Management Of Papillary Thyroid Carcinoma Research Articles

Discriminatory miRNAs for the Management of Papillary Thyroid Carcinoma and Noninvasive Follicular Thyroid Neoplasms with Papillary-Like Nuclear Features.

Papillary thyroid carcinoma (PTC) variants have several overlapping clinical and pathological features. The World Health Organization recently published a new classification of thyroid tumors containing significant revisions. Encapsulated papillary thyroid carcinoma (EPTC) has been recognized as a distinctive variant of PTC. The noninvasive encapsulated follicular variant of PTC has been reclassified as noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). Different neoplasms are associated with different outcomes and require different clinical management. The objective of this study was to explore the miRNA expression patterns specific for classic PTC (cPTC), EPTC, follicular variant of PTC, and NIFTP in order to identify biomarkers of diagnostic and prognostic utility aiming for better clinical decisions. The expression of 84 miRNAs was determined by quantitative real-time polymerase chain reaction in 113 thyroid tissues of PTC (classic, encapsulated, and follicular), NIFTP, and hyperplasia lesions. Expression of the same miRNAs was tested in pre- and postoperative whole-blood samples. Several miRNAs were differentially expressed in the different groups. Expression profile of miRNAs in the tissue was similarly reflected in the circulation. Receiver operating characteristic curve analysis showed that miR-7-5p, miR-222-3p, and miR-146b-5p can discriminate between the different groups with high sensitivity and specificity. Downregulation of miR-144-3p, miR-15a-5p, miR-20a-5p, miR-32-5p miR-142-5p, miR-143-3p, and miR-20b-5p is associated with aggressive behavior in cPTC. Circulating miR-146b-5p, miR-222-3p, miR-155-5p, and miR-378a-3p are potential diagnostic and follow up biomarkers for PTC. Downregulation of miR-7-5p discriminates NIFTP from hyperplasia. Upregulation of miR-222-3p discriminates follicular variant of PTC from NIFTP. High levels of miR-146b-5p distinctively characterize cPTC. These miRNAs are useful biomarkers in the diagnosis of PTC and NIFTP, and help to avoid unnecessary thyroidectomy and improve clinical management.

Impact of tall cell variant histology on predicting relapse and changing the management of papillary thyroid carcinoma patients.

There has been much discussion recently about the risk category of tall cell variant (TVC) histology and its effects on the management of papillary thyroid carcinoma (PTC). We, therefore, undertook a retrospective study to compare stage-matched risk factors and recurrence rates between classical PTC (cPTC) patients and patients with TCV histology. A total of 3128 well-differentiated thyroid carcinoma patients who were treated and followed-up for more than 5 years in our clinic from 1995 to 2016 were included in this study. There were 2783 PTC (89%) patients, 1113 (40%) of them were cPTC and 56 (2%) of them were TCV patients. In all stages, the stage-matched incidence of extrathyroidal extension (ETE), lymphovascular invasion and initial lymph node metastases were significantly higher in TCV patients than in cPTC patients (P<0.001). Recurrence was in 10 of 27 patients (37%) with TCV and in 91 of 890 (10%) patients with cPTC diagnosed in stage I (odds ratio (OR)=5.16); in 4 of 6 patients with TCV and 18 of 84 (21%) patients with cPTC in stage II (OR=7.33); in 5 of 6 patients with TCV and 11 of 46 (23%) patients with cPTC in stage III (OR=15.90); and in 13 of 17 patients with TCV and 31 of 93 (33%) patients with cPTC in stage IV (OR=6.50). Stage-matched recurrence rates were found significantly higher in all stages of TCV patients than in cPTC patients (OR=8.49, P<0.001). Recurrence with distant metastases was seen more frequently in TCV patients than in cPTC patients (P<0.001) and treatment of metastatic disease was more difficult in TCV patients. Tall cell variant was an independent poor prognostic factor in papillary thyroid carcinoma patients even if they were diagnosed at early stages of the disease. Patients with tall cell variant histology required more aggressive therapeutic approach and closer follow-up than classical patients.

Surgical management of papillary thyroid carcinoma: an overview.

The surgical management of papillary thyroid carcinoma remains contentious and the optimal surgical strategy has not been yet established. The extent of thyroid resection has been the nub of this debate. Literature lacks prospective randomized controlled trials that could help put this debate to rest, and these have been labeled as being impractical. Consequently, large retrospective studies and expert opinion have constituted the basis of clinical practice guidelines. Recent American Thyroid Association and National Comprehensive Cancer Network guidelines consider a conservative approach in the form of a thyroid lobectomy sufficient for low-risk disease and that total thyroidectomy remains the standard of care in the presence of high-risk features. Nevertheless, many authorities still advocate more aggressive therapy for low-risk disease. The challenge in standardizing the surgical strategy to papillary thyroid carcinoma is mainly related to a major tumor characteristic: the high frequency of occult cancerous foci whether within the thyroid gland itself or within loco-regional lymph nodes as this tumor characteristic has been incriminated for a higher risk of recurrent disease and its adverse sequelae. The purpose of this article is to provide an overview of the surgical management of papillary thyroid carcinoma and the main arguments surrounding this hotly debated topic. All evidences for this review article were drawn from PubMed articles in English language mostly cross-referenced with international guideline statements.

Surgical management of papillary thyroid carcinoma according to BRAF mutation

Surgical management of papillary thyroid carcinoma according to BRAF mutation

Prophylactic Central Neck Dissection in the Management of Papillary Thyroid Carcinoma; is there a Meaningful Outcome?

Prophylactic Central Neck Dissection in the Management of Papillary Thyroid Carcinoma; is there a Meaningful Outcome?

Surgical management of papillary thyroid carcinoma in childhood and adolescence: an Italian multicenter study on 250 patients.

The extent of surgery for pediatric papillary thyroid carcinoma is debatable. The aim of this study was to evaluate the feasibility of offering pediatric patients a tailored surgical approach based on certain clinical features. A national multicenter retrospective review of 250 pediatric patients treated for papillary thyroid carcinoma in a 14-year period was performed. Outcomes of interest included tumor-related features, type of surgery, surgical morbidity, disease-free and overall survival rates. Recurrence was thoroughly analyzed with particular focus on how it correlated with certain patient- and tumor-related features. The majority of patients (58.8%) had tumors >2cm in size. Nodal involvement occurred in 115/250 (46%) patients and distant metastasis in 4% (10/250). Total thyroidectomy and lobectomy were performed in 90.4% (226/250) and 9.6% (24/250) of patients, respectively. The overall rate of surgical complications was 20.8% (52/250). These included transient and permanent hypoparathyroidism (13.6 and 4.4%, respectively), and vocal fold palsy (2.8%). All surgical complications occurred exclusively in the total thyroidectomy group. The rate of recurrent disease was 12% (30/250) with the vast majority of recurrences (96.6%) occurring in the total thyroidectomy group. The risk of recurrence correlated significantly with certain tumor-related features (size>2cm, multifocality, extrathyroidal invasion, nodal positivity, and distant metastasis). However, it did not correlate with the patient's age or sex. Overall survival was 100%. Pediatric patients are likely to benefit from a tailored surgical strategy. Uniformly offering patients total thyroidectomy seems to be an overly radical approach.

Risk Factors Associated with Disease Recurrence among Patients with Low-Risk Papillary Thyroid Cancer Treated at the University of the Philippines-Philippine General Hospital.

BackgroundThe management of papillary thyroid carcinoma (PTC) in high-risk patients is well-standardized. However, this is not the case for low-risk patients. Filipinos show a high incidence of recurrence of thyroid cancer. Thus, the identification of risk factors for recurrence in this population could potentially identify individuals for whom radioactive iodine (RAI) therapy might be beneficial.MethodsWe reviewed the medical records of adult Filipinos with low-risk PTC who underwent near-total or total thyroidectomy at the University of the Philippines-Philippine General Hospital. Multivariate logistic regression analysis was used to determine risk factors for recurrence.ResultsRecurrence was documented in 51/145 of patients (35.17%) included in this study. Possible risk factors such as age, sex, family history, smoking history, tumor size, multifocality, prophylactic lymph node dissection, initial thyroglobulin (Tg) level, initial anti-thyroglobulin (anti-Tg) antibody concentration, suppression of thyroid stimulating hormone production, and RAI therapy were analyzed. Multivariate analysis revealed that a tumor diameter 2 to 4 cm (odds ratio [OR], 9.17; 95% confidence interval [CI], 1.62 to 51.88; P=0.012), a tumor diameter >4 cm (OR, 16.46; 95% CI, 1.14 to 237.31; P=0.04), and a family history of PTC (OR, 67.27; 95% CI, 2.03 to 2228.96; P=0.018) were significant predictors of recurrence. In addition, RAI therapy (OR, 0.026; 95% CI, 0.01 to 0.023; P≤0.005), an initial Tg level ≤2 ng/mL (OR, 0.049; 95% CI, 0.01 to 0.23; P≤0.005), and an anti-Tg antibody level ≤50 U/mL (OR, 0.087; 95% CI, 0.011 to 0.67; P=0.019) were significant protective factors.ConclusionA tumor diameter ≥2 cm and a family history of PTC are significant predictors of recurrence. RAI therapy and low initial titers of Tg and anti-Tg antibody are significant protective factors against disease recurrence among low-risk PTC patients.

Association of sociodemographic factors with nonguideline treatment in papillary thyroid carcinoma.

e17096 Background: There is wide variability in the management of papillary thyroid carcinoma (PTC). National Comprehensive Cancer Network (NCCN) and 2009 American Thyroid Association guidelines ar...

The Benefits and Risks of Prophylactic Central Neck Dissection for Papillary Thyroid Carcinoma: Prospective Cohort Study.

Objectives. This study evaluated the benefits of performing prophylactic central neck dissection (CND) with total thyroidectomy (TT) in management of papillary thyroid carcinoma (PTC) patients who were clinically node-negative at presentation. Methods. A total of 257 patients with stage T1 or T2 PTC and without preoperative evidence of lymph node involvement (N0) were enrolled in this prospective study. The patients were randomly assigned to two groups: (1) a total thyroidectomy (TT) group (n = 104) or (2) a TT plus CND group (n = 153). The two groups were compared for their perioperative data, complication rates, disease recurrence rates, and clinical outcomes. Results. The two groups of patients were similar in age, sex ratio, follow-up duration, and tumor size (P = 0.227, 0.359, 0.214, and 0.878, resp.). The two groups showed similar rates of disease recurrence (3.9% in the TT group versus 3.3% in the TT plus CND group); however, complications occurred more frequently in the TT plus CND group; especially transient hypocalcemia (P = 0.043). Conclusions. Patients treated with TT plus CND had a higher rate of complications with similar recurrence rate. We believe that CND may not be routinely recommended when treating patients with PTC.

Risk-adapted management of papillary thyroid carcinoma according to our own risk group classification system: Is thyroid lobectomy the treatment of choice for low-risk patients?

Our original system for risk group classification for predicting cause-specific death from papillary thyroid carcinoma (PTC) defined patients with distant metastasis and older patients (≥ 50 years) with either massive extrathyroidal extension or large (≥ 3 cm) lymph node metastasis as high risk; all others are low risk. For unilateral, low-risk PTC, the extent of thyroidectomy (less-than-total thyroidectomy vs total or near-total thyroidectomy) has been determined based on the choice of the patient since 2005. Of 1,187 patients who underwent initial thyroidectomy for PTC (tumor size [T] >1 cm) between 1993 and 2010, 967 (82%) were classified as low risk. Among low-risk patients, 791 (82%) underwent less than total thyroidectomy. The 10-year cause-specific survival and disease-free survival rates did not differ between patients who underwent total thyroidectomy versus less than total thyroidectomy (cause-specific survival, 99% vs 99% [P = .61]; disease-free survival, 91% vs 87% [P = .90]). Age ≥ 60 years, T ≥ 3 cm, and lymph node metastases >3 cm represented significant risk factors for distant recurrence. The favorable overall survival of low-risk patients, regardless of the extent of thyroidectomy, supports patient autonomy in treatment-related decision making. Low-risk patients possessing risk factors for distant recurrence would be likely to benefit from total thyroidectomy followed by radioactive iodine.

Role of BRAF molecular analysis in the management of papillary thyroid carcinoma: analysis of cytological and histological samples.

Although fine needle aspiration (FNA) is the standard diagnostic test for the characterization of a suspicious thyroid nodule, in some cases cytological evaluation is inconclusive. The aim of this study was to determine the role of BRAF mutation in aiding diagnosis and to verify whether archival cytological samples could be suitable for molecular analysis. Eighty-five patients with suspicious (Thy4) or follicular (Thy3) lesions on cytology were resubmitted to a second FNA for BRAF mutation analysis. Of these, 56 subsequently underwent surgery. The usefulness of archival samples for molecular analysis was also studied in a second cohort of 42 patients with a confirmed diagnosis of papillary thyroid carcinoma for whom both archived paraffin-embedded histological samples and cytological smears were available. A further 15 patients with paired fresh FNA and archived cytological and histological samples were recruited. BRAF mutation was found in the fresh FNA samples from 10 of 56 patients who had surgery with previous inconclusive cytology (4/45, 9%, Thy3 and 6/11, 55%, Thy4). The BRAF test showed a specificity and positive predictive value of 100% (26/26 and 10/10, respectively), sensitivity of 33% (10/30) and negative predictive value of 57% (26/46). There was absolute concordance between the BRAF results obtained with 42 histological and cytological archived samples. BRAF analysis on 15 archived cytological samples showed absolute concordance with histology, whereas there was one false negative on the matched fresh FNA. BRAF analysis is a highly specific test that can facilitate cytological diagnosis in some cases and can also be performed on archived cytological samples.

The pros and cons of prophylactic central neck dissection in papillary thyroid carcinoma.

Prophylactic central neck dissection (pCND) for management of papillary thyroid carcinoma (PTC) is controversial. Compared to many malignancies, PTC has a high overall survival but local recurrence due to lymph node metastases continue to present management challenges. Unlike lateral cervical nodal metastasis metastasis, central neck nodal metastasis are unable to be reliably detected clinically or radiologically at pre-operative assessment. Residual disease (recurrent or persistent) typically requires re-operative surgery in the central compartment, which carries a heightened risk of significant morbidity. These nodal groups can be accessed during the index thyroidectomy for PTC. Thus, pCND offers potential to reduce the rates of recurrence and the need for re-operative surgery in the central neck. This benefit needs to be balanced with the potential morbidity risk from pCND itself at the index resection. This review will discuss the advantages and disadvantages of pCND with regard to long-term outcomes and potential morbidity. The rationale of pCND will be discussed, along with the indications for ipsilateral and contralateral pCND, the role of re-operative surgery for recurrence and the use of selective versus routine pCND. Strategies to select higher risk patients for pCND with the use of molecular markers will be addressed, along with a discussion of quality of life (QoL) research in PTC.

Lymphatic drainage, regional metastases and surgical management of papillary thyroid carcinoma arising in pyramidal lobe – a single institution experience

Papillary thyroid carcinoma (PTC) arising in pyramidal lobe (PL) is very rare. The aim of this study was to determine the incidence of single PTC focus in PL and its lymphonodal metastases, as well as to present a single surgeon experience in management of PL PTC. We performed a retrospective analysis of records of all patients surgically treated for PTC in our institution from year 2003 to 2013. Only patients with single PTC focus in PL were included. Out of total 753 patients, majority (66.52%) had PTC focus in one of the lobes, while only 3 patients (0.4%) had solitary PTC focus in PL. They were all females, aged 36, 41 and 22. During surgery, methylene-blue dye was injected peritumorally. After frozen section analysis of excised PL and isthmus and confirmation of malignancy, we performed total thyroidectomy with central neck dissection, as well as sentinel lymph node biopsy in both jugulo-carotid regions. Pathology showed encapsulated PTC stage T1 and solitary metastasis in Delphian lymph node of the youngest patient. All patients were disease free in the follow-up. PTC single focus in PL is very rare and only individual experiences can be discussed regarding the extent of the surgery.

Level VII is an Important Component of Central Neck Dissection for Papillary Thyroid Cancer

Therapeutic central neck dissection (CND) is an accepted part of the management of papillary thyroid carcinoma (PTC), while prophylactic CND remains controversial. Regardless of the indication for CND, the lower anatomic border of the central compartment, specifically the inclusion or otherwise of level VII, is not always clearly defined in the literature. This study aimed to determine if the routine inclusion of level VII lymph node dissection as part of CND confers increased utility in the detection of macrometastatic lymph nodes compared with level VI dissection alone. This was a prospective cohort study of patients undergoing CND for PTC at a tertiary referral center. All patients received either a prophylactic or therapeutic CND. The CND specimens were divided by the surgeon into level VI and level VII at the level of the suprasternal notch and submitted separately for histopathology. Criteria for macroscopic lymph node disease were taken from the American Joint Committee on Cancer (AJCC) recommendations for breast cancer. A total of 45 patients with PTC underwent total thyroidectomy and routine CND, at a tertiary referral center; 77 % of the therapeutic CND group had positive level VI lymph nodes, and 38 % had positive level VII lymph nodes. Of the prophylactic CND group, 50 % of patients had positive level VI nodes and 16 % has positive level VII nodes detected. All patients with positive level VII lymph nodes in the prophylactic CND group had macrometastatic disease. Temporary hypocalcemia rate was 31 % in the therapeutic group and 6 % in the prophylactic CND group. One patient experienced permanent hypoparathyroidism. There was no vascular injury or recurrent laryngeal nerve palsy in either group. CND incorporating both level VI and level VII can be undertaken safely through a cervical incision with no increased risk of permanent complications of hypoparathyroidism or recurrent laryngeal nerve injury. Failure to include level VII as part of CND will leave significant macrometastatic nodal disease behind in both therapeutic and prophylactic dissections. As level VII is in direct anatomic continuity with the pretracheal level VI nodes, it should be routinely included as part of every CND.

Endocrine surgery as a model for value-based health care delivery

Background:Experts advocate restructuring health care in the United States into a value-based system that maximizes positive health outcomes achieved per dollar spent. We describe how a value-based system implemented by the University of California, Los Angeles UCLA Section of Endocrine Surgery (SES) has optimized both quality and costs while increasing patient volume.Methods:Two SES clinical pathways were studied, one allocating patients to the most appropriate surgical care setting based on clinical complexity, and another standardizing initial management of papillary thyroid carcinoma (PTC). The mean cost per endocrine case performed from 2005 to 2010 was determined at each of three care settings: A tertiary care inpatient facility, a community inpatient facility, and an ambulatory facility. Blood tumor marker levels (thyroglobulin, Tg) and reoperation rates were compared between PTC patients who underwent routine central neck dissection (CND) and those who did not. Surgical patient volume and regional market share were analyzed over time.Results:The cost of care was substantially lower in both the community inpatient facility (14% cost savings) and the ambulatory facility (58% cost savings) in comparison with the tertiary care inpatient facility. Patients who underwent CND had lower Tg levels (6.6 vs 15.0 ng/mL; P = 0.024) and a reduced need for re-operation (1.5 vs 6.1%; P = 0.004) compared with those who did not undergo CND. UCLA maintained its position as the market leader in endocrine procedures while expanding its market share by 151% from 4.9% in 2003 to 7.4% in 2010.Conclusions:A value-driven health care delivery system can deliver improved clinical outcomes while reducing costs within a subspecialty surgical service. Broader application of these principles may contribute to resolving current dilemmas in the provision of care nationally.

BRAF gene mutation in the natural history of papillary thyroid carcinoma: diagnostic and prognostic implications

The papillary carcinoma is the most prevalent malignant neoplasm of the thyroid gland, representing 85-90% of all cases, and its incidence has been increasing in recent years. It is relatively indolent, however other types poorly differentiated or anaplastic, are more aggressive and usually associated with poor prognosis. Approximately half of these papillary carcinomas harbor a thymine-to-adenine transversion (T1799A) point mutation, in the gene encoding the serine/threonine-kinase B-type Raf kinase (BRAF), with substitution of valine by glutamate (V600E). Mutated BRAF, generates a constitutive activation of the mitogen-activated protein kinases (MAPK) signaling pathway, which plays a critical role in transmitting proliferative signals generated by cell surface receptors and cytoplasmic signaling elements, to the nucleus. BRAF mutation is mutually exclusive with other common genetic alterations, supporting its independent oncogenic role in cell proliferation, survival and tumor de-differentiation. The BRAFV600E occurs exclusively in papillary thyroid carcinoma and papillary carcinoma-derived anaplastic cancer, rising as a specific diagnostic marker for this tumor when identified in cytological / histological exams. This mutation has recently emerged, as a potential prognostic marker for papillary thyroid carcinoma, after several studies have found this mutation to be associated with some clinicopathological characteristics, known to predict tumor recurrence and progression, including, for instance, old patient age, extrathyroidal invasion and lymph node metastasis. It is therefore considered a marker of aggressive disease in these tumors, associated with increased cancer recurrence and even loss of radioiodine avidity. Several studies were not able to confirm these associations. It has become clearer that BRAF mutation will likely have significant impact on the clinical management of papillary thyroid carcinoma.

Risks and Adequacy of an Optimized Surgical Approach to the Primary Surgical Management of Papillary Thyroid Carcinoma Treated During 1999–2006

Intense disease surveillance and frequent lymph node metastases (LNMs) in papillary thyroid cancer (PTC) have resulted in increased locoregional recurrences. We examined the safety and efficacy of an optimized surgical approach including preoperative ultrasonography (US), bilateral thyroidectomy, routine compartment VI dissection, and lateral neck dissection for LNM. During 1999-2006, a total of 420 patients underwent optimized primary surgery; 291(69%) females, median age 46 years; follow-up 98%, median 4.4 years. Patients were reviewed for tumor characteristics, pattern of LNM, staging, and outcomes. Total or near-total thyroidectomy was performed in 212 (51%) and 208 (49%) patients, respectively. Tumors were multicentric, 40% (average 1.7 cm); were bilateral, 30%; and showed extrathyroidal extension, 17%. Overall, 223 (53%) patients had LNMs: 213 (51%) were central and 85 (20%) were lateral jugular. pTNM staging: I, 258 (61%); II, 35 (8%); III, 88 (21%); IV, 39 (9%). AGES (age, grade, extension, and size-thyroid tumor; and MACIS (metastasis, age, completeness of resection, invasion, and size) prognostic scores were low risk in 362 (86%) and 352 (84%), respectively. Relapse developed in 57 (14%) patients: LNM in 44, soft tissue local recurrence (LR) in 5, distant metastases (DM) in 8. Hypoparathyroidism occurred in 5 (1.2%) patients and 1 had unintentional laryngeal nerve damage. Relapse with LNM occurred in previously operated fields in 19 (5%) patients, 11(3%) from disease virulence (LR or DM), preoperative false-negative (FN) US in 12 (3%), and combination of FN-US and recurrence in the operated field in 5 (1%) patients. Recurrence was limited to 5% of patients when the extent of disease was accurately defined and potentially curable. This optimized surgical strategy is relatively safe.

A Vision for the Surgical Management of Papillary Thyroid Carcinoma: Extensive Lymph Node Compartmental Dissections and Selective Use of Radioiodine

The natural history of papillary thyroid cancer (PTC) is such that many patients reach normal life expectancy after total thyroidectomy and radioiodine therapy (1). Still, a large number of patients experience locoregional recurrences, usually in cervical lymph nodes, and within 10 yr of initial therapy, about 7% die of disease (2). Yet despite the slow tumor growth and favorable prognosis for survival of patients with small PTCs, the major challenge is controlling locoregional recurrence. Whether this is best accomplished with surgery or radioiodine—or whether they should be treated at all—has been a matter of debate, especially in patients with microcarcinomas. What are the risks of lymph node metastases? The initial management of small PTCs has received considerable attention stemming from the relentlessly increasing incidence of small PTCs that has been observed over the past three decades in the United States (3). Nearly half were papillary microcarcinomas 1 cm or smaller, and nearly 90% were PTCs 2 cm or smaller, both of which have favorable survival rates. Yet a study of over 52,000 patients found the recurrence rate to be 4.6% for tumors smaller than 1 cm and 7.1% in patients with tumors 1–1.9 cm, with 10-yr cancer-specific mortality rates of 2 and 2.6%, respectively (4). To obfuscate initial management decisions further, the rates of lymph node metastases in both lowand high-risk patients range from 25 to 60%, depending upon the extent of surgery (5, 6). Although regional lymph node metastases have generally been regarded to increase local recurrence rates without affecting survival, several large studies suggest otherwise. A study of almost 10,000 patients found the 14-yr survival rate was 82% for patients with and 79% for patients without lymph node metastases (P 0.05) (7). Another study (8) of 33,088 patients found a 46% increased risk for death with lymph node metastases in patients with follicular thyroid cancer and in patients 45 yr or older with PTC (P 0.001) (8). Lastly, residual metastatic lymph nodes that remain after initial therapy are the most common cause of subsequent recurrence (5, 6). These facts sharply focus the debate concerning initial therapy for lymph node metastases, especially concerning the risks and benefits of surgery and radioiodine remnant ablation. What are the risks and benefits of central lymph node dissection? For lymph node metastases, the American Thyroid Association (ATA) guidelines (9) suggest systematic neck lymph node dissection, which refers to en bloc dissection of anatomic neck compartments, as compared with selectively excising lymph nodes (“berry picking”), which is not recommended. Prophylactic dissection denotes removal of lymph nodes that are considered normal preoperatively or intraoperatively, and therapeutic dissection refers to removal of malignant lymph nodes identified before or during surgery. The ATA guidelines under revision suggest that prophylactic central-compartment neck dissection (ipsilateral or bilateral) may be performed in patients with PTC with clinically uninvolved central neck lymph nodes, especially for advanced primary tumors (T3 or T4), which is a Grade C Recommendation (Expert Opinion), and that near-total or total thyroidectomy without prophylactic central neck dissection may be appropriate for small (T1 or T2) noninvasive clinically node-negative PTCs and most follicular cancers (Grade C Recommendation). The ATA guidelines suggest preoperative cervical ultrasonography in all patients undergoing thyroidectomy. Although this may identify suspicious cervical adenopathy in up to half the cases, potentially altering the surgical approach in many patients, it has several limitations, particularly in evaluating extracapsular invasion in deep locations in the neck and lymph node metastasis in the central neck, which may lower the sensitivity of ultrasonography to 35% (10).

Expression of p21cip1, p27kip1, and p16INk4a Cyclin-Dependent Kinase Inhibitors in Papillary Thyroid Carcinoma: Correlation with Clinicopathological Factors

In a variety of human malignancies, aberrant expression of proteins involved in the control of cell-cycle progression has been reported. In this study, p21cip1, p27kip1, and p16INk4a cyclin-dependent kinase inhibitors were analyzed to evaluate their usefulness in clinical management of papillary thyroid carcinoma (PTC). Archived material derived from 46 cases of PTC was analyzed immunohistochemically. Protein expression was ascertained on tissue microarrays, and results were correlated with clinicopathological features of the patients. Positive immunostaining was observed in 14 (30,4%) p21cip1, 26 (56,5%) p27kip1, and 14 (30,4%) p16INk4a cases. No significant correlation between p21cip1 or p27kip1 and clinical factors was found. In contrast, p16INk4a expression showed a significant correlation with initial extension of the disease. Therefore, 45.8% of patients with loco-regional extension were p16INk4a positive, whereas overexpression was only seen in 15.7% of cases with intrathyroid disease (p < 0.05). Moreover, all patients with simultaneous p16INk4a positivity and lack of p27kip1 staining (four patients) presented lymph node metastases. In contrast, only 12 (28.5%) of the remaining patients showed lymph node tumor involvement. In conclusion, p16INk4a expression suggests extrathyroid neck extension of PTC. This effect is enhanced when p27kip1 is negative. We think that their analysis by immunohistochemistry could be useful in the management of patients with PTC.

Surgical management of papillary thyroid carcinoma with endotracheal infiltration

To investigate the diagnosis and treatment of papillary thyroid carcinoma with endotracheal infiltration. Clinical data of 12 patients treated from January 1999 to December 2006 were retrospectively analyzed. Six patients received tracheal partial resection-sternocleidomastoid musculoperiosteal flap reconstruction (group A). Six patients received tracheal sleeve resection-end to end anastomosis (group B). Ten patients had the symptoms which indicated the tracheal invasion. Endotracheal focuses were detected in the region from 2 cm to 4 cm under glottis by endoscopy and positive rate of smear biopsy was 33%. Positive rate of CT scan was 92%. Mean diameter of carcinoma focus was 3.8 cm (from 3 cm to 7 cm), and mean number of tracheal ring resected was 4. For group A, even 7 rings were resected, and the longest longitude and latitude was 7 cm and 3 cm, respectively. For group B, the greatest number of rings resected was 4. Incidence rate of perioperative complication and mortality was 58% and 0%, respectively. Mean duration of follow-up was 49 months. One patient died of local recurrence, 1 patient died of lung metastasis. Two patients with tumor recurrence were also alive. For group A, extubation was successful in all patients. Comprehensive use of diagnostic methods, especially MRI, will give detailed information for operation. Tracheal partial resection-sternocleidomastoid musculoperiosteal flap reconstruction and tracheal sleeve resection-end to end anastomosis are safe and useful methods to reconstruct the defects caused by tracheal operation.