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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 -
Cancers Nov 2023Ovarian cancer (OC) has a high rate of mortality and is the fifth most common cause of death in females all over the world. The etiology is still unclear. Numerous... (Review)
Review
Ovarian cancer (OC) has a high rate of mortality and is the fifth most common cause of death in females all over the world. The etiology is still unclear. Numerous factors such as smoking, obesity, and unhealthy diet may affect the risk of OC. Having a family history of breast and OC is one of the main risks for developing OC. Mutations of BRCA1/2 are associated with OC risk as well. The histopathological classification of OC reveals the four most common types: serous, clear cell, endometrioid, and mucinous; these are epithelial OC types, and other types are rare. Furthermore, OC can be subdivided into types I and II. Type I tumors are most probably caused by atypical proliferative tumors. Type II tumors include high-grade carcinoma of the serous type, carcinosarcoma, and carcinoma, which are not differentiated and generally originate from tubal intraepithelial carcinoma of the serous type. Typically, type I tumors are present in early stages, usually with good prognosis. Type II tumors are classified as high-grade tumors and are most often diagnosed at advanced FIGO stages with poor prognosis. High-grade serous OC accounts for 90% of serous OC. Tumor heterogeneity aggravates OC treatment. The standard care for primary epithelial ovarian cancer (EOC) is cytoreductive surgery followed by platinum-based chemotherapy. Neoadjuvant chemotherapy can be used in certain cases followed by cytoreductive surgery. The main prognostic factor is complete tumor resection. However, about 70% of patients relapse. Resistance to chemotherapeutic agents remains a major challenge in EOC treatment, in which many different factors are involved. In recent years, the examination of molecular parameters and their prognostic impact has become increasingly relevant in EOC, and furthermore, the use of immunotherapy has expanded the therapeutic range. As the clinical need is greatest for relapsed patients, this systematic review will focus on recent advances in molecular biology with prognostic and predictive markers and treatment options for recurrent/refractory OC. Inclusion criteria for the review: potential prospective or predictive biomarkers in preclinical or clinical use in relapsed and refractory OC, prognostic impact, clinical and preclinical trials, and immunotherapy. Exclusion criteria for the review: primary OC, no full text or abstract available, not the topic mentioned above, and text not available in English. Risk of bias: the included studies were evaluated descriptively for the topics mentioned above, and data were not compared with each other. The objective is to highlight the molecular mechanisms of the most promising targeted agents under clinical investigation to demonstrate their potential relevance in recurrent/refractory OC.
PubMed: 38001616
DOI: 10.3390/cancers15225356 -
Current Issues in Molecular Biology May 2024The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the... (Review)
Review
The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries ( < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.
PubMed: 38785526
DOI: 10.3390/cimb46050258 -
International Journal of Gynecological... Dec 2023To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the prognostic value of cancer antigen 125 (CA125) related variables on progression free survival and overall survival in primary and recurrent ovarian cancers.
METHOD
A comprehensive review of the Medline, Embase, and Cochrane Library databases was conducted to identify relevant literature on survival outcomes according to the ELIMination Rate Constant K (KELIM), Gynecologic Cancer InterGroup (GCIG) CA125 response criteria, CA125 half-life, and CA125 nadir levels during first line or later line chemotherapy. The search included articles published before February 2023. Cut-off values determining the favorable/unfavorable score of each study were extracted, and pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were analyzed using a random effects model to identify the relationship between survival outcomes of the favorable/unfavorable groups, which was determined by an individual model using CA125 kinetics.
RESULTS
A total of 27 studies with 14 444 patients with epithelial ovarian cancer were included in this meta-analysis. In primary ovarian cancer, a favorable KELIM score, determined by individual modeled cut-off values, was associated with a significant progression free survival (HR 0.53, 95% CI 0.45 to 0.62) and overall survival (HR 0.51, 95% CI 0.43 to 0.62) benefit in the primary setting. The favorable KELIM scored group also correlated with a better progression free survival (HR 0.54, 95% CI 0.47 to 0.62) in relapsed disease. We failed to demonstrate a better prognostic value of the GCIG response criteria and the CA125 half-life for progression free survival and overall survival.
CONCLUSION
Novel chemotherapy response scores, such as KELIM, may be more clinically relevant than other prognostic models using CA125 kinetics, being directly associated with a more favorable survival in both the primary and relapsed setting in patients with epithelial ovarian cancer.
STUDY REGISTRATION
The systemic review and meta-analysis were registered in PROSPERO (CRD42023385512).
Topics: Humans; Female; Carcinoma, Ovarian Epithelial; Prognosis; Ovarian Neoplasms; Half-Life; CA-125 Antigen; Neoplasm Recurrence, Local
PubMed: 37949486
DOI: 10.1136/ijgc-2023-004825 -
Cancers Oct 2023Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on... (Review)
Review
BACKGROUND
Conflicting results about the prognostic relevance of signet ring cell histology in gastric cancer have been reported. We aimed to perform a meta-analysis focusing on the clinicopathological features and prognosis of this subgroup of cancer compared with other histologies.
METHODS
A systematic literature search in the PubMed database was conducted, including all publications up to 1 October 2021. A meta-analysis comparing the results of the studies was performed.
RESULTS
A total of 2062 studies referring to gastric cancer with signet ring cell histology were identified, of which 262 studies reported on its relationship with clinical information. Of these, 74 were suitable to be included in the meta-analysis. A slightly lower risk of developing nodal metastases in signet ring cell tumours compared to other histotypes was found (especially to undifferentiated/poorly differentiated/mucinous and mixed histotypes); the lower risk was more evident in early and slightly increased in advanced gastric cancer. Survival tended to be better in early stage signet ring cell cancer compared to other histotypes; no differences were shown in advanced stages, and survival was poorer in metastatic patients. In the subgroup analysis, survival in signet ring cell cancer was slightly worse compared to non-signet ring cell cancer and differentiated/well-to-moderately differentiated adenocarcinoma.
CONCLUSIONS
Most of the conflicting results in signet ring cell gastric cancer literature could be derived from the lack of standardisation in their classification and the comparison with the different subtypes of gastric cancer. There is a critical need to strive for a standardised classification system for gastric cancer, fostering clarity and coherence in the forthcoming research and clinical applications.
PubMed: 37958365
DOI: 10.3390/cancers15215191 -
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 -
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 -
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 -
Langenbeck's Archives of Surgery Nov 2023Studies evaluating the rate and histology of appendiceal neoplasms between complicated and uncomplicated appendicitis include a small number of patients. Therefore, we... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Studies evaluating the rate and histology of appendiceal neoplasms between complicated and uncomplicated appendicitis include a small number of patients. Therefore, we sought a meta-analysis and systematic review comparing the rates and types of appendiceal neoplasm between complicated and uncomplicated appendicitis.
METHODS
We included articles published from the time of inception of the datasets to September 30, 2022. The electronic databases included English publications in Ovid MEDLINE In-Process & Other Non-Indexed Citations, Ovid MEDLINE, Ovid EMBASE, and Scopus.
RESULTS
A total of 4962 patients with appendicitis enrolled in 4 comparative studies were included. The mean age was 43.55 years (16- 94), and half were male (51%). Based on intra-operative findings, 1394 (38%) had complicated appendicitis, and 3558 (62%) had uncomplicated appendicitis. The overall incidence rate of neoplasm was 1.98%. No significant difference was found in the incidence rate of appendiceal neoplasm between complicated (3.29%) and uncomplicated (1.49%) appendicitis (OR 0.44, 95% CI 0.16- 1.23; p < 0.087; I2 = 54.9%). The most common appendiceal neoplasms were Neuroendocrine Tumors (NET) (49.21%), Nonmucinous Adenocarcinoma (24.24%), Mixed Adeno-Neuroendocrine Tumor (MANEC) (11.40%), Mucinous Adenocarcinoma (4.44%). There was a significant difference between complicated and uncomplicated appendicitis in rates of adenocarcinoma (50% vs. 13%), NET (31% vs. 74%), MANEC (19% vs. 13%) (P < 0.001).
CONCLUSION
While there was no significant difference in the overall neoplasm rate between complicated and uncomplicated appendicitis, the NET rate was significantly higher in uncomplicated appendicitis. In comparison, the Adenocarcinoma rate was considerably higher in Complicated appendicitis. These findings emphasize the importance of evaluating risk factors for neoplasm when considering appendectomy in patients with appendicitis.
Topics: Humans; Male; Adult; Female; Appendiceal Neoplasms; Appendicitis; Incidence; Risk Factors; Appendectomy; Neuroendocrine Tumors; Adenocarcinoma; Retrospective Studies
PubMed: 37940770
DOI: 10.1007/s00423-023-03164-0 -
Journal of Interferon & Cytokine... Aug 2023Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and... (Meta-Analysis)
Meta-Analysis
Osteosarcoma is the most prevalent type of primary bone malignancy in children and adolescents. The effect of cytokines on osteosarcoma prognosis has been studied and reported. This meta-analysis aimed to assess the prognostic value of cytokines as osteosarcoma biomarkers. Databases including PubMed, Embase, and Cochrane Library were searched for studies on the prognostic value of cytokines in osteosarcoma. From the eligible studies, data on overall survival (OS), disease-free survival, and metastasis-free survival (MFS) were extracted. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated. A total of 11 studies involving 755 patients were included in this analysis. High macrophage migration inhibitory factor (MIF) expression in tumors was significantly associated with shortened OS (HR = 2.01, 95% CI: 1.18-3.42, = 0.010) and MFS (HR = 2.51, 95% CI: 1.47-4.01, = 0.001). Elevated T cell immunoglobulin and mucin domain-3 (Tim-3) levels in serum correlated with increased risk of disease progression in patients with osteosarcoma (HR = 3.14, 95% CI: 2.88-3.03, 0.001). However, interleukin 6 (IL-6) and tumor necrosis factor were not substantially associated with osteosarcoma prognosis. Owing to a paucity of research, other relevant cytokines [interferon-α/β receptor, tissue factor, macrophage inhibitory cytokine 1 (MIC-1), and IL-23] could not be combined. In conclusion, MIF levels in tumors and Tim-3 levels in serum can be potential biomarkers of poor prognosis in osteosarcoma. To confirm this finding and implement these biomarkers into clinical applications, additional large-scale, high-quality studies are needed.
Topics: Adolescent; Child; Humans; Cytokines; Prognosis; Hepatitis A Virus Cellular Receptor 2; Biomarkers, Tumor; Osteosarcoma; Bone Neoplasms
PubMed: 37566475
DOI: 10.1089/jir.2023.0083