Risk Assessment of Liver-related Events Using Transient Elastography in Patients With Chronic Hepatitis B Receiving Entecavir

Kim, Mi Na,Kim, Seung Up,Park, Jun Yong,Kim, Do Young,Han, Kwang-Hyub,Chon, Chae Yoon,Ahn, Sang Hoon RAVEN PRESS PUBLISHERS 2014 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.48 No.3

GOALS:: We investigated whether liver stiffness (LS) values can predict liver-related events (LREs) development in patients with chronic hepatitis B (CHB). BACKGROUND:: LS values using transient elastography provides accurate assessment of liver fibrosis in patients with chronic liver disease. METHODS:: Between June 2007 and May 2010, a total of 162 patients with CHB who completed 2-year entecavir (ETV) treatment were evaluated. The primary endpoint was LRE development (hepatic decompensation, hepatocellular carcinoma, or liver-related death) during the 2-year ETV treatment. RESULTS:: The median age of the patients (99 men, 63 women) was 51 years, and the median LS value was 14.8 kPa. During the 2-year ETV treatment, 15 (9.3%) patients experienced LREs. On univariate analysis, age, the proportion of patients with liver cirrhosis, platelet counts, and baseline LS values were significantly associated with LRE development (all P<0.05). Together with age, multivariate analysis identified baseline LS values as an independent predictor of LRE development (P=0.046; hazard ratio, 1.040; 95% confidence interval, 1.101-1.084). The cutoff LS value maximizing the sum of sensitivity and specificity was 12.0 kPa (area under the receiver operating characteristics curve, 0.736; P=0.003; sensitivity, 93.3%; specificity, 42.2%). In addition, the changes in LS values between baseline and 1-year ETV treatment showed significant correlations with LRE development (P=0.030). CONCLUSIONS:: Our data suggest that LS values are predictive of LRE development during 2-year ETV treatment in patients with CHB. The potential role of LS value as a monitoring tool for predicting dynamic changes in the risk of LRE development during long-term ETV treatment should be investigated further.

Prediction of Malignancy With Endoscopic Ultrasonography in Patients With Branch Duct–Type Intraductal Papillary Mucinous Neoplasm

Lee, Kwang Hyuck,Lee, Se-Joon,Lee, Jong Kyun,Ryu, Ji Kon,Kim, Eun Young,Kim, Tae Hyeon,Moon, Jong Ho,Lee, Woo Jin,Cho, Yu Kyung,Kim, Jae J. RAVEN PRESS PUBLISHERS 2014 PANCREAS Vol.43 No.8

OBJECTIVE: We evaluated the accuracy of a new endoscopic ultrasonography (EUS) scoring system to predict malignancy in branch duct–type intraductal papillary mucinous neoplasms (BD-IPMNs). METHODS: We performed a retrospective multicenter study of patients who underwent EUS within 3 months before surgery and were diagnosed as having BD-IPMNs by postoperative pathologies at 8 hospitals in Korea from August 2002 to December 2011. To predict the malignancy, we applied the EUS scoring system consisting of pancreatic cyst size, height of mural nodules, main duct dilatation, septal thickening, and patulous orifice. We evaluated the diagnostic accuracy of the new EUS scoring system and compared it with previous individual risk factors. RESULTS: Eighty-four patients (male-to-female ratio, 55:29; mean [SD] age, 64.7 [7.1] years) had 68 benign BD-IPMNs and 16 malignant intraductal papillary mucinous neoplasms. The EUS scoring system showed 75.0% sensitivity and 94.1% specificity at 7 points. This system (area under the curve, 0.939; 95% confidence interval, 0.884–0.994) resulted in a more accurate prediction than the previous known other factors including Sendai criteria, dilatation of ducts, size of the cyst, and presence of septal thickening and mural nodules. CONCLUSIONS: The EUS scoring system predicted BD-IPMN malignancy more accurately than the Sendai criteria and individual risk factors.

Role of Hepatitis B Surface Antigen (HBsAg) in Identifying True Inactive HBsAg Carriers Infected With Genotype C Hepatitis B Virus

Yim, Sun Young,Um, Soon Ho,Jung, Jin Young,Seo, Yeon Seok,Yim, Hyung Joon,Ryu, Ho Sang,Chun, Hoon Jai,Jeen, Yoon Tae,Kim, Chang Duck,Keum, Bora,Lee, Hong Sik RAVEN PRESS PUBLISHERS 2014 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.48 No.2

BACKGROUND:: Inactive and active phases of hepatitis B e antigen-negative chronic hepatitis B virus (HBV) infection are diagnosed by serum HBV DNA levels, with cutoff at 2000 IU/mL. However, it is difficult to distinguish inactive carriers at a single time point because HBV DNA levels can transiently decrease to <2000 IU/mL even in noninactive carriers. GOALS:: We aimed to establish the role of serum hepatitis B surface antigen (HBsAg) in identifying “true inactive carriers” among treatment-naive genotype C HBV-infected patients with low viremia. STUDY:: A total of 133 hepatitis B e antigen-negative carriers with serum HBV DNA levels of <2000 IU/mL and normal alanine aminotransferase levels were enrolled and followed up for >12 months. RESULTS:: Forty patients (30.1%) were classified as noninactive carriers (HBV DNA ≥2000 IU/mL and/or alanine aminotransferase >40 IU/L) during 12 months from enrollment. No baseline serum HBV DNA levels could identify true inactive carriers with 100% specificity, whereas baseline serum HBsAg levels (50 IU/mL) identified true inactive carriers with 100% specificity and 29% detection rate. Detection rate increased when different cutoff levels were applied to different age groups according to median age (46 y). It was comparable in both younger and older groups (37.2% vs. 38%) even when HBsAg cutoff level was increased in the former (400 vs. 50 IU/mL). Furthermore, none reversed to noninactive phase during long-term follow-up when these cutoff levels were applied. CONCLUSIONS:: Baseline serum HBsAg levels at a single time point can identify persistently true inactive carriers, with different cutoff levels according to age.

Regional Cerebral Blood Flow Abnormalities Associated With Apathy and Depression in Alzheimer Disease

Kang, Ji Yeon,Lee, Jae Sung,Kang, Hyejin,Lee, Hae-Woo,Kim, Yu Kyeong,Jeon, Hong Jin,Chung, June-Key,Lee, Myung Chul,Cho, Maeng Je,Lee, Dong Soo RAVEN PRESS PUBLISHERS 2012 ALZHEIMER DISEASE AND ASSOCIATED DISORDERS Vol.26 No.3

The aim of this study was to identify brain areas related to apathy or depression in patients with Alzheimer disease (AD). Eighty-one AD patients were enrolled in this prospective study. Tc-HMPAO single photon emission computed tomography was performed to evaluate regional cerebral blood flow (rCBF). According to the Neuropsychiatric Inventory subscores of apathy and depression, 9 patients were classified as clinically significant (cs) depressed and non-cs-apathetic (D+) groups and 9 were classified as cs-apathetic and non-cs-depressed (A+) groups. In addition, 18 patients were classified as age-matched and Mini-Mental State Examination-matched disease control groups (D−, A−). The significance of rCBF differences between groups and the correlation between rCBF and subscores in 81 AD patients were estimated by SPM (uncorrected P<0.005) analysis. D+ patients had significantly lower perfusion in the right orbitofrontal and inferior frontal gyri than D− patients, whereas A+ patients had this in the right amygdala, temporal, posterior cingulate, right superior frontal, postcentral, and left superior temporal gyri than A− patients. The negatively correlated areas with depression subscores included the left inferior frontal and the right middle frontal gyri and those with apathy subscores included the right temporal and right medial frontal gyri. We suggest that this finding may indicate that apathy and depression in AD patients involve distinct functional circuits.

Risk and Clinical Characteristics of Lymphoma in Korean Patients With Inflammatory Bowel Diseases: A Multicenter Study

Park, Soo-Kyung,Ye, Byong Duk,Lee, Changhyun,Im, Jong Pil,Kim, Young-Ho,Kim, Seon-Ok,Byeon, Jeong-Sik,Myung, Seung-Jae,Yang, Suk-Kyun,Kim, Jin-Ho RAVEN PRESS PUBLISHERS 2015 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.49 No.2

BACKGROUND AND AIMS:: Studies of lymphoma risk in Western inflammatory bowel disease (IBD) patients show conflicting results; however, none have examined the lymphoma risk and clinical characteristics of Asian IBD patients. METHODS:: Patients with lymphoma were identified in an IBD database from 3 tertiary referral centers in Seoul, Korea. The standardized incidence ratio (SIR) of lymphoma was estimated using data from the Korea Central Cancer Registry of the National Cancer Center. The risk of lymphoma in relation to specific medications was also explored. RESULTS:: Seven cases of lymphoma (0.1%) were identified in 6585 IBD patients. The median age at lymphoma diagnosis was 43 years (range, 33 to 70 y) and the median duration of IBD at lymphoma diagnosis was 96.1 months (range, 15.1 to 171.6 mo). Three patients had underlying ulcerative colitis and 4 had Crohn’s disease (CD). Non-Hodgkin lymphoma was diagnosed in 5 patients (71.4%) and Hodgkin disease (HD) in 2 patients (28.6%). The SIR of lymphoma was 2.03 [95% confidence interval (CI), 0.81-4.18] in the entire IBD patients. Both the SIR of lymphoma in CD patients (9.31; 95% CI, 1.13-33.62) and the SIR of HD (13.16; 95% CI, 1.59-47.53) in IBD patients were increased. The SIR of lymphoma in patients who were exposed to thiopurines was 5.93 (95% CI, 1.61-15.18). CONCLUSIONS:: The risk of lymphoma in CD patients and the risk of HD in IBD patients seem to be increased in Korea. Thiopurine may be related with the risk of lymphoma in Korean IBD patients.

Low Frequency of KRAS Mutation in Pancreatic Ductal Adenocarcinomas in Korean Patients and Its Prognostic Value

Kwon, Mi Jung,Jeon, Jang Yong,Park, Hye-Rim,Nam, Eun Sook,Cho, Seong Jin,Shin, Hyung Sik,Kwon, Ji Hyun,Kim, Joo Seop,Han, Boram,Kim, Dong Hoon,Choi, Yoon-La RAVEN PRESS PUBLISHERS 2015 PANCREAS Vol.44 No.3

OBJECTIVES: Low prevalence and prognostic relevance of KRAS mutations in Korean pancreatic ductal adenocarcinomas (PDACs) need to be validated with sensitive detection method. METHODS: Peptide nucleic acid (PNA)–mediated polymerase chain reaction (PCR) clamping was used to precisely detect KRAS mutation in 72 paraffinized tumor samples and was validated by pancreatic cell lines to compare the efficiency of direct sequencing. RESULTS: The PNA-mediated PCR clamping detected mutant allele proportions of as low as 0.5% against a background of wild-type DNA and was 20-fold more sensitive than direct sequencing through the validation of pancreatic cell lines. Peptide nucleic acid–mediated PCR clamping detected KRAS mutations in 47.2% of 72 PDACs. Low tumor cellularity and low PCR amplification efficiency led to be undetected or failed by direct sequencing in pancreatic paraffinized samples.KRAS mutations were an independent worse prognostic factor predicting a reduced progression-free survival rate in the postoperative chemotherapy group. CONCLUSIONS: Peptide nucleic acid clamp real-time PCR was a sensitive method for detecting KRAS status in paraffinized PDAC samples. We identified a low KRAS mutation rate among the Korean PDAC patients using PNA clamp real-time PCR, potentially implicating epidemiological characteristics. The low KRAS mutation rate and its prognostic role may suggest the further survival benefit in Korean PDAC patients.

Novel Disposable Transnasal Endoscopy for Assessment of Esophageal Motor Function

Lim, Chul-Hyun,Choi, Myung-Gyu,Baeg, Myong-Ki,Moon, Sung Jin,Kim, Jin Su,Cho, Yu Kyung,Park, Jae Myung,Lee, In Seok,Kim, Sang Woo,Choi, Kyu Yong RAVEN PRESS PUBLISHERS 2014 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.48 No.5

BACKGROUND:: A novel disposable transnasal endoscopy (DTE) with a portable system has been developed to provide unsedated esophagoscopy by modifying capsule endoscopy. The aim of this study was to assess the feasibility of DTE to evaluate esophageal motor function. MATERIALS AND METHODS:: Patients with or suspected esophageal motility disorders and healthy volunteers were enrolled. Participants underwent esophageal high-resolution manometry and DTE in random order on different days. Motility was observed with DTE at 1, 8, and 16 cm above the gastroesophageal junction. RESULTS:: Twenty healthy volunteers and 20 symptomatic subjects participated (8 achalasia, 5 scleroderma, 3 diffuse esophageal spasm, 1 hypertensive peristalsis, 1 peristaltic dysfunction, and 22 normal esophageal function). The normal findings on DTE were as follows. As the subject swallowed water, swallow-induced relaxation with elevation of the lower esophageal sphincter caused the endoscope to cross the Z-line into the gastric lumen. After the passage of water and air, complete closure of the lower esophageal sphincter occurred, with the return of the endoscope to its previous position. During the resting stage of the esophageal body, an air bubble could be seen in the center of the radially wrinkled and occluded lumen. The endoscopic diagnosis was in agreement with the clinical diagnosis in all but 2. Most of the participants reported acceptable discomfort during DTE and 62.5% of the subjects preferred DTE to manometry. CONCLUSIONS:: DTE can accurately characterize normal esophageal motor function, allowing the diagnosis of esophageal motility disorders. DTE has potential widespread applications, especially in outpatient clinics.

Pancreatic Cancer Induced by In Vivo Electroporation-Enhanced Sleeping Beauty Transposon Gene Delivery System in Mouse

Park, June-Shine,Lim, Kyung-Min,Park, Sung Goo,Jung, Sun Young,Choi, Hyun-Ji,Lee, Do Hee,Kim, Woo-Jin,Hong, Seung-Mo,Yu, Eun-Sil,Son, Woo-Chan RAVEN PRESS PUBLISHERS 2014 PANCREAS Vol.43 No.4

OBJECTIVE: The aim of this study was to establish a pancreatic tumor model of mouse using the electroporation-enhanced Sleeping Beauty (SB) transposon system. METHODS: The SB transposon system was used in conjunction with electroporation to deliver oncogenes, c-Myc and HRAS, and shRNA against p53 into the mouse pancreas to induce tumors. Oncogenes (c-Myc and HRAS) and shRNA against p53 gene were directly injected into the pancreas of the mouse along with in vivo electroporation applied on the injection site. The tumors were identified grossly and confirmed using animal positron emission tomographic imaging. The tumors were then characterized using histological and immunohistochemical techniques. The expression of the targeted genes (c-Myc, HRAS, and p53) was analyzed by a real-time quantitative polymerase chain reaction. RESULTS: Pancreatic tumors were successfully induced. The tumor phenotype was a sarcomatoid carcinoma, which was verified through immunohistochemistry. Some cysts or duct-like structures suggested to be metaplastic acinar cells were visible in the induced tumor. CONCLUSIONS: The SB transposon enhanced with electroporation can readily generate pancreatic tumors in the mice, and thus, this model serves as a valuable resource for the mouse models of pancreatic cancer.

Outcomes of Three Patients With Intracranially Invasive Sino-orbital Aspergillosis

Yoon, Jin Sook,Park, Hyung Kyu,Cho, Nam Hoon,Lee, Sang Yeul RAVEN PRESS PUBLISHERS 2007 OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY Vol.23 No.5

PURPOSE:: Although rare, invasive aspergillosis with intracranial spread usually is fatal and necessitates prompt diagnosis and treatment. We describe the prognoses for survival and vision in 3 consecutive patients with vision-threatening invasive sino-orbital aspergillosis. METHODS:: A case series of 3 patients, with review of treatments and outcomes. RESULTS:: Three diabetic patients presented with significant eye pain and headache, followed by progressive ophthalmic symptoms including vision loss and limitation of ocular motility. Histologic examination showed numerous hyphae of Aspergillus fumigatus. Following early diagnosis and surgical debridement, 1 patient (case 1) showed vision improvement, from counting fingers to 20/20. The other 2 patients, who were initially treated with corticosteroids after presumptive diagnoses of nonspecific orbital inflammation, showed no recovery of vision from no light perception, and 1 (case 3) died of massive intracranial spread and side effects of antifungal agents caused by delayed diagnosis and long-term use of corticosteroids. CONCLUSIONS:: Invasive sino-orbital aspergillosis with intracranial invasion often may resemble inflammatory conditions. Early diagnosis and surgical intervention are required to improve vision and survival. Repeated biopsies often are necessary to rule out fungal sinus infection before considering steroid use, especially in diabetic patients.

Fecal Microbiota Differences According to the Risk of Advanced Colorectal Neoplasms :

Yang, Hyo-Joon,Kwon, Min-Jung,Chang, Yoosoo,Song, Seul-Ki,Ahn, Kwang-Sung,Kim, Han-Na,Yun, Yeojun,Kim, Hyung-Lae,Park, Dong Il RAVEN PRESS PUBLISHERS 2019 JOURNAL OF CLINICAL GASTROENTEROLOGY Vol.53 No.3