Y (HR 2.58, 95 CI 1.45?.95), and otolaryngology (HR 2.47, 95 CI 1.25?.15) were all associated with shorter time to thyroid cancer diagnosis (Table 5).DiscussionIn this study, there is a malignancy rate of 3.6 among patients who underwent thyroid aspiration biopsy. Among the malignant cases, 61.6 have only one aspiration biopsy prior to diagnosis fpsyg.2017.00209 and 81.2 have been identified Caspase-3 InhibitorMedChemExpress Caspase-3 Inhibitor within one year after the first aspiration biopsy. The frequency of aspiration and ultrasonography, as well as older age, male sex, and aspiration biopsies arranged by surgery, endocrinology, or otolaryngology subspecialties are associated with a shorter time to thyroid cancer diagnosis. Many studies have investigated the malignancy rate of fpsyg.2014.00726 patients who underwent thyroid aspiration biopsies. The malignancy rate ranges from 1.6 to 14.9 [14, 22, 23]. Yet thyroidTable 3. Number of thyroid fine-needle aspiration before thyroid cancer diagnosis. Aspiration(s) 1 2 3 4 5 6 >6 doi:10.1371/journal.pone.0127354.t003 No. of patients (n) 170 58 21 16 6 3 2 Cancer ( ) 61.6 21.0 7.6 5.8 2.2 1.1 0.7 Cumulative ( ) 61.6 82.6 90.2 96.0 98.2 99.3 100.0 Undiagnosed ( ) 38.4 17.4 9.8 4.0 1.8 0.7 0.PLOS ONE | DOI:10.1371/journal.pone.0127354 May 28,6 /Thyroid FNA and Thyroid Cancer DiagnosisTable 4. Median time to thyroid cancer diagnosis among patients with thyroid fine-needle aspirations (n = 276/7700). Patient group Low CPI-455MedChemExpress CPI-455 intensity Medium intensity High intensity Extremely high intensity Overall * Log-Rank Test:p < 0.0001 doi:10.1371/journal.pone.0127354.t004 Mean aspiration interval 2 years 1 2 years 0.5 1 year < 0.5 year Patients 3236 1787 1255 1422 7700 Thyroid Cancer ( ) 5 (0.2) 18 (1.0) 26 (2.1) 227 (16.0) 276 (3.6) Median time to diagnosis (yr)* 3.25 (2.03, 4.30) 1.88 (1.15, 2.47) 1.21 (0.67, 1.85) 0.13 (0.10, 0.15)cancer incidence may vary by age, sex, ethnic group, and geographical area [5, 24, 25]. This variability may result from differences in the underlying characteristics of the enrolled subjects, as well as the aggressiveness of screening. The malignancy rate in the present study (3.6 ) is similar to that of a northern Taiwan medical center report (3.9 , 858/21748 cases) [26]. The reported sensitivity of thyroid fine needle aspiration may be as low as 65 in some studies [19]. Among the 276 thyroid cancer patients in this series, 38.4 received more than one aspiration before cancer was diagnosed. This may result from the known pitfalls in thyroid aspiration, including inappropriate target selection [13], inadequate sampling [13, 15], gray zones in thyroid cytology interpretation [13, 27], and newly-developed tumor. In a retrospective study, 46.7 of the aspirated thyroid cancers were initially concluded as benign or insufficient for diagnosis [28]. The initially non-diagnostic rates may be as high as 10?0 [29], andTable 5. Cox proportional hazard model for time to thyroid cancer diagnosis (n = 276). HR* Age Gender Male Female Initial diagnosis Thyrotoxicosis Hypothyroidism, Hashimoto Goiter, Neoplasm Others Aspiration frequency Ultrasound frequency Hospital Center, Regional Area, Clinic Physician Surgery Endocrine ENT Internal medicine Others 2.55 2.58 2.47 1.71 1.00 1.39?.02 1.45?.95 1.25?.15 0.87?.52 1.20 1.00 0.83?.78 0.84 0.81 1.08 1.00 1.07 1.02 1.06?.08 1.01?.03 0.32?.86 0.19?.27 0.78?.52 1.18 1.00 1.00?.38 1.01 95 CI 1.00?.* A hazard ratio (HR) >1.0 indicated an association with shorter time to thyroid cancer diagnosis, whereas an HR <1.0 indicated an as.Y (HR 2.58, 95 CI 1.45?.95), and otolaryngology (HR 2.47, 95 CI 1.25?.15) were all associated with shorter time to thyroid cancer diagnosis (Table 5).DiscussionIn this study, there is a malignancy rate of 3.6 among patients who underwent thyroid aspiration biopsy. Among the malignant cases, 61.6 have only one aspiration biopsy prior to diagnosis fpsyg.2017.00209 and 81.2 have been identified within one year after the first aspiration biopsy. The frequency of aspiration and ultrasonography, as well as older age, male sex, and aspiration biopsies arranged by surgery, endocrinology, or otolaryngology subspecialties are associated with a shorter time to thyroid cancer diagnosis. Many studies have investigated the malignancy rate of fpsyg.2014.00726 patients who underwent thyroid aspiration biopsies. The malignancy rate ranges from 1.6 to 14.9 [14, 22, 23]. Yet thyroidTable 3. Number of thyroid fine-needle aspiration before thyroid cancer diagnosis. Aspiration(s) 1 2 3 4 5 6 >6 doi:10.1371/journal.pone.0127354.t003 No. of patients (n) 170 58 21 16 6 3 2 Cancer ( ) 61.6 21.0 7.6 5.8 2.2 1.1 0.7 Cumulative ( ) 61.6 82.6 90.2 96.0 98.2 99.3 100.0 Undiagnosed ( ) 38.4 17.4 9.8 4.0 1.8 0.7 0.PLOS ONE | DOI:10.1371/journal.pone.0127354 May 28,6 /Thyroid FNA and Thyroid Cancer DiagnosisTable 4. Median time to thyroid cancer diagnosis among patients with thyroid fine-needle aspirations (n = 276/7700). Patient group Low intensity Medium intensity High intensity Extremely high intensity Overall * Log-Rank Test:p < 0.0001 doi:10.1371/journal.pone.0127354.t004 Mean aspiration interval 2 years 1 2 years 0.5 1 year < 0.5 year Patients 3236 1787 1255 1422 7700 Thyroid Cancer ( ) 5 (0.2) 18 (1.0) 26 (2.1) 227 (16.0) 276 (3.6) Median time to diagnosis (yr)* 3.25 (2.03, 4.30) 1.88 (1.15, 2.47) 1.21 (0.67, 1.85) 0.13 (0.10, 0.15)cancer incidence may vary by age, sex, ethnic group, and geographical area [5, 24, 25]. This variability may result from differences in the underlying characteristics of the enrolled subjects, as well as the aggressiveness of screening. The malignancy rate in the present study (3.6 ) is similar to that of a northern Taiwan medical center report (3.9 , 858/21748 cases) [26]. The reported sensitivity of thyroid fine needle aspiration may be as low as 65 in some studies [19]. Among the 276 thyroid cancer patients in this series, 38.4 received more than one aspiration before cancer was diagnosed. This may result from the known pitfalls in thyroid aspiration, including inappropriate target selection [13], inadequate sampling [13, 15], gray zones in thyroid cytology interpretation [13, 27], and newly-developed tumor. In a retrospective study, 46.7 of the aspirated thyroid cancers were initially concluded as benign or insufficient for diagnosis [28]. The initially non-diagnostic rates may be as high as 10?0 [29], andTable 5. Cox proportional hazard model for time to thyroid cancer diagnosis (n = 276). HR* Age Gender Male Female Initial diagnosis Thyrotoxicosis Hypothyroidism, Hashimoto Goiter, Neoplasm Others Aspiration frequency Ultrasound frequency Hospital Center, Regional Area, Clinic Physician Surgery Endocrine ENT Internal medicine Others 2.55 2.58 2.47 1.71 1.00 1.39?.02 1.45?.95 1.25?.15 0.87?.52 1.20 1.00 0.83?.78 0.84 0.81 1.08 1.00 1.07 1.02 1.06?.08 1.01?.03 0.32?.86 0.19?.27 0.78?.52 1.18 1.00 1.00?.38 1.01 95 CI 1.00?.* A hazard ratio (HR) >1.0 indicated an association with shorter time to thyroid cancer diagnosis, whereas an HR <1.0 indicated an as.