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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.

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.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.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).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.

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., Graphical Abstract

Concurrent presentation of acute hepatitis A virus (HAV) infection and Graves' disease has not been reported in literature worldwide. Although there is no well-established mechanism that explains the induction of Graves' disease by HAV to date, our case suggests that HAV infection may be responsible for inducing Graves' disease. A healthy 27-year-old female presented fever, palpitation, and diarrhea, and she was subsequently diagnosed as acute HAV infection. Concurrently, she showed hyperthyroidism, and the diagnosis was made as Graves' disease. She had never had symptoms that suggested hyperthyroidism, and previous thyroid function test was normal. Acute HAV infection was recovered by conservative management, however, thyroid dysfunction was maintained even after normalization of liver enzymes. Methimazole was used to treat Graves' disease. We report a case of concurrent acute HAV infection and Graves' disease in a patient without preexisting thyroid disease. This suggests that HAV infection may be a trigger for an autoimmune thyroid disease in susceptible individuals.

Objectives. Terlipressin is safely used for acute variceal bleeding. However, side effects, such as hyponatremia, although very rare, can occur. We investigated the development of hyponatremia in cirrhotic patients who had acute variceal bleeding treated with terlipressin and the identification of the risk factors associated with the development of hyponatremia. Design and Methods. This retrospective, case-control study investigated 88 cirrhotic patients who developed hyponatremia and 176 controls that did not develop hyponatremia and were matched in terms of age and gender during the same period following terlipressin administration. Results. The overall change in serum sodium concentration and the mean lowest serum sodium concentration were 3.44 ± 9.55 and 132.44 ± 8.78 mEq/L during treatment, respectively. Multivariate analysis revealed that baseline serum sodium was an independent positive predictor, and the presence of baseline serum creatinine, HBV, DM, creatinine, and shock on admission was independent negative predictors of hyponatremia (P<0.05). Conclusion. The presence of HBV, DM, the baseline serum sodium, shock on admission, and especially baseline creatinine may be predictive of the development of hyponatremia after terlipressin treatment. Therefore, physicians conduct vigilant monitoring associated with severe hyponatremia when cirrhotic patients with preserved renal function are treated with terlipressin for variceal bleeding.

Postoperative fluid collection is a major complication after pancreaticoduodenectomy and can lead to increased mortality and hospital length of stay. External drainage has widely been used for postoperative fluid collections. Recently, EUS-guided drainage has also been used successfully in treating postoperative fluid collections. A 60-year-old woman was admitted due to weight loss and jaundice. She underwent pancreaticoduodenectomy for cholangiocarcinoma of the common bile duct. After 2 weeks, she had fever with abdominal pain and leukocytosis. CT showed a increased fluid collection in superior recess of lesser sac and EUS-guided drainage was performed. The symptoms resolved without any complication after drainage. This is the first case report of EUS-guided drainage for lesser sac in Korea. Korean J Pancreatobiliary 2015;20(4):228-233

Hepatic stellate cells (HSCs) play pivotal roles in hepatic fibrosis as they synthesize glial fibrillary acidic protein (GFAP), which is increased in activated HSCs. GFAP-expressing HSCs and myofibroblasts accumulate in and around hepatic fibrosis lesions. Peptidylarginine deiminase 2 (PAD2) is responsible for the citrullination of GFAP (cit-GFAP). However, the involvement of PAD2 and cit-GFAP in hepatic fibrosis remains unclear. To determine the expression of PAD2 and cit-GFAP in hepatic fibrosis, C57BL/6 mice underwent bile duct ligation (BDL) or a sham operation. In BDL livers, the expression of PAD2 and its enzyme activity were significantly increased compared with controls. In addition, PAD2-postitive cells were rarely observed in only the portal vein and the small bile duct in sham-operated livers, whereas an increased number of PAD2-positive cells were detected in the bile duct and Glisson's sheath in BDL livers. Interestingly, PAD2 was colocalized with α-SMA-positive cells and CK19-positive cells in BDL livers, indicating upregulated PAD2 in activated HSCs and portal fibroblasts of the livers of BDL mice. We also found that citrullinated proteins were highly accumulated in the livers of BDL mice compared with controls. Moreover, the expression level of GFAP and the amount of cit-GFAP were higher in BDL livers than in control livers. In correlation with PAD2 localization, cit-GFAP was observed in α-SMA-positive and CK19-positive cells in the livers of BDL mice. These results suggest that the increased expression and activation of PAD2 along with increased citrullinated proteins, specifically cit-GFAP, may play important roles in the pathogenesis of hepatic fibrosis.

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.

A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC). Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m2 intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m2 oral S-1 on days 1–14 of each cycle. The treatment was repeated every 3 weeks. Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6 %), intrahepatic and extrahepatic bile ducts in 23 (60.5 %), and the ampulla of Vater in 3 (7.9 %) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6 % (95 % CI 8.5–36.7] in the per-protocol (PP) population, and 18.4 % (95 %CI 6.1–30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5 % (95 %CI 60.6–87.6) in the PP population. The median progression-free survival was 4.4 months (95 %CI 1.8–6.9), and the median overall survival was 9.0 months (95 %CI 4.0–13.9) with a 1-year survival rate of 44.7 % (95 %CI 29.0–61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1 %), 9 (25.7 %), 2 (5.7 %), and 2 (5.7 %) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4 %), anorexia (2.9 %), and renal toxicity (2.9 %). Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

The reactivation of hepatitis B virus (HBV) is well known complication among lymphoma patient related with chemotherapy. Rituximab is monoclonal antibody that targets B-lymphocytes for treatment of lymphoma and it increases reactivation of HBV. Although most of reactivation occurs in HBV carrier, it can also rarely occur when hepatitis B surface antigen (HBsAg) is negative. Furthermore it is less frequently reported in lymphoma patient when HBV serology shows HBsAg is negative and anti-HBs is positive. We report a case of HBV reactivation following 6 cycle of rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy for diffuse large B-cell lymphoma in HBsAg negative/anti-HBs positive 58-year-old male, with a review of the literature.

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.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.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).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.

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.

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. Graphical Abstract Keywords: Hepatitis B Virus, Multilocus Sequence Typing, Mutation, Infectious Disease Transmission, Vertical INTRODUCTION Chronic hepatitis B virus (HBV) infection is considered as a major risk factor of chronic liver diseases including cirrhosis and hepatocellular carcinoma (HCC). Parenteral infection during the adulthood is a main route of chronic HBV infection in western countries, whereas vertical (or perinatal) transmission from mother to child is thought of a critical one in the East Asia (1, 2). Of importance, the modes of infection, together with other factors such as viral titer, genotype, genetic mutations of HBV, age and gender of the host may determine the long-term clinical course of chronic HBV infection. The mode of vertical transmission, in particular, is one of the most important determinants for the therapeutic responsiveness to antiviral therapies, or the natural course in terms of hepatitis e antigen seroconversion and even the development of complications (3, 4, 5). Previous studies using a comparison of HBV DNA sequences and phylogenetic analyses have shown that HBV of chronically infected children originates mainly from their respective mothers or fathers (6, 7, 8). Although there has been hitherto a molecular evidence of vertical transmission of HBV in the pairs of mother-young child, it is improbable to identify exactly the mode of infection (especially vertical vs non-vertical) in real clinical settings because medical information from the adults for the source of HBV, relying on history taking alone, is highly obscure and there could be recall bias. There have been, so far, no reports about whether it was possible to demonstrate the molecular evidence of vertical transmission of HBV even after several decades of infection. Taken together, 'Vertical or non-vertical transmission' is so crucially informative that it enables clinicians to manage effectively the patients with chronic HBV infection and also foresee the prognosis or therapeutic responses. Therefore, this study was conducted to prove the vertical transmission by showing the molecular closeness of HBVs between adult patients with clinically presumed vertical transmission and their respective mothers with the phylogenetic analyses of pre-S/S genes of HBV. It must provide valuable information to design a further strategy of management if the mode of HBV infection can be disclosed even after long-term period of infection.

Intraductal papillary mucinous neoplasm of the pancreas (IPMN) is characterized by the production of mucin and marked dilatation of pancreatic duct. There are only several cases reports about fistula formation with adjacent organs in IPMN. A 61-year-old man was admitted due to jaundice and weight loss. CT scans showed that multiloculated cystic mass had replaced the body and tail of the pancreas. Interestingly, a fistula was found between cystic mass and duodenal bulb. With a diagnosis of malignant IPMN and pancreatoduodenal fistula, endoscopic forcepbiopsy was performed at the orifice of the fistula and pancreatic duct, through the fistula, under a fluoroscopic guidance. Pathologic examination showed only inflammatory cells. Direct peroral pancreatoscopy was performed through the pancreatoduodenal fistula using a standard upper endoscope with saline irrigation. Endoscopic forcep-biopsy was performed on the papillary tumor. Pathologic examination revealed intestinal type IPMN and radical total pancreatectomy was performed. Pathologic examination of the surgical specimen showed tubular adenocarcinoma arising from 15 cm sized intestinal type IPMN.

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.

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.

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.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 (6HVPG≤10), HS-3 (10HVPG≤12), HS-4 (12HVPG≤20), and HS-5 (20HVPG). CS was classified as follows: CS-0 (no cirrhosis), CS-1 (cirrhosis without varix), CS-2 (cirrhosis with varix), CS-3 (varix bleeding without other complications), CS-4 (first nonbleeding decompensating event), and CS-5 (any second decompensating event). The HCC development and risk factors for HCC were evaluated in all patients and patients with cirrhosis, respectively.HCC developed in 53 patients (6.6%). The incidence densities of HCC according to HS-1 to HS-5 and CS-0 to CS-5 were 4, 16, 36, 45, and 49/1000 person years and 0, 15, 25, 33, 36, and 53/1000 person years of observation, respectively. Ascites aggravation [P=0.008, odd ratio (OR)=2.33], HVPG12 mm Hg (P=0.033, OR=2.17), CS2 (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), HVPG12 mm Hg (OR=2.46), and CS2 (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.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.

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

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 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.

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.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.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, p0.001) than the surgery group. There were no recurrences in either group during the follow-up period.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.

Summary. This study aimed to evaluate the long-term efficacy of entecavir (ETV) in adefovir (ADV)-refractory chronic hepatitis B (CHB) patients with prior lamivudine (LMV) resistance. A total of 55 ADV-refractory CHB patients with prior LMV resistance, who received rescue therapy with ETV 1 mg daily for at least 12 months, were consecutively enrolled and analysed. Forty-four patients were men, and their median age was 47 (25–69). Ten patients had liver cirrhosis and 46 patients were positive for hepatitis B e antigen (HBeAg). Median hepatitis B virus DNA levels were 6.6 (4.3–8.0) log10 copies/mL, and the median duration of ETV therapy was 24 (12–47) months. Cumulative virologic response rates at 6, 12, 24 and 36 months were 18%, 29%, 58% and 75%, respectively. HBeAg loss occurred in 10 (21.7%) of 46 HBeAg-positive patients. In multivariate analysis, only initial virologic response at 3 months remained as an independent predictor for virologic response (RR 3.143; 95% CI 1.387–7.120; P = 0.006). The patients with a virological response at 3 months had not only a significantly higher probability of achieving a virologic response (P

Antibody to hepatitis B surface antigen (HBsAg) (anti-HBs) can exist in patients with chronic hepatitis B virus (HBV) infection. To date, little is known about the association of concurrent HBsAg and anti-HBs (concurrent HBsAg/ anti-HBs) with hepatocellular carcinoma (HCC). The aim of this study was to investigate the clinical relevance of concurrent HBsAg/anti-HBs with preS deletion mutations and HCC in chronic HBV infection. A total of 755 patients with chronic HBV infection were included consecutively at a tertiary center. Logistic regression analysis was used to identify risk factors for HCC, and serum HBV DNA was amplified, followed by direct sequencing to detect preS deletions. The prevalence of concurrent HBsAg/anti-HBs was 6.4% (48/755) and all HBVs tested were genotype C. HCC occurred more frequently in the concurrent HBsAg/anti-HBs group than in the HBsAg only group [22.9% (11/48) vs. 7.9% (56/707), P = 0.002]. In multivariate analyses, age >40 years [odds ratio (OR), 14.712; 95% confidence interval (CI), 4.365-49.579; P < 0.001], male gender (OR 2.431; 95% CI, 1.226-4.820; P = 0.011), decompensated cirrhosis (OR, 3.642; 95% CI, 1.788-7.421; P < 0.001) and concurrent HBsAg/anti-HBs (OR, 4.336; 95% CI, 1.956-9.613; P < 0.001) were associated independently with HCC. In molecular analysis, preS deletion mutations were more frequent in the concurrent HBsAg/anti-HBs and HCC groups than in the HBsAg without HCC group (42.3% and 32.5% vs. 11.3%; P = 0.002 and 0.012, respectively). In conclusion, concurrent HBsAg/anti-HBs is associated with preS deletion mutations and may be one of the risk factors for HCC in chronic HBV infection with genotype C.

Background/Aims: Subcellular localization of hepatitis B virus (HBV) core antigen (HBcAg) and HBV surface antigen (HBsAg) is known to be related to the activity of liver disease and the level of HBV replication. The aim of this study was to determine the correlation between histologic activity, viral replication, and the intracellular distributions of HBcAg and HBsAg. Methods: We enrolled 670 patients with chronic hepatitis B who underwent liver biopsy at Bundang CHA hospital between 1997 to 2007. The data from medical records were reviewed retrospectively. Results: The stage of fibrosis was higher (3.31±1.34 vs. 2.43±1.39, mean±SD, p＜0.01) and the grade of necroinflammatory activity was higher (9.39±3.11 vs. 6.13±3.40, p＜0.001) for the cytoplasmic expression of HBcAg (cHBcAg) than for the nuclear expression of HBcAg (nHBcAg). The serum HBV DNA level was 677.30±983.14 pg/mL in cHBcAg, 1274.46±1417.28 pg/mL in nHBcAg, 1121.01±1121.0 pg/mL in c-nHBcAg, and 229.47±678.92 pg/mL in negative (p＜0.001). HBeAg was seropositive in 74.7% of patients with cHBcAg, 90.6% in those with nHBcAg, 90.3% in those with n-cHBcAg, and 55.6% in those with negative (p＜0.001). The histologic stage and grade of hepatitis were not significantly correlated with the subcellular localization of intrahepatic HBsAg (p＞0.05). Conclusions: These observations suggest that the histologic activity of hepatitis is higher and viral replication is lower in cHBcAg positive patients than in those with nHBcAg. (Gut and Liver 2008;2:166173)

To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer.Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1-14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60-75 mg/m(2) and S-1 60-80 mg/m(2). A phase II study was conducted with the recommended dose (RD) based on phase I.Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m(2) and S-1 60 mg/m(2). Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m(2) and S-1 80 mg/m(2)) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35-66%) and median survival was 15.3 months (95% CI, 10.0-20.6 months).Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities.

Patients with Type 2 diabetes mellitus may be at increased colorectal adenoma and cancer risk. Moreover, chronic insulin therapy may increase the risk of colorectal cancer among patients with Type 2 diabetes mellitus. We investigated to determine whether insulin therapy might increase the risk of colorectal adenoma among clinically confirmed patients with Type 2 diabetes mellitus. We conducted a retrospective study among patients with Type 2 diabetes mellitus who underwent total colonoscopy between January 2003 and July 2006 at Hallym University Sacred Heart Hospital. Among them (n = 325), patients with histologically confirmed colorectal adenomas (n = 100) and the same number of controls matched by age and sex were selected and analyzed. Adenoma cases showed significantly higher rate of chronic insulin therapy (more than 1 year) than controls (P = 0.018). In multivariate regression analysis, patients who received chronic insulin therapy had three times the risk of colorectal adenoma compared with patients who received no insulin (odds ratio, 3; 95 percent confidence interval, 1.1–8.9; P = 0.04). Chronic insulin therapy was associated with increased colorectal adenoma risk among Type 2 diabetes mellitus patients. This result may provide a need for more intensive colorectal cancer screening program in patients with Type 2 diabetes mellitus, especially those who receive chronic insulin therapy.

BACKGROUND/AIMS Several simple tests for hepatic fibrosis employ indirect markers. However, the efficacy of using direct and indirect serum markers to predict significant fibrosis in clinical practice is inconclusive. We analyzed the efficacy of a previously reported indirect marker of hepatic fibrosis - the aspartate aminotransferase to platelet ratio index (APRI) - in patients with nonalcoholic chronic liver diseases (CLDs). METHODS A total of 134 patients who underwent a percutaneous liver biopsy with a final diagnosis of chronic hepatitis B (n=93), chronic hepatitis C (n=18), or nonalcoholic fatty liver disease (n=23) were enrolled. A single-blinded pathologist staged fibrosis from F0 to F4 according to the METAVIR system, with significant hepatic fibrosis defined as a METAVIR fibrosis score of >/=2. RESULTS The mean area under the receiver operating characteristic curve (AUROC) of APRI for predicting significant fibrosis in nonalcoholic CLDs was 0.84 [95% confidence interval (CI), 0.78-0.91]. APRI yielded the highest mean AUROC in the patients with chronic hepatitis B (0.85; 95% CI, 0.771-0.926). The positive predictive value of APRI >/=1.5 for predicting significant fibrosis was 89%. The negative predictive value of APRI

Background Successful colonoscopy depends on insertion of the instrument to the cecum, precise observation, and minimal patient discomfort during the procedure. This prospective study was designed to identify factors, apart from the endoscopist's skill, that predict patient pain and technical difficulty during sedation-free colonoscopy. Methods A total of 426 sedation-free colonoscopies performed by one experienced endoscopist were evaluated in a prospective manner. Factors were recorded, including patient pain level, intubation time, demographic data, history of abdominal surgery, bowel preparation status, diverticular disease, bowel habits, anxiety level, and number of previous colonoscopies. These factors were analysed to determine their association with difficulty and pain during the procedure. Results Four hundred six colonoscopies were completed to the cecum (95.3%). Mean insertion time for complete colonoscopy was 6.5 ± 3.5 min. Multivariate logistic regression analyses revealed that older age, lower body mass index, previous hysterectomy, diarrhoea, 1st time colonoscopy and anxiety were predictors of patient pain. Older age, lower body mass index and previous hysterectomy were predictors of difficulty of intubation. Conclusions This prospective study identified several factors that may predict patient pain and technical difficulty associated with the procedure. These findings have implications for the practice and teaching of colonoscopy.

Summary Objectives The high incidence of invasive liver abscess caused by Klebsiella pneumoniae in Taiwan, contrasted with the rareness of this disease in Western countries, has aroused special interest. There have been few detailed reports from other Asian countries. To investigate a current epidemiology of K. pneumoniae liver abscess in Korea and to determine K serotype distribution in K. pneumoniae strains causing liver abscess, we performed a nationwide prospective study. Methods Community-acquired, culture-proven liver abscess cases were enrolled between 2004 and 2005. Etiologies and clinical features were analyzed. K. pneumoniae isolates were serotyped according to K antigen. Meta-analysis was done to determine the time trend of the etiologies of liver abscess in Korea. Results Out of 371 cases collected prospectively, 290 (78.2%) were caused by K. pneumoniae . Most K. pneumoniae liver abscesses were monomicrobial. Diabetes mellitus was the most common underlying disease (39.9%). Distant metastatic infections were frequently observed (8.7%). magA PCR revealed that 95 (59.4%) out of 160 K. pneumoniae isolates belonged to the K1 serotype. Conclusions Our study indicates that K. pneumoniae has emerged as a major etiologic agent of liver abscess in Korea, and these emerging infections seem to be attributable to invasive K. pneumoniae strains with capsular K1 serotype.

Vascular lesions of the colon are being recognized with increasing frequency as a cause of lower intestinal hemorrhage in the elderly [1–3]. Colonic arteriovenous malformation (AVM) is also known as vascular ectasia or angiodysplasia, and it is thought to be caused by degenerative changes [1, 4]. Unlike small vascular abnormalities such as vascular ectasia or angiodysplasia, AVMs have several distinguishing characteristics based on the analyses of various reported cases [4–6]: they are not restricted to the elderly, are usually solitary, can be identified endoscopically, are not confined to the right colon, and are larger. We report a case of segmental AVM in a patient with familial adenomatous polyposis (FAP) that presented as a chronic limited colitis mimicking inflammatory bowel disease. While initial biopsies were suggestive of an ischemic etiology, the final diagnosis was made on surgical resection.

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.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.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%).The loop-tip wire can be an alternative instrument for wire-assisted selective cannulation in patients with Billroth II anastomosis.

Background: Capecitabine plus oxaliplatin (XELOX) is considered one of the primary chemotherapy regimens for patients with metastatic colorectal cancer (CRC). Oxaliplatin plus S-1 (OS) has also demonstrated significant efficacy in CRC. We performed this randomized phase II study to evaluate the efficacy and toxicity of XELOX versus OS as first-line chemotherapy in patients with metastatic CRC. Methods: Patients were assigned randomly to receive either OS or XELOX chemotherapy. Oxaliplatin was administered intravenously to all patients at a dose of 130 mg/m2 on day 1. Patients received either S-1 (40 mg/m2) or capecitabine (1,000 mg/m2), twice a day for 2 weeks, followed by a 1-week rest. Results: Forty-two patients were assigned to the OS arm and 44 to the XELOX arm. The overall response rate was 33.3% (95% CI, 18.8-47.2) in the OS arm and 40.9% (95% CI, 25.5-54.4) in the XELOX arm (P = 0.230). The disease control rate was significantly higher in the OS arm than the XELOX arm [92.9% (95% CI, 83.7-100) versus 77.3% (95% CI, 64.5-89.4), P = 0.044]. With a median follow up of 17.9 months, the median progression-free survival was 6.1 months in the OS arm and 7.4 months in the XELOX arm, respectively (P = 0. 599). The median survival time was 18.7 months in the OS arm and 20.1 months in the XELOX arm (P = 0.340). The most common grade 3/4 hematologic toxicity was thrombocytopenia in both arms (19.0% for OS and 28.6% for XELOX). Grade 3/4 neutropenia was observed more frequently in the XELOX arm than the OS arm (16.7% vs. 2.4%, P = 0.026). Conclusion: Both OS and XELOX were effective and well tolerated in patients with metastatic CRC. Our results indicate that the combination of oxaliplatin and S-1 is a possible additional therapeutic strategy for such patients.

To identify the factors that differentiate acute hepatitis B (AHB) from chronic hepatitis B with acute exacerbation (CHB-AE).From 2004 to 2013, a total of 82 patients (male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen (IgM anti-HBc) were retrospectively enrolled and divided into two groups; AHB (n = 53) and CHB-AE (n = 29). The AHB group was defined as patients without a history of hepatitis B virus (HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff (S/CO) ratio of IgM anti-HBc were compared to determine the differential diagnostic factors.The multivariate analysis demonstrated that, the S/CO ratio of IgM anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of IgM anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of IgM anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log₁₀ IU/mL, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of IgM anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of IgM anti-HBc and HBV DNA levels were not significantly different (0.933 vs 0.844, P = 0.105). When combining IgM anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone (P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively.The combination of the S/CO ratio of IgM anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive IgM anti-HBc.

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.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.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.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.

Fundic gland polyps (FGPs) are currently the most common type of gastric polyps and are usually benign. However, although rare, gastric adenocarcinoma of FGP has been recently proposed as a new variant of gastric adenocarcinoma. Here we report the first case of a 49-year-old woman with focal signet ring cell carcinoma that arose from an FGP of the stomach. The tumor was completely excised by endoscopic snare polypectomy. FGPs should therefore be evaluated for malignant changes although they occur rarely, if the FGP has an erosive or irregular surface.

e15778 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, 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 at 1,000 mg/m2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on days 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2was permitted from 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 overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and 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. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.

476 Background: Gemcitabine-based chemotherapy is considered as a standard front-line treatment for patients with advanced pancreatic cancer. Although addition of erlotinib or S-1 to gemcitabine has yielded better outcomes, it has showed just modest improvement in survival. To overcome this limitation, we evaluated the efficacy and safety of the combination of gemcitabine, 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 at 1,000 mg/m2 was administered intravenously on day 1, and 8, erlotinib at 100 mg/day was administered on day 1-21, and S-1 at 60 mg/m2 was administered on days 1-14 every 21 days and continued to maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from 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 31 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 overall response rate was 12.9% [95% confidence interval (CI), 5.1-28.9%] and disease control rate was 74.2% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.4 months (95 % CI, 2.3-4.5 months) and 5.7 months (95 % CI, 3.9-7.6 months), respectively. Conclusions: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer. Clinical trial information: NCT01693419.

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.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.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).Prophylactic low-dose PPI can reduce the risk of non-variceal UGIB in dialysis patients receiving aspirin.

AIM: To determine the cutoff values and to compare the diagnostic role of alpha-fetoprotein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II) in chronic hepatitis B (CHB). METHODS: A total of 1255 patients with CHB, including 157 patients with hepatocellular carcinoma (HCC), 879 with non-cirrhotic CHB and 219 with cirrhosis without HCC, were retrospectively enrolled. The areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP and their combination were calculated and compared. RESULTS: The optimal cutoff values for PIVKA-II and AFP were 40 mAU/mL and 10 ng/mL, respectively, for the differentiation of HCC from nonmalignant CHB. The sensitivity and specificity were 73.9% and 89.7%, respectively, for PIVKA-II and 67.5% and 90.3% for AFP, respectively. The AUROC curves of both PIVKA-II and AFP were not significantly different (0.854 vs 0.853, P = 0.965) for the differentiation of HCC from nonmalignant CHB, whereas the AUROC of PIVKA-II was significantly better than that of AFP in patients with cirrhosis (0.870 vs 0.812, P = 0.042). When PIVKA-II and AFP were combined, the diagnostic power improved significantly compared to either AFP or PIVKA-II alone for the differentiation of HCC from nonmalignant CHB (P < 0.05), especially when cirrhosis was present (P < 0.05). CONCLUSION: Serum PIVKA-II might be a better tumor marker than AFP, and its combination with AFP may enhance the early detection of HCC in patients with CHB.

Corrosive esophagitis is characterized by caustic injury due to the ingestion of chemical agents, mainly alkaline substances such as detergents. Esophageal bleeding, perforation, or stricture can be worsened by high-degree corrosive esophagitis. Picosulfate is a commonly used laxative frequently administered for bowel preparation before colonoscopy or colon surgery. Picosulfate powder should be completely dissolved in water before ingestion because the powder itself may cause chemical burning of the esophagus and stomach. Here, we report a case of corrosive esophagitis due to the ingestion of picosulfate powder that was not completely dissolved in water.

Background. The association of gastric cancer and chronic duodenal ulcer disease is considered rare. In fact duodenal ulcer disease is believed to somehow “protect” against the development of gastric cancer. Helicobacter pylori infection is an important factor in the development of gastric cancer. No detailed investigation on the prevalence of H.pylori in coexistence of gastric cancer and duodenal ulcer disease has been performed. We evaluated the frequency of H. pylori infection in the patients with co-existence of gastric cancer and duodenal ulcer disease. Materials and Methods. During the period March 1994 to February 1995, we collected data from 3,652 patients in whom esophagogastroduodenoscopy was done. During this period, when the cancerous or ulcerative lesions in stomach or duodenum were found, rapid urease tests were performed. Results. Six patients had concurrent gastric carcinoma and duodenal ulcer disease. Three of the cases had early gastric carcinoma; 2 had active duodenal ulcers and one had a duodenal ulcer scar; all 3 had positive rapid urease tests. The patients with early gastric cancer were younger than the individuals with advanced gastric cancer. Conclusions. The co-existence of both diseases may be higher than reported from Western countries or from Peru which may either reflect the high prevalence of circulation of H.pylori ulcer and cancer strains in Korea and the co-infection with both types of organism in some individuals.

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 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.

To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of 1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but 1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival.Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild.Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

A 32-year-old male patient, diagnosed as a hepatic solitary angiomyolipoma post-operatively, is reported. The tumor was well definedly inhomogenous fat density mass on ultrasonography, computerized tomography (CT) and magnetic resonance imaging (MRI). The lesion was hypervascular on arteriography. The diagnosis was confirmed by an extended right lobectomy and histological examination.

AIM To identify the frequency, clinicopathological risk factors, and prognostic significance of lymphovascular invasion (LVI) in endoscopically resected small rectal neuroendocrine tumors (NETs). METHODS Between June 2005 and December 2015, 104 cases of endoscopically resected small (≤ 1 cm) rectal NET specimens at Hallym University Sacred Heart Hospital in Korea were retrospectively evaluated. We compared the detected rate of LVI in small rectal NET specimens by two methods: hematoxylin and eosin (H&E) and ancillary immunohistochemical staining (D2-40 and Elastica van Gieson); in addition, LVI detection rate difference between endoscopic procedures were also evaluated. Patient characteristics, prognosis and endoscopic resection results were reviewed by medical charts. RESULTS We observed LVI rates of 25.0% and 27.9% through H&E and ancillary immunohistochemical staining. The concordance rate between H&E and ancillary studies was 81.7% for detection of LVI, which showed statistically strong agreement between two methods (κ = 0.531, P < 0.001). Two endoscopic methods were studied, including endoscopic submucosal resection with a ligation device and endoscopic submucosal dissection, and no statistically significant difference in the LVI detection rate was detected between the two (26.3% and 26.8%, P = 0.955). LVI was associated with large tumor size (> 5 mm, P = 0.007), tumor grade 2 (P = 0.006). Among those factors, tumor grade 2 was the only independent predictive factor for the presence of LVI (HR = 4.195, 95%CI: 1.321-12.692, P = 0.015). No recurrence was observed over 28.8 mo regardless of the presence of LVI. CONCLUSION LVI may be present in a high percentage of small rectal NETs, which may not be associated with short-term prognosis.

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