PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-9 (9)
 

Clipboard (0)
None

Select a Filter Below

Journals
Year of Publication
Document Types
1.  Effect of Flexible Sigmoidoscopy-Based Screening on Incidence and Mortality of Colorectal Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials 
PLoS Medicine  2012;9(12):e1001352.
A systematic review and meta-analysis of randomized trials conducted by B. Joseph Elmunzer and colleagues reports that that flexible sigmoidoscopy-based screening reduces the incidence of colorectal cancer in average-risk patients, as compared to usual care or no screening.
Background
Randomized controlled trials (RCTs) have yielded varying estimates of the benefit of flexible sigmoidoscopy (FS) screening for colorectal cancer (CRC). Our objective was to more precisely estimate the effect of FS-based screening on the incidence and mortality of CRC by performing a meta-analysis of published RCTs.
Methods and Findings
Medline and Embase databases were searched for eligible articles published between 1966 and 28 May 2012. After screening 3,319 citations and 29 potentially relevant articles, two reviewers identified five RCTs evaluating the effect of FS screening on the incidence and mortality of CRC. The reviewers independently extracted relevant data; discrepancies were resolved by consensus. The quality of included studies was assessed using criteria set out by the Evidence-Based Gastroenterology Steering Group. Random effects meta-analysis was performed.
The five RCTs meeting eligibility criteria were determined to be of high methodologic quality and enrolled 416,159 total subjects. Four European studies compared FS to no screening and one study from the United States compared FS to usual care. By intention to treat analysis, FS-based screening was associated with an 18% relative risk reduction in the incidence of CRC (0.82, 95% CI 0.73–0.91, p<0.001, number needed to screen [NNS] to prevent one case of CRC = 361), a 33% reduction in the incidence of left-sided CRC (RR 0.67, 95% CI 0.59–0.76, p<0.001, NNS = 332), and a 28% reduction in the mortality of CRC (relative risk [RR] 0.72, 95% CI 0.65–0.80, p<0.001, NNS = 850). The efficacy estimate, the amount of benefit for those who actually adhered to the recommended treatment, suggested that FS screening reduced CRC incidence by 32% (p<0.001), and CRC-related mortality by 50% (p<0.001).
Limitations of this meta-analysis include heterogeneity in the design of the included trials, absence of studies from Africa, Asia, or South America, and lack of studies comparing FS with colonoscopy or stool-based testing.
Conclusions
This meta-analysis of randomized controlled trials demonstrates that FS-based screening significantly reduces the incidence and mortality of colorectal cancer in average-risk patients.
Please see later in the article for the Editors' Summary
Editor's Summary
Background
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Regular CRC screening has been shown to reduce the risk of dying from CRC by 16%, and CRC screening can identify early stage cancers in otherwise healthy people, which allows for early treatment and management of the disease. Screening for colorectal cancer is frequently performed using a flexible sigmoidoscopy (FS), which is a thin, flexible tube with a tiny camera and light on the end, allowing a doctor to look at the inside wall of the bowel and remove any small growths or polyps. Although screening may detect early cancers, the life-saving and health benefits of screening are uncertain because the polyp may not necessarily progress. This could lead to anxiety and unnecessary interventions and treatments amongst those screened. Randomized controlled trials (RCTs) are needed to determine all of the risks involved in cancer screenings, however the guidelines that recommend FS-based screening do not rely upon RCT data. Recently, the results of four large-scale RCTs evaluating FS screening for CRC have been published. The conflicting results with respect to the incidence and mortality of CRC in these studies have called into question the effectiveness of endoscopic screening.
Why Was This Study Done?
The results of RCTs measuring the risks and outcomes of CRC screening have shown varying estimates of the benefits of using FS screening. If better estimates of the risks and benefits of FS screening are developed, then the current CRC screening guidelines may be updated to reflect this new information. In this study, the authors show the results of a meta-analysis of published RCTs, which more precisely estimates the effects of FS-based screening on the incidence and mortality of colorectal cancer.
What Did the Researchers Do and Find?
The researchers used the Medline and Embase databases to find relevant studies from 1966 to May 28, 2012. After screening 3,319 citations and 29 potentially relevant articles, five RCTs of high methodologic quality and 416,159 total subjects evaluating the effect of FS screening on the incidence and mortality of CRC were identified. The data were extracted and random effects meta-analysis was performed. The meta-analysis revealed that FS-based screening was associated with an 18% relative risk reduction in the incidence of CRC (0.82, 95% CI 0.73–0.91, p<0.001, number needed to screen (NNS) to prevent one case of CRC = 361), a 33% reduction in the incidence of left-sided CRC (RR 0.67, 95% CI 0.59–0.76, p<0.001, NNS = 332), and a 28% reduction in the mortality of CRC (RR 0.72, 95% CI 0.65–0.80, p<0.001, NNS = 850). The amount of benefit for those who adhered to the recommended treatment suggested that FS screening reduced CRC incidence by 32% (p<0.001), and CRC-related mortality by 50% (p<0.001).
What Do These Findings Mean?
This meta-analysis of RCTs evaluating the effect of FS on CRC incidence and mortality demonstrates that a FS-based strategy for screening is very effective in reducing the incidence and mortality of CRC in patients. The current recommendations for endoscopic screening are based on observational studies, which may not accurately reflect the effect of FS-based screening on the incidence and mortality of CRC. Here, the authors performed a systematic review and meta-analysis of five recent RCTs to better estimate the true effect of FS-based screening on the incidence and mortality of CRC. Thus, the results of this meta-analysis may affect health policy, and directly impact patients and clinicians.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001352.
Cancer research UK provides comprehensive information about screening for colorectal cancers as does the UK National Screening Committee
PubMed Health has general information about colon cancer
The National Cancer Institute also has comprehensive resources on colorectal cancer and treatment
The Mayo Clinic provides an overview of all aspects of colon cancer
doi:10.1371/journal.pmed.1001352
PMCID: PMC3514315  PMID: 23226108
2.  A survey of expert follow-up practices after successful endoscopic eradication therapy for Barrett's esophagus with high-grade dysplasia and intramucosal adenocarcinoma 
Gastrointestinal endoscopy  2013;78(5):696-701.
Background
Despite the increasing number of patients undergoing endoscopic therapy for Barrett's esophagus (BE) with high-grade dysplasia (HGD) or intramucosal cancer (IMC), there are few data to guide clinical decision making and research initiatives in the area of posttreatment follow-up.
Objectives
We aimed to define expert practice patterns regarding follow-up after endoscopic treatment of BE with HGD and IMC.
Design
Electronic survey.
Subjects
Forty-eight endoscopists in the United States with expertise in BE endotherapy based on high-impact publications and national reputation.
Intervention
A 21-item Web-based survey inquiring about post-BE endotherapy follow-up practices.
Results
Of 48 expert endoscopists, 42 completed the survey. After successful treatment of BE with HGD or IMC, all experts perform surveillance upper endoscopy, most commonly at 3-month intervals in the first posttreatment year, every 6 months during the second year, and annually thereafter. None of the experts perform surveillance EUS after treatment of HGD, and only 19% perform EUS after treatment of IMC. After cancer eradication, only 36% of experts refer patients for CT, and 24% refer patients for positron emission tomography. Thirty-eight percent of experts refer patients for a surgical opinion when IMC extends into the muscularis mucosa; 100% refer when IMC extends into submucosa.
Limitations
Not a consensus document; only U.S. experts included.
Conclusions
This study reports the follow-up practices of expert endoscopists after successful endotherapy for BE with HGD and IMC. Additional research is necessary to establish optimal surveillance intervals, the role of follow-up EUS, CT, and positron emission tomography, as well as the surgical implications of low-risk IMC extending into the muscularis mucosa.
doi:10.1016/j.gie.2013.04.196
PMCID: PMC3961573  PMID: 23711553
3.  Does Rectal Indomethacin Eliminate the Need for Prophylactic Pancreatic Stent Placement in Patients Undergoing High-Risk ERCP? Post hoc Efficacy and Cost-Benefit Analyses Using Prospective Clinical Trial Data 
OBJECTIVES
A recent large-scale randomized controlled trial (RCT) demonstrated that rectal indomethacin administration is effective in addition to pancreatic stent placement (PSP) for preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. We performed a post hoc analysis of this RCT to explore whether rectal indomethacin can replace PSP in the prevention of PEP and to estimate the potential cost savings of such an approach.
METHODS
We retrospectively classified RCT subjects into four prevention groups: (1) no prophylaxis, (2) PSP alone, (3) rectal indomethacin alone, and (4) the combination of PSP and indomethacin. Multivariable logistic regression was used to adjust for imbalances in the prevalence of risk factors for PEP between the groups. Based on these adjusted PEP rates, we conducted an economic analysis comparing the costs associated with PEP prevention strategies employing rectal indomethacin alone, PSP alone, or the combination of both.
RESULTS
After adjusting for risk using two different logistic regression models, rectal indomethacin alone appeared to be more effective for preventing PEP than no prophylaxis, PSP alone, and the combination of indomethacin and PSP. Economic analysis revealed that indomethacin alone was a cost-saving strategy in 96% of Monte Carlo trials. A prevention strategy employing rectal indomethacin alone could save approximately $150 million annually in the United States compared with a strategy of PSP alone, and $85 million compared with a strategy of indomethacin and PSP.
CONCLUSIONS
This hypothesis-generating study suggests that prophylactic rectal indomethacin could replace PSP in patients undergoing high-risk ERCP, potentially improving clinical outcomes and reducing healthcare costs. A RCT comparing rectal indomethacin alone vs. indomethacin plus PSP is needed.
doi:10.1038/ajg.2012.442
PMCID: PMC3947644  PMID: 23295278
4.  Clinical yield of diagnostic ERCP in orthotopic liver transplant recipients with suspected biliary complications 
Background and aims
Diagnostic endoscopic retrograde cholangiopancreatography (ERCP) is commonly performed for the evaluation of biliary complications after orthotopic liver transplantation (OLT). This practice is contrary to national trends towards reserving ERCP for therapeutic purposes. Our aim was to evaluate the clinical yield and complications of diagnostic ERCP in OLT recipients.
Methods
In this retrospective study, 165 OLT recipients who underwent ERCP between 1/2006 and 12/2010 at the University of Michigan were divided into 2 groups: 1) therapeutic ERCP group (T-ERCP) if they met pre-specified criteria that suggested a high likelihood of endoscopic intervention, and 2) diagnostic ERCP group (D-ERCP) if they had a clinical suspicion of biliary disease but did not meet any criteria. The two groups were compared with regard to the proportion of subjects in each group who underwent a high-yield ERCP, defined as a procedure that resulted in a clinically important intervention that modified disease course.
Results
66.3% of diagnostic ERCPs were classified as high-yield, compared to 90.1% of therapeutic ERCPs (p<0.001). Serious complications were infrequent in both groups. A survey of practitioners caring for OLT recipients suggested that the rate of high-yield D-ERCP seen in this study is congruent with that considered acceptable in clinical practice.
Conclusions
Although T-ERCP was more likely to reveal a pathologic process requiring intervention, diagnostic ERCP appears to be an acceptable clinical strategy in OLT recipients because of the high likelihood of a high-yield study and the low rate of serious complications.
doi:10.1002/lt.23535
PMCID: PMC3900243  PMID: 22888069
All appear in the title
5.  Targeted imaging of esophageal neoplasia with a fluorescently labeled peptide: First in-human results 
Science translational medicine  2013;5(184):10.1126/scitranslmed.3004733.
Esophageal adenocarcinoma is rising rapidly in incidence, and usually develops from Barrett’s esophagus, a precursor condition commonly found in patients with chronic acid reflux. Pre-malignant lesions are challenging to detect on conventional screening endoscopy because of their flat appearance. Molecular changes can be used to improve detection of early neoplasia. We have developed a peptide that binds specifically to high-grade dysplasia and adenocarcinoma. We first applied the peptide ex vivo to esophageal specimens from 17 patients to validate specific binding. Next, we performed confocal endomicroscopy in vivo in 25 human subjects after topical peptide administration and found 3.8-fold greater fluorescence intensity for esophageal neoplasia compared with Barrett’s esophagus and squamous epithelium with 75% sensitivity and 97% specificity. No toxicity was attributed to the peptide in either animal or patient studies. Therefore, our first-in-humans results show that this targeted imaging agent is safe, and may be useful for guiding tissue biopsy and for early detection of esophageal neoplasia and potentially other cancers of epithelial origin, such as bladder, colon, lung, pancreas, and stomach.
doi:10.1126/scitranslmed.3004733
PMCID: PMC3859345  PMID: 23658246
6.  Lymphocytic Esophagitis: A Diagnosis of Increasing Frequency 
Background
Despite being found with increasing frequency on esophageal biopsies, the clinical significance of lymphocytic esophagitis (LE) remains poorly understood.
Goals
The primary aim of our study was to characterize the clinical presentation and natural history of LE among adult patients.
Study
We retrospectively reviewed records for all 81 adult patients at the University of Michigan Medical Center who had a histopathological diagnosis of LE between January 1998 and November 2009. Patient demographics, clinical history, laboratory data, and imaging results from the time of diagnosis were obtained through review of computerized medical records. A telephone survey was conducted to collect natural history data.
Results
The number of LE diagnoses increased over time, with 81.5% (n=66) of patients being diagnosed in the last three years. The most frequent symptoms at the time of presentation were dysphagia (n=54), chest/abdominal pain (n=36), and heartburn (n=38). The majority (58.6%) of patients reported improvement in their initial gastrointestinal symptoms – most commonly associated with initiation of a proton pump inhibitor. Upon follow-up, most patients reported a good quality of life and satisfaction with their current health status.
Conclusions
Lymphocytic esophagitis is a new clinical entity with an increasing incidence. LE appears to have a benign natural history, with most patients reporting an improvement in symptoms and satisfaction with their health-related quality of life. Prospective studies are needed to better characterize the natural history and potential treatments for this clinical entity.
doi:10.1097/MCG.0b013e3182500de8
PMCID: PMC3465631  PMID: 22751335
Lymphocytic esophagitis; epidemiology; clinical presentation; natural history; quality of life
7.  Retroperitoneal germ cell tumor diagnosed by endoscopic ultrasound-guided fine needle aspiration 
Isolated extragonadal germ cell tumors can be primary in nature or metastatic from a burned out testicular cancer. Accurate diagnosis is critical as appropriate therapy can be highly curative. We present the case of an isolated extragonadal germ cell tumor in the retroperitoneum diagnosed by endoscopic ultrasound-guided fine needle aspiration. This case underscores the importance of considering germ cell tumors in the differential diagnosis of an unexplained retroperitoneal mass, particularly since immunophenotypic staining may be necessary to establish the diagnosis.
doi:10.4251/wjgo.v2.i12.443
PMCID: PMC3011098  PMID: 21191538
Germ cell tumor; Endoscopic ultrasound; Fine needle aspiration
8.  Factors associated with esophageal stricture formation after endoscopic mucosal resection for neoplastic Barrett’s esophagus 
Gastrointestinal endoscopy  2011;74(4):753-760.
Background
EMR for early neoplastic Barrett’s esophagus is gaining favor over esophagectomy. Esophageal stricture development has been reported as a common complication of EMR, photodynamic therapy, and combination endoscopic therapy.
Objective
To determine clinical and procedural predictors of symptomatic stricture formation after EMR.
Design
Retrospective analysis.
Setting
Tertiary-care referral university hospital.
Patients
Data were retrospectively reviewed on 73 patients at our institution who underwent EMR monotherapy for Barrett’s esophagus with high-grade dysplasia or intramucosal cancer since January 2006.
Intervention
EMR.
Main Outcome Measurements
Symptomatic esophageal stricture formation.
Results
Symptomatic esophageal stricture formation was noted in 24.7% of patients undergoing EMR. Stricture formation on univariate analysis was associated with percentage of circumference of esophageal lumen resected, total pieces resected, number of EMR sessions, and tobacco use. A threshold effect was found at 50% of esophageal circumference resected (66.7% vs 27.2% developed strictures above and below the threshold, respectively; P = .004). A 25-pack-year or greater history of tobacco use had a threshold effect on esophageal stricture formation (77.8% vs 7.2% developed strictures above and below the threshold, respectively; P =.02). In multivariate analysis, resection of >50% of the circumference was strongly associated with stricture formation (odds ratio [OR] 4.17; 95% confidence interval [CI], 1.27–13.7). A 25-pack-year or greater history of tobacco use also trended toward stricture formation (OR 3.33; 95% CI, 0.929–12.1).
Limitations
Retrospective design, sample size.
Conclusion
Resection of at least 50% of the esophageal mucosal circumference is strongly associated with stricture formation. Patients with strong histories of tobacco use also may be more likely to develop esophageal strictures following EMR.
doi:10.1016/j.gie.2011.05.031
PMCID: PMC3481547  PMID: 21820109
9.  A Randomized Trial of Rectal Indomethacin to Prevent Post-ERCP Pancreatitis 
The New England Journal of Medicine  2012;366(15):1414-1422.
Background
Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP).
Methods
In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights.
Results
A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P = 0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P = 0.03).
Conclusions
Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.)
doi:10.1056/NEJMoa1111103
PMCID: PMC3339271  PMID: 22494121

Results 1-9 (9)