Prognostic Impact of the Turin Criteria in Poorly Differentiated Thyroid Carcinoma.

BACKGROUND: The Turin criteria including solid, trabecular, and/or insular architecture, lack of typical nuclear features of papillary carcinoma, and mitoses, necrosis, or convoluted nuclei were adopted in the recent 4th edition of the World Health Organization classification published in 2017. MATERIALS AND METHODS: Between 2006 and 2017, 11,001 cases underwent initial surgery for primary malignant thyroid tumor derived from follicular cells. A total of 75 (0.7%) cases were diagnosed with PDTC according to the 2004 WHO classification. Based on the Turin criteria, 30 (40%) cases were re-classified as PDTC-Turin (+) and 45 (60%) cases were PDTC-Turin (-). Clinicopathological features and prognosis were compared between PDTC-Turin (+) and PDTC-Turin (-). RESULTS: Seventy-five patients (48 females and 27 males) had a median age at the time of surgery of 57 years. Preoperative diagnosis was benign in 16 (21%), follicular tumor in 40 (53%), and malignant in 19 (25%). The 5-year cause-specific survival (CSS) and disease-free survival (DFS) rates were 97% and 44% for PDTC-Turin (+) and 100% and 88% for PDTC-Turin (-). On univariate analysis, CSS and DFS rates were significantly worse in the PDTC-Turin (+) than in the PDTC-Turin (-) (p = 0.0096, and p = 0.0016). Multivariate analysis showed that Turin criteria status, Ki-67 labeling index ≥ 10%, and age 55 ≥ years were the independent prognostic factors for recurrence. CONCLUSIONS: The prevalence of PDTC diagnosed with the Turin criteria was low, but it showed more aggressive behavior. The 2017 WHO classification reflects the prognosis more accurately than the 2004 WHO classification.

Usefulness of Stereotactic Radiotherapy Using the CyberKnife for Patients with Inoperable Locoregional Recurrences of Differentiated Thyroid Cancer.

BACKGROUND: Surgical resection is the preferred treatment for locoregional recurrence of differentiated thyroid cancer (DTC). However, some recurrences are unresectable because of their aggressive invasion or severe adhesions. On the other hand, stereotactic radiotherapy (SRT) enables high-dose irradiation to target lesions, and its usefulness for various cancers has been reported. The objective of the present study was to investigate the feasibility and efficacy of SRT as salvage treatment for locoregional recurrence of DTC. METHODS: Between August 2011 and December 2017, 52 locoregional recurrent lesions in 31 patients with recurrent DTC were treated by SRT using the CyberKnife system. Information on the adverse events associated with SRT was retrospectively collected from the patients' medical records. Of the 52 lesions, 33 could be evaluated for therapeutic effectiveness by follow-up CT, and response was assessed using the RECIST criteria. RESULTS: Twenty-five patients had papillary carcinoma, 5 had follicular carcinoma, and 1 had poorly differentiated cancer. SRT was delivered in one to 20 fractions, and the median dose was 30 Gy (range 15-60 Gy). Adverse events were not frequent, but 1 patient developed bilateral vocal cord palsy that required emergent tracheostomy. The median follow-up period of 33 lesions was 14 months (range 1-54 months). Complete response, partial response, stable disease, and progressive disease were seen in 10, 11, 9, and 3 patients, respectively. The 3-year local control rate was 84.6%. CONCLUSION: SRT using the CyberKnife system was found to be a feasible and effective treatment to suppress the growth of locoregional recurrence of DTC.

Change of surgical strategy for Graves' disease from subtotal thyroidectomy to total thyroidectomy: a single institutional experience.

The extent of thyroidectomy in Graves' disease remains controversial. In our institution, long-term euthyroidism without thyroxin replacement therapy has been the aim, and it has long been the standard surgical procedure used to treat Graves' disease in many institutions, including our hospital. Based our several clinical studies, it was concluded that subtotal thyroidectomy is not suitable as a standard surgical procedure for the treatment of Graves' disease. In 2009, the surgical strategy for Graves' disease was changed from subtotal thyroidectomy to total thyroidectomy in our hospital. In this study, how surgical complications have changed after this modification was examined. The subjects were 1,476 patients with Graves' disease treated by thyroidectomy between 2006 and 2014. There were 1,119 females and 357 males with a median age of 39 years. A total of 660 patients underwent bilateral subtotal thyroidectomy (ST group), and 816 patients underwent total thyroidectomy (TT group). Both transient hypocalcemia and prolonged hypocalcemia were observed significantly more frequently in the TT group than in the ST group (p < 0.001). Total thyroidectomy was identified as risk factors for prolonged hypocalcemia on multivariate analysis. In conclusion, total thyroidectomy is a reliable and effective therapy for controlling hyperthyroidism in terms of controlling of hyperthyroidism. However, it should be noted that total thyroidectomy resulted in increased rate of prolonged hypocalcemia. Surgeons should try to reduce the surgical complication rate as much as possible.

Cribriform-Morular Variant of Papillary Thyroid Carcinoma: Clinical and Pathological Features of 30 Cases.

BACKGROUND: Cribriform-morular variant of papillary thyroid carcinoma (CMV-PTC) is rare; it may occur in cases of familial adenomatous polyposis (FAP) or be sporadic. To clarify the clinicopathological features of CMV-PTC, the medical records of these patients were investigated retrospectively. MATERIALS AND METHODS: Between 1979 and 2016, a total of 17,062 cases with PTC underwent initial surgery at Ito Hospital. Of these, 30 (0.2%) cases histologically diagnosed with CMV-PTC were reviewed. RESULT: The patients were all women, with a mean age at the time of surgery of 24 years. Seven (23%) cases were thought to have FAP because they had colonic polyposis or a family history of FAP or APC gene mutation. The remaining 23 (77%) were thought to be sporadic. Multiple tumors were detected in 6 cases, with a solitary tumor in 24. One patient had lung metastasis at diagnosis. Eleven patients underwent total thyroidectomy or subtotal thyroidectomy, and 19 underwent lobectomy. Twenty-six (87%) patients underwent neck lymph node dissection. Three patients had tumor metastasis in central lymph nodes, but these were incidentally detected metastatic classical PTC (cPTC) based on histological examination. In this series, there were no cases of LN metastases of CMV-PTC. During a mean follow-up of 15 years, one patient had new cPTC in the remnant thyroid after initial surgery, and the other patients showed no signs of recurrence. CONCLUSION: CMV-PTC occurred in young women, their long-term prognosis was excellent. Total thyroidectomy is recommended for FAP-associated CMV-PTC, but modified neck lymph node dissection is not necessary.

Clinical factors related to the efficacy of tyrosine kinase inhibitor therapy in radioactive iodine refractory recurrent differentiated thyroid cancer patients.

New insights in thyroid cancer biology propelled the development of targeted therapies as salvage treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC), and the tyrosine kinase inhibitor (TKI) lenvatinib has recently become available as a new line of therapy for RR-DTC. The aim of this study is to investigate clinical factors related to the efficacy of TKI therapy in recurrent RR-DTC patients and identify the optimal timing for the start of TKI therapy. The subjects consisted of 29 patients with progressive RR-DTC, 9 males and 20 females, median age 66 years. A univariate analysis was conducted in relation to progression free survival (PFS) and overall survival (OS) by the Kaplan-Meier method for the following variables: age, sex, histology of the primary tumor, thyroglobulin doubling time before the start of lenvatinib therapy, site of the target lesions, presence of a tumor-mediated symptom at the start of lenvatinib therapy, and baseline tumor size of the target lesions. Median duration of lenvatinib therapy was 14.7 months and median drug intensity was 9.5 mg. At the time of the data cut-off for the analysis, 9 patients (31.0%) have died of their disease (DOD), and a PR (partial response), SD (stable disease), and PD (progressive disease) were observed in 20 patients (69%), 6 patients (20.7%), 3 patients (10.3%), respectively. Univariate analyses showed that the presence of a symptom was the only factor significantly related to poorer PFS and OS. Clinical benefit of TKI therapy will be possibly limited when the therapy starts after tumor-mediated symptoms appear.

Globus Symptoms in Patients Undergoing Thyroidectomy: Relationships with Psychogenic Factors, Thyroid Disease, and Surgical Procedure.

BACKGROUND: The number of patients who need thyroid surgery has increased worldwide in recent decades. Patients with thyroid disease experience globus pharyngeus as a result of direct compression and edema of the surrounding organs. Thyroid surgery is needed to improve these symptoms or as treatment for thyroid cancer. After thyroid surgery, globus symptoms may become worse and may affect the daily life of the patient for a long time. Psychogenic problems have also been thought to cause the globus sensation. A prospective analysis of globus symptoms and psychogenic factors following thyroidectomy was performed. MATERIAL AND METHODS: Patients scheduled to undergo thyroid surgery between February and September 2016 completed the foreign-body sensation in the throat score (FBST; range 0-8.2) and the self-rating depression scale (SDS; range 0-100) preoperatively and three days, one month, three months, six months, and 12 months postoperatively. RESULTS: Long-term follow-up was completed in 616 patients (491 females). A total of 365 patients had thyroid cancer, 169 had benign tumors, and 82 had diffuse goiters with Graves' disease. The percentage of patients who complained about neck discomfort (FBST >2) was 29.4% before surgery. A preoperative high FBST showed a significant direct correlation with a high SDS, but thyroid volume did not. A postoperative high FBST was seen in 75.3% of patients at two days and 78.9% at one month after surgery, and it then gradually decreased to 49.3% at 12 months after surgery. At three days after the operation, the median FBST was significantly higher in patients who had total thyroidectomy with lateral neck dissection or total thyroidectomy only compared to those who had lobectomy only (p < 0.05). These differences were still present 12 months after surgery. A higher preoperative SDS score was also identified as an independent predictor for a high FBST at 12 months after surgery, but not at one or three months postoperatively, on multivariate analyses. CONCLUSION: Preoperative globus symptoms appear directly related to psychological factors. The area of the surgical procedure and preoperative psychological factors were related to persistent neck discomfort.

Lenvatinib induces early tumor shrinkage in patients with advanced thyroid carcinoma.

Although advanced thyroid carcinoma patients who cannot be cured by conventional therapy have lacked effective treatment, multitargeted tyrosine kinase inhibitors have recently become available. Phase 3 trials of lenvatinib showed a median time to objective response of 2 (95 % confidence interval (CI) 1.9-3.5) months, demonstrating that shrinks tumors rapidly. The phenomenon of immediate tumor shrink is known as early tumor shrinkage (ETS) which is related to clinical outcome in other malignancies. However, precisely when within 8 weeks lenvatinib starts to affect tumors remains unclear. In tumors near the carotid arteries, trachea, or esophagus, a rapid therapeutic effect can induce fistula formation or arterial bleeding. To prevent such treatment-emergent serious adverse events (SAE), early imaging evaluation seems to be very important. In this study, the point in time when lenvatinib started to shrink tumors was retrospectively investigated. The subjects were 16 patients who started lenvatinib administration between May and August 2015. Tumor size was evaluated by computed tomography (CT) scans frequently within the first 8 weeks according to the Response Evaluation Criteria In Solid Tumors (RECIST) guideline. Initial tumor response was defined as ≥ 10% tumor reduction. Serum thyroglobulin (Tg) level was monitored in 8 differentiated thyroid carcinoma (DTC) without TgAb patients. At the first evaluation, 13 patients (83.3 %) showed tumor reduction and that decreased with time. Thirteen patients (83.3 %) showed >10 % tumor reduction within 8 weeks. In all DTC patients, serum Tg level was markedly decreased. In conclusion, lenvatinib immediately shrinks tumors, the so-called ETS phenomenon. Therefore, careful attention should be paid to fistula formation from the early phase.

Outcome and characteristics of patients with malignant pleural effusion from differentiated thyroid carcinoma.

Metastatic differentiated thyroid carcinoma (DTC) is an uncommon cause of malignant pleural effusion (MPE) and the characteristics and clinical course have been rarely described. Herein, we report a retrospective review of the clinical course of 18 patients (15 women and 3 men) with MPE from DTC who underwent treatment at our institution between January 2005 and December 2014. MPE from DTC was diagnosed based on cytology and/or level of thyroglobulin in the pleural fluid. Pathologically, papillary carcinoma was found in 16 patients and follicular carcinoma in 2 patients. Median ages at initial diagnosis of DTC and MPE were 64 years (range, 22-79) and 74 years (range, 39-86), respectively. All patients showed radiologically apparent lung metastases, with MPE developing after 0-212 months (median, 25). In 16 patients (88.9%), other coexistent distant metastases at the time of MPE diagnosis were found in the bone (n = 10), brain (n = 5), and skin (n = 2). All patients were treated conservatively with palliative thoracentesis or chest tube drainage with or without pleurodesis. Recurrent MPE after treatment was seen in 9 patients; discharge to home health care after treatment for MPE was possible for 14 patients. The overall survival after initial diagnosis varied considerably from 14 months to 37 years, but the median survival after appearance of MPE was 10 months (range, 1-28). Systemic therapy for iodine-resistant recurrent thyroid disease may need to be considered as a treatment option for patients with MPE.