Summary Background Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum ...regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3–4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis. Methods We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression. Findings Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42–0·88) for fluorouracil, 0·68 (0·44–1·07) for gemcitabine, 0·91 (0·55–1·46) for chemoradiation, 0·54 (0·15–1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10–1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49–0·84) and gemcitabine (0·59, 0·41–0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12–2·54) or gemcitabine (1·86, 1·04–3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01–169·36). Interpretation Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy. Funding None.
Gastric cancer (GC) remains the leading cause of cancer mortality worldwide. Conceivably, early diagnosis may be achievable through screening of the high-risk population. Therefore, it is important ...to identify individuals harboring premalignant lesions that include atrophic gastritis, intestinal metaplasia, and mucosal dysplasia. The age threshold for GC screening depends on the regional incidence and the individual risk. In high-incidence countries such as Japan and Korea, the age to screen GC may be as early as 40 years. The mass screening by endoscopy in these countries would be able to detect a substantial portion of patients with early GCs as well as precancerous lesions. For the purpose of eliminating GC, however, these screening programs should be conducted in conjunction with Helicobacter pylori eradication. In low-incidence countries, it seems feasible to adopt a stepwise approach to identify high-risk individuals at first. The initial screening should focus on epidemiologic factors, genetic or hereditary risks, and the status of H pylori infection. Measurement of serum pepsinogen I and II and gastrin may detect atrophic gastritis in a noninvasive manner. Patients with these premalignant lesions should then receive endoscopic examination and enter surveillance. To date, there is no cost-effective strategy for an average-risk individual from a population with low incidence of GC, and therefore screening is unwarranted and cannot be recommended for them.
Nonalcoholic fatty liver disease (NAFLD) may be a cause of hepatocellular carcinoma (HCC), but its high prevalence challenges current surveillance strategies. We aimed to evaluate HCC incidences in ...different risk stratifications for noncirrhotic NAFLD. Using Taiwan's National Health Insurance Research Database, we located 31,571 patients with NAFLD between the years 1998 and 2012. After excluding other causes of hepatitis, underlying cirrhosis or malignancy, 18,080 patients were recruited for final analysis. Cumulative incidences of HCC were analyzed after adjusting for competing mortality. With a median follow-up duration of 6.32 years in the study cohort, the 10-year cumulative incidence of HCC was 2.73% 95% confidence interval (CI): 1.69-3.76%. Hepatoprotectant was used as a surrogate marker for elevated serum alanine transaminase (ALT). After adjusting for age, gender, hypertension, hypercholesterolemia, diabetes mellitus, gout, statin use, metformin use and aspirin use, elevated ALT was independently associated with an increased HCC risk hazard ratio (HR) 6.80, 95% CI: 3.00-15.42; p < 0.001. Multivariate stratified analysis verified this association in all subgroups (HR> 1.0). Moreover, increased age (HR 1.08 per year, 95% CI: 1.05-1.11) and statin use (HR 0.29, 95% CI: 0.12-0.68) were also identified as independent risk factors. The 10-year cumulative HCC incidence was highest in older (age >55 years) patients with ALT elevation (12.41%, 95% CI: 5.99-18.83%), but lowest in younger patients without ALT elevation (0.36%, 95% CI: 0-1.08%). The incidence of HCC was relatively low in patients with clinically noncirrhotic NAFLD, however, HCC risk was significantly increased in older patients experiencing an elevated serum ALT.
Tumor recurrence is a major issue for patients with hepatocellular carcinoma (HCC) following curative liver resection.
To investigate the association between nucleoside analogue use and risk of tumor ...recurrence in patients with hepatitis B virus (HBV)--related HCC after curative surgery.
A nationwide cohort study between October 2003 and September 2010. Data from the Taiwan National Health Insurance Research Database. Among 100 938 newly diagnosed HCC patients, we identified 4569 HBV-related HCC patients who received curative liver resection for HCC between October 2003 and September 2010.
The risk of first tumor recurrence was compared between patients not taking nucleoside analogues (untreated cohort, n = 4051) and patients taking nucleoside analogues (treated cohort, n = 518). Cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality.
The treated cohort had a higher prevalence of liver cirrhosis when compared with the untreated cohort (48.6% vs 38.7%; P < .001), but lower risk of HCC recurrence (n = 106 20.5% vs n = 1765 43.6%; P < .001), and lower overall death (n = 55 10.6% vs n = 1145 28.3%; P < .001). After adjusting for competing mortality, the treated cohort had a significantly lower 6-year HCC recurrence rate (45.6%; 95% CI, 36.5%-54.6% vs untreated, 54.6%; 95% CI, 52.5%-56.6%; P < .001). Six-year overall mortalities for treated cohorts were 29.0% (95% CI, 20.0%-38.0%) and for untreated 42.4% (95% CI, 40.0%-44.7%; P < .001). On modified Cox regression analysis, nucleoside analogue use (HR, 0.67; 95% CI, 0.55-0.81; P < .001), statin use (HR, 0.68; 95% CI, 0.53-0.87; P = .002), and nonsteroidal anti-inflammatory drugs or aspirin use (HR, 0.80; 95% CI, 0.73-0.88; P < .001) were independently associated with a reduced risk of HCC recurrence. Multivariable stratified analyses verified the association in all subgroups of patients, including those who were noncirrhotic (HR, 0.56; 95% CI, 0.42-0.76) and diabetic (HR, 0.52; 95% CI, 0.31-0.89).
Nucleoside analogue use was associated with a lower risk of HCC recurrence among patients with HBV-related HCC after liver resection.
Diet and exercise are conventional methods for controlling body weight and are linked to alterations in gut microbiota. However, the associations of diet, exercise, and gut microbiota in the control ...of obesity remain largely unknown. In the present study, using 16S rRNA amplicon sequencing and fecal microbiota transplantation (FMT), normal fat diet (NFD), exercise and their combination resulted in improved metabolic profiles in comparison to sedentary lifestyle with high fat diet (HFD). Moreover, diet exerted more influence than exercise in shaping the gut microbiota. HFD-fed mice receiving FMT from NFD-exercised donors not only showed remarkably reduced food efficacy, but also mitigated metabolic profiles (p < 0.05). The transmissible beneficial effects of FMT were associated with bacterial genera Helicobacter, Odoribacter and AF12 and overrepresentation of oxidative phosphorylation and glycolysis genes. Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT, suggesting a potential therapeutic treatment for obesity.
Summary
Background
There remains an unmet need for convenient biomarkers to assess the risks of discontinuing nucleos(t)ide analogues (NAs) in chronic hepatitis B (CHB).
Aim
To investigate if ...hepatitis B core‐related antigen (HBcrAg) is an independent of surface antigen (HBsAg) for risk prediction of NA cessation.
Methods
This prospective multicentre study enrolled 135 CHB patients who stopped entecavir or tenofovir after achieving viral remission for a median of 25.2 months. All patients stopped NA with negative HBeAg and undetectable viral DNA, and were then observed for clinical relapse and HBsAg loss. Predictors including HBsAg and HBcrAg levels were explored using Cox proportional hazard model and weighted to develop a risk score.
Results
During a median follow‐up of 25.9 months, clinical relapse and HBsAg loss occurred in 66 and eight patients, respectively, with a 5‐year cumulative incidence of 56.1% (95% CI 46.7‐66.0%) and 8.8% (95% CI 4.3‐17.4%), respectively. HBcrAg was an independent relapse predictor, as well as HBsAg, age, ALT and tenofovir use. A score (SCALE‐B) was calculated by the equation of 35*HBsAg (log IU/mL) + 20*HBcrAg (log U/mL) + 2*age (year) + ALT (U/L) + 40 for tenofovir use. The concordance rates for clinical relapse were 0.87, 0.88, 0.87, 0.85 and 0.90 at 1, 2, 3, 4 and 5 years, respectively. Moreover, HBsAg loss occurred exclusively in low‐risk patients predicted by the score.
Conclusions
Serum HBcrAg and HBsAg levels were independent predictors of off‐NA relapse and can be factored into a risk score to guide treatment cessation in patients with CHB.
Radiofrequency ablation (RFA) is the best choice for curative treatment of hepatocellular carcinoma (HCC) cases not suitable for surgical intervention, but efforts should be made to reduce the risk ...of tumor recurrence. We aimed to investigate the association between nucleos(t)ide analog (NA) therapy for hepatitis B virus (HBV) and the risk of HCC recurrence post‐RFA. Using the Taiwan National Health Insurance Research Database between July 1, 2004 and December 31, 2012, we screened 48,807 patients with newly diagnosed HBV‐related HCC. We identified 850 patients (200 patients who used NAs for more than 90 days and 650 who never used NA post‐RFA) who received RFA as a potentially curative treatment for HCC. Patients in the NA‐treated cohort were randomly matched 1:2 with patients in the untreated cohort by age, sex, cirrhosis, and the time period between RFA and initiation of NA therapy. Finally, 133 patients were recruited in the NA‐treated group and 266 in the untreated group for analysis. Cumulative incidences of and hazard ratios (HRs) for HCC recurrence were analyzed after adjusting for competing mortality. The HCC recurrence rate of the NA‐treated group was significantly lower than that of the untreated group (2‐year recurrence rate: 41.8%; 95% confidence interval CI: 32.9‐50.6 vs. 54.3%; 95% CI: 48.0‐60.6; modified log‐rank test: P < 0.05). In modified Cox's regression analysis, NA therapy was independently associated with a decreased risk of HCC recurrence (HR, 0.69; 95% CI: 0.50‐0.95; P < 0.05). Multivariate stratified analyses verified the association of NA therapy and decreased HCC recurrence in almost all patient subgroups. Conclusion: NA therapy was associated with a decreased risk of HCC recurrence among patients with HBV‐related HCC post‐RFA. (Hepatology 2016;63:1517‐1527)
Hepatitis C virus (HCV) infection is causally associated with insulin resistance and diabetes mellitus. This population‐based cohort study aimed to investigate whether antiviral therapy for HCV ...infection was associated with improved clinical outcomes related to diabetes. From the Taiwan National Health Insurance Research Database, 2,267,270 Taiwanese residents diagnosed with diabetes mellitus were screened for eligibility. HCV infection was defined by a specific diagnosis code and measurement of serum antibody. After excluding patients with serious comorbidity, we enrolled a total of 1,411 eligible patients who received pegylated interferon plus ribavirin (treated cohort), and matched them 1:1 with 1,411 untreated controls by propensity scores (untreated cohort). We also matched the treated cohort 1:4 with 5,644 diabetic patients without HCV infection (uninfected cohort). Participants were followed up for the occurrence of endstage renal disease (ESRD), ischemic stroke, and acute coronary syndrome (ACS) after receiving antiviral treatment or the corresponding calendar date. From 2003 to 2011, the 8‐year cumulative incidences of ESRD in the treated, untreated, and uninfected cohorts were 1.1% (95% confidence interval CI, 0.3‐2.0%), 9.3% (95% CI, 5.9‐12.7%), and 3.3% (95% CI, 2.3‐4.3%), respectively (P < 0.001); those of stroke were 3.1% (95% CI, 1.1‐5.0%), 5.3% (95% CI, 3.0‐7.5%), and 6.1% (95% CI, 4.8‐7.4%), respectively (P = 0.01); and those for ACS were 4.1% (95% CI, 2.1‐6.1%), 6.6% (95% CI, 3.7‐9.5%), and 7.4% (95% CI, 5.9‐9.0%), respectively (P = 0.05). As compared with the untreated cohort, antiviral treatment was associated with multivariate‐adjusted hazard ratios of 0.16 (95% CI, 0.07‐0.33%) for ESRD, 0.53 (95% CI, 0.30‐0.93) for ischemic stroke, and 0.64 (95% CI, 0.39‐1.06) for ACS. Conclusion: Antiviral treatment for HCV infection is associated with improved renal and cardiovascular outcomes in diabetic patients. (Hepatology 2014;59:1293‐1302)
Helicobacter pylori infection is the major cause of gastric cancer, and removal of H. pylori infection from a population could theoretically decrease the number of cases by about 89%. However, in ...real‐life settings, few studies have reported the effect of screening and treating this pathogen in population‐based programs. This is mainly because of the lack of an adequate infrastructure for delivery of systematic screening services to asymptomatic individuals, the lack of standardization to ensure that each subject receives the correct diagnostic testing and antibiotic treatment, and limited resources. We illustrate our method of implementing two population‐based screen‐and‐treat programs in Taiwan, where the epidemiological characteristics of disease burden have changed from the traditionally Eastern pattern towards that of the Western countries. Our first example is a high‐risk population that resides on an offshore island, in which a strategy of mass eradication of H. pylori was applied. The other example is an intermediate‐risk population, which is representative of the general average‐risk population, in which there is integration of the screen‐and‐treat method with the established framework of colorectal cancer screening using the fecal‐occult blood test. The information provided here may be useful for integration of gastric cancer prevention measures into the healthcare priorities of populations with different gastric cancer risks, such as those with limited resources.
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