Continuing Quality Assessment Program Improves Clinical Outcomes of Hospitalized Community-Acquired Pneumonia: A Nationwide Cross-Sectional Study in Korea.

BACKGROUND: Pneumonia, which is the third leading cause of death in South Korea, is continuously increasing with the aging society. The Health Insurance Review and Assessment of South Korea conducted a quality assessment (QA) for improving the outcome of community-acquired pneumonia (CAP). METHODS: We conducted a nationwide cross-sectional study of hospitalized CAP in South Korea. First to third QA data were gathered into a single database. The national health insurance database was merged with the QA database for analyzing the medical claims data. Comorbidities, pneumonia severity, and pneumonia care appropriateness were calculated using Charlson comorbidity index (CCI), CURB-65, and core assessment of CAP scores (CAP scores), respectively. RESULTS: Overall, 54,307 patients were enrolled. The CAP scores significantly improved on QA program implementation (P < 0.001). All the variables demonstrated an association with in-hospital mortality, hospital length of stay (LOS), and 30-day mortality in the univariate analyses. Following the adjustments, higher CCI and CURB-65 scores were associated with higher in-hospital mortality, longer hospital LOS, and higher 30-day mortality. Male sex was associated with higher in-hospital/30-day mortality and shorter hospital LOS. Higher CAP scores were associated with shorter hospital LOS (P < 0.001). Upon QA program implementation, in-hospital mortality (P < 0.001), hospital LOS (P < 0.001), and 30-day mortality (P < 0.001) improved. CONCLUSION: Continuing QA program is effective in improving the clinical outcomes of hospitalized CAP.

The need for histological subclassification of cirrhosis: a systematic review and meta-analysis.

BACKGROUND & AIMS: The need for further histological subclassification of cirrhosis has been increasingly recognized because of the heterogeneity of severity within cirrhosis. We sought to identify evidence in the literature regarding the histological subclassification of cirrhosis using the Laennec stage. METHODS: We conducted a systematic review and meta-analysis by searching databases, including MEDLINE, EMBASE and the COCHRANE library, for relevant studies. RESULTS: Of 208 studies identified, 16 were eligible according to the inclusion criteria. With higher grades of the Laennec stage, clinical stages of cirrhosis and Child-Pugh scores/Model for end-stage liver disease scores increased (P < 0.05). Higher Laennec stages were statistically associated with the development of liver-related events, such as liver-related death, liver cancer progression and variceal haemorrhage, as well as higher hepatic venous pressure gradients and higher liver stiffness values (P < 0.05). Two open-labelled studies showed the usefulness of the Laennec system with regard to the evaluation of whether antifibrotic treatments were effective. The mean kappa value was 0.81 (range 0.61-0.87) for inter-observer agreement. CONCLUSIONS: Based on this systematic review and meta-analysis, histological subclassification of cirrhosis using the Laennec system is useful to better predict prognosis and complications of portal hypertension.

Therapeutic Effects of Mesenchymal Stem Cells for Patients with Chronic Liver Diseases: Systematic Review and Meta-analysis.

Based on their ability to differentiate into multiple cell types including hepatocytes, the transplantation of mesenchymal stem cells (MSCs) has been suggested as an effective therapy for chronic liver diseases. The aim of this study was to evaluate the safety, efficacy and therapeutic effects of MSCs in patients with chronic liver disease through a literature-based examination. We performed a systematic review (SR) and meta-analysis (MA) of the literature using the Ovid-MEDLINE, EMBASE and Cochrane Library databases (up to November 2014) to identify clinical studies in which patients with liver diseases were treated with MSC therapy. Of the 568 studies identified by the initial literature search, we analyzed 14 studies and 448 patients based on our selection criteria. None of the studies reported the occurrence of statistically significant adverse events, side effects or complications. The majority of the analyzed studies showed improvements in liver function, ascites and encephalopathy. In particular, an MA showed that MSC therapy improved the total bilirubin level, the serum albumin level and the Model for End-stage Liver Disease (MELD) score after MSC treatment. Based on these results, MSC transplantation is considered to be safe for the treatment of chronic liver disease. However, although MSCs are potential therapeutic agents that may improve liver function, in order to obtain meaningful insights into their clinical efficacy, further robust clinical studies must be conducted to evaluate the clinical outcomes, such as histological improvement, increased survival and reduced liver-related complications, in patients with chronic liver disease.

Histological improvement following administration of autologous bone marrow-derived mesenchymal stem cells for alcoholic cirrhosis: a pilot study.

BACKGROUND: In experimental models, bone marrow-derived mesenchymal stem cells (BM-MSCs) have the capacity to differentiate into hepatocytes and exhibit antifibrotic effects. However, there have been no studies in humans with alcoholic cirrhosis. AIM: The aim of this study was to elucidate the antifibrotic effect of BM-MSCs in patients with alcoholic cirrhosis, as a phase II clinical trial. METHODS: Twelve patients (11 males, 1 female) with baseline biopsy-proven alcoholic cirrhosis who had been alcohol free for at least 6 months were enrolled. BM-MSCs were isolated from each patient's BM and amplified for 1 month, and 5 × 10(7) cells were then injected twice, at weeks 4 and 8, through the hepatic artery. One patient was withdrawn because of ingestion of alcohol. Finally, 11 patients completed the follow-up biopsy and laboratory tests at 12 weeks after the second injection. The primary outcome was improvement in the patients' histological features. RESULTS: According to the Laennec fibrosis system, histological improvement was observed in 6 of 11 patients (54.5%). The Child-Pugh score improved in ten patients (90.9%) and the levels of transforming growth factor-ß1, type 1 collagen and α-smooth muscle actin significantly decreased (as assessed by real-time reverse transcriptase polymerase chain reaction) after BM-MSCs therapy (P < 0.05). No significant complications or side effects were observed during this study. CONCLUSIONS: Bone marrow-derived mesenchymal stem cells therapy in alcoholic cirrhosis induces a histological and quantitative improvement of hepatic fibrosis.

Effect of bone marrow-derived mesenchymal stem cells on hepatic fibrosis in a thioacetamide-induced cirrhotic rat model.

BACKGROUND: Cirrhosis is a long-term consequence of chronic hepatic injury with fibrosis. No effective therapy is currently available for decompensated cirrhosis except liver transplantation. Hence, we investigated the effect of bone marrow-derived mesenchymal stem cells (BM-MSCs) on hepatic fibrosis in a thioacetamide (TAA)-induced cirrhotic rat model. METHODS: The BM-MSCs were injected directly into the right liver lobe twice, at 6 and 8 weeks during the 12-week TAA administration, in thioacetamide (TAA)-induced cirrhotic rats model, and hepatic fibrosis was evaluated. At 12 weeks, the effect of BM-MSCs on hepatic fibrosis was analyzed histomorphologically using the Laennec fibrosis scoring system, and the collagen proportionate area was quantified. Cirrhosis-related factors, such as transforming growth factor ß1 (TGF-ß1), type 1 collagen (collagen-1), α-smooth muscle actin (α-SMA), and P-Smad3/Smad3 expression levels, were evaluated using real-time polymerase chain reaction and western blot assays. RESULTS: According to the Laennec fibrosis scoring system, histological improvement was observed in hepatic fibrosis after BM-MSC treatment (P <0.01). The percentage of the collagen proportionate area decreased from 16.72 ± 5.51 to 5.06 ± 1.27 after BM-MSC treatment (P <0.01). The content of hepatic hydroxyproline was significantly lower in the BM-MSC treated group (46.25 ± 13.19) compared to the untreated cirrhotic group (85.81 ± 17.62; P <0.01). BM-MSC administration significantly decreased TGF-ß1, collagen-1, and α-SMA expression in TAA-induced cirrhotic rats (P <0.01). We also confirmed P-Smad3/Smad3, downstream effectors of the TGF-ß1 signaling pathway, and found that MSC transplantation inhibited Smad3 phosphorylation. CONCLUSIONS: BM-MSC treatment attenuated hepatic fibrosis in rats with TAA-induced cirrhosis, raising the possibility of the clinical use of BM-MSCs in the treatment of cirrhosis.

A randomized trial to determine the diagnostic accuracy of conventional vs. jumbo forceps biopsy of gastric epithelial neoplasias before endoscopic submucosal dissection; open-label study.

BACKGROUND AND AIMS: Larger biopsy specimens or increasing the number of biopsies may improve the diagnostic accuracy of gastric epithelial neoplasia (GEN). The aims of this study was to compare the diagnostic accuracies between conventional and jumbo forceps biopsy of GEN before endoscopic submucosal dissection (ESD) and to confirm that increasing the number of biopsies is useful for the diagnosis of GEN. RESULTS: The concordance rate between EFB and ESD specimens was not significantly different between the two groups [83.1 % (54/65) in JG vs. 79.1 % (53/67) in CG]. On multivariate analyses, two or four EFBs significantly increased the cumulating concordance rate [coefficients; twice: 5.1 (P = 0.01), four times: 5.9 (P = 0.02)]. But, the concordance rate was decreased in high grade dysplasia (coefficient -40.32, P = 0.006). PATIENTS AND METHODS: One hundred and sixty GENs from 148 patients were randomized into two groups and finally 67 GENs in 61 patients and 65 GENs in 63 patients were allocated to the conventional group (CG) or jumbo group (JG), respectively. Four endoscopic forceps biopsy (EFB) specimens were obtained from each lesion with conventional (6.8 mm) forceps or jumbo (8 mm) forceps. The histological concordance rate between 4 EFB specimens and ESD specimens was investigated in the two groups. CONCLUSIONS: Before ESD, the diagnostic accuracy of GENs was significantly increased not by the use of jumbo forceps biopsy but by increasing the number of biopsies.

Relationship between tetrahydrobiopterin and portal hypertension in patients with chronic liver disease.

Tetrahydrobiopterin (BH4) is an essential cofactor in NO synthesis by endothelial nitric oxide synthase (eNOS) enzymes. It has been previously suggested that reduced intrahepatic BH4 results in a decrease in intrahepatic NO and contributes to increased hepatic vascular resistance and portal pressure in animal models of cirrhosis. The main aim of the present study was to evaluate the relationship between BH4 and portal hypertension (PHT). One hundred ninety-three consecutive patients with chronic liver disease were included in the study. Liver biopsy, measurement of BH4 and hepatic venous pressure gradient (HVPG) were performed. Hepatic fibrosis was classified using the Laennec fibrosis scoring system. BH4 levels were determined in homogenized liver tissues of patients using a high performance liquid chromatography (HPLC) system. Statistical analysis was performed to evaluate the relationship between BH4 and HVPG, grade of hepatic fibrosis, clinical stage of cirrhosis, Child-Pugh class. A positive relationship between HVPG and hepatic fibrosis grade, clinical stage of cirrhosis and Child-Pugh class was observed. However, the BH4 level showed no significant correlation with HVPG or clinical features of cirrhosis. BH4 concentration in liver tissue has little relation to the severity of portal hypertension in patients with chronic liver disease.

Hepatic vein arrival time as assessed by contrast-enhanced ultrasonography is useful for the assessment of portal hypertension in compensated cirrhosis.

The measurement of the hepatic venous pressure gradient (HVPG) for the estimation of portal hypertension (PH) in cirrhosis has some limitations, including its invasiveness. Hepatic vein arrival time (HVAT), as assessed by microbubble contrast-enhanced ultrasonography (CEUS), is negatively correlated with the histological grade of liver fibrosis because of the associated hemodynamic abnormalities. Anatomical and pathophysiological changes in liver microcirculation are the initial events leading to PH. However, the direct relationship between HVAT and PH has not been evaluated. The present study measured both HVPG and HVAT in 71 consecutive patients with compensated cirrhosis and analyzed the relationship between the two parameters (i.e., the derivation set). Results were validated in 35 compensated patients with cirrhosis at another medical center (i.e., the validation set). The derivation set had HVPG and HVAT values of 11.4 ± 5.0 mmHg (mean ± standard deviation; range, 2-23) and 14.1 ± 3.4 seconds (range, 8.4-24.2), respectively; there was a statistically significant negative correlation between HVPG and HVAT (r(2) = 0.545; P < 0.001). The area under the receiver operating characteristic curve (AUROC) was 0.973 for clinically significant PH (CSPH; HVPG, ≥ 10 mmHg), and the sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios for CSPH for an HVAT cut-off value of 14 seconds were 92.7%, 86.7%, 90.5%, 89.7%, 6.95, and 0.08, respectively. In addition, a shorter HVAT was associated with worse Child-Pugh score (P < 0.001) and esophageal varices (P = 0.018). In the validation set, there was also a significant negative correlation between HVAT and HVPG (r(2) = 0.538; P < 0.001), and AUROC = 0.953 for CSPH. HVAT was significantly correlated with PH. These results indicate that measuring HVAT is useful for the noninvasive prediction of CSPH in patients with compensated cirrhosis.

Hepatogenous diabetes in cirrhosis is related to portal pressure and variceal hemorrhage.

BACKGROUND AND AIM: The clinical impact and complications of hepatogenous diabetes (HD) on cirrhosis have not been elucidated. This study aimed to evaluate the relationship of HD with portal hypertension (PHT) and variceal hemorrhage and to assess the prevalence of HD. METHODS: From July 2007 to December 2009, 75-g oral glucose tolerance test and insulin resistance (IR) were evaluated for 195 consecutive cirrhotic liver patients (M:F = 164:1, 53.0 ± 10.2 years) who had no history of diabetes mellitus. IR was calculated using the homeostasis model of assessment-insulin resistance (HOMA-IR) formula. Endoscopy for varices, hepatic venous pressure gradient (HVPG), and serologic tests were also conducted. RESULTS: HD was observed in 55.4 % (108/194) of the patients. Among them, 62.0 % required OGTT for diagnosis because they did not show an abnormal fasting plasma glucose level. The presence of HD showed a significant correlation with high Child-Pugh's score, variceal hemorrhage, and HVPG (p = 0.004, 0.002, and 0.019, respectively). In multivariate analysis, Child-Pugh's score (OR 1.43, 95 % CI 1.005-2.038) and HVPG (OR 1.15, 95 % CI 1.003-2.547) had significant relationships with HD. Patients with recent variceal hemorrhages (within 6 months) exhibited significantly higher glucose levels at 120 min in OGTT compared to patients without hemorrhages (p = 0.042). However, there was no difference in fasting glucose levels. The 120-min glucose level and HOMA-IR score were significantly and linearly correlated with HVPG (r (2) = 0.189, p < 0.001 and r (2) = 0.033, p = 0.011, respectively). CONCLUSION: HD and IR have significant relationships with PHT and variceal hemorrhage. Postprandial hyperglycemia in particular had a significant relationship with variceal hemorrhage.

Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis - a randomized open-label controlled study.

BACKGROUND: Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was done in humans with alcoholic liver disease. AIM: To investigate the antifibrotic effect of angiotensin II type 1 receptor (AT1-R) blocking agents (ARB) in patients with alcoholic liver disease. METHODS: The primary outcome was improvement in patients' histological features. Eighty-five patients with compensated alcoholic liver fibrosis (≥ F2) which was confirmed by baseline liver biopsy were randomized (intention-to-treat (ITT)) to receive either ARB, candesartan (8 mg/day) with ursodeoxycholic acid (UDCA) (600 mg/day) (n = 42) or UDCA alone (n = 43) as control for 6 months and follow-up liver biopsies were conducted. RESULTS: According to the Laennec fibrosis system, candesartan showed significantly higher rates of histological improvements (ITT, 33.3% vs. 11.6%, P = 0.020). In addition, the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 (P = 0.005) in the candesartan group. Candesartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 (%), and the hydroxyproline levels (µg/g liver tissue) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively (P < 0.05). In addition, the relative expression of transforming growth factor-ß1(TGF-ß1), collagen-1, AT1-R, tissue inhibitor of metalloproteinase 1 (TIMP-1), metalloproteinases2 (MMP2), Rac1 and p22phox by real-time RT-PCR decreased in the candesartan group (P < 0.05). Mean arterial blood pressure in the candesartan group decreased mildly but significantly (P < 0.001). No significant complications and side effects were observed during the present study. CONCLUSIONS: Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements.

Histological subclassification of cirrhosis using the Laennec fibrosis scoring system correlates with clinical stage and grade of portal hypertension.

BACKGROUND & AIMS: Further histological subclassification of cirrhosis may be useful because of heterogeneity of severity within cirrhosis. We aimed to determine the relationship between histological subclassification and clinical stage of cirrhosis as well as grade of portal hypertension. METHODS: One hundred-twenty-three biopsy-proven cirrhosis patients, whose clinical stage of cirrhosis and hepatic venous pressure gradient (HVPG) could be estimated, were included in this prospective study. Histology of cirrhosis was blindly subclassified using the Laennec fibrosis scoring system semi-quantitatively without knowledge of the clinical stage or the HVPG results. The Laennec system subclassifies cirrhosis as mild - thin septa, moderate - at least two broad septa, and severe - at least one very broad septum or many minute nodules. Clinical stages were determined by the presence or absence of varices, ascites, and variceal hemorrhage. Biological and laboratory data were also collected. RESULTS: Alcohol intake was the most common cause of cirrhosis in this cohort (87, 70.7%). Histology of cirrhosis subclassified using the Laennec scoring system significantly correlated with both the clinical stage of cirrhosis (p < 0.001) and HVPG (mild: 8.1 ± 2.6 mm Hg, moderate: 12.4 ± 3.3mm Hg, severe: 16.3 ± 4.0 mm Hg, p < 0.001). With higher grades of histological subclassification of cirrhosis, increased frequency in both severe portal hypertension (HVPG ≥ 12 mm Hg) and episodes of variceal hemorrhage were observed (p < 0.001). CONCLUSIONS: Histological subclassification of cirrhosis by the Laennec fibrosis scoring system is tightly correlated with both the clinical stage of cirrhosis and grade of portal hypertension. This suggests that cirrhosis should be subclassified into different stages according to its histological severity.

Portal hypertensive gastropathy: correlation with portal hypertension and prognosis in cirrhosis.

BACKGROUND: Portal hypertensive gastropathy (PHG) is a common endoscopic finding in patients with cirrhosis. However, the relationship between PHG and portal hypertension is controversial. Furthermore, nothing is known regarding the correlation between PHG and prognosis in patients with cirrhosis. METHODS: The hepatic venous pressure gradient (HVPG), endoscopic PHG grade, Child-Pugh score, and model for end-stage liver disease (MELD) score were assessed at baseline and were followed prospectively in 331 cirrhotic patients (284 males, 85.8%; mean age, 52.16 ± 9.05 years) from January 2001 to April 2009. The relationship between PHG with HVPG and survival was investigated. RESULTS: The HVPG was significantly higher in patients with severe PHG than in those with mild or no PHG (absent, 4.9 ± 1.7 mmHg; mild, 10.7 ± 4.1 mmHg; severe, 15.6 ± 4.6 mmHg; P < 0.001). During follow-up, 28 patients (8.5%) died from liver-related disease. In the Cox regression analysis, severe PHG (none and mild vs. severe) (hazard ratio 1.153, 95% confidence interval: 1.048-1.269) showed a significantly high relative risk of mortality, and in the Kaplan-Meier analysis, severe PHG showed a significantly shorter expected survival time than none or mild PHG (median survival time, 77.6 ± 9.6 months in severe PHG; log-rank test, P = 0.030). CONCLUSIONS: PHG was associated with portal hypertension severity and prognosis in patients with cirrhosis.

Dobutamine stress echocardiography for evaluating cirrhotic cardiomyopathy in liver cirrhosis.

BACKGROUND/AIMS: The blunted ventricular systolic and diastolic contractile responses to physical and pharmacological stress in cirrhosis are termed cirrhotic cardiomyopathy (CCM). CCM has been known to involve multiple defects in the ß-adrenergic signaling pathway. The aim of this study was to determine whether cirrhotic patients have blunted cardiac responses to catecholamine stimulation through dobutamine stress echocardiography (DSE). METHODS: Seventy-one cirrhotic patients with normal left ventricular (LV) chamber size and ejection fraction were enrolled. The LV systolic and diastolic functions were evaluated by two-dimensional and Doppler echocardiography at rest and during peak dobutamine infusion (40 µg/kg/min). An abnormal response was defined as a decrease of less than 10% in LV end-diastolic volume, a decrease of less than 20% in end-systolic volume, and an increase of less than 10% in LV ejection fraction (EF) at peak dobutamine infusion, based on previously used criteria. The early/late diastolic flow (E/A) ratio and diastolic parameters were also measured. RESULTS: A blunted LV response to dobutamine was observed in 18 of 71 cirrhotic patients (25.4%). The baseline EF was significantly higher in 18 patients with a blunted DSE response than that of those with a normal DSE response (P<0.05). The baseline and peak E/A ratios, which are common diastolic dysfunction markers, were higher in the cirrhosis group than in the control group (P<0.001). No adverse events associated with DSE were observed. CONCLUSIONS: Blunted cardiac responses to dobutamine stimulation, which are implicated in defects in the ß-adrenergic signaling pathway, might contribute to the pathogenesis of CCM in patients with cirrhosis.

Gallbladder wall thickening in patients with acute hepatitis.

BACKGROUND: Gallbladder wall thickening (GWT) is often observed in patients with acute hepatitis (AH). However, little is known regarding the relationship between AH and GWT. We analyzed the characteristics of GWT in patients with AH. METHOD: Between April 2002 and April 2007, 232 patients with AH underwent a sonographic examination. The clinical and laboratory findings of patients with GWT were evaluated and compared with patients without GWT. Data were recorded for the following variables: gender, age, laboratory findings, duration of symptom, presence of gallstone, and etiology of GWT. RESULTS: A total of 147 (63%) patients with AH had GWT. GWT in patients with an alanine aminotransferase level more than 500 IU/l (5.2 +/- 3.4 mm) was greater than that in other patients (3.9 +/- 2.3 mm; p < 0.05). Hepatitis A virus infection (odds ratio = 3.17 [1.42-7.09]), female gender (odds ratio = 2.47 [1.34-4.56]), and an elevated total bilirubin level (odds ratio = 1.09 [1.03-1.15]) were positively associated with GWT. CONCLUSION: The incidence of GWT in patients with AH was 63%, and there was an association with hepatitis A virus infection, female gender, and an elevated total bilirubin level.

Angiotensin receptor blockers are superior to angiotensin-converting enzyme inhibitors in the suppression of hepatic fibrosis in a bile duct-ligated rat model.

BACKGROUND: Angiotensin blockade such as with an angiotensin II receptor blocker (ARB) or angiotensinconverting enzyme inhibitor (ACEI) has antifibrotic properties. The aim of this study was to evaluate and compare the antifibrotic effect between ARBs and ACEIs. METHODS: Common bile duct-ligated (BDL) adult Sprague-Dawley rats were allocated to five groups (each group, n = 8) as follows: G1, BDL without drug; G2, BDL + captopril 100 mg/kg per day; G3, BDL + ramipril 10 mg/kg per day; G4, BDL + losartan 10 mg/kg per day; G5, BDL + irbesartan 15 mg/kg per day. Four weeks post-BDL, hepatic fibrosis was analyzed histomorphologically using Batts and Ludwig scores. alpha-Smooth muscle actin (alpha-SMA) expression by immunohistochemical staining, hydroxyproline contents of liver tissue by spectrophotometry, and angiotensin receptor, collagen, procollagen, and transforming growth factor beta (TGF-beta) expressions were evaluated by real-time reverse transcriptase-polymerase chain reaction. Angiotensin receptor expression was also determined by Western blotting. RESULTS: Batts and Ludwig scores were 3.8, 2.6, 2.4, 1.8, and 1.6 in G1, G2, G3, G4, and G5, respectively. Histologically, ARB groups (G4, G5) showed significant suppression of hepatic fibrosis compared with ACEI groups or the control. Expressions of alpha-SMA (%) and the content of hydroxyproline (microg liver tissue) were significantly lower in ARB groups (G4, G5) than in ACEI groups (G2, G3) (P < 0.05). Also, ARB reduced the expression of angiotensin receptor, collagen, procollagen, and TGF-beta1 compared with ACEI. Western blot analysis showed that the expression of angiotensin receptor was inhibited in both ARB and ACEI groups. CONCLUSIONS: Both ARB and ACEI attenuate hepatic fibrosis through inhibiting hepatic stellate cell activation, and the inhibitory effect of ARBs on hepatic fibrosis is superior to that of ACEIs in the BDL rat model.

Thickening of the gastric wall on transabdominal sonography: a sign of gastric cancer.

PURPOSE: To determine the value of a thickened gastric wall detected during transabdominal sonography (TAS) in the diagnosis of gastric cancer. METHOD: This prospective study comprised 312 patients who underwent both TAS and endoscopy. Transverse TAS scanning was performed using a 3.5-MHz curved transducer to measure gastric wall thickness in the antrum and body of the stomach. Based on endoscopic and histologic findings, we classified the patients into 3 groups: normal or benign disease (BD), early gastric cancer (EGC), and advanced gastric cancer (AGC). TAS findings were then compared. RESULTS: The thickness of the gastric wall was 4.9 +/- 1.6 mm in 262 patients with BD, 5.6 +/- 2.4 mm in 21patients with EGC, and 10.3 +/- 4.7 mm in 29 patients with AGC (p < 0.01). A gastric wall thickness of greater than 7 mm had a 75.0% sensitivity, 92.6% specificity, 50.0% positive predictive value, and 97.4% negative predictive value in the diagnosis of AGC. CONCLUSION: Although not suitable as a screening method for gastric cancer, a thickening of the gastric wall of >7 mm may be a marker for AGC.

Risk factors for delayed postendoscopic mucosal resection hemorrhage in patients with gastric tumor.

OBJECTIVE: Although endoscopic mucosal resection has been recognized as the standard treatment for gastric mucosal neoplasm, postendoscopic mucosal resection hemorrhage remains a major complication of endoscopic mucosal resection, and this problem seems to be increasing owing to the development of invasive techniques. The aims of this study were to determine the incidence and grade of postendoscopic mucosal resection hemorrhage and to identify risk factors for delayed postendoscopic mucosal resection hemorrhage in patients with gastric neoplasm. METHODS: Data of endoscopic mucosal resections performed by three endoscopists were retrospectively collected over 8 years and then analyzed. Immediate postendoscopic mucosal resection hemorrhage was defined as bleeding during the procedure. Delayed postendoscopic mucosal resection hemorrhage was defined when two of the four following parameters were satisfied after the endoscopic mucosal resection period; (i) hematemesis, melena or dizziness, (ii) hemoglobin loss >2 g/dl, (iii) blood pressure decrease >20 mmHg or pulse rate increase >20/min and (iv) Forrest I or IIa-IIb on follow-up endoscopy. RESULTS: A total of 157 patients (mean age: 64 years, male : female=44 : 113) were reviewed. Twenty-nine (18.5%) and 13 patients (8.3%) presented with immediate and delayed postendoscopic mucosal resection hemorrhage, respectively. Multivariate logistic regression analysis revealed that the patient's age (15 mm; odds ratio 5.90, 95% confidence interval 1.13-30.87) and the experience of the endoscopist (

[Inhibitory effect of angiotensin blockade on hepatic fibrosis in common bile duct-ligated rats].

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. MATERIAL AND METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microg/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.

Rifaximin and Propranolol Combination Therapy Is More Effective than Propranolol Monotherapy for the Reduction of Portal Pressure: An Open Randomized Controlled Pilot Study.

BACKGROUND/AIMS: Non-selective beta blockers (NSBBs) are currently the only accepted regimen for preventing portal hypertension (PHT)-related complications. However, the effect of NSBBs is insufficient in many cases. Bacterial translocation (BT) is one of the aggravating factors of PHT in cirrhosis; therefore, selective intestinal decontamination by rifaximin is a possible therapeutic option for improving PHT. We investigated whether the addition of rifaximin to propranolol therapy can improve hepatic venous pressure gradient (HVPG) response. METHODS: Sixty-four cirrhosis patients were randomly assigned to propranolol monotherapy (n=48) versus rifaximin and propranolol combination therapy (n=16). Baseline and post-treatment HVPG values, BT-related markers (lipopolysaccharide [LPS], LPS-binding protein [LBP], interleukin-6 [IL-6], and tumor necrosis factor α [TNF-α]), serological data, and adverse event data were collected. HVPG response rate was the primary endpoint. RESULTS: Combination therapy was associated with better HVPG response rates than monotherapy (56.2% vs 87.5%, p=0.034). In combination therapy, posttreatment BT-related markers were significantly decreased (LPS, p=0.005; LBP, p=0.005; IL-6, p=0.005; TNF-α, p=0.047). CONCLUSIONS: Rifaximin combination therapy showed an additive effect in improving PHT compared to propranolol monotherapy. These pilot data suggest that the addition of rifaximin to NSBBs could be a good therapeutic option for overcoming the limited effectiveness of NSBBs.

[Modulation of colon cancer cell invasiveness induced by deoxycholic acid].

BACKGROUND/AIMS: Deoxycholic acid (DCA), a secondary bile acid, has been implicated to promote colon cancer growth and progression. However, its molecular mechanisms are largely unknown. In this study, we investigated the effects of DCA on proliferation, migration, and invasiveness of colon cancer cells (HT-29). METHODS: HT-29 cells were incubated with either medium (control) only or DCA for 24-48 hours. Time courses of RT-PCR for vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1alpha mRNA expression, Western blotting for VEGF and matrix metalloproteinase (MMP)-9, zymography for MMP-9 activation, and wound-migration assay were determined after various concentrations of DCA (0-80 microM) treatment. Moreover, these experiments were reassessed after pretreatments (2-6 hours) with specific inhibitors of various signal pathways. RESULTS: DCA enhanced HIF-1alpha mRNA expression, VEGF mRNA and VEGF protein expression, MMP-9 protein expression/activation, and cell migration ability in a dose-related manner. DCA-induced VEGF protein expression was inhibited by pretreatment with NS-398 (COX-2 inhibitor), PDTC (NF-kappaB inhibitor), or tauroursodeoxycholic acid (TUDC). DCA-induced cell migration ability was inhibited by pretreatment of GF109203X, a protein kinase C inhibitor. DCA-induced MMP-9 protein expression/activation was inhibited by pretreatment with SB203580, U0126, or PDTC. CONCLUSIONS: DCA significantly upregulates invasive and angiogenic potentials of human colon cancer cells through multiple signal transduction pathways.