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Breast Cancer Research and Treatment Dec 2017Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we... (Review)
Review
PURPOSE
Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age.
METHODS
We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer.
RESULTS
Compared to patients 70-79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01).
CONCLUSION
Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.
Topics: Age Factors; Aged; Aged, 80 and over; Breast Neoplasms; Estrogens; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Tumor Microenvironment
PubMed: 28803352
DOI: 10.1007/s10549-017-4448-5 -
PloS One 2014Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
METHODS
We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model.
RESULTS
25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation.
CONCLUSIONS
This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.
Topics: Colorectal Neoplasms; Genetic Association Studies; Genetic Markers; Humans; Mutation, Missense; Odds Ratio; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf
PubMed: 24594804
DOI: 10.1371/journal.pone.0090607 -
Pancreatology : Official Journal of the... 2016The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.
METHODS
A systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.
RESULTS
MCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93-95%). They are usually found incidentally at the age of 40-60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0-34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.
CONCLUSIONS
Compared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.
Topics: Humans; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 27681503
DOI: 10.1016/j.pan.2016.09.011 -
Gastrointestinal Endoscopy May 2021Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a... (Meta-Analysis)
Meta-Analysis
Molecular analysis of EUS-acquired pancreatic cyst fluid for KRAS and GNAS mutations for diagnosis of intraductal papillary mucinous neoplasia and mucinous cystic lesions: a systematic review and meta-analysis.
BACKGROUND AND AIMS
Although molecular analysis of pancreatic cyst fluid may aid pancreatic cyst classification, clinical practice remains highly variable. Therefore, we performed a systematic review and meta-analysis to evaluate the diagnostic performance of KRAS and GNAS mutations in EUS-acquired pancreatic cyst fluid for diagnosis of intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic lesions (MCLs).
METHODS
Individualized searches were developed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines and meta-analysis analyzed according to the Cochrane Diagnostic Test Accuracy working group methodology. A bivariate model was used to compute the pooled sensitivity and specificity and to plot the summary receiver operating characteristics curve with summary point and corresponding 95% confidence interval (95% CI).
RESULTS
Six studies (785 lesions) were included. For IPMNs and MCLs, KRAS + GNAS (combination) had significantly higher diagnostic accuracy than KRAS alone and GNAS alone (all P < .001). The pooled sensitivity, specificity, and diagnostic accuracy of KRAS + GNAS mutations for diagnosis of IPMNs were 94% (95% CI, 72-99; I = 86.74%), 91% (95% CI, 72-98; I = 89.83), and 97% (95% CI, 95-98), respectively, with each significantly higher compared with carcinoembryonic antigen (CEA) alone (all P < .001). For diagnosis of MCLs, KRAS + GNAS had a similar sensitivity and specificity compared with CEA alone; however, diagnostic accuracy was significantly improved (97% [95% CI, 95-98] vs 89% [95% CI, 86-91]; P < .001).
CONCLUSIONS
Molecular analysis for KRAS + GNAS mutations in EUS-acquired pancreatic cyst fluid has high sensitivity and specificity with significantly improved diagnostic accuracy for diagnosis of IPMNs and MCLs when compared with CEA alone.
Topics: Biomarkers, Tumor; Chromogranins; Cyst Fluid; GTP-Binding Protein alpha Subunits, Gs; Humans; Mutation; Pancreatic Cyst; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras)
PubMed: 33359054
DOI: 10.1016/j.gie.2020.12.014 -
Archives of Gynecology and Obstetrics Apr 2016Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa) is a rare tumour. Prognosis and optimal management are not well established. In view of a case managed in our... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Primary retroperitoneal mucinous cystadenocarcinoma (PRMCa) is a rare tumour. Prognosis and optimal management are not well established. In view of a case managed in our Centre, we performed a systematic review and meta-analysis.
METHOD
Systematic review of medical electronic databases for published data (1950-12/10/2015). No RCTs identified. Individual patient data detracted from case reports and case series were analysed
RESULTS
In total, 73 female and 5 male cases of PRMCa identified including our case. Median age at diagnosis was 42.0 years (range 18-86 years), with women being significantly younger than men at diagnosis (42.0 years versus 62.2 years, p = 0.005). A palpable abdominal mass and abdominal pain were the most common presentations in 42.9 and 23.8 % of cases, respectively. Twenty-six women were <38 years old. There were 16 women <38 years old that had surgical data reported, of which 14 underwent fertility-sparing surgery with excision of the mass. Adjuvant chemotherapy was given in 24.1 % (13/72) women. Follow-up ranged from 1 to 130 months with a median of 15 months. Of the 57 cases that had follow-up reported, recurrence occurred in 23 cases (40.4 %) within a median of 8 months from diagnosis. Median disease-free survival was 15 months (range 1-130 months). Of the women who recurred, 14 died of their disease giving 1, 2 and 5-year disease-specific survival rates of 85.9, 80.7 and 75.4 %, respectively.
CONCLUSION
PRMCa are rare and potentially aggressive tumours that often occur in young women. Removal of the tumour, adequate staging and adjuvant chemotherapy needs to be considered.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Cystadenocarcinoma, Mucinous; Disease-Free Survival; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retroperitoneal Neoplasms; Survival Rate; Treatment Outcome; Young Adult
PubMed: 26681306
DOI: 10.1007/s00404-015-3975-8 -
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 -
Pancreatology : Official Journal of the... Feb 2024This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of... (Review)
Review
BACKGROUND
This systematic review aimed to assess the diagnostic accuracy of the International Consensus Fukuoka Guidelines (ICG2017) in identifying high-risk lesions of Intraductal Papillary Mucinous Neoplasms (IPMNs).
METHODS
The ICG2017 revision committee conducted a comprehensive literature review to establish evidence-based statements on IPMNs. The review focused on articles examining the diagnostic value of imaging features (e.g., cyst or main pancreatic duct diameter), clinical symptoms associated with IPMN, and serum biomarkers. Five clinical questions regarding high-risk stigmata (HRS) and worrisome features (WF) in the ICG2017 guidelines were addressed.
RESULTS
A total of 210 articles were reviewed. The findings revealed a significant association between the presence of mural nodules ≥5 mm in diameter or solid components with contrast enhancement and the diagnosis of high-grade dysplasia or invasive carcinoma. Contrast-enhanced diagnostic tools, such as CT, MRI, or EUS, demonstrated the highest prediction rate and were recommended. Positive cytology was identified as an HRS, while symptoms like acute pancreatitis and cyst diameter growth ≥2.5 mm per year were considered WFs. The use of nomograms and multiple diagnostic factors was recommended for optimal IPMN management.
CONCLUSIONS
This systematic review provides evidence supporting the improved diagnostic accuracy of ICG2017 in identifying high-risk lesions of IPMN. The multidisciplinary incorporation of HRS and WF based on imaging findings and clinical symptoms is crucial. These findings should inform the revision of ICG2017, enhancing the evaluation and management of IPMN patients. By implementing these recommendations, clinicians can make more informed decisions, leading to better diagnosis and treatment outcomes for high-risk IPMN cases.
Topics: Humans; Acute Disease; Carcinoma, Pancreatic Ductal; Cysts; Neoplasms, Cystic, Mucinous, and Serous; Pancreatic Ducts; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Pancreatitis; Retrospective Studies
PubMed: 38161091
DOI: 10.1016/j.pan.2023.12.002 -
International Journal of Medical... 2023The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5,... (Review)
Review
The members of the transmembrane emp24 domain-containing protein (TMED) family are summarized in human as four subfamilies, α (TMED 4, 9), β (TMED 2), γ (TMED1, 3, 5, 6, 7) and δ (TMED 10), with a total of nine members, which are important regulators of intracellular protein transport and are involved in normal embryonic development, as well as in the pathogenic processes of many human diseases. Here we systematically review the composition, structure and function of TMED family members, and describe the progress of TMED family in human diseases, including malignancies (head and neck tumors, lung cancer, breast cancer, ovarian cancer, endometrial cancer, gastrointestinal tumors, urological tumors, osteosarcomas, etc.), immune responses, diabetes, neurodegenerative diseases, and nonalcoholic fatty liver disease, dilated cardiomyopathy, mucin 1 nephropathy (MKD), and desiccation syndrome (SS). Finally, we discuss and prospect the potential of TMED for disease prognosis prediction and therapeutic targeting, with a view to laying the foundation for therapeutic research based on TMED family causative genes.
Topics: Pregnancy; Female; Humans; Membrane Proteins; Protein Transport; Non-alcoholic Fatty Liver Disease; Vesicular Transport Proteins
PubMed: 37928880
DOI: 10.7150/ijms.87272 -
Pancreatology : Official Journal of the... 2014Differential diagnosis of malignant and benign intraductal papillary mucinous neoplasms (IPMNs) is essential to determine the optimal treatment. Endoscopic... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Differential diagnosis of malignant and benign intraductal papillary mucinous neoplasms (IPMNs) is essential to determine the optimal treatment. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is currently used to diagnose pancreatic cystic lesions worldwide, but few studies have focused on the diagnostic yield to distinguish malignant and benign IPMNs. Therefore, we aim to systematically review the diagnostic yield of EUS-FNA-based cytology to distinguish malignant and benign IPMNs.
METHODS
Relevant studies with a reference standard of definitive surgical histology which published between 2002 and 2012 were identified via MEDLINE and SCOPUS. Malignant IPMNs included invasive adenocarcinoma, carcinoma in situ, and high-grade dysplasia.
RESULTS
Four studies with 96 patients were included in this meta-analysis. For diagnostic yield of EUS-FNA-based cytology distinguishing malignant and benign IPMNs, the pooled sensitivity and specificity were 64.8% (95% CI, 0.44-0.82) and 90.6% (95% CI, 0.81-0.96), respectively. Similarly, the positive likelihood ratio and negative likelihood ratio were 6.35 (95% CI, 2.95-13.68) and 0.43 (95% CI, 0.14-1.34), respectively. Malignant IPMNs were observed in 20.8% (20/96) of patients in EUS-FNA studies.
CONCLUSIONS
EUS-FNA-based cytology has good specificity but poor sensitivity in differentiating benign from malignant IPMNs. Newer techniques or markers are needed to improve diagnostic yield.
Topics: Adenoma; Carcinoma in Situ; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Likelihood Functions; Pancreas; Pancreatic Neoplasms; Sensitivity and Specificity
PubMed: 25278308
DOI: 10.1016/j.pan.2014.07.006 -
Cancer Metastasis Reviews Mar 2023Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low... (Review)
Review
Pseudomyxoma peritonei (PMP) is a rare, progressive, slowly growing neoplastic condition which is poorly understood, with a 5-year progression-free survival rate as low as 48%. PMP is most commonly caused by appendiceal mucinous neoplasms (AMN), and understanding their genetic biology and pathogenicity may allow for the development of better novel systemic treatments to target key deleterious mutations and the implicated pathways. The primary aim of this systematic review was to identify the genetic profile of histologically confirmed human PMP or AMN samples. The secondary aim was to identify whether genetic marks could be used to predict patient survival. Ovid EMBASE, Ovid MEDLINE, PubMed, and Web of Science were searched to identify studies investigating the genetic profile of histologically-confirmed human PMP or AMN samples. We review findings of 46 studies totalling 2181 tumour samples. The most frequently identified somatic gene mutations in patients with PMP included KRAS (38-100%), GNAS (17-100%), and TP53 (5-23%); however, there were conflicting results of their effect on survival. Three studies identified molecular subtypes based on gene expression profiles classifying patients into oncogene-enriched, immune-enriched, and mixed molecular subtypes with prognostic value. This review summarises the current literature surrounding genetic aberrations in PMP and AMNs and their potential utility for targeted therapy. Given the recent advances in clinical trials to directly target KRAS and GNAS mutations in other cancers, we propose a rationale to explore these mutations in future pre-clinical studies in PMP with a view for a future clinical trial.
Topics: Humans; Pseudomyxoma Peritonei; Peritoneal Neoplasms; Appendiceal Neoplasms; Genetic Profile; Proto-Oncogene Proteins p21(ras)
PubMed: 36723696
DOI: 10.1007/s10555-023-10088-0