Tae-Yon Sung’s research while affiliated with University of Ulsan and other places

Purpose Pediatric papillary thyroid cancer (PTC) is recommended to perform aggressive surgery to reduce the risk of recurrence. This study was designed to evaluate the concurrent association between multifocality, bilaterality, and the risk of recurrence in pediatric PTC. Materials and Methods This retrospective cohort study included pediatric patients (age <19 years) who underwent total thyroidectomy for PTC between 1996 and 2014 in a single tertiary center. Clinicopathological parameters were analyzed to evaluate the prevalence of multifocality, bilaterality, recurrence, and their association. Results We analyzed 58 pediatric patients with PTC. There was no factor related to the presence of multifocality or bilaterality in multivariate analysis. Also, in univariate analysis, multifocality and bilaterality were not independent risk factors of each other’s presentation (p=0.061 and p=0.061, respectively). Recurrence was observed in 19 (32.8%) patients. In multivariate analysis of recurrence, clear cell subtype, multifocality, and gross extrathyroidal extension (ETE) were independent risk factors (p=0.027, p=0.035, and p=0.038, respectively). Most recurrences (68.4%) happened during the first 4 years of follow-up after the initial thyroidectomy. Conclusion Multifocality and bilaterality were not independent risk factors of each other’s presentation; however, multifocality was the risk factor for recurrence in pediatric PTC. For pediatric PTC, close monitoring for recurrence within the initial 4 years is recommended, particularly in patients with clear cell subtype, multifocality, and gross ETE.

The impact of obesity on outcomes after adrenalectomy for pheochromocytoma is unclear. This study aims to evaluate outcomes after minimally invasive and open adrenalectomy for pheochromocytoma in patients with obesity and to determine factors that may affect outcomes. Patients undergoing adrenalectomy for pheochromocytoma in 46 international centers between 2012 and 2022 were reviewed, analyzing baseline information, length of hospital stay (LOS), and postoperative complications. Obese (body mass index (BMI) ≥ 30 kg/m2) and nonobese patients were compared. Multivariable analysis was utilized to evaluate outcomes and risk factors for complications, LOS, and increased comprehensive complication index (CCI). Of the 2016 patients, 639 (31.7%) had obesity. Operative time (110.0 versus 105.0 min; p = 0.467), conversion to open rate (3.1% versus 4.7%; p = 0.079), estimated blood loss (20.0 versus 20.0 ml, p = 0.088), rate of complications (19.3% versus 20.8%; p = 0.425), and CCI were similar. However, patients with obesity required a median of 1 day longer LOS (4.0 days versus 5.0 days; p < 0.001). On multivariable analysis, obesity was not significantly associated with complications or higher CCI. Analyzing solely obese patients, laparoscopic (OR 0.24; p < 0.001) and robotic (OR 0.22; p = 0.011) approaches were independently associated with less morbidity. Additionally, multivariable modeling demonstrated that a retroperitoneal approach in patients with BMI ≥ 30 kg/m2 was independently associated with reduced CCI (− 3.74; p = 0.017). Similar results were demonstrated when analyzing severe obesity (BMI ≥ 35). Obesity does not increase complications or CCI following pheochromocytoma resection, but it does increase LOS. A retroperitoneal approach may uniquely benefit patients with obesity. In view of rising obesity rates, these results warrant further research to validate findings.

Backgruound: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by tumors in multiple endocrine organs, caused by variants in the MEN1 gene. This study analyzed the clinical and genetic features of MEN1 in a Korean cohort, identifying prevalent manifestations and genetic variants, including novel variants. Methods: This multicenter retrospective study reviewed the medical records of 117 MEN1 patients treated at three tertiary centers in Korea between January 2012 and September 2022. Patient demographics, tumor manifestations, outcomes, and MEN1 genetic testing results were collected. Variants were classified using American College of Medical Genetics and Genomics (ACMG) and French Oncogenetics Network of Neuroendocrine Tumors propositions (TENGEN) guidelines. Results: A total of 117 patients were enrolled, including 55 familial cases, with a mean age at diagnosis of 37.4±15.3 years. Primary hyperparathyroidism was identified as the most common presentation (84.6%). The prevalence of gastroenteropancreatic neuroendocrine tumor and pituitary neuroendocrine tumor (PitNET) was 77.8% (n=91) and 56.4% (n=66), respectively. Genetic testing revealed 61 distinct MEN1 variants in 101 patients, with 18 being novel. Four variants were reclassified according to the TENGEN guidelines. Patients with truncating variants (n=72) exhibited a higher prevalence of PitNETs compared to those with non-truncating variants (n=25) (59.7% vs. 36.0%, P=0.040). Conclusion: The association between truncating variants and an increased prevalence of PitNETs in MEN1 underscores the importance of genetic characterization in guiding the clinical management of this disease. Our study sheds light on the clinical and genetic characteristics of MEN1 among the Korean population.

The continued advancement of targeted therapies for actionable gene rearrangements has increased the demand for cost-effective screening methods for detecting these gene rearrangements in papillary thyroid carcinoma (PTC). Herein, ribonucleic acid (RNA) sequencing was performed on 106 patients with PTC having wild-type BRAF . The patients were divided into two groups: Group 1 (n = 58) included patients selected by an endocrine pathologist based on characteristic pathological features, including multinodular invasive growth, prominent intratumoral stromal fibrosis, mixed-growth patterns with varying degrees of nuclear atypia, pale eosinophilic to clear cytoplasm, and/or multiple lymph node (LN) metastasis. These patients were prescreened and then subjected to pan-tyrosine receptor kinase (TRK) immunohistochemistry (IHC) staining and RNA sequencing. In Group 2, RNA sequencing was conducted on samples from 48 randomly selected patients. Gene rearrangements were identified in 66 patients (62.3%), with a significantly higher proportion in Group 1 (77.6%) than in Group 2 (43.8%) ( p < 0.001). NTRK was the most common gene rearrangement, which was detected in 31 patients (29.2%). The second most common gene rearrangement was RET (18.9%), followed by ALK (9.4%), and then BRAF (2.8%). Patients with gene rearrangements were significantly younger and had smaller primary tumors, although they demonstrated greater extrathyroidal extension and LN metastasis than those without rearrangements. Pan-TRK IHC revealed a sensitivity of 52% and a specificity of 94% for the prediction of NTRK gene rearrangements. This study demonstrates that pathological screening combined with pan-TRK IHC is a cost-effective method for examining targetable gene rearrangements in patients with PTC having wild-type BRAF.

Purpose Adrenocortical carcinoma (ACC) is a rare primary carcinoma originating in the adrenal gland with a poor prognosis and a high recurrence rate. This study evaluated the risk factors associated with recurrence in patients with early stage ACC after curative surgical resection. Methods The present study retrospectively evaluated the risk factors for recurrence in 38 patients with stages 1 and 2 ACC who underwent curative resection between 1995 and 2020. Results Recurrence was observed in 21 patients (55.3%), with no significant difference between stages 1 and 2 ACC (P = 0.640). The overall recurrence rate was higher in patients who underwent minimally invasive surgery than open adrenalectomy (71.4% vs. 51.6%). Of the 33 patients with gross tumor margins negative for malignancy, 16 (48.5%) experienced tumor recurrence, and all 5 patients with positive and unknown gross resection margins had recurrence. Recurrences were observed in 14 of the 30 patients (46.7%) negative for pathologic resection margins, 6 of the 7 patients (85.7%) with pathologically indeterminate margins, and 1 patient with pathologically positive margins. Conclusion The recurrence rates are high even in patients with early stage ACC, being higher in patients who undergo minimally invasive surgery than open adrenalectomy. Obtaining clear resection margins during surgery may reduce tumor recurrence; however, gross or pathologic margin safety was not a secure factor in preventing recurrence. None of the factors analyzed was a definitive predictor of poor prognosis.

Background: Adrenocortical carcinomas (ACCs) are rare tumors with aggressive but varied prognosis. Stage, Grade, Resection status, Age, Symptoms (S-GRAS) score, based on clinical and pathological factors, was found to best stratify the prognosis of European ACC patients. This study assessed the prognostic performance of modified S-GRAS (mS-GRAS) scores including modified grade (mG) by integrating mitotic counts into the Ki67 index (original grade), in Korean ACC patients. Methods: Patients who underwent surgery for ACC between January 1996 and December 2022 at three medical centers in Korea were retrospectively analyzed. mS-GRAS scores were calculated based on tumor stage, mG (Ki67 index or mitotic counts), resection status, age, and symptoms. Patients were divided into four groups (0-1, 2-3, 4-5, and 6-9 points) based on total mS-GRAS score. The associations of each variable and mS-GRAS score with recurrence and survival were evaluated using Cox regression analysis, Harrell's concordance index (C-index), and the Kaplan-Meier method. Results: Data on mS-GRAS components were available for 114 of the 153 patients who underwent surgery for ACC. These 114 patients had recurrence and death rates of 61.4% and 48.2%, respectively. mS-GRAS score was a significantly better predictor of recurrence (C-index=0.829) and death (C-index=0.747) than each component (P<0.05), except for resection status. mS-GRAS scores correlated with shorter progression-free survival (P=8.34E-24) and overall survival (P=2.72E-13). Conclusion: mS-GRAS scores showed better prognostic performance than tumor stage and grade in Asian patients who underwent surgery for ACC.

Background: Longer follow-up after radiofrequency ablation (RFA) of benign thyroid nodules is needed to understand regrowth and other causes of delayed surgery and long-term complications. Methods: This retrospective study included consecutive patients treated with RFA for symptomatic benign nonfunctioning thyroid nodules between March 2007 and December 2010. RFA was performed according to the standard protocol. We followed up patients at 1, 6, and 12 months, then yearly, until August 2022, and calculated the volume reduction ratio (VRR) at each follow-up. We assessed the incidence of regrowth according to three published criteria, delayed surgery, and complications. The Kaplan-Meier method was used to evaluate the cumulative incidence of regrowth, and univariable and multivariable Cox regression analyses were performed to identify risk factors for regrowth. Results: This study included 421 patients (mean age, 47 ± 13 years; 372 women) with 456 nodules (mean volume, 21 ± 23 mL). The median follow-up period was 90 months (interquartile range, 24-143 months). The mean VRR was 81% at 2 years, 90% at 5 years, and 94% at ≥10 years. Overall regrowth was noted in 12% (53/456) of nodules and was treated with repeat RFA (n = 33) or surgery (n = 4) or left under observation (n = 16). Thyroid nodules with ≥20 mL initial volume had significantly higher risk of regrowth compared with nodules with <10 mL initial volume (hazard ratio, 2.315 [95% confidence interval, 1.183-4.530]; p = 0.014 on multivariable Cox regression analysis). Delayed surgery was performed in 6% (26/421) of patients because of regrowth and/or persistent symptoms (n = 4) or newly detected thyroid tumors (n = 22), one benign and 21 malignant. The overall complication rate was 2.4% (10/421), with no procedure-related deaths or long-term complications. Conclusion: RFA is safe and effective for treating benign thyroid nodules, with a high VRR at long-term follow-up. Regular follow-up after initial success is warranted because of the possibility of regrowth of ablated nodules and the need for delayed surgery in some patients.

To investigate the diagnostic performance and interobserver agreement of quantitative CT parameters indicating strong lymph node (LN) enhancement in differentiated thyroid cancer (DTC), comparing them with qualitative analysis by radiologists of varying experience. This study included 463 LNs from 399 patients with DTC. Three radiologists independently analyzed strong LN enhancement on CT. Qualitative analysis of strong enhancement was defined as LN cortex showing greater enhancement than adjacent muscles on the arterial phase. Quantitative analysis included the mean attenuation value (MAV) of LN on arterial phase (LNA) and venous phase (LNV), LNA normalized to the common carotid artery (NAVCCA), internal jugular vein (NAVIJV), and sternocleidomastoid muscle (NAVSCM), attenuation difference [AD; (LNA − MAVSCM)], and relative washout ratio [((LNA − LNV)/LNA) × 100]. The interobserver agreement and diagnostic performance of the quantitative and qualitative analyses were evaluated. Interobserver agreement was excellent for all quantitative CT parameters (ICC, 0.83–0.94) and substantial for qualitative assessment (κ = 0.61). All CT parameters except for LNV showed good diagnostic performance for metastatic LNs (AUC, 0.81–0.85). NAVCCA (0.85, 95% CI: 0.8–0.9) and AD (0.85, 95% CI: 0.81–0.89) had the highest AUCs. All quantitative parameters except for NAVIJV had significantly higher AUCs than qualitative assessments by inexperienced radiologists, with no significant difference from assessments by an experienced radiologist. Quantitative assessment of LN enhancement on arterial phase CT showed higher interobserver agreement and AUC values than qualitative analysis by inexperienced radiologists, supporting the need for a standardized quantitative CT parameter-based model for determining strong LN enhancement. When assessing strong LN enhancement in DTC, quantitative CT parameters indicating strong enhancement can improve interobserver agreement, regardless of experience level. Therefore, the development of a standardized diagnostic model based on quantitative CT parameters might be necessary. Accurate preoperative assessment of LN metastasis in thyroid cancer is crucial. Quantitative CT parameters indicating strong LN enhancement demonstrated excellent interobserver agreement and good diagnostic performance. Quantitative assessment of contrast enhancement offers a more objective model for the identification of metastatic LNs.