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(1) Background: The complication rates for nonagenarians receiving therapeutic endoscopic retrograde cholangiopancreatography (ERCP) remain poorly understood. We aimed to determine whether nonagenarians were at an increased risk of ERCP-related complications. (2) Methods: We performed a retrospective study on therapeutic ERCP in nonagenarians from 2011 to 2016 at Taichung Veterans General Hospital. A control group comprising patients aged 65 to 89 years was used to compare demographic data and the outcomes of therapeutic ERCP with the nonagenarians. The risk factors for complications were determined by logistic regression model. (3) Results: There were 35 nonagenarians and 111 patients in the control group. Overall, complication rates were not statistically different between the two groups. However, advanced age was an independent predictor of complications in the multivariate analysis (odds ratio [OR] = 1.06; 95% confidence interval [CI] = 1.01–1.12; p = 0.049). End stage renal disease (ESRD) was another independent predictor of complications (OR = 4.87; 95% CI = 1.11–21.36; p = 0.036). Post-ERCP pancreatitis and bleeding were more common in ESRD patients than patients without ESRD. (4) Conclusions: Although nonagenarians receiving ERCP did not have more complications compared to elderly patients younger than 90 years, advanced age and comorbidity still affect the outcome of therapeutic ERCP in the elderly patients.

Aim: Hepatocellular carcinoma (HCC) is one of the most common cancers. Tyrosine kinase inhibitors (TKIs), including sorafenib (SOR) and lenvatinib (LEN), as well as immune checkpoint inhibitors (ICIs), including nivolumab (NIVO) and pembrolizumab (PEMBRO), have been approved for the treatment of advanced HCC. The aim of the study is to determine whether advanced-stage HCC patients should receive a combination of TKI and ICI as first-line therapy. Methods: Data for subjects with BCLC stage C HCC, who were receiving combining TKI and ICI as first-line therapy at Taichung Veterans General Hospital from April 2019 to July 2021, were evaluated. The general and therapeutic outcome data were collected and analyzed. Results: A total of 33 patients were enrolled (8 SOR/NIVO, 4 SOR/PEMBRO, 11 LEN/NIVO, and 10 LEN/PEMBRO). All cases belonged to Child-Pugh class A. The objective response rate was 48.5%, and disease control rate was 72.7%. The average progression-free survival (PFS) and overall survival (OS) of all patients was 9.2 and 17.0 months, respectively. The use of PEMBRO, when compared with NIVO, had a significantly positive impact towards achieving an objective response, defined as either complete response or partial response (OR 5.54, p = 0.045). PFS and OS between the different TKIs or ICIs had no differences. The most adverse event was fatigue (36.4%), and most cases were mild and manageable. Conclusion: Combining TKI and ICI provides an acceptable antitumor efficacy in first-line therapy for advanced-stage HCC patients. The survival outcomes between different TKIs or ICIs display no differences.

Objective Systemic therapy, such as sorafenib, has been used clinically to treat patients with advanced stage or Barcelona Clinic Liver Cancer staging system (BCLC) stage C hepatocellular carcinoma (HCC). The aim of the study was to evaluate the therapeutic benefit of combined sorafenib and transarterial chemoembolization (TACE) in this group of patients. Methods Data on patients with HCC at BCLC stage C from August 2012 to September 2017 were collected. Patients who were given sorafenib alone were classified as the monotherapy group and those taking sorafenib and TACE were classed as the combined therapy group. Results A total of 118 patients were enrolled. There were 65 and 53 patients in the monotherapy and the combined therapy group, respectively. The groups' general characteristics were similar. Compared with the monotherapy group the combined therapy group experienced prolonged time-to-progression (TTP) (mean 6.42 mo vs 3.63 mo, P = 0.003) and overall survival (OS) (mean 11.21 mo vs 5.98 mo, P = 0.001). A subgroup analysis found that patients with macroscopic vascular invasion (MVI) also had prolonged TTP and OS in the combined therapy group than the monotherapy group (mean TTP, 7.93 mo vs 3.43 mo, P = 0.007; mean OS, 13.41 mo vs 5.50 mo, P = 0.001), however, these significant differences did not exist for those with extrahepatic spread (EHS). Conclusion Combined sorafenib and TACE therapy has significant better outcomes than sorafenib alone in patients with stage C HCC, particularly those with MVI.

Severe acute cholangitis is a life-threatening medical emergency. Endoscopic biliary drainage (EBD) or percutaneous transhepatic biliary drainage (PTBD) is usually used for biliary decompression. However, it can be risky to transport a critical patient to the radiology unit. We aimed to compare clinical outcomes between bedside, radiation-free EBD and fluoroscopic-guided PTBD in patients under critical care. Methods: A retrospective study was conducted on critically ill patients admitted to the intensive care unit with biliary obstruction and cholangitis from January 2011 to April 2020. Results: A total of 16 patients receiving EBD and 31 patients receiving PTBD due to severe acute cholangitis were analyzed. In the EBD group, biliary drainage was successfully conducted in 15 (93.8%) patients. Only one patient (6.25%) encountered post-procedure pancreatitis. The 30-day mortality rate was no difference between the 2 groups (32.72% vs. 31.25%, p = 0.96). Based on multivariate analysis, independent prognostic factors for the 30-day mortality were a medical history of malignancy other than pancreatobiliary origin (HR: 5.27, 95% confidence interval [CI]: 1.01–27.57) and emergent dialysis (HR: 7.30, 95% CI: 2.20–24.24). Conclusions: Bedside EBD is safe and as effective as percutaneous drainage in critically ill patients. It provides lower risks in patient transportation but does require experienced endoscopists to perform the procedure.

Aim: Currently, atezolizumab combined with bevacizumab is the standard first-line treatment for unresectable hepatocellular carcinoma (HCC), but lenvatinib or sorafenib are still recommended for these patients for some reasons. The aim of the study was to determine the outcomes of Taiwanese patients with advanced-stage HCC who received lenvatinib or sorafenib. Methods: Data on patients with BCLC stage C HCC who were receiving lenvatinib or sorafenib as the first-line therapy from May 2018 to August 2020 was collected. The individuals with lenvatinib and sorafenib were propensity score-matched at a ratio of 1:2. Results: A total of 22 patients with lenvatinib and 44 patients with sorafenib were enrolled. The ORR (36.4% vs. 11.4%, p = 0.023) and DCR (81.9% vs. 56.9%, p = 0.039) were both higher in the lenvatinib group compared with the sorafenib group. The median overall survival (OS) of the lenvatinib group and the sorafenib group was 9.36 months and 8.36 months, respectively. The best median OS was detected in patients receiving lenvatinib and having an objective tumor response (11.29 months), with a significant difference (p = 0.031) compared with the other groups. Conclusion: Lenvatinib, compared to sorafenib, had better ORR and DCR, but similar OS, in Taiwanese patients with advanced-stage HCC. The patients with an objective tumor response had a better OS.

BACKGROUND/AIM Matrix metalloproteinase-9 (MMP-9) is responsible for modifying extracellular components and plays a crucial role in the metastatic behavior of cancer. This study aimed at examining the role of MMP-9 rs3918242 genotypes on colorectal cancer (CRC) risk. MATERIALS AND METHODS A total of 362 CRC patients and 362 healthy subjects in Taiwan, were examined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. RESULTS The MMP-9 rs3918242 TT genotype carriers had a slightly increased risk of CRC compared to CC carriers (p=0.1642, OR=1.88, 95% CI=0.84-4.16). Patients of CT/TT genotypes were on significantly higher risk of metastasis (p=0.0027) than those of CC genotype. No obvious association was found between MMP-9 genotype and CRC risk among ever-smokers, non-smokers, non-alcohol drinkers or alcohol drinkers. No significant correlation was observed between MMP-9 genotypic distributions with age, gender, tumor size or location. CONCLUSION MMP-9 rs3918242 genotypes may interact with BMI to serve as a predictor for higher CRC risk, and independently as a predictor for metastasis.

Transarterial chemoembolization (TACE) is a recommended treatment for patients with intermediate stage hepatocellular carcinoma (HCC) but with variable treatment outcomes.To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC.Patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009. Patients were assigned to either the objective responder (OR) group or the non-OR group according to mRECIST criteria. Clinical and radiological characteristics were compared between the 2 groups. The overall survival of enrolled subjects was analyzed.In 128 enrolled patients, 66 (51.6%) were in the OR group and 62 (48.4%) in the non-OR group. Compared with the non-OR group, the OR group had a significantly smaller HCC size (6.55 cmBCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE. BCLC stage B subgroup is useful to predict refractoriness to TACE.

Isoamylamine (IA) is an aliphatic monoamine molecule present in cheese, eggs, and wine. It belongs to the family of polyamines and also can be synthesized endogenously. It has been known that regulation of polyamines in cells is related to cell cycle and tumor formation. Malignant melanoma is difficult to treat and easily resistant to chemotherapy/radiotherapy through autophagy. In this study, we aim to clarify whether IA has a growth control effect on melanoma tumor cells and the regulatory mechanism. We treated B16-F1 melanoma cells with IA at concentrations of 0, 200, 400, and 600 ppm for 24 h. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay was checked for cell viability and results showed that IA has an inhibitory effect on B16-F1 melanoma cells. The signaling molecules, which included Raf/MEK/ERK, were activated, while MSK1 and protein kinase B (AKT) were suppressed. Autophagy was also confirmed to be induced by IA. The acridine orange stain-positive cells were increased and BECN-1/LC3 upregulated. The data also showed that the autophagy regulatory molecule, 5'-adenosine monophosphate-activated protein kinase (AMPK), was induced after IA treatment, so we used dorsomorphin to inhibit AMPK and found that it could suppress autophagy. In conclusion, IA has an effect of inducing autophagy in B16-F1 cells and it is regulated through AMPK.

Brain-derived neurotrophic factor (BDNF) is an important factor for memory consolidation and cognitive function. Protein kinase A (PKA) signaling interacts significantly with BDNF-provoked downstream signaling. Glucosamine (GLN), a common dietary supplement, has been demonstrated to perform a variety of beneficial physiological functions. In the current study, an in vivo model of 7-week-old C57BL/6 mice receiving daily intraperitoneal injection of GLN (0, 3, 10 and 30 mg/animal) was subjected to the novel object recognition test in order to determine cognitive performance. GLN significantly increased cognitive function. In the hippocampus GLN elevated tissue cAMP concentrations and CREB phosphorylation, and upregulated the expression of BDNF, CREB5 and the BDNF receptor TrkB, but it reduced PDE4B expression. With the in vitro model in the HT22 hippocampal cell line, GLN exposure significantly increased protein and mRNA levels of BDNF and CREB5 and induced cAMP responsive element (CRE) reporter activity, the GLN-mediated BDNF expression and CRE reporter induction were suppressed by PKA inhibitor H89. Our current findings suggest that GLN can exert a cognition-enhancing function and this may act at least in part by upregulating the BDNF levels via a cAMP/PKA/CREB-dependent pathway.

Hepatocellular carcinoma (HCC) is associated with a poor prognosis and a low chemotherapeutic efficiency except for when sorafenib is administered. The aim of this study was to evaluate the efficacy and adverse events (AEs) of sorafenib therapy in a Chinese population diagnosed with HCC. Method Data for the subjects with HCC receiving sorafenib at Taichung Veterans General Hospital from June 2012 to October 2016 were evaluated. All enrolled cases belonged to the HCC Barcelona Clinic Liver Cancer (BCLC) classification stage C. The AEs were defined as appearances of hand-foot syndrome reaction (HFSR), hypertension (HTN), or diarrhea. The exclusion criteria included a poor performance status, lack of compliance to drugs, and loss of follow-up within the following day. Results Of a total of 116 subjects enrolled, there were 43 (37.1%), 13 (11.2%), and 15 (12.9%) cases experiencing HFSR, HTN, and diarrhea, respectively. The cases with AE had both a longer time to progression (TTP) (HFSR 5.16 vs. 3.33 months, P = 0.003; HTN 6.62 vs. 3.68 months, P = 0.001; diarrhea 6.67 vs. 3.61 months, P = 0.001) and overall survival (OS) (HFSR 8.12 vs. 4.75 months, P = 0.001; HTN 9.08 vs. 5.61 months, P = 0.008; diarrhea 8.20 vs. 5.67 months, P = 0.042) than those without. More AEs were correlated with a longer TTP and OS. Conclusion The appearance of sorafenib AEs, including HFSR, HTN, and diarrhea, can predict a positive therapy efficacy to HCC.

Hepatocellular carcinoma (HCC) is associated with a poor prognosis and a low chemotherapeutic efficiency except for when sorafenib is administered. The aim of this study was to evaluate the efficacy and adverse events (AEs) of sorafenib therapy in a Chinese population diagnosed with HCC. Method Data for the subjects with HCC receiving sorafenib at Taichung Veterans General Hospital from June 2012 to October 2016 were evaluated. All enrolled cases belonged to the HCC Barcelona Clinic Liver Cancer (BCLC) classification stage C. The AEs were defined as appearances of hand–foot syndrome reaction (HFSR), hypertension (HTN), or diarrhea. The exclusion criteria included a poor performance status, lack of compliance to drugs, and loss of follow‐up within the following day. Results Of a total of 116 subjects enrolled, there were 43 (37.1%), 13 (11.2%), and 15 (12.9%) cases experiencing HFSR, HTN, and diarrhea, respectively. The cases with AE had both a longer time to progression (TTP) (HFSR 5.16 vs. 3.33 months, P = 0.003; HTN 6.62 vs. 3.68 months, P = 0.001; diarrhea 6.67 vs. 3.61 months, P = 0.001) and overall survival (OS) (HFSR 8.12 vs. 4.75 months, P = 0.001; HTN 9.08 vs. 5.61 months, P = 0.008; diarrhea 8.20 vs. 5.67 months, P = 0.042) than those without. More AEs were correlated with a longer TTP and OS. Conclusion The appearance of sorafenib AEs, including HFSR, HTN, and diarrhea, can predict a positive therapy efficacy to HCC.

Background Clearance of hepatitis C virus (HCV) has been reported to induce the reactivation of hepatitis B virus (HBV). The aim of this study was to investigate the rate of HBV reactivation in HCV-infected Chinese patients who received treatment with pan-oral direct-acting antivirals (DAAs). Methods Data from HCV subjects receiving oral DAA therapy were retrospectively collected from October 2015 to May 2017. Patients who were seropositive for HBsAg or anti-HBc were enrolled. The efficacy of DAAs, including end-of-treatment virologic response (ETVR) and sustained virologic response (SVR) 12, was recorded. HBV virologic reactivation was defined as a reappearance of HBsAg, or increased HBV DNA by at least one log10 IU/mL. HBV clinical reactivation was defined as virologic reactivation and serum alanine aminotransferase (ALT) over two-fold of the upper limit of normal. Results There were 11 (7.2%) cases and 53 (34.6%) cases in the HBsAg group and the anti-HBc group among all 153 subjects. All individuals achieved ETVR and SVR12. There were no cases with reappearance of HBsAg during DAAs therapy. Among seven cases in the HBsAg group whose HBV DNA level was determined, HBV virological reactivation was detected in two subjects (28.6%). Among all 11 subjects in the HBsAg group, there was one (9.1%) case with HBV clinical reactivation, which was resolved following treatment with Entaclavir. The case with HBV clinical reactivation had a higher baseline HBV DNA viral load (1,380 IU/mL) compared with that of the other patients (20 - 296 IU/mL). Conclusion HBV virological and clinical reactivation occurred in 28.5% and 9.1% of subjects with HBsAg seropositivity. No HBV reactivation was observed in the cases with past HBV infection.

Background Non-alcoholic fatty liver disease (NAFLD) is associated with features of metabolic syndrome. The aim of this study was to investigate the association between NAFLD and metabolic syndrome in a Chinese population. Methods Data from subjects were retrospectively collected from 2006 to 2009. The exclusion criteria included significant consumption of alcohol and chronic hepatitis B and C. The patients were assigned to two groups according to ultrasound findings: normal group and fatty liver group. The liver function of patients was determined by assessing serum alanine aminotransferase (ALT). Metabolic syndrome was diagnosed based on the 2005 International Diabetes Federation criteria. Results A total of 7568 subjects were enrolled and 5736 (75.8%) and 1832 (24.2%) patients were assigned to the normal and fatty liver groups, respectively. The fatty liver group had significant male predominance (69.7% vs 56.0%), higher body mass index (mean, 26.67 vs 23.55 kg/m2) compared with the normal group. There were 441 (7.7%) and 377 (20.6%) cases with metabolic syndrome in the normal and fatty liver groups, respectively, with significant difference (P=0.001), and the subgroup of 385 cases with fatty liver and elevated ALT had higher prevalence (28.8%) of metabolic syndrome. The strongest association of an individual component of metabolic syndrome with NAFLD was hyperlipidemia (adjusted OR=2.55, 95% CI: 2.22-2.94). Conclusion The individuals with NAFLD had a higher ratio of metabolic syndrome. Hyperlipidemia had the strongest positive association with NAFLD.

BACKGROUND Proton pump inhibitors (PPIs) are widely applied for acid related disorders, and possess pleiotropic biological functions. The effect of PPIs on the gastric mucosa, neutrophil and Helicobacter pylori (H. pylori) infiltration and glandular atrophy has not been well investigated, particularly the duration of the effects of PPIs. OBJECTIVES To investigate the effects of PPIs on neutrophil infiltration, H. pylori infiltration and the gastric mucosa. MATERIAL AND METHODS A total of 76 adult patients with gastrointestinal symptoms who had undergone upper gastrointestinal endoscopy were enrolled in the study. Each patient's history was recorded, including smoking, alcohol consumption and the duration of PPI use prior to gastric biopsy. Endoscopic biopsies of gastric antral mucosa were performed and evaluated by histology. Neutrophil and H. pylori infiltration were graded by H & E staining in accordance with the updated Sydney system. RESULTS Among the 76 patients, 44 patients had H. pylori infection and 19 patients had taken PPIs for varying durations prior to gastric biopsy. Neutrophil infiltration was significantly inhibited by PPIs (p = 0.005). The duration of PPI use was correlated with inhibition of neutrophil and H. pylori infiltration. A logistical regression analysis demonstrated that PPIs significantly inhibited neutrophil infiltration in the gastric mucosa and were associated with atrophy of the mucosa. CONCLUSIONS PPIs attenuated neutrophil infiltration of gastric mucosa, and may be related to atrophy of the mucosa.

Aim The aim of this study was to investigate the incidence of dysplastic transformation of Barrett's esophagus (BE) in a Chinese population. Method Data from nondysplastic BE patients at Taichung Veterans General Hospital were collected from May 2008 to June 2017. The enrolled individuals received regular upper gastrointestinal (UGI) endoscopy during follow up. The pathological transformations, including low-grade dysplasia (LGD), high-grade dysplasia (HGD), or esophageal adenocarcinoma (EAC), were collected prospectively until June 2017. Rates of progression were calculated in cases with a diagnosis of dysplasia or EAC. Results There were 51 subjects who met the inclusion criteria, with a mean follow up of 3.71 years (SD, 1.61) and a total follow up of 189.1 patient-years. Eight cases (15.7%) developed LGD, with a calculated incidence rate of 2.9% per year. The mean time to development of LGD was 3.26 years (SD, 2.68-3.84). One subject (2%) developed EAC, with a calculated incidence rate of 0.4% per year. No case with HGD was detected. Conclusion In a Chinese population with nondysplastic BE, 15.7% of cases developed LGD, with an incidence rate of 2.9% per year, and 2% of cases developed EAC, with an incidence rate of 0.4% per year.

Sorafenib is of proven efficacy in treating patients of hepatocellular carcinoma (HCC). Our study was aimed to determine the factors influence the sorafenib efficacy. We evaluated data of HCC patients receiving sorafenib from June 2012 to October 2016. All HCC cases were of the Barcelona Clinic Liver Cancer (BCLC) classification stage C. The exclusion criteria: those of BCLC classification stage A or B, with the absence or co-infection of hepatitis B (HBV) and hepatitis C (HCV). The presence of HBV, HCV, macoscopic vascular invasion (MVI) or extrahepatic spread (EHS) was recorded for each patient. Time-to-progression (TTP) and overall survival (OS) were analyzed. Among a total of 90 HCC patients, 48 (53.3%) had HBV infection, 42 (46.7%) had HCV infection, 51 (56.7%) had MVI, and 39 (43.3%) had EHS. Patients with HCV infection showed better TTP and OS than those with HBV infection. Patients with EHS had a longer TTP and OS than those with MVI. For patients with HBV infection, those with EHS had a longer TTP (mean 4.60 vs 2.64 months, P = .002) and OS (mean 6.65 vs 4.53 months, P = .045) compared to those with MVI. Among those with MVI, patients with HBV infection had a poorer TTP (mean 2.64 vs 4.74 months, P = .019) and shorter OS (mean 4.53 vs 7.00 months, P = .059) compared to those with HCV infection. HCC patients with HCV infection or with the presence of EHS showed better sorafenib efficacy.

Objective Transarterial chemoembolization (TACE) is the treatment modality for intermediate, or Barcelona Clinic Liver Cancer stage B, hepatocellular carcinoma (HCC), but its beneficial effect on outcomes is still unsatisfactory. This study aimed to assess the outcomes of combined TACE and sorafenib for patients with intermediate HCC. Methods Patients with intermediate HCC who were receiving TACE alone (the monotherapy group), or combined TACE and sorafenib (the combined therapy group) from January 2013 to June 2018 were enrolled. Results Altogether 64 patients were enrolled, of whom 34 were assigned to the monotherapy group and 30 to the combined therapy group. A prolonged time-to-progression (TTP) (mean 14.46 mo vs 6.39 mo, P = 0.001) was noted in the combined therapy group compared with the monotherapy group. Overall survival (OS) (mean 18.96 mo vs15.44 mo, P = 1.000) between the two groups did not differ significantly. After adjustment, there were no significant differences in the 12-18 month mortality rate between the two groups. Conclusion Patients with intermediate HCC receiving combined TACE and sorafenib had a better TTP, but not OS, than those receiving TACE alone.

Background Metabolic syndrome has been highlighted as a risk factor for several gastrointestinal diseases, including gastroesophageal reflux disease and Barrett’s esophagus (BE). The aim of this study was to investigate the association of metabolic syndrome with erosive esophagitis (EE) and BE. Methods Data were retrospectively collected from patients who visited the Medical Screening Center at Taichung Veterans General Hospital, Taichung, Taiwan from January 2006 to December 2009. All patients underwent an open-access transoral upper gastrointestinal endoscopy, and serum laboratory data were collected. The exclusion criteria included prior gastric surgery, or presence of esophageal varices or peptic ulcers. These patients were assigned to groups according to their endoscopic findings as follows: (1) normal group; (2) EE group; and (3) BE group. Metabolic syndrome was diagnosed based on the International Diabetes Federation criteria. Results There were 560/6499 (8.6%) patients, 214/1118 (9.6%) patients, and 19/95 (20%) patients with metabolic syndrome in the normal, EE, and BE groups, respectively. There was a significantly higher percentage of cases with hypertriglyceridemia in the EE group (67%) compared with the other groups. The BE group had significantly higher rates of central obesity (33%) and hypertension (29.5%) compared with rates in the normal and EE groups. After adjusting for confounders, the positive association with metabolic syndrome still existed in both the EE group (adjusted odds ratio = 2.43; 95% confidence interval = 1.02–3.44) and the BE group (adjusted odds ratio = 2.82; 95% confidence interval = 2.05–3.88). Conclusion Our research indicated that in fact there is a greater risk of concurrent metabolic syndrome in patients with EE or BE.

Background: Gastroesophageal reflux disease (GERD) is a chronic disease with a negative impact on the quality of life. The aim of this study was to investigate the reflux symptoms and the health-related quality of life in a population with GERD. Methods: Data from patients with GERD, according to the Montreal definition, were collected between January and December 2009. The enrolled patients were classified by different reflux symptoms according to the modified Chinese GERDQ. The general demographic data, the modified GERD impact scores and the SF-36 questionnaire scores of these groups of patients were analyzed. Results: A total of 173 patients were enrolled, and the general data, endoscopic findings and lifestyle habits of the participants with different severity of heartburn or regurgitation were all similar. The patients with moderate severity of reflux symptoms had significant lower SF-36 scores than those with mild severity. The cases with advanced heartburn severity owned the lowest scores among all cases. The impact on the daily activity of each affected individual had a positive association with the stronger severity of reflux symptom. Conclusion: The life quality of a population with GERD achieved the meaningful declination in participants with the moderate severity of heartburn or regurgitation. The severity of the reflux symptoms had a greater impact on the normal daily activity of the patients with GERD. The cases with advanced severity of heartburn had the worst well-being. Gastroenterol Res. 2017;10(2):78-83 doi: https://doi.org/10.14740/gr753w

Cyclooxygenase-2 (COX-2) and IL-8 are two inflammatory mediators induced by protein kinase C (PKC) via various stimuli. Both contribute significantly to cancer progression. Bufalin, a major active component of the traditional Chinese medicine Chan Su, is known to induce apoptosis in various cancer cells. This study clarifies the role and mechanism of bufalin action during PKC regulation of COX-2/IL-8 expression and investigates the associated impact on breast cancer. Using MB-231 breast cancer cells, bufalin augments PKC induction of COX-2/IL-8 at both the protein and mRNA levels, and the production of prostaglandin E2 (PGE2) and IL-8. The MAPK and NF-κB pathways are involved in both the PKC-mediated and bufalin-promoted PKC regulation of COX-2/IL-8 production. Bufalin increases PKC-induced MAPKs phosphorylation and NF-κB nuclear translocation. PGE2 stimulates the proliferation/migration of breast cancer cells. Furthermore, PKC-induced matrix metalloproteinase 3 expression is enhanced by bufalin. Bufalin significantly enhances breast cancer xenograft growth, which is accompanied by an elevation in COX-2/IL-8 expression. In conclusion, bufalin seems to promote the inflammatory response in vitro and in vivo, and this occurs, at least in part, by targeting the MAPK and NF-κB pathways, which then enhances the growth of breast cancer cells.

Background and Aim Colonic diverticular disease may cause a chronic systemic effect, but its role in the development of dementia remains unclear. The purpose of this study was to investigate the potential increased risk for dementia in colonic diverticular disease. Methods We conducted a population-based cohort study using data from Taiwan's National Health Insurance Research Database. A total of 66 377 sex-matched, age-matched, and index year-matched (1:4) pairs of patients with colonic diverticular disease and 265 508 patients without colonic diverticular disease, who served as controls, were selected from all potential participants aged 20 years or older in the database. Each subject was individually tracked from 2000 to 2011 to identify incident cases of dementia. Cox proportional hazards regression was employed to calculate the hazard ratios and 95% confidence intervals for the association between colonic diverticular disease and dementia. Results There were 1057 dementia cases in the diverticular disease cohort during the follow-up period of 315 171 person-years; the overall incidence rate of dementia differed from that of the control group (3.35 vs 2.43 per 1000 person-years, P

Purpose – The purpose of this paper is to examine the relationship between workplace bullying and workplace deviance. This study also examined the mediating effect of emotional exhaustion and the moderating effect of core self-evaluations (CSE) in the relationship between workplace bullying and workplace deviance. Design/methodology/approach – Convenience sampling was used in this study; 262 caregivers at a long-term care institution in Taiwan participated in the study. Findings – The results of this study showed that workplace bullying positively and significantly influenced workplace deviance; emotional exhaustion fully mediated the relationship between workplace bullying and deviance; and CSE significantly moderated the relationship between workplace bullying and deviance. Research limitations/implications – The self-reporting method and cross-sectional research design adopted in this study might have resulted in common method variance and limited the ability to make causal inferences. This study suggest future studies to obtain measures of predictor and criterion variables from different sources or ensure a temporal, proximal, or psychological separation between predictor and criterion in the collection of data to avoid the common method bias. Practical implications – Businesses should establish a friendly work environment and prevent employees from encountering workplace bullying. Next, an unbiased process for internal complaints should be established. Finally, this study suggests recruiting employees with high CSE. Originality/value – This study was the first to simultaneously consider the effect of emotional exhaustion (a mediator) and CSE (a moderator) on the relationship between workplace bullying and workplace deviance.

Ovulation is a critical inflammation-like event that is central to ovarian physiology. IL-1β is an immediate early pro-inflammatory cytokine that regulates production of several other inflammatory mediators, such as cyclooxygenase 2 (COX)-2 and IL-8. NS-398 is a selective inhibitor of COX-2 bioactivity and thus this drug is able to mitigate the COX-2-mediated production of downstream prostaglandins and the subsequent inflammatory response. Here we have investigated the action of NS-398 using a human ovarian granulosa cell line, KGN, by exploring IL-1β-regulated COX-2 and IL-8 expression. First, NS-398, instead of reducing inflammation, appeared to further enhance IL-1β-mediated COX-2 and IL-8 production. Using selective inhibitors targeting various signaling molecules, MAPK and NF-κB pathways both seemed to be involved in the impact of NS-398 on IL-1β-induced COX-2 and IL-8 expression. NS-398 also promoted IL-1β-mediated NF-κB p65 nuclear translocation but had no effect on IL-1β-activated MAPK phosphorylation. Flow cytometry analysis demonstrated that NS-398, in combination with IL-1β, significantly enhanced cell cycle progression involving IL-8. Our findings demonstrate a clear pro-inflammatory function for NS-398 in the IL-1β-mediated inflammatory response of granulosa cells, at least in part, owing to its augmenting effect on the IL-1β-induced activation of NF-κB.

Background: The use of a nonthermal plasma (NTP) jet in the treatment of living tissue has been the subject of considerable interest in the field of medical technology, and has the potential to reduce the recovery time of open wounds. We aimed to investigate the wound-healing process by clinical observation, blood tests, and expression of cell adhesion markers and reactive oxygen species in NTP jet-treated rats. Methods: This study utilized Sprague-Dawley (SD) rats as experimental subjects, and wounds measuring 2 cm × 2 cm were produced on the animals' backs. The experimental group was treated with NTP for 5 min/d for 4 weeks. The NTP was injected in a diffused manner into the cage housing the rats. The SD rats that had not received plasma treatment were designated as the control group. Blood was drawn on Postoperative Day 2, Day 4, and at 3 months. An immunohistochemical stain of E-cadherin and 4-hydroxy-2-nonenal (4-HNE), a reactive oxygen species marker, were evaluated and quantified for analysis using a CMYK color model. Results: A total of 35 SD rats were included in the study (25 in the NTP group and 10 in the control group). Low dose plasma treatment shortened the wound-healing time without damaging organs. In the NTP group, the white blood cell counts at Day 2 post-NTP treatment was not increased significantly more than that in the control group. After quantification of immunohistochemical staining, 4-HNE was increased at Day 14 compared with Day 7 (16.16 ± 12.81% vs. 55.11 ± 8.11%, p

We read with interest the study by Cheung et al confirming the risk of proton pump inhibitors (PPIs) for gastric cancer regarding the patients after Helicobacter pylori (H. pylori) eradication with long-term PPIs use.1 Most concerns about the safety of PPIs pertain to the increased risk for enteric infections, fractures and nutritional deficiencies.2 To date, the association of PPIs use and risk of gastric cancer is still controversial in patients with gastro-oesophageal reflux diseases (GERD). For GERD, PPIs are the mainstay of treatment in the management of patients with acid-related disorders.3 Thus, patients with GERD usually take long-term PPIs,and possibly carry the risk of gastric cancer. In the present study, we performed a case–control study to investigate the association of PPIs use and risk of gastric cancer using data from a nationwide population database, the National Health Insurance Research Database (NHIRD) in Taiwan.4 This study also used a subdataset of the NHIRD, which comprises one million randomly sampled beneficiaries enrolled in the NHI programme in 2000 (Longitudinal Health Insurance Database …

Purpose: To investigate the use of proton pump inhibitors (PPIs) and the risk of pancreatic cancer. Methods: A nested case–control analysis was conducted. Patients with pancreas cancer were matched with controls by propensity score. Univariate and multivariate logistic regression models were used to determine whether PPIs use affected the risk of pancreas cancer. Dose effect was analyzed based on the cumulative defined daily dose (DDD), which was calculated using the total supply of PPIs to individual patients in terms of days and quantity. Results: A total of 1087 patients with pancreas cancer were matched with 1087 control patients from the database. The overall adjusted odds ratio (OR) of PPI use associated with pancreas cancer was 1.69 (95% confidence interval [CI], 1.44-2.05). Dose analysis by cumulative DDD, based on all types of PPI combined, revealed a lower adjusted OR of 0.92 (95% CI, 0.64-1.33) for those on Conclusions: Risk of pancreas cancer was associated with PPI use in patients with peptic ulcer diseases or gastroesophageal reflux disease.

G protein-coupled receptor (GPCR) activation-mediated PKA and PKC pathways have been recognized to be important in ovarian physiology. Expression of regulator of G-protein signaling 2 (RGS2) has been reported in ovarian granulosa cells. The detailed mechanisms in PKA- and PKC-regulated RGS2 expression and cellular translocation in granulosa cells remain mostly unclear. PKA activator 8-bromo-cAMP and PKC activator phorbol-12, 13-didecanoate appeared to rapidly elevate both protein and mRNA levels and promoter activation of RGS2 gene. Two consensus Sp1 elements within the shortest 78 bp fragment of RGS2 promoter sequence were essential for the full responsiveness to PKA and PKC. PKC activation appeared to increase the RGS2 translocation from nucleus to cytosol. PKA- and PKC-mediated RGS2 transcription in a Sp-1-dependent manner and a PKC-mediated RGS2 intracellular translocation were noted in granulosa cells.

Aim The aim of this study was to investigate the incidence of dysplastic transformation of Barrett's esophagus (BE) in a Chinese population. Method Data from nondysplastic BE patients at Taichung Veterans General Hospital were collected from May 2008 to June 2017. The enrolled individuals received regular upper gastrointestinal (UGI) endoscopy during follow up. The pathological transformations, including low‐grade dysplasia (LGD), high‐grade dysplasia (HGD), or esophageal adenocarcinoma (EAC), were collected prospectively until June 2017. Rates of progression were calculated in cases with a diagnosis of dysplasia or EAC. Results There were 51 subjects who met the inclusion criteria, with a mean follow up of 3.71 years (SD, 1.61) and a total follow up of 189.1 patient‐years. Eight cases (15.7%) developed LGD, with a calculated incidence rate of 2.9% per year. The mean time to development of LGD was 3.26 years (SD, 2.68–3.84). One subject (2%) developed EAC, with a calculated incidence rate of 0.4% per year. No case with HGD was detected. Conclusion In a Chinese population with nondysplastic BE, 15.7% of cases developed LGD, with an incidence rate of 2.9% per year, and 2% of cases developed EAC, with an incidence rate of 0.4% per year.

Aims This study aimed to evaluate the risk of bowel events among elderly patients treated using only PTGBD (Percutaneous Gallbladder Drainage), or a cholecystectomy on its own, or PTGBD combined with a subsequent cholecystectomy. Methods A retrospective population-based cohort study was conducted with newly diagnosed cholelithiasis and cholecystitis patients who had no bowel obstruction history and were aged over 65 years during the period of January 1, 2000 to December 31, 2010. These patients were placed into 3 separate study cohorts; PTGBD alone, cholecystectomy alone and PTGBD with subsequent laparoscopic cholecystectomy, with the cohort frequencies matched by age and gender. We defined the index date as the time of the initial cholelithiasis and cholecystitis diagnosis date and began observation and suspended follow-up when the patient had either withdrawn from their health insurance, developed bowel obstruction or reached the date of December 31, 2011. Results The incidences of bowel obstruction were 24.6, 19.2 and 13.6 per 1000 person-years for PTGBD cohort, cholecystectomy cohort and PTGBD respectively, with a subsequent laparoscopic cholecystectomy cohort. Compared with the PTGBD cohort, (which was adjusted for age, gender, CCI score and laparotomy history), the hazard ratio of bowel obstruction was 0.77 (95% Confidence Interval (CI) = 0.59–1.00) and 0.57 (95% CI = 0.43–0.76) for the cholecystectomy cohort and PTGBD with a subsequent laparoscopic cholecystectomy cohort respectively. Conclusion For treatment of cholelithiasis and cholecystitis in elderly patients, PTGBD with a subsequent cholecystectomy could benefit patients by providing a lower risk of ileus or intestinal obstruction.