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Frontiers in Oncology 2022Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in...
BACKGROUND
Goblet cell adenocarcinoma (GCA) of the appendix is a rare and aggressive tumour with varying nomenclature and classification systems. This has led to heterogeneity in published data, and there is a lack of consensus on incidence, survival, and management.
METHODS
We provide an overview of GCA with a comprehensive systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and a retrospective analysis of all cases recorded in the English National Cancer Registration and Analysis Service database between 1995 and 2018. The Kaplan-Meier estimator was used to calculate overall survival, and Cox proportional hazards regression was used to identify prognostic factors.
RESULTS
The systematic review demonstrated an incidence of 0.05-0.3 per 100,000 per year among North American registry studies. The 1-, 3-, and 5-year survival rate was 95.5%, 85.9%-87.6%, and 76.0%-80.6%, respectively. Age, stage, and grade were identified as prognostic factors for survival. Our analysis included 1,225 cases. Age-standardised incidence was 0.0335 per year in 1995 and gradually rose to 0.158 per year in 2018. The 1-, 3-, and 5-year survival rate was 90.0% [95% confidence interval (95% CI): 85.4-94.0], 76.0% (95% CI: 73.8-80.9), and 68.6% (95% CI: 65.9-72.2), respectively. On univariate Cox regression analyses, female sex, stage, and grade were associated with worse overall survival. On multivariate analysis, only stage remained a statistically significant prognostic factor.
CONCLUSIONS
GCA of the appendix is rare, but incidence is increasing. We report a lower incidence and survival than North American registry studies. Higher stage was associated with decreased survival. Further prospective studies are required to establish optimal management.
PubMed: 35903705
DOI: 10.3389/fonc.2022.915028 -
Clinical Cancer Research : An Official... Nov 2008A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
A meta-analytic approach was used to estimate the frequency of: (a) microsatellite instability-high (MSI-H) phenotype in unselected ovarian cancers and (b) various histologic subtypes of mismatch repair (MMR)-deficient epithelial ovarian cancers.
METHODS
A systematic search of the Medline electronic database was conducted to identify articles published between January 1, 1966, and December 31, 2007, that examined MMR deficiency in ovarian cancers. Data were extracted on the study population, sample size, MSI-H frequency, and histology of MMR-deficient ovarian tumors.
RESULTS
The pooled proportion of MSI-H ovarian cancers was 0.12 [95% confidence interval (CI), 0.08-0.17] from 18 studies with 977 cases. The proportion of histologic subtypes in the pooled analysis from 15 studies with 159 cases was serous at 0.32 (95% CI, 0.20-0.44), mucinous at 0.19 (95% CI, 0.12-0.27), endometrioid at 0.29 (95% CI, 0.22-0.36), clear cell at 0.18 (95% CI, 0.09-0.28), and mixed at 0.24 (95% CI, 0.07-0.47). There was significant heterogeneity between studies.
CONCLUSIONS
The frequency of the MSI-H phenotype in unselected ovarian cancers approximates 12%. MMR-deficient ovarian cancers also seem to be characterized by an overrepresentation of nonserous histologic subtypes. Knowledge of histologic subtype may aid clinicians in identifying the relatively large proportion of ovarian cancers due to MMR defects; such knowledge has potential implications for medical management.
Topics: DNA Mismatch Repair; Female; Humans; Microsatellite Instability; Ovarian Neoplasms; Phenotype
PubMed: 18980979
DOI: 10.1158/1078-0432.CCR-08-1387 -
Computational and Mathematical Methods... 2022To evaluate the value of combined detection of serum CA125, CA199, and HE4 in the diagnosis of ovarian cancer. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate the value of combined detection of serum CA125, CA199, and HE4 in the diagnosis of ovarian cancer.
METHODS
Relevant articles retrieved from PubMed, Elsevier Science, Springer, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP databases were screened strictly according to inclusion and exclusion criteria. Included literature published from January 2005 to December 2021. (2) Serum HE4, CA125, CA199, and their combination for ovarian cancer diagnostic tests were studied, and healthy subjects or patients with the benign disease were taken as a control group. (3) Pathological tissue diagnosis as the gold standard. (4) Complete original data can be obtained. (5) The sample size was ≥20. (6) Language is limited to Chinese and English. Data features and QUADAS table were extracted from the included literature, and QUADAS evaluation tool detail table was used for the included study. Conduct quality evaluation. Statistical analysis was carried out using meta-disc software version 1.4. Appropriate effect model was selected to merge the effect size, and the forest maps of merge sensitivity, merge specificity, and merge likelihood ratio were obtained.
RESULTS
The results of meta-analysis showed that there was a statistical difference in diagnostic specificity analysis of CA125 (OR = 1.91, 95% CI (1.58, 2.32), < 0.00001, = 67%, = 6.58); diagnostic sensitivity analysis of CA125 (OR = 2.50, 95% CI (1.73, 3.62), < 0.00001, = 0%, = 4.90); diagnostic specificity analysis of CA199 (OR = 1.98, 95% CI (1.60, 2.44), < 0.00001, = 89%, = 6.35); diagnostic sensitivity analysis of CA199 (OR = 1.92, 95% CI (1.46, 2.52), < 0.00001, = 73%, = 4.70); diagnostic specificity analysis of HE4 (OR = 2.08, 95% CI (1.65, 2.63), < 0.00001, = 73%, = 6.19); diagnostic sensitivity analysis of HE4 (OR = 2.37, 95% CI (1.87, 3.00), < 0.00001, = 83%, = 7.19).
CONCLUSION
In the clinical assisted diagnosis of ovarian cancer, combined detection of CA125, CA199, and HE4 has the stronger discriminant ability and higher accuracy than single detection of CA125, which can improve the diagnostic efficiency.
Topics: Biomarkers, Tumor; CA-125 Antigen; Databases, Factual; Female; Humans; Ovarian Neoplasms; WAP Four-Disulfide Core Domain Protein 2
PubMed: 35664644
DOI: 10.1155/2022/9339325 -
Cancer Causes & Control : CCC Nov 2012Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic inflammation has been proposed as a risk factor for ovarian cancer. Some data suggest that anti-inflammatory medications may be protective against ovarian cancer; however, results have been inconsistent.
METHODS
We evaluated the risk of epithelial ovarian cancer with regular use of NSAIDs prospectively in the NIH-AARP Diet and Health Study, using Cox proportional hazard models. We also examined the risk of common subtypes of epithelial ovarian cancer (serous, mucinous, endometrioid, clear cell, and other epithelial) with regular use of NSAIDs. In addition, we performed meta-analyses summarizing the risk of ovarian cancer with "regular use" of NSAIDs in previously published studies.
RESULTS
We did not observe a significant association between regular use of NSAIDs with ovarian cancer risk in the AARP cohort (aspirin: RR 1.06, 95 % CI 0.87-1.29; non-aspirin NSAIDs: RR 0.93, 95 % CI 0.74-1.15); however, summary estimates from prospective cohort studies demonstrated that use of non-aspirin NSAIDs may reduce the risk of ovarian cancer (RR 0.88, 95 % CI 0.77-1.01). Although not significant, we found that mucinous tumors were inversely associated with non-aspirin NSAID use (RR 0.69, 95 % CI 0.23-2.10) in the AARP cohort, which was supported by the meta-analysis (RR 0.69, CI 0.50-0.94.)
CONCLUSION
Although results from the NIH-AARP cohort study were not statistically significant, our meta-analysis suggests that non-aspirin NSAIDs may be protective against ovarian cancer. Additional analyses, focusing on dose, duration, and frequency of NSAID use and accounting for ovarian cancer heterogeneity are necessary to further elucidate the association between NSAID use and ovarian cancer risk.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Diet; Female; Humans; Middle Aged; National Institutes of Health (U.S.); Ovarian Neoplasms; Proportional Hazards Models; Prospective Studies; Risk Factors; United States
PubMed: 22972000
DOI: 10.1007/s10552-012-0063-2 -
Cellular Physiology and Biochemistry :... 2017Published data on the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer are controversial. We conducted this meta-analysis to obtain a more... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Published data on the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer are controversial. We conducted this meta-analysis to obtain a more accurate assessment of prognostic significance of NLR in ovarian cancer.
MATERIALS AND METHODS
We conducted a systematic literature search using the electronic databases PubMed, Web of Science, and Embase up to May 2016. Hazard ratio (HR) and odd ratio (OR) with 95% confidence interval (95% CI) were calculated. Subgroup analyses were carried out to explore the source of heterogeneity. Statistical analysis was performed using Stata 10.0.
RESULTS
A total of 12 studies, consisting of 3,854 patients, which met our criterion were selected in this meta-analysis. Our pooled results showed that high pre-treatment NLR level was significantly associated with poorer overall survival (OS) (HR: 1.69, 95% CI 1.29-2.22) and shorter progression free survival (PFS) (HR 1.63, 95% CI 1.27-2.09). Additionally, increased NLR was also significantly correlated with advanced FIGO stage (OR 2.32, 95% CI1.79-3.00), higher serum level of CA-125 (OR 3.33, 95% CI 2.43-4.58), more extensive ascites (OR 3.54, 95% CI 2.31-5.42) as well as less chemotheraputic response (OR 0.53, 95% CI 0.40-0.70). The findings from most of subgroup meta-analyses were consistent with those from the overall meta-analyses.
CONCLUSIONS
Elevated pre-treatment NLR could served as a predicative factor of poor prognosis for ovarian cancer patients.
Topics: CA-125 Antigen; Databases, Factual; Disease-Free Survival; Female; Humans; Lymphocytes; Neutrophils; Odds Ratio; Ovarian Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 28467978
DOI: 10.1159/000475911 -
JAMA Network Open May 2022Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival...
Overall Survival in Phase 3 Clinical Trials and the Surveillance, Epidemiology, and End Results Database in Patients With Metastatic Colorectal Cancer, 1986-2016: A Systematic Review.
IMPORTANCE
Phase 3 trials for patients with metastatic colorectal cancer (mCRC) have been conducted with varying designs and often with surrogate end points for overall survival (OS).
OBJECTIVES
To critically examine the factors associated with clinically relevant improvement in OS (defined as ≥2 months) in these trials and to evaluate their association with outcomes reflected in Surveillance, Epidemiology, and End Results (SEER) registry data.
EVIDENCE REVIEW
Medline, EMBASE, Cochrane, Web of Science, ClinicalTrials.gov, EU Clinical Trials Register, and the International Clinical Trials Registry Platform were searched for phase 3 trials of systemic therapy for patients with mCRC by decade (1986-1996, 1997-2006, and 2007-2016), excluding early or pilot studies, studies that did not involve an anticancer drug, studies on cancer screening and prevention, reports of pooled data from multiple trials, and studies with nonpharmaceutical approaches. The association of drug development with OS outside the clinical trial setting was evaluated using data from the SEER registry, including adult patients with a primary cancer site in the colon or rectum, including adenocarcinoma, mucinous adenocarcinoma, or signet ring cell carcinoma; a distant stage; and receipt of chemotherapy as first-line therapy. Kaplan-Meier curves and log-rank tests were used to assess OS.
FINDINGS
The literature search identified 150 phase III clinical trials with 77 494 total enrollments, and 67 126 patients with mCRC were identified from the SEER database. Significant increases in survival were noted over time, best reflected in the experimental arm of first-line therapy (OS increased by 5.7 months per 10 years; 95% CI, 4.7-6.6 months; progression-free survival increased by 1.4 months per 10 years; 95% CI, 0.7-2.1 months). Although 69 of 148 trials (46.6%) met their predefined primary end point (including 20 of 44 trials [45.5%] with OS as the primary end point), only 35 of 132 trials (26.5%) resulted in improvement in OS by 2 months or more (including 13 of 42 trials [31.0%] with OS as the primary end point). Multivariable logistic regression showed that third-line therapies or later (odds ratio, 0.57; 95% CI, 0.51-0.63) and funding by pharmaceutical companies (odds ratio, 0.57; 95% CI, 0.54-0.60) were less often associated with improvement in OS. Furthermore, there was a decrease in the novelty of targets and agents over time, with trials that evaluated regimens composed entirely of previously approved drugs for mCRC increasing from 28% to 50%. Data from the SEER database showed that median OS increased from 12 months (95% CI, 12-13 months) (1986-1996) to 21 months (95% CI, 21-22 months) (2007-2015) (P < .001), but the 5-year OS continued to be low at 12.2% in 2011.
CONCLUSIONS AND RELEVANCE
In this systematic review, OS for patients with mCRC appeared to improve significantly in trials, translating into meaningful benefits outside the clinical trial setting; however, these advances, although significant cumulatively, are largely incremental individually. These data should be a call to aim for larger gains from future trials with novel drugs, building on the increasing understanding of the biology of mCRC and sophisticated translational research tools.
Topics: Adult; Antineoplastic Agents; Colorectal Neoplasms; Databases, Factual; Humans; Progression-Free Survival
PubMed: 35608860
DOI: 10.1001/jamanetworkopen.2022.13588 -
Scandinavian Journal of Immunology Jun 2016Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to... (Meta-Analysis)
Meta-Analysis Review
Tumour-associated autoantibodies may be promising biomarkers that could facilitate breast cancer (BC) diagnosis and improve patient outcomes. This review aims to identify the tumour-associated autoantibodies with the greatest diagnostic potential. Systematic searches were conducted using PubMed and Web of Science. The most studied tumour-associated autoantibody was included in a meta-analysis, and its clinical value was determined using Fagan's nomogram. The analysis included 84 studies regarding tumour-associated autoantibodies with the diagnostic value. Anti-p53 antibody was the most frequently studied autoantibody, followed by autoantibodies against MUC1, HER2 and cyclin B1. Although individual tumour-associated autoantibodies showed low diagnostic sensitivity, combinations of autoantibodies offered relatively high sensitivity. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method, and nucleic acid programmable protein microarrays appeared preferable to common protein microarrays. As the most commonly studied autoantibody, anti-p53 antibody was included in a meta-analysis. When it had been detected using ELISA and cut-off values were defined as the mean +2 or 3 standard deviations, the summary area under the receiver operating characteristic curve for the presence of BC was 0.78. Fagan's nomogram showed post-test probabilities of 32% and 6% for positive and negative results, respectively. Mammography might be supplemented by the use of tumour-associated autoantibodies as biomarkers for BC diagnosis in younger women with increased risks of BC. Even though several studies have investigated the diagnostic use of tumour-associated autoantibodies as biomarkers for BC detection, a high-quality prospective study is needed to validate their diagnostic value in practice.
Topics: Animals; Biomarkers, Tumor; Breast Neoplasms; Cyclin B1; Enzyme-Linked Immunosorbent Assay; Female; Humans; Mammography; Mucin-1; Predictive Value of Tests; Protein Array Analysis; Receptor, ErbB-2; Reference Standards; Sensitivity and Specificity; Tumor Suppressor Protein p53
PubMed: 26991924
DOI: 10.1111/sji.12430 -
World Journal of Gastroenterology Nov 2014The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active... (Review)
Review
The potential for the positive manipulation of the gut microbiome through the introduction of beneficial microbes, as also known as probiotics, is currently an active area of investigation. The FAO/WHO define probiotics as live microorganisms that confer a health benefit to the host when administered in adequate amounts. However, dead bacteria and bacterial molecular components may also exhibit probiotic properties. The results of clinical studies have demonstrated the clinical potential of probiotics in many pathologies, such as allergic diseases, diarrhea, inflammatory bowel disease and viral infection. Several mechanisms have been proposed to explain the beneficial effects of probiotics, most of which involve gene expression regulation in specific tissues, particularly the intestine and liver. Therefore, the modulation of gene expression mediated by probiotics is an important issue that warrants further investigation. In the present paper, we performed a systematic review of the probiotic-mediated modulation of gene expression that is associated with the immune system and inflammation. Between January 1990 to February 2014, PubMed was searched for articles that were published in English using the MeSH terms "probiotics" and "gene expression" combined with "intestines", "liver", "enterocytes", "antigen-presenting cells", "dendritic cells", "immune system", and "inflammation". Two hundred and five original articles matching these criteria were initially selected, although only those articles that included specific gene expression results (77) were later considered for this review and separated into three major topics: the regulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver. Particular strains of Bifidobacteria, Lactobacilli, Escherichia coli, Propionibacterium, Bacillus and Saccharomyces influence the gene expression of mucins, Toll-like receptors, caspases, nuclear factor-κB, and interleukins and lead mainly to an anti-inflammatory response in cultured enterocytes. In addition, the interaction of commensal bacteria and probiotics with the surface of antigen-presenting cells in vitro results in the downregulation of pro-inflammatory genes that are linked to inflammatory signaling pathways, whereas other anti-inflammatory genes are upregulated. The effects of probiotics have been extensively investigated in animal models ranging from fish to mice, rats and piglets. These bacteria induce a tolerogenic and hyporesponsive immune response in which many genes that are related to the immune system, in particular those genes expressing anti-inflammatory cytokines, are upregulated. By contrast, information related to gene expression in human intestinal cells mediated by the action of probiotics is scarce. There is a need for further clinical studies that evaluate the mechanism of action of probiotics both in healthy humans and in patients with chronic diseases. These types of clinical studies are necessary for addressing the influence of these microorganisms in gene expression for different pathways, particularly those that are associated with the immune response, and to better understand the role that probiotics might have in the prevention and treatment of disease.
Topics: Animals; Bacteria; Disease Models, Animal; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Inflammation Mediators; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Liver; Liver Diseases; Probiotics
PubMed: 25400447
DOI: 10.3748/wjg.v20.i42.15632 -
Journal of Gastrointestinal and Liver... Sep 2016The mucus layer of the intestinal tract is the main barrier between luminal microbes and the mucosa, and has an essential role in the body defense mechanisms. Previous... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
The mucus layer of the intestinal tract is the main barrier between luminal microbes and the mucosa, and has an essential role in the body defense mechanisms. Previous research could not establish consistent results for mucin genes expression in Crohn's disease (CD) patients. In this meta-analysis we looked at the mucin expression in CD patients and compared it with healthy controls.
METHOD
English medical literature searches were conducted for mucin expression in the mucosa of the ileum and colon of CD patients and compared it with normal mucosa. Case-control studies were included. Meta-analysis was performed by using Comprehensive meta-anaslysis software. Pooled odds ratios and 95% confidence intervals were calculated.
RESULTS
We found 160 eligible studies. Twenty studies were rejected because they have been performed in animals or did not have full text, and 134 studies were excluded because of language, being editorials, review articles, or because of duplications. We were left with 6 case-control studies from 4 countries that fulfilled the inclusion criteria, published till 31.12.2015. No significant heterogeneity was demonstrated: Q = 149.256, df (Q) = 40.00, I2= 73.2% (less than 75%). We found a decrease of 34% in the total mucin expression in CD patients (Odds Ratio 0.660, 95% CI 0.486-0.897, P = 0.008). We also found a significantly decreased expression in CD patients for MUC5AC, MUC5B and MUC7.
CONCLUSION
We demonstrated a global decrease in mucin expression in CD patients when compared with healthy controls.
Topics: Colon; Crohn Disease; Down-Regulation; Humans; Ileum; Intestinal Mucosa; Mucins; Odds Ratio
PubMed: 27689200
DOI: 10.15403/jgld.2014.1121.253.niv -
Oncotarget May 2017Accumulated studies have demonstrated the important role of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and indicated... (Meta-Analysis)
Meta-Analysis Review
Accumulated studies have demonstrated the important role of T cell immunoglobulin- and mucin-domain-containing molecule-3 (TIM-3) in various solid tumors and indicated its correlation with patients' survival. To further verify the prognostic significance of TIM-3 in cancer patients and its correlation with tumor, we performed this meta-analysis including seven studies searched from PubMed, Web of Science, and Embase till July 2016. A total of 869 patients were used to analyze the association between TIM-3 expression and patients' overall survival (OS). The pooled results showed that higher expression of TIM-3 was significantly correlated to shorter OS (7 studies, HR=1.89; 95% CI: 1.38-2.57; P< 0.001). In addition, higher TIM-3 expression was associated with advanced tumor stage (3 studies, III/IV vs. I/II, RR=2.02; 95% CI: 1.45-2.81; P< 0.001). In conclusion, our study highlights the role of TIM-3 as a potential prognostic marker and a promising therapeutic target in solid tumors.
Topics: Biomarkers, Tumor; Hepatitis A Virus Cellular Receptor 2; Humans; Neoplasm Grading; Neoplasm Staging; Neoplasms; Prognosis; Publication Bias
PubMed: 28423646
DOI: 10.18632/oncotarget.15954