Myriam Martel

International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding

DESCRIPTION A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from 2003. METHODS The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RECOMMENDATIONS Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.

The Canadian Registry on Nonvariceal Upper Gastrointestinal Bleeding and Endoscopy (RUGBE): Endoscopic Hemostasis and Proton Pump Inhibition are Associated with Improved Outcomes in a Real-Life Setting

OBJECTIVES:From the Canadian Registry of patients with Upper Gastrointestinal Bleeding and Endoscopy (RUGBE), we determined clinical outcomes and explored the roles of endoscopic and pharmacologic therapies in a contemporary real-life setting.METHODS:Analysis of randomly selected patients endoscoped for nonvariceal upper gastrointestinal bleeding at 18 community and tertiary care institutions between 1999 and 2002. Covariates and outcomes were defined a priori and 30-day follow-up obtained. Logistic regression models identified predictors of outcomes.RESULTS:One thousand eight-hundred and sixty-nine patients were included (66 ± 17 yr, 38% female, 2.5 ± 1.6 comorbid conditions, hemoglobin, 96 ± 27 g/L, 54% received a mean of 2.9 ± 1.7 units of blood). Endoscopy was performed within 24 h in 76%, with ulcers (55%) most commonly noted. High-risk endoscopic stigmata and endoscopic therapy were reported in 37%. Rebleeding, surgery, and mortality rates were 14.1%, 6.5%, and 5.4%, respectively. Decreased rebleeding was significantly and independently associated with PPI use (85% of patients, mean daily dose 56 ± 53 mg) in all patients regardless of endoscopic stigmata, (odds ratio (OR):0.53, 95% confidence interval, 95% CI:0.37–0.77) and endoscopic hemostasis in patients with high-risk stigmata (OR:0.39, 95% CI:0.25–0.61). PPI use (OR:0.18, 95% CI:0.04–0.80) and endoscopic therapy (OR:0.31, 95% CI:0.11–0.91) were also each independently associated with decreased mortality in patients with high-risk stigmata.CONCLUSIONS:These results appear to confirm the protective role of endoscopic therapy in patients with high-risk stigmata, and suggest that acute use of PPIs may be associated with a reduction of rebleeding in all patients, and lower mortality in patients with high-risk stigmata. Independent prospective validation of these observational findings is now required.

Obesity and colorectal cancer

Excess body weight, as defined by the body mass index (BMI), has been associated with several diseases and includes subjects who are overweight (BMI≥25–29.9 kg/m2) or obese (BMI≥30 kg/m2). Overweight and obesity constitute the fifth leading risk for overall mortality, accounting for at least 2.8 million adult deaths each year. In addition around 11% of colorectal cancer (CRC) cases have been attributed to overweight and obesity in Europe. Epidemiological data suggest that obesity is associated with a 30–70% increased risk of colon cancer in men, whereas the association is less consistent in women. Similar trends exist for colorectal adenoma, although the risk appears lower. Visceral fat, or abdominal obesity, seems to be of greater concern than subcutaneous fat obesity, and any 1 kg/m2 increase in BMI confers additional risk (HR 1.03). Obesity might be associated with worse cancer outcomes, such as recurrence of the primary cancer or mortality. Several factors, including reduced sensitivity to antiangiogenic-therapeutic regimens, might explain these differences. Except for wound infection, obesity has no significant impact on surgical procedures. The underlying mechanisms linking obesity to CRC are still a matter of debate, but metabolic syndrome, insulin resistance and modifications in levels of adipocytokines seem to be of great importance. Other biological factors such as the gut microbita or bile acids are emerging. Many questions still remain unanswered: should preventive strategies specifically target obese patients? Is the risk of cancer great enough to propose prophylactic bariatric surgery in certain patients with obesity?

Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses

BACKGROUND AND OBJECTIVE Optimal endoscopic hemostasis remains undetermined. This was a systematic review of contemporary methods of endoscopic hemostasis for patients with bleeding ulcers that exhibited high-risk stigmata. SETTING Randomized trials that evaluated injection, thermocoagulation, clips, or combinations of these were evaluated from MEDLINE, EMBASE, and CENTRAL (1990-2006). PATIENTS A total of 4261 patients were evaluated. OUTCOMES Outcomes were rebleeding (primary), surgery, and mortality (secondary). Summary statistics were determined; publication bias and heterogeneity were sought by using funnel plots or by subgroup analyses and meta-regression. RESULTS Forty-one trials assessed 4261 patients. All endoscopic therapies decreased rebleeding versus pharmacotherapy alone, including sole intravenous (IV) proton pump inhibition (PPI) (OR 0.56 [95% CI, 0.34-0.92]); only one trial assessed high-dose IV PPI. Injection alone was inferior compared with other methods, except for thermal hemostasis (OR 1.02 [95% CI, 0.74-1.40]), with a strong trend of increased rebleeding if 1 injectate is used rather than 2 (OR 1.40 [95% CI, 0.95-2.05]). Injection followed by thermal therapy did not decrease rebleeding compared with clips (OR 0.82 [95% CI, 0.28-2.38]) or thermal therapy alone (OR 0.79 [95% CI, 0.24-2.62]). Subgroup analysis, however, suggested that injection followed by thermal therapy was superior to thermal therapy alone. Clips were superior to thermal therapy (OR 0.24 [95% CI, 0.06-0.95]) but, when followed by injection, were not superior to clips alone (OR 1.30 [95% CI, 0.36-4.76]). Surgery or mortality was not altered in most comparisons. CONCLUSIONS All endoscopic treatments are superior to pharmacotherapy alone; only 1 study assessed high-dose IV PPI. Optimal endoscopic therapies include thermal therapy or clips, either alone or in combination with other methods. Additional data are needed that compare injection followed by thermal therapy to clips alone or clips combined with another method.

Effect of statin therapy on colorectal cancer

Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, also called statins, are commonly prescribed medications that lower serum cholesterol and decrease cardiac morbidity and mortality. They also possess beneficial effects beyond their cholesterol-lowering properties. Preclinical data suggest statins exhibit pleiotropic antineoplastic effects in a variety of tumours, but clinical studies have provided conflicting data as to whether statins influence the risk of cancer. The biological underpinning of potential effects of statins in colorectal cancer and their role in its prevention or as adjuvant therapy are reviewed. Following a meta-analysis of both randomised clinical trials and epidemiological studies, it is concluded that available clinical data only support a modest, although statistically significant, protective effect of statins in colorectal cancer. Statins may impact on outcomes by decreasing the invasiveness or metastatic properties of colorectal cancer. The data supporting these hypotheses, however, are few and further studies are required to better assess these hypotheses. Statins may also exert a beneficial effect on colorectal cancer by sensitising the tumour to chemotherapeutic agents. Further research is needed to better define the role of statins in overcoming chemoresistance. The combination of statins with other drugs, such as low-dose aspirin or safer non-steroidal anti-inflammatory medications, may be useful in both the prevention and treatment of colorectal cancer.

No Benefit of Covered vs Uncovered Self-Expandable Metal Stents in Patients With Malignant Distal Biliary Obstruction: A Meta-analysis

BACKGROUND & AIMS Self-expandable metal stents (SEMS) are used in patients with malignant distal biliary obstruction; trials that compared covered and uncovered SEMS reported different results because of heterogeneous designs and patient populations. These studies compared patency of uncovered SEMS and covered SEMS, along with rates of pancreatitis, cholecystitis, cholangitis, SEMS migration, bleeding, perforation, and recurrent biliary obstruction. METHODS We performed a meta-analysis to compare the effects of covered and uncovered SEMS in patients with malignant distal biliary obstruction. We identified randomized controlled trials by using a literature search from 1980 through March 2012. We evaluated data from 5 full articles and 4 abstracts, comprising 1061 patients, and assessed statistical heterogeneity and publication bias. RESULTS The weighted mean difference in the stent patency duration could only be calculated on the basis of 2 studies, but it was 67.9 days longer for covered SEMS than for uncovered SEMS (95% confidence interval [CI], 60.3-75.5). A summary analysis of data from 4 trials demonstrated no differences in patency of covered vs uncovered SEMS after 6 months (odds ratio [OR], 1.82; 95% CI, 0.62-5.25) or 12 months (OR, 1.25; 95% CI, 0.65-2.39). There were also no differences in the rates of pancreatitis, cholecystitis, perforation, bleeding, or cholangitis; length of hospital stay; or number of recurrent biliary obstructions. However, covered SEMS had a higher migration rate (OR, 7.13; 95% CI, 2.29-22.21). Patients with covered SEMS had a lower rate of tumor ingrowth (OR, 0.19; 95% CI, 0.07-0.55) but a higher rate of tumor overgrowth (OR, 1.88; 95% CI, 1.02-3.45). No summary calculations could be completed to confidently assess patient survival. CONCLUSIONS The use of covered SEMS, compared with uncovered SEMS, in patients with distal malignant biliary obstruction is of unclear benefit; covered SEMS have a higher rate of migration and do not appear to have longer patency.

Proton Pump Inhibitors vs. Histamine 2 Receptor Antagonists for Stress-Related Mucosal Bleeding Prophylaxis in Critically Ill Patients: A Meta-Analysis

OBJECTIVES:H2-receptor antagonists (H2RA) have been shown to reduce stress-related mucosal bleeding (SRMB), yet randomized controlled trials assessing proton pump inhibitors (PPIs) have yielded conflicting results. The objective of this study was to evaluate the efficacy of PPIs vs. H2RAs in the prophylaxis of SRMB in critically ill adults with risk factors for bleeding.METHODS:Tailored literature searches of the past four decades were conducted. Outcomes measured were the decreases in rates of clinically significant bleeding (B, primary outcome of the meta-analysis), nosocomial pneumonia (P), and mortality (M) (secondary outcomes). Study heterogeneity was sought and quantified. Results are reported as odd ratios (ORs) with 95% confidence intervals (CIs).RESULTS:Eight fully published randomized controlled trials and five abstracts met the inclusion criteria. Prophylactic PPI administration significantly decreased the incidence of bleeding (N=1,587 patients, OR=0.30; 95% CI: 0.17–0.54), number needed to treat=39; 95% CI: 21–303 with no observed statistical heterogeneity among the relevant comparisons (P=0.93, I2=0.0%). No statistical differences were noted for the development of nosocomial pneumonia (n=7, N=1,017 patients, OR=1.05; 95% CI: 0.69–1.62) or mortality (n=8, N=1,260 patients, OR=1.19; 95% CI: 0.84–1.68) or (and no heterogeneity was found for either: P=0.85, I2=0.0%, and P=0.96, I2=0%, respectively).CONCLUSIONS:In critically ill patients at risk for the development of SRMB, PPI prophylaxis significantly decreased rates of clinically significant bleeding compared with H2RA, without affecting the development of nosocomial pneumonia or mortality rates. The magnitude of the beneficial effect, and its clinical relevance, now requires further characterization using cost-effectiveness analysis considering the incidence of stress-related mucosal disease-related bleeding.

Laparoscopic Heller's myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: a meta-analysis of randomized, controlled trials

BACKGROUND Pneumatic dilation (PD) and laparoscopic Hellers myotomy (LHM) are the mainstays of therapy in idiopathic achalasia. Equipoise exists in choosing the first-line therapy. OBJECTIVE To assess comparative efficacies and adverse event rates of these methods. DESIGN Intention-to-treat, fixed-model, Mantel-Haenszel meta-analysis of randomized, controlled trials comparing PD with LHM. SETTING Randomized controlled trial comparing PD versus LHM. PATIENTS Patients with newly diagnosed idiopathic achalasia. INTERVENTION Comprehensive electronic and manual literature search from 1966 to March 2012 independently by two reviewers. MAIN OUTCOME MEASUREMENTS Response rate, rate of different adverse events, and quality of life after each therapy. RESULTS Three of 161 retrieved studies between 2007 and 2011, including 346 patients, were included. At 1 year, the cumulative response rate was significantly higher with LHM (86% vs 76%, odds ratio 1.98 (confidence interval 1.14-3.45); P = .02), with no significant heterogeneity (P = .39; I(2) 0%). Rates of major mucosal tears requiring subsequent intervention with LHM were significantly lower than those of esophageal perforation with PD requiring postprocedural medical or surgical therapy (0.6% and 4.8%, respectively; P = .04). Postprocedural rates of gastroesophageal reflux, lower esophageal sphincter pressures, and quality of life scores did not differ in trials with sufficient data. Data on longer follow-up were not available. LIMITATIONS Lack of data on follow-ups over 1 year and a small number of included studies. CONCLUSION This meta-analysis suggests that LHM may provide greater response rates as compared with graded PD in the treatment of newly diagnosed idiopathic achalasia, with lesser rates of major adverse events, in up to 1 year after treatment, although additional data are needed to confirm the validity of this conclusion in long-term follow-up.

Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer

Optimizing Adequacy of Bowel Cleansing for Colonoscopy: Recommendations From the US Multi-Society Task Force on Colorectal Cancer

Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. multi-society task force on colorectal cancer.

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States.(1) Colonoscopy can prevent CRC by the detection and removal of precancerous lesions. In addition to CRC screening and surveillance, colonoscopy is used widely for the diagnostic evaluation of symptoms and other positive CRC screening tests. Regardless of indication, the success of colonoscopy is linked closely to the adequacy of preprocedure bowel cleansing. Unfortunately, up to 20%-25% of all colonoscopies are reported to have an inadequate bowel preparation.(2,3) The reasons for this range from patient-related variables such as compliance with preparation instructions and a variety of medical conditions that make bowel cleansing more difficult to unit-specific factors (eg, extended wait times after scheduling of colonoscopy).(4) Adverse consequences of ineffective bowel preparation include lower adenoma detection rates, longer procedural time, lower cecal intubation rates, increased electrocautery risk, and shorter intervals between examinations.(3,5-7) Bowel preparation formulations intended for precolonoscopy cleansing are assessed based on their efficacy, safety, and tolerability. Lack of specific organ toxicity is considered to be a prerequisite for bowel preparations. Between cleansing efficacy and tolerability, however, the consequences of inadequate cleansing suggest that efficacy should be a higher priority than tolerability. Consequently, the choice of a bowel cleansing regimen should be based on cleansing efficacy first and patient tolerability second. However, efficacy and tolerability are closely interrelated. For example, a cleansing agent that is poorly tolerated and thus not fully ingested may not achieve an adequate cleansing. The goals of this consensus document are to provide expert, evidence-based recommendations for clinicians to optimize colonoscopy preparation quality and patient safety. Recommendations are provided using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) scoring system, which weighs the strength of the recommendation and the quality of the evidence.(8)