A Prospective Cohort Study Exploring the Effect of Lenvatinib Planned Drug Holidays in Treatment of Differentiated Thyroid Cancer.

Background: Although lenvatinib is the preferred treatment for unresectable radioactive iodine-refractory differentiated thyroid cancer (RR-DTC), this agent exerts considerable toxicities, which can lead to frequent dose interruptions and modifications. The adoption of planned drug holidays has been recently suggested as one means of minimizing or avoiding these severe adverse events. Our retrospective study demonstrated that planned drug holidays appear to be a promising strategy for continuing of lenvatinib. However, the benefits of planned drug holidays in a prospective study have yet to be clarified. Here, we investigated the impact of planned drug holidays on clinical outcomes in patients treated with lenvatinib in the COLLECT study. Methods: In COLLECT, a prospective observational study, patients with RR-DTC were treated with lenvatinib in a real-world clinical setting. Lenvatinib was administered orally at a dose of 24 mg daily. Dose modification for toxicities was permitted. Furthermore, planned drug holidays were allowed to avoid severe or intolerable toxicities. The present post hoc analysis focused on evaluating the impact of planned drug holidays on clinical outcomes, including overall survival (OS), time to treatment failure (TTF), time to failure strategy (TFS), and progression-free survival (PFS), in patients in the COLLECT study who were treated with lenvatinib. Results: In total, 262 patients were included. Of the 253 patients evaluable for efficacy, 73 undertook a planned drug holiday at the discretion of the attending physician. OS, TTF, TFS, and PFS were significantly longer in patients who used a planned drug holiday than in those who did not. The planned drug holiday group demonstrated notable clinical outcomes, with a 1-year OS of 95.8% and a 1-year PFS of 94.5%. Moreover, planned drug holidays demonstrated a clinically meaningful advantage in clinical outcomes. The planned drug holiday group had a significantly longer duration of administration at a dose of ≥10 mg. Conclusions: Planned drug holidays for lenvatinib were associated with significantly improved clinical outcomes compared to daily oral administration. Further investigation of the optimal treatment schedule for lenvatinib is warranted. Clinical Trial Registration: UMIN000022243.

Surgical and Biochemical Outcomes in Nerve Monitored Reoperation Surgery for Recurrent Papillary Thyroid Carcinoma.

OBJECTIVE: To study the surgical and biochemical outcomes in nerve-monitored reoperation or revision surgery for recurrent thyroid cancers. STUDY DESIGN: A single-center retrospective study. SETTING: Tertiary center. METHODS: We identified patients with recurrent papillary thyroid carcinoma (PTC) who underwent reoperation/revision surgery. Study outcomes were surgical complications frequency, recurrence, distant metastasis, and biological complete response (BCR) by comparing preoperative and postoperative thyroglobulin (Tg) levels. RESULTS: Out of 227 patients, 33.9% presented for ≥2 reoperation surgeries. Nineteen (8.4%) had permanent preoperative hypoparathyroidism while 22 patients (9.7%) had preoperative vocal cord paralysis (VCP). Following reoperation surgery, there were 12 cases (5.3%) of permanent hypocalcemia and no cases of unexpected postoperative VCP. BCR was achieved in 31 patients (35.2%) with complete Tg data. Mean preoperative Tg was 47.7 ng/mL and was 19.7 ng/mL postoperatively (p = .003). The cervical nodal recurrence rate after final surgery was 7.0% (n = 16). CONCLUSION: Reoperation surgery for recurrent PTC may help achieve biochemical remission regardless of age or the number of prior surgeries.

Role of Surgery in Patients with Stage IE Primary Thyroid MALT Lymphoma Staged by a Modified Classification System: The Tokyo Classification.

PURPOSES: To establish the appropriate staging system and assess the role of curative thyroidectomy alone (Surgery) vs. involved-site radiation therapy after open biopsy (OB-ISRT) in stage IE mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: We examined the Tokyo Classification as a modified classification. This retrospective cohort study included 256 patients with thyroid MALT lymphoma; 137 underwent standard therapy (i.e., OB-ISRT) and were enrolled for the Tokyo classification. Sixty stage IE patients with the same diagnosis were examined to compare Surgery with OB-ISRT. RESULTS: Overall survival (p = 0.0092) and relapse-free survival (0.00113) were significantly better in stage IE vs. stage IIE under the Tokyo classification. No OB-ISRT and Surgery patients died, but three OB-ISRT patients relapsed. The incidence of permanent complications was 28% in OB-ISRT (mainly dry mouth) and 0% in Surgery (p = 0.027). The number of painkiller prescription days was significantly greater in OB-ISRT (p < 0.001). During follow-up, the rate of the new appearance/change of the low-density area in the thyroid gland was significantly higher in OB-ISRT (p = 0.031). CONCLUSIONS: The Tokyo classification allows an appropriate discrimination between stages IE and IIE MALT lymphoma. Surgery can provide a good prognosis in stage IE cases; it also avoids complications, shortens painful periods during treatment, and simplifies ultrasound follow-up.

Combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomy: a novel approach for cervicomediastinal goiters.

PURPOSE: After our group described the first remote-access thyroidectomy series in 2000, the procedure has been further developed. Although a thoracoscopic approach with a conventional open cervical incision for thyroid goiters with mediastinal extension has been performed at many institutions, remote-access thyroidectomy for cervicomediastinal goiters has not been established. We have performed combined thoracoscopic and axillary subcutaneous endoscopic thyroidectomies (axillo-thoracic endoscopic thyroidectomies). Here, we describe a novel technique for performing a remote-access thyroidectomy for a cervicomediastinal goiter (CMG). PATIENTS AND METHODS: The patients with CMGs who agreed to an axillo-thoracic endoscopic thyroidectomy at one of two hospitals in Japan underwent a remote-access thyroidectomy. RESULTS: We performed the axillo-thoracic endoscopic right or left hemithyroidectomy successfully, but most of the patients did not require the thoracoscopic procedure. None of the patients had complications, and none was converted to an open thyroidectomy. CONCLUSIONS: Most thyroid goiters with substernal extension can be removed by the axillary approach, but some cases require a thoracoscopic approach. The novel approach described herein (axillo-thoracic endoscopic thyroidectomy) enables the safe excision of a CMG with high patient satisfaction for selected patients.

Scoping review of approaches used for remote-access parathyroidectomy: A contemporary review of techniques, tools, pros and cons.

After our coauthors described the first remote-access parathyroidectomy (RAP) series in 2000, several other approaches were developed. No systematic review has been performed to classify and evaluate RAP techniques. We performed a literature search using PubMed and Cochrane Library (CENTRAL). A total of 71 studies met our inclusion/exclusion criteria. RAP can be categorized into five approaches: (1) endoscopic and robotic axillary, (2) anterior chest, (3) transoral, (4) retroauricular, and (5) a combination of these approaches. The limited data in the literature suggest that the cure rates and safety of RAP are in no way inferior to those of open parathyroidectomy. Each approach has its advantages and disadvantages, and the recommendations for the selection of each approach are listed. The selection of approach methods might depend on the surgeon's experience and familiarity and the patient's preference and disease status.

Remote-access hemithyroidectomy in a patient with papillary thyroid cancer after ipsilateral irradiation: a case report.

Remote-access thyroidectomy (RAT) is becoming a more frequently used approach that can avoid scars in the neck and provide better cosmetic results than open surgery. However, there has been no surgical indication for RAT in patients who have a history of cervical treatment (surgery or irradiation), and the use of RAT has been avoided in such patients. Here, we report a case in which a remote-access endoscopic hemithyroidectomy and central lymph node dissection by the anterior chest approach was successfully performed in a patient with papillary thyroid carcinoma (a 77-year-old Japanese male) after he had undergone ipsilateral cervical radiation therapy to parotid gland cancer (mucoepidermoid carcinoma) thirteen years earlier. Regarding trocar insertion, a 30-mm skin incision was made in the left anterior chest approx. 5 cm below the clavicle. Two 5-mm trocars were inserted through the 30-mm incision. We then insufflated with carbon dioxide to 6 mmHg. One additional 5-mm trocar was placed cephalad to the 30-mm incision. When we performed this RAT, we detected no effect of the prior irradiation. To the best of our knowledge, this is the first report of RAT after irradiation. The cosmetic outcome of RAT is clearly superior, and the present case demonstrates that a RAT can be safely performed in carefully selected patients even after irradiation.

Varied Recurrent Laryngeal Nerve Course Is Associated with Increased Risk of Nerve Dysfunction During Thyroidectomy: Results of the Surgical Anatomy of the Recurrent Laryngeal Nerve in Thyroid Surgery Study, an International Multicenter Prospective Anatomic and Electrophysiologic Study of 1000 Monitored Nerves at Risk from the International Neural Monitoring Study Group.

Background: The recurrent laryngeal nerve (RLN) can be injured during thyroid surgery, which can negatively affect a patient's quality of life. The impact of intraoperative anatomic variations of the RLN on nerve injury remains unclear. Objectives of this study were to (1) better understand the detailed surgical anatomic variability of the RLN with a worldwide perspective; (2) establish potential correlates between intraoperative RLN anatomy and electrophysiologic responses; and (3) use the information to minimize complications and assure accurate and safe intraoperative neuromonitoring (IONM). Methods: A large international registry database study with prospectively collected data was conducted through the International Neural Monitoring Study Group (INMSG) evaluating 1000 RLNs at risk during thyroid surgery using a specially designed online data repository. Monitored thyroid surgeries following standardized IONM guidelines were included. Cases with bulky lymphadenopathy, IONM failure, and failed RLN visualization were excluded. Systematic evaluation of the surgical anatomy of the RLN was performed using the International RLN Anatomic Classification System. In cases of loss of signal (LOS), the mechanism of neural injury was identified, and functional evaluation of the vocal cord was performed. Results: A total of 1000 nerves at risk (NARs) were evaluated from 574 patients undergoing thyroid surgery at 17 centers from 12 countries and 5 continents. A higher than expected percentage of nerves followed an abnormal intraoperative trajectory (23%). LOS was identified in 3.5% of NARs, with 34% of LOS nerves following an abnormal intraoperative trajectory. LOS was more likely in cases of abnormal nerve trajectory, fixed splayed or entrapped nerves (including at the ligament of Berry), extensive neural dissection, cases of cancer invasion, or when lateral lymph node dissection was needed. Traction injury was found to be the most common form of RLN injury and to be less recoverable than previous reports. Conclusions: Multicenter international studies enrolling diverse patient populations can help reshape our understanding of surgical anatomy during thyroid surgery. There can be significant variability in the anatomic and intraoperative characteristics of the RLN, which can impact the risk of neural injury.

Is total endoscopic parathyroidectomy an acceptable treatment for patients with primary hyperparathyroidism due to a presumed solitary adenoma?-comparison of minimally invasive total endoscopic parathyroidectomy and open minimally invasive parathyroidectomy.

BACKGROUND: Remote-access thyroidectomy and its cosmetic merit have been widely accepted, but remote-access parathyroidectomy has not become common. There are few reports about the risks and effectiveness of a remote-access endoscopic parathyroidectomy. Herein, we evaluated the risks and benefits of total endoscopic parathyroidectomy (TEP) for patients with primary hyperparathyroidism (PHPT). We retrospectively compared the surgical outcomes of TEP and open minimally invasive parathyroidectomy (MIP). METHODS: We analyzed the cases of 28 patients with PHPT who were scheduled to undergo a MIP at Mita Hospital (Tokyo) during the period from April 2015 to March 2019, all of whom were presumed preoperatively to have a single adenoma. RESULTS: Eleven of the patients underwent a TEP (10 females, one male; mean age 54.2 years). The other 17 patients underwent an open MIP (11 females, 6 males; mean age 63.5 years). The younger patients and the females tended to select endoscopic surgery as their treatment. The operation time was significantly longer in the TEP group compared to the open MIP group (106 vs. 50 min; P<0.001). Common postoperative complications (such as recurrent laryngeal nerve paralysis and seroma) did not occur in this series. For the TEP patients who did not undergo a partial thyroidectomy, the mean amount of drainage on the first postoperative day was only 19±10 mL. The operative cure rate of the minimally invasive parathyroidectomies was 96.4%. CONCLUSIONS: TEP is a good surgical procedure for hyperparathyroidism caused by a single adenoma, and it achieves superior cosmetic results without increasing the rate of complications.

Total endoscopic thyroidectomy after open neck biopsy of the follicular lymphoma of the thyroid gland.

Remote-access total endoscopic thyroidectomy (TET) is a recently established approach that can avoid producing scars in the neck. There are no clear surgical indications for TET for benign nodules or for malignant tumors at present. We report a successful TET in a 50-year-old Japanese woman with follicular lymphoma of the thyroid gland after an open neck biopsy. She had been referred to us with a neck tumor noted 2 months earlier. Because of adhesion, we performed a combined resection of the thyroid and partial right sternohyoid muscle. To the best of our knowledge, there is no other report of a TET performed after open neck surgery. Our patient's case demonstrates that (a) the cosmetic outcome of TET is clearly superior to that of conventional open neck surgery, and (b) a TET can be suitable even for reoperation if carefully selected.

Clinical outcomes and risk stratification for papillary thyroid carcinoma presenting with distant metastasis before the era of tyrosine kinase inhibitors.

Radioactive iodine (RAI) therapy has been the mainstay of treatment for papillary thyroid carcinoma (PTC) patients with distant metastasis (DM). Although tyrosine kinase inhibitors (TKIs) were introduced for the treatment of RAI refractory metastatic thyroid carcinoma several years ago, clinical outcomes for PTC patients with DM treated using RAI therapy remain unclear. We retrospectively examined 64 PTC patients (9 men, 55 women) with DM at diagnosis treated using RAI therapy without administration of any kind of chemotherapy or TKIs. Median age of patients was 58 years. Site of DM was the lungs (n = 59), bone (n = 3), and pleural dissemination (n = 2). No patients showed multiple-organ metastases at diagnosis. By the end of the study period, 21 patients had died of PTC. Cause-specific survival rates at 10, 15, and 20 years after initial surgery were 68.2%, 63.6% and 61.1%, respectively. Uni- and multivariate analyses identified age ≥55 years (HR 3.1, p = 0.023), site of DM other than the lungs (HR 13.4, p < 0.0001), and DM with no RAI avidity (HR 5.1, p = 0.0098) as factors independently associated with disease-related death. When analyses were restricted to patients with lung metastasis (n = 59), surgical non-curability was another independent risk factor (HR 5.2, p = 0.0047) in addition to age and RAI avidity. According to risk stratification analysis based on these risk factors, patients with site of DM other than the lungs or with lung metastasis showing ≥2 risk factors among age ≥55 years, DM with no RAI avidity, and surgical non-curability are expected to show higher mortality rates.

Thyroid and Parathyroid Functions After Pharyngo-Laryngo-Esophagectomy for Cervical Esophageal Cancer.

BACKGROUND: Cervical esophageal cancer (CEC) patients whose larynx function cannot be preserved often undergo chemoradiotherapy, whereas those with residual or recurrent lesions undergo a pharyngo-laryngo-esophagectomy (PLE); however, some need to undergo a pharyngolaryngectomy with total esophagectomy (PLTE) for synchronous or metachronous esophageal cancer. We retrospectively evaluated the relationship between preoperative irradiation (or the extent of esophageal resection) and postoperative endocrine complications in CEC, including hypothyroidism and hypoparathyroidism. METHODS: The cancers of 35 (5.4%) of 678 esophageal cancer patients with esophagectomy treated in 2000-2017 were CECs. We also analyzed the 17 cases of CEC patients who underwent PLE with thyroid lobectomy-11 with irradiation before PLE and 6 without irradiation. Seven patients underwent a PLTE. RESULTS: Hypothyroidism and hypoparathyroidism occurred in 14 and 12 patients, respectively. The hypothyroidism rate was significantly higher in patients with irradiation versus those without irradiation (100% vs. 50%; p = 0.010), and the hypoparathyroidism rate was significantly higher in the PLTE versus non-PLTE patients (100% vs. 50%; p = 0.026). The mean levothyroxine dosage was 1.60 µg/kg/day in the PLE patients post-irradiation. CONCLUSIONS: Irradiation appears to be a risk factor for hypothyroidism after PLE with thyroid lobectomy, while PLTE might have some effect on hypoparathyroidism. Due to vocal function loss, PLE patients may experience symptoms from endocrine complications. Levothyroxine treatment soon after PLE for post-irradiation patients and patients requiring as-needed calcium or vitamin D supplementation based on biochemical hypocalcemia for PLE (especially PLTE), may be effective in preventing symptomatic endocrine complications.

The impact of completion thyroidectomy followed by radioactive iodine ablation for patients with lymph node recurrence of papillary thyroid carcinoma.

BACKGROUND: Although lobectomy is considered acceptable as a primary surgical treatment for papillary thyroid carcinoma in properly selected patients, a standard treatment for postlobectomy lymph node recurrence has not been established. Here we compared the effectiveness of therapy with lymphadenectomy alone to that of treatment with completion thyroidectomy and lymphadenectomy followed by radioactive iodine. METHODS: This was a retrospective study of patients with papillary thyroid carcinoma who underwent surgery for lymph node recurrence in the period from January 2003 to December 2008, all of whom had previously undergone initial lobectomy with or without lymph node dissection. One-hundred and twenty-five patients were included in the primary analysis. RESULTS: Ninety-eight of these patients underwent lymphadenectomy alone (L group), and 27 received lymphadenectomy and completion thyroidectomy followed by radioactive iodine (LC&R group). The median follow-up time was 10.2 years. The overall survival, distant relapse-free survival, and lymph node relapse-free survival were not significantly different between the LC&R and L groups (P = .89, 0.58, and .22, respectively), whereas the LC&R group patients had significantly longer operation time, higher blood loss, and a higher rate of postoperative hypoparathyroidism compared with the L group (P < .001, respectively). CONCLUSION: Compared with completion thyroidectomy and lymphadenectomy followed by radioactive iodine, lymphadenectomy alone was considered an acceptable therapeutic option which decreased the surgical disadvantages but did not decrease survival for at least 10 years after recurrence surgery for PTC patients with only lymph node recurrence.

Cohort study exploring the effect of lenvatinib on differentiated thyroid cancer.

Lenvatinib is a molecular-targeting agent that was recently approved in Japan for treatment of curatively unresectable, radioactive iodine-refractory, progressive differentiated thyroid cancer (DTC). Because only a few Japanese patients have received lenvatinib in clinical trials, there are limited domestic data on its safety and efficacy or prognostic factors. Therefore, a prospective observational study has been designed to collect safety and efficacy data in at least 300 patients with curatively unresectable DTC receiving lenvatinib therapy (24 mg/day), in order to find predictors of antitumor activity and survival. Patients with progressive curatively unresectable DTC refractory to radioiodine therapy will be enrolled and the primary endpoint will be overall survival. This study is designed to estimate the 95% confidence intervals of the 1-year and 2-year survival rates with a two-sided width of less than 10%. Secondary endpoints will be the time to treatment failure, time to strategy failure, progression-free survival time with clinical progressive disease, response rate, quality of life, safety, and patient reports. The ultimate goal is to obtain information for developing evidence-based guidelines for treatment of DTC, including recommendations on patient selection, dosages, and duration of treatment. This study has been registered with the UMIN Clinical Trials Registry (UMIN000022243).

Clinical Status and Treatment of Liver Metastasis of Differentiated Thyroid Cancer Using Tyrosine Kinase Inhibitors.

BACKGROUND: Treatment of patients with liver metastasis of differentiated thyroid carcinoma (DTC) has not been sufficiently defined, because liver metastasis of DTC has been described mostly as case reports. Additionally, such patients are considered end-of-treatment responders. A relatively new approach using tyrosine kinase inhibitors (TKIs) may provide opportunities to manage systemic metastasis. This study aims to define the clinical features of DTC patients with liver metastasis and evaluate the benefits of TKIs. METHODS: We retrospectively analyzed clinical features of 29 patients (mean age 67.8 years) diagnosed with liver metastasis of DTC at our institution between January 1981 and May 2017. RESULTS: All patients had distant metastasis at other organ sites upon diagnosis of liver metastasis; 41% of them developed new metastasis afterward. Management after diagnosis of liver metastasis comprised palliative care (48%), radioactive iodine therapy (28%), and TKI therapy (24%). The median survival after diagnosis of liver metastasis was only 4.8 months. Survival rates were significantly better in patients with performance statuses between 0 and 2 on the Eastern Cooperative Oncology Group scale at diagnosis of liver metastasis (n = 22, 76%) treated with TKI compared to those who were not (P = 0.017; log-rank test; hazard ratio 0.19). One-year survival rates were 71.4 and 26.7% for patients treated with or without TKI, respectively. CONCLUSIONS: Patients with liver metastasis had poor clinical prognosis. When other distant metastases existed at diagnosis of liver metastasis, TKI therapy was considered an effective therapeutic option for patients with liver metastasis of DTC.

Great Saphenous Vein Flow Pattern as a Simple Ultrasonographic Sign of Early Recanalization of Deep Vein Thrombosis: A Case Series Report.

We retrospectively examined patients with ultrasonographically occlusive acute proximal deep vein thrombosis (DVT). All patients were categorized into two groups on the basis of whether great saphenous vein (GSV) flow toward the common femoral vein was detected (flow [+]; n=10) or undetected (flow [-]; n=10). We investigated the relationship between the GSV flow pattern and DVT recanalization. Thrombus recanalization, which is defined as diameter reduction to lower than 40% of the vessel diameter, was confirmed in seven of the flow (+), and none of the flow (-). This study proposes that the GSV flow pattern may be a simple marker for the recanalization of proximal occlusive DVT.

Development of a functional thyroid model based on an organoid culture system.

The low turnover rate of thyroid follicular cells and the lack of a long-term thyroid cell culture system have hampered studies of thyroid carcinogenesis. We have now established a thyroid organoid culture system that supports thyroid cell proliferation in vitro. The established mouse thyroid organoids performed thyroid functions including thyroglobulin synthesis, iodide uptake, and the production and release of thyroid hormone. Furthermore, transplantation of the organoids into recipient mice resulted in the formation of normal thyroid-like tissue capable of iodide uptake and thyroglobulin production in vivo. Finally, forced expression of oncogenic NRAS (NRASQ61R) in thyroid organoids established from p53 knockout mice and transplantation of the manipulated organoids into mouse recipients generated a model of poorly differentiated thyroid cancer. Our findings suggest that this newly developed thyroid organoid culture system is a potential research tool for the study of thyroid physiology and pathology including thyroid cancer.

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.

Late cardiac effect of radiation therapy on a young woman with mediastinal Hodgkin's lymphoma.

We experienced an excision of the mediastinal tumor located in left anterior mediastinum found in a 21-year-old woman. The histologic diagnosis of Hodgkin's lymphoma was obtained. After operation, she was treated with mantle field radiotherapy (total 42 Gy) followed by chemotherapy. At 43-year old, she developed constrictive pericarditis and heart failure resulted in the late cardiac effects of mediastinal irradiation. Despite pericardiectomy followed by medical treatment, her cardiac symptoms gradually worsened and she died at 51-year old. At autopsy, her heart was smaller than normal person. The residual pericardium and the surface of the myocardium had fibrous degeneration with tight adhesion and thickness that were dominant at the right atrium and ventricle. Likewise, we demonstrated that pericardiectomy scarcely led to a favorable outcome in this patient. These facts might be based on the radiation-associated cardiac effects involving any components of the cardiac structure.

The Frequency of Fish-Eating Could Negatively Associate with Visceral Adiposity in Those Who Eat Moderately.

Visceral fat accumulation is regarded as one of the major phenotypes of metabolic syndrome. There have not been enough data on the relationship between the fish-eating habit and visceral adiposity. A total of 94 male participants received abdominal CT for the measurement of the visceral fat area (VFA), serum sampling for the fatty acid composition and questionnaires about their life-style. We divided the participants into two groups: whether they ate their fill (group F, n=70) or they ate in moderation (group M, n=24). Stepwise multiple linear regression analyses showed that usual alcohol consumption and lower daily physical activity in group F, and infrequent fish-eating and frequent fat-rich deserts in group M were the significant positive correlates with the VFA. The serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio showed significant correlation with the frequency of fish-eating in both groups. Interestingly, in group M, the serum EPA/AA ratio negatively correlated with the VFA, while it failed in group F. In conclusion, the present data suggest that the fish-eating habit might negatively associate with visceral fat accumulation only in those who are moderate in eating in the general population.

Development of molecular targeted drugs for advanced thyroid cancer in Japan.

Up until now there have been no promising drugs for the treatment of advanced thyroid cancer, but the development of novel therapeutic agents is now anticipated as a result of the advent of molecular targeted drugs that inhibit tumor growth signals or angiogenesis. Against a background in which the development of numerous molecular targeted drugs for advanced thyroid cancer is being pursued worldwide, the development of sorafenib, vandetanib, and lenvatinib is currently also under way in Japan. All three of these compounds are undergoing phase 3 trials or have been approved abroad, and because they are in the final stage of development in Japan, they are expected to be introduced in clinical settings in the near future. After they have been introduced, it will be necessary to understand the differences between these compounds and to administer them to patients appropriately.