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Annals of Internal Medicine Mar 2019Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies report inconsistent performance of fecal immunochemical tests (FITs) for colorectal cancer (CRC) and advanced adenomas.
PURPOSE
To summarize performance characteristics of FITs for CRC and advanced adenomas in average-risk persons undergoing screening colonoscopy (reference standard) and to identify factors affecting these characteristics.
DATA SOURCES
Ovid MEDLINE, PubMed, Embase, and the Cochrane Library from inception through October 2018; reference lists of studies and reviews.
STUDY SELECTION
Two reviewers independently screened records to identify published English-language prospective or retrospective observational studies that evaluated FIT sensitivity and specificity for colonoscopic findings in asymptomatic, average-risk adults.
DATA EXTRACTION
Two authors independently extracted data and evaluated study quality.
DATA SYNTHESIS
Thirty-one studies (120 255 participants; 18 FITs) were included; all were judged to have low to moderate risk of bias. Performance characteristics depended on the threshold for a positive result. A threshold of 10 µg/g resulted in sensitivity of 0.91 (95% CI, 0.84 to 0.95) and a negative likelihood ratio of 0.10 (CI, 0.06 to 0.19) for CRC, whereas a threshold of greater than 20 µg/g resulted in specificity of 0.95 (CI, 0.94 to 0.96) and a positive likelihood ratio of 15.49 (CI, 9.82 to 22.39). For advanced adenomas, sensitivity was 0.40 (CI, 0.33 to 0.47) and the negative likelihood ratio was 0.67 (CI, 0.57 to 0.78) at 10 µg/g, and specificity was 0.95 (CI, 0.94 to 0.96) and the positive likelihood ratio was 5.86 (CI, 3.77 to 8.97) at greater than 20 µg/g. Studies had low to high heterogeneity, depending on the threshold. Although several FITs had adequate performance, sensitivity and specificity for CRC for 1 qualitative FIT were 0.90 and 0.91, respectively, at its single threshold of 10 µg/g; positive and negative likelihood ratios were 10.13 and 0.11, respectively. Comparison of 3 FITs at 3 thresholds was inconclusive: CIs overlapped, and the comparisons were across rather than within studies.
LIMITATIONS
Only English-language studies were included. Incomplete reporting limited quality assessment of some evidence. Performance characteristics are for 1-time rather than serial testing.
CONCLUSION
Single-application FITs have moderate to high sensitivity and specificity for CRC, depending on the positivity threshold. Sensitivity of 1-time testing for advanced adenomas is low, regardless of the threshold.
PRIMARY FUNDING SOURCE
Department of Medicine, Indiana University School of Medicine.
Topics: Adenomatous Polyposis Coli; Colonoscopy; Colorectal Neoplasms; Early Detection of Cancer; Feces; Humans; Immunochemistry; Occult Blood
PubMed: 30802902
DOI: 10.7326/M18-2390 -
Arab Journal of Urology Jun 2017To assess the diagnostic accuracy and safety of photodynamic diagnosis (PDD) in upper urinary tract urothelial carcinoma (UUTUC). (Review)
Review
OBJECTIVE
To assess the diagnostic accuracy and safety of photodynamic diagnosis (PDD) in upper urinary tract urothelial carcinoma (UUTUC).
MATERIALS AND METHODS
A systematic literature search was conducted. Included studies were assessed for the risks of bias and quality using appropriate tools. Dedicated data extraction forms were used. Diagnostic accuracy in terms of sensitivity and specificity were quoted whenever provided by individual studies. A combined toxicity profile of 5-aminolevulinic acid (5ALA) was given after reviewing individual studies.
RESULTS
In all, 17 studies were identified. After screening seven studies were included involving a total of 194 patients. None of the studies were randomised. All the available studies were of low-to-moderate quality. The largest available study, with 106 patients, reported a sensitivity of 95.8% and 53.5% for PDD and white-light (WL) ureterorenoscopy (URS) respectively, with a statistically significant difference. The specificity was 96.6% for PDD and 95.2% for WL-URS with no statistical significance. PDD showed better ability in detecting carcinoma and dysplasia. One study compared PDD to computed tomography urogram (CTU) and found PDD to have better sensitivity and statistically significantly better specificity. 5ALA-associated toxicity was minor in nature and hypotension was the most common adverse event.
CONCLUSION
PDD in UUTUC appears to be more accurate than WL-URS and CTU, with no significant toxicity. Larger scale randomised trials are needed.
PubMed: 29071138
DOI: 10.1016/j.aju.2017.01.003 -
The Journal of Allergy and Clinical... Feb 2018The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the...
The goal of this series is to offer a survey of the latest literature for clinicians and scientists alike, providing a list of important recent advances relevant to the broad field of allergy and immunology. This particular assignment was to cover the topic of eosinophils. In an attempt to highlight major ideas, themes, trends, and advances relevant to basic and clinical aspects of eosinophil biology, a search of articles published since 2015 in the Journal of Allergy and Clinical Immunology and other high-impact journals was performed. Articles were then reviewed and organized, and then key findings were summarized. Given space limitations, many outstanding articles could not be included, but the hope is that what follows provides a succinct overview of recently published work that has significantly added to our knowledge of eosinophils and eosinophil-associated diseases.
Topics: Eosinophils; Humans; Immune System Diseases
PubMed: 29045815
DOI: 10.1016/j.jaci.2017.09.022 -
Digestive Diseases and Sciences Oct 2017Hereditary hemorrhagic telangiectasia (HHT), also called Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous... (Review)
Review
Hereditary hemorrhagic telangiectasia (HHT), also called Osler-Weber-Rendu syndrome, is an autosomal dominant genetic disease that affects the vasculature of numerous organs. The prevalence of HHT is estimated to be between 1.5 and 2 persons per 10,000. While there is still much to learn about this condition, there is an increasing understanding its underlying pathophysiology, genetic basis, presentations, and management. Recognizing that the clinical manifestations of HHT can involve a number of organ systems will provide clinicians with a higher index of suspicion for the disease. This early diagnosis and genotyping can greatly reduce mortality for a patient with HHT through appropriate screening for complications. This review will focus on the gastrointestinal manifestations of HHT and how these can dictate treatment and prognosis.
Topics: Animals; Biopsy; Endoscopy, Gastrointestinal; Gastrointestinal Diseases; Genetic Predisposition to Disease; Humans; Molecular Diagnostic Techniques; Phenotype; Physical Examination; Predictive Value of Tests; Prevalence; Prognosis; Risk Factors; Telangiectasia, Hereditary Hemorrhagic; Tomography, X-Ray Computed
PubMed: 28836046
DOI: 10.1007/s10620-017-4719-3 -
Journal of Cancer 2016The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and... (Review)
Review
The growing interest in enhancing and spreading colorectal cancer (CRC) screening has been stimulating the exploration of novel biomarkers with greater sensitivity and specificity than immunochemical faecal occult blood test (iFOBT). The present study provides i) a systematic review of the urinary biomarkers that have been tested to achieve early CRC diagnosis and assess the risk of colorectal adenoma and adenocarcinoma, and ii) a meta-analysis of the data regarding the urinary prostaglandin (PG) metabolite PGE-M. As regard to gene markers, we found significantly different percent methylation of the vimentin gene in CRC patients and healthy controls (HC) (p<0.0001). Respect to metabolism of nitrogenous bases, cytidine, 1-methyladenosine, and adenosine, have higher concentrations in CRC patients than in HC (respectively, p<0.01, p=0.01, and p<0.01). As regard to spermine we found that N1,N12 diacetyl spermine (DiAcSpm) and N1, N8 diacetylspermidine (DiAcSpd) were significantly higher in CRC than in HC (respectively p=0.01 and p<0.01). Respect to PGE-M, levels were higher in CRC than in those with multiple polyposis (p<0.006) and HC subjects (p<0.0004). PGE-M seems to be the most interesting and promising urinary marker for CRC and adenoma risk assessment and for CRC screening. In conclusion, evidence suggests that urinary biomarker could have a potential role as urinary biomarkers in the diagnosis of colorectal cancer. Particularly, PGE-M seems to be the most promising urinary marker for CRC early detection.
PubMed: 27877214
DOI: 10.7150/jca.16244 -
Gastroenterology Jan 2017High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1,... (Review)
Review
High-throughput sequencing analysis has accelerated searches for genes associated with risk for colorectal cancer (CRC); germline mutations in NTHL1, RPS20, FANCM, FAN1, TP53, BUB1, BUB3, LRP6, and PTPN12 have been recently proposed to increase CRC risk. We attempted to validate the association between variants in these genes and development of CRC in a systematic review of 11 publications, using sequence data from 863 familial CRC cases and 1604 individuals without CRC (controls). All cases were diagnosed at an age of 55 years or younger and did not carry mutations in an established CRC predisposition gene. We found sufficient evidence for NTHL1 to be considered a CRC predisposition gene-members of 3 unrelated Dutch families were homozygous for inactivating p.Gln90Ter mutations; a Canadian woman with polyposis, CRC, and multiple tumors was reported to be heterozygous for the inactivating NTHL1 p.Gln90Ter/c.709+1G>A mutations; and a man with polyposis was reported to carry p.Gln90Ter/p.Gln287Ter; whereas no inactivating homozygous or compound heterozygous mutations were detected in controls. Variants that disrupted RPS20 were detected in a Finnish family with early-onset CRC (p.Val50SerfsTer23), a 39-year old individual with metachronous CRC (p.Leu61GlufsTer11 mutation), and a 41-year-old individual with CRC (missense p.Val54Leu), but not in controls. We therefore found published evidence to support the association between variants in NTHL1 and RPS20 with CRC, but not of other recently reported CRC susceptibility variants. We urge the research community to adopt rigorous statistical and biological approaches coupled with independent replication before making claims of pathogenicity.
Topics: Adenomatous Polyposis Coli; Colorectal Neoplasms; Deoxyribonuclease (Pyrimidine Dimer); Genetic Predisposition to Disease; Germ-Line Mutation; Humans; Ribosomal Proteins
PubMed: 27713038
DOI: 10.1053/j.gastro.2016.09.041 -
Alimentary Pharmacology & Therapeutics Nov 2016A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A causal association between proton pump inhibitor (PPI) use and fundic gland polyps has been suggested, but the data are conflicting.
AIM
To clarify the relationship through a meta-analysis of the existing data.
METHODS
A systematic retrieval and selection of records was performed. The main inclusion criteria were original studies reporting the prevalence of fundic gland polyps in PPI users or the reverse, compared to controls. Key outcomes were the odds ratios (OR) for fundic gland polyp prevalence in association with PPI use, prevalence of PPI use amongst subjects with fundic gland polyps and fundic gland polyp prevalence among PPI users. Statistical analysis was performed using Mix 2.0 Pro.
RESULTS
The initial search using electronic databases and manual searching retrieved 339 peer-reviewed articles and abstracts. Twenty articles met all inclusion and exclusion criteria, with a total of 40 218 subjects included. The meta-analysis of 12 studies revealed an increase in fundic gland polyps amongst PPI users compared to controls (OR 2.46, 95% CI 1.42-4.27, P = 0.001), particularly among individuals taking PPIs for at least 6 months (OR: 4.71, 95% CI 2.22-9.99, P < 0.001) or 12 months (OR: 5.32, 95% CI 2.58-10.99, P < 0.001).
CONCLUSIONS
Proton pump inhibitor usage is associated with a significantly increased prevalence of fundic gland polyps, and there is a trend for this to increase with longer length of PPI exposure. However, the meta-analysis is limited mainly to cohort studies.
Topics: Adenomatous Polyps; Cohort Studies; Gastric Fundus; Humans; Polyps; Proton Pump Inhibitors; Stomach Neoplasms
PubMed: 27634363
DOI: 10.1111/apt.13800 -
The Journal of Pathology. Clinical... Jul 2016Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of... (Review)
Review
Serrated polyposis is a rare disorder characterised by the presence of multiple serrated polyps in the large intestine, and an increased personal and familial risk of colorectal cancer. Knowledge of the molecular characteristics of colonic lesions which develop in this syndrome is fragmented, making it difficult to understand the underlying genetic basis of this condition. We conducted a systematic review and meta-analysis of all studies which evaluated the molecular characteristics of colorectal neoplasms found in individuals with serrated polyposis. We identified 4561 potentially relevant studies, but due to a lack of consensus in the reporting of findings, only fourteen studies were able to be included in the meta-analysis. BRAF mutation was found in 73% (95% CI 65-80%) of serrated polyps, 0% (95% CI 0-3%) of conventional adenomas and 49% (95%CI 33-64%) of colorectal cancers. In contrast, KRAS mutation was present in 8% (95% CI 5-11%) of serrated polyps, 3% (95% CI 0-13%) of conventional adenomas and 6% (95% CI 0-13%) of colorectal cancers. Absence of MLH1 immunostaining was found in 3% (95% CI 0-10%) of serrated polyps and 53% (95% CI 36-71%) of colorectal cancers. Overall, microsatellite instability was found in 40% (95% CI 18-64%) of colorectal cancers arising in the setting of serrated polyposis. Our results indicate that diverse molecular pathways are likely to contribute to the increased predisposition for colorectal cancer in individuals with serrated polyposis. We also propose a set of minimum standards for the reporting of future research in serrated polyposis as this is a rare syndrome and collation of research findings from different centres will be essential to identify the molecular mechanisms involved in the pathogenesis of this condition.
PubMed: 27499922
DOI: 10.1002/cjp2.44 -
International Forum of Allergy &... Dec 2016Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary... (Review)
Review
BACKGROUND
Chronic rhinosinusitis (CRS) in aspirin-exacerbated respiratory disease (AERD) represents a recalcitrant form of sinonasal inflammation for which a multidisciplinary consensus on patient management has not been reached. Several medical interventions have been investigated, but a formal comprehensive evaluation of the evidence has never been performed. The purpose of this article is to provide an evidence-based approach for the multidisciplinary management of CRS in AERD.
METHODS
A systematic review of the literature was performed and the guidelines for development of an evidence-based review with recommendations were followed. Study inclusion criteria included: adult population >18 years old; CRS based on published diagnostic criteria, and a presumptive diagnosis of AERD. We focused on reporting higher-quality studies (level 2 or higher) when available, but reported lower-quality studies if the topic contained insufficient evidence. Treatment recommendations were based on American Academy of Otolaryngology (AAO) guidelines, with defined grades of evidence and evaluation of research quality and risk/benefits associated with each treatment.
RESULTS
This review identified and evaluated the literature on 3 treatment strategies for CRS in AERD: dietary salicylate avoidance, leukotriene modification, and desensitization with daily aspirin therapy.
CONCLUSION
Based on the available evidence, dietary salicylate avoidance and leukotriene-modifying drugs are options following appropriate treatment with nasal corticosteroids and saline irrigation. Desensitization with daily aspirin therapy is recommended following revision endoscopic sinus surgery (ESS).
Topics: Asthma, Aspirin-Induced; Chronic Disease; Humans; Nasal Polyps; Rhinitis; Sinusitis
PubMed: 27480830
DOI: 10.1002/alr.21826 -
Multidisciplinary Respiratory Medicine 2016The inflammatory diseases of the nose, rhino-pharynx and paranasal sinuses (allergic and non allergic rhinitis, NARES; rhinosinusitis with/without nasal polyposis,... (Review)
Review
UNLABELLED
The inflammatory diseases of the nose, rhino-pharynx and paranasal sinuses (allergic and non allergic rhinitis, NARES; rhinosinusitis with/without nasal polyposis, adenoidal hypertrophy with/without middle ear involvement) clinically manifest themselves with symptoms and complications severely affecting quality of life and health care expenditure. Intranasal administration of corticosteroids, being fast, simple, and not requiring cooperation, is the preferred way to treat the patients, to optimize their quality of life, at the same time minimizing the risk of exacerbations and complications. Among the different topical steroids available on the market, we performed a comparative analysis in terms of effectiveness and safety between mometasone furoate (MF) and its main competitors. Searching through Pub Med and Google Scholar and using as entries "mometasone furoate", "rhinitis", "sinusitis", "asthma", "polyposis", "otitis media with effusion", and "adenoid hypertrophy" we found 344 articles, 300 of which met the eligibility criteria. Taking into account relevance and date of publication, a sample of 40 articles was considered for the review. MF effectiveness for treatment and/or prophylaxis of nasal symptoms in seasonal and perennial allergic rhinitis has been fully established with a level of evidence Ia. Even though it has not been assessed for MF in particular, topical steroids are the most appropriate treatment in mixed rhinitis and NARES. In acute rhinosinusitis (ARS) evidences support their use as mono-therapy or as adjuvant to antibiotics for reducing the recurrence rate, and decrease the usage of related prescriptions and medical consultations. In chronic rhinosinusitis (CRS) with Nasal polyposis, MF reduces polyps size, nasal congestion, improves quality of life and sense of smell and it is also effective in the treatment of daytime cough. The topical use of MF has great efficacy in the management of adenoidal hypertrophy and otitis media of atopic children. As regards the safety, MF has demonstrated an excellent safety profile: pregnant women can safely use it; no systemic effects on growth velocity and adrenal suppression have been shown; no changes in epithelial thickness or atrophy have been observed after long term administration of the drug.
CONCLUSIONS
MF has been demonstrated to be effective in the treatment of the inflammatory diseases of the nose and paranasal sinuses; when compared to its competitors it shows a greater symptom control; it is a reliable treatment in the long term thanks not only to its proven efficacy, but also to its safety being on the market since more than 17 years.
PubMed: 27141307
DOI: 10.1186/s40248-016-0054-3