Sex difference in the associations among risk factors with gastroesophageal reflux disease in a large Taiwanese population study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants. METHODS: We enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis. RESULTS: The overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD. CONCLUSIONS: Our results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.

Loss of MTA2-mediated downregulation of PTK7 inhibits hepatocellular carcinoma metastasis progression by modulating the FAK-MMP7 axis.

The expression of metastasis tumor-associated protein 2 (MTA2) and protein tyrosine kinase 7 (PTK7) is associated with hepatocellular carcinoma (HCC) progression. However, the functional effect and mechanism through which MTA2 regulates PTK7-mediated HCC progression remains unclear. Here, we found that MTA2 knockdown significantly down-regulated PTK7 expression in HCC cells (SK-Hep-1 and PLC/PRF/5). Data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases show that the PTK7 expression level was higher in HCC tissues than in normal liver tissues. In HCC patients, the PTK7 expression level clearly correlated with tumor stage and grade, lower overall survival (OS) correlated positively with MTA2 level, and PTK7 expression acted as a downstream factor for MTA2 expression. In addition, matrix metalloproteinase 7 (MMP7) expression was closely regulated by PTK7, and the mRNA and protein expression levels of MTA2 and PTK7 correlated positively with lower OS. MMP7 downregulation by PTK7 knockdown clearly decreased the migration and invasion abilities of HCC cells. In HCC cells, recombinant human MMP7 reversed the PTK7 knockdown-induced suppression of migration and invasion. Furthermore, deactivation of FAK using siFAK or FAK inhibitor (PF-573228, PF) synergistically contributed to PTK7 knockdown-inhibited FAK activity, MMP7 expression, and the migration and invasion abilities of HCC cells. Collectively, our findings show that PTK7 mediates HCC progression by regulating the MTA2-FAK-MMP7 axis and may be a diagnostic value for HCC patients.

Independent Signaling of Hepatoma Derived Growth Factor and Tumor Necrosis Factor-Alpha in Human Gastric Cancer Organoids Infected by Helicobacter pylori.

We prepared three-dimensional (3-D) organoids of human stomach cancers and examined the correlation between the tumorigenicity and cytotoxicity of Helicobacter pylori (H. pylori). In addition, the effects of hepatoma-derived growth factor (HDGF) and tumor necrosis factor (TNFα) on the growth and invasion activity of H. pylori-infected gastric cancer organoids were examined. Cytotoxin-associated gene A (CagA)-green fluorescence protein (GFP)-labeled H. pylori was used to trace the infection in gastric organoids. The cytotoxicity of Cag encoded toxins from different species of H. pylori did not affect the proliferation of each H. pylori-infected cancer organoid. To clarify the role of HDGF and TNFα secreted from H. pylori-infected cancer organoids, we prepared recombinant HDGF and TNFα and measured the cytotoxicity and invasion of gastric cancer organoids. HDGF controlled the growth of each organoid in a species-specific manner of H. pylori, but TNFα decreased the cell viability in H. pylori-infected cancer organoids. Furthermore, HDGF controlled the invasion activity of H. pylori-infected cancer organoid in a species-dependent manner. However, TNFα decreased the invasion activities of most organoids. We found different signaling of cytotoxicity and invasion of human gastric organoids in response to HDGF and TNFα during infection by H. pylori. Recombinant HDGF and TNFα inhibited the development and invasion of H. pylori-infected gastric cancer differently. Thus, we propose that HDGF and TNFα are independent signals for development of H. pylori-infected gastric cancer. The signaling of growth factors in 3-D organoid culture systems is different from those in two-dimensional cancer cells.

Heterogeneity of Phase II Enzyme Ligands on Controlling the Progression of Human Gastric Cancer Organoids as Stem Cell Therapy Model.

Gastric cancer (GC) organoids are frequently used to examine cell proliferation and death as well as cancer development. Invasion/migration assay, xenotransplantation, and reactive oxygen species (ROS) production were used to examine the effects of antioxidant drugs, including perillaldehyde (PEA), cinnamaldehyde (CA), and sulforaphane (SFN), on GC. PEA and CA repressed the proliferation of human GC organoids, whereas SFN enhanced it. Caspase 3 activities were also repressed on treatment with PEA and CA. Furthermore, the tumor formation and invasive activities were repressed on treatment with PEA and CA, whereas they were enhanced on treatment with SFN. These results in three-dimensional (3D)-GC organoids showed the different cancer development of phase II enzyme ligands in 2D-GC cells. ROS production and the expression of TP53, nuclear factor erythroid 2-related factor (NRF2), and Jun dimerization protein 2 were also downregulated on treatment with PEA and CA, but not SFN. NRF2 knockdown reversed the effects of these antioxidant drugs on the invasive activities of the 3D-GC organoids. Moreover, ROS production was also inhibited by treatment with PEA and CA, but not SFN. Thus, NRF2 plays a key role in the differential effects of these antioxidant drugs on cancer progression in 3D-GC organoids. PEA and CA can potentially be new antitumorigenic therapeutics for GC.

An extended 36-week oral esomeprazole improved long-term recurrent peptic ulcer bleeding in patients at high risk of rebleeding.

BACKGROUND: Patients with Rockall scores ≥6 have an increased risk of long-term peptic ulcer rebleeding. This study was aimed toward investigating whether an extended course of oral esomeprazole up to 1 year decreased ulcer rebleeding in such patients. METHODS: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After an initial 16-week oral proton pump inhibitor (PPI) treatment, patients were randomized to receive a 36-week course of oral twice-daily esomeprazole 20 mg (Group D, n = 60) or once-daily (Group S, n = 60). Thereafter, they were divided into the PPI-on-demand (n = 32) and PPI-discontinued (n = 77) subgroups. Our previous cohort with Rockall scores ≥6 served as the controls (Group C, n = 135); they received only an initial 8- to 16-week oral PPI. The primary and secondary outcomes were peptic ulcer rebleeding during the first year and the second year-and-thereafter, respectively. RESULTS: For the primary outcome, groups D and S comprised a higher proportion of rebleeding-free than Group C (P = 0.008 and 0.03, log-rank test). The competing-risks regression analysis confirmed that extended PPI use and American Society of Anesthesiologists classification were independent factors contributing to the primary outcome. For the secondary outcome, PPI-on-demand had a borderline higher proportion of rebleeding-free than Group C (P = 0.07, log-rank test); however, only the Rockall score was the independent factor. CONCLUSIONS: An extended 36-week course of oral esomeprazole 20 mg, twice- or once-daily for patients with Rockall scores ≥6 reduced ulcer rebleeding during the first year, but the effect needed to be further validated when PPIs were shifted to on-demand or discontinued thereafter (NCT02456012, 28/05/2015).

Nutritional and dietary strategy in the clinical care of inflammatory bowel disease.

The incidence and prevalence of inflammatory bowel disease have been increasing for decades and IBD has become a worldwide disease. Epidemiology studies demonstrated higher incidence rates in the more westernized countries. The change of habitual diets in these countries is perceived as the reason for the development of IBD. Besides, molecular biological studies showed some pathogenic substances produced after digestion of daily diet decrease the diversity of intestinal microbiota and cause dysbiosis of microbiome. Then, chronic inflammation occurs in some genetically susceptible subjects and IBD developed. As a result, many researchers started to investigate the potential therapeutic effects of nutrients and dietary intervention on the clinical course and pathogenesis of IBD. Carbohydrates, fats, proteins and fibers are investigated and their molecular roles in the inflammatory process are discovered gradually. The undigested carbohydrates are proved to cause overgrowth of colonic bacteria and inflammation occurs by altering colonic microbiome. ω-3 poly-unsaturated fatty acids are more favored over ω-6 poly-unsaturated fatty acids due to its less pro-inflammatory properties. High fibers produce more short-chain fatty acids in colon and facilitate the diversity of colonic microbiota. Moreover, some dietary interventions were designed and studied with promising results. Low FODMAP is recommended in IBS and is also suggested in patients of IBD with IBS-like symptoms. Specific Carbohydrate Diet was designed for celiac disease at first and is proved to be effective to decrease inflammation and to induce remission by decreasing non-digested carbohydrates into colon. Exclusive Enteral Nutrition has been investigated and is suggested to be the first line of management in pediatric CD in many literatures. Paleolithic diet and semi-vegetarian diet are evaluated and might be beneficial in some clinical settings. These findings are promising but limited to the evidence without high quality level. Some more well-designed studies with randomization and double-blind are needed and the primary endpoints should be more focused on the decrease of inflammation in pathology and mucosal healing in endoscopy instead of relief of the symptoms.

Gastric juice-based PCR assay: An alternative testing method to aid in the management of previously treated Helicobacter pylori infection.

BACKGROUND: Culture of Helicobacter pylori with previous eradication failure has been emphasized in clinical guidelines. The current unmet need to manage previously treated H pylori is one tool with diagnostic accuracy and ability for antibiotics susceptibility. Gastric juice PCR can provide diagnosis and antibiotics susceptibility; however, whether treatment failure affects its accuracy remains uninvestigated. Our study aimed to investigate diagnostic accuracy and antibiotics susceptibility of juice PCR in previously treated H pylori and to compare with the current standard of culture. METHODS: We categorized all 547 patients into treatment-naïve, post-1st treatment, post-2nd treatment, and post-3rd treatment. Helicobacter pylori infection was confirmed using gold standards. Sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and area under ROC curve (AUC) of juice PCR and culture were calculated. Intra-gastric H pylori density was evaluated. Lastly, the antibiotics susceptibility results of gastric juice and culture were compared. RESULTS: Our findings demonstrated AUC was higher in juice PCR than culture in all patients (96.7% vs 91.3%, P < 0.0001). The superiority of juice PCR was statistically significant in previously treated patients (P < 0.0001) but not in treatment-naïve patients (P = 0.13). Antral H pylori density was less marked in previously treated patients (P = 0.014). The comparisons of PCR-RFLP and E-test for Clarithromycin resistance showed reliable AUC = 89.8%. CONCLUSION: Compared with the current standard of culture, the gastric juice PCR contains the strengths of performing the antibiotics susceptibility and overcomes the shortcomings of low accuracy. Consequently, gastric juice PCR suits the unmet need to manage previously treated H pylori.

Predictor of slower gastric emptying in gastroesophageal reflux disease: Survey of an Asian-Pacific cohort.

BACKGROUND AND AIM: Asian populations have relatively lower prevalence of gastroesophageal reflux disease and tend to exhibit symptoms of prolonged gastric retention. However, it remains unknown if slower gastric emptying influences its features in Asian countries. We prospectively assessed the potential implications of slower gastric emptying in an Asian-Pacific cohort of gastroesophageal reflux disease by a hospital-based survey. METHODS: One hundred fifty-two patients of gastroesophageal reflux disease complete the scintigraphic measurement of solid phase of gastric emptying. Clinical symptoms and psychological stress are recorded by self-report questionnaire. The status of Helicobacter pylori infection, blood level of pepsinogen I, and I/II ratio are assessed. RESULTS: Forty-seven percent and 28% of the patients have slower gastric emptying rate, depending on the incremental defined cut-off values of slower gastric emptying, respectively. Multiple logistic regression analysis indicates that older age and depression score are independently related to slower gastric emptying. Subgroup analysis discloses that patients with slower gastric emptying and higher depression score tend to present with non-erosive esophagitis whereas higher body mass index level and male gender in patients with normal gastric emptying predict the presence of erosive reflux disease. CONCLUSIONS: Our study cohort of Asian patients indicates distinctive clinical implications of slower gastric emptying in patients with gastroesophageal reflux disease.

Fecal microbiota transplantation: Review and update.

Fecal microbiota transplantation (FMT) is a method to directly change the recipient's gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Donor selection with questionnaire, interview, blood tests, and stool examinations should be strictly performed before FMT to reduce and prevent occurrence of any adverse events. Step-by-step cautious fecal and recipient preparation along with adequately choosing delivery methods based on individual clinical situations are key points of the FMT process. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. In the future, we will look forward to personalized FMT for different patients and conditions according to varied hosts and diseases.

Short- and long-term outcomes of laparoscopic-assisted surgery, mini-laparotomy and conventional laparotomy in patients with Stage I-III colorectal cancer.

BACKGROUND: Three operative techniques have been used for colorectal cancer (CRC) resection: Conventional laparotomy (CL) and the mini-invasive techniques (MITs)- laparoscopic-assisted surgery (LAS) and mini-laparotomy (ML). The aim of the study was to compare the short- and long-term outcomes of patients undergoing the three surgical approaches for Stage I-III CRC resection. PATIENTS AND METHODS: This study enrolled 688 patients with Stage I-III CRC undergoing curative resection. The primary endpoints were perioperative quality and outcomes. The secondary endpoints were oncological outcomes including disease-free survival (DFS), overall survival (OS) and local recurrence (LR). RESULTS: Patients undergoing LAS had significantly less blood loss (P < 0.001), earlier first flatus (P = 0.002) and earlier resumption of normal diet (P = 0.025). Although post-operative complication rates were remarkably higher in patients undergoing CL than in those undergoing MITs (P = 0.002), no difference was observed in the post-operative mortality rate (P = 0.099) or 60-day re-intervention rate (P = 0.062). The quality of operation as assessed by the number of lymph nodes harvested and rates of R0 resection did not differ among the groups (all P > 0.05). During a median follow-up of 5.42 years, no significant difference was observed among the treatment groups in the rates of 3-year late morbidity, 3-year LR, 5-year LR, 5-year OS or 5-year DFS (all P > 0.05). CONCLUSIONS: Patients undergoing CL had higher post-operative morbidities. Moreover, the study findings confirm the favourable short-term and comparable long-term outcomes of LAS and ML for curative CRC resection. Therefore, both MITs may be feasible and safe alternatives to CL for Stage I-III CRC resection.

Ten-Day Quadruple Therapy Comprising Proton Pump Inhibitor, Bismuth, Tetracycline, and Levofloxacin is More Effective than Standard Levofloxacin Triple Therapy in the Second-Line Treatment of Helicobacter pylori Infection: A Randomized Controlled Trial.

OBJECTIVES: Proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy is recommended as a second-line treatment of Helicobacter pylori infection in the Maastricht V/Florence Consensus Report. However, the eradication rate of this standard salvage treatment is suboptimal. The objective of this study is to compare the efficacy of esomeprazole-bismuth-tetracycline-levofloxacin therapy (TL quadruple therapy) and esomeprazole-amoxicillin-levofloxacin triple therapy (AL triple therapy) in rescue treatment for H. pylori infection. METHODS: Consecutive H. pylori-infected subjects after failure of first-line therapies were randomly allocated to receive either TL quadruple therapy (esomeprazole 40 mg b.d., bismuth 120 mg q.d.s., tetracycline 500 mg q.d.s., and levofloxacin 500 mg o.d.) or AL triple therapy (esomeprazole 40 mg b.d., amoxicillin 500 mg q.d.s., and levofloxacin 500 mg o.d.) for 10 days. H. pylori status was assessed 6 weeks after the end of treatment. RESULTS: The study was stopped after an interim analysis. Of 50 patients in the TL quadruple therapy, 49 (98.0%) had successful eradication of H. pylori infection. Cure of H. pylori infection was achieved in 36 of 52 patients (69.2%) receiving AL triple therapy. Intention-to-treat analysis demonstrated that TL quadruple therapy achieved a markedly higher eradication rate than AL triple therapy (difference: 28.8%; 95% confidence interval: 15.7% to 41.9%; P<0.001). Per-protocol analysis yielded a similar result (97.8% vs. 68.6%; P<0.001). The two treatment groups exhibited comparable frequencies of overall adverse events (22.0% vs. 11.5%) and drug compliance (90.0% vs. 98.1%). The subgroup analysis showed that TL quadruple therapy was superior to AL triple therapy in patients with failure of either standard triple therapy (100% vs. 75.0%; P=0.010) or non-bismuth quadruple therapy (95.0% vs. 52.6%; P=0.003). CONCLUSIONS: Ten-day PPI-bismuth-tetracycline-levofloxacin quadruple therapy is a good option for rescue treatment of H. pylori infection following failure of standard triple or non-bismuth quadruple therapy.

Robotic surgery with high dissection and low ligation technique for consecutive patients with rectal cancer following preoperative concurrent chemoradiotherapy.

PURPOSE: We present the preliminary experiences with and short-term outcomes of 50 consecutive patients with rectal cancer who underwent preoperative concurrent chemoradiotherapy (CCRT) followed by robotic surgery by using the high dissection and low ligation technique. METHODS: Between October 2013 and August 2015, 50 patients with rectal cancer underwent robotic surgery after preoperative CCRT at a single institution. We performed D3 lymph node dissection and low tie ligation of the inferior mesenteric artery (IMA); this technique is referred to as the high dissection and low ligation technique. Clinicopathological features, perioperative parameters, and postoperative outcomes were retrospectively analyzed. RESULTS: FOLFOX regimen was used for preoperative CCRT in 26 (52 %) patients. Long-course radiotherapy was concurrently administered. A pathological complete response (pCR) was obtained in 14 (28 %) patients. Of the 50 patients, 23 (46 %) patients received intersphincteric resection (ISR) with coloanal anastomosis, 25 (50 %) patients received lower anterior resection (LAR), and 2 (4 %) patients received abdominoperineal resection (APR). Apical nodes were pathologically harvested in 47 (94 %) patients, and the median number of harvested apical lymph nodes was 2 (range, 0-10). The overall complication rate was 24 % (10 patients with 12 episodes), and most complications were mild. CONCLUSION: Roboic rectal surgery combined with appropriate preoperative CCRT helps in achieving a favorable pCR, circumferential resection margin, and sphincter preservation. Moreover, high dissection and low ligation of the IMA can be safely performed using the da Vinci(®) Surgical System safely which yield favorable short-term clinical outcomes.

Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control study.

BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.

17ß-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.

Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17ß-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17ß-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17ß-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.

FOLFIRI combined with bevacizumab as first-line treatment for metastatic colorectal cancer patients with hyperbilirubinemia after UGT1A1 genotyping.

OBJECTIVE: To report a metastatic colorectal cancer patient with hyperbilirubinemia treated with a combination of bevacizumab and FOLFIRI (5-fluorouracil, leucovorin, and irinotecan) using uridine diphosphate glucuronosyl transferase (UGT1A1) genotyping. CLINICAL PRESENTATION AND INTERVENTION: A 46-year-old male was diagnosed with rectosigmoid colon cancer with liver metastases and hyperbilirubinemia presenting with severe jaundice. UGT1A1 genotyping was used before therapy to ascertain whether genotype-adjusted dosages of irinotecan plus bevacizumab could alleviate the toxicity. Then, the patient was treated with FOLFIRI. CONCLUSION: The FOLFIRI regimen was successfully used in this patient without concerns regarding toxicity.

Management of gastric cancer in Asia: resource-stratified guidelines.

Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.

Sex difference in the associations among hyperuricemia with self-reported peptic ulcer disease in a large Taiwanese population study.

Background: Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD. Methods: Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis. Results: The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084-1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879-0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837-0.947; p < 0.001) but not in females (p = 0.139). Conclusion: The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.

High obesity indices are associated with gastroesophageal reflux disease, but low obesity indices are associated with peptic ulcer disease in a large Taiwanese population study.

INTRODUCTION: Gastro-esophageal reflux disease (GERD) and peptic ulcer disease (PUD) are prevalent in Taiwan. Few studies have investigated the associations between obesity indices with GERD and PUD simultaneously. This study aimed to investigate the correlations among obesity indices with GERD and PUD in a large cohort of participants, around 120,000, in the Taiwan Biobank (TWB). METHODS: A total of 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) were included to analyze the associations among obesity indices, including body mass index (BMI), waist-hip ratio (WHR), waist-to-height ratio (WHtR), body roundness index (BRI), abdominal volume index (AVI), lipid accumulation product (LAP), visceral adiposity index (VAI) and triglyceride-glucose Index (TyG index), with GERD and PUD. Self-reported GERD and PUD were obtained by questionnaires. Multivariate logistic regression analysis was employed to analyze the relationship between obesity indices with GERD and PUD. RESULTS: The prevalence of GERD and PUD was 13.7% and 14.6%, respectively. After multivariable analysis, high WHR (odds ratio [OR] = 1.009, p < 0.001), WHtR (OR = 1.005, p = 0.003), BRI (OR = 1.022, p =0.005), AVI (OR = 1.013, p < 0.001), LAP (OR = 1.001, p < 0.001), TyG index (OR = 1.068, p < 0.001) and VAI (OR = 1.013, p = 0.002) were significantly associated with GERD, except BMI (p = 0.384). On the other hand, low BMI (OR = 0.984; p < 0.001), and AVI (OR = 0.994; p = 0.036) were significantly associated with PUD. However, the value of WHR (p = 0.151), WHtR (p = 0.304), BRI (p = 0.452), LAP (p = 0.799), VAI (p = 0.347), and TyG index (p = 0.642) were not. CONCLUSION: This study found that high obesity indices are associated with GERD, but low obesity indices are associated with PUD in a large Taiwanese population study. Our findings may alert physicians to notice that different obesity index may be associated with different gastrointestinal disorder.

Comparison of 10 day bismuth quadruple therapy with high-dose metronidazole or levofloxacin for second-line Helicobacter pylori therapy: a randomized controlled trial.

OBJECTIVES: This prospective study was designed to compare the efficacies of levofloxacin-containing and high-dose metronidazole-containing quadruple therapies after failure of standard triple therapies. METHODS: A total of 150 Helicobacter pylori-infected patients were enrolled in our study and randomly assigned to levofloxacin-containing quadruple therapy (EBTL group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of levofloxacin once daily for 10 days) (n = 76) or high-dose metronidazole-based quadruple therapy (EBTM group) (40 mg of esomeprazole twice daily, 300 mg of bismuth subcitrate four times daily, 500 mg of tetracycline four times daily and 500 mg of metronidazole four times daily for 10 days) (n = 74). Follow-up endoscopy or urea breath test was done 16 weeks later to assess the treatment response. Patients' responses, CYP2C19 genotypes and antibiotic resistances were also examined. All participants, caregivers and those assessing the outcomes were blinded to group assignment. RESULTS: Intention-to-treat analysis revealed that both groups showed similar eradication rates: EBTL, 78.9% (60/76) (95% CI 69.7%-88.1%) and EBTM, 79.7% (59/74) (95% CI 70.5%-88.7%) [risk ratio (RR) 0.97, 95% CI 0.44-2.14]. Per-protocol results were EBTL = 87.0% (60/69) (95% CI 79.4%-94.9%) and EBTM = 90.8% (59/65) (95% CI 83.8%-97.8%) (RR 0.68, 95% CI 0.23-2.0). We did not find significant differences in compliance (RR 0.5, 95% CI 0.54-2.3) and adverse events (RR 1.11, 95% CI 0.54-2.3) between the two groups. Logistic regression analysis showed that only compliance was an important predictor for eradication failure. CYP2C19 polymorphism did not influence the eradicating effect. CONCLUSIONS: The 10 day bismuth quadruple therapies with high-dose metronidazole or levofloxacin were effective even in areas with high resistance. These two therapies were equally safe and tolerated. Besides this, the metronidazole-containing therapy was cheaper. So it is persuasive that high-dose metronidazole-containing quadruple therapy could be a good choice for second-line H. pylori eradication in areas with high resistance.

A phase Ib/II trial of PEP503 (NBTXR3, radioenhancer) with radiotherapy and chemotherapy in patients with rectal cancer.

Aims: To investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy and concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer. Methods: Patients will receive a single intratumoral injection of the nanoparticles, followed by radiotherapy and intravenous infusion of fluorouracil or oral capecitabine concurrently. In phase Ib (escalation phase, 3 + 3 design), volume escalation is based on the tumor volume of 5, 10, 15 and 22% of total baseline tumor volume. In phase II (expansion phase), 18 additional patients will be enrolled. Discussion: This study will be the first prospective, open-label, single-arm, nonrandomized study to investigate the efficacy and safety profile of PEP503 (NBTXR3) nanoparticles with radiotherapy and chemotherapy in these patients. Trial registration number: NCT02465593 (ClinicalTrials.gov).

Preoperative concurrent chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer. PEP503 (NBTXR3) has radioenhancement properties. Therefore, the dose per fraction during radiotherapy could be reduced, and the same therapeutic efficacy could be retained when PEP503 (NBTXR3) nanoparticles are used during radiotherapy. This study reveals the protocol of a phase Ib/II study to investigate the safety profile, dose-limiting toxicity and antitumor activity of PEP503 (NBTXR3) nanoparticles with radiotherapy combined with concurrent chemotherapy in patients with locally advanced or unresectable rectal cancer.