Vertebral Fractures in Type 2 Diabetes Patients: Utility of Trabecular Bone Score and Relationship With Serum Bone Turnover Biomarkers.

BACKGROUND: Patients with type 2 diabetes (T2D) have an increased risk for vertebral fracture (VF). The aim of this study is to determine the utility of trabecular bone score (TBS) in T2D patients with VF and the relationship of TBS with serum bone turnover biomarkers (SBTBs). METHODOLOGY: Postmenopausal T2D female patients were prospectively enrolled. All patients received: (1) dual-energy X-ray absorptiometry exam for bone mineral density (BMD), T-score, and TBS values; (2) lateral lumbar spine radiographs for VF assessment; and (3) SBTBs: bone specific alkaline phosphatase and Beta-C-Terminal telopeptides. BMD, T-score, TBS, and SBTBs were tested for association with VF. RESULTS: The study included 285 T2D patients (mean age = 61.1 years) and 32 patients had VF (11.2%). TBS had the strongest association with VF in T2D patients (area under curve 0.775). The TBS cutoff values for VF are 1.279 in T-score ≥1 and 1.236 in T-score <-1. In patients without VF, all sites of BMD and TBS are significantly associated with SBTBs, but in patients with VF, no associations are found between SBTBs and all sites of BMD and TBS. CONCLUSIONS: TBS can assess bone quality in the spine. The low TBS cutoff values for T2D patients with VF imply T2D does impair bone quality. Thus, TBS should be incorporated in VF risk assessment in T2D patients. In addition, a dissociated relationship between BMD and TBS with SBTBs represents imbalanced bone turnover rate and results in bone fragility and VF.

Low vitamin D level was associated with metabolic syndrome and high leptin level in subjects with nonalcoholic fatty liver disease: a community-based study.

BACKGROUND: This study aimed to evaluate the association between serum vitamin D levels and nonalcoholic fatty liver disease (NAFLD) parameters, such as metabolic syndrome (MS), inflammatory cytokines (tumor necrosis factor, high sensitive C-reactive protein) and adipokines (adiponectin, leptin). METHODS: From August 2013 to August 2016, a community-based study was performed in the north-eastern region of Taiwan. All subjects received a demographic survey, blood testing and abdominal ultrasonography (US). The vitamin D level was evaluated by quartile divide or used the classification of deficiency (< 20 ng/ml), insufficiency (20-30 ng/ml) and sufficiency (> 30 ng/ml). RESULTS: Subjects were divided into NAFLD group and normal control (subjects number = 564 in each group) following abdominal US study and matching age and gender. The mean age was 57.1 years in NAFLD group and 57.5 in control group. Subjects in NAFLD group had a lower mean vitamin D than those in the control group (28.5 ± 9.5 ng/ml vs. 29.9 ± 10.2 ng/ml, P = 0.018). Subjects with serum vitamin D deficiency or insufficiency had higher odds for MS than those with sufficient vitamin D levels [deficiency vs. sufficiency, adjusted odds ratio (aOR) =1.860 (95% CI = 1.234-2.804), P = 0.003; insufficiency vs. sufficiency, aOR = 1.669 (95% CI = 1.237-2.251), P = 0.001]. Similarly, subjects in the lowest quartile of vitamin D had higher odds for MS than those in the highest quartile of vitamin D (aOR = 2.792, 95% CI = 1.719-4.538, P < 0.001). Vitamin D level was positively correlated with age and male, but negatively correlated with serum leptin level. CONCLUSION: Subjects with low vitamin D level had higher odds for MS, but higher levels of leptin, compared to those with high vitamin D levels.

Differentiation of the Follicular Variant of Papillary Thyroid Carcinoma From Classic Papillary Thyroid Carcinoma: An Ultrasound Analysis and Complement to Fine-Needle Aspiration Cytology.

OBJECTIVES: It is difficult to establish a diagnosis of the follicular variant of papillary thyroid carcinoma (PTC) using fine-needle aspiration cytology (FNAC). Preoperative features on ultrasound (US) imaging are different between follicular PTC and classic PTC. This study developed a risk score system to differentiate follicular PTC from classic PTC and to correlate the risk score of follicular PTC with its FNAC categories and pathologic features. METHODS: The US features, FNAC results, and pathologic reports of 156 follicular PTC nodules and 152 classic PTC nodules from 296 patients with PTC along with their clinical characteristics were reviewed retrospectively. A risk score system based on US features was developed by multivariate logistic regression to differentiate classic PTC from follicular PTC nodules. The risk scores were then correlated with the FNAC category and pathologic features of the nodules. RESULTS: The US risk score (5 × echogenicity + 3 × calcifications + 3 × marginal regularity) had an area under the receiver operating characteristic curve of 0.85 and a cutoff value of 8.0, with specificity of 87% and sensitivity of 69% for predicting a classic PTC nodule. The follicular PTC nodules with low Bethesda categorization (I-III) had a median US risk score of 6 (range, 0-11), which was higher than that of nodules with high categorization (IV-VI; median, 3; range, 0-11). CONCLUSIONS: The US risk score may be useful in differentiating classic PTC from follicular PTC and complementary to FNAC in identifying follicular PTC.

25(OH)D Is Effective to Repress Human Cholangiocarcinoma Cell Growth through the Conversion of 25(OH)D to 1α,25(OH)2D3.

Cholangiocarcinoma (CCA) is a devastating disease without effective treatments. 1α,25(OH)2D3, the active form of Vitamin D, has emerged as a new anti-cancer regimen. However, the side effect of hypercalcemia impedes its systemic administration. 25(OH)D is biologically inert and needs hydroxylation by CYP27B1 to form 1α,25(OH)2D3, which is originally believed to only take place in kidneys. Recently, the extra-renal expression of CYP27B1 has been identified and in vitro conversion of 25(OH)D to 1α,25(OH)2D3 has been found in some cancer cells with CYP27B1 expression. In this study, CYP27B1 expression was demonstrated in CCA cells and human CCA specimens. 25(OH)D effectively represses SNU308 cells growth, which was strengthened or attenuated as CYP27B1 overexpression or knockdown. Lipocalcin-2 (LCN2) was also found to be repressed by 25(OH)D. After treatment with 800 ng/mL 25(OH)D, the intracellular 1α,25(OH)2D3 concentration was higher in SNU308 cells with CYP27B1 overexpression than wild type SNU308 cells. In a xenograft animal experiment, 25(OH)D, at a dose of 6 µg/kg or 20 µg/kg, significantly inhibited SNU308 cells' growth without inducing obvious side effects. Collectively, our results indicated that SNU308 cells were able to convert 25(OH)D to 1α,25(OH)2D3 and 25(OH)D CYP27B1 gene therapy could be deemed as a promising therapeutic direction for CCA.

The Vitamin D Analog, MART-10, Attenuates Triple Negative Breast Cancer Cells Metastatic Potential.

Regarding breast cancer treatment, triple negative breast cancer (TNBC) is a difficult issue. Most TNBC patients die of cancer metastasis. Thus, to develop a new regimen to attenuate TNBC metastatic potential is urgently needed. MART-10 (19-nor-2α-(3-hydroxypropyl)-1α,25(OH)2D3), the newly-synthesized 1α,25(OH)2D3 analog, has been shown to be much more potent in cancer growth inhibition than 1α,25(OH)2D3 and be active in vivo without inducing obvious side effect. In this study, we demonstrated that both 1α,25(OH)2D3 and MART-10 could effectively repress TNBC cells migration and invasion with MART-10 more effective. MART-10 and 1α,25(OH)2D3 induced cadherin switching (upregulation of E-cadherin and downregulation of N-cadherin) and downregulated P-cadherin expression in MDA-MB-231 cells. The EMT(epithelial mesenchymal transition) process in MDA-MB-231 cells was repressed by MART-10 through inhibiting Zeb1, Zeb2, Slug, and Twist expression. LCN2, one kind of breast cancer metastasis stimulator, was also found for the first time to be repressed by 1α,25(OH)2D3 and MART-10 in breast cancer cells. Matrix metalloproteinase-9 (MMP-9) activity was also downregulated by MART-10. Furthermore, F-actin synthesis in MDA-MB-231 cells was attenuated as exposure to 1α,25(OH)2D3 and MART-10. Based on our result, we conclude that MART-10 could effectively inhibit TNBC cells metastatic potential and deserves further investigation as a new regimen to treat TNBC.

Postoperative recurrence of papillary thyroid carcinoma with lymph node metastasis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to retrospectively analyze the features of patients with papillary thyroid carcinoma (PTC) presenting with neck lymph node (LN) metastasis. METHODS: The study enrolled 909 patients with PTC who had undergone total thyroidectomy. After a median follow-up of 14.6 years, 73 (8.0%) patients died of thyroid cancer. A total of 536 patients had the tumor confined to the thyroid (intra-thyroid), 111 had lymph node (LN) metastasis, 225 showed soft tissue invasion, and 37 had distant metastasis. RESULTS: Compared with the intra-thyroid group, the group with LN metastases showed larger tumor size, higher postoperative thyroglobulin levels, advanced TNM stage, higher recurrence rates (5.2% vs. 31.5%), and higher disease-specific mortality (1.3% vs. 12.6%). Of the 111 patients with PTC and LN metastases, 35 (31.5%) were diagnosed with recurrence during a mean follow-up period of 16.9 ± 0.6 years. Among the 35 patients with recurrent PTC, 14 (40.0%) died of thyroid cancer. The mortality group was characterized by older, mostly male patients who presented with larger initial tumor size compared with survivors. CONCLUSIONS: In patients with PTC, the rates of recurrence and cancer mortality were higher in the group with LN metastasis than that in the intra-thyroid tumor group.

Axial length and proliferative diabetic retinopathy.

PURPOSE: To determine the correlation between axial length and diabetic retinopathy (DR) in patients with diabetes mellitus for 10 years or more. METHODS: This study was a prospective, observational, cross-sectional study. Patients with diabetes for 10 years or more were included. We excluded eyes with any other significant ocular disease or any prior intraocular surgery, except uncomplicated cataract surgery. Only one eye of each patient was included as the study eye. The severity of DR was graded as no DR, non-proliferative DR (NPDR), or proliferative DR (PDR). Axial length was measured by A-scan ultrasound (10 MHz Transducer, AL-2000 Biometer/Pachymeter; Tomey, Phoenix, AZ). Univariate logistic regression models were used to evaluate the relationship between the dependent variables (any DR, PDR) and all potential risk factors. Axial length and other factors with p value <0.1 were included in multivariate logistic regression models. Backward selection based on the likelihood ratio statistic was used to select the final models. RESULTS: We included 166 eyes from 166 patients (93 female and 73 male; mean age, 68.8 years). The mean diabetes duration was 15.4 years. Fifty-four (32.5%) eyes had no DR, 72 (43.4%) eyes had NPDR, and 40 (24.1%) eyes had PDR. In univariate analysis, hypertension (p = 0.009), renal impairment (p = 0.079), and insulin use (p = 0.009) were associated with developing any DR. Hypertension (p = 0.042), renal impairment (p = 0.014), insulin use (p = 0.040), pseudophakia (p = 0.019), and axial length (p = 0.076) were associated with developing PDR. In multivariate analysis, hypertension (p = 0.005) and insulin use (p = 0.010) were associated with developing any DR. Hypertension (p = 0.020), renal impairment (p = 0.025), pseudophakia (p = 0.006), and axial length (p = 0.024) were associated with developing PDR. CONCLUSIONS: This observational study suggests an inverse relationship between axial length and the development of PDR in patients with diabetes for 10 years or more. No relationship was found between axial length and the development of any DR.

Prognostic evaluation of patients with multicentric papillary thyroid microcarcinoma.

BACKGROUND/PURPOSE: Patients with papillary thyroid microcarcinoma (PTMC) often have an excellent prognosis. We hypothesize that patients with multicentric PTMC are associated with good clinical outcome, although multicentricity in papillary thyroid carcinoma may be associated with poor prognosis. METHODS: Retrospective analysis of multicentric PTMC cases in one medical center enrolled from 1987 to 2008 was conducted. At the end of follow-up, patients were classified as "recurrence-free" or "recurrence or persistent disease". The tumor-node-metastasis (TNM) staging system was used, and (T1, N0, M0) was regarded as "early clinical stage", whereas (T3-4, any N, any M) or (any T, N1, or M1) was regarded as "advanced clinical stage". RESULTS: There were 61 patients with a median age of 45 years. After a median follow-up period of 7.3 years (range: 2.1-22.1 years), the overall cause-specific survival rate was 98.36%. The patients with tumor diameters < 0.5 cm were all recurrence-free. Advanced clinical stage, especially distant metastasis, was highly associated with recurrence or persistent disease. CONCLUSION: Our results demonstrate excellent prognosis in multicentric PTMC patients. No patients with tumor diameter < 0.5 cm had recurrence or persistent disease. Tumor size is an important risk factor in patients with multicentric PTMC.

High interleukin-12 production from stimulated peripheral blood mononuclear cells of type 2 diabetes patients.

UNLABELLED: Sugar control is important in patients with sepsis. Interleukin (IL)-12 induces the polarization of CD4(+) T cells to the T helper 1 (Th1) phenotype. Regulatory T (T(reg)) cells are important in immunity and disease. The aim of this work is to determine whether hyperglycemia or insulin alters IL-12 response in peripheral mononuclear cells (PBMCs). METHODS: The PBMCs from 15 type 2 diabetes mellitus (DM) patients and 13 healthy controls were used for cell analysis and culture with or without treatment by glucose and insulin or stimulation by lipopolysaccharide (LPS) for 1, 2, and 3 days. RESULTS: The IL-12 level in the supernatant of LPS-stimulated PBMCs in the DM patients was significantly higher than that of healthy controls from day 1 to day 3. Kinetic IL-12 responses of LPS-stimulated PBMCs in the DM patients from day 1 to day 3 were significantly higher than that in healthy controls. The LPS-stimulated PBMCs under glucose treatment produced more IL-12 in DM patients but this did not happen in healthy controls. In DM patients, insulin could suppress IL-12 production from stimulated PBMCs but not with additional glucose treatment. CONCLUSION: The PBMCs of LPS-treated DM patients produced more IL-12 than that of LPS-treated healthy controls did. Hyperglycemia influenced IL-12 response from PBMCs in DM patients to some degree during infection.

High recurrent rate of multicentric papillary thyroid carcinoma.

BACKGROUND: Multicentric papillary thyroid carcinoma (PTC) is not unusual in patients with PTC. However, its clinical features concerning cancer recurrence and mortality are not well described. METHODS: A total of 1682 PTC patients at a single institution who underwent total thyroidectomy were retrospectively reviewed; the mean follow-up period was 7.7 +/- 0.1 years. Postoperative radioactive iodide ablation for thyroid remnant was performed after surgery for most patients. RESULTS: Of all the PTC cases reviewed, 337 cases (20.0%) were categorized as multicentric PTC. Compared with patients with unifocal PTC, multicentric PTC patients demonstrated older age, advanced TNM staging, and higher recurrence. A higher recurrence rate for multicentric PTC (20.2%) was observed compared with that for unifocal PTC; 45.8% of multicentric PTC cases with >or= 5 foci experienced cancer recurrence. Mean tumor size of the largest nodule in patients with multicentric PTC was significantly smaller than that found in unifocal PTC. Patients with multicentric papillary microcarcinoma (

Diagnostic pitfalls and therapeutic outcomes of the macrofollicular variant of papillary thyroid carcinoma.

BACKGROUND: The macrofollicular variant of papillary thyroid cancer (MFVPTC) is a rare histological variant of papillary thyroid cancer (PTC), with only 71 cases reported through 2014. This study analyzed the clinical, preoperative thyroid ultrasonography (US), and fine needle aspiration cytology (FNAC) features; and therapeutic outcomes of 11 patients with MFVPTC. METHODS: The records of 393 patients with histologically diagnosed follicular variant of papillary thyroid carcinoma (FVPTC), including 11 with MFVPTC, were retrospectively reviewed. Preoperative thyroid US findings, clinical presentation, treatment outcomes, and survival rates were analyzed. RESULT: Mean tumor size was significantly greater in patients with MFVPTC than that in those with FVPTC (4.2 ± 2.1 cm vs. 2.9 ± 1.7 cm; p = 0.016). No patient with MFVPTC had lymph node involvement, but one had a micrometastasis to the lung, which responded well to therapeutic radioiodine. All MFVPTC lesions were isoechoic on US. Eight nodules had calcifications and eight had irregular margins. FNAC showed that these tumors had low cellularity, absence or focal presence of enlarged clear nuclei, and subtle or focal nuclear features of PTC. Cells were, arranged in microfollicular pattern, with abundant colloid background. Multifocal PTCs were detected in the opposite lobe of two patients. All 11 patients with MFVPTC had excellent outcomes. No patient experienced recurrence, and survival rates were high. CONCLUSIONS: Malignant US criteria combined with FNAC features have a low preoperative diagnostic rate for MFVPTC. Surgery is recommended for patients with thyroid nodules larger than 4 cm and those with subtle and focal atypical nuclei in FNAC.

Status of bone strength and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes.

OBJECTIVE: The aim of this study was to assess the status of bone mass, microarchitecture, and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: We consecutively enrolled 285 women (aged 60.7 ±â€Š6.9 y) with T2DM who underwent bone mineral density (BMD) and trabecular bone score (TBS) assessment using dual-energy x-ray absorptiometry; T8-S1 lateral spine radiographs; laboratory evaluation; and interviews regarding clinical risk factors based on the fracture risk assessment tool (FRAX). RESULTS: Low bone mass and deteriorated bone microarchitecture were observed in 63.2% and 72.6% of women with T2DM, respectively. TBS was correlated with lumbar spine, femoral neck, and total hip BMD. Significant differences in TBS were observed between the normal BMD, osteopenia, and osteoporosis groups. Age, vertebral fracture, and bone-specific alkaline phosphatase significantly differed among groups with different T scores or those classified by TBS categories. Bone-specific alkaline phosphatase was inversely correlated with BMD and TBS but positively with glycated hemoglobin. BMD showed a weaker correlation with vertebral fracture than TBS, TBS and BMD, FRAX, and TBS-adjusted FRAX. CONCLUSIONS: Low bone mass and deteriorated TBS were noted in approximately two-thirds of T2DM women and was also associated with vertebral fracture. In addition to aging, poor glycemic control may play an important role in bone remodeling, which may be associated with changes in bone strength in T2DM women. Bone strength together with clinical risk factors has the strongest association with fracture, and may potentially be useful to identify women with T2DM at risk.

Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival.

OBJECTIVE: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. MATERIALS AND METHODS: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. RESULTS: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. CONCLUSION: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment.

Incidental and nonincidental papillary thyroid microcarcinoma.

BACKGROUND: Subtotal thyroidectomy or lobectomy without radioactive iodide ((131)I) treatment is sufficient for postoperative treatment of incidental papillary thyroid microcarcinoma (PTMC). Aggressive surgical treatment with (131)I therapy is indicated for nonincidental PTMC. METHODS: This is a retrospective analysis of 335 PTMC patients who received primary thyroid surgical treatment and long-term follow-up in a single medical center. All PTMC patients were categorized as incidental (group I) or nonincidental (group II). Group II patients (209 cases) were categorized as intrathyroid (group II A), neck lymph node or local regional soft-tissue invasion (group II B) and distant metastasis (group II C) groups. RESULTS: In group I, 105 of 126 cases received only subtotal thyroidectomy or lobectomy. None died of thyroid cancer. Histological evaluation revealed multicentric PTMC in 12 (9.5%) and 52 (24.9%) cases (P < 0.05) in groups I and II, respectively. In group II, 55 of the 209 patients (26.3%) presented with extrathyroidal involvement. Two cases of relapse occurred in group I and 20 in group II by the end of follow-up. One patient in group II B and two patients in group II C died of thyroid cancer. Nine out of ten patients in group II C were diagnosed with distant metastases before primary thyroid surgical treatment. CONCLUSION: Subtotal thyroidectomy is effective surgical treatment for incidental PTMC. For nonincidental cases, aggressive treatment is essential for reducing the risk of cancer relapse or mortality following surgery.

Prognosis and risk stratification in young papillary thyroid carcinoma patients.

Controversies remain regarding to the therapeutic methods of papillary thyroid cancer (PTC) in young patients. TNM staging and other risk evaluation system are not perfectly applicable for all young PTC patients in view of disease outcome. The aims of this study are to identify the clinical presentations, prognostic factors and risk analysis methods. From January, 1977, to June, 2006, seventy-seven patients with primary PTC younger than 20 years old at Chang Gung Medical Center in Taiwan were enrolled in this retrospective study. The patients were classified as disease-free or non-disease-free according to presence or absence of distant metastases or local recurrence at the end of follow-up. Clinical data of these patients were analyzed and compared. The average follow-up period was 10.3 years. Two patients died of PTC during the follow-up period; one died of brain metastasis, and one died of airway obstruction. Patients undergoing total thyroidectomy, especially those with disease beyond the thyroid, had better outcomes than patients not undergoing total thyroidectomy (p = 0.003). Moreover, the DeGroot clinical classification system was a better predictor of prognosis than TNM (p<0.001 vs p = 0.007). Our results suggest that prognosis for PTC is not worse in younger patients. However, patients who had undergone total thyroidectomy might have a better prognosis. Clinical classification is a good alternative classification system for predicting disease outcome in young PTC patients. Patients with confined intrathyroid lesion (

A community-based study on the association between Helicobacter pylori Infection and obesity.

Helicobacter pylori (H. pylori) infection can induce chronic inflammation and is associated with insulin resistance, metabolic syndrome and body mass index (BMI, kg/m2) changes. This study aimed to evaluate the association between H. pylori infection and overweight/obesity. This research was a cross-sectional study conducted from March 2014 to November 2016, using data from the three districts in the northeastern region of Taiwan. The inclusion criteria were an age >30 years and the absence of pregnancy. Ultimately, 2686 subjects (1713 women) were included in this study. Among the subjects aged less than 50 years, the subjects with H. pylori infection had higher mean BMI values than those without H. pylori infection (40-49 years: 25.7 ± 4.4 vs. 24.7 ± 3.8, P = 0.025; 30-39 years: 24.9 ± 4.4 vs. 24.0 ± 4.1, P = 0.063). H. pylori infection increased the risk of being obese 2 (BMI ≥30) (odds ratio, OR = 1.836, 95% CI = 1.079-3.125, P = 0.025) with adjustments for demographic factors in subjects aged less than 50 years. In conclusions, subjects with H. pylori infection and age less than 50 years may increase a risk of being obesity (BMI ≥30) compared to those without this type of infection.

The efficacy of radioactive iodine for the treatment of well-differentiated thyroid cancer with distant metastasis.

OBJECTIVE: Radioactive iodine (I) has been used as a treatment for high-risk well-differentiated thyroid cancer after thyroidectomy. The aim of this study was to evaluate the long-term follow-up results after using high accumulated doses of I (>600 mCi) for the treatment of well-differentiated thyroid cancer. PATIENTS AND METHODS: In this study, we retrospectively evaluated prospectively enrolled patients with well-differentiated thyroid cancer who were treated and followed up in Chang Gung Memorial Hospital in Linkou and Keelung, Taiwan. All the patients underwent thyroidectomy between 1979 and 2016. RESULTS: For our study, 228 patients with papillary and follicular thyroid carcinoma with distant metastases were enrolled. Of the 228 patients, 71 (31.1%) received I therapy with an accumulated dose of at least 600 mCi. Forty-four died because of disease-specific mortality (DSM) after a mean follow-up of 10.6±6.3 years. Compared with the patients in the DSM group, which included 27 survival cases, patients who were younger, and those with a multifocal tumor, more extensive thyroidectomy, and papillary thyroid carcinoma showed better prognosis. The DSM group included a higher percentage of patients who developed a secondary primary cancer after receiving a diagnosis of thyroid cancer than the survival group (18.2 vs. 3.7%). However, the difference did not reach statistical significance (P=0.075). CONCLUSION: I provided an effective therapeutic modality for well-differentiated thyroid cancer patients with distant metastasis. After a mean of follow-up 10 years, more than 60% of cases resulted in DSM when high accumulated I doses were administered.

MART-10, a 1α,25(OH)2D3 Analog, Potently Represses Metastasis of ER+ Breast Cancer Cells with VEGF-A Overexpression.

BACKGROUND: Breast cancer ranks second in the list of cancer-related deaths for women. Even under multidisciplinary treatment, 25-50% of patients with breast cancer still ultimately develop metastasis, leading to poor prognosis. In addition to inducing angiogenesis, vascular endothelial growth factor-A (VEGF-A) is believed to directly increase cancer cell metastatic potential and overexpression of VEGF-A is associated with higher invasiveness of breast cancer. 1α,25(OH)2D3, the active form of vitamin D, and its analogs have been widely applied as anticancer agents in the past. MATERIAL AND METHODS: Western blot, migration and invasion assays, enzyme-linked immunosorbent assay, and immunofluorescent stain were applied in this study. RESULT: VEGF-A increased cell migration and invasion in estrogen receptor-positive (ER+) breast cancer MCF-7 cells. VEGF-A induced an autocrine loop in MCF-7 cells as VEGF-A treatment increased both VEGF-A expression and secretion. The expression of VEGF receptor type 2 (VEGFR2) and neuropilin 1 was also up-regulated by VEGF-A in MCF-7 cells. In addition, F-actin synthesis and LIM domain kinase 1 (LIMK-1) phosphorylation were increased by VEGF-A. VEGF-A also increased ß-catenin expression and nuclear translocation of both ß-catenin and nuclear factor-ĸB (NF-ĸB), indicating increased ß-catenin and NF-ĸB activity. 1α,25(OH)2D3 and MART-10, an analog of 1α,25(OH)2D3, effectively repressed VEGF-A-induced MCF-7 cell migration and invasion and other VEGF-A-induced effects on MCF-7 cells, with MART-10 being more potent than 1α,25(OH)2D3 Conclusion: MART-10 can be deemed as a promising agent for prevention and treatment of metastasis of ER+ breast cancer with VEGF-A overexpression.

Concurrent papillary thyroid cancer with pituitary ACTH-secreting tumor.

Concomitant thyroid cancer with pituitary tumor is uncommon. This study reports a case of advanced papillary thyroid carcinoma with pituitary adrenocorticotropic hormone (ACTH)-secreting tumor. A 58-year-old male patient had thyroid cancer in 1991 and presented with headache caused by pituitary tumor with apoplexy in 1993. Due to hypopituitarism, the patient underwent radioactive iodide ((131)I) for detection and treatment of metastatic thyroid cancer after the use of recombinant human thyroid-stimulating hormone (rhTSH) in 2000. During follow-up for thyroid cancer, (201)thallium scan proved to be an effective tool for detecting metastatic thyroid cancer in the patient without pituitary TSH reserve. Pituitary ACTH-secreting tumor was confirmed in 2001 based on the high serum ACTH level and positive immunohistochemical stain for ACTH. The patient had no Cushingoid features. Moreover, serum ACTH levels were 337 and 232 pg/mL with normal serum cortisol and urine-free cortisol. Although the patient underwent three operations and a total of 370 mCi (131)I therapy for recurrent thyroid cancer, the cancer continued to progress. Finally, the patient died of pneumonia with septic shock 12 years after the diagnosis of thyroid cancer.