Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy.

Backgrounds and Aim: Chronic hepatitis C (CHC) patients who fail antiviral therapy have a high risk of developing hepatocellular carcinoma (HCC). We investigated the effects of metformin and statins, commonly used to treat diabetes mellitus (DM) and hyperlipidemia (HLP), on HCC risk in CHC patients who failed antiviral therapy. Methods: CHC patients with failed interferon-based therapy were enrolled in a large-scale multicenter cohort study in Taiwan (T-COACH). HCC occurrence 1.5 years after the end of antiviral therapy was identified by linking to the cancer registry databases from 2003 to 2019. After considering death and liver transplantation as competing risks, Gray's cumulative incidence and Cox sub-distribution hazards for HCC development were used. Results: Among the 2,779 CHC patients, 480 (17.3%) developed new-onset HCC and 238 (8.6%) died after antiviral therapy. Metformin non-users with DM had a 51% higher risk of liver cancer than patients without DM, while statin users with HLP had a 50% lower risk of liver cancer than patients without HLP. The 5-year cumulative incidence of HCC was 16.5% in metformin non-users, significantly higher in metformin non-users than in patients without DM (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Conversely, HLP statin users had a significantly lower HCC risk than patients without HLP (3.8% vs. 12.5%; aSHR=0.50; P<0.001). Notably, the unfavorable effect of non-metformin use on increased HCC risk was mainly observed among patients without cirrhosis but not in patients with cirrhosis. In contrast, a favorable effect of statins reduced the risk of HCC in both cirrhotic and non-cirrhotic patients. Conclusion: Metformin for DM and statins for HLP have chemopreventive effects on HCC risk in CHC patients who failed antiviral therapy. These findings emphasize the importance of personalized preventive strategies for managing patients with these clinical profiles.

Recommendations and guidelines for endoscope reprocessing: Current position statement of digestive endoscopic society of Taiwan.

Reprocessing of gastrointestinal (GI) endoscopes and accessories is an essential part of patient safety and quality control in GI endoscopy centers. However, current endoscopic reprocessing guidelines or procedures are not adequate to ensure patient-safe endoscopy. Approximately 5.4 % of the clinically used duodenoscopes remain contaminated with high-concern microorganisms. Thus, the Digestive Endoscopy Society of Taiwan (DEST) sets standards for the reprocessing of GI endoscopes and accessories in endoscopy centers. DEST organized a task force working group using the guideline-revision process. These guidelines contain principles and instructions of step-by-step for endoscope reprocessing. The updated guidelines were established after a thorough review of the existing global and local guidelines, systematic reviews, and health technology assessments of clinical effectiveness. This guideline aims to provide detailed recommendations for endoscope reprocessing to ensure adequate quality control in endoscopy centers.

Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan.

BACKGROUND & AIMS: Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS: Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS: Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS: Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS: The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.

Risk stratification of hepatocellular carcinoma incidence using a fibrosis-4-based prediction model in patients with chronic hepatitis C receiving antiviral therapy: a nationwide real-world Taiwanese cohort study.

A total of 1,589 patients who had received interferon-based treatment were enrolled and analyzed for the risk of hepatocellular carcinoma (HCC) in a real-world nationwide Taiwanese chronic hepatitis C cohort (T-COACH). We aimed to stratify HCC risk by non-invasive fibrosis index-based risk model. Of 1589 patients, 1363 (85.8%) patients achieved sustained virological response (SVR). Patients with SVR had 1, 3, 5 and 10-year cumulative HCC incidence rates of 0.55%, 1.87%, 3.48% and 8.35%, respectively. A Cox proportional hazards model revealed that non-SVR (adjusted hazard ratio [aHR]: 1.92, 95% confidence interval [CI]: 1.19-3.12, p = 0.008), diabetes mellitus (aHR: 2.11, 95% CI: 1.25-3.55, p = 0.005), and fibrosis (FIB)-4 at the end of follow-up (EOF; aHR: 5.60, 95% CI: 2.97-10.57, p < 0.0001) were independent predictors of HCC. Risk score models based on the three predictors were developed to predict HCC according to aHR. In model 1, the 10-year cumulative incidence rates of HCC were 43.35% in patients at high risk (score 9-10), 25.48% in those at intermediate risk (score 6-8), and 4.06% in those at low risk (score 3-5) of HCC. In model 2, the 10-year cumulative incidence rates of HCC were 39.64% in patients at high risk (at least two risk predictors), 19.12% in those at intermediate risk (with one risk predictor), and 2.52% in those at low risk (without any risk predictors) of HCC. The FIB-4-based prediction model at EOF could help stratify the risk of HCC in patients with chronic hepatitis C after antiviral treatment.

Long-term outcome of liver complications in patients with chronic HBV/HCV co-infection after antiviral therapy: a real-world nationwide study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

BACKGROUND AND AIM: The long-term outcome of hepatitis B virus (HBV) infection among patients dually infected with HBV and hepatitis C virus (HCV) remains unclear. We aimed to investigate the long-term liver outcomes of HBV/HCV-coinfected patients after antiviral therapy. METHODS: A total of 11,359 chronically HCV-infected patients with interferon-based therapy were registered in a nationwide Taiwanese Chronic Hepatitis C Cohort. A propensity score matched (PSM) cohort of HCV mono-infected (n = 7020) and HBV/HCV (n = 702) co-infected patients by age, sex, and fibrosis was recruited for outcome analysis. The primary outcome was liver-related complications, including hepatocellular carcinoma (HCC) and liver decompensation during a mean follow-up period of 4.44 years. RESULTS: Among HBV/HCV co-infected patients, patients without HCV-SVR had a significantly higher 10-year cumulative incidence of major liver-related complications than those with HCV-SVR. However, among patients with HCV-SVR in the PSM cohort, the risk of major liver-related complications, both HCC and liver decompensation, did not differ between HBV/HCV co-infected and HCV mono-infected patients. Similar results were observed among those without HCV-SVR. A substantial lower risk of major liver-related complications was found in HBV/HCV co-infected patients with HCV SVR and subsequent anti-HBV nucleot(s)ide analogues treatment. Overall, factors associated with major liver-related complications included age ≥ 65 year-old, BMI ≥ 27 kg/m2, FIB-4 ≥ 3.25, eGFR < 60 ml/min/1.73 m2, and non-HCV SVR, but not HBV co-infection. CONCLUSION: Interferon-based therapy reduced the long-term risk of major liver-related complications among HBV/HCV co-infected patients, as among HCV mono-infected patients. Nevertheless, post-HCV-SVR surveillance for major liver-related complications is mandatory among those high-risk groups.

Hepatitis C virus eradication decreases the risks of liver cirrhosis and cirrhosis-related complications (Taiwanese chronic hepatitis C cohort).

BACKGROUND AND AIM: It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. METHODS: Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10 693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications (DLD or HCC). RESULTS: Of the 10 693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46 798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2-7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4-32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0.001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1-37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1-86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0.001). CONCLUSIONS: Hepatitis C virus eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.

Long-term risk of end-stage renal diseases with maintenance dialysis among chronic hepatitis C patients after antiviral therapy in Taiwan.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is associated with impaired renal function. The aim of this study is to explore the risk of and factors associated with end-stage renal diseases (ESRD) under maintenance dialysis among HCV patients after anti-HCV therapy. METHODS: A total of 12 696 HCV-infected patients with interferon-based therapy, including 9679 (76.2%) achieving sustained virological response (SVR), were enrolled from 23 hospitals in Taiwan. RESULTS: During a mean follow-up period of 5.3 years (67 554 person-years), the annual incidence of 4.1/10 000 person-years, 4.0/10 000 and 4.7/10 000 person-years among SVR patients and non-SVR patients, respectively. History of diabetes and baseline estimated glomerular filtration rate < 60 mL/min/m2 , instead of SVR, were the significant risk factors for developing ESRD with maintenance dialysis after anti-HCV therapy (adjusted hazard ratio 7.75 and 9.78). CONCLUSION: Diabetes and baseline impaired renal function were strongly associated with progression to ESRD with maintenance dialysis among chronic HCV-infected patients after antiviral therapy.

Successful Antiviral Therapy Reduces Risk of Schizophrenia Among Chronic Hepatitis C Patients: A Nationwide Real-World Taiwanese Cohort (T-COACH).

BACKGROUND: Chronic hepatitis C (CHC) has been associated with major psychoses, and interferon (IFN)-based therapy may cause psychiatric sequelae. We aimed to evaluate the effects of sustained virological response (SVR) on the incidence of major psychoses in a nationwide Taiwanese CHC cohort. METHODS: Fifteen thousand eight hundred thirty-six CHC Taiwanese who received IFN-based therapy were enrolled between 2003 and 2015. Of those, 12 723 patients were linked to the National Health Insurance Research Databases for the incidence of major psychoses. Death before major psychoses was considered a competing risk. RESULTS: Twenty-four patients developed new-onset major psychoses during 67 554 person-years (3.6 per 10 000 person-years), including 16 affective psychoses, 7 schizophrenia, and 1 organic psychotic condition. The incidence of major psychoses and affective psychoses did not differ between the SVR and non-SVR groups. The 10-year cumulative incidence of schizophrenia were significantly higher in the non-SVR than in SVR patients (0.14% vs 0.04%, P = .036). Cox subdistribution hazards showed that SVR and older age were associated with a significantly lower risk of schizophrenia (hazard ratio = 0.18 and 0.17). Sustained virological response was associated with decreased incidence of schizophrenia and majorly observed among patients with age <45 (P = .02). CONCLUSIONS: Successful IFN-based therapy might reduce the incidence of schizophrenia among CHC patients, especially among younger patients.

The Impact of Gastric Juice pH on the Intraluminal Therapy for Helicobacter pylori Infection.

BACKGROUND: Helicobacter pylori (H. pylori) can be topically eradicated in stomach lumen on endoscopic examination. The procedures of intraluminal therapy for H. pylori infection (ILTHPI) include the control of intragastric pH, mucolytic irrigation of the gastric mucosal surface, and a single-dose medicament containing antimicrobial agents. AIMS: To detect gastric juice pH and evaluate its impact on the success rate of ILTHPI. METHODS: We enrolled 324 patients with upper abdominal discomfort for endoscopic examinations. Among them, 13C-urea breath test was positive in 218 patients, where 100 underwent ILTHPI, and negative in 106. All patients had their gastric juice pH detected and set into three ranges, including normal acidity (pH < 4.0), low-level hypoacidity (pH 4.0-5.5), and high-level hypoacidity (pH ≥ 6.0). The impact of gastric juice pH on the success rate of ILTHPI was evaluated. RESULTS: Distribution of pH level showed no significant difference between two groups of H. pylori-infected patients (p = 0.942). The eradication rate of ILTHPI is significantly lower in patients with gastric juice pH below 4 (p < 0.001). CONCLUSIONS: Detection of gastric juice pH in ILTHPI is extremely important. Rapid control of stomach pH at or above 4 for patients prior to ILTHPI is strongly recommended. (NCT03124420).

Sustained virological response to hepatitis C therapy does not decrease the incidence of systemic lupus erythematosus or rheumatoid arthritis.

In patients with chronic hepatitis C (CHC), the effects of baseline characteristics, virological profiles, and therapeutic outcome to pegylated interferon plus ribavirin (PR) therapy on autoimmune diseases are unknown. Taiwanese Chronic Hepatitis C Cohort is a nationwide hepatitis C virus registry cohort comprising 23 hospitals of Taiwan. A total of 12,770 CHC patients receiving PR therapy for at least 4 weeks between January 2003 and December 2015 were enrolled and their data were linked to the Taiwan National Health Insurance Research Database for studying the development of 10 autoimmune diseases. The mean follow-up duration was 5.3 ± 2.9 years with a total of 67,930 person-years, and the annual incidence of systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) was 0.03%. Other autoimmune diseases were not assessable due to few events. Body mass index ≥24 kg/m2 was an independent predictor of the low incidence of SLE or RA (hazard ratio 0.40, 95% confidence interval 0.17-0.93, p = 0.034). A sustained virological response (SVR) to PR therapy was not associated with the low incidence of SLE or RA in any subgroup analysis. CHC patients achieving SVR to PR therapy did not exhibit an impact on the incidence of SLE or RA compared with non-SVR patients.

Extrahepatic Malignancy Among Patients With Chronic Hepatitis C After Antiviral Therapy: A Real-World Nationwide Study on Taiwanese Chronic Hepatitis C Cohort (T-COACH).

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is associated with nonhepatocellular carcinoma malignancies. We aimed to evaluate whether achieving a sustained virological response (SVR, defined as HCV RNA seronegativity throughout posttreatment 24-week follow-up) could reduce the risk of non-hepatocellular carcinoma malignancy in a real-world nationwide Taiwanese Chronic Hepatitis C Cohort (T-COACH). METHODS: A total of 10,714 patients with chronic hepatitis C who had received interferon-based therapy (8,186 SVR and 2,528 non-SVR) enrolled in T-COACH and were linked to the National Cancer Registry database for the development of 12 extrahepatic malignancies, including those with potential associations with HCV and with the top-ranking incidence in Taiwan, over a median follow-up period was 3.79 years (range, 0-16.44 years). RESULTS: During the 44,354 person-years of follow-up, 324 (3.02%) patients developed extrahepatic malignancies, without a difference between patients with and without SVR (annual incidence: 0.69% vs 0.87%, respectively). Compared with patients with SVR, patients without SVR had a significantly higher risk of gastric cancer (0.10% vs 0.03% per person-year, P = 0.004) and non-Hodgkin lymphoma (NHL) (0.08% vs 0.03% per person-year, respectively, P = 0.03). When considering death as a competing risk, non-SVR was independently associated with gastric cancer (hazard ratio [HR]/95% confidence intervals [CIs]: 3.29/1.37-7.93, P = 0.008). When patients were stratified by age, the effect of SVR in reducing gastric cancer (HR/CI: 0.30/0.11-0.83) and NHL (HR/CI: 0.28/0.09-0.85) was noted only in patients aged <65 years but not those aged >65 years. DISCUSSION: HCV eradication reduced the risk of gastric cancer and NHL, in particular among younger patients, indicating that patients with chronic hepatitis C should be treated as early as possible.

A randomized trial comparing the efficacy of single-dose and double-dose administration of rectal indomethacin in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis.

BACKGROUND AND AIMS: The before-procedure or after-procedure rectal indomethacin administration was shown to be useful in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We designed this prospective randomized study to compare the efficacy of single-dose and double-dose rectal indomethacin administration in preventing post-ERCP pancreatitis (PEP). METHODS: We enrolled patients who underwent the ERCP in Taipei Mackay Memorial Hospital from 2016 June to 2017 November. Patients were randomly assigned to 2 groups: single and double-dose groups. The primary endpoint was the frequency of post-ERCP pancreatitis. RESULTS: A total 162 patients participated in this study, and there were 87 patients randomly assigned to the single-dose group, and 75 patients were assigned to the double-dose group. In the high-risk patients, the incidence of PEP was lower in double-dose patients (4.8%) than the single-dose patients (9.5%), but there was no significant difference (P =.24). Difficult cannulation was the only 1 risk factor for PEP after rectal indomethacin treatment. CONCLUSIONS: Single-dose rectal indomethacin administration immediately after ERCP in general population is good enough to prevent PEP, but difficult cannulation could induce the PEP frequency up to 15.4% even under rectal indomethacin use.

Intraluminal therapy for Helicobacter pylori infection.

BACKGROUND AND AIM: Several strategies have been proposed to increase the eradication rate of Helicobacter pylori. However, the widespread increasing resistance rates to current multiple-dose oral antibiotic therapies call for alternative therapeutic approaches. We aim to develop a novel intraluminal therapy for H. pylori infection (ILTHPI). METHODS: From April 2017 to December 2017, 100 H. pylori-infected treatment-naïve patients with upper abdominal pain or discomfort underwent endoscopic examinations and concomitant ILTHPI, which comprised the control of intragastric pH, the irrigation of gastric mucosal surface with a mucolytic agent, and the application of single-dose medicaments containing antibiotic powders. The safety profiles while conducting ILTHPI and adverse events after ILTHPI were evaluated. The success of eradication was assessed based on the result of the 13 C-urea breath test 6 weeks after ILTHPI. In addition, a patient with successful ILTHPI was reconfirmed by a negative H. pylori stool antigen test four to 6 months after ILTHPI to exclude short-term recurrence. RESULTS: All the 100 enrolled patients completed the ILTHPI with good safety profiles and mild adverse events (6%). Five patients dropped out, and 51 of 95 patients (53.7%) achieved successful eradication immediately after endoscopic examinations. All 51 patients revealed negative stool H. pylori antigen tests four to 6 months after successful ILTHPI. No short-term recurrence was observed. CONCLUSIONS: We have developed a novel therapeutic approach. With the ILTHPI, H. pylori can be eradicated immediately by administrating a single-dose regimen while conducting an endoscopic examination. CLINICAL TRIALS NUMBER: NCT03124420.

High percentage atypical hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs.

Nucleos(t)ide analogs are used for preventing liver cirrhosis in chronic hepatitis B patients, but the risk factors of hepatocellular carcinoma (HCC) in these patients remain unclear. We designed this retrospective cohort study, the aim is to determine the risk factors for HCC development and its image presentation under nucleos(t)ide analogs treatment.In this study, patients were treated with lamivudine (LAM), entecavir 0.5 mg (ETV), or telbivudine (LdT), and followed-up for at least 2 years to detect HCC and its presentation. Assessment of the risk factors for HCC included age, sex, HBeAg, viral load, liver cirrhosis, current and previous medications, and liver function tests.Totally, 396 patients were recruited, and 18 patients developed HCC. The mean time from the treatment to HCC development was 28.5 ±â€Š16.7 months. The clinical characteristics in HCC and no-HCC groups showed significant differences among age (52.8 ±â€Š6.1 vs 47.1 ±â€Š12.6 years, P <.01), baseline alanine transaminase (ALT) levels (161.4 ±â€Š177.3 vs 361.7 ±â€Š496.3, P <.01), and baseline liver cirrhosis (72.2% vs 29.9%, P <.01). In patients aged ≥45 years, the hazard ratio of HCC was 10.2 and liver cirrhosis was 4.1. Majority of HCCs developed in the right liver (14/18), were single numbered (13/18), had tumor size about 1.9 ±â€Š0.7 cm, were classified as T1 (14/18, TNM staging), and the atypical image occupied 88% of the HCC cases.The patients aged ≧45 years on long-term nucleos(t)ide analog therapy, and with baseline liver cirrhosis were at a high risk of HCC. Regular alpha-fetoprotein (AFP) assessment and image study of these patients are the gold standards for early HCC detection in patients with high percentage atypical HCC appearances.

Decreased Colorectal Adenoma Risk After Helicobacter pylori Eradication: A Retrospective Cohort Study.

BACKGROUND: Helicobacter pylori infection is associated with colorectal adenoma and confers a 1.3- to 2.26-fold increased risk. We evaluated the association between H. pylori and the progression of colorectal adenoma. METHODS: This retrospective cohort study included 615 adults with no history of colorectal adenoma or cancer at baseline who participated in a repeated, regular health screening examination, which included a bidirectional gastrointestinal endoscopy, between July 2006 and June 2015. A gastric biopsy specimen from each subject was tested for H. pylori. RESULTS: During follow-up, the incidence rates of colorectal adenoma progression in participants with persistent H. pylori infections (persistent group) and those whose infections had previously been successfully eradicated (eradication group) were 160.52 and 51.60 per 1000 person-years, respectively (P = .0003). After adjustment for confounding factors, the persistent group exhibited a higher risk of colorectal adenoma than the eradication group (hazard ratio = 3.04, 95% CI 1.899, 5.864). The colorectal adenoma ratio of patients uninfected with H. pylori was similar to that of the eradication group (23.93% vs 20.12%, P = .328). CONCLUSIONS: Persistent H. pylori infection was associated significantly with the independent development of colorectal adenoma. H. pylori infection may have a pathophysiological role in colorectal adenoma development and, after successful eradication of H. pylori, the colorectal adenoma ratio might decrease.

Colonization of Helicobacter pylori in the gastric cardia: A comparison between the UFT300 and CLO tests.

BACKGROUND AND AIM: To assess the detection rates of Helicobacter pylori colonization in the gastric cardia with two commercial kits of rapid urease test: 5 min UFT300 and 24 h CLO test in H. pylori-infected patients. METHODS: Eighty consecutive dyspeptic patients with confirmed H. pylori infection (serology and 13C-urea breath test) were prospectively studied. During endoscopy, tissue samples using separate biopsy forceps from the cardia were taken for the UFT300 and CLO tests. The results of the UFT300 were read at 5 and 30 min, and those of the CLO test were read at 24 h. RESULTS: Of 80 enrolled patients, 17 (21.3%) and 44 (55%) had positive findings with the UFT300 at 5 and 30 min, respectively, while 72 (90%) had positive findings with the CLO test at 24 h. The CLO test is significantly more sensitive than the UFT300 in evaluating H. pylori status in the cardia. On comparing patients with and without carditis, the detection rates of the CLO test were similar (91.1% vs 88.6%; P = 0.724), and the rates of the UFT300 were also similar at 5 and 30 min. CONCLUSIONS: The rate of H. pylori colonization in the gastric cardia was 90% in H. pylori-infected patients detected with the CLO test. Although the UFT300 provides a more rapid reading of H. pylori status, the diagnostic yield of the CLO test is much higher than that of the UFT300. However, a positive result of the UFT300 may indicate a higher bacterial load in the cardia, which warrants a more effective therapeutic strategy.

Lactobacillus casei Variety rhamnosus Probiotic Preventively Attenuates 5-Fluorouracil/Oxaliplatin-Induced Intestinal Injury in a Syngeneic Colorectal Cancer Model.

Adjuvant 5-fluorouracil (5-FU)-based chemotherapy, including FOLFOX (5-FU, leucovorin, and oxaliplatin), is recommended for colorectal cancer. However, intestinal mucositis remains a common adverse effect for which no effective preventive strategies are available. To develop a convenient and novel way to alleviate mucositis, we investigated the effect of Lactobacillus casei variety rhamnosus (Lcr35) on FOLFOX-induced mucosal injury. BALB/c mice subcutaneously injected with syngeneic CT26 colorectal adenocarcinoma cells were orally administered Lcr35 daily before, during, and after 5-day injection of FOLFOX regimen, for 14 days. The following methods were used: diarrhea score for toxicity, ELISA for cytokine production, histopathology for intestinal injury, immunohistochemistry for apoptosis/proliferation and regulatory proteins, RT-PCR for cytokine mRNA expression, and DNA sequencing for fecal gut microbiota. FOLFOX administration to colorectal cancer-bearing mice significantly inhibited tumor growth and the accompanying marked diarrhea and intestinal injury histologically characterized by the shortening of villi and destruction of intestinal crypts. Preventive administration of Lcr35 dose-dependently reduced the severity of diarrhea and intestinal mucositis without affecting the anti-tumor effect of FOLFOX. The numbers of apoptotic, NF-κB-, and BAX-activated cells increased after FOLFOX, and these responses were mitigated by Lcr35. TNF-α and IL-6 upregulation by FOLFOX treatment was attenuated by Lcr35. The fecal gut microbiota composition of Firmicutes and Bacteroidetes disturbed by FOLFOX was significantly reversed by Lcr35 toward a preferential profile. In conclusion, the oral probiotic Lcr35 prevented FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. The putative mechanism might involve modulation of gut microbiota and proinflammatory responses with suppression of intrinsic apoptosis in intestinal injury.

Small bowel tumors: A digestive endoscopy society of Taiwan (DEST) multicenter enteroscopy-based epidemiologic study.

BACKGROUND/PURPOSE: Small bowel (SB) accounts for the majority of gastrointestinal tract but its tumors are rare and always overlooked. In this study, we aimed to evaluate the epidemiology of SB tumors. METHODS: This multicenter retrospective study utilized endoscopy database from 2006/11 to 2016/07. Baseline demographic characteristics, clinical, radiologic and endoscopic findings were collected. RESULTS: Totally 103 (34 benign, 69 malignant lesions) patients with SB tumors in 1070 enteroscopic examinations were enrolled. There were male preponderance (56.3% males, 43.7% females), both in benign (52.9%, 49.1%) and malignant (58.0%, 42.0%) lesions, except for subtype gastrointestinal stromal tumors (GISTs) (31.6%, 68.4%). The age (mean ± SD) at diagnosis in malignant SB tumors (62.2 ± 15.6) was older than those with benign tumors (50.7 ± 21.4) (p < 0.01). Bleeding (43.7%), abdominal pain (40.8%) and ileus (10.7%) were the most common clinical presentations. Hamartoma (32.4%) and adenoma (14.7%) were the most common benign histology. Four major malignant histological subtypes were lymphomas (29.0%), GISTs (27.5%), adenocarcinomas (26.1%) and metastatic cancers (14.5%). SB adenocarcinoma patients (>60-year-old, 77.8%) were older than lymphomas (60%) and GISTs (50%). Proximally location rates of lymphomas, GISTs, adenocarcinomas were 25.0% (5/20), 84.2% (16/19), and 88.9% (16/18), respectively. CONCLUSION: This endoscopy-based study revealed the most common histology of benign SB tumors were hamartoma and adenoma, and malignant ones were lymphomas, GISTs, adenocarcinomas and metastatic cancers. Most of them were male gender, except for GISTs, and with proximal location, except for lymphomas. Further large-scale investigation efforts are warranted to elucidate the epidemiology of SB tumors.

Challenges in the diagnosis of ulcerative colitis with concomitant bacterial infections and chronic infectious colitis.

Ulcerative colitis (UC) is a chronic inflammation of the large bowel characterized by diarrhea and a negative stool culture. However, several enteropathogens have been implicated as causative agents in UC. The differentiation between chronic infectious colitis (IC) and UC with concurrent infection is difficult owing to their similar clinical presentations. The study aimed to explore the presentations and diagnostic clues that enable differentiation between UC with concomitant infections and chronic IC. The study included 17 UC patients with a bacterial infection and 46 with chronic IC. The UC patients (47 ± 19 years) were younger than the chronic IC patients (58 ± 20 years) (P = 0.022). Bloody diarrhea was more common in UC than in chronic IC (58.8% vs 10.9%, P < 0.001). Previous antibiotic usage was a risk factor for chronic IC (5.9% vs 32.6%, P = 0.031). Malignancy was a common comorbidity of chronic IC (5.9% vs 34.8%, P = 0.022). UC patients had lower antibiotic response rates than chronic IC patients (60.0% vs 87.2%, P = 0.026). Aeromonas species and Clostridium difficile were common in both groups. Histological features of cryptitis and crypt abscess were useful in the diagnosis of UC (P = 0.052 and P = 0.016, respectively). Bloody diarrhea in a young adult, decreased response to antibiotic treatment, and results of endoscopy with biopsy are important features in the diagnosis of UC with bacterial infection.