Abstract
Cervical lymph nodes (CLNs) are the most common site of metastases in papillary thyroid cancer (PTC). Ultrasound scan (US) is the most commonly used imaging modality in the evaluation of CLNs in PTC. Computerised tomography (CT) and 18fluorodeoxyglucose positron emission tomography (18FDG PET–CT) are used less commonly. It is widely believed that the above imaging techniques should guide the surgical approach to the patient with PTC.
Methods
We performed a systematic review of imaging studies from the literature assessing the usefulness for the detection of metastatic CLNs in PTC. We evaluated the author's interpretation of their numeric findings specifically with regard to ‘sensitivity’ and ‘negative predictive value’ (NPV) by comparing their use against standard definitions of these terms in probabilistic statistics.
Results
A total of 16 studies used probabilistic terms to describe the value of US for the detection of LN metastases. Only 6 (37.5%) calculated sensitivity and NPV correctly. For CT, out of the eight studies, only 1 (12.5%) used correct terms to describe analytical results. One study looked at magnetic resonance imaging, while three assessed 18FDG PET–CT, none of which provided correct calculations for sensitivity and NPV.
Conclusion
Imaging provides high specificity for the detection of cervical metastases of PTC. However, sensitivity and NPV are low. The majority of studies reporting on a high sensitivity have not used key terms according to standard definitions of probabilistic statistics. Against common opinion, there is no current evidence that failure to find LN metastases on ultrasound or cross-sectional imaging can be used to guide surgical decision making.
Introduction
Papillary thyroid cancer (PTC) is the most common thyroid cancer. Metastases from PTC most commonly involve the cervical lymph nodes (CLNs). The incidence of CLN metastases (CLNM) is reported between 30 and 80% (1, 2). Some studies have concluded that in PTC with no other adverse features, the state of the CLNs does not influence prognosis (3). Despite the high incidence of metastases, prophylactic CLN dissection has been discouraged because CLNM has not been considered to be a prognostic factor for survival (4, 5). However, the presence of CLNM has been shown to increase local recurrence rates (6, 7) to up to 31% of patients (8). There is an ongoing debate about the role of systematic central lymph node (LN) dissection in PTC (9).
The preoperative diagnosis of LN metastasis is important for selecting surgical strategies (10). Ultrasound scan (US) is currently the most favoured diagnostic modality to evaluate nodal status preoperatively. It is recommended for this purpose by the American Thyroid Association (ATA) (11) and supported by other thyroid associations (12). Confirmation of metastatic LN with suspicious features on US is achieved by US-guided fine needle aspiration for cytology and/or measurement of thyroglobulin in needle washout (11). Although this method is useful, it does improve sensitivity of US. A number of studies have reported the ‘usefulness’ and ‘diagnostic accuracy’ of US and other imaging modalities, namely computerised tomography (CT), magnetic resonance imaging (MRI) and 18fluorodeoxyglucose positron emission tomography (18FDG PET–CT) in the evaluation of metastatic cervical LN in PTC.
We set out to understand whether the commonly reported ‘high sensitivity’ of imaging techniques to exclude LN metastasis is based on factual evidence. For this purpose, we have tabled the actual data reported by the authors and have analysed whether their use of the terms ‘sensitivity’ and ‘negative predictive value’ (NPV) conforms to textbook definitions of probabilistic statistics. This study does not set out to analyse or critically comment on the impact of LN metastases on prognosis. Our analysis does not directly impact decision making as to the choice of surgical intervention.
Materials and methods
In designing this systematic review, we reviewed published work available from the NIH database PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and Thompson resource ‘ISI Web of Knowledge’ (http://apps.isiknowledge.com/). Accordingly, we included the following criteria for studies to be entered into the systematic review.
Studies involving imaging modalities in detection of CLNs in PTC published in the last 17 years.
All studies had to be published in English.
The authors searched for articles reported over the last 17 years from 1995 up to June 2011 in PubMed, with the combination of search terms ‘papillary thyroid cancer’, ‘LNs dissection’, ‘sensitivity’, specificity, ‘therapeutic LN dissection, US, CT, MRI’ and ‘18FDG PET–CT’. The search was restricted to the presence of one or more of these key words in the title or abstract of the articles.
The preliminary search using these terms yielded 1129 publications. The abstracts of these were read and 32 publications with potential data identified. These 32 publications were read in full text and scrutinised for the presence of relevant data. This process identified 28 studies appropriate for analysis based on the criteria set out above.
Sixteen studies looked at sensitivity of US (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28). Eight studies provided data for CT (13, 15, 21, 24, 25, 27, 29, 30), one study involved MRI (31) and three studies provided data for 18FDG PET–CT (21, 30, 32).
Results
US
Seven studies were identified assessing the use of US in detecting central LN in PTC (Table 1). Out of these, only four studies calculated the sensitivity and NPV correctly. Out of the 11 studies providing data for lateral LN detection, only one (19) was accurate in their calculation of sensitivity and NPV. Five studies provided clustered results for both central and lateral CLN detection, out of which only one (16) calculated the sensitivity and NPV correctly.
Ultrasonography in detection of cervical LN in PTC. Figures in brackets indicate erroneous calculations.
| Study | Total patients (n) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
|---|---|---|---|---|---|
| Central | |||||
| (19) | 600 | 10.5 | 99.1 | 90 | 59.5 |
| (26) | 231 | 29 | 91 | 82 | 47 |
| (28) | 133 | 61 | 93 | 92 | 63 |
| (25) | 165 | (38) | 93 | 77 | (70) |
| (24) | 37 | (55) | 69 | 77 | (44) |
| (27) | 299 | 53 | 80 | 61 | 74 |
| (13) | 589 | (47.2) | 94.8 | 90.4 | (63.5) |
| Lateral | |||||
| (19) | 560 | 27.2 | 96.5 | 93.3 | 43 |
| (21) | 26 | (41.3) | 97.4 | 73.1 | (90.6) |
| (22) | 551 | (83.5) | 97.7 | 88.8 | NA |
| (26) | 361 | NA | NA | 98 | NA |
| (28) | 133 | NA | NA | NA | NA |
| (25) | 165 | (64) | 92 | 83 | (82) |
| (24) | 37 | (65) | 82 | 86 | (59) |
| (27) | 299 | (93.9) | 25 | 93.9 | (25) |
| (13) | 589 | (69.1) | 94.8 | 57.6 | (96.8) |
| (14)a | 70 | (78.3) | 98.7 | 99.5 | (58.2) |
| (15) | 113 | (74.3) | 82.7 | 85.3 | (70.5) |
| Combined central and lateral | |||||
| (16) | 77 | 36.7 | 89.3 | NA | NA |
| (17) | 63 | (70) | 100 | 100 | (87.6) |
| (18) | 456 | (100) | 100 | NA | NA |
| (22)b | 219 | (90.4) | 78.9 | 93.9 | NA |
| (23) | 60 | (92) | 98 | 92 | (98) |
| Mean (of correct calculations) | 36.2 | 57.3 |
Unclear if all LN were dissected.
Re-operated group of patients.
Computerised tomography
A total eight studies were included. Five provided data for central CLN out of which in only one (27), the calculations were correct (Table 2). For lateral LN, seven studies provided the data; however, none of these calculated sensitivity and NPV correctly. One study (30) with clustered results for both central and lateral CLN again was incorrect in the calculations.
CT in the detection of cervical LN metastases in PTC. Figures in brackets indicate erroneous calculations.
| Study | Patients total (n) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
|---|---|---|---|---|---|
| Central LN | |||||
| (25) | 165 | (50) | 91 | 79 | (74) |
| (29) | 102 | (58) | 72 | 72 | (58) |
| (24) | 37 | (74) | 44 | 72 | (47) |
| (27) | 299 | 67 | 79 | 65 | 80 |
| (13) | 589 | (41.9) | 97.4 | 93.6 | (65.1) |
| Lateral LN | |||||
| (21) | 26 | (42.3) | 96.6 | 57.9 | (93.8) |
| (25) | 165 | (74) | 95 | 89 | (86) |
| (29) | 102 | (50) | 71 | 50 | (63) |
| (24) | 37 | (78) | 78 | 86 | (68) |
| (27) | 299 | (81.7) | 100 | 100 | (30.8) |
| (13) | 589 | (78.2) | 93.3 | 54.4 | (97.7) |
| (15) | 113 | (68.6) | 78.8 | 81.4 | (65.1) |
| Combined central and lateral LN | |||||
| (30) | 11 | (75) | 87.5 | 95.9 | (50) |
| Mean (of correct calculations) | 67 | 80 |
Magnetic resonance imaging
One study provided data for use of MRI in detection of cervical LN, which was again not calculated in a correct manner (Table 3).
18FDG PET–CT and MRI in the detection of CLN in PTC. Figures in brackets indicate erroneous calculations.
| Study | Total patients (n) | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) |
|---|---|---|---|---|---|
| 18-F PET–CT | |||||
| Lateral | |||||
| (21) | 27 | (50) | 97 | 65 | (94.6) |
| Combined central and lateral | |||||
| (32)a | 22 | (80) | 83 | 90 | (69) |
| (30)a | 11 | (35.7) | 87.5 | 90.9 | (28) |
| MRI | |||||
| (31) | 105 | (95) | 51 | 84 | (78) |
Patients with local recurrence in cervical LN.
18Fluorodeoxyglucose positron emission tomography–computerised tomography
Three studies provided information for this, one for lateral and two with combined results. None of these studies calculated the sensitivity accurately (Table 3).
In summary, sensitivity was calculated incorrectly in 15 studies (13, 14, 15, 17, 18, 21, 22, 23, 24, 25, 27, 29, 30, 31, 32) and the NPV was calculated incorrectly in 13 studies (13, 14, 15, 17, 21, 23, 24, 25, 27, 29, 30, 31, 32). The most common error made in the calculation of sensitivity and NPV was to assume the number of false negative (FN) LNs to be zero.
Discussion
The frequency of metastases to the cervical LN in PTC is in the region 60–70% (9, 33). The presence of LN metastases is known to be associated with regional recurrence (34). Micro-metastases (<2 mm in diameter) have an incidence of up to 90% depending on the technique used. The clinical implications of this are unclear and possibly less significant than macro-metastases (11). For planning any cancer treatment, it is imperative to have accurate staging as it impacts on the treatment strategy, prognosis and ultimately on long-term survival (35). In PTC, the importance of a thorough preoperative evaluation and subsequent appropriate initial surgery has been emphasised in many studies (7, 36).
US is the most popular imaging modality used in preoperative evaluation of cervical LN in PTC and is recommended by ATA guidelines (11). CT and MR are other modalities utilised. Preoperative staging in PTC therefore largely depends on these imaging modalities. The assessment of ‘usefulness’ and ‘diagnostic accuracy’ of these imaging modalities relies on four criteria, namely sensitivity, specificity, positive predictive value (PPV) and NPV. The ideal scenario for any imaging modality used for preoperative staging of cancer would be a high score on all the aforementioned values. The most serious error in cancer surgery would be under treatment, and this error would be provoked by under-staging or in other words by a false high sensitivity or NPV of the test(s) employed. This argument is not faulted by any claim that the presence of the finding (metastatic LN) tested for is irrelevant. This holds true for logical reasons, as this reasoning would conform with the fallacy of the appeal to consequences or ‘argumentum ad consequentiam’. In addition, it has been shown that CLN status at presentation affects long-term outcomes (37). In the absence of exact data how LN metastases impact outcome in PTC, a merely hypothetical and not factual statement does not substitute for a rational debate around methodological issues of identifying LN metastases.
Sensitivity is defined as the ‘proportion of true positives (TP) that are correctly identified by the test’ (38). In other words, it is the ability of a test to identify those patients with the disease (39). It is defined by the formula TP/TP+FN.
‘NPV’ is defined as the ‘proportion of subjects with a negative test result who are correctly diagnosed’ (38). In other words, it is the likelihood of a patient not having the disease when the test result is negative (39). It is defined by the formula TN/TN+FN (true negatives (TN)).
It is obvious from the above formulae that for calculation of sensitivity and NPV, FN values are required. Although specificity and PPV are important, it is the sensitivity and NPV that define a test in cancer staging as these represent those cases ‘missed’ by the test.
The only empiric method to obtain FN values in PTC is dissection of all cervical LN during surgery irrespective of image findings followed by comparison of histology results to those detected by preoperative imaging. This alone will ascertain that all ‘FN’ cases are included.
This systematic review provides evidence that out of the 16 studies providing values for sensitivity and NPV of US in cervical LN detection, only six studies calculated these values accurately leaving ten studies with either incomplete or inaccurate data (Tables 4 and 5). For studies involving CT, out of eight studies included, only one (27) provided accurate results for sensitivity and NPV. The results from the remaining seven studies are incorrect (Tables 4 and 5). The same applies to 18FDG PET–CT and MR studies; all four studies included calculated the values incorrectly. Overall, only seven out of 28 studies included have performed the calculations correctly, which in effect means that the results and conclusions from the 21 studies are incorrect.
Study details and validity: central and combined cervical LN.
| Study | Patients included | Study hypothesis | TP | TN | FP | FN | Sen | Spec | PPV | NPV | Validity of conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Central | |||||||||||
| (31) | 28 | To determine the ability of MRI imaging to detect the presence of metastatic thyroid cancer in cervical LN | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (20) | 600 | Investigate the clinical significance of LN in the central compartment | 27 | 339 | 3 | 231 | –b | –b | –b | –b | Valid |
| (26) | 231 | To prospectively analyse the outcomes of selective LND to determine when prophylactic lateral neck dissection is advisable | 40 | 86 | 9 | 96 | –a | –b | –b | –a | Invalid |
| (28)c | 133 | Evaluation of preoperative US in detecting cervical metastases in PTC | NA | NA | NA | NA | –b | –b | –b | –b | Valid |
| (27) | 299 | To compare the diagnostic accuracy of US with that of CT in patients with PTC | NA | NA | NA | NA | –b | –b | –b | –b | Valid |
| (25) | 165 | Determine the diagnostic accuracies of US, CT and combined US and CT | 20 | 75 | 6 | 32 | –a | –b | –b | –a | Invalid |
| (24) | 9 | Investigate the diagnostic ability of CT and US of cervical LN in thyroid cancer | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (13) | 589 | To evaluate the diagnostic accuracy of preoperative US and CT of the neck | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (29) | 102 | Sensitivity, specificity. PPV and NPV calculated | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| Central and lateral | |||||||||||
| (17) | 63 | The usefulness of US in diagnosing cervical LNM in PTC was investigated | 14 | 43 | 0 | 6 | –a | –b | –b | –a | Invalid |
| (16) | 77 | To evaluate the usefulness of US for preoperative staging of PTC | NA | NA | NA | NA | –b | –b | NA | NA | Invalid |
| (18) | 456 | Determine the sensitivity of neck US to detect LN metastases | 38 | NA | NA | 418 | –a | –b | –b | –a | Invalid |
| (30) | 11 | If PET–CT is more accurate than CT for detecting metastatic cervical LN in PTC | 21 | 7 | 1 | 7 | –a | –b | –b | –a | Invalid |
| (32)c | 22 | Evaluate whether FDG PET is feasible as a pre-surgical evaluation modality for I-131 scan-negative thyroid carcinoma patients | 45 | 24 | 5 | 11 | –a | –b | –b | –a | Invalid |
| (23) | 60 | To determine the frequency of occult macroscopic metastasis detected by preoperative US | 11 | 47 | 1 | 1 | –a | –b | –b | –a | Invalid |
| (22) | 551 | Preoperative US will increase detection and assessment of the extent of LNM in PTC | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
Sen, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value; TP, true positives; TN, true negatives; FP, false positives; FN, false negatives.
Incorrectly calculated.
Correctly calculated.
Figures available by levels, no overall figures.
Study details and validity: lateral LN.
| Study | Patients included | Study hypothesis | TP | TN | FP | FN | Sen | Spec | PPV | NPV | Validity of conclusion |
|---|---|---|---|---|---|---|---|---|---|---|---|
| (24) | 28 | Investigate the diagnostic ability of CT and US of cervical LN in thyroid cancer | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (25) | 165 | Determine the diagnostic accuracies of US, CT and combined US and CT | 20 | 75 | 6 | 32 | –a | –b | –b | –a | Invalid |
| (19) | 560 | Investigate the prognostic impact of lateral LNM detected by US | 98 | 194 | 7 | 261 | –b | –b | –b | –b | Valid |
| (26) | 130 | To prospectively analyse the outcomes of selective LND to determine when prophylactic lateral neck dissection in advisable | 127 | 0 | 3 | 0 | –a | –b | –b | –a | Invalid |
| (28)c | 34 | Evaluation of preoperative US in detecting cervical metastases in PTC | NA | NA | NA | NA | NA | NA | NA | NA | Invalid |
| (21) | 26 | To compare the diagnostic of 18F-FDG PET–CT with US | 14 | 229 | 5 | 12 | –a | –b | –b | –a | Invalid |
| (13) | 589 | To evaluate the diagnostic accuracy of preoperative US and CT of the neck | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (14) | 70 | To investigate the usefulness and limits of US in PTC | 199 | 76 | 1 | 55 | –a | –b | –b | –a | Invalid |
| (15) | 112 | To evaluate the most accurate criteria using US and CT in predicting lateral LN in PTC | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (29) | 102 | Sensitivity, specificity. PPV and NPV calculated | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
| (27) | 53 | To compare the diagnostic accuracy of US with that of CT in patients with PTC | NA | NA | NA | NA | –a | –b | –b | –a | Invalid |
Sen, sensitivity; Spec, specificity; PPV, positive predictive value; NPV, negative predictive value; TP, true positives; TN, true negatives; FP, false positives; FN, false negatives.
Incorrectly calculated.
Correctly calculated.
Figures available by levels, no overall figures.
These inaccuracies reflect misunderstandings or simply incorrect definitions of the terms ‘sensitivity’ and ‘NPV’ in the context of imaging in PTC. In all those studies that have calculated sensitivity and NPV incorrectly, all cervical LN were not dissected, hence providing unreliable ‘FN’ values.
A recent meta-analysis by Wu et al. (40) looked at the accuracy of US in the detection of metastatic LN. They provide ‘pooled sensitivity’ figures of 0.72 and 0.63 for patient- and region-based LND respectively. This pooled sensitivity is essentially weighted sensitivity calculated from studies some of which have performed therapeutic LND. The results provided by the meta-analysis are incorrect as FN values would not have been known. It seems to us that sensitivity is a widely misunderstood term certainly in the case of imaging in PTC.
The foundation of scientific analysis is correct methodology. Based on this approach, the mean sensitivity and NPV of US was 36.2 and 57.3% respectively. The only study, which provided correct results for CT, had a sensitivity of 67% and NPV of 80% for central compartment only (27).
From the available data, US or indeed CT cannot be considered reliable imaging modalities for cervical LN detection in PTC. It needs to be acknowledged that US is operator dependent and individual results may be better than what has been published in the peer-reviewed literature. However, such operator dependency puts obvious limitations to the use of the results obtained and requires rigorous internal audit procedures. Properly designed studies calculating FN correctly and thereby providing accurate values for sensitivity and NPV are required to resolve this issue.
It is beyond the remit of this study to provide recommendations on the surgical approach to potential lateral LN metastases. Our purpose was to look at the quality of the evidence underlying eventual current assumptions and recommendations.
Conclusion
The majority of data on sensitivity and accuracy of imaging for preoperative detection of LN in PTC is misleading and hence cannot be relied upon for its preoperative staging. The few studies reporting accurate figures have identified low sensitivities to detect locoregional LN metastases of PTC. Reliance on preoperative imaging for planning of the surgical approach is currently unsupported by published evidence. Studies with appropriate design are needed to inform the discussion.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
References
- 1
Tubiana M, Schlumberger M, Rougier P, Laplanche A, Benhamou E, Gardet P, Caillou B, Travagli JP, Parmentier C. Long-term results and prognostic factors in patients with differentiated thyroid carcinoma. Cancer 1985 55 794–804. (doi:10.1002/1097-0142(19850215)55:4<794::AID-CNCR2820550418>3.0.CO;2-Z).
- 2
Mazzaferri EL. Management of a solitary thyroid nodule. New England Journal of Medicine 1993 328 553–559. (doi:10.1056/NEJM199302253280807).
- 3↑
Shaha AR, Shah JP, Loree TR. Risk group stratification and prognostic factors in papillary carcinoma of thyroid. Annals of Surgical Oncology 1996 3 534–538. (doi:10.1007/BF02306085).
- 4
Singer PA, Cooper DS, Daniels GH, Ladenson PW, Greenspan FS, Levy EG, Braverman LE, Clark OH, McDougall IR, Ain KV, Dorfman SG. Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association. Annals of Internal Medicine 1996 156 2165–2172. (doi:10.1001/archinte.1996.00440180017002).
- 5
Shaha AR. Management of the neck in thyroid cancer. Otolaryngologic Clinics of North America 1998 31 823–831. (doi:10.1016/S0030-6665(05)70090-6).
- 6
Marshall CL, Lee JE, Xing Y, Perrier ND, Edeiken BS, Evans DB, Grubbs EG. Routine pre-operative ultrasonography for papillary thyroid cancer: effects on cervical recurrence. Surgery 2009 146 1063–1072. (doi:10.1016/j.surg.2009.09.027).
- 7
Mazzaferri EL. A vision for the surgical management of papillary thyroid carcinoma: extensive lymph node compartmental dissections and selective use of radioiodine. Journal of Clinical Endocrinology and Metabolism 2009 94 1086–1088. (doi:10.1210/jc.2009-0298).
- 8↑
Simon D, Goretzki PE, Witte J, Röher HD. Incidence of regional recurrence guiding radicality in differentiated thyroid carcinoma. World Journal of Surgery 1996 20 860–866.(discussion 866) (doi:10.1007/s002689900131).
- 9↑
Mulla M, Schulte KM. Central cervical lymph node metastases in papillary thyroid cancer: a systematic review of imaging-guided and prophylactic removal of the central compartment. Clinical Endocrinology 2012 76 131–136. (doi:10.1111/j.1365-2265.2011.04162.x).
- 10↑
Park JS, Son KR, Na DG, Kim E, Kim S. Performance of preoperative sonographic staging of papillary thyroid carcinoma based on the sixth edition of the AJCC/UICC TNM classification system. AJR. American Journal of Roentgenology 2009 192 66–72. (doi:10.2214/AJR.07.3731).
- 11↑
Cooper DS, Doherty GM, Haugen BR, Kloos RT, Lee SL, Mandel SJ, Mazzaferri EL, McIver B, Pacini F, Schlumberger M, Sherman SI, Steward DL, Tuttle RM. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 2009 19 1167–1214. (doi:10.1089/thy.2009.0110).
- 12↑
British Thyroid Association. In Guidelines for the Management of Thyroid Cancer, 2nd edn. Ed P Perros. Report of the Thyroid Cancer Guidelines Update Group. London: Royal College of Physicians, 2007
- 13↑
Choi YJ, Yun JS, Kook SH, Jung EC, Park YL. Clinical and imaging assessment of cervical lymph node metastasis in papillary thyroid carcinomas. World Journal of Surgery 2010 34 1494–1499. (doi:10.1007/s00268-010-0541-1).
- 14↑
Lee K, Kawata R, Nishikawa S, Yoshimura K, Takenaka H. Diagnostic criteria of ultrasonographic examination for lateral node metastasis of papillary thyroid carcinoma. Acta Oto-Laryngologica 2010 130 161–166. (doi:10.3109/00016480903015143).
- 15↑
Yoon JH, Kim JY, Moon HJ, Youk JH, Son EJ, Kim EK, Han KH, Kwak JY. Contribution of computed tomography to ultrasound in predicting lateral lymph node metastasis in patients with papillary thyroid carcinoma. Annals of Surgical Oncology 2011 18 1734–1741. (doi:10.1245/s10434-010-1527-9).
- 16↑
Shimamoto K, Satake H, Sawaki A, Ishigaki T, Funahashi H, Imai T. Preoperative staging of thyroid papillary carcinoma with ultrasonography. European Journal of Radiology 1998 29 4–10. (doi:10.1016/S0720-048X(97)00184-8).
- 17↑
Kessler A, Rappaport Y, Blank A, Marmor S, Weiss J, Graif M. Cystic appearance of cervical lymph nodes is characteristic of metastatic papillary thyroid carcinoma. Journal of Clinical Ultrasound 2003 31 21–25. (doi:10.1002/jcu.10130).
- 18↑
Torlontano M, Attard M, Crocetti U, Tumino S, Bruno R, Costante G, D'Azzò G, Meringolo D, Ferretti E, Sacco R, Arturi F, Filetti S. Follow-up of low risk patients with papillary thyroid cancer: role of neck ultrasonography in detecting lymph node metastases. Journal of Clinical Endocrinology and Metabolism 2004 89 3402–3407. (doi:10.1210/jc.2003-031521).
- 19↑
Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A. Ultrasonographically and anatomopathologically detectable node metastases in the lateral compartment as indicators of worse relapse-free survival in patients with papillary thyroid carcinoma. World Journal of Surgery 2005 29 917–920. (doi:10.1007/s00268-005-7789-x).
- 20↑
Ito Y, Tomoda C, Uruno T, Takamura Y, Miya A, Kobayashi K, Matsuzuka F, Kuma K, Miyauchi A. Clinical significance of metastasis to the central compartment from papillary microcarcinoma of the thyroid. World Journal of Surgery 2006 30 91–99. (doi:10.1007/s00268-005-0113-y).
- 21↑
Jeong HS, Baek CH, Son YI, Choi JY, Kim HJ, Ko YH, Chung JH, Baek HJ. Integrated 18F-FDG PET/CT for the initial evaluation of cervical node level of patients with papillary thyroid carcinoma: comparison with ultrasound and contrast-enhanced CT. Clinical Endocrinology 2006 65 402–407. (doi:10.1111/j.1365-2265.2006.02612.x).
- 22↑
Stulak JM, Grant CS, Farley DR, Thompson GB, van Heerden JA, Hay ID, Reading CC, Charboneau JW. Value of preoperative ultrasonography in the surgical management of initial and reoperative papillary thyroid cancer. Archives of Surgery 2006 141 489–494.(discussion 494–496) (doi:10.1001/archsurg.141.5.489).
- 23↑
Gonzalez HE, Cruz F, O'Brien A, Goñi I, León A, Claure R, Camus M, Dominguez F, Mosso L, Arteaga E, González G, López JM, Rodriguez JA, Carrasco C, Fardella C. Impact of preoperative ultrasonographic staging of the neck in papillary thyroid carcinoma. Archives of Otolaryngology – Head & Neck Surgery 2007 133 1258–1262. (doi:10.1001/archotol.133.12.1258).
- 24↑
Ahn JE, Lee JH, Yi JS, Shong YK, Hong SJ, Lee DH, Choi CG, Kim SJ. Diagnostic accuracy of CT and ultrasonography for evaluating metastatic cervical lymph nodes in patients with thyroid cancer. World Journal of Surgery 2008 32 1552–1558. (doi:10.1007/s00268-008-9588-7).
- 25↑
Kim E, Park JS, Son KR, Kim JH, Jeon SJ, Na DG. Preoperative diagnosis of cervical metastatic lymph nodes in papillary thyroid carcinoma: comparison of ultrasound, computed tomography, and combined ultrasound with computed tomography. Thyroid 2008 18 411–418. (doi:10.1089/thy.2007.0269).
- 26↑
Sugitani I, Fujimoto Y, Yamada K, Yamamoto N. Prospective outcomes of selective lymph node dissection for papillary thyroid carcinoma based on preoperative ultrasonography. World Journal of Surgery 2008 32 2494–2502. (doi:10.1007/s00268-008-9711-9).
- 27↑
Choi JS, Kim J, Kwak JY, Kim MJ, Chang HS, Kim EK. Preoperative staging of papillary thyroid carcinoma: comparison of ultrasound imaging and CT. AJR. American Journal of Roentgenology 2009 193 871–878. (doi:10.2214/AJR.09.2386).
- 28↑
Roh JL, Park JY, Kim JM, Song CJ. Use of preoperative ultrasonography as guidance for neck dissection in patients with papillary thyroid carcinoma. Journal of Surgical Oncology 2009 99 28–31. (doi:10.1002/jso.21164).
- 29↑
Soler ZM, Hamilton BE, Schuff KG, Samuels MH, Cohen JI. Utility of computed tomography in the detection of subclinical nodal disease in papillary thyroid carcinoma. Archives of Otolaryngology – Head & Neck Surgery 2008 134 973–978. (doi:10.1001/archotol.134.9.973).
- 30↑
Lee DH, Kang WJ, Seo HS, Kim E, Kim JH, Son KR, Na DG. Detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma: computed tomography versus positron emission tomography–computed tomography. Journal of Computer Assisted Tomography 2009 33 805–810. (doi:10.1097/RCT.0b013e31818fb3f1).
- 31↑
Gross ND, Weissman JL, Talbot JM, Andersen PE, Wax MK, Cohen JI. MRI detection of cervical metastasis from differentiated thyroid carcinoma. Laryngoscope 2001 111 (11 Pt 1) 1905–1909. (doi:10.1097/00005537-200111000-00006).
- 32↑
Yeo JS, Chung JK, So Y, Kim S, Lee E, Lee DS, Youn YK, Hong SJ, Ahn IM, Lee MC, Cho BY. F-18-fluorodeoxyglucose, positron emission tomography as a presurgical evaluation modality for I-131 scan-negative thyroid carcinoma patients with local recurrence in cervical lymph nodes. Head & Neck 2001 23 94–103. (doi:10.1002/1097-0347(200102)23:2<94::AID-HED1004>3.0.CO;2-R).
- 33
Rotstein L. The role of lymphadenectomy in the management of papillary carcinoma of the thyroid. Journal of Surgical Oncology 2009 99 186–188. (doi:10.1002/jso.21234).
- 34↑
Sivanandan R, Soo KC. Pattern of cervical lymph node metastases from papillary carcinoma of the thyroid. British Journal of Surgery 2001 88 1241–1244. (doi:10.1046/j.0007-1323.2001.01843.x).
- 35↑
Tan LK, Giri D, Panageas KS, Brogi E, Norton L, Hudis C, Borgen PI, Cody HS III. Occult axillary node metastases in breast cancer are prognostically significant: results in 368 node-negative patients with 20-year follow-up. Journal of Clinical Oncology 2008 26 1803–1809. (doi:10.1200/JCO.2007.12.6425).
- 36
Chow SM, Law SC, Chan JK, Au SK, Yau S, Lau WH. Papillary microcarcinoma of the thyroid–Prognostic significance of lymph node metastasis and multifocality. Cancer 2003 98 31–40. (doi:10.1002/cncr.11442).
- 37↑
Lundgren CI, Hall P, Dickman PW, Zedenius J. Clinically significant prognostic factors for differentiated thyroid carcinoma: a population-based, nested case–control study. Cancer 2006 106 524–531. (doi:10.1002/cncr.21653).
- 38↑
Altman DG, Bland JM. Diagnostic tests. 1: sensitivity and specificity. BMJ 1994 308 1552. (doi:10.1136/bmj.308.6943.1552).
- 39↑
Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. Continuing Education in Anaesthesia, Critical Care & Pain 2008 8 221–223. (doi:10.1093/bjaceaccp/mkn041).
- 40↑
Wu LM, Gu HY, Qu XH, Zheng J, Zhang W, Yin Y, Xu JR. The accuracy of ultrasonography in the preoperative diagnosis of cervical lymph node metastasis in patients with papillary thyroid carcinoma: a meta-analysis. European Journal of Radiology 2012 81 1798–1805. (doi:10.1016/j.ejrad.2011.04.028).
