Response-Guided Therapy With Cefotaxime, Ceftriaxone, or Ciprofloxacin for Spontaneous Bacterial Peritonitis: A Randomized Trial: A Validation Study of 2021 AASLD Practice Guidance for SBP.

INTRODUCTION: For the treatment of spontaneous bacterial peritonitis (SBP), cefotaxime, ceftriaxone, and ciprofloxacin were used as first-line agents. However, considering the increasing rate of antibiotic resistance, it is unclear which of these drugs can be initially recommended. This study aimed to compare the current efficacy of the 3 antibiotics, namely cefotaxime, ceftriaxone, and ciprofloxacin, for the treatment of SBP in patients with cirrhosis with ascites, when guided by therapeutic responses. METHODS: This study was a multicenter, prospective, randomized controlled trial. The inclusion criteria were 16- to 75-year-old patients with liver cirrhosis with ascites, having polymorphonuclear cell count of >250/mm 3 . We performed a follow-up paracentesis at 48 hours to decide continuing or changing the assigned antibiotics and then assessed the resolution rates at 120 and 168 hours of treatment. RESULTS: A total of 261 patients with cirrhosis who developed SBP were enrolled. Most of the patients were diagnosed as those with SBP within 48 hours of admission. The resolution rates at 120 hours, which is the primary endpoint, were 67.8%, 77.0%, and 73.6% in the cefotaxime, ceftriaxone, and ciprofloxacin groups, respectively ( P = 0.388), by intension-to-treat analysis. The 1-month mortality was similar among the groups ( P = 0.770). The model for end-stage liver disease score and the SBP resolution were significant factors for survival. CONCLUSION: The efficacy of empirical antibiotics, such as cefotaxime, ceftriaxone, and ciprofloxacin, against SBP was not significantly different. In addition, these antibiotics administered based on response-guided therapy were still efficacious as initial treatment for SBP, especially in those with community-acquired infections.

Water quality trend and pollutant load and source analysis of Tamjin River water system.

To systematically manage water quality based on watersheds, it is necessary to understand the characteristics of changes in river water quality. This study used observational data of the Tamjin River water system to analyze changes in water quality due to farming activities during the farming period. Water quality trends were analyzed through a long-term trend analysis. Furthermore, the loads and sources of substances regulated under the total maximum daily load system were evaluated. Biochemical oxygen demand and total phosphorous, water quality factors of the target basin, showed recent increasing trends. Loads increased from April, which corresponded to the non-farming period before farming activities began, and characteristics of pollutant discharged in the basin from farming activities were observed. Pollutant sources were different from those observed in water systems with a high proportion of farming activities, and water quality management measures considering the target basin's characteristics were proposed. The results of this study will serve as logical baseline data for establishing water quality management plans.

Long-term Outcomes of Antiviral Therapy in Patients With Advanced Chronic HBV Infection.

Hepatitis B virus (HBV) suppression with nucleot(s)ide analogue therapy reduces the risk of hepatic decompensation and hepatocellular carcinoma (HCC) in patients with advanced liver disease.1 In the present era of potent antiviral therapies, the prognostic significance of the serum HBV DNA level as a biological gradient has substantially diminished; the majority of treated patients achieve virologic suppression.2,3 After control of viremia, a higher baseline fibrosis level is a useful predictor for disease progression.4 Few "prospective" studies on the effects of antiviral agents, especially in chronic hepatitis B (CHB) patients with advanced liver disease, have been reported.

Long-Term Efficacy and Safety of Partial Splenic Embolization in Hepatocellular Carcinoma Patients with Thrombocytopenia Who Underwent Transarterial Chemoembolization.

BACKGROUND: Performing transarterial chemoembolization (TACE) is difficult with the occurrence of thrombocytopenia in cirrhotic patients with hepatocellular carcinoma (HCC). We aimed to evaluate the long-term efficacy and safety of partial splenic embolization (PSE) combined with TACE in patients with HCC with severe thrombocytopenia related to splenomegaly. METHODS: We conducted a case-control study consisting of 18 HCC patients with severe thrombocytopenia (< 50 × 109/L) who underwent PSE concurrently with TACE (PSE group) and 72 controls who underwent TACE alone (non-PSE group). RESULTS: Mean platelet counts at 1 month and 1, 3, and 5 years after concurrent PSE and TACE significantly increased compared with baseline (all P < 0.05), whereas the platelet count did not significantly increase after TACE alone. In addition, the platelet count at several time points after treatment in the PSE group was significantly higher than that in the non-PSE group, although the baseline platelet count in the PSE group was significantly lower than that in the non-PSE group. The platelet increase after PSE significantly reduced the need for platelet transfusions (P = 0.040) and enabled the subsequent TACE procedures in time (P = 0.046). The leukocyte counts and hemoglobin concentrations after concurrent PSE and TACE were also significantly increased, without deterioration of Child-Turcotte-Pugh score and unexpected side effects. CONCLUSION: PSE combined with TACE is effective in inducing and maintaining long-term thrombocytopenia improvement which reduces the need for the platelet transfusion and helps to perform initial and serial TACE, and is well-tolerated in patients with HCC and thrombocytopenia. PSE may be a promising treatment option for HCC patients with severe thrombocytopenia associated with splenomegaly who will undergo TACE.

Daily Norfloxacin vs. Weekly Ciprofloxacin to Prevent Spontaneous Bacterial Peritonitis: A Randomized Controlled Trial.

OBJECTIVES: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP. METHODS: This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm3. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP. RESULTS: One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function. CONCLUSION: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites.

Association between cotinine-verified smoking status and risk of nonalcoholic fatty liver disease.

BACKGROUND & AIMS: The relationship between cigarette smoking and nonalcoholic fatty liver disease (NAFLD) has been controversial. Most relevant studies have relied on self-reported questionnaires. We aimed to elucidate the association between smoking status and NAFLD using an objective biomarker of tobacco exposure (urinary cotinine) and self-reported questionnaire. METHODS: A cross-sectional study was conducted on 160 862 asymptomatic examinees who underwent abdominal ultrasonography and urinary cotinine measurements between April 2011 and December 2015. Cotinine-verified current smokers were defined as participants with urinary cotinine levels ≥50 ng/mL. RESULTS: The mean age of the study population was 36.1 years, and the proportion of men was 51.7%. The proportions of self-reported and cotinine-verified current smokers were 17.6% and 17.7% respectively. After adjusting for confounding factors, self-reported current smoking was associated with an increased risk of NAFLD (adjusted odds ratio [AOR], 1.10; 95% confidence interval [CI], 1.06-1.14). Moreover, among the current smokers, the risk of NAFLD increased with an increase in the amount of cigarette smoking (<10 and ≥10 pack-years vs never smokers; AOR, 1.04 and 1.11; 95% CI, 1.01-1.08 and 1.05-1.16 respectively). Cotinine-verified current smoking was also associated with an increased risk of NAFLD (AOR, 1.10; 95% CI, 1.06-1.14). CONCLUSIONS: Cotinine-verified current smoking and self-reported current smoking were independent risk factors for NAFLD. Further longitudinal studies are needed to more clearly elucidate the impact of smoking on the development of NAFLD.

Impact of clinically evident portal hypertension on clinical outcome of patients with hepatocellular carcinoma treated by transarterial chemoembolization.

BACKGROUND AND AIM: The aim of this study is to determine the impact of clinically evident portal hypertension (CEPH) on prognosis of hepatocellular carcinoma (HCC) patients with Child-Pugh A cirrhosis who underwent transarterial chemoembolization (TACE). METHODS: A retrospective data analysis was performed for a total of 388 treatment-naïve HCC patients with Child-Pugh A cirrhosis who underwent TACE as first-line treatment from January 2000 to June 2014. Cumulative occurrence rate of complete response (CR), progression-free survival (PFS), and overall survival (OS) were compared between patients with CEPH and those without CEPH (esophageal/gastric varices or low platelet count [< 100 000 per mm3 ] associated with splenomegaly). RESULTS: Among 388 patients, 252 (64.9%) had CEPH, while 136 (35.1%) had no evidence of CEPH at the time of HCC diagnosis. Cumulative probability of the occurrence of CR was significantly lower in patients with CEPH than that in patients without CEPH (P < 0.001). Median PFS was significantly shorter in patients with CEPH than that in patients without CEPH (5 vs 31 months, P < 0.001). Five-year OS rate was significantly lower in patients with CEPH than that in patients without CEPH (41.5% vs 77.5%, P < 0.001). Multivariate analysis indicated that the presence of CEPH was the most powerful poor prognostic factor for the occurrence of CR (adjusted hazard ratio [aHR], 0.16; 95% confidence interval [CI], 0.09-0.28; P < 0.001), PFS (aHR, 5.01; 95% CI, 3.08-8.12; P < 0.001), and OS (aHR, 2.95; 95% CI, 1.66-5.23; P < 0.001). CONCLUSIONS: The presence of CEPH should be considered as a major negative prognostic factor for patients with HCC who will undergo TACE.

Effect of Metabolic Syndrome on the Clinical Outcomes of Chronic Hepatitis B Patients with Nucleos(t)ide Analogues Treatment.

BACKGROUND: No data are available about the effect of MS on oral nucleos(t)ide analogues (NUCs) treatment and clinical outcomes in chronic hepatitis B (CHB) patients. AIMS: We aimed to elucidate whether coexistence of MS and CHB affects the long-term prognosis of CHB patients with oral NUCs treatment. METHODS: We performed a retrospective data analysis for a total of 587 CHB patients who started oral NUCs treatment for the first time in our institution from January 2006 to March 2016. RESULTS: Among the 587 patients, 70 (11.9%) had MS, but 517 (88.1%) had no evidence of MS when oral NUCs treatment was initiated. Cumulative occurrence rates of viral breakthrough, genotypic resistance, HCC, disease progression (PD), and overall adverse outcomes (OAO) were significantly higher in CHB patients with MS than in those without MS, although HBV-DNA suppression and cumulative occurrence rates of HBeAg negative conversion and seroconversion were not significantly different between the two groups. The overall survival (OS) was also significantly shorter in CHB patients with MS than in those without MS. Multivariate analysis indicated that the MS was an independent, poor prognostic factor for occurrence of genotypic resistance (adjusted hazard ratio [aHR], 22.3; 95% confidence interval [CI] 6.61-75.02; P < 0.001), HCC (aHR, 3.98; 95% CI 2.07-7.66; P < 0.001), PD (aHR, 6.18; 95% CI 3.43-11.14; P < 0.001), OAO (aHR, 8.10; 95% CI 4.68-14.02; P < 0.001), and OS (aHR, 12.29; 95% CI 2.25-67.24; P < 0.001). CONCLUSIONS: MS is an independent determinant of poor prognosis in CHB patients receiving oral NUCs treatment.

Natural courses of branch duct intraductal papillary mucinous neoplasm.

PURPOSE: The study was done to elucidate the clinico-radiologic predictive factors for cancerous change detected by disease progression (PD) mainly defined by interval increase in cyst size and change of cyst morphology, for branch duct intraductal papillary mucinous neoplasm (BD-IPMN) patients with relatively long-term follow-up. METHODS: Retrospective analysis of medical records and imaging findings were performed on 107 patients with BD-IPMN enrolled from July 2005 to May 2013, in whom the communication between the cystic lesion and pancreatic duct was confirmed by either endoscopic ultrasonography (EUS), magnetic resonance cholangiopancreatography (MRCP), or endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: During the mean ± SD follow-up period of 51.5 ± 24.5 months, PD was noticed in 43 (40.2%) of 107 BD-IPMN patients. Among these 107 patients, 21 (19.6%) displayed cancerous change. By univariate analyses, septated/multilocular cyst morphology, cyst size larger than 30 mm, cyst wall thickening, mural nodules, and the presence of symptoms were significant predictive factors for cancerous changes in BD-IPMN patients. A Cox forward stepwise linear regression model revealed that cyst wall thickening (OR 9.187, 95% CI 1.883~44.820, P < 0.01) and mural nodules (OR 6.224, 95% CI 1.311~29.549, P = 0.021) were significant and independent predictive factors for cancerous change in BD-IPMN patients. CONCLUSIONS: A significant proportion of patients with BD-IPMN showed PD and cancerous change during the long-term follow-up. Cyst wall thickening and mural nodules were significant and independent predictive factors of cancerous change in patients with BD-IPMN.

Increased Risk of Advanced Colorectal Neoplasia Among Korean Men With Metabolic Abnormality and Obesity.

BACKGROUND & AIMS: Obesity and metabolic abnormality are risk factors for colorectal cancer and adenoma. We evaluated the risk of advanced colorectal neoplasm (AN) according to metabolic status and obesity in Koreans. METHODS: We performed a retrospective cross-sectional study of 70,428 individuals in Korea who underwent colonoscopy and whose metabolic state and body mass index were examined, from 2003 through 2012, at Kangbuk Samsung Hospital in Korea. We calculated odds ratios (ORs) for AN in people who were metabolically healthy but obese, people with metabolic abnormality who were not obese, and people with metabolic abnormality who were obese. The reference group was metabolically healthy nonobese peoples. AN was defined as adenoma ≥10 mm in diameter, adenoma with any component of villous histology, high-grade dysplasia, or invasive cancer. RESULTS: No increased risk of AN was observed in the metabolically healthy but obese (OR, 0.99; 95% confidence interval [CI], 0.67-1.46; P = .825) and metabolic abnormality who were not obese groups (OR, 1.01; 95% CI, 0.85-1.21; P = .765). In contrast, risk of AN was increased in the metabolic abnormality who were obese group (OR, 1.33; 95% CI, 1.12-1.58; P = .006). In men, risk of AN showed a greater increase in the metabolic abnormality who were obese group (OR, 1.48; 95% CI, 1.20-1.83; P = .001). This association was not observed in women (OR, 1.21; 95% CI, 0.84-1.75; P = .476). CONCLUSIONS: Men with 1 or more metabolic abnormality and obesity are at increased risk for AN.

Endosonographer's macroscopic evaluation of EUS-FNAB specimens after interactive cytopathologic training: a single-center prospective validation cohort study.

BACKGROUND: In many centers, rapid on-site evaluation (ROSE) for the specimens obtained from endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) is not available. The aim of this study was to compare the diagnostic yields of EUS-FNAB in the presence or absence of ROSE. METHODS: Seventy-five patients who underwent EUS-FNAB for the pancreatic, gastric subepithelial, and mesenteric mass lesions at our institution from November 2013 to August 2014 were included. For 20 patients in the pilot cohort, EUS-FNAB was performed with ROSE, and simultaneously, training of the staff endosonographer for tissue adequacy by an on-site cytopathologist was also performed. RESULTS: The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EUS-FNAB in the pilot cohort were 91.7, 100.0, 100.0, 88.9, and 95.0 %, respectively. The 3.2 ± 0.8 [mean ± standard deviation (SD)] needle passes were needed in this cohort. Fifty-five patients were enrolled as a validation cohort from April 2014 to August 2014, and tissue adequacies were assessed by an experienced endosonographer without ROSE in this cohort. The sensitivity, specificity, PPV, NPV, and accuracy of EUS-FNAB in this validation cohort were 92.1, 100.0, 100.0, 85.0, and 94.6 %, respectively. The 4.5 ± 0.6 (mean ± SD) needle passes were needed in this cohort (p < 0.01 compared to pilot cohort). CONCLUSIONS: Diagnostic accuracy of EUS-FNAB in which the adequacy of sample was assessed by an attending endosonographer was acceptable. This study suggests that on-site evaluation by a trained endosonographer may be an alternative tool to ROSE where ROSE is not available.

The combination of transcatheter arterial chemoembolization and sorafenib is well tolerated and effective in Asian patients with hepatocellular carcinoma: final results of the START trial.

This phase II, investigator-initiated, prospective single-arm multinational study (ClinicalTrials.gov registration NCT00990860) evaluated sorafenib in combination with doxorubicin-based transarterial chemoembolization (TACE) in patients with intermediate-stage, unresectable hepatocellular carcinoma (HCC). Patients with histologically or clinically diagnosed HCC received TACE with interrupted dosing of sorafenib (sorafenib discontinued for 3 days before and 4-7 days after TACE). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary and secondary objectives were, respectively: to evaluate the safety and tolerability of TACE combined with sorafenib, and also their efficacy. The full analysis set comprised 192 patients (mean age 56.1 years). Most were male (87.0%), Eastern Cooperative Oncology Group (ECOG) score 0 (81.8%), Child-Pugh A (91.8%) and Barcelona Clinic Liver Cancer (BCLC) stage B (81.5%); 81.2% had chronic hepatitis B. Combined TACE/sorafenib was well tolerated, with only 8.1% of patients discontinuing owing to adverse events (AEs). The most common grade ≥3 AEs were palmar-plantar erythrodysesthesia syndrome (15.1%) and decreased platelet count (10.9%). Serious AEs (SAEs) occurred in 52 patients during the study; however, only four were considered related to sorafenib. A mean of 2.7 TACE cycles were administered and 52.6% of patients achieved complete response in target lesions; 16.8% achieved partial response, and 5.8% had progression of disease as their best response, evaluated by modified RECIST. Median progression-free survival and time to progression were 384 and 415 days, respectively, and the estimated 3-year overall survival was 86.1%. This study suggests that the combination of TACE and sorafenib is well tolerated and efficacious; the interrupted sorafenib dosing schedule may have contributed to a considerably lower AE profile than observed in other combination trials.

γ-Glutamyl Transferase Is Associated with Mortality Outcomes Independently of Fatty Liver.

BACKGROUND: High serum enzyme activity levels of γ-glutamyl transferase (GGT) are associated with increased risk of mortality, but whether this is mediated by fatty liver, as a common cause of high GGT levels, is uncertain. Our aim was to test whether GGT levels are associated with all-cause, cancer, and cardiovascular (CVD) mortality, independently of fatty liver. METHODS: In an occupational cohort (n = 278 419), causes of death (International Statistical Classification of Diseases and Related Health Problems, 10th revision) were recorded over 7 years. Liver function tests and liver fat [measured by ultrasonographic standard criteria or fatty liver index (FLI)] were assessed at baseline. We used Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% CIs of all-cause, cancer, and CVD mortality for GGT quartiles (with lowest GGT quartile as reference). RESULTS: There were 136, 167, 265, and 342 deaths across increasing GGT quartiles. After adjusting for liver fat (by ultrasound diagnosis) in the fully adjusted model, all-cause and cancer mortality were increased in the highest GGT quartile [HR 1.50 (95% CI 1.15-1.96) and 1.57 (1.05-2.35), respectively]. For CVD mortality, the hazard was attenuated: HR 1.35 (95% CI 0.72-2.56). After adjusting for FLI in the fully adjusted model, HRs for all-cause, cancer, and CVD mortality were 1.46 (0.72-2.56), 2.03 (1.02-4.03), and 1.16 (0.41,3.24), respectively. CONCLUSIONS: There were similar hazards for all-cause and cancer mortality and attenuated hazards for CVD mortality for people in the highest GGT quartile, adjusting for fatty liver assessed by either ultrasound or FLI.

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.

Risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years.

BACKGROUND: Very little is known about risk factors associated with colorectal neoplasia in persons aged <50 years. In particular, there has been no study thus far focusing on the risk factors for colorectal neoplasia in persons aged 30 to 39 years. OBJECTIVE: To investigate risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years and to compare those data with those of persons aged 50 to 59 years. DESIGN: Cross-sectional observational study. SETTING: Screening center in a university hospital in Korea. PATIENTS: A cohort of 28,504 Korean adults (13,678 aged 30-39 years, 12,507 aged 40-49 years, and 2319 aged 50-59 years) who underwent colonoscopy as part of their routine preventive health care. INTERVENTIONS: Colonoscopy. MAIN OUTCOME MEASUREMENTS: Risk factors for colorectal neoplasia in persons aged 30 to 39 years and 40 to 49 years. RESULTS: In the 30-to-39-years group, male sex, smoking, fatty liver, metabolic syndrome (MetS), obesity, elevated fasting blood glucose levels, and elevated triglyceride levels were associated with overall neoplasia, whereas for advanced neoplasia, the independent risk factors were smoking, fatty liver, and elevated triglyceride levels. Moreover, the prevalence of overall neoplasia in men aged 30 to 39 years exhibiting all risk factors was not lower than that in average-risk women aged >50 years (20.8% vs 18.8%; P = .546). The risk factors of overall neoplasia in the 40-to-49-years group were similar to those in the 30-to-39-years group. For advanced neoplasia, the independent risk factors in the 40-to-49-years group were male sex, smoking, MetS, and obesity. LIMITATIONS: Selection bias may exist for participants of ethnic Korean heritage in 2 centers. CONCLUSION: Obese male smokers with fatty liver and MetS might benefit from screening colonoscopy starting before age 50 years.

Associations Between Parameters of Glucose and Lipid Metabolism and Risk of Colorectal Neoplasm.

BACKGROUND: Diabetes and dyslipidemia have been linked to an increased risk of colorectal neoplasm (CRN). However, previous studies evaluating these associations have shown inconsistent results, and large-scale studies are few in number. AIM: To investigate the associations between the parameters of glucose and lipid metabolism and the presence of CRN. METHODS: A cross-sectional study was performed on 38,490 Korean adults aged ≥30 years undergoing their first colonoscopy as part of routine preventive health care between 2010 and 2011. RESULTS: The prevalence of overall CRN increased with increasing levels of glucose, hemoglobin A1c (HbA1c), insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (ApoB) and with decreasing level of apolipoprotein A1 (ApoA1). The adjusted prevalence ratios for overall CRN comparing the fourth with the first quartiles of fasting glucose, HbA1c, insulin, HOMA-IR, triglycerides, total cholesterol, LDL-C, ApoB, and ApoA-1 were 1.83 (95% CI 1.62-2.06), 1.17 (95% CI 1.03-1.33), 1.09 (95% CI 0.97-1.23), 1.22 (95% CI 1.08-1.37), 1.31 (95% CI 1.16-1.48), 1.19 (95 % CI 1.07-1.33), 1.38 (95% CI 1.23-1.54), 1.30 (95% CI 1.14-1.47), and 0.85 (95% CI 0.76-0.95), respectively. There was also a significant association between higher levels of glucose, LDL-C, and ApoB with a higher prevalence of advanced CRN. Moreover, the risk of CRN increased further in cases in which the parameters of glucose metabolism and lipid metabolism worsened simultaneously. CONCLUSIONS: The levels of parameters of glucose and lipid metabolism are significantly associated with the prevalence of CRN. Altered glucose and lipid metabolism may contribute to the development of CRN.

Radiologic response to transcatheter hepatic arterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: The current study analysed the association between radiologic tumour response and survival times of patients with hepatocellular carcinoma (HCC) who were treated with transcatheter hepatic arterial chemoembolization (TACE). METHODS: Among 493 consecutive patients presenting to our institution between July 2002 and June 2010 with radiologically (n = 398) or histologically (n = 95) confirmed HCC, 368 patients who met inclusion criteria, underwent TACE and had confirmed survival data were retrospectively reviewed. The radiologic response was assessed using RECIST 1.1, EASL and mRECIST criteria at 1 month after the initial TACE. RESULTS: By univariate analysis, higher Child-Turcotte-Pugh (CTP) score, bilobar and multifocal distribution of tumours, larger tumour size (>5 cm), higher serum alpha-foetoprotein (AFP) level (>200 ng/ml), no subsequent radiofrequency ablation, advanced ECOG, UNOS and BCLC staging, absence of complete necrosis and non-responder (SD or PD) in RECIST 1.1, EASL and mRECIST response assessment were significantly associated with shorter overall survival times. By Cox proportional hazards model, advanced age, presence of ascites, higher MELD score, advanced BCLC staging, absence of complete necrosis and non-responder by RECIST 1.1, EASL and mRECIST criteria were independent and significant prognosticators for overall survival times in patients with HCC who underwent TACE. By time-dependent ROC curve analysis, mRECIST response criteria showed greatest accuracy in predicting survival (AUROC = 0.8676), followed by EASL (AUROC = 0.8471) and RECIST 1.1 (AUROC = 0.7986). CONCLUSION: mRECIST and EASL criteria for assessing radiologic response 1 month after initial TACE more consistently predict the differences in overall survival between responders and non-responders than conventional RECIST 1.1 criteria.

Comparison of brush and basket cytology in differential diagnosis of bile duct stricture at endoscopic retrograde cholangiopancreatography.

BACKGROUND: A previous report has identified a significantly higher sensitivity of cancer detection for dedicated grasping basket than brushing at endoscopic retrograde cholangiopancreatography (ERCP). This study aimed to compare the diagnostic accuracy of Geenen brush and Dormia basket cytology in the differential diagnosis of bile duct stricture. METHOD: The current study enrolled one hundred and fourteen patients who underwent ERCP with both Geenen brush and Dormia basket cytology for the differential diagnosis of bile duct stricture at our institution between January 2008 and December 2012. RESULTS: We adopted sequential performances of cytologic samplings by using initial Geenen brush and subsequent Dormia basket cytology in 59 patients and initial Dormia basket and subsequent Geenen brush cytology in 55 patients. Presampling balloon dilatations and biliary stentings for the stricture were performed in 17 (14.9%) and 107 patients (93.9%), respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of Geenen brush cytology for the diagnosis of malignant bile duct stricture were 75.0%, 100.0%, 100.0%, 66.7% and 83.3%, respectively, and those of Dormia basket cytology were 64.5%, 100.0%, 100.0%, 58.5% and 76.3%, respectively (P=0.347 and 0.827 for sensitivity and accuracy, respectively). The good and excellent cellular yields (≥grade 2) were obtained by Geenen brush and Dormia basket cytology in 88 (77.2%) and 79 (69.3%) patients, respectively. CONCLUSION: The sensitivity, specificity and accuracy of biliary sampling with a Dormia basket are comparable to those with conventional Geenen brush cytology in the detection of malignant bile duct stricture.

Interim analysis of START: Study in Asia of the combination of TACE (transcatheter arterial chemoembolization) with sorafenib in patients with hepatocellular carcinoma trial.

Transarterial chemoembolization (TACE) represents a first-line noncurative therapy for hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, has been shown to be effective and safe monotherapy in patients with advanced HCC and the current study reports the interim results of a prospective Phase II, open label, trial investigating the safety and efficacy of the combination of sorafenib and conventional TACE in patients from the Asia-Pacific region with intermediate HCC. Patients with histologically or clinically diagnosed HCC were treated with conventional TACE followed by sorafenib 4 to 7 days later. TACE was performed by selective transarterial chemotherapy in the vessels feeding the tumor with an emulsion of lipiodol (5-20 ml) and doxorubicin (30-60 mg) followed by embolization with absorbable particles (gel foam). TACE/sorafenib cycles were repeated every 6-8 weeks. Primary objectives were to evaluate the safety and tolerability, in addition to the efficacy of TACE combined with sorafenib for HCC. A total of 147 patients were included in the intention-to-treat analysis and received at least one dose of sorafenib. Gastrointestinal AEs were reported by 62.6% of patients while 57.8% reported skin AEs although most were mild to moderate. The mean number of cycles undertaken was 2.1 and 63.3% of patients achieved either partial response or stable disease. Clinically, the disease control rate was 91.2% while the overall response rate was calculated as 52.4%. Our study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects.

Genetic predisposition of hand-foot skin reaction after sorafenib therapy in patients with hepatocellular carcinoma.

BACKGROUND: Sorafenib currently sets the new standard for advanced hepatocellular carcinoma (HCC). It has been suggested that Asian patients with HCC have increased susceptibility to hand-foot skin reaction (HFSR) related to sorafenib therapy. The authors investigated the association between sorafenib-induced HFSR and genetic polymorphisms in Korean patients with HCC. METHODS: For this prospective cohort study, the authors enrolled 59 consecutive patients with intermediate stage HCC from 5 centers in Korea. All patients received sorafenib 400 mg twice daily in combination with transarterial chemoembolization (TACE). Genotyping was performed on a total of 49 single nucleotide polymorphisms (SNPs) in 8 candidate genes (minor allelic frequency ≥5%). Serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays before therapy and 1 month after therapy. RESULTS: During a median treatment period of 18 months, 55 patients (93%) developed sorafenib-induced HFSR, including grade 1 reactions in 15 patients, grade 2 reactions in 27 patients, and grade 3 reaction in 13 patients. The SNPs TNF-α -308GG, VEGF -94GG, VEGF 1991CC, VEGF IVS3-28CC, and uridine diphosphate glucuronosyltransferase 1 family-polypeptide A9 (UGT1A9) IVS1-37431AA were associated significantly with the development of high-grade (grade 2 or 3) HFSR in univariate analysis (P < .05). In multivariate analysis, the SNPs VEGF 1991CC (odds ratio, 45.7), TNF-α -308GG (odds ratio, 44.1), and UGT1A9 IVS1-37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high-grade HFSR (P = .01, P = .02, and P = .02, respectively). He serum TNF-α level measured 1 month after sorafenib therapy was correlated significantly with the development of high-grade HFSR (odds ratio, 3.56; P = .026). CONCLUSIONS: Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the TNF-α, VEGF, and UGT1A9 genes, especially in relation to the expression of serum TNF-α after sorafenib therapy.