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Current Oncology (Toronto, Ont.) Nov 2023Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. (Review)
Review
BACKGROUND
Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare.
METHODS
This is a retrospective, single-center observational study conducted over 16 years (2001-2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy.
RESULTS
Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases.
CONCLUSIONS
The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin.
Topics: Humans; Male; Carcinoma, Medullary; Carcinoma, Papillary; Observational Studies as Topic; Proto-Oncogene Proteins c-ret; Retrospective Studies; Thyroid Cancer, Papillary; Thyroid Neoplasms; Female
PubMed: 38132379
DOI: 10.3390/curroncol30120745 -
European Thyroid Journal Jul 2023The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves' disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules... (Observational Study)
Observational Study
AIM
The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves' disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves' disease.
METHODS
Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models.
RESULTS
We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th-75th percentiles 1.5-5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classification as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not significantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04-2.49) and with larger nodules (OR 2.96, 95%CI 1.08-8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis.
CONCLUSION
Patients with Graves' disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.
Topics: Adult; Humans; Thyroid Nodule; Thyroid Neoplasms; Graves Disease; Thyroid Cancer, Papillary; Long-Acting Thyroid Stimulator
PubMed: 37235699
DOI: 10.1530/ETJ-23-0055 -
Nagoya Journal of Medical Science Nov 2023Endoscopic papillectomy is widely performed to treat duodenal papillary tumors, particularly at high-volume centers. It is indicated for adenomas without intraductal... (Review)
Review
Endoscopic papillectomy is widely performed to treat duodenal papillary tumors, particularly at high-volume centers. It is indicated for adenomas without intraductal extension of the bile or pancreatic ducts. However, despite numerous reports of carcinomas that expand the indications to include well-differentiated adenocarcinomas that do not invade the sphincter of Oddi, the low agreement between biopsy and final pathological diagnosis, as well as the current inability of imaging modalities to diagnose sphincter of Oddi invasion, makes it difficult to consider expanding indications. Although complications can be prevented by certain methods, such as pancreatic duct stenting, and the frequency of severe complications has decreased, the safety of the procedure remains unconfirmed. In the future, this technology is expected to progress and enable wider applications, including those in tumors with extensive horizontal spread and those with intraductal extension of the bile and pancreatic ducts. Such technology may also improve the safety and accuracy of diagnosis.
Topics: Humans; Ampulla of Vater; Endoscopy; Pancreatic Ducts; Biopsy; Adenocarcinoma; Treatment Outcome
PubMed: 38155621
DOI: 10.18999/nagjms.85.4.648 -
Frontiers in Endocrinology 2023Recommendations for the performance of prophylactic central neck dissection (pCND) in patients with clinically node-uninvolved (cN0) papillary thyroid carcinoma (PTC)... (Meta-Analysis)
Meta-Analysis
Prophylactic central neck dissection for cN0 papillary thyroid carcinoma: is there any difference between western countries and China? A systematic review and meta-analysis.
BACKGROUND
Recommendations for the performance of prophylactic central neck dissection (pCND) in patients with clinically node-uninvolved (cN0) papillary thyroid carcinoma (PTC) are not the same. This meta-analysis set out to compare the effectiveness of pCND with total thyroidectomy (TT) in different countries and regions, mainly between western countries and China.
METHODS
The electronic databases PubMed, EMBASE, and Cochrane Library were searched for studies published until August 2022. The incidence rate of cervical lymph node metastases (LNMs), locoregional recurrences (LRRs), and postoperative complications were pooled by a random-effects model. Subgroup analyses based on different countries and regions were performed.
RESULTS
Eighteen studies involving 5,346 patients were analyzed. In the subgroup of western countries, patients undergoing pCND with TT had a significantly lower LRR rate [69/1,804, 3.82% vs. 139/2,541, 5.47%; odds ratio (OR) = 0.56; 95% CI 0.37-0.85] and a higher rate of temporary hypoparathyroidism (HPT) (316/1,279, 24.71% vs. 194/1,467, 13.22%; OR = 2.23; 95% CI 1.61-3.08) than that of the TT alone group, while no statistically significant difference was found in the rate of permanent HPT and temporary and permanent recurrent laryngeal nerve (RLN) injury. In the Chinese subgroup, the pCND with TT group had a significantly higher incidence rate of both temporary HPT (87/374, 23.26% vs. 36/324, 11.11%; OR = 2.24; 95% CI 1.32-3.81) and permanent HPT (21/374, 5.61% vs. 4/324, 1.23%; OR = 3.58; 95% CI = 1.24-10.37) than that of the TT alone group, while no significant difference was detected in the rate of LRR and temporary and permanent RLN injury.
CONCLUSION
Compared with the TT alone for cN0 PTC patients, pCND with TT had a significantly lower LRR rate while having a higher temporary HPT rate in Europe, America, and Australia; however, it showed no significant difference in decreasing LRR rate while having a significantly raised rate of temporary and permanent HPT in China. More population-based results are required to advocate precision medicine in PTC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022358546.
Topics: Humans; Carcinoma, Papillary; China; Neck Dissection; Recurrent Laryngeal Nerve Injuries; Thyroid Cancer, Papillary; Thyroid Neoplasms
PubMed: 37576962
DOI: 10.3389/fendo.2023.1176512 -
International Journal of Surgery... Jan 2024Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a...
BACKGROUND
Papillary thyroid cancer (PTC) is one of the most common endocrine malignancies with different risk levels. However, preoperative risk assessment of PTC is still a challenge in the worldwide. Here, the authors first report a Preoperative Risk Assessment Classifier for PTC (PRAC-PTC) by multidimensional features including clinical indicators, immune indices, genetic feature, and proteomics.
MATERIALS AND METHODS
The 558 patients collected from June 2013 to November 2020 were allocated to three groups: the discovery set [274 patients, 274 formalin-fixed paraffin-embedded (FFPE)], the retrospective test set (166 patients, 166 FFPE), and the prospective test set (118 patients, 118 fine-needle aspiration). Proteomic profiling was conducted by FFPE and fine-needle aspiration tissues from the patients. Preoperative clinical information and blood immunological indices were collected. The BRAFV600E mutation were detected by the amplification refractory mutation system.
RESULTS
The authors developed a machine learning model of 17 variables based on the multidimensional features of 274 PTC patients from a retrospective cohort. The PRAC-PTC achieved areas under the curve (AUC) of 0.925 in the discovery set and was validated externally by blinded analyses in a retrospective cohort of 166 PTC patients (0.787 AUC) and a prospective cohort of 118 PTC patients (0.799 AUC) from two independent clinical centres. Meanwhile, the preoperative predictive risk effectiveness of clinicians was improved with the assistance of PRAC-PTC, and the accuracies reached at 84.4% (95% CI: 82.9-84.4) and 83.5% (95% CI: 82.2-84.2) in the retrospective and prospective test sets, respectively.
CONCLUSION
This study demonstrated that the PRAC-PTC that integrating clinical data, gene mutation information, immune indices, high-throughput proteomics and machine learning technology in multicentre retrospective and prospective clinical cohorts can effectively stratify the preoperative risk of PTC and may decrease unnecessary surgery or overtreatment.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Retrospective Studies; Prospective Studies; Proteomics; Carcinoma, Papillary; Machine Learning; Risk Assessment; Proto-Oncogene Proteins B-raf
PubMed: 37916932
DOI: 10.1097/JS9.0000000000000814 -
Scientific Reports Sep 2023Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific... (Randomized Controlled Trial)
Randomized Controlled Trial
Accurate prognostic prediction is crucial for treatment decision-making in lung papillary adenocarcinoma (LPADC). The aim of this study was to predict cancer-specific survival in LPADC using ensemble machine learning and classical Cox regression models. Moreover, models were evaluated to provide recommendations based on quantitative data for personalized treatment of LPADC. Data of patients diagnosed with LPADC (2004-2018) were extracted from the Surveillance, Epidemiology, and End Results database. The set of samples was randomly divided into the training and validation sets at a ratio of 7:3. Three ensemble models were selected, namely gradient boosting survival (GBS), random survival forest (RSF), and extra survival trees (EST). In addition, Cox proportional hazards (CoxPH) regression was used to construct the prognostic models. The Harrell's concordance index (C-index), integrated Brier score (IBS), and area under the time-dependent receiver operating characteristic curve (time-dependent AUC) were used to evaluate the performance of the predictive models. A user-friendly web access panel was provided to easily evaluate the model for the prediction of survival and treatment recommendations. A total of 3615 patients were randomly divided into the training and validation cohorts (n = 2530 and 1085, respectively). The extra survival trees, RSF, GBS, and CoxPH models showed good discriminative ability and calibration in both the training and validation cohorts (mean of time-dependent AUC: > 0.84 and > 0.82; C-index: > 0.79 and > 0.77; IBS: < 0.16 and < 0.17, respectively). The RSF and GBS models were more consistent than the CoxPH model in predicting long-term survival. We implemented the developed models as web applications for deployment into clinical practice (accessible through https://shinyshine-820-lpaprediction-model-z3ubbu.streamlit.app/ ). All four prognostic models showed good discriminative ability and calibration. The RSF and GBS models exhibited the highest effectiveness among all models in predicting the long-term cancer-specific survival of patients with LPADC. This approach may facilitate the development of personalized treatment plans and prediction of prognosis for LPADC.
Topics: Humans; Adenocarcinoma of Lung; Adenocarcinoma, Papillary; Lung; Lung Neoplasms; Machine Learning
PubMed: 37684259
DOI: 10.1038/s41598-023-40779-1 -
Journal of Translational Medicine Feb 2024Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for...
BACKGROUND
Although the long-term prognosis of papillary thyroid cancer (PTC) is favorable, distant metastasis significantly compromises the prognosis and quality of life for patients with PTC. The Cadherin family plays a pivotal role in tumor metastasis; however, the involvement of Cadherin 4 (CDH4) in the metastatic cascade remains elusive.
METHODS
The expression and subcellular localization of CDH4 were determined through immunohistochemistry, immunofluorescence, and western blot analyses. The impact of CDH4 on cell migration, invasion, angiogenesis, and metastasis was assessed using transwell assays, tube formation assays, and animal experiments. Immunoprecipitation assay and mass spectrometry were employed to examine protein associations. The influence of CDH4 on the subcellular expression of β-catenin and active β-catenin was investigated via western blotting and immunofluorescence. Protein stability and ubiquitination assay were employed to verify the impact of CDH4 on β-catenin degradation. Rescue experiments were performed to ensure the significance of CDH4 in regulating nuclear β-catenin signaling.
RESULTS
CDH4 was found to be significantly overexpressed in PTC tissues and predominantly localized in the cytoplasm. Furthermore, the overexpression of CDH4 in tumor tissues is associated with lymph node metastasis in PTC patients. Cytosolic CDH4 promoted the migration, invasion, and lung metastasis of PTC cells and stimulated the angiogenesis and tumorigenesis of PTC; however, this effect could be reversed by Tegavivint, an antagonist of β-catenin. Mechanistically, cytosolic CDH4 disrupted the interaction between β-catenin and β-TrCP1, consequently impeding the ubiquitination process of β-catenin and activating the nuclear β-catenin signaling.
CONCLUSIONS
CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin.
Topics: Animals; Humans; Angiogenesis; beta Catenin; Cadherins; Carcinoma, Papillary; Cell Line, Tumor; Cell Movement; Cell Proliferation; Quality of Life; Thyroid Cancer, Papillary; Thyroid Neoplasms; Ubiquitination; Wnt Signaling Pathway
PubMed: 38402159
DOI: 10.1186/s12967-024-05012-1 -
International Journal of Surgery... Nov 2023Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis...
BACKGROUND
Preoperative evaluation of the metastasis status of lateral lymph nodes (LNs) in papillary thyroid cancer is challenging. Strategies for using deep learning to diagnosis of lateral LN metastasis require additional development and testing. This study aimed to build a deep learning-based model to distinguish benign lateral LNs from metastatic lateral LNs in papillary thyroid cancer and test the model's diagnostic performance in a real-world clinical setting.
METHODS
This was a prospective diagnostic study. An ensemble model integrating a three-dimensional residual network algorithm with clinical risk factors available before surgery was developed based on computed tomography images of lateral LNs in an internal dataset and validated in two external datasets. The diagnostic performance of the ensemble model was tested and compared with the results of fine-needle aspiration (FNA) (used as the standard reference method) and the diagnoses made by two senior radiologists in 113 suspicious lateral LNs in patients enrolled prospectively.
RESULTS
The area under the receiver operating characteristic curve of the ensemble model for diagnosing suspicious lateral LNs was 0.829 (95% CI: 0.732-0.927). The sensitivity and specificity of the ensemble model were 0.839 (95% CI: 0.762-0.916) and 0.769 (95% CI: 0.607-0.931), respectively. The diagnostic accuracy of the ensemble model was 82.3%. With FNA results as the criterion standard, the ensemble model had excellent diagnostic performance ( P =0.115), similar to that of the two senior radiologists ( P =1.000 and P =0.392, respectively).
CONCLUSION
A three-dimensional residual network-based ensemble model was successfully developed for the diagnostic assessment of suspicious lateral LNs and achieved diagnostic performance similar to that of FNA and senior radiologists. The model appears promising for clinical application.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Prospective Studies; Deep Learning; Lymphatic Metastasis; Lymph Nodes; Tomography, X-Ray Computed; Retrospective Studies
PubMed: 37578434
DOI: 10.1097/JS9.0000000000000660 -
International Journal of Molecular... Mar 2024Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of 12.5%. PDAC predominantly arises from non-cystic pancreatic...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with a 5-year survival rate of 12.5%. PDAC predominantly arises from non-cystic pancreatic intraepithelial neoplasia (PanIN) and cystic intraductal papillary mucinous neoplasm (IPMN). We used multiplex immunofluorescence and computational imaging technology to characterize, map, and compare the immune microenvironments (IMEs) of PDAC and its precursor lesions. We demonstrate that the IME of IPMN was abundantly infiltrated with CD8 T cells and PD-L1-positive antigen-presenting cells (APCs), whereas the IME of PanIN contained fewer CD8 T cells and fewer PD-L1-positive APCs but elevated numbers of immunosuppressive regulatory T cells (Tregs). Thus, immunosuppression in IPMN and PanIN seems to be mediated by different mechanisms. While immunosuppression in IPMN is facilitated by PD-L1 expression on APCs, Tregs seem to play a key role in PanIN. Our findings suggest potential immunotherapeutic interventions for high-risk precursor lesions, namely, targeting PD-1/PD-L1 in IPMN and CTLA-4-positive Tregs in PanIN to restore immunosurveillance and prevent progression to cancer. Tregs accumulate with malignant transformation, as observed in PDAC, and to a lesser extent in IPMN-associated PDAC (IAPA). High numbers of Tregs in the microenvironment of PDAC went along with a markedly decreased interaction between CD8 T cells and cancerous epithelial cells (ECs), highlighting the importance of Tregs as key players in immunosuppression in PDAC. We found evidence that a defect in antigen presentation, further aggravated by PD-L1 expression on APC, may contribute to immunosuppression in IAPA, suggesting a role for PD-L1/PD-1 immune checkpoint inhibitors in the treatment of IAPA.
Topics: Humans; B7-H1 Antigen; Pancreatic Intraductal Neoplasms; CD8-Positive T-Lymphocytes; Programmed Cell Death 1 Receptor; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Carcinoma in Situ; Tumor Microenvironment
PubMed: 38474199
DOI: 10.3390/ijms25052953 -
Journal of Endocrinological... Jun 2024Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA...
PURPOSE
Papillary thyroid carcinoma (PTC) is characterized by lymph-node metastasis (LNM), which affects recurrence and prognosis. This study analyzed PTC LNM by single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing (RNA-seq) to find diagnostic markers and therapeutic targets.
METHODS
ScRNA-seq data were clustered and malignant cells were identified. Differentially expressed genes (DEGs) were identified in malignant cells of scRNA-seq and bulk RNA-seq, respectively. PTC LNM diagnostic model was constructed based on intersecting DEGs using glmnet package. Next, PTC samples from 66 patients were used to validate the two most significant genes in the diagnostic model, S100A2 and type 2 deiodinase (DIO2) by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC). Further, the inhibitory effect of DIO2 on PTC cells was verified by cell biology behavior, western blot, cell cycle analysis, 5-ethynyl-2'-deoxyuridine (EdU) assay, and xenograft tumors.
RESULTS
Heterogeneity of PTC LNM was demonstrated by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. A total of 19 differential genes were used to construct the diagnostic model. S100A2 and DIO2 differ significantly at the RNA (p < 0.01) and protein level in LNM patient tissues (p < 0.001). And differed in PTC tissues with different pathologic typing (p < 0.001). Further, EdU (p < 0.001) and cell biology behavior revealed that PTC cells overexpressed DIO2 had reduced proliferative capacity. Cell cycle proteins were reduced and cells are more likely to be stuck in G2/M phase (p < 0.001).
CONCLUSIONS
This study explored the heterogeneity of PTC LNM using scRNA-seq. By combining with bulk RNA-seq data, diagnostic markers were explored and the model was established. Clinical diagnostic efficacy of S100A2 and DIO2 was validated and the treatment potential of DIO2 was discovered.
Topics: Humans; Thyroid Cancer, Papillary; Thyroid Neoplasms; Biomarkers, Tumor; Lymphatic Metastasis; Single-Cell Analysis; Animals; Mice; Sequence Analysis, RNA; Female; Male; S100 Proteins; Prognosis; Gene Expression Regulation, Neoplastic; Iodide Peroxidase; Iodothyronine Deiodinase Type II; Cell Proliferation; Middle Aged; Gene Expression Profiling; Chemotactic Factors
PubMed: 38146045
DOI: 10.1007/s40618-023-02262-6