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Biomedical subjects

M Makuuchi

Publications and source records attributed to M Makuuchi.

At least 37 records · Page 2Linked to original sources

Prediction of hepatic artery thrombosis by protocol Doppler ultrasonography in pediatric living donor liver transplantation.

Hepatic arterial thrombosis (HAT) after liver transplantation is a life-threatening event. Previous reports have suggested that the resistive index (RI) of the hepatic artery predicts HAT. Doppler ultrasonography (US) to measure RI, however, is not routinely performed. The subjects were 70 pediatric patients who underwent living donor liver transplantation (LDLT). Protocol Doppler US was performed once or twice a day for 2 weeks postoperatively and 692 records were examined. Changes in RI values were examined separately in patients with and without HAT complications. The incidence of HAT was 10% (seven of 70). HAT was diagnosed an average of 6.2 days after LDLT. In patients without HAT complications ( n = 63), average RI levels at 14 days after LDLT were 0.71 +/- 0.1 (records, n = 625). In patients with HAT complications, RI decreased gradually within 2 days before the onset of HAT. RI values of less than 0.6 predicted HAT within 2 days before onset, with 83% sensitivity and 85% specificity. RI during the first 2 weeks after LDLT is a sensitive predictor for HAT. Thrombectomy and reanastomosis should be considered when RI values are less than 0.6 in Doppler US.

Adolescent↗

Living donor liver transplantation for end-stage hepatitis C.

Living donor liver transplantation is important for patients with end-stage viral hepatitis because of the shortage of organs from deceased donors. However, preliminary results indicate that living liver donation might be disadvantageous for hepatitis C virus-positive patients. Twenty-seven patients who underwent living donor liver transplantation for hepatitis C virus cirrhosis preemptively received antiviral therapy using interferon-alpha2b and ribavirin, which was started an average of 32 days after the operation and continued for at least 6 months thereafter. The serum hepatitis C virus RNA became negative in the 8 of 16 patients with more than 1 year follow-up. The cumulative 3-year patient survival was 85%, which was comparable to that of hepatitis C virus negative patients (n = 93; 90%). Preemptive antiviral therapy after transplantation may be necessary for satisfactory results after living donor liver transplantation.

Adult↗

Effect of hematocrit on pharmacokinetics of tacrolimus in adult living donor liver transplant recipients.

OBJECTIVE: Plasma drug concentrations are generally considered to reflect efficacy and pharmacokinetics more directly than those in whole blood. However, whole blood has been selected as the matrix to monitor concentrations of tacrolimus (FK506), because it is difficult to accurately measure plasma FK506 concentrations. Because FK506 highly and saturably binds in blood cells, a change in hematocrit value (Hct) may affect FK506 pharmacokinetics. Therefore, we investigated effects of Hct on FK506 pharmacokinetics. METHODS: First, we analyzed data on FK506 distribution among human blood cells in vitro. Briefly, we employed an equation, which describes saturable binding of FK506 to blood cells, and simulated plasma FK506 concentrations and clearances using the above equation with respect to a variable Hct. Subsequently, we retrospectively analyzed dosages and whole blood FK506 concentrations to predict plasma FK506 concentrations in living donor transplant recipients. RESULTS: In the simulation study, the Hct changed plasma FK506 concentrations and clearances based in whole blood. In living donor liver transplant recipients, whole blood FK506 concentrations were maintained within a therapeutic range, while the Hct varied after transplantation. The correlation of Hct with the ratio of dose/trough concentrations of FK506 (D/C) in plasma (D/Cp) (R = -0.23, n = 343) was weaker than that for D/C in whole blood (D/CWB) (R = -0.53, n = 343). CONCLUSION: Hct may be an important factor affecting the pharmacokinetics of FK506 in living donor liver transplantation recipients. It may be necessary to take Hct into consideration in the FK506 dosing regimen, especially when the Hct is low.

Adult↗

Classification of portal vein anatomy for partial liver transplantation.

The anatomy of the portal vein is usually classified as 3 to 5 patterns and simple compared with the anatomy of the hepatic artery. The variety of portal vein anatomy was examined in 287 living donors for liver transplantation. More than 90% of donors showed a normal bifurcation type; 6% showed the trifurcation type. Only 3% displayed a separate origin of the right paramedian and the right lateral branches. There was no anomalous pattern that had not been reported previously. In our series, we conclude that it is rare for 2 or more stumps of portal vein to appear in partial liver transplantation. The frequency is much less if the left liver or the right lateral liver graft is used for adult-to-adult living donor liver transplantation.

Functional Laterality↗

Simultaneous hepatic artery and portal vein thrombosis after living donor liver transplantation.

Simultaneous hepatic artery and portal vein thrombosis rarely occurs after liver transplantation. The etiology is unknown. Of 213 patients (72 children and 141 adults) that underwent living donor liver transplantation (LDLT) from January 1996 to March 2003, 4 (2%) developed simultaneous thrombosis at 3 hours to 7 days (median, 4 days) after the operation. Emergent thrombectomy was performed in three patients; the remaining patient was registered in the Japan organ transplant network. All of the patients died due to hepatic failure (range, 18 hours to 6 days after the diagnosis; median, 2 days). Portal vein, hepatic artery, and hepatic vein velocity in the liver graft were measured every 12 hours by Doppler ultrasonography for 2 weeks after liver transplantation. These parameters were stable until just before the simultaneous thrombosis. These findings indicate that protocol Doppler ultrasonography can diagnose, but not predict, this fatal complication.

Adolescent↗

Conversion to cyclosporine provides valuable rescue therapy for living donor adult liver transplant patients intolerant to tacrolimus: A single-center experience at the University of Tokyo.

Tacrolimus-based immunosuppression is currently accepted as mainstream therapy in many transplant centers worldwide due to its potent immunosuppressive activity compared to cyclosporine. A tacrolimus-based regimen has been successfully used for our living donor liver transplantation (LDLT) recipients. Adverse effects such as neurotoxicity, nephrotoxicity, and new-onset diabetes mellitus, however, have limited its clinical application. In deceased donor liver transplantation, cyclosporine rescue therapy is valuable for such complications, but few reports have described a strategy for conversion in LDLT. Herein, we present our experience of conversion from tacrolimus to cyclosporine therapy in adult LDLT recipients. Among 203 recipients, 37 patients (18%) required conversion, primarily for neurotoxicity (41%), diabetes mellitus (16%), hematopoietic disorder (16%), and gastrointestinal intolerance (11%). Primary adverse events resolved within 2 months after conversion in 35/37 (94%) of the patients. For LDLT recipients unable to maintain effective immunosuppression with tacrolimus, conversion to cyclosporine is an effective option.

Adult↗

Efficacy of immunoadsorbent devices for maintaining hepatic function in ex vivo direct xenogenic hemoperfusion.

We have developed a new system for direct xenogenic hemoperfusion of a bioartificial liver support system adopting two types of immunoadsorbent devices. In this study, we compared the efficacy of each immunoadsorbent device in maintaining porcine hepatocyte function during 3 h perfusion treatment in a canine liver failure model. Suppression of humoral immunity by the immunoglobulin adsorber prevented immunogenic hepatocyte injury more effectively, and the system showed higher hepatic function when compared with suppression of cell-mediated immunity by the leukocyte adsorber. However, single use of immunoglobulin adsorber was less effective in reducing patients' systemic ammmonia levels and modulating the Fischer's ratio compared with the case of combined use of both immunoadsorbent devices. These results suggest that suppression of humoral immunity was of primary importance in preventing immunogenic hepatocyte injury, however the adsorption of leukocytes may have a synergic effect on maintaining hepatocyte function in direct xenogenic hemoperfusion.

Alanine Transaminase↗

Ultrasound-guided finger compression in liver subsegmentectomy for hepatocellular carcinoma.

Systematic subsegmentectomy is now accepted as the best option for the surgical management of hepatocellular carcinoma in patients with cirrhosis because it optimizes the balance between oncological requirements and the need to spare functioning liver parenchyma. However, this technique can be difficult because it requires a strong background in ultrasound-guided interventional procedures. We describe a new, simplified technique for the anatomical subsegmental hepatic resection of segment 2 or 3. It consists of IOUS-guided blunt portal branch compression to disclose the subsegmental area to be removed. This technique is a further evolution of so-called systematic subsegmentectomy for tumors located in segments 2 and 3. Its main advantages are that it is easy, fast, and reversible. We believe that it has the potential to lead to new opportunities in subsegmental anatomic liver resection.

Carcinoma, Hepatocellular↗

Duct-to-duct biliary reconstruction for living donor liver transplantation: experience of 92 cases.

Bile duct-to duct reconstruction is now performed in living donor liver transplantation (LDLT) for adult patients. To confirm the feasibility, the results after the reconstruction were retrospectively analyzed. The subjects were 92 adult patients who underwent LDLT at the University of Tokyo Hospital. During the observation period (median 546 days), biliary complications were observed in 28 cases (30%). The complications included bile juice leakage in 11, stenosis at the anastomotic site in 9, and tube trouble in 8. Of these, 20 patients required surgical revision. The results suggest that duct-to-duct reconstruction provides satisfactory results, although long-term observation will be necessary.

Bile Ducts↗

Left liver grafts for patients with MELD score of less than 15.

Left liver grafts are now seldom used for adult recipients of living donor liver transplantations because the left liver is believed to be insufficient to meet patient metabolic demands. At the University of Tokyo Hospital, left liver grafts have been limited to patients with fulminant hepatic failure or chronic hepatic failure with a model for end-stage liver disease (MELD) score of less than 15. Since 2000 25 adult patients received left liver grafts. The mean graft weight to standard liver volume ratio was 44%. The rates of acute rejection, vascular, and biliary complications were 24%, 0%, and 25%, respectively. All patients survived the operation and are doing well with a mean follow-up of 17 months. The present results suggest that left liver grafts provide acceptable results among patients satisfying our criteria.

Adult↗

EBAG9/RCAS1 expression in hepatocellular carcinoma: correlation with tumour dedifferentiation and proliferation.

The oestrogen-responsive gene, EBAG9, whose product is identical to the cancer cell surface antigen RCAS1, is reported to be associated with tumour progression and invasiveness in various carcinomas. In this study, we examined the expression of EBAG9/RCAS1 in hepatocellular carcinoma (HCC), with special reference to its relationship with the stepwise evolution of HCC. Expression was examined by immunohistochemistry and western blotting analysis in 143 HCCs, as well as in non-cancerous liver tissues. After which, the association between enhanced EBAG9/RCAS1 expression and various clinicopathological parameters including Ki-67 labelling index (LI), a marker of proliferative activity, was evaluated. There was a constant low level of EBAG9/RCAS1 expression in non-cancerous liver tissues, with a regular cytoplasmic distribution. Positive immunoreactivity for EBAG9/RCAS1 was detected on the surface and in the cytoplasm of 84 HCC tumours, with an irregular staining pattern. Enhanced EBAG9/RCAS1 expression was correlated with a lower degree of differentiation and Ki-67 LI. Interestingly, expression was enhanced specifically in the less differentiated lesions within 'nodule-in-nodule' tumours. In conclusion, EBAG9/RCAS1 was associated with HCC tumour dedifferentiation and increased proliferative activity. Its exact functional role remains to be established.

Adolescent↗

Smallest Todani's type II choledochal cyst.

A choledochal cyst is defined as an isolated or combined congenital dilation of the extra hepatic or intrahepatic biliary tree. Todani and colleagues proposed the five types of congenital choledochal cysts which have gained widespread acceptance. Type II choledochal cyst, a diverticulum of common bile duct, is rarest, and most reported cases of Type II were as large as several centimeters in size. We herein report the case of a small Type II choledochal cyst which was resected at pancreatoduodenectomy for carcinoma of the papilla of Vater. A 58-year-old Japanese male was referred to our hospital for the evaluation of jaundice. Preoperative cholangiogram via the percutaneous transhepatic biliary drainage tube revealed a complete obstruction at the narrow terminal segment. Furthermore, a small diverticular protrusion was demonstrated on the lower part of the common bile duct. The resected specimen showed a 2.2 x 1.7 x 1.2 cm carcinoma of the major papilla, and a deep, 2 mm in diameter and 5 mm in depth, depression on the posterior wall of the common bile duct. The anomalous pancreatobiliary duct was not seen. The deep depression was confirmed microscopically to penetrate the fibromuscular layer of the common bile duct and diagnosed as a Todani's Type II choledochal cyst. To our knowledge, the current case is the smallest Type II choledochal cyst which was completely resected.

Cholangiography↗

Association of histochemical expression of Maackia amurensis leukoagglutinin-positive glycoconjugates with behaviour of human gastric cancer.

AIMS: To investigate the relationship between sialylation of glycoconjugates and clinicopathological characteristics of gastric cancer. METHODS AND RESULTS: Sialylation of glycoconjugates was examined histochemically in 71 gastric cancers using Maackia amurensis leukoagglutinin (MAL), a lectin that recognizes the trisaccharide sequence NeuAc alpha 2,3Gal beta 1,4GlcNAc/Glc. Positive staining with MAL was observed in the tumour region of all of the samples, but the populations of MAL-positive tumour cells in the tumour region varied among the samples. In the corresponding non-cancerous regions, however, no positive staining was observed. Calculating the percentage of MAL-positive tumour cells as part of the total tumour cells with respect to the MAL-staining index (MI) allowed the gastric cancer to be classified into two distinct groups: high and low levels of MI, with a cut-off level of 40% of MI. Furthermore, statistical analyses using the MI level and clinicopathological characteristics of the tumour indicated that a high MI level in gastric tumour tissues is related to a poorer prognosis. CONCLUSIONS: The appearance of MAL-positive glycoconjugates in gastric tumour cells is associated with the behaviour of gastric cancer.

Adult↗