The significance of Hippo pathway protein expression in oral squamous cell carcinoma.

Introduction: The Hippo pathway consists of mammalian sterile 20-like kinase 1/2 (MST1/2), large tumor suppressor 1/2 (LATS1/2), and yes-associated protein (YAP)1. Herein, we present the first report on the significance of major Hippo pathway protein expression in oral squamous cell carcinoma (OSCC). Methods: The analyses included oral epithelial dysplasia (OED, n = 7), carcinoma in situ (CIS, n = 14), and oral squamous cell carcinoma (OSCC, n = 109). Results: Cytoplasmic expression of MST1, LATS1, and LATS2 was low in OED, CIS, and OSCC. The cytoplasmic expression of MST2 was high in OED (5/7 cases), CIS (9/14 cases), and poorly differentiated OSCC (8/8 cases) but was low/lost in a proportion of differentiated OSCC (60/101 cases). The expression of YAP1 was associated with differentiation; low YAP expression was significantly more frequent in well-differentiated OSCC (35/71 cases), compared to moderately and poorly differentiated OSCC (11/38 cases). An infiltrative invasion pattern was associated with a high expression of MST2 and high expression of YAP1. The high expression of YAP1 was associated with features of epithelial-to-mesenchymal transition (EMT), such as the loss of E-cadherin and high expression of vimentin, laminin 5, and Slug. High expression of protein arginine methyltransferase (PRMT) 1 or 5, which positively regulates YAP activity, was associated with the high expression of YAP1 (p < 0.0001). Conclusion: Among the major Hippo pathway proteins, MST2 displayed a distinctive expression pattern in a significant proportion of differentiated OSCC, suggesting a possible differential role for MST2 depending on the course of OSCC progression. A high YAP1 expression may indicate aggressive OSCC with EMT via PRMTs at the invasive front.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

Vibration receptor organs in the insect leg: neuroanatomical diversity and functional principles.

Detecting substrate vibrations is essential for insects in different behavioural contexts. These vibrational behaviours are mediated by mechanoreceptor organs detecting and processing vibrational stimuli transmitted in the environment. We discuss recently gained insights about the functional principles of insect vibration receptors, mainly leg chordotonal organs highly sensitive to vibrational stimuli, and the mechanisms of their diversification in neuroanatomy and functional morphology, in relation to the attachment structures and mechanical coupling. The two main input pathways for vibration stimuli transferred by the insect legs to vibrosensory organs via the cuticle and via the hemolymph are fundamental for explaining sensory specialisations. The vibroreceptor organs can diversify in their neuroanatomy and morphology in several key aspects. This provides the structural basis for complex adaptations in sensory evolution.

Abscopal Effect after Stereotactic Body Radiotherapy with Nivolumab for Lung Metastasis of Head and Neck Cancer: A Case Report.

Introduction: The abscopal effect (AE) is a phenomenon, in which radiotherapy exerts an antitumour effect on distant lesions outside the primary irradiated area. Although immune checkpoint inhibitors have been widely studied for their potential to enhance the AE and improve patient outcomes, findings in cases of head and neck cancers remain limited. Case Presentation: We report the case of a 72-year-old man who experienced lung oligoprogression during nivolumab treatment for metastatic hypopharyngeal cancer. Stereotactic body radiotherapy (SBRT) was administered to one of the lung lesions, after which both irradiated and nonirradiated lesions regressed. Upon an 18-month follow-up period after SBRT, the patient showed no disease progression or toxicity, and continued receiving nivolumab therapy. Conclusion: The intent behind presenting this case report was to contribute to the accumulation of evidence regarding the AE in cases of head and neck cancer.

Clinical Outcomes of Radiotherapy for Stage 1 Glottic Carcinoma: Comparing Accelerated Hyperfractionation and Once-daily Fractionation.

BACKGROUND/AIM: Accelerated hyperfractionation (AHF) is used in head and neck cancer to improve the local control (LC) rate, but reports of outcomes for early-stage GC are limited. The outcomes of radiotherapy (RT) for stage 1 glottic carcinoma (GC) were retrospectively analyzed, comparing AHF and once-daily fractionation (ODF) using 2.0-2.4 Gy. PATIENTS AND METHODS: A total of 102 patients with stage 1 GC underwent RT alone between 2007 and 2021, with 43 in the AHF group and 59 in the ODF group. A p-value less than 0.05 was considered to indicate a significant difference. RESULTS: The 5-year LC rate was 98% in the AHF group and 91% in the ODF group (p=0.19). During RT, significantly more patients in the AHF group required opioids due to mucositis than in the ODF group (74% vs. 25%, p<0.001), and the rate of aspiration pneumonia tended to be higher in the AHF group than in the ODF group (7% vs. 0%, p=0.072). CONCLUSION: There was no difference in the LC rate between AHF and ODF for stage 1 GC. Moreover, the AHF group required opioids at a higher rate and tended to have a higher risk of developing aspiration pneumonia.

Spatial odor map formation, development, and possible function in a nocturnal insect.

An odor plume is composed of fine filamentous structures interspersed by clean air. Various animals use bilateral comparison with paired olfactory organs for detecting spatial and temporal features of the plume. American cockroaches are capable of locating a sex pheromone source with one long antenna spanning 5 cm, so-called unilateral odor sampling. This capability stems from an antennotopic map in which olfactory sensory neurons located proximo-distally in the antenna send axon terminals proximo-distally in a given glomerulus, relative to axonal entry points. Multiple output neurons (projection neurons) utilize this spatial map in the pheromone-receptive glomerulus. Here, I summarize neuronal underpinnings of receptive field formation, development, and how this intraglomerular spatial map can be utilized for odor localization.

The efficacy of radiation therapy using the Quad Shot regimen in cutaneous metastasis from parotid gland cancer: A case report.

Cutaneous metastasis from malignant tumors can cause symptoms such as exudates, bleeding, and pain, which remarkably reduce patient's quality of life. Herein, we report a case in which radiation therapy using the Quad Shot regimen was effective in the treatment of cutaneous metastasis from parotid gland cancer.

Successful Preoperative QUAD SHOT for Bulky Parotid Carcinoma: Potential Preoperative Ultra-Hypofractionated Radiotherapy for Conversion Surgery.

QUAD SHOT is an ultra-hypofractionated radiotherapy (RT) technique that prescribes 14.0-14.8 Gy over 2 days. Although this technique has already gained some status as an effective palliative treatment for inoperable head and neck cancer (HNC), its application in other situations has not been given much consideration. Herein, we report a case of a 62-year-old woman who received preoperative QUAD SHOT therapy for poorly differentiated parotid carcinoma. In this case, after two courses of QUAD SHOT plus a standard chemotherapy regimen with pembrolizumab, the patient's inoperable, bulky tumor shrank dramatically and became operable. Best of all, while adequate therapeutic effects were achieved, the patient's time commitment and physical exertion were limited. RT during this period consisted of only eight fractions over 4 days. According to previous reports, the response rate for QUAD SHOT is sufficiently high, and the rate of serious adverse events is quite low. This case asks the question of whether the indications for QUAD SHOT irradiation can be expanded as one of the preoperative interventions undertaken by HNC surgeons to achieve conversion surgery.

Cuticular hydrocarbon reception by sensory neurons in basiconic sensilla of the Japanese carpenter ant.

To maintain the eusociality of a colony, ants recognize subtle differences in colony-specific sets of cuticular hydrocarbons (CHCs). The CHCs are received by female-specific antennal basiconic sensilla and processed in specific brain regions. However, it is controversial whether a peripheral or central neural mechanism is mainly responsible for discrimination of CHC blends. In the Japanese carpenter ant, Camponotus japonicus, about 140 sensory neurons (SNs) are co-housed in a single basiconic sensillum and receive colony-specific blends of 18 CHCs. The complexity of this CHC sensory process makes the neural basis of peripheral nestmate recognition difficult to understand. Here, we electrophysiologically recorded responses of single basiconic sensilla to each of 18 synthesized CHCs, and identified CHC responses of each SN co-housed in a single sensillum. Each CHC activated different sets of SNs and each SN was broadly tuned to CHCs. Multiple SNs in a given sensillum fired in synchrony, and the synchronicity of spikes was impaired by treatment with a gap junction inhibitor. These results indicated that SNs in single basiconic sensilla were electrically coupled. Quantitative analysis indicated that the Japanese carpenter ants have the potential to discriminate chemical structures of CHCs based on the combinational patterns of activated SNs. SNs of ants from different colonies exhibited different CHC response spectra. In addition, ants collected from the same colony but bred in separate groups also exhibited different CHC response spectra. These results support the hypothesis that the peripheral sensory mechanism is important for discrimination between nestmate and non-nestmate ants.

Magnetic Resonance Imaging Findings of Lymphoepithelial Carcinoma of the Submandibular Gland: A Case Report.

Lymphoepithelial carcinoma (LEC) is an uncommon neoplasm strongly associated with Epstein-Barr virus (EBV). LEC of the salivary glands (LECSG) is very rare: the most commonly affected site is the parotid gland, followed by the submandibular gland. This report describes the case of a 58-year-old man who presented with a left submandibular mass that had gradually increased in size over five years. On magnetic resonance imaging (MRI), the mass showed low apparent diffusion coefficient (ADC) values, rapid initial enhancement before reaching a plateau on dynamic contrast-enhanced MRI (DCE-MRI), and internal septal-like enhancement. Histopathologically, the tumor comprised polygonal or round tumor cells with atypical or pleomorphic nuclei and numerous lymphocytes, separated by heavy fibrosis. Immunohistological findings were positive for AE/AE3, CD20, and EBV-encoded small RNA in situ hybridization (EBER-ISH), consistent with LEC. A low ADC value with rapid initial enhancement before reaching a plateau on DCE-MRI was thought to reflect abundant cellular components with tumor neoangiogenesis, whereas internal septal-like enhancement reflects separating heavy fibrosis. To the best of our knowledge, this is the first case report describing ADC value and DCE-MRI findings of LECSG, and these findings can be considered characteristic MRI findings of LECSG.

Nintedanib-Induced Delayed Mucosal Healing after Adjuvant Radiation in a Case of Oropharyngeal Carcinoma.

Since the launch of imatinib in 2001, tyrosine kinase inhibitors are being used in chemotherapy for a wide range of malignant tumors. Drugs that inactivate multiple molecular mechanisms are called multikinase inhibitors (MKIs). Nintedanib is a type of MKI that inhibits downstream cascades in three systems: vascular endothelial growth factor receptor, fibroblast growth factor receptor, and platelet-derived growth factor receptor inhibitions. It was initially developed as an anticancer drug for non-small-cell lung carcinoma; however, it was also found to inhibit the proliferation of fibroblasts associated with chronic inflammation in the lungs. Therefore, it is being more widely used to treat idiopathic pulmonary fibrosis, a benign disease, than as an antineoplastic agent. Several studies have reported adverse events associated with the concurrent use of MKIs with surgery or radiotherapy. Specifically, there has been a report cautioning against delayed wound healing associated with the use of nintedanib in patients undergoing surgery. However, there is no specific mention of its concurrent use during irradiation. We describe a case of a 72-year-old man with severely delayed recovery from radiation mucositis when nintedanib was being administered for benign disease.

Management of Nuisance Macromoths in Expressways through Academic-Industrial Collaboration: Light Trap Designed on the Basis of Moths' Preferences for Light Attributes.

Aggregation of flying insects such as gypsy moths at commercial light sources in summer not only has an aesthetically negative impact on public facilities but also permits the establishment of new insect populations there from the next year. Although energy-efficient light traps equipped with light-emitting diodes (LEDs) have recently been used for controlling pest insects in agriculture, there are very few maintenance-free light traps that are available on the market. Based on the results of field surveys, we fabricated a prototype light trap in which the preferences of insects for light irradiation angle and wavelength are implemented. Field experiments revealed that flying moths were attracted more to light with a narrow irradiation angle than to light with a wide irradiation angle. Moreover, there was a tendency for fewer moths to be collected when fluorescent paint was applied to the surface of the flight-interception board, indicating that a high contrast made by illumination and the background is preferred by flying moths. Taken together with our previous results, we found that the moth catch was influenced more by modification of the light design than by change in visible light wavelengths. A semi-portable light trap, named the "Kurihara trap" after the primary contributor to its development, is made of light-weight plastic and is driven by solar power. This light trap is omnidirectional and maintenance-free and is therefore suitable for deployment in the backyards of rest areas as well as at houses for long-term macromoth sampling.

Rearrangement of Methylenebis(cyclohexane-1,3-dione) Enols Induced by Mn(III)-Catalyzed Aerobic Oxidation.

The Mn(III)-catalyzed aerobic oxidation of methylenebis(cyclohexane-1,3-dione) enols 1 resulted in 6a-hydroxy-2,3,4,6a,7,8,9,10a-octahydro-1H-benzo[c]chromene-1,6,10-triones 3 during the formation of 4,5,8,10,11,12-hexahydro-2H-benzo[b]oxecine-2,6,7,9(3H)-tetraones 2. The mechanism for the formation of 3 was proposed on the basis of the isolation of intermediates 2, which were transformed into 3 under Claisen and retro-Claisen conditions.

Clinicopathological and Prognostic Significance of Stromal Patterns in Oral Squamous Cell Carcinoma.

Background: Stromal patterns (SP), especially desmoplastic reactions, have recently gained attention as indicators of malignant potential in cancer. In this study, we explored the clinicopathological and prognostic significance of the SP in oral squamous cell carcinoma (OSCC). Materials and Methods: We reviewed 232 cases of surgically resected OSCC that were not treated with neoadjuvant chemoradiotherapy. We categorized the SP of the OSCC into four groups: immune/inflammatory (84 cases), mature (14 cases), intermediate (78 cases), or immature (56 cases). Results: The SP category was significantly associated with various clinicopathological factors, such as the histological grade, lymphovascular invasion, neural invasion, and a diffuse invasion pattern. For each of the factors, the immune/inflammatory type was associated with favorable categories, while the immature type was associated with unfavorable categories (p ≤ 0.001). The SP category was also shown to be a prognostic predictor: the 5-year relapse-free survival (RFS) rate was 72.0% for the immune/inflammatory type, 66.7% for the intermediate/mature type, and 31.2% for the immature type (p < 0.0001), and the 5-year overall survival (OS) rate was 85.1% for the immune/inflammatory type, 76.4% for the intermediate/mature type, and 50.0% for the immature type (p < 0.0001). In multivariate analyses, the SP category was identified as an independent prognostic factor for RFS and OS. Conclusion: Our SP categorization method provides valuable prognostic information in OSCC.

Silencing the odorant receptor co-receptor impairs olfactory reception in a sensillum-specific manner in the cockroach.

Insects detect odors via a large variety of odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs). The insect OR is a heteromeric complex composed of a ligand-specific receptor and the co-receptor (ORco). In this study, we identified the ORco gene of the cockroach, Periplaneta americana (PameORco), and performed RNAi-based functional analysis of PameORco. All OSNs in the basiconic sensilla expressed PameORco and received a large variety of odors including sex pheromones. In trichoid sensilla, a PameORco-positive OSN was consistently paired with a PameORco-negative OSN tuned to acids. In adult cockroaches injected with PameORco dsRNA at the nymphal stage, the expression of PameORco, odor receptions via ORs, and its central processing were strongly suppressed. These results provide new insights into the molecular basis of olfactory reception in the cockroach. The long-lasting and irreversible effects of PameORco RNAi would be an effective method for controlling the household pest.

Effect of intracordal injection under local anesthesia on vital signs in high-risk patients.

OBJECTIVE: Intracordal injection under local anesthesia is widely performed; however, few studies show hemodynamic changes in the heart rate, blood oxygen saturation, and blood pressure during intracordal injection under local anesthesia. This study examined changes in vital signs (heart rate, blood oxygen saturation, systolic blood pressure, diastolic blood pressure) during intracordal injection under local anesthesia among high-risk patients and investigated whether intracordal injection under local anesthesia could be safely conducted. METHODS: A retrospective chart review was adopted as the research design. We investigated the changes in vital signs (heart rate, blood oxygen saturation, blood pressure) before and after intracordal injection with basic fibroblast growth factor (bFGF) preparations under local anesthesia in 46 patients who visited our institution and developed unilateral vocal cord paralysis after a thoracic aortic aneurysm, thoracic aortic dissection surgery, thyroid disease, esophageal disease, idiopathic disease, etc. RESULTS: The average operation time for the high-risk group was 3.67 minutes, with the shortest operating time being 2 minutes and the maximum operating time being 13 minutes. The average operation time for the control group was 3.73 minutes, with the shortest operating time being 1 minute and the maximum operating time being 9 minutes. Results before and after intracordal injection with bFGF preparations under local anesthesia for heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.324, 0.394, 0.215, and 0.508, respectively, in the high-risk group, and no significant differences were found. Conversely, heart rate, blood oxygen saturation, systolic blood pressure, and diastolic blood pressure had P-values of 0.057, 0.232, 0.265, and 0.091, respectively, in the control group, and no significant differences were found. CONCLUSION: Intracordal injection under local anesthesia may be safe, even for patients who require blood pressure management after thoracic aortic disease surgery.

Expression and localisation of methylthioadenosine phosphorylase (MTAP) in oral squamous cell carcinoma and their significance in epithelial-to-mesenchymal transition.

Methylthioadenosine phosphorylase (MTAP) is a rate-limiting enzyme in the methionine salvage pathway, which recycles one carbon unit that is lost during polyamine synthesis back into the methionine cycle. Although MTAP deficiency has been reported in various tumours, MTAP is overexpressed and might promote oncogenesis in other cancers, including prostate and colon cancer. Currently, little is known about the MTAP status of oral squamous cell carcinoma (OSCC). In this study, we immunohistochemically examined the expression of MTAP in surgically resected oral epithelial dysplasia (OED, n=7), carcinoma in situ (CIS) (n=16), and OSCC (n=118). In the normal epithelium, MTAP was only weakly expressed in the cytoplasm of the basal layer cells. In OED, CIS, and OSCC, MTAP was uniformly expressed in the cytoplasm of the dysplastic and cancer cells. In addition to cytoplasmic MTAP expression, 45 of 118 cases (38.1%) exhibited increased nuclear expression of MTAP in the cancer cells at the invasive front. Statistical analysis showed that the concomitant nuclear and cytoplasmic expression of MTAP was associated with a high budding score (p=0.0023); poor differentiation (p=0.0044); aggressive invasion patterns (p=0.0001); and features of epithelial-to-mesenchymal transition (EMT), such as loss of E-cadherin expression (p=0.0003) and upregulated expression of vimentin (p=0.0002), slug (p=0.0002), and laminin 5 (p<0.0001). High expression of protein arginine methyltransferase 1 or 5, the functions of which are reported to be inhibited in MTAP-deficient cancer, was associated with the concomitant nuclear and cytoplasmic expression of MTAP (p<0.0001). Concomitant nuclear and cytoplasmic expression of MTAP was marginally significantly associated with worse 5-year relapse-free survival (p=0.045). These findings suggest that MTAP not only plays a role in the oncogenesis of OSCC, but that it might also make it more aggressive by inducing EMT through its activity in the methionine salvage pathway.

Reconstructing the ecology of a Cretaceous cockroach: destructive and high-resolution imaging of its micro sensory organs.

Animals highly depend on their sensory organs to detect information about their surrounding environment. Among animal sensory organs, those of insects have a notable ability to detect information despite their small size, which might be, therefore, one of the reasons for the evolutionary success of insects. However, insect sensory organs are seldom fossilized in sediments due to their small size and fragility. A potential solution for this problem is the study of exceptionally well-preserved fossil material from amber. Unfortunately, the resolution of existing non-destructive analysis is insufficient to observe details of these micro sensory organs even with amber preservation. Here, we focus on the analysis of the micro sensory organs of an extinct male cockroach (Huablattula hui Qiu et al., 2019) in Cretaceous amber by combining destructive and non-destructive methods. Compared to extant species inhabiting dark environments, H. hui has relatively large compound eyes, and all the antennal sensilla for detecting multimodal information observed here are fewer or smaller. The characteristics of these sensory organs support the diurnality of the bright habitats of H. hui in contrast to many extant cockroaches. Like extant male mantises, grooved basiconic type sensilla exist abundantly on the antenna of the fossilized specimen. The abundance of grooved basiconic sensilla in mantid males results from using sex pheromones, and therefore, H. hui may have likewise used mantis-like intersexual communication. These lines of evidence suggest that the ecology and behavior of Cretaceous cockroaches were more diverse than those of related extant species.

COVID-19 findings revealed via otolaryngological examination: Findings of a Japan Otorhinolaryngologist Association questionnaire.

OBJECTIVE: In Japan, many otolaryngologists provide primary care for patients with coronavirus disease 2019 (COVID-19). The purpose of this study was to analyze the characteristics of otorhinolaryngological findings in order to improve COVID-19 diagnostic systems in a primary care setting. METHODS: A total of 351 patients (mean age, 36.0 ± 15.4 years) diagnosed with COVID-19 by otolaryngologists who belong to the Japan Otorhinolaryngologists Association were included in the study. A web-based questionnaire was used to collect information regarding the timing of positive identification of COVID-19, the route of infection, symptoms, and findings in the tonsils, nasal cavity, pharynx, ear, and neck. A modified Centor score was calculated for cases in which age, symptoms, and tonsil and neck findings were described. RESULTS: Symptoms included fever (56%), olfactory disturbance (46%), and a sore throat (56%). Of the individuals considered, 63% had ordinary rhinoscopic findings, 21% experienced watery rhinorrhea, and 12% had observable mucosal redness. Further, 87% had ordinary tonsillar findings, 13% displayed tonsillar redness, with enlargement and white mucus observe in 2% and 1% of participants, respectively. A total of 193 patients had a calculated Centor score of 3 points in 2%, and scores of the remaining participants were ≤2 points. CONCLUSION: Of all patients considered, 40% had nasal findings and 4% had purulent nasal discharge. In contrast, only 13% of the patients had tonsillar findings, and no patients had Centor scores ≥4 points. Symptom differentiation from that of bacterial infections is difficult. In areas where COVID-19 is prevalent, the disease should be considered in patients presenting with fever, olfactory disturbances, and sore throat with minimal or no clinical findings in the nasal cavity and pharynx.

Long-term survival after surgical resection of metachronous lung, brain and thyroid gland metastases from rectal cancer: A case report.

INTRODUCTION AND IMPORTANCE: Brain and thyroid metastasis from rectal cancer are uncommon, and the prognosis is poor. We report a patient with rectal cancer who developed metachronous lung, brain and thyroid metastases. Each metastatic lesion was curatively resected resulting in prolonged survival. CASE PRESENTATION: A 60-year-old male underwent rectal cancer resection, and the pathological diagnosis was tubular adenocarcinoma, pT2,pN1a,M0, pStageⅢa. Ten years after rectal resection, a solitary tumor in the left lung was detected. The tumor was resected thoracoscopically and the pathological diagnosis was metastatic tumor. Three years after the pulmonary resection, a solitary brain tumor was detected. The tumor was removed surgically, and the pathology was metastatic tumor. Two years after brain resection, a thyroid mass was detected. A partial thyroidectomy was performed and the pathology with immunohistochemical staining confirmed the thyroid lesion as a metastasis from the previous rectal cancer. Four years after thyroid resection (19 years after the initial rectal resection), he died from multiple lung and bone metastases. CLINICAL DISCUSSION: Colorectal metastases to the brain and thyroid gland are uncommon and are usually found with other distant metastases. Overall survival has been reported to be extremely poor. In this patient, lung, brain, and thyroid metastases were solitary and metachronous, and each lesion was curatively resected. Surgical treatment might contribute to prolonged survival. CONCLUSION: The treatment strategy of each patient should be individualized and depends on the timing of metastasis development. Selected patients with complete resection of metachronous metastases may have prolonged survival.