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European Journal of Radiology Open Dec 2023Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While... (Review)
Review
RATIONALE AND OBJECTIVES
Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While IPMN-P is a well described entity for which guidelines were formulated and revised, IPMN-B is a poorly described entity.We carried out a systematic review to evaluate the existing literature, emphasizing the role of MRI in IPMN-B depiction.
MATERIALS AND METHODS
PubMed database was used to identify original studies and case series that reported MR Imaging features of IPMN-B. The search keywords were "IPMN OR intraductal papillary mucinous neoplasm OR IPNB OR intraductal papillary neoplasm of the bile duct AND Biliary OR biliary cancer OR hepatic cystic lesions". Risk of bias and applicability were evaluated using the QUADAS-2 tool.
RESULTS
884 Records were Identified through database searching. 12 studies satisfied the inclusion criteria, resulting in MR features of 288 patients. All the studies were retrospective. Classic features of IPMN-B are under-described. Few studies note worrisome features, concerning for an underlying malignancy. 50 % of the studies had a high risk of bias and concerns regarding applicability.
CONCLUSIONS
The MRI features of IPMN-B are not well elaborated and need to be further studied. Worrisome features and guidelines regarding reporting the imaging findings should be established and published. Radiologists should be aware of IPMN-B, since malignancy diagnosis in an early stage will yield improved prognosis.
PubMed: 37609049
DOI: 10.1016/j.ejro.2023.100515 -
International Journal of Gynecological... Jul 2017Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis.
Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.
Topics: Adenocarcinoma; Adenocarcinoma in Situ; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Cervix Uteri; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 27801764
DOI: 10.1097/PGP.0000000000000345 -
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 -
World Journal of Surgical Oncology Feb 2024Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA.
METHODS
A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors.
RESULTS
A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA.
CONCLUSION
In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.
Topics: Humans; Adenocarcinoma of Lung; Adenocarcinoma, Mucinous; Lung; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Pneumonia; Prognosis; Retrospective Studies; Male; Female
PubMed: 38303008
DOI: 10.1186/s12957-024-03326-4 -
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 -
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 -
World Journal of Gastroenterology Jun 2015To analyze the available evidence about the risk of extrapancreatic malignancies and pancreatic ductal adenocarcinoma associated to pancreatic intraductal papillary... (Review)
Review
AIM
To analyze the available evidence about the risk of extrapancreatic malignancies and pancreatic ductal adenocarcinoma associated to pancreatic intraductal papillary mucinous tumors (IPMNs).
METHODS
A systematic search of literature was undertaken using MEDLINE, EMBASE, Cochrane and Web-of-Science libraries. No limitations for year of publication were considered; preference was given to English papers. All references in selected articles were further screened for additional publications. Both clinical series and Literature reviews were selected. For all eligible studies, a standard data extraction form was filled in and the following data were extracted: study design, number of patients, prevalence of pancreatic cancer and extrapancreatic malignancies in IPMN patients and control groups, if available.
RESULTS
A total of 805 abstracts were selected and read; 25 articles were considered pertinent and 17 were chosen for the present systematic review. Eleven monocentric series, 1 multicentric series, 1 case-control study, 1 population-based study and 3 case report were included. A total of 2881 patients were globally analyzed as study group, and the incidence of pancreatic cancer and/or extrapancreatic malignancies ranged from 5% to 52%, with a mean of 28.71%. When a control group was analyzed (6 papers), the same incidence was as low as 9.4%.
CONCLUSION
The available Literature is unanimous in claiming IPMNs to be strongly associated with pancreatic and extrapancreatic malignancies. The consequences in IPMNs management are herein discussed.
Topics: Carcinoma, Pancreatic Ductal; Humans; Incidence; Neoplasms, Cystic, Mucinous, and Serous; Neoplasms, Second Primary; Pancreatic Neoplasms; Prevalence; Prognosis; Risk Assessment; Risk Factors
PubMed: 26109820
DOI: 10.3748/wjg.v21.i23.7313 -
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 -
Surgery Open Science Apr 2022Clinicopathological characteristics of intraductal papillary mucinous neoplasm derived from the ectopic pancreas have not been elucidated owing to its rarity. (Review)
Review
BACKGROUND
Clinicopathological characteristics of intraductal papillary mucinous neoplasm derived from the ectopic pancreas have not been elucidated owing to its rarity.
METHODS
MEDLINE databases from 1985 to 2021 were searched. Data regarding patient characteristics, diagnostic modalities, treatment, and prognosis were extracted from the identified articles.
RESULTS
Comprehensive data on 13 patients (10 men and 3 women) with intraductal papillary mucinous neoplasm derived from ectopic pancreas were extracted. The median age was 69 years (range, 42-80 years). The tumors were located in the stomach in 6 patients, the duodenum in 1 patient, jejunum in 3 patients, ileum in 1 patient, and Meckel diverticulum in 2 patients. Histopathological examination revealed intraductal papillary mucinous neoplasm in 10 patients and intraductal papillary mucinous carcinoma in 3 patients. The median size of the tumor was not significantly different between the intraductal papillary mucinous carcinoma group and the intraductal papillary mucinous neoplasm group (P = .611).
CONCLUSION
Accurate preoperative diagnosis and differential diagnosis between intraductal papillary mucinous neoplasm and intraductal papillary mucinous carcinoma remain difficult despite recent advances in imaging modalities.
PubMed: 35392578
DOI: 10.1016/j.sopen.2022.03.001