Ipragliflozin Ameliorates Endoplasmic Reticulum Stress and Apoptosis through Preventing Ectopic Lipid Deposition in Renal Tubules.

BACKGROUND: Chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH) are major health burdens closely related to metabolic syndrome. A link between CKD and NASH has been assumed; however, the underlying mechanism is still unknown. Ectopic lipid deposition (ELD) in the hepatocyte results in endoplasmic reticulum (ER) stress, which plays an important role in the development of steatohepatitis. ELD is also assumed to play a role in the development of kidney injury. We aimed to investigate the role of ELD and ER stress in the development of CKD, and evaluate the efficacy of a sodium glucose cotransporter-2 inhibitor, ipragliflozin. METHODS: Male FLS-ob/ob mice that closely imitate the pathophysiology of NASH were treated with vehicle or ipragliflozin. Metabolic characteristics, histology of the kidney, ER stress, and apoptotic signals were evaluated. RESULTS: The serum triglyceride was significantly lower in mice treated with ipragliflozin. Ipragliflozin reduced ELD in renal tubules. Ipragliflozin also reduced the expression levels of GRP78 and CHOP, apoptotic cells, and interstitial fibrosis. CONCLUSIONS: ELD induced kidney injury through ER stress. Ipragliflozin improved the pathogenesis of CKD by reducing ELD and ER stress in NASH-model mice. Our results suggest ipragliflozin has therapeutic effect on CKD in NASH.

Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts the development of hepatocellular carcinoma in patients with non-alcoholic fatty liver disease.

AIM: As it is not practical to perform regular screening for hepatocellular carcinoma (HCC) in all patients with non-alcoholic fatty liver disease (NAFLD), there is a need to identify NAFLD patients who are at high risk for HCC. Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+ -M2BP) has been shown to be a surrogate marker for predicting HCC as well as a liver fibrosis marker in patients with chronic hepatitis B and C. The aim of this study was to investigate whether WFA+ -M2BP predicts HCC development in NAFLD patients. METHODS: Serum WFA+ -M2BP was retrospectively measured in 331 patients with histologically proven NAFLD, 51 of whom developed HCC. The association of WFA+ -M2BP and HCC development in NAFLD patients was investigated. RESULTS: The WFA+ -M2BP values were significantly greater in NAFLD patients with HCC than in those without HCC among patients with liver fibrosis ≥stage 3. Multivariate analysis identified WFA+ -M2BP as one of the predictive factors for HCC development (odds ratio, 1.57; 95% confidence interval, 1.083-2.265; P = 0.017). The optimal cut-off index of WFA+ -M2BP for predicting HCC was 1.255 with specificity of 78.4% and sensitivity of 70.4%. The area under the receiver operating characteristic curve value for the prediction of HCC development was 0.806. The cumulative incidence rate of HCC was significantly greater in patients with WFA+ -M2BP ≥ 1.255 (n = 61) than in those with WFA+ -M2BP < 1.255 (n = 137) among patients who were followed up for more than 2 years after the diagnosis of NAFLD. CONCLUSIONS: Wisteria floribunda agglutinin-positive Mac-2 binding protein predicts HCC development and is a useful surrogate marker for identifying NAFLD patients who are at a high risk for HCC.

Renal shear wave velocity by acoustic radiation force impulse did not reflect advanced renal impairment.

AIM: Acoustic radiation force impulse is a noninvasive method for evaluating tissue elasticity on ultrasound. Renal shear wave velocity measured by this technique has not been fully investigated in patients with renal disease. The aim of the present study was to compare renal shear wave velocity in end-stage renal disease patients and that in patients without chronic kidney disease and to investigate influencing factors. METHODS: Renal shear wave velocities were measured in 59 healthy young subjects (control group), 31 subjects without chronic kidney disease (non-CKD group), and 39 end-stage renal disease patients (ESRD group). Each measurement was performed 10 times at both kidneys, and the mean value of eight of 10 measurements, excluding the maximum and minimum values, was compared. RESULTS: Renal shear wave velocity could be measured in all subjects. Renal shear wave velocity in the control group was higher than in the non-CKD group and in the ESRD group, and no difference was found between the non-CKD group and the ESRD group. Age and depth were negatively correlated to the renal shear wave velocity. In multiple regression analysis, age and depth were independent factors for renal shear wave velocity, while renal impairment was not. There was no difference between the non-CKD group and the ESRD group, even when ages were matched and depth was adjusted. CONCLUSION: Renal shear wave velocity was not associated with advanced renal impairment. However, it reflected alteration of renal aging, and this technique may be useful to detect renal impairment in the earlier stages.

Clinical usefulness of the ablative margin assessed by magnetic resonance imaging with Gd-EOB-DTPA for radiofrequency ablation of hepatocellular carcinoma.

BACKGROUND & AIMS: The aim of this study was to investigate the feasibility of ablative margin (AM) grading by magnetic resonance imaging (MRI) with Gd-EOB-DTPA administered prior to radiofrequency ablation (RFA), and to identify factors for achieving a sufficient AM and predictors for local tumor progression. METHODS: A total of 124 hepatocellular carcinomas (HCCs) were treated by RFA after Gd-EOB-DTPA administration. MRI and enhanced CT were performed within seven hours and one month after RFA. The AM assessment was categorized using three grades: AM (+), low-intensity area with continuous high-intensity rim; AM zero, low-intensity area with discontinuous high-intensity rim; and AM (-), low-intensity area extends beyond the high-intensity rim. Patients were followed and local tumor progression was observed. RESULTS: AM (+), AM zero, AM (-), and indeterminate were found in 34, 33, 26, and 31 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 56.8%. The κ coefficient was 0.326 (p<0.001), indicating moderate agreement. Multivariate logistic regression analysis showed that a significant factor for the achievement of AM (+) on MRI was no contiguous vessels. The cumulative local tumor progression rates (0% at 1, 2, and 3 years) in 33 AM (+) nodules were significantly lower than those (3.6%, 11.5%, and 18.3% at 1, 2, and 3 years respectively) in 32 AM zero nodules. A multivariate Cox proportional hazards model identified tumor size as an independent predictor for local tumor progression. CONCLUSION: Gd-EOB-DTPA-MRI enabled an early assessment of RFA effectiveness in the majority ofHCC nodules. Local tumor progression was not detected in AM (+) nodules during the follow-up.

Usefulness of contrast-enhanced ultrasound with Sonazoid for evaluating liver abscess in comparison with conventional B-mode ultrasound.

AIM: The purpose of this study was to evaluate the usefulness of contrast-enhanced ultrasound (CEUS) with Sonazoid (perfluorobutane) in patients with liver abscess. Sonazoid is a contrast agent with a low mechanical index and is phagocytosed by Kupffer cells. METHODS: Twenty-two patients with liver abscess were evaluated with conventional US, real-time CEUS with Sonazoid, and enhanced computed tomography (CT). After 0.5 mL of Sonazoid was administrated i.v., CEUS images in the vascular and post-vascular phases were observed. RESULTS: Conventional US showed hypoechoic lesions in 13 (59.1%), isoechoic in four (18.2%), hyperechoic in two (9.1%), mixed echoic in two (9.1%) and undetected in one (4.8%) patient. CEUS showed perilesional enhancement in 19 (86.4%) lesions in the vascular phase and well-defined unenhanced areas in 22 (100%) lesions in the post-vascular phase. CEUS revealed that 18 abscesses were cystic type and three were honeycomb type. Twenty-one abscesses (95.5%) had clearer appearances on CEUS than on conventional US in regard to the extent of necrotic or liquefied lesions seen. We could confirm reduction of the lesions after therapy in 13 (92.9%) of 14 patients followed up by CEUS. CONCLUSION: Most of the liver abscesses showed perilesional enhancement in the vascular phase and unenhanced areas in the post-vascular phase. The appearance of liver abscesses was clearer on CEUS than on conventional US. CEUS with Sonazoid can be a more effective diagnostic and therapeutic tool for liver abscess.

Association between serum soluble low-density lipoprotein receptor levels and metabolic factors in healthy Japanese individuals.

BACKGROUND: Soluble low-density lipoprotein receptor (sLDL-R) is formed by cleavage of the extracellular domain of low-density lipoprotein receptor (LDL-R). It is unclear whether serum sLDL-R is a marker of diseases associated with triglyceride (TG) metabolism. We investigated the association between serum sLDL-R concentrations and other biochemical parameters in healthy Japanese individuals. METHODS: Study subjects consisted of 102 healthy adult Japanese volunteers (42 men, 60 women) with body mass index (BMI) < 30 kg/m(2) and serum TGs, LDL cholesterol (LDL-C), aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, and glucose concentrations within normal ranges. Serum sLDL-R concentrations were determined by enzyme-linked immunosorbent assay and their correlations with biochemical parameters were analyzed. RESULTS: Mean serum sLDL-R concentration was 120.9 ± 39.9 ng/ml. Serum sLDL-R levels were significantly and positively correlated with BMI (rs = 0.252) and TG (rs = 0.408) and LDL-C (rs = 0.325) concentrations. Multiple regression analysis adjusted for age, gender, and smoking showed that BMI (ß = 0.274), TG (ß = 0.328), and LDL-C (ß = 0.224) were factors independently correlated with sLDL-R levels. CONCLUSION: Serum sLDL-R concentration may be a marker of diseases associated with TG metabolism. This is the first report to date describing the clinical relevance of sLDL-R.

Successful treatment of myelodysplastic syndrome and chronic hepatitis C using combined peginterferon-α-2b and ribavirin therapy.

We report a patient with myelodysplastic syndrome (MDS) and hepatitis C virus (HCV) infection who was successfully treated with a combination of peginterferon and ribavirin therapy. A 65-year-old man was referred to our hospital for treatment of chronic hepatitis C and close examination of pancytopenia. MDS of "refractory cytopenia with multilineage dysplasia" was diagnosed on the basis of bone marrow findings. Although the patient was not a good candidate for interferon (IFN) therapy because of his pancytopenia, we decided to proceed with IFN therapy for the following reasons: his elevated transaminases could not be controlled; he had a high possibility of recovery from chronic hepatitis C in consideration of his HCV genotype 2a and relatively low RNA titer; and his pancytopenia was expected to worsen in the future. After combination peginterferon/ribavirin therapy, the patient achieved sustained viral response, and the bone marrow findings showed neutrophils with normal granulation and megakaryocytes with normal morphological features. Additionally, the normal 46, XY karyotype converted from 45, X0 which was found before IFN therapy. This suggested that the patient's MDS was completely resolved.

Therapeutic effects of the direct renin inhibitor, aliskiren, on non-alcoholic steatohepatitis in fatty liver Shionogi ob/ob male mice.

AIM: Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome in the liver that is characterized by hepatic fat accumulation, inflammation and varying degrees of fibrosis. The renin-angiotensin system (RAS) appears to play important roles in NASH. Direct renin inhibitors (DRI) reduce plasma renin activity (PRA) through interaction with the active site of the enzyme and reduce the formation of angiotensin-II (AT-II). Therefore, the DRI aliskiren may further suppress the RAS. This study examined the effects of aliskiren on NASH in fatty liver Shionogi (FLS)-ob/ob male mice that are the closest animal model of metabolic syndrome-related NASH in humans. METHODS: Aliskiren (100 mg/kg per day, aliskiren group) or a placebo (control group) was p.o. administrated to eight FLS-ob/ob mice each for 16 weeks and factors including steatosis, fibrosis, inflammation and oxidative stress were compared between the two groups. RESULTS: Amounts of hepatic fibrosis were significantly lower in the aliskiren group than in the control group. Areas of α-smooth muscle actin positivity, the numbers of F4/80 positive, 8-hydroxy-2-deoxyguanosine positive cells and immunohistochemical staining of 4-hydroxynonenal were also significantly decreased in the aliskiren group. Levels of RNA expression for transforming growth factor-ß1, connective tissue growth factor and monocyte chemoattractant protein-1 were significantly lower in the aliskiren group. CONCLUSION: Aliskiren attenuated the progression of hepatic fibrosis by inhibiting the activation of hepatic stellate and Kupffer cells and by reducing oxidative stress.

Myocardial perfusion defects in patients with chronic hepatitis B infection.

BACKGROUND AND AIM: The association between hepatitis B virus (HBV) infection and myocardial injury has yet to be elucidated. We sought to investigate myocardial conditions in patients with chronic HBV infection. METHODS: In 47 consecutive patients with chronic hepatitis B who had no overt heart disease, we performed electrocardiography, echocardiography, serum tests for myocardial injury, and thallium-201 myocardial scintigraphy. Myocardial perfusion defects were confirmed by the severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. The SS was followed before and after interferon (IFN) therapy in 10 patients. RESULTS: Abnormal ECGs were found in 9% of patients with chronic hepatitis B. SS values in the hepatitis group were significantly higher than in the control group (P < 0.0001). Abnormal SS values were found in 47% of the chronic hepatitis B patients. Independent factors related to higher pretreatment SS were serum HBV DNA titer and IgG level. After interferon (IFN) therapy, the SS values of responders were significantly reduced (P ≤ 0.02); SS values of nonresponders were not significantly different before and after IFN therapy. SS values altered following IFN therapy, along with serum IgG concentrations. CONCLUSIONS: Myocardial perfusion defects were found in 47% of the patients with chronic hepatitis B and improved along with HBV reduction with IFN administration. SS improvement was closely correlated with decreases in serum IgG levels.

Fusion Imaging Objectively Demonstrates Improved Pancreas Visualization through Manipulation Techniques: A Prospective Interventional Study.

Objective Abdominal ultrasonography (AUS) is used to screen for abdominal diseases owing to its low cost, safety, and accessibility. However, the detection rate of pancreatic disease using AUS is unsatisfactory. We evaluated the visualization area of the pancreas and the efficacy of manipulation techniques for AUS with fusion imaging. Methods Magnetic resonance imaging (MRI) volume data were obtained from 20 healthy volunteers in supine and right lateral positions. The MRI volume data were transferred to an ultrasound machine equipped with a fusion imaging software program. We evaluated the visualization area of the pancreas before and after postural changes using AUS with fusion imaging and assessed the liquid-filled stomach method using 500 ml of de-aerated water in 10 randomly selected volunteers. Patients This study included 20 healthy volunteers (19 men and 1 woman) with a mean age of 33.0 (21-37.5) years old. Results Fusion imaging revealed that the visualization area of the entire pancreas using AUS was 55%, which significantly improved to 75% with a postural change and 90% when using the liquid-filled stomach method (p=0.043). Gastrointestinal gas is the main obstacle for visualization of the pancreas. Conclusion Fusion imaging objectively demonstrated that manipulation techniques can improve pancreatic visualization.

Myocardial injury in patients with chronic hepatitis C infection.

BACKGROUND & AIMS: The existence of a direct pathogenic link between hepatitis C virus (HCV) infection and myocardial injury has not been confirmed. We investigated the association between myocardial conditions and HCV in patients with HCV-related chronic hepatitis using thallium-201 myocardial scintigraphy. METHODS: In 217 consecutive cases of chronic HCV infection without overt heart disease, we performed electrocardiography (ECG), echocardiography, serum tests on myocardial injury and thallium-201 myocardial scintigraphy. Myocardial injury was confirmed by severity score (SS), which was calculated as the sum of thallium-201 perfusion defect scores. SS was followed prior to and after interferon (IFN) therapy in 200 patients with chronic hepatitis C. RESULTS: An abnormal ECG was found in 9% of the patients with chronic hepatitis C. Abnormal SS was found in 87% of the chronic hepatitis C patients. Independent factors related to higher pretreatment SS were histology activity index score, serum HCV RNA titer, and indocyanine green disappearance rate. After IFN therapy, SS was improved in patients with sustained virologic response. Among relapsers, SS improved at the initial disappearance of HCV RNA, but it worsened with the reappearance of HCV RNA. SS in non-viral responders did not change with IFN therapy. CONCLUSIONS: Myocardial perfusion defects were found in 87% of the patients with chronic hepatitis C and improved with viral eradication with IFN therapy.

Right diaphragmatic defect in hepatic hydrothorax exposed by contrast-enhanced ultrasonography after radiofrequency ablation.

A 68-year-old male with liver cirrhosis and hepatocellular carcinoma treated by radiofrequency ablation was hospitalized for right hepatic hydrothorax and ascites. Perflubutane injected into the peritoneal cavity after an ultrasonography contrast agent revealed jet-like flow from the ascites to a pleural effusion, indicating a diaphragmatic defect. A hepatic hydrothorax was sutured under thoracoscopy and did not recur. An intraperitoneal injection of perflubutane enables a less-invasive diagnosis of a diaphragmatic defect.

Hypovascular hepatic nodules showing hypointense on the hepatobiliary-phase image of Gd-EOB-DTPA-enhanced MRI to develop a hypervascular hepatocellular carcinoma: a nationwide retrospective study on their natural course and risk factors.

OBJECTIVE: We aimed to investigate the natural outcome of nonhypervascular lesions detected in the hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI by performing a longitudinal study retrospectively enrolled in a nationwide manner. METHODS: Between February 2008 and March 2011, 224 patients with 504 nodules that were diagnosed as nonhypervascular by imaging were recruited from institutions that participated in the present study. We examined the natural outcome of nonhypervascular lesions and evaluated the risk factors. RESULTS: Of the 504 nodules, 173 (34.3%) showed hypervascular transformation. The overall cumulative incidence of hypervascular transformation was 14.9% at 12 months and 45.8% at 24 months. Multivariate analysis using the Cox regression model revealed previous treatment history for hepatocellular carcinoma (HCC; relative risk = 1.498; p = 0.036, 95% CI 1.03-2.19) and hyperintensity on T2-weighted images (relative risk = 1.724; p = 0.015, 95% CI 1.11-2.67) were identified as independent factors for hypervascular transformation. CONCLUSIONS: Patients who have a previous treatment history for HCC and with hypointense nodules showing hyperintensity on T2-weighted images need careful follow-up because of the high incidence of hypervascular transformation.

Fatty liver Shionogi-ob/ob mouse: A new candidate for a non-alcoholic steatohepatitis model.

AIM: The fatty liver Shionogi (FLS) mouse develops hereditary fatty liver without obesity. The FLS-ob/ob mouse made by transferring the leptin(ob) gene demonstrates several metabolic disorders and marked fat deposition in the liver. The aim was to evaluate which mouse model, the FLS or FLS-ob/ob, is more useful for non-alcoholic steatohepatitis research. METHODS: FLS (n = 40) and FLS-ob/ob (n = 40) mice were fed a standard diet for 12, 24, 36 and 48 weeks, and then killed. The degree of fat deposition, oxidative stress, fibrosis and apoptosis were analyzed in the liver. Hepatic mRNA expression of fibrogenic and pro-inflammatory cytokines was measured. RESULTS: FLS mice developed hepatic steatosis and slight fibrosis without obesity between 12 and 48 weeks of age. Conversely, FLS-ob/ob mice developed severe steatosis at 12 weeks of age, and steatohepatitis with increased oxidative stress and advanced fibrosis between 24 and 36 weeks of age. At 48 weeks of age, some FLS-ob/ob but not FLS mice, progressed to cirrhosis. Transforming growth factor-ß1, connective tissue growth factor and tumor necrosis factor-α mRNA expression levels were greater in FLS-ob/ob than FLS mice between 24 and 48 weeks of age. The number of apoptotic cells in the liver was greater at 12 weeks of age in FLS mice and at 48 weeks of age in FLS-ob/ob mice. CONCLUSION: FLS-ob/ob mice developed more severe steatohepatitis with fibrosis than FLS mice, and had increased oxidative stress and apoptosis. These findings indicate that the FLS-ob/ob mouse is a more useful model for steatohepatitis research.

The Natural History and Management of Hepatic Hemangioma.

BACKGROUND: Knowledge of the natural history and management of hepatic hemangiomas is lacking. The aim of this study was to investigate the natural history of hemangiomas and to elucidate the factors that determine tumor growth and optimal management. METHODS: A total of 211 adult patients were enrolled, with follow-up for more than three years. Follow-up was performed with repeated ultrasonography (US) and laboratory tests for liver function and coagulation factors (platelets, prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), D-dimer, and fibrin and fibrinogen degradation products (FDP)). RESULTS: Tumor size decreased in 38.9% of patients, showed no change in 31.3%, and increased in 29.8%. The incidence of a size increase was very high in patients under 40 years of age and decreased gradually with age, whereas the incidence of a size decrease increased with age and increased markedly over 60 years of age. The incidence of an increase in size decreased gradually with size enlargement, whereas the incidence of a decrease in size increased markedly with tumor size and further increased rapidly when hemangiomas became larger than 60 mm. Values of TAT, D-dimer, FDP, and Mac-2 binding protein glycosylation isomer (M2BPGi) were closely related to the change in size of hemangiomas. CONCLUSIONS: Hemangiomas in older patients (>60 years of age) and larger tumors (>60 mm in size) had a tendency to decrease in size, resulting from the reduction in coagulation disorders and the progression of liver fibrosis. Therefore, the majority of patients with hemangiomas can be safely managed by clinical observation.

Effects of Using a Video-Sharing Application on Multidisciplinary Staff During Pre-discharge Home Assessment Visits for Elderly Hospitalized Patients.

Background: Pre-discharge home assessment visits for elderly hospitalized patients are conducted by the hospital staff to ensure a smooth transition to home care and are effective in preventing falls and reducing the rehospitalization rates. However, the effect of an application that enables the viewing of videos of the patient's home activities during the pre-discharge visit on the multidisciplinary professionals who provide services to the patient has not yet been fully clarified. Methods: Multidisciplinary professionals at 23 facilities located in western Tottori Prefecture who used a video-sharing application (Patto-Mie Net) were invited to be interview participants. Those who agreed were interviewed about the usefulness of the application in their work and its effect on multidisciplinary collaboration. A verbatim transcript was made, and thematic analysis was conducted using the qualitative analysis software NVivo. Results: Twenty-eight people participated in the interviews, including nurses, care managers, rehabilitation specialists, care workers, and other social care professions. Fourteen themes and five categories were generated from the analysis: comprehensive information visualization and transferability, identification of changes over time and prognostic prediction, promoting multidisciplinary collaboration, patient and family reality, and disadvantages and concerns. Conclusion: The use of an application that allows video-sharing of a patient's home movement status during a pre-discharge visit has revealed a variety of benefits for multiple professionals in hospitals and other facilities. In particular, the results were characterized by the psychological closeness between multiple professionals, promotion of interprofessional communication, and sharing of reality, including the psychosocial background of the patient and family.

Late-Onset Intracranial Hemorrhage Presenting as Refractory Hyponatremia: A Case Report.

Here, we report a case of refractory hyponatremia and delayed intracranial hemorrhage following a head injury. A 70-year-old male patient was admitted with complaints of left chest pain and light-headedness after a fall. Hyponatremia recurred despite the correction with intravenous saline. Head computed tomography revealed a chronic subdural hematoma. The subsequent introduction of tolvaptan improved hyponatremia and disorientation. Delayed intracranial hemorrhage is a differential cause of refractory hyponatremia after head contusion. This case is clinically relevant because (i) the diagnostic delay of late-onset intracranial hemorrhage is common but fatal, and (ii) refractory hyponatremia can be a hint of late-onset intracranial hemorrhage.

The Effectiveness of the Multiple-Attending-Physicians System Compared With the Single Attending-Physician System in Inpatient Setting: A Mixed-Method Study.

OBJECTIVES: Medical facilities have been required to effectively utilize insufficient human resources in many countries. Therefore, we qualitatively and quantitively compared physicians' working burden, and assessed advantages and disadvantages of the single- and the multiple-attending physicians systems in inpatient care. METHODS: In this cross-sectional study, we extracted electronic health record of patients from a hospital in Japan from April 2017 to October 2018 to compare anonymous statistical data between the single-attending and multiple-attending-physicians system. Then, we conducted a questionnaire survey for all physicians of single and multiple-attending systems, asking about their physical and psychiatric workload, and their reasons and comments on their working styles. RESULTS: The average length of hospital stay was significantly shorter in the multiple-attending system than in the single-attending system, while patients' age, gender, and diagnoses were similar. From the questionnaire survey, no significant difference was found in all categories although physical burden in multiple-attending system tended to be lower than that in single-attending system. Advantages of multiple-attending system extracted from qualitative analysis are (1) improvement of physicians' quality of life (QOL), (2) lifelong-learning effect, and (3) improving the quality of medical care, while disadvantages were (1) risk of miscommunications, (2) conflicting treatment policies among physicians, and (3) patients' concern. CONCLUSIONS: The multiple-attending physician system in the inpatient setting can reduce the average length of stay for patients and also reduce the physical burden on physicians without compromising their clinical performance.

[Evaluation of the surveillance program for hepatocellular carcinoma].

We examined the compliance with, and efficacy of, the clinical guideline for the diagnosis of hepatocellular carcinoma (HCC). We classified 74 patients with HCC into 3 categories;23 surveillance cases, 18 non-surveillance cases, and 33 incidental cases. Patients from affiliated hospitals included more non-surveillance and incidental cases than in university hospital-treated cases. HCC was diagnosed at an earlier stage in the surveillance group than the incidental group, and the surveillance group had a better outcome than the incidental group. There was no significant difference in HCC stage or outcome between surveillance and non-surveillance groups. The guidelines appeared to be useful for early diagnosis of HCC except for the fact that some in the surveillance group were diagnosed at an advanced stage and around 30% of the incidental group had some risk factors of HCC. Those conducting surveillance must improve their skills for early diagnosis of HCC and both doctors and patients must increase compliance with the guidelines.

Prevalence and Characteristics of Hepatic Hemangioma Associated with Coagulopathy and Its Predictive Risk Factors.

Background: Knowledge of the relationships between hepatic hemangiomas and coagulopathy and the risk factors for hemangiomas is lacking. The aim of this study was to investigate the prevalence and characteristics of hepatic hemangiomas associated with coagulopathy, elucidate the causes of coagulopathy, and identify the predictive factors for hemangioma-related complications. Methods: In 281 consecutive patients with hepatic hemangiomas, we performed ultrasonography and conducted serum laboratory tests for liver function and six coagulation factors, i.e., platelets, as well as five coagulation fibrinolytic markers (prothrombin time (PT), fibrinogen, thrombin-antithrombin III complex (TAT), d-dimer, and fibrin and fibrinogen degradation products (FDP)) as indicators of coagulation disorder. Results: Among 281 patients, 56 (19.9%) had abnormal coagulation factors. Abnormal values of d-dimer were most frequently found among the six coagulation factors. The number of abnormal coagulation factors was significantly correlated with tumor size, M2BPGi, and HDL cholesterol, among which tumor size was the most significant independent predictor of the number of abnormal coagulation factors. Conclusions: The prevalence of hepatic hemangiomas associated with coagulopathy was relatively high and became more frequent with increases in tumor size. Predictive factors of hemangioma-related complications were found to be a tumor size of >5 cm in diameter and coagulopathy, especially the elevation of d-dimer.