INTRODUCTIONThis study aims to assess the early tumour outcome and morbidity associated with radiation therapy (RT) in tumours of the central nervous system (CNS).

MATERIALS AND METHODSPatients receiving RT with radical intent were entered on a prospective database. Tumour types were categorised into glioma, base of skull, pituitary, germ cell or primitive neuroectodermal tumour (PNET) and other malignant CNS tumours. Study endpoints were overall survival and progression free survival. Acute and late toxicity endpoints included Common Terminology Criteria version 3.0 (CTC) grade 3 or 4 events, need for admission during RT and change in performance status at 12 months.

RESULTSOne hundred and fifty-two patients with CNS tumours were managed with radical intent over the 4-year period. The median age was 49 years and 68.4% were Eastern Co-operative Group (ECOG) 0-1 performance status. The major pathology groups were glioma (59.9%) and base of skull tumours (17.1%). Gross total resection was performed in 28.3% only and RT was delayed after diagnosis until time of progression in 19.7%. For the 91 patients with glioma, the median survival and 2-year survival rate was 19.1 months and 44.1%, respectively. The 2-year survival rates for the subgroups of WHO Grade I or II, III and IV were 100%, 52% and 35%, respectively. For the non-glioma tumour groups, the relapse varied with pathology. Toxicity was minimal with only 3 acute and 3 late CTC grade 3 or 4 events occurring. Overall, 47 or 31% of patients required some inpatient hospitalisation during RT, although this was determined to have some causative relationship to RT in only 12 or 8% of patients. In the 12 months post-RT, performance status was stable or improved in 76.2% of patients, and most deterioration was associated with tumour relapse.

CONCLUSIONSRT for CNS tumours using modern techniques was well-tolerated with good tumour outcome and minimal morbidity.

Adolescent ; Adult ; Aged ; Central Nervous System ; physiopathology ; Central Nervous System Neoplasms ; radiotherapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Radiotherapy ; methods ; standards ; Singapore ; Survival Analysis

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC).METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups.RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI.CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.
Acute Kidney Injury ; Azotemia ; Creatinine ; Diagnosis ; Diagnosis, Differential ; Hand ; Hepatorenal Syndrome ; Hospital Mortality ; Humans ; Kidney Tubular Necrosis, Acute ; Lipocalins ; Liver Cirrhosis ; Liver Diseases ; Liver ; Necrosis ; Neutrophils ; Prospective Studies

BACKGROUND/AIMS: A diagnosis of hepatorenal syndrome (HRS) is based on a differential evaluation of acute kidney injury (AKI), which may aggravate the clinical course. This study assessed the clinical significance of the urinary neutrophil gelatinase-associated lipocalin (u-NGAL) levels in a differential diagnosis of AKI in patients with liver cirrhosis (LC). METHODS: Patients with LC who developed AKI were enrolled prospectively. Clinically, patients with AKI were classified into prerenal azotemia (PRA), HRS, and acute tubular necrosis (ATN) groups. RESULTS: Fifty-five patients (male, 74.5%) with LC who exhibited AKI upon admission were enrolled; 28, 9, and 18 patients were included in the PRA, HRS, and ATN groups, respectively. The baseline model for end-stage liver disease (MELD) scores was similar in the subgroups. The median event creatinine level, measured at the time of the AKI diagnosis, was similar in the HRS and ATN subgroups. On the other hand, the median event u-NGAL level differed significantly between the three subgroups (PRA, HRS, and ATN: 37 vs. 134 vs. 2,625 ng/mL, p=0.003). In particular, the median u-NGAL level of the HRS group was clearly different from those of the PRA (p<0.001) and ATN (p<0.001) groups. Multivariable analysis revealed the natural logarithm of the u-NGAL level (hazard ratio [HR] 1.77, p=0.031) and the MELD score (HR 1.17, p=0.027) to be independent prognostic factors for in-hospital mortality in patients with LC and AKI. CONCLUSIONS: The median u-NGAL level differentiated HRS from ATN and served as a clinical indicator of in-hospital mortality for patients with LC and AKI.
Acute Kidney Injury ; Azotemia ; Creatinine ; Diagnosis ; Diagnosis, Differential ; Hand ; Hepatorenal Syndrome ; Hospital Mortality ; Humans ; Kidney Tubular Necrosis, Acute ; Lipocalins ; Liver Cirrhosis ; Liver Diseases ; Liver ; Necrosis ; Neutrophils ; Prospective Studies

Clinical practice guidelines are important for guiding the management of specific diseases by medical practitioners, trainees, and nurses. In some cases, the guidelines are utilized as a reference for health policymakers in controlling diseases with a large public impact. With this in mind, practice guidelines for the management of chronic hepatitis B (CHB) have been developed in the United States, Europe, and Asian-Pacific regions to suggest the best-fit recommendations for each social and medical circumstance. Recently, the Korean Association for the Study of the Liver published a revised version of its clinical practice guidelines for the management of CHB. The guidelines included updated information based on newly available antiviral agents, the most recent opinion on the initiation and cessation of treatment, and updates for the management of drug resistance, partial virological response, and side effects. Additionally, CHB management in specific situations was comprehensively revised. This review compares the similarities and differences among the various practice guidelines to identify unmet needs and improve future recommendations.

Heterogeneous features of liver cancer can mimic liver abscess. Therefore it is essential to double-check tumor markers in the diagnosis of liver abscess. Herein, we report a case of combined hepatocellular-cholangiocarcinoma (cHC) occurred in an unrecognized chronic hepatitis B patient initially misdiagnosed as liver abscess. A 49-year old male initially presented with chill, right upper quadrant pain, and a liver mass. Mass showed peripheral enhancement in arterial phase of computed tomography, which was not typical for hepatocellular carcinoma (HCC). Strikingly elevated alpha-fetoprotein and fine needle aspirated pathology revealed HCC. Despite discordant image findings he was treated with transarterial chemoembolization. He was treated with sorafenib due to metastatic retrocaval lymphadenopathy afterwards. The mass presumed to be HCC progressed with sorafenib. It was surgically resected and he was finally confirmed as cHC. Discordant tumor markers with presumptive image findings should prompt the suspicion of rare type of primary liver cancer, the cHC.
alpha-Fetoproteins ; Biomarkers, Tumor ; Carcinoma, Hepatocellular ; Diagnosis ; Hepatitis B, Chronic ; Humans ; Liver ; Liver Abscess ; Liver Abscess, Pyogenic* ; Liver Neoplasms ; Lymphatic Diseases ; Male ; Needles ; Pathology

Background/Aims: A comprehensive analysis of trends in the incidence of hepatocellular carcinoma (HCC) is important for planning public health initiatives. We aimed to analyze the trends in HCC incidence in South Korea over 10 years and to predict the incidence for the year 2028. Methods: Data from patients with newly diagnosed HCC between 2008 and 2018 were obtained from Korean National Health Insurance Service database. Age-standardized incidence rates (ASRs) were calculated to compare HCC incidence. A poisson regression model was used to predict the future incidence of HCC. Results: The average crude incidence rate (CR) was 22.4 per 100,000 person-years, and the average ASR was 17.6 per 100,000 person-years between 2008 and 2018. The CR (from 23.9 to 21.2 per 100,000 person-years) and ASR (from 21.9 to 14.3 per 100,000 person-years) of HCC incidence decreased during the past ten years in all age groups, except in the elderly. The ASR of patients aged ≥80 years increased significantly (from 70.0 to 160.2/100,000 person-years; average annual percent change, +9.00%; P<0.001). The estimated CR (17.9 per 100,000 person-years) and ASR (9.7 per 100,000 person-years) of HCC incidence in 2028 was declined, but the number of HCC patients aged ≥80 years in 2028 will be quadruple greater than the number of HCC patients in 2008 (from 521 to 2,055), comprising 21.3% of all HCC patients in 2028. Conclusions The ASRs of HCC in Korea have gradually declined over the past 10 years, but the number, CR, and ASR are increasing in patients aged ≥80 years.

Background/Aims: We aimed to define an optimal target population and drug-specific biomarkers that may predict dipeptidyl peptidase (DPP)-4 inhibitor responses in non-alcoholic fatty liver disease (NAFLD). Methods: An exploration study (study I) was performed using three different NAFLD models (basket study design; high-fat diet [HFD], methionine choline-deficient diet [MCD], and high-cholesterol Western diet [WD] models). RNA transcriptome analysis was performed on pre-studied liver tissues to identify biomarkers that could predict the response to DPP-4 inhibitors. In the validation study (study II), the HFD-induced NAFLD model was divided into high and low hepatic insulin-like growth factor binding protein 1 (Igfbp-1) groups based on the pre-study liver biopsy. Results: DPP-4 inhibitor attenuated the NAFLD activity score and fibrosis stage in the HFD model but not in the WD and MCD models. The overall response rate was 19% across the modified basket NAFLD trial and 42%, 25%, and 0% in the HFD, WD, and MCD models. Hepatic Igfbp-1 expression was higher in the responder group than in the non-responder group in pre-study biopsy samples. In contrast, hepatic Igfbp-1 expression was lower in the responder group than in the non-responder group in the end-study biopsy samples. DPP-4 inhibitor response rates were 83% and 17% in the baseline hepatic high Igfbp-1 and low Igfbp-1 groups, respectively. Hepatic messenger RNA Igfbp-1 expression was positively correlated with serum IGFBP-1 levels. Conclusions The DPP-4 inhibitor response was higher in the HFD phenotype and pre-treatment levels of hepatic or serum IGFBP-1 were high.

BACKGROUND/AIMS: Recent studies have shown that serum interferon gamma-inducible protein-10 (IP-10) concentration decreased after pegylated interferon and ribavirin therapy, and was associated with a sustained virologic response (SVR). The aim of this study was to investigate the clinical significance of the pretreatment IP-10 level and change in serum IP-10 level between 1 month before and after treatment and its association with various virologic responses in patients having chronic hepatitis C (CHC) with genotype 1 undergoing pegylated interferon and ribavirin therapy. METHODS: Thirty-six patients having CHC with genotype I undergoing pegylated interferon and ribavirin therapy who had available stored sera 1 month before and after treatment were enrolled retrospectively. Serum IP-10 levels were measured by ELISA. Serum HCV RNA was measured by RT-PCR (detection limit<50 IU/mL). RESULTS: The mean age of patients (n=36; 21 men) was 53.5 years, and the mean of pretreatment HCV RNA levels was 5.7 log10 IU/mL. The serum IP-10 level at 1 month after treatment significantly decreased from 432.2 to 306.5 pg/mL (p=0.033). The rate of rapid virologic response (RVR), early virologic response (EVR), end-of-treatment response (ETR), and SVR were 58%, 83%, 74%, and 57%, respectively. No significant difference in pretreatment IP-10 levels was observed between the patients with (RVR, EVR, ETR, and SVR) and without various virologic responses (p>0.05). The change in serum IP-10 between 1 month before and after treatment had no clinical meaning based on various virologic responses (p>0.05). CONCLUSIONS: The level of pretreatment IP-10 and change in IP-10 level between 1 month before and after treatment were not predictive factors of a SVR. Additional large-scale studies to determine the SVR-predicting role of serum IP-10 levels in patients with CHC are needed.
Enzyme-Linked Immunosorbent Assay ; Genotype ; Hepatitis C, Chronic ; Hepatitis, Chronic ; Humans ; Interferons ; Retrospective Studies ; Ribavirin ; RNA

BACKGROUND/AIMS: An association between past history of hepatitis B virus (HBV) infection and pancreatic cancer (PC) has recently been reported. We investigated whether HBV and hepatitis C virus (HCV) infections are associated with the development of PC in Korea. METHODS: We retrospectively recruited patients with PC and sex- and, age-matched control patients with stomach cancer (SC) during the previous 5 years. Serum HBsAg and anti-HCV were examined, and data on smoking, alcohol intake, diabetes, and the history of chronic pancreatitis (CP) were collected. RESULTS: A total of 506 PC and 1008 SC were enrolled, with respectively 58.1% and 97.3% of these cases being confirmed histologically. The mean age and sex ratio (male:female) were 63.5 years and 1.5:1 in the PC patients and 63.9 years and 1.5:1 in the SC patients respectively (P>0.05). The odds ratios (95% confidence interval, 95% CI) in univariate analysis were 0.90 (0.52-1.56; P=0.70) for HBsAg, 1.87 (0.87-4.01; P=0.11) for anti-HCV, 2.66 (2.04-3.48; P<0.001) for the presence of diabetes, 2.30 (1.83-2.90; P<0.001) for smoking, 1.14 (0.89-1.46; P=0.31) for alcohol intake, and 4.40 (1.66-11.66; P=0.003) for the history of CP. Independent risk factors for PC were presence of diabetes (OR, 2.67; 95% CI, 2.00-3.56; P<0.001), smoking (OR, 2.49; 95% CI, 1.93-3.21; P<0.001) and history of CP (OR, 4.60; 95% CI, 1.56-13.53; P=0.006). CONCLUSIONS: There was no significant association between seropositivity for HBsAg or anti-HCV and PC. Further studies are warranted to clarify the association between HBV infection and PC in regions where HBV is endemic.
Aged ; Case-Control Studies ; Data Interpretation, Statistical ; Female ; Hepatitis B/*complications/diagnosis ; Hepatitis C/complications/diagnosis ; Humans ; Incidence ; Male ; Middle Aged ; Odds Ratio ; Pancreatic Neoplasms/diagnosis/*epidemiology/etiology ; Retrospective Studies ; Risk Factors

Background/Aims: The pathophysiology of lean nonalcoholic fatty liver disease (NAFLD) is unclear but has been shown to be associated with more diverse pathogenic mechanisms than that of obese NAFLD. We investigated the characteristics of genetic or metabolic lean NAFLD in a health checkup cohort. Methods: This retrospective cross-sectional study analyzed single nucleotide polymorphism data for 6,939 health examinees. Lean individuals were categorized according to a body mass index cutoff of 23 kg/m 2 . Single nucleotide polymorphisms were analyzed using genotyping arrays. Results: The prevalence of lean NAFLD was 21.6% among all participants with NAFLD, and the proportion of lean NAFLD was 18.5% among lean participants. The prevalence of metabolic syndrome and diabetes among lean patients with NAFLD was 12.4% and 10.4%, respectively.Lean NAFLD appeared to be metabolic-associated in approximately 20.1% of patients. The homozygous minor allele (GG) of PNPLA3 (rs738409) and heterozygous minor alleles (CT, TT) of TM6SF2 (rs58542926) were associated with lean NAFLD. However, the prevalence of fatty liver was not associated with the genetic variants MBOAT7 (rs641738), HSD17B13 (rs72613567), MARC1 (rs2642438), or AGXT2 (rs2291702) in lean individuals. Lean NAFLD appeared to be associated with PNPLA3 or TM6SF2 genetic variation in approximately 32.1% of cases. Multivariate risk factor analysis showed that metabolic risk factors, genetic risk variants, and waist circumference were independent risk factors for lean NAFLD. Conclusions In a considerable number of patients, lean NAFLD did not appear to be associated with known genetic or metabolic risk factors. Further studies are required to investigate additional risk factors and gain a more comprehensive understanding of lean NAFLD.