Thyroid cancer and lymph node metastases
Department of Surgery, Mt. Zion Medical Center, University of California San Francisco, San Francisco, California 94115, USA. Journal of Surgical Oncology
(Impact Factor: 3.24).
05/2011; 103(6):615-8. DOI: 10.1002/jso.21804
There is considerable controversy about the prognostic implications of lymph node metastases in patients with papillary thyroid cancer and whether patients with papillary thyroid cancer should have a prophylactic or selective central (level VI) neck dissection. Some experts report that a prophylactic ipsilateral neck dissection results in fewer patients having elevated thyroglobulin levels but others do not agree. A comprehensive review of the literature suggests that the presence of macroscopic metastases of papillary thyroid cancer in cervical lymph nodes results in a higher recurrence rate and increased death rate, especially in patients 45 years of age or older, whereas microscopic nodal metastases do not appear to adversely influence survival. Until more information is available we recommend preoperative ultrasonography and a selective ipsilateral neck dissection for patients with papillary thyroid cancer.
Available from: Marene IB Landström
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ABSTRACT: Anaplastic thyroid carcinoma (ATC) is one of the most malignant tumors in humans, and currently there is no effective treatment. In the present study we investigated the effect of an endogenous estrogen metabolite, 2-methoxyestradiol (2-ME), on the growth of human ATC cells. 2-ME treatment had a strong growth inhibitory effect on five human ATC cell lines (HTh7, HTh 74, HTh83, C643, and SW1736), but showed no effect on one cell line (KAT-4). Cell cycle analysis of the growth-inhibited cells showed that 2-ME induced a G(2)/M-arrest, followed by an increased fraction of cells in sub-G(1). Analysis of internucleosomal DNA laddering as well as DNA fragmentation in a terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) assay demonstrated a high number of cells undergoing apoptosis after 2-ME treatment. An increased activation of caspase-3 and caspase-8 by 2-ME was observed, and inhibition of caspase-3 decreased the apoptotic effect. Addition of 2-ME increased activity of p38 mitogen-activated protein kinase (MAPK) in the sensitive HTh7 as well as the refractory KAT-4 cells, however, activation of stress-activated protein kinase/c-jun aminoterminal kinase (SAPK/JNK) was seen only in the HTh7 cells. Inhibitors of p38 MABK and SAPK/JNK significantly attenuated the 2-ME effect. Taken together, our data demonstrate an antiproliferative and apoptotic effect of 2-ME on ATC cells involving activation of MAPKs.
Thyroid 02/2006; 16(2):143-150. DOI:10.1089/thy.2006.16.143 · 4.49 Impact Factor
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ABSTRACT: This review on the unique patterns of metastases by common and rare types of cancer addresses regional lymphatic metastases but also demonstrates general principles by consideration of vital organ metastases. These general features of successfully treated metastases are relationships to basic biological behavior as illustrated by disease-free interval, organ-specific behavior, oligo-metastatic presentation, genetic control of the metastatic pattern, careful selection of patients for surgical resection, and the necessity of complete resection of the few patients eligible for long-term survival after resection of vital organ metastasis. Lymph node metastases, while illustrating these general features, are not related to overall survival because lymph node metastases themselves do not destroy a vital organ function, and therefore have no causal relationship to overall survival. When a cancer cell spreads to a regional lymph node, does it also simultaneously spread to the systemic site or sites? Alternatively, does the cancer spread to the regional lymph node first and then it subsequently spreads to the distant site(s) after an incubation period of growth in the lymph node? Of course, if the cancer is in its incubation stage in the lymph node, then removal of the lymph node in the majority of cases with cancer cells may be curative. The data from the sentinel lymph node era, particularly in melanoma and breast cancer, is consistent with the spectrum theory of cancer progression to the sentinel lymph node in the majority of cases prior to distant metastasis. Perhaps, different subsets of cancer may be better defined with relevant biomarkers so that mechanisms of metastasis can be more accurately defined on a molecular and genomic level. J. Surg. Oncol. 2011;103:607–614. © 2011 Wiley-Liss, Inc.
Journal of Surgical Oncology 05/2011; 103(6):607 - 614. DOI:10.1002/jso.21841 · 3.24 Impact Factor
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ABSTRACT: The diffuse sclerosing (DSV) and tall cell (TCV) variants are considered aggressive subtypes of papillary thyroid cancer (PTC) for which data are limited.
The Surveillance, Epidemiology, and End Results (SEER) database (1988-2008) was used to compare the incidence and clinical/pathologic characteristics of DSV and TCV with classic PTC. Prognostic factors associated with survival were analyzed by chi-square test, analysis of variance, log rank test, and Cox multivariate regression.
There were 261 DSV, 573 TCV, and 42,904 PTC patients. Compared to a 60.8% increase in classic PTC incidence, DSV and TCV incidence increased by 126% (P (trend) = 0.052) and 158% (P (trend) = 0.002), respectively. Aggressive variants were associated with higher rates of extrathyroidal extension, multifocality, and nodal and distant metastasis (all P < 0.001) compared to classic PTC. Nodal metastasis was more likely with DSV (72.2% vs. 66.8% TCV vs. 56.3% PTC, P < 0.001); distant metastasis was most common with TCV (11.1% vs. 7.3% DSV vs. 4.3% PTC, P < 0.001). After adjustment, DSV [hazard ratio (HR) 1.8, P = 0.007] and TCV (HR 1.9, P < 0.001) histologies were associated with significantly reduced survival (5-year overall: 87.5% DSV, 80.6% TCV vs. 93.5% PTC, P < 0.001). Tumor size independently predicted worse prognosis for TCV (HR 1.29, P < 0.001) but not DSV patients. Thyroid surgery and radioiodine improved survival of DSV and TCV patients (all P < 0.05). Patients with aggressive variants who received external-beam radiotherapy did not experience improved survival.
DSV and TCV are rare, increasing in incidence, and have a worse prognosis than classic PTC. Patients with these variants should be treated aggressively with thyroidectomy and radioiodine, regardless of tumor size.
Annals of Surgical Oncology 11/2011; 19(6):1874-80. DOI:10.1245/s10434-011-2129-x · 3.93 Impact Factor
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