Comparison of the Efficacy and Safety of Insulin Detemir Administered Once Daily According to Two Titration Algorithms (3-0-3 and 2-4-6-8) in Patients with Type 2 Diabetes Mellitus

BACKGROUND: This study was conducted to compare glycaemic control with insulin detemir administered according to two titration algorithms (3-0-3 and 2-4-6-8) after 20 weeks of treatment in subjects with type 2 diabetes mellitus inadequately controlled on metformin.METHODS: This was a 20-week, randomised, multicentre, open-labelled, treat-to-target trial. Forty-six patients were randomised in a 1:1 manner to either the 3-0-3 (G3, n=23) or 2-4-6-8 (G2, n=23) algorithm. The primary endpoint was change of haemoglobin A1c (HbA1c), and the secondary safety endpoint included hypoglycaemic events.RESULTS: After 20 weeks, HbA1c decreased similarly in the G3 and G2 groups, with a mean change of −0.9% from baseline. The mean change in fasting plasma glucose was numerically similar in both groups. The hypoglycaemia event rate per 100-patient-years of exposure (r) in the G2 group (r=1,427) was higher than that in the G3 group (r=807).CONCLUSION: Both treatment groups had numerically similar HbA1c reductions. A trend towards fewer hypoglycaemia episodes after dose stabilisation was seen with the simpler G3. Clinically, this may be an important observation, as a simpler titration algorithm may support self-management and maintenance of insulin therapy.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Indoor pet ownership in infancy is a risk factor for the development of sensitization to pets and asthma in childhood

PURPOSE: It is controversial whether indoor pet exposure is either a risk or protective factor developing sensitization to pet allergens or asthma. Therefore, we investigated whether indoor pet ownership entails a risk for the development of asthma and sensitization in childhood. METHODS: The Panel Study of Korean Children (PSKC) is a general-population-based birth cohort study that recruited 2,078 mother-baby dyads in Korea between April and July of 2008. Among 1,577 children who were followed up in 2015, 559 underwent skin prick tests, spirometry and bronchial provocation tests using Provocholine. Having a cat or a dog and the prevalence of asthma were evaluated by using self-reported questionnaires and physicians’ medical records. RESULTS: During infancy, the rate of dog ownership was 4.5% (71 of 1,574) and that of cat ownership was 0.5% (8 of 1,574). Of the subjects, 7.9% (n=109) currently had at least 1 dog and 2.5% (n=34) had at least 1 cat. Pet ownership during infancy was associated with sensitization to cats or dogs (adjusted odds ratio [aOR], 4.24; 95% confidence interval [CI], 1.29–13.98), wheezing within 12 months (aOR, 5.56; 95% CI, 1.65–18.75) and current asthma (wheezing episode in the last 12 months+diagnosed asthma by physicians) (aOR, 6.36; 95% CI, 1.54–26.28). In contrast, pet ownership during the last 12 months was not associated with sensitization to cats or dogs or current asthma. CONCLUSION: Indoor pet exposure during infancy can be critical for developing sensitization to cats or dogs and asthma in childhood. Avoidance of pet exposure in early life may reduce sensitization to cats or dogs and development of asthma.

Multicenter Adherence Study of Asthma Medication for Children in Korea

PURPOSE: Adherence is a major component of successful medical treatment. However, non-adherence remains a barrier to effective delivery of healthcare worldwide. METHODS: Twenty healthcare facilities (secondary or tertiary hospitals) belonging to the Korean Academy of Pediatric Allergy and Respiratory Diseases (KAPARD) participated. Questionnaires were given to patients currently receiving treatment in the form of inhalant useor oral intake or transdermal patch for mild to moderate asthma. RESULTS: A total of 1,838 patients responded to the questionnaire. Mean age was 5.98 ± 3.79 years (range: 0-18 years). With help from their caregivers, the percentage of patients that answered “taking as prescribed” was 38.04% for inhalant users, 50.09% for oral medication users and 67.42% for transdermal users. Transdermal patch users had significantly greater adherence compared to the other 2 groups (P < 0.001). The 34.15% of inhalant users, 70.33% of oral medication users and 93.00% of transdermal patch users felt that their medication delivery system was “Easy” or “Very easy” to use (P < 0.001). “Method of administration” was deemed to be the most difficult part of the treatment regimen to follow, and 76.7% of patients preferred once-daily administration (i.e., “Frequency of administration”). CONCLUSIONS: Asthma medication adherence in young children was found to be better in the transdermal patch group. This may be due to requiring fewer doses and easy to follow instructions. From an adherence point of view, the transdermal patch seems more useful for long-term asthma control in children compared to oral or inhaled medicine.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Clinical Implications of Using Post-Challenge Plasma Glucose Levels for Early Diagnosis of Type 2 Diabetes Mellitus in Older Individuals

BACKGROUND: The aim of this study was to explore the differences in the clinical characteristics and diagnostic rates of diabetes mellitus (DM) according to various criteria in different age groups and to evaluate the efficacy of each criterion for screening older patients. METHODS: We studied 515 patients and measured the fasting plasma glucose level (FPG), 2-hour plasma glucose level after the 75 g oral glucose tolerance test (2-hour postload glucose [2-h PG]), and glycosylated hemoglobin (HbA1c) for re-evaluation of hyperglycemia without a history of diabetes. Patients with newly diagnosed DM were grouped by age as younger ( < 65 years) or older (≥65 years). RESULTS: Older patients had significantly lower HbA1c, FPG, and 2-h PG levels and a higher homeostatic level of pancreatic β-cell function compared with younger patients (P < 0.001). The older group had the lowest diagnostic rate when using the FPG level (45.5%) and the highest diagnostic rate when using the 2-h PG level (84.6%). These results were mostly due to the higher frequency of isolated post-challenge hyperglycemia in the older patients than in the younger group (28.8% vs. 9.2%). The use of both the FPG and HbA1c levels significantly enhanced the low diagnostic power when employing only the FPG levels in the older group (71.2% vs. 45.5%). CONCLUSION: In the older patients, the 2-h PG level was the most accurate diagnostic criterion. When we consider the costs and convenience, a combination of the FPG and HbA1c criteria may be recommended as a screening test for DM in older people.

Risk factors, lung function and bronchial hyperresponsiveness in current dust mite-induced allergic rhinitis

PURPOSE: We analyzed the pulmonary function and risk factors of allergic rhinitis (AR) in dust mite-sensitized children with current AR and no history of asthma. METHODS: In this cross-sectional study, demographic and disease-related information was obtained from 1,792 Korean children aged 9-12 years using a questionnaire, skin-prick testing, spirometric analysis, and methacholine challenge testing. RESULTS: A total of 672 children were analyzed. The control group consisted of 583 children without any allergic diseases who were not sensitized to 16 common allergens. The group with current AR and dust mite sensitization consisted of 89 children. Binary logistic regression analysis showed that helminth infection (adjusted odds ratio [aOR], 2.88; 95% confidence interval [CI], 1.23-6.77) and antibiotic use during infancy (aOR, 1.89; 95% CI, 1.10-3.25) were the risk factors. Pet ownership (aOR, 0.32; 95% CI, 0.15-0.69) and older siblings (aOR, 0.58; 95% CI, 0.35-0.96) were protective factors. Spirometry results did not differ between the control and dust mite-induced AR groups. None of the children showed a bronchodilator response. However, 8.5%, 7.1%, and 2.1% of the control-group children and 28.7%, 23.0%, and 8.0% of the dust mite-induced AR-group children showed methacholine PC20 (provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second) values of < or =25 mg/mL, < or =16 mg/mL, and < or =8 mg/mL, respectively (P<0.01). CONCLUSION: The prevalence of current dust mite-induced AR may be reduced by controlling environmental factors. Even though the spirometry results seemed to be normal, bronchial hyperresponsiveness occurred more frequently in children with dust mite-induced AR than in normal children.

The Future of Diabetes Education / 임상당뇨병

Diabetes mellitus is one of the most arduous chronic illnesses, both physically and psychologically. To live with a chronic incurable illness is to live in a state of constant uncertainty. Treatment motivation is an important factor in the success of diabetes management. The most important factor of treatment motivation in diabetic patients is resolving illness uncertainty. Diabetes educator teams must be oriented to focus on glycemic control. In addition, removal of negative thoughts about poor prognosis is the starting point for success. Through diabetic education, patients can reduce illness uncertainty, maintain therapy and adapt to the illness. By adopting a lifestyle appropriate for the disease, patients can improve their quality of life and add years to their life and life to their years.

The Effect of Vildagliptin on Visfatin in Korean Patients with Type 2 Diabetes: A Multicenter, Double-Blind, Randomized, Placebo-Controlled, Prospective Study / 임상당뇨병

BACKGROUND: The effects of dipeptidyl peptidase-4 inhibitors on adipokines remain obscure. The aim of this study was to evaluate the effect of the addition of vildagliptin on visfatin, an adipokine that represents inflammatory biomarkers of adipose tissue, in patients with type 2 diabetes inadequately controlled with prior metformin monotherapy. METHODS: In this 16-week, double-blind, randomized, parallel-group, placebo-controlled study, 71 patients were randomly assigned to vildagliptin 50 mg twice a day (n = 35) or placebo (n = 36) added to ongoing metformin therapy. Fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), plasma lipids, and visfatin levels were measured at baseline and 16 weeks after treatment. RESULTS: After 16 weeks, significant reduction in HbA1c and FPG was observed with vildagliptin addon treatment compared to placebo (-0.54 +/- 0.52%, P = 0.001 and -14.80 +/- 19.21 mg/dL, P = 0.004, respectively). However, no other clinically meaningful changes in lipid parameters or visfatin were observed. CONCLUSION: Vildagliptin add-on to metformin significantly improved fasting blood glucose and HbA1c. However, in this study, no significant differences in lipid parameters or visfatin level were observed between the two groups.

Interactions Between Innate Immunity Genes and Early-Life Risk Factors in Allergic Rhinitis

PURPOSE: Allergic rhinitis (AR) is a common chronic disease. Many factors could affect the development of AR. We investigated early-life factors, such as delivery mode, feeding method, and use of antibiotics during infancy, which could affect the development of AR. In addition, how interactions between these factors and innate gene polymorphisms influence the development of AR was investigated. METHODS: A cross-sectional study of 1,828 children aged 9-12 years was conducted. Three early-life factors and AR were assessed by a questionnaire. Skin prick tests were done. Polymorphisms of TLR4 (rs1927911) and CD14 (rs2569190) were genotyped. RESULTS: Use of antibiotics during infancy increased the risk of AR (aOR [95% CI] 1.511 [1.222-2.037]) and atopic AR (aOR [95% CI], 1.565 [1.078-2.272]). There were synergistic interactions between caesarean delivery, formula feeding, and use of antibiotics in the rate of atopic AR (aOR [95% CI], 3.038 [1.256-7.347]). Additional analyses revealed that the risk for the development of AR or atopic AR subjects with the TLR4 CC genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.127 [1.265-20.780] for AR; 6.078 [1.499-24.649] for atopic AR). In addition, the risk for the development of AR or atopic AR in subjects with the CD14 TT genotype were highest when all the 3 early-life factors were present (aOR [95% CI], 5.960 [1.421-15.002] for AR; 6.714 [1.440-31.312] for atopic AR). CONCLUSIONS: Delivery mode, feeding method, and use of antibiotics during infancy appeared to have synergistic interactions in the development of AR. Gene-environment interactions between polymorphism of innate genes and early- life risk factors might affect the development of AR.

ERRATUM: Affiliation Correction. Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

According to the author's request, in this paper, the eighth author's (Bong-Seong Kim) affiliation should be corrected.

Arterial Stiffness by Aerobic Exercise Is Related with Aerobic Capacity, Physical Activity Energy Expenditure and Total Fat but not with Insulin Sensitivity in Obese Female Patients with Type 2 Diabetes

BACKGROUND: Arterial stiffness is an important factor in atherosclerosis. Thus we examined whether aerobic exercise could reduce arterial stiffness in obese women with type 2 diabetes without diabetic complication. METHODS: A total of 35 women with type 2 diabetes (body mass index, 26.6+/-2.8 kg/m2; age, 56.4+/-1.9 years; duration of diabetes, 4.7+/-4.8 years) were assigned to aerobic exercise group (AEG) or control group (CG). AEG completed a 12-week exercise program (3.6 to 5.2 metabolic equivalents, 3 day/week, 60 min/day), with their exercise activities monitored by accelerometers. We measured abdominal total fat area (TFA), visceral fat area (VFA), and subcutaneous fat area (SFA) by computed tomography, insulin sensitivity by insulin tolerance test (K(ITT)), and augmentation index (AIx) by SphygmoCor at baseline and at the end of the 12-week program. RESULTS: The AIx was improved in the AEG compared with the CG (P<0.001). The percent change of AIx had significant correlation with the improvement of physical activity energy expenditure (PAEE), aerobic capacity, TFA, and SFA (r=-0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intake, or VFA. CONCLUSION: Improvement in aortic stiffness by aerobic exercise is related with the improvement of aerobic capacity, PAEE, and total fat but not with insulin sensitivity or energy intake in obese women with type 2 diabetes.

Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.

Evaluation of the association of vegetation of allergenic plants and pollinosis with meteorological changes

PURPOSE: There are a number of reports suggesting that widespread propagation of weeds and high concentration of weed pollen have been contributed to climate change. We investigated the interrelationship between allergenic pollen concentration, allergic symptom and meteorological factor. METHODS: We collected data of pollen concentration and meteorological factors in 7 stations nationwide during between 1998 and 2012. We recruited total 297 allergic patients sensitized to weed pollens from each station, conducted a survey about allergic symptom, and calculated symptom index. We surveyed the vegetation area of ragweed and Japanese hop. Based on these data, we performed the long-term trend analysis (X11-ARIMA, autoregressive integrated moving average) on regional pollen concentration, and correlation analysis to investigate the interrelation between weed pollen concentration, allery symptom index and meteorological factor. We have also done regression analysis on vegetation area and maximal pollen concentration. RESULTS: Long-term trend analysis showed the increasing trend of pllen concentration in Seoul. Weed pollen concentration, allergy symptom index and each meteorological factor were not correlated significantly. Regression analysis revealed that increase of weed vegetation area results in increase of weed pollen concentration. Through this regression equation, we estimated the vegetation area that can product pollen concentration triggering allergenic risk. CONCLUSION: Meteorological factors, pollen concentration and allergic symptoms should be consistently assessed and the relationship between each factor should be analyzed, considering climate change. It is necessary to verify the equation for pollen estimation by vegetation area and set up a policy for vegetation control focused on the reduction of allergenic pollen.

Breastfeeding Might Have Protective Effects on Atopy in Children With the CD14C-159T CT/CC Genotype

Breastfeeding is widely recommended to reduce risk of sensitization, eczema and asthma. However, the role of breastfeeding in prevention of allergic diseases is uncertain. We aimed to investigate whether the relationship between breastfeeding and sensitization to aeroallergens is modified by cluster of differentiation 14 (CD14) genotype. This study included 1,828 school children aged 9-12. We administered a detailed questionnaire and genotyped the CD14C-159T polymorphism. Skin prick tests for 12 aeroallergens were performed. School children who had been breastfed were less likely sensitized to aeroallergens (adjusted odds ratio [aOR] 0.712, 95% confidence interval [CI]: 0.555-0.914). There was no significant association between CD14C-159T genotype and atopy. Breastfeeding was associated with a decreased risk of atopic sensitization in children with CT/CC genotype (aOR 0.667, 95% CI: 0.463-0.960). Our data might identify the gene-environment interaction between the CD14C-159T polymorphism and breastfeeding in relation to aeroallergen sensitization.

Ectopic Adrenocorticotropic Hormone Syndrome Associated With Thymic Carcinoma in Old Age

A 70-year-old woman who developed a moon face was hospitalized. At admission, adrenocorticotropic hormone (ACTH) and serum cortisol levels were elevated. A high-dose dexamethasone suppression test demonstrated that cortisol secretion was uninhibited. Furthermore, chest computed tomography revealed an anterior mediastinal mass. On the basis of these results, ectopic ACTH syndrome was diagnosed and complete resection of the thymic tumor was performed. Histological examination revealed large cell neuroendocrine carcinoma of the thymus and positive immunoreactivity for ACTH. However, despite complete excision of the thymic tumor, ACTH and serum cortisol levels were high. Therefore, we investigated whether the lesion had recurred or metastasized; however, the results were inconclusive. Finally, laparoscopic bilateral adrenalectomy was performed to control the hypercortisolemia. After the surgery, the serum cortisol level was well-controlled and the general condition of the patient was good.

Safety and Efficacy of Modern Insulin Analogues

BACKGROUND: A1chieve(R) was a noninterventional study evaluating the clinical safety and efficacy of biphasic insulin aspart 30, insulin detemir, and insulin aspart. METHODS: Korean type 2 diabetes patients who have not been treated with the study insulin or have started it within 4 weeks before enrollment were eligible for the study. The patient selection and the choice of regimen were at the discretion of the physician. The safety and efficacy information was collected from the subjects at baseline, week 12, and week 24. The number of serious adverse drug reactions (SADRs) was the primary endpoint. The changes of clinical diabetic markers at week 12 and/or at week 24 compared to baseline were the secondary endpoints. RESULTS: Out of 4,058 exposed patients, 3,003 completed the study. During the study period, three SADRs were reported in three patients (0.1%). No major hypoglycemic episodes were observed and the rate of minor hypoglycemic episodes marginally decreased during 24 weeks (from 2.77 to 2.42 events per patient-year). The overall quality of life score improved (from 66.7+/-15.9 to 72.5+/-13.5) while the mean body weight was slightly increased (0.6+/-3.0 kg). The 24-week reductions in glycated hemoglobin, fasting plasma glucose and postprandial plasma glucose were 1.6%+/-2.2%, 2.5+/-4.7 mmol/L, and 4.0+/-6.4 mmol/L, respectively. CONCLUSION: The studied regimens showed improvements in glycemic control with low incidence of SADRs, including no incidence of major hypoglycemic episodes in Korean patients with type 2 diabetes.

Graves' Disease that Developed Shortly after Surgery for Thyroid Cancer

Graves' disease is an autoimmune disorder that may present with various clinical manifestations of hyperthyroidism. Patients with Graves' disease have a greater number of thyroid nodules and a higher incidence of thyroid cancer compared with patients with normal thyroid activity. However, cases in which patients are diagnosed with recurrence of Graves' disease shortly after partial thyroidectomy for thyroid cancer are very rare. Here we report a case of hyperthyroid Graves' disease that occurred after partial thyroidectomy for papillary thyroid cancer. In this case, the patient developed hyperthyroidism 9 months after right hemithyroidectomy, and antithyroglobulin autoantibody and thyroid stimulating hormone receptor stimulating autoantibody were positive. Therefore, we diagnosed Graves' disease on the basis of the laboratory test results and thyroid ultrasonography findings. The patient was treated with and maintained on antithyroid drugs. The mechanism of the recurrence of Graves' disease in this patient is still unclear. The mechanism may have been the improper response of the immune system after partial thyroidectomy. To precisely determine the mechanisms in Graves' disease after partial thyroidectomy, further studies based on a greater number of cases are needed.

Papillary Thyroid Carcinoma: Four Cases Required Caution during Long-Term Follow-Up

Due to the increased prevalence of papillary thyroid carcinoma (PTC), difficult cases and unexpected events have become more common during long-term follow-up. Herein we reported four cases that exhibited poor progress during long-term follow-up. All the cases were diagnosed with PTC and treated with total thyroidectomy before several years, and the patients had been newly diagnosed with recurrent and metastatic PTC. These four cases included recurred PTC with invasion of large blood vessels, a concomitant second malignancy, malignant transformation, and refractoriness to treatment. Physicians should closely monitor patients to promptly address unforeseen circumstances during PTC follow-up, including PTC recurrence and metastasis. Furthermore, we suggest that the development of a management protocol for refractory or terminal PTC is also warranted.

Papillary Thyroid Carcinoma: Four Cases Required Caution during Long-Term Follow-Up

Due to the increased prevalence of papillary thyroid carcinoma (PTC), difficult cases and unexpected events have become more common during long-term follow-up. Herein we reported four cases that exhibited poor progress during long-term follow-up. All the cases were diagnosed with PTC and treated with total thyroidectomy before several years, and the patients had been newly diagnosed with recurrent and metastatic PTC. These four cases included recurred PTC with invasion of large blood vessels, a concomitant second malignancy, malignant transformation, and refractoriness to treatment. Physicians should closely monitor patients to promptly address unforeseen circumstances during PTC follow-up, including PTC recurrence and metastasis. Furthermore, we suggest that the development of a management protocol for refractory or terminal PTC is also warranted.