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Skin Appendage Disorders May 2022Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases...
INTRODUCTION
Hematohidrosis and hemolacria are 2 conditions surrounded in religiousness, mysticism, and supernatural superstitions. While the mechanism is still unclear, these cases have amazed physicians for centuries.
METHODS
We performed a systematic review in PubMed from 2000 to mid-2021 accounting for 75 studies from which we included 60 cases in 53 articles which were described.
RESULTS
The median age of apparition was 24 years with the youngest case being 12 and the oldest 81. Some of the diseases were secondary to other causes such as hemangiomas and other neoplasias or epistaxis episodes. Most of the cases have been reported in India and the USA; most of them correspond to hemolacria alone (51.6%).
DISCUSSION
We have stated the basics of the substances involved in the coagulation process that have been described as genetically altered in some patients such as mucins, metalloproteinases, and fibrinogen, as well as propose a mechanism that can explain the signs of this particular entity and approach to its treatment as well as provide the first trichoscopy image of a patient with hemolacria.
PubMed: 35707284
DOI: 10.1159/000520648 -
Epidemiology (Cambridge, Mass.) Jan 2018It has been posited that there is an association between perineal talc use and the incidence of ovarian cancer. To date, this has only been explored in observational... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
It has been posited that there is an association between perineal talc use and the incidence of ovarian cancer. To date, this has only been explored in observational studies.
OBJECTIVES
To perform a meta-analysis to evaluate the association between perineal talc use and risk of ovarian cancer.
METHODS
Studies were identified using six electronic databases. Observational studies involving at least 50 cases of ovarian cancer were eligible for inclusion. We analyzed the association between ovarian cancer, including specific types, and any perineal talc use, long-term (>10 years) use, total lifetime applications, and use on diaphragms or sanitary napkins. A subgroup analysis was performed, stratifying by study design and population.
RESULTS
We identified 24 case-control (13,421 cases) and three cohort studies (890 cases, 181,860 person-years). Any perineal talc use was associated with increased risk of ovarian cancer (OR = 1.31; 95% CI = 1.24, 1.39). More than 3600 lifetime applications (OR = 1.42; 95% CI = 1.25, 1.61) were slightly more associated with ovarian cancer than <3600 (OR = 1.32; 95% CI = 1.15, 1.50). An association with ever use of talc was found in case-control studies (OR = 1.35; 95% CI = 1.27, 1.43), but not cohort studies (OR = 1.06; 95% CI = 0.90, 1.25). However, cohort studies found an association between talc use and invasive serous type ovarian cancer (OR = 1.25; 95% CI = 1.01, 1.55). We found an increased risk of serous and endometrioid, but not mucinous or clear cell subtypes.
CONCLUSIONS
In general, there is a consistent association between perineal talc use and ovarian cancer. Some variation in the magnitude of the effect was found when considering study design and ovarian cancer subtype.
Topics: Antiperspirants; Carcinoma, Endometrioid; Case-Control Studies; Female; Humans; Incidence; Neoplasms, Cystic, Mucinous, and Serous; Odds Ratio; Ovarian Neoplasms; Perineum; Risk Factors; Talc
PubMed: 28863045
DOI: 10.1097/EDE.0000000000000745 -
Cancers Nov 2023Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with... (Review)
Review
Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960-December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies ( = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy ( = 101) followed by oesophageal adenocarcinoma (OAc, = 24) and squamous cell carcinoma (OSqCc, = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers.
PubMed: 37958425
DOI: 10.3390/cancers15215252 -
Histopathology Sep 2022Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with... (Review)
Review
AIMS
Intraductal tubulopapillary neoplasm (ITPN) of the pancreas is a recently recognized pancreatic tumor entity. Here we aimed to determine the most important features with a systematic review coupled with an integrated statistical approach.
METHODS AND RESULTS
PubMed, SCOPUS, and Embase were searched for studies reporting data on pancreatic ITPN. The clinicopathological, immunohistochemical, and molecular data were summarized. Then a comprehensive survival analysis and a comparative analysis of the molecular alterations of ITPN with those of pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) from reference cohorts (including the International Cancer Genome Consortium- ICGC dataset and The Cancer Genome Atlas, TCGA program) were conducted. The core findings of 128 patients were as follows: (i) Clinicopathological parameters: pancreatic head is the most common site; presence of an associated adenocarcinoma was reported in 60% of cases, but with rare nodal metastasis. (ii) Immunohistochemistry: MUC1 (>90%) and MUC6 (70%) were the most frequently expressed mucins. ITPN lacked the intestinal marker MUC2; unlike IPMN, it did not express MUC5AC. (iii) Molecular landscape: Compared with PDAC/IPMN, the classic pancreatic drivers KRAS, TP53, CDKN2A, SMAD4, GNAS, and RNF43 were less altered in ITPN (P < 0.001), whereas MCL amplifications, FGFR2 fusions, and PI3KCA mutations were commonly altered (P < 0.001). (iv) Survival analysis: ITPN with a "pure" branch duct involvement showed the lowest risk of recurrence.
CONCLUSION
ITPN is a distinct pancreatic neoplasm with specific clinicopathological and molecular characteristics. Its recognition is fundamental for its clinical/prognostic implications and for the enrichment of potential targets for precision oncology.
Topics: Carcinoma, Pancreatic Ductal; Carcinoma, Papillary; Humans; Pancreas; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Precision Medicine
PubMed: 35583805
DOI: 10.1111/his.14698 -
Digestive Diseases (Basel, Switzerland) 2021Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
BACKGROUND
Mucus protects the epithelium against invaders and toxic materials. Sticky and thick mucus is characteristic of CF.
OBJECTIVE
The aim of this systematic review is to characterize the specific mucins secreted in the lung and intestinal tract of CF patients.
METHODS
A systematic literature search was conducted up to December 31, 2019. The following terms were used: "cystic fibrosis" AND "mucin." Case-control studies comparing mucin expression in CF patients to healthy controls were included.
RESULTS
We found 741 eligible studies, 694 studies were rejected because they were performed in animals and not in full text, and 32 studies were excluded being editorials, duplications, review articles, meta-analysis, or not in English. Fifteen studies were eligible for our study, including 150 CF patients compared to 82 healthy controls, all fulfilled the inclusion criteria. The main mucin types expressed in the sinus submucosal glands, sputum, tracheobronchial surface epithelium, and lung submucosal glands were MUC5AC and MUC5B. Increase in the number of sinusoidal submucosal glands and expression of MUC5B was found in CF patients, but no such difference from healthy controls was found for the number of goblet cells in the surface epithelium nor in the expression of -MUC5AC. The opposite was found in the tracheobronchial surface epithelium and in the lungs.
CONCLUSIONS
Increased expression of MUC5AC in the surface epithelium and of MUC5B in the subepithelial glands may be the result of higher secretion rate of mucin into the lumen of the respiratory tract, causing mucus plaque, infection, and inflammation.
Topics: Animals; Bodily Secretions; Case-Control Studies; Cystic Fibrosis; Gastrointestinal Tract; Humans; Lung; Mucin 5AC; Mucin-5B; Mucins
PubMed: 33049746
DOI: 10.1159/000512268 -
Gynecologic Oncology Mar 2023Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes.
METHODS
We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing.
RESULTS
A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%).
CONCLUSION
MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid.
PRECIS
The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.
Topics: Humans; Female; Colorectal Neoplasms, Hereditary Nonpolyposis; Carcinoma, Ovarian Epithelial; Microsatellite Instability; Ovarian Neoplasms; Carcinoma, Endometrioid; Endometrial Neoplasms; Protein Deficiency; DNA Mismatch Repair; MutL Protein Homolog 1
PubMed: 36682091
DOI: 10.1016/j.ygyno.2022.12.008 -
Pancreatology : Official Journal of the... Nov 2023Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are...
BACKGROUND
Intraductal papillary mucinous neoplasms (IPMNs) are a cystic precursor to pancreatic cancer. IPMNs deemed clinically to be at high-risk for malignant progression are frequently treated with surgical resection, and pathological examination of the pancreatectomy specimen is a key component of the clinical care of IPMN patients.
METHODS
Systematic literature reviews were conducted around eight topics of clinical relevance in the examination of pathological specimens in patients undergoing resection of IPMN.
RESULTS
This review provides updated perspectives on morphological subtyping of IPMNs, classification of intraductal oncocytic papillary neoplasms, nomenclature for high-grade dysplasia, assessment of T stage, distinction of carcinoma associated or concomitant with IPMN, role of molecular assessment of IPMN tissue, role of intraoperative assessment by frozen section, and preoperative evaluation of cyst fluid cytology.
CONCLUSIONS
This analysis provides the foundation for data-driven approaches to several challenging issues in the pathology of IPMNs.
Topics: Humans; Carcinoma, Pancreatic Ductal; Pancreatic Intraductal Neoplasms; Adenocarcinoma, Mucinous; Retrospective Studies; Pancreatic Neoplasms
PubMed: 37604731
DOI: 10.1016/j.pan.2023.08.002 -
Frontiers in Allergy 2023Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and... (Review)
Review
BACKGROUND
Epigenetics facilitates insights on the impact of host environment on the genesis of chronic rhinosinusitis (CRS) through modulations of host gene expression and activity. Epigenetic mechanisms such as DNA methylation cause reversible but heritable changes in gene expression over generations of progeny, without altering the DNA base-pair sequences. These studies offer a critical understanding of the environment-induced changes that result in host predisposition to disease and may help in developing novel biomarkers and therapeutics. The goal of this systematic review is to summarize the current evidence on epigenetics of CRS with a focus on chronic rhinosinusitis with nasal polyps (CRSwNP) and highlight gaps that merit further research.
METHODS
A systematic review of the English language literature was performed to identify investigations related to epigenetic studies in subjects with CRS.
RESULTS
The review identified 65 studies. These have focused on DNA methylation and non-coding RNAs, with only a few on histone deacetylation, alternative polyadenylation, and chromatin accessibility. Studies include those investigating and changes or both. Studies also include animal models of CRS. Almost all have been conducted in Asia. The genome-wide studies of DNA methylation found differences in global methylation between CRSwNP and controls, while others specifically found significant differences in methylation of the CpG sites of the thymic stromal lymphopoietin (), , and . In addition, DNA methyltransferase inhibitors and histone deacetylase inhibitors were studied as potential therapeutic agents. Majority of the studies investigating non-coding RNAs focused on micro-RNAs (miRNA) and found differences in global expression of miRNA levels. These studies also revealed some previously known as well as novel targets and pathways such as tumor necrosis factor alpha, TGF beta-1, IL-10, , aryl hydrocarbon receptor, PI3K/AKT pathway, mucin secretion, and vascular permeability. Overall, the studies have found a dysregulation in pathways/genes involving inflammation, immune regulation, tissue remodeling, structural proteins, mucin secretion, arachidonic acid metabolism, and transcription.
CONCLUSIONS
Epigenetic studies in CRS subjects suggest that there is likely a major impact of the environment. However, these are association studies and do not directly imply pathogenesis. Longitudinal studies in geographically and racially diverse population cohorts are necessary to quantify genetic vs. environmental risks for CRSwNP and CRS without nasal polyps and assess heritability risk, as well as develop novel biomarkers and therapeutic agents.
PubMed: 37284022
DOI: 10.3389/falgy.2023.1165271 -
Pancreatology : Official Journal of the... Nov 2023Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mucinous pancreatic cysts harbor the potential to progress to highly lethal pancreatic ductal adenocarcinoma (PDAC). Since these precursor cysts require cancer surveillance or surgical resection, they need to be reliably distinguished from harmless pancreatic cysts. Current clinical and radiographic assessment is imperfect and the value of cyst fluid analysis for differential diagnosis is unclear. Therefore, we set out to investigate the value of cyst fluid biomarkers in distinguishing pancreatic cysts.
METHODS
We performed a systematic review of the current literature to identify articles that evaluated the diagnostic performance of clinically relevant and promising candidate cyst fluid biomarkers, with a particular emphasis on DNA-based biomarkers. Meta-analysis was performed for biomarkers targeted at identifying cyst type and presence of high-grade dysplasia or PDAC.
RESULTS
Data from a total of 42 studies was analyzed. Mutations in KRAS and/or GNAS allowed identification of mucinous cysts with a sensitivity of 79% and specificity of 98%. This exceeded the performance of the traditional biomarker carcinoembryonic antigen (CEA; sensitivity 58%, specificity 87%). Mutations in VHL were specific for serous cystadenomas (SCAs; sensitivity 56%, specificity 99%) and help to exclude mucinous cysts. Mutations in CDKN2A, PIK3CA, SMAD4, and TP53 each had high specificities of 97%, 97%, 98%, and 95%, respectively, to identify high-grade dysplasia or PDAC in mucinous cysts.
CONCLUSIONS
Cyst fluid analysis can be a valuable tool in the characterization of pancreatic cysts, with relevant clinical implications. Our results support the use of DNA-based cyst fluid biomarkers in the multidisciplinary diagnostic work-up of pancreatic cysts.
Topics: Humans; Cyst Fluid; Pancreatic Neoplasms; Carcinoembryonic Antigen; Carcinoma, Pancreatic Ductal; Pancreatic Cyst; DNA; Biomarkers, Tumor
PubMed: 37230894
DOI: 10.1016/j.pan.2023.05.005 -
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572