Dietary habits and physical activity during the third wave of the COVID-19 pandemic: associated factors, composite outcomes in a cross-sectional telephone survey of a Chinese population, and trend analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic created many challenges for Hong Kong residents attempting to maintain healthy lifestyle habits. This study aimed to measure the prevalences of unhealthy dietary habits and physical inactivity levels in Hong Kong Chinese, identify associated factors, and conduct a time trend analysis during the third wave of the COVID-19 pandemic. METHODS: A cross-sectional telephone survey was conducted in Hong Kong by simple random sampling. The survey comprised socio-demographic characteristics, clinical information, the Hong Kong Diet Score (HKDS), smoking and alcohol consumption, and a Chinese version of the International Physical Activity Questionnaire Short Form. The composite outcome was low HKDS, physical inactivity, smoking, and alcohol consumption. We used 14 Health Behaviour Survey reports from 2003 to 2019 to establish a trend analysis regarding fruit and vegetable consumption, physical activity level, smoking, and alcohol consumption. RESULTS: We performed 1500 complete telephone surveys with a response rate of 58.8%. Most participants were older adults (≥65 years, 66.7%), women (65.6%), and married (77.9%). The HKDS was significantly lower in men, single individuals, low-income participants, alcohol drinkers, and patients with diabetes mellitus or renal disease. Participants who were single, undergoing long-term management of medical diseases, or had diabetes or renal diseases exhibited greater likelihood of physical inactivity. CONCLUSION: Prevalences of unhealthy lifestyle habits were high among men, single individuals, and chronic disease patients during the third wave of the COVID-19 pandemic in Hong Kong. The adoption of physical activity habits tended to decrease in the past two decades.

Faecal microbiota transplantation for treatment of recurrent or refractory Clostridioides difficile infection in Hong Kong.

INTRODUCTION: Clostridioides difficile infection (CDI) is a leading cause of healthcare-associated infection globally, causing significant morbidity and mortality. Faecal microbiota transplantation (FMT) has emerged as a promising option for recurrent and refractory CDI. This study aimed to assess the safety, efficacy, and feasibility of FMT for CDI in Hong Kong. METHODS: We conducted a single-centre, retrospective study for all consecutive cases of recurrent or refractory CDI who underwent FMT from 2013 to 2018. Clinical demographics, outcome, and safety parameters were collected. RESULTS: A total of 24 patients with recurrent or refractory CDI (median age 70 years, interquartile range=45.0-78.3 years; 67% male) were included. Over 80% had been recently hospitalised or were long-term care facility residents. Faecal microbiota transplantation was delivered by feeding tube in 11 (45.8%), oesophagogastroduodenoscopy in eight (33.3%), and colonoscopy in six (25%) of the patients. Resolution of diarrhoea without relapse within 8 weeks was achieved in 21 out of 24 patients (87.5%) after FMT. No deaths occurred within 30 days. The FMT was well tolerated and no serious adverse events attributable to FMT were reported. CONCLUSION: Our results confirm that FMT is a safe, efficacious, and feasible intervention for patients with refractory or recurrent CDI in Hong Kong. Given the increasing disease burden and the lack of effective alternatives in Hong Kong for difficult-to-treat cases of CDI, we recommend that a territory-wide FMT service be established to address increasing demand for this treatment.

An updated Asia Pacific Consensus Recommendations on colorectal cancer screening.

OBJECTIVE: Since the publication of the first Asia Pacific Consensus on Colorectal Cancer (CRC) in 2008, there are substantial advancements in the science and experience of implementing CRC screening. The Asia Pacific Working Group aimed to provide an updated set of consensus recommendations. DESIGN: Members from 14 Asian regions gathered to seek consensus using other national and international guidelines, and recent relevant literature published from 2008 to 2013. A modified Delphi process was adopted to develop the statements. RESULTS: Age range for CRC screening is defined as 50-75 years. Advancing age, male, family history of CRC, smoking and obesity are confirmed risk factors for CRC and advanced neoplasia. A risk-stratified scoring system is recommended for selecting high-risk patients for colonoscopy. Quantitative faecal immunochemical test (FIT) instead of guaiac-based faecal occult blood test (gFOBT) is preferred for average-risk subjects. Ancillary methods in colonoscopy, with the exception of chromoendoscopy, have not proven to be superior to high-definition white light endoscopy in identifying adenoma. Quality of colonoscopy should be upheld and quality assurance programme should be in place to audit every aspects of CRC screening. Serrated adenoma is recognised as a risk for interval cancer. There is no consensus on the recruitment of trained endoscopy nurses for CRC screening. CONCLUSIONS: Based on recent data on CRC screening, an updated list of recommendations on CRC screening is prepared. These consensus statements will further enhance the implementation of CRC screening in the Asia Pacific region.

microRNA-221 and microRNA-18a identification in stool as potential biomarkers for the non-invasive diagnosis of colorectal carcinoma.

BACKGROUND: The detection of microRNA (miRNA) dysregulation in stool is a novel approach for the diagnosis of colorectal carcinoma (CRC). The aim of this study is to investigate the use of miR-221 and miR-18a in stool samples as non-invasive biomarkers for CRC diagnosis. METHODS: A miRNA expression array containing 667 miRNAs was performed to identify miRNA dysregulation in CRC tissues. We focused on miR-221 and miR-18a, two significantly upregulated miRNAs which were subsequently verified in 40 pairs of CRC tissues and 595 stool samples (198 CRCs, 199 polyps and 198 normal controls). RESULTS: miR-221 and miR-18a were upregulated in the miRNA expression array. miR-221 and miR-18a levels were also significantly higher in 40 CRC tumours compared with their respective adjacent normal tissues. In stool samples, miR-221 and miR-18a showed a significant increasing trend from normal controls to late stages of CRC (P<0.0001). The levels of stool miR-221 and miR-18a were both significantly higher in subjects with stages I+II (miR-221: P<0.0001, miR-18a: P<0.0001) and stages III+IV of CRC (miR-221: P=0.0004, miR-18a: P<0.0001) compared with normal controls. The AUC of stool miR-221 and miR-18a were 0.73 and 0.67 for CRC patients as compared with normal controls, respectively. No significant differences in stool miR-221 and miR-18a levels were found between patients with proximal and distal CRCs. The use of antibiotics did not influence stool miRNA-221 and miRNA-18a levels. CONCLUSIONS: Stool-based miR-221 can be used as a non-invasive biomarker for the detection of CRC.

Capsule endoscopy in acute upper gastrointestinal hemorrhage: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy may play a role in the evaluation of patients presenting with acute upper gastrointestinal hemorrhage in the emergency department. PATIENTS AND METHODS: We evaluated adults with acute upper gastrointestinal hemorrhage presenting to the emergency departments of two academic centers. Patients ingested a wireless video capsule, which was followed immediately by a nasogastric tube aspiration and later by esophagogastroduodenoscopy (EGD). We compared capsule endoscopy with nasogastric tube aspiration for determination of the presence of blood, and with EGD for discrimination of the source of bleeding, identification of peptic/inflammatory lesions, safety, and patient satisfaction. RESULTS: The study enrolled 49 patients (32 men, 17 women; mean age 58.3 ±â€†19 years), but three patients did not complete the capsule endoscopy and five were intolerant of the nasogastric tube. Blood was detected in the upper gastrointestinal tract significantly more often by capsule endoscopy (15 /18 [83.3 %]) than by nasogastric tube aspiration (6 /18 [33.3 %]; P = 0.035). There was no significant difference in the identification of peptic/inflammatory lesions between capsule endoscopy (27 /40 [67.5 %]) and EGD (35 /40 [87.5 %]; P = 0.10, OR 0.39 95 %CI 0.11 - 1.15). Capsule endoscopy reached the duodenum in 45 /46 patients (98 %). One patient (2.2 %) had self-limited shortness of breath and one (2.2 %) had coughing on capsule ingestion. CONCLUSIONS: In an emergency department setting, capsule endoscopy appears feasible and safe in people presenting with acute upper gastrointestinal hemorrhage. Capsule endoscopy identifies gross blood in the upper gastrointestinal tract, including the duodenum, significantly more often than nasogastric tube aspiration and identifies inflammatory lesions, as well as EGD. Capsule endoscopy may facilitate patient triage and earlier endoscopy, but should not be considered a substitute for EGD.

Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding.

BACKGROUND AND STUDY AIMS: Endoscopic therapy of upper gastrointestinal bleeding remains challenging with conventional endoscopic devices. Use of Hemospray, where a nanopowder with clotting abilities is sprayed onto the bleeding site, had been highly effective for management of arterial bleeding in a heparizined animal model. The safety and effectiveness of Hemospray for hemostasis of active peptic ulcer bleeding in humans was evaluated. PATIENTS AND METHODS: In a prospective, single-arm, pilot clinical study, consecutive adults with confirmed peptic ulcer bleeding (Forrest score Ia or Ib), who had all given informed consent to participation, underwent upper gastrointestinal endoscopy and application of Hemospray within 24 hours of hospital admission once hemodynamically stable. Up to two applications of Hemospray, not exceeding a total of 150 g were allowed. Bleeding recurrence was monitored post procedurally, by second-look endoscopy (72 hours post treatment), and by phone at 30 days. Rate of hemostasis, recurrent bleeding, mortality, need for surgical intervention, and treatment-related complications were assessed. RESULTS: 20 patients were recruited (18 men, 2 women; mean age 60.2 years). Acute hemostasis was achieved in 95 % (19 / 20) of patients; 1 patient had a pseudoaneurysm requiring arterial embolization. Bleeding recurred in 2 patients within 72 hours (shown by hemoglobin drop); neither had active bleeding identified at the 72-hour endoscopy. No mortality, major adverse events, or treatment- or procedure-related serious adverse events were reported during 30-day follow-up. CONCLUSION: These pilot results indicate that Hemospray is safe in humans. Hemospray was effective in achieving acute hemostasis in active peptic ulcer bleeding.

Pharmacogenetics of esomeprazole or rabeprazole-based triple therapy in Helicobacter pylori eradication in Hong Kong non-ulcer dyspepsia Chinese subjects.

OBJECTIVE: Our study aimed to assess the effectiveness of esomeprazole or rabeprazole in combination with amoxicillin and clarithromycin for the eradication of Helicobacter pylori in Hong Kong non-ulcer dyspepsia (NUD) patients. METHODS: A prospective clinical trial was conducted at the Alice Ho Miu ling Nethersole Hospital outpatient endoscopy center from June 2004 to December 2005. Participants received amoxicillin 1 g, clarithromycin 500 mg, and, esomeprazole 20 mg (EAC) or rabeprazole 20 mg (RAC), all given twice daily for 1 week. The H. pylori status was determined by the [13C] urea breath test at least 4 weeks after completion of the treatment. Mutation status of CYP2C19 in exon 4 and exon 5 associated with the poor metabolizer phenotype was determined. RESULTS: The intention-to-treat eradication rates in patients treated with RAC and EAC were 77% and 84.6% respectively, and per protocol-based eradication rates were 83.7% and 88.9% respectively. The eradication rates did not vary with CYP2C19 phenotype found. For clarithromycin-sensitive strains, the cure rates were statistically significant regardless of CYP2C19 polymorphism (P < 0.0001). CONCLUSION: Triple therapy with either EAC or RAC is effective for Hong Kong Chinese NUD patients with H. pylori infection. Success eradication was related to clarithromycin resistance and not CYP2C19 genotype.

Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.

Identification of retinoic acid-regulated nuclear matrix-associated protein as a novel regulator of gastric cancer.

BACKGROUND: Retinoic acid-regulated nuclear matrix-associated protein (RAMP) is a WD40 repeat-containing protein that is involved in various biological functions, but little is known about its role in human cancer. This study aims to delineate the oncogenic role of RAMP in gastric carcinogenesis. METHODS: RAMP expression was examined by real-time quantitative RT-PCR, immunohistochemistry and western blotting. Inhibition of RAMP expression was performed by siRNA-mediated knockdown. The functional effects of RAMP on cell kinetics were measured by cell viability assay, colony formation assay and flow cytometry. Cell lines stably expressing RAMP were established to investigate the oncogenic effects of RAMP in vitro. RESULTS: Ramp was readily expressed in all seven gastric cancer cell lines and was significantly increased in human gastric cancer tissues when compared with their adjacent non-cancerous tissues (P<0.001). In keeping with this, expression of RAMP protein was higher in gastric cancer tissues compared with their adjacent non-cancerous tissues, whereas moderate protein expression were noted in intestinal metaplasia. Knockdown of RAMP in gastric cancer cells significantly reduced cell proliferation (P<0.01) and soft agar colony formation (P<0.001), but induced apoptosis and G(2)/M arrest. In additional, knockdown RAMP induced cell apoptosis is dependent on functional accumulation of p53 and p21 and induction of cleaved caspases-9, caspases-3 and PARP. Strikingly, overexpression of RAMP promoted anchorage-independent cell growth in soft agar. CONCLUSION: Our findings demonstrate that RAMP plays an oncogenic role in gastric carcinogenesis. Inhibition of RAMP may be a promising approach for gastric cancer therapy.

Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.

Asia Pacific consensus recommendations for colorectal cancer screening.

Colorectal cancer (CRC) is rapidly increasing in Asia, but screening guidelines are lacking. Through reviewing the literature and regional data, and using the modified Delphi process, the Asia Pacific Working Group on Colorectal Cancer and international experts launch consensus recommendations aiming to improve the awareness of healthcare providers of the changing epidemiology and screening tests available. The incidence, anatomical distribution and mortality of CRC among Asian populations are not different compared with Western countries. There is a trend of proximal migration of colonic polyps. Flat or depressed lesions are not uncommon. Screening for CRC should be started at the age of 50 years. Male gender, smoking, obesity and family history are risk factors for colorectal neoplasia. Faecal occult blood test (FOBT, guaiac-based and immunochemical tests), flexible sigmoidoscopy and colonoscopy are recommended for CRC screening. Double-contrast barium enema and CT colonography are not preferred. In resource-limited countries, FOBT is the first choice for CRC screening. Polyps 5-9 mm in diameter should be removed endoscopically and, following a negative colonoscopy, a repeat examination should be performed in 10 years. Screening for CRC should be a national health priority in most Asian countries. Studies on barriers to CRC screening, education for the public and engagement of primary care physicians should be undertaken. There is no consensus on whether nurses should be trained to perform endoscopic procedures for screening of colorectal neoplasia.

Fibulin 1 is downregulated through promoter hypermethylation in gastric cancer.

Tumour suppressor genes (TSGs) were frequently inactivated through promoter hypermethylation in gastric carcinoma as well as pre-malignant gastric lesions, suggesting that promoter hypermethylation can be used as a marker to define novel TSGs and also biomarkers for early detection of gastric cancer. In an effort to search for such genes aberrantly methylated in gastric cancer development, fibulin 1 (FBLN1) was found as a candidate TSG epigenetically downregulated in gastric cancer. FBLN1 expression was downregulated in all of gastric cancer cell lines used (100%, 7 out of 7) and the primary gastric carcinoma tissues (84%, 86 out of 102) and significantly restored after pharmacological demethylation. Hypermethylation of the FBLN1 promoter was frequently (71%, 5 out of 7) detected in gastric cancer cell lines and primary gastric carcinoma tissues. Ectopic expression of FBLN1 led to the growth inhibition of gastric cancer cells through the induction of apoptosis. In summary, FBLN1 was identified as a novel candidate TSG epigenetically downregulated in gastric cancer.

Prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease is prevalent in affluent countries and is strongly associated with metabolic syndrome. AIM: To study the prevalence of undiagnosed diabetes and postchallenge hyperglycaemia in Chinese patients with non-alcoholic fatty liver disease. METHODS: 73 consecutive patients with biopsy-proven non-alcoholic fatty liver disease and no history of diabetes underwent comprehensive metabolic screening. Diagnosis of diabetes and impaired glucose regulation was based on the 2006 American Diabetes Association criteria. RESULTS: The prevalence of undiagnosed diabetes and impaired glucose tolerance in non-alcoholic fatty liver disease patients was 33% and 29%, respectively. Among patients with 2-h plasma glucose above 7.8 mm, 47% had normal fasting glucose (below 5.6 mm). Impaired glucose tolerance was more common in patients with non-alcoholic steatohepatitis than those with simple hepatic steatosis (P = 0.036), and 2-h plasma glucose correlated with fibrosis stage (Spearman coefficient: 0.25, P = 0.046). In a binary logistic regression analysis, high fasting glucose and low high-density lipoprotein cholesterol were independent factors associated with diabetes. Nevertheless, if oral glucose tolerance test was only performed in non-alcoholic fatty liver disease patients with impaired fasting glucose, 20.8% of diabetes cases would be missed. CONCLUSIONS: Isolated postchallenge hyperglycaemia is common among Chinese non-alcoholic fatty liver disease patients without history of diabetes. It is associated with histological severe disease, and cannot be accurately predicted by any fasting glucose cut-off.

Helicobacter pylori eradication prior to initiation of long-term non-steroidal anti-inflammatory drug therapy in Chinese patients-a cost-effectiveness analysis.

BACKGROUND: Recent randomized clinical trials suggested that eradication of Helicobacter pylori prior to initiation of non-steroidal anti-inflammatory drug (NSAID) therapy would reduce the rate of peptic ulcer disease (PUD). OBJECTIVE: To analyze the cost-effectiveness of H. pylori eradication prior to initiation of long-term NSAID therapy for prevention of NSAID-induced PUD in a cohort of Chinese patients at high risk for PUD. METHODS: Clinical and economic data of 100 participants from a previously reported clinical trial conducted in Hong Kong were analyzed. Patients with a history of peptic ulcers were randomized to 1-week omeprazole 20 mg, amoxicillin 1 g and clarithromycin 500 mg twice daily (eradication group; n = 51) or 1-week omeprazole 20 mg twice daily (omeprazole group; n = 49) before initiation of diclofenac 100 mg daily for 6 months. The rates of PUD and healthcare utilization for routine follow-up as well as for management of symptomatic PUD of the 2 groups were retrieved from medical records. RESULTS: The rate of symptomatic ulcers in eradication group and omeprazole group were 3.9% and 18%, respectively. The mean direct medical cost of the eradication group was significantly lower than that of the omeprazole group by 30% (US dollar 797 (95% CI = 685 - 909) versus US dollar 1,128 (95% CI = 879 - 1,377)) (p = 0.018). The results were robust to variation of all the cost items. CONCLUSIONS: H. pylori eradication prior to initiation of NSAID therapy appeared to reduce the ulcer rate and mean direct medical cost when compared to no eradication for Chinese H. pylori-infected NSAID users at high risk for PUD.

Systematic review with network meta-analysis: comparative effectiveness and safety of strategies for preventing NSAID-associated gastrointestinal toxicity.

BACKGROUND: Many strategies are used to prevent nonsteroidal anti-inflammatory drug (NSAID)-associated gastrointestinal toxicity, but the comparative effectiveness remains unclear. AIM: To evaluate the comparative effectiveness of clinical strategies for preventing gastrointestinal toxicity induced by NSAIDs. METHODS: MEDLINE, EMBASE and the Cochrane Library (from their inception to May 2015) were searched for randomised controlled trials comparing the risk of gastrointestinal adverse events in patients taking nonselective NSAIDs, selective cyclooxygenase(COX)-2 inhibitors or nonselective NSAIDs/COX-2 inhibitors plus gastroprotective agents [proton pump inhibitors (PPIs), histamine-2 receptor antagonists, misoprostol]. Both pairwise meta-analysis and Bayesian network meta-analysis were performed. RESULTS: Analyses were based on 82 trials including 125 053 participants. Network meta-analysis demonstrated that selective COX-2 inhibitors + PPIs [Risk ratio (RR), 95% Credible Interval (CrI): ulcer complications 0.07, 0.02-0.18], selective COX-2 inhibitors (RR, 95% CrI: ulcer complications 0.25, 0.15- 0.38; symptomatic ulcer 0.12, 0.04-0.30), nonselective NSAIDs + PPIs (RR, 95% CrI: ulcer complications 0.28, 0.18-0.41; symptomatic ulcer 0.11, 0.04-0.23), nonselective NSAIDs + misoprostol (RR, 95% CrI: ulcer complications 0.47, 0.24-0.81; symptomatic ulcer 0.41, 0.13-1.00) were associated with significantly lower risk of clinical gastrointestinal events compared with nonselective NSAIDs. For all effectiveness endpoints, selective COX-2 inhibitors + PPIs was associated with the lowest absolute event probability and the highest rank, followed by selective COX-2 inhibitors and thirdly by nonselective NSAIDs + PPIs. CONCLUSION: The combination of selective COX-2 inhibitors plus PPIs provides the best gastrointestinal protection, followed by selective COX-2 inhibitors, and thirdly by nonselective NSAIDs plus PPIs.

Systematic review with meta-analysis: faecal occult blood tests show lower colorectal cancer detection rates in the proximal colon in colonoscopy-verified diagnostic studies.

BACKGROUND: The performance of faecal occult blood tests (FOBTs) to screen proximally located colorectal cancer (CRC) has produced inconsistent results. AIM: To assess in a meta-analysis, the diagnostic accuracy of FOBTs for relative detection of CRC according to anatomical location of CRC. METHODS: Diagnostic studies including both symptomatic and asymptomatic cohorts assessing performance of FOBTs for CRC were searched from MEDINE and EMBASE. Primary outcome was accuracy of FOBTs according to the anatomical location of CRC. Bivariate random-effects model was used. Subgroup analyses were performed to evaluate test performance of guaiac-based FOBT (gFOBT) and immunochemical-based FOBT (iFOBT). RESULTS: Thirteen studies, with 17 cohorts, reporting performance of FOBT were included; a total of 26 342 patients (mean age 58.9 years; 58.1% male) underwent both colonoscopy and FOBT. Pooled sensitivity, specificity, positive likelihood ratio and negative likelihood ratio of FOBTs for CRC detection in the proximal colon were 71.2% (95% CI 61.3-79.4%), 93.6% (95% CI 90.7-95.7%), 11.1 (95% CI 7.8-15.8) and 0.3 (95% CI 0.2-0.4) respectively. Corresponding findings for CRC detection in distal colon were 80.1% (95% CI 70.9-87.0%), 93.6% (95% CI 90.7-95.7%), 12.6 (95% CI 8.8-18.1) and 0.2 (95% CI 0.1-0.3). The area-under-curve for FOBT detection for proximal and distal CRC were 90% vs. 94% (P = 0.0143). Both gFOBT and iFOBT showed significantly lower sensitivity but comparable specificity for the detection of proximally located CRC compared with distal CRC. CONCLUSION: Faecal occult blood tests, both guaiac- and immunochemical-based, show better diagnostic performance for the relative detection of colorectal cancer in the distal colon than in the proximal bowel.

Epigenetic silencing of GDF1 disrupts SMAD signaling to reinforce gastric cancer development.

Accumulating evidence reveals the effectiveness of epigenetic therapy in gastric cancer. However, the molecular mechanisms and targets underlying such therapeutic responses remain elusive. Herein, we report an aberrant yet therapeutically rectifiable epigenetic signaling in gastric carcinogenesis. Administration of DNA-demethylating drug 5-aza-2'-deoxycytidine (5-aza-dC) reduced gastric cancer incidence by ~74% (P < 0.05) in N-nitroso-N-methylurea-treated mice. Through genome-wide methylation scanning, novel promoter hypermethylation-silenced and drug-targeted genes were identified in the resected murine stomach tumors and tissues. We uncovered that growth/differentiation factor 1 (Gdf1), a member of the transforming growth factor-ß superfamily, was silenced by promoter hypermethylation in control tumor-bearing mice, but became reactivated in 5-aza-dC-treated mice (P < 0.05). In parallel, the downregulated SMAD2/3 phosphorylation in gastric cancer was revived by 5-aza-dC in vivo. Such hypermethylation-dependent silencing and 5-aza-dC-mediated reactivation of GDF1-SMAD2/3 activity was conserved in human gastric cancer cells (P < 0.05). Subsequent functional characterization further revealed the antiproliferative activity of GDF1, which was exerted through activation of SMAD2/3/4-mediated signaling, transcriptional controls on p15, p21 and c-Myc cell-cycle regulators and phosphorylation of retinoblastoma protein. Clinically, hypermethylation and loss of GDF1 was significantly associated with reduced phosphorylated-SMAD2/3 and poor survival in stomach cancer patients (P < 0.05). Taken together, we demonstrated a causal relationship between DNA methylation and a tumor-suppressive pathway in gastric cancer. Epigenetic silencing of GDF1 abrogates the growth-inhibitory SMAD signaling and renders proliferation advantage to gastric epithelial cells during carcinogenesis. This study lends support to epigenetic therapy for gastric cancer chemoprevention and identifies a potential biomarker for prognosis.

Histological progression of non-alcoholic fatty liver disease in Chinese patients.

BACKGROUND: Non-alcoholic fatty liver disease is an important cause of chronic hepatitis and cryptogenic cirrhosis. The natural history of non-alcoholic fatty liver disease is not well understood especially in Asian populations. AIM: To investigate the histological progression in Chinese patients with biopsy-proven non-alcoholic fatty liver disease. METHODS: Chinese patients who had liver biopsy at least 3 years ago and confirmed to have non-alcoholic fatty liver disease were invited for a second liver biopsy. Clinical and laboratory parameters related to their liver function and metabolic syndrome were recorded and analysed. Liver biopsies were scored for the degree of steatosis, necroinflammation and fibrosis. Correlation coefficients were calculated to assess the association between changes in histological scores and metabolic parameters. RESULTS: Seventeen patients who had been followed up for a median period of 6.1 (range: 3.8-8.0) years underwent a second liver biopsy. Nine (53%) patients had progressive disease with worsening of fibrosis score. No statistically significant correlation was found between the changes in histological scores and metabolic parameters. Seven patients developed hypertension or diabetes mellitus during the period of follow-up. CONCLUSIONS: Non-alcoholic fatty liver disease is a progressive disease in Chinese patients as in their Caucasian counterparts. Diagnosis of non-alcoholic fatty liver disease may predate development of new components of metabolic syndrome.