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ABSTRACT: BACKGROUNDAIMS: Although mucosal mast cell tryptase is known to significantly increase intestinal permeability, the relationship between mucosal mast cells and intestinal permeability remains unclear. The objective of this study was to evaluate the correlation among intestinal permeability, tryptase activity and mucosal mast cell count.
Rectal biopsies from 16 patients with diarrhea-predominant irritable bowel syndrome (IBS-D) and 7 normal subjects were assessed for tryptase activity and macromolecular permeability using horseradish peroxidase in Ussing chambers. In addition, mucosal mast cell levels were immunohistochemically quantified via image analysis.
Rectal biopsy of tissues from IBS-D patients showed significantly increased permeability compared with those from normal controls (0.644 ± 0.08 and 0.06 ± 0.00 ng/2 hr/mm(2), P < 0.01). Tryptase activity was also substantially higher in rectal biopsy samples from IBS-D patients than those from normal controls (0.86 ± 0.18 and 0.28 ± 0.04 mU/mg protein, P < 0.05). Mucosal mast cell counts were not significantly different between the 2 groups (P > 0.05). However, correlation analysis revealed that only mucosal mast cell count was significantly correlated with intestinal permeability in IBS-D patients (r = 0.558, P < 0.05).
This study demonstrated a positive correlation between the number of mucosal mast cells and intestinal permeability, suggesting that mucosal mast cells play an important role for increased intestinal permeability in patients with IBS-D.
Journal of neurogastroenterology and motility 04/2013; 19(2):244-50.
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ABSTRACT: BACKGROUND/AIMS: The apolipoprotein B/AI (ApoB/AI) ratio is a strong new risk factor for cardiovascular (CV) disease. Although recent reports have shown the effects of nonalcoholic fatty liver disease (NAFLD) on CV disease, NAFLD is under-recognized as a predictable risk factor for CV disease. This study was performed to assess the independent association between ApoB/AI ratio and NAFLD. METHODS: This cross sectional study was performed in 9,162 subjects who participated in a health checkup program in South Korea in 2009. The presence of NAFLD was defined by ultrasonographic examination. Logistic regression analysis was applied to estimate the association between ApoB/AI ratio and NAFLD. The odds ratio (OR) and P were estimated according to the categorized level of the ApoB/AI ratio. RESULTS: The overall prevalence of NAFLD was 27.9% (n=2,554, 41.7% of the men, 10.8% of the women). Men had a 5.91-fold (95% CI 5.28-6.62) greater risk for NAFLD than women. After adjusting for confounding factors, the ApoB/AI ratio was more closely associated with the prevalence of NAFLD than with any other lipid profiles (OR 8.537 in men, 16.6 in women). NAFLD risk increased as the quartiles of the ApoB/AI ratio increased from the first to the fourth quartile (OR 1.359, 2.173 and 3.124, P for trend <0.001). CONCLUSION: The ApoB/AI ratio was associated with the prevalence of NAFLD in nondiabetic subjects and was independent of obesity and other metabolic components. This result suggests that NAFLD may provide additional information for atherosclerosis progression and CV risks.
Journal of Gastroenterology and Hepatology 12/2012; · 2.87 Impact Factor
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ABSTRACT: Transarterial chemoembolization (TACE) represents a first-line non-curative therapy for 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 embolisation 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. 62.6% of patients reported gastrointestinal AEs and 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 (ORR) was calculated as 52.4%. This study shows that concurrent sorafenib and TACE therapy is safe and effective with no unexpected side effects. © 2012 Wiley Periodicals, Inc.
International Journal of Cancer 11/2012; · 5.44 Impact Factor
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ABSTRACT: BACKGROUND: Clinical outcomes associated with Gram-negative bacterial isolates with extended spectrum beta-lactamase (ESBL) in patients with biliary tract infection are largely unknown. The objective of the present study was to compare the demographics, risk factors, and clinical outcomes between patients with biliary tract infection caused by ESBL-producing and non-producing Klebsiella pneumoniae and Escherichia coli. METHODS: Between February 2005 and August 2010, we collected 159 cases with biliary tract infection caused by K. pneumoniae and E. coli identified by blood or bile cultures obtained before endoscopic or surgical treatment performed at our institution. We also retrospectively collected the data of patients' demographic characteristics, co-morbid conditions, antimicrobial therapy, and clinical outcomes. RESULTS: Among the 159 strains isolated, 21 strains (13.2 %) were positive for phenotypical ESBL-test. Sepsis was more common in ESBL-positive strains, but did not reach statistical significance (23.8 % for ESBL-positive strains and 9.4 % for ESBL-negative strains, P = 0.066). Thirty-day mortality was significantly higher in ESBL-positive strains (3/21, 14.3 %) compared to ESBL-negative strains (4/138, 2.9 %, P = 0.049). However, there were no significant differences in overall survival between ESBL-positive and ESBL-negative strains. By multivariate analysis, inadequate antimicrobial therapy (HR 4.06, 95 % CI 1.08-16.46, P = 0.049) and sepsis (HR 6.54, 95 % CI 1.26-33.85, P = 0.025) were independent and significant predictors of 30-day mortality. CONCLUSION: ESBL status of bacterial isolates for patients with biliary tract infection caused by K. pneumoniae and E. coli has clinical impact, especially on the short-term outcomes of those patients.
Digestive Diseases and Sciences 09/2012; · 2.12 Impact Factor
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Tae Sun Kim,
Dong Il Park,
Do Young Lee,
Jang Hyuk Yoon,
Jung Ho Park,
Hong Joo Kim,
Yong Kyun Cho,
Chong Il Sohn,
Woo Kyu Jeon, Byung Ik Kim,
Jae Wan Lim
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ABSTRACT: The aim of this study was to assess the effects of endoscopy nurse participation on polyp detection rate (PDR) and adenoma detection rate (ADR) of second-year fellows during screening colonoscopies.
This was a single-center, prospective, randomized study comparing a fellow alone and a fellow plus an endoscopy nurse as an additional observer during afternoon outpatient screening colonoscopies. The primary end points were PDR and ADR.
One hundred ninety-one colonoscopies performed by a fellow alone and 192 colonoscopies performed by a fellow plus an endoscopy nurse were analyzed. The PDR was significantly higher when the nurse was involved (53.1% vs. 41.3%, p<0.05); however, there was no significant difference in the ADR between the two groups (38.5% vs. 29.8%, p=0.073). There was no difference in the percentage of patients with ≥2 polyps, advanced adenomas, polyp size, polyp location, and polyp shapes between the two groups. There was no difference in the PDR according to the level of experience of the endoscopy nurse.
Endoscopy nurse participation as an additional observer during screening colonoscopy performed by second-year fellow increases the PDR; however, the level of experience of the nurse was not an important factor.
Gut and liver 07/2012; 6(3):344-8. · 0.83 Impact Factor
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Ki Tae Suk,
Dong Joon Kim,
Chang Hoon Kim,
Seung Ha Park,
Jai Hoon Yoon,
Yeon Soo Kim,
Gwang Ho Baik,
Jin Bong Kim,
Young Oh Kweon, Byung Ik Kim, [......],
Byung Min Ahn,
Soon Ho Um,
Heon Ju Lee,
Mong Cho,
Myoung Kuk Jang,
Sung Kyu Choi,
Seong Gyu Hwang,
Ho Taik Sung,
Jong Young Choi,
Kwang Hyub Han
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ABSTRACT: To address a growing concern about drug-induced liver injury (DILI), a nationwide study was performed to investigate the significance of DILI in Korea.
From May 2005 to May 2007, cases of DILI (alanine transferase >3 × upper normal limit or total bilirubin >2 × upper normal limit) from 17 referral university hospitals were prospectively enrolled. Adjudication by the seven review boards was considered for the confirmation of causality and the Roussel Uclaf Causality Assessment Method (RUCAM) scale was used.
A total of 371 cases were diagnosed with DILI. The extrapolated incidence of hospitalization at university hospital in Korea was 12/100,000 persons/year. The causes included "herbal medications" (102, 27.5%), "prescription or non-prescription medications" (101, 27.3%), "health foods or dietary supplements" (51, 13.7%), "medicinal herbs or plants" (35, 9.4%), "folk remedies" (32, 8.6%), "combined" (30, 8.2%), "herbal preparations" (12, 3.2%), and others (8, 2.2%). Nine cases were linked to acetaminophen. The frequencies of hepatocellular, mixed, and cholestatic types were 76.3, 14.8, and 8.9%, respectively. A total of 234 cases met the criteria for Hy's law. Five patients died or underwent transplantation. Twenty-five cases (21 herbs and 4 medications) did not meet the time-to-onset criteria of the RUCAM.
DILI appears to be a highly relevant health problem in Korea. "Herbal medications" are the principal cause of DILI. A more objective and reproducible causality assessment tool is strongly desired as the RUCAM scale frequently undercounts the cases caused by herbs owing to a lack of previous information and incompatible time criteria.
The American Journal of Gastroenterology 06/2012; 107(9):1380-7. · 7.28 Impact Factor
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Joo Ho Lee,
Young-Hwa Chung,
Jeong A Kim,
Ju Hyun Shim,
Danbi Lee,
Han Chu Lee,
Eun-Soon Shin,
Jung Hwan Yoon, Byung Ik Kim,
Si Hyun Bae,
Kwang Cheol Koh,
Neung-Hwa Park
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ABSTRACT: 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. Cancer 2012. © 2012 American Cancer Society.
Cancer 06/2012; · 4.77 Impact Factor
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ABSTRACT: The aim of this study was to analyze the clinical impacts of obesity and hazardous alcohol use on the outcome of entecavir (ETV) therapy in chronic hepatitis B (CHB) patients.
The medical records of 88 treatment-naïve patients who were diagnosed with CHB and received ETV between March 2007 and September 2009 were analyzed retrospectively. Body mass index (BMI) values and Alcohol Use Disorders Identification Test (AUDIT) scores were obtained at 6 months after the initiation of ETV (0.5 mg daily) treatment.
A BMI of 25 kg/m(2) or more was recognized as an indicator of obesity, and a total AUDIT score of 8 or more was recognized as an indicator of hazardous alcohol use. Of the cohort, 24 patients (27.3%) were obese and 17 (19.3%) were hazardous alcohol users. The rate of seroconversion, alanine aminotransferase (ALT) normalization, and hepatitis B virus (HBV)-DNA negativity (<300 copies/mL) at 3, 6, and 12 months of treatment did not differ significantly between the normal-BMI and high-BMI groups. Moreover, the rate of seroconversion and HBV-DNA negativity at 3, 6, and 12 months of treatment did not differ significantly between the nonhazardous and hazardous alcohol users. However, the frequency of ALT normalization at 12 months was significantly lower among hazardous alcohol users (91.5% vs. 70.6%; P=0.033).
Obesity and hazardous alcohol drinking have no significant impact on the outcome of ETV treatment. However, the ALT normalization rate at 12 months after initiation of ETV treatment was significantly lower among the hazardous alcohol users.
Clinical and molecular hepatology. 06/2012; 18(2):195-202.
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ABSTRACT: Nonselective β-blockers (NSBBs), such as propranolol, reportedly exert a pleiotropic effect in liver cirrhosis. A previous report suggested that survival was higher in patients receiving adjusted doses of NSBBs than in ligation patients. This study investigated whether low-dose NSBB medication has beneficial effects in patients with liver cirrhosis, especially in terms of overall survival.
We retrospectively studied 273 cirrhotic patients (199 males; age 53.6±10.2 years, mean±SD) who visited our institution between March 2003 and December 2007; follow-up data were collected until June 2011. Among them, 138 patients were given a low-dose NSBB (BB group: propranolol, 20-60 mg/day), and the remaining 135 patients were not given an NSBB (NBB group). Both groups were stratified randomly according to Child-Turcotte-Pugh (CTP) classification and age.
The causes of liver cirrhosis were alcohol (n=109, 39.9%), hepatitis B virus (n=125, 45.8%), hepatitis C virus (n=20, 7.3%), and cryptogenic (n=19, 7.0%). The CTP classes were distributed as follows: A, n=116, 42.5%; B, n=126, 46.2%; and C, n=31, 11.4%. Neither the overall survival (P=0.133) nor the hepatocellular carcinoma (HCC)-free survival (P=0.910) differed significantly between the BB and NBB groups [probability of overall survival at 4 years: 75.1% (95% CI=67.7-82.5%) and 81.2% (95% CI=74.4-88.0%), respectively; P=0.236]. In addition, the delta CTP score did not differ significantly between the two groups.
Use of low-dose NSBB medication in patients with liver cirrhosis is not indicated in terms of overall and HCC-free survival.
Clinical and molecular hepatology. 06/2012; 18(2):203-12.
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Kyung-Hee Kim,
Scott D Nelson,
Dong-Hoon Kim,
Kyung Un Choi,
Su Jin Kim,
Kyueng-Whan Min,
Ki-Seok Jang,
Seung Sam Paik,
Young-Ha Oh,
Seoung Wan Chae, [......],
Hee-Yeon Woo,
Yong Lai Park,
Se Jin Park,
Sang Hyuk Lee,
Seungho Ryu,
Sung-Im DO,
Guhyun Kang,
Kyungeun Kim,
Young Hye Cho,
Jung-Soo Pyo
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ABSTRACT: We investigated the clinicopathological and immunohistochemical characteristics, genetic aberrations and prognostic factors in 28 patients with extragastrointestinal stromal tumors (EGISTs) from six centers in South Korea.
Immunohistochemistry was performed for c-KIT (CD117), PKC-θ (protein kinase C theta), DOG-1 (discovered on GIST-1), CD34, alpha-smooth muscle actin (α-SMA), vimentin, desmin and S-100 protein. Genetic analyses for the KIT gene (exon 9, 11, 13 and 17) and the platelet-derived growth factor receptor alpha (PDGFRA) gene (exons 12 and 18) were performed by direct sequencing of PCR products. The relationships of various clinicopathological characteristics and outcomes were also examined.
Of the tumor samples, 78.6% (22/28) were located in the intra-abdominal cavity including the omentum and mesentery, and 10.7% (3/28) were located in the retroperitoneum. All patients were older than 39 years. The median size of the tumors was 10 cm for the maximum diameter. When first detected, 57.1% of EGISTs were large in size, measuring more than 10 cm. Tumors that were larger than 10 cm were found more frequently among tumors with more than 10 mitoses per 50 high-power fields (HPFs) and this finding was statistically significant (p<0.05). Based on immunohistochemical results, the EGISTs were positive for c-KIT in 96.4% (27/28) of samples, PKC-θ in 82.1% (23/28), DOG-1 in 85.7% (24/28), PDGFRA in 82.1% (23/28), CD34 in 67.9% (19/28), vimentin in 100% (28/28), α-SMA in 28.6% (8/28), S-100 protein in 39.3% (11/28) and desmin in 28.6% (8/28). c-KIT, DOG-1 and PKC-θ immunostains were sensitive and specific, but the PDGFRA stain was not specific for EGISTs. c-KIT expression was correlated with DOG-1 expression (p<0.05). One c-KIT-negative EGIST was also negative for DOG-1, but positive for PDGFRA and PKC-θ immunostains. Out of all EGISTs, 57.1% had tumor necrosis and most of these were more than 10 cm in size, and had obvious nuclear atypia and high mitotic counts (>10/50 HPFs). Overall survival (OS) was correlated with tumor size >10 cm, tumor necrosis, obvious nuclear atypia, mitotic counts >10/50 HPFs and epithelioid or mixed cell type (p<0.05). Eleven EGISTs (44.0%) had mutations in the KIT gene and 6 (24.0%) had mutations in the PDGFRA gene, the most common being missense mutations or deletions affecting exon 11 of the KIT gene (n=9) or exon 18 of the PDGFRA gene (n=6). Three cases showed co-existence of both KIT and PDGFRA gene mutations. There were no mutations of exon 17 of KIT and exon 12 of PDGFRA genes.
The c-KIT, PKC-θ and DOG-1 antigens are the most sensitive and specific immunomarkers for confirming EGISTs. PKC-θ and PDGFRA immunostains are helpful markers for c-KIT-negative EGISTs. Survival analyses indicated that tumor size >10 cm, mitotic rate >10/50 HPFs, tumor necrosis, obvious nuclear atypia, and epithelioid or mixed cell type were significant predictors of survival. We found that the combination of these parameters helped to predict aggressive tumor behavior and may be useful for predicting the prognosis of EGISTs. The majority of gene mutations were identified in exon 11 of the KIT gene or exon 18 of the PDGFRA gene. The pattern of KIT and PDGFRA mutations in EGISTs was essentially similar to the one in GISTs. From the immunohistochemistry and molecular genetics perspective, EGISTs may be a special subtype of GISTs. Both immunohistochemical and molecular evaluation are useful for classifying tumors as EGISTs.
Anticancer research 03/2012; 32(3):923-37. · 1.73 Impact Factor
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ABSTRACT: Endoscopic biopsy is necessary to confirm a histopathologic diagnosis. Currently, 6 to 8 biopsies are recommended for diagnosis of a suspected malignant lesion. However, multiple biopsies may result in several problems, such as an increased risk of bleeding, procedure prolongation, and increased workload to pathologists. The aim of this study was to clarify the optimal number of endoscopic biopsy specimens required in diagnosis of advanced gastrointestinal cancer. Patients who were diagnosed with advanced gastrointestinal cancer during endoscopy were included. Five specimens were obtained sequentially from viable tissue of the cancer margin. Experienced pathologists evaluated each specimen and provided diagnoses. A total of 91 patients were enrolled. Fifty-nine subjects had advanced gastric cancer, and 32 had advanced colon cancer. Positive diagnosis rates of the first, second, and third advanced gastric cancer specimens were 81.3%, 94.9%, and 98.3%, respectively, while positive diagnosis rates of advanced colon cancer specimens were 78.1%, 87.5%, and 93.8%. Further biopsies did not increase positive diagnosis cumulative rates. This study demonstrated that three specimens were sufficient to make correct pathologic diagnoses in advanced gastrointestinal cancer. Therefore, we recommend 3 or 4 biopsies from viable tissue in advanced gastrointestinal cancer to make a pathologic diagnosis during endoscopy.
Journal of Korean medical science 01/2012; 27(1):36-9. · 0.84 Impact Factor
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ABSTRACT: Recent studies have suggested that a higher red blood cell distribution width (RDW) is associated with disease activity in patients with inflammatory bowel disease (IBD). However, the RDW in IBD patients without anemia has not been investigated.
This study aimed to determine whether or not RDW could be used for the assessment of disease activity in IBD patients with and without anemia.
The serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), hemoglobin concentration, platelet and white blood cell counts, and RDW were assessed in 221 IBD patients, comprised of 120 patients with ulcerative colitis (UC) and 101 patients with Crohn's disease (CD). Disease activity was determined for UC and CD with the Mayo score and the Crohn's disease activity index, respectively.
The CRP level, ESR, hemoglobin concentration, hematocrit, and RDW increased according to disease activity in patients with and without anemia (all P < 0.05). Multivariate analysis demonstrated that RDW was the best independent indicator for predicting disease activity in CD patients without anemia [odd ratios (OR), 1.702; 95% confidence interval (CI), 1.185-2.445; P = 0.004] and UC patients without anemia (OR, 4.921; 95% CI, 2.281-10.615; P < 0.001). Also, ROC curve analysis showed the RDW to be the most significant indicator of non-anemic active IBD [area under curve (AUC) in CD, 0.852, P < 0.001; AUC in UC, 0.827, P < 0.001].
The association between increased RDW and active IBD was evident in IBD patients with and without anemia.
Digestive Diseases and Sciences 12/2011; 57(4):1033-8. · 2.12 Impact Factor
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ABSTRACT: Hepatic hydrothorax in patients with decompensated liver cirrhosis is a challenging problem. Treatment with diuretics and intermittent thoracentesis can be effective in selected patients. However, there are few effective therapeutic options in patients who are intolerant of these therapies. This study investigated the clinical usefulness of chemical pleurodesis with or without video-assisted thoracoscopic surgery (VATS) for patients with refractory hepatic hydrothorax.
Eleven consecutive patients with refractory hepatic hydrothorax who underwent chemical pleurodesis with or without VATS between July 2007 and February 2011 were enrolled in this study. The medical records and radiologic imagings of these patients were thoroughly reviewed.
The median number of chemical pleurodesis sessions performed was 3 (range: 2-10). Successful pleurodesis was achieved in 8 of the 11 patients (72.7%), 5 (62.5%) of whom remained asymptomatic and hydrothorax free for a median follow-up of 16 weeks (range: 2-52 weeks). Complications were low-grade fever/leukocytosis (n=11, 100%), pneumonia (n=1, 9.1%), pneumothorax (n=4, 36.4%), azotemia/acute renal failure (n=6, 54.6%), and hepatic encephalopathy (n=4, 36.4%). Five patients were suspected as having procedure-related mortality (45.5%) due to the occurrence of acute renal failure with hepatic failure. The overall survival was significantly longer in the success group than in the non-success group.
Although chemical pleurodesis may improve the clinical symptoms and the radiologic findings in as many as 72.7% of patients with refractory hepatic hydrothorax, a significantly high prevalence of procedure-related morbidity and mortality hinders the routine application of this procedure for such patients.
The Korean journal of hepatology. 12/2011; 17(4):292-8.
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Sung Keun Park,
Dong Il Park,
Seung Ha Park,
Jung Ho Park,
Hong Joo Kim,
Yong Kyun Cho,
Chong Il Sohn,
Woo Kyu Jeon, Byung Ik Kim,
Min-Kyung Kim,
Jeong Seon Ji,
Seon Ja Park,
Dong Soo Han
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ABSTRACT: This study was designed to determine the prevalence of microsatellite instability (MSI) among colorectal adenomas detected in patients ≤ 40 years of age and to compare the prevalence of MSI in young (≤ 40 years) and older (>40 years) patients with colorectal adenomas. Additionally, we attempted to identify the underlying cause of MSI in these patients.
We prospectively tested for the presence of MSI using five NCI markers in samples from the two patient groups. The frequency of MSI was compared and the underlying causes of MSI were determined by methylation specific PCR and germ-line mutation analysis for mismatch repair genes.
The frequency of MSI was higher in the ≤ 40 group than the >40 group (31.4% and 6.4%, respectively, p=0.0004). The MSI-high pattern was also more prevalent in the ≤ 40 group than the >40 group (15.7% and 2.5%, respectively, p=0.014). The hypermethylated hMLH1 gene was demonstrated in 7/8 (87.5%) patients with MSI-high in the ≤ 40 group and in 1/2 (50.0%) patients with MSI-high in the >40 group. No study subject showed a germline mutation of hMLH1 or hMSH2.
MSI-high was more frequent in young (≤ 40 years) patients with colorectal adenoma than in older (>40 years) patients. Hypermethylation of the hMLH1 gene appears to be an important cause of MSI-high in these patients.
Hepato-gastroenterology 11/2011; 58(110-111):1531-7. · 0.66 Impact Factor
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ABSTRACT: The aim of this study was to assess the patterns of lamivudine (LAM)-resistant mutations and the influence on biochemical and virological responses to adefovir (ADV) add-on LAM combination therapy in patients with LAM-resistant chronic hepatitis B (CHB).
Seventy-eight CHB patients with confirmed genotypic resistance to LAM, who initiated ADV add-on LAM combination treatment, were enrolled at our institution between April 2007 and April 2009.
The baseline tyrosine-methionine-aspartate-aspartate (YMDD) mutation patterns were as follows: rtM204I 45 (57.7%); and rtM204V + rtM204I/V 33 (42.3%). The decrease in the mean ± standard deviation (SD) serum log(10) HBV-DNA level did not differ between the patients carrying the rtM204I vs. rtM204IV +rtM204I/V mutations at 3, 6 and 12 months after the initiation of ADV add-on LAM combination treatment. The proportion of patients who achieved ALT normalization (<40 IU/L) 12 months after the initiation of ADV add-on LAM combination treatment were significantly higher in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations (39 [86.7%] vs. 22 [66.7%], P = 0.05). The proportion of patients in whom the log(10) HBV-DNA decreased <2 log(10) copies/ml, 6 months after the initiation of ADV add-on LAM combination treatment (non-responders), was significantly higher in patients with a rtM204V + rtM204I/V mutations than rtM204I mutation (7 [21.2%] vs. 2 [4.4%], P = 0.032).
Biochemical response at 12 months from baseline was better in patients with a rtM204I mutation than rtM204V+ rtM204I/V mutations. In addition, early treatment failure was more common in patients with rtM204V+ rtM204I/V mutations than a rtM204I mutation.
Liver international: official journal of the International Association for the Study of the Liver 09/2011; 32(2):303-10. · 3.82 Impact Factor
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ABSTRACT: The differential diagnosis of gallbladder (GB) cancer from inflammatory diseases in patients with a thickened GB wall is difficult, whereas the pre-operative diagnosis of GB cancer is critical for selecting the appropriate surgical modality. We evaluated the clinical usefulness of endoscopic ultrasonography (EUS) for the differential diagnosis of GB wall thickening.
The medical records, post-operative pathology reports, and images of EUS for 134 patients with GB wall thickening (>3 mm) who underwent laparoscopic or open cholecystectomies at our institution between December 2006 and February 2010 were retrospectively reviewed.
Thirteen patients (9.7%) had neoplastic GB wall thickening (11 with adenocarcinomas and two with adenosquamous carcinomas) and the remaining 121 patients (90.3%) had non-neoplastic GB wall thickening (117 with inflammatory GB wall thickening and four with adenomyomatosis). The mean (± standard deviation [SD], mm) GB wall thickness was 6.5 ± 3.3 and 19.4 ± 7.7 for non-neoplastic and neoplastic GB wall thickening, respectively (P < 0.01). The EUS variables which had a statistically significant association with neoplastic GB wall thickening were GB wall thickening >10 mm, disruption of the normal two layers of the GB wall, hypoechoic internal echogenecity, and the absence of gallstones. Based on the multivariate analyses, GB wall thickening >10 mm and hypoechoic internal echogenecity were independent predictive factors for neoplastic GB wall thickening.
The diagnostic power of EUS for differentiating neoplastic and non-neoplastic GB wall thickening could be improved by the appropriate application of some EUS variables.
Digestive Diseases and Sciences 08/2011; 57(2):508-15. · 2.12 Impact Factor
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ABSTRACT: Recent studies have suggested that the model for end-stage liver disease (MELD) score is superior to the Child-Turcotte-Pugh (CTP) score as a predictor of postoperative mortality, especially up to 90 days. This study aimed to determine whether MELD score can predict the postoperative outcome of patients with liver cirrhosis in Korea.
We reviewed the medical records of 98 patients with liver cirrhosis who underwent intra-abdominal surgery under generalized anesthesia between March 2003 and December 2008 at Kangbuk Samsung Hospital. Univariate and multivariate cox proportional hazards analyses were performed to determine the correlation between risk factors and mortality.
Eighty-two percent of patients (n=80) were male. Mean MELD score was 10.82 ± 3.84. Common causes of liver cirrhosis were hepatitis B (57.2%) and alcohol (22.4%). Ninety-day mortality ranged from 2.1% (MELD score, ≤ 9) to 25% (MELD score, ≥ 17). By multivariate analysis, MELD score > 9 (HR 2.490; [95% CI 1.116-5.554; p=.026]) and American Society of Anesthesiologists Class ≥ IV (HR 2.433; [95% CI 1.039-5.695; p=.041]) predicted mortality at 30 days after surgery. Only MELD score was a predictor of prognosis at 90 days (HR 2.446; [95% CI 1.118-5.352; p=.025]). Etiology of cirrhosis and CTP score were not predictors of mortality.
MELD score was a useful predictive parameter of postoperative mortality at 30 days and 90 days, independent of the etiology of cirrhosis.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 06/2011; 57(6):340-5.
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In Kyung Sung,
Young Choon Kim,
Jung Won Yun,
Hyun Il Seo,
Dong Il Park,
Yong Kyun Cho,
Hong Joo Kim,
Jung Ho Park,
Chong Il Sohn,
Woo Kyu Jeon, Byung Ik Kim,
Suk Joong Oh,
Byung Ho Son,
Chang Hak Yoo,
Jin Hee Sohn,
Hwa Young Lee,
Kyung Hee Won
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ABSTRACT: Stomach cancer can be easily diagnosed via endoscopy, but also possible to be missed. The aim of this study was to investigate the clinical and endoscopic characteristics of advanced gastric cancers that were not diagnosed based on endoscopic examination.
We evaluated patients who had newly diagnosed advanced gastric cancer that was undetected via endoscopy within the last six months.
Sixteen patients were included in this study. The locations of the cancers were the cardia in six cases, the greater curvature side of the body in eight cases and the antrum in two cases. The histological findings were tubular type adenocarcinoma in 11 cases, with ten cases of moderately to poorly differentiated adenocarcinoma and five cases of signet ring cell type adenocarcinoma.
Even advanced gastric cancer lesions may not be detected during endoscopy. If a patient continues to complain of upper gastrointestinal symptoms, even though endoscopy does not find abnormal findings, repeated endoscopy and/or additional diagnostic studies should be considered.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 05/2011; 57(5):288-93.
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Young-Choon Kim,
Yong-Kyun Cho,
Won-Young Lee,
Hong-Joo Kim,
Jung-Ho Park,
Dong-Il Park,
Chong-Il Sohn,
Woo-Kyu Jeon, Byung-Ik Kim,
Se-Eun Park,
Eun-Jung Rhee,
Cheol-Young Park,
Ki-Won Oh,
Sung-Woo Park,
Sun-Woo Kim,
Seung-Ho Ryu
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ABSTRACT: Adipocyte-specific fatty acid-binding protein (A-FABP) is a cytoplasmic protein that is expressed in adipocytes and is closely associated with insulin resistance, metabolic syndrome, and Type 2 diabetes. We investigated the relationship between A-FABP as a surrogate marker of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD) in apparently healthy subjects. We assessed clinical and biochemical metabolic parameters and measured serum levels of A-FABP, high-sensitivity C-reactive protein and tumor necrosis factor-α (TNF-α) in 494 subjects who were divided into two groups according to the presence of NAFLD by abdominal ultrasonography. All parameters associated with metabolic syndrome were significantly higher in patients with NAFLD (P<.001). A-FABP showed positive correlation with TNF-α, homeostasis model assessment index of insulin resistance (HOMA-IR), and metabolic syndrome (P<.001) when adjusted for age and sex. The odds ratio for the risk of NAFLD in the highest tertile of A-FABP compared with the lowest tertile was 7.36 (CI 3.80-14.27, P<.001) after adjustment for age and sex; 4.52 (CI 2.22-9.20, P<.001) after adjustment for age, sex, HOMA-IR and metabolic syndrome and 2.86 (CI 1.11-7.35, P<.05) after further adjustment for all metabolic parameters including TNF-α. The serum level of A-FABP was independently associated with NAFLD and showed significant correlation with TNF-α, HOMA-IR, and metabolic syndrome.
The Journal of nutritional biochemistry 03/2011; 22(3):289-92. · 4.29 Impact Factor
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ABSTRACT: There have been no trials comparing the prophylactic effect of oral quinolone and intravenous cephalosporin antibiotics and elucidating the predictive factors for the occurrence of bacterial infections in cirrhotic patients with gastrointestinal bleeding in Asian-Pacific region.
One hundred and thirteen patients with advanced liver cirrhosis and active gastrointestinal hemorrhage were enrolled in our study. The patients were randomly allocated into either the oral ciprofloxacin group (n = 50, 500 mg every 12 h) or the intravenous ceftriaxone group (n = 63, 2.0 g per day for 7 days).
Proven or possible infections were significantly more frequent in the patients in the oral ciprofloxacin group (34.0%) than the intravenous ceftriaxone group (14.3%, P = 0.002). The intestinal permeability index (IPI, mean [SD]) measured the day after admission was significantly higher in the patients with proven or possible infections (1.45 [0.96]) compared with the no infection group (0.46 [0.48], P <0.01). By multivariate analysis, oral ciprofloxacin prophylaxis and higher IPI at the time of inclusion were independent and significant predictors for proven or possible infections. By receiver operating characteristic curve analysis, the best cutoff value of IPI for the prediction of the occurrence of bacterial infection was 0.62%.
The frequency of proven or possible infections was significantly lower in the intravenous ceftriaxone group compared with the oral ciprofloxacin group. The IPI measured the day after admission is a good clinical parameter predicting the occurrence of infection in these patients.
Journal of Gastroenterology and Hepatology 03/2011; 26(3):550-7. · 2.87 Impact Factor
