Clinical impact of proteinuria on renal function and treatment outcomes in patients with radioiodine-refractory thyroid cancer treated with lenvatinib.

Proteinuria has been described as a major on-target adverse event of lenvatinib, although its long-term impact on renal function and clinical outcomes remains unclear. We conducted a retrospective observational study to assess renal function and prognosis in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) receiving lenvatinib. Overall, 70 patients with RR-DTC treated with lenvatinib were enrolled. When proteinuria was observed, the dose and schedule of lenvatinib were adjusted to achieve a urine protein-to-creatinine ratio (UPCR) of less than 3.5 g/gCre according to the study protocols of recent pivotal trials. In total, 50 (71%) and 25 (36%) patients presented with any-grade and grade 3 proteinuria, respectively. Multivariate analysis revealed that age [>65; odds ratio (OR) 8.24, 95% confidence interval (CI) 1.74-39.00, p < 0.01], history of diabetes mellitus (OR 7.79, 95% CI 1.31-46.20, p = 0.02), and hypertension (OR 4.07, 95% CI 1.22-13.60, p = 0.02) were significantly associated with the development of grade 3 proteinuria. Overall, the median estimating glomerular filtration rate (eGFR) gradually decreased every 3 months during treatment. However, no significant deterioration in eGFR was observed in patients with grade 3 proteinuria compared with patients with grades 0-2 proteinuria until 48 months. Patients who developed proteinuria had better survival outcomes than those without proteinuria. In conclusion, the proteinuria grade was not significantly associated with decreased eGFR under UPCR monitoring in our study. Therefore, lenvatinib can carefully be continued targeting UPCR of less than 3.5 g/gCre.

Long-Term Outcomes After Lobectomy for Patients with High-Risk Papillary Thyroid Carcinoma.

BACKGROUND: Guidelines universally recommend total thyroidectomy for high-risk papillary thyroid carcinoma (PTC). However, in Japan, thyroid-conserving surgery had been widely applied for such patients until recently. We investigated long-term outcomes for this strategy. METHODS: A prospectively recorded database was retrospectively analyzed for 368 patients who had undergone curative surgery for high-risk PTC without distant metastasis between 1993 and 2013. High-risk PTC was defined for tumors showing tumor size > 4 cm, extrathyroidal extension, or large nodal metastasis ≥ 3 cm. RESULTS: Median age was 59 years and 243 patients were female. Mean duration of follow-up was 12.7 years. Lobectomy was conducted for 207 patients (LT group) and total or near-total thyroidectomy for 161 patients (TT group). The frequency of massive extrathyroidal invasion and large nodal metastasis was lower in the LT group than in the TT group. After propensity score matching, no significant differences were seen between groups for overall survival, cause-specific survival or distant recurrence-free survival. In the overall cohort, multivariate analysis identified age ≥ 55 years, large nodal metastasis, tumor size > 4 cm and massive extrathyroidal invasion as significantly associated with cause-specific survival, whereas extent of thyroidectomy was not. CONCLUSIONS: For patients with high-risk PTC without distant metastasis, curative surgery with lobectomy showed almost identical oncological outcomes compared to total thyroidectomy. The benefits of total thyroidectomy for high-risk PTC should be reevaluated in the future prospective studies.

Patient-Reported Outcomes in Patients with Low-Risk Papillary Thyroid Carcinoma: Cross-Sectional Study to Compare Active Surveillance and Immediate Surgery.

BACKGROUND: This cross-sectional study compared patient-reported outcomes of low-risk papillary thyroid carcinoma (PTC, T1N0M0) between patients who underwent active surveillance (AS) and those who received immediate surgery, METHODS: Using the State-Trait Anxiety Inventory, Short-Form 36 version 2, and a visual analog scale for neck symptoms, 249 patients under AS and 32 patients underwent immediate surgery were compared. To match the difference in time from the onset of treatment to the survey, we conducted propensity score matching. We also investigated factors affecting anxiety in patients under AS in multiple linear regression analysis. RESULTS: In the entire group, patients under AS had significantly longer time from the onset to the survey than patients underwent immediate surgery (7.9 vs. 4.0 years). After matching, AS group showed significantly better trait anxiety and mental component summary (MCS) compared to surgery group, while surgery group showed better role-social component summary. AS group also had significantly better MCS than the Japanese norm-based score. Surgery group displayed worse neck symptoms than AS group. Among AS group, trait anxiety and time from the onset were significant predictors of state anxiety. Compared with the group with < 5 years since starting AS, the group with ≥ 5 years of follow-up showed a significantly better state anxiety only in patients with better trait anxiety. CONCLUSIONS: Low-risk PTC patients under AS showed better trait anxiety and mental health than surgery group. After a certain period, the anxiety of patients under AS seems to be improved, especially in patients with better trait anxiety.

Correlation between low expression of protein disulfide isomerase A3 and lymph node metastasis in papillary thyroid carcinoma and poor prognosis: a clinicopathological study of 1,139 cases with long-term follow-up.

The incidence of papillary thyroid carcinoma (PTC) is increasing worldwide. The biomarkers to identify aggressive types of PTC are limited, illustrating the need to establish reliable novel biomarkers. Protein disulfide isomerase A3 (PDIA3) is a chaperone protein that modulates the folding of newly synthesized glycoproteins and stress-responsive proteins in the endoplasmic reticulum. Although the role of PDIA3 in various cancers such as breast, uterine cervix, head and neck, and gastrointestinal tract has been examined, its expression in thyroid cancer has not been reported. We retrospectively reviewed accumulated data with long-term follow-up of 1,139 PTC patients, and investigated the correlation between immunohistochemical expression of PDIA3 in PTC patients and clinicopathological features and prognosis. PDIA3 expression was significantly lower in PTCs compared to normal thyroid tissues (NTT; n = 80, p = 0.002). In PTCs, correlation between low PDIA3 expression and lymph node metastasis (p = 0.018) and the number of positive nodes (p = 0.004) was observed. Patients with low PDIA3 expression exhibited worse cause-specific survival compared to those with high PDIA3 expression (p = 0.013). Our findings indicate that low PDIA3 expression is related to poor clinical outcome in PTC patients, and that PDIA3 may potentially be a novel ancillary biomarker. Further clarification of the biological role of PDIA3 in PTC is warranted for the future clinical application.

Multifocality and Progression of Papillary Thyroid Microcarcinoma During Active Surveillance.

BACKGROUND: Prospective trials of active surveillance (AS) have shown low rates of progression in low-risk papillary thyroid microcarcinoma (PTMC; T1aN0M0). However, the significance of multifocality as a prognostic factor remains controversial. METHODS: Data from 571 patients (mean age, 53.1 years; 495 females) who underwent AS were reviewed. PTMC was unifocal in 457 patients (80.0%) and multifocal in 114 patients (20.0%), with 2-5 lesions each (261 tumors in total). Tumor progression was defined as tumor size enlargement ≥ 3 mm and/or development of clinically evident lymph node metastasis (LNM). RESULTS: After a mean duration of AS of 7.6 years, 53 patients (9.3%) showed tumor enlargement and 8 patients (1.4%) developed LNM. The 10-year progression rate was 13.1%. Age, sex, and calcification pattern did not differ significantly between uni- and multifocal diseases. However, anti-thyroglobulin antibody and/or anti-thyroid peroxidase antibody was more frequently positive with multifocal PTMCs (46.7%) than with unifocal disease (34.4%, p = 0.024). Patients with uni- and multifocal disease showed no significant differences in 10-year rate of tumor enlargement (11.4% vs. 14.8%), LNM development (1.1% vs. 2.4%), or progression (12.4% vs 15.9%). Multivariate analysis of predictors for progression showed multifocality was not a significant risk factor (odds ratio, 1.45; 95% confidence interval, 0.79-2.54; p = 0.22). Eventually, 9 patients (7.9%) with multifocal PTMCs underwent surgery and 7 needed total thyroidectomy, although 7 still showed T1N0M0 low-risk cancer. CONCLUSIONS: Even patients with multiple PTMCs (T1amN0M0) are good candidates for AS. Many patients can avoid total thyroidectomy and subsequent surgical complications.

Prognostic significance of 8 weeks' relative dose intensity of lenvatinib in treatment of radioiodine-refractory differentiated thyroid cancer patients.

Lenvatinib is a standard therapy for radioiodine-refractory differentiated thyroid cancer (RR-DTC). However, because of the high incidence of adverse events resulting from this treatment, it is not easy to maintain the dose intensity of lenvatinib, especially in Japanese patients. Although the prognostic impact of lenvatinib dose interruption has been reported, the target dose intensity of lenvatinib to optimize survival benefits remains unknown. We therefore propose a target dose intensity of lenvatinib during the first 8 weeks of treatment. We retrospectively analyzed 42 RR-DTC patients who were treated with lenvatinib for more than 8 weeks. We performed receiver operating characteristic curve analysis to determine the cut-off value of 8 weeks' relative dose intensity (8w-RDI) to predict treatment response, and identified that the optimal cut-off value of 8w-RDI was 60% (sensitivity: 81.8%; specificity: 80.6%). Median progression-free survival (PFS) (not reached [NR] vs. 11.0 months; hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.11-0.72; p < 0.01) and overall survival (NR vs. 27.6 months; HR 0.44; 95% CI 0.11-0.91; p = 0.03) were longer in the higher 8w-RDI (≥60%) patients than in the lower 8w-RDI (<60%) patients. Multivariate analysis revealed that 8w-RDI at ≥60% was an independent prognostic factor for PFS (HR 0.29; 95% CI 0.09-0.96; p = 0.04). Targeting for ≥60% of the relative dose intensity during the first 8 weeks of lenvatinib treatment can be sufficient to achieve significant tumor shrinkage and prolong PFS in RR-DTC patients.

A Phase II study of the safety and efficacy of lenvatinib in patients with advanced thyroid cancer.

AIM: To investigate the safety and efficacy of lenvatinib in advanced thyroid cancer. PATIENTS/METHODS: In this Phase II study, 51 Japanese patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC), medullary thyroid cancer (MTC) or anaplastic thyroid cancer (ATC) received once-daily lenvatinib 24 mg. The primary end point was safety. RESULTS: All patients experienced ≥1 adverse event (AE); only one patient experienced an AE leading to discontinuation. The most common any-grade AEs were hypertension, decreased appetite, palmar-plantar erythrodysesthesia, fatigue and proteinuria. Response rates for RR-DTC: 68%; MTC: 22%; ATC: 24%. Median progression-free survival for RR-DTC: 25.8 months; MTC: 9.2 months; ATC: 7.4 months. CONCLUSION: Lenvatinib demonstrated a manageable safety profile, proven antitumor activity in RR-DTC and promising efficacy in MTC and ATC. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT01728623.

Natural History of Asymptomatic Papillary Thyroid Microcarcinoma: Time-Dependent Changes in Calcification and Vascularity During Active Surveillance.

BACKGROUND: Prospective trials of non-surgical observation have shown progression rates of only 5-10% in patients with asymptomatic papillary microcarcinoma (PMC). This study investigated time-dependent changes in calcification patterns and tumor vascularity on ultrasonography (US) to clarify the natural course of PMC. METHODS: We examined calcification patterns and tumor vascularity for 480 lesions in 384 patients. Calcification patterns were classified as: (A) none; (B) micro; (C) macro; or (D) rim. Tumor vascularity was classified as rich or poor via color Doppler US. RESULTS: After a mean of 6.8 years of observation, 29 lesions (6.0%) had increased in size. Mean age for initial calcification pattern was 52.1 years for A (n = 135), 54.2 years for B (n = 235), 56.3 years for C (n = 96), and 60.1 years for D (n = 14), and the incidence rates of tumor enlargement were 9.6, 5.5, 3.2, and 0%, respectively. The cumulative rate of upgrade in calcification pattern was 51.8% at 10 years. Lesions with initially rich vascularity (n = 70) had significantly higher rate of tumor enlargement than those with poor vascularity (n = 410); however, the majority of tumor (61.4%) with initially rich vascularity had decreased their blood supply during the follow-up. Multivariate analysis showed that strong calcification (C or D) and poor vascularity at last examination correlated significantly with non-progressive disease. CONCLUSIONS: PMCs in older patients showed significantly stronger calcification patterns and poorer vascularity. Both consolidation of calcification and loss of vascularity occurred in a time-dependent manner during observation and were significant indicators for non-progressive disease.

Histopathological analysis of anaplastic thyroid carcinoma cases with long-term survival: A report from the Anaplastic Thyroid Carcinoma Research Consortium of Japan.

The aim of this study was to clarify the histopathological features of anaplastic thyroid carcinoma in patients who achieved long-term survival. We reviewed 88 anaplastic thyroid carcinoma cases in which the patient survived less than 3 months (short-term survival), and 68 anaplastic thyroid carcinoma cases in which the patient survived more than one year (long-term survival) from the database of the Anaplastic Thyroid Carcinoma Research Consortium of Japan. We examined these cases both histologically and immunohistochemically. Six (6.8%) short-term survival cases and 27 (39.7%) long-term survival cases were considered not to be anaplastic thyroid carcinoma after central review. Of these, 12 were revised to papillary carcinoma with squamous cell carcinoma. In cases without chemotherapy, long-term survival was significantly more common if there was a pre-existing tumor, epithelial growth, or lymphocytic infiltration, and short-term survival was more common if neutrophilic infiltration was present. In cases with chemotherapy, long-term survival was significantly more common if epithelial growth or a squamous cell carcinoma component was present, whereas short-term survival was more common in cases with rhabdoid cells. Immunohistochemical results were not related to survival. Some long-term survival cases showed histological findings other than those typically associated with anaplastic thyroid carcinoma. The presence of a pre-existing tumor, epithelial growth, a squamous cell carcinoma component, no neutrophilic infiltration and lymphocytic infiltration may therefore be favorable prognostic factors in anaplastic thyroid carcinoma.

Prospective Evaluation of Zoledronic Acid in the Treatment of Bone Metastases from Differentiated Thyroid Carcinoma.

PURPOSE: The objectives of this study were to prospectively delineate the efficacy and safety of zoledronic acid for treating bone metastases (BM) from differentiated thyroid carcinoma (DTC), and to evaluate the relationships between levels of bone metabolic markers and occurrence of skeletal-related events (SREs). METHODS: This was a prospective, single-arm, single-center study. Nineteen patients with BM from DTC were assigned to receive zoledronic acid therapy every 4-5 weeks. Imaging studies for sites of BM were conducted every 6 months, and levels of bone metabolic markers, including serum bone-specific alkaline phosphatase (BAP) and urinary N-telopeptide of type I collagen (NTx), were assessed every 3 months. To evaluate the efficacy of zoledronic acid use, data of SREs were compared with those of 16 historical controls. RESULTS: SREs developed in eight patients (42 %), but metastatic spinal cord compression (MSCC) appeared in only one patient. Pain scores were ameliorated in five patients, but aggravated in six patients. Ten patients had stable disease, six showed progressive disease, and none showed partial or complete response during the observation period. Decreases in levels of bone metabolic markers were observed in ten patients for BAP and 15 for NTx. However, no significant correlations were identified between changes in bone metabolic marker levels and development of SREs. CONCLUSIONS: Zoledronic acid may offer a mainstay of multidisciplinary treatment for patients with BM for the purpose of reducing SREs. Levels of serum BAP and urinary NTx do not appear reliable as indicators of amelioration of BM symptoms.

Concept and design of a nationwide prospective feasibility/efficacy/safety study of weekly paclitaxel for patients with pathologically confirmed anaplastic thyroid cancer (ATCCJ-PTX-P2).

BACKGROUND: Anaplastic thyroid cancer (ATC) is one of the most aggressive malignancies in humans, often demonstrating resistance to multimodal therapeutic approaches. The median survival of ATC patients after initial diagnosis was reported to be <6 months due to the rapid progression of disease by dissemination and/or invasion. There have been several reports describing possible effective chemotherapies, but these studies might be biased by the nature of retrospective accumulations of clinical experiences, and thus reliable data concerning the efficacies of the treatment efforts are required. DESIGN: In 2009, we established the research organization Anaplastic Carcinoma Research Consortium Japan (ATCCJ) to investigate this highly malignant disease. Using this nationwide organization, we conducted a prospective clinical study to investigate the feasibility, safeness, and efficacy of chemotherapy with weekly paclitaxel for ATC patients. This trial is registered on the clinical trials site of the University Hospital Medical Information Network Clinical Trials Registry Web site (UMIN000008574). The study was started in 2012, and enrollment was closed in March 2014 after accumulating 71 patients from 28 registered institutes. The follow-up data will be available in April 2015. DISCUSSION: Important information concerning the management of this disease is expected to be revealed by this study. The concept and design of the study are described herein.

Chemotherapy for anaplastic thyroid cancer using docetaxel and cisplatin: report of eight cases.

Anaplastic thyroid carcinoma has a dismal prognosis and lacks an established therapeutic strategy. We have recently conducted chemotherapy with docetaxel and cisplatin as part of multimodal treatment for eight patients with anaplastic thyroid carcinoma. Docetaxel (75 mg/m2) and cisplatin (75 mg/m2) were administered on day 1 every 4 weeks for six courses. This chemotherapy was used as induction therapy in one patient, as therapy for distant metastases in five patients and as postoperative adjuvant therapy in two patients. Three patients showed partial responses and three patients showed stable disease. After excluding the two patients receiving the treatment as adjuvant therapy the response rate was 50 %. Grade 3 or 4 leukocytopenia occurred in seven patients (88 %), but these adverse events were tolerable. Chemotherapy with docetaxel and cisplatin may thus be feasible for anaplastic thyroid carcinoma.

Surgical management of retropharyngeal nodes metastases from papillary thyroid carcinoma.

BACKGROUND: Papillary thyroid carcinoma (PTC) often metastasizes to the central and lateral neck lymph nodes, but rarely affects retropharyngeal nodes (RPN). METHODS: We retrospectively reviewed 12 patients (three men, nine women) with PTC who underwent dissection of RPN metastases between 1994 and 2012. Mean age at dissection was 65 years (range 23-77). RESULTS: Dissection was performed with the initial surgery for PTC in eight patients, while the remaining four patients underwent dissection as secondary surgery. RPN metastases arose from an ipsilateral primary in nine patients, bilateral in two, and contralateral in one, with primaries located at the superior pole of the thyroid lobe in nine patients. All patients showed simultaneous or previous lymph node metastases in the upper jugular chain. A transcervical approach was applied for RPN dissection in 11 patients, while a transcervical-transparotid approach was applied in the remaining patient. No patients needed mandibulotomy or showed severe complications. Median duration of follow-up after RPN dissection was 48 months (range 3-206). No recurrences in the retropharyngeal space were identified. Two patients died of the disease, one died from other carcinoma, and five survived with distant metastases from PTC. The remaining four patients remain free of the disease as at the time of writing. CONCLUSIONS: If lymph node metastases are identified in the upper jugular chain, the possibility of RPN metastases should be checked. Most RPN metastases from PTC can be dissected safely without mandibulotomy. In particular, low-risk patients can expect favorable outcomes.

Metastatic thyroid tumors: ultrasonographic features, prognostic factors and outcomes in 29 cases.

PURPOSE: Metastatic thyroid tumors (MTT) are rare and have a poor prognosis. The aim of this retrospective study was to determine the diagnostic features and clinical outcomes of MTT. METHODS: The study subjects comprised 29 patients (age range, 37-78 years) diagnosed with MTT and treated during a 22-year period between 1987 and 2008 at a single tertiary oncology referral center. RESULTS: The primary cancer was breast cancer in 10 patients, lung cancer in six, digestive tract in six, kidney in three, head and neck in three and sarcoma in one patient. In seven patients, the diagnoses of primary cancer and MTT were synchronous. In 22 patients, the mean latency between the diagnosis of the primary cancer and MTT was 66 months (range 7 months-16 years). Based on ultrasonography (US), MTTs were classified into two categories: diffuse type (DT) (n = 9) and nodular type (NT) (n = 18). Eight patients who underwent thyroid surgery showed no survival benefit, but none needed tracheostomy. CONCLUSIONS: MTT should be considered for patients with a history of malignant disease. The findings from US are useful to diagnose MTT. Careful preoperative evaluation can avoid unnecessary thyroidectomy.

Chemotherapy for anaplastic thyroid cancer using docetaxel and cisplatin: report of eight cases.

Anaplastic thyroid carcinoma has a dismal prognosis and lacks an established therapeutic strategy. We have recently conducted chemotherapy with docetaxel and cisplatin as part of multimodal treatment for eight patients with anaplastic thyroid carcinoma. Docetaxel (75 mg/m²) and cisplatin (75 mg/m²) were administered on day 1 every 4 weeks for six courses. This chemotherapy was used as induction therapy in one patient, as therapy for distant metastases in five patients and as postoperative adjuvant therapy in two patients. Three patients showed partial responses and three patients showed stable disease. After excluding the two patients receiving the treatment as adjuvant therapy the response rate was 50 %. Grade 3 or 4 leukocytopenia occurred in seven patients (88 %), but these adverse events were tolerable. Chemotherapy with docetaxel and cisplatin may thus be feasible for anaplastic thyroid carcinoma.

Cytopathological review of patients that underwent thyroidectomies based on the diagnosis of papillary thyroid carcinoma by fine needle aspiration cytology but were later found to have benign tumors by histopathology.

PURPOSE: The aim of this study is to evaluate the specificity of diagnosing PTC by fine needle aspiration (FNA) cytology. METHODS: This study retrospectively reviewed the cytopathological reports of 1066 patients that underwent thyroidectomy based on a diagnosis of PTC by FNA between January 1993 and December 2008. This study re-evaluated the cytology and histopathology of the patients that received false positive diagnoses of PTC by FNA. RESULTS: Ten patients (0.9 %) received false positive diagnoses of PTC by FNA. Three patients were overdiagnosed as having PTC by FNA cytology. In contrast, the nuclear features of PTC in the other seven cases were confirmed by the retrospective reviews of the patients' FNA cytology. Three of the seven patients showed follicular structures in their resection specimens, thus resulting in a diagnosis of either adenomatous goiter or follicular adenoma. However, PTC could not be diagnosed by histopathology in the remaining four patients, even though the histopathology showed the nuclear features of PTC. CONCLUSIONS: Most cases of PTC can be easily diagnosed by cytological and morphological atypia with certain limitations. The difficulty in diagnosing PTC by cytology is because the pathological features of PTC also occur in some benign thyroid tumors. Therefore, immunohistochemical or molecular biological approaches must be combined with current cytological diagnostic techniques for the diagnosis of PTC.

Sonographic findings in three cases of carcinoma showing thymus-like differentiation.

Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor of the thyroid gland or soft tissues of the head and neck. To our knowledge, there have been only a few reports concerning imaging findings of CASTLE. We report herein the sonographic appearances of three cases of CASTLE. Two tumors were located at the lower part of the thyroid and one had spread throughout the thyroid. Sonograms showed heterogeneously solid tumors without cystic components or calcification. The central part of the tumor was slightly hyperechoic compared with the peripheral part of the tumor. Histologically, the tumors were composed of a mixture of fibrous stroma and epithelial nests.

Surgical strategy for patients with papillary thyroid carcinoma invading the trachea: a comparison of tracheal sleeve resection with end-to-end anastomosis and window resection with tracheocutaneous fistula.

Background: Sleeve resection with end-to-end anastomosis (Procedure A) and window resection with a tracheocutaneous fistula (Procedure B) are the major surgical procedures for patients with papillary thyroid carcinoma (PTC) exhibiting transluminal tracheal invasion. For each procedure, the indications, postoperative course, and treatment results were examined retrospectively. Methods: Of 1,456 patients with PTC (maximum tumor diameter >1 cm) who received initial treatment between 1993 and 2013, we reviewed 51 patients. Of these 51 cases, 45 showed full-layer tracheal invasion, and 6 did not reach the tracheal mucosa, but required full-layer tracheal resection. Twenty-four patients underwent Procedure A, and 27 patients underwent Procedure B. Results: Regarding surgical procedure selection, Procedure B was selected significantly more frequently than Procedure A for cases with preoperative recurrent laryngeal nerve (RLN) palsy, tumor invasion of the esophagus, clinical lymph node metastasis, or a large number of resected tracheal rings. Postoperative airway-related complications were not significantly different between the procedures, but decreased with the use of intraoperative neuromonitoring (IONM). The postoperative hospital stay was significantly longer for Procedure B than for Procedure A. In addition, the rate of a permanent postoperative tracheostoma was higher with Procedure B than with Procedure A. Local recurrence-free survival (LRFS) and cause-specific survival (CSS) did not differ significantly between the two procedures. Conclusions: Certain patients may benefit from Procedure A with IONM in terms of a shorter hospital stay and avoiding the need for a permanent tracheostoma. Although Procedure B was indicated for patients with more advanced disease than Procedure A, treatment outcomes were similar.

A novel definition of extrathyroidal invasion for patients with papillary thyroid carcinoma for predicting prognosis.

OBJECTIVES: Extrathyroidal invasion is one of the most significant risk factors for patients with papillary thyroid carcinoma (PTC). The purpose of this study was to evaluate a novel definition of extrathyroidal invasion for patients with PTC as a method for predicting a patient's prognosis. METHODS: The prospective study was conducted for consecutive 930 patients with primary PTC who received surgery during 1993-2009. We defined only patients who had preoperative recurrent laryngeal nerve palsy or patients in whom the tumor had invaded to the mucosa of the trachea and/or esophagus as Ex3. Patients with minimal invasion were classified as Ex1, and patients with massive invasion, when we could shave off the tumors, were classified as Ex2. Patients without extrathyroidal invasion were classified as Ex0. RESULTS: Patients classified Ex3 showed significantly shorter disease-free survival (p = 0.03) and disease-specific survival (p = 0.007) than patients classified Ex2. The time to recurrence at resection sites was shorter in patients classified Ex3 than in patients classified Ex2 (p = 0.02). The time to death due to distant metastasis of patients classified Ex3 was significantly shorter than that of patients classified Ex2 (p = 0.02). Within the patients classified Ex3, disease-specific survival of patients with invasion to other nearby structures was shorter than that of patients with invasion to only recurrent laryngeal nerve (p = 0.008). CONCLUSIONS: The degree and site of invasion is an important prognostic factor for PTC. Our novel classification of extrathyroidal invasion is valuable in predicting the prognosis of PTC.

[Thyroid tumors in daily clinical settings].

Due to the widespread use of neck ultrasonography, physicians often encounter thyroid nodules in daily clinical settings. Most of them are benign such as adenomatous goiter or follicular adenoma; however, some malignant tumors can be contaminated. Thyroid malignancies are classified into several histological varieties including papillary, follicular, anaplastic, medullary thyroid carcinomas and so on. Each histological type of thyroid carcinoma has distinct biological characteristics and should be diagnosed and treated differentially. The majority of thyroid cancers fortunately have a favorable prognosis, while some of them need a multidisciplinary treatment by specialists. In order to minimize patients' anxiety, physicians have to be knowledgeable about these features and discriminate risky tumors from others properly.