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.

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.

OBJECTIVE: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility. METHODS: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated. RESULTS: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as “EC” by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (ĸ=0.55). CONCLUSION: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01594879
Biopsy, Needle ; Carcinoma, Endometrioid ; Dilatation and Curettage ; Endometrial Neoplasms ; Endometrium ; Female ; Fertility ; Fertility Preservation ; Follow-Up Studies ; Humans ; Levonorgestrel ; Medroxyprogesterone Acetate ; Prospective Studies

BACKGROUND: Osteoporosis is a systemic skeletal disease characterized by reduced bone mineral density and skeletal microstructural abnormalities. We investigated the correlation between serum uric acid (SUA) levels and bone mineral content (BMC) values as a surrogate marker of bone health. Additionally, we assessed whether the correlation, if any, was evident even after classifying the study population into two groups based on a diagnosis of obesity in these individuals.METHODS: This study included 936 women who visited the healthcare centers that participated in this study. Fasting blood samples were obtained from all women to measure SUA, BMC of the lumbar spine was measured using dual-energy X-ray absorptiometry. We evaluated the correlation between SUA and BMC in obese and non-obese groups.RESULTS: SUA concentration and BMC were positively correlated (β=0.257, P=0.001); however, this correlation was significant only in the obese group (β=0.203, P=0.001).CONCLUSION: SUA concentration and BMC are positively correlated in women diagnosed obesity.
Absorptiometry, Photon ; Biomarkers ; Body Mass Index ; Bone Density ; Delivery of Health Care ; Diagnosis ; Fasting ; Female ; Humans ; Obesity ; Osteoporosis ; Spine ; Uric Acid

Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.
Glioblastoma ; Gliosarcoma* ; Humans ; Prevalence* ; Prognosis

PURPOSE: Endoscopic thyroidectomy using a cervico-axillary approach (CAA) provides optimal visualization with a smaller dissection plane. Despite the excellent cosmetic results and high patient satisfaction, the surgical and oncologic safety of CAA endoscopic surgery has not been fully established. The present study evaluated the feasibility, safety, and surgical outcomes of CAA endoscopic thyroidectomy. METHODS: From October 2009 to April 2012, 100 patients with papillary thyroid cancer underwent CAA endoscopic thyroidectomy. Patient demographics, pathologic features, and surgical outcomes including complications and recurrence were collected. RESULTS: CAA endoscopic thyroidectomy was successful in all patients, and none required conversion to open thyroidectomy. All patients underwent ipsilateral thyroid lobectomy with or without central compartment neck dissection. The mean tumor size was 1.0±0.6 cm (range, 0.5~1.6), and 35.0% of tumors showed extrathyroidal extension. The mean number of harvested lymph nodes was 4.1±4.4, and metastasis was found in 12.0% of patients. The mean surgical time was 175.2±50.4 min, mean intraoperative blood loss was 42.5±69.2 ml, and the mean hospital stay was 3.3±0.6 days. There were five cases of postoperative transient hypocalcemia and eight cases of vocal cord palsy. No permanent complication or postoperative bleeding was observed. Patients continued to be seen for a median period of 63.7 months, and no recurrence of thyroid cancer was seen. CONCLUSION: CAA endoscopic thyroidectomy is a feasible and safe procedure for low-risk thyroid cancer, with excellent cosmesis. It can be recommended as an alternative option for selected patients with low-risk thyroid cancer.
Demography ; Hemorrhage ; Humans ; Hypocalcemia ; Length of Stay ; Lymph Nodes ; Neck Dissection ; Neoplasm Metastasis ; Operative Time ; Patient Satisfaction ; Recurrence ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy* ; Vocal Cord Paralysis

PURPOSE: Many stresses produce reactive oxygen species and bring about mechanism of antioxidant reaction. Cytokine and a neurotransmitter through the cell membrane, as well as signal transduction through the cell membrane, are used for various pathological condition of the brain, such as neurodegenerative disease. There are several antioxidant enzymes in cells (superoxcide dismutase, glutathion peroxidasae, peroxiredoxin catalase, etc.) METHODS: This study used single- or double-label immunohistochemical techniques to analyze mouse spinal neuron cells expressing Prx I and Prx III after acute mobilization stress. RESULTS: Prx I was observed in dendritic cell of the gray matter of the spinal cord, and Prx III was observed in the cytoplasm of the GM of the spinal cord. CONCLUSION: The results of this study will help to explain differences of expression in the distributions of the peroxiredoxin enzymes of the spinal cord.
Animals ; Brain ; Catalase ; Cell Membrane ; Cytoplasm ; Dendritic Cells ; Immobilization* ; Mice ; Neurodegenerative Diseases ; Neurons ; Neurotransmitter Agents ; Peroxiredoxins* ; Reactive Oxygen Species ; Signal Transduction ; Spinal Cord*

PURPOSE: Many stresses produce reactive oxygen species and bring about mechanism of antioxidant reaction. Cytokine and a neurotransmitter through the cell membrane, as well as signal transduction through the cell membrane, are used for various pathological condition of the brain, such as neurodegenerative disease. There are several antioxidant enzymes in cells (superoxcide dismutase, glutathion peroxidasae, peroxiredoxin catalase, etc.) METHODS: This study used single- or double-label immunohistochemical techniques to analyze mouse spinal neuron cells expressing Prx I and Prx III after acute mobilization stress. RESULTS: Prx I was observed in dendritic cell of the gray matter of the spinal cord, and Prx III was observed in the cytoplasm of the GM of the spinal cord. CONCLUSION: The results of this study will help to explain differences of expression in the distributions of the peroxiredoxin enzymes of the spinal cord.
Animals ; Brain ; Catalase ; Cell Membrane ; Cytoplasm ; Dendritic Cells ; Immobilization* ; Mice ; Neurodegenerative Diseases ; Neurons ; Neurotransmitter Agents ; Peroxiredoxins* ; Reactive Oxygen Species ; Signal Transduction ; Spinal Cord*

PURPOSE: Maturity-onset diabetes of the young(MODY) is a subtype of type 2 diabetes defined by autosomal dominant mode of inheritance, onset of diabetes usually before the age of 25 yrs, and a primary defect in the function of the beta cells of the pancreas. MODY3 is known as the most common form and is caused by mutations in hepatocyte nuclear factor(HNF)-1alpha. We examined the prevalence of MODY3 in children with type 2 diabetes mellitus(DM). METHODS: Children with type 2 DM(N=17) and their family members with type 2 DM(N=5) were enrolled. Inclusion criteria for the children were fasting C-peptide and postprandial C-peptide more than 1.0 ng/mL and 1.5 ng/mL respectively, familial type 2 DM in at least two generations, and body mass index(BMI)(kg/m(2)) less than 95th percentile. Genomic DNA was extracted from blood samples. We analyzed HNF-1alpha for mutation by DNA microarray method and direct sequencing. RESULTS: We found one case with a mutation of the promoter region of HNF-1alpha(5'-ctaGGCTAGTGGGGTTTTGCGGGGGCAGTGGGTGCAAGG-3') in one child's family member among 22 children and adult subjects with type 2 DM. CONCLUSION: Although we found a mutation of HNF-1alpha in an adult family member with type 2 DM, we did not find this mutation in a child with type 2 DM. The further investigation of MODY in children, including other types, is required.
Adult ; C-Peptide ; Child* ; Diabetes Mellitus, Type 2* ; DNA ; Family Characteristics ; Fasting ; Hepatocyte Nuclear Factor 1-alpha ; Hepatocytes ; Humans ; Oligonucleotide Array Sequence Analysis ; Pancreas ; Prevalence* ; Promoter Regions, Genetic ; Wills

Moyamoya disease(MMD) is defined as the development of collateral anastomosis pathways, associated with bilateral chronic progressive stenosis of the carotid fork. We have reviewed the types of presentation, angiograms, and single photon emission computed tomographs(SPECT). Ninety-nine patients were divided into three groups (aged below 5 years, between 5 and 15 years, and 16 or over) to investigate whether there were differences in clinical presentation and hemodynamic characteristics between the age groups. Mean age of the 99 patients was 13.6 years and the mean duration of symptoms was 26.2 months. In the 17 children aged less than five, the duration of symptoms was shorter(4.8 months) than in older patients(p<0.05). The former presented mostly with cerebral infarction(59%) with a widespread cerebral perfusion defect(50%). Among 56 children who were 5 to 15 years old, 42 (75%) presented with transient ischemic attacks and 10(18%) with cerebral infarction; the latter was less frequent in this age group than in other age groups. Twelve(46%) out of 26 adult patients had hemorrhage at the initial diagnosis, which was the most frequent presentation in this age group. Stenosis of the posterior cerebral artery was detected in 27% of adult MMD patients, while it was detected in 39% of children. Moreover, no case showed widespread perfusion defects in the adult group. The results suggest that the patterns of presentation and the hemodynamic features differ according to the age at which initial major symptoms occur. Children aged less than five suffer rapid progression of the disease and severe cerebral pefusion defect, and should therefore undergo early surgery. The less frequent involvement of MMD in the posterior circulation and better-preserved cerebral perfusion are characteristic findings of the disease in adults, and this seems to account for its delayed onset.
Adolescent ; Adult ; Cerebral Infarction ; Child ; Constriction, Pathologic ; Diagnosis ; Hemodynamics* ; Hemorrhage ; Humans ; Infarction ; Ischemic Attack, Transient ; Moyamoya Disease* ; Perfusion ; Posterior Cerebral Artery