Etsushi Kawamura

Physical inactivity and insufficient dietary intake are associated with the frequency of sarcopenia in patients with compensated viral liver cirrhosis.

The association between sarcopenia and nutritional status is thought to be an important problem in patients with cirrhosis. In this study, we investigated whether nutritional factors were related to sarcopenia in patients with liver cirrhosis.

Distinguishing benign from malignant gallbladder wall thickening using FDG-PET.

ObjectiveBecause thickening of the gallbladder wall is observed not only in patients with gallbladder cancer but also in those with benign diseases such as chronic cholecystitis and gallbladder adenomyosis, it is difficult to distinguish between benign and malignant gallbladder wall thickening by conventional techniques of diagnostic imaging such as computed tomography (CT), magnetic resonance imaging (MRI), and abdominal ultrasonography (US). In the present study, we attempted to distinguish between benign and malignant gallbladder wall thickening by means of fluorine- 18-fluorodeoxyglucose (FDG)- Positron emission tomography (PET).MethodsFDG-PET was performed in 12 patients with gallbladder wall thickening detected by CT or US, to determine whether it was benign or malignant. Emission scans were taken, beginning 45 minutes after intravenous administration of FDG, and SUV was calculated as an indicator of glucose metabolism.ResultsOf the 12 patients, 4 showed positive uptake of FDG in the gallbladder wall. Of these 4 patients, 3 had gallbladder cancer. The remaining one, who had chronic cholecystitis, had false-positive findings. The other 8 patients had negative uptake of FDG in the gallbladder wall. Two of these 8 underwent surgical resection, which yielded a diagnosis of chronic cholecystitis. The other 6 patients exhibited no sign of gallbladder malignancy and have been followed without active treatment.ConclusionsFDG-PET appears able to distinguish between benign and malignant gallbladder wall thickening.

A Randomized Pilot Trial of Oral Branched-Chain Amino Acids in Early Cirrhosis: Validation Using Prognostic Markers for Pre-Liver Transplant Status

Because of the chronic shortage of liver donors, hepatologists are required to prolong the liver transplant waiting period by preserving the hepatic reserve of scheduled recipients. This study examined the effectiveness of oral branched‐chain amino acids (BCAAs), using outcome markers indicating pretransplant hepatic reserve. Fifty‐six consecutive eligible patients with Child class A cirrhosis without major complications were randomly assigned to receive oral BCAA granules (12.45 g/day) for least 1 year or no BCAAs. Differences between groups in the Model for End‐Stage Liver Disease (MELD) score, Child‐Turcotte‐Pugh (CTP) score, asialoscintigraphic clearance index (CI), and complications were examined. Of 50 remaining patients, 27 received BCAAs, and 23 received no BCAAs (mean duration, 3.2 years). The mean annual changes in the MELD score, CTP score, and asialoscintigraphic CI were smaller in the BCAA group than in the control group (−0.06 ± 0.23 versus 0.10 ± 0.40, P = 0.024, 0.06 ± 0.30 versus 0.30 ± 0.48, P = 0.037, and 0.00 ± 0.02 versus 0.02 ± 0.04, P = 0.040, respectively). The mean annual changes in the serum total bilirubin and the serum albumin in the BCAA group were better preserved than those in the control group (−0.07 ± 0.20 versus 0.12 ± 0.18 mg/dL, P < 0.001, and 0.07 ± 0.13 versus −0.02 ± 0.19 g/dL, P = 0.005, respectively); other laboratory variables were not significant. The incidence of overall major cirrhotic complications was lower in the BCAA group than in the control group [14.8% (4 of 27 patients) versus 30.4% (7 of 23 patients) at 3 years, P = 0.043]; only ascites was significant individually. In conclusion, early interventional oral BCAAs might prolong the liver transplant waiting period by preserving hepatic reserve in cirrhosis. Liver Transpl 15:790–797, 2009.

Comprehensive analysis of transcriptome and metabolome analysis in Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma

Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are liver originated malignant tumors. Of the two, ICC has the worse prognosis because it has no reliable diagnostic markers and its carcinogenic mechanism is not fully understood. The aim of this study was to integrate metabolomics and transcriptomics datasets to identify variances if any in the carcinogenic mechanism of ICC and HCC. Ten ICC and 6 HCC who were resected surgically, were enrolled. miRNA and mRNA expression analysis were performed by microarray on ICC and HCC and their corresponding non-tumor tissues (ICC_NT and HCC_NT). Compound analysis was performed using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Principle component analysis (PCA) revealed that among the four sample groups (ICC, ICC_NT, HCC, and HCC_NT) there were 14 compounds, 62 mRNAs and 17 miRNAs with two distinct patterns: tumor and non-tumor, and ICC and non-ICC. We accurately (84.38%) distinguished ICC by the distinct pattern of its compounds. Pathway analysis using transcriptome and metabolome showed that several pathways varied between tumor and non-tumor samples. Based on the results of the PCA, we believe that ICC and HCC have different carcinogenic mechanism therefore knowing the specific profile of genes and compounds can be useful in diagnosing ICC.

Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver.

Cytoglobin (CYGB) is ubiquitously expressed in the cytoplasm of fibroblastic cells in many organs, including hepatic stellate cells. As yet, there is no specific marker with which to distinguish stellate cells from myofibroblasts in the human liver. To investigate whether CYGB can be utilized to distinguish hepatic stellate cells from myofibroblasts in normal and fibrotic human liver, human liver tissues damaged by infection with hepatitis C virus (HCV) and at different stages of fibrosis were obtained by liver biopsy. Immunohistochemistry was performed on histological sections of liver tissues using antibodies against CYGB, cellular retinol-binding protein-1 (CRBP-1), α-smooth muscle actin (α-SMA), thymocyte differentiation antigen 1 (Thy-1), and fibulin-2 (FBLN2). CYGB- and CRBP-1-positive cells were counted around fibrotic portal tracts in histological sections of the samples. The expression of several of the proteins listed above was examined in cultured mouse stellate cells. Quiescent stellate cells, but not portal myofibroblasts, expressed both CYGB and CRBP-1 in normal livers. In fibrotic and cirrhotic livers, stellate cells expressed both CYGB and α-SMA, whereas myofibroblasts around the portal vein expressed α-SMA, Thy-1, and FBLN2, but not CYGB. Development of the fibrotic stage was positively correlated with increases in Sirius red-stained, α-SMA-positive, and Thy-1-positive areas, whereas the number of CYGB- and CRBP-1-positive cells decreased with fibrosis development. Primary cultured mouse stellate cells expressed cytoplasmic CYGB at day 1, whereas they began to express α-SMA at the cellular margins at day 4. Thy-1 was undetectable throughout the culture period. In human liver tissues, quiescent stellate cells are CYGB positive. When activated, they also become α-SMA positive; however, they are negative for Thy-1 and FBLN2. Thus, CYGB is a useful marker with which to distinguish stellate cells from portal myofibroblasts in the damaged human liver.

A case of hepatic inflammatory pseudotumor identified by FDG-PET

A 53-year-old man with a history of nausea and elevated liver functions presented to our clinic. A CT scan showed a small tumor in the right lobe of the liver. Fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography confirm abnormal metabolic activity with a high standardized uptake value of 7.3 in the lesion. These findings could indicate a malignancy such as well-differentiated hepatocellular carcinoma or cholangiocarcinoma, or a benign lesion such as hepatic abscess. He was diagnosed by histopathological examination as having an epithelioid granuloma with many inflammatory cells. This is the rare report of hepatic inflammatory pseudotumor featuring markedly increased18F-FDG uptake.

A case of diffuse hepatic angiosarcoma diagnosed by FDG-PET

A 76-year-old woman was admitted to our hospital with a 2-month history of increasing abdominal distension, leg edema, and dyspnea. The serum transaminase level was about twice the upper limit of normal. The CT showed no tumor. Fluorine-18 2-deoxy-2-fluoro-D-glucose (FDG)-positron emission tomography (PET) showed diffuse abnormal accumulation throughout the entire liver. She was diagnosed by histopathological examination as having hepatic angiosarcoma causing veno-occlusive disease (VOD). This is the first report of hepatic angiosarcoma with FDG-PET.

Nutritional status in relation to lifestyle in patients with compensated viral cirrhosis.

AIM To assess the nourishment status and lifestyle of non-hospitalized patients with compensated cirrhosis by using noninvasive methods. METHODS The subjects for this study consisted of 27 healthy volunteers, 59 patients with chronic viral hepatitis, and 74 patients with viral cirrhosis, from urban areas. We assessed the biochemical blood tests, anthropometric parameters, diet, lifestyle and physical activity of the patients. A homeostasis model assessment-insulin resistance (HOMA-IR) value of ≥ 2.5 was considered to indicate insulin resistance. We measured height, weight, waist circumference, arm circumference, triceps skin-fold thickness, and handgrip strength, and calculated body mass index, arm muscle circumference (AMC), and arm muscle area (AMA). We interviewed the subjects about their dietary habits and lifestyle using health assessment computer software. We surveyed daily physical activity using a pedometer. Univariate and multivariate logistic regression modeling were used to identify the relevant factors for insulin resistance. RESULTS The rate of patients with HOMA-IR ≥ 2.5 (which was considered to indicate insulin resistance) was 14 (35.9%) in the chronic hepatitis and 17 (37.8%) in the cirrhotic patients. AMC (%) (control vs chronic hepatitis, 111.9% ± 10.5% vs 104.9% ± 10.7%, P = 0.021; control vs cirrhosis, 111.9% ± 10.5% vs 102.7% ± 10.8%, P = 0.001) and AMA (%) (control vs chronic hepatitis, 128.2% ± 25.1% vs 112.2% ± 22.9%, P = 0.013; control vs cirrhosis, 128.2% ± 25.1% vs 107.5% ± 22.5%, P = 0.001) in patients with chronic hepatitis and liver cirrhosis were significantly lower than in the control subjects. Handgrip strength (%) in the cirrhosis group was significantly lower than in the controls (control vs cirrhosis, 92.1% ± 16.2% vs 66.9% ± 17.6%, P < 0.001). The results might reflect a decrease in muscle mass. The total nutrition intake and amounts of carbohydrates, protein and fat were not significantly different amongst the groups. Physical activity levels (kcal/d) (control vs cirrhosis, 210 ± 113 kcal/d vs 125 ± 74 kcal/d, P = 0.001), number of steps (step/d) (control vs cirrhosis, 8070 ± 3027 step/d vs 5789 ± 3368 step/d, P = 0.011), and exercise (Ex) (Ex/wk) (control vs cirrhosis, 12.4 ± 9.3 Ex/wk vs 7.0 ± 7.7 Ex/wk, P = 0.013) in the cirrhosis group was significantly lower than the control group. The results indicate that the physical activity level of the chronic hepatitis and cirrhosis groups were low. Univariate and multivariate logistic regression modeling suggested that Ex was associated with insulin resistance (odds ratio, 6.809; 95% CI, 1.288-36.001; P = 0.024). The results seem to point towards decreased physical activity being a relevant factor for insulin resistance. CONCLUSION Non-hospitalized cirrhotic patients may need to maintain an adequate dietary intake and receive lifestyle guidance to increase their physical activity levels.

Effectiveness of preoperative PET examination of huge angiosarcoma of the heart.

Abstract: We report a 60-year-old-woman with a huge intracardiac angiosarcoma in whom preoperative F-18 fluorodeoxyglucose (FDG) PET was useful for confirming malignancy of the tumor and determining whether surgery was indicated for it. Her chief complaint was dyspnea. Because she was suspected to have a huge intracardiac tumor on the basis of transthoracic echocardiographic and computed tomography (CT) findings, FDG PET was performed, and the maximum standardized uptake value (SUV) of the tumor was found to be 5.6. Because other tests and SUV level suggested a malignant cardiac tumor, surgical resection of it was attempted. On histopathological examination, the tumor was found to be an angiosarcoma. Our experience with this case indicates that, when dealing with patients suspected to have very large tumors, FDG PET is useful in examination for malignant potential and is indispensable in exploration for distant metastases.

Natural course of changes in hepatic functional reserve in patients with chronic liver diseases evaluated by scintigraphy with GSA

Hepatic functional reserve can be evaluated in a noninvasive way by scintigraphy with 99mTc-DTPA-galactosyl human serum albumin (99mTc-GSA). We monitored hepatic functional reserve in patients with chronic hepatitis and cirrhosis using scintigraphy with 99mTc-GSA to determine the natural course of changes in their hepatic functional reserve. Computer acquisition of gamma-camera data was started before the injection of 185 MBq of 99mTc-GSA and was stopped 20 min later. Time-activity curves were generated from ROI for the heart and liver. A receptor index and index of blood clearance were calculated from radioactivity in the heart and liver. Scintigraphy with 99mTc-GSA was performed in 12 healthy subjects, 86 patients with chronic hepatitis, and 226 patients with cirrhosis. Seventy-two patients (23 with chronic hepatitis, 32 with cirrhosis in Child-Pugh stage A, 15 in stage B, and 2 in stage C) were examined at least twice with 12-72 months intervening. The receptor index was lower for more severe disorders, decreasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The index of blood clearance was higher for more severe disorders, increasing in the order of chronic hepatitis and cirrhosis in stages A, B, and C. The mean annual change in the receptor index with chronic hepatitis was -0.0007, that with cirrhosis in stage A was -0.0023, and that with cirrhosis in stage B or C was -0.0117. The difference between the median annual change with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was not significant (P=0.064 and 0.251, respectively). The mean annual change in the index of blood clearance with chronic hepatitis was 0.0018, that with cirrhosis in stage A was 0.0060, and that with cirrhosis in stage B or C was 0.0330. The difference between the median annual change in the index of blood clearance with cirrhosis in stage B or C and that with chronic hepatitis or cirrhosis in stage A was significant (P=0.004 and 0.007, respectively). Hepatic receptor imaging with 99mTc-GSA could be used to noninvasively evaluate the hepatic reserve of various liver diseases. Changes in hepatic functional reserve were not steady; it decreased gradually as disease advanced from chronic hepatitis to cirrhosis in Child-Pugh stage A, and decrease rapidly after development of stage B cirrhosis.