[Initial clinical experience of early cardiac rehabilitation for very elderly patients over 85 years old following open heart surgery].

In this study, we evaluated the initial clinical experience of early cardiac rehabilitation( CR) for very elderly patients over 85 years old after open heart surgery. From September 2007 to January 2011, 7 consecutive patients (85~90 years, mean 85.9 years, male:female=4:3) who underwent cardiac surgery in our institute were selected. Preoperative activity of daily living (ADL) scores were similar in all cases, and 1 patient used a cane for walking. Preoperative New York Heart Association (NYHA) classification was class III :3, class IV:4. Three patients were admitted for acute congestive heart failure approximately 1 month prior to surgery. Standard open heart surgery using bioprosthesis was performed: 3 patients underwent mitral valve replacement( MVR), 3 had aortic valve replacement( AVR), and 1 had tricuspid valve replacement (TVR). Postoperative clinical course was uneventful, and the mean time of ventilator support was 12.1 hours. Thereafter, early CR was introduced at the intensive care unit( ICU) in all patients, and the mean time of introduction of early rehabilitation was 1.7 days. In the last 4 cases, early CR was done the 1st day following surgery. CR was effectively performed in all cases without any problems or cardiac events, and all patients improved enough to leave their beds at 3~7 days, a mean of 4.4 days after surgery. The mean hospital stay after surgery was 30.9 days( 23 ~ 42 days), almost all patients were able to walk independently, and ADL scores at discharge were improved. Only 2 patients required a cane for walking. Postoperative NYHA classification was improved to class I :5, class II :2. From these results, early CR for very elderly patients over 85 years old could be a safe and effective tool to improve and maintain the ADL and quality of life following surgical intervention.

Effects of Yokukansan on behavioral and psychological symptoms of dementia in regular treatment for Alzheimer's disease.

Yokukansan (YKS) is used frequently against behavioral and psychological symptoms of dementia (BPSD) together with donepezil in patients with Alzheimer's disease (AD). Here, we investigated the efficacy and safety of YKS in patients with AD in a non-blinded, randomized, parallel-group comparison study. Patients who had at least one symptom score of four or more on the Neuropsychiatric Inventory (NPI) subscales were enrolled in the study. The subjects were randomly assigned to the YKS-treated group (YKS/donepezil combination therapy group) and the non-YKS-treated group (donepezil monotherapy group). TSUMURA Yokukansan (TJ-54, 7.5g, t.i.d.) was administered in a four-week study treatment period. The subjects were evaluated twice at the start (Week 0) and completion (Week 4) of the study treatment in terms of NPI, Mini-Mental Status Examination (MMSE), Disability Assessment for Dementia (DAD), Zarit Burden Interview, and Self-rating Depression Scale (SDS). The efficacy analysis was performed in 29 patients (YKS-treated group) and 32 patients (non-YKS-treated group). The NPI total score improved significantly more in the YKS-treated group than in the non-YKS-treated group. In the NPI subscales of agitation/aggression and irritability/lability, the YKS-treated group showed significantly greater improvement than the non-YKS-treated group, but no statistically significant improvement was seen with YKS in the other subscales. There were no significant differences between the YKS-treated group and the non-YKS-treated group in MMSE, DAD, Zarit Burden Interview and SDS. No adverse reactions were noted in either group. The results of this study showed that YKS is safe and effective in the treatment of BPSD in AD patients.

[A case of portal-systemic shunt-through inferior mesenteric vein and right internal iliac vein-encephalopathy cured by balloon-occluded retrograde transvenous obliteration].

We encountered a case of portal-systemic shunt encephalopathy cured by balloon-occluded retrograde transvenous obliteration (B-RTO). A 73-year-old man had been observed for membranous nephropathy at our hospital since 1987. There was no past history of liver dysfunction. He was admitted with encephalopathy. Abdominal enhanced computed tomography showed a portosystemic shunt through the inferior mesenteric vein and right internal iliac vein. We diagnosed hepatic encephalopathy due to this porto-systemic shunt, and B-RTO was performed. After B-RTO, he has not had repeated encephalopathy. B-RTO can be effective for portosystemic encephalopathy. Inferior mesenteric-right internal iliac shunt encephalopathy is rare and our patient is the first case of B-RTO performed in cases with this shunt.

The level of fasting serum insulin, but not adiponectin, is associated with the prognosis of early stage hepatocellular carcinoma.

Impaired glucose tolerance influences the prognosis of hepatocellular carcinoma (HCC), but this mechanism is still not fully understood. We investigated the impact of the fasting serum levels of insulin and adiponectin on the prognosis of HCC and its recurrence. One hundred and forty patients with newly diagnosed HCC were enrolled in the prognosis study. Their fasting serum levels of insulin and adiponectin were determined. Of 140 patients, 59 patients who underwent curative treatment were subjected to analysis of the recurrence-free survival. The 140 patients were divided into two groups by the 50th percentile value of insulin (7.73 microIU/ ml) or total adiponectin (6.95 microg/ml). Kaplan-Meier analysis indicated that high insulin group (>7.73 microIU/ml) exhibited a significantly poorer prognosis than low insulin group (<7.73 microIU/ml) in early stage HCC (P=0.018). In contrast, the level of total adiponectin had no impact on the prognosis of HCC. Multivariate analysis indicated that fasting hyper-insulinemia was an independent risk factor for a poorer prognosis in early stage HCC (P=0.044). Likewise, Kaplan-Meier analysis indicated that the recurrence-free survival of high insulin group was significantly lower than that of low insulin group (P=0.017). The level of total adiponectin had no impact on the recurrence-free survival of HCC. Multivariate analysis indicated that fasting hyperinsulinemia was an independent risk factor for the lower recurrence-free survival of HCC (P=0.049). In conclusion, our study suggests that the fasting insulin level affects the clinical course of early stage HCC.

The significance of enzyme immunoassay for the assessment of hepatitis B virus core-related antigen following liver transplantation.

PURPOSE: Recently, a new enzyme immunoassay for the detection of hepatitis B virus (HBV) core-related antigen (HBcrAg) has been reported. In this study, we proposed to account for feasibility of HBcrAg assay, and discuss the dynamics of HBV seen in patients following HBV-related living donor liver transplantation (LDLT). METHODS AND RESULTS: This study involved 12 patients; 11 patients had positive serum HBcrAg, and 6 patients had negative HBV-DNA. In the post-operation period, all cases were negative for HBV-DNA and HBsAg in sera under prophylaxis therapy. At post-operation, 5 of the 12 had positive serum HBcrAg, and at stable state, 6 had positive serum HBcrAg postoperatively. The mean levels of HBcrAg following LDLT were significantly lower than those seen in the preoperative-operation stage. CONCLUSION: This enzyme immunoassay is a readily utilizable marker of HBV replication in the post transplantation stage. Furthermore, the evaluation of HBV activity by HBcrAg assay must be studied to determine the appropriate prophylaxis for controlling replication of HBV following LDLT.

Portal hypertensive gastropathy with portal thrombosis successfully treated with partial splenic embolization.

A 60-year-old man with alcoholic liver cirrhosis was admitted to our hospital with severe anemia and tarry stool. Upper gastrointestinal endoscopy revealed grade 4 esophageal varices without bleeding and severe portal hypertensive gastropathy (PHG) of the fornix of the stomach with oozing. These findings suggested that PHG was the cause of progression of anemia. Abdominal computed tomography demonstrated no enhancement of the main portal vein and its first branches, indicating portal thrombosis and cavernous transformation. The patient underwent partial splenic embolization (PSE) to reduce portal hypertension. Two months after PSE was performed, upper gastrointestinal endoscopy showed improvement of PHG and endoscopic variceal ligation was performed to treat the esophageal varices. Contrast-enhanced CT revealed partial enhancement of the main portal vein indicating improvement of portal thrombosis. One year after PSE, hemoglobin had increased from 6.0 to 11.0 g/dl without blood transfusion. Moreover, albumin level had risen from 2.8 to 3.7 g/dl, cholinesterase from 51 to 150 IU/l, and prothrombin time from 47% to 66%. PSE can be an effective alternative for the management of severe PHG with portal vein thrombosis, and it might also be effective in improving liver function.

Significance of trans-hepatic arterial chemotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombus.

Portal vein tumor thrombus (PVTT) is observed in a considerable number of hepatocellular carcinoma (HCC) cases. It is an exacerbating factor for patients afflicted with HCC. The sequelae of PVTT are considered to be a contraindication for the treatment of HCC in such patients. The survival of 10 HCC patients with PVTT treated with trans-hepatic arterial continuous injection chemotherapy was compared to 13 HCC patients with PVTT, who received best supportive care only, as a control to validate the efficacy of continuous trans-hepatic arterial injection chemotherapy using an implanted catheter for HCC with PVTT. There were no differences in the liver function and HCC stage between the two groups. The survival was significantly different between the two groups (P=0.01 by the log-rank test). The median survival time was 106 days in the treatment patients, whereas it was 65 days in the control patients. Multivariate analyses showed the therapy to be the only predictor for survival (risk ratio 0.144, P=0.016). The therapy was strongly associated with the PVTT prognosis. In conclusion, the importance of trans-arterial chemotherapy was demonstrated even in advanced dysfunctional cirrhotic HCC patients with PVTT. It is therefore necessary to develop a basic protocol to treat HCC with PVTT.

A high glucose condition sensitizes human hepatocytes to hydrogen peroxide-induced cell death.

Oxidative stress is known to play a key role in the progression of liver disease, including non-alcoholic steatohepatitis (NASH), which is often accompanied by hyperglycemia. This study examined the influence of high glucose on oxidative stress-induced hepatic cell death. Hc cells, a normal human hepatocyte-derived cell line, were cultured in normal-to-high glucose (5.5-22 mM)-containing medium with varying concentrations (0.01-1 mM) of hydrogen peroxide. In certain experiments, cyclosporine A (CyA), which inhibits the mitochondrial permeability transition (MPT) pore, or Z-VAD-FMK (z-VAD), a pan-caspase inhibitor, were added to the medium. Cell viability was evaluated using a colorimetric assay. The mode of cell death was determined by nuclear staining methods using Hoechst 33258 and Sytox green. Neither high glucose (22 mM) nor 0.05-0.5 mM of hydrogen peroxide alone killed Hc cells. However, a combination of the two induced cell death, causing the nuclei of Hc cells to become expanded rather than condensed, and the nuclear membrane to become weak. CyA, but not z-VAD, blocked cell death. These results suggest that a high glucose condition may cause human hepatocytes to undergo hydrogen peroxide-induced necrotic cell death.

Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Pituitary dysfunction including growth hormone (GH) deficiency may be associated with non-alcoholic fatty liver disease (NAFLD). Since the relationships among GH, IGF-1, IGFBP-3, and development of NAFLD without hypopituitarism are unclear, we examined the role of these hormones in the development of NAFLD based on clinical, laboratory and liver histology data. PATIENTS AND METHODS: A total of 55 consecutive patients (20 males and 35 females) with NAFLD. RESULTS: Aspartate amino transferase (AST), AST/ALT, platelet count and IGF-1, levels were significantly associated with differences in fibrosis, since these variables differed between stage 0-1 and stage 2-3 NAFLD. In multivariate analysis, platelet count (P = 0.0223, relative risk (RR), 5.899; 95% confidence interval (CI), 1.288-27.017), and IGF-1 (P = 0.0363, RR, 4.568; 95% CI, 1.101-18.945) showed significant associations with stage 2-3 NAFLD. Additionally, hyaluronic acid levels had a negative relationship with IGF-1 and the IGF-1/IGFBP-3 ratio. There was no relationship of fibrosis with GH level, but decreased GH (P = 0.0414, RR, 0.199; 95% CI, 0.042-0.989) was significantly associated with steatosis of stage 2-3. Low GH/IGF-1 and GH/IGFBP-3 ratios were found in advanced steatosis. CONCLUSION: GH, IGF-1 and IGFBP-3 are associated with hepatic fibrosis and steatosis in NAFLD. Low levels of IGF-1 might be associated with fibrosis while low level of GH with hepatic steatosis.

Association between liver fibrosis and insulin sensitivity in chronic hepatitis C patients.

BACKGROUND: Several clinical studies have suggested a possible link between chronic hepatitis caused by hepatitis C virus (HCV) and the development of diabetes mellitus. We investigated the association between liver fibrosis and glucose intolerance in HCV-infected patients by measuring insulin sensitivity and beta-cell function. METHOD: A total of 83 chronic HCV-infected patients were recruited into this study. We evaluated insulin sensitivity and beta-cell function of all patients in a fasting state (homeostasis model assessment of insulin resistance [HOMA-R] and homeostasis model assessment of beta-cell function [HOMA-beta]) and after an oral load of 75 g glucose (whole-body insulin sensitivity index [WBISI] and Delta-insulin/Delta-glucose 30). RESULTS: In a multivariate analysis, severe fibrosis was the only independent factor associated with insulin resistance. There were significant differences in both HOMA-R (P= 0.0063) and WBISI (P= 0.0159) between patients with mild fibrosis (N = 34) and those with severe fibrosis (N = 49). Although HOMA-beta was increased significantly in the subjects with severe fibrosis compared with those with mild fibrosis (P= 0.0169), Delta-insulin/Delta-glucose 30 showed no significant difference in stage of liver fibrosis, suggesting an uncertain association between liver fibrosis and beta-cell function. CONCLUSION: Our findings suggest that the development of liver fibrosis is associated with insulin resistance in HCV-infected patients.

Aging of patients with hepatitis C virus-associated hepatocellular carcinoma: long-term trends in Japan.

The incidence of hepatocellular carcinoma (HCC) in Japan has been increasing. The aim of the present study was to analyze epidemiological changes in Japanese HCC patients. A total of 463 patients with HCC diagnosed at our hospital between 1982 and 2001 were recruited for this study. Cohorts of patients with HCC were categorized into intervals of five years. The number of HBV- and HCV-associated HCC cases had decreased and increased in 1987-1991, respectively, and thereafter reached a plateau. The mean age of patients at diagnosis of HCV-associated HCC showed a steady significant increase from 60 to 68 years of age during the period, suggesting that these findings were associated with a shift toward an older-age group that had the highest rate of HCV infection. The mean age of patients with other types of HCC did not significantly change during the period. Since it is known that the prevalence of HCV infection in young Japanese persons is low and that the incidence of HCV infection is very low at present, our findings may indicate that the prevalence of HCC will decline in Japan, an advanced country with regard to HCV-associated HCC, in the near future.

The impact of newer treatment modalities on survival in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, although the therapeutic approaches for HCC have progressed rapidly, it remains unknown whether the current management of patients with HCC has reduced its mortality. We analyzed changes of survival rate in patients with HCC over a 20-year period. METHODS: Between 1982 and 2001, 463 patients were diagnosed with HCC at our hospital. Subjects were enrolled in the current cohort according to the following inclusion criteria: HCC lesion measuring less than 3 cm in diameter, no evidence of extrahepatic metastasis, and no evidence of main portal vein infiltration/thrombosis. A total of 257 patients with HCC were recruited for this study, and categorized into 5-year intervals. RESULTS: The survival rates improved significantly during the study period. When the patients were stratified according to Child-Pugh score, only patients with Child's B showed improved survival rates. Furthermore, patients with surgical resection or transarterial chemoembolization during the latter period had a better prognosis than those during the early period. CONCLUSIONS: Our findings suggest that the development of therapeutic interventions for HCC have led to improvements in the prognosis for HCC patients.