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1.  A Large Nonmetastatic Anaplastic Thyroid Cancer with Complete Thyroidal Confinement 
Case Reports in Medicine  2011;2011:583978.
Anaplastic thyroid cancer (ATC) is rare but extremely aggressive, which accounts for about 2% of all thyroid cancers yet nearly 50% of thyroid-cancer-associated deaths in the United States. The median survival time from diagnosis is 5 months, with a 1-year survival rate of only 20%. We report here a case of ATC in a 56-year-old man who survived a large ATC. Preoperative fine-needle aspiration biopsy study to a large right thyroid mass suggested ATC. Total thyroidectomy with radical lateral neck and central neck dissection removed a well-circumscribed 9.5 cm tumor without extrathyroidal extension or lymphovascular invasion. All 73 lymph nodes removed were negative for metastasis. The tumor consisted of highly pleomorphic, undifferentiated cells with large zones of necrosis and loss of thyroid transcription factor-1 and thyroglobulin expression. A focal well-differentiated component and PAX8 expression confirmed its thyroid follicular cell origin. Nine months after postsurgical adjuvant concurrent radiation therapy and chemotherapy, the patient remained well without clinical, biochemical, and radiographical evidence for cancer recurrence. This is an unusual case of ATC in that it is one of the largest ATC tumors reported to display mild pathologic behavior and relatively long-term patient survival.
doi:10.1155/2011/583978
PMCID: PMC3170804  PMID: 21912554
2.  Aggressive Multimodal Approach for Anaplastic Thyroid Cancer and Long-Term Survival 
Anaplastic thyroid cancer (ATC) comprises 1-2% of all thyroid cancers and is one of the most aggressive cancers with a median survival rate of around four months. The average 5-year survival rate has been reported to be around 3.6%. In this paper, we have discussed management and prognostic variables of a patient with ATC who has survived for more than 5 years. A 59-year-old female was referred to our facility for an elective thyroid and parathyroidectomy for concerns of thyroid papillary cancer and hyperparathyroidism. At the time of surgery, the tumor mass had invaded the muscular layer of esophagus; radicle thyroidectomy parathyroidectomy along with removal of muscle layer of esophagus was performed, and diagnosis of ATC was made. The patient was treated with chemoradiation with a good treatment response and no recurrence of tumor for two and a half years until PET/CT followed by wedge biopsy of lung confirmed ATC recurrence. The patient was treated with another course of radiation treatment with a good treatment response. Since then, the patient has been following in our outpatient oncology clinic and has no evidence of tumor recurrence. Aggressive multimodal approach of combining radicle surgery with chemoradiation treatment in select patients of ATC with no distant metastasis helps improve prognosis.
doi:10.1155/2013/783862
PMCID: PMC3600220  PMID: 23533874
3.  Anaplastic Thyroid Cancer: Experience of the Philippine General Hospital 
Endocrinology and Metabolism  2015;30(2):195-200.
Background
Anaplastic thyroid cancer (ATC) is a rare type of thyroid malignancy and one of the most aggressive solid tumors, responsible for between 14% and 50% of the total annual mortality associated with thyroid cancer.
Methods
A retrospective study was made of all ATC cases diagnosed by biopsy in the Philippine General Hospital between 2008 and 2013.
Results
A total of 15 patients were identified, with a median age at diagnosis of 63 years. All tumors were at least 6 cm in size upon diagnosis. All patients had a previous history of thyroid pathology, presenting with an average duration of 11 years. Eleven patients presented with cervical lymphadenopathies, whereas seven exhibited signs of distant metastases, for which the lungs appeared to be the most common site. More than 70% of the patients presented with a rapidly growing neck mass, leading to airway obstruction. Only three patients were treated using curative surgery; the majority received palliative and supportive forms of treatment. In addition, only three patients were offered radiotherapy. Chemotherapy was not offered to any patient. Only two patients were confirmed to still be alive during the study period. The median survival time for the other patients was 3 months; in the majority of cases the patient died within the first year following diagnosis.
Conclusion
Our experience with ATC demonstrated concordance with other institutions with respect to current clinical profile, presentation, and prognosis. An absence of distant metastases and lymph node involvement was associated with improved survival outcomes, whereas age at diagnosis and tumor size did not affect survival. Curative surgery offers the most effective means of prolonging survival. Radiotherapy and chemotherapy in combination with surgery represents a promising treatment strategy.
doi:10.3803/EnM.2015.30.2.195
PMCID: PMC4508264  PMID: 26194079
Thyroid cancer, anaplastic; Philippines; Thyroid neoplasms; Thyroid; Poorly differentiated thyroid cancer
4.  Indications for the Gasless Transaxillary Robotic Approach to Thyroid Surgery: Experience of Forty-Seven Procedures at the American Hospital of Paris 
European Thyroid Journal  2013;2(2):102-109.
Background
Thyroid surgery is in a state of evolution from traditional open approaches to novel robotic techniques. The gasless transaxillary approach to thyroid surgery is effective in the management of thyroid cancer, and complications after robotic thyroidectomy are no higher than experienced after open or endoscopic techniques. The transaxillary robotic approach also avoids an anterior neck scar. This paper presents what the authors believe to be the largest cohort of patients reported in Europe undergoing gasless transaxillary robotic thyroid surgery, with the aim of defining the indications for this procedure.
Methods
Forty-six patients underwent robotic thyroid surgery via the transaxillary approach and were enrolled in this study between March 2010 and September 2012. All patients were operated on by one surgeon at one clinical center. Reviewed data included patient characteristics, pathological characteristics, extent of surgery and postoperative complications. The mean follow-up time was 7.29 months.
Results
Forty-six patients underwent 47 procedures, the average age of the patients was 43 years and the male to female ratio was 1:22. Undertaken were 30 lobectomies, 3 subtotal thyroidectomies, 13 total thyroidectomies and 1 totalization. One case was converted to an open procedure. The ratio of malignant to benign disease was 1:6.67 (6:40 cases) and analysis of the surgical specimens showed 6 follicular lesions, 24 follicular adenomas, 3 colloid lesions, 1 case of thyroiditis/lymphatic lesion, 3 adenomatoid lesions, 3 oncocytic adenomas, 3 papillary cancers and 3 microcapillary cancers. The overall average size of an individual specimen removed was 45.40 ± 28.95 cm3 (range 5-160, n = 47) and the average largest diameter of the lesion removed was 3.72 ± 0.95 cm (range 1.4-6.0, n = 47). Postoperatively, there were 5 recurrent laryngeal nerve injuries (4 transient), 2 transient brachial plexopathies, 1 case of postoperative dysphagia and 1 of collection of blood at the site of surgery. There were no cases of disease recurrence at follow-up.
Conclusions
The gasless robotic transaxillary approach to thyroid surgery has been predicted to become a standard technique. It has been shown to be efficacious in the management of thyroid cancer with lateral neck metastases; however, more data relating to oncological safety in long-term follow-up is required. This intervention is also appropriate for benign thyroid disease including Graves' disease. To achieve consistently successful results, careful patient selection is fundamental in terms of patient characteristics and the anatomical aspects of the lesion. This is especially important with a geographical expansion to include North America and Europe. The excellent cosmetic results of this procedure make it ideal for patients who have esthetic concerns regarding particular difficulties with healing; however, in common with all new surgical procedures, further evidence must be sought to confirm its indications over time.
doi:10.1159/000350854
PMCID: PMC3821510  PMID: 24783047
Thyroid disease; Transaxillary robotic thyroid surgery; Cosmesis

5.  Results of combined treatment of anaplastic thyroid carcinoma (ATC) 
BMC Cancer  2011;11:469.
Background
Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies. It is associated with a high rate of local recurrence and with poor prognosis.
Methods
We retrospectively reviewed 44 consecutive patients treated between 1996 and 2010 at Leon Berard Cancer Centre, Lyon, France. The combined treatment strategy derived from the one developed at the Institut Gustave Roussy included total thyroidectomy and cervical lymph-node dissection, when feasible, combined with 2 cycles of doxorubicin (60 mg/m2) and cisplatin (100 mg/m2) Q3W, hyperfractionated (1.2 Gy twice daily) radiation to the neck and upper mediastinum (46-50 Gy), and then four cycles of doxorubicin-cisplatin.
Results
Thirty-five patients received the three-phase combined treatment. Complete response after treatment was achieved in 14/44 patients (31.8%). Eight patients had a partial response (18.2%). Twenty-two (50%) had progressive disease. All patients with metastases at diagnosis died shortly afterwards. Thirteen patients are still alive. The median survival of the entire population was 8 months.
Conclusion
Despite the ultimately dismal prognosis of ATC, multimodality treatment significantly improves local control and appears to afford long-term survival in some patients. There is active ongoing research, and results obtained with new targeted systemic treatment appear encouraging.
doi:10.1186/1471-2407-11-469
PMCID: PMC3219746  PMID: 22044775
6.  Utility of Thyroglobulin Measurements Following Prophylactic Thyroidectomy in Patients with Hereditary Medullary Thyroid Cancer 
Surgery  2014;156(2):394-398.
Introduction
Prophylactic thyroidectomy can be curative for patients with hereditary medullary thyroid cancer (MTC) caused by RET proto-oncogene mutations. Calcitonin is a sensitive tumor marker used to follow patients. We suggest that thyroglobulin (Tg) levels should also be monitored postoperatively in these patients.
Methods
We reviewed patients with RET mutations who underwent prophylactic thyroidectomy between 1981 and 2011 at an academic endocrine surgery center. Patients were excluded if they had no postoperative Tg levels.
Results
Of the 22 patients who underwent prophylactic thyroidectomy, 14 were included in final analysis. The average age at thyroidectomy was 9.8 years (range 4 to 29). Tg levels were detectable 1.5 months to 31 years postoperatively in 11 patients (79%), all of whom were younger than 15 years-old at thyroidectomy. Median TSH was 2.5 mIU/L and 13.4 mIU/L in patients with undetectable and detectable Tg, respectively. Of those with detectable Tg, five had neck ultrasounds: Two showed no residual tissue in the thyroid bed, and three showed remnant thyroid tissue.
Conclusions
Tg levels can identify patients with remnant thyroid tissue after prophylactic thyroidectomy. Ultrasound can determine if thyroid tissue remains posterolaterally and is at risk of MTC recurrence. Maintaining normal TSH may prevent growth of remaining thyroid follicular cells.
doi:10.1016/j.surg.2014.03.037
PMCID: PMC4099273  PMID: 24882762
7.  Anaplastic Thyroid Carcinoma Following Radioactive Iodine Therapy for Graves' Disease 
Endocrinology and Metabolism  2013;28(1):61-64.
Radioactive iodine (RAI) therapy has been used as a treatment option for Graves' disease, and it has been widely accepted to be safe. On the other hand, some evidence suggests that RAI therapy is possibly associated with a small increased risk of thyroid cancer. Herein, we report a rare case of anaplastic thyroid carcinoma (ATC) associated with Graves' disease, following RAI treatment. A 42-year-old woman had been diagnosed with Graves' disease and although she was treated with an antithyroid drug, she remained in a hyperthyroid state, which led to two RAI treatments. More than 10 years later, the patient revisited our clinic due to hoarseness, dysphagia, and dyspnea, which had lasted for 2 months. Neck computed tomography suggested thyroid carcinoma and a lymph node biopsy showed metastatic papillary carcinoma. The patient underwent total thyroidectomy and was finally diagnosed as having an ATC. It is not clear if the occurrence of ATC reported here was influenced by the RAI therapy or alternatively, it may only represent the delayed recognition of a rare change in the natural history of Graves' disease. Nevertheless, this report is worthwhile since it presents a very rare case of ATC that occurred eleven years after the RAI therapy for Graves' disease.
doi:10.3803/EnM.2013.28.1.61
PMCID: PMC3811800  PMID: 24396653
Thyroid cancer, anaplastic; Graves disease; Radioactive iodine therapy
8.  Anaplastic thyroid carcinoma: A comprehensive review of current and future therapeutic options 
Anaplastic thyroid carcinoma (ATC) is the rarest, but deadliest histologic type among thyroid malignancies, with a dismal median survival of 3-9 mo. Even though ATC accounts for less than 2% of all thyroid tumors, it is responsible for 14%-39% of thyroid carcinoma-related deaths. ATC clinically presents as a rapidly growing mass in the neck, associated with dyspnoea, dysphagia and vocal cord paralysis. It is usually locally advanced and often metastatic at initial presentation. For operable diseases, the combination of radical surgery with adjuvant radiotherapy or chemotherapy, using agents such as doxorubicin and cisplatin, is the best treatment strategy. Cytotoxic drugs for advanced/metastatic ATC are poorly effective. On the other hand, targeted agents might represent a viable therapeutic option. Axitinib, combretastatin A4, sorafenib and imatinib have been tested in small clinical trials of ATC, with a promising disease control rate ranging from 33% to 75%. Other clinical trials of targeted therapy for thyroid carcinoma are currently ongoing. Biological agents that are under investigation include pazopanib, gefitinib and everolimus. With the very limited therapeutic armamentarium available at the present time, targeted therapy constitutes an exciting new horizon for ATC. In future, biological agents will probably represent the standard of care for this aggressive malignancy, in the same fashion as it has recently occurred for other chemo-refractory tumors, such as kidney and hepatic cancer.
doi:10.5306/wjco.v2.i3.150
PMCID: PMC3100480  PMID: 21611089
Anaplastic thyroid cancer; Targeted agents
9.  Long-term results of radiotherapy in anaplastic thyroid cancer 
Background
Anaplastic thyroid cancer (ATC) is an aggressive malignant tumour with a poor prognosis. The median overall survival is described in the literature to be just 6 months, however, in series of selected patients treated by multimodal therapy cases of long-time-survival have been reported. We analyzed the role of radiotherapy and the impact of other therapies and clinical features on survival in patients with ATC.
Methods
In a retrospective analysis of all patients (n = 40), who presented with histologically proven ATC at a single centre between 1989 and 2008, patient and treatment characteristics with a focus on details of radiotherapy were registered and the survival status determined.
Results
39 of 40 patients received radiotherapy, 80% underwent surgery and 15% had chemotherapy. The median dosis of radiation was 50 Gy (6–60.4 Gy), in 87.5% fractionation was once daily. In 49.4% opposing-field techniques were applied, in 14% 3D-conformal-techniques and 32.5% combinations of both.
The median overall survival (OS) was 5 months, 1-year survival 35.2% and 5-year-survival 21.6%. Interestingly, 24.3% survived 2 years or longer. Three factors could be identified as predictors of improved overall survival: absence of lymph node metastasis (N0) (median OS 18.3 months), median dose of radiation of 50 Gy or more (median OS 10.5 months) and the use of any surgery (median OS 10.5 months).
Conclusions
Despite the generally poor outcome, the combination of surgery and intensive radiotherapy can result in long-term survival in selected patients with ATC.
doi:10.1186/1748-717X-9-90
PMCID: PMC3994242  PMID: 24685141
Anaplastic thyroid cancer (ATC); Undifferentiated thyroid cancer (UTC); Radiotherapy; Multimodal therapy; Prognostic factors; Long-term survival
10.  Anaplastic Thyroid Carcinoma 
Thyroid cancers represent about 1% of all human cancers. Differentiate thyroid carcinomas (DTCs), papillary and follicular cancers, are the most frequent forms, instead Anaplastic Thyroid Carcinoma (ATC) is estimated to comprise 1–2% of thyroid malignancies and it accounts for 14–39% of thyroid cancer deaths. The annual incidence of ATC is about one to two cases/million, with the overall incidence being higher in Europe (and area of endemic goiter) than in USA. ATC has a more complex genotype than DTCs, with chromosomal aberrations present in 85–100% of cases. A small number of gene mutations have been identified, and there appears to be a progression in mutations acquired during dedifferentiation. The mean survival time is around 6 months from diagnosis an outcome that is frequently not altered by treatment. ATC presents with a rapidly growing fixed and hard neck mass, often metastatic local lymph nodes appreciable on examination and/or vocal paralysis. Symptoms may reflect rapid growth of tumor with local invasion and/or compression. The majority of patients with ATC die from aggressive local regional disease, primarily from upper airway respiratory failure. For this reason, aggressive local therapy is indicated in all patients who can tolerate it. Although rarely possible, complete surgical resection gives the best chance of long-term control and improved survival. Therapy options include surgery, external beam radiation therapy, tracheostomy, chemotherapy, and investigational clinical trials. Multimodal or combination therapy should be useful. In fact, surgical debulking of local tumor, combined with external beam radiation therapy and chemotherapy as neoadjuvant (before surgery) or adjuvant (after surgery) therapy, may prevent death from local airway obstruction and as best may slight prolong survival. Investigational clinical trials in phase I or in phase II are actually in running and they include anti-angiogenetic drugs, multi-kinase inhibitor drugs.
doi:10.3389/fendo.2012.00084
PMCID: PMC3389605  PMID: 22783225
anaplastic; cancer; genetic alteration; prognosis; therapy; thyroid; treatment; tumor
11.  Genetic mutations in the treatment of anaplastic thyroid cancer: a systematic review 
BMC Surgery  2013;13(Suppl 2):S44.
Background
Anaplastic thyroid cancer (ATC) is a rare, lethal disease associated with a median survival of 6 months despite the best multidisciplinary care. Surgical resection is not curative in ATC patients, being often a palliative procedure. Multidisciplinary care may include surgery, loco-regional radiotherapy, and systemic therapy. Besides conventional chemotherapy, multi kinase-targeted inhibitors are emerging as novel therapeutic tools. The numerous molecular alteration detected in ATC are targets for these inhibitors. The aim of this review is to determine the prevalence of the major genetic alterations occurring in ATC and place the results in the context of the emerging kinase-targeted therapies.
Methods
The study is based on published PubMed studies addressing the prevalence of BRAF, RAS, PTEN, PI3KCA and TP53 mutations and RET rearrangements in ATC.
Results
21 articles dealing with 652 genetic analyses of the selected genes were used. The overall prevalence determined were the following: RET/PTC, 4%; BRAF, 23%; RAS, 60%; PTEN, 16%; PI3KCA, 24%; TP53, 48%. Genetic alterations are sometimes overlapping.
Conclusions
Mutations of BRAF, PTEN and PI3KCA genes are common in ATC, with RAS and TP53 being the most frequent. Given ATC genetic complexity, effective therapies may benefit from individualized therapeutic regimens in a multidisciplinary approach.
doi:10.1186/1471-2482-13-S2-S44
PMCID: PMC3851243  PMID: 24267151
12.  Anaplastic Thyroid Cancer: Ultrasonographic Findings and the Role of Ultrasonography-Guided Fine Needle Aspiration Biopsy 
Yonsei Medical Journal  2013;54(6):1400-1406.
Purpose
To investigate the ultrasonographic (US) features of anaplastic thyroid cancer (ATC) and the diagnostic performance of US-guided fine needle aspiration biopsy (FNAB) therein.
Materials and Methods
Eighteen cases of ATC diagnosed between January 2001 and May 2011 were included. FNAB was performed in all cases. Initial FNAB results were divided into three groups: 1) the cytological ATC group, cytological diagnosis of ATC; 2) the underestimated group, cytological diagnoses of malignancy other than ATC; and 3) the false negative group, cytological diagnoses of atypical, benign and non-diagnostic lesions. We retrospectively reviewed US findings and compared treatment modalities between each group.
Results
Among the 18 patients, there were nine in the initially cytological ATC group, four in the underestimated group and five in the false negative group. The most common US features of ATC were a solid (64.7%) and irregular shaped (88.2%) mass with lymph node involvement (76.4%). However, except for lymph node involvement (p=0.003), US findings for each group were not statistically different. The initial cytological diagnostic accuracy of ATC was 50% (9/18). Surgery was performed less in the ATC group (11%) and the false negative group (20%) than the underestimated group (75%).
Conclusion
The US features of ATC were not especially different from other types of aggressive thyroid cancer. A correct diagnosis of ATC by initial US-FNAB was made in 50% of the patients, which is significant in that therapeutic surgery can be undertaken in lower numbers if correctly diagnosed.
doi:10.3349/ymj.2013.54.6.1400
PMCID: PMC3809886  PMID: 24142644
Anaplastic thyroid cancer; fine needle aspiration biopsy; ultrasonography
13.  Alternative surgical strategies in patients with sporadic medullary thyroid carcinoma: Long-term follow-up 
Oncology Letters  2011;2(5):975-980.
The extent of surgical resection in patients with sporadic medullary thyroid carcinoma (SMTC) remains controversial. The aim of the present study was to discuss the prognosis of sporadic medullary thyroid carcinoma with different surgical treatments. Of 73 patients with SMTC (mean age of 43.78 years at diagnosis), 70 patients were followed up for 12.0-169.0 months (median 90.0). Having given their informed consent, 12 patients underwent total thyroidectomy with bilateral central neck dissection (group A), 40 underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with ipsilateral modified radical neck dissection (group B), and 18 patients underwent subtotal thyroidectomy preserving contralateral thyroid tissue on the entrance point of the recurrent laryngeal nerve into the larynx with bilateral modified radical neck dissection (group C). The diagnosis was confirmed by a pathology examination. The incidences of hypoparathyroidism and recurrent laryngeal nerve injury, the cancer recurrence rates and survival time were investigated post-operatively. Significant differences were found between groups A, B and C in the incidence of hypoparathyroidism (χ2=40.9, P<0.01), as well as that of recurrent laryngeal nerve injury (χ2=32.9, P<0.01). The cancer recurrence rates in groups A, B and C were 75.0% (9/12), 2.5% (1/40) and 44.4% (8/18) respectively, (χ2=31.1, P<0.01) and the cure rates were 25, 97.5 and 55.6% respectively (χ2=31.1, P<0.01). The mean survival times in groups A, B and C were 77.8, 106.1 and 111.0 months respectively, but significant difference was noted (χ2=3.2, P>0.05). In conclusion, compared to total thyroidectomy with bilateral central neck dissection, subtotal thyroidectomy with ipsilateral/bilateral modified radical neck dissection showed a lower incidence of hypoparathyroidism, recurrent laryngeal nerve injury and lower rates of recurrence, along with a similar cumulative survival.
doi:10.3892/ol.2011.344
PMCID: PMC3408028  PMID: 22866159
14.  Transoral endoscopic thyroidectomy: A case report 
Highlights
•Endoscopic thyroidectomies aim to provide patients with minimal or no scars.•Transoral endoscopic thyroidectomy is based on the principles of natural orifice translumenal endoscopic surgery (NOTES).•Involves minimal dissection and is truly scar-free.•Transoral endoscopic thyroidectomy has proven to be a feasible procedure.•It provides easy access to the thyroid gland with aesthetically pleasing results.
Introduction
Endoscopic thyroidectomy, initially an experimental procedure, is now being performed in increasing frequency. It aims to provide patients undergoing thyroidectomy with a ‘scar-free’ surgery. Transoral endoscopic thyroidectomy is one such novel procedure that is based on the principles of natural orifice translumenal surgery (NOTES) and allows for a truly scar-free surgery with minimal dissection.
Presentation of case
A 21-year-old female presented with a swelling over the left side of her neck. Ultrasound revealed a solitary nodule and FNAC showed features suggestive of a follicular adenoma.
Discussion
The patient underwent transoral endoscopic hemi-thyroidectomy. The procedure lasted for 2 h and is one of the few documented cases of transoral endoscopic thyroidectomy performed on live patients.
Conclusion
Transoral endoscopic thyroidectomy is proving to be a feasible technique with little or no complications as compared to other endoscopic thyroid surgeries. It provides surgeons with easy access to the thyroid gland and patients with aesthetically pleasing results.
doi:10.1016/j.ijscr.2015.04.010
PMCID: PMC4485686  PMID: 26048629
Transoral thyroidectomy; Endoscopic thyroidectomy; NOTES; Thyroidectomy
15.  Molecular diagnosis and comprehensive treatment of multiple endocrine neoplasia type 2 in Southeastern Chinese 
Background
Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant inherited endocrine malignancy syndrome. Early and normative surgery is the only curative method for MEN 2-related medullary thyroid carcinoma (MTC). In patients with adrenal pheochromocytoma, cortical-sparing adrenalectomy (CSA) can be utilized to preserve adrenocortical function.
Methods
We present twenty-six of 33 MEN2 patients underwent prophylactic thyroidectomy with varying neck dissection and eight of 24 MEN2A patients with PHEO underwent adrenal-sparing surgery. Direct sequencing of entire RET exons was performed in all participants.
Results
The RET mutations (p.C634Y [n = 10], p.C634R [n = 9], p.C634F [n = 2], p.C618Y [n = 8], p.C618R [n = 3], and p.M918T [n = 1]) were confirmed in 20 symptomatic patients and identified in 13 at-risk relatives (RET carriers). Twenty-six of 33 MEN2 patients underwent thyroidectomies with neck dissections; the mean age at the time of the first thyroid surgery and the tumor diameter of the 6 RET carriers was decreased compared with 20 symptomatic patients (P < 0.001 and P = 0.007, respectively), while the disease-free survival was increased (80% vs.10%, P = 0.0001). Seven RET carriers who were declined surgery. One of 20 symptomatic patients with MTC bone metastases after surgery received vandetanib therapy for 20 months and responded well. Additionally, 8 of 24 MEN2A patients who initially had unilateral pheochromocytomas underwent CSA, 1 developed contralateral pheochromo cytomas 10 years later, then also accepted and also agreed to a CSA. None of the patients required steroid replacement therapy.
Conclusions
Based on our results, integrated RET screening and the pre-operative calcitonin level is an excellent strategy to ensure earlier diagnosis and standard thyroidectomy. CSA can be utilized to preserve adrenocortical function in patients with pheochromocytomas.
doi:10.1186/s13053-015-0026-1
PMCID: PMC4307225  PMID: 25628771
Multiple endocrine neoplasia type 2; Mutation screening; RET; Prophylactic thyroidectomy; Cortical-sparing adrenalectomy
16.  Thyroid Function after Subtotal Thyroidectomy in Patients with Graves' Hyperthyroidism 
The Scientific World Journal  2012;2012:548796.
Background. Subtotal thyroidectomy is a surgical procedure, in which the surgeon leaves a small thyroid remnant in situ to preserve thyroid function, thereby preventing lifelong thyroid hormone supplementation therapy. Aim. To evaluate thyroid function after subtotal thyroidectomy for Graves' hyperthyroidism. Subjects and Methods. We retrospectively reviewed the medical records of all patients (n = 62) who underwent subtotal thyroidectomy for recurrent Graves' hyperthyroidism between 1992 and 2008 in our hospital. Thyroid function was defined according to plasma TSH and free T4 values. Results. Median followup after operation was 54.6 months (range 2.1–204.2 months). Only 6% of patients were euthyroid after surgery. The majority of patients (84%) became hypothyroid, whereas 10% of patients had persistent or recurrent hyperthyroidism. Permanent recurrent laryngeal nerve palsy and permanent hypocalcaemia were noted in 1.6% and 3.2% of patients, respectively. Conclusion. In our series, subtotal thyroidectomy for Graves' hyperthyroidism was associated with a high risk of postoperative hypothyroidism and a smaller, but significant, risk of persistent hyperthyroidism. Our data suggest that subtotal thyroidectomy seems to provide very little advantage over total thyroidectomy in terms of postoperative thyroid function.
doi:10.1100/2012/548796
PMCID: PMC3290451  PMID: 22448136
17.  Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma 
BMC Cancer  2014;14:235.
Background
Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC.
Methods
13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed. The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy). Seven patients received surgical intervention and eleven patients had chemotherapy.
Results
The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks. The median survival time of the 13 patients was 9 months. The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%). Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress.
Conclusion
The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control. Further new therapies are needed to control metastases.
doi:10.1186/1471-2407-14-235
PMCID: PMC3976675  PMID: 24690325
Anaplastic thyroid carcinoma; ATC; Intensity modulated radiotherapy; Locoregional control; Distant metastases
18.  Video-assisted thyroidectomy: lessons learned after more than one decade 
Summary
In selected patients, video-assisted thyroidectomy can be considered a safe and validated procedure offering significant advantages over conventional surgery, with no additional morbidity. Aim of this study was to evaluate the results obtained in a series of patients selected for video-assisted thyroidectomy over a 10-years period. All patients who underwent video-assisted thyroidectomy from June 1998 to June 2009 were considered. The eligibility criteria for video-assisted thyroidectomy are: thyroid nodules ≤ 35 mm; estimated thyroid volume < 30 ml; no previous conventional neck surgery and/or radiation therapy; small, low-risk papillary thyroid carcinoma. A total of 1363 video-assisted thyroidectomies were attempted in the time period considered. Conversion to the conventional procedure was necessary in 7 cases. Thyroid lobectomy was successfully performed in 157 cases, total thyroidectomy in 1175, and completion thyroidectomy in 24. In 126 patients, the central neck nodes were removed through the same access. Simultaneous video-assisted parathyroidectomy, for a parathyroid adenoma, was performed in 42 patients. Pathological studies showed benign disease in 986 cases, papillary thyroid carcinoma in 368 cases, C-cells hyperplasia in 1 case, and medullary microcarcinoma in 1 patients with RET germline mutation. Post-operative complications included 27 transient and 1 definitive recurrent laryngeal nerve palsy, 230 transient hypocalcemia, 10 definitive hypoparathyroidism, 4 postoperative hematoma and 5 wound infection.
PMCID: PMC2868209  PMID: 20463836
Thyroidectomy; Minimally invasive thyroidectomy; Endoscopic thyroidectomy
19.  Total Thyroidectomy in the Mouse: the Feasibility Study in the Non-thyroidal Tumor Model Expressing Human Sodium/Iodide Symporter Gene 
Purpose
This study sought to probe the feasibility of performing total thyroidectomy in the mouse using a non-thyroidal hNIS expressing tumor model.
Materials and Methods
Our thyroidectomy protocol included thorough excision of both lobes and the isthmus. For evaluating the completeness of thyroidectomy, we compared the 99mTc-pertechnetate scans taken before and after thyroidectomy. The prostate cancer cell line was subcutaneously inoculated 2 weeks after the thyroidectomy. When the tumor reached 5-10 mm in diameter, Ad5/35-E4PSESE1a-hNIS was injected intratumorally, and 131I scans were performed. The radioiodine uptakes of the neck and the tumor were compared with those of the other regions.
Results
Total thyroidectomy was performed in 13 mice. Although 38.5% died during or just after thyroidectomy, the others survived in good health for 2 months. Thyroid tissue was completely eliminated using our protocol; the residual uptake of 99mTc-pertechnetate was minimal in the neck area. The neck/background uptake ratio after thyroidectomy was significantly lower than that before thyroidectomy (p < 0.05). Non-thyroidal tumor models were successfully established in all the surviving mice. Radioiodine accumulation in the tumors was visualized on 131I scans, and the neck uptakes were minimal.
Conclusion
Using our total thyroidectomy protocol, we successfully established a hNIS-transfected prostate cancer model with a minimal accumulation of radioiodine in the neck. The relatively high mortality after surgery can be a problem, and this might be reduced by minimizing the surgical stress.
doi:10.1007/s13139-011-0076-x
PMCID: PMC4043020  PMID: 24899988
Mouse; Total thyroidectomy; Surgical technique; Human sodium/iodide symporter
20.  Endoscopic Total Thyroidectomy 
Endoscopic transaxillary total thyroidectomy (ETTT) was found to be a safe and feasible alternative to open thyroidectomy.
Background and Objective:
Endoscopic neck surgery for the thyroid and parathyroid is being tested as an alternative to open thyroidectomy. The aim of this study was to determine the safety and feasibility of endoscopic transaxillary total thyroidectomy (ETTT).
Methods and Results:
Twenty-two consecutive patients from January 2006 to September 2008 underwent ETTT. No conversions to open were necessary. Mean age was 49.3±12.9 years, 20 were female, and 2 were male. Mean operating time was 238 minutes±72.7. Mean blood loss was 40mL±28.3mL. Mean weight of the gland was 137.05g±129.21g. The recurrent laryngeal nerve was identified with no permanent injury. Six patients developed hoarseness of the voice for a mean of 15.1±8.01 days. No patient developed tetany or hypocalcemia requiring treatment. Six patients experienced transient numbness in the anterior chest wall lasting 2 weeks in 5 patients and 2 months in one. All patients were discharged within 24 hours of admission.
Conclusion:
ETTT requires additional operative time compared with the open approach, but is cosmetically favorable. Visualization of the nerve and parathyroid is much better. Although the learning curve is steep, with experience the operative time will decrease. ETTT is different but safe and feasible.
doi:10.4293/108680809X12589998404209
PMCID: PMC3030786  PMID: 20202393
Minimal; Invasive; Endoscopic; Thyroidectomy; Transaxillary
21.  Predictors of thyroid tumor aggressiveness. 
Western Journal of Medicine  1996;165(3):131-138.
Thyroid cancers are classified as papillary, follicular (including Hürthle cell), medullary, and anaplastic. Papillary cancers account for about 82% of all thyroid cancers, follicular about 8%, medullary about 6%, Hürthle cell 3%, and anaplastic 1%. The prognosis of patients with papillary thyroid cancer is usually favorable, whereas most patients with anaplastic cancer die within 6 months. The behavior of papillary thyroid cancer can be predicted by patient age, sex, tumor size, local invasion, angioinvasion, lymph node metastases, distant metastases, as well as tumor differentiation and ability to take up radioactive iodine. Thus, older male patients with larger or invasive tumors, with angioinvasion, lymph node or distant metastases, and with tumors that do not take up radioactive iodine or cannot be completely surgically resected have a worse prognosis. Anaploid tumors, tumors with a low adenylate cyclase response to thyroid-stimulating hormone tumors, tumors that are ras-and gsp-positive, and tumors that are p21-positive and p53-positive also appear to behave in a more aggressive manner. In contrast, lymphocytic thyroiditis associated with papillary thyroid cancer predicts fewer recurrences and an improved survival. The treatment of patients with papillary thyroid cancer is controversial primarily because most patients do well with relatively minimal therapy, and there are no prospective studies concerning the merits of various treatments. Much of the controversy relates to the safety of thyroidectomy versus other procedures and, to a lesser extent, when to do a central or modified radical neck dissection. The rate of recurrence is lower, and the death rate may also be lower when patients are treated initially by total thyroidectomy. The rationale for total thyroidectomy is that it enables one to use radioactive iodine to detect and treat local and distant metastases, and it makes serum thyroglobulin determination more sensitive for detecting persistent disease. Total thyroidectomy should be associated with a permanent complication rate of less than 2%. Thyroid-stimulating hormone suppression therapy is recommended by most experts for patients with differentiated thyroid cancer and supported by most clinical and laboratory studies. Central and lateral node selection is recommended for patients with palpable lymphadenopathy.
Images
PMCID: PMC1303719  PMID: 8909165
22.  Anaplastic Thyroid Carcinoma: A Therapeutic Dilemma 
Yonsei Medical Journal  2005;46(6):759-764.
Anaplastic thyroid carcinoma (ATC) is one of the most malignant human neoplasms and has a grave prognosis. This study gives an update on our experience with this unusual neoplasm, with specific focus on the response to various treatment modalities. Forty-seven patients with histologically proven ATCs were enrolled (19 men, 28 women; mean age, 62.8 years). This number represents 1.5% among a total of 3,088 thyroid cancers treated between 1977 and 2002. The mean tumor diameter was 8.8 cm, and 22 patients had distant metastasis. Extrathyroidal extension was seen in 26 (89.7%) of the cases that underwent surgery. Treatment modalities adopted could be classified into 5 groups: Group 1, biopsy only; Group 2, biopsy and chemoradiotherapy; Group 3, debulking only; Goup 4, debulking and chemoradiotherapy; Group 5, complete excision and chemoradiotherapy. Survival was calculated from the time of diagnosis, and comparisons of survival were done by log-rank analysis. The mean survival was 4.3 months (range, 1.0-21 months). The mean survival based on treatment modalities were as follows: Group 1 (n = 10), 2.1 months, Group 2 (n = 8); 3.6 months; Group 3 (n = 7), 3.0 months; Group 4 (n = 14), 3.5 months, Group 5 (n = 8), 9.4 months. There was no significant difference in survival time between the various types of treatment modalities. Even though a small improvement in survival was observed with complete excision and aggressive multimodality therapy, nearly all ATCs remain unresponsive to ongoing treatment modalities and as such, present a therapeutic dilemma. A more effective treatment regimen should be sought in order to improve survival.
doi:10.3349/ymj.2005.46.6.759
PMCID: PMC2810588  PMID: 16385650
Anaplastic thyroid cancer; treatment modalities; treatment outcome
23.  Robotic Thyroidectomy for Cancer in the US: Patterns of Use and Short-Term Outcomes 
Annals of surgical oncology  2014;21(12):3859-3864.
Background
We describe nationally representative patterns of utilization and short-term outcomes from robotic versus open thyroidectomy for thyroid cancer.
Methods
Descriptive statistics and multivariable analysis were used to analyze patterns of use of robotic thyroidectomy from the National Cancer Database (2010–2011). Short-term outcomes were compared between patients undergoing robotic versus open thyroidectomy, while adjusting for confounders.
Results
A total of 68,393 patients with thyroid cancer underwent thyroidectomy; 225 had robotic surgery and 57,729 underwent open surgery. Robotic thyroid surgery use increased by 30 % from 2010 to 2011 (p = 0.08). Robotic cases were reported from 93 centers, with 89 centers performing <10 robotic cases. Compared with the open group, the robotic group was younger (51 vs. 47 years; p < 0.01) and included more Asian patients (4 vs. 8 %; p = 0.006) and privately-insured patients (68 vs. 77 %; p = 0.01). Tumor size was similar between patients undergoing robotic versus open surgery. Total thyroidectomy was performed less frequently in the robotic group (67 vs. 84 % open; p < 0.0001). Patients were relatively more likely to undergo robotic surgery if they were female (odds ratio [OR] 1.6; p = 0.04), younger (OR 0.8/10 years; p < 0.0001), or underwent lobectomy (OR 2.4; p < 0.0001). In adjusted multivariable analysis, there were no differences in the number of lymph nodes removed or length of stay between groups; however, there was a non-significant increase in the incidence of positive margins with robotic thyroidectomy.
Conclusions
Use of robotic thyroidectomy for thyroid cancer is limited to a few institutions, with short-term outcomes that are comparable to open surgery. Multi-institutional studies should be undertaken to compare thyroidectomy-specific complications and long-term outcomes.
doi:10.1245/s10434-014-3838-8
PMCID: PMC4519825  PMID: 24934584
24.  Endoscopic thyroidectomy: Our technique 
Minimally invasive surgery is widely employed for the treatment of thyroid diseases. Several minimal access approaches to the thyroid gland have been described. The commonly performed surgeries have been endoscopic lobectomies. We have performed endoscopic total thyroidectomy by the anterior chest wall approach. In this study, we have described our technique and evaluated the feasibility and efficacy of this procedure.
Materials and Methods:
From June 2005 to August 2006, 15 cases of endoscopic thyroidectomy were done at our institute. Five patients were male and 10 were female. Mean age was 45 years. (Range 23 to 71 years). Four patients had multinodular goiter and underwent near-total thyroidectomy; four patients had follicular adenoma and underwent hemithyroidectomy. Out of the seven patients of papillary carcinoma, four were low-risk and so a hemithyroidectomy was performed while three patients in the high risk group underwent total thyroidectomy. A detailed description of the surgical technique is provided.
Results:
The mean nodule size was 48 mm (range 20-80 mm) and the mean operating time was 85 min (range 60-120 min). In all cases, the recurrent laryngeal nerve was identified and preserved intact, the superior and inferior parathyroids were also identified in all patients. No patients required conversion to an open cervicotomy. All patients were discharged the day after surgery. All thyroidectomies were completed successfully. No recurrent laryngeal nerve palsies or postoperative tetany occurred. The postoperative course was significantly less painful and all patients were satisfied with the cosmetic results.
Conclusions:
It is possible to remove large nodules and perform as well as total thyroidectomies using our endoscopic approach. It is a safe and effective technique in the hands of an appropriately trained surgeon. The patients get a cosmetic benefit without any morbidity.
doi:10.4103/0972-9941.37191
PMCID: PMC2749190  PMID: 19789664
Endoscopy; technique; thyroidectomy
25.  Primary Squamous Cell Carcinoma of the Thyroid Diagnosed as Anaplastic Carcinoma: Failure in Fine-Needle Aspiration Cytology? 
Case Reports in Pathology  2014;2014:301780.
A case of primary squamous-cell carcinoma (SCC) of the thyroid which had been initially diagnosed as an anaplastic carcinoma (ATC) is described: female, 73 years old, with a fast-growing cervical nodule on the left side and hoarseness for 3 months. Ultrasonography showed a 4.5 cm solid nodule. FNA was compatible with poorly differentiated carcinoma with immunoreactivity for AE1/AE3, EMA. Thyroidectomy was performed. Histopathological examination showed a nonencapsulated tumor. Immunohistochemistry disclosed positivity for AE1/AE3, p53,p63, and Ki67. The diagnosis was ATC. A second opinion reported tumor consisting of squamous cells, with intense inflammatory infiltrate both in tumor and in the adjacent thyroid, with final diagnosis of SCC, associated with Hashimoto thyroiditis. No other primary focus of SCC was found. Patient has shown a 48-month survival period. Clinically, primary SCCs of the thyroid and ATCs are similar. The distinction is often difficult particularly when based on the cytological analysis of FNA material.
doi:10.1155/2014/301780
PMCID: PMC4175754  PMID: 25295208

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