Increased Expression of S100B and RAGE in a Mouse Model of Bile Duct Ligation-induced Liver Fibrosis.

BACKGROUND: Liver fibrosis is defined as the accumulation of the extracellular matrix and scar formation. The receptor for advanced glycation end products (RAGE) has been demonstrated to participate in fibrogenesis. S100B is a ligand of RAGE and exerts extracellular functions by inducing a series of signal transduction cascades. However, the involvement of S100B and RAGE in cholestasis-induced liver fibrosis remains unclear. In this study, we investigated S100B and RAGE expression during liver fibrosis in mice that underwent common bile duct ligation (BDL). METHODS: BDL was performed in 10-week-old male C57BL/6J mice with sham control (n = 26) and BDL (n = 26) groups. Expression levels of S100B, RAGE and fibrotic markers in the livers from both groups at week 1 and 3 after BDL were examined by western blot and quantitative real-time reverse transcription polymerase chain reaction analysis. Liver fibrotic changes were examined by histological and ultrastructural analysis. RESULTS: Histological staining with Sirius Red and the evaluation of the messenger RNA expression of fibrotic markers showed noticeable periportal fibrosis and bile duct proliferation. S100B was mainly present in bile duct epithelial cells, and its expression was upregulated in proportion to the ductular reaction during fibrogenesis by BDL. RAGE expression was also increased, and interestingly, triple immunofluorescence staining and transmission electron microscopy showed that both S100B and RAGE were expressed in proliferating bile duct epithelial cells and activated hepatic stellate cells (HSCs) of the BDL livers. In addition, in rat HSCs (HSC-T6), treatment with recombinant S100B protein significantly increased fibrotic markers in a dose-dependent manner, and RAGE small interfering RNA (siRNA) suppressed S100B-stimulated upregulation of fibrotic markers compared with cells treated with scramble siRNA and S100B. CONCLUSION: These findings suggest that the increased expression of S100B and RAGE and the interaction between S100B and RAGE may play an important role in ductular reaction and liver fibrosis induced by BDL.

Effect of gastroprotective agents on upper gastrointestinal bleeding in patients receiving direct oral anticoagulants.

OBJECTIVES: Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs. METHODS: We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan-Meier method was performed to determine the rate of UGIB and its association with GPAs administration. RESULTS: Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p < .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065). CONCLUSIONS: The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.

Prognostic Significance of Hemodynamic and Clinical Stages in the Prediction of Hepatocellular Carcinoma.

BACKGROUND & GOALS: Early identification of hepatocellular carcinoma (HCC) is associated with improved survival for patients with chronic liver disease (CLD). We evaluated the prognostic significance of hemodynamic stage (HS) and clinical stage (CS) in predicting HCC in CLD patients. METHODS: Between January 2006 and May 2014, 801 patients with CLD who underwent hepatic venous pressure gradient (HVPG) measurement were prospectively enrolled. HS was classified by HVPG (mm Hg) as follows: HS-1 (HVPG≤6), HS-2 (612 mm Hg (P=0.033, OR=2.17), CS>2 (P=0.039, OR=2.36), and alpha-fetoprotein (AFP; P=0.017, OR=1.01) were significant predictors of HCC development in all patients. For patients with cirrhosis, ascites aggravation (OR=2.51), HVPG >12 mm Hg (OR=2.46), and CS >2 (OR=2.62) were correlated with HCC development. Areas under receiver operating characteristic curves of the prediction-model, CS, HVPG score, and AFP were 0.797, 0.707, 0.701, and 0.653, respectively. CONCLUSIONS: HCC development correlates with advancing liver fibrosis or disease as measured by HS and CS. In addition, ascites aggravation and elevated AFP appears to be associated with increased incidence of HCC.

Is it beneficial to perform surgical resection in elderly patients more than 80 years old with advanced gastric cancer?

OBJECTIVES: With the aging population, the number of elderly patients diagnosed with gastric cancer is increasing. However, determining treatment strategies for elderly patients with gastric cancer is controversial. The aim of this study is to evaluate the usefulness of surgical treatment on elderly patients aged ≥80 years with advanced gastric cancer. METHODS: A total of 147 elderly patients who were diagnosed with advanced gastric cancer from August 2001 to December 2015 were retrospectively analyzed. We compared the clinicopathological features and prognoses of 94 elderly patients (80-85 years) and 53 extreme-elderly patients (≥86 years) according to treatment modalities. RESULTS: In the elderly group, the 3-year overall survival (OS) rates of the surgical resection group and supportive care group were 42.1% and 4.0%, respectively (p < .001). In the extreme-elderly group, the 3-year OS rates of the surgical resection group and supportive care group were 36.4% and 8.0%, respectively (p = .028). The post-operative mortality rate of the elderly group and extreme-elderly group was 5.6% and 9.1%, respectively. In the analysis of risk factors associated with survival, surgical resection was a significantly good prognostic factor in the elderly group (hazard ratio [HR] = 0.277; p = .003) compared with supportive care. In the extreme-elderly group, surgical resection was associated with good prognosis but did not reach statistical significance (HR = 0.491; p = .099). CONCLUSIONS: These results suggest that elderly patients aged 80-85 years with advanced gastric cancer could expect a better prognosis with surgical resection. However, extreme-elderly patients aged ≥86 years should consider the risks and benefits of surgical treatment.

Comparison of the long-term efficacy between entecavir and tenofovir in treatment- naïve chronic hepatitis B patients.

BACKGROUND: There have been limited studies directly comparing the long-term efficacy between entecavir (ETV) and tenofovir disoproxil fumarate (TDF). This study was aimed to compare the long-term efficacy between them in treatment-naïve chronic hepatitis B (CHB). METHODS: Out of 345 CHB patients who received first line therapy with ETV (n = 200) or TDF (n = 145) in a cohort, 210 patients were analyzed using propensity score matching, at a ratio of 1:1. RESULTS: Two groups showed no difference in baseline characteristics. During the follow-up of 12 months, HBV DNA levels were similarly suppressed in both groups (ETV vs. TDF; -5.01 vs. -5.242 log10IU/mL, P = 0.559). At month 12, both groups showed no difference in terms of the serologic, biochemical and virologic (VR) response. In multivariate analysis, the initial virologic response at 3 months (IVR-3) was independent factor for VR at 1 year. During the long-term follow-up, HBV DNA levels were more strongly suppressed by TDF than ETV in hepatitis B e antigen (HBeAg) positive patients (P = 0.035), especially with high viral load (P = 0.012), although there was no significant difference in overall VR between two groups. The type of antivirals was not an independent factor for long-term VR. CONCLUSIONS: Although either ETV or TDF, overall, may show a comparable long-term antiviral efficacy in treatment-naïve CHB, TDF might be better regimen than ETV in the subgroup of HBeAg-positive CHB, especially with a higher HBV DNA levels.

Comparison of endoscopic submucosal dissection and surgical resection for treating gastric subepithelial tumours.

OBJECTIVE: For subepithelial tumours (SETs) of the stomach, surgical resection is the gold standard treatment. With the recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative treatment for SETs. The aim of our study was to evaluate the clinical outcomes of ESD for treating gastric SETs compared with surgical resection. METHODS: Between January 2006 and September 2014, 55 patients with gastric SETs (13 gastrointestinal stromal tumours (GISTs), 27 leiomyomas, and 15 others) were treated by ESD and 27 patients (19 GISTs, two leiomyomas, and six others) underwent surgical resection. We retrospectively reviewed the therapeutic outcomes, procedure-related complications, post-procedure hospital stays, and medical costs of the two groups. RESULTS: The complete resection rate of the ESD group was lower than that of the surgery group (81.8% vs. 100%, p = 0.026). Although the incidence of complications that occurred with ESD was higher than that associated with surgical resection, there were no significant between-group differences (12.5% vs. 3.7%, p = 0.261), and all complicated cases were successfully treated without mortality. The ESD group had significantly shorter post-procedural hospital stays (median five days vs. eight days, p = 0.034) and lower medical costs (median $2374 vs. $4954, p <0.001) than the surgery group. There were no recurrences in either group during the follow-up period. CONCLUSIONS: ESD is an efficient treatment tool for gastric SETs in selected patients. Additionally, ESD has the advantages of shorter hospital stays and lower medical costs compared with surgery.

Portal hypertensive gastropathy as a prognostic index in patients with liver cirrhosis.

BACKGROUND: Portal hypertensive gastropathy (PHG) is a frequently overlooked complication of liver cirrhosis (LC). The clinical implications of PHG as a prognostic factor of LC or a predictive factor for the development of hepatocellular carcinoma (HCC) have not been established. The aim of this study was to assess the clinical significance of PHG in patients with LC. METHODS: Patients with LC were prospectively enrolled and followed in a single tertiary hospital in the Republic of Korea. Baseline hepatic vein pressure gradient (HVPG) was measured, and esophagogastroduodenoscopy (EGD) was performed. The associations of PHG with HVPG, survival and the development of HCC were evaluated. RESULTS: A total of 587 patients were enrolled. The mortality rate was 20.3 % (n = 119), and HCC developed in 9.2 % (n = 54) during the follow-up period (32.6 ± 27.8 months). The grade of PHG was well correlated with HVPG (no PGH: median 9.2 [IQR: 7.2-16.7], mild PHG: 14.6 [10.1-19.3], and severe PHG: 17.3 [12.3-21.5], P < 0.001), as well as with Child-Pugh class, MELD score or survival. However, it was not associated with the development of HCC. The grade of PHG (HR 3.29, 95 % CI: 1.12-9.63, severe vs. no PHG) and Child-Pugh class (HR 3.53, 95 % CI: 1.79-6.97, Child C vs A) showed significant associations with mortality. CONCLUSION: PHG was well correlated with portal hypertension and could be used as a prognostic factor for LC but not for the prediction of HCC.

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer.

BACKGROUND: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. METHODS: Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day cycle. RESULTS: Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. CONCLUSION: These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

Effect of low-dose proton pump inhibitor on preventing upper gastrointestinal bleeding in chronic kidney disease patients receiving aspirin.

BACKGROUND AND AIM: Upper gastrointestinal bleeding (UGIB) leads to significant morbidity and mortality in chronic kidney disease (CKD) patients. This study determined the efficacy of using a low-dose proton pump inhibitor (PPI) to reduce the risk of non-variceal UGIB in CKD patients receiving aspirin. METHODS: We retrospectively reviewed the medical records of 500 CKD patients who received aspirin between January 2008 and March 2013. Cumulative incidence analysis using the Kaplan-Meier method was performed to analyze the rate of non-variceal UGIB and association with the administration of low-dose PPI. RESULTS: Of the 500 patients, 191 received low-dose PPI. Over the follow-up period, which lasted 1067 person-years, three patients in the low-dose PPI group (8.9 per 1000 person-years) and 19 patients in the non-PPI group (25.9 per 1000 person-years) developed non-variceal UGIB, respectively (P = 0.113). Low-dose PPI use did not decrease the risk of UGIB in CKD patients, including patients who did not receive dialysis (P = 0.127). However, according to the subgroup analysis of 230 patients who received dialysis, the low-dose PPI group (14.4 per 1000 person-years) demonstrated significantly reduced incidence and risk of non-variceal UGIB in comparison with the non-PPI group (53.8 per 1000 person-years) (P = 0.032). CONCLUSION: Prophylactic low-dose PPI can reduce the risk of non-variceal UGIB in dialysis patients receiving aspirin.

Adefovir and lamivudine combination therapy in patients with entecavir-resistant chronic hepatitis B: antiviral responses and evolution of mutations.

OBJECTIVE: This study was designed to prospectively evaluate the antiviral responses and evolution of resistance mutations during adefovir (ADV) plus lamivudine (LMV) therapy in patients with entecavir (ETV)-resistant hepatitis B virus (HBV) infection. METHODS: Twenty chronic hepatitis B (CHB) patients who had been receiving ETV for more than 6 months and developed virologic breakthrough due to ETV resistance were consecutively enrolled. RESULTS: Patients received ADV plus LMV therapy for 12 months. The baseline mean serum HBV DNA level was 5.59 ± 1.28 log10 IU/ml. The rtT184L/I/A/F (50%), rtS202G (25%) and mixed ETV-resistant mutations (25%) were detected at enrollment. The mean reduction in serum HBV DNA levels from baseline to 12 months was -2.3 ± 1.06 log10 IU/ml (p < 0.001). Seventeen patients were followed up for the full 12 months, and complete virologic response (HBV DNA <20 IU/ml) was observed in 4 patients (23.5%). Among the remaining 13 patients who still had detectable HBV DNA, 7 patients showed disappearance of ETV-resistant mutations or reduction of the proportion of ETV-resistant mutants. An ADV- and LMV-resistant mutant (rtA181T) emerged in 2 patients (11.7%). CONCLUSIONS: ADV plus LMV combination therapy suppresses ETV-resistant mutants in the viral population and significantly reduces serum HBV DNA levels in ETV-resistant CHB patients.

The Loop-Tip Wire for Selective Cannulation during ERCP in Patients with Billroth II Anastomosis: A Preliminary Feasibility Study.

BACKGROUND/AIMS: Selective cannulation of common bile duct remains technically challenging in patients with Billroth II anastomosis due to an altered anatomy. We aimed to determine the feasibility of performing wire-assisted cannulation using a loop-tip wire during ERCP in patients with Billroth II anastomosis. METHODOLOGY: We retrospectively analyzed a database of nine patients with Billroth II anastomosis who underwent ERCP using a loop-tip wire from January 2009 to July 2013 in the Hallym University Sacred Heart Hospital. Clinical characteristics and procedure-associated clinical outcomes were analyzed. RESULTS: The mean age of the patients was 73.7 years, and the male/female ratio was 2:1. The success rate of selective biliary cannulation was 77.8%. The mean cannulation time was 3.6 minutes (range, 1-9 minutes). Two patients who had failed in selective cannulation underwent infundibulotomy using a needle-knife papillotome, but one of the two patients had failed in biliary stone removal and finally underwent surgery. Six patients underwent endoscopic sphincterotomy. Complete clearance of bile duct stones was achieved in seven patients in one session. There was one case of mild post-ERCP pancreatitis (11.1%). CONCLUSIONS: The loop-tip wire can be an alternative instrument for wire-assisted selective cannulation in patients with Billroth II anastomosis.

Phylogenetic analyses of HBV pre-s/s genes in mother-child pairs with long-term infection by presumed vertical transmission.

Vertical transmission from mother to child, the main route of chronic hepatitis B virus (HBV) infection in the East Asia, is considered one of the most important predictors for the response to antiviral therapies as well as its complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is critical in both etiologic and prognostic aspects to confirm whether or not chronic HBV infection is acquired vertically. This study investigated whether mother-to-child infection could be proved by the phylogenetic analyses of HBV pre-S/S genes ever since several decades have elapsed in mother-child pairs with presumed vertical transmission. The pre-S and S regions of HBVs were compared and analyzed phylogenetically in a total of 36 adults (18 mother-child pairs) with chronic HBV infection. All of the isolates of HBV were genotype C and serotype adr. The divergence between mothers and offsprings was 0 to 1.5%. Phylogenetic trees revealed that 17 of 18 pairs (94%) with presumed vertical transmission were grouped into the same cluster. Vertical transmission from mother to child could be strongly suggested even in adults with a history of several decades of HBV infection using the phylogenetic analyses of pre-S and S genes.

Adding adefovir vs. switching to entecavir for lamivudine-resistant chronic hepatitis B (ACE study): a 2-year follow-up randomized controlled trial.

BACKGROUND: Management of lamivudine-resistant chronic hepatitis B (CHB) remains challenging, as inappropriate choice of treatment may cause multidrug resistance. Until now, randomized trials directly comparing adding adefovir and switching to entecavir monotherapy have not been reported. AIMS: This multicentre prospective randomized study was designed to compare the efficacy of these two strategies. METHODS: Two hundred and nineteen lamivudine-resistant CHB patients were randomized to either adefovir-lamivudine combination group or entecavir monotherapy group (n = 110 vs. 109), and followed up for 24 months. RESULTS: One hundred and eighty patients completed this study. At month 24, virological response rate [hepatitis B virus (HBV) DNA <60 IU/ml] was higher in the adefovir-lamivudine combination group compared with entecavir group (56.7% vs. 40%, P = 0.025), although biochemical and serological response rates were not significantly different. Genotypic resistance (9.2% vs. 24.6%, P = 0.005) and combined viral breakthrough (2.0% vs. 17.6%, P < 0.001) were more frequent in the entecavir group. However, by subgroup analysis, virological response rates were not significantly different between the two therapies in HBeAg-positive patients (44.9% vs. 35.7%, P = 0.268) or in patients with high baseline HBV DNA (≥7 log IU/ml) (40.7% vs. 31.3%, P = 0.320) at month 24. CONCLUSION: This study showed that adefovir-lamivudine combination provides significantly higher antiviral efficacy and the lower resistance rate compared with the entecavir monotherapy in the management of lamivudine-resistant CHB. However, it had limited efficacy in HBeAg-positive patients or in patients with high baseline HBV DNA.

Multicenter comparison of PEG-IFN α2a or α2b plus ribavirin for treatment-naïve HCV patient in Korean population.

BACKGROUND: Two recent Italian studies suggested that Pegylated-interferon (PEG-IFN) alfa-2a achieves a higher sustained virological response (SVR) rate than PEG-IFN alfa-2b. We intended to compare the efficacy and safety of PEG-IFN alfa-2a with those of PEG-IFN alfa-2b in Korean patients with chronic hepatitis C virus (HCV). METHODS: This retrospective, multi-center trial was conducted on 661 treatment-naïve chronic HCV patients. Patients received PEG-IFN alfa-2a (180 µg/week; n=402) or PEG-IFN alfa-2b (1.5 µg/kg/week; n=259) with ribavirin (800-1200 mg/day) for 24 or 48 weeks according to HCV genotypes. RESULTS: Early virologic response and sustained virologic response (SVR) rates were not significantly different between two PEG-IFN groups both in patients with HCV genotype 1 (all P-values>0.05) and 2/3 (all P-values>0.05). SVR rates were not different between two groups in each categorized baseline characteristics: age (years) (≤ 50 and >50), HCV viral load (IU/mL) (≤ 7 × 10(5) and >7 × 10(5)), and hepatic fibrosis (F0-2 and F3-4) (all P-values >0.05). In additional analysis for 480 patients who sufficiently complied with treatment doses and duration (80/80/80 rule) and propensity-score matched analysis, SVR rates were not different between two groups both in patients with HCV genotype 1 and 2/3 (all P-values >0.05). Adverse event rates were similar between two groups. CONCLUSIONS: Unlike the Western data, efficacy and safety of PEG-IFN alfa-2a were similar to those of PEG-IFN alfa-2b in chronically HCV-infected Korean patients regardless of age, HCV viral load, and hepatic fibrosis.

Clinical features of autoimmune hepatitis and comparison of two diagnostic criteria in Korea: a nationwide, multicenter study.

BACKGROUND AND AIM: As a rare liver disease, little is known about autoimmune hepatitis (AIH). This study investigated the clinical features and compared two diagnostic criteria of AIH in Korea. METHODS: A nationwide, multicenter, retrospective analysis was done of data of adult patients diagnosed with AIH from January 2005 to December 2009. RESULTS: The enrolled patients (n = 343; mean age, 52.8 years; range, 19-87 years; 12% male, 88% female) met diagnostic criteria of AIH according to the revised original criteria (n = 311) or the simplified criteria (n = 250). At diagnosis, 30.6% were asymptomatic, 22.7% were cirrhotic, and 4.3% displayed hepatic decompensation. The positive results for anti-nuclear antibody, smooth muscle antibody, and anti-liver/kidney microsomal antibody were 94.2%, 23.0%, and 2.9%, respectively. Definite AIH and probable AIH according to the revised original criteria were 24.8% and 65.3%, respectively, while those according to the simplified criteria were 34.4% and 38.5%, respectively. The diagnostic sensitivity and positive predictive value of simplified criteria in comparison with the revised original criteria were 69.9% and 86.4%, respectively. As an initial therapy, corticosteroid (37.7%) or corticosteroid with azathioprine (36.8%) was administered. Remission, incomplete response, and treatment failure were noted with 85.7%, 10.5%, and 3.9% of patients, respectively. CONCLUSIONS: Autoimmune hepatitis in Korea is mostly type I, showing a mean age of 53 years with comparable clinical features to other countries. The concordant rate of the two diagnostic criteria was rather low with modest sensitivity of the simplified criteria. Further studies on the validation of the diagnostic criteria are warranted.

Endoscopic submucosal dissection as a treatment for gastric subepithelial tumors that originate from the muscularis propria layer: a preliminary analysis of appropriate indications.

BACKGROUND: Endoscopic submucosal dissection (ESD) is a well-established method for the treatment of gastrointestinal epithelial tumors. However, the treatment of gastric subepithelial tumors (SETs) that originate from the muscularis propria layer still depends primarily on surgical techniques. We evaluated the appropriate indications for ESD in the treatment of SETs that originate from the muscularis propria layer. METHODS: Thirty-five patients with gastric SETs that originate from the muscularis propria layer who underwent ESD were enrolled, and the charts were retrospectively reviewed to investigate the parameters predictive complete resection and complications. RESULTS: The mean age of the patients was 54.15 ± 9.3 years, and the male/female ratio was 2:3. Twenty-eight of the 35 SETs (85.7%) were movable, and 15 (45.7%) had a positive rolling sign. The most frequent location of the SETs was high body (n = 14). The most common pathological diagnoses were leiomyoma (60%) and gastrointestinal stromal tumor (28.6%). The complete resection rate was 74.3%. A positive rolling sign (p = 0.022) and small tumor size (≤20 mm; p = 0.038) were significantly associated with complete resection. Two patients (6.1 %) developed perforations that required surgical treatment; their SMTs were neurogenic tumors with fixed lesion. Tumor mobility was significantly associated with perforation (p = 0.017). CONCLUSIONS: The ESD method appears to be relatively safe for use in the complete resection of SETs that originate from the muscularis propria layer. Small tumor size (≤20 mm) and a positive rolling sign are appropriate indications for ESD.

Clinical characteristics of patients with Mycoplasma pneumoniae-related acute hepatitis.

BACKGROUND/AIMS: Although the hepatobiliary manifestations of Mycoplasma pneumoniae infection have been described in several previous studies, controversies still remain. The aim of this study was to evaluate the clinical characteristics of patients with M. pneumoniae-related hepatitis and compare to those with M. pneumoniae infection but not hepatitis. METHODS: We reviewed the medical chart of patients diagnosed with M. pneumoniae infection serologically. RESULTS: Among the 117 patients with M. pneumoniae infection enrolled in the study, 25 showed acute hepatitis without any evidence of another cause. Patients with hepatitis presented with prodromal symptoms more frequently and also had a higher body temperature and C-reactive protein (CRP) levels than patients without hepatitis. Frequencies of respiratory tract involvement were not different between two groups. Clinical signs recovered within three weeks in both groups following the institution of antibiotic therapy. Multivariate analysis revealed that male sex, age <40 years, and high CRP levels were significantly linked to M. pneumoniae-related hepatitis. CONCLUSIONS: We found that acute hepatitis associated with M. pneumoniae occurred in about 21% of all M. pneumoniae infections, and gender, age, and CRP levels were factors related to the occurrence of M. pneumoniae-related hepatitis.

A phase II study of gemcitabine, erlotinib and S-1 in patients with advanced pancreatic cancer.

Background: We evaluated the efficacy and safety of gemcitabine in combination with erlotinib and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically-proven locally advanced, recurrent, or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine was administered at 1,000 mg/m2 intravenously on days 1 and 8, erlotinib was administered at 100 mg/day on days 1-21, and S-1 was administered at 60 mg/m2 on days 1-14 every 21 days and continued to a maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from the second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1-8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The confirmed overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and the disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusion: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer.

[Gastritis cystica profunda accompanied by multiple early gastric cancers].

Gastritis cystica profunda (GCP) is a rare disease which shows multiple cystic gastric glands within the submucosa of the stomach. GCP lesions mainly develop at the site of gastroenterostomy and exhibit benign behavior. However, there have been a number of debates over its malignant potential. Several reports have documented GCP accompanied by gastric carcinomas, but the relationship between the two conditions remains uncertain. Here we report two cases of GCP with dysplasia accompanied by synchronous multiple early gastric cancers without previous gastric surgery.

[Validity and reliability of the nonalcoholic fatty liver diseases activity score (NAS) in Korean NAFLD patients and its correlation with clinical factors].

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is commonly diagnosed using the semi-quantitative grading and staging system proposed by Brunt et al. in 1999. The Pathology Committee of the NASH established the nonalcoholic fatty liver diseases (NAFLD) activity score (NAS) in 2005. The aim of this study was to elucidate the validity and reliability of the NAS in Korean NAFLD patients. METHODS: Fifty-six patients on whom sonography-guided liver biopsy for well-defined NAFLD was performed between 1999 and 2007 were identified retrospectively. Two pathologists evaluated each biopsy sample. NAFLD was evaluated using both the grading system developed by Brunt et al. and the NAS. Each pathologist was blinded to the patients' clinical data and scored independently. We evaluated the body mass index (BMI), liver enzymes, lipid profile, peripheral insulin resistance, leptin, insulin/c-peptide ratio, ferritin, and fasting blood glucose. RESULTS: The patients were aged 32.1+/-12.5 years (mean+/-SD) and comprised 44 males (78.6%). Patients with different grades at the two grading systems had mild steatosis or ballooning changes with fibrosis, and 36.6% of them were borderline cases (NAS of 3 or 4). The interobserver agreement on diagnostic category was 0.748 (P<0.001) for the NAS (using weighted kappa statistics). Elevated fasting glucose, ALT, and triglyceride were associated with the NAS. CONCLUSIONS: The simple and reproducible NAS was found to be a useful pathologic grading system in Korean NAFLD patients. However, the proportion of borderline cases based on the NAS was high. The "wait and see" strategy is necessary for evaluating the long-term prognosis.