Medullary Thyroid Carcinoma: 25-year Experience and the Results of the RET Proto-oncogene Screening Test

Purpose: Medullary thyroid carcinoma (MTC) is a rare thyroid tumor and its clinical course is quite variable. The aim of this study was to retrospectively analyze our clinical and laboratory data for 25 years to review the clinicopathologic characteristics, the operation methods, the tumor recurrence and the prognosis of medullary thyroid carcinoma. We also reevaluate the limits of the previous diagnostic and treatment modalities. The positivity for and the location of the RET mutation are also evaluated. Finally, we want to contribute to a systemic approach for the diagnosis, treatment, patient management and clinical study of medullary thyroid carcinoma. Methods: We conducted a retrospective review of the records of 77 patients with MTC that were seen at our hospital from 1982 to 2007. The medical records were reviewed for the demographic data, the laboratory data and the clinical course, the treatment, the long-term outcome and the RET proto-oncogene mutation. The mean follow-up period was 69.6 months (range: 6∼201). Results: There were 50 females and 27 males. The mean patient age was 44.2 years (range: 1∼80). There were 16 cases of the sporadic form (79.2%) and 16 cases of the hereditary form. At diagnosis, 73 patients (94.8%) had local disease and 4 patients (5.2%) had distant metastasis. The patients with the hereditary form were younger than the patients with the sporadic form (P=0.004), and they had more muticentric (P=0.002) and bilateral tumor (P＜0.001). The initial surgery consisted of total thyroidectomy in 74 patients (96.1%), and lateral neck dissection in 41 patients (53.2%) (therapeutic: 23, prophylactic: 18), except for 3 cases with less than total thyroidectomy. Forty-four patients (57.1%) achieved a long-term remission state, 13 patients (16.9%) had biochemical persistent disease, and 20 patients (26.0%) had metastasis. The 5- and 10-year survival rates were 86.5% and 74.1% respectively. On univariate analysis, tumor size (more than 2 cm), extracapsular invasion, involvement of the neck nodes and distant metastasis at the time of diagnosis were the significant prognostic factors of persistent or recurrence disease. Conclusion: Patients with MTC generally have a favorable outcome. The presence of distant metastasis at the time of diagnosis is predictive of persistent or recurrence disease by multivariate analysis. In order to achieve an early diagnosis and administer prompt treatment, we suggest that optimal RET oncogene screening and counseling should be performed for medullary patients and their relatives.ope

Anaplastic Transformation of Metastatic Papillary Thyroid Carcinomas in the Cervical Lymph Nodes: Report of 3 Cases

Anaplastic thyroid carcinoma (ATC) is a rare disease that shows very aggressive behavior. Most ATCs arise from pre-existing thyroid carcinomas. However, anaplastic transformation occurring in metastatic cervical nodes is extremely rare. We report herein on 3 cases of anaplastic transformation of metastatic lateral cervical lymph nodes from primary papillary thyroid carcinoma (PTC), which happened long after the initial surgical treatment. All the patients died of disease within 4 months in spite of aggressive treatment for the lesions. Our experience supports that appropriate lymph node dissection is mandatory at the time of initial surgery even for differentiated thyroid carcinomas.ope

Robot-assisted Endoscopic Thyroid Surgery for Thyroid Cancer; Initial Experience of Consecutive 100 Patients

Background and Objectives: Various surgical procedures have been performed using surgical robot in recent years and most reports proved that application of robotic technology for surgery is technically feasible and safe. The aim of this study is to introduce our technique of robot-assisted endoscopic thyroid surgery and demonstrate its utility in the surgical management of thyroid cancer. Materials and Methods: From October 4th 2007 through March 14th 2008, 100 patients with papillary thyroid cancer underwent robot-assisted endoscopic surgeries using a gasless trans-axillary approach. This novel robotic surgical approach allowed adequate endoscopic access for thyroid surgeries. All the procedures were completed successfully using the da Vinci surgical system (Intuitive Surgical, Sunnyvale, California, USA). We used four robotic arms with this system; a 12 mm telescope and three 5 mm instruments. The 3-dimensional magnified visualization obtained by the dual-channel endoscope and tremor-free instruments controlled by robot system helped surgeon do sharp and precise endoscopic dissection. Results: We performed 84 less-than total and 16 total thyroidectomies with ipsilateral central compartment node dissection. Mean operation times was 136.5 min. (range 79∼267 min.) in which the actual time for thyroidectomy with lymphadenectomy (console time) was 60.0 min. (range 25∼157 min). The average number of lymph nodes resected was 5.3 (range 1 to 28). There was no serious complication. Most patients could go home within 3 days after surgery. Conclusion: Our technique of robotic-assisted endoscopic thyroid surgery using a gasless trans-axillary approach is feasible, safe and promising for the selected patients with thyroid cancer. We suggest application of robotic technology for endsocopic thyroid surgeries could overcome the limitations of conventional endoscopic surgeries in the surgical management of thyroid cancer.ope

Gasless Endoscopic Thyroidectomy using the Trans-axillary Approach for Benign Thyroid Tumor

Purpose: The techniques for minimally invasive surgery in various surgical fields have recently become markedly developed. The endoscopic surgical methods for head and neck surgery have been introduced somewhat later due to some technical limitations. However, various endoscopic techniques have been remarkably developed during the last 10 years. We also introduced a novel method of gasless endoscopic thyroidectomy using the trans-axillary approach. The aim of this study is to evaluate the feasibility and surgical outcome of this method for treating patients with benign thyroid tumor. Methods: From Jan. 2002 to Dec. 2007, 171 patients with benign thyroid tumors underwent gasless endoscopic thyroidectomy via an axillary approach. We retrospectively analyzed the clinical and pathologic characteristics of the patients, the type of operation, the operative time, the post-operative hospital stay and the post-operative complications. Results: Among the 171 patients, the mean age of the patients was 33.3±10.0 years and the gender ratio was 1： 84.5 (males-2, females-169). The type of operation was classified according to the extent of surgery and there was no conversion to open thyroidectomy. The mean operation time and the mean length of the post-operative hospital stay were 129.7±51.6 minutes and 3.3±1.7 days, respectively. The mean tumor size was 2.70±1.18 cm and the most common pathologic diagnosis was adenomatous hyperplasia (106 cases, 62%). For the post-operative complications, transient hoarseness occurred in 6 patients, transient hypocalcemia occurred in 1 patient and trachea and esophageal injury occurred in 1 patient each. A tumor size larger than 5 cm and concurrent thyroiditis at time of the operation both increased the mean operation time (P= 0.009, P=0.023). Conclusion: According to our experience, gasless endoscopic thyroidectomy using a trans-axillary approach is a feasible and safe method for treating benign thyroid tumor. Moreover, the cosmetic benefits can be maximized by this method as compared with the other methods. Endoscopic thyroid surgery has become a new treatment modality for selected patients with benign thyroid tumorsope

Application of Robotic-assisted Mediastinal Lymph Node Dissection for Papillary Thyroid Cancer

There are three compartments of regional lymph node to which metastases from thyroid cancers can occur: central, lateral, and mediastinal compartment. The mediastinal metastases from thyroid cancers are extremely rare, comparing the relatively common forms of metastases to central or lateral compartments. The importance of complete surgical lymph node dissection of central or lateral compartment for thyroid cancer has been well described, but mediastinal lymph node dissection has been sporadically reported. For mediastinal compartment metastases, operation techniques consist of sternal split, thoracoscopic surgery, or VATS (Video-assisted thoracoscopic surgery). Robotic surgery system was introduced recently with the objective of enhancing the dexterity and view during procedure that uses a videoscope. Many institutions report the experience with minimally invasive resection of mediastinal mass using robotic surgery system. We report that one case of robot-assisted mediastinal lymph node dissection for metastatic papillary thyroid cancer.ope

Clnicopathologic Features of Warthin-like Papillary Carcinoma of the Thyroid

Purpose: Warthin-like papillary carcinomawas named owing to its close histologic resemblance to a tumor encountered in salivary gland, and this tumor is a variant of papillary thyroid carcinoma. Among the variants of papillary thyroid carcinoma, the tall cell variant and diffuse sclerosing variant have more aggressive behavior than the classic papillary carcinoma. But Warthin-like papillary carcinoma arises in a background of thyroiditis and it behaves in an indolent fashion. Since then, a few case have reported in Korea. We report here on the clinicopathologic features of five cases of warthin-like papillary carcinoma. Methods: From Jan. 1996 to Feb. 2008, five patients who were diagnosed with Warthin-like papillary thyroid carcinoma at YUMC were retrospectively reviewed. Results: All 5 patients whose pathologic features were warthin-likepapillary thyroid carcinoma were women (age range: 34∼60 years). The tumor size ranged from 0.6 to 2.4 cm. 3 tumors were confined to the thyroid, but 2 tumors had invaded the strap muscles. 3 of the 5 tumors arose in a background of lymphocytic thyroditis. Central nodal metastases were identified in 2 cases. But no lateral nodal or distant metastasis had occurred. The mean duration of follow-up was 16.5 months (range: 5∼50 months). 1 patient died because of lung cancer, and there was no recurrence for the other 4 cases during the follow-up period. Conclusion: Although the long-term follow-up data on patients with Warthin-like papillary carcinoma is not available, the clinicopathologic data does not show that Warthin-like papillary carcinoma is any more aggressive than the usual papillary carcinoma.ope

(The) lymphnode dissection above the spinal accessory nerve (Level IIB) for thyroid carcinoma patients with

의학과/석사[한글]배경 및 목적: 두경부 계통 암에서 경부 림프절 전이는 암의 1차 치료 후 재발 및 원격 전이와 직접적으로 연관되며 나아가 전반적인 예후와 밀접한 관계를 이루고 있다. 따라서, 원발병소에 대한 수술적 치료 시 경부 림프절 전이 정도를 예측하여 청소술의 범위를 결정하는 것이 중요하다. 그러나 갑상선암 수술시 경부 림프절 전이에 따른 측경부 림프절 청소술의 범위에 대해서는 아직도 논란이 있다. 특히 척수부신경 (spinal accessory nerve) 의 하측 림프절인 level IIA에 전이가 의심되지 않을 때 수술의 복잡성과 척수부신경 손상 및 기타 경부 감각 신경들의 손상 가능성이 있는 level IIB의 예방적인 청소술의 필요성에 대해서는 의견이 일치 되지 않고 있다. 본 논문은 유두상 갑상선암 환자만을 대상으로 경부 림프절의 전이 양상과 측경부 림프절 청소술시 level IIA와 level IIB의 연관 관계, level IIB의 예방적 청소술의 필요성, 및 적절한 청소술의 범위를 알아보고자 하였다.재료 및 방법: 본 연구는 2005년 9월부터 2006년 5월까지 전향적 방법으로 측경부 림프절 청소술을 시행 받은 71명의 유두상 갑상선암 환자를 대상으로 하였으며, 이 중 6명이 양측성 측경부 림프절 청소술을 시행 받았다. 71명 모두 level II, III, IV, 와 V 림프절 청소술을 시행 받았으며 level II 는 IIA와 IIB로 구분하였다. 정확한 구획 설정에 따른 림프절 절제술이 진행되었으며 자료의 정확성을 위해서 동일 시술팀에 의해 수술이 진행되었다.결과: 가장 높은 측경부 림프절 전이를 보인 군은 level III로 71.4%의 전이율을 보였으며 다음으로 level IV와 II가 59.7%와 51.9%의 전이율을 보였다. Level II에서는 IIA가 51.9%, IIB가 5.2%를 보였다. 본 연구에서 level IIA와 IIB를 비교함에 있어서 IIA에 림프절 전이가 있을 때에만 IIB에 전이가 일어날 수 있음을 확인하였으며 IIB에 단독으로 나타나는 전이는 없었다.결론: 경부 림프절 전이가 있는 갑상선암 환자에서 측경부 림프절 청소술을 시행 할 때에 수술 중 동결절편 검사에서 level IIA의 전이가 없다면 level IIB의 예방적 림프절 청소술은 생략해도 될 것으로 판단된다. [영문]Introduction: Cervical lymphnode metastasis in head and neck carcinoma, including thyroid carcinoma, is directly related to locoregional recurrence of primary tumor, distant metastasis, and overall prognosis of the disease. Therefore, it is very important to decide the extent of lymphnode dissection at the time of surgical treatment. However, there is no standard in deciding the extent of lateral cervical lymph node dissection in surgical treatment of thyroid carcinoma. Especially, prophylactic node dissection above the spinal accessory nerve (SAN) is still in debate.Materials and methods: From November 2005 to May 2006, 71 papillary thyroid carcinoma patients with cervical lymphnode metastasis underwent lateral neck lymphnode dissection. Among them, 6 patients had bilateral lateral lymphnode dissection. All of them received level II, III, IV and V lymphnode dissection. Level IIA and IIB nodes were individually dissected in all cases. All of the neck dissections were performed with strict leveling by single operating team.Results: The most common site of metastasis was level III showing 71.4%, followed by level IV(59.7%) and II(51.9%). In level II, IIA and IIB showed 51.9% and 5.2% metastatic rates, respectively. In this study, level IIB metastases were seen only when level IIA metastases were evident clinicopathologically.Conclusion: The level IIB lymphnode dissection is not necessary when level IIA shows negative metastases.ope

난치성 갑상선암의 혁신적인 치료

Dept. of Medicine/박사In general, thyroid carcinomas can be classified as well differentiated thyroid carcinomas and undifferentiated thyroid carcinomas. Fortunately, more than 95% of the thyroid carcinomas are well differentiated types showing favorable prognosis, and for these carcinomas, surgery with radioiodine ablation is the most effective therapy. However, only a few therapeutic options are available to treat the patients with undifferentiated thyroid carcinomas, especially with refractory thyroid carcinomas that are not amenable to surgery or radioiodine ablation. Recently, many institutions are under investigation to find a new treatment modality for such carcinomas. For the hope of finding an innovative drug therapy for refractory thyroid carcinomas, we investigated the anticancer effects of 20 drugs on 8 thyroid carcinoma cell lines. We analyzed the effects of 12 well acknowledged chemotherapy drugs each tested at 3 different concentrations, and 8 additional chemotherapy and hormonal therapy drugs at 9 concentrations. In vitro chemosensitivity was tested using the adenosine-triphosphate-based chemotherapy response assay (ATP-CRA). The tumor inhibition rate (TIR; or cell death rate) or half maximal inhibitory concentration (IC50) was analyzed to interpret the results. For 12 well acknowledged chemotherapy drugs, the active drugs showing better chemosensitivity were defined as those resulting in ≥30% TIR. Of the 12 chemotherapy drugs, etoposide and vincristine were the most active drugs showing the highest chemosensitivity and of the 8 additional drugs, trichostatin A showed favorable outcome as an anticancer drug. The study was to find an innovative therapy for the refractory thyroid carcinomas and the results showed that chemotherapy drugs such as etoposide and vincristine showed evidence as active anticancer drugs in thyroid carcinoma cell lines. Also, trichostatin A result came out to be the next promising drug. Further investigation of the above drugs and combination test for their interaction effects should be continued for clinical application in near future.ope

Is level IIb lymph node dissection always necessary in N1b papillary thyroid carcinoma patients?

INTRODUCTION: Papillary thyroid carcinoma (PTC) patients show a high rate of cervical lymphatic metastasis. However, there are no universal binding guidelines for the extent of lateral cervical lymph node dissection (LND) in such cases. In particular, the need for LND above the spinal accessory nerve (SAN) remains controversial. The present study examined whether level IIb lymph node (LN) dissection is always necessary in PTC patients with lateral cervical LN metastasis. MATERIALS AND METHODS: The study prospectively examined 167 PTC patients with lateral cervical LN metastasis who underwent modified radical neck dissection (MRND) in our institution from November 2005 to March 2007. The MRND was bilateral in 24 cases. All patients underwent level II, III, IV, and V LND. Levels IIa and IIb LNs were individually dissected in all cases. All LND was performed using strict leveling criteria by a single operating team. The patterns of lymphatic metastasis and potential risk factors for level IIb LN involvement were evaluated. RESULTS: The most common site of metastasis was level III (80.6% of cases), followed by level IV (74.9%) and II (55.5%). The metastasis rates in level IIa and IIb were 55.5% and 6.8%, respectively; all level IIb LN metastasis was accompanied by level IIa metastasis (p=0.001). In addition, level IIb LN metastasis was found to be associated with the aggressiveness of lymphatic metastasis (i.e., the total number of metastatic LNs) (p<0.0001). CONCLUSIONS: A level IIb LND should be performed when there is clinical or radiological evidence of lymphatic metastasis. In the absence of such evidence, the findings suggest that level IIb LND is not necessary in N1b PTC patients when there is no level IIa LN metastasis, or when the metastasis is not aggressive.ope

Primary intrathoracic goiter

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