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.

Effectiveness of regdanvimab on mortality in COVID-19 infected patients on hemodialysis.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (COVID-19), there are lack of effective and proven treatments for end-stage renal disease (ESRD). The present study aims to evaluate the effectiveness of regdanvimab on mortality in COVID-19-infected patients on hemodialysis (HD). METHODS: We conducted an observational retrospective study in 230 COVID-19-infected patients on HD, of whom 77 (33.5%) were administered regdanvimab alone or in combination with dexamethasone or remdesivir during hospitalization (regdanvimab group) and 153 patients (66.5%) were not (no regdanvimab group). The primary outcome was in-hospital mortality. We compared mortality rates according to the use of regdanvimab and investigated the factors associated with mortality. RESULTS: Fifty-nine deaths occurred during hospitalization, 49 in the no regdanvimab group (32.0%) and 10 in the regdanvimab group (13.0%), and the mortality rate was significantly higher in the no regdanvimab group than that in the regdanvimab group (p = 0.001). Multivariate Cox regression analysis showed that malignancy (p = 0.001), SPO2 of <95% at admission (p = 0.003), and administration of antibiotics and regdanvimab (p = 0.007 and p = 0.002, respectively) were significantly associated factors with mortality. CONCLUSION: Regdanvimab administration is beneficial in improving prognosis in hospitalized COVID-19 patients on HD. Considering the vulnerability to infection and high mortality of ESRD patients, regdanvimab may be considered as a therapeutic option in COVID-19 patients on HD.

Machine-learning-based diagnosis of thyroid fine-needle aspiration biopsy synergistically by Papanicolaou staining and refractive index distribution.

We developed a machine learning algorithm (MLA) that can classify human thyroid cell clusters by exploiting both Papanicolaou staining and intrinsic refractive index (RI) as correlative imaging contrasts and evaluated the effects of this combination on diagnostic performance. Thyroid fine-needle aspiration biopsy (FNAB) specimens were analyzed using correlative optical diffraction tomography, which can simultaneously measure both, the color brightfield of Papanicolaou staining and three-dimensional RI distribution. The MLA was designed to classify benign and malignant cell clusters using color images, RI images, or both. We included 1535 thyroid cell clusters (benign: malignancy = 1128:407) from 124 patients. Accuracies of MLA classifiers using color images, RI images, and both were 98.0%, 98.0%, and 100%, respectively. As information for classification, the nucleus size was mainly used in the color image; however, detailed morphological information of the nucleus was also used in the RI image. We demonstrate that the present MLA and correlative FNAB imaging approach has the potential for diagnosing thyroid cancer, and complementary information from color and RI images can improve the performance of the MLA.

Mortality and Risk Factors in Very Elderly Patients Who Start Hemodialysis: Korean Renal Data System, 2016-2020.

INTRODUCTION: The number of elderly patients with end-stage renal disease (ESRD) is increasing worldwide. However, decision-making about elderly patients with ESRD remains complex because of the lack of studies, especially in very elderly patients (≥75 years). We examined the characteristics of very elderly patients starting hemodialysis (HD) and the associated mortality and prognostic factors. METHODS: Data were analyzed retrospectively using a nationwide cohort registry, the Korean Renal Data System. Patients who started HD between January 2016 and December 2020 were included and divided into three groups according to age at HD initiation (<65, 65-74, and ≥75 years). The primary outcome was all-cause mortality during the study period. Risk factors for mortality were analyzed using Cox proportional hazard models. RESULTS: In total, 22,024 incident patients were included with 10,006, 5,668, and 6,350 in each group (<65, 65-74, and ≥75 years, respectively). Among the very elderly group, women had a higher cumulative survival rate than men. The survival rate was lower in patients with vascular access via a catheter than in those with an arteriovenous fistula or graft. Very elderly patients with more comorbid diseases had a significantly lower survival rate than those with fewer comorbidities. In the multivariate Cox models, old age, cancer presence, catheter use, low body mass index, low Kt/V, low albumin concentration, and capable status of partial self-care were associated with high risk of mortality. CONCLUSION: Preparation of an arteriovenous fistula or graft when starting HD should be considered in very elderly patients with fewer comorbid diseases.

Active Surveillance Versus Immediate Surgery for Low-Risk Papillary Thyroid Microcarcinoma Patients in South Korea: A Cost-Minimization Analysis from the MAeSTro Study.

Background: Active surveillance (AS) has been established as an alternative to immediate surgery for low-risk papillary thyroid microcarcinoma (PTMC). Nonetheless, it remains difficult to decide between AS and immediate surgery, since limited objective evidence exists regarding risks and benefits. The aim of study is to compare the cumulative costs of AS and immediate surgery. Methods: To estimate cumulative costs, a hypothetical model is simulated based on the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Micro-Carcinoma (MAeSTro) study, a multicenter prospective cohort study of AS for PTMC. Direct and indirect costs are estimated from diagnosis to the treatment decision and follow-up for 10 years and a longer period. In the case of the scenarios, AS, AS to surgery due to changing their mind, and lobectomy (analyzed regardless of levothyroxine [LT4] treatment, as well as subdivided into lobectomy/LT4[-] and lobectomy/LT4[+]) are considered. A sensitivity analysis is performed using different discount rates to address uncertainties in future time costs. To compare the cumulative costs, we referred to previous research conducted in Hong Kong, the United States, and Japan. Results: The initial cost of AS is estimated to be 5.6 times lower than that of lobectomy (regardless of LT4 use), while the 10-year cumulative costs of AS ($2545) and lobectomy regardless of LT4 ($3045) are similar under a discount rate of 3%. However, in the long-term follow-up period, immediate surgery is going to be estimated more economical than AS. The costs of the two management approaches are similar in Hong Kong, but substantially different in the United States and Japan, implying that it could be affected by each country's national health insurance coverage and the thyroid ultrasound interval during follow-up. Conclusion: Considering both direct and indirect costs, the cumulative costs of AS and immediate surgery in low-risk PTMC patients are similar during 10 years, and surgery could be more economical for patients with a life expectancy in long-term follow-up. However, careful interpretation is needed for long-term follow-up and the country's health care system and environment. Nevertheless, considering the representative protocols and objective costs in South Korea, it is expected to be a key to suggest the appropriate treatment for PTMC patients.

Can computed tomography scanning in adults lead to an increased risk of thyroid cancer? A nationwide nested case-control study.

OBJECTIVE: To evaluate the association between computed tomography (CT) scanning and newly diagnosed thyroid cancer cases in relation to the confounding effect of the healthcare utilization rate. METHODS: This nested case-control study used the Korean National Health Insurance Service-National Sample Cohort 2002-2015: 3557 adult thyroid cancer cases were matched to 17,785 controls by age, sex, and diagnosis date. Odds ratios (ORs) were estimated for thyroid cancer associated with cumulative exposure to CT scanning > 3 years before cancer diagnosis. Changes in estimated ORs with and without adjustment for outpatient visit frequency were investigated. RESULTS: ORs for newly diagnosed thyroid cancer increased according to the higher number of total CT scans and thyroid-exposing CT scans (CT scans of the head, neck, or chest compartment; OR and 95% confidence interval [CI], 1.09 [1.03-1.16] and 1.28 [1.05-1.57], respectively). ORs for thyroid cancer increased according to higher outpatient visit frequency. The association between thyroid cancer incidence and CT scans became insignificant when outpatient visit frequency was adjusted in the models (OR [95% CI], 1.03 [0.97-1.10]: total CT scans, 1.14 [0.93-1.41]: thyroid-exposing CT scans). Subgroup analyses stratified by age, sex, and history of other malignancies did not reveal independent associations between CT scanning and thyroid cancer. CONCLUSIONS: The high incidence of thyroid cancer in adults exposed to ionizing radiation during CT scanning can be largely explained by the confounding effect of the healthcare utilization rate. These effects should be considered to avoid overestimation of the CT scanning-associated risk of thyroid cancer. KEY POINTS: • Studies indicate that diagnostic imaging using low-ionizing radiation may increase risks for thyroid cancer in adults. • Our findings suggest that the risk for radiation-induced thyroid cancer following CT scanning in adults may have been overestimated in observational studies due to medical surveillance-related biases.

Metabolic Effects of Gastrectomy and Duodenal Bypass in Early Gastric Cancer Patients with T2DM: A Prospective Single-Center Cohort Study.

We evaluated the metabolic effects of gastrectomies and endoscopic submucosal dissections (ESDs) in early gastric cancer (EGC) patients with type 2 diabetes mellitus (T2DM). Forty-one EGC patients with T2DM undergoing gastrectomy or ESD were prospectively evaluated. Metabolic parameters in the patients who underwent gastrectomy with and without a duodenal bypass (groups 1 and 2, n = 24 and n = 5, respectively) were compared with those in patients who underwent ESD (control, n = 12). After 1 year, the proportions of improved/equivocal/worsened glycemic control were 62.5%/29.2%/8.3% in group 1, 40.0%/60.0%/0.0% in group 2, and 16.7%/50.0%/33.3% in the controls, respectively (p = 0.046). The multivariable ordered logistic regression analysis results showed that both groups had better 1-year glycemic control. Groups 1 and 2 showed a significant reduction in postprandial glucose (-97.9 and -67.8 mg/dL), body mass index (-2.1 and -2.3 kg/m2), and glycosylated hemoglobin (group 1 only, -0.5% point) (all p < 0.05). Furthermore, improvements in group 1 were more prominent when preoperative leptin levels were high (p for interaction < 0.05). Metabolic improvements in both groups were also observed for insulin resistance, leptin, plasminogen activator inhibitor-1, and resistin. Gastrectomy improved glycemic control and various metabolic parameters in EGC patients with T2DM. Patients with high leptin levels may experience greater metabolic benefits from gastrectomy with duodenal bypass.

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.

A Multicenter, Randomized, Controlled Trial for Assessing the Usefulness of Suppressing Thyroid Stimulating Hormone Target Levels after Thyroid Lobectomy in Low to Intermediate Risk Thyroid Cancer Patients (MASTER): A Study Protocol.

BACKGROUND: Postoperative thyroid stimulating hormone (TSH) suppression therapy is recommended for patients with intermediate- and high-risk differentiated thyroid cancer to prevent the recurrence of thyroid cancer. With the recent increase in small thyroid cancer cases, the extent of resection during surgery has generally decreased. Therefore, questions have been raised about the efficacy and long-term side effects of TSH suppression therapy in patients who have undergone a lobectomy. METHODS: This is a multicenter, prospective, randomized, controlled clinical trial in which 2,986 patients with papillary thyroid cancer are randomized into a high-TSH group (intervention) and a low-TSH group (control) after having undergone a lobectomy. The principle of treatment includes a TSH-lowering regimen aimed at TSH levels between 0.3 and 1.99 µIU/mL in the low-TSH group. The high-TSH group targets TSH levels between 2.0 and 7.99 µIU/mL. The dose of levothyroxine will be adjusted at each visit to maintain the target TSH level. The primary outcome is recurrence-free survival, as assessed by neck ultrasound every 6 to 12 months. Secondary endpoints include disease-free survival, overall survival, success rate in reaching the TSH target range, the proportion of patients with major cardiovascular diseases or bone metabolic disease, the quality of life, and medical costs. The follow-up period is 5 years. CONCLUSION: The results of this trial will contribute to establishing the optimal indication for TSH suppression therapy in low-risk papillary thyroid cancer patients by evaluating the benefit and harm of lowering TSH levels in terms of recurrence, metabolic complications, costs, and quality of life.

Stepwise achievement of high convection volume in post-dilution hemodiafiltration: A prospective observational study.

High-volume online hemodiafiltration (HDF) has been reported to reduce the patient's mortality. However, achieving a high convection volume is challenging. In this prospective study, we investigated the feasibility of achieving high-volume HDF with ≥21 L substitution volume via modification of blood flow rate (BFR), needle size, and dialysis membrane. In 30 patients undergoing hemodialysis, we followed a stepwise protocol and gradually increased the BFR (280→300→330 ml/min; steps 1, 2, and 3) and needle size (16→15 G; step 4). After changing dialyzer surface area (1.8 m2 →2.5 m2 ), the BFR and needle size were similarly increased stepwise (steps 5, 6, 7, and 8). The mean substitution volume was 18.7 ± 2.2 L at step 1 and it significantly increased to 25.1 ± 2.6 L by step 8. A substitution volume of 21 L was achieved by 13.3% of patients in step 1 and by 96.7% after step 8. The substitution volume was higher for the dialyzer with a large surface area and for the larger needle (15 G). Between steps 1 and 8, the Kt/V and ß2 microglobulin reduction ratios also improved significantly. High-volume HDF is feasible through a stepwise increase in the BFR, needle size, and surface area of the dialysis membrane.

Factors Affecting Central Node Metastasis and Metastatic Lymph Node Ratio in Papillary Thyroid Cancer.

OBJECTIVE: Despite the growing evidence that metastatic lymph node ratio (MLNR) is a valuable predictor for the prognosis of papillary thyroid carcinoma, it has not yet been fully determined which factors give the ratio predictive value independent of the number of metastatic lymph nodes (MLNs). STUDY DESIGN: Retrospective cohort study. SETTING: A comprehensive cancer center. METHODS: Recurrence and clinicopathologic factors were analyzed in 2409 patients with papillary thyroid carcinoma who underwent total thyroidectomy and central node dissection. RESULTS: Cutoff values of MLNs ≥2 and MLNR ≥28.2% increased the recurrence risk (hazard ratio [95% CI], 9.97 [4.73-21.0] and 11.4 [5.53-23.3], respectively). Younger age, male sex, multifocality, tumor size, lymphatic and vascular invasion, and gross extrathyroidal extension positively correlated with MLN and MLNR (all P < .05). Meanwhile, lymphocytic thyroiditis negatively correlated with MLNR in female patients (P < .001), by increasing total lymph node yields as compared with papillary thyroid carcinoma without lymphocytic thyroiditis. In multivariate analysis, younger age, tumor size, and lymphatic invasion remained significant in male and female patients for MLN and MLNR; lymphocytic thyroiditis was also significantly correlated with MLNR in female patients. CONCLUSION: Our study demonstrates that MLN and MLNR are independently observed prognostic markers for tumor recurrence. However, lymphocytic thyroiditis in female patients seems to have lower MLNR by increasing total lymph node yields. In light of their association, a different cutoff for MLNR needs to be applied according to the presence or absence of underlying lymphocytic thyroiditis in the use of MLNR for predicting the recurrence. LEVEL OF EVIDENCE: 4.

Long Work Hours Are Associated with Hypothyroidism: A Cross-Sectional Study with Population-Representative Data.

Background: Studies have highlighted the adverse effects of long work hours on workers' health; however, the association of long work hours with thyroid function has not been studied. This study aimed at assessing long work hours as a risk factor for thyroid dysfunction. Methods: This cross-sectional study was based on data obtained from the Korea National Health and Nutrition Examination Survey conducted from 2013 to 2015. A total of 2160 adults who worked 36-83 hours per week were included. Thyroid function was defined based on the population thyroid-stimulating hormone reference ranges, after excluding individuals with positive results for thyroid peroxidase antibody. The association between work hours and thyroid function was confirmed via multinomial logistic regression. Results: Hypothyroidism was more prevalent among those with longer work hours (3.5% vs. 1.4% for 53-83 and 36-42 work hours per week, respectively). Individuals who worked longer hours had an increased odds for hypothyroidism (odds ratio 1.46, confidence interval 1.12 - 1.90, per 10-hour increase in work hours per week), after adjustment for age, sex, body mass index, urine iodine concentration, smoking status, work schedule, and socioeconomic status. The association between work hours and hypothyroidism was consistent in various subgroups stratified by sex or socioeconomic status. Conclusions: To our knowledge, this study is the first to show that long work hours are associated with hypothyroidism. Further large longitudinal studies are needed to clarify causality.

Aspirin Use Is Not Associated with Lower Thyroid Cancer Risk: A Nationwide Nested Case-Control Study.

Background: While aspirin use is known to be associated with reduced incidence of various cancer types, it is unclear whether this benefit extends to thyroid cancer. We aimed to evaluate the association between aspirin use and thyroid cancer development. Methods: This nested case-control study used nationwide data from the Korean National Health Insurance Service-National Sample Cohort 2002-2015. In total, 4547 individuals with newly developed thyroid cancer were matched with 13,641 controls based on age, sex, and follow-up period. Odds ratios (ORs) and 95% confidence intervals (CIs) for thyroid cancer development according to aspirin use were analyzed using a multivariable conditional logistic regression model. Results: The number of days for which patients with thyroid cancer used aspirin (the proportions of no use, <30 days/year, 30-90 days/year, and ≥90 days/year were 93.03%, 6.51%, 0.31%, and 0.15%, respectively) was comparable with that of the controls (p = 0.371, chi-squared test). The risk of thyroid cancer development was not associated with the duration of aspirin use (ORs [CI] for aspirin use <30 days/year, 30-90 days/year, and ≥90 days/year were 1.11 [0.96-1.28], 1.01 [0.54-1.88], and 1.23 [0.50-3.06], respectively, compared with no use) after adjusting for body mass index, smoking status, hypertension, Charlson comorbidity index, and number of outpatient visits per year. In addition, subgroup analyses stratified by age, sex, and follow-up duration did not reveal any significant association between aspirin use and thyroid cancer. Conclusions: Our findings suggest that even extended aspirin use may not impact the prevention or onset of thyroid cancer.

The relationship of comorbidities to mortality and cause of death in patients with differentiated thyroid carcinoma.

Understanding how comorbidities contribute to death in cancer patients is becoming an important topic. The present study assessed the role of comorbidities in overall mortality and causes of death in patients with differentiated thyroid carcinoma (DTC). This retrospective cohort study included 2070 patients who underwent thyroidectomy for DTC at a single institution between 2002 and 2005. Probabilities of overall, DTC-specific and other-cause death were examined according to the number of comorbidities, with consideration for competing events. The estimated 15-year cumulative incidences of overall, DTC-specific, and other-cause death were 7.3%, 1.6%, and 5.7%, respectively. Taking the group without comorbidities as a reference, we found that the group with 1-2 comorbidities and the group with ≥3 comorbidities had higher probabilities of other-cause death (subhazard ratios = 2.48 and 9.41, respectively; p < 0.01) and consequently shorter overall survival (hazard ratio = 1.95 and 5.33, respectively; p < 0.01), with adjustment for age, sex, and tumor-node-metastasis classification. In contrast, the probability of DTC-specific death was reduced in patients with ≥3 comorbidities (subhazard ratio = 6.81e-10, p < 0.01). For overall death, the relative proportion of death from DTC reduced when the number of comorbidities increased, and DTC-specific death was not observed in patients with ≥3 comorbidities. Our results show that death from DTC itself accounted for only a fraction of the overall deaths among patients who underwent surgery for DTC. Comorbidities increased overall mortality by increasing the probability of other-cause death. Patients with multiple comorbidities had a low probability of dying from DTC because they died earlier from comorbidities.

Association between Thyroid-Stimulating Hormone Level after Total Thyroidectomy and Hypercholesterolemia in Female Patients with Differentiated Thyroid Cancer: A Retrospective Study.

Less-intense TSH suppression strategies can be used for differentiated thyroid cancer (DTC) patients with a low recurrence risk, but their metabolic outcomes are not well known. We aimed to evaluate changes in the serum cholesterol levels and the risk of hypercholesterolemia according to postoperative TSH levels in 1092 female DTC patients receiving levothyroxine after total thyroidectomy. The preoperative-to-follow-up change in total cholesterol (TC) levels in the TSH level <0.03, 0.03-0.3, 0.3-2, and 2-5 mIU/L groups was -3.69 mg/dL (p = 0.006), +0.13 mg/dL (p = 0.926), +12.46 mg/dL (p < 0.001), and +16.46 mg/dL (p < 0.001), respectively. When compared with TSH levels of 0.03-0.3 mIU/L, those of 0.3-2 mIU/L were found to be associated with hypercholesterolemia (adjusted odds ratio (AOR) = 1.86 and 5.08 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-low-density lipoprotein (LDL)-cholesterolemia (AOR = 2.76 for LDL-cholesterol ≥160 vs. <130 mg/dL). Additionally, TSH levels of 2-5 mIU/dL were associated with hypercholesterolemia (AOR = 2.85 and 6.95 for TC 200-240 and ≥240 vs. <200 mg/dL) and hyper-LDL-cholesterolemia (AOR = 2.08 and 4.17 for LDL-cholesterol 130-159 and ≥160 mg/dL vs. <130 mg/dL). In patients with normal TSH level maintenance following thyroidectomy, TC levels markedly increased, resulting in an increased hypercholesterolemia prevalence. Metabolic derangement risk due to insufficient levothyroxine replacement should be considered in the adoption of less-intense TSH suppression strategies, postoperatively, in DTC patients.

Changes in the Diagnostic Efficiency of Thyroid Fine-Needle Aspiration Biopsy during the Era of Increased Thyroid Cancer Screening in Korea.

PURPOSE: The volume of thyroid cancer screening and subsequent thyroid fine-needle aspiration (FNA) have rapidly increased in South Korea. We analyzed the thyroid cancer diagnoses/thyroid FNA ratio according to the annual number of FNA to evaluate changes in the diagnostic efficiency of FNA. MATERIALS AND METHODS: This was a nationwide population-based retrospective cohort study. The overall thyroid cancer diagnoses/thyroid FNA ratio and annual incremental thyroid cancer diagnoses/incremental thyroid FNA ratio were indirectly calculated using data obtained from the Korea Central Cancer Registry database and the Korean National Health Insurance Service claims database from 2004 to 2012. Pearson correlation analyses were performed to evaluate the strength of linear associations between variables. RESULTS: The number of thyroid FNA increased from 28,596 to 177,805 (6.2-fold increase) from 2004 to 2012. The overall thyroid cancer diagnoses/thyroid FNA ratio decreased from 36.5% in 2004 to 25.1% in 2012 and was negatively correlated to the number of FNA (R=‒0.977, p < 0.001). The annual incremental thyroid cancer diagnoses/incremental thyroid FNA ratios (range, 15.3% to 30.7%) were always lower than the overall thyroid cancer diagnoses/thyroid FNA ratio in each year and also worsened according to the increase in the number of FNA (R=‒0.853, p=0.007). CONCLUSION: The diagnostic performance of both overall and annual incremental thyroid FNA worsened, whereas the number of thyroid FNA procedures increased. More sophisticated indications for FNA are required to improve its diagnostic efficiency, considering the increased burden of screening-detected thyroid nodules.

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.

Effects of aspirin resistance and mean platelet volume on vascular access failure in hemodialysis patients.

BACKGROUND/AIMS: Maintaining the patency of vascular access (VA) in hemodialysis (HD) patients is important and can be life-saving. We investigated the effects of aspirin resistance and mean platelet volume (MPV) on VA failure in HD patients. METHODS: We enrolled 163 patients on maintenance HD. VA failure was defined as thrombosis or a decrease of > 50% of the normal vessel diameter, as revealed by angiography. RESULTS: Aspirin resistance was observed in 17 of 109 patients in whom this parameter was measured, and was not significantly associated with VA failure (p = 0.051). The mean MPV was 9.15 ± 0.05 fL. The 163 patients were grouped by the median MPV value (9.08 fL) at baseline; patients with higher MPVs (n = 82) had lower platelet counts (p = 0.002) and albumin levels (p = 0.009). During 34 months of follow-up, 65 VA failures (39.9%) occurred. The Kaplan-Meier curve revealed significant differences between the two groups in terms of cumulative VA failure (54.1% vs. 35.3%, p = 0.018). On multivariate analysis, the MPV (hazard ratio [HR], 1.794; 95% confidence interval [CI], 1.066 to 3.020; p = 0.028), platelet count (HR, 1.003; 95% CI, 1.001 to 1.006; p = 0.01), and smoking status (HR, 1.894; 95% CI, 1.019 to 3.519; p = 0.043) independently predicted VA failure. CONCLUSION: A high MPV was associated with an increased risk of VA failure, whereas aspirin resistance showed only a weak association. The MPV may predict VA survival in HD patients.

Association between diffuse lymphocytic infiltration and papillary thyroid cancer aggressiveness according to the presence of thyroid peroxidase antibody and BRAFV600E mutation.

BACKGROUND: Diffuse lymphocytic infiltration (DLI) is frequently found with papillary thyroid cancer (PTC), so there has been long interest in how it affects the characteristics of PTC. This purpose of this study was to define the association between DLI and PTC aggressiveness according to thyroperoxidase antibody (TPOAb) and B-type Raf (BRAF)V600E mutation positivity. METHODS: There were 1879 patients with PTC who underwent surgery and were enrolled in this study. Clinicopathologic characteristics were compared between groups according to the presence of DLI and TPOAb. Multiple logistic regression analysis was conducted to assess odds ratio (OR) for each dependent variable (BRAFV600E mutation, tumor size >1.0 cm, multifocality, extrathyroidal extension, and lymph node metastasis) of each group according to the presence of DLI and TPOAb, with the group with neither DLI or TPOAb (DLI-negative TPOAb-negative PTC) as the reference. RESULTS: The DLI-positive PTC showed more frequent multifocality and less frequent BRAFV600E mutation than DLI-negative PTC. Among patients with DLI-positive PTC, extrathyroidal extension and BRAFV600E mutation was less frequent when serum TPOAb was positive. In multiple logistic regressions, DLI-positive TPOAb-positive PTC showed a high OR for multifocality (1.410; P = .017), but low ORs for BRAFV600E mutation (0.521; P < .001) and extrathyroidal extension (0.691; P = .008). The patients with DLI-positive TPOAb-positive PTCs showed a high OR for multifocality (1.588; P = .002), and high ORs for tumor size >1.0 cm (2.205; P = .019) and lymph node metastasis (2.005; P = .032) in subgroup analyses of PTC with wild-type BRAF. The DLI-negative TPOAb-positive group was not associated with any tumor aggressiveness-related variables. CONCLUSION: Although DLI was associated with multifocality regardless of TPOAb positivity, it was associated with an indolent feature when TPOAb was positive but with aggressive features in PTC with wild-type BRAF when TPOAb was negative. The TPOAb and BRAF status may help to define the clinical implication of lymphocytic infiltration found with PTC.

Acid-base disorders after orthotopic bladder replacement: comparison of an ileal neobladder and an ileal conduit.

OBJECTIVES: For many years, creation of an orthotopic neobladder after cystectomy has been popular. In the present study, we measured the extent of metabolic acidosis in patients with ileal neobladders compared with ileal conduits and defined risk factors for development of metabolic acidosis. METHODS: We retrospectively studied 95 patients, who underwent radical cystectomy and urinary diversion to treat invasive bladder cancer from January 2001 to December 2014 at Hallym University Kangnam Sacred Heart Hospital, through investigation of acid-base balance, serum electrolyte levels and renal function one month and one year after operation. RESULTS: One month after the operation, metabolic acidosis was found from 18 patients (31.0%) in an ileal neobladder group and from 4 (14.8%) in an ileal conduits group. One year after the operation, the numbers became 11 (22.9%) and 2 (10.0%), respectively. However, there was not a statistical difference. The blood biochemical profiles of the two groups did not differ significantly after urinary diversion. Logistic analysis revealed that lower estimated glomerular filtration rate (eGFR) was associated with metabolic acidosis at one month (odds ratio, OR = 0.94 [0.91-0.97]; p < 0.001) and one year (OR = 0.94 [0.92-0.97]; P = 0.001) after urinary diversion. In multivariate analysis, lower eGFR is a significant risk factor for metabolic acidosis at one month. CONCLUSIONS: Patients with ileal neobladders and conduits are at the similar risk of metabolic acidosis. A close association between renal function and development of metabolic acidosis was observed, especially stronger in an early period after operation.