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Fatemeh A, Mohammad Ali Y, Hassan M, Masoud M, Parvin L, Leila V, Maliheh DM, Zahra A, Ghazaleh T. The Relationship Between Serum Levels of Thyroglobulin Antibody and the Risk of Recurrence in Patients With Differentiated Thyroid Cancer. Cancer Rep (Hoboken) 2025; 8:e70191. [PMID: 40423684 PMCID: PMC12108441 DOI: 10.1002/cnr2.70191] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 03/14/2025] [Accepted: 03/21/2025] [Indexed: 05/28/2025] Open
Abstract
OBJECTIVE Thyroid Autoantibodies (TgAbs) are associated with autoimmune thyroid disorders and are also used in thyroid cancer follow-up to monitor for recurrence of disease. This study aimed to explore the potential utility of TgAbs as a surrogate tumor marker and examine the relationship between fluctuations in TgAbs levels and disease recurrence in patients with Differentiated Thyroid Cancer (DTC). METHODS This cohort study was conducted on a sample of 97 patients who underwent thyroidectomy for differentiated thyroid cancer (DTC) between the years 2017 and 2021. Following surgery (with or without lymph node dissection), levothyroxine therapy and 131 iodine were prescribed (as necessary). Regular laboratory evaluations were conducted, which involved measuring Tg and TgAb at 3 and 6 months postoperatively. Patients were classified based on recurrence rate and different levels of TgAb, and ROC analysis was applied. All data were analyzed with SPSS24, and a p-value < 0.05 was considered statistically significant. RESULTS For low-risk patients, TgAb trends over time showed an increase at 6 months, while for high-risk patients, TgAb levels continuously rose starting from 3 months. Although TgAb levels above the functional sensitivity threshold did not predict recurrence overall, changes in TgAb levels at 6 months compared to 3 months after surgery were indicative of recurrence. CONCLUSION In the entire population, having TgAb levels higher than the functional sensitivity threshold had no risk of various relapses. However, changes in TgAb serum levels at 6 months after surgery, compared to 3 months after surgery, can serve as an indication of tumor recurrence.
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Affiliation(s)
- Amirian Fatemeh
- Faculty of Medicine, Department of Internal MedicineMashhad University of Medical SciencesMashhadIran
| | | | - Mehrad‐Majd Hassan
- Cancer Molecular Pathology Research CenterMashhad University of Medical SciencesMashhadIran
- Clinical Research Development UnitGhaem Hospital, Faculty of Medicine, Mashhad University of Medical SciencesMashhadIran
| | - Mohebbi Masoud
- Endocrine Research CenterMashhad University of Medical SciencesMashhadIran
| | - Layegh Parvin
- Endocrinology & Metabolism Member of Metabolic Syndrome Research Center (MSRC)Mashhad University of Medical SciencesMashhadIran
| | | | | | - Amirian Zahra
- University of Medicine, Trauma and General Surgery Wards, Imam Ali HospitalZahedanIran
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Jin Y, Zhai T, Wang Y, Li J, Wang T, Huang J. Recent advances in liquid chromatography-tandem mass spectrometry for the detection of thyroid hormones and thyroglobulin in clinical samples: A review. J Sep Sci 2024; 47:e2400466. [PMID: 39294846 DOI: 10.1002/jssc.202400466] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Revised: 08/21/2024] [Accepted: 08/24/2024] [Indexed: 09/21/2024]
Abstract
Thyroid hormones (THs), including triiodothyronine (T3), thyroxine (T4), and their metabolites, are essential for regulating development, growth, and energy metabolism. Thyroglobulin (Tg) produced by thyroid follicular cells acts as an essential substrate for TH synthesis. The combination of THs with Tg is a widely used serological laboratory test for thyroid function assessment. Early detection and timely intervention are significant for preventing and managing thyroid disease. In recent years, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for the precise detection of small molecular analytes and steroid hormones in clinical practice as a result of its high sensitivity and specificity. While LC-MS/MS has been increasingly used for detecting THs and Tg recently, its application in clinical practice is still in its early stages. Recent advances in the assessment of thyroid metabolism using LC-MS/MS in clinical samples published during 2004-2023 were reviewed, with a special focus on the use of this technique for quantifying molecules involved in thyroid diseases.
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Affiliation(s)
- Yuting Jin
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
| | - Taiyu Zhai
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
| | - Ying Wang
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
| | - Jiuyan Li
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
| | - Tingting Wang
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
| | - Jing Huang
- Department of Laboratory Medicine, The First Hospital of Jilin University, Changchun, China
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Chandekar KR, Satapathy S, Bal C. Positron Emission Tomography/Computed Tomography in Thyroid Cancer: An Updated Review. PET Clin 2024; 19:131-145. [PMID: 38212213 DOI: 10.1016/j.cpet.2023.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2024]
Abstract
PET/computed tomography (CT) is a valuable hybrid imaging modality for the evaluation of thyroid cancer, potentially impacting management decisions. 18F-fluorodeoxyglucose (FDG) PET/CT has proven utility for recurrence evaluation in differentiated thyroid cancer (DTC) patients having thyroglobulin elevation with negative iodine scintigraphy. Aggressive histologic subtypes such as anaplastic thyroid cancer shower higher FDG uptake. 18F-FDOPA is the preferred PET tracer for medullary thyroid cancer. Fibroblast activation protein inhibitor and arginylglycylaspartic acid -based radiotracers have emerged as promising PET agents for radioiodine refractory DTC patients with the potential for theranostic application.
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Nesari Javan F, Askari E, Shafiei S, Roshanravan V, Aghaei A, Ayati N, Zakavi SR. The Prognostic Power of Preablation Stimulated Thyroglobulin in Children With Differentiated Thyroid Cancer. Endocr Pract 2024; 30:209-217. [PMID: 38092290 DOI: 10.1016/j.eprac.2023.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 11/30/2023] [Accepted: 12/06/2023] [Indexed: 01/06/2024]
Abstract
OBJECTIVE To analyze prognostic factors in children with differentiated thyroid carcinoma (DTC) who have been treated in a single center in the last 27 years. METHODS We studied 126 children (≤18 years old) who have been treated with near-total thyroidectomy followed by radioiodine therapy and thyroid hormone replacement. Follow-up of the patients was done 2, 6, and 12 months after treatment and then by yearly evaluation. Response to treatment was defined according to the American Thyroid Association guidelines. RESULTS Papillary thyroid cancer was the main pathology (93.7%), and 52.4% of the patients had lymph node metastasis at presentation, which was extensive (>5) in 30% of the patients. Distant metastasis was seen in 8.8%. The mean initial dose of I-131 was 74 ± 42.2 MBq/kg. The median follow-up was 59 months and the median time to achieve an excellent response was 29 months. The preablation stimulated thyroglobulin (psTg) level was 202.4 ± 301.8 ng/mL in patients with first-year incomplete response compared with 11.2 ± 17.5 ng/mL in others (P =.001). Furthermore, using logistic regression, the psTg level was found to be the only significant predictor of distant metastasis, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response. Moreover, distant metastasis was more common in boys than in girls, and it took longer time for boys to achieve an excellent response. CONCLUSION The psTg level was the only significant predictor of distant metastases in children with DTC, and psTg ≥ 13.75 ng/mL was the most powerful predictor of first-year incomplete response.
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Affiliation(s)
- Farnaz Nesari Javan
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Emran Askari
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Susan Shafiei
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Vahid Roshanravan
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Atena Aghaei
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Narjess Ayati
- Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Seyed Rasoul Zakavi
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Anderson H, Lim KH, Gull S, Oprean R, Spence K, Cvasciuc T. Predicting clinical outcomes of patients with serum thyroglobulin antibodies after thyroidectomy for differentiated thyroid cancer: a retrospective study from a UK regional center. Minerva Endocrinol (Torino) 2024; 49:60-68. [PMID: 37428110 DOI: 10.23736/s2724-6507.23.03939-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/11/2023]
Abstract
BACKGROUND Twenty-twenty-five percent of patients with differentiated thyroid cancer (DTC) can have elevated thyroglobulin antibodies (TgAb). The study aimed to find any prognostic significance of elevated TgAb during follow-up. METHODS Ten-year retrospective study from a tertiary center including 79 patients with raised TgAb after total/staged thyroidectomy for DTC. We identified patients with stable (7.6%), increasing (15%) and decreasing levels of TgAb (77.2%); groups 1, 2 and 3 respectively. During follow-up we analyzed TgAb in subcategories by TgAb trend (>50% rise, <50% rise, >50% decline, <50% decline, positive to negative/normalization, negative to positive and stable levels), gender, age, surgery, autoimmune disease, histology, RAI uptake, distant metastases, and recurrence. RESULTS The incidence of raised TgAb levels was 33.2%, with female predominance. No connection was identified regarding other parameters. 11.4% had distant metastases. The highest mean maximum levels of TgAb was in group 2 (1918.75 IU/mL) and the lowest in group 3 (412.70 IU/mL). The recurrence rate changed significantly between the 3 groups: 50% in group 1, 75% in group 2, and 25% in group 3 (P=0.002). Recurrence rates decreased to 15% in the subcategory where TgAb became negative/normal from positive (P=0.0001). In patients with a negative to positive TgAb level trend or >50% rise, recurrence rates were 100% (P=0.041) and 70% (P=0.012) respectively. CONCLUSIONS Patients with increasing TgAb levels during follow-up have a higher rate of recurrence, distinctly for those with negative to positive trend and >50% rise in TgAb. These patients need closer follow-up, and TgAb may be used as a dynamic follow-up marker.
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Affiliation(s)
- Hannah Anderson
- Department of Endocrine Surgery, Royal Victoria Hospital, Belfast, UK -
| | - Kah H Lim
- Department of Endocrine Surgery, Royal Victoria Hospital, Belfast, UK
| | - Sadaf Gull
- Department of Endocrine Surgery, Royal Victoria Hospital, Belfast, UK
| | - Raluca Oprean
- Department of Endocrinology, Royal Victoria Hospital, Belfast, UK
| | - Kirsty Spence
- Endocrine Laboratory, Royal Victoria Hospital, Belfast, UK
| | - Titus Cvasciuc
- Department of Endocrine Surgery, Royal Victoria Hospital, Belfast, UK
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Han CL, Lai CT, Reyes AJ, Yang HC, Lu JY, Shih SR, Chen KY, Hoofnagle AN, Yu SL, Bocik W, Hiltke T, Chiu HC, Wan CY, Rodriguez H, Zhang V, Chen YJ. Lessons learned: establishing a CLIA-equivalent laboratory for targeted mass spectrometry assays - navigating the transition from research to clinical practice. Clin Proteomics 2024; 21:12. [PMID: 38389054 PMCID: PMC10882921 DOI: 10.1186/s12014-024-09455-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Accepted: 01/24/2024] [Indexed: 02/24/2024] Open
Abstract
Mass spectrometry (MS) assays offer exceptional capabilities in high multiplexity, specificity, and throughput. As proteomics technologies continue advancements to identify new disease biomarkers, transition of these innovations from research settings to clinical applications becomes imperative. To meet the rigorous regulatory standards of clinical laboratories, development of a clinical protein MS assay necessitates adherence to stringent criteria. To illustrate the process, this project focused on using thyroglobulin (Tg) as a biomarker and an immuno-multiple reaction monitoring (iMRM) MS-based assay as a model for establishing a Clinical Laboratory Improvement Amendments (CLIA) compliant laboratory within the Centers of Genomic and Precision Medicine, National Taiwan University. The chosen example also illustrates the clinical utility of MS assays to complement conventional immunoassay-based methods, particularly in cases where the presence of autoantibodies in 10-30% of patients hinders accuracy. The laboratory design entails a comprehensive coordination in spatial layout, workflow organization, equipment selection, ventilation systems, plumbing, electrical infrastructure, documentation procedures, and communication protocols. Practical aspects of the transformation process, including preparing laboratory facilities, testing environments, instrument validation, assay development and validation, quality management, sample testing, and personnel competency, are discussed. Finally, concordant results in proficiency testing demonstrate the harmonization with the University of Washington Medical Center and the quality assurance of the CLIA-equivalent Tg-iMRM MS assay established in Taiwan. The realization of this model protein MS assay in Taiwan highlights the feasibility of international joint development and provides a detailed reference map to expedite the implementation of more MS-based protein assays in clinical laboratories for patient care.
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Affiliation(s)
- Chia-Li Han
- Master Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
| | - Chi-Ting Lai
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
| | | | - Hao-Chin Yang
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
| | - Jin-Ying Lu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shyang-Rong Shih
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kuen-Yuan Chen
- Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan
| | - Andrew N Hoofnagle
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
| | - Sung-Liang Yu
- Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan
- Centers for Genomics and Precision Medicine, National Taiwan University, Taipei, Taiwan
| | - William Bocik
- Cancer Research Technology Program, Proteome Characterization Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
| | - Tara Hiltke
- Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD, USA
| | - Huan-Chi Chiu
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
| | - Ching-Yi Wan
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan
| | - Henry Rodriguez
- Office of Cancer Clinical Proteomics Research, National Cancer Institute, Rockville, MD, USA
| | - Victoria Zhang
- Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
| | - Yu-Ju Chen
- Institute of Chemistry, Academia Sinica, Taipei, Taiwan.
- Department of Chemistry, National Taiwan University, Taipei, Taiwan.
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Miller JJ, Bohn MK, Higgins V, Nichols M, Mohammed-Ali Z, Henderson T, Selvaratnam R, Sepiashvili L, Adeli K. Pediatric reference intervals for endocrine markers in healthy children and adolescents on the Liaison XL (DiaSorin) immunoassay system. Clin Biochem 2023; 120:110644. [PMID: 37673294 DOI: 10.1016/j.clinbiochem.2023.110644] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 08/29/2023] [Accepted: 08/31/2023] [Indexed: 09/08/2023]
Abstract
OBJECTIVES Prominent physiological changes occurring throughout childhood and adolescence necessitate the consideration of age and sex in biomarker interpretation. Critical gaps exist in pediatric reference intervals (RIs) for specialized endocrine markers, despite expected influence of growth and development. The current study aimed to establish and/or verify RIs for six specialized endocrine markers on a specialized immunoassay system. METHODS Samples were collected from healthy children and adolescents (5 to <19 years) and apparently healthy outpatients (0 to <5 years) as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER). Serum samples were analysed for aldosterone, renin (plasma), thyroglobulin, anti-thyroglobulin, growth hormone, and insulin-like growth factor-1 (IGF-1) on the Liaison XL (DiaSorin) immunoassay platform. RIs (2.5th and 97.5th percentiles) were established for aldosterone, renin, thyroglobulin, anti-thyroglobulin, and growth hormone. Manufacturer-recommended pediatric RIs for IGF-1 were verified. RESULTS Age-specific RIs were established for aldosterone, renin, and thyroglobulin, while no age-specific differences were observed for anti-thyroglobulin or growth hormone. IGF-1 was the only endocrine marker studied that demonstrated significant sex-specific differences. Manufacturer-recommended IGF-1 RIs were verified for children aged 6 to <19 years, while those for children aged 0 to <6 years did not verify. CONCLUSIONS This study marks the first time that pediatric RIs for aldosterone and renin were established in the CALIPER cohort and highlights the dynamic changes that occur in water and sodium homeostasis during the first years of life. Overall, these data will assist pediatric clinical laboratories in test result interpretation and improve clinical decision-making for patients tested using Liaison immunoassays.
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Affiliation(s)
- J J Miller
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada
| | - M K Bohn
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada; CALIPER Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - V Higgins
- DynaLIFE Medical Labs, Edmonton, AB, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada
| | - M Nichols
- Department of Pathology and Laboratory Medicine, Schulich Medicine and Dentistry, Western University, London, ON, Canada
| | | | - T Henderson
- CALIPER Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - R Selvaratnam
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada; Laboratory Medicine Program, Division of Clinical Biochemistry, University Health Network, Toronto, ON, Canada
| | - L Sepiashvili
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada; CALIPER Program, The Hospital for Sick Children, Toronto, ON, Canada
| | - K Adeli
- Department of Laboratory Medicine & Pathobiology, University of Toronto, Canada; CALIPER Program, The Hospital for Sick Children, Toronto, ON, Canada.
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Evans C, Lotz J, Bhandari M, Hellier RT, Wang XY, Lott R, Lackner KJ, Müller R, Kulasingam V. Multi-center evaluation of the highly sensitive Abbott ARCHITECT and Alinity thyroglobulin chemiluminescent microparticle immunoassay. J Clin Lab Anal 2022; 36:e24595. [PMID: 35837992 PMCID: PMC9459248 DOI: 10.1002/jcla.24595] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 05/13/2022] [Accepted: 05/21/2022] [Indexed: 11/16/2022] Open
Abstract
Background Thyroglobulin (Tg) is an essential part for the management of patients with differentiated thyroid carcinoma (DTC) after thyroidectomy. Highly sensitive Tg assays are now established in clinical practice as they facilitate follow‐up of DTC patients. In this study, we evaluated the recently launched highly sensitive Abbott Tg assay for Alinity and ARCHITECT. Methods In this three‐center study, Tg values of 447 routine patient samples, characterized for the presence of anti‐Tg, were measured with the ARCHITECT Tg assay and compared with the Roche Elecsys TgII assay. In addition, a subset of 154 samples was compared also with the Beckman Tg Access assay and another subset (n = 122) with Abbott Tg on the Alinity i analyzer. Results LoQ was verified to be less than or equal to 0.1 ng/ml confirming that the Tg assay on ARCHITECT and Alinity is highly sensitive. Correlation of ARCHITECT, Alinity, and Roche was excellent with a slope between 0.9 and 1.1 and a correlation coefficient >0.98. Correlation to Beckmann Tg was also very good, but the differences in absolute values were significant (slope: 1.477). Conclusions The Abbott Thyroglobulin assay, which is standardized to CRM‐457, demonstrated a high correlation to the Roche and Beckman Tg assays, though good agreement of absolute values was only observed between Abbott and Roche. Strength of correlation and slope were not affected by the presence of anti‐Tg indicating that all assays included in the study have a similar susceptibility to anti‐Tg.
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Affiliation(s)
- Carol Evans
- Department of Medical Biochemistry & Immunology, University Hospital of Wales (UHW), Cardiff, UK
| | - Johannes Lotz
- Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center (UMC), Johannes Gutenberg University Mainz, Mainz, Germany
| | | | - Rowan T Hellier
- Department of Medical Biochemistry & Immunology, University Hospital of Wales (UHW), Cardiff, UK
| | - Xiao Yan Wang
- Department of Clinical Biochemistry, Laboratory Medicine Program, University Health Network (UHN), Toronto, Ontario, Canada
| | - Rosemarie Lott
- Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center (UMC), Johannes Gutenberg University Mainz, Mainz, Germany
| | - Karl J Lackner
- Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center (UMC), Johannes Gutenberg University Mainz, Mainz, Germany
| | | | - Vathany Kulasingam
- Department of Clinical Biochemistry, Laboratory Medicine Program, University Health Network (UHN), Toronto, Ontario, Canada.,Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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Sun P, Zhan J, Chong TH, Li J, Wang C. Endoscopic central lymph node dissection of thyroid cancer via chest-breast approach: results, indications, and strategies. Surg Endosc 2022; 36:4239-4247. [PMID: 35169879 DOI: 10.1007/s00464-021-08758-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Accepted: 09/27/2021] [Indexed: 01/29/2023]
Abstract
BACKGROUND Surgery for thyroid cancer via endoscopic approach was still controversial. Herein, we report the indications, strategies for operative techniques, as well as results for endoscopic central lymph node dissection of thyroid cancer via chest-breast approach (ETCB-CLND). METHODS A retrospective analysis was conducted on the cases of DTC, whom underwent ETCB-CLND from January 2013 to June 2020. Three hundred and twenty-three cases underwent ETCB-CLND (endoscopic group) and 267 cases underwent open surgery (open group). General characteristic, surgical results, thyroglobulin (Tg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the thyroid residual area (RITRA), and radionuclide imaging of suspicious lymph nodes metastasis (RISLNM) were analyzed and compared between the two groups. RESULTS The age of the endoscopic group were lower than that of the open group. The operation time of lobectomy in endoscopic group were longer than that in open group. The gender distribution (P = 0.831), operation time of total thyroidectomy (P = 0.311), intraoperative blood loss (P = 0.672), postoperative hospital stay (P = 0.852), tumor size (P = 0.259), number of cases of lymph node metastasis (P = 0.618), number of dissected lymph nodes (P = 0.681), number of metastatic lymph nodes (P = 0.723), and complications (P = 0.749) did not differ significantly between groups, nor did the surgical range (P = 0.661), Tg at 1 month (P = 0.61) and 1 year (P = 0.67) after surgery, before (P = 0.589) and after (P = 0.593) radioiodine therapy, RAIU-2 h/24 h (P = 0.906/0.582), RATU (P = 0.532), (99mTc 15 min:P = 0.503; 131I 24 h:P = 0.377; 131I 3d:P = 0.919), RISLNM (none: P = 0.887; central: P = 0.630; lateral: P = 0.659). CONCLUSION The rational and normative application of the endoscopic technique in central lymph node dissection of DTC is safe, feasible, and consistent with the principle of radical tumor cure for selected cases by well-trained surgeons.
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Affiliation(s)
- Peng Sun
- Department of Thyroid Surgery, Jinan University First Affiliated Hospital, No. 613 Huangpu Road West, Guangzhou, Guangdong, People's Republic of China.
| | - Jialin Zhan
- Department of Dermatology and STD, Jinan University First Affiliated Hospital, Guangzhou, China
| | - Tsz Hong Chong
- Department of Thyroid Surgery, Jinan University First Affiliated Hospital, No. 613 Huangpu Road West, Guangzhou, Guangdong, People's Republic of China
| | - Jinyi Li
- Department of Thyroid Surgery, Jinan University First Affiliated Hospital, No. 613 Huangpu Road West, Guangzhou, Guangdong, People's Republic of China.
| | - Cunchuan Wang
- Department of General Surgery, Jinan University First Affiliated Hospital, Guangzhou, China
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HOCAOĞLU E, AYDEMİR E, ATEŞ C, MERCAN SARIDAŞ F, NAS OF, İNECİKLİ MF, CANDER S, ÖZ GÜL Ö, ERTÜRK E, ERSOY C. A Single Center Retrospective Analysis of Patients with Recurrent Papillary Thyroid Carcinoma Undergoing Radiofrequency Ablation. TURKISH JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.46310/tjim.1073526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
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Rao KN, Satpute S, Nagarkar NM, Singh A. Revision Thyroid Surgery. Indian J Surg Oncol 2022; 13:199-207. [PMID: 35462649 PMCID: PMC8986899 DOI: 10.1007/s13193-021-01467-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 10/19/2021] [Indexed: 11/28/2022] Open
Abstract
The incidence of recurrence in well-differentiated thyroid malignancies range from 10 to 30%. It is estimated that about 31-46% of patients with differentiated thyroid cancer will have the persistent disease and 1.2-6.8% will have structural recurrences during post-operative monitoring, depending on the initial therapy and prognostic variables. It is challenging to decide on treatment versus active monitoring following repeated or persistent tumour detection. The biological factors of the tumour and the patient guide us in the overall decision-making. Revision thyroid surgery is technically challenging. The morbidity encountered during the revision surgery is related to the anatomy of the region undergoing dissection, the degree of fibrosis and scarring from prior surgery and the operating surgeon's experience. Successful comprehensive management of revision thyroid surgery needs a multi-disciplinary approach. This review article highlights the definition, indications for revision surgery, identification of recurrent disease, management of parathyroid and recurrent laryngeal nerves with neuromonitoring.
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Affiliation(s)
- Karthik Nagaraja Rao
- Department of Head and Neck Oncology, All India Institute of Medical Sciences, Raipur, India
| | - Satish Satpute
- Department of Otolaryngology and Head Neck Surgery, All India Institute of Medical Sciences, Raipur, India
| | | | - Ambesh Singh
- Department of Head and Neck Oncology, All India Institute of Medical Sciences, Raipur, India
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Karmakar S, Purkayastha K, Dhar R, Pethusamy K, Srivastava T, Shankar A, Rath G. The issues and challenges with cancer biomarkers. J Cancer Res Ther 2022; 19:S20-S35. [PMID: 37147979 DOI: 10.4103/jcrt.jcrt_384_22] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
A biomarker is a measurable indicator used to distinguish precisely/objectively either normal biological state/pathological condition/response to a specific therapeutic intervention. The use of novel molecular biomarkers within evidence-based medicine may improve the diagnosis/treatment of disease, improve health outcomes, and reduce the disease's socio-economic impact. Presently cancer biomarkers are the backbone of therapy, with greater efficacy and better survival rates. Cancer biomarkers are extensively used to treat cancer and monitor the disease's progress, drug response, relapses, and drug resistance. The highest percent of all biomarkers explored are in the domain of cancer. Extensive research using various methods/tissues is carried out for identifying biomarkers for early detection, which has been mostly unsuccessful. The quantitative/qualitative detection of various biomarkers in different tissues should ideally be done in accordance with qualification rules laid down by the Early Detection Research Network (EDRN), Program for the Assessment of Clinical Cancer Tests (PACCT), and National Academy of Clinical Biochemistry. Many biomarkers are presently under investigation, but lacunae lie in the biomarker's sensitivity and specificity. An ideal biomarker should be quantifiable, reliable, of considerable high/low expression, correlate with the outcome progression, cost-effective, and consistent across gender and ethnic groups. Further, we also highlight that these biomarkers' application remains questionable in childhood malignancies due to the lack of reference values in the pediatric population. The development of a cancer biomarker stands very challenging due to its complexity and sensitivity/resistance to the therapy. In past decades, the cross-talks between molecular pathways have been targeted to study the nature of cancer. To generate sensitive and specific biomarkers representing the pathogenesis of specific cancer, predicting the treatment responses and outcomes would necessitate inclusion of multiple biomarkers.
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Sun P, Mak TK, Li J, Wang C. Endoscopic Left Central Lymph Node Dissection of Thyroid Cancer: Safe, Feasible, and Relatively Easy. Surg Innov 2021; 28:747-753. [PMID: 33830818 DOI: 10.1177/1553350620983640] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Purpose. The purpose of this study was to explore the feasibility of left central lymph node dissection (CLND) in endoscopic thyroidectomy via chest-breast approach (ETCB). Methods. Retrospective analysis of 57 cases of left CLND (group A) via ETCB, 35 cases of open left CLND (group B), and 90 cases of right CLND via ETCB (Group C) were performed from October 2014 to October 2019. Surgical data, complications, and follow-up data were compared among group A and group B, group A and group C, respectively. Results. There were no significant differences between group A and group B in intraoperative blood loss, tumor size, lymph node (LN) metastasis rate, dissected LN number, metastatic LN number, serum thyroglobulin (sTg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the residual area (RITRA), and radionuclide imaging of suspicious lymph node metastasis (RISLNM). There were no significant differences between group A and group C in age, operation time, intraoperative blood loss, postoperative hospital stay, tumor size, LN metastasis rate, dissected LN number, metastatic LN number, hypoparathyroidism, sTg, RAIU, RATU, RITRA, and RISLNM. There were 5 cases of temporary recurrent laryngeal nerve (RLN) palsy and 1 case of recurrence in group C. Besides, 1 case of lymphatic leakage was in group A. Conclusion. For selected cases, endoscopic left CLND is safe, feasible, efficient, and more easier than endoscopic right CLND.
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Affiliation(s)
- Peng Sun
- Department of Thyroid Surgery, 162698Jinan University First Affiliated Hospital, Guangzhou, China
| | - Tsz Kin Mak
- Department of General Surgery, 162698Jinan University First Affiliated Hospital, Guangzhou, China
| | - Jinyi Li
- Department of Thyroid Surgery, 162698Jinan University First Affiliated Hospital, Guangzhou, China
| | - Cunchuan Wang
- Department of General Surgery, 162698Jinan University First Affiliated Hospital, Guangzhou, China
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Zahra HO, Omran GA, Gewely AG, Eldehn AF, Abdo W, Elmahallawy EK, Okda TM. Prognostic Value of Serum Thyroglobulin and Anti-Thyroglobulin Antibody in Thyroid Carcinoma Patients following Thyroidectomy. Diagnostics (Basel) 2021; 11:diagnostics11112080. [PMID: 34829426 PMCID: PMC8622548 DOI: 10.3390/diagnostics11112080] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 10/27/2021] [Accepted: 10/29/2021] [Indexed: 11/26/2022] Open
Abstract
Well-differentiated thyroid cancer (WDTC) is a malignant head and neck tumor with a very high incidence. Thyroidectomized WDTC patients have been referred to nuclear medicine for radioactive iodine (RAI) ablation therapy and/or annual follow-up with diagnostic whole-body imaging. Serum thyroglobulin (TG) and thyroglobulin antibodies (TGAb) are biochemical tumor markers used to monitor WDTC. A global rise in the prevalence of WDTC is increasing the number of thyroidectomized patients requiring lifelong monitoring for persistent or recurrent diseases. The present study aimed to identify the most successful prognostic factors in well-defined thyroid carcinoma patients following total thyroidectomy and RAI therapy, followed by an estimation of the cutoff value of TG and TGAb. In this context, a total of 100 subjects were recruited and classified as follows: 60 thyroid carcinoma patients underwent total thyroidectomy and successful RAI therapy, while 40 normal healthy individuals matched for age, sex, and socioeconomic status constituted the control group. Interestingly, the levels of TG did not differ significantly between the relapsed and non-relapsed cases, but the levels of TGAb differed significantly between the relapsed and non-relapsed cases. Collectively, TG and TGAb are considered the most successful prognostic factors in well-defined thyroid carcinoma patients after total thyroidectomy and RAI therapy. The present study also concluded that the TGAb determination was better than that of the TG level, with a cutoff value of 10 ng/mL. These findings provide baseline information for follow-up and lifelong monitoring of thyroidectomized WDTC patients. Further research is warranted to explore more about serum TG and TGAb in thyroid carcinoma patients on a larger scale.
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Affiliation(s)
- Hashem O. Zahra
- Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (H.O.Z.); (G.A.O.); (T.M.O.)
| | - Gamal A. Omran
- Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (H.O.Z.); (G.A.O.); (T.M.O.)
| | - Ahmed G. Gewely
- Department of Oncology Medicine, Faculty of Medicine, Alexandria University, Alexandria 21111, Egypt;
| | - Ahmed Fathy Eldehn
- Department of Otorhinolaryngology, Kasr Al-Ainy Medical School, Cairo University, Cairo 12613, Egypt;
| | - Walied Abdo
- Department of Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 35516, Egypt;
| | - Ehab Kotb Elmahallawy
- Department of Zoonoses, Faculty of Veterinary Medicine, Sohag University, Sohag 82524, Egypt
- Correspondence:
| | - Tarek M. Okda
- Department of Biochemistry, Faculty of Pharmacy, Damanhour University, Damanhour 22511, Egypt; (H.O.Z.); (G.A.O.); (T.M.O.)
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Kim SY, Kim YI, Kim HJ, Chang H, Kim SM, Lee YS, Kwon SS, Shin H, Chang HS, Park CS. New approach of prediction of recurrence in thyroid cancer patients using machine learning. Medicine (Baltimore) 2021; 100:e27493. [PMID: 34678881 PMCID: PMC8542129 DOI: 10.1097/md.0000000000027493] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 09/23/2021] [Indexed: 01/05/2023] Open
Abstract
Although papillary thyroid cancers are known to have a relatively low risk of recurrence, several factors are associated with a higher risk of recurrence, such as extrathyroidal extension, nodal metastasis, and BRAF gene mutation. However, predicting disease recurrence and prognosis in patients undergoing thyroidectomy is clinically difficult. To detect new algorithms that predict recurrence, inductive logic programming was used in this study.A total of 785 thyroid cancer patients who underwent bilateral total thyroidectomy and were treated with radioiodine were selected for our study. Of those, 624 (79.5%) cases were used to create algorithms that would detect recurrence. Furthermore, 161 (20.5%) cases were analyzed to validate the created rules. DELMIA Process Rules Discovery was used to conduct the analysis.Of the 624 cases, 43 (6.9%) cases experienced recurrence. Three rules that could predict recurrence were identified, with postoperative thyroglobulin level being the most powerful variable that correlated with recurrence. The rules identified in our study, when applied to the 161 cases for validation, were able to predict 71.4% (10 of 14) of the recurrences.Our study highlights that inductive logic programming could have a useful application in predicting recurrence among thyroid patients.
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Affiliation(s)
- Soo Young Kim
- Department of Surgery, Ajou University College of Medicine, Suwon, Korea
| | | | - Hee Jun Kim
- Department of Surgery, CHA Ilsan Medical Center, Goyang-si, Korea
| | - Hojin Chang
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, Korea
| | - Seok-Mo Kim
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, Korea
| | - Yong Sang Lee
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, Korea
| | - Soon-Sun Kwon
- Department of Mathematics/AI & Data Science, Ajou University, Suwon, Korea
| | - Hyunjung Shin
- Department of Industrial Engineering, Ajou University, Suwon, Korea
| | - Hang-Seok Chang
- Department of Surgery, Thyroid Cancer Center, Gangnam Severance Hospital, Institute of Refractory Thyroid Cancer, Yonsei University College of Medicine, Seoul, Korea
| | - Cheong Soo Park
- Department of Surgery, CHA Ilsan Medical Center, Goyang-si, Korea
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16
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Guastapaglia L, Kasamatsu TS, Nakabashi CCD, Camacho CP, Maciel RMB, Vieira JGH, Biscolla RPM. The role of a new polyclonal competitive thyroglobulin assay in the follow-up of patients with differentiated thyroid cancer with structural disease but low levels of serum thyroglobulin by immunometric and LC-MS/MS methods. Endocrine 2021; 72:784-790. [PMID: 33222120 DOI: 10.1007/s12020-020-02526-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 10/13/2020] [Indexed: 10/22/2022]
Abstract
PURPOSE The aims of this study were to assess the role of an in-house competitive thyroglobulin assay (Tg-c) in the follow-up of metastatic differentiated thyroid carcinoma (DTC) patients who presented underestimated Tg measurements by immunometric assays (Tg-IMA) and to compare the results with IMA and LC-MS/MS Tg methods. METHODS This prospective study included 40 patients. Twenty-one with metastatic disease: 14 had Tg-IMA levels inappropriately low or undetectable (eight patients with positive and six with borderline TgAb) and seven had high Tg-IMA levels. Nineteen had an excellent response to therapy. The competitive assay employs a polyclonal antibody produced in rabbits immunized with human Tg, Tg labeled with biotin, and for the solid phase separation, a monoclonal anti-rabbit IgG antibody adsorbed to microtiter plates. RESULTS All 14 patients with structural disease and underestimated levels of Tg-IMA presented detectable Tg-c levels. The median Tg-c level in the group with positive TgAb was 183 µg/L (range: 22-710 µg/L), and 58 µg/L (range 23-148 µg/L) in the borderline TgAb group. The levels of Tg-LC-MS/MS were detectable in some patients (range < 0.5-18 µg/L). All seven patients with high Tg-IMA presented also high levels of Tg-c. Only 2/19 patients with excellent response had Tg-c levels above the functional sensitivity. CONCLUSIONS The competitive assay was able to detect Tg in all patients, even in the presence of serum TgAb, and may be an option in patients with underestimated Tg-IMA and relevant structural disease.
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Affiliation(s)
- Leila Guastapaglia
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Teresa S Kasamatsu
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
| | - Claudia Cristina D Nakabashi
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
- Fleury Medicina e Saúde, São Paulo, Brazil
| | - Cléber P Camacho
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
- Molecular Innovation and Biotechnology Laboratory, Medical Postgraduation Division, Universidade Nove de Julho (Uninove), São Paulo, Brazil
| | - Rui M B Maciel
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
- Fleury Medicina e Saúde, São Paulo, Brazil
| | - José Gilberto H Vieira
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil
- Fleury Medicina e Saúde, São Paulo, Brazil
| | - Rosa Paula M Biscolla
- Thyroid Diseases Center and Laboratory of Molecular and Translational Endocrinology, Division of Endocrinology, Department of Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil.
- Fleury Medicina e Saúde, São Paulo, Brazil.
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Nabhan F, Dedhia PH, Ringel MD. Thyroid cancer, recent advances in diagnosis and therapy. Int J Cancer 2021; 149:984-992. [PMID: 34013533 DOI: 10.1002/ijc.33690] [Citation(s) in RCA: 96] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2020] [Revised: 05/07/2021] [Accepted: 05/10/2021] [Indexed: 12/23/2022]
Abstract
Over the past several decades, the approach to the diagnosis and management of patients with follicular cell-derived thyroid cancer has evolved based on improved classification of patients better matching clinical outcomes, as well as advances in imaging, laboratory, molecular technologies and knowledge. While thyroid surgery, radioactive iodine therapy and TSH suppression remain the mainstays of treatment, this expansion of knowledge has enabled de-escalation of therapy for individuals diagnosed with low-risk well-differentiated thyroid cancer; better definition of treatment choices for patients with more aggressive disease; and improved ability to optimize treatments for patients with persistent and/or progressive disease. Most recently, the advancement of knowledge regarding the molecular aspects of thyroid cancer has improved thyroid cancer diagnosis and has enabled individualized therapeutic options for selected patients with the most aggressive forms of the disease. Guidelines from multiple societies across the world reflect these changes, which focus on taking a more individualized approach to clinical management. In this review, we discuss the current more personalized approach to patients with follicular cell-derived thyroid cancer and point toward areas of future research still needed in the field.
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Affiliation(s)
- Fadi Nabhan
- Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.,Cancer Biology Program, Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
| | - Priya H Dedhia
- Cancer Biology Program, Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA.,Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Matthew D Ringel
- Division of Endocrinology, Diabetes, and Metabolism, Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.,Cancer Biology Program, Arthur G. James Comprehensive Cancer Center, Columbus, Ohio, USA
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Clinical Indications for Treatment with Multi-Kinase Inhibitors in Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Cancers (Basel) 2021; 13:cancers13092279. [PMID: 34068664 PMCID: PMC8126102 DOI: 10.3390/cancers13092279] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2021] [Revised: 05/05/2021] [Accepted: 05/07/2021] [Indexed: 12/21/2022] Open
Abstract
Differentiated thyroid cancer is usually a slow-growing disease, even if the patients develop distant metastasis. For recurrent or metastatic disease, radioactive iodine therapy is a standard treatment. However, the disease gradually progresses in some of the patients and can ultimately develop into life-threatening conditions. For patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), multi-kinase inhibitors (MKIs) including sorafenib and lenvatinib prolonged progression-free survival compared with placebo in pivotal randomized phase 3 trials, although the benefit in overall survival has not been clearly confirmed, possibly because the patients who received placebo were permitted to cross-over to lenvatinib upon disease progression. Moreover, the adverse events related to MKIs were not negligible. Therefore, the optimal timing of MKI initiation has long been controversial, and physicians should consider various patient and disease factors. Herein, we comprehensively review the clinical factors that can be helpful in determining the initiation of MKIs for patients with RR-DTC.
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Silaghi CA, Lozovanu V, Silaghi H, Georgescu RD, Pop C, Dobrean A, Georgescu CE. The Prognostic Value of MicroRNAs in Thyroid Cancers-A Systematic Review and Meta-Analysis. Cancers (Basel) 2020; 12:E2608. [PMID: 32932713 PMCID: PMC7563665 DOI: 10.3390/cancers12092608] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2020] [Revised: 08/26/2020] [Accepted: 09/03/2020] [Indexed: 02/06/2023] Open
Abstract
Thyroid cancer (TC) includes various phenotypes, from indolent to highly aggressive cancer. The limitations of the current prognostication systems to predict the recurrence risk and the variability in expression of the genes involved in the thyroid carcinogenesis uncover the need for new prognostic biomarkers by taking into account potential epigenetic differences. We aimed to summarize the current knowledge regarding the prognostic impact of microRNAs (miRNAs) in TC. A literature search was conducted in PubMed, Embase, Scopus, and Web of Science databases. Both upregulated and downregulated miRNAs are significantly correlated with worse overall survival (hazard ratio (HR) = 5.94, 95% CI: 2.73-12.90, p < 0.001; HR = 0.51, 95% CI: 0.26-0.96, p = 0.048) disease/recurrence-free survival (HR = 1.58, 95% CI: 1.08-2.32, p = 0.003; HR = 0.37, 95%, CI: 0.24-0.60, p < 0.001). Sensitivity analysis revealed a significant association between the higher expression of miR-146b, miR-221, and miR-222 and the recurrence of papillary TC (OR = 9.11, 95% CI 3.00 to 27.52; p < 0.001; OR = 3.88, 95% CI 1.34 to 11.19, p < 0.001; OR = 6.56, 95% CI 2.75 to 15.64, p < 0.001). This research identified that miR-146b, miR-221, and miR-222 could serve as potential prognostic biomarkers in TC, particularly in PTC. Further studies are needed to strengthen these findings and sustain its clinical applicability.
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Affiliation(s)
- Cristina Alina Silaghi
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Victor Babes Street 8, 400012 Cluj-Napoca, Romania; (C.A.S.); (V.L.); (C.E.G.)
| | - Vera Lozovanu
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Victor Babes Street 8, 400012 Cluj-Napoca, Romania; (C.A.S.); (V.L.); (C.E.G.)
| | - Horatiu Silaghi
- Department of Surgery V, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Victor Babes Street 8, 400012 Cluj-Napoca, Romania;
| | - Raluca Diana Georgescu
- International Institute for The Advanced Studies of Psychotherapy and Applied Mental Health, Babeș-Bolyai University, Republicii Street 37, 400015 Cluj-Napoca, Romania
| | - Cristina Pop
- Department of Pharmacology, Physiology, and Pathophysiology, Faculty of Pharmacy, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Louis Pasteur Street 6A, 400349 Cluj-Napoca, Romania
| | - Anca Dobrean
- Department of Clinical Psychology and Psychotherapy, Babeş-Bolyai University, Republicii Street 37, 400015 Cluj-Napoca, Romania;
| | - Carmen Emanuela Georgescu
- Department of Endocrinology, “Iuliu Hatieganu” University of Medicine and Pharmacy Cluj-Napoca, Victor Babes Street 8, 400012 Cluj-Napoca, Romania; (C.A.S.); (V.L.); (C.E.G.)
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Endoscopic Lateral Neck Dissection (IIA, IIB, III, and IV) Using a Breast Approach: Outcomes From a Series of the First 24 Cases. Surg Laparosc Endosc Percutan Tech 2020; 31:66-70. [PMID: 32925819 DOI: 10.1097/sle.0000000000000849] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/10/2020] [Indexed: 01/13/2023]
Abstract
INTRODUCTION In order to avoid large neck scar caused by conventional lateral neck dissection. We have explored and introduced endoscopic lateral neck dissection (IIA, IIB, III, and IV) using a breast approach. Now, we summarized and shared the outcomes of the first 24 cases. MATERIALS AND METHODS All the patients were treated in our institute from January 2017 to May 2018, and followed-up for more than 1 year. The details of patients and this technique have been summarized and analyzed retrospectively. RESULTS A series of first 24 cases were successfully managed with this technique, and no cases were converted to an open approach. Among these 24 patients, levels III + IV dissection had been performed in 6 patients and levels II+III+IV dissection had been performed in 18 patients. The mean age, body mass index, and sex were 39.3±10.5 years old, 24.1±3.5, and 2 male/22 female, respectively. The average operative time of total operation and lateral neck dissection was 238.8±37.2 minutes and 128.8±21.1 minutes, respectively. The mean dissected lateral lymph nodes were 5.9±2.2 (level II) in 18 cases and 15.9±3.9 (levels III+IV) in 24 cases. In addition, with no severe complications to date, such as asphyxia, main nerves injury (cervical plexus, vagus nerve, etc.), and permanent hypoparathyroidism, nor permanent recurrent laryngeal nerve injury, and so on. However, unexpectedly, had some mild and common complications like transient hypocalcemia in 4 cases (16.67%), transient horse 1 case (4.2%), controllable lymphatic leakage in 2 cases (8.3%), and controllable jugular vein injury in 2 cases (8.3%). One year after the operation, 1 case found lung metastasis but no local recurrence. In other 23 patients, no recurrence/metastasis and the average of serum thyroglobulin is 3.2±3.8 ng/mL. CONCLUSIONS This technique can yield adequate oncological dissection for selected patients. Endoscopic thyroidectomy along with lateral neck dissection using a breast approach may provide an option for selected patients who favor avoiding a visible neck incision.
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The Transareola Endoscopic Approach Yields Adequate Oncological Dissection as Open Approach in the Treatment of Papillary Thyroid Carcinoma. Surg Laparosc Endosc Percutan Tech 2019; 29:489-492. [PMID: 31584497 DOI: 10.1097/sle.0000000000000729] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVE This study aimed to evaluate and discuss whether the transareola endoscopic surgery has similar outcome outcomes to open surgery in the treatment of papillary thyroid carcinoma (PTC). METHOD A total of 102 patients with PTC were enrolled in this study. Among them, 53 patients were treated by transareola endoscopic surgery (endoscopic group) and 49 patients were treated by open surgery (open group). Some specific factors, including thyroglobulin (Tg), radioactive iodine uptake (RAIU), postoperative nuclide imaging in thyroid area, postoperative nuclide imaging of lymph nodes suspicious for metastasis (PNILNSM), etc. were analyzed and compared between the 2 groups. RESULTS There were no significant differences between the 2 groups regarding body mass index (22.9±3.4 vs. 24.0±3.3, P=0.103), operation time (173.3±43.2 vs. 158.8±47.9 min, P=0.110), intraoperative blood loss (41.8±19.4 vs. 35.8±31.0 mL, P=0.251, P=0.251), tumor diameter (19.0±6.8 vs. 20.2±7.2 mm, P=0.400), and overall complications (11.3% vs. 10.2%, P=0.868). No significant difference was found in the specific factors between the 2 groups concerning RAIU-2h/24h (2.44±1.34 vs. 2.58±1.65%/2.83±3.75 vs. 2.35±3.44%, P=0.646/ P=0.506), number of dissected lymph nodes (4.4±1.4 vs. 4.6±1.5, P=0.595), Tg before radioiodine therapy (4.46±5.50 vs. 5.60±8.36; P=0.495), Tg after radioiodine therapy (1.03±1.93 vs. 1.11±1.61, P=0.812, P=0.812), postoperative nuclide imaging in thyroid area (1.76±1.50 vs. 2.19±1.85 cm, P=0.195), PNILNSM before radioiodine (none: 79.2% vs. 83.7%, P=0.566; central: 17.0% vs. 12.2%, P=0.653; lateral: 1.9% vs. 4.1%, P=0.450; central+lateral: 1.9% vs. 0%, P=1.000), and PNILNSM after radioiodine (none: 94.3% vs. 95.9%, P=0.111; central: 3.8% vs. 2.0%, P=1.000; lateral: 0 vs. 2.0%, P=0.480; central+lateral: 1.9% vs. 0%, P=1.000). CONCLUSIONS Transareola endoscopic total thyroidectomy and central lymph nodes dissection are safe and effective. According to the evaluated postoperative specific factors, this technique achieves similar outcomes to open surgery in selected patients with PTC.
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Rubio-Gómez C, Rojas W, Polo JF, Alvarado A, Chaparro D, Torres-Tobar L, Gutiérrez-Castañeda LD. Absence of RET/PTC1 rearrangement in a sample of Colombian individuals with papillary thyroid carcinoma. REVISTA DE LA FACULTAD DE MEDICINA 2019. [DOI: 10.15446/revfacmed.v67n4.64560] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Introduction: Papillary thyroid carcinoma is the most common endocrine neoplasm; therefore, markers with possible prognostic utility have been evaluated.Objective: To analyze the presence of RET/PTC1 rearrangement, lymphocytic thyroiditis and associated clinical features in patients with papillary thyroid cancer treated at the Hospital de San José in Bogotá, Colombia.Materials and methods: Clinical records of patients with complete thyroidectomy and diagnosis of papillary cancer were retrospectively identified. RNA was extracted from tumor tissue, and cDNA was obtained using inverse transcriptase to detect the rearrangement of the RET/PTC1 gene by means of qPCR.Results: 55 patients with papillary thyroid cancer were selected; 93% were females, and the mean age was 45.8 years. The most frequent histological variant was classic (49%). A relationship was found between lymphocytic thyroiditis and the number of positive nodes in segments other than central draining, as well as thyroiditis and antithyroid antibody value. No RET/PTC1 rearrangement expression was found.Conclusions: A relationship between lymphocytic thyroiditis and the number of positive nodes in segments other than central draining was found. Other molecular markers should be searched to differentiate the prognosis of these patients.
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Qu R, Li J, Yang J, Sun P, Gong J, Wang C. Treatment of differentiated thyroid cancer: can endoscopic thyroidectomy via a chest-breast approach achieve similar therapeutic effects as open surgery? Surg Endosc 2018; 32:4749-4756. [PMID: 29761277 DOI: 10.1007/s00464-018-6221-1] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2017] [Accepted: 05/09/2018] [Indexed: 01/08/2023]
Abstract
BACKGROUND An analysis of some special factors was performed to further evaluate and discuss whether endoscopic surgery and traditional open surgery have similar therapeutic outcomes for differentiated thyroid cancer (DTC). METHODS A retrospective study was performed on 76 patients undergoing surgery to treat DTC. Forty patients were treated by endoscopic thyroidectomy via the chest-breast approach (endoscopic group) and thirty-six patients were treated by open surgery (open group). Serum thyroglobulin (sTg), radioactive iodine uptake (RAIU), radioactive technetium uptake (RATU), radionuclide imaging of the thyroid residual area (RITRA), radionuclide imaging of suspicious lymph nodes metastasis (RISLNM), and other general indexes were analyzed and compared between the two groups. RESULTS All surgeries were successfully completed in both groups. There were no significant differences between the two groups regarding gender (P = 0.120), postoperative hospital stay (P = 0.766), operation time (P = 0.065), intra-operative blood loss (P = 0.064), tumor diameter (P = 0.059), and overall complications (P = 0.828). Among these complications, there was no significant difference between the two approaches in transient hypoparathryoidism (P = 0.771), transient recurrent laryngeal injury (P = 0.474) and serious neck skin traction sensation (2.5 vs. 0%, P = 1.000). Age and body mass index were lower in the endoscopic group than the open group (P < 0.05). No significant difference was found in special factors between two groups concerning surgical range (P = 0.872), RAIU-2 h/24 h (P = 0.660/P = 0.955), RATU (P = 0.116), number of dissected lymph nodes (P = 0.157), sTg before radioiodine therapy (P = 0.188), sTg after radioiodine therapy (P = 0.159), RITRA at different time points (99mTc 15 min: P = 0.144; 131I 24 h: P = 0.243; 131I 72 h: P = 0.624) and RISLNM (none: P = 0.805; central: P = 0.744; lateral: P = 1.000; central + lateral: P = 0.958). CONCLUSION Endoscopic total thyroidectomy and central lymph nodes dissection via a chest-breast approach are safe and effective. Through the detection of the postoperative special factors, a well-trained surgeon can achieve similar therapeutic results for selected patients with DTC, compared with open surgery.
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Affiliation(s)
- Rui Qu
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
- Department of Thyroid Surgery, First People's Hospital of Zunyi City, Zunyi, 563000, China
| | - Jinyi Li
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Jingge Yang
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Peng Sun
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Jian Gong
- Department of Nuclear Medicine, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China
| | - Cunchuan Wang
- Department of General Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
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Côrtes MCS, Rosario PW, Oliveira LFF, Calsolari MR. Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective Study. Thyroid 2018; 28:229-235. [PMID: 29325506 DOI: 10.1089/thy.2017.0350] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND Interference of antithyroglobulin antibodies (TgAb) with serum thyroglobulin (Tg) can occur even at detectable TgAb concentrations below the reference limit (borderline TgAb). Thus, borderline TgAb is considered as TgAb positivity in patients with thyroid cancer. This prospective study evaluated patients with papillary thyroid carcinoma with undetectable Tg and normal neck ultrasonography (US) after total thyroidectomy and ablation with 131I, and compared tumor persistence/recurrence and long-term Tg and TgAb behavior in those with borderline versus undetectable TgAb. METHODS A total of 576 patients were evaluated, divided into two groups: group A with undetectable TgAb (n = 420), and group B with borderline TgAb (n = 156). RESULTS Groups A and B were similar in terms of patient and tumor characteristics. The time of follow-up ranged from 24 to 120 months. During follow-up, 11 (2.6%) patients in group A and 5 (3.2%) in group B developed a recurrence (p = 0.77). In group A, recurrences occurred in 9/390 patients who continued to have undetectable TgAb and in 1/9 patients who progressed to borderline TgAb. In group B, recurrences were detected in 1/84 patients who progressed to have undetectable TgAb, in 1/45 who still had borderline TgAb, and in 3/12 who developed elevated TgAb. In the presence of Tg levels <0.2 ng/mL, recurrences were detected in 2/486 patients with undetectable TgAb, in 0/67 with borderline TgAb, and in 3/12 with elevated TgAb. The results of post-therapy whole-body scanning (RxWBS) of 216 patients with Tg ≤0.2 ng/mL and normal US at the time of ablation were also analyzed. In low-risk patients, none of the 40 patients with borderline TgAb and none of the 94 with undetectable TgAb exhibited ectopic uptake on RxWBS. In intermediate-risk patients, lymph node metastases were detected by RxWBS in 1/25 (4%) with borderline TgAb and in 2/57 (3.5%) with undetectable TgAb. CONCLUSIONS The results suggest that among low- or intermediate-risk patients with undetectable Tg and normal US after thyroidectomy, those with borderline TgAb are at no greater risk of tumor persistence or recurrence than those with undetectable TgAb. When undetectable Tg levels persist, recurrence should be suspected in the case of a TgAb elevation above the reference limit.
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Affiliation(s)
| | - Pedro Weslley Rosario
- 1 Postgraduation Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
- 2 Endocrinology Service, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
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25
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Giovanella L, Imperiali M, Verburg FA, Trimboli P. Early post-treatment risk stratification of differentiated thyroid cancer: comparison of three high-sensitive Tg assays. Eur J Endocrinol 2018; 178:75-82. [PMID: 29142052 DOI: 10.1530/eje-17-0663] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 09/28/2017] [Accepted: 10/12/2017] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To assess the diagnostic performance of three high-sensitive assays in a cohort of TgAb-negative and TgAb-positive differentiated thyroid cancer (DTC) patients. DESIGN Retrospective study on prospectively selected DTC patients. METHODS Serum samples from 154 DTC patients were obtained 6-12 months after radioiodine ablation and tested by Beckman, Roche, BRAHMS Tg and TgAb assays, respectively. Receiver operating characteristics curves for Tg were plotted using outcome over time as benchmark and assay-specific Tg thresholds were obtained for TgAb-negative and TgAb-positive patients. RESULTS The frequency of positive TgAb was 21, 20 and 20% for Beckman, Roche and BRAHMS, respectively. In TgAb-negative patients, clinical sensitivities and specificities of 100% and 85-95%, respectively, were observed across all assays. In TgAb-positive patients, clinical sensitivities and specificities of 80-100% and 92-96%, respectively, were observed using lower thresholds than in patients without TgAb. CONCLUSIONS Adopting appropriate thresholds, lower than those for TgAb-negative patients, is possible to reliably follow TgAb-positive patients using highly sensitive Tg assays.
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Affiliation(s)
- Luca Giovanella
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
- Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Mauro Imperiali
- Department of Laboratory Medicine, Ente Ospedaliero Cantonale, Bellinzona, Switzerland
| | - Frederik A Verburg
- Department of Nuclear Medicine, Marburg University Hospital, Marburg, Germany
| | - Pierpaolo Trimboli
- Department of Nuclear Medicine and Thyroid Centre, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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26
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Li YR, Tseng CP, Hsu HL, Lin HC, Chen YA, Chen ST, Liou MJ, Lin JD. Circulating epithelial cells as potential biomarkers for detection of recurrence in patients of papillary thyroid carcinoma with positive serum anti-thyroglobulin antibody. Clin Chim Acta 2017; 477:74-80. [PMID: 29229463 DOI: 10.1016/j.cca.2017.12.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2017] [Revised: 11/28/2017] [Accepted: 12/07/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Serum thyroglobulin (Tg) is not a reliable tumor marker for monitoring disease status after treatment in patients with papillary thyroid carcinoma (PTC) with positive anti-thyroglobulin antibody (TgAb). The aim of this study was to evaluate the clinical role of circulating epithelial cells (CECs) in PTC patients with positive serum TgAb and undetectable serum Tg. METHODS A pilot study was performed to evaluate CECs in 25 PTC patients with positive serum TgAb and undetectable serum Tg. CECs were isolated and enriched from peripheral blood with a negative selection system PowerMag. Immunofluorescence staining with anti-epithelial cell adhesion molecule (anti-EpCAM) and anti-thyroid stimulating hormone receptor (anti-TSHR) antibodies were used to define EpCAM+-CECs and TSHR+-CECs. After CECs testing, 25 patients were classified into two groups: recurrence group (n=7) and remission group (n=18) based on biopsy or imaging studies. The diagnostic accuracy and cutoff points of EpCAM+-CECs and TSHR+-CECs were evaluated using receiver operating characteristic (ROC) curves. The optimal cut-off values of CECs were determined by the Youden index (sensitivity+specificity-1). RESULTS The median numbers of EpCAM+-CECs (72.5 vs. 10.75) and TSHR+-CECs (54 vs. 5.25) were significantly increased in recurrence group compared to remission group. The area under the curve (AUC) showed good performance of EpCAM+-CECs (0.937) and TSHR+-CECs (0.825) to discriminate between recurrence and remission. The cut-off value for EpCAM+-CECs and TSHR+-CECs were set at 48cells/ml and 10cells/ml, respectively and showed a sensitivity (EpCAM+-CECs: 85.7%; TSHR+-CECs: 85.7%) and a specificity (EpCAM+-CECs: 100%; TSHR+-CECs: 77.8%) in predicting the recurrence. CONCLUSIONS Our study suggests CECs testing could be a potential biomarker to identify recurrence in PTC patients with positive serum TgAb and undetectable serum Tg.
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Affiliation(s)
- Yan-Rong Li
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan
| | - Ching-Ping Tseng
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taiwan; Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taiwan; Molecular Medicine Research Center, Chang Gung University, Taiwan; Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taiwan
| | - Hsueh-Ling Hsu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taiwan
| | - Hung-Chih Lin
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taiwan
| | - Yi-An Chen
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taiwan
| | - Szu-Tah Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan
| | - Miaw-Jene Liou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan
| | - Jen-Der Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taiwan.
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27
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de Meer SGA, Vorselaars WMCM, Kist JW, Stokkel MPM, de Keizer B, Valk GD, Borel Rinkes IHM, Vriens MR. Follow-up of patients with thyroglobulin-antibodies: Rising Tg-Ab trend is a risk factor for recurrence of differentiated thyroid cancer. Endocr Res 2017; 42:302-310. [PMID: 28509618 DOI: 10.1080/07435800.2017.1319858] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE Differentiated thyroid cancer is the most common endocrine malignancy. Recurrences (5-20%) are the main reason for follow-up. Thyroglobulin (Tg) has proven to be an excellent disease marker, but thyroglobulin-antibodies (Tg-Ab) may interfere with Tg measurement, leading to over or underestimation. It is proposed that the Tg-Ab trend can be used as a marker for disease recurrence, yet few studies define trend and have a long-term follow-up. The objective of our study was to investigate the value of a well-defined Tg-Ab trend as a surrogate marker for disease recurrence during long-term follow-up. METHODS We retrospectively studied patients treated at the Nuclear Department of the University Medical Center Utrecht from 1998 to 2010 and the Netherlands Cancer Institute from 2000 to 2009. All patients with Tg-Ab 12 months after treatment were included. The definition of a rise was >50% increase of the Tg-Ab value in a 2 year time period. A decline as >50% decrease of the Tg-Ab value. RESULTS Twenty-five patients were included. None of the patients with declining or stable Tg-Ab without a concomitant rise in Tg developed a recurrence. Four patients did suffer a recurrence. Three of these patients had a rising Tg-Ab trend, in two of these patients Tg was undetectable. CONCLUSIONS Tg-Ab trend can be used as a crude surrogate marker for long-term follow-up of Tg-Ab patients. A rising trend in Tg-Ab warrants further investigation to detect recurrent disease. Stable or declining Tg-Ab levels do not seem to reflect a risk for recurrence.
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Affiliation(s)
- Siegrid G A de Meer
- a Department of Surgical Oncology and Endocrine Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
| | - Wessel M C M Vorselaars
- a Department of Surgical Oncology and Endocrine Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
| | - Jakob W Kist
- a Department of Surgical Oncology and Endocrine Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
- b Department of Nuclear Medicine , Netherlands Cancer Institute , Amsterdam , The Netherlands
| | - Marcel P M Stokkel
- b Department of Nuclear Medicine , Netherlands Cancer Institute , Amsterdam , The Netherlands
| | - Bart de Keizer
- c Department of Nuclear Medicine and Radiology , University Medical Center, Utrecht , Utrecht , The Netherlands
| | - Gerlof D Valk
- d Department of Endocrinology , University Medical Center Utrecht , Utrecht , The Netherlands
| | - Inne H M Borel Rinkes
- a Department of Surgical Oncology and Endocrine Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
| | - Menno R Vriens
- a Department of Surgical Oncology and Endocrine Surgery , University Medical Center Utrecht , Utrecht , The Netherlands
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28
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Tseng CP, Leong KK, Liou MJ, Hsu HL, Lin HC, Chen YA, Lin JD. Circulating epithelial cell counts for monitoring the therapeutic outcome of patients with papillary thyroid carcinoma. Oncotarget 2017; 8:77453-77464. [PMID: 29100400 PMCID: PMC5652792 DOI: 10.18632/oncotarget.20512] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 08/08/2017] [Indexed: 12/24/2022] Open
Abstract
Loco-regional recurrence or distant metastasis usually leads to the death of patients with papillary thyroid carcinoma (PTC). Whether or not circulating epithelial cells (CECs) count is a valuable marker in monitoring the therapeutic outcome of PTC was investigated. Patients with PTC (n=129) were treated in our medical center and were categorized into 4 groups with excellent (n=45), biochemical incomplete (n=15), indeterminate (n=37), and structural incomplete (n=32) responses. CECs were enriched from the peripheral blood by the PowerMag negative selection system. Three subtypes of CECs expressing epithelial cell adhesion molecule (EpCAM), thyroid-stimulating hormone receptor (TSHR, a marker for thyroid cells), and podoplanin (PDPN, a marker related to poor prognosis in patients with PTC) were defined by immunofluorescence staining, respectively. The median number of CECs (cells/mL of blood) expressing EpCAM, TSHR, and PDPN was 23 (interquartile range 10-61), 19 (interquartile range 8-50), and 8 (interquartile range 3-22), respectively, for patients enrolled in this study. The number of EpCAM+-CECs, TSHR+-CECs, and PDPN+-CECs was statistically different among patients in different treatment response groups without interference from anti-thyroglobulin antibody (P<0.0001). Patients with structural incomplete response had higher counts for all three CECs subtypes when compared to other patients. EpCAM+-CECs was better in distinguishing patients with excellent response from structural incomplete response among the three subtypes of CECs. The sensitivity and specificity of the assay was 84.4% and 95.6%, respectively, when the cut off value was 39 EpCAM+-CECs/mL. CECs testing can supplement the current standard methods for monitoring the therapeutic outcome of PTC.
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Affiliation(s)
- Ching-Ping Tseng
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC
- Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Kong-Kit Leong
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Miaw-Jene Liou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Hsueh-Ling Hsu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Hung-Chih Lin
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Yi-An Chen
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Jen-Der Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
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29
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Wu H, Zhang B. Serum thyroglobulin or thyroglobulin in fine-needle aspiration washout of metastatic lymph nodes: which one should we have confidence in for the surveillance of thyroid carcinoma? J Am Soc Cytopathol 2017; 6:66-72. [PMID: 31042636 DOI: 10.1016/j.jasc.2016.12.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 12/22/2016] [Accepted: 12/22/2016] [Indexed: 06/09/2023]
Abstract
BACKGROUND The objective of this study was to evaluate the diagnostic performance of serum thyroglobulin (S-Tg), thyroglobulin in fine-needle aspiration washout (FNA-Tg) and fine-needle aspiration cytology (FNAC) in the detection of lateral metastatic lymph nodes (LNs) in patients with thyroid carcinoma. METHODS The study included 19 lateral metastatic LNs from 19 patients with thyroid carcinoma who underwent FNAC for the suspicion of metastatic disease on ultrasonogrphy (US). The S-Tg, FNA-Tg, FNAC, and histopathological results were correlated. RESULTS Compared with S-Tg, both FNAC and FNA-Tg showed higher sensitivity (89.5%, 89.5% versus 68.4%, respectively) and accuracy (89.5%, 89.5% versus 68.4%, respectively). The combined use of FNAC and FNA-Tg or FNAC and S-Tg showed superior diagnostic power. CONCLUSIONS S-Tg measurement is a less reliable method for follow-up in patients with thyroid carcinoma in comparison with FNA-Tg. For patients with negative S-Tg but suspicious features in US, FNAC combined with FNA-Tg is strongly recommended to confirm the diagnosis.
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Affiliation(s)
- Hongxun Wu
- Department of Ultrasound, Jiangyuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine (Key Laboratory of Nuclear Medicine, Ministry of Health/Jiangsu Key Laboratory of Molecular Nuclear Medicine), Wuxi, China.
| | - Bingjie Zhang
- Department of Ultrasound, Jiangyuan Hospital Affiliated to Jiangsu Institute of Nuclear Medicine (Key Laboratory of Nuclear Medicine, Ministry of Health/Jiangsu Key Laboratory of Molecular Nuclear Medicine), Wuxi, China
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30
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Powers JL, Strathmann FG, Straseski JA. Thyroglobulin Antibody Screen Prior to Mass Spectrometry Provides Measurable Cost Savings and Optimal Laboratory Utilization. Am J Clin Pathol 2017; 147:309-314. [PMID: 28395053 DOI: 10.1093/ajcp/aqw228] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
OBJECTIVES Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that allow accurate quantitation of thyroglobulin (Tg) in the presence of Tg antibodies (TgAbs) have recently become available. Due to cost differences between LC-MS/MS and immunoassay, some laboratories now offer a reflex test strategy that uses LC-MS/MS only for TgAb-positive samples. The goal of this study was to examine utilization of Tg testing strategies and cost savings. METHODS Test ordering patterns were examined for over 150,000 orders for TgAb and Tg in our laboratory. The average list price was determined from three separate commercial laboratories offering this testing. RESULTS Data showed that 89% of orders for Tg used the reflex test option, resulting in a savings of over $3 million compared with testing all samples by LC-MS/MS. Of the Tg by LC-MS/MS orders not using the reflex option, 1,663 also included a separate order for TgAb on the same patient sample, representing approximately $170,000 in potentially unnecessary costs from TgAb-negative samples. CONCLUSIONS Identifying situations to use more expensive testing methods (eg, LC-MS/MS) only when necessary, such as for TgAb-positive patients, leads to considerable cost savings and a more economical use of valuable health care resources.
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Affiliation(s)
- Jennifer L Powers
- From the Department of Pathology, University of Utah, Salt Lake City
| | | | - Joely A Straseski
- From the Department of Pathology, University of Utah, Salt Lake City
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31
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Indrasena BSH. Use of thyroglobulin as a tumour marker. World J Biol Chem 2017; 8:81-85. [PMID: 28289520 PMCID: PMC5329716 DOI: 10.4331/wjbc.v8.i1.81] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 11/22/2016] [Accepted: 01/14/2017] [Indexed: 02/05/2023] Open
Abstract
It is worthwhile to measure serum thyroglobulin (TG) level in thyroid cancer before subjecting patients to surgery for two reasons. Firstly, if the level is high, it may give a clue to the local and metastatic tumour burden at presentation; secondly, if the level is normal, it identifies the patients who are unlikely to show rising TG levels in the presence of thyroid cancer. Those who have high serum TG before surgery will show up recurrence as rising serum TG during the postoperative period. Those who do not have high serum TG before surgery will not show up rising serum TG in the presence of recurrent disease. In the latter situation, normal TG level gives only a false reassurance regarding recurrence of disease. Nevertheless, rising serum TG during the postoperative period must be interpreted cautiously because this could be due to the enlargement of non-cancerous residual thyroid tissue inadvertently left behind during surgery.
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32
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Azmat U, Porter K, Senter L, Ringel MD, Nabhan F. Thyroglobulin Liquid Chromatography-Tandem Mass Spectrometry Has a Low Sensitivity for Detecting Structural Disease in Patients with Antithyroglobulin Antibodies. Thyroid 2017; 27:74-80. [PMID: 27736322 PMCID: PMC5206681 DOI: 10.1089/thy.2016.0210] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Thyroglobulin (Tg) measurement in patients with positive antithyroglobulin antibodies (anti-TgAbs) is not reliable. Tg measurement using liquid chromatography-tandem mass spectrometry (LC/MS) may be useful in this setting. METHODS This is a retrospective study with the objective of determining the accuracy of Tg-LC/MS in patients with thyroid cancer with anti-TgAbs. All patients with follicular cell-derived thyroid cancer (TC) who had thyroglobulin measured using LC/MS assay from November 1, 2013, to November 7, 2014, were evaluated. The frequency of detectable Tg-LC/MS was evaluated, with a functional sensitivity (FS) of 0.5 ng/mL in patients with structural disease. Then performance of Tg-LC/MS versus Tg immunometric assay (IMA) was compared using either Immulite assay (Tg-1) with a FS of 0.9 ng/mL or Beckman assay (Tg-B) with a FS of 0.1 ng/mL in detecting structural disease in patients with positive anti-TgAbs. RESULTS A total of 154 consecutive patients were included in this evaluation. Of these, 116 (75%) patients were positive for anti-TgAbs. In patients with structural disease and positive anti-TgAbs, Tg-LC/MS was undetectable in 43.7% of patients. Then the diagnostic accuracy for structural disease of Tg-LC/MS was compared with each Tg-IMA assay separately. In the 26 patients with positive anti-TgAbs where a Tg-I assay was used, the sensitivity and specificity for detecting structural disease were 33.3% and 88.2%, respectively, for the Tg-I assay, and 44.4% and 94.1%, respectively, for the Tg-LC/MS assay. In the 74 patients with positive anti-TgAbs where Tg-B was used, the sensitivity and specificity for detection of structural disease were 72.7% and 71.4%, respectively, for the Tg-B assay, and 62.6% and 93.7%, respectively, for the Tg-LC/MS assay. CONCLUSION In patients with thyroid cancer with positive anti-TgAbs, Tg-LC/MS was frequently undetectable and was less sensitive for detecting disease than a Tg assay was with a functional sensitivity of 0.1 ng/mL. For patients with detectable Tg-LC/MS and anti-TgAbs, use of the assay for monitoring requires further prospective studies.
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Affiliation(s)
- Umal Azmat
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio
| | - Kyle Porter
- Center for Biostatistics, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio
| | - Leigha Senter
- Division of Human Genetics, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio
| | - Matthew D. Ringel
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio
| | - Fadi Nabhan
- Division of Endocrinology, Diabetes, and Metabolism, The Ohio State University and Arthur G. James Cancer Center, Columbus, Ohio
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Wang Z, Zhang H, Zhang X, Sun J, Han C, Li C, Li Y, Teng X, Fan C, Liu A, Shan Z, Liu C, Weng J, Teng W. Serum thyroglobulin reference intervals in regions with adequate and more than adequate iodine intake. Medicine (Baltimore) 2016; 95:e5273. [PMID: 27902589 PMCID: PMC5134814 DOI: 10.1097/md.0000000000005273] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
The purpose of this study was to establish normal thyroglobulin (Tg) reference intervals (RIs) in regions with adequate and more than adequate iodine intake according to the National Academy of Clinical Biochemistry (NACB) guidelines and to investigate the relationships between Tg and other factors.A total of 1317 thyroid disease-free adult subjects (578 men, 739 nonpregnant women) from 2 cities (Guangzhou and Nanjing) were enrolled in this retrospective, observational study. Each subject completed a questionnaire and underwent physical and ultrasonic examination. Serum Tg, thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), Tg antibody (TgAb), and urinary iodine concentration (UIC) were measured. Reference groups were established on the basis of TSH levels: 0.5 to 2.0 and 0.27 to 4.2 mIU/L.The Tg RIs for Guangzhou and Nanjing were 1.6 to 30.0 and 1.9 to 25.8 ng/mL, respectively. No significant differences in Tg were found between genders or among different reference groups. Stepwise linear regression analyses showed that TgAb, thyroid volume, goiter, gender, age, and TSH levels were correlated with Tg.In adults from regions with adequate and more than adequate iodine intake, we found that Tg may be a suitable marker of iodine status; gender-specific Tg RI was unnecessary; there was no difference between Tg RIs in regions with adequate and more than adequate iodine intake; and the TSH criterion for selecting the Tg reference population could follow the local TSH reference rather than 0.5 to 2.0 mIU/L.
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Affiliation(s)
- Zhaojun Wang
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Hanyi Zhang
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Xiaowen Zhang
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Jie Sun
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Cheng Han
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Chenyan Li
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Yongze Li
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Xiaochun Teng
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Chenling Fan
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Aihua Liu
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Zhongyan Shan
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
| | - Chao Liu
- Department of Endocrinology and Metabolism, Jiangsu Province Hospital on Integration of Chinese and Western Medicine, Nanjing University of Traditional Chinese Medicine, Jiangsu
| | - Jianping Weng
- Guangdong Provincial Key Laboratory of Diabetology, Department of Endocrinology and Metabolic Disease, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong, China
| | - Weiping Teng
- The Endocrine Institute and The Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Liaoning
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Liu RQ, Wiseman SM. Quality indicators for thyroid cancer surgery: current perspective. Expert Rev Anticancer Ther 2016; 16:919-28. [PMID: 27559618 DOI: 10.1080/14737140.2016.1222274] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
INTRODUCTION While the disease specific mortality of differentiated thyroid cancer has remained low with current treatments, its incidence has been steadily rising over the past several decades, and cancer related recurrence and morbidity have remained a significant problem. Quality indicators currently employed are relevant to the surgical intervention, but do not necessarily reflect oncological outcomes. Therefore, thyroid cancer specific surgical quality indicators, that offer insight into risk of cancer related morbidity and mortality are needed. AREAS COVERED This review aims to discuss the role of measuring quality in thyroid surgical oncology and carry out a comprehensive review of potential quality indicators for thyroid cancer operations. The three quality indicators reviewed here are the postoperative radioactive iodine update by remnant thyroid tissue, the proportion of resected lymph nodes with evidence of metastases, and the post-operative serum thyroglobulin level. Expert commentary: Together, these quality indicators may be utilized to guide improvement of the quality of surgical care for this unique patient population. A critical future step in establishing the role of quality indicators for thyroid cancer surgery is the determination of cutoff values of each indicator in an evidence-based manner.
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Affiliation(s)
- Rachel Q Liu
- a Department of Surgery , St. Paul's Hospital and University of British Columbia , Vancouver , British Columbia, Canada
| | - Sam M Wiseman
- a Department of Surgery , St. Paul's Hospital and University of British Columbia , Vancouver , British Columbia, Canada
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Rosario PW, Carvalho M, Mourão GF, Calsolari MR. Comparison of Antithyroglobulin Antibody Concentrations Before and After Ablation with 131I as a Predictor of Structural Disease in Differentiated Thyroid Carcinoma Patients with Undetectable Basal Thyroglobulin and Negative Neck Ultrasonography. Thyroid 2016; 26:525-31. [PMID: 26831821 DOI: 10.1089/thy.2015.0445] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
BACKGROUND Patients with differentiated thyroid carcinoma are submitted to a first assessment several months after initial therapy to evaluate their response to treatment. At that assessment, measurement of basal thyroglobulin (Tg) and antithyroglobulin antibodies (TgAb) and neck ultrasonography (US) are recommended. Serum Tg may be falsely negative in the presence of TgAb, and the management of patients with negative Tg but positive TgAb represents a challenge. The objective of this study was to correlate the variation in TgAb concentrations (comparison before and after ablation with (131)I) with the risk of structural disease. METHODS The sample consisted of 116 low- or intermediate-risk patients who had undetectable Tg, negative US at initial assessment, and positive TgAb 8-12 months after thyroidectomy and ablation with (131)I. RESULTS Comparison of TgAb concentrations before and after ablation with (131)I showed a reduction of >50% in 56 patients (group A), a reduction of <50% in 35 patients (group B), and an increase in 25 patients (group C). Metastases were detected in 5/116 (4.3%) patients during initial assessment (lymph nodes in two, pulmonary in two, and bone in one). They were diagnosed in 0/56, 2/35 (5.7%), and 3/25 (12%) patients of groups A, B, and C, respectively. During follow-up, metastases were detected in 7/111 (6.3%) patients (lymph nodes in six, and pulmonary in one). They occurred in 1/56 (1.8%), 3/33 (9%), and 3/22 (13.6%) patients of groups A, B, and C, respectively. Thus, structural disease was found in 1.8%, 14.3%, and 24% of groups A, B, and C, respectively. This rate was 4% in low-risk patients and 15.4% in intermediate-risk patients. CONCLUSIONS Among patients with undetectable Tg, negative US, and positive TgAb after ablation with (131)I, the frequency of structural disease was <5% in patients, with >50% reduction in TgAb. Among patients without a significant reduction in TgAb, approximately 10% of low-risk patients and >20% of intermediate-risk patients had structural disease. These results help define the indication for imaging methods other than US during initial assessment and long-term follow-up.
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Affiliation(s)
- Pedro Weslley Rosario
- 1 Postgraduation Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
- 2 Endocrinology Service, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
| | - Marina Carvalho
- 1 Postgraduation Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
| | - Gabriela Franco Mourão
- 1 Postgraduation Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
- 2 Endocrinology Service, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
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Lin HC, Liou MJ, Hsu HL, Hsieh JCH, Chen YA, Tseng CP, Lin JD. Combined analysis of circulating epithelial cells and serum thyroglobulin for distinguishing disease status of the patients with papillary thyroid carcinoma. Oncotarget 2016; 7:17242-53. [PMID: 26684026 PMCID: PMC4941384 DOI: 10.18632/oncotarget.6587] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2015] [Accepted: 11/25/2015] [Indexed: 12/11/2022] Open
Abstract
Papillary thyroid carcinoma (PTC) accounts for about 80% of the cases in thyroid cancer. Routine surveillance by serum thyroglobulin (Tg) and medical imaging is the current practice to monitor disease progression of the patients. Whether enumeration of circulating epithelial cells (CECs) helps to define disease status of PTC patients was investigated. CECs were enriched from the peripheral blood of the healthy control subjects (G1, n = 17) and the patients at disease-free status (G2, n = 26) or with distant metastasis (G3, n = 22). The number of CECs expressing epithelial cell adhesion molecule (EpCAM) or thyroid-stimulating hormone receptor (TSHR) was determined by immunofluorescence microscopy analyses. The medium number of EpCAM+-CECs was 6 (interquartile range 1-11), 12 (interquartile range 7-16) and 91 (interquartile range 31-206) cells/ml of blood for G1, G2 and G3, respectively. EpCAM+-CEC counts were significantly higher in G3 than in G1 (p < 0.05) and G2 (p < 0.05). The medium number of TSHR+-CECs was 9 (interquartile range 3-13), 16 (interquartile range 10-24) and 100 (interquartile range 31-226) cells/ml of blood for G1, G2 and G3, respectively. The TSHR+-CEC counts also distinguished G3 from G1 (p < 0.05) and G2 (p < 0.05). With an appropriate cut off value of CEC count, the disease status for 97.9% (47/48) of the cases was clearly defined. Notably, the metastatic disease for all patients in G3 (22/22) was revealed by combined analysis of serum Tg and CEC. This study implicates that CEC testing can supplement the current standard methods for monitoring disease status of PTC.
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Affiliation(s)
- Hung-Chih Lin
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Miaw-Jene Liou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Hsung-Ling Hsu
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Jason Chia-Hsun Hsieh
- Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
- Department of Chemical and Materials Engineering, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Yi-An Chen
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
| | - Ching-Ping Tseng
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
- Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan, ROC
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan, ROC
- Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
| | - Jen-Der Lin
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan, ROC
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Guelho D, Ribeiro C, Melo M, Carrilho F. Long-term survival in a patient with brain metastases of papillary thyroid carcinoma. BMJ Case Rep 2016; 2016:bcr-2015-213824. [PMID: 26961557 DOI: 10.1136/bcr-2015-213824] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
We present the case of a 43-year-old woman who underwent total thyroidectomy with bilateral lymphadenectomy for a papillary thyroid carcinoma (PTC), solid variant (T4bN1bMx), with V600E BRAF mutation. After ablative therapy, she presented undetectable thyroglobulin (Tg) but progressively increasing anti-Tg antibodies (TgAbs). During follow-up, nodal, lung and brain metastases were identified. She was submitted to surgical excision of lung lesions, radiosurgery of brain metastases and five radioiodine treatments. The latest brain MRI showed no lesions, pulmonary CT showed stable micronodules and there was progressive reduction in TgAbs. This is a peculiar case of a PTC with lung and brain metastatic lesions detected through TgAbs. Initial histological and molecular study suggested a more aggressive clinical behaviour, which was eventually confirmed. Although PTC brain metastases are extremely rare and present poor prognosis, our patient presented a good response to treatment and longer survival than usually reported for similar cases.
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Affiliation(s)
- Daniela Guelho
- Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Cristina Ribeiro
- Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal
| | - Miguel Melo
- Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal Faculty of Medicine of University of Coimbra, Coimbra, Portugal
| | - Francisco Carrilho
- Endocrinology, Diabetes and Metabolism Department, Coimbra Hospital and University Centre, Coimbra, Portugal
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Kurien BT, Lane JT, Scofield RH. Letter to the Editor: Getting to the True Values of Thyroglobulin and Anti-Thyroglobulin Antibodies. J Clin Endocrinol Metab 2016; 101:L38-9. [PMID: 26938377 PMCID: PMC7378859 DOI: 10.1210/jc.2015-4159] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
Affiliation(s)
- Biji T Kurien
- Department of Medicine (B.T.K., J.T.L., R.H.S.), University of Oklahoma Health Sciences Center, Arthritis and Clinical Immunology Program (B.T.K., R.H.S.), Oklahoma Medical Research Foundation, and Department Veterans Affairs Medical Center (B.T.K., R.H.S.), Oklahoma, City, Oklahoma 73104
| | - James T Lane
- Department of Medicine (B.T.K., J.T.L., R.H.S.), University of Oklahoma Health Sciences Center, Arthritis and Clinical Immunology Program (B.T.K., R.H.S.), Oklahoma Medical Research Foundation, and Department Veterans Affairs Medical Center (B.T.K., R.H.S.), Oklahoma, City, Oklahoma 73104
| | - R Hal Scofield
- Department of Medicine (B.T.K., J.T.L., R.H.S.), University of Oklahoma Health Sciences Center, Arthritis and Clinical Immunology Program (B.T.K., R.H.S.), Oklahoma Medical Research Foundation, and Department Veterans Affairs Medical Center (B.T.K., R.H.S.), Oklahoma, City, Oklahoma 73104
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Pacini F, Brianzoni E, Durante C, Elisei R, Ferdeghini M, Fugazzola L, Mariotti S, Pellegriti G. Recommendations for post-surgical thyroid ablation in differentiated thyroid cancer: a 2015 position statement of the Italian Society of Endocrinology. J Endocrinol Invest 2016; 39:341-347. [PMID: 26264386 PMCID: PMC4761012 DOI: 10.1007/s40618-015-0375-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 07/28/2015] [Indexed: 02/08/2023]
Abstract
UNLABELLED Post-surgical ablation of thyroid remnant with radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is aimed to destroy any thyroid remnant in the thyroid bed (remnant ablation) and any microscopic foci of cancer cells eventually present within the thyroid remnant (adjuvant therapy). The present text is an attempt to offer practice guidelines for the indication of thyroid ablation and the preparation of DTC patients considering the latest achievement in the field and the changing epidemiology of DTC observed in the last 10 years. METHODOLOGY The executive committee of the Italian Society of Endocrinology appointed a task force of thyroid cancer expert including Nuclear Medicine Physicians and Endocrinologists to provide a consensus on the post-surgical ablation in thyroid cancer patients. The task force had no conflict of interest and had no commercial support. A number of specific topics were selected and the members selected relevant papers by searching in the Pubmed for articles published from 2000 to January 2015. Selected studies were categorized by level of evidence, and the recommendations were graded according to the level of evidence as high (A), moderate (B), or low (C).
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Affiliation(s)
- F Pacini
- Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
- Department of Endocrinology, University of Siena, Via Bracci, 53100, Siena, Italy.
| | - E Brianzoni
- Nuclear Medicine Unit, Ospedale Civile di Macerata, Macerata, Italy
| | - C Durante
- Department of Internal Medicine and Medical Specialties, University of Rome Sapienza, Rome, Italy
| | - R Elisei
- Endocrine Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - M Ferdeghini
- Nuclear Medicine Unit, University of Verona, Verona, Italy
| | - L Fugazzola
- Endocrine Unit, Fondazione IRCCS Ca' Granda Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - S Mariotti
- Department Medical Sciences "M. Aresu", University of Cagliari, Cagliari, Italy
| | - G Pellegriti
- Endocrinology Division, Garibaldi Nesima Hospital, Palermo, Italy
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Circulating epithelial cell enumeration facilitates the identification and follow-up of a patient with early stage papillary thyroid microcarcinoma: A case report. Clin Chim Acta 2016; 454:107-11. [PMID: 26751809 DOI: 10.1016/j.cca.2015.12.030] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 12/21/2015] [Accepted: 12/21/2015] [Indexed: 01/19/2023]
Abstract
BACKGROUND This study examines whether the measurement of circulating epithelial cells (CECs) facilitates the identification and follow-up of a patient with thyroid cancer. METHODS A 29-y-old woman with no cancer history was enrolled as a healthy control in a CEC study. CECs were enriched from the peripheral blood by the negative selection system PowerMag. Various medical examinations were performed on the patient to establish the diagnosis and to follow-up her disease status during treatment. RESULTS This patient had unexpectedly high CEC counts that were sustained for more than two weeks. Thyroid gland ultra-sonography revealed lesions in the left lobe that could not be confirmed as cancer by magnetic resonance imaging, (18)F-fludeoxyglucose-positron emission tomography-computed tomography or cytopathological analysis, but were histologically confirmed after thyroidectomy as papillary thyroid microcarcinoma. Both the CEC count and serum thyroglobulin (Tg) concentration were significantly decreased after thyroidectomy, and they and the patient's disease status were correlated during remnant ablation therapy. The CEC count returned to normal when the patient was disease-free 10 months after thyroidectomy. CONCLUSIONS CEC testing facilitates the identification of individuals at risk for cancer. Longitudinal follow-up of the CEC count may complement serum Tg testing for monitoring the status of patients with thyroid cancer.
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Netzel BC, Grebe SKG, Carranza Leon BG, Castro MR, Clark PM, Hoofnagle AN, Spencer CA, Turcu AF, Algeciras-Schimnich A. Thyroglobulin (Tg) Testing Revisited: Tg Assays, TgAb Assays, and Correlation of Results With Clinical Outcomes. J Clin Endocrinol Metab 2015; 100:E1074-83. [PMID: 26079778 PMCID: PMC4524993 DOI: 10.1210/jc.2015-1967] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT Measurement of thyroglobulin (Tg) by mass spectrometry (Tg-MS) is emerging as a tool for accurate Tg quantification in patients with anti-Tg autoantibodies (TgAbs). OBJECTIVE The objective of the study was to perform analytical and clinical evaluations of two Tg-MS assays in comparison with immunometric Tg assays (Tg-IAs) and Tg RIAs (Tg-RIAs) in a cohort of thyroid cancer patients. METHODS A total of 589 samples from 495 patients, 243 TgAb-/252 TgAb+, were tested by Beckman, Roche, Siemens-Immulite, and Thermo-Brahms Tg and TgAb assays, two Tg-RIAs, and two Tg-MS assays. RESULTS The frequency of TgAb+ was 58%, 41%, 27%, and 39% for Roche, Beckman, Siemens-Immulite, and Thermo-Brahms, respectively. In TgAb- samples, clinical sensitivities and specificities of 100% and 74%-100%, respectively, were observed across all assays. In TgAb+ samples, all Tg-IAs demonstrated assay-dependent Tg underestimation, ranging from 41% to 86%. In TgAb+ samples, the use of a common cutoff (0.5 ng/mL) for the Tg-MS, three Tg-IAs, and the USC-RIA improved the sensitivity for the Tg-MSs and Tg-RIAs when compared with the Tg-IAs. In up to 20% of TgAb+ cases, Tg-IAs failed to detect Tg that was detectable by Tg-MS. In Tg-RIAs false-high biases were observed in TgAb+ samples containing low Tg concentrations. CONCLUSIONS Tg-IAs remain the method of choice for Tg quantitation in TgAb- patients. In TgAb+ patients with undetectable Tg by immunometric assay, the Tg-MS will detect Tg in up to 20% additional cases. The Tg-RIA will detect Tg in approximately 35% cases, but a significant proportion of these will be clinical false-positive results. The undetectable Tg-MS seen in approximately 40% of TgAb+ cases in patients with disease need further evaluation.
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Affiliation(s)
- Brian C Netzel
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Stefan K G Grebe
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - B Gisella Carranza Leon
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - M Regina Castro
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Penelope M Clark
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Andrew N Hoofnagle
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Carole A Spencer
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Adina F Turcu
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
| | - Alicia Algeciras-Schimnich
- Department of Laboratory Medicine and Pathology (B.C.N., S.K.G.G., A.A.-S.), Division of Endocrinology, Metabolism, and Nutrition (S.K.G.G., B.G.C.L., M.R.C., A.F.T.), Mayo Clinic, Rochester, Minnesota 55905; Queen Elizabeth Hospital Birmingham (P.M.C.), Birmingham B15 2TH, United Kingdom; Department of Laboratory Medicine (A.N.H.), University of Washington, Seattle, Washington 98108; and University of Southern California (C.A.S.), Los Angeles, California 90089
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Rosario PW, Mourão GF, Siman TL, Calsolari MR. Serum Thyroglobulin Measured With a Second-Generation Assay in Patients Undergoing Total Thyroidectomy Without Radioiodine Remnant Ablation: A Prospective Study. Thyroid 2015; 25:769-75. [PMID: 25763842 DOI: 10.1089/thy.2014.0496] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Follow-up consisting of the measurement of nonstimulated serum thyroglobulin (Tg) combined with neck ultrasonography is recommended for patients with papillary thyroid carcinoma without indication for radioiodine ablation. There is no recommendation of thyrotropin suppression during this follow-up. New-generation Tg assays have been increasingly used, but few studies involve patients submitted only to thyroidectomy and they have several limitations. The objective of this prospective study was to define expected concentrations of nonstimulated Tg measured with a second-generation assay after total thyroidectomy in the absence of tumor. METHODS Serum Tg was measured using a second-generation assay in 69 patients without tumor and serum thyrotropin between 0.5 and 2 mIU/L, 3, 6, 12, and 24 months after total thyroidectomy. All patients had undetectable anti-Tg antibodies. RESULTS Serum Tg was undetectable in 44.4%, 57%, 62.5%, and 62.1% of the patients 3, 6, 12, and 24 months after thyroidectomy, respectively, and was ≤0.5 ng/mL in 60.3%, 80%, 90.6%, and 90.9% of patients. All patients had a Tg≤2 ng/mL 6 months after thyroidectomy, and 97% had a Tg≤1 ng/mL 24 months after surgery. There was no case of Tg conversion from undetectable to detectable and none of the patients presented an increase in Tg. CONCLUSIONS An important decline in serum Tg occurred between 3 and 6 months after total thyroidectomy. One year after surgery, Tg was undetectable in approximately 60% of the patients and was ≤2 ng/mL in all of them.
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Affiliation(s)
- Pedro Weslley Rosario
- 1 Postgraduate Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
- 2 Endocrinology Service, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
| | - Gabriela Franco Mourão
- 1 Postgraduate Program, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
- 2 Endocrinology Service, Santa Casa de Belo Horizonte , Minas Gerais, Brazil
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Bevilacqua V, Chan MK, Chen Y, Armbruster D, Schodin B, Adeli K. Pediatric Population Reference Value Distributions for Cancer Biomarkers and Covariate-Stratified Reference Intervals in the CALIPER Cohort. Clin Chem 2014; 60:1532-42. [DOI: 10.1373/clinchem.2014.229799] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Abstract
BACKGROUND
Cancer biomarkers are commonly used in pediatrics to monitor cancer progression, recurrence, and prognosis, but pediatric reference value distributions have not been well established for these markers. The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) sought to develop a pediatric database of covariate-stratified reference value distributions for 11 key circulating tumor markers, including those used in assessment of patients with childhood or adult cancers.
METHODS
Healthy community children from birth to 18 years of age were recruited to participate in the CALIPER project with informed parental consent. We analyzed serum samples from 400–700 children (depending on the analyte in question) on the Abbott Architect ci4100 and established reference intervals for α-fetoprotein (AFP), antithyroglobulin (anti-Tg), human epididymis protein 4 (HE4), cancer antigen 125 (CA125), CA15-3, CA19-9, progastrin-releasing peptide (proGRP), carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and total and free prostate specific antigen (PSA) according to CLSI C28-A3 statistical guidelines.
RESULTS
We observed significant fluctuations in biomarker concentrations by age and/or sex in 10 of 11 biomarkers investigated. Age partitioning was required for CA153, CA125, CA19-9, CEA, SCC, proGRP, total and free PSA, HE4, and AFP, whereas sex partitioning was also required for CA125, CA19-9, and total and free PSA.
CONCLUSIONS
This CALIPER study established a database of childhood reference intervals for 11 tumor biomarkers and revealed dramatic fluctuations in tumor marker concentrations between boys and girls and throughout childhood. In addition, important differences between the adult and pediatric population were observed, further highlighting the need for pediatric-specific reference intervals.
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Affiliation(s)
- Victoria Bevilacqua
- CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
| | - Man Khun Chan
- CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and
| | - Yunqi Chen
- CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and
| | | | - Beth Schodin
- Abbott Diagnostics, Abbott Laboratories, Abbott Park, IL
| | - Khosrow Adeli
- CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, and
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada
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Spencer C, Petrovic I, Fatemi S, LoPresti J. Serum thyroglobulin (Tg) monitoring of patients with differentiated thyroid cancer using sensitive (second-generation) immunometric assays can be disrupted by false-negative and false-positive serum thyroglobulin autoantibody misclassifications. J Clin Endocrinol Metab 2014; 99:4589-99. [PMID: 25226290 PMCID: PMC4297889 DOI: 10.1210/jc.2014-1203] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
CONTEXT Reliable thyroglobulin (Tg) autoantibody (TgAb) detection before Tg testing for differentiated thyroid cancer (DTC) is critical when TgAb status (positive/negative) is used to authenticate sensitive second-generation immunometric assay ((2G)IMA) measurements as free from TgAb interference and when reflexing "TgAb-positive" sera to TgAb-resistant, but less sensitive, Tg methodologies (radioimmunoassay [RIA] or liquid chromatography-tandem mass spectrometry [LC-MS/MS]). OBJECTIVE The purpose of this study was to assess how different Kronus (K) vs Roche (R) TgAb method cutoffs for "positivity" influence false-negative vs false-positive serum TgAb misclassifications that may reduce the clinical utility of reflex Tg testing. METHODS Serum Tg(2G)IMA, TgRIA, and TgLC-MS/MS measurements for 52 TgAb-positive and 37 TgAb-negative patients with persistent/recurrent DTC were compared. A total of 1426 DTC sera with TgRIA of ≥ 1.0 μg/L had false-negative and false-positive TgAb frequencies determined using low Tg(2G)IMA/TgRIA ratios (<75%) to indicate TgAb interference. RESULTS TgAb-negative patients with disease displayed Tg(2G)IMA, TgRIA, and TgLC-MS/MS serum discordances (% coefficient of variation = 24 ± 20%, range, 0%-100%). Of the TgAb-positive patients with disease, 98% had undetectable/lower Tg(2G)IMA vs either TgRIA or TgLC-MS/MS (P < .01), whereas 8 of 52 (15%) had undetectable Tg(2G)IMA + TgLC-MS/MS associated with TgRIA of ≥ 1.0 μg/L. Receiver operating characteristic curve analysis reported more sensitivity for TgAb method K vs R (81.9% vs 69.1%, P < .001), but receiver operating characteristic curve cutoffs (>0.6 kIU/L [K] vs >40 kIU/L [R]) had unacceptably high false-negative frequencies (22%-32%), whereas false positives approximated 12%. Functional sensitivity cutoffs minimized false negatives (13.5% [K] vs 21.3% [R], P < .01) and severe interferences (Tg(2G)IMA, <0.10 μg/L) (0.7% [K] vs 2.4% [R], P < .05) but false positives approximated 23%. CONCLUSIONS Reliable detection of interfering TgAbs is method and cutoff dependent. No cutoff eliminated both false-negative and false-positive TgAb misclassifications. Functional sensitivity cutoffs were optimal for minimizing false negatives but have inherent imprecision (20% coefficient of variation) that, exacerbated by TgAb biologic variability during DTC monitoring, could cause TgAb status to fluctuate for patients with low TgAb concentrations, prompting unnecessary Tg method changes and disrupting Tg monitoring. Laboratories using reflexing should limit Tg method changes by considering a patient's Tg + TgAb testing history in addition to current TgAb status before Tg method selection.
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Affiliation(s)
- Carole Spencer
- University of Southern California (C.S., I.P., J.L.), Los Angeles, California 90089; and Kaiser Permanente (S.F.), Panorama City, California 91402
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Smallridge RC, Diehl N, Bernet V. Practice trends in patients with persistent detectable thyroglobulin and negative diagnostic radioiodine whole body scans: a survey of American Thyroid Association members. Thyroid 2014; 24:1501-7. [PMID: 25058708 PMCID: PMC4195231 DOI: 10.1089/thy.2014.0043] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
BACKGROUND Management of patients with thyroglobulin (Tg)-positive/scan-negative thyroid cancer remains challenging. American Thyroid Association (ATA) guidelines recommend potential use of empiric (131)I therapy and various scanning modalities, but no standard for managing such cases exists. METHODS We surveyed ATA members to assess current practice in management of patients with Tg-positive/scan-negative disease. Members participated in a web-based survey of six case scenarios of Tg elevations but iodine scan negativity. RESULTS A total of 288 ATA members (80% male) participated. Patient age, sex, and basal and stimulated Tg varied between the cases. Respondents were asked their opinion regarding empiric (131)I therapy use, including (131)I dose, use and duration of low-iodine diet, thyroxine withdrawal or recombinant human thyrotropin (rhTSH), and utilization of additional imaging (neck ultrasound (US) or positron emission tomography/computed tomography (PET/CT)) and reconsideration of (131)I therapy. Between 16% and 51% recommended initial use of empiric (131)I for the various scenarios. The majority chose a (131)I dose between 75 and 150 mCi, and 73% employed a low-iodine diet for two or more weeks. Preference between thyroxine withdrawal versus rhTSH was evenly split. More than 98% obtained a neck US if empiric (131)I was not given; 52-89% would proceed to PET/CT if US was negative. Only 44% used rhTSH stimulation in PET scan preparation. (131)I use was more common with stimulated Tg significantly >10 ng/mL. (131)I therapy was slightly more likely with PET-positive (56%) than PET-negative status (45%). Respondents were split regarding empiric (131)I if basal and stimulated Tg increased ≥150% over two years. Providers in North America less commonly utilized (131)I treatment than those from other areas. In the face of possible heterophilic antibody interference in the Tg assay, the majority did not recommend (131)I therapy. CONCLUSIONS Empiric (131)I therapy is still utilized for patients with Tg-positive/scan-negative disease. Neck US is frequently used to further evaluate such cases as (18)FDG-PET/CT, albeit the latter is used somewhat less often. Use of (131)I therapy correlated with the degree of Tg elevation or development of Tg antibodies, and was recommended more commonly with PET-positive than PET-negative status in patients with lower Tg levels. (131)I was less commonly used by providers within North America.
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Affiliation(s)
| | - Nancy Diehl
- Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida
| | - Victor Bernet
- Division of Endocrinology and Metabolism, Mayo Clinic, Jacksonville, Florida
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Loh TP, Chong HW, Kao SL. Thyroglobulin and thyroglobulin autoantibodies: interpret with care. Endocrine 2014; 46:360-1. [PMID: 24272592 DOI: 10.1007/s12020-013-0103-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 10/25/2013] [Indexed: 11/28/2022]
Affiliation(s)
- Tze Ping Loh
- Department of Laboratory Medicine, National University Hospital, 5 Lower Kent Ridge Road, 119074, Singapore, Singapore,
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