Eaum Seok Lee

The Effects of Lifestyle Modification on Symptoms and Quality of Life in Patients with Irritable Bowel Syndrome: A Prospective Observational Study

Background/Aims Although notably common, irritable bowel syndrome (IBS) has no specific cure. Lifestyle modification may be as important as medication; however, few studies support the effectiveness of such modifications. We performed this observational study of IBS patients to explore further the role of lifestyle changes in treatment. Methods This study included 831 men who enlisted in 2010 as armed surgeon cadets and 85 women who concurrently entered the Armed Forces Nursing Academy. Of these 916 participants, 89 were diagnosed with IBS using the Rome III criteria. Subjective changes in bowel habits, quality of life, pain, stress, stool frequency and stool consistency were surveyed before and after 9 weeks of army training. We evaluated the lifestyle risk factors that impacted improvement in IBS symptoms by comparing those who responded to lifestyle modification (the responding group) to those who did not respond (the nonresponding group). Results More than half of the participants (63%) reported that their symptoms improved after training. The quality of life and levels of pain and stress significantly improved after military training. Initial stress levels before military training and smoking history affected IBS symptom improvement. Conclusions Lifestyle modification may be effective in managing IBS patients.

Prognostic significance of p53, mTOR, c-Met, IGF-1R, and HSP70 overexpression after the resection of hepatocellular carcinoma.

Background/Aims The current study examines the expression of molecular biomarkers in hepatocellular carcinoma (HCC) and whether these findings correlate with the clinicopathologic features of the disease and patient survival. Methods We analyzed the immunohistochemical expression of p53, mammalian target of rapamycin (mTOR), c-Met, and insulin-like growth factor 1 receptor (IGF-1R) heat shock protein 70 (HSP70) with the clinicopathologic features of 83 HCCs. Results p53 expression was higher in the male patients with undifferentiated histological tumor grades, cirrhosis, and portal vein invasion. High 48 c-Met expression correlated with cirrhosis, and high mTOR expression correlated with the tumor grade and cirrhosis. High IGF-1R expression correlated with the tumor grade and cirrhosis. A multivariate analysis identified a significant relationship between the high expression of p53, tumor grade, and portal vein invasion. In addition, a high expression of mTOR was related to tumor grade and cirrhosis, and a high expression of HSP70 was related to portal vein invasion in a multivariate analysis. The Kaplan-Meier survival curve for patients with high versus low Edmondson grades and p53 expression was statistically significant. Conclusions p53, mTOR, and IGF-1R expression correlated with the Edmondson tumor grade in a univariate analysis, while p53 and mTOR correlated with the Edmondson tumor grade in a multivariate analysis. In addition, the tumor grade was found to predict survival. p53 was primarily related to the clinicopathologic features compared to other markers, and it is a poor prognostic factor of survival.

Risk factors and therapeutic results of early local recurrence after transcatheter arterial chemoembolization

AIM To identify factors affecting early local recurrence after transcatheter arterial chemoembolization (TACE) and investigate treatments and outcomes for local recurrence. METHODS Early local recurrence and no early local recurrence groups drawn from 134 patients who were initially diagnosed with hepatocellular carcinoma (HCC) and showed a complete response (CR) to TACE treatment between January 1, 2006, and January 31, 2012, were analyzed by univariate and multivariate analyses. Additionally, the subsequent treatment for patients with recurrence was analyzed, and in cases in which TACE had been performed, the cumulative recurrence rates were calculated using the Kaplan-Meier method and compared with those of the primary lesion. RESULTS The 1-, 2-, and 3-year survival rates were 92.3%, 60.2%, and 39.8%, respectively, in the early local recurrence group, which were significantly lower than those in both the late local and no local recurrence groups (P < 0.001). On multivariate analyses, non-compact lipiodol uptake, large tumor size, and an alpha-fetoprotein > 20 ng/mL after achieving a CR were significant predictors. When TACE was performed for early and late locally recurrent lesions, a CR was observed in 15 patients (41.7%) and 11 patients (78.6%), and the cumulative recurrence rates at 6, 12, and 24 mo were 17.9%, 43.3%, and 71.2%, respectively, which did not differ significantly from those after the first CR of 20.5%, 44.0%, and 58.6%, respectively (P = 0.639). CONCLUSION Closer monitoring and active treatments must be provided to patients with risk factors for early local recurrence of HCC.

Inhibitory effects of rapamycin on the different stages of hepatic fibrosis.

AIM To investigate and compare the inhibitory effects of rapamycin in the different stages of liver fibrosis. METHODS We performed bile duct ligation (BDL) in male Wistar rats (n = 24). The experimental rats were classified into four groups: the BDL(+)/Rapa(-) group (un-treated control, n = 4), the BDL(+)/Rapa(+) group (treated 14 d after BDL, n = 8), the BDL(+)/Rapa(++) group (treated on the day after BDL, n = 8), and the BDL(-)/Rapa(-) group (un-treated, sham -operated control, n = 4). The BDL(+)/Rapa(+) and BDL(+)/Rapa(++) groups were administered rapamycin (2 mg/kg) for 28 d. The liver tissues were tested by immunohistochemical staining for α-smooth muscle actin (α-SMA) and cytokeratin. RESULTS The liver mRNA levels of transforming growth factor (TGF)-β1 and platelet-derived growth factor (PDGF) were measured using the polymerase chain reaction. The protein levels of liver p70s6K and p-p70s6k were determined using Western blotting. α-SMA expression was lowest in the BDL(+)/Rapa(++)group. TGF-β1 and PDGF expression levels in the rapamycin-treated group were lower than those in the un-treated group and higher than those in the control groups (TGF-β1: 0.23 ± 0.00 vs 0.34 ± 0.01, 0.23 ± 0.0 vs 0.09 ± 0.00, P < 0.0001; PDGF: 0.21 ± 0.00 vs 0.34 ± 0.01, 0.21 ± 0.0 vs 0.09 ± 0.00, P < 0.0001). The p70s6k and p-p70s6k levels decreased in the treated groups and were lowest in the BDL(+)/Rapa(++)group (p70s6k: 1.05 ± 0.17 vs 1.30 ± 0.56, 0.40 ± 0.01 vs 1.30 ± 0.56, P < 0.0001; p-p70s6k: 1.40 ± 0.5 vs 1.67 ± 0.12, 0.70 ± 0.01 vs 1.67 ± 0.12, P < 0.0001). CONCLUSION The results of our study indicate that rapamycin has inhibitory effects on liver fibrosis, and the treatment is most effective in the early stages of fibrosis.

Spectrum of final pathological diagnosis of gastric adenoma after endoscopic resection

AIM To investigate how many discrepancies occur in patients before and after endoscopic treatment of referred adenoma and the reason for these results. METHODS We retrospectively reviewed data from 554 cases of 534 patients who were referred from primary care centres for adenoma treatment and treated for endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) at Chungnam National University Hospital, from July 2006 to June 2009. Re-endoscopy was examined in 142 cases and biopsy was performed in 108 cases prior to treatment. Three endoscopists (1, 2 and 3) performed all EMRs or ESDs and three pathologists (1, 2 and 3) diagnosed most of the cases. Transfer notes, medical records and endoscopic pictures of these cases were retrospectively reviewed and analyzed. RESULTS Adenocarcinoma was 72 (13.0%) cases in total 554 cases after endoscopic treatment of referred adenoma. When the grade of dysplasia was high (55.0%), biopsy number was more than three (22.7%), size was no smaller than 2.0 cm (23.2%), morphologic type was depressed (35.8%) or yamada type IV (100%), and color was red (30.9%) or mixed-or-undetermined (25.0%), it had much more malignancy rate than the others (P < 0.05). All 18 cases diagnosed as adenocarcinoma in the re-endoscopic forceps biopsy were performed by endoscopist 1. There were different malignancy rates according to the pathologist (P = 0.027). CONCLUSION High grade dysplasia is the most important factor for predicting malignancy as a final pathologic diagnosis before treating the referred gastric adenoma. This discrepancy can occur mainly through inappropriately selecting a biopsy site where cancer cells do not exist, but it also depends on the pathologist to some extent.

Clinical Outcomes of Endoscopic Submucosal Dissection for Undifferentiated or Submucosal Invasive Early Gastric Cancer

Background/Aims Early gastric cancer (EGC) that is undifferentiated or shows submucosal invasion has not been generally accepted as an indication for endoscopic treatment. But recently, experiences with endoscopic submucosal dissection (ESD) for undifferentiated EGC or submucosal invasive (SM) EGC have increased. The aim of this study was to evaluate clinical outcomes of ESD for EGC with undifferentiation or submucosal invasion. Methods Between August 2005 and August 2009, among 210 EGCs treated using ESD at our hospital, 18 lesions were diagnosed as undifferentiated gastric cancer and 41 as SM gastric cancer. A retrospective analysis was done on the medical records of these patients. Results Mean follow-up periods were 19.39±11.2 months. During the follow-up period, local recurrence was noted in 4 lesions. Local recurrence rates of the EGC groups (group 1, mucosal cancer with undifferentiation; group 2, SM cancer with differentiation; group 3, SM cancer with undifferentiation) were 10%, 4.5%, and 50%, respectively. Groups 1 and 2 were not significantly different in local recurrence rates compared to the mucosal cancer with differentiation group (p=0.061, p=0.125, respectively). The undifferentiated EGC group was significantly lower in curability using ESD than the differentiated EGC group (55.6% vs. 89.6%, p=0.000). The curability of the SM EGC group was lower than the mucosal EGC group (36.6% vs. 98.9%). Conclusions Complete resection using ESD is difficult in undifferentiated and SM gastric cancers. SM cancer with undifferentiation should be treated immediately by salvage operation. For mucosal cancer with undifferentiation or SM cancer with differentiation, one should consider careful short-term follow-up.

Growth Differentiation Factor-15 Predicts Chronic Liver Disease Severity.

Background/Aims Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. Methods The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. Results Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). Conclusions This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease.

Long-term treatment outcomes of clevudine in antiviral-naive patients with chronic hepatitis B.

AIM To evaluate the treatment outcomes of clevudine compared with entecavir in antiviral-naive patients with chronic hepatitis B (CHB). METHODS We retrospectively analyzed the clinical data of CHB patients treated with clevudine 30 mg/d and compared their clinical outcomes with patients treated with entecavir 0.5 mg/d. The biochemical response, as assessed by serum alanine aminotransferase (ALT) activity, virologic response, as assessed by serum hepatitis B virus DNA (HBV DNA) titer, serologic response, as assessed by hepatitis B e antigen (HBeAg) status, and virologic breakthrough with genotypic mutations were assessed. RESULTS Two-hundred and fifty-four patients [clevudine (n = 118) vs entecavir (n = 136)] were enrolled. In clevudine-treated patients, the cumulative rates of serum ALT normalization were 83.9% at week 48 and 91.5% at week 96 (80.9% and 91.2% in the entecavir group, respectively), the mean titer changes in serum HBV DNA were -6.03 and -6.55 log(10) copies/mL (-6.35 and -6.86 log(10) copies/mL, respectively, in the entecavir group), and the cumulative non-detection rates of serum HBV DNA were 72.6% and 83.1% (74.4% and 83.8%, respectively, in the entecavir group). These results were similar to those of entecavir-treated patients. The cumulative rates of HBeAg seroconversion were 21.8% at week 48 and 25.0% at week 96 in patients treated with clevudine, which was similar to patients treated with entecavir (22.8% and 27.7%, respectively). The virologic breakthrough in the clevudine group occurred in 9 (7.6%) patients at weeks 48 and 15 (12.7%) patients at week 96, which primarily corresponded to genotypic mutations of rtM204I and/or rtL180M. There was no virologic breakthrough in the entecavir group. CONCLUSION In antiviral-naive CHB patients, long-term treatment outcomes of clevudine were not inferior to those of entecavir, except for virologic breakthrough.

A case of concomitant Gilbert's syndrome and hereditary spherocytosis

We describe moderate hyperbilirubinemia in a 28-year-old man who suffered from gallstones and splenomegaly, with combined disorders of hereditary spherocytosis (HS) and Gilberts syndrome (GS). Since it is difficult to diagnose HS in the absence of signs of anemia, we evaluated both the genetic mutation in the UGT1A1 gene and abnormalities in the erythrocyte membrane protein; the former was heterozygous for a UGT1A1 allele with three mutations and the latter was partially deficient in ankyrin expression. This is the first report of the concomitance of HS and GS with three heterozygous mutations [T-3279G, A (TA)7TAA, and G211A] in the UGT1A1 gene.

Reactivation of tuberculosis in hepatocellular carcinoma treated with transcatheter arterial chemoembolization: A report of 3 cases.

Pulmonary tuberculosis is an opportunistic infection that can be reactivated in immunocompromised conditions, for example, in malignancy or after liver transplantation. Hepatocellular carcinoma (HCC) has a high mortality rate because it is frequently diagnosed at an advanced stage. Although surgical resection is the established curative measure for HCC, it is only feasible for early-stage HCC. Transcatheter arterial chemoembolization (TACE) is the most common treatment modality for patients with unresectable HCC. However, repeated TACE sessions and, occasionally, the tumor itself can further impair the reserve hepatic function and immunity. We report 3 recent cases of HCC with reactivation of pulmonary tuberculosis after TACE.