 18,629 cases of carcinoma of the pancreas registered by the JPS (1981-1996) with the goal of making the General Rules simple, easy to understand, and reliable for predicting outcome. The 2 classifications are compared by analyzing the data on 3979 resected patients with tubular adenocarcinoma of the pancreatic head registered by the JPS, focusing on the reliability of predicting outcome. In the extent of the primary tumor (T category), survival rates differed significantly among the 4 groups (T1, T2, T3, T4) in the JPS and UICC classifications. In the extent of lymph node metastasis (N category), survival rates differed significantly among the 4 groups (N0, N1, N2, N3) in the JPS classification and also did significantly between the 2 groups (N0, N1) in the UICC classification. In the stage grouping, however, 2 classifications differed considerably. More than half of the cases of UICC stage II are equivalent to JPS stage IV. Comparison of survival curves according to stage reveals that stratification is much better in the JPS classification than in the UICC classification. These results indicate that the JPS classification is more reliable for predicting outcome as compared with the UICC classification.
Adenocarcinoma↗
Intrahepatic hepatic vein stenosis after living-related liver transplantation treated by insertion of an expandable metallic stent.
Although the incidence of stenosis and obstruction of the hepatic venous anastomosis after right hepatic living-related liver transplantation (LRLT) has been found to be higher than after orthotopic liver transplantation (OLT), to the best of our knowledge, intrahepatic stenosis of the venous trunk in the early period after right hepatic LRLT has never been reported in the literature. A 53-year-old man who underwent right hepatic LRLT, postoperatively, developed liver dysfunction and an increasing amount of ascites, and a Doppler sonogram showed a flat waveform and low-flow velocity in the hepatic vein. Based on these findings an outflow block was suspected, and a hepatic venogram and manometry revealed intrahepatic stenosis of a tortuous hepatic venous trunk and a pressure gradient of 14 mmHg at the site of the stenosis. We inserted an expandable metallic stent (EMS) at the site of intrahepatic venous stenosis, and its insertion was followed by a decrease in pressure gradient. Liver function recovered, and the volume of ascitic fluid decreased after placement of the EMS. The results of an analysis of the venogram and CT volumetric data suggested that the pathogenesis of the stenosis was twisting of the venous trunk during hypertrophy of the liver parenchyma.
Ascitic Fluid↗
Early graft hemodynamics in living related liver transplantation evaluated by Doppler ultrasonography.
The aim of this study was to clarify the perioperative hemodynamics of liver grafts without vascular complications during and early after liver transplantation from living donors. This study was carried out in 4 child recipients (lateral segment left lobe grafts) and 6 adult recipients (right lobe grafts) of liver transplantation from living donors. The hemodynamics of the hepatic artery, portal vein, and hepatic vein of the grafts during and until 7 days after surgery were studied by Doppler ultrasonography. The maximum flow velocity of the hepatic artery, mean portal blood flow velocity, and pulsatility index (PI) of the hepatic artery increased in all 10 grafts with no vascular complication after vascular anastomosis. After surgery, the mean portal blood flow velocity showed a peak 3 days after surgery and reached a nadir 7 days after surgery in both the lateral segment left lobe grafts in children and the right lobe grafts in adults, but it was significantly higher in the right lobe grafts in adults (mean +/- SD 31.0 +/- 6.3 vs. 22.4 +/- 0.9 cm/sec). Also, as the hepatic artery blood flow velocity increased the portal blood flow velocity decreased, the hepatic blood flow during liver regeneration was suggested to be controlled by both the artery and portal vein. The range of PI of the hepatic artery was 0.60-1.86. The mean hepatic venous blood flow was stable throughout the observation period (30.4 +/- 8.8 cm/sec). Although the hepatic venous flow waves changed widely from pulsed waves to a flat flow, its changes did not suggest a vascular complication. Evaluation of changes by Doppler ultrasonography in the hemodynamics of the liver grafts without vascular complications during and early after liver transplantation from living donors is considered to be useful for accurate monitoring of the hemodynamics during liver regeneration and early detection of abnormalities.
Adult↗
[Surgical indications and timing in severe acute pancreatitis].
Infected pancreatic necrosis is the major risk factor with regard to morbidity and mortality in severe acute pancreatitis. Whereas surgery for sterile necrosis can only be recommended in selected cases, infected pancreatic necrosis is a well-accepted indication for surgery. Surgery should be postponed until 4 weeks after the onset of symptoms, as necrosis is well demarcated at that time. Two surgical techniques can be performed with comparable results regarding mortality: necrosectomy combined with closed continuous local lavage or open drainage. Selection of these techniques depends on the extent of infected peripancreatic fat necrosis. Open drainage seems to be selected for the cases in which infected tissue is extensively found. However, local lavage is associated with the lower morbidity than open drainage.
Abscess↗
Bacterial analysis of infected pancreatic necrosis and its prevention (Symposium 8: Pancreatobiliary infection (IHPBA)).
In severe acute pancreatitis, sepsis mainly due to pancreatic or peripancreatic infection have emerged as the most serious complications and now accounts for more than 80% of deaths. Collective review of organisms associated with secondary pancreatic infection in patients with acute pancreatitis has revealed that most of them are intestinal flora. Several experimental studies including ours have revealed that acute pancreatitis promotes bacterial translocation (BT), which in turn leads to infection of the pancreas and septic complications. Prophylactic antibiotics given intravenously have been demonstrated to be beneficial in reducing the rate of pancreatic infection, but their survival benefit remains unclear. We have demonstrated that continuous regional arterial infusion (CRAI) of an antibiotic is more effective than intravenous administration in preventing pancreatic infection and improving survival, in a canine model of acute necrotizing pancreatitis. Our recent experimental study has revealed that CRAI of an antibiotic via the superior mesenteric artery (SMA) is effective in mitigating intestinal mucosal damage and preventing BT in acute pancreatitis, thereby improving survival. BT aggravates pancreatic necrosis and remote organ damage in acute pancreatitis, and SMA infusion of antibiotics is effective in preventing BT and is practical for clinical use.
Acute Disease↗
Quantitative PCR to evaluate small amounts of BCL2 mRNA in human peripheral T cells: implication of equimolar target and competitor end products.
BACKGROUND: It is difficult to reliably and reproducibly quantitate small amounts of mRNA by conventional PCR. The method we describe here enabled us to more accurately quantitate a small amount of BCL2 mRNA in human peripheral T cells. METHODS: The sample was amplified in four tubes containing three-fold serial dilutions of competitor so that when the PCR products in the four tubes were totaled, the number of target and competitor components were approximately equal. An unknown concentration of target molecules should be assessed only within a narrow range, requiring that several reactions be performed for each sample. RESULTS AND CONCLUSION: With this method, conventional PCR machines can be used to perform quantitative PCR on very small amounts of BCL2, and would be especially useful for samples that contain substance(s) that affect PCR amplification efficiency.
Adolescent↗
Monosegmental living-donor liver transplantation for infantile hepatic hemangioendothelioma.
Infantile hepatic hemangioendothelioma (IHHE) is a rare vascular tumor that presents before the age of 6 months. The patients with IHHE suffer from high-output congestive heart failure caused by major arteriovenous fisutulas in the liver, which leads to respiratory compromise and results in a high mortality rate despite medical treatments. A case of 4-month-old baby with liver failure caused by IHHE is reported. The baby received an urgent liver transplantation from a living donor. A monosegmental graft was used to mitigate graft-to- recipient size mismatching. The surgical procedure of monosegmental living donor liver transplantation also is discussed.
Hemangioendothelioma↗
Circulating antibody to hepatitis B core antigen does NOT always reflect the latent hepatitis B virus infection in the liver tissue.
Accumulating evidence suggests the presence of latent hepatitis B virus (HBV) infection in the liver of individuals negative for HBV surface antigen (HBsAg) but positive for antibodies to HBV core antigen (anti-HBc) at low titer. It remains unclear, however, whether positive anti-HBc in the serum invariably reflects latent HBV infection. In this study, we examined the presence of HBV genomes in the liver tissue of 33 donors and 30 recipients of living-related liver transplantation with positive for anti-HBc together with time course changes in their anti-HBc titer. None of these anti-HBc-positive healthy donors or recipients was positive for HBV-DNA nor anti-HBc at high titer (200 dilution) in their sera. However, HBV-DNA was detected in the liver tissue of 24 of 33 healthy anti-HBc-positive donors (72.7%) and five of 30 anti-HBc-positive recipients (16.7%). Interestingly, anti-HBc was continuously positive in all healthy donors tested. In contrast, anti-HBc titers in 75% of recipients, who were positive for anti-HBc at the time of liver transplantation, gradually decreased after the operation, and finally became negative after the mean follow up period of 9.0 months (range 1.2-45.1). Notably, HBV-DNA was never detected in the liver of those recipients who were transiently positive for anti-HBc. In conclusion, our findings suggested the possibility that presence of circulating anti-HBc does not always reflect the presence of HBV genomes in the liver tissue of anti-HBc-positive patients.
Journal Article↗
Lens culinaris agglutinin-A-reactive alpha-fetoprotein as a marker for liver atrophy in fulminant hepatic failure.
Liver atrophy is frequently found at autopsy of patients with fulminant hepatic failure (FHF). Imaging studies in patients with FHF demonstrate that estimation of total liver volume correlates with prognosis. In this study, in order to determine serum markers for evaluating liver atrophy, we measured the weight of whole livers resected from 31 transplant recipients with FHF, and assessed the relation between the liver weights and several prognostic markers. The level of liver atrophy was evaluated by calculating the ratio of the removed whole liver weight to the body weight of each recipient, and 16 major variables including several serological markers were analyzed among those recipients. We found that the serum Lens culinaris agglutinin-A-reactive alpha-fetoprotein (AFP-L3) levels were significantly higher in patients with FHF than in those with other liver diseases. In FHF patients, the serum AFP-L3 level at the onset of encephalopathy was significantly higher in cases with mild atrophy than in those with severe atrophy (P<0.05). Notably, the residual liver volume was significantly correlated with the serum AFP-L3 level (Pearson's correlation coefficient=0.63), but not with AFP. In conclusion, AFP-L3 is a possible serum marker for evaluating liver atrophy and/or liver regeneration in patients with FHF.
Journal Article↗
Long-term effects of liver transplantation on bone mineral density in children with end-stage liver disease: a 2-year prospective study.
In children with end-stage liver disease, little is known regarding the long-term effects of liver transplantation on bone. In this 2-year prospective study, we evaluated the effects of liver transplantation on bone mineral density (BMD) and on other parameters of bone metabolism in 30 consecutive children with biliary atresia who underwent liver transplantation after failed Kasai operation. Tacrolimus and steroids were used as immunosuppressants. BMD of the first through fourth lumbar spine (L1-4) was measured by dual-energy radiographic absorptiometry (QDR-2000, Hologic) and expressed in Z-values. Before transplantation, Z-values of BMD, height, and weight were low in all patients (-3.4 +/- 0.34, -2.0 +/- 0.28, and -1.67 +/- O.16 [mean +/- SEM], respectively). Low BMD states were associated with low levels of serum 25-hydroxyvitamin D and serum levels of insulin-like growth factor-I (IGF-I), one of the most potent anabolic skeletal growth factors. Liver transplantation resulted in marked improvement in BMD values as well as in height and body weight: 24 months after transplantation, recovery was achieved in each parameter (0.16 +/- 0.30, -0.29 +/- 0.23, and 0.42 +/- 0.18, respectively). BMD recovery first was observed 3 months after transplantation. Moreover, these favorable effects of transplantation were accompanied by increases in serum levels of 25-hydroxyvitamin D and IGF-I. We conclude that liver transplantation effectively reverses the low bone mass status and growth retardation of children with end-stage liver disease.
Adolescent↗
Enhanced expression of enterocyte P-glycoprotein depresses cyclosporine bioavailability in a recipient of living donor liver transplantation.
We evaluated levels of intestinal expression of absorptive-barrier P-glycoprotein (PGP) and cytochrome P-450 IIIA4 (CYP3A4) and immunosuppressant therapy in a patient who underwent living donor liver transplantation (LDLT) and received a second living donor liver transplant after chronic rejection of the first. PGP and CYP3A4 expression were measured using part of a Roux-en-Y limb. After the first LDLT, the concentration-dose ratio of orally administered tacrolimus was 159.8 +/- 125.3 (average +/- SD of 32 different days), similar to the average for 46 recipients of living donor liver transplants in our hospital (161.3 +/- 88.1). However, the recipient required very large oral doses of cyclosporine (703.9 +/- 385.4 mg/d, average +/- SD of 13 different days) after the second LDLT. Although intestinal PGP level was increased markedly at the second LDLT, CYP3A4 level was decreased. In addition, levels of messenger RNA expression of several gene products related to the local inflammation, such as cyclooxygenase 2, interleukin-1beta (IL-1beta), IL-2, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha, were increased. These results suggest that hepatic failure after LDLT, including chronic rejection and/or cholangitis, was accompanied by upregulation of intestinal PGP expression, which could depress the bioavailability of the immunosuppressant.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Laparoscopic splenectomy for a huge splenic cyst without preoperative drainage: report of a case.
Laparoscopic splenectomy currently is a safe procedure and offers better cosmetic results, less pain, and a shorter hospital stay than the traditional open procedure. However, there have been only a few reports of laparoscopic removal of giant splenic cysts. An 18-year-old woman was admitted with abdominal fullness. CT scans and MRI images of the upper abdomen revealed a cystic mass having a diameter of 19 cm. Preoperative diagnosis was a large splenic cyst, and laparoscopic splenectomy with intraoperative cyst drainage (amount of drained fluid: 3,000 mL) was performed. Histologically, almost the entire cyst wall was lined with fibrous tissue, but a small portion was covered with stratified squamous epithelium. The final diagnosis was epidermoid cyst. The postoperative course was uneventful. Laparoscopic splenectomy should be tried first even in patients with a huge cyst, and intraoperative drainage under laparoscopic guidance facilitates laparoscopic splenectomy.
Adolescent↗
Forecasting of blood tacrolimus concentrations based on the Bayesian method in adult patients receiving living-donor liver transplantation.
OBJECTIVE: To evaluate Bayesian prediction of blood tacrolimus concentrations in adult patients receiving living-donor liver transplantation (LDLT) using previously obtained population pharmacokinetic parameters. PATIENTS AND METHODS: Data were retrospectively collected from 47 adult patients receiving LDLT who were not included in the estimation of population pharmacokinetic parameters. Blood tacrolimus concentrations were predicted without or with the empirical Bayesian method using sparse samples obtained in the previous week. Predictive performance of the concentrations was evaluated by the mean prediction error (ME), mean absolute prediction error (MAE) and root mean square error (RMSE) as well as the percentage of successful predictions (percentage of absolute prediction error less than 3 microg/L, %PRED3). RESULTS: Concentrations predicted by the population mean pharmacokinetic parameter values coincided well with observed concentrations during the period of tacrolimus infusion immediately after the operation. For concentrations during subsequent oral therapy with tacrolimus, predictability by the population mean pharmacokinetic parameter values alone was not satisfactory. Bayesian forecasting using one or two blood concentrations obtained in the previous week significantly decreased (p<0.05) MAE and RMSE compared with predictions based on the population mean pharmacokinetic parameters on postoperative days 21 and 28, but not on day 14. During postoperative days 15-21, %PRED3 was increased to 68.6% or 71.2% with the Bayesian method using one or two blood concentrations, respectively, from 44.9% with the population mean pharmacokinetic parameter values. CONCLUSION: The present study demonstrated the applicability of the Bayesian method with use of one or two samples for prediction of blood tacrolimus concentrations in adult patients receiving LDLT.
Administration, Oral↗
Role of HLA compatibility in pediatric living-related liver transplantation.
BACKGROUND: Human leukocyte antigen (HLA) matching is, at present, not used for the allocation of cadaveric hepatic allografts because the liver is generally believed to be less susceptible to HLA-mediated rejection. However, the exact role of HLA compatibility in the long-term outcome of liver transplantation is not yet clearly defined. One of the advantages of living-related liver transplantation (LRLT) could be a better histocompatibility between donor and recipient. This study aimed at an assessment of the influence of HLA compatibility in a large series of LRLTs. METHODS: A total of 321 pediatric patients who underwent ABO-identical or ABO-compatible primary LRLT from the parental donors in the period between June 1990 and August 2000 were involved in the study. Graft survival, rejection episodes, and immunosuppression were evaluated from the viewpoint of HLA compatibility. RESULTS: The overall 1- and 5-year graft survivals were 85.7% and 84.1%, respectively. The cumulative 5-year graft survivals in HLA 0-, 1-, 2- and 3-mismatch groups (A, B, and DR) were 100% (n=10), 78.9% (n=19), 86.2% (n=87), and 82.9% (n=205), respectively (P=0.525). The overall incidence of rejection during the follow-up period (median 66 months, range 16-139 months) was 46.1%. No significant difference was found in the incidence of rejection and rejection-free survival among the four groups. However, steroid-resistant rejection that necessitated OKT3 treatment (n=6) and chronic rejection (n=2) were recognized only in the 3-mismatch group. The whole-blood trough level of tacrolimus and the duration of steroid administration were not significantly different among the groups. The rate of the patients who succeeded in withdrawal from immunosuppression was also similar among the groups. However, the trough level of tacrolimus needed for maintenance of an acceptable liver function test during the chronic phase tended to be lower in well-matched pairs, and a high percentage of immunosuppressant-free patients were found in the 0-mismatch group. Fatal graft-versus-host disease developed in one patient with a complete one-way HLA-matched transplant. CONCLUSION: We could not find any supportive evidence of beneficial effects of HLA-matching in pediatric LRLT. The potential benefit of HLA-matching for the reduction protocol for immunosuppressants may play a role in the withdrawal program. It appears unnecessary to pay attention to HLA compatibility in donor selection in LRLT, except for one-way HLA matching, or to adjust immunosuppression according to HLA compatibility.
Acute Disease↗
MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.
Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.
Adult↗
Anatomical variations and surgical strategies in right lobe living donor liver transplantation: lessons from 120 cases.
BACKGROUND: Anatomical variations in right liver lobe are common. However, clinical implications and surgical management of these variations in living donor liver transplantation have not been analyzed systematically. METHODS: Surgical anatomy of vascular and biliary structures in 120 right lobe grafts were reevaluated by reviewing the results of preoperative (computerized tomography and Doppler ultrasonography) and intraoperative (cholangiography) imaging as well as surgical findings. The data were analyzed in relation to surgical management of anatomical variations. RESULTS: The incidence of variants leading to multiple portal vein anastomoses was 7.5%. The incidence of dual right hepatic veins was 0.8%; 30% of the grafts had significant accessory hepatic veins (>5 mm) and 13.9% of these were multiple. All of them were successfully reconstructed with technical modifications including venoplasty and venous grafts, except for two cases with multiple intraparenchymal portal vein branches to the anterior segment. The incidence of dual hepatic arteries was 1.7%, but only one of them was reconstructed without negative sequelae. The incidence of variants potentially leading to multiple bile duct anastomoses was 35.0%, and eventually 39.2% of the grafts had multiple orifices. With a variety of techniques including ductoplasty, hepaticohepaticostomy, and biliary stent, total incidence of leakage and stenosis was 10.8% and 9.2%, respectively. Although ductoplasty, internal stent or no stenting, seemed to be associated with increased risk of complications, anatomical variants, multiple bile ducts, and duct-to-duct reconstruction did not bear a significant risk. CONCLUSIONS: Anatomical variations of vascular and biliary structures in right lobe grafts are common. However, most can be managed safely with technical modifications. Only cases with intraparenchymal origin of the anterior portal vein(s) may form a relative contraindication, especially when combined with similar biliary variants. Otherwise, intraoperative assessment of biliary anatomy was enough for successful management. Detailed and precise assessment of vascular and biliary anatomy is vital for appropriate surgical management.
Adult↗
Presence of autoantibody against ATTR Val30Met after sequential liver transplantation.
BACKGROUND: Recently, sequential liver transplantation has been performed with an explanted liver from a patient with familial amyloidotic polyneuropathy (FAP) because of the shortage of donors. However, metabolism of amyloidogenic transthyretin (ATTR), the pathogenic protein of FAP, has not been well studied in patients who have undergone sequential liver transplantation. The purpose of this study was to examine the changes in serum ATTR levels and to investigate the presence of an autoantibody in patients who underwent sequential liver transplantation with an explanted organ from a patient with heterozygotic FAP (FAP ATTR Val30Met). METHODS: This was a case study performed at the Kumamoto University School of Medicine, Kumamoto, Japan, and Kyoto University School of Medicine, Kyoto, Japan. Intervention occurred by sequential liver transplantation with an explanted FAP patient's liver. Levels of normal TTR and ATTR in the two patients who received the transplanted liver were analyzed by means of an enzyme-linked immunosorbent assay (ELISA) and a matrix-assisted laser desorption/time-of-flight mass spectrometry. In addition, the presence of an autoantibody against ATTR Val30Met was evaluated via ELISA using purified ATTR Val30Met from homozygotic FAP patients' sera. RESULTS: After the operation, the variant TTR levels were unexpectedly lower than levels of normal TTR in serum samples from patients with a transplanted liver from the FAP patient. An autoantibody against the variant TTR was detected on day 3 after the operation in the serum of those patients and continued to be present for at least 2 months after the operation. CONCLUSIONS: An autoantibody against the variant TTR may reduce the serum levels of variant TTR. Although the antibody may play a beneficial role in reducing the pathogenic protein, the long-term effect of the antibody must be investigated further.
Adolescent↗