Kelvin K.F. Tsoi

Causes of Mortality in Patients With Peptic Ulcer Bleeding: A Prospective Cohort Study of 10,428 Cases

OBJECTIVES:Despite advances in endoscopic and pharmacological treatment for peptic ulcer bleeding (PUB), mortality remains at 5–10% worldwide. Our aim was to investigate the causes of death in a prospective cohort of PUB in a tertiary referral center.METHODS:Between 1993 and 2005, all patients with upper gastrointestinal bleeding (UGIB) admitted to the Prince of Wales Hospital were prospectively registered. Demographic data, characteristics of ulcer, and pharmacological, endoscopic, and surgical therapy, were documented. Mortality cases were classified as (A) bleeding-related death (A1: uncontrolled bleeding, A2: within 48 h after endoscopy, A3: during surgery for uncontrolled bleeding, A4: surgical complications or within 1 month after surgery, and A5: endoscopic related mortality) or (B) non-bleeding-related death (B1: cardiac causes, B2: pulmonary causes, B3: cerebrovascular disease, B4: multiorgan failure, and B5: terminal malignancy).RESULTS:In all, 18,508 cases of UGIB were enrolled; among them, 10,428 cases from 9,375 patients were confirmed to have PUB, and 577 (6.2%) patients died. There were significantly more patients who died of non-ulcer bleeding causes (79.7%) than bleeding causes (18.4%). The mean (s.d.) age of those who died of bleeding-related causes was higher (75.4 (12.6) years) than that of those who died of non-bleeding causes (71.7 (13.1) years) (P=0.010). Most bleeding-related deaths occurred when immediate control of bleeding failed (29.2%) or when patients died within 48 h after endoscopic therapy (25.5%). Among those who died of non-bleeding-related causes, multiorgan failure (23.9%), pulmonary conditions (23.5%), and terminal malignancy (33.7%) were most common.CONCLUSIONS:The majority of PUB patients died of non-bleeding-related causes. Optimization of management should aim at reducing the risk of multiorgan failure and cardiopulmonary death instead of focusing merely on successful hemostasis.

Endoscopic clipping versus injection and thermo-coagulation in the treatment of non-variceal upper gastrointestinal bleeding: a meta-analysis

Background: Hemoclips, injection therapy and thermocoagulation (heater probe or electrocoagulation) are the most commonly used types of endoscopic hemostasis for the control of non-variceal gastrointestinal bleeding. Aim: To compare the efficacy of hemoclips versus injection or thermocoagulation in endoscopic hemostasis by pooling data from the literature. Method: Publications in the English literature (MEDLINE, EMBASE and Cochrane Library) as well as abstracts in major international conferences were searched using the keywords “hemoclips” and “bleeding”, and 15 trials fulfilling the search criteria were found. Outcome measures included: initial hemostasis (after endoscopic intervention); recurrent bleeding; definitive hemostasis (no recurrent bleeding until the end of follow-up); the requirement for surgical intervention; and all-cause mortality. The heterogeneity of trials was examined and the effects were pooled by meta-analysis. Results: Of 1156 patients recruited in the 15 studies, 390 were randomly assigned to receive clips alone, 242 received clips combined with injection, 359 received injection alone, and 165 received thermocoagulation with or without injection. Definitive hemostasis was higher with hemoclips (86.5%) than injection (75.4%; RR 1.14, 95% CI 1.00–1.30), or endoscopic clips with injection (88.5%) compared with injections alone (78.1%; RR 1.13, 95% CI 1.03–1.23), leading to a reduced requirement for surgery but no difference in mortality. Compared with thermocoagulation, there was no improvement in definitive hemostasis with clips (81.5% versus 81.2%; RR 1.00, 95% CI 0.77–1.31). These estimates were robust in sensitivity analyses. There was also no difference between clips and thermocoagulation in rebleeding, the need for surgery and mortality. The reported locations of failed hemoclip applications included posterior wall of duodenal bulb, posterior wall of gastric body and lesser curve of the stomach. Conclusion: Successful application of hemoclips is superior to injection alone but comparable to thermocoagulation in producing definitive hemostasis. There was no difference in all-cause mortality irrespective of the modalities of endoscopic treatment.

The Asia-Pacific Colorectal Screening score: a validated tool that stratifies risk for colorectal advanced neoplasia in asymptomatic Asian subjects

Objective To develop and validate a clinical risk score predictive of risk for colorectal advanced neoplasia for Asia. Methods A prospective, cross-sectional and multicentre study was carried out in tertiary hospitals in 11 Asian cities. The subjects comprise 2752 asymptomatic patients undergoing screening colonoscopy. From a development set of 860 asymptomatic subjects undergoing screening colonoscopy, multiple logistic regression was applied to identify significant risk factors for advanced colorectal neoplasia defined as invasive carcinoma or advanced adenoma. The ORs for significant risk factors were utilised to develop a risk score ranging from 0 to 7 (Asia-Pacific Colorectal Screening (APCS) score). Three tiers of risk were arbitrarily defined: 0–1 ‘average risk’ (AR); 2–3 ‘moderate risk’ (MR); and 4–7 ‘high risk’ (HR). Subjects undergoing screening colonoscopy between July 2006 and December 2007 were prospectively enrolled to form an independent validation group. Each subject had a personal APCS score calculated by summing the points attributed from the presence of risk factors in the individuals. The performance of the APCS score in predicting risk of advanced neoplasia was evaluated. Results There were 860 subjects in the derivation set and 1892 subjects in the validation set, with a baseline prevalence of advanced neoplasia of 4.5% and 3%, respectively. Applying the APCS stratification in the validation set, 559 subjects (29.5%) were in the AR tier, 966 subjects (51.1%) in the MR tier and 367 (19.4%) subjects in the HR tier. The prevalence of advanced neoplasia in the AR, MR and HR groups was 1.3, 3.2 and 5.2%, respectively. The subjects in the MR and HR tiers had 2.6-fold (95% CI 1.1 to 6.0) and 4.3-fold (95% CI 1.8 to 10.3) increased prevalence of advanced neoplasia, respectively, than those in the AR tier. Conclusions The APCS score based on age, gender, family history and smoking is useful in selecting asymptomatic Asian subjects for priority of colorectal screening.

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.

Genetics of inflammatory bowel disease in Asia: Systematic review and meta-analysis

Background: Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease‐predisposing genes in Asian IBD patients. Methods: A systematic review and meta‐analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews. Results: In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age‐ and sex‐matched controls. Major nucleotide oligomerization domain (NOD)‐2 variants in Western Crohns disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy‐related protein 16‐linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84–1.13). Interleukin (IL)‐23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16–2.82) and a single nucleotide polymorphism in IL‐23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15–0.60). Tumor necrosis factor (TNF) superfamily gene‐15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86–3.86), while TNF‐308 polymorphisms (OR 1.82; 95% CI 1.15–2.9), cytotoxic T lymphocyte antigen (CTLA)‐4 (OR 2.75; 95% CI 1.22–6.22) and MICA allele (OR 2.41; 95% CI 1.89–3.07) were associated with ulcerative colitis in Asians. Conclusions: Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease‐associated mechanisms in this population of rising incidence. (Inflamm Bowel Dis 2012;)

Cognitive Tests to Detect Dementia A Systematic Review and Meta-analysis

IMPORTANCE Dementia is a global public health problem. The Mini-Mental State Examination (MMSE) is a proprietary instrument for detecting dementia, but many other tests are also available. OBJECTIVE To evaluate the diagnostic performance of all cognitive tests for the detection of dementia. DATA SOURCES Literature searches were performed on the list of dementia screening tests in MEDLINE, EMBASE, and PsychoINFO from the earliest available dates stated in the individual databases until September 1, 2014. Because Google Scholar searches literature with a combined ranking algorithm on citation counts and keywords in each article, our literature search was extended to Google Scholar with individual test names and dementia screening as a supplementary search. STUDY SELECTION Studies were eligible if participants were interviewed face to face with respective screening tests, and findings were compared with criterion standard diagnostic criteria for dementia. Bivariate random-effects models were used, and the area under the summary receiver-operating characteristic curve was used to present the overall performance. MAIN OUTCOMES AND MEASURES Sensitivity, specificity, and positive and negative likelihood ratios were the main outcomes. RESULTS Eleven screening tests were identified among 149 studies with more than 49,000 participants. Most studies used the MMSE (n = 102) and included 10,263 patients with dementia. The combined sensitivity and specificity for detection of dementia were 0.81 (95% CI, 0.78-0.84) and 0.89 (95% CI, 0.87-0.91), respectively. Among the other 10 tests, the Mini-Cog test and Addenbrookes Cognitive Examination-Revised (ACE-R) had the best diagnostic performances, which were comparable to that of the MMSE (Mini-Cog, 0.91 sensitivity and 0.86 specificity; ACE-R, 0.92 sensitivity and 0.89 specificity). Subgroup analysis revealed that only the Montreal Cognitive Assessment had comparable performance to the MMSE on detection of mild cognitive impairment with 0.89 sensitivity and 0.75 specificity. CONCLUSIONS AND RELEVANCE Besides the MMSE, there are many other tests with comparable diagnostic performance for detecting dementia. The Mini-Cog test and the ACE-R are the best alternative screening tests for dementia, and the Montreal Cognitive Assessment is the best alternative for mild cognitive impairment.

Cigarette smoking and the risk of colorectal cancer: a meta-analysis of prospective cohort studies.

BACKGROUND & AIMS Smoking has been implicated in many malignant diseases, but its association with colorectal cancer (CRC) is controversial. We quantitatively evaluated the relation between smoking and incidence of CRC in a meta-analysis of cohort studies. METHODS Full publications of prospective cohort studies were identified in MEDLINE and EMBASE from 1950 to 2008. Subjects were classified as current smokers, former smokers, or never smokers. The quantity of smoking was assessed by number of cigarettes per day, years of smoking, and pack-years. The reported relative risks of CRC were pooled by random-effects model. Sensitivity analysis was conducted, and publication bias was evaluated. RESULTS A total of 1,463,796 subjects were recruited in 28 prospective cohorts from America, Europe, and Asia, with median follow-up of 13 years (range, 4-30 years). Current smokers showed a modestly higher risk of CRC (relative risk [RR], 1.20; 95% confidence interval [CI], 1.10-1.30) than never smokers. The risk of CRC among male smokers (RR, 1.38; 95% CI, 1.22-1.56) was more significant than among female smokers (RR, 1.06; 95% CI, 0.95-1.19). Rectal cancer was more closely related to smoking (RR, 1.36; 95% CI, 1.15-1.61) than colonic cancer. Former smokers still carried a higher CRC risk than never smokers. The increased risk of CRC was related to cigarettes per day, longer years of smoking, or larger pack-years. CONCLUSIONS Smoking was associated with a significantly increased risk of CRC. The associated risk was higher for men and for rectal cancers. The association of tobacco consumption and CRC risk appeared to be dose-related.

The Efficacy of Cap-Assisted Colonoscopy in Polyp Detection and Cecal Intubation: A Meta-Analysis of Randomized Controlled Trials

OBJECTIVES:The role of cap-assisted colonoscopy (CAC) in polyp detection and cecal intubation is unclear. We conducted a meta-analysis to compare the efficacy of CAC vs. standard colonoscopy (SC).METHODS:Publications in English and non-English literatures (OVID, MEDLINE, and EMBASE) and abstracts in major international conferences were searched for controlled trials comparing CAC and SC. Outcome measures included the proportion of patients with polyps or adenomas detected, cecal intubation rate, cecal intubation time, and total colonoscopy time. The statistical heterogeneity of trials was examined and the effects were pooled by random-effects model. The risk of bias was evaluated by the assessment tool from the Cochrane Handbook. Subgroup analyses were performed for possible clinical and methodological heterogeneities.RESULTS:From 2,358 citations, 16 randomized controlled clinical trials were included consisting of 8,991 subjects (CAC: 4,501; SC: 4,490). Mean age of subjects was 61.0 years old and 60% were males. CAC detected a higher proportion of patients with polyp(s) (relative risk (RR): 1.08; 95% confidence interval (CI): 1.00–1.17) and reduced the cecal intubation time (mean difference: −0.64 min; 95% CI: −1.19 to −0.10). Cecal intubation rate (RR: 1.00; 95% CI: 0.99–1.02) and total colonoscopy time (mean difference: –0.97 min; 95% CI: −2.33 to 0.40) were comparable between the two groups. In subgroup analyses, a short cap (≤4 mm) was associated with improved polyp detection, whereas a long cap (≥7 mm) was associated with a shorter cecal intubation time.CONCLUSIONS:CAC demonstrated marginal benefit over SC for polyp detection and shortened the cecal intubation time.

Guidewire versus conventional contrast cannulation of the common bile duct for the prevention of post-ERCP pancreatitis: a systematic review and meta-analysis

BACKGROUND The use of a guidewire (GW) for cannulation of the bile duct during ERCP may prevent post-ERCP pancreatitis (PEP). OBJECTIVES A systematic review and meta-analysis of GW-guided versus conventional contrast (CC)-guided bile duct cannulation for the prevention PEP. DESIGN A November 2008 search of gray literature, databases, reference lists, and meeting abstracts was conducted for randomized, controlled trials comparing GW and CC. Two independent reviewers extracted the data. The outcomes included PEP, primary cannulation success, and other adverse events. RESULTS From 2132 citations, 7 randomized, controlled trials (5 noncrossover trials and 2 crossover trials) were included. Among noncrossover trials only, there was significant reduction in PEP when using a GW (3.2%) compared with CC (8.7%) (relative risk [RR] 0.38; 95% CI, 0.19-0.76). Subgroup analysis showed a significantly lower occurrence of PEP after GW entry versus CC injection of the pancreatic duct (1.1% vs 9.5%; RR 0.19; 95% CI, 0.06-0.58). Among patients with a precut sphincterotomy from a failed primary cannulation, there was less PEP with GW cannulation compared with CC (2.4% vs 21.7%; RR 0.21; 95% CI, 0.04-1.04). The other adverse event rates were comparable between GW and CC groups (2% vs 2%; RR 1.05; 95% CI, 0.39-2.83). Primary cannulation success was significantly greater with GW use compared with CC (89% vs 78%; RR 1.19; 95% CI, 1.05-1.35). CONCLUSION ERCP GW cannulation reduces the risk of PEP compared with the use of CC. GW cannulation is associated with a higher cannulation success rate and less PEP after pancreatic duct entry.

Predicting Mortality in Patients With Bleeding Peptic Ulcers After Therapeutic Endoscopy

BACKGROUND & AIMS Despite advances in management of patients with bleeding peptic ulcers, mortality is still 10%. This study aimed to identify predictive factors and to develop a prediction model for mortality among patients with bleeding peptic ulcers. METHODS Consecutive patients with endoscopic stigmata of active bleeding, visible vessels, or adherent clots were recruited, and risk factors for mortality were identified in this deprivation cohort by using multiple stepwise logistic regression. A prediction model was then built on the basis of these factors and validated in the evaluation cohort. RESULTS From 1993 to 2003, 3220 patients with bleeding peptic ulcers were treated. Two hundred eighty-four of the patients developed rebleeding (8.8%); emergency surgery was performed on 47 of these patients, whereas others were managed with endoscopic retreatment. Two hundred twenty-nine of these sustained in-hospital death (7.1%). In patients older than 70 years, presence of comorbidity, more than 1 listed comorbidity, hematemesis on presentation, systolic blood pressure below 100 mm Hg, in-hospital bleeding, rebleeding, and need for surgery were significant predictors for mortality. Helicobacter pylori-related ulcers had lower risk of mortality. The receiver operating characteristic curve comparing the prediction of mortality with actual mortality showed an area under the curve of 0.842. From 2004 to 2006, data were collected prospectively from a second cohort of patients with bleeding peptic ulcers, and mortality was predicted by using the model developed. The receiver operating characteristic curve showed an area under the curve of 0.729. CONCLUSIONS Among patients with bleeding peptic ulcers after endoscopic hemostasis, advanced age, presence of listed comorbidity, multiple comorbidities, hypovolemic shock, in-hospital bleeding, rebleeding, and need for surgery successfully predicted in-hospital mortality.