Recurrent Thyroid Research Articles

患者背景に応じた甲状腺癌治療戦略

甲状腺分化癌は予後良好であるが，局所進行や病理学的な高悪性を有するものは局所や遠隔再発をきたしやすい。2014年に放射線ヨウ素不応の甲状腺分化癌の遠隔および局所再発（切除不能）例に対して，分子標的薬が本邦でも承認された。使用件数も増加しているが，局所進行再発癌の切除不能についての議論は少ない。局所再発進行癌のうち手術が困難なものとして，器官では頸動脈などの大血管への浸潤が，部位では副咽頭や縦隔への転移が考えられる。また局所進行再発癌の特徴は，局所では浸潤傾向が強いこと，遠隔転移を高率に認めることであり，切除による機能の維持と予後の両面で難治例が多い。しかし自験の成績では，切除可能であったものの局所制御は良好であり，手術療法が治療の中心と考えられる。切除不能局所再発癌に対して分子標的治療が適応となったことを受けて，今後さらに局所再発癌の手術適応について議論していく必要がある。

Radioguided Occult Lesion Localization in Patients With Locally Recurrent Papillary Thyroid Carcinoma: How We Do It?

Radioguided Occult Lesion Localization in Patients With Locally Recurrent Papillary Thyroid Carcinoma: How We Do It?

胸骨切開を要した再発甲状腺癌症例

今回われわれは, 初回手術後に上縦隔にリンパ節再発を認めた甲状腺乳頭癌の3症例を経験した. いずれの症例も頸部アプローチでは大血管に至るまで瘢痕組織の処理を避けられず, 安全性を考慮し胸骨切開を選択した. 一般的に腕頭静脈より頭側の病変は頸部アプローチのみで操作が可能とする報告が多いが, 再手術症例や節外浸潤を疑う症例では術操作の安全性から必ずしも賢明とは言えない. 胸骨切開によって, 十分な視野を得ることに加えて, 瘢痕組織や浸潤の疑われる部位をいったん回避し, 尾側の新鮮な部位で大血管を確保することは, その後の操作の安全性の向上をもたらし, 大きな利点と考えられる.

Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.

Ultrasound-guided Ethanol Ablation: Where does It fit in the Treatment of Recurrent Metastatic Papillary Thyroid Cancer?

ABSTRACT Introduction Ethanol (ETOH) ablation of metastatic neck nodes has been described as a potentially safe and effective alternative to surgical excision. We sought to describe a subset of these patients well suited for ETOH ablation. Materials and methods We report ultrasound-guided ETOH ablation of metastatic papillary thyroid cancer (PTC) at a Tertiary Care Endocrine Surgery Unit over 5 years. A retrospective review of all reoperative lymph node dissections was undertaken. Ethanol injection was used as second-line treatment to operative excision and was standardized with ultrasound guidance and the use of 1 cc/cm3 of 100% ETOH solution. Results Five treatments of ultrasound-guided ETOH ablation were studied. All patients had been previously treated with radioactive iodine (RAI) (mean: 1.25 treatments of 174mCi), however, in three cases with pretreatment I-131 scan, no uptake of radioiodine was seen in the treated disease. In four cases with pretreatment fludeoxyglucose-positron emission tomography (FDG-PET), treated lesions were avid. Median follow-up time for treatment was 28.5 months, with no disease progression in all ablated lesions. Serum thyroglobulin (Tg) values in patients without Tg-antibody were lower after treatment. There were no complications. Conclusion Surgeons seeking a less-invasive approach for nodal metastases in the neck can consider ETOH ablation. Small ultrasound detectable lesions in scarred necks (irradiated and/or reoperative) which are radioiodine non-avid and FDG-PET avid may be best suited for this treatment. As demonstrated by a small set of patients in a Tertiary Care Endocrine Surgery Unit, ETOH ablation is safe and effective at controlling progression of targeted local disease. How to cite this article Pasternak JD, Kluijfhout W, Seiser N, Gosnell JE, Suh I, Duh Q-Y, Shen WT. Ultrasound-guided Ethanol Ablation: Where does It fit in the Treatment of Recurrent Metastatic Papillary Thyroid Cancer? World J Endoc Surg 2016;8(3):199-202.

Lenvatinibを投与した治療抵抗性再発甲状腺未分化癌の1例

甲状腺未分化癌（anaplastic thyroid cancer:ATC）は，急速に進展し，ほとんどの治療には抵抗性を示すため予後は不良で，これまで治療方針は確立できていなかった．多分子標的薬Lenvatinibが使用可能となったが，これまでの治療とは異なった有害事象が出現するため，投与に当たっては十分な注意が必要である．腫瘍に近接した大血管からの出血は致死的となる可能性も高く，広く注意喚起がなされている．66歳，女性．化学療法，手術，放射線外照射による集学的治療後，治療抵抗性の再発に対してLenvatinibが奏効したが，総頸動脈破綻が見られ手術および鎖骨下動脈へのステント内挿術による緊急処置により救命しえた．集学的治療により長期生存が得られた今回の経験から対処法や考慮すべきポイントを考察した．

Anesthesia Management of Total Thyroidectomy Using a NIM EMG Endotracheal Tube: A Case Report

Total thyroidectomy is not routinely performed for indications other than malignancy until the last quarter of the twentieth century. Despite significant advancement in surgical techniques of total thyroidectomy developed by Theodore Kocher and William Halsted, significant risks including damage to the recurrent laryngeal nerve, hematoma, and thyroid storm are still important considerations when weighing against surgical benefits. Currently the use of neural integrity monitor (NIM) electromyogram (EMG) tracheal tube has become increasingly popular among surgeons to reduce risks of damage to the recurrent laryngeal nerves. The purpose of this case report is to discuss anesthetic management in a 48-year-old female patient undergoing total thyroidectomy using a NIM endotracheal tube (Medtronic Xomed, Jacksonville, Florida).

Robotic Resection of Metastatic Papillary Thyroid Cancer

Abstract The case is a 28-year-old woman with multiple recurrent papillary thyroid cancer, whose sole remaining site of known disease in the upper mediastinum was inaccessible through a cervical incision due to scar from previous operations. This brachiocephalic lymph node was removed safely and completely at a subsequent transthoracic robotic procedure with minimal impact on the patient. The operative technique and pathology are reviewed. No competing financial interests exist. Runtime of video: 4 mins 8 secs

5. Stem cells in undifferentiated, recurrent and metastatic thyroid cancers: A new direction for development of targeted therapies.

5. Stem cells in undifferentiated, recurrent and metastatic thyroid cancers: A new direction for development of targeted therapies.

Tubercle of Zuckerkandl as a Landmark for Identification of Recurrent Laryngeal Nerve Enabling Safe Thyroid Surgery- A Prospective Comparitive Study

Tubercle of Zuckerkandl as a Landmark for Identification of Recurrent Laryngeal Nerve Enabling Safe Thyroid Surgery- A Prospective Comparitive Study

Percutaneous Ethanol Injection vs Reoperation for Locally Recurrent Papillary Thyroid Cancer

Reoperation for recurrent papillary thyroid cancer (PTC) can be associated with a high rate of complications and failure to provide lasting remission. Percutaneous ethanol injection (PEI) may be an effective nonsurgical management option for locally recurrent PTC. This systematic analysis of the current literature compares the efficacy and complications related to PEI vs reoperative surgical intervention for treatment of locally recurrent PTC. Original studies were identified using the keywords "thyroid/ethanol" and "recurrent thyroid cancer/repeat surgery." Studies evaluating reoperation or PEI for lymph node metastases in patients with primary surgery of total thyroidectomy with appropriate lymph node dissection where indicated were included in the analysis for both reoperation and PEI. Animal studies, single case reports, and studies with fewer than 10 lesions were excluded. Outcomes included interval to detection of recurrence, success and failure rates, recurrence rates, complication rates, and follow-up duration. Between-group outcome differences were calculated using random-effects models, and pooled data cross-tabulation and logistic regression analysis were used. In all, 945 publications were identified, and 27 studies met the inclusion criteria. There were no studies that directly compared the 2 treatment techniques. A total of 1617 patients were included in this analysis; 168 (11.4%) were treated with PEI, and 1449 (88.6%) were treated with reoperation. Reoperation was successful in 94.8% of cases compared with an 87.5% success rate for PEI (odds ratio [OR], 2.58; 95% CI, 1.55-4.31; P < .001). The recurrence rates for PEI and reoperation at the site of the treated lesion or elsewhere in the neck were also similar (OR, 1.07; 95% CI, 0.65-1.77; P = .78). Reoperation was associated with a 3.5% pooled risk of complications, while PEI incurred a pooled risk of 1.2% (OR, 2.9; 95% CI, 0.72-12.3; P = .08). However, most studies did not report routine preoperative and postoperative laryngoscopies, an evaluation needed for accurate neural complication analysis associated with each procedure. High-quality, well-designed studies are needed to evaluate the feasibility of incorporating PEI into the treatment protocol of PTC. Although presently inferior to reoperation, PEI has the potential to be a widely accepted and effective nonsurgical treatment option for limited recurrent PTC in poor surgical candidates or patients seeking to avoid multiple reoperations.

BRAF mutation correlates with recurrent papillary thyroid carcinoma in Chinese patients.

We investigated correlations of somatic BRAF V600E mutation and RET/PTC1 rearrangement with recurrent disease in Chinese patients with papillary thyroid carcinoma (ptc). This prospective study included 214 patients with ptc histologically confirmed between November 2009 and May 2011 at a single institute. We found somatic BRAF V600E mutation in 68.7% and RET/PTC1 rearrangement in 25.7% of the patients. Although BRAF mutation was not significantly associated with clinicopathologic features such as patient sex or age, multicentric disease, thyroid capsule invasion, tumour stage, or nodal metastasis, it was significantly associated with recurrent disease. Multivariate analysis revealed that BRAF mutation and tumour size were independent risk factors associated with recurrent disease, with odds ratios of 9.072 and 2.387 respectively. The area under the receiver operating characteristic curve increased 8.3% when BRAF mutation was added to the traditional prognostic factors, but that effect was statistically nonsignificant (0.663 vs. 0.746, p = 0.124). RET/PTC1 rearrangement and nodal metastasis were significantly associated in all patients (p = 0.042), marginally associated in ptc patients (p = 0.051), but not associated in microptc patients (p = 0.700). RET/PTC1 rearrangement was not significantly associated with recurrent disease. BRAF positivity is an independent predictor of recurrent disease in ptc.

Papillary Thyroid Carcinoma

Abstract Introduction: Papillary thyroid carcinoma is the most common form of thyroid malignancy. Numerous clinicopathologic studies have documented its generally indolent clinical course and excellent overall prognosis. However older patients have more aggressive disease with a worse prognosis. Material and Methods: A retrospective study was done, including all the patients who had presented to our department East Surgical ward of Mayo hospital, in Lahore during 8 years period from October 2006 to November 2013 with papillary thyroid carcinoma. Results: There were 30 male and 100 female patients, resulting in a male to female ratio of 1:3.33. The range was from 13 to 83 years, and the mean was 40 years. All the patients presented initially with clinically evident disease in the neck. This was located within the thyroid gland in 72 (67.2%), in the thyroid gland plus cervical nodes in 54 (41.5%), and in the cervical nodes only in 1 (0.76%). Conclusion: Total thyroidectomy followed by RAI therapy is the treatment of choice for primary and recurrent papillary thyroid carcinoma.

Clinical analysis of 109 cases of recurrent papillary thyroid carcinoma

Objective: To explore the factors related to recurrence of PTC (papillary thyroid carcinoma) and the sites of recurrence, in order to seek for the proper treatment of these cases. Methods: The clinical and follow-up data of 109 cases of recurrent PTC in Tianjin Medical University Cancer Hospital from January 2008 to January 2012 were analyzed retrospec­tively, and 350 cases of PTC without recurrence in the same period were also collected as the controls. The univariate and multivariate analyses were performed to find out the recurrence-related factors. Results: The univariate analysis revealed that initial operative approach, TNM stage and pathological subtype were associated with recurrence (P 0.05). Multivariate analysis indicated that initial operative approach and pathological subtype were the dependent factors for recurrence (P < 0.05). Of 109 cases, 20 (18.3%) were confirmed as residual carcinoma by pathology. The involved sites of recurrence included regions of lymph nodes (34 in group Ⅱ, 54 in group Ⅲ, 58 in group Ⅳ, 12 in group Ⅴ, 68 in group Ⅵ), soft tissues (5 in group Ⅱ, 6 in group Ⅲ, 9 in group Ⅳ, 0 in group Ⅴ, 8 in group Ⅵ), muscles (2 in anterior cervical muscle, 1 in extrinsic laryngeal muscle, and 0 in sternocleidomastoid), parathyroid (n = 1), laryngeal recurrent nerve (n = 3), esophagus (n = 1) and trachea (n = 2). Five cases developed pulmonary metastasis, and 1 case developed liver and bone metastases. Conclusion: For the PTC patients who have the possibility of recurrence, the reinforced postoperative follow-up should be required. Furthermore, regular reexamination is also needed for possible recurrent regions. Once the recurrence occurres, active and standardized therapy is suggested for PTC. DOI:10.3781/j.issn.1000-7431.2013.08.012

Safe thyroidectomy with intraoperative methylene blue spraying

BackgroundWe aimed to minimalize operative complications by spraying of methylene blue stain on thyroid glands and the perithyroidal area.Material and methodsThe intra-operative methylene blue spraying technique was used prospectively on a total of 56 patients who had undergone primary (not recurrent) thyroid surgery for a variety of thyroid diseases. Bilateral total thyroidectomy was performed in all cases. After superior but before inferior pole ligation, 0.5ml of methylene blue was sprayed over the thyroid lobe and perilober area. Tissues, especially parathyroides, the recurrent laryngeal nerve, and the inferior thyroid artery, were identified and evaluated.ResultsRecurrent laryngeal nerve and arteries were not stained and thus they remained white in all cases while all other tissues were stained blue. Within three minutes parathyroid glands washed out the blue stain and the original yellow color was regained. Thyroid tissue wash-out time was not less than 15 minutes; perithyroideal muscles, tendinous and lipoid structures took no less than 25 minutes.ConclusionThe safety of intravascular methylene blue guidance on thyroid surgery is known. This research demonstrates the effectiveness of the spraying technique, a new technique which ensures not only identification of parathyroid glands within three minutes, but also identification of recurrent laryngeal nerves and inferior thyroid arteries.

Long-term results of surgery for papillary thyroid carcinoma with local recurrence

Surgical treatment of local recurrent papillary thyroid carcinoma is still controversial because of the increased morbidity in comparison to primary surgery, and the unclear efficacy. This study analyzed the efficacy and safety of surgery for recurrent disease. A retrospective cohort analysis of 86 patients who underwent surgery for local recurrent papillary thyroid carcinoma at a single institution during the period 1979-2009. The cause-specific survival rates of all patients at 5, 10, and 20 years were 86 % (95 % CI 77-95 %), 74 % (95 % CI 62-87 %), and 36 % (95 % CI 18-54 %), respectively. A univariate analysis found that gender, age >45 years at reoperation and macroscopic non-curative surgery for recurrence affected the cause-specific survival rates. The latter two features remained significant in a multivariate analysis. Permanent recurrent nerve paralysis and hypoparathyroidism developed in 4 (4.7 %) and 5 (5.8 %) patients, respectively. Surgery for local recurrent papillary thyroid carcinoma could be effective when macroscopic curative dissection was possible, and that the procedure was safe and was associated with minimal morbidity. Therefore, repeat surgery for local recurrent papillary thyroid carcinoma is worthwhile.

Fluorodeoxyglucose-positron emission tomography scan-positive recurrent papillary thyroid cancer and the prognosis and implications for surgical management

BackgroundTo compare outcomes for patients with recurrent or persistent papillary thyroid cancer (PTC) who had metastatic tumors that were fluorodeoxyglucose-positron emission tomography (FDG-PET) positive or negative, and to determine whether the FDG-PET scan findings changed the outcome of medical and surgical management.MethodsFrom a prospective thyroid cancer database, we retrospectively identified patients with recurrent or persistent PTC and reviewed data on demographics, initial stage, location and extent of persistent or recurrent disease, clinical management, disease-free survival and outcome. We further identified subsets of patients who had an FDG-PET scan or an FDG-PET/CT scan and whole-body radioactive iodine scans and categorized them by whether they had one or more FDG-PET-avid (PET-positive) lesions or PET-negative lesions. The medical and surgical treatments and outcome of these patients were compared.ResultsBetween 1984 and 2008, 41 of 141 patients who had recurrent or persistent PTC underwent FDG-PET (n = 11) or FDG-PET/CT scans (n = 30); 22 patients (54%) had one or more PET-positive lesion(s), 17 (41%) had PET-negative lesions, and two had indeterminate lesions. Most PET-positive lesions were located in the neck (55%). Patients who had a PET-positive lesion had a significantly higher TNM stage (P = 0.01), higher age (P = 0.03), and higher thyroglobulin (P = 0.024). Only patients who had PET-positive lesions died (5/22 vs. 0/17 for PET-negative lesions; P = 0.04). In two of the seven patients who underwent surgical resection of their PET-positive lesions, loco-regional control was obtained without evidence of residual disease.ConclusionPatients with recurrent or persistent PTC and FDG-PET-positive lesions have a worse prognosis. In some patients loco-regional control can be obtained without evidence of residual disease by reoperation if the lesion is localized in the neck or mediastinum.

Impact of FDG-PET Computed Tomography for Surgery of Recurrent or Persistent Differentiated Thyroid Carcinoma

Fluorodeoxyglucose-positron emission tomography (FDG-PET)/computed tomography (CT) is able to localize persistent or recurrent disease in differentiated thyroid carcinoma (DTC). The aim of the study was to correlate PET/CT results with precise intraoperative localization of persistent or recurrent papillary and follicular thyroid carcinoma. Patients with differentiated thyroid carcinoma who received FDG-PET scans were prospectively documented. The PET/CT results were correlated with other localization studies (neck ultrasound, ¹³¹I whole-body scan) and accurately compared to intraoperative findings and histopathological examinations. FDG-PET/CT scans were performed in 18 patients, between 16 and 84 years of age, from December 2008 to June 2011. Fourteen patients had papillary thyroid carcinomas and 4 had follicular thyroid carcinomas. All patients had a previous thyroidectomy and radioiodine ablation. Before cervical re-exploration, FDG-PET/CT-positive findings were reported in 14 individuals, whereas 4 PET scans provided no evidence of disease. Intraoperatively, 13 of 14 FDG-PET/CT-positive localizations of recurrent or persistent thyroid carcinomas were verified and confirmed by histopathology (sensitivity 93%). In another patient lymph node metastases of lung cancer were detected intraoperatively. However, FDG-PET/CT underestimated the number of lesions in 5 of 6 patients undergoing systematic lymphadenectomy. No lymph node or soft tissue metastases were found intraoperatively in 3 of the 4 patients with negative FDG-PET scans. A solitary cystic lymph node metastasis was found in the fourth patient but was not detected by FDG-PET/CT (specificity 75%). FDG-PET/CT has high sensitivity and specificity for the detection of persistent or recurrent differentiated thyroid carcinoma. FDG-PET/CT helps to select patients who might benefit from surgery because it provides precise anatomical details.

Excellent long-term control in locoregionally recurrent radioactive iodine-refractory papillary thyroid cancer with the addition of external beam radiation therapy to maximal surgical resection.

e16035 Background: Locoregionally recurrent radioactive iodine (RAI) refractory papillary thyroid cancer represents a small percentage of papillary thyroid cancers but is an aggressive disease with significantly lower survival rates. This retrospective review is our experience with these cancers treated with maximal surgical resection followed by external beam radiotherapy. Methods: 26 patients treated from 2001-2011 were eligible for review. After obtaining IRB approval, medical records were reviewed for clinical outcome. All patients had histologically proven recurrences that were negative on I-131 scans. All patients were maximally resected. All patients received external radiotherapy to the thyroid bed, bilateral cervical lymph node levels II-IV, level VI, and superior mediastinal nodes. 15/26 patients received intensity modulated, 9/26 patients received 3-D conformal, and 2/26 patients received Tomotherapy radiation treatment. The mean dose was 5790 cGy (range 5280-6800 cGy). Results: All histologies were papillary thyroid cancer with 4/26 exhibiting tall cell features and 1/26 diffuse sclerosing features. All patients had locoregional relapse in the cervical nodes (16/26) or in the mediastinum (5/26) or both areas (5/26). The mean pre-treatment thyroglobulin was 5.2 (range &lt;0.1 to 599.1). The mean post-treatment thyroglobulin was 1.0 (range &lt;0.1-5.2). Median follow-up was 55 months (range 7-123 months). 0/26 patients failed locoregionally. 2/26 patients failed distantly (lungs). 20/26 patients (77%) of patients had undetectable thyroglobulin at last follow-up. 4/26 patients had detectable thyroglobulin (2.5-16.9), but had not recurred on imaging. 2/26 required PEG placement during treatment, but 0/26 patients were PEG-dependent on long-term follow-up. 1/26 patients experienced grade III osteoradionecrosis of the mandible. Conclusions: External beam radiotherapy provides excellent locoregional control for locoregionally recurrent radioactive iodine-refractory papillary thyroid cancers. Long-term grade III and IV toxicities are uncommon.

Review of Molecular Markers for Thyroid Cancer

The incidence of thyroid cancer has been rapidly increased in Korea. Although fine needle aspiration cytology is recommended for diagnosis of cancer, there are some limitations. Patients with indeterminate or suspicious cytology category in which malignancy cannot be ruled out usually undergone a thyroidectomy, however, only 10∼25% of them finally diagnosed as cancer. According to the progress in understanding molecular mechanism, some mutations or other molecular alterations have been studied for the diagnostic and prognostic markers for thyroid cancer. The majority of papillary thyroid cancers have BRAF and RAS mutations or RET/PTC rearrangement, and approximately 80% of follicular thyroid cancers harbor a RAS mutation or PAX8/PPARγ rearrangement. These genetic alterations are mostly studied and current clinical guidelines suggested that these molecular markers may help management for patients with indeterminate cytology. In addition, recent studies demonstrated the high sensitivity and specificity of thyroid-stimulating hormone receptor mRNA in diagnosing cancer in patients with indeterminate cytology. For the detection of recurrent or residual thyroid cancer, serum thyroglobulin is the only circulating marker in clinical practice. However, it lacks sensitivity and is unreliable specifically in the presence of antibodies to thyroglobulin. Recent studies demonstrated a significant role of measuring the mRNA of thyroglobulin, thyroid peroxidase, thyroid-stimulating hormone receptor, and sodium/iodine symporter in peripheral blood for monitoring of the recurrence of thyroid cancer. (Ewha Med J 2012;35(1):3-10)