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Archives of Pathology & Laboratory... Jun 2024Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem...
The Diagnostic Accuracy of Claudin-4 Immunochemistry in Differentiating Metastatic Carcinomas From Mesothelial Processes in Serous Effusion Cytology: A Systematic Review and Meta-analysis.
CONTEXT.—
Distinguishing metastatic carcinomas from mesotheliomas or reactive mesothelial cells in pleural, peritoneal, and pericardial effusions is a common diagnostic problem cytopathologists encounter.
OBJECTIVE.—
To perform the first meta-analysis on the pooled diagnostic accuracy of claudin-4 immunochemistry in serous effusion cytopathology.
DESIGN.—
This report followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for diagnostic test accuracy studies. Three databases (PubMed, Scopus, and the Cochrane Library) were searched until October 9, 2023, followed by study selection using specific inclusion and exclusion criteria and data extraction. The study quality assessment was performed by using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Statistical analysis was performed by using R to calculate the pooled sensitivity and specificity of claudin-4 immunochemistry. In addition, the diagnostic odds ratio was measured, representing the odds ratio of a positive result indicating a carcinoma rather than a mesothelial process in serous effusion cytology.
RESULTS.—
Fourteen observational studies, published between 2011 and 2023, fulfilled the selection criteria and were included. All 14 studies used the 3E2C1 clone. Claudin-4 immunochemistry showed a high diagnostic accuracy in serous effusion cytology. The pooled sensitivity and specificity were 98.02% (95% CI, 93.96%-99.37%) and 99.72% (95% CI, 97.36%-99.97%), respectively. Lastly, the pooled diagnostic odds ratio was 1660.5 (95% CI, 760.0-3627.8) and no evidence of statistical heterogeneity between the included studies was found (I2 = 0%, τ2 = 0).
CONCLUSIONS.—
Claudin-4 may be used as a single pan-carcinoma immunochemical biomarker in the differential diagnosis between metastatic carcinomas and mesotheliomas or reactive mesothelial cells in serous effusion cytology.
PubMed: 38871358
DOI: 10.5858/arpa.2023-0560-RA -
Frontiers in Endocrinology 2024Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Well-differentiated pancreatic neuroendocrine tumors (PNETs) can be non-functional or functional, e.g. insulinoma and glucagonoma. The majority of PNETs are sporadic, but PNETs also occur in hereditary syndromes, primarily multiple endocrine neoplasia type 1 (MEN1). The Knudson hypothesis stated a second, somatic hit in as the cause of PNETs of MEN1 syndrome. In the recent years, reports on genetic somatic events in both sporadic and hereditary PNETs have emerged, providing a basis for a more detailed molecular understanding of the pathophysiology. In this systematic review and meta-analysis, we made a collation and statistical analysis of aggregated frequent genetic alterations and potential driver events in human grade G1/G2 PNETs.
METHODS
A systematic search was performed in concordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) reporting guidelines of 2020. A search in Pubmed for published studies using whole exome, whole genome, or targeted gene panel (+400 genes) sequencing of human G1/G2 PNETs was conducted at the 25 of September 2023. Fourteen datasets from published studies were included with data on 221 patients and 225 G1/G2 PNETs, which were divided into sporadic tumors, and hereditary tumors with pre-disposing germline variants, and tumors with unknown germline status. Further, non-functioning and functioning PNETs were distinguished into two groups for pathway evaluation. The collated genetical analyses were conducted using the 'maftools' R-package.
RESULTS
Sporadic PNETs accounted 72.0% (162/225), hereditary PNETs 13.3% (30/225), unknown germline status 14.7% (33/225). The most frequently altered gene was , with somatic variants and copy number variations in overall 42% (95/225); hereditary PNETs (germline variations in , , , , , , and/or ) 57% (16/30); sporadic PNETs 36% (58/162); unknown germline status 64% (21/33). The point mutations/indels were distributed throughout . Overall, (16%, 37/225) and -variants (12%, 27/225) were also abundant with missense mutations clustered in mutational hotspots associated with histone binding, and translocase activity, respectively. mutations occurred more frequently in PNETs with mutations, p<0.05. While functioning PNETs shared few variated genes, non-functioning PNETs had more recurrent variations in genes associated with the Phosphoinositide 3-kinase, Wnt, NOTCH, and Receptor Tyrosine Kinase-Ras signaling onco-pathways.
DISCUSSION
The somatic genetic alterations in G1/G2 PNETs are diverse, but with distinct differences between sporadic vs. hereditary, and functional vs. non-functional PNETs. Increased understanding of the genetic alterations may lead to identification of more drivers and driver hotspots in the tumorigenesis in well-differentiated PNETs, potentially giving a basis for the identification of new drug targets. (Funded by Novo Nordisk Foundation, grant number NNF19OC0057915).
Topics: Humans; Pancreatic Neoplasms; Neuroendocrine Tumors; Sequence Analysis, DNA; Mutation
PubMed: 38868744
DOI: 10.3389/fendo.2024.1351624 -
BMC Medical Imaging Jun 2024Esophageal cancer, a global health concern, impacts predominantly men, particularly in Eastern Asia. Lymph node metastasis (LNM) significantly influences prognosis, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Esophageal cancer, a global health concern, impacts predominantly men, particularly in Eastern Asia. Lymph node metastasis (LNM) significantly influences prognosis, and current imaging methods exhibit limitations in accurate detection. The integration of radiomics, an artificial intelligence (AI) driven approach in medical imaging, offers a transformative potential. This meta-analysis evaluates existing evidence on the accuracy of radiomics models for predicting LNM in esophageal cancer.
METHODS
We conducted a systematic review following PRISMA 2020 guidelines, searching Embase, PubMed, and Web of Science for English-language studies up to November 16, 2023. Inclusion criteria focused on preoperatively diagnosed esophageal cancer patients with radiomics predicting LNM before treatment. Exclusion criteria were applied, including non-English studies and those lacking sufficient data or separate validation cohorts. Data extraction encompassed study characteristics and radiomics technical details. Quality assessment employed modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and Radiomics Quality Score (RQS) tools. Statistical analysis involved random-effects models for pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC). Heterogeneity and publication bias were assessed using Deek's test and funnel plots. Analysis was performed using Stata version 17.0 and meta-DiSc.
RESULTS
Out of 426 initially identified citations, nine studies met inclusion criteria, encompassing 719 patients. These retrospective studies utilized CT, PET, and MRI imaging modalities, predominantly conducted in China. Two studies employed deep learning-based radiomics. Quality assessment revealed acceptable QUADAS-2 scores. RQS scores ranged from 9 to 14, averaging 12.78. The diagnostic meta-analysis yielded a pooled sensitivity, specificity, and AUC of 0.72, 0.76, and 0.74, respectively, representing fair diagnostic performance. Meta-regression identified the use of combined models as a significant contributor to heterogeneity (p-value = 0.05). Other factors, such as sample size (> 75) and least absolute shrinkage and selection operator (LASSO) usage for feature extraction, showed potential influence but lacked statistical significance (0.05 < p-value < 0.10). Publication bias was not statistically significant.
CONCLUSION
Radiomics shows potential for predicting LNM in esophageal cancer, with a moderate diagnostic performance. Standardized approaches, ongoing research, and prospective validation studies are crucial for realizing its clinical applicability.
Topics: Humans; Esophageal Neoplasms; Lymphatic Metastasis; Sensitivity and Specificity; Artificial Intelligence; Radiomics
PubMed: 38867143
DOI: 10.1186/s12880-024-01278-5 -
BMC Endocrine Disorders Jun 2024Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph...
OBJECTIVE
Activating mutation in Ubiquitin-specific peptidase (USP8) is identified to enhance cell proliferation and adrenocorticotropic hormone (ACTH) secretion from corticotroph pituitary adenoma. We investigated the USP8 variant status in a population of Iranian people with functional corticotroph pituitary adenoma (FCPA). Moreover, a systematic review was conducted to thoroughly explore the role of USP8 variants and the related pathways in corticotroph adenomas, genotype-phenotype correlation in USP8-mutated individuals with FCPA, and the potential role of USP8 and epidermal growth factor receptor (EGFR) as targeted therapies in PFCAs.
METHODS
Genetic analysis of 20 tissue samples from 19 patients with PFCAs was performed using Sanger sequencing. Moreover, a systematic literature review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Scopus, web of Sciences, and Cochrane databases were searched. The last search was performed on 20 September 2023 for all databases.
RESULTS
In our series, we found two somatic mutations including a 7-bp deletion variant: c.2151_2157delCTCCTCC, p. Ser718GlnfsTer3, and a missense variant: c.2159 C > G, p. Pro720Arg (rs672601311) in exon 14. The Systematic review indicated USP8 variant in 35% of corticotroph adenomas, with the highest frequency (25%) in 720 code regions, p. Pro720Arg. Data regarding the impact of USP8 mutational status on clinical characteristics and outcomes in FCPAs are inconsistent. Moreover, Pasireotide as well as inhibitors of EGFR such as Gefitinib and Lapatinib, as well as USP8 inhibitors including -ehtyloxyimino9H-indeno (1, 2-b) pyrazine-2, 3-dicarbonitrile, DUBs-IN-2, and RA-9 indicated promising results in treatment of corticotroph adenomas.
CONCLUSION
Although the USP8-EGFR system has been identified as the main trigger and target of corticotroph tumorigenesis, more precise multicenter studies are required to yield more consistent information regarding the phenotype-genotype correlation and to develop effective targeted therapies.
Topics: Humans; Ubiquitin Thiolesterase; Iran; Endosomal Sorting Complexes Required for Transport; Pituitary ACTH Hypersecretion; Adult; Female; Male; Endopeptidases; Mutation; Middle Aged; ACTH-Secreting Pituitary Adenoma; Middle Eastern People
PubMed: 38862897
DOI: 10.1186/s12902-024-01619-z -
Medical Education Online Dec 2024Non-clinical approaches such as meditation, yoga, and mindfulness are popular traditional therapeutical interventions adopted by many educational institutions to improve... (Meta-Analysis)
Meta-Analysis Review
Non-clinical approaches such as meditation, yoga, and mindfulness are popular traditional therapeutical interventions adopted by many educational institutions to improve the physical and mental well-being of learners. This study aimed to evaluate the effectiveness of yoga intervention in improving cardiopulmonary parameters such as blood pressure, heart rate, pulmonary function tests and psychosomatic symptoms such as depression, anxiety and stress in medical and dental students. Using the PRISMA protocol, a search from databases such as PubMed, Scopus, and Embase resulted in 304 relevant articles. After screening the title and abstracts, 47 papers were analyzed thoroughly and included in the qualitative analysis. 18 articles with homogenous statistical data on physiology and psychological parameters were included for meta-analysis. In comparison to the control group, the study showed a significant reduction of systolic blood pressure (SBP: 6.82 mmHg, z = -3.06, = 0.002), diastolic blood pressure (DBP: 2.92 mmHg, z = -2.22, = 0.03), and heart rate (HR: 2.55 beats/min, z = -2.77, = 0.006). Additionally, data from 4 studies yielded a significant overall effect of a stress reduction of 0.77 on standardized assessments due to the yoga intervention (z = 5.29, < 0.0001). Lastly, the results also showed a significant (z = -2.52, = 0.01) reduction of 1.2 in standardized anxiety tests in intervention group compared to the control. The findings offer promising prospects for medical educators globally, encouraging them to consider reformation and policymaking in medical curricula to enhance academic success and improve the overall quality of life for medical students worldwide.
Topics: Yoga; Humans; Blood Pressure; Heart Rate; Stress, Psychological; Anxiety; Education, Medical; Depression; Students, Medical; Respiratory Function Tests
PubMed: 38861675
DOI: 10.1080/10872981.2024.2364486 -
Photodiagnosis and Photodynamic Therapy Jun 2024This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC). (Review)
Review
BACKGROUND
This systematic review assessed the effectiveness of photodynamic therapy (PDT) in patients with recurrent oral squamous cell carcinoma (OSCC).
METHODS
Clinical studies on recurrent OSCC treated with PDT alone were included. Combined treatment strategies were excluded. The search was performed on Medline/Pubmed, Cochrane Library, Embase, Web of Science and ClinicalTrials.gov, manual search, and grey literature.
RESULTS
The eleven included studies were observational. The risk of bias and methodological quality were evaluated using the Newcastle-Ottawa Quality Assessment Scale. The studies reported the use of hematoporphyrin derivative, Photofrin, Foscan and 5-aminolevulinic acid. Data on treatment response and survival was collected. Secondarily, postoperative courses and patient's quality of life/acceptance were reported whenever available. Photofrin and Foscan were the most used photosensitisers, with more complete responses. Lesions responding less favourably were on posterior regions or deep-seated in the tissue.
CONCLUSIONS
Although treatment response differs between treatment protocols, PDT stands as a viable treatment option to be considered, as it can achieve therapeutic results and disease-free, long-lasting periods. Partial treatment responses may be of interest when achieving eligibility for other treatment strategies. Despite this study's limitations, which considered four photosensitisers, Photofrin was the most used but more recent photosensitisers like Foscan have greater chemical stability, tissue penetration, and may be more efficacious on recurrent OSCC.
PubMed: 38857775
DOI: 10.1016/j.pdpdt.2024.104242 -
PloS One 2024We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive... (Meta-Analysis)
Meta-Analysis
The prognostic significance of additional localized treatment to primary lesion in patients undergoing hormone therapy for metastatic hormone-sensitive prostate cancer: A systematic review and meta-analysis.
BACKGROUND
We aimed to compare the prognostic values of 'localized treatment to the primary lesion (LT) plus hormone therapy (HT)' versus 'HT alone' in metastatic hormone-sensitive prostate cancer (mHSPC).
METHODS
We conducted a systematic search through the databases of PubMed®, Web of Science®, and Cochrane library® in April 2023 based on the PRISMA (Preferred Reporting Items for Systemic Reviews and Meta-Analyses) statement. A pooled meta-analysis was performed to assess the prognostic differences between LT + HT and HT alone according to randomized and non-randomized controlled studies (RCTs and NRCTs, respectively).
RESULTS
The search identified three RCTs and eight NRCTs. In RCTs, LT did not show prognostic benefits regarding biochemical-failure free rate nor overall survival (OS), although in patients with low tumor burdens, the LT + HT group showed better OS (HR: 0.68, 95% CI: 0.54-0.86). In the NRCTs, the LT+HT group showed superior progression-free survival (hazard ratio (HR): 0.42, 95% confidence interval (CI): 0.21-0.87), cancer-specific survival (HR: 0.39, 95% CI: 0.20-0.76), and OS (HR: 0.63, 95% CI: 0.57-0.69) to the HT alone group. In addition, better OS was observed in the LT +HT group regardless of the type of treatment modality for LT; radical prostatectomy (HR: 0.52, 95% CI: 0.39-0.69), radiotherapy (HR: 0.63, 95% CI: 0.56-0.71) in NRCTs.
CONCLUSIONS
LT to the primary lesion in metastatic hormone-sensitive prostate cancer may provide prognostic benefits and especially in patients with low tumor burden.
Topics: Humans; Male; Prostatic Neoplasms; Prognosis; Neoplasm Metastasis; Antineoplastic Agents, Hormonal
PubMed: 38857208
DOI: 10.1371/journal.pone.0304963 -
European Urology Open Science Jul 2024No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to... (Review)
Review
Role of Follicle-stimulating Hormone, Inhibin B, and Anti-Müllerian Hormone in Predicting Sperm Retrieval from Men with Nonobstructive Azoospermia Undergoing Microdissection Testicular Sperm Extraction: A Systematic Review and Meta-analysis.
BACKGROUND AND OBJECTIVE
No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE.
METHODS
We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis.
KEY FINDINGS AND LIMITATIONS
Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and -SR groups, with lower FSH (SMD -0.30), higher InhB (SMD 0.54), and lower AMH (SMD -0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00-1.06) or InhB (OR 1.01, 95% CI 1.00-1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73-0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend.
CONCLUSIONS AND CLINICAL IMPLICATIONS
Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE.
PATIENT SUMMARY
We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.
PubMed: 38854995
DOI: 10.1016/j.euros.2024.05.001 -
Clinical Radiology May 2024To examine the accuracy of CT radiomics to predict histopathological features of aggressiveness in lung cancer using a systematic review of test accuracy studies. (Review)
Review
PURPOSE
To examine the accuracy of CT radiomics to predict histopathological features of aggressiveness in lung cancer using a systematic review of test accuracy studies.
METHODS
Data sources searched included Medline, Embase, Web of Science, and Cochrane Library from up to 3 November 2023. Included studies reported test accuracy of CT radiomics models to detect the presence of: spread through air spaces (STAS), predominant adenocarcinoma pattern, adenocarcinoma grade, lymphovascular invasion (LVI), tumour infiltrating lymphocytes (TIL) and tumour necrosis, in patients with lung cancer. The primary outcome was test accuracy. Two reviewers independently assessed articles for inclusion and assessed methodological quality using the QUality Assessment of Diagnostic Accuracy Studies-2 tool. A single reviewer extracted data, which was checked by a second reviewer. Narrative data synthesis was performed.
RESULTS
Eleven studies were included in the final analysis. 10/11 studies were in East Asian populations. 4/11 studies investigated STAS, 6/11 investigated adenocarcinoma invasiveness or growth pattern, and 1/11 investigated LVI. No studies investigating TIL or tumour necrosis met inclusion criteria. Studies were of generally mixed to poor methodological quality. Reported accuracies for radiomic models ranged from 0.67 to 0.94.
CONCLUSION
Due to the high risk of bias and concerns regarding applicability, the evidence is inconclusive as to whether radiomic features can accurately predict prognostically important histopathological features of cancer aggressiveness. Many studies were excluded due to lack of external validation. Rigorously conducted prospective studies with sufficient external validity will be required for radiomic models to play a role in improving lung cancer outcomes.
PubMed: 38853080
DOI: 10.1016/j.crad.2024.04.022 -
BMC Cancer Jun 2024Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Poly (ADP- ribose) polymerase inhibitors (PARPi) has been increasingly adopted for metastatic castration-resistance prostate cancer (mCRPC) patients with homologous recombination repair deficiency (HRD). However, it is unclear which PARPi is optimal in mCRPC patients with HRD in 2nd -line setting.
METHOD
We conducted a systematic review of trials regarding PARPi- based therapies on mCRPC in 2nd -line setting and performed a Bayesian network meta-analysis (NMA). Radiographic progression-free survival (rPFS) was assessed as primary outcome. PSA response and adverse events (AEs) were evaluated as secondary outcomes. Subgroup analyses were performed according to specific genetic mutation.
RESULTS
Four RCTs comprised of 1024 patients (763 harbored homologous recombination repair (HRR) mutations) were identified for quantitative analysis. Regarding rPFS, olaparib monotherapy, rucaparib and cediranib plus olaparib showed significant improvement compared with ARAT. Olaparib plus cediranib had the highest surface under cumulative ranking curve (SUCRA) scores (87.5%) for rPFS, followed by rucaparib, olaparib and olaparib plus abiraterone acetate prednisone. For patients with BRCA 1/2 mutations, olaparib associated with the highest probability (98.1%) of improved rPFS. For patients with BRCA-2 mutations, olaparib and olaparib plus cediranib had similar efficacy. However, neither olaparib nor rucaparib showed significant superior effectiveness to androgen receptor-axis-targeted therapy (ARAT) in patients with ATM mutations. For safety, olaparib showed significantly lower ≥ 3 AE rate compared with cediranib plus olaparib (RR: 0.72, 95% CI: 0.51, 0.97), while olaparib plus cediranib was associated with the highest risk of all-grade AE.
CONCLUSION
PARPi-based therapy showed considerable efficacy for mCRPC patients with HRD in 2nd -line setting. However, patients should be treated accordingly based on their genetic background as well as the efficacy and safety of the selected regimen.
TRIAL REGISTRATION
CRD42023454079.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Bayes Theorem; Prostatic Neoplasms, Castration-Resistant; Mutation; Male; Phthalazines; Network Meta-Analysis; Piperazines; BRCA2 Protein; Recombinational DNA Repair; Antineoplastic Combined Chemotherapy Protocols; Randomized Controlled Trials as Topic; Progression-Free Survival; Indoles; BRCA1 Protein; Treatment Outcome; Quinazolines
PubMed: 38851712
DOI: 10.1186/s12885-024-12388-2