Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections-Results from the ICA "Global Study" (EABCIR-Global Study).

BACKGROUND: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites "Global Study." METHODS: Patients hospitalized with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. RESULTS: From October 2015 to September 2016, 1302 patients were included at 46 centers. A clinical response was achieved in only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR = 1.16; 95% CI = 1.02-1.31), blood leukocyte count (OR = 1.39;95% CI = 1.09-1.77), serum albumin (OR = 0.70; 95% CI = 0.55-0.88), nosocomial infections (OR = 1.96; 95% CI = 1.20-2.38), pneumonia (OR = 1.75; 95% CI = 1.22-2.53), and ineffective treatment according to antibiotic susceptibility test (OR = 5.32; 95% CI = 3.47-8.57). Patients with a lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55% vs. 96%; p < 0.001), a higher incidence of second infections (29% vs. 15%; p < 0.001), shock (35% vs. 7%; p < 0.001) and new organ failures (52% vs. 19 %; p < 0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival ( subdistribution = 0.20; 95% CI = 0.14-0.27). CONCLUSIONS: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with a high degree of inflammation, low serum albumin levels, and severe liver impairment.

Evogliptin Directly Inhibits Inflammatory and Fibrotic Signaling in Isolated Liver Cells.

Chronic liver inflammation can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Kupffer cells (KC) secrete proinflammatory and fibrogenic cytokines in response to lipopolysaccharide (LPS), and so play an important role in liver inflammation, where they induce hepatocellular damage. LPS also activates hepatic stellate cells and induces extracellular matrix deposition. In this study, we used isolated primary KC, primary hepatocytes, and primary hepatic stellate cells (HSC) to investigate whether evogliptin directly inhibits inflammatory and fibrotic signaling. We found that evogliptin inhibited LPS-induced secretion of inducible nitric oxide synthase and transforming growth factor ß (TGF-ß) from KC. Moreover, evogliptin inhibited inflammatory mediator release from hepatocytes and hepatic stellate cell activation that were induced by KC-secreted cytokines. In hepatocytes, evogliptin also inhibited LPS-induced expression of proinflammatory cytokines and fibrotic TGF-ß. In addition, evogliptin inhibited TGF-ß-induced increases in connective tissue growth factor levels and HSC activation. These findings indicate that evogliptin inhibits inflammatory and fibrotic signaling in liver cells. We also showed that the inhibitory effect of evogliptin on inflammatory and fibrotic signaling is associated with the induction of autophagy.

Epidemiology and Effects of Bacterial Infections in Patients With Cirrhosis Worldwide.

BACKGROUND & AIMS: Bacterial infections are common and life-threatening in patients with cirrhosis. Little is known about the epidemiology of bacterial infections in different regions. We performed a multicenter prospective intercontinental study to assess the prevalence and outcomes of bacterial and fungal infections in patients with cirrhosis. METHODS: We collected data from 1302 hospitalized patients with cirrhosis and bacterial or fungal infections at 46 centers (15 in Asia, 15 in Europe, 11 in South America, and 5 in North America) from October 2015 through September 2016. We obtained demographic, clinical, microbiology, and treatment data at time of diagnosis of infection and during hospitalization. Patients were followed until death, liver transplantation, or discharge. RESULTS: The global prevalence of multidrug-resistant (MDR) bacteria was 34% (95% confidence interval 31%-37%). The prevalence of MDR bacteria differed significantly among geographic areas, with the greatest prevalence in Asia. Independent risk factors for infection with MDR bacteria were infection in Asia (particularly in India), use of antibiotics in the 3 months before hospitalization, prior health care exposure, and site of infection. Infections caused by MDR bacteria were associated with a lower rate of resolution of infection, a higher incidence of shock and new organ failures, and higher in-hospital mortality than those caused by non-MDR bacteria. Administration of adequate empirical antibiotic treatment was independently associated with improved in-hospital and 28-day survival. CONCLUSIONS: In a worldwide study of hospitalized patients, we found a high prevalence of infection with MDR bacteria in patients with cirrhosis. Differences in the prevalence of MDR bacterial infections in different global regions indicate the need for different empirical antibiotic strategies in different continents and countries. While we await new antibiotics, effort should be made to decrease the spread of MDR bacteria in patients with cirrhosis.

Changes in Characteristics of Patients with Liver Cirrhosis Visiting a Tertiary Hospital over 15 Years: a Retrospective Multi-Center Study in Korea.

BACKGROUND: Liver cirrhosis has become a heavy burden not only for patients, but also for our society. However, little is known about the recent changes in clinical outcomes and characteristics of patients with cirrhosis-related complications in Korea. Therefore, we aimed to evaluate changes in characteristics of patients with liver cirrhosis in Daegu-Gyeongbuk province in Korea over the past 15 years. METHODS: We retrospectively reviewed the medical records of 15,716 liver cirrhotic patients from 5 university hospitals in Daegu-Gyeongbuk province from 2000 to 2014. The Korean Standard Classification of Diseases-6 code associated with cirrhosis was investigated through medical records and classified according to the year of first visit. RESULTS: A total of 15,716 patients was diagnosed with cirrhosis. A number of patients newly diagnosed with cirrhosis has decreased each year. In 2000, patients were most likely to be diagnosed with hepatitis B virus (HBV) cirrhosis, followed by alcoholic cirrhosis. There was a significant decrease in HBV (P < 0.001), but alcohol, hepatitis C virus (HCV), and non-alcoholic fatty liver disease (NAFLD) showed a significant increase during the study period (alcohol, P = 0.036; HCV, P = 0.001; NAFLD, P = 0.001). At the time of initial diagnosis, the ratio of Child-Turcotte-Pugh (CTP) class A gradually increased from 23.1% to 32.9% (P < 0.001). The most common cause of liver-related hospitalization in 2000 was hepatocellular carcinoma (HCC) (25.5%); in 2014, gastrointestinal bleeding with esophageal and gastric varices (21.4%) was the most common cause. Cases of hospitalization with liver-related complication represented 76.4% of all cases in 2000 but 70.9% in 2014. Incidence rate of HCC has recently increased. In addition, HCC-free survival was significantly lower in CTP class A than in classes B and C. Finally, there was significant difference in HCC occurrence according to causes (P < 0.001). HBV and HCV cirrhosis had lower HCC-free survival than alcoholic and NAFLD cirrhosis. CONCLUSION: In recent years, the overall number of cirrhosis patients has decreased. This study confirmed the recent trend in decrease of cirrhosis, especially of cirrhosis due to HBV, and the increase of HCV, alcoholic and NAFLD cirrhosis. Targeted screening for at-risk patients will facilitate early detection of liver diseases allowing effective intervention and may have decreased the development of cirrhosis and its complications.

Polymorphisms in the 3'-UTR of SCD5 gene are associated with hepatocellular carcinoma in Korean population.

The purpose of the study was to assess the relationship between polymorphisms of the SCD5 and MMP1 gene and hepatocellular carcinoma (HCC). The gene polymorphisms with a minor allele frequency (MAF) > 0.05 were selected eight SNPs (rs6840, rs1065403, rs3821974, and rs3733230 in 3'-UTR; rs4693472, rs3733227, rs1848067, and rs6535374 in intron region) of SCD5 gene and two SNPs (rs1799750 and rs1144393 in promoter region) of MMP1 gene. The genotype of SCD5 and MMP1 gene SNPs were determined by direct sequencing and pyrosequencing, respectively. One hundred sixty-two patients with HCC and two hundred twenty-five control subjects were recruited in Korean male population. In terms of genotype frequencies, SCD5 genotype TC, GA, AG, and CG of rs6840, rs1065403, rs3821974, and rs3733230, respectively were higher in control group than HCC. In addition, these genotype decreased the risk (rs6840; OR 0.55, 95% CI 0.31-0.99; rs1065403; OR 0.46, 95% CI 0.26-0.83; rs3821974; OR 0.56, 95% CI 0.31-0.99; rs3733230; OR 0.62, 95% CI 0.34-1.12) of HCC, which may work as a prevention of HCC. At least one minor allele carrier of SCD5 gene polymorphisms were related to decreased risk of HCC for AFP cut-point levels > 200 or > 400 ng/ml, respectively. Our results indicate that polymorphisms in the 3'-UTR of the SCD5 gene may associated with HCC in the Korean male population.

Temporal improvement in survival of patients with hepatocellular carcinoma in a hepatitis B virus-endemic population.

BACKGROUND AND AIM: Over the past decade, the management of hepatocellular carcinoma (HCC) and viral hepatitis has been improved. We explored survival trends and factors affecting survival of HCC in a hepatitis B virus (HBV)-endemic population. METHODS: From 31 521 and 38 167 HCC registrants to the population-based national cancer registry in Korea, an HBV-endemic country, in the period of 2003-2005 and 2008-2010, we randomly sampled cohorts of 4515 and 4582 patients, respectively, for the investigation of clinical characteristics and survival. RESULTS: Compared with Cohort 2003-2005, Cohort 2008-2010 had significantly better liver function (Child-Turcotte-Pugh class A, 64.2% vs 71.6%; P < 0.001) and had more advanced tumor stages (Barcelona Clinic Liver Cancer stage B-D, 45.8% vs 50.4%; P < 0.001). HBV was the predominant cause of HCC in both cohorts (62.5% vs 62.2%; P = 0.70). Cohort 2008-2010 had significantly better overall survival than Cohort 2003-2005 by age-adjusted univariate, multivariable, and propensity score-matched analyses (median survival time, 17.2 vs 28.4 months; P < 0.001). In a subcohort analysis, a consistently significant inter-cohort improvement in survival was observed only in patients with HBV-related HCC (median survival, 16.1 vs 30.4 months; P < 0.001). The annual number of patients with HCC receiving oral antiviral agents for HBV precipitously increased from 93 in 2005 to 28 520 in 2010 in the country. CONCLUSIONS: The consistent improvement in survival of patients with HCC was confined to HBV-related HCC subcohort over the last decade in an HBV-endemic population. The survival improvement coincided with the exponential use of oral antiviral agents for HBV in the patients.

Serum cystatin C level: An excellent predictor of mortality in patients with cirrhotic ascites.

BACKGROUND AND AIM: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. METHODS: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS-1). RESULTS: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS-1. Serum creatinine level was not significantly associated with mortality and development of HRS-1 on multivariate analysis. CONCLUSION: Serum cystatin C level was an independent predictor of mortality and development of HRS-1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites.

Lack of difference among terlipressin, somatostatin, and octreotide in the control of acute gastroesophageal variceal hemorrhage.

UNLABELLED: Vasoactive drugs are recommended to be started as soon as possible in suspected variceal bleeding, even before diagnostic endoscopy. However, it is still unclear whether the therapeutic efficacies of the various vasoactive drugs used are comparable. The aim of this prospective, multicenter, randomized, noninferiority trial was to characterize the effects of terlipressin, somatostatin, and octreotide when they are initiated before endoscopic treatment in patients with acute variceal bleeding. Patients with liver cirrhosis and significant upper gastrointestinal bleeding were randomly assigned to receive early administration of terlipressin, somatostatin, or octreotide, followed by endoscopic treatment. Patients with nonvariceal bleeding were excluded after endoscopy. The primary endpoint was 5-day treatment success, defined as control of bleeding without rescue treatment, rebleeding, or mortality, with a noninferiority margin of 0.1. In total, 780 patients with variceal bleeding were enrolled: 261 in the terlipressin group; 259 in the somatostatin group; and 260 in the octreotide group. At the time of initial endoscopy, active bleeding was noted in 43.7%, 44.4%, and 43.5% of these patients, respectively (P=0.748), and treatment success was achieved by day 5 in 86.2%, 83.4%, and 83.8% (P=0.636), with similar rates of control of bleeding without rescue treatment (89.7%, 87.6%, and 88.1%; P=0.752), rebleeding (3.4%, 4.8%, and 4.4%; P=0.739), or mortality (8.0%, 8.9%, and 8.8%; P=0.929). The absolute values of the lower bound of confidence intervals for terlipressin versus somatostatin, terlilpressin versus octreotide, and octreotide versus somatostatin were 0.095, 0.090, and 0.065, respectively. CONCLUSION: Hemostatic effects and safety did not differ significantly between terlipressin, somatostatin, and octreotide as adjuvants to endoscopic treatment in patients with acute gastroesophageal variceal bleeding.

Comparison of quality of life and worry of cancer recurrence between endoscopic and surgical treatment for early gastric cancer.

BACKGROUND: The quality of life (QOL) of patients who survive early gastric cancer (EGC) is an area of increasing interest. OBJECTIVE: To compare the QOL and degree of worry of cancer recurrence in EGC patients who underwent endoscopic submucosal dissection (ESD) or surgery. DESIGN: Cross-sectional study. SETTINGS: A tertiary referral center. PATIENTS: A total of 565 patients with EGC who received ESD or surgery. INTERVENTION: Questionnaires. MAIN OUTCOME MEASUREMENTS: QOL was evaluated using the Short-form Health Survey and the European Organization for Research and Treatment of Cancer QOL questionnaires (QLQ-C30 and EORTC-QLQ-STO22). Mood disorders and the worry of cancer recurrence were estimated using the Hospital Anxiety and Depression Scale (HADS) and Worry of Cancer Scale, respectively. RESULTS: Questionnaires were completed by 55.7% of the ESD (137/246) and 58.9% of the surgery (188/319) patients. The surgery group had more QOL-related symptomatic and functional problems, including fatigue (P=.044), nausea/vomiting (P=.032), appetite loss (P=.023), diarrhea (P<.001), pain (P=.013), reflux symptoms (P=.005), eating restrictions (P<.001), anxiety (P=.015), taste impairment (P=.011), and poor body image (P<.001). The ESD group had significantly higher worry of cancer recurrence scores after adjusting for covariates, especially when visiting their physicians. The HADS results did not differ between the groups. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Endoscopic treatment for EGC provides a better QOL, but stomach preservation might provoke cancer recurrence worries. Endoscopists should address this issue for relieving a patient's concern of cancer recurrence during follow-up period after ESD. ( CLINICAL TRIAL REGISTRATION NUMBER: WHO ICTRP KCT0000791.).

Impact of reinforced education by telephone and short message service on the quality of bowel preparation: a randomized controlled study.

BACKGROUND AND STUDY AIMS: High quality bowel preparation is essential for successful colonoscopy. This study aimed to assess the impact of reinforced education by telephone or short message service (SMS) on the quality of bowel preparation. PATIENTS AND METHODS: A prospective, endoscopist-blinded, randomized, controlled study was conducted. Reinforced education groups received additional education via reminders by telephone or SMS 2 days before colonoscopy. The primary outcome was the quality of the bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The secondary outcomes included polyp detection rate (PDR), adenoma detection rate (ADR), tolerance, and subjective feelings of patients. RESULTS: A total of 390 patients were included. Total BBPS score was significantly higher in the reinforced education groups than in the control group (mean [SD] telephone vs. CONTROL: 7.1 [1.2] vs. 6.3 [1.4], P < 0.001; SMS vs. CONTROL: 6.8 [1.3] vs. 6.3 [1.4], P = 0.027). Between the two interventions, there was no significant difference in total BBPS score. PDR and ADR were not different among groups. Reinforced education groups showed lower anxiety and better tolerance compared with controls. A preparation-to-colonoscopy time of > 6 hours and < 80 % of the purgative ingested were independent factors associated with inadequate bowel preparation (BBPS < 5), whereas re-education by telephone was inversely related to inadequate bowel preparation. CONCLUSION: SMS was the optimal education modality, and was as effective as telephone reminders for the quality of bowel preparation. A reinforced educational approach via telephone or SMS should be individualized, depending on the resource availability of each clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01911052).

Individual prediction model for lamivudine treatment response in hepatitis B virus e antigen-positive chronic hepatitis B patients.

BACKGROUND AND AIMS: Although prolonged lamivudine (LAM) therapy is associated with the emergence of LAM-resistant mutations, it is still a commonly used therapy in many Asian countries because of its established long-term safety and low cost. The aim of our study was to assess the predictors of long-term LAM treatment response and to establish an individual prediction model (IPM) for hepatitis B virus e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B (CHB) patients. METHODS: This was a multicenter analysis of 838 patients treated with LAM between January 1999 and August 2004. Of these, 748 patients were followed up for at least 24 months. RESULTS: The median age was 43.0 years (range, 19-79 years) and the mean duration of LAM monotherapy was 34.2 ± 0.7 months. In the multivariate analysis, age (odds ratio [OR] = 0.974, P < 0.001), baseline alanine aminotransferase level (OR = 1.001, P = 0.014), and baseline hepatitis B virus DNA level (OR = 0.749, P < 0.001) were independent factors for HBeAg seroconversion. Based on the predictors, an IPM was established. Patients were classified into high (> 50%), intermediate (30-50%), or low (≤ 30%) response groups based on their probability of HBeAg seroconversion according to the IPM. The cumulative HBeAg seroconversion rate at 6 years for the high, intermediate, and low response groups was 66.0%, 48.5%, and 21.8%, respectively (P < 0.001). CONCLUSIONS: An IPM was developed based on predictors of HBeAg seroconversion in HBeAg-positive CHB patients on LAM monotherapy. This model will allow screening of LAM responders prior to the commencement of antiviral treatment.

Efficacy and safety of human placental extract for alcoholic and nonalcoholic steatohepatitis: an open-label, randomized, comparative study.

Human placental extract (HPE) is a traditional medicine that has been used for the symptomatic treatment of liver disease without any verifying clinical evidence. This study aimed to evaluate the efficacy and safety of HPE in patients with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this clinical trial as a multicenter, open-label, randomized, comparative noninferiority study to improve the reliability of analyses. The enrollment criteria were limited to ASH or NASH patients with serum alanine aminotransferase (ALT) 1.5-fold higher than the normal level. Patients in the control group were treated with a commercially available mixture of liver extract and flavin adenine dinucleotide (LE­FAD). Intention-to-treat (ITT) analysis was applied to 194 patients, and per-protocol (PP) analysis was available for 154 patients. The rate of primary goal achievement of treatment efficacy was arbitrarily defined as 20% or greater improvement in ALT level compared with the pretreatment level and did not differ significantly between the HPE and control groups [62.9% (44/70) vs. 48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree occurred in 3.1% of patients. The ADR and treatment compliance rates were similar in both groups. In conclusion, the clinical value of HPE in the treatment of ASH and NASH is equivalent to that of LE­FAD.

Shifting prevalence of gallbladder polyps in Korea.

Only a few studies have evaluated the population-adjusted prevalence of gallbladder polyps (GBP). This study aimed to evaluate the changes in GBP prevalence and risk factors at a single health screening center in Korea from 2002 to 2012. Of 48,591 adults who underwent health screening between 2002 and 2012, 14,250 age- and gender-matched subjects were randomly selected to evaluate prevalence. Risk factors were analyzed between the GBP-positive and GBP-negative groups during 2002-2004 (Period A) and 2010-2012 (Period B). The annual prevalence of GBP over the 11-yr period was 5.4%. Annual prevalence increased from 3.8% in Period A to 7.1% in Period B. Male gender and obesity were independent risk factors for GBP in both periods. Hepatitis B virus surface antigen (HBsAg) positivity was a risk factor for GBP in Period A but not in Period B. The risk factors for GBP changed from HBsAg positivity to lipid profile abnormalities. Other variables including age, hypertension, diabetes, impaired fasting glucose, chronic hepatitis C virus infection, and liver function tests did not correlate with GBP. In conclusion, GBP prevalence is increasing and risk factors for GBP have changed in Korea. More attention should be paid to this issue in the future.

The Clinical Significance of Myosteatosis in Survival Outcomes in Patients with Hepatocellular Carcinoma Treated with Sorafenib.

The role of body composition parameters in sorafenib-treated hepatocellular carcinoma (HCC) patients is still not fully elucidated. Here, we aimed to evaluate the impact of computed tomography (CT)-based body composition parameters on the survival of such patients. In this multicenter study, we analyzed the data of 245 sorafenib-treated HCC patients from January 2008 to December 2019. Sarcopenia, visceral obesity, and myosteatosis were defined by using cross-sectional CT images at the third lumbar vertebra level. The effects of these parameters on overall survival (OS) and progression-free survival (PFS) were evaluated. The median age was 67.0 years (interquartile range: 61.0-78.0 year), and 211 patients (86.1%) were male. The median OS and PFS were 7.9 months and 4.8 months, respectively. Vascular invasion (hazard ratio (HR), 1.727; 95% confidence interval (CI), 1.258-2.371; p = 0.001), extrahepatic metastasis (HR, 1.401; 95% CI, 1.028-1.908; p = 0.033), alpha-fetoprotein level > 200 ng/mL (HR, 1.559; 95% CI, 1.105-2.201; p = 0.012), and myosteatosis (HR, 1.814; 95% CI, 1.112-2.960; p = 0.017) were associated with OS. Patient mortality was significantly higher in the group with two or more risk factors than in the group with fewer risk factors. In conclusion, myosteatosis may be a novel prognostic CT-based radiological biomarker in sorafenib-treated HCC patients.

Prevalence and predictive value of sarcopenia in hospitalized patients with ischemic colitis.

Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P < 0.001). Sarcopenia was associated with extended hospitalization (median: 8 vs. 6 days, P < 0.001) and fasting periods (4 vs. 3 days, P = 0.004), as well as prolonged antibiotic use (9 vs. 7 days, P = 0.039). Sarcopenia was linked to a higher risk of surgery or mortality (9.0% vs. 0%, P = 0.001) and independently predicted this outcome (odds ratio [OR], 11.17; 95% confidence interval [CI], 1.24‒1467.65, P = 0.027). It was prevalent among hospitalized patients with IC, potentially indicating severe IC and a worse prognosis. This underscores the importance of meticulous monitoring, immediate medical intervention, and timely surgical consideration.

Proteomic and cytokine plasma biomarkers for predicting progression from colorectal adenoma to carcinoma in human patients.

In the present study, we screened proteomic and cytokine biomarkers between patients with adenomatous polyps and colorectal cancer (CRC) in order to improve our understanding of the molecular mechanisms behind turmorigenesis and tumor progression in CRC. To this end, we performed comparative proteomic analysis of plasma proteins using a combination of 2DE and MS as well as profiled differentially regulated cytokines and chemokines by multiplex bead analysis. Proteomic analysis identified 11 upregulated and 13 downregulated plasma proteins showing significantly different regulation patterns with diagnostic potential for predicting progression from adenoma to carcinoma. Some of these proteins have not previously been implicated in CRC, including upregulated leucine-rich α-2-glycoprotein, hemoglobin subunit ß, Ig α-2 chain C region, and complement factor B as well as downregulated afamin, zinc-α-2-glycoprotein, vitronectin, and α-1-antichymotrypsin. In addition, plasma levels of three cytokines/chemokines, including interleukin-8, interferon gamma-induced protein 10, and tumor necrosis factor α, were remarkably elevated in patients with CRC compared to those with adenomatous polyps. Although further clinical validation is required, these proteins and cytokines can be established as novel biomarkers for CRC and/or its progression from colon adenoma.

Inhibition of constitutively activated phosphoinositide 3-kinase/AKT pathway enhances antitumor activity of chemotherapeutic agents in breast cancer susceptibility gene 1-defective breast cancer cells.

Loss or decrease of wild type BRCA1 function, by either mutation or reduced expression, has a role in hereditary and sporadic human breast and ovarian cancers. We report here that the PI3K/AKT pathway is constitutively active in BRCA1-defective human breast cancer cells. Levels of phospho-AKT are sustained even after serum starvation in breast cancer cells carrying deleterious BRCA1 mutations. Knockdown of BRCA1 in MCF7 cells increases the amount of phospho-AKT and sensitizes cells to small molecule protein kinase inhibitors (PKIs) targeting the PI3K/AKT pathway. Restoration of wild type BRCA1 inhibits the activated PI3K/AKT pathway and de-sensitizes cells to PKIs targeting this pathway in BRCA1 mutant breast cancer cells, regardless of PTEN mutations. In addition, clinical PI3K/mTOR inhibitors, PI-103, and BEZ235, showed anti-proliferative effects on BRCA1 mutant breast cancer cell lines and synergism in combination with chemotherapeutic drugs, cisplatin, doxorubicin, topotecan, and gemcitabine. BEZ235 synergizes with the anti-proliferative effects of gemcitabine by enhancing caspase-3/7 activity. Our results suggest that the PI3K/AKT pathway can be an important signaling pathway for the survival of BRCA1-defective breast cancer cells and pharmacological inhibition of this pathway is a plausible treatment for a subset of breast cancers.

Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study.

BACKGROUND AND AIM: As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea. METHODS: A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009. RESULTS: The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively. CONCLUSIONS: Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.

Comparison of clinical outcomes among different endoscopic resection methods for treating colorectal neoplasia.

BACKGROUND/AIM: Endoscopic treatments of colorectal neoplasms have yet to be standardized. This study aimed to compare efficacy and tolerability of different endoscopic resection methods for colorectal epithelial tumors. METHODS: Patients with non-pedunculated colorectal tumors undergoing endoscopic treatments were consecutively enrolled, and their medical records were reviewed retrospectively. The resection methods were classified into three groups: endoscopic mucosal resection with circumferential precutting (EMR-P), endoscopic submucosal dissection with snaring (ESD-S), and endoscopic submucosal dissection alone (ESD). We compared en bloc resection, pathological complete resection, and complications associated with these methods. RESULTS: Overall, 206 lesions from 203 patients were included in the study (mean size 25.2 ± 10.1 mm). The number of lesions treated with EMR-P, ESD-S, and ESD was 91 (44.2 %), 57 (27.7 %), and 58 (28.2 %), respectively. There was a significant difference in both the en bloc resection rates (EMR-P, 61.5 %; ESD-S, 64.9 %; ESD, 96.6 %; p = 0.001) and complete resection rates (EMR-P, 51.6 %; ESD-S, 54.4 %; ESD, 75.9 %; p = 0.009). Bleeding and perforation were less frequently observed in the EMR-P group. In the subgroup-analysis of lesions less than 20 mm, however, these differences were not observed. CONCLUSIONS: All endoscopic resection methods, including EMR-P, ESD-S, and ESD, were effective and safe for the treatment of colorectal neoplasms. Technically demanding ESD with high en bloc and complete resection rate should be reserved for the suspicious cancer lesion, which requires the precise histological evaluation. EMR-P with good feasibility can be considered an alternative to ESD for the lesions less than 20 mm.

Predictors for underestimated pathology in forceps biopsy compared with resection specimen of colorectal neoplasia; focus on surface appearance.

BACKGROUND: There have been substantial differences in pathologic results between forceps biopsies (FB) and resection specimen (RS) of the colorectal neoplasm. The aim of this study was to investigate predictive factors of the underestimated pathology in FB compared with RS. METHODS: Data from 248 consecutive patients with colorectal intraepithelial neoplasm ≥10 mm, which was removed by endoscopic mucosal resection or endoscopic submucosal dissection, were reviewed retrospectively. We excluded patients with no FB on the neoplasm before the resection. Demographic data and tumor characteristics including size, locations, surface appearances, and the number of FB fragments were evaluated as potential factors associated with the discrepancies by logistic regression analysis. RESULTS: Overall, 179 lesions from 171 patients were included in the study (size, 28.37 ± 12.00 mm; range 10-80 mm). The overall number of discrepancy cases was 103 (57.5%), where 90 (50.3%) were underestimated in FB and 13 (7.2%) downgraded in their RS. In the multivariate analysis, round [odds ratio (OR) 4.46, 95% confidence interval (CI) 1.76-11.30, p = 0.002], depressed (OR 3.23, 95% CI 1.11-9.39, p = 0.031), and mixed type of surface appearance (OR 5.47, 95% CI 2.38-12.60, p < 0.001), and tumor size ≥30 mm (OR 2.14, 95% CI 1.12-4.10, p = 0.021) were significant predictive factors for underestimated pathology in FB. CONCLUSIONS: Underestimation in FB is remarkable in colorectal tumors ≥10 mm in size. This discrepancy is associated with the tumor characteristics, such as surface appearance and size. Endoscopic characteristics of tumor should be carefully examined for an adequate management strategy of colorectal epithelial neoplasm.