The Efficacy and Safety of an Indocyanine Green-Macroaggregated Albumin-Hyaluronic Acid Mixture (LuminoMark™) for Surgical Localization of Recurrent Thyroid Cancer.

BACKGROUND: The recurrence of thyroid cancer poses challenges compounded by postoperative fibrosis and anatomic changes. By overcoming the limitations of current localizing dye techniques, indocyanine green-macroaggregated albumin-hyaluronic acid (ICG-MAA-HA) mixture dye promises improved localization. This study aimed to evaluate the efficacy and safety of the dye for recurrent thyroid cancer. METHODS: The nine patients in this study underwent surgery and postoperative ultrasonography. The dye was injected into recurrent lesions in all the patients preoperatively. During surgery, the lesions were confirmed with an imaging system before and after excision. If the lesion was unidentifiable with the naked eye, surgical excision was performed under the corresponding fluorescent guide. Side effects related to the dye injection and completeness of the surgery were evaluated. RESULTS: No side effects such as bleeding, skin tattooing, or pain during or after the dye injection were reported, and no discoloration occurred that interfered with the surgical field of view during surgery. In three cases (33.3 %), because it was difficult to localize metastatic lesions with the naked eye, the operation was successfully completed using an imaging system. The completeness of the surgical resection was confirmed by ultrasonography after an average of 5 months postoperatively. CONCLUSION: The study found that ICG-MAA-HA dye effectively located metastatic and recurrent thyroid cancer and had favorable results in terms of minimal procedural side effects and potential for assisting the surgeon. A large-scale multi-institutional study is necessary to prove the clinical significance regarding patient survival and disease control.

Surgical Outcomes in Patients With Low-risk Papillary Thyroid Microcarcinoma From MAeSTro Study: Immediate Operation Versus Delayed Operation After Active SurveillanceA Multicenter Prospective Cohort Study.

OBJECTIVE: To investigate surgical, and clinical outcomes in patients with low-risk papillary thyroid microcarcinoma (PTMC) according to treatment options [immediate operation (IOP) vs delayed operation after active surveillance (AS) (DOP)]. BACKGROUND: AS has been adopted as an alternative to immediate surgery in patients with low-risk PTMC. Although some patients undergo surgery during AS, there is little information on surgical, and clinical outcomes after delayed operation after AS. METHODS: A multicenter prospective cohort study including 1177 patients was conducted at 3 tertiary hospitals in Korea from June 2016 to January 2020. Patients with low-risk PTMC were enrolled. The participants were self-assigned into AS or IOP, and during AS, the patients underwent surgery if there were signs of disease progression or if the patient's choice changed. RESULTS: A total of 516 patients underwent operation; 384 (74.4%) in the IOP group and 132 (25.6%) in the DOP group. Compared with the IOP group, the DOP group was significantly associated with a larger tumor size ( P =0.002), higher rates of lymphatic invasion ( P =0.002), and multifocality ( P =0.008). However, the rates of total thyroidectomy, postoperative hypoparathyroidism and vocal cord palsy did not differ significantly between the groups ( P = 0.283, P =0.184, and P =0.284, respectively). Of the 132 patients in the DOP group, disease progression was present in 39 (29.5%) patients. The DOP group with disease progression had a significantly higher rate of lymph node metastasis ( P =0.021) and radioiodine therapy ( P =0.025) than the DOP group without disease progression. CONCLUSIONS: These results suggest that AS might be considered an alternative treatment option for patients with low-risk PTMC regarding the extent of thyroidectomy and postoperative complications in the DOP group. To assess oncologic outcomes, long-term follow-up will be needed. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02938702.

The emergence of oral cavity cancer and the stabilization of oropharyngeal cancer: Recent contrasting epidemics in the South Korean population.

BACKGROUND: By analyzing the recent epidemiologic trajectory of head and neck squamous cell carcinoma (HNSCC) in South Korea, we tracked 2 findings that have been reported recently in other countries: the stabilization of human papillomavirus (HPV)-related HNSCC incidence and the acceleration of oral cavity cancer incidence. METHODS: We analyzed data from the comprehensive population-based Korean Central Cancer Registry for the period 1999 to 2017. The age-standardized incidence rate (ASR), annual percent change (APC), and relative survival were calculated. RESULTS: The ASR of total HNSCC decreased from 1999 to 2017 (APC, -0.2 [95% CI, -0.3 to -0.0]), as did the ASR of HPV-unrelated HNSCC (APC, -0.6 [95% CI, -0.8 to -0.5]); however, the ASR of HPV-related HNSCC increased (APC, 2.9 [95% CI, 2.5 to 3.2]). The rapidly increasing incidence of tonsil squamous cell carcinoma, which was the main subsite of HPV-related HNSCC, stabilized after 2011 (APC pre-2011, 6.8 [95% CI, 5.0 to 8.3]; APC post-2011, 1.6 [95% CI, -2.1 to 5.5]), and the difference was significant (P = .017). In contrast, oral cavity cancer incidence demonstrated the only increase among HPV-unrelated subsites, with the increase occurring after 2006 (APC pre-2006, 1.6 [95% CI, 0.3 to 2.8]; APC post-2006, 2.8 [95% CI, 2.2 to 3.5]); the main cause of this change was an increase in the ASR of tongue cancer. CONCLUSION: This study demonstrates the recent stabilization of tonsil cancer incidence and the contrasting increase in oral cavity cancer incidence, unlike other HPV-unrelated cancers. These trends require further surveillance and understanding in terms of tumor biology and prevention.

Utility of the Patient-Reported Outcomes Measurement Information System (PROMIS) to measure primary health outcomes in cancer patients: a systematic review.

OBJECTIVE: To systematically review the literature on how the Patient-Reported Outcomes Measurement Information System (PROMIS) measure system is used to assess patient-reported outcomes (PROs) in cancer patients. METHODS: We conducted a systematic review following the PRISMA guidelines. Articles were identified through searches of PubMed, EMBASE, and additional manual review of the publications listed on the PROMIS website. We included studies measuring outcomes, including physical function, fatigue, pain, anxiety, and depression in cancer patients. Eligible articles included interventional and observational studies published in English between 2009 and 2019. RESULTS: A total of 1789 records were identified and screened by three reviewers, 118 articles were reviewed in full text, and 42 articles met the inclusion criteria. The majority of studies used the PROMIS measure system to prospectively assess longitudinal changes in PROs; the number of measurements ranges from 2 to 4 with the time points of follow-up set at 3, 6, and 12 months after the baseline assessment. Depression and fatigue were the most frequently measured outcomes. Fixed-length short forms with four items were the most common measure types. A transition toward utilizing a web- or smartphone-based electronic tool was observed to limit the burden of the conventional paper-based survey to collect and store PROs. CONCLUSION: The PROMIS measure system is increasingly popular to measure PROs in cancer patients with acceptance of its various short forms and electronic-based systems to administer data electronically. Findings from this review highlight various aspects of PROMIS and may help health professionals in their choice of PRO tools for optimizing care and support for cancer patients.

Singing voice range profile: New objective evaluation methods for voice change after thyroidectomy.

BACKGROUND: After surgery in the thyroid region, patients may present with phonation or singing difficulty, even within their vocal range. We designed a novel voice evaluation method that reflects subjective and objective voice complications of the surgery. METHODS: This tool recorded patients' voice ranges while singing, which was named the singing voice range profile (singing VRP). Patients were asked to sing "Happy Birthday," which has a one-octave scale, at a comfortable tone and intensity. The singing VRP, standard VRP and voice handicap index-10 (VHI-10) results were recorded before thyroidectomy and 1 and 3 months after thyroidectomy for 128 patients. For subgroup analysis, a group where the maximum F0 of standard VRP in 1 month postoperatively was lower than the highest singing F0 of the preoperative singing VRP was defined as "Collapsed group" and the other group was "Preserved group." RESULTS: The changes in the highest, lowest and range of singing fundamental frequency (F0 ) had decreased at 1 month postoperatively. Subsequently, they had improved significantly at 3 months postoperatively but were lower than those preoperatively (all P < .05, except for the change in the lowest singing F0 between 1 and 3 months postoperatively, P = .274). In the subgroup analysis, the singing range of the collapsed group (n = 65) showed significantly lower VHI-10 scores, range of vocal F0 and singing F0 than those of the preserved group (n = 63) at 1 and 3 months postoperatively (all P < .001). At 3 months postoperatively, the singing F0 range in the preserved group had recovered to the range before surgery (13.0 ± 1.3 vs. 13.1 ± 1.4, P = .746 for the preserved group, and 13.0 ± 1.3 vs 11.5 ± 2.4, P < .001 for the collapsed group). CONCLUSIONS: Parameters measured by singing VRP showed a trend similar to the change in VHI-10 and the maximum F0 of standard VRP. In addition, singing VRP allowed a qualitative classification of the postoperative voice function when combined with standard VRP. Therefore, it can be used as a supplementary voice evaluation tool to reflect the physiologic and functional aspects of voice.

Association Between Eight Autoimmune Diseases and Thyroid Cancer: A Nationwide Cohort Study.

Background: It has often been reported that thyroid-specific autoimmune diseases (ADs), such as Hashimoto's thyroiditis and Graves' disease, could increase the risk of thyroid cancer, but the association between other ADs beyond thyroid and thyroid cancer has not been well investigated. This study aimed to examine the risk of thyroid cancer in patients with eight ADs compared with those without ADs. Methods: This nationwide retrospective matched cohort study was conducted to investigate the relationship of eight ADs (Hashimoto's thyroiditis, Graves' disease, type 1 diabetes mellitus, Sjogren's disease, inflammatory bowel disease [IBD], vitiligo, systemic lupus erythematosus, and rheumatoid arthritis [RA]) with the risk of incident thyroid cancer using the National Health Insurance Service-National Sample Cohort. The Cox-proportional hazard model was used to estimate the adjusted hazard ratio (HR) and confidence intervals (CI) for thyroid cancer in relation to each of AD compared with control group without AD. Results: During the average follow-up of 9.49 years, 138 thyroid cancer cases were newly developed in control group and 268 cases were occurred in group with 8 ADs. For all of study participants, the risk of thyroid cancer was significantly increased in patients with Hashimoto's thyroiditis (HR = 2.10 [1.57-2.81]), Graves' disease (HR = 2.67 [1.99-3.62]), IBD (HR = 2.06 [1.50-2.83]), vitiligo (HR = 1.71 [1.13-2.59]), RA (HR = 1.76 [1.07-2.90]), and total of 8 ADs (HR = 1.97 [1.60-2.42]) compared with control group without ADs. When ADs were divided into three types, thyroid-specific ADs (HR = 2.37 [1.85-3.03]) showed the strongest and significant association with thyroid cancer, followed by local ADs (HR = 1.83 [1.41-2.38]), and systemic ADs (HR = 1.77 [1.14-2.74]). Conclusions: Specific ADs-especially for thyroid-specific AD, vitiligo, IBD, and RA-were associated with increased risk for thyroid cancer.

Adenovirus expressing nc886, an anti-interferon and anti-apoptotic non-coding RNA, is an improved gene delivery vector.

Recombinant adenovirus (rAdV) vector is the most promising vehicle to deliver an exogenous gene into target cells and is preferred for gene therapy. Exogenous gene expression from rAdV is often too inefficient to induce phenotypic changes and the amount of administered rAdV must be very high to achieve a therapeutic dose. However, it is often hampered because a high dose of rAdV is likely to induce cytotoxicity by activating immune responses. nc886, a 102-nucleotide non-coding RNA that is transcribed by RNA polymerase III, acts as an immune suppressor and a facilitator of AdV entry into the nucleus. Therefore, in this study, we have constructed an rAdV expressing nc886 (AdV:nc886) to explore whether AdV:nc886 overcomes the aforementioned drawbacks of conventional rAdV vectors. When infected into mouse cell lines and mice, AdV:nc886 expresses a sufficient amount of nc886, which suppresses the induction of interferon-stimulated genes and apoptotic pathways triggered by AdV infection. As a result, AdV:nc886 is less cytotoxic and produces more rAdV-delivered gene products, compared with the parental rAdV vector lacking nc886. In conclusion, this study demonstrates that the nc886-expressing rAdV could become a superior gene delivery vehicle with greater safety and higher efficiency for in vivo gene therapy.

Long-term Survivorship and Non-cancer Competing Mortality in Head and Neck Cancer: A Nationwide Population-Based Study in South Korea.

PURPOSE: As the survival of head and neck cancer (HNC) improves, survivors increasingly confront non-cancer-related deaths. This nationwide population-based study aimed to investigate non-cancer-related deaths in HNC survivors. MATERIALS AND METHODS: Data from the Korean Central Cancer Registry were obtained to characterize causes of death, mortality patterns, and survival in patients with HNC between 2006 and 2016 (n=40,890). Non-cancer-related mortality relative to the general population was evaluated using standardized mortality ratios (SMRs). The 5- and 10-year cause-specific competing risks probabilities of death (cumulative incidence function, CIF) and subdistribution hazards ratios (sHR) from the Fine-Gray models were estimated. RESULTS: Comorbidity-related mortality was frequent in older patients, whereas suicide was predominant in younger patients. The risk of suicide was greater in patients with HNC than in the general population (SMR, 3.1; 95% confidence interval [CI], 2.7 to 3.5). The probability of HNC deaths reached a plateau at 5 years (5-year CIF, 33.9%; 10-year CIF, 39.5%), whereas the probability of non-HNC deaths showed a long-term linear increase (5-year, CIF 5.6%; 10-year CIF, 11.9%). Patients who were male (sHR, 1.56; 95% CI, 1.41 to 1.72), diagnosed with early-stage HNC (localized vs. distant: sHR, 1.86; 95% CI, 1.58 to 2.21) and older age (65-74 vs. 0-44: sHR, 6.20; 95% CI, 4.92 to 7.82; ≥ 75 vs. 0-44: sHR, 9.81; 95% CI, 7.76 to 12.39) had an increased risk of non-cancer mortality. CONCLUSION: Non-HNC-related deaths continue increasing. HNC survivors are at increased risk of suicide in the younger and comorbidity-related death in the older. Better population-specific surveillance awareness and survivorship plans for HNC survivors are warranted.

Novel thrombospondin-1 transcript exhibits distinctive expression and activity in thyroid tumorigenesis.

Thrombospondin 1 (TSP1) is known for its cell-specific functions in cancer progression, such as proliferation and migration. It contains 22 exons that may potentially produce several different transcripts. Here, we identified TSP1V as a novel TSP1-splicing variant produced by intron retention (IR) in human thyroid cancer cells and tissues. We observed that TSP1V functionally inhibited tumorigenesis contrary to TSP1 wild-type, as identified in vivo and in vitro. These activities of TSP1V are caused by inhibiting phospho-Smad and phospho-focal adhesion kinase. Reverse transcription polymerase chain reaction and minigene experiments revealed that some phytochemicals/non-steroidal anti-inflammatory drugs enhanced IR. We further found that RNA-binding motif protein 5 (RBM5) suppressed IR induced by sulindac sulfide treatment. Additionally, sulindac sulfide reduced phospho-RBM5 levels in a time-dependent manner. Furthermore, trans-chalcone demethylated TSP1V, thereby preventing methyl-CpG-binding protein 2 binding to TSP1V gene. In addition, TSP1V levels were significantly lower in patients with differentiated thyroid carcinoma than in those with benign thyroid nodule, indicating its potential application as a diagnostic biomarker in tumor progression.

Detection of Cancer Recurrence Using Systemic Inflammatory Markers and Machine Learning after Concurrent Chemoradiotherapy for Head and Neck Cancers.

Pretreatment values of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are well-established prognosticators in various cancers, including head and neck cancers. However, there are no studies on whether temporal changes in the NLR and PLR values after treatment are related to the development of recurrence. Therefore, in this study, we aimed to develop a deep neural network (DNN) model to discern cancer recurrence from temporal NLR and PLR values during follow-up after concurrent chemoradiotherapy (CCRT) and to evaluate the model's performance compared with conventional machine learning (ML) models. Along with conventional ML models such as logistic regression (LR), random forest (RF), and gradient boosting (GB), the DNN model to discern recurrences was trained using a dataset of 778 consecutive patients with primary head and neck cancers who received CCRT. There were 16 input features used, including 12 laboratory values related to the NLR and the PLR. Along with the original training dataset (N = 778), data were augmented to split the training dataset (N = 900). The model performance was measured using ROC-AUC and PR-AUC values. External validation was performed using a dataset of 173 patients from an unrelated external institution. The ROC-AUC and PR-AUC values of the DNN model were 0.828 ± 0.032 and 0.663 ± 0.069, respectively, in the original training dataset, which were higher than the ROC-AUC and PR-AUC values of the LR, RF, and GB models in the original training dataset. With the recursive feature elimination (RFE) algorithm, five input features were selected. The ROC-AUC and PR-AUC values of the DNN-RFE model were higher than those of the original DNN model (0.883 ± 0.027 and 0.778 ± 0.042, respectively). The ROC-AUC and PR-AUC values of the DNN-RFE model trained with a split dataset were 0.889 ± 0.032 and 0.771 ± 0.044, respectively. In the external validation, the ROC-AUC values of the DNN-RFE model trained with the original dataset and the same model trained with the split dataset were 0.710 and 0.784, respectively. The DNN model with feature selection using the RFE algorithm showed the best performance among the ML models to discern a recurrence after CCRT in patients with head and neck cancers. Data augmentation by splitting training data was helpful for model performance. The performance of the DNN-RFE model was also validated with an external dataset.

Exploring Connections between Oral Microbiota, Short-Chain Fatty Acids, and Specific Cancer Types: A Study of Oral Cancer, Head and Neck Cancer, Pancreatic Cancer, and Gastric Cancer.

The association between oral microbiota and cancer development has been a topic of intense research in recent years, with compelling evidence suggesting that the oral microbiome may play a significant role in cancer initiation and progression. However, the causal connections between the two remain a subject of debate, and the underlying mechanisms are not fully understood. In this case-control study, we aimed to identify common oral microbiota associated with several cancer types and investigate the potential mechanisms that may trigger immune responses and initiate cancer upon cytokine secretion. Saliva and blood samples were collected from 309 adult cancer patients and 745 healthy controls to analyze the oral microbiome and the mechanisms involved in cancer initiation. Machine learning techniques revealed that six bacterial genera were associated with cancer. The abundance of Leuconostoc, Streptococcus, Abiotrophia, and Prevotella was reduced in the cancer group, while abundance of Haemophilus and Neisseria enhanced. G protein-coupled receptor kinase, H+-transporting ATPase, and futalosine hydrolase were found significantly enriched in the cancer group. Total short-chain fatty acid (SCFAs) concentrations and free fatty acid receptor 2 (FFAR2) expression levels were greater in the control group when compared with the cancer group, while serum tumor necrosis factor alpha induced protein 8 (TNFAIP8), interleukin-6 (IL6), and signal transducer and activator of transcription 3 (STAT3) levels were higher in the cancer group when compared with the control group. These results suggested that the alterations in the composition of oral microbiota can contribute to a reduction in SCFAs and FFAR2 expression that may initiate an inflammatory response through the upregulation of TNFAIP8 and the IL-6/STAT3 pathway, which could ultimately increase the risk of cancer onset.

Progression of Low-Risk Papillary Thyroid Microcarcinoma During Active Surveillance: Interim Analysis of a Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma in Korea.

Background: Active surveillance (AS) is an alternative to thyroidectomy for the management of low-risk papillary thyroid microcarcinoma (PTMC). However, prospective AS data collected from diverse populations are needed. Methods: This multicenter prospective cohort study enrolled patients from three referral hospitals in Korea. The participants were self-assigned into two groups, AS or immediate surgery. All patients underwent neck ultrasound every 6-12 months to monitor for disease progression. Progression under AS was evaluated by a criterion of tumor size increment by 3 mm in one dimension (3 mm), 2 mm in two dimensions (2 × 2 mm), new extrathyroidal extension (ETE), or new lymph node metastasis (LNM), and a composite outcome was defined using all four criteria. Results: A total of 1177 eligible patients with PTMC (919 female, 78.1%) with a median age of 48 years (range 19-87) were enrolled; 755 (64.1%) patients chose AS and 422 (35.9%) underwent surgery. Among 755 patients under AS, 706 (female 537, 76.1%) underwent at least two ultrasound examinations and were analyzed. Over a follow-up period of 41.4 months (standard deviation, 16.0), 163 AS patients (23.1%) underwent surgery. Progression defined by the composite outcome was observed in 9.6% (68/706) of patients, and the 2- and 5-year progression estimates were 5.3% and 14.2%, respectively. The observed progression rates were 5.8% (41/706) and 5.4% (38/706) as defined by tumor size enlargement by 3 mm and 2 × 2 mm, respectively, and 1.3% (9/706) and 0.4% (3/706) for new LNM and ETE, respectively. No distant metastases developed during AS. In multivariate logistic regression analysis examining variables associated with progression under AS, age at diagnosis <30 years (odds ratio [OR], 2.86; 95% confidence interval [CI], 1.10 - 7.45), male sex (OR, 2.48; 95% CI, 1.47 - 4.20), and tumor size ≥6 mm (OR, 1.89; 95% CI, 1.09 - 3.27) were independently significant. Conclusions: The progression of low-risk PTMC during AS in the Korean population was low, but slightly higher than previously reported in other populations. Risk factors for disease progression under AS include younger age, male sex, and larger tumor size. Clinical trial registration: Clinicaltrials.gov NCT02938702.

A Cross-Sectional Survey of Patient Treatment Choice in a Multicenter Prospective Cohort Study on Active Surveillance of Papillary Thyroid Microcarcinoma (MAeSTro).

Background: Active surveillance (AS) is offered as a choice to patients with low-risk papillary thyroid microcarcinoma (PTMC). This study aimed to identify patient and physician factors associated with the choice of AS. Methods: We conducted a cross-sectional survey of patients with low-risk PTMC who were enrolled in a prospective study comparing outcomes following AS and surgery. Patients completed a questionnaire to assess their prior knowledge of the disease, considerations in the decision-making process, and reasons for choosing the treatment. We also surveyed 19 physician investigators about their disease management preferences. Variables affecting the patients' choice of AS, including patients' characteristics and their decision-making process, were analyzed in a multivariable analysis. Results: The response rate of the patient survey was 72.8% (857/1177). Among the patients who responded to the survey, 554 patients (128 male; mean age 49.4 ± 11.6 years; response rate 73.4%) with low-risk PTMC chose AS (AS group), whereas 303 patients (55 male; 46.6 ± 10.7 years; 71.8%) chose immediate surgery (iOP group). In the AS group, 424 patients (76.5%) used a decision aid, and 144 (47.5%) used it in the iOP group. The choice of AS was associated with the following variables: patient age >50 years (odds ratio 1.713 [confidence interval, CI 1.090-2.690], p = 0.020), primary tumor size ≤5 mm (odds ratio 1.960 [CI 1.137-3.379], p = 0.015), and consulting an endocrinologist (odds ratio 114.960 [CI 48.756-271.057], p < 0.001), and use of a decision aid (odds ratio 2.469 [CI 1.320-4.616], p = 0.005). The proportion of patients who were aware of AS before their initial consultation for treatment decision was higher in the AS group than in the iOP group (64.6% vs. 56.8%). Family members were reported to have influenced the treatment decisions more in the iOP group (p = 0.025), whereas the AS group was more influenced by information from the media (p = 0.017). Physicians' attitudes regarding AS of low-risk PTMC tended to be more favorable among endocrinologists than surgeons and all became more favorable as the study progressed. Conclusions: Emerging evidence suggests that physicians' attitudes and communication tools influence the treatment decision of low-risk PTMC patients. Support is needed for patient-centered decision making. (Clinical trial No: NCT02938702).

A Personalized 3D-Printed Model for Obtaining Informed Consent Process for Thyroid Surgery: A Randomized Clinical Study Using a Deep Learning Approach with Mesh-Type 3D Modeling.

The aim of this study was to evaluate the usefulness of a personalized 3D-printed thyroid model that characterizes a patient's individual thyroid lesion. The randomized controlled prospective clinical trial (KCT0005069) was designed. Fifty-three of these patients undergoing thyroid surgery were randomly assigned to two groups: with or without a 3D-printed model of their thyroid lesion when obtaining informed consent. We used a U-Net-based deep learning architecture and a mesh-type 3D modeling technique to fabricate the personalized 3D model. The mean 3D printing time was 258.9 min, and the mean price for production was USD 4.23 for each patient. The size, location, and anatomical relationship of the tumor and thyroid gland could be effectively presented using the mesh-type 3D modeling technique. The group provided with personalized 3D-printed models showed significant improvement in all four categories (general knowledge, benefits and risks of surgery, and satisfaction; all p < 0.05). All patients received a personalized 3D model after surgery and found it helpful to understand the disease, operation, and possible complications and their overall satisfaction (all p < 0.05). In conclusion, the personalized 3D-printed thyroid model may be an effective tool for improving a patient's understanding and satisfaction during the informed consent process.

Estimated incidence of juvenile-onset recurrent respiratory papillomatosis in Korea.

OBJECTIVES: Recurrent respiratory papillomatosis (RRP) is caused by human papillomavirus (HPV) types 6 and 11 and is potentially preventable through vaccination. This study estimated the incidence of juvenile-onset RRP before the implementation of the national HPV vaccination program in Korea. METHODS: We conducted a cohort study using claims data provided by a mandatory insurance program to estimate the incidence of RRP and associated healthcare use. Patients with juvenile RRP were defined as those aged ≤12 years with ≥2 admissions or ≥2 outpatient visits during which they received the International Classification of Diseases, 10th revision code for benign neoplasms of the larynx (D14.1). RESULTS: During 2002-2014, 123 children (74 boys and 49 girls) were diagnosed with RRP. The patients had a mean of 6.5 person-years of follow-up. The incidence was estimated at 0.30/100,000 person-years. The median age at diagnosis was 4.0 years (mean, 4.3). Thirty-six (29.3%) patients underwent surgery, including 23 patients (18.7%) who underwent 2 or more surgical procedures. Severe disease, measured by more frequent surgical procedures and shorter time intervals between consecutive operations, was associated with a younger age at diagnosis. CONCLUSIONS: The estimated incidence of juvenile-onset RRP in Korea was similar to that reported in other countries. The RRP burden should continue to be monitored using National Health Insurance Service claims data.

Wireless parathyroid detection device using autofluorescence and smart glasses: A preliminary study.

BACKGROUND: Autofluorescence imaging technology has been utilized for preserving or identifying parathyroid glands (PTGs) during thyroid surgery. We developed a wireless PTGs detection device linked with smart glasses that allows for real-time video recording and screen switching according to the light source. OBJECTIVE: This study aimed to confirm the feasibility of the device and whether it would help preserve the PTG during the surgery. METHODS: This prospective study was conducted in 30 patients with 66 PTGs. The device's agreement with the physician's judgment was evaluated, and we determined how many PTGs were preserved from thyroidectomy. RESULTS: The positive agreement rate for PTGs detection between the surgeon and device was 70.9%. Inadvertent parathyroidectomy was identified in surgical specimens of 6 patients (20%). No PTG was removed when it was confirmed by the device (0/39). Of the 27 glands not detected by the device, there was inadvertent removal of 6 PTGs. CONCLUSIONS: PTGs can be preserved successfully when the detection of them by the device is consistent with the surgeon's discretion. A large-scale controlled study is necessary to demonstrate the practical effect of this device on hypoparathyroidism after thyroidectomy.

Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells.

Although the treatment of thyroid cancer has improved, unnecessary surgeries are performed due to a lack of specific diagnostic and prognostic markers. Therefore, the identification of novel biomarkers should be considered in the diagnosis and treatment of thyroid cancer. In this study, antibody arrays were performed using tumor and adjacent normal tissues of patients with papillary thyroid cancer, and several potential biomarkers were identified. Among the candidate proteins chosen based on the antibody array data, mature NAG-1 exhibited increased expression in tumor tissues compared to adjacent normal tissues. In contrast, pro-NAG-1 expression increased in normal tissues, as assessed by western blot analysis. Furthermore, pro-NAG-1 expression was increased when the thyroid cancer cells were treated with phytochemicals and nonsteroidal anti-inflammatory drugs in a dose-dependent manner. In particular, quercetin highly induced the expression of pro-NAG-1 but not that of mature NAG-1, with enhanced anticancer activity, including apoptosis induction and cell cycle arrest. Examination of the NAG-1 promoter activity showed that p53, C/EBPα, or C/EBPδ played a role in quercetin-induced NAG-1 expression. Overall, our study indicated that NAG-1 may serve as a novel biomarker for thyroid cancer prognosis and may be used as a therapeutic target for thyroid cancers.

Decreasing trends in thyroid cancer incidence in South Korea: What happened in South Korea?

BACKGROUND: South Korea has the highest incidence of thyroid cancer in the world. Our study examined the trends in thyroid cancer incidence by the histologic type, cancer stage, and age group and explored possible factors that affected thyroid cancer trends. METHODS: We conducted a descriptive epidemiological study using the national cancer registry data and cause of death data from 1999 to 2016 in South Korea. Age-standardized rates were calculated using Segi's world standard population. Joinpoint regression analysis was applied to determine the changing point of thyroid cancer trends according to histologic type; Surveillance, Epidemiology, and End Results (SEER) summary stage; and age groups by sex. RESULTS: The age-standardized incidence of thyroid cancer in both men and women increased from 6.3 per 100,000 people in 1999 to 63.4 per 100,000 in 2012 but declined from 2012 to 2016, before the debates for over diagnosis of thyroid cancer began in 2014. The age-standardized mortality rate of thyroid cancer, incidence of distant thyroid cancer, and incidence of regional and localized thyroid cancer started to decline since early 2000, 2010, and 2012, respectively. In addition, thyroid cancer prevalence in thyroid nodules showed decreasing trends from 1999-2000 to 2013-2014. CONCLUSIONS: The incidence of thyroid cancer began declining from 2012, before the debates for over diagnosis of thyroid cancer began in 2014. Changes in guidelines for thyroid nodule examinations may have affected this inflection point. Moreover, the debates for over diagnosis of thyroid cancer may have accelerated the decline in thyroid cancer.

Cardiovascular Outcomes in Thyroid Cancer Patients Treated With Thyroidectomy: A Meta-analysis.

CONTEXT: Thyroid dysfunction is associated with an increased risk of cardiovascular disease (CVD) in the general population; however, it remains controversial whether differentiated thyroid cancer (DTC) treatment, including thyroidectomy and thyroid-stimulating hormone suppression, further increases the risk of CVD. OBJECTIVE: This study aimed to evaluate the risk of CVD in patients with DTC. METHODS: We performed a review of observational studies on associations between DTC and cardiovascular outcomes, indexed in MEDLINE, Embase, and Web of Science. We excluded studies that evaluated CVD as comorbidity before DTC diagnosis and those that used active surveillance without thyroidectomy as an intervention. Risk estimates were pooled using random- and fixed-effects models when 3 or more studies reported on the outcome of interest. Echocardiographic and hemodynamic parameters were examined. RESULTS: Eighteen studies were included in the quantitative analysis (193 320 cases with DTC and 225 575 healthy controls). DTC was associated with an increased risk of atrial fibrillation (pooled risk ratio [RR] = 1.55 [95% CI: 1.30-1.84]), coronary artery disease (RR = 1.10 [1.00-1.21]), cerebrovascular accidents (RR = 1.15 [1.09-1.20]), and all-cause mortality (RR = 1.95 [1.03-3.69]). DTC was associated with higher diastolic blood pressure (standardized mean difference [SMD], 0.22 [0.01-0.42]), heart rate (0.37 [0.17-0.57]), left ventricular mass index (0.66 [0.45-0.88]), and interventricular septal thickness (0.91 [0.33-1.49]) and lower early to late ventricular filling velocities (-0.42 [-0.79 to -0.05]), but not with ejection fraction. CONCLUSION: Patients with DTC are at an increased risk of atrial fibrillation, CVD, increased heart rate, and left ventricular mass development.

Local adenoviral delivery of soluble CD200R-Ig enhances antitumor immunity by inhibiting CD200-ß-catenin-driven M2 macrophage.

CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization. As an in vivo model, C57BL/6 mice were subcutaneously injected with MEER/CD200High cells, CD200-overexpressing mouse HNSCC cells. Adenovirus-expressing sCD200R1-Ig (Ad5sCD200R1) was designed, and its effect was tested. Components in the tumor-immune microenvironment (TIME) were quantified using flow cytometry. CD200 promoted tumor growth and induced the expression of immune-related genes, especially macrophage colony-stimulating factor (M-CSF). Interestingly, CD200 induced M2-like polarization both in vitro and in vivo. Consequently, CD200 recruited more regulatory T (Treg) cells and fewer CD8+ effector T cells. These effects were effectively abolished by local injection of Ad5sCD200R1. These protumor effects of CD200 were driven through the ß-catenin/NF-κB/M-CSF axis. CD200 upregulated PD-L1, and the combined targeting of CD200 and PD-1 thus showed synergy. The immune checkpoint CD200 upregulated immune-related genes through ß-catenin signaling, reprogrammed the TIME, and exerted protumor effects. Ad5sCD200R1 injection could be an effective targeted strategy to enhance antitumor immunoediting.