Robotic Adrenalectomy Using the da Vinci SP Robotic System: Technical Feasibility Comparison with Single-Port Access Using the da Vinci Multi-arm Robotic System.

BACKGROUND: Laparoscopic adrenalectomy is the gold standard for adrenal tumor; however, robotic adrenal surgery has gained interest recently. For minimally invasive surgeries, we first reported on robotic adrenalectomy using a single-port access performed using the da Vinci multi-arm robotic system (RA-SA) in 2011. Since its introduction in 2018, we first performed robotic adrenalectomy using the da Vinci SP robotic system in 2020. OBJECTIVE: We aimed to introduce the novel single-port robotic system (RA-SP) for adrenalectomy and evaluate its technical feasibility by comparing it with the surgical outcomes of patients who underwent robotic adrenalectomy using the RA-SA. METHODS: Eight patients who underwent robotic adrenalectomy using the RA-SP from February 2020 to June 2021 were compared with 11 patients who underwent RA-SA from 2011 to 2015 by a single surgeon. RESULTS: The two groups were similar in age, sex, body mass index, type of operation, and final pathologic diagnosis. Despite no significant differences, RA-SP resulted in moderately less mean operation time, estimated blood loss, and length of hospitalization. CONCLUSIONS: The Da Vinci SP robotic system is a novel, safe, and feasible technique to improve the convenience of operation and cosmetic effect for adrenalectomy.

Comparisons Between Normocalcemic Primary Hyperparathyroidism and Typical Primary Hyperparathyroidism.

BACKGROUND: Normocalcemic primary hyperparathyroidism (NPHPT) was first described in 2008. It is defined as consistently elevated serum parathyroid hormone (PTH) levels with normal serum calcium (sCa) concentration, after excluding secondary causes of PTH elevation. However, the exact definition and management strategy for NPHPT remain controversial. We retrospectively investigated the clinicopathological features and short-term outcomes of NPHPT patients. METHODS: A total of 280 patients who were surgically indicated for primary hyperparathyroidism (PHPT) at the Yonsei Severance Medical Center between 2015 and 2019 were included. Patients were classified according to preoperative PTH, corrected sCa, and ionized calcium (iCa) levels as follows: typical primary hyperparathyroidism (TPHPT, elevated PTH, sCa, and iCa, n = 158) and NPHPT (elevated PTH, normal sCa, n = 122). RESULTS: NPHPT was commonly seen in younger individuals (aged < 50 years, P = 0.025); nephrolithiasis and bone fractures were common. Preoperative PTH level was higher in the TPHPT group (P < 0.001). The NPHPT group had higher numbers of multiple parathyroid lesions (P = 0.004) that were smaller (P = 0.011). NPHPT patients were further divided into two subgroups according to iCa levels: the elevated (n = 95) and normal iCa (n = 27) groups. There was no significant difference between the two subgroups regarding symptoms and multiplicity of lesions. CONCLUSION: We found that NPHPT may be a heterogeneous disease entity of PHPT with high rates of multi-gland disease, which appears to be biochemically milder but symptomatic. Intraoperative PTH monitoring might help increase the surgery success rate. Moreover, the short-term outcomes of NPHPT after surgery did not differ from that of TPHPT.

Impact of Dyslipidemia on the Risk of Second Cancer in Thyroid Cancer Patients: A Korean National Cohort Study.

BACKGROUND: Studies have shown that radioactive iodine therapy (RAIT) affects the development of second cancer in thyroid cancer patients. The impact of other factors, such as dyslipidemia are not clear. METHODS: A retrospective analysis of thyroid cancer patients with a 1,251,913 person-year follow-up was conducted using data from the Health Insurance Review and Assessment database in South Korea from January 2008 to December 2018. We investigated factors related to second cancer development using a nested case-control analysis to avoid length bias. RESULTS: The overall risk of developing second cancer was higher in thyroid cancer patients than in the general population [standardized incidence ratio, 3.34; 95% confidence interval (CI) 3.30-3.39]. Second cancer incidence was higher in patients who received RAIT than in those who did not [odds ratio (OR) 1.130; 95% CI 1.094-1.169]. Moreover, the risk of second cancer was higher in patients with dyslipidemia than in those without dyslipidemia (OR 1.265; 95% CI 1.223-1.309). After adjustment for RAIT, the incidence of a second cancer was higher in patients with dyslipidemia than in those without dyslipidemia (OR 1.262; 95% CI 1.221-1.306). CONCLUSIONS: The risk of second cancer development in patients with thyroid cancer appears to be high. Dyslipidemia may be associated with an increased risk of several types of second cancers.

Feasibility and safety of the posterior retroperitoneoscopic approach in the resection of aortocaval and infrarenal paraganglioma: a single-center experience.

BACKGROUND: The posterior retroperitoneoscopic approach (PRA) has been under attention as a method for resection of paraganglioma (PGL) for the past few years. However, only a few studies have explored the effectiveness and safety of the PRA for aortocaval and infrarenal PGL resection. METHODS: We designed this retrospective study to investigate the safety and effectiveness of the PRA for aortocaval and infrarenal PGL resection in a single center. We retrospectively reviewed the medical records of patients who underwent PRA for PGL resection at our medical center from January 2006 to March 2021. Eight patients were enrolled, of whom six had aortocaval PGL. We investigated the surgical outcomes of enrolled patients. RESULTS: The locations of the tumors in relation to the renal vein were: suprarenal in two (25.0%) patients, at the renal vein level in three (37.5%) patients, and infrarenal in three (37.5%) patients. The mean operative time of the enrolled patients was 101.5 ± 39.1 min. The mean postoperative stay was 3.5 ± 1.5 days, and the estimated blood loss was 31.3 ± 51.4 ml. There was one minor complication (chyle leakage), and two hypotensive events occurred during the surgery. Focusing on the results of the renal vein level and infrarenal PGL resection, the mean operative time, mean postoperative stay, and estimated blood loss of the patients were 109.2 ± 41.3 min, 3.5 ± 1.8 days, and 41.7 ± 56.4 ml, respectively. CONCLUSION: The PRA for aortocaval and infrarenal PGL resection is feasible and safe. Additional data analysis and long-term follow-up are needed in the future.

Correction to: Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

The article "Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution", written by Kim et al., was originally published electronically on the publisher's internet portal (currently SpringerLink) on May 21, 2020, with open access. With the authors' decision to step back from Open Choice, the copyright of the article changed on September 14, 2020 to © Société Internationale de Chirurgie 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

Clinical Assessment of Pediatric Patients with Differentiated Thyroid Carcinoma: A 30-Year Experience at a Single Institution.

BACKGROUND: Thyroidectomy is the typical treatment for pediatric thyroid carcinoma; total thyroidectomy is commonly performed. We aimed to report our experience at a single tertiary institution and to evaluate the risk factors for recurrence, especially based on surgical extent, in pediatric patients with differentiated thyroid carcinoma (DTC). METHODS: A data of 94 pediatric patients who underwent thyroid surgery for DTC from January 1982 to December 2012 at Yonsei University Hospital (Seoul, Korea) were reviewed. The clinicopathologic features and surgical outcomes were retrospectively analyzed through complete chart reviews. RESULTS: The mean age was 16.6 ± 3.0 (range, 5-19) years. Fourteen patients had recurrence. Tumor size >2 cm (hazard ratio [HR], 14.241; p = 0.011) and positive lymph nodes (HR, 1.056; p = 0.039) were significant risk factors for disease-free survival (DFS) in multivariate analysis. In Kaplan-Meier analysis, a statistically significant difference was noted in the DFS according to tumor size 2 cm (p < 0.001). However, the DFS was not significantly different between the bilateral total thyroidectomy (BTT) and less than BTT groups (p = 0.215). CONCLUSIONS: BTT remains the treatment of choice in pediatric patients with DTC. Lobectomy may be considered for patients with limited disease, including those with tumor size <2 cm, no suspicious lymph nodes, intrathyroidal lesion, and no multifocal disease.

Robotic Transaxillary Hemithyroidectomy Using the da Vinci SP Robotic System: Initial Experience With 10 Consecutive Cases.

Background: Many studies have shown the operative feasibility and safety of robotic thyroidectomy. However, there is still a concern on the operative invasiveness of robotic thyroidectomy owing to the wide flap dissection. The aim of this study was to introduce our novel robotic technique, which can minimize the dissection extent using the da Vinci SP robotic system. Methods: Ten patients underwent robotic transaxillary thyroidectomy using the da Vinci SP robotic system between December 2018 and April 2019 at Yonsei University Hospital (Seoul, Korea). All procedures were performed successfully using the single-port robotic system. Results: All 10 patients were women and diagnosed with papillary thyroid carcinoma. The mean operative time was 148.7 ± 26.8 minutes. The mean operative time using the gasless method was shorter than that using the gas insufflation method (130.5 ± 14.1 vs 176.0 ± 12.8 minutes). All patients were discharged on the third day after operation without any complications. Conclusions: Robotic transaxillary thyroidectomy using the da Vinci SP robotic system is technically feasible and safe with a short length of incision, shorter than what earlier reported. To our knowledge, this is the first study to use a single-port robotic system for thyroidectomy. To verify the superior operative outcomes, further clinical trials are necessary.

The Prognosis of Papillary Thyroid Cancer with Initial Distant Metastasis is Strongly Associated with Extensive Extrathyroidal Extension: A Retrospective Cohort Study.

BACKGROUND: Extensive extrathyroidal extension (ETE) has a significant role in the prognosis of papillary thyroid cancer (PTC) without distant metastasis, but its role in PTC with initial distant metastasis has never been studied. This study aimed to evaluate the prognostic significance of extensive ETE regarding disease progression, survival, and remission in PTC patients with initial distant metastasis. METHODS: This retrospective cohort study included PTC patients with initial distant metastasis who underwent total thyroidectomy with a median follow-up period of 6.7 years. The prognostic significance of extensive ETE was assessed in terms of time to tumor progression (TTP), cancer-specific survival (CSS), and cumulative incidence of remission with all-cause death as the competing event. RESULTS: The study enrolled 64 patients. Of these patients, 21 (32.8%) had extensive ETE, which was associated with a shorter TTP (adjusted hazard ratio [HR], 4.10; p = 0.015) and a lower CSS rate (p = 0.002, log-rank), particularly for patients 55 years of age or older with stage 4b disease (10-year CSS rate: 33.3% in those with and 92.3% in those without extensive ETE; p = 0.017). Additionally, remission was observed only in patients without extensive ETE (10-year cumulative incidence of remission: 0.0% in those with and 29.3% in those without extensive ETE; p = 0.013). CONCLUSIONS: Extensive ETE of the primary lesion results in poorer prognoses for PTC patients with initial distant metastasis. The high CSS rate for patients with stage 4b PTC but no extensive ETE indicates that the prognosis of this patient population should be distinguished from that of other stage 4 cases.

Clinical outcomes of parathyroidectomy versus cinacalcet in the clinical management of secondary hyperparathyroidism.

Parathyroidectomy (PTX) is the standard treatment for secondary hyperparathyroidism (SHPT); however, the administration of cinacalcet has gained prominence as a noninvasive treatment. We aimed to determine whether PTX or cinacalcet is more effective in preventing morbidity and mortality through reviewing follow-up data concerning surgical management of SHPT. We retrospectively analyzed and divided 209 patients with SHPT into two treatment groups: PTX (n = 78) and cinacalcet (n = 131) groups. We compared clinical features, the over-the-target range rate during pre- and post-intervention periods, new cardiovascular events, and all-cause mortality between both groups. Almost all biochemical parameters were well controlled in the post-intervention period, and were within the recommended target range for the PTX group but not for the cinacalcet group. A significant difference was observed in the over-the-target range rate during the post-intervention period between the groups. PTX and cinacalcet interventions significantly lowered the over-the-target range rates for serum intact parathyroid hormone (iPTH) (>300 pg/mL), corrected calcium (>10.5 mg/mL), serum phosphorus (>5.5 mg/dL), and calcium-phosphorus product (>55) in both groups (p = 0.001). PTX reduced the risk of new cardiovascular events by 86% compared to cinacalcet (p = 0.001); however, all-cause mortality did not differ significantly (14.1% vs. 7.6%, p = 0.132). For patients with SHPT, PTX helps prevent cardiovascular events through normalizing biochemical variables, according to recommended guidelines. PTX should be considered before cinacalcet treatment to prevent new cardiovascular events. Early PTX for appropriate patients can help prevent immediate postoperative complications and mortality.

Yonsei Experience of 5000 Gasless Transaxillary Robotic Thyroidectomies.

BACKGROUND: Since the use of robot systems in thyroid surgery was introduced in 2007, we have advanced a novel method of robotic thyroidectomy (RT) using a gasless transaxillary approach (TAA). We report our experience with this technique and detail the surgical outcome of 5000 robotic thyroidectomies. METHODS: From October 2007 to May 2016, we successfully performed 5000 robotic thyroidectomies using a gasless TAA at the Department of Surgery, Yonsei University Health System. The medical records of the patients are reviewed retrospectively, and the details of clinicopathologic characteristics, operation times, perioperative complications, and oncologic outcomes are analyzed. RESULTS: The 5000 patients with thyroid tumor (4804 with cancer and 196 with benign tumor) underwent RT using a gasless TAA. Mean operation time was 134.5 ± 122.0 min. The most common histologic subtype of thyroid cancer was papillary (98%), and the mean tumor size was 8.0 ± 6.0 mm. Stage I was found in 85.4% patients regarding tumor nodes metastasis staging. The 196 benign tumors consisted of 104 adenomatous hyperplasias (53.0%), 43 follicular adenomas (21.9%), 30 Graves' diseases (15.3%), and 19 others (9.7%). Postoperative complication occurred in 24.1% without any serious one, and overall morbidity tended to decrease over time. No disease-specific mortality was observed during the follow-up period. Locoregional recurrence was developed in 26 patients (0.5%). CONCLUSION: The authors have tried to improve RT technique using gasless TAA and achieved acceptable surgical outcomes. The rapid evolution of surgical robot technology and our constant effort to advance RT technique using gasless TAA would make it possible to reduce the perioperative morbidity and gain the best possible operative and oncologic outcomes.

Whole Exome Sequencing Identifies a Novel Hedgehog-Interacting Protein G516R Mutation in Locally Advanced Papillary Thyroid Cancer.

Locally advanced thyroid cancer exhibits aggressive clinical features requiring extensive neck dissection. Therefore, it is important to identify changes in the tumor biology before local progression. Here, whole exome sequencing (WES) using tissues from locally advanced papillary thyroid cancer (PTC) presented a large number of single nucleotide variants (SNVs) in the metastatic lymph node (MLN), but not in normal tissues and primary tumors. Among those MLN-specific SNVs, a novel HHIP G516R (G1546A) mutation was also observed. Interestingly, in-depth analysis for exome sequencing data from the primary tumor presented altered nucleotide 'A' at a very low frequency indicating intra-tumor heterogeneity between the primary tumor and MLN. Computational prediction models such as PROVEAN and Polyphen suggested that HHIP G516R might affect protein function and stability. In vitro, HHIP G516R increased cell proliferation and promoted cell migration in thyroid cancer cells. HHIP G516R, a missense mutation, could be a representative example for the intra-tumor heterogeneity of locally advanced thyroid cancer, which can be a potential future therapeutic target for this disease.

Transaxillary robotic modified radical neck dissection: a 5-year assessment of operative and oncologic outcomes.

BACKGROUND: Robotic modified radical neck dissection (MRND) using a gasless transaxillary approach has been reported to be a safe and meticulous technique in patients with papillary thyroid carcinoma (PTC) and lateral neck node metastasis (N1b). Few studies, however, have attempted to assess the long-term oncologic outcomes of robotic MRND in these patients. This study aimed to compare perioperative and 5-year oncologic outcomes of robotic MRND with conventional open procedures in patients with N1b PTC. METHODS: Between September 2007 and February 2010, 193 patients with N1b PTC underwent total thyroidectomy and MRND by a single surgeon. Of these, 42 (21.8 %) underwent robotic procedures and 151 (78.2 %) underwent conventional open procedures. All patients received 3.7- to 5.5-GBq radioactive iodine (RAI) ablation, post-therapy whole-body scans (TxWBSs), and diagnostic WBS (DxWBSs) during follow-up. An exact 1:3 matching for age and stage was performed to minimize selection bias, and perioperative and 5-year oncologic outcomes were compared in the matched groups. RESULTS: The mean follow-up period was 66.0 months (range 60-90 months). Number of retrieved cervical lymph nodes (LNs) (p = .102) and postoperative ablation success rates (p = .864) were similar between the two groups. TSH-suppressed serum Tg concentrations after 5 years (0.7 ± 1.5 vs. 2.4 ± 14.1 ng/ml; p = .471) and recurrence rates in the robotic and open groups (1/41 [2.4 %] vs. 3/102 [2.9 %]; p = .864) were similar for the 5-year follow-up period. Four patients experienced recurrence: Three exhibited regional lymph node metastasis, and one showed bilateral lung metastases. CONCLUSION: The perioperative and 5-year oncologic outcomes were similar after robotic and conventional open MRND. Large, prospective randomized controlled trials with long-term follow-up data are needed to validate these results.

Long-term oncologic outcome of robotic versus open total thyroidectomy in PTC: a case-matched retrospective study.

PURPOSE: The role of the robot in thyroid surgery remains uncertain, and it is unclear whether robotic total thyroidectomy (R-TT) can be justified as a standard treatment for patients with thyroid cancer. This study compared the long-term operative results and oncologic outcomes of R-TT and conventional open TT (O-TT) after propensity score matching of the cohorts. METHODS: This study retrospectively evaluated patients with papillary thyroid cancer (PTC) who underwent TT with central compartment node dissection (CCND) by a single surgeon in tertiary medical center. Of the 833 patients, 94 (11.3 %) were lost to follow-up. 245 (33.2 %) underwent R-TT, and 494 (66.8 %) underwent O-TT. The mean follow-up duration was 74 (range 61-91) months. Propensity score matching in age, gender, tumor size, extrathyroidal invasion, multiplicity, bilaterality, and TNM stage identified 206 pairs of patients. The long-term oncologic outcomes were assessed in the R-TT and O-TT groups before and after adjustment for baseline covariates. RESULTS: After adjustment for baseline covariates, serum thyroglobulin (Tg) (p = 0.746) and anti-thyroglobulin antibody (TgAb) (p = 0.394) concentrations were similar in the two groups 5 years after surgery. Nine patients experienced locoregional recurrence, six in the O-TT and three in the R-TT group, with all recurrences in regional LNs. Disease-free survival (DFS) was similar in the R-TT and O-TT groups before matching (p = 0.890) and after adjustment for baseline covariates (p = 0.882). CONCLUSION: This represents the first report of 5-year surgical outcomes in patients who underwent R-TT for thyroid cancer. Long-term oncologic quality was similar after R-TT and O-TT.

Association Between Obesity and BRAFV600E Mutation Status in Patients with Papillary Thyroid Cancer.

BACKGROUND: The prevalence of papillary thyroid cancer (PTC) is thought to be related to obesity, which affects the prognosis for PTC patients. However, the mechanisms implicated in the relationship between obesity and PTC is a matter for debate. In this study, we aimed to gain insight into the relationship between obesity and the clinicopathological features of PTC, including the BRAFV600E mutation. METHODS: The medical records of 1121 PTC patients were reviewed and the relationships between anthropometric factors, biochemical parameters, and clinicopathological parameters, including BRAFV600E mutation status, were analyzed. RESULTS: Body mass index (BMI) showed a strong association with advanced TNM stage (p < 0.001) and BRAFV600E mutation status (p = 0.008). We also found that BRAFV600E (+) patients had a higher body weight (p = 0.024) and a higher BMI (p = 0.003) than patients with BRAFV600E (-) PTC. In addition, BRAFV600E (+) PTC patients had a significantly higher incidence of extrathyroidal extension (p = 0.025) and more advanced T, N, TNM stage (p < 0.001) than BRAFV600E (-) PTC patients. Consistent with this observation, female BRAFV600E (+) PTC patients had a higher BMI (p = 0.011) and more aggressive tumor behaviors than female BRAFV600E (-) PTC patients. In multivariate analysis, BMI was persistently associated with BRAFV600E mutation in the entire cohort (odds ratio [OR] 1.387; 95 % CI 1.036-1.859; p = 0.028) and in the female subcohort (OR 1.221; 95 % CI 1.014-1.631; p = 0.046). CONCLUSION: The positive association between BMI and BRAFV600E supports the hypothesis that excessive bodyweight influences tumor progression.

A comparison of postoperative pain after conventional open thyroidectomy and transaxillary single-incision robotic thyroidectomy: a prospective study.

BACKGROUND: The aim of this study was to compare conventional open thyroidectomy with robotic thyroidectomy in terms of postoperative pain. METHODS: We compared the intensity of postoperative pain experienced by patients who received conventional open thyroidectomy (n = 45) versus those who underwent robotic thyroidectomy (n = 45). During surgery, we carefully controlled the anesthetic conditions. All the patients underwent a total thyroidectomy with ipsilateral central compartment node dissection. Postoperative pain in the 2 groups was compared using a visual analog scale and the amount of rescue analgesic at 30 min, 4 h, 1, 2, 3, and 10 days after surgery. RESULTS: The postoperative pain at 30 min and 4 h after surgery were 3.0 ± 0.9 and 2.6 ± 0.9 (p = .066) and 4.9 ± 1.3 and 4.4 ± 1.3 (p = .055) in the conventional open group and the robotic group, respectively. The mean pain scores at 1, 2, 3, and 10 days after surgery were 3.8 ± 1.3 and 3.0 ± 1.3 (p = .001), 2.6 ± 1.2 and 2.0 ± 0.9 (p = .005), 1.7 ± 0.9 and 1.3 ± 0.6 (p = .034), and 0.9 ± 0.7 and 1.2 ± 1.1 (p = .093), respectively. No significant differences were observed between the 2 groups in terms of postoperative rescue analgesic use (1.1 ± 1.1 and 0.8 ± 0.9, p = .264). CONCLUSIONS: Even though robotic thyroidectomy using the transaxillary technique requires a more extensive subcutaneous dissection than conventional open thyroidectomy, robotic thyroidectomy does not result in more postoperative pain or use of analgesic when compared with open thyroidectomy.

Impact of thyroid hormone replacement on the risk of second cancer after thyroidectomy: a Korean National Cohort Study.

We aimed to investigate the effect of thyroid hormone administration on the risk of second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer. Data were extracted from the medical billing data of the Health Insurance Review and Assessment Service in South Korea. Patients between 19 and 80 years old who underwent thyroid surgery at least once between January 2009 and June 2020 were included. Data of patients with second primary cancer and control patients with matched age, sex, operation date, and follow-up duration were extracted at a ratio of 1:4. A nested case-control analysis was performed to exclude length bias to confirm the correlation between the duration of thyroid hormone administration, dose, and incidence of second primary cancer. Of the 261,598 patients who underwent surgery for thyroid cancer included in the study, 11,790 with second primary cancer and 47,160 without second primary cancer were matched. The average dose of thyroid hormone increased the adjusted odds ratio (OR) for both low (≤ 50 µg, OR 1.29, confidence interval (CI) 1.12-1.48) and high (< 100 µg, OR 1.24, CI 1.12-1.37) doses. Analyzing over time, the adjusted OR of second primary cancer increased, especially in short (≤ 1 year) (OR 1.19; CI 1.06-1.34) and long (> 5 years) duration (OR 1.25; CI 1.10-1.41). In conclusion, insufficient and excessive thyroid hormone replacement might be linked to increased second primary cancer in patients who underwent thyroidectomy for differentiated thyroid cancer.

Impact of thyroid cancer on the cancer risk in patients with non-alcoholic fatty liver disease or dyslipidemia.

The raised prevalence of obesity has increased the incidence of obesity-related metabolic diseases such as dyslipidemia (DL) and non-alcoholic fatty liver disease (NAFLD), along with the development and progression of various types of cancer, including thyroid cancer. In this study, we investigated whether thyroid cancer in patients with DL and NAFLD could be a risk factor for other cancers. To achieve our goal, we generated two independent cohorts from our institution and from the National Health Insurance System in South Korea. Based on the ICD-10 code, we conducted exact matching (1:5 matching) and estimated the overall risk of thyroid cancer for other cancers in patients with DL or NAFLD. Univariate and multivariate analyses showed that the hazard ratio (HR) of thyroid cancer was 2.007 (95% Confidence Interval [CI], 1.597-2.522) and 2.092 (95% CI, 1.546-2.829), respectively in the institutional cohort and 1.329 (95% CI, 1.153-1.533) and 1.301 (95% CI, 1.115-1.517), respectively in the nationwide cohort. Risk analysis revealed a significant increase in the HR in lip, tongue, mouth, lung, bone, joint, soft tissue, skin, brain, male cancers and lymphoma after thyroid cancer occurred. Thyroid cancer in patients with DL or NAFLD might be a valuable factor for predicting the development of other cancers.

Comparative Analysis of Driver Mutations and Transcriptomes in Papillary Thyroid Cancer by Region of Residence in South Korea.

BACKGRUOUND: Radiation exposure is a well-known risk factor for papillary thyroid cancer (PTC). South Korea has 24 nuclear reactors in operation; however, no molecular biological analysis has been performed on patients with PTC living near nuclear power plants. METHODS: We retrospectively included patients with PTC (n=512) divided into three groups according to their place of residence at the time of operation: inland areas (n=300), coastal areas far from nuclear power plants (n=134), and nuclear power plant areas (n=78). After propensity score matching (1:1:1) by age, sex, and surgical procedure, the frequency of representative driver mutations and gene expression profiles were compared (n=50 per group). Epithelial-mesenchymal transition (EMT), BRAF, thyroid differentiation, and radiation scores were calculated and compared. RESULTS: No significant difference was observed in clinicopathological characteristics, including radiation exposure history and the frequency of incidentally discovered thyroid cancer, among the three groups. BRAFV600E mutation was most frequently detected in the groups, with no difference among the three groups. Furthermore, gene expression profiles showed no statistically significant difference. EMT and BRAF scores were higher in our cohort than in cohorts from Chernobyl tissue bank and The Cancer Genome Atlas Thyroid Cancer; however, there was no difference according to the place of residence. Radiation scores were highest in the Chernobyl tissue bank but exhibited no difference according to the place of residence. CONCLUSION: Differences in clinicopathological characteristics, frequency of representative driver mutations, and gene expression profiles were not observed according to patients' region of residence in South Korea.

Immune response and mesenchymal transition of papillary thyroid carcinoma reflected in ultrasonography features assessed by radiologists and deep learning.

INTRODUCTION: Ultrasonography (US) features of papillary thyroid cancers (PTCs) are used to select nodules for biopsy due to their association with tumor behavior. However, the molecular biological mechanisms that lead to the characteristic US features of PTCs are largely unknown. OBJECTIVES: This study aimed to investigate the molecular biological mechanisms behind US features assessed by radiologists and three convolutional neural networks (CNN) through transcriptome analysis. METHODS: Transcriptome data from 273 PTC tissue samples were generated and differentially expressed genes (DEGs) were identified according to US feature. Pathway enrichment analyses were also conducted by gene set enrichment analysis (GSEA) and ClusterProfiler according to assessments made by radiologists and three CNNs - CNN1 (ResNet50), CNN2 (ResNet101) and CNN3 (VGG16). Signature gene scores for PTCs were calculated by single-sample GSEA (ssGSEA). RESULTS: Individual suspicious US features consistently suggested an upregulation of genes related to immune response and epithelial-mesenchymal transition (EMT). Likewise, PTCs assessed as positive by radiologists and three CNNs showed the coordinate enrichment of similar gene sets with abundant immune and stromal components. However, PTCs assessed as positive by radiologists had the highest number of DEGs, and those assessed as positive by CNN3 had more diverse DEGs and gene sets compared to CNN1 or CNN2. The percentage of PTCs assessed as positive or negative concordantly by radiologists and three CNNs was 85.6% (231/273) and 7.1% (3/273), respectively. CONCLUSION: US features assessed by radiologists and CNNs revealed molecular biologic features and tumor microenvironment in PTCs.