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1.
BMJ Case Rep ; 15(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357113

RESUMO

A woman in her 40s presented with a 3-month history of lower abdominal pain and intermenstrual bleeding. Ultrasound of the pelvis disclosed a 4 cm left adnexal mass. An MRI of the pelvis revealed a 2.2×3.6×2.4 cm solid, enhancing left ovarian mass. Due to high suspicion for malignancy, she underwent laparoscopic left salpingo-oophorectomy and resection of the tumour. Histopathology revealed papillary thyroid carcinoma in the background of struma ovarii as confirmed by thyroglobulin and thyroid transcription factor-1 positivity on immunohistochemistry. BRAF mutation analysis was negative. An ultrasound of the thyroid gland showed two low-risk nodules. An iodine-123 whole-body scan showed normal uptake in the thyroid gland. Thyroid-stimulating hormone (TSH) was 1.070 mcIU/mL (0.450-4.500), and thyroglobulin was 6.8 ng/mL (1.5-38.5). We risk-stratified this patient as low risk for recurrence. Risk stratification of malignant struma ovarii is essential to determine suitable thyroid targeting adjuvant therapy and reduce the risk of recurrence.


Assuntos
Carcinoma Papilar , Neoplasias Ovarianas , Estruma Ovariano , Neoplasias da Glândula Tireoide , Feminino , Humanos , Estruma Ovariano/diagnóstico , Estruma Ovariano/cirurgia , Estruma Ovariano/patologia , Câncer Papilífero da Tireoide/cirurgia , Tireoglobulina , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/patologia
2.
Front Endocrinol (Lausanne) ; 13: 971038, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353232

RESUMO

Background: This study is a meta-analysis based on evidence-based medicine to explore the long-term (≥3 years) efficacy of thermal ablation in the treatment of papillary thyroid carcinoma (PTC). Methods: We searched the PubMed, Embase, and Cochrane Library databases for studies published during the time between the establishment of the databases through June 2022. We included 13 non-randomized-controlled trials (non-RCTs) that reported the application of ultrasound-guided thermal ablation in PTC. We excluded studies that were repeated publications, research without full text, contained incomplete information, lacked data extraction, involved animal experiments, reviews, and systematic reviews. STATA 15.1 software was used to analyze the data. Results: Tumor volume after thermal ablation at 3-year follow-up was significantly lower than pre-ablation (standardized mean difference [SMD] = -1.06, 95% CI: -1.32~-0.80). The pooled results indicated that the maximum diameter after thermal ablation at 3-year follow-up was significantly lower than pre-ablation (SMD = -1.93, 95% CI: -12.13~-1.73). The pooled results indicated that volume reduction rate (VRR) after thermal ablation at 3-year follow-up was 98.91% (95% CI: 97.98-99.83%), and complete disappearance rate (CDR) after thermal ablation at 3-year follow-up was 83% (95% CI: 67-94%). In addition, the incidence of newly discovered mPTC and lymph node metastases after thermal ablation was 0.3% (95% CI: 0.0-1.0%) and 0.0% (95% CI: 0.0-0.0%), respectively. Conclusion: Overall, the long-term (≥3 years) efficacy of ultrasound-guided thermal ablation in the treatment of PTC was significant, with favorable disease progression. Ultrasound-guided thermal ablation can be considered an alternative approach for patients with PTC who refuse surgery or are unable to undergo surgery.


Assuntos
Carcinoma Papilar , Ablação por Radiofrequência , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Seguimentos , Ablação por Radiofrequência/métodos
3.
BMC Surg ; 22(1): 374, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36324095

RESUMO

BACKGROUND: While the most suitable approach for treating persistent/recurrent papillary thyroid carcinoma (PTC) remains controversial, reoperation may be considered an effective method. The efficacy of reoperation in patients with locoregional persistent/recurrent PTC, especially those with unsatisfactory radioactive iodine (RAI) ablation results, is still uncertain. This study aimed to clarify the clinical management strategies for locoregional persistent/recurrent PTC and to explore factors that may affect long-term patient outcomes after reoperation. METHODS: In total, 124 patients who initially underwent thyroidectomy and variable extents of RAI therapy and finally received reoperation for locoregionally persistent/recurrent PTC were included. The parameters associated with recurrence-free survival (RFS) were analysed using a Cox proportional hazards model. RESULTS: Overall, 124 patients presented with structural disease after initial therapy and underwent secondary surgical resection, of whom 32 patients developed further structural disease during follow-up after reoperation. At the time of reoperation, metastatic lymph nodes with extranodal extension (P = 0.023) and high unstimulated thyroglobulin (unstim-Tg) levels after reoperation (post-reop) (P = 0.001) were independent prognostic factors for RFS. Neither RAI avidity nor the frequency and dose of RAI therapies before reoperation affected RFS. CONCLUSIONS: Reoperation is an ideal clinical treatment strategy for structural locoregional persistent/recurrent PTC, and repeated empirical RAI therapies performed prior to reoperation may not contribute to the long-term outcomes of persistent/recurrent PTC patients. Metastatic lymph nodes with extranodal extension and post-reop unstim-Tg > 10.1 ng/mL may predict a poor prognosis.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Radioisótopos do Iodo/uso terapêutico , Reoperação , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Prognóstico , Extensão Extranodal , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Doença Crônica
5.
Sci Rep ; 12(1): 16538, 2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36192513

RESUMO

Human cancers display a restricted set of expression profiles, despite diverse mutational drivers. This has led to the hypothesis that select sets of transcription factors act on similar target genes as an integrated network, buffering a tumor's transcriptional state. Noninvasive papillary urothelial carcinoma (NIPUC) with higher cell cycle activity has higher risk of recurrence and progression. In this paper, we describe a transcriptional network of cell cycle dysregulation in NIPUC, which was delineated using the ARACNe algorithm applied to expression data from a new cohort (n = 81, RNA sequencing), and two previously published cohorts. The transcriptional network comprised 121 transcription factors, including the pluripotency factors SOX2 and SALL4, the sex hormone binding receptors ESR1 and PGR, and multiple homeobox factors. Of these 121 transcription factors, 65 and 56 were more active in tumors with greater and less cell cycle activity, respectively. When clustered by activity of these transcription factors, tumors divided into High Cell Cycle versus Low Cell Cycle groups. Tumors in the High Cell Cycle group demonstrated greater mutational burden and copy number instability. A putative mutational driver of cell cycle dysregulation, such as homozygous loss of CDKN2A, was found in only 50% of High Cell Cycle NIPUC, suggesting a prominent role of transcription factor activity in driving cell cycle dysregulation. Activity of the 121 transcription factors strongly associated with expression of EZH2 and other members of the PRC2 complex, suggesting regulation by this complex influences expression of the transcription factors in this network. Activity of transcription factors in this network also associated with signatures of pluripotency and epithelial-to-mesenchymal transition (EMT), suggesting they play a role in driving evolution to invasive carcinoma. Consistent with this, these transcription factors differed in activity between NIPUC and invasive urothelial carcinoma.


Assuntos
Carcinoma in Situ , Carcinoma Papilar , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Carcinoma Papilar/patologia , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/patologia , Ciclo Celular/genética , Redes Reguladoras de Genes , Humanos , Fatores de Transcrição/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia
6.
Thyroid ; 32(11): 1328-1336, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36205563

RESUMO

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Prospectivos , Conduta Expectante , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Metástase Linfática , Fatores de Risco , Progressão da Doença , Estudos Retrospectivos
7.
J Coll Physicians Surg Pak ; 32(8): S156-S158, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36210680

RESUMO

Medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC) are two different types of thyroid carcinoma. They have different features in terms of cellular origin, histopathology, clinical features, prevalence, and prognosis. PTC originates from follicular cells, while MTC from parafollicular cells. MTC and PTC co-existence is a rare phenomenon and occurs in less than 1% of all thyroid tumors. We report three cases with coexistent MTC and PTC in the same thyroid. The papillary component was dominant in two cases and the medullary in one case. While the first case was given radioactive iodine therapy, the third was treated with vandetanib. The second case was followed up postoperatively and did not receive treatment other than levothyroxine replacement. The co-existence of these tumors requires a different clinical approach in treatment and follow-up, depending on which type is dominant. Key Words: Mixed thyroid carcinoma, Papillary thyroid carcinoma, Medullary thyroid carcinoma.


Assuntos
Carcinoma Neuroendócrino , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Neuroendócrino/patologia , Carcinoma Papilar/patologia , Humanos , Radioisótopos do Iodo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Tiroxina
8.
J Coll Physicians Surg Pak ; 32(8): S186-S188, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36210690

RESUMO

We, herein, present a case of a micropapillary variant of bladder cancer metastasizing to lymph nodes in an 87-year male with elevated serum carcinoembryonic antigen (CEA) levels (2637.8 ng/mL). The patient was evaluated for dyspeptic symptoms and elevated CEA levels. Colonoscopy and upper gastrointestinal endoscopy were normal. Contrast-enhanced computed tomography revealed a bladder tumour. Transurethral resection of bladder tumour (TUR-BT) was performed, and histologically, the tumour was reported as urothelial carcinoma (UC), high grade, and pT1. Intravesical Bacillus Calmette-Guérin (BCG) was started three weeks after TUR-BT and continued for two years. F-18 FDG PET/CT scans were performed every six months during the follow-up due to persistently elevated CEA levels. During follow-up, there was no recurrence of UC in the bladder. Two years later, he was admitted again with lymph node swelling in the left inguinal area. A tru-cut biopsy was performed, which showed UC with a micropapillary component. Gemcitabine monotherapy was given, which resulted in partial response, and a significant decline in serum CEA levels (490.17 ng/mL). Key Words: Carcinoembryonic antigen, Urothelial carcinoma, Bladder cancer, Micropapillary variant, Gemcitabine monotherapy.


Assuntos
Adenocarcinoma Papilar , Carcinoma Papilar , Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Idoso , Vacina BCG , Antígeno Carcinoembrionário , Carcinoma Papilar/patologia , Carcinoma de Células de Transição/patologia , Fluordesoxiglucose F18 , Humanos , Masculino , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
9.
Pancreas ; 51(6): 678-683, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36206470

RESUMO

OBJECTIVES: It is challenging to preoperatively distinguish malignant and benign forms of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The aims of this study were to investigate whether telomere length is associated with pathological grade of IPMNs and age and to clarify the utility of telomere length as a marker to identify malignant IPMNs. METHODS: Pancreas tissue was obtained from 28 patients after resection. We measured the telomere lengths of tumor cells in IPMNs and normal duct cells by quantitative fluorescence in situ hybridization. The association of normalized telomere-centromere ratio (NTCR) to pathological grade of IPMNs and age were determined. RESULTS: The NTCR showed a gradual decrease with increasing pathological grade of IPMNs. The NTCR in intermediate- and high-grade dysplasia and adenocarcinoma lesions was significantly shorter than in normal pancreatic ducts (P < 0.05). In multivariate analysis, telomere length was most associated with carcinogenesis. When the cutoff value of NTCR was set to 0.74, the sensitivity for detection of high-grade dysplasia and adenocarcinoma was 82.8%, with a specificity of 87.5%. CONCLUSIONS: Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Carcinoma Papilar , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/patologia , Envelhecimento , Carcinogênese , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Humanos , Hibridização in Situ Fluorescente , Pâncreas/patologia , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/patologia , Telômero/genética
10.
Endocrinol Metab (Seoul) ; 37(5): 703-718, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36193717

RESUMO

The fifth edition of the World Health Organization (WHO) histologic classification of thyroid neoplasms released in 2022 includes newly recognized tumor types, subtypes, and a grading system. Follicular cell-derived neoplasms are categorized into three families (classes): benign tumors, low-risk neoplasms, and malignant neoplasms. The terms "follicular nodular disease" and "differentiated high-grade thyroid carcinoma" are introduced to account for multifocal hyperplastic/neoplastic lesions and differentiated thyroid carcinomas with high-grade features, respectively. The term "Hürthle cells" is replaced with "oncocytic cells." Invasive encapsulated follicular and cribriform morular variants of papillary thyroid carcinoma (PTC) are now redefined as distinct tumor types, given their different genetic alterations and clinicopathologic characteristics from other PTC subtypes. The term "variant" to describe a subclass of tumor has been replaced with the term "subtype." Instead, the term "variant" is reserved to describe genetic alterations. A histologic grading system based on the mitotic count, necrosis, and/or the Ki67 index is used to identify high-grade follicular-cell derived carcinomas and medullary thyroid carcinomas. The 2022 WHO classification introduces the following new categories: "salivary gland-type carcinomas of the thyroid" and "thyroid tumors of uncertain histogenesis." This review summarizes the major changes in the 2022 WHO classification and their clinical relevance.


Assuntos
Adenocarcinoma Folicular , Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Adenocarcinoma Folicular/genética , Câncer Papilífero da Tireoide , Organização Mundial da Saúde
11.
Pan Afr Med J ; 42: 248, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36303817

RESUMO

Papillary thyroid cancer (PTC) coexistent with esophageal squamous cell carcinoma (SCC) is of rare occurrence. We report a 45-year-old female who presented with painless anterior neck swelling for the past year. Ultrasonography showed a left hypoechoic thyroid mass measured 20x13 mm without lymph node enlargement. The fine-needle aspiration cytology was suggestive of PTC. Consequently, total thyroidectomy with bilateral neck dissection was performed. Incidentally, a small mass measuring 4x2 cm arising from the esophageal wall was identified and resected. Postoperatively, the patient developed a small esophageal fistula which was treated conservatively. The histopathological examination confirmed the diagnosis of PTC and SCC of esophageal mass. The patient underwent radiotherapy, and radioactive iodine therapy, and had acceptable conditions within two years of follow-up. In conclusion, even though the coexistence of PTC and esophageal SCC is rare, the possibility of concurrence of both tumors should be considered if an incidental mass was identified intraoperatively.


Assuntos
Carcinoma Papilar , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias da Glândula Tireoide , Feminino , Humanos , Pessoa de Meia-Idade , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/epidemiologia , Radioisótopos do Iodo , Carcinoma de Células Escamosas do Esôfago/diagnóstico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Tireoidectomia
12.
Front Endocrinol (Lausanne) ; 13: 1025739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36277684

RESUMO

Background: The preoperative risk stratification for patients with papillary thyroid carcinoma (PTC) plays a crucial role in guiding individualized treatment. We aim to construct a predictive model that aids in distinguishing between patients with low-risk and high-risk PTC based on preoperative clinical and ultrasound characteristics. Materials and methods: Patients who underwent open surgery and were diagnosed with PTC via a postoperative pathological report between January 2020 and December 2020 were retrospectively reviewed. Data including basic information, preoperative ultrasound characteristics, thyroid function, and postoperative pathology characteristics were obtained. Univariate logistic regression analysis and least absolute shrinkage and selection operator regression analysis were performed to screen candidate variables. Finally, the preoperative predictive model for PTC was established based on the results of the multivariate logistic regression analysis. Results: A total of 1,875 patients with PTC were enrolled. Eight variables (sex, age, number of foci, maximum tumor diameter on ultrasound, calcification, capsule, lymph node status on ultrasound, and thyroid peroxidase (TPO) antibody level) significantly associated with risk stratification were included in the predictive model. A nomogram was constructed for clinical utility. The model showed good discrimination, and the area under the curve was 0.777 [95% confidence interval (CI): 0.752-0.803] and 0.769 (95% CI: 0.729-0.809) in the training set and validation set, respectively. The calibration curve exhibited a rather good consistency with the perfect prediction. Furthermore, decision curve analysis and clinical impact curve showed that the model had good efficacy in predicting the prognostic risk of PTC. Conclusions: The nomogram model based on preoperative indicators for predicting the prognostic stratification of PTC showed a good predictive value. This could aid surgeons in deciding on individualized precision treatments.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico por imagem , Câncer Papilífero da Tireoide/cirurgia , Iodeto Peroxidase , Prognóstico , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Estudos Retrospectivos , Metástase Linfática , Medição de Risco
13.
Oral Oncol ; 134: 106185, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36191477

RESUMO

PURPOSES: To quantitatively predict central lymph node metastasis (CLNM) risks by comparing the clinicopathological features of different multifocal manifestations in papillary thyroid carcinomas (PTC) patients. METHODS: A total of 998 PTC patients from three medical centers were retrospectively analyzed. RESULTS: PTC patients with multifocal lesions in at least one thyroid lobe (MF group) yielded significantly higher CLNM rates than those with unifocal lesions in one or both lobes (UF group). Multifocality in at least one lobe rather than bilateral presence was confirmed to be an independent risk factor of CLNM for PTC patients. Four (age, gender, maximum tumor diameter, and thyroid capsular invasion (TCI)) and three (age, gender, and TCI) factors were proven to be independent risk factors of CLNM for patients within UF and MF groups, respectively. Predictive nomograms were established for these patients based on their respective high-risk factors. The accuracy and validity of these newly-created models were verified using C-index and calibration curves. Patients within UF and MF groups possessing significantly different CLNM risks based on individualized nomogram risk scores were further classified into different subgroups. A detailed CLNM risk stratification flow chart covering all PTC patients was then established. CONCLUSION: A meticulous evaluating system that quantifiesCLNM risk for PTC patients with unifocal lesions in one or both lobes and multifocal lesions in at least one lobe was established.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Estudos Retrospectivos , Fatores de Risco , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
14.
Cells ; 11(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36231143

RESUMO

Papillary thyroid cancer is the most common endocrine malignancy, occurring at an incidence rate of 12.9 per 100,000 in the US adult population. While the overall 10-year survival of PTC nears 95%, the presence of lymph node metastasis (LNM) or capsular invasion indicates the need for extensive neck dissection with possible adjuvant radioactive iodine therapy. While imaging modalities such as ultrasound and CT are currently in use for the detection of suspicious cervical lymph nodes, their sensitivities for tumor-positive nodes are low. Therefore, advancements in preoperative detection of LNM may optimize the surgical and medical management of patients with thyroid cancer. To this end, we analyzed bulk RNA-sequencing datasets to identify candidate markers highly predictive of LNM. We identified MEG3, a long-noncoding RNA previously described as a tumor suppressor when expressed in malignant cells, as highly associated with LNM tissue. Furthermore, the expression of MEG3 was highly predictive of tumor infiltration with cancer-associated fibroblasts, and single-cell RNA-sequencing data revealed the expression of MEG3 was isolated to cancer-associated fibroblasts (CAFs) in the most aggressive form of thyroid cancers. Our findings suggest that MEG3 expression, specifically in CAFs, is highly associated with LNM and may be a driver of aggressive disease.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Papilar , RNA Longo não Codificante/genética , Neoplasias da Glândula Tireoide , Adulto , Fibroblastos Associados a Câncer/patologia , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Radioisótopos do Iodo , Metástase Linfática , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
15.
Mol Cancer ; 21(1): 195, 2022 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-36217175

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is one of the most common forms of thyroid cancer with a cure rate of over 90% after surgery. However, aggressive forms may still occur, and personalized therapeutic strategies are increasingly required. METHODS: We performed integrated genomic and proteomic analysis of PTC tumor samples from patients who did not harbor BRAF or RAS mutations. We validate the analysis and present in-depth molecular analysis of the identified genetic rearrangement by employing biochemical and cell biological assays. Finally, we employ 3D spheroid models, loss of function studies and chemical inhibitors to target the hitherto upregulated factors. The data are analysed with appropriate statistical tests which are mentioned in the legends section. RESULTS: In a 23-year-old patient with thyroiditis, we identified a novel rearrangement leading to a BAIAP2L1-BRAF fusion that transforms immortalized human thyroid cells in a kinase and CC-domain dependent manner. Moreover, quantitative proteomic analysis of the same patient samples revealed the upregulation of several proteins including the Ubiquitin E3 ligase TRIM25, PDE5A, and PKCδ. Further, in a cohort of PTC patients, we observed higher expression of TRIM25 and PKCδ in the tumor and metastatic lesions, when compared to the matched normal tissue. Inhibition of TRIM25, PDE5A and PKCδ with small molecules or RNA interference affected not only viability and proliferation of BAIAP2L1-BRAF transformed cells, but also the viability, growth and invasion of corresponding 3D spheroid cultures. CONCLUSIONS: Apart from unveiling a novel oncogenic BRAF fusion in PTCs, our data may open a novel avenue of therapeutic targeting in human PTCs.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Adulto , Carcinogênese , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Humanos , Mutação , Proteômica , Proteínas Proto-Oncogênicas B-raf/genética , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Fatores de Transcrição/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Ubiquitinas/genética , Adulto Jovem
16.
Int J Hyperthermia ; 39(1): 1300-1309, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36195326

RESUMO

BACKGROUND: We comprehensively evaluate the efficacy and safety of US-guided radiofrequency ablation (RFA) in the treatment of papillary thyroid microcarcinoma (PTMC) via a systematic review and meta-analysis. METHODS: We searched the PubMed, Embase and Cochrane Library databases for studies published during the time between the establishment of the database through October 2021. We included a 10 non-randomized controlled trial (non-RCT) that reported the application of US-guided RFA in PTMC. The sample size of patients totaled 1279. We evaluated the ablation efficacy by analyzing the volume reduction rate (VRR), complete disappearance rate (CDR) and recurrence rate of PTMC treated by RFA. We analyzed all data using STATA version 15.1 (Stata Corporation, College Station, TX). RESULTS: Our pooled results proved RFA treatment significantly reduces the volume of tumors (Weighted Mean Difference [WMD] = -103.20, 95% CI: -111.93 - -94.48, p = 0.000). We also found the VRR at 12 months after RFA was 93.27% (95% CI: 84.68-101.86), and the CDR at 12 months after RFA was 64% (95% CI: 39-89%). Additionally, pooled results showed the incidence of mPTC residue in ablation area, newly discovered mPTC and lymph node metastases after RFA treatment were respectively 0.3% (95% CI: -0.1-0.7%), 2.5% (95% CI: 1.1-3.9%) and 1.0% (95% CI: 0.2-1.9%), and the incidence of complications after RFA treatment was 1.8% (95% CI: 0.7-3.2%). CONCLUSIONS: US-guided RFA is effective and safe for treating PTMC. It could be an excellent alternative to the existing treatment options.


Assuntos
Carcinoma Papilar , Ablação por Radiofrequência , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Humanos , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento , Ultrassonografia de Intervenção
17.
Dis Markers ; 2022: 9714140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36217504

RESUMO

Background: Papillary thyroid microcarcinoma (PTMC) refers to papillary thyroid carcinoma (PTC) with a maximum diameter of 10 mm. Thermal ablation, including radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA), has been applied in the treatment of benign thyroid nodules and captured extensive attention. At present, the application of thermal ablation in PTMC has been extensively reported, but outcomes such as volume reduction rate (VRR), complete remission rate (CRR), and adverse reaction rate (ARR) vary considerably. Therefore, this meta-analysis was performed to evaluate the safety and efficacy of different treatment methods of PTMC. Methods: We did a systematic review and network meta-analysis. We searched PubMed, EMBase, and Cochrane-Library from the date of inception to January 10, 2022, to retrieve the VRR, CRR, and ARR of MWA, RFA, LA and surgical treatment of PTMC, and a meta-analysis was performed using the R meta-package. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and sensitivity analyses, cumulative meta-analyses, and publication bias were also performed. Relevant literature was retrieved with keywords; the eligible cohort studies were screened based on the established inclusion and exclusion criteria. Results: A total of 1515 patients were included in the 12-month follow-up. The overall VRR was 86.25% (95% CI: 77.89, 94.60), and the VRR was RFA > WMA > LA, but the differences were not significant. A total of 1483 patients were included in the last follow-up. The overall VRR was 99.41% (95% CI: 99.11, 99.72), and the VRR was RFA > WMA > LA, but the differences were not significant. A total of 1622 patients showed complete remission at the last follow-up, and the overall CRR was 0.63 (95% CI: 0.46, 0.79). The CRR was RFA > LA > WMA, but the differences were not significant. A total of 1883 patients had adverse reactions at the last follow-up, and the overall ARR was 0.06 (95% CI: 0.03, 0.08). The ARR at the last follow-up was RFA = Surg < LA < WMA. The ARR of the RFA and Surg subgroups was significantly lower than that of the WMA subgroup. Conclusions: Similar good efficacy and safety profiles were observed in WMA, RFA, LA, and surgical treatment in PTMC, among which RFA showed the best volume reduction, complete remission rate, and adverse reaction reduction. However, there is a slight bias in the limited literature included in this study, and we did not conduct or refer to mechanistic studies to confirm its specific mechanism of action. Clinicians are advised to use their discretion in the choice of treatment.


Assuntos
Carcinoma Papilar , Ablação por Cateter , Ablação por Radiofrequência , Neoplasias da Glândula Tireoide , Carcinoma Papilar/patologia , Carcinoma Papilar/cirurgia , Ablação por Cateter/efeitos adversos , Humanos , Ablação por Radiofrequência/métodos , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/cirurgia , Resultado do Tratamento
18.
World J Surg Oncol ; 20(1): 340, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36242015

RESUMO

BACKGROUND: The importance of stroma for tumor progression is recognized for many cancer types. In this study, we aim to evaluate the expression of types I (Col1) and IV (Col4) collagens, alpha-smooth muscle actin (a-SMA), and matrix metallopeptidase 9 (MMP-9) in the tumor stroma of small papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: Twenty-five non-metastatic small PTCs (pT1N0) and nineteen metastatic small PTCs (pT1N1b) including corresponding metastatic lateral lymph nodes were selected and paraffinized tissue blocks retrieved. The samples were stained for Col1, COL4, a-SMA, and MMP-9 antibodies using immunohistochemistry. The expression of the stromal proteins was scored and analyzed based on the location, intensity, and distribution. RESULTS: Col1 and Col4 expression were significantly higher in normal thyroid tissue compared to PTC tissue. On the contrary, expression of a-SMA and MMP-9 was higher in PTC tissue compared to normal thyroid tissue. Both Col1 and Col4 were significantly more highly expressed in the non-metastatic tumors compared with metastatic tumors. The expression of a-SMA and MMP9 was slightly, but not significantly, higher in the metastasized tumors and their respective lymph nodes. There was a significant correlation between the metastasized tumors and their respective lymph nodes in Col1 and MMP-9 expression. CONCLUSIONS: Col1, Col4, a-SMA, and MMP-9 expression in PTCs differs significantly from that of normal thyroid tissue. The higher expression of Col1 and Col4 in normal thyroid tissue and in the non-metastasized tumors indicates that Col1 and 4 might have a potential protective role in tumor progression. The higher expression of a-SMA and MMP9 in PTCs indicates that these proteins might have a role in promoting PTC progression and aggressiveness.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Actinas , Biomarcadores , Carcinoma Papilar/patologia , Humanos , Metástase Linfática , Metaloproteinase 9 da Matriz , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
19.
Front Endocrinol (Lausanne) ; 13: 1019037, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36299455

RESUMO

Objective: To develop a web-based machine learning server to predict lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) patients. Methods: Clinical data for PTC patients who underwent primary thyroidectomy at our hospital between January 2015 and December 2020, with pathologically confirmed presence or absence of any LLNM finding, were retrospectively reviewed. We built all models from a training set (80%) and assessed them in a test set (20%), using algorithms including decision tree, XGBoost, random forest, support vector machine, neural network, and K-nearest neighbor algorithm. Their performance was measured against a previously established nomogram using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), precision, recall, accuracy, F1 score, specificity, and sensitivity. Interpretable machine learning was used for identifying potential relationships between variables and LLNM, and a web-based tool was created for use by clinicians. Results: A total of 1135 (62.53%) out of 1815 PTC patients enrolled in this study experienced LLNM episodes. In predicting LLNM, the best algorithm was random forest. In determining feature importance, the AUC reached 0.80, with an accuracy of 0.74, sensitivity of 0.89, and F1 score of 0.81. In addition, DCA showed that random forest held a higher clinical net benefit. Random forest identified tumor size, lymph node microcalcification, age, lymph node size, and tumor location as the most influentials in predicting LLNM. And the website tool is freely accessible at http://43.138.62.202/. Conclusion: The results showed that machine learning can be used to enable accurate prediction for LLNM in PTC patients, and that the web tool allowed for LLNM risk assessment at the individual level.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Metástase Linfática/patologia , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Estudos Retrospectivos , Fatores de Risco , Linfonodos/patologia , Aprendizado de Máquina
20.
Thyroid ; 32(11): 1337-1345, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36178355

RESUMO

Background: The change in size of the papillary thyroid cancer (PTC) nodule during active surveillance has traditionally been characterized as either stable, increasing, or decreasing based on changes in maximal tumor diameter or tumor volume. More recently, it has been observed that the changes in tumor size observed during observation are more complex with tumor volume kinetic patterns that can be characterized either as stable (Pattern I), early increase in volume (Pattern II), later increase in volume (Pattern III), early increase in volume followed by stability (Pattern IV), stability followed by an increase in volume (Pattern V), or a decrease in tumor volume (Pattern VI). Methods: The frequency, time course, and clinical correlates of these six tumor volume kinetic patterns were analyzed in a cohort of 483 patients with low-risk PTC up to 1.5 cm in maximal diameter followed with active surveillance at our center for a median of 3.7 years. Results: The cumulative incidence of an increase in tumor volume for the entire cohort was 15.9% [confidence interval (CI) 11.8-20.0] at 5 years. At 5 years, most tumors demonstrated stability (78.8%, Pattern I) with 10.0% showing early growth (Pattern II), 4.1% late growth (Pattern III), 1.9% growth then stability (Pattern IV), 0.6% stability then growth (Pattern V), and 5.6% with a decrease in tumor volume (Pattern VI). Tumor volume doubling time during exponential growth significantly differed across the kinetic patterns, with median values of 2.4, 7.1, and 3.3 years for Patterns II, III, and IV, respectively (p < 0.01). Similarly, the time to a change in tumor volume was significantly different across the kinetic patterns, with median values of 1.5, 3, 1.6, 4.7, and 4.1 years for Patterns II, III, IV, V, and VI, respectively (analysis of variance, p < 0.01). Clinical correlates at baseline were not associated with tumor volume kinetic pattern. Conclusions: These six kinetic tumor volume patterns provide a comprehensive description of the changes in PTC tumor volume observed during the first 5 years of active surveillance.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/patologia , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Carga Tumoral , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Conduta Expectante , Estudos Retrospectivos
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