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Frontiers in Endocrinology 2024The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph...
Nomogram model of serum thymidine kinase 1 combined with ultrasonography for prediction of central lymph node metastasis risk in patients with papillary thyroid carcinoma pre-surgery.
OBJECTIVE
The aim of this study was to develop a nomogram, using serum thymidine kinase 1 protein (STK1p) combined with ultrasonography parameters, to early predict central lymph node metastasis (CLNM) in patients with papillary thyroid carcinoma (PTC) pre-surgery.
METHODS
Patients with PTC pre-surgery in January 2021 to February 2023 were divided into three cohorts: the observation cohort (CLNM, = 140), the control cohort (NCLNM, = 128), and the external verification cohort (CLNM, = 50; NCLNM, = 50). STK1p was detected by an enzyme immunodot-blot chemiluminescence analyzer and clinical parameters were evaluated by ultrasonography.
RESULTS
A suitable risk threshold value for STK1p of 1.7 pmol/L was selected for predicting CLNM risk by receiver operating characteristic (ROC) curve analysis. Multivariate analysis identified the following six independent risk factors for CLNM: maximum tumor size >1 cm [odds ratio (OR) = 2.406, 95% confidence interval (CI) (1.279-4.526), = 0.006]; capsule invasion [OR = 2.664, 95% CI (1.324-5.360), = 0.006]; irregular margin [OR = 2.922; 95% CI (1.397-6.111), = 0.004]; CLN flow signal [OR = 3.618, 95% CI (1.631-8.027), = 0.002]; tumor-foci number ≥2 [OR = 4.064, 95% CI (2.102-7.859), < 0.001]; and STK1p ≥1.7 pmol/L [OR = 7.514, 95% CI (3.852-14.660), < 0.001]. The constructed nomogram showed that the area under the ROC curve for the main dataset was 0.867 and that for the validation dataset was 0.830, exhibiting effectivity, and was recalculated to a total score of approximately 383. Through monitoring the response post-surgery, all patients were assessed as tumor-free at 12 months post-surgery, which was significantly associated with a reduction in STK1p to disease-free levels.
CONCLUSION
We demonstrate for the first time that a novel nomogram including STK1p combined with ultrasonography can assist in the clinical prevention of CLNM, by facilitating timely, individualized prophylactic CLNM dissection, thereby reducing the risk of secondary surgery and the probability of recurrence.
Topics: Humans; Male; Female; Thymidine Kinase; Nomograms; Middle Aged; Lymphatic Metastasis; Adult; Thyroid Cancer, Papillary; Thyroid Neoplasms; Ultrasonography; Biomarkers, Tumor; Risk Factors; ROC Curve; Prognosis; Aged; Young Adult; Lymph Nodes
PubMed: 38887267
DOI: 10.3389/fendo.2024.1366219 -
Cancer Imaging : the Official... Jun 2024The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model...
OBJECTIVE
The aim of our study is to find a better way to identify a group of papillary thyroid carcinoma (PTC) with more aggressive behaviors and to provide a prediction model for lymph node metastasis to assist in clinic practice.
METHODS
Targeted sequencing of DNA/RNA was used to detect genetic alterations. Gene expression level was measured by quantitative real-time PCR, western blotting or immunohistochemistry. CCK8, transwell assay and flow cytometry were used to investigate the effects of concomitant gene alterations in PTC. LASSO-logistics regression algorithm was used to construct a nomogram model integrating radiomic features, mutated genes and clinical characteristics.
RESULTS
172 high-risk variants and 7 fusion types were detected. The mutation frequencies in BRAF, TERT, RET, ATM and GGT1 were significantly higher in cancer tissues than benign nodules. Gene fusions were detected in 16 samples (2 at the DNA level and 14 at the RNA level). ATM mutation (ATM) was frequently accompanied by BRAF, TERT or gene fusions. ATM alone or ATM co-mutations were significantly positively correlated with lymph node metastasis. Accordingly, ATM knock-down PTC cells bearing BRAF, KRAS or CCDC6-RET had higher proliferative ability and more aggressive potency than cells without ATM knock-down in vitro. Furthermore, combining gene alterations and clinical features significantly improved the predictive efficacy for lymph node metastasis of radiomic features, from 71.5 to 87.0%.
CONCLUSIONS
Targeted sequencing of comprehensive genetic alterations in PTC has high prognostic value. These alterations, in combination with clinical and radiomic features, may aid in predicting invasive PTC with higher accuracy.
Topics: Humans; Lymphatic Metastasis; Thyroid Cancer, Papillary; Male; Female; Thyroid Neoplasms; Middle Aged; Mutation; Adult; Proto-Oncogene Proteins B-raf; Ataxia Telangiectasia Mutated Proteins; Nomograms; Biomarkers, Tumor; Telomerase; Radiomics
PubMed: 38886866
DOI: 10.1186/s40644-024-00719-2 -
BMC Gastroenterology Jun 2024Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in...
BACKGROUND
Dilatation of common bile duct (CBD) is mostly pathological and mainly occurs secondary to mechanical causes. We aimed to explore the prevalence of CBD dilatation in Intraductal Papillary Mucinous Neoplasms of the pancreas (IPMN) among patients referred to EUS.
METHODS
A retrospective study of all patients who had an EUS diagnosis of IPMN from 2011 to 2019 at Galilee Medical Center were extracted. Control group including patients with other types of pancreatic cysts.
RESULTS
Overall, 2400 patients were included in the study, of them 158 patients were diagnosed with pancreatic cysts, 117 patients (74%) diagnosed with IPMN (group A), and 41 patients (26%) diagnosed with other pancreatic cysts (group B). Univariate analysis showed significant association of IPMN (OR 3.8, 95% CI 1.3-11.5), resected gallbladder (GB) (OR 7.75, 95% CI 3.19-18.84), and age (OR 1, 95% CI 1.01-1.08) with CBD dilatation. Classifying IPMN to sub-groups using adjusted multivariate logistic regression analysis, only main duct-IPMN (MD-IPMN) significantly correlated with CBD dilatation compared to branch duct (BD)-IPMN and mixed type-IPMN (OR 19.6, 95% CI 4.57-83.33, OR 16.3, 95% CI 3.02-88.08).
CONCLUSION
MD-IPMN was significantly correlated with dilated CBD. Assessment of the pancreas is warranted in encountered cases of dilated CBD without obvious mechanical cause.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Dilatation, Pathologic; Aged; Common Bile Duct; Pancreatic Intraductal Neoplasms; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Adenocarcinoma, Mucinous
PubMed: 38886637
DOI: 10.1186/s12876-024-03291-y -
Journal of Thoracic Disease May 2024The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential...
BACKGROUND
The preoperative differential diagnosis of nodular lung adenocarcinoma has long been a challenging issue for thoracic surgeons. This study aimed to explore differential diagnosis of nodular lung adenocarcinoma by comprehensively analyzing its clinical, computed tomography (CT) imaging, and postoperative pathological and genetic features.
METHODS
The clinical, CT imaging, and postoperative pathological features of different classifications of nodular lung adenocarcinoma were retrospectively analyzed through univariate and multivariate statistical methods.
RESULTS
There were 132 patients with nodular lung adenocarcinoma enrolled. Firstly, compared with ground-glass nodular lung adenocarcinoma, solid nodular lung adenocarcinoma was more common in women [odds ratio (OR), 3.662; 95% confidence interval (CI): 1.066-12.577] and older adults (OR, 1.061; 95% CI: 1.007-1.119), and CT signs were mostly lobulation (OR, 4.957; 95% CI: 1.714-14.337) and spiculation (OR, 8.214; 95% CI: 2.740-24.621); the mean CT (CT) value of solid nodular lung adenocarcinoma was significantly higher than that of ground-glass nodular lung adenocarcinoma, and the optimal diagnostic threshold was -267.5 Hounsfield units (HU). Secondly, the maximum diameter of nodule size (NS) of invasive adenocarcinoma (IAC) was significantly greater than that of minimally IAC (MIA; OR, 6.306; 95% CI: 1.191-33.400) or atypical adenomatous hyperplasia (AAH)/adenocarcinoma in situ (AIS; OR, 189.539; 95% CI: 4.720-7,610.476), and the optimal diagnostic threshold between IAC and MIA was 1.35 cm; the CT value of IAC was significantly higher than that of MIA, and the optimal diagnostic threshold was -460.75 HU. Thirdly, lepidic-predominant adenocarcinoma (LPA) manifest more commonly as pure ground-glass nodule (pGGN; OR, 6.252; 95% CI: 1.429-27.358) or mixed ground-glass nodule (mGGN; OR, 4.224; 95% CI: 1.223-14.585). Moreover, the mutation rate of epidermal growth factor receptor () in IAC was 70.69% (41/58). The mutation rates of mGGNs (OR, 8.794; 95% CI: 1.489-51.933) and solid nodules (SNs; OR, 12.912; 95% CI: 1.597-104.383) were significantly higher than that of pGGNs. Furthermore, compared with those of micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), or invasive mucinous adenocarcinoma (IMA), there were significantly higher mutation rates in acinar-predominant adenocarcinoma/papillary-predominant adenocarcinoma (APA/PPA; OR, 55.925; 95% CI: 4.045-773.284) and LPA (OR, 38.265; 95% CI: 2.307-634.596).
CONCLUSIONS
Different classifications of nodular lung adenocarcinoma have their own clinicopathological and CT imaging features, and the latter is the main predictor.
PubMed: 38883620
DOI: 10.21037/jtd-24-510 -
Frontiers in Endocrinology 2024The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary...
The mucosa-associated lymphoid tissue (MALT) lymphoma subtype, specifically extranodal marginal zone B-cell lymphoma, is a rare variant. Within this subtype, primary thyroid MALT lymphoma is an uncommon occurrence. The literature provides limited documentation on thyroid MALT lymphomas, as their prevalence is comparatively lower than in other organ sites. The coexistence of papillary thyroid carcinoma (PTC) and thyroid MALT lymphomas is exceedingly rare. It presents a rare case of primary thyroid MALT lymphoma accompanied by PTC, thyroid lymphoma not being considered before surgery. A 64-year-old female patient, who had been experiencing symptoms related to a substantial thyroid tumor for a duration of three years, she refused to do a needle biopsy before surgery and expressed a preference for surgical resection. Consequently, the patient underwent a total thyroidectomy along with lymphadenectomy of the central compartment. A histological examination subsequently confirmed the presence of papillary thyroid carcinoma (PTC) and mucosa-associated lymphoid tissue (MALT) lymphoma. Due to the favorable response of the MALT lymphoma to local treatment and the absence of metastasis in other organs, no further treatment was administered for the MALT lymphoma following the surgery. Currently, the patient exhibits no signs of tumor recurrence based on ultrasound and laboratory evaluations. We also provide an overview of the clinical findings on PTC and MALT lymphoma patients already reported and discuss the possible treatment strategy.
Topics: Humans; Lymphoma, B-Cell, Marginal Zone; Female; Middle Aged; Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroidectomy; Neoplasms, Multiple Primary
PubMed: 38883595
DOI: 10.3389/fendo.2024.1372661 -
Cancer Control : Journal of the Moffitt... 2024Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The...
BACKGROUND AND OBJECTIVE
Cervical lymph node metastasis (CLNM) is considered a marker of papillar Fethicy thyroid cancer (PTC) progression and has a potential impact on the prognosis of PTC. The purpose of this study was to screen for predictors of CLNM in PTC and to construct a predictive model to guide the surgical approach in patients with PTC.
METHODS
This is a retrospective study. Preoperative dual-energy computed tomography images of 114 patients with pathologically confirmed PTC between July 2019 and April 2023 were retrospectively analyzed. The dual-energy computed tomography parameters [iodine concentration (IC), normalized iodine concentration (NIC), the slope of energy spectrum curve (λ)] of the venous stage cancer foci were measured and calculated. The independent influencing factors for predicting CLNM were determined by univariate and multivariate logistic regression analysis, and the prediction models were constructed. The clinical benefits of the model were evaluated using decision curves, calibration curves, and receiver operating characteristic curves.
RESULTS
The statistical results show that NIC, derived neutrophil-to-lymphocyte ratio (dNLR), prognostic nutritional index (PNI), gender, and tumor diameter were independent predictors of CLNM in PTC. The AUC of the nomogram was .898 (95% CI: .829-.966), and the calibration curve and decision curve showed that the prediction model had good predictive effect and clinical benefit, respectively.
CONCLUSION
The nomogram constructed based on dual-energy CT parameters and inflammatory prognostic indicators has high clinical value in predicting CLNM in PTC patients.
Topics: Humans; Male; Female; Lymphatic Metastasis; Thyroid Cancer, Papillary; Middle Aged; Retrospective Studies; Tomography, X-Ray Computed; Adult; Thyroid Neoplasms; Nomograms; Neck; Lymph Nodes; Prognosis; Aged; Inflammation
PubMed: 38881040
DOI: 10.1177/10732748241262177 -
Nature Communications Jun 2024Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are...
Childhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Topics: Humans; Thyroid Cancer, Papillary; Chernobyl Nuclear Accident; Lymphatic Metastasis; Male; Adult; Female; Thyroid Neoplasms; Mutation; Iodine Radioisotopes; Adolescent; Proto-Oncogene Proteins B-raf; Young Adult; Lymph Nodes; Proto-Oncogene Proteins c-ret; Child; Genomics; Middle Aged; Homeodomain Proteins; Gene Expression Profiling; MicroRNAs; Neoplasms, Radiation-Induced; Neck; Gene Expression Regulation, Neoplastic
PubMed: 38871684
DOI: 10.1038/s41467-024-49292-z -
Frontiers in Oncology 2024With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the...
BACKGROUND
With a rise in recent years, thyroid cancer (TC) is the most prevalent hormonal cancer worldwide. It is essential to investigate the inherent variability at the molecular level and the immune environment within tumors of various thyroid cancer subtypes in order to identify potential targets for therapy and provide precise treatment for patients with thyroid adenocarcinoma.
METHODS
First, we analyzed the expression of IRX5 in pan-cancer and papillary thyroid carcinoma by bioinformatics methods and collected paired samples from our center for validation. Subsequently, we analyzed the significance of IRX5 on the prognosis and diagnosis of PTC. Next, we explored the possible mechanisms by which IRX5 affects the prognosis of thyroid cancer patients by GO/KEGG enrichment analysis, and further investigated the effect of IRX5 on immune infiltration of thyroid cancer. Ultimately, by conducting experiments on cells and animals, we were able to show how IRX5 impacts the aggressive characteristics of thyroid cancer cells and its influence on macrophages within the immune system of thyroid cancer.
RESULTS
In 11 malignant tumors, including PTC, IRX5 is overexpressed and associated with a poor prognosis. IRX5 may affect the prognosis of PTC through embryonic organ development, ossification, mesenchyme development, etc. Increased IRX5 expression decreases the presence of cytotoxic and Th17 cells in papillary thyroid cancer. IRX5 was highly expressed in different PTC cell lines, such as K-1 and TPC-1. Silencing IRX5 effectively halted the growth and movement of PTC cells while also decreasing M2 polarization and enhancing M1 polarization in tumor-associated macrophages.
CONCLUSION
IRX5 could impact the outlook of individuals with PTC by stimulating the shift of macrophages to M2 in the immune surroundings of thyroid cancer growths, suggesting a potential new focus for treating thyroid cancer, particularly through immunotherapy.
PubMed: 38868535
DOI: 10.3389/fonc.2024.1399484 -
Practical Laboratory Medicine May 2024While recent studies have demonstrated several genetic alterations are associated with pathogenesis of RCC, the significance of cyclin-dependent kinase inhibitor 2A and...
OBJECTIVES
While recent studies have demonstrated several genetic alterations are associated with pathogenesis of RCC, the significance of cyclin-dependent kinase inhibitor 2A and cyclin-dependent kinase inhibitor 2B in tumorigenesis of RCC is less clear. We investigate the distribution of and mutations in patients with RCC and analyze the impact of and mutations on RCC.
METHODS
A pathological examination was conducted using thirty fresh renal tissue samples with renal masses that had undergone partial or radical nephrectomy. Multiplex ligation-dependent probe amplification (MLPA) was used to detect genetic aberrations of and in genomic DNA isolated from samples. Subsequently, and mutations were confirmed using chromosomal microarray technique.
RESULTS
Twenty-one patients were diagnosed with RCC, eight with benign diseases, including angiomyolipoma (AML) and oncocytoma, and one with mucinous adenocarcinoma of renal pelvis. Two of twenty-one patients (9.5 %) with clear-cell RCC were positive for and gene deletions. Interestingly, patients with and mutations were associated with sarcomatoid patterns of RCC (2 out of 4, 50 %). In contrast, no or deletions were detected in samples from benign renal tumors, papillary RCC, or other kidney cancers.
CONCLUSIONS
This study demonstrated the potential use of and as biomarkers for the prognostic and molecular classification of renal cancer. and mutations may be associated with RCC development and sarcomatoid changes. Further research is needed to understand the underlying molecular mechanisms of and in the pathogenesis of RCC.
PubMed: 38867760
DOI: 10.1016/j.plabm.2024.e00410 -
Hereditary Cancer in Clinical Practice Jun 2024Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing...
Current National Comprehensive Cancer Network ® (NCCN ®) guidelines for Colorectal Genetic/Familial High-Risk Assessment provide limited guidance for genetic testing for individuals with already diagnosed hereditary cancer conditions. We are presenting the case of a 36-year-old woman who was diagnosed with Lynch Syndrome at age 23 after genetic testing for a familial variant (c.283del) in the MLH1 gene. The patient had a previous history of Hodgkin Lymphoma at the time of familial variant testing, and she would later develop stage IIIa cecal adenocarcinoma at age 33 and metastatic papillary thyroid carcinoma at age 35. The patient's family history included a first-degree relative who was diagnosed with colorectal cancer at age 39, multiple second-degree relatives with colorectal, endometrial, and stomach cancer, and third and fourth-degree relatives with breast cancer. In light of her personal and family history, a comprehensive cancer panel was recommended. This panel found a second hereditary cancer predisposition syndrome: a likely pathogenic variant (c. 349 A > G) in the CHEK2 gene. This specific CHEK2 variant was recently reported to confer a moderately increased risk for breast cancer. The discovery of this second cancer predisposition syndrome had important implications for the patient's screening and risk management. While uncommon, the possibility of an individual having multiple cancer predisposition syndromes is important to consider when evaluating patients and families for hereditary cancer, even when a familial variant has been identified.
PubMed: 38867252
DOI: 10.1186/s13053-024-00281-9