Vandetanib in locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine therapy.

VERIFY study is a randomized, double-blind, multicenter phase III clinical trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic differentiated thyroid cancer (DTC), refractory to radioiodine (RAI) therapy with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib and 118 patients received placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio [HR] 0.75; 95% confidence interval [CI] 0.55-1.03; p = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events [CTCAE] adverse events of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo though the difference in OS was not statistically significant.

Ultrasonographic Detective Flow Imaging for Evaluating Parathyroid Adenoma in Patients with Primary Hyperparathyroidism.

BACKGROUND: Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow, which is difficult to visualize on conventional color Doppler ultrasonography (CDU). In this study, we compared the usefulness of DFI with that of CDU and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for detecting parathyroid adenoma (PA) in patients with primary hyperparathyroidism (PHPT). METHODS: From March 2021 to March 2023, 87 PHPT patients underwent surgery, and 66 had a single PA. We performed preoperative conventional ultrasonography with CDU, MIBI scintigraphy, and DFI for 42 patients (5 males and 37 females; mean age: 61.6 ± 15.4 years). RESULTS: MIBI scintigraphy detected PA in 85.7% (36/42) patients, and both CDU and DFI detected PA in all patients. The rates of vascularity in PA detected by CDU and DFI were 71.4% (30/42) and 85.7% (36/42), respectively. Vascularity was detected by DFI in 6 patients who were negative for vascularity on MIBI scintigraphy. Furthermore, DFI detected blood supply in 6 of the 12 patients with undetectable blood supply on CDU. Fisher's exact test revealed that high or low blood flow, as determined by DFI, was significantly associated with detection of feeding vessels in PA by CDU (P < 0.001). CONCLUSIONS: DFI was useful for preoperative detection of PA blood flow.

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.

A Phase 2 Study of Encorafenib in Combination with Binimetinib in Patients with Metastatic BRAF-Mutated Thyroid Cancer in Japan.

Background: Driver mutations at BRAF V600 are frequently identified in papillary thyroid cancer and anaplastic thyroid cancer (ATC), in which BRAF inhibitors have shown clinical effectiveness. This Japanese phase 2 study evaluated the efficacy and safety of a BRAF inhibitor, encorafenib, combined with an MEK inhibitor, binimetinib, in patients with BRAF V600-mutated thyroid cancer. Methods: This phase 2, open-label, uncontrolled study was conducted at 10 institutions targeted patients with BRAF V600-mutated locally advanced or distant metastatic thyroid cancer not amenable to curative treatment who became refractory/intolerant to ≥1 previous vascular endothelial growth factor receptor-targeted regimen(s) or were considered ineligible for those. The primary endpoint was centrally assessed objective response rate (ORR). The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: We enrolled 22 patients with BRAFV600E-mutated thyroid cancer: 17 had differentiated thyroid cancer (DTC), and 5 had ATC. At data cutoff (October 26, 2022), the median follow-up was 11.5 (range = 3.4-19.0) months. The primary endpoint of centrally assessed ORR was 54.5% (95% confidence interval [CI] 32.2-75.6; partial response in 12 patients and stable disease in 10). The ORRs in patients with DTC and ATC were 47.1% (8 of 17) and 80.0% (4 of 5), respectively. The medians for DOR and PFS by central assessment and for OS were not reached in the overall population, the DTC subgroup, or the ATC subgroup. At 12 months, the rate of ongoing response was 90.9%, and the PFS and OS rates were 78.8% and 81.8%, respectively. All patients developed ≥1 adverse events (AEs): grade 3 AEs in 6 patients (27.3%). No patients developed grade 4-5 AEs. The most common grade 3 AE was lipase increased (4 patients [18.2%]). Those toxicities were mostly manageable with appropriate monitoring and dose adjustment. Conclusions: Treatment with encorafenib plus binimetinib met the primary endpoint criteria and demonstrated clinical benefit in patients with BRAFV600E-mutated thyroid cancer regardless of its histological type, such as DTC or ATC, with no new safety concerns identified. Encorafenib plus binimetinib could thus be a new treatment option for BRAF V600-mutated thyroid cancer. Clinical Trial Registration number: Japan Registry of Clinical Trials: jRCT2011200018.

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.

Active surveillance of low-risk papillary thyroid microcarcinoma.

Recently, the incidence of thyroid carcinoma has been increasing rapidly worldwide. This is interpreted as an increase in the incidental detection of small papillary thyroid carcinomas by the widespread use of high-resolution imaging techniques such as ultrasonography. However, the mortality rates of thyroid carcinoma have not changed, suggesting that small papillary thyroid carcinomas may be overdiagnosed and overtreated. Active surveillance management has been introduced from Japan since the 1990s, as one of the measures to prevent overtreatment of low-risk papillary thyroid microcarcinoma. Based on the favorable outcomes, active surveillance has been gradually adopted worldwide as an alternative to immediate surgery. The management should be carried out with strict eligibility criteria and close monitoring for cancer progression, under a multidisciplinary team. In addition, an adequate shared decision-making is mandatory for individual patients. Papillary thyroid microcarcinomas with clinically apparent lymph node metastasis, distant metastasis, or invasion to adjacent organs should have surgery.

Use of Ultrasonographic Shear Wave Measurements to Diagnose Thyroid Metastasis from Breast Carcinoma.

A metastatic thyroid tumor (MTT) arising from breast carcinoma (BC) is rare and sometimes difficult to diagnose. We present a case of MTT from BC; we suspected anaplastic thyroid carcinoma at initial presentation. The patient was a 58-year-old female with a hard nodule in the right anterior neck and a history of breast cancer. Computed tomography indicated tumors on both thyroid lobes, and ultrasonography (US) with shear wave measurement (SWM) showed malignant features. We performed fine needle aspiration cytology (FNAC), the results of which led us to strongly suspect MTT from BC. The surgically resected specimen was evaluated histopathologically, including by immunohistochemistry (IHC), and the diagnosis was confirmed. In addition to FNAC and IHC, SWM is useful to diagnose MTT from BC.

Downhill Varices in the Hypopharynx of a Patient with a Large Thyroid Tumor: A Case Report.

Downhill varices are usually caused by superior vena cava (SVC) obstruction due to bronchogenic carcinoma or mediastinal tumors. These structures exhibit retrograde blood flow and are located in the proximal esophagus. Varices in the hypopharynx resulting from mediastinal thyroid tumor are extremely rare. A 70-year-old man with a 35-year history of a growing thyroid tumor on the right side of his neck visited a local hospital. Fine-needle aspiration cytology of the tumor revealed benign goiter. Contrast-enhanced computed tomography showed a huge tumor (13 × 10 × 5 cm) in the right to left lobe of the thyroid that extended into the mediastinum. A well-enhanced mass mimicking hypopharyngeal cancer was identified in the hypopharynx. Endoscopic examination showed varices in the postcricoid region, so biopsy was contraindicated. The preoperative diagnosis was adenomatous goiter and hypopharyngeal varices caused by obstruction of the internal jugular and brachiocephalic vein by the goiter. Total thyroidectomy was performed and the hypopharyngeal varices had disappeared by the next day. The histopathological diagnosis of the thyroid tumor was poorly differentiated carcinoma. Mediastinal thyroid tumor rarely causes downhill varices due to SVC obstruction. However, signs of SVC obstruction were absent in this case, and varices were present in the hypopharynx, not in the upper esophagus. Obstructed venous flow from the thyroid plexus might circulate via the superior laryngeal vein and cause varices in the postcricoid region. When a patient with a large mediastinal tumor has a tumor-like lesion in the hypopharynx, downhill varices should be considered before scheduling a biopsy.

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.

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.

A case of pheochromocytoma associated with liver abscess and intestinal pseudo-obstruction.

Pheochromocytomas can present with various symptoms. Nonspecific manifestations of pheochromocytoma include intestinal pseudo-obstruction and weight loss. Here, we present a case of pheochromocytoma in which prolonged intestinal pseudo-obstruction due to excess catecholamines was one of the factors leading to the development of a liver abscess. An 18-year-old male patient with a history of status epilepticus and severe intellectual disability was transferred to our hospital for a thorough examination of fever and constipation that had lasted for 2 months. When admitted to our hospital, he had fever, and his body mass index was 9.5 kg/m2. Upon comprehensive examination of the patient's fever, the blood culture was found positive for Bacteroides. Computed tomography showed findings of intestinal pseudo-obstruction and a low density region in the liver that indicated a liver abscess. Imaging studies also revealed a right adrenal mass and endocrinological test showed elevated plasma norepinephrine and urine normetanephrine levels. In addition, the right adrenal mass showed uptake on 123I-metaiodobenzylguanidine scintigraphy. These findings led to a definite diagnosis of pheochromocytoma. The patient was eventually diagnosed with a pheochromocytoma coexisting with a liver abscess. After treating the liver abscess with antibiotics and ultrasound-guided drainage, an adrenalectomy was performed. The pathological findings were consistent with pheochromocytoma. Postoperatively, the catecholamine excess normalized and intestinal pseudo-obstruction and weight loss improved. We suspected that prolonged intestinal pseudo-obstruction resulted in bacterial translocation and development of a liver abscess. To the best of our knowledge, this is the first report of a pheochromocytoma associated with a liver abscess. Moreover, the clinical presentation of this patient was unusual for pheochromocytoma, as the patient did not have typical symptoms such as hypertension or tachycardia, but rather presented with constipation, intestinal pseudo-obstruction, and weight loss. This case provides valuable insight regarding the impact of catecholamine excess on the intestinal tract and body weight.

Usefulness of ultrasonographic detective flow imaging to diagnose parathyroid tumors: two case reports.

Parathyroid tumors (PTs) are sometimes difficult to diagnose because they are small and have a low-velocity blood flow, which can be missed by current imaging modalities. PTs consist of parathyroid adenoma (PA), parathyroid cyst, and parathyroid carcinoma (PC). Detective flow imaging (DFI) is a new imaging technology that displays a low-velocity blood flow. Herein, we report two cases in which DFI was useful for the diagnosis of PTs. One case consisted of a PA and a parathyroid cyst in close proximity, and the other was a PC. To the best of our knowledge, this is the first report to demonstrate the usefulness of DFI in the diagnosis of PTs.

Phase II study of the efficacy and safety of lenvatinib for anaplastic thyroid cancer (HOPE).

PURPOSE: Anaplastic thyroid cancer (ATC) is a rare and highly aggressive cancer for which effective systemic therapy has long been sought. Here, we assessed the efficacy and safety of lenvatinib in patients with unresectable ATC. PATIENTS AND METHODS: The study was investigator-initiated and conducted under a multicenter, open-label, nonrandomized, phase II design. Eligibility criteria included pathologically proven ATC; unresectable measurable lesion as defined by RECIST 1.1; age 20 years or older; ECOG PS 0-2; and adequate organ function. The primary end-point was overall survival. Secondary end-points were progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety. RESULTS: Of 52 patients enrolled from 17 institutions, 42 patients who were confirmed to have ATC were included for efficacy analysis, and 50 patients were included for safety analysis. The estimated 1-year overall survival rate was 11.9% (95% CI, 4.4%-23.6%). One patient (2.4%) achieved complete response, four patients (9.5%) partial response, and 26 patients (61.9%) stable disease, including nine patients (21.4%) who demonstrated durable stable disease, giving an objective response rate of 11.9%, disease control rate of 73.8%, and clinical benefit rate of 33.3%. Adverse events of any grade were observed in 45 patients (90.0%), the most common of which of any grade included loss of appetite (48.0%), fatigue (48.0%), hypertension (44.0%), and palmar-plantar erythrodysesthesia syndrome (26.0%). CONCLUSION: Lenvatinib treatment resulted in disappointing survival for unresectable ATC patients. Although the number of responders was small, responses were durable, indicating that lenvatinib may be beneficial for selected patients. Further investigation to identify suitable candidates for lenvatinib monotherapy is needed.

Multikinase Inhibitors for the Treatment of Asymptomatic Radioactive Iodine-Refractory Differentiated Thyroid Cancer: Global Noninterventional Study (RIFTOS MKI).

Background: Sorafenib and lenvatinib are multikinase inhibitors (MKIs) approved for patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC). There is no consensus on when to initiate MKI treatment. The objective of this study was to evaluate time to symptomatic progression (TTSP) in patients with RAI-R DTC for whom the decision to treat with an MKI was made at study entry. Methods: International, prospective, open-label, noninterventional cohort study (NCT02303444). Eligible patients had asymptomatic progressive RAI-R DTC, with ≥1 lesion ≥1 cm in diameter and life expectancy ≥6 months. The decision to treat with an MKI was at the treating physician's discretion. Primary endpoint was TTSP from study entry. Two cohorts were evaluated: patients for whom a decision to initiate an MKI was made at study entry (Cohort 1) and patients for whom there was a decision not to initiate an MKI at study entry (Cohort 2). Cohorts were compared descriptively. Results: The full analysis set (FAS) comprised 647 patients. The median duration of observation was 35.5 months (range <1-59.4). Of 344 MKI-treated patients, 209 received sorafenib, 191 received lenvatinib, and 19 received another MKI at some point. Median TTSP was 55.4 months (interquartile range [IQR] 18.6-not estimable [NE]) overall, 55.4 months (IQR 15.2-NE) in Cohort 1 (n = 169), and 51.4 months (IQR 20.0-NE) in Cohort 2 (n = 478). TTSP ≥36 months was achieved in 64.5% of patients overall, 59.5% of patients in Cohort 1, and 66.4% of patients in Cohort 2. Median overall survival from classification as RAI-R was 167 months and median progression-free survival from start of MKI therapy was 19.2 months and from start of sorafenib therapy 16.7 months. Among sorafenib-treated patients, 70% had dose modifications, 35% had a dose reduction, 89% experienced ≥1 treatment-emergent adverse event (TEAE), and 82% experienced ≥1 drug-related TEAE. Conclusions: This real-world study provides valuable insight into outcomes in patients with asymptomatic, progressive RAI-R DTC under observation or receiving MKI treatment. TTSP in the FAS provides insight into the current prognosis for patients with RAI-R DTC in the era of MKIs. Registration: NCT02303444.

VsN, a Reliability-index of Shear-wave Measurement in Sonoelastography, Is Useful for the Diagnosis of Thyroid Tumor Malignancy.

BACKGROUND/AIM: Shear wave measurement (SWM) is a new elastography modality that quantifies the shear wave velocity (Vs) and the percentage of the net effective shear wave velocity (VsN). This study examined whether these parameters could be used to differentiate between malignant and benign thyroid tumors. PATIENTS AND METHODS: The study of SWM enrolled 111 patients (133 nodules) who underwent thyroid surgery. Overall, 61 nodules were diagnosed as benign and 72 as malignant, of which 68 nodules were diagnosed as papillary thyroid carcinoma (PTC) and 4 as follicular thyroid carcinoma (FTC). RESULTS: A preoperative SWM revealed that Vs was significantly higher and VsN significantly lower in the PTC compared to the benign nodules. The VsN of FTC was significantly lower than that of follicular adenoma. Multivariate analysis revealed that VsN significantly correlated with nodule malignancy. CONCLUSION: SWM parameters, especially VsN, can potentially differentiate between benign and malignant thyroid nodules non-invasively.

Learning Curve for Endoscopic Thyroidectomy Using Video-Assisted Neck Surgery: Retrospective Analysis of a Surgeon's Experience with 100 Patients.

BACKGROUND: Endoscopic thyroidectomy offers excellent cosmetic outcomes but requires some time for surgeons to become proficient. We examined the learning curve for the first 100 patients treated by a single surgeon using a subclavian approach for video-assisted neck surgery (VANS). METHODS: We retrospectively studied the records of 100 patients (99 women, 1 man; mean age, 36.2 years) with either benign or malignant thyroid disease treated between 2016 and 2020. RESULTS: Preoperative diagnosis was papillary thyroid carcinoma (PTC) in 36 cases and other (non-PTC) in 64 cases. All patients underwent lobectomy, with additional unilateral central node dissection for patients with PTC. Mean operative time was 125 min for non-PTC cases and 129 min for PTC cases (p = 0.43); blood loss was 33.8 mL and 7.6 mL, respectively (p = 0.01). Recurrent laryngeal nerve paralysis (RNP) was observed in 12 patients (12%) and hemorrhage in 2 patients (2%). In a comparison of the first 30 cases and subsequent 70 cases, no significant differences in operative time or blood loss were evident, although tumor size was significantly greater among later non-PTC cases (32.4 mm vs. 39.5 mm, p = 0.039). RNP was significantly lower in later cases (26.7% vs. 5.7%, p = 0.003). Multivariate analysis revealed that tumor size was a significant risk factor for increased blood loss, and increased experience significantly correlated with a decrease in RNP. CONCLUSIONS: In VANS, satisfactory surgical proficiency was reached after treating 30 patients.

Clinical Utility of Fine-Needle Aspiration Cytology for Adenoid Cystic Carcinoma of the Trachea with Thyroid Invasion: A Case Report.

BACKGROUND: Adenoid cystic carcinoma of the trachea (ACCT) is a rare cancer; ACCT with thyroid invasion is particularly rare. We first suspected anaplastic thyroid carcinoma (ATC) but diagnosed ACC after performing fine-needle aspiration cytology (FNAC). Tracheal origin was confirmed postoperatively. CASE DESCRIPTION: A 77-year-old woman presented to our hospital with acute inspiratory dyspnea requiring emergency tracheotomy. Physical examination revealed swelling of the right anterior neck and a hard, immobile mass. Computed tomography (CT) and ultrasonography (US) showed tumor extension to the right thyroid lobe and between the first and third tracheal rings, which caused severe stenosis of the lumen. We performed FNAC. Clinical findings were highly suggestive of ACCT with thyroid invasion. She underwent total laryngectomy, cervical esophagectomy, and thyroidectomy with bilateral selective neck dissection at another hospital. The tumor was located in the right posterior wall of the trachea and extended into the right thyroid gland. Pathological examination showed infiltrative carcinomatous proliferation with tubular and cribriform patterns. The tumor was classified as pT4N1. A definite diagnosis was made after histopathological analysis of the surgical specimen confirmed ACCT. The tumor was positive for FABP7, a putative prognostic marker of ACC, and metastasized to the lungs 3 years after surgery. CONCLUSIONS: ACCT with thyroid invasion is an extremely rare malignant neoplasm. FNAC was useful for differentiating ACCT from other diagnoses and enabled appropriate surgical treatment.

The impact of COVID-19 on surgical procedures in Japan: analysis of data from the National Clinical Database.

BACKGROUND AND PURPOSE: The spread of COVID-19 has restricted the delivery of standard medical care to surgical patients dramatically. Surgical triage is performed by considering the type of disease, its severity, the urgency for surgery, and the condition of the patient, in addition to the scale of infectious outbreaks in the region. The purpose of this study was to evaluate the impact of the COVID-19 pandemic on the number of surgical procedures performed and whether the effects were more prominent during certain periods of widespread infection and in the affected regions. METHODS: We selected 20 of the most common procedures from each surgical field and compared the weekly numbers of each operation performed in 2020 with the respective numbers in 2018 and 2019, as recorded in the National Clinical Database (NCD). The surgical status during the COVID-19 pandemic as well as the relationship between surgical volume and the degree of regional infection were analyzed extensively. RESULTS: The rate of decline in surgery was at most 10-15%. Although the numbers of most oncological and cardiovascular procedures decreased in 2020, there was no significant change in the numbers of pancreaticoduodenectomy and aortic replacement procedures performed in the same period. CONCLUSION: The numbers of most surgical procedures decreased in 2020 as a result of the COVID-19 pandemic; however, the precise impact of surgical triage on decrease in detection of disease warrants further investigation.

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.

Congenital hemophilia A diagnosed with postoperative hemorrhage after thyroidectomy for papillary thyroid carcinoma: a case report.

BACKGROUND: Postoperative bleeding in thyroid surgery is a serious complication with fatal outcomes. Risk factors for postoperative hemorrhage have been reported as old age, male sex, Graves' disease, use of anticoagulants, and hematological disorders. Among the hematological diseases, congenital hemophilia is an inherited bleeding disorder characterized by absence or reduced levels of clotting factors VIII or IX. Most patients with hemophilia display bleeding symptoms during infancy or childhood, but diagnosis could be delayed in mild cases. We report a case of congenital hemophilia A that was diagnosed after three episodes of postoperative bleeding after thyroid surgery. CASE PRESENTATION: A 46-year-old man developed repeated postoperative hemorrhage after thyroid surgery for thyroid cancer. In this case, several irregularities were seen in the postoperative course, such as a relatively long interval between surgery and bleeding, the lack of an obvious bleeding point, fresh red blood dripping from the drain insertion site on the second postoperative day, and repeated bleeding three times. We therefore considered that the cause of postoperative hemorrhage might be other than the surgical operations. After a thorough examination, hemophilia A was diagnosed. CONCLUSIONS: Hemophilia is a risk factor for postoperative bleeding in thyroid surgery. However, mild hemophilia shows normal prothrombin time and activated partial thromboplastin time. We encountered a case of papillary thyroid carcinoma associated with congenital hemophilia A, which was diagnosed after repeated bleeding.